Amines, Aliphatic 1

Amines, Aliphatic
Ethanolamines and Propanolamines and Methylamines are separate keywords; quaternary ammonium
compounds, fatty amine oxides → Surfactants
Karsten Eller, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic of Germany (Chaps. 2 – 9)
Erhard Henkes, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic of Germany (Chaps. 2 – 9)
Roland Rossbacher, BASF Aktiengesellschaft, Ludwigshafen, Federal Republic of Germany (Chap. 10)
Hartmut Höke, Weinheim, Federal Republic of Germany (Chap. 10)

1. Introduction . . . . . . . . . . . . . . 1 4.4. Production . . . . . . . . . . . . . . . . 9

2. General Chemical Properties . . . 2 4.5. Uses . . . . . . . . . . . . . . . . . . . . 12
2.1. Salt Formation . . . . . . . . . . . . . 2 4.6. Economic Aspects . . . . . . . . . . . 14
2.2. Conversion to Carboxamides . . . 2 5. Cycloalkylamines . . . . . . . . . . . 14
2.3. Conversion to Sulfonamides . . . . 2 6. Cyclic Amines . . . . . . . . . . . . . 19
2.4. Reaction with Carbonyl Com- 7. Fatty Amines . . . . . . . . . . . . . . 25
pounds . . . . . . . . . . . . . . . . . . 3 7.1. Properties . . . . . . . . . . . . . . . . 25
2.5. Reaction with Carbon Dioxide and 7.2. Production . . . . . . . . . . . . . . . . 27
Carbon Disulfide . . . . . . . . . . . 3 7.3. Analysis and Quality Control . . . 29
2.6. Reaction with Epoxides . . . . . . . 3 7.4. Uses . . . . . . . . . . . . . . . . . . . . 30
2.7. Alkylation . . . . . . . . . . . . . . . . 3 7.5. Economic Aspects . . . . . . . . . . . 31
2.8. Formation of Isocyanates 8. Diamines and Polyamines . . . . . . 32
and Ureas . . . . . . . . . . . . . . . . 3 8.1. Diamines . . . . . . . . . . . . . . . . . 32
2.9. Reaction with Acrylonitrile . . . . . 4 8.1.1. 1,2-Diaminoethane
2.10. Formation of Isonitriles . . . . . . . 4 (Ethylenediamine) . . . . . . . . . . . 32
2.11. Oxidation . . . . . . . . . . . . . . . . 4 8.1.2. Diaminopropanes . . . . . . . . . . . . 34
2.12. Dealkylation . . . . . . . . . . . . . . 4 8.1.3. Higher Diamines . . . . . . . . . . . . 36
3. General Production Methods . . . 5 8.2. Oligoamines and Polyamines . . . 37
3.1. Production from Alcohols . . . . . . 5 8.2.1. Physical Properties . . . . . . . . . . . 37
3.2. Production 8.2.2. Chemical Properties . . . . . . . . . . 39
from Carbonyl Compounds . . . . 6 8.2.3. Production, Analysis, and Uses . . . 39
3.3. Production from Nitriles . . . . . . 6 9. Chiral Amines . . . . . . . . . . . . . 40
3.4. Production from Alkyl Halides . . 7 10. Toxicology and Occupational
3.5. Production from Nitro Compounds 7 Health . . . . . . . . . . . . . . . ... 40
3.6. Production from Olefins . . . . . . . 7 10.1. General Aspects . . . . . . . . . ... 40
3.7. Other Processes . . . . . . . . . . . . 8 10.2. Toxicology of Specific Amines ... 42
4. Lower Alkylamines . . . . . . . . . . 8 10.2.1. Alkylamines, Cyclic Amines,
4.1. Physical Properties . . . . . . . . . . 8 and Polyamines . . . . . . . . . . ... 42
4.2. Storage and Transportation . . . . 9 10.2.2. Fatty Amines . . . . . . . . . . . ... 46
4.3. Quality Specifications and Analysis 9 11. References . . . . . . . . . . . . . ... 46

Based on the corresponding article from the
fifth edition, written by Gerd Heilen, Hans
Jochen Mercker, Dieter Frank, Richard A.
Reck, and Rudolf Jäckh
1. Introduction
Primary, secondary, and tertiary amines are dis-
tinguished on the basis of the number of hy-
drogen atoms in ammonia that have been re-
placed by organic groups. Substitution at the
nitrogen atom by a fourth substituent gives
quaternary ammonium compounds. The lower
aliphatic amines are those with up to six carbon
atoms per alkyl chain. Long-chain amines, with
more than eight atoms per carbon chain, are gen-
erally known as fatty amines and are discussed
in Chapter 7.

c 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

10.1002/14356007.a02 001
2 Amines, Aliphatic

In 1849, Wurtz prepared methylamines and 2.2. Conversion to Carboxamides

ethylamines by hydrolysis of the corresponding
alkyl isocyanates, trialkyl cyanurates, and alky-
lureas [1]. However, Hofmann was the first to
use the terms “primary”, “secondary”, and “ter-
tiary” and to carry out fundamental work on the
synthesis, properties, and structure of amines
[2].
In general, naturally occurring amines are rel-
atively complex compounds (e.g., alkaloids, vi-
tamins, and amino acids); however, some lower
alkylamines and diamines, such as tetramethy-
lenediamine (putrescine) and pentamethylene-
diamine (cadaverine), are known as degradation
or decomposition products of proteins.
With a worldwide production (2000) of sev-
eral 100 000 t/a, the aliphatic amines are among
the most important organic intermediates in the
chemical industry. The range of uses of these
compounds is correspondingly wide. Major uses
include those in the production of agrochemicals
(in particular, herbicides), dyes, drugs, surfac-
tants, and plastics, as auxiliaries for the rubber,
textile, and paper industries, and as anticorrosion
agents and process chemicals for gas scrubbing.
2. General Chemical Properties
The chemistry of the aliphatic amines is deter-
mined by the electron lone pair on the nitrogen
atom and by the tendency of the hydrogen atoms
bonded to nitrogen to be replaced by other sub-
stituents.
Amines react with carboxylic acids and their es-
ters, chlorides, and anhydrides to give the corre-
sponding substituted carboxamides:
Very good yields are obtained, particularly
with carboxylic acid chlorides, for which the
reaction is highly exothermic. With carboxylic
acids, the reaction often stops at the initially
formed ammonium salt. This type of reaction
is utilized industrially, for example, in the syn-
thesis of various herbicides with an acid amide
structure.
2.3. Conversion to Sulfonamides
The reaction with benzenesulfonyl chloride is
utilized for distinguishing among primary, sec-
ondary, and tertiary amines (Hinsberg test),
as well as for their preparative separation.
Whereas primary amines form alkali-soluble N-
alkyl benzenesulfonamides, secondary amines
give alkali-insoluble N,N-dialkyl benzenesul-
fonamides, and tertiary amines do not react un-
der these conditions. Limitations can arise with
long-chain primary amines, which are alkali-
insoluble despite their acidic hydrogen, and with
tertiary amines, which may undergo quaterniza-
tion with the sulfonyl chloride.

2.1. Salt Formation

Because they carry alkyl substituents, the

aliphatic amines are stronger bases than ammo-
nia (see Table 1); with acids, they form salts that
are very soluble in water but insoluble in or-
ganic solvents. This property, combined with the
difference in solubility between amine and salt,
makes amines good acid acceptors and solvents
for gas scrubbing and for certain extraction pro-
cesses (e.g., in the synthesis of semisynthetic
penicillins).

2.4. Reaction with Carbonyl
Compounds
Depending on the reaction conditions and the
compound employed, carbonyl compounds re-
act with amines to form imines (Schiff bases) (2)
or enamines (3); these products can be hydro-
genated to give more highly alkylated amines.
This reaction is an important method for syn-
thesizing higher amines. The intermediate hemi-
aminals (1) are usually not isolable. Aldehydes
generally react faster than ketones. Secondary
amines can only form enamines, and tertiary
amines neither of the two products.
An amine, an aldehyde, and a compound with
an activated hydrogen atom, such as a ketone,
can react to form a Mannich base.
In this case, the condensation product be-
tween the aldehyde and the amine is attacked
by the C – H acidic compound, in this case the
ketone.
2.5. Reaction with Carbon Dioxide and
Carbon Disulfide
The carbamic acid or dithiocarbamic acid
formed in this reaction is unstable but can be
isolated as a salt or an ester.
Amines, Aliphatic 3
Dithiocarbamates obtained from various
amines play a key role as vulcanization accel-
erators in the rubber industry.
2.6. Reaction with Epoxides
Primary amines react with epoxides to give a
mixture of mono- and dioxyalkylated deriva-
tives, whereas secondary amines give only
monooxyalkylated compounds, and tertiary
amines form quaternary ammonium com-
pounds.
This oxyalkylation reaction is one of the
most important industrial reactions of aliphatic
amines and is utilized for the preparation of
flocculants, surface coating resins, drug in-
termediates, and products for gas scrubbing
(→ Ethanolamines and Propanolamines).
2.7. Alkylation
The reaction of amines with alkyl halides and
dialkyl sulfates to give, ultimately, quaternary
ammonium compounds is utilized in preparative
pharmaceutical chemistry and for the prepara-
tion of anticorrosion agents and biocides.
The reaction of alkyl halides with ammonia is
not very useful for the preparation of primary or
secondary amines since these are stronger bases
and preferentially attack the halides. Tertiary
amines can be prepared, though. On a laboratory
scale, primary amines can be obtained by using
tetramethylenehexamine, and secondary amines
with cyanamide.
2.8. Formation of Isocyanates and Ureas
The reaction of phosgene with primary amines
leads first to the corresponding carbonyl chlo-
ride; subsequent cleavage of hydrogen chloride
4 Amines, Aliphatic
gives the alkyl isocyanate. Excess amine reacts
with the isocyanate with formation of ureas:
This reaction is important in the preparation
of various herbicides with urea, carbamate, or
thiocarbamate structures and, particularly in the
case of polyfunctional amines, in polyurethane
chemistry. The reaction of secondary amines
with phosgene proceeds via an analogous inder-
mediate chloride to form N,N
-tetraalkylureas.
2.9. Reaction with Acrylonitrile
The addition of a primary or secondary amine
to acrylonitrile to form an aminopropionitrile
is utilized industrially on a large scale for the
preparation of higher diamines and polyamines,
because the nitrile can be readily hydrogenated
to the amine.
RNH2 + CH2 =CHCN −→ RNHCH2 CH2 CN
[−→ RNH(CH2 )3 NH2 ]
2.10. Formation of Isonitriles
Primary amines react with trichloromethane un-
der basic conditions to form isonitriles:
RNH2 + CHCl3 + 3 KOH −→ RNC + 3 KCl + 3 H2 O
Because of the strong unpleasant odor of the
isonitriles, the reaction can be used as a test for
primary amines. For the lower amines, the re-
action can be used synthetically as well. An al-
ternative route uses the N-alkylformamides to
synthesize isonitriles.
2.11. Oxidation
In contrast to their salts, the free amines are
sensitive to oxidation, giving various products,
depending on the oxidizing agent and the type
of amine. Tertiary amines are oxidized by hy-
drogen peroxide to amine oxides, whereas the
corresponding compounds formed from primary
and secondary amines undergo further reaction
to give the corresponding hydroxylamines or al-
doximes:
Oxidation with nitrous acid can be used to
distinguish among primary, secondary, and ter-
tiary amines. Primary amines undergo diazoti-
zation followed by loss of gaseous nitrogen and
afford alcohols by reaction of the intermediate
carbenium ion with water. Secondary amines re-
act to give yellow N-nitrosoamines. Normally,
tertiary amines do not react.
RCH2 NH2 + HNO2 −→ RCH2 OH + H2 O + N2
(RCH2 )2 NH + HNO2 −→ (RCH2 )2 N – N=O + H2 O
The formation of nitrosamines can be a seri-
ous problem, particulary with secondary amines,
since they are highly mutagenic. During nor-
mal use they are not formed, but upon contact
with nitrites or nitrous oxides traces can be pro-
duced that give rise to problems during handling.
Air contamination with secondary amines is thus
considered quite problematic.
2.12. Dealkylation
Tertiary amines can be dealkylated by con-
verting them to basic quaternary ammonium
salts, which decompose upon heating. If only
methyl groups are present, they are eliminated
as methanol or dimethyl ether; all higher alkyl
groups furnish alkenes, e.g.,

This reaction, known as the Hofmann degra-
dation, is seldom utilized synthetically, but used
to be important for elucidating the structure of
unknown amines.
3. General Production Methods
3.1. Production from Alcohols
The reaction of the appropriate alcohol with
ammonia over a suitable catalyst is now the
most common process for the preparation of
lower alkylamines. In this reaction, the prod-
uct is always a mixture of primary, secondary,
and tertiary amines because the primary amine
formed initially can react further with one or
two molecules of alcohol. While the initial con-
version of the alcohol to the primary amine is
close to thermoneutral, the formation of sec-
ondary and tertiary amines is exothermic and
thus thermodynamically favored. Also, the pri-
mary amine is more nucleophilic than ammonia
and hence has a higher reactivity. The product
distribution can be controlled to a certain ex-
tent by means of the reaction conditions (tem-
perature, excess of ammonia, residence time).
Because the mixture of products usually ob-
tained does not correspond to market require-
ments, amines that are not marketable can be
recycled. Thus, the yield of the desired amine
can be increased to above 90 %.
Previously, this reaction was carried out
with pure dehydration catalysts (e.g., alumina,
silica, titania, thorium oxide, tungsten oxide,
chromium oxides, phosphates or various mixed
oxides such as silica – alumina, clays, or zeolites
[3]) and temperatures up to 500 ◦ C; however, use
of these catalysts is now restricted to the produc-
tion of methylamines. For the conversion of an
alcohol containing two or more carbon atoms,
catalysts possessing hydrogenating and dehy-
drogenating properties have become important.
The catalysts used are mainly based on nickel,
cobalt, copper or iron, and to a lesser extent plat-
inum or palladium. Noble metal catalysts have a
Amines, Aliphatic 5
tendency to cause C – C or C – N bond cleavage
and can hence give lower selectivities. Promot-
ers such as Ag, Zn, In, Mn, Mo, and alkali met-
als are added to improve catalyst performance.
Mostly, the active components are supported on
a carrier such as Al2 O3 , SiO2 , or ZrO2 . Zeo-
lites have been suggested as carriers to improve
the selectivity towards primary amines [4]. In
this process, the alcohol, ammonia, and hydro-
gen are passed continuously over the catalyst
in a fixed-bed reactor. The reaction takes place
at about 0.5 – 25 MPa and about 100 – 250 ◦ C,
depending on the catalyst and on whether the
liquid-phase or the gas-phase process is used.
Mechanistic details of the process have been
reviewed [5]. The first and rate-determining step
is the dehydrogenation of the alcohol to the car-
bonyl compound. Addition of ammonia is fol-
lowed by loss of water to yield an imine or
an enamine, which is hydrogenated to the final
amine. Side reactions are amine disproportiona-
tion, especially at higher reaction temperatures,
and to a lesser degree aldol condensation of the
intermediate aldehydes, formation of Schiff base
from these aldehydes and the amine product, and
nitrile formation, which occurs at high temper-
atures and low hydrogen pressures.
A two- to eightfold excess of ammonia is
used to shift the equilibrium towards the pri-
mary amines. Although hydrogen is not required
as a direct reactant, in its absence imines, enam-
ines, and even nitriles are formed. Hydrogen also
maintains the activity of the catalyst by remov-
ing carbonaceous deposits and metal carbides or
nitrides and prevents disproportionation of the
amine products [6]. The various versions of the
process have been reviewed in detail [7]. Sev-
eral surface-bound intermediates were identified
6 Amines, Aliphatic
by Fourier transform IR spectroscopy [8]. While
the amination of diols and polyols in principle
follows the same rules as for the monools, the
occurrence of numerous side reactions, for in-
stance, cyclizations, is a complicating factor [9].
The same method is also useful for alkylat-
ing primary or secondary amines instead of am-
monia. When an amine and an alcohol having
different aliphatic substituents react, the prod-
uct is a mixed aliphatic amine. For example,
N,N-dimethylethylamine can be obtained from
dimethylamine and ethanol. To avoid transalkyl-
ation at the nitrogen atom in reactions of this
type, copper catalysts are recommended [10].
Copper chromite is a particularly effective cat-
alyst for long-chain tertiary amines such as di-
methyldodecylamine [11].
3.2. Production from Carbonyl
Compounds
Aldehydes and ketones are used in preference
to alcohols for amine synthesis if this is more
economical. Generally, this is the case only for
the lower aldehydes (obtained from oxo synthe-
sis) and acetone obtained as a byproduct in the
production of phenol (Hock synthesis).
The reaction between a carbonyl compound
and ammonia or an amine occurs in two steps:
the imine or Schiff base formed initially is hy-
drogenated with hydrogen in a second step to
give the amine. The usual procedure is similar
to that for the conversion of alcohols; the re-
action mixture, comprising the carbonyl com-
pound, ammonia and hydrogen, is passed over
a fixed-bed catalyst. In some cases, it can be
advantageous to carry out the reaction in two
stages. The carbonyl compound and ammonia
or the amine react first, the water of reaction
is removed, and only then is the hydrogenation
carried out [12].
The essential difference between the amina-
tion of an aldehyde or ketone and that of an al-
cohol is that in the former hydrogen is a reac-
tant and is consumed in a stoichiometric amount.
The substantially higher heat of reaction of this
process (e.g., 60.4 kJ/mol for acetone [13] ver-
sus 7.1 kJ/mol for isopropyl alcohol) necessi-
tates a fundamentally different reactor design.
In general, the process is carried out in the va-
por phase at 100 – 160 ◦ C and atmospheric or
slightly above atmospheric pressure. High-pres-
sure processes can also be employed if the heat
of reaction can be removed by appropriate mea-
sures, such as a high recycle rate or with a multi-
tubular reactor. Since the reaction temperatures
are lower than for the reaction of alcohols, in
principle, higher selectivities can be achieved.
Generally, the same catalysts as for the hy-
drogenative amination of alcohols can be used;
control of product distribution by adjusting the
amount of excess ammonia and workup by dis-
tillation are also much the same. Comprehen-
sive reviews of industrial and preparative pos-
sibilities for synthesis of amines from carbonyl
compounds are available [7], [14].
It is also possible to use other reducing
agents instead of hydrogen, but these are of lit-
tle industrial importance. This is often due to
the difficulty of handling and the cost of the
reagents (e.g., selenophenol or NaBH4 ). The
Leuckart – Wallach reaction, in which ammo-
nium formate is used to aminate the carbonyl
compound with formation of CO2 as byproduct,
has found some use.
3.3. Production from Nitriles
Frequently, nitriles can be obtained more eco-
nomically than the corresponding alcohols or
carbonyl compounds. They are synthesized by
ammoxidation, the addition of an amine or an al-
cohol to acrylonitrile, or from the corresponding
carboxylic acid. Nitriles are converted into the
corresponding amines, preferably by catalytic
hydrogenation:
Noble metal (palladium, platinum, rhodium),
nickel, or cobalt catalysts are generally em-

ployed, but iron catalysts have been used to an
increasing extent [15], largely for economic rea-
sons. Whereas the supported noble metals per-
mit the use of relatively mild reaction conditions
(20 – 100 ◦ C, 0.1 – 0.5 MPa), pressures as high
as 25 MPa and temperatures of up to 180 ◦ C are
required with nickel or cobalt catalysts. When
di- or polynitriles are hydrogenated to di- or
polyamines, a base such as NaOH is often added
to the catalyst [16]. There are various versions
of the process, but those most often used are the
batch process with a suspended catalyst and the
continuous process with a fixed-bed catalyst.
Side reactions resulting in the formation of
secondary amines always occur, but these can be
suppressed by the addition of ammonia, sodium
hydroxide solution, or an acid [7]. Alternatively,
process conditions can be adjusted to make the
formation of secondary or tertiary amines the
principal reaction. This alternative is of interest,
for example, in the synthesis of di- and triethy-
lamines from acetonitrile [17] or dibutylamine
from butyronitrile [18].
The hydrogenation of acrylonitrile is a spe-
cial case. Whereas saturated amines are nor-
mally the only products of this reaction, the use
of copper chromite as a catalyst instead of noble
metals, nickel, or cobalt leads to allylamine and
diallylamine [19].
Many important nitrile hydrogenations to
form the corresponding amines are based on pre-
vious addition reactions of acrylonitrile. Alco-
hols add to acrylonitrile only in the presence of
a basic catalyst such as NaOH, KOH, or qua-
ternary ammonium hydroxides. Since amines
are themselves sufficiently basic, addition oc-
curs readily. Sometimes higher temperatures are
needed for cyanoethylation, and stabilizers have
been described to avoid polymerization of acry-
lonitrile [20].
3.4. Production from Alkyl Halides
The reaction of an alkyl halide with ammonia or
an amine gives an alkylammonium halide, from
which the amine can be liberated with a caus-
tic alkali solution. Although a standard method
of preparative chemistry, this route is industri-
ally important only for the preparation of ethyl-
enediamine, the homologous polyamines, and a
few special amines such as allylamine and some
Amines, Aliphatic 7
small-volume pharmaceuticals. The reasons for
this restricted use are the lack of cheap starting
materials, corrosion and product-quality prob-
lems that arise in the processing of halides, and
the need to dispose of the salt that is formed.
3.5. Production from Nitro Compounds
Whereas the reduction of nitro compounds is
one of the most important methods for the syn-
thesis of aromatic amines, this route has not be-
come important for the production of aliphatic
amines. Because the availability of appropriate
nitroalkanes is restricted, this method is used
only in a few special cases, e.g., the production
of 2-amino-1-butanol, the precursor for the an-
tituberculotic ethambutol.
The reduction proceeds via the nitroso or hy-
droxylamine intermediate, in some cases even at
room temperature, and gives the amine in yields
of 90 % or more. Platinum, palladium, rhodium,
nickel, or copper is used as the hydrogenation
catalyst [7]. The reaction is highly exothermic
(ca. 500 kJ/mol per nitro group), and therefore
heat must be removed rapidly to control the pro-
cess. Nitroparaffins are more difficult to hydro-
genate than their aromatic counterparts [21].
Functionalization of alkenes with NO or NO2
has been described; the reaction follows a radical
path and affords a mixture of products, among
them nitroalkenes. Reduction of the latter also
leads to amines, but has found no industrial ap-
plication so far. Likewise, primary amines were
obtained from paraffins by nitration with HNO3
or liquid NO2 and hydrogenation of the resulting
nitroparaffin/ketone mixture in the presence of
ammonia [22]. The preparation of 1,2-diamines
from nitroolefins and O-alkylhydroxylamines
has been described [23].
3.6. Production from Olefins
Amines having a tertiary alkyl group adjacent to
the nitrogen atom (e.g., tert-butylamine) are dif-
ficult to obtain by conventional synthetic meth-
ods. These compounds can be prepared readily
by addition of hydrogen cyanide to an alkene,
e.g., 2-methylpropene, in an acidic medium:
8 Amines, Aliphatic
This process, known as the Ritter reaction
[24], is carried out at 30 – 60 ◦ C, and the result-
ing formamide intermediate is hydrolyzed when
the reaction mixture is heated to ca. 100 ◦ C. To
liberate the amine, the acidic mixture is neu-
tralized to give sodium formate and the salt
of the original acid, i.e., sodium sulfate. Be-
cause hydrocyanic acid is difficult to handle
and causes corrosion problems, one carbon atom
is lost as formate, and significant amounts of
salts (ca. 3.3 kg/kg tert-butylamine) must be dis-
posed of in deep wells, this process is restricted
to amines that cannot be obtained by one of
the methods described in Sections 3.1, 3.2, 3.3,
3.4, and 3.5. Besides tert-butylamine and tert-
octylamine, these are only a few amines of phar-
maceutical interest.
Although advantageous thermodynamically,
the direct addition of ammonia or an amine to an
olefinic double bond is restricted to a few cases in
which either an activated amine or a compound
with an activated double bond is employed, for
example, the addition of an amine to acryloni-
trile. It is however possible to achieve the ad-
dition of ammonia to unactivated alkenes under
pressure and by using catalysts. The most effec-
tive catalysts are acidic zeolites. The first suc-
cessful demonstration was the formation of ethy-
lamines from ethylene and ammonia with H-
mordenite [25]. Although the conversion for the
direct amination of alkenes is low, being limited
by kinetic factors and the thermodynamic equi-
librium, the selectivity for monoalkylamines can
be excellent given the proper choice of zeolite
and alkene. Small-pore zeolites are most suit-
able for ethylamines [26], while medium-pore
zeolites can be used to prepare tert-butylamine
[27]. Certain large-pore zeolites have been found
to offer improvements over medium-pore zeo-
lites [28–30].
Homogeneously catalyzed amination of
alkenes is restricted to some special cases [31],
[32]. Although not very selective, hydroformy-
lation of alkenes in the presence of ammonia or
amines [33] might find applications in future.
So far it is hampered by the fact that in addition
to the amines arising from the n-aldehyde and
isoaldehyde, significant amounts of alcohols are
formed besides dimerization products [34].
3.7. Other Processes
The hydrogenation of aromatic amines to cy-
cloalkylamines is industrially restricted to the
production of cyclohexylamines (see Chap. 5).
A process for synthesizing amines from carbon
monoxide, hydrogen, and ammonia or amines
over an activated iron catalyst by a method of
the Fischer – Tropsch-type was described [35],
but this is not used on an industrial scale. All
other synthetic routes described in the literature,
for instance reduction of amides [36], are so far
essentially laboratory methods that are suitable
for the preparation of small quantities and are
carried out on an industrial scale only in isolated
cases. For details see [3].
4. Lower Alkylamines
4.1. Physical Properties
Ethylamine is gaseous at room temperature; di-
ethylamine, triethylamine, and higher amines up
to about twelve carbon atoms per alkyl chain
are liquid, and long-chain amines containing still
higher alkyl groups are solid.
The short-chain amines are readily soluble in
water, alcohol, ether, and conventional organic
solvents. Amines containing more than five car-
bon atoms are only partially or very sparingly
soluble in water. The solubility in water gener-
ally decreases with increasing temperature, and
in some cases the miscibility gap vanishes at
lower temperatures. For example, triethylamine
is completely miscible with water below about
18 ◦ C but is only partially miscible with wa-
ter above this temperature. Therefore, industrial
phase separations (amine/water) are often car-
ried out at elevated temperatures.
All alkylamines, but particularly the lower
members, which have high vapor pressures, have
a characteristic ammonia odor. The odor de-
creases with increasing substitution.

Physical properties of importance for charac-
terizing and handling the alkylamines are sum-
marized in Table 1. For further data, reference
may be made to the relevant tables and the pro-
ducers’ data sheets.
4.2. Storage and Transportation
The aliphatic amines are usually stored in car-
bon steel or stainless steel containers; relatively
small amounts can be kept in glass or ceramic
vessels. Nonferrous metals such as copper, alu-
minum, zinc, lead, and their alloys (e.g., brass)
are not resistant to amines. Aqueous amine so-
lutions are basic and slowly etch glass. Ethy-
lamine must be stored under pressure because it
boils below room temperature. Isopropylamine
(bp 32.4 ◦ C) is usually stored in cooled and iso-
lated tanks or in pressurized containers. To facil-
itate storage and transport, these amines are also
produced and distributed in the form of aque-
ous solutions (e.g., 40 % or 70 %). The aliphatic
amines have a virtually unlimited shelf life, but
they should be stored under nitrogen to avoid
contact with carbon dioxide (resulting in forma-
tion of carbamates) and atmospheric moisture.
All of the amines discussed here are in-
flammable. Some of them have very low flash
points (see Table 1), and they form explosive
mixtures with air. Hence, when these com-
pounds are stored and transported, the relevant
statutory regulations for inflammable liquids or
pressurized gases must be observed. Because
these vary greatly from country to country, they
cannot be discussed in detail here.
To prevent odor nuisance (odor thresholds are
below 0.1 ppm in some cases) and impermissi-
ble emissions, special precautions must be taken
during storage and, in particular, during transfer
from one container to another. Where the pro-
cess cannot be carried out in a closed system and
relatively large amounts are handled, absorption
plants for washing off-gas must be provided.
Scrubbing with water is frequently adequate, but
better treatment of off-gas is achieved by scrub-
bing with an acid. For smaller plants, adsorp-
tion on active carbon filters is advisable under
certain circumstances. This method has the ad-
ditional advantage that the adsorbed amines can
be recovered.
Amines, Aliphatic 9
The toxicity (Chap. 10) of these amines also
makes it necessary to take certain precautions
with regard to occupational safety. These in-
clude, in particular, avoiding inhalation of amine
vapors by using respiratory equipment and reli-
able prevention of skin and eye contact with fluid
amines by wearing protective clothing.
4.3. Quality Specifications and Analysis
In the case of individual amines, the quality spec-
ifications are very high. Particularly for amines
with a wide range of uses (e.g., ethylamine),
specifications require a purity of above 99.7 %,
although usually 98.0 – 99.5 % purity is consid-
ered adequate. Some end uses impose additional
maximum values on the content of water, am-
monia, and unsaturated amines or, in the case of
tertiary amines, on the content of primary and
secondary amines.
The amine content is determined by acid titra-
tion of the basic nitrogen, and the purity is deter-
mined preferably by gas chromatography. Also
of importance is the determination of the water
content by the Karl Fischer method, titration of
the imine content by oximation, and the deter-
mination of physical properties.
4.4. Production
With few exceptions, aliphatic amines of indus-
trial importance are produced by any one of
the methods described in Chapter 3. The main
routes start from the corresponding hydroxyl or
carbonyl compounds. The choice of process de-
pends mainly on the following criteria:
1) Price of the starting materials
2) Availability of the starting materials
3) Conversion of any existing plants to allow
for different pressures in the two processes
4) Availability of hydrogen (hydrogen con-
sumption and pressure differ in the two pro-
cesses)
5) Fiscal reasons (taxes or subsidies on partic-
ular materials, e.g., ethanol)
Because these factors vary greatly from coun-
try to country, and in some cases even from re-
gion to region, and are changing continually, the
Table 1. Physical properties of commercial alkylamines

10
Compound CAS registry Formula Mr mp, ◦ C bp, ◦ C d 20
4 n20
D Flash point, ◦ C pKb (25 ◦ C)
number

Ethylamine [75-04-7] C2 H5 NH2 45.09 −80.6 16.6 0.6829 1.3663 −52 3.25
Diethylamine [109-89-7] (C2 H5 )2 NH 73.14 −50 56.3 0.7056 1.3864 −23 2.88
Triethylamine [121-44-8] (C2 H5 )3 N 101.19 −115 89.3 0.7275 1.4010 −11 3.24

Propylamine [107-10-8] C3 H7 NH2 59.11 −83 47.8 0.7173 1.3870 −30 3.41
Dipropylamine [142-84-7] (C3 H7 )2 NH 101.19 −63 109.2 0.7400 1.4050 7 3.09
Tripropylamine [102-69-2] (C3 H7 )3 N 143.26 −93.5 156 0.7558 1.4171 36 3.35

Isopropylamine [75-31-0] (CH3 )2 CHNH2 59.11 −95.2 32.4 0.6886 1.3742 −37 3.37
Diisopropylamine [108-18-9] [(CH3 )2 CH]2 NH 101.19 −61 84 0.7169 1.3924 −17 3.43 (20 ◦ C)

Amines, Aliphatic
Butylamine [109-73-9] C4 H9 NH2 73.14 −49.1 77.8 0.7414 1.4031 −8 3.39
Dibutylamine [111-92-2] (C4 H9 )2 NH 129.25 −62 159 0.7670 1.4177 39 3.04
Tributylamine [102-82-9] (C4 H9 )3 N 185.36 −70 213 0.7771 1.4291 70 3.11

Isobutylamine [78-81-9] (CH3 )2 CHCH2 NH2 73.14 −85.5 68 0.7360 1.3988 −16 3.59
Diisobutylamine [110-96-3] [(CH3 )2 CHCH2 ]2 NH 129.25 −77 139 0.7450 1.4090 25.5 3.18
Triisobutylamine [1116-40-1] [(CH3 )2 CHCH2 ]3 N 185.36 −21.8 191.5 0.7684 1.4252 3.68
1-Methylpropylamine (d, [13952-84-6] C2 H5 CH(CH3 )NH2 73.14 −10.4 63.5 0.7246 1.3932 −20 3.43
l)
Bis(1-methyl)pro- [626-23-3] [C2 H5 CH(CH3 )]2 NH 129.25 −70 135 0.7534 1.4111 21
pylamine (d,
l)
1,1-Dimethylethylamine [75-64-9] (CH3 )3 CNH2 73.14 −67.5 44.4 0.6958 1.3784 −9 3.39

Pentylamine [110-58-7] C5 H11 NH2 87.16 −55 104.4 0.7547 1.4118 7 3.36
Dipentylamine [2050-92-2] (C5 H11 )2 NH 157.30 −32 202 0.7771 1.4272 71 2.82
Tripentylamine [621-77-2] (C5 H11 )3 N 227.44 240 – 5 0.7907 1.4366 88
2-Pentylamine [625-30-9] C3 H7 CH(CH3 )NH2 87.16 91.5 0.7384 1.4027
3-Pentylamine [616-24-0] (C2 H5 )2 CHNH2 87.16 91 0.7479 1.4063
2-Methylbutylamine [96-15-1] C2 H5 CH(CH3 )CH2 NH2 87.16 95.4 0.7490 1.4114 3
3-Methylbutylamine [107-85-7] (CH3 )2 CH(CH2 )2 NH2 87.16 −60 95 0.7505 1.4083 4 3.98
Bis(3-methylbutyl)amine [544-00-3] [(CH3 )2 CH(CH2 )2 ]2 NH 157.30 −44 188 0.7669 1.4235
Tris(3-methylbutyl)amine [645-41-0] [(CH3 )2 CH(CH2 )2 ]3 N 227.44 235 0.7848 1.4331 82

Hexylamine [111-26-2] C6 H13 NH2 101.19 −19 130 0.7660 1.4180 34 3.44
 Amines, Aliphatic 11

reasons for the choice of a particular process de-

pend strongly on individual circumstances. Cur-
pKb (25 ◦ C)

rently (2000) the commercial use of the alcohol

route is prevalent.
3.35

3.36

4.28
4.87

The aliphatic amines of large-scale industrial

6

importance (mainly C2 – C4 ) can be produced

Flash point, ◦ C

in a multipurpose plant that can be used for the

production of various amines under similar re-
58
53

0
9

10

21

48
−45
−27

−20

action conditions, with only small differences in

workup.
The reaction of an alkyl halide with ammo-
nia or an amine typically results in formation
1.4294
1.4313
1.4369

1.4010
1.4040
1.3720
1.3905

1.4140
1.4205
1.4387

1.4286

1.4358

1.4191

of sodium halide as an undesired byproduct.

n20
D

This synthetic route is used for ethylenediamine

and special amines such as allylamines (Chap-
ter 3.4). Ethylenediamine can also be produced
from ethanolamine and ammonia or directly
0.7826
0.7894
0.7936

0.7341
0.7398
0.6754
0.7151

0.7621
0.7874

0.9166

0.8727
0.751
d 20

from ethylene oxide.

4

Other production processes have become im-

portant only for a few amines. Examples are the
production of tert-butylamine from isobutene
108 – 9

146 – 7

116 – 9
bp, ◦ C

179.6
169.2
220.5

53.2

and hydrogen cyanide or, since 1987, by direct

91

36
66

127

111

110

amination [37] (Section 3.6).

Another industrial route to alkylamines is
the addition of amines to acrylonitrile fol-
lowed by hydrogenation. Examples are 1,3-
mp, ◦ C

<−70

<−70

<−50
17

−75
−70

−136

−88
−88
0

diaminopropane and dipropylenetriamine, pro-

duced by combination of ammonia and acry-
lonitrile and subsequent hydrogenation, and the
hydrogenation of 3-alkoxypropionitriles, which
129.25
129.25
157.30

87.16
101.19
73.14
87.16

129.25
57.09
97.16

107.58

135.64

89.14

are produced by addition of alcohols to acryloni-

Mr

trile to give 3-alkoxypropylamines (Section 3.3).

When the conversion of alcohol to amine is
C4 H9 CH(C2 H5 )CH2 NH2

performed in the liquid phase under high pres-

ClCH2 CH2 N(C2 H5 )2
[(CH3 )2 CH]2 NC2 H5

sure (typically 20 MPa) the plant can consist of a

(CH2 =CH-CH2 )2 NH

ClCH2 CH2 N(CH3 )2

CH2 =CH-CH2 -NH2
(CH3 )2 CHN(CH3 )2

CH3 O(CH2 )3 NH2

synthesis unit with a cylindrical reactor, heat ex-

C4 H9 NHC2 H5
C2 H5 N(CH3 )2
C4 H9 NHCH3

changers, high- and medium-pressure (3 MPa)

C10 H21 NH2
C8 H17 NH2

separators and a distillation unit. The distilla-

Formula

tion towers separate ammonia/low-boiling alky-

lamine, water, and high-boiling residues and
remove the monoalkylamine from di- and tri-
[13360-63-9]

alkylamine. Ammonia/low-boiling alkylamine

CAS registry

[5332-73-0]
[7087-68-5]
[2016-57-1]

[124-02-7]
[104-75-6]

[100-35-6]
[996-35-0]
[110-68-9]

[107-11-9]
[111-86-4]

[598-56-1]

[107-99-3]

is generally used in excess and recycled to the

number

synthesis reactor. Water is typically isolated by

phase separation and fed to a wastewater treat-
N-Ethyldiisopropylamine
N,N-Dimethylethylamine

ment system. If the reaction mixture does not

3-Methoxypropylamine
N,N-Dimethylisopro-
N-Methylbutylamine
Table 1. (Continued)

meet market requirements, the excess amines

N-Ethylbutylamine
2-Ethylhexylamine

chloroethylamine
chloroethylamine
N,N-Dimethyl-2-

can be returned to synthesis stage since the

N,N-Diethyl-2-
Diallylamine
Decylamine

mono-, di-, and trialkylamines are in thermo-

Octylamine

Allylamine
Compound

pylamine

dynamic equilibrium (see Section 3.1).

Reactions in the gas phase are typically car-
ried out in low-pressure reactor systems which
12 Amines, Aliphatic
require only one gas – liquid separator (3 MPa)
and can be set up with cheaper equipment. Fig-
ure 1 shows a simplified flow diagram of the cat-
alytic gas-phase reaction of ethanol with ammo-
nia. In this case all three ethylamines are sepa-
rated in a specially designed distillation unit and
marketed.
To construct a multipurpose plant, it must first
be decided whether the synthesis is to be run
at low to medium (0.1 – 3 MPa) or high pres-
sure (5 – 30 MPa). The design of the distilla-
tion unit depends on the range of amines to be
produced. For the whole range of lower alky-
lamines (starting with ethylamines) a compli-
cated system of five to six distillation towers is
needed. With three distillation towers, a plant for
a restricted portfolio of alkylamines can be run.
The first pressure tower (typically 1.5 – 1.8 MPa)
separates ammonia/low-boiling amine, the sec-
ond water, and the third the desired alkylamine.
The excess amines are reycled to the synthe-
sis unit. For instance, a monoalkylamine can be
produced by feeding pure alcohol and ammonia
or by feeding recycled di- and trialkylamines,
fresh alcohol, and ammonia. Instead of ammo-
nia low-boiling amines such as methylamine or
dimethylamine can be used for the synthesis of
mixed amines. An example is the production of
N,N-dimethylethylamine from ethanol and di-
methylamine.
4.5. Uses
Ethylamines. Of the amines discussed here,
with a worldwide market volume (2000) of about
80 000 t/a, the ethylamines are the most impor-
tant lower aliphatic alkylamines. For tax rea-
sons, in Japan ethylamines are produced from
acetaldehyde, while in other countries ethanol
is mostly used. The general production pro-
cesses are similar; differences lie in the catalyst
used, the distillation conditions, and the recy-
cle streams (e.g., [39]). Production of di- and
triethylamine from acetonitrile is described in
[17].
The principal use of monoethylamine is in
the production of herbicides of the triazine
type by reaction with cyanuric chloride. Im-
portant commercial products are atrazine (No-
vartis), ametryne (Novartis), cyanazine (ACC,
DuPont), simazine (Novartis), terbutryn (No-
vartis), desmetryn (Novartis), terbumeton (No-
vartis), secbumeton (Novartis), simetryn (No-
vartis) and terbutylazine. Lately, the demand
for atrazine has decreased due to environmental
concerns, and it has been banned in certain west-
ern European countries. A triazine derivative has
also been suggested as stabilizer for chlorine
in swimming pools [40]. Ethylamine, via N-
ethylcyclohexylamine, also ends up in the herbi-
cide cycloate (see below). The fungicide cymox-
anil (DuPont) is also made from ethylamine. The
ethylamine demand for rubber applications, for
instance, toluene ethylsulfonamide, is declining.
A large percentage of the total diethy-
lamine production is used for N,N-diethylami-
noethanol, which is formed by reaction with eth-
ylene oxide and finds application as a corrosion
inhibitor and in coatings. Diethylamine is also
used for the production of vulcanization accel-
erators. Reaction with carbon disulfide gives a
dithiocarbamate that can be oxidized to a thi-
uram disulfide. The most important commer-
cial products are sodium and zinc diethyldithio-
carbamate and tetraethylthiuram disulfide. Di-
ethylamine is used for the production of cer-
tain agrochemicals, such as rice herbicides
[e.g., Napropamide (Zeneca) and Thiobencarb
(Kumiai)] or insecticides [e.g., Phosphami-
don (Novartis, DuPont) and Pirimiphos-methyl
(Zeneca)], pharmaceuticals, radical scavengers
(diethylhydroxylamine), and insect repellents
(N,N-diethyl-3-methylbenzamide, Autan).
Of the three ethylamines, triethylamine has
the widest range of uses and is also the most
expensive product owing to the unfavorable dis-
tribution of monoethylamine, diethylamine, and
triethylamine in production. Much of the tri-
ethylamine is used as an organic acid accep-
tor in synthesis or as a salt former in precipita-
tion and purification operations. Important ex-
amples of these uses are in the synthesis of
semisynthetic penicillins and cephalosporins,
and as solubilizers for herbicides in combi-
nation with 2,4-dichlorophenoxyacetic acid or
2,4,5-trichlorophenoxyacetic acid. Triethylam-
monium is the cationic component of the her-
bicide Garlon 3A (Dow Elanco). Other impor-
tant fields of use include polyurethane cat-
alysts (for example, the hardening of core
sands in cold-box casting), curing catalyst
for phenol – formaldehyde resins, anticorrosion

Figure 1. Continuous process for the production of ethylamines [38]
a) Vaporizer; b) Heat exchanger; c) Superheater; d) Catalytic converter; e) Product cooler; f) Gas separator; g) Ammonia
column; h) Monoethylamine column; i) Diethylamine column; j) Decanter; k) Triethylamine column
agents, paper, textile and photographic auxil-
iaries, and anodic electrocoating.
Propylamines. The commercial demand for
n-propylamines and isopropylamines is together
about the same as that for the ethylamines.
Monoisopropylamine is the most important
product and is used particularly in the produc-
tion of herbicides such as bentazon (BASF),
Roundup (Monsanto), imazapyr (ACC) and the
triazines ametryne (Novartis), atrazine (Novar-
tis), desmetryn (Novartis), prometryn (Novar-
tis), pramitol (Novartis), dipropetryn (Novar-
tis), and propazine (Novartis, Makteshim-Agan
and Drexel). Other applications encompass the
nematicide fenamiphos (Bayer), the fungicide
iprodione (Rhône-Poulenc), insecticides, phar-
maceuticals, and surfactants.
Dipropylamine is required principally as a
starting material for the synthesis of herbi-
cides, e.g., trifluralin (Dow), oryzalin (Dow),
EPTC (Zeneca), and vernolate (Zeneca). The
other propylamines are of minor importance
compared to monoisopropylamine and dipro-
pylamine. Diisopropylamine is mostly used for
agrochemicals such as the herbicides diallate
and triallate (Monsanto), but also for rubber
accelerators such as DIBS (N,N-diisopropyl-
2-benzothiazylsulfenamide). n-Propylamine is
used for agrochemicals and pharmaceuticals.
Amines, Aliphatic 13
Tripropylamine is an intermediate for pharma-
ceuticals and corrosion inhibitors.
Butylamines. Diisobutylamine is the prin-
cipal starting material for the herbicide Buty-
late (Zeneca). tert-Butylamine is primarily
employed for the synthesis of vulcaniza-
tion accelerators, for instance, TBBS (N-tert-
butyl-2-benzothiazylsulfenamide) and TBSI
(N-tert-butyl-2-benzothiazylsulfenimide). tert-
Butylamine is also used for the production of
herbicides, i.e., terbacil (DuPont) and the tri-
azines terbutylazine, terbumeton (Novartis), and
terbutryn (Novartis) and insecticides (e.g., di-
afenthiuron from Novartis). A derivative has
also been proposed as stabilizer for cosmetics
[41]. The synthesis of vulcanization accelera-
tors of the sulfenamide type is an important out-
let for dibutylamine (e.g., sodium dibutylthio-
carbamate, zinc dibutyldithiocarbamate or tetra-
butylthiuram disulfide); the demand for this
amine for other purposes (e.g., corrosion protec-
tion, flotation agents, cutting oils, plastics, and
intermediates for insecticides (e.g., carbosulfan)
and pharmaceuticals) is less important.
Monobutylamine is an intermediate for the
production of plasticizers (e.g., the rubber ac-
celerator dibutylthiourea), agrochemicals (e.g.,
DuPont’s fungicide benomyl), pharmaceuticals
(e.g., the antidiabetic tolbutamide), emulsifying
agents, dyes, and UV absorbers.
14 Amines, Aliphatic
Tributylamine is also used commercially (a
few 100 t/a) as a polymerization catalyst and as
an acid acceptor. sec-Butylamine is consumed in
small amounts for herbicides such as bromacil
(DuPont) or secbumeton (Novartis).
Other Amines. Of the C4+ monoamines,
only few are of commercial importance. Octy-
lamine is required, for example, for the pro-
duction of biocides, as a solvent for pesti-
cides, and as precursor for N-octylpyrrolidone –
which is used for the cleaning of printing ma-
chines – whereas 2-ethylhexylamine is employed
for the production of oil additives and for in-
secticides. Di-2-ethylhexylamine is used for oil
additives, dyes, and pharmaceutical applica-
tions. Tri-2-ethylhexylamine (bp 337.9 ◦ C) is
also commercially available and mainly used
in coatings. Tridecylamine (mixture of isomers)
is used for the production of the fungicide
tridemorph (BASF). A mixture of the penty-
lamines finds use in drilling applications. N,N-
Dimethylethylamine is an important epoxy and
urethane catalyst, for instance, in sand-core ap-
plications. It is made from ethanol and dimethyl-
amine. N,N-Dimethylisopropylamine, usually
obtained from acetone and dimethylamine un-
der hydrogenating conditions, is also used in
foundry applications. N-Ethyldiisopropylamine
(Hünig’s base) finds use as a good acid acceptor.
Mono-, di-, and trihexylamine are also commer-
cially available, but represent very minor prod-
ucts. Isoamylamine (3-methyl-1-butaneamine)
is an intermediate for pharmaceuticals and agro-
chemicals.
Some 10 000 t/a of tertiary alkyl primary
amines are manufactured by Rohm & Haas by
means of the Ritter reaction. These primene
amines range from tert-octylamine to C18 – C22 .
Of the unsaturated amines, diallylamine
has the most significant market (ca. 1000 t/a);
it is used for the production of N,N-
diallyldichloracetamide. Copolymers of di-
methyldiallylammonium chloride with acrylates
or acrylamides are used for water treatment. N-
Ethylmethallylamine is employed for herbicide
production (Dow’s sonalan).
Although chloroalkylamines (mainly
chloroethyl- and chloropropyl-N,N-
dialkylamines) are not important in terms of
the amounts employed, they are important start-
ing materials for the production of a number of
pharmaceuticals (principally neuroleptics).
Although not a lower alkylamine, poly-
isobutenamine (PIBA) is produced with the
same technology by amination of the hydro-
formylation product of polyisobutene (PIB) with
a molecular mass of about 1000 [42]. About
10 000 t/a PIBA is used as an detergent in fin-
ished additive packages for gasoline to improve
the mechanical functioning of the engine, lower
fuel consumption, and give improved emission
characteristics.
4.6. Economic Aspects
Worldwide production capacity for aliphatic
amines including fatty amines but excluding
methylamines is estimated to be ca. 500 000 t/a,
of which about 40 % is attributable to the United
States and about 30 % to western Europe. Be-
cause of the large number of producers and the
varying capacities of multipurpose plants, exact
figures for annual worldwide production are not
available. Apart from those who produce mainly
for their own requirements, the most impor-
tant producers of lower aliphatic amines are Air
Products, Hoechst Celanese, and Elf Atochem in
the United States; BASF, Elf Atochem, Hoechst
Celanese, and ICI in Western Europe; Daicel in
Japan; and Nordeste/Oxiteno in Brazil.
Manufacturing costs vary significantly de-
pending on the availability of the starting ma-
terials and the type of process, e.g., continuous
dedicated plant vs. batch process in a multipur-
pose plant.
5. Cycloalkylamines
Cyclopentylamine [1003-03-8], aminocy-
clopentane, C5 H11 N, M r 85.15, is a color-
less liquid, mp − 85 ◦ C, bp 106 – 108 ◦ C (at
101.3 kPa), d 20 20
4 0.8689, nD 1.4482, flash point
◦
17 C, with an ammoniacal odor.
Production. Cyclopentylamine is produced
from cyclopentanone and ammonia over nickel
 Amines, Aliphatic 15

catalysts at 20 MPa and 150 – 200 ◦ C in the pres- alkyl halides, alkyl sulfates, or alkyl phos-
ence of circulating hydrogen over a fixed-bed phates, cyclohexylamine can be alkylated with
catalyst. an alcohol in the presence of a catalyst, such
Uses. Cyclopentylamine is used in small as aluminum oxide, copper, nickel, cobalt, or
amounts as an intermediate for the potato platinum (reviewed in [48], [49]), or by the
and rice fungizide pencycuron (Bayer, Nihon Leuckart – Wallach method [50].
Tokushu, Noyaku Seizo). Production. Cyclohexylamine can be pro-
duced by catalytic hydrogenation of aniline un-
Cyclohexylamine [108-91-8], aminocy- der pressure. High yields are obtained with
clohexane, cyclohexanamine, hexahy- nickel or cobalt catalysts treated with basic ox-
droaniline, hexahydrobenzenamine, ami- ides [51]. Raney cobalt treated with calcium
nohexahydrobenzene, C6 H13 N, M r 99.18, is oxide and sodium carbonate gives a cyclo-
a colorless liquid, mp − 17.8 ◦ C, bp 134.5 ◦ C hexylamine yield of more than 96 % at 6 MPa
(at 101.3 kPa), d 25 20
4 0.8647, nD 1.4592. and 230 ◦ C [52]. Noble metals also are employed
as catalysts [53].
The alternative synthesis from cyclohexanol
and ammonia over supported cobalt catalysts
[54] is also an important method; calcium sil-
icoaluminates are also suitable catalysts [55].
Viscosity In this process, cyclohexanol reacts at 20 MPa
and 220 ◦ C with at least 3 mol of ammonia
t, ◦ C 0 20 50 75
η, Pa · s 3.73 2.10 1.14 0.77
in the presence of circulating hydrogen over a
fixed-bed catalyst. Using the same continuous
Vapor pressure procedure, cyclohexanone can be hydrogenated
t, ◦ C 20 60 100 120 with ammonia under amination conditions [56];
p, kPa 1.43 8.66 35.99 65.31 nickel or cobalt catalysts are used for this pro-
Specific heat capacity
cess, which is carried out at 0.1 – 20 MPa. Cy-
clohexylamine can also be obtained by react-
t, ◦ C 20 70 145 ing phenol with hydrogen and ammonia over a
c, J g−1 K−1 2.366 2.583 2.910
rhodium catalyst [57].
Quality. The purity of the commercial prod-
Heat of vaporization 399.86 J/g
Flash point (closed cups) 26.5 ◦ C uct is above 99.5 % and is determined by
Ignition temperature (class T3) 265 ◦ C gas chromatography; contaminants are ammo-
Ignition range in air 1.6 – 9.4 vol %
nia and water.
Storage and Transportation. Cyclohexy-
Cyclohexylamine is infinitely miscible with lamine can be stored and shipped in iron
water and conventional organic solvents. With tanks. Nonferrous metals, particularly copper-
water it forms an azeotrope that contains 44.2 % containing materials, are attacked and are there-
cyclohexylamine and boils at 96.4 ◦ C. fore unsuitable. The amine discolors on contact
Chemical Properties. Chemically cyclo- with air and therefore must be kept under nitro-
hexylamine has much in common with the gen.
acyclic aliphatic amines [3], [43]. Cyclohexy- Uses. Cyclohexylamine is used primarily as
lamine reacts with chlorine to form N,N- corrosion inhibitor and vulcanization accelera-
dichlorocyclohexylamine [44]. For conver- tor. Alone or mixed with other compounds, it
sion to azomethines and their chemistry, see has an anticorrosive action [58], for example,
[45]. N-Cyclohexylidenecyclohexylamine re- when used as an additive in heating oil or in the
acts with chloramine to give 1-cyclohexyl- operation of steam boilers. It is also employed as
3,3-pentamethylenediaziridine, which can be a salt-forming and amide-forming component
hydrolyzed to give cyclohexylhydrazine [46]. in many applications, for example, in the above
Cyclohexylamine and formaldehyde together mentioned vulcanization accelerators (CBS, N-
react with peracetic acid to give 2-cyclo- cyclohexyl-2-benzothiazylsulfenamide [59]),
hexyloxaziridine [47]. In addition to using plasticizers [salts with dodecanethiol and mer-
16 Amines, Aliphatic
captobenzothiazole (CMBT)] [60]], emulsifiers
(emulsification of active ingredients in water
with cyclohexylammonium alkylbenzenesul-
fonate [61]) and coagulators (salt with acetic
acid). Salts of C10 – C14 fatty acids prevent foam
formation in mineral oils [62]. Cyclohexylamine
functions as a hardener for epoxy resins and as a
catalyst for polyurethanes. Sodium cyclohexyl-
sulfamate and calcium cyclohexylsulfamate (cy-
clamates) are important artificial sweeteners. In
polyamide polymerizations, cyclohexylamine
is employed as chain terminator to control the
molecular mass. Other applications of cyclo-
hexylamine are for instance in herbicide produc-
tion. An example is DuPont’s Hexazinone [3-
cyclohexyl-6-(dimethylamino)-1-methyl-1,3,5-
triazine-2,4-(1H,3H)-dione]. The total market
for cyclohexylamine is around 20 000 t/a. Man-
ufacturers include Air Products, BASF, Bayer,
and Hoechst Celanese.
N-Methylcyclohexylamine [100-60-7],
C7 H15 N, M r 113.2, is a colorless liquid, mp
− 9 ◦ C, bp 150 ◦ C (at 101.3 kPa), d 25
4 0.8533,
n20
D 1.4551, η 5 mPa · s (at 25 ◦
C).
Vapor pressure
t, ◦ C 20 40 60 80 100 120 140
p, kPa 0.48 1.72 4.68 11.48 24.13 46.26 81.31
Flash point 36.1 ◦ C
Ignition temperature (class T3) 255 ◦ C
2.2 and 10.5 vol %
Explosion limits in air (corresponding to 103 and
494 g/m3 )
2.14 J g−1 K−1 (at 20 ◦ C)
Specific heat capacity
2.47 J g−1 K−1 (at 140 ◦ C)
N-Methylcyclohexylamine is infinitely mis-
cible with water, methanol, acetone, toluene, and
cyclohexane.
Production. N-Methylcyclohexylamine can
be prepared by a procedure similar to that used
for cyclohexylamine, i.e., by hydrogenation of
methylaniline over a supported nickel catalyst
[63] or from cyclohexanone and methylamine
under hydrogenation conditions [64]. Cyclo-
hexylamine reacts with methanol over copper,
zinc, or copper – calcium catalysts [65].
Uses. N-Methylcyclohexylamine is used as
a component of vulcanization accelerators [66],
but the market size is relatively small.
N,N-Dimethylcyclohexylamine [98-94-2],
cyclohexyldimethylamine, C8 H17 N, M r 127.23,
is a colorless liquid, mp <–50 ◦ C, bp 159 ◦ C (at
101.3 kPa), d 25 20
4 0.8467, nD 1.4519, η 3 mPa · s
(at 25 ◦ C).
Vapor pressure
t, ◦ C 20 40 60 80 100 120 140
p, kPa 0.29 1.05 3.21 8.29 18.13 35.99 63.72
Flash point 38.1 ◦ C
Ignition temperature (class T4) 200 ◦ C
0.79 and 7.0 vol %
Explosion limits in air (corresponding to 41.8
and 370 g/m3 )
Heat of vaporization 285.6 J/g
1.88 J g−1 K−1 (at 20 ◦ C)
Specific heat capacity
2.51 J g−1 K−1 (at 140 ◦ C)
The compound is sparingly soluble (1 %) in
water, but the solubility of water in dimethylcy-
clohexylamine is ca. 20 %. N,N-Dimethylcy-
clohexylamine is miscible with conventional or-
ganic solvents.
Production. N,N-Dimethylcyclohexylamine
is produced by hydrogenation of di-
methylaniline at 180 ◦ C and 6 MPa [67] or by
amination of cyclohexanone under hydrogena-
tion conditions in the presence of dimethylamine
[68]. In principle, it could also be obtained from
phenol by reaction with dimethylamine, but this
route is commercially less attractive.
Uses. N,N-Dimethylcyclohexylamine is a
catalyst for the production of polyurethane, par-
ticularly for making foams, and for this pur-
pose it is used as the free base [69] or as
the salt of an organic acid [70]. The cur-
ing temperature of baking finishes compris-
ing polyurethane-forming substances can be re-
duced by 50 – 80 ◦ C by adding weakly acidic
derivatives of the amine [71]. Like pyridine, di-
methylcyclohexylamine catalyzes certain reac-
tions and is slightly more efficient than pyridine
in the preparation of acid chlorides with thionyl

chloride [72]. It can be used as corrosion in-
hibitor and as an antioxidant in fuel oils.
N-Ethylcyclohexylamine [5459-93-8],
C8 H17 N, M r 127.2, is a colorless liquid, mp
− 43 ◦ C, bp 165 ◦ C (at 101.3 kPa), d 20
4 0.846,
n20 ◦
D 1.4525, η 1.39 mPa · s (at 20 C).
Vapor pressure
t, ◦ C 20 40 80
p, kPa 0.24 0.84 6.13
Flash point 46 ◦ C
Ignition temperature (class T3) 245 ◦ C
Explosion limit in air 1.2 and 7.6 vol %
N-Ethylcyclohexylamine is only slightly sol-
uble (2.3 %) in water, but the solubility of water
in ethylcyclohexylamine is 25 %. The amine is
miscible with conventional organic solvents.
Ethylcyclohexylamine is produced by hydro-
genation of ethylaniline at 180 ◦ C and 6 MPa
[67] or by amination of cyclohexanone un-
der hydrogenation conditions in the presence
of ethylamine [68]. The amine is a starting
material for the preplant sugar beet, grass,
and spinach herbicide cycloate (Zeneca’s Ro-
Neet), which is obtained by converting N-
ethylcyclohexylamine into S-ethyl-N-ethyl-N-
cyclohexylthiocarbamate. A minor use of N-
ethylcyclohexylamine is for vulcanization ac-
celerators.
Dicyclohexylamine [101-83-7], dodecahy-
drodiphenylamine, N,N-dicyclohexylamine,
N-cyclohexylcyclohexanamine, perhydrodi-
phenylamine, C12 H23 N, M r 181.32, is a col-
orless liquid, mp − 0.1 ◦ C, bp 256 ◦ C (at
101.3 kPa), bp 133 ◦ C (at 2.6 kPa), d 25
4 0.9104,
n20
D 1.4852.
Amines, Aliphatic 17
Flash point 105 ◦ C
Ignition temperature (class T3) 240 ◦ C
0.83 and 4.6 vol %
Explosion limits in air (corresponding to 62 and
350 g/m3 )
1.88 J g−1 K−1 (at 20 ◦ C)
Specific heat capacity
2.47 J g−1 K−1 (at 140 ◦ C)
Dicyclohexylamine is sparingly soluble in
water (ca. 0.16 % at 28 ◦ C) but is readily sol-
uble in the conventional solvents.
Production. Dicyclohexylamine can be
formed as a byproduct in the production of cy-
clohexylamine from aniline or cyclohexanol/cy-
clohexanone [73]. When desired as the end
120
27.59 product, dicyclohexylamine is obtained by am-
ination of cyclohexanone under hydrogenation
conditions [74] or, in higher yield, from cyclo-
hexanone and cyclohexylamine over Pd/C at a
hydrogen pressure of 0.4 MPa [75]. Dicyclo-
hexylamine can also be obtained by amination
of phenol under hydrogenation conditions, or by
the reaction of phenol with aniline over Pd/C at
0.5 MPa under hydrogenation conditions [76].
Uses. Dicyclohexylamine and its salts have
good anticorrosion properties in the vapor
phase [77]. Paper treated with the nitrite is
used as anticorrosion paper. The nitrite also
imparts these properties when incorporated
into alkyd resins [78]. Like the other cy-
clohexylamines, dicyclohexylamine is useful
as a component of vulcanization accelera-
tors (for instance DCBS, N,N-dicyclohexyl-2-
benzothiazylsulfenamide, or DCMBT, the salt
with 2-mercaptobenzothiazole) and of pesti-
cides. It is also consumed as a processing chem-
ical for antibiotics and as fuel oil additive.
N-Methyldicyclohexylamine [7560-83-0],
N,N-dicyclohexylmethylamine, N-cyclohexyl-
N-methyl-cyclohexanamine, C13 H25 N, M r
195.35, is a liquid, bp 275 ◦ C (at 101.3 kPa),
d 25 25 ◦
4 0.9207, nD 1.4881, η 10.2 mPa · s (at 25 C),
flash point 66 ◦ C.
18 Amines, Aliphatic
Vapor pressure
t, ◦ C 63 90 150 190 248
p, kPa 0.133 0.599 2.66 13.33 66.65
N-Methyldicyclohexylamine is sparingly
soluble in water and THF but readily soluble
in acetone, methanol, toluene, cyclohexane, and
chloroform. It is prepared by methylating dicy-
clohexylamine with dimethyl sulfate or by the
Leuckart – Wallach reaction [79] and has uses
similar to those of the other cyclohexylamines,
e.g., as a urethane foam catalyst.
4,4
-Diaminodicyclohexylmethane
[1761-71-3], methylene bis(4,4
-cyclo-
hexylamine), bis(4-aminocyclohexyl)methane,
4,4
-methylenebiscyclohexanamine, C13 H26 N2 ,
M r 210.36, mp 60 – 62 ◦ C (cis,cis), 64 – 65 ◦ C
(trans,trans), bp 330 – 331 ◦ C (at 101.3 kPa), d 20
4
0.96, flash point 153.5 ◦ C, is a water insoluble
solid.
The large-volume product 4,4
-diaminodicy-
clohexylmethane is manufactured by several
companies by the catalytic hydrogenation of
methylene dianiline. The isomer distribution in
the yield is controlled, since the main product
from the amine is the isocyanate, which is used
in urethane coatings. Other applications include
fibers, pigments, films, and epoxy curing agents.
2,2-Bis(4-aminocyclohexyl)propane
[3377-24-0], isopropylidenedi(cyclohexyl-
amine), C15 H30 N2 , M r 238.42, mp 51 – 53 ◦ C,
bp 155 – 160 ◦ C (at 0.65 kPa), d 20
4 0.99.
2,2-Bis(4-aminocyclohexyl)propane can be
obtained by amination of the corresponding
bishydroxy compound in the liquid phase un-
der pressure. Product yields of ca. 90 % are ob-
tained over hydrogenation catalysts containing
palladium [57], ruthenium [80] or cobalt, man-
ganese, and phosphoric acid [81]. Alternatively,
hydrogenation of the condensation product of
aniline and acetone, bisaniline A, furnishes the
same compound. The industrial product is a mix-
ture of three stereoisomers. Concentration of the
trans,trans isomer by treating the isomer mixture
with phosphoric acid under reduced pressure at
230 ◦ C or by recrystallization from branched oc-
tanes [82] is important because polymerization
of the pure isomer gives polyamides of better
quality.
Cyclooctylamine [5452-37-9], C8 H17 N, M r
127.23, is a liquid, mp − 48 ◦ C, bp 80 ◦ C (at
1.3 kPa), mp of hydrochloride 244 – 245 ◦ C, mp
of picrate 193 – 194 ◦ C, d 20 20
4 0.9280, nD 1.4804,
◦
flash point 62 C.
The amine can be produced by the Ritter re-
action of cyclooctanol with hydrocyanic acid
[83], by reduction of cyclooctanone oxime with
sodium and an alcohol [84], by Ritter reaction
of cyclooctene with hydrocyanic acid [85], or by
catalytic hydrogenation of cyclooctanone under
amination conditions [86]. Cyclooctylamine is
used as a component of urea herbicides, e.g.,
cycluron (BASF). Its chemical behavior is anal-
ogous to that of other primary amines.
Cyclododecylamine [1502-03-0], C12 H25 N,
M r 183.34, mp 31 – 32 ◦ C, bp 95 – 96 ◦ C (at
0.25 kPa), n32.5
D 1.4849; mp of hydrochloride
268 – 270 ◦ C, mp of picrate 232 – 234 ◦ C, flash
point 121 ◦ C.
Cyclododecylamine is produced by reduction
of cyclododecanone oxime with sodium and an
alcohol [87], by catalytic reduction of nitrocy-
clododecane with hydrogen [88], by Ritter re-
action of cyclododecene with hydrocyanic acid
[89], or by hydrogenation of cyclododecanone
under amination conditions [90]. The reaction of
cyclododecylamine with propylene oxide leads
to a product that can undergo cyclization to give
 Amines, Aliphatic 19

the fungicide Dodemorph (BASF). The com- 101.3 kPa), d 20 20

4 0.7992, nD 1.4236, flash point
◦
pound behaves chemically as a primary amine. − 21 C.

6. Cyclic Amines
Pyrrolidine [123-75-1], tetrahydropyrrole,
C4 H9 N, M r 71.12, is a colorless liquid, mp Piperidine [110-89-4], hexahydropyridine,
− 60 ◦ C, bp 87 – 88 ◦ C (at 101.3 kPa), d 20
4
pentamethyleneimine, azacyclohexane, cy-
0.8576, n20 ◦
D 1.4428, η 1.1 mPa · s (at 20 C).
clopentimine, cypentil, hexazane, C5 H11 N, M r
85.15, derives its name from the alkaloid piper-
ine, the pepper flavoring, in which piperidine is
present as piperic acid piperidide.

Flash point
Ignition temperature (class T2)
Explosion limits in air
Specific heat capacity
Heat of vaporization
3 ◦C
345 ◦ C
1.6 and 10.6 vol %
(corresponding to 47 Piperidine, a colorless liquid, mp − 10.5 ◦ C,
and 314 g/m3 ) bp 106.4 ◦ C (at 101.3 kPa), with a sharp ammo-
2.20 J g−1 K−1 (at 21 ◦ C)
2.25 J g−1 K−1 (at 65 ◦ C)
nia odor, is hygroscopic and fumes in air; d 20 4
2.27 J g−1 K−1 (at 77 ◦ C) 0.8613 (the temperature dependence of the den-
529 J/g (at 0.1 MPa) sity is given in [94]), n20
D 1.4532.

Vapor pressure
Pyrrolidine is infinitely miscible with wa- t, ◦ C 13.0 25.0 40.0 51.0 67.8 78.8 87.2
ter and conventional organic solvents such as p, kPa 2.0 4.0 8.0 13.3 26.7 40.0 53.3
methanol, acetone, ether, and chloroform. It acts
as a lachrymator. The vapor pressure curve is given in
Chemically, pyrrolidine behaves like a sec- [95]; flash point 3 ◦ C, dissociation constant
ondary amine in every respect. For example, it 1.6 × 10−3 (at 25 ◦ C). Piperidine is infinitely
undergoes Leuckart – Wallach and Mannich re- soluble in water, lower alcohols and ketones,
actions and is readily converted into an enam- ethers, aliphatic and aromatic hydrocarbons,
ine. In the presence of a catalyst, such as plat- ethyl acetate, and DMF. It forms an azeotrope
inum at 360 ◦ C or rhodium at 650 ◦ C [91], pyr- with water:
role is formed. In the presence of a copper cat-
alyst, N-methylpyrrolidone is converted into N- p, kPa 100.8 53.3 26.7
bp, ◦ C 93.7 76.9 61.4
methylpyrrolidine. Piperidine, 63.7 68.1 76.0
Production. Pyrrolidine can be produced mass fraction in
%
from butanediol and ammonia, e.g., over an alu-
minum thorium oxide catalyst at 300 ◦ C [92] or
over a nickel catalyst at 200 ◦ C and 20 MPa un- The preparation of enamines from piperi-
der hydrogenation conditions. It can also be pro- dine takes place particularly smoothly [96], [97],
duced from THF and ammonia over aluminum [98]. Unlike open-chain amines, cyclic amines
oxide at 275 – 375 ◦ C [93]. react with aldehydes to give aminals as inter-
Uses. Pyrrolidine is used virtually exclu- mediates [99]. Only pyrrolidine is comparably
sively for the synthesis of pharmaceuticals, in- versatile.
cluding antibiotics. In addition, it is used for pro- Production. Pyridine obtained from tar dis-
ducing vulcanization accelerators. tillation is contaminated by sulfur-containing
compounds and therefore can be hydrogenated
N-Methylpyrrolidine [120-94-5], 1- economically only in a two-stage process. The
methylpyrrolidine, C5 H11 N, M r 85.15, col- crude pyridine is first hydroraffined over a sul-
orless liquid; mp − 90 ◦ C, bp 80 – 81 ◦ C (at fidic metal catalyst at 280 – 310 ◦ C and then
hydrogenated quantitatively to piperidine at
20 Amines, Aliphatic
120 – 160 ◦ C over a Ni – Al2 O3 catalyst [100].
Sulfur-free pyridine can be hydrogenated over a
ruthenium [101] or cobalt catalyst.
The preparation of piperidine by aminolysis
of 1,5-pentanediol under hydrogenation condi-
tions at 225 – 260 ◦ C and 20 MPa over a cobalt
catalyst has been described [102], but can also be
affected with nickel catalysts. A similar prepa-
ration from tetrahydrofurfuryl alcohol also has
been described [103]. When piperidine is pre-
pared by hydrogenating glutarates [104], glu-
taric acid [105], or glutaraldehyde [106], the re-
action is carried out in the presence of a large
excess of ammonia.
Uses. The secondary amine piperidine is
highly reactive and is therefore frequently em-
ployed as an intermediate for pharmaceuticals
[107] and for plant protection agents. It is also
used as a vulcanization accelerator in rubber
manufacture and as an oil or fuel additive [108].
Piperidine and, in many cases, piperidine ac-
etate are useful catalysts for condensation reac-
tions, e.g., the Knoevenagel reaction [109], al-
dol condensation [110], and the condensation
of a nitroparaffin with an aldehyde [111]. How-
ever, for the last of these reactions, diethylamine
is the preferred catalyst. The use of piperidine
is particularly advisable where the reactants or
products are unstable in the presence of stronger
bases.
N-Methylpiperidine [626-67-5], C6 H13 N,
M r 99.18, colorless liquid; mp − 18 ◦ C, bp
106 – 107 ◦ C (at 101.3 kPa), d 20 20
4 0.8157, nD
◦
1.4378, flash point 3 C.
Uses. N-Methylpiperidine is used for the
production of a growth regulator for cotton
plants.
N-Ethylpiperidine [766-09-6], C7 H15 N,
M r 113.20, colorless liquid; bp 131 ◦ C (at
101.3 kPa), d 20 20
4 0.8237, nD 1.4440, flash point
◦
19 C.
Uses. N-Ethylpiperidine has found use as a
catalyst in polycarbonate manufacture.
Hexamethyleneimine [111-49-9], HMI,
azacycloheptane, hexahydroazepine, ho-
mopiperidine, perhydroazepine, C6 H13 N, M r
99.18, is a liquid, mp − 37 ◦ C, bp 139 ◦ C (at
101.3 kPa), d 20 20
4 0.8799, nD 1.4658, flash point
30 ◦ C, ignition temperature 255 ◦ C.
Hexamethyleneimine and water form a
1/1 azeotrope that boils at 95 – 95.5 ◦ C. The
hexamethyleneimine – water solubility curve is
given in [112]. The chemical behavior of
hexamethyleneimine is determined entirely by
the secondary amino group.
Production. Hexamethyleneimine is pro-
duced in 84 % yield by heating hexamethy-
lenediamine at 350 ◦ C in a stream of hydro-
gen. The catalyst, ammonium vanadate on ac-
tivated alumina, is prereduced with hydrogen at
500 ◦ C [113]. Residues from the industrial dis-
tillation of hexamethylenediamine can be con-
verted into hexamethyleneimine over aluminum
silicate or aluminum oxide in a stream of nitro-
gen [114]. For the preparation from caprolactam,
see [115]. Hexamethyleneimine can be prepared
by dimerizing acrolein, reducing the product
to 2-hydroxymethyltetrahydropyran, expanding
the ring to give oxepane, followed by treatment
with ammonia over aluminum oxide at 350 ◦ C
[116].
Uses. The most important use is the
conversion of hexamethyleneimine into S-
ethylhexahydro-1H-azepine-1-carbothioate, the
selective rice herbicide Molinate (C2 H5 S–
CO–NC6 H12 , Zeneca). Minor amounts of
hexamethyleneimine are used for the produc-
tion of rubber vulcanization accelerators, resins,
pharmaceuticals, and textile auxiliaries; numer-
ous patents describe the anticorrosive action of
hexamethyleneimine and its derivatives.
Morpholine [110-91-8], tetrahydro-2H-1,4-
oxazine, diethylene oximide, diethylenimide
oxide, 1-oxa-4-azacyclohexane, C4 H9 NO, M r
87.12, is a colorless hygroscopic liquid; mp

− 5 ◦ C, bp 128.2 ◦ C (at 101.3 kPa), d 20
4 1.007,
n20 ◦
D 1.4542, η 2.3 mPa · s (at 20 C).
Vapor pressure
t, ◦ C 10 20 40 60 80 100
p, kPa 0.57 1.1 3.2 8.3 20.5 40.9
Critical pressure 5.302 MPa
Critical temperature 344 ◦ C
Flash point 43 ◦ C
Ignition temperature 275 ◦ C
Explosion limits in air 1.8 vol % and 15.2 vol %
1.2 J g−1 K−1 (at 25 ◦ C)
Specific heat capacity
2.15 J g−1 K−1 (at 100 ◦ C)
505 J/g (at 25 ◦ C)
Heat of vaporization
425 J/g (at 128 ◦ C)
Morpholine is infinitely miscible with wa-
ter and conventional solvents such as methanol,
acetone, benzene, and glycol. The mixture con-
sisting of 88 % morpholine and 12 % water has
a freezing point below − 50 ◦ C and a viscosity
of 7.45 mPa · s at 20 ◦ C.
Chemically, morpholine behaves as a sec-
ondary amine in every respect. It forms com-
plexes with many cations. In addition to the
Leuckart – Wallach and Mannich reactions, the
conversion to enamines has become important
[96], [97]. Morpholine, pyrrolidine, and piperi-
dine are preferred to the open-chain amines for
these reactions because they react faster with the
carbonyl component.
Production. Morpholine can be obtained
from diethanolamine by cyclization with sul-
furic acid or via diethanolamine hydrochloride
[117] or from di(2-chloroethyl) ether and am-
monia [118]. Industrially more important is the
amination of diglycol under hydrogen pressure
and over a cobalt or nickel catalyst [42], [119].
Other catalysts are described in [120]. An impor-
tant byproduct frequently obtained is 2-(2-ami-
noethoxy)ethanol, which is the result of simple
amination without subsequent cyclization; after
separation of morpholine, this compound can be
recycled to the synthesis reactor.
Quality and Storage. When produced from
diglycol, commercial morpholine is more than
99 % pure; the main impurities are N-ethylmor-
pholine and ethylenediamine. Morpholine can
be stored for an unlimited time in iron contain-
ers if it is protected from atmospheric moisture
Amines, Aliphatic 21
and carbon dioxide. Copper, zinc, and their al-
loys are unstable towards morpholine.
Uses. Morpholine is an intermediate for a
large number of pharmaceuticals, crop pro-
tection agents, dyes, and optical brighten-
ers. An important use is the conversion to
vulcanization accelerators or sulfur donors,
which are based on 2-mercaptobenzothiazole,
120
81.8 dithiocarbamic acid, thiuram polysul-
fides, or sulfenamides, e.g., MBS [2-(4-
morpholinylmercapto)benzothiazole], DTDM
(4,4
-dithiodimorpholine), and MBSS (4-
morpholinyl-2-benzothiazyl disulfide). Salts of
morpholine with long-chain fatty acids, such as
oleic or stearic acid, have waxlike properties
and are used as emulsifiers.
Because water and morpholine have simi-
lar volatilities and the latter is an anticorrosion
agent, it is useful in steam cycles [121], aqueous
hydraulic liquids [122], and similar systems. Up
to 550 ◦ C, no substantial loss occurs as a result
of decomposition.
An aqueous solution of morpholine (2 M) can
be used for removing CO2 , H2 S, or HCN from
gases [123]. In the extraction of aromatic com-
pounds from hydrocarbon mixtures, morpholine
is highly selective [124].
Morpholine Derivatives. N-Methylmor-
pholine and N-ethylmorpholine are used as cat-
alysts for the production of polyurethane foams.
N-Formylmorpholine is used as a selective sol-
vent for the extraction of high-purity aromatic
compounds in the Formex process (Snampro-
getti).
N-Methylmorpholine [109-02-4], 4-methyl-
1-oxa-4-azacyclohexane, C5 H11 NO, Mr
101.15, mp − 65 ◦ C, bp 114 ◦ C (at 101.3 kPa),
d 20 20 ◦
4 0.919, nD 1.4347, η 0.90 mPa · s (at 20 C),
flash point 13 ◦ C.
Methylmorpholine can be obtained from
diethylene glycol and methylamine or by re-
acting morpholine with formaldehyde to give
N-hydroxymethylmorpholine and reducing the
product with excess formaldehyde [125], formic
acid [126], or hydrogen over cobalt or man-
ganese catalysts under pressure [127]. Another
important reaction is the alkylation of morpho-
22 Amines, Aliphatic
line with methanol at a total pressure above
3.5 MPa and a hydrogen partial pressure above
1 MPa [128].
Alkylmorpholines are also obtained by cy-
clization of bis(2-chloroethyl) ether with an
amine [129] or of diethylene glycol with an
amine in the presence of hydrogen and a hy-
drogenation catalyst [130].
N-Ethylmorpholine [100-74-3], C6 H13 NO,
M r 115.18, mp − 63 ◦ C, bp 134 – 137.5 ◦ C (at
101.3 kPa), d 20 20
4 0.913, nD 1.4415, η 1.05 mPa · s
(at 20 C), flash point 27 ◦ C, is miscible with wa-
◦ p, kPa
ter.
N-Formylmorpholine [4394-85-8], 4-mor-
pholinecarbaldehyde, C5 H9 NO2 , M r 115.13,
mp 20 – 21 ◦ C (anhydrous), 9 ◦ C (5 % water),
–3 ◦ C (10 % water), bp 244 ◦ C (anhydrous),
172 ◦ C (2 % water), 151 ◦ C (5 % water), 132 ◦ C
(8 % water) (all at 101.3 kPa), d 20
4 1.1268, nD
20
1.4835, flash point 124 ◦ C, is hygroscopic.
N-(2-Hydroxyethyl)morpholine [622-40-2],
4-(2-hydroxyethyl)morpholine, 4-morpholino-
ethanol, C6 H13 NO2 , M r 131.17, mp − 1 ◦ C, bp
227 ◦ C (at 100.9 kPa), d 20 20
4 1.0733, nD 1.4760,
◦ zine can be distilled from the reaction mixture,
flash point 99 C, is used as an intermediate for
pharmaceuticals.
N-(2-Aminoethyl)morpholine [2038-03-1],
2-morpholinoethylamine, 4-(2-aminoethyl)-
morpholine, C6 H14 N2 O, M r 130.19, mp 24 ◦ C,
bp 205 ◦ C (at 101.3 kPa), d 20 20
4 1.001, nD 1.4755,
flash point 175 ◦ C, is used as an intermediate
for pharmaceuticals.
Piperazine [110-85-0], 1,4-diethylene-
diamine, hexahydropyrazine, dispermine,
hexahydro-1,4-diazine, C4 H10 N2 , M r 86.14,
forms strongly hygroscopic, colorless lamellar
crystals with a typical amine odor, mp 109.6 ◦ C,
bp 148 ◦ C (at 101.3 kPa), mp of the hexahydrate
42.0 ◦ C.
Vapor pressure
t, ◦ C 110.8 121.7 125 140.6
30.3 44.6 49.6 79.7
Flash point 98 ◦ C
Ignition temperature 340 ◦ C
3.93 kPa and 12.0 kPa
Explosion limits in air (corresponding to 139 g/m3
and 430 g/m3 )
These are the saturated vapor pressures above piperazine at
64.0 ◦ C and 90.5 ◦ C.
2.94 J g−1 K−1 (at 130 ◦ C)
Specific heat capacity
2.99 J g−1 K−1 (at 140 ◦ C)
Heat of vaporization 47.3 J/g
Piperazine is readily soluble in water,
methanol, and ethanol but only slightly soluble
in diethyl ether, benzene, and heptane. Piper-
azine has the chemical properties of a secondary
amine. Vapor-phase dehydrogenation over cop-
per chromite or palladium gives pyrazine.
Production. Piperazine is obtained as a by-
product in the production of ethylenediamine, in
particular when ethanolamine is used as starting
material [131]. If ethanolamine reacts with am-
monia at 150 – 220 ◦ C and 10 – 25 MPa, pipera-
which also contains unreacted ethanolamine,
ethylenediamine, diethylenetriamine, amino-
ethylethanolamine, and polyamines.
Piperazine is obtained with a purity of 99 %,
and can be converted to flakes, even after conver-
sion to the hexahydrate. Frequently, it is trans-
ported as an approximately 65 % aqueous so-
lution, which has a low melting point of about
45 ◦ C and hence corresponds roughly to an eu-
tectic mixture. The purity is determined in most
cases by gas chromatography. If it can be as-
sumed that organic impurities are absent, the
purity can be determined titrimetrically (HCl or
HClO4 ) in aqueous solution.
Storage. Since piperazine is corrosive, the
flakes are stored in barrels lined with a polyethyl-
ene sack. To avoid yellowing, the barrels should
be air tight and not exposed to direct sunlight.

The aqueous solution is stored at 50 – 60 ◦ C in
insulated iron tanks that can be heated.
Uses. Piperazine, in the form of the hexahy-
drate or as salts, is used as an anthelmintic in
human and veterinary medicine. Furthermore,
the piperazine ring is a constituent of a large
number of other pharmaceuticals. It is also an
intermediate for dyes, corrosion inhibitors, rub-
ber vulcanization accelerators, insecticides, and
surfactants.
The production of polyamides from pipera-
zine and aliphatic dicarboxylic acids has long
been known [132], but has remained unim-
portant. The polymers so formed have a heat
resistance superior to that of conventional
polyamides but require the use of stabilizers
[133].
The use of 1,4-bis(1-aziridinylcarbonyl)-
piperazine or 1,4-bis(chloroacetyl)piperazine
for curing gelatine for photographic purposes
was proposed [134].
N-Methylpiperazine [109-01-3],
1-methylpiperazine, C5 H12 N2 , M r 100.16, col-
orless hygroscopic liquid, mp − 6 ◦ C, bp 138 ◦ C
(at 101.3 kPa), d 20 20
4 0.9021, nD 1.4658, flash
◦
point 42 C.
N-Ethylpiperazine [5308-25-8],
1-ethylpiperazine, C6 H14 N2 , M r 114.19, col-
orless liquid, mp − 60 ◦ C, bp 157 ◦ C (at
101.3 kPa), d 20 20
4 0.8989, nD 1.4690, flash point
◦
47 C.
N,N
-Dimethylpiperazine [106-58-1], 1,4-
dimethylpiperazine, C6 H14 N2 , M r 114.19, col-
orless liquid, mp − 1 ◦ C, bp 131 – 132 ◦ C (at
101 kPa), d 20 20
4 0.8509, nD 1.4463, flash point
◦
18 C, can be used as catalyst for polyurethane
foams and as an intermediate for cationic sur-
factants. It is obtained from piperazine and
methanol or formaldehyde under aminating con-
ditions.
Amines, Aliphatic 23
N-(2-Aminoethyl)piperazine [140-31-8],
AEP, 1-(2-aminoethyl)piperazine, 2-piperazin-
1-ylethylamine, C6 H15 N3 , M r 129.21, color-
less liquid, mp − 19 ◦ C, bp 218 – 222 ◦ C (at
101.3 kPa), d 20 20
4 0.9842, nD 1.5000, flash point
◦ ◦
93 C, η 15 mPa · s (at 20 C) is corrosive, toxic,
and hygroscopic. AEP is a byproduct of ethyl-
enediamine production and is used as a hardener
for epoxy resins, as an urethane catalyst, and also
acts as a corrosion inhibitor [135]. It is also an
intermediate for dyes, surfactants and various
pharmaceuticals.
N-(2-Hydroxyethyl)piperazine [103-76-4],
HEP, 1-(2-hydroxyethyl)piperazine, 1-piper-
azineethanol, C6 H14 N2 O, M r 130.19, mp
− 10 ◦ C, bp 246 ◦ C (at 101.3 kPa), d 20
4 1.0595,
n20
D 1.5058, flash point 135 ◦
C. HEP is obtained
during ethyleneamine production and used for
corrosion inhibitors, pharmaceuticals, surfac-
tants, and synthetic fibers.
Triethylenediamine [280-57-9], TEDA,
1,4-diazabicyclo[2.2.2]octane, Dabco,
C6 H12 N2 , M r 112.17, is a highly symmetrical
molecule with a cage structure. The colorless ex-
tremely hygroscopic crystals melt at 159.8 ◦ C;
bp 174 ◦ C, pK a1 2.95, pK a2 8.60, flash point
50 ◦ C.
Triethylenediamine reacts virtually quantita-
tively with bromine to give a 1/1 adduct. With
alkyl halides it forms quaternary salts, even in
nonpolar solvents. Apart from its highly nucle-
24 Amines, Aliphatic
ophilic nature, triethylenediamine exhibits cat-
alytic activity in base-catalyzed reactions.
Production. Triethylenediamine can be pro-
duced from ethylenediamine or ethanolamine
[136], diethanolamine [137], or diethyl-
enetriamine [138] with a variety of different
catalysts. All processes give only moderate
yields. For example, in the presence of a cat-
alyst consisting of 86 % silicon dioxide and
12 % aluminum oxide at 360 ◦ C and atmo-
spheric pressure, diethylenetriamine gives about
equal amounts of piperazine, alkylpiperazines,
pyrazines, and ethylenediamine and homo-
logues in addition to the bicyclic compound.
Fractional distillation, subsequent recrystalliza-
tion from acetone, and washing with petroleum
ether give 95 % pure triethylenediamine; sub-
limation gives a 98 % pure product. Pro-
cesses starting from piperazine derivatives
(N-hydroxyethylpiperazine, N,N
-bishydroxy-
ethylpiperazine or N-aminoethylpiperazine) are
described in [137], [139]. Dealuminated or
untreated ZSM-5 zeolites are claimed to pro-
duce TEDA from various precursors, including
ethanolamine and piperazine [140]. Compared
to the amorphous catalysts, the zeolite catalysts
have the advantage of shape selectivity.
Uses. The only important industrial use
of triethylenediamine is as a hardener for
polyurethane foams [141]. However, more ef-
fective aza- and diazabicyclooctane derivatives
intended for the same purpose have been the sub-
ject of patent applications [142].
Hexamethylenetetramine [100-97-0],
HMTA, hexamine, methenamine, 1,3,5,7-
tetraazaadamantane, 1,3,5,7-tetraazatricy-
clo[3.3.1.1(3,7)]decane, C6 H12 N4 , M r 140.19,
is a highly symmetrical molecule with an
adamantane structure. Trade names: Urotropin,
Formin, Aminoform. It crystallizes from ethanol
as colorless, hygroscopic rhombododecahedra.
At reduced pressure (2 kPa), hexamethy-
lenetetramine sublimes at 230 – 270 ◦ C, virtu-
ally without decomposition, mp > 270 ◦ C (de-
comp.),  1.3394 g/cm3 (at 22 ◦ C), enthalpy of
formation 124.1 ± 0.75 kJ/mol. For further ther-
modynamic data, see [143]. For the IR spec-
trum, see [144]. The vapor pressure between 20
and 280 ◦ C can be calculated from the formula
log(p/kPa) = – 524.8/(T /K) + 1.334 [145]. Flash
point 250 ◦ C.
At 12 ◦ C, 81.3 g of hexamethylenetetramine
dissolves in 100 g of water; the solubility de-
creases slightly with increasing temperature.
The dissociation constant is 1.4 × 10−9 (temper-
ature not given). The solubility of hexamethy-
lenetetramine in 100 g of various solvents at
20 ◦ C is as follows: 13.4 g in chloroform, 7.25 g
in methanol, 2.89 g in absolute ethanol, 0.65 g
in acetone, 0.23 g in benzene, 0.14 g in xylene,
0.06 g in ether, and near zero in petroleum ether.
Hexamethylenetetramine gives a monobasic
reaction, but with strong acids it is dibasic.
The equilibrium C6 H12 N4 + 6 H2 O
6 CH2 O
+ 4 NH3 in aqueous solution permits the use of
hexamethylenetetramine as a formaldehyde or
ammonia donor. Thermolysis leads to hydro-
cyanic acid in a yield of 73 % at 800 ◦ C, and
92 % at 1200 ◦ C [146]. Nitration gives 1,2,3-
trinitro-1,2,3-triazine, which is an important ex-
plosive (hexogen, cyclonite, RDX). The intact
tricyclic structure can be alkylated and arylated
at the nitrogen atom and halogenated at the car-
bon atom. It undergoes a large number of addi-
tion reactions: adduct formation with phosgene,
disulfur dichloride, and many inorganic salts.
Production. Formaldehyde and ammonia can
be converted into hexamethylenetetramine in the
gas phase, in aqueous solution, or in a suspension
in an inert solvent, although the most important
of these procedures is that carried out in water.
The usual process gives a pure product in yields
near 90 % and includes an economical drying
step.
If aqueous solutions of ammonia (27 %) and
formaldehyde (30 %) react continuously at up
to 95 ◦ C in a V4A stainless steel tubular reac-
tor, it is necessary to dewater a 14 % solution of
hexamethylenetetramine [147]. If formaldehyde
and ammonia are reacted in the vapor phase, the
product is precipitated with cold water [148]
or is discharged with an aqueous solution of
hexamethylenetetramine [149].
The heat of reaction in aqueous solution is
230 kJ/mol, and in the vapor phase 745 kJ/mol.
Therefore, the presence of a minimum amount
of water is desirable. In this method [150], am-
monia gas and formaldehyde gas are passed
 Amines, Aliphatic 25

continuously into the boiling reaction solution. 7.1. Properties

The boiling point is brought to 50 – 70 ◦ C. The
heat of hydration and heat of reaction vapor- Physical Properties. Table 2 lists typical
ize the water of condensation. The hexamethy- compositions of fatty amine mixtures. The prop-
lenetetramine is removed in crystalline form or erties of these can be varied to some extent by
as a concentrated solution. blending chain lengths with the desired physical
In another method, ammonia gas and characteristics. Fatty acids are also available in
formaldehyde solution react at pH 7.5 – 8 fractionated form and thus narrower ranges of
and 50 – 90 ◦ C, and the product is granu- fatty amines may be produced.
lated by spray drying in a hot inert gas Solubilities of selected fatty amines in po-
stream (220 – 250 ◦ C), or by spraying it onto lar and nonpolar organic solvents are given in
hexamethylenetetramine particles in a fluidized Table 3. Only the short-chain fatty amines with
bed in an air stream at 80 – 115 ◦ C [151]. 8 – 10 C atoms per alkyl chain are of limited sol-
Quality. As a rule, the industrial product is ubility in water.
99 % pure. The compound is purified by step-
Table 3. Solubility (g per 100 mL at 30◦ C) of fatty amines in organic
wise crystallization (see [152]). The addition of solvents [158]
paraffin, benzoic acid, acid amides, or diatoma-
2-Propanol Hexane
ceous earth gives free-flowing products [153].
Uses. Hexamethylenetetramine can be used Primary amines
Dodecylamine ∞ ∞
as an ammonia or formaldehyde donor, for Tetradecylamine 458 216
example, in the production of phenol resins, Hexadecylamine 169 64.8
urea – formaldehyde resins and in fuel tablets. Octadecylamine 86 27.9
Secondary amines
Further uses are the production of the high explo- Dioctylamine ∞ ∞
sives hexogen and octogen, vulcanization accel- Didodecylamine 55 27.5
Dioctadecylamine 1.2 (50 ◦ C) 2.1 (40 ◦ C)
erators, and anticorrosion agents. Proposed uses Tertiary amines
relate to the activation of chlorites as bleaches Trioctylamine ∞ ∞
[154] and the preservation of foodstuffs [155], Tridodecylamine 23.9 ∞
Trioctadecylamine 36.4
paints, finishes, and latexes [156], and as an-
tibacterial agent for the urinary tract.
Vapor pressures at ambient temperature
are generally very low and decrease from
26.5 Pa for dodecylamine to 2.7 × 10−2 Pa
7. Fatty Amines (0.27 × 10−3 mbar) for eicosylamine. Some
physical properties of pure compounds and com-
Straight-chain primary, secondary, and tertiary mercial mixtures are given in Tables 4 and 5.
amines with chain lengths between 8 and 24 car- The oscillation of melting points between the
bon atoms are commonly known as fatty amines. series of odd-chain and even-chain homologues
This group of compounds also includes deriva- is shown in Figure 2. This effect disappears in
tives such as the N-alkyl-1,3-propanediamines. derivatives of primary fatty amines.
Of commercial importance are fatty amine mix-
tures, such as coco amine, tallow amine, hy-
drogenated tallow amine, oleylamine, and soya
amine, which are derived from naturally occur-
ring fatty acids. More recently, alkylamines of
similar structure were produced from synthetic
feedstocks such as olefins or paraffins, and these
also are called fatty amines (β-amines, branched
chain amines, aminoalkanols). Only partly cov-
ered are fatty amine ethoxylates, fatty alkyl qua-
ternary ammonium salts, alkyl betaines and fatty
amine oxides, although all of these are fatty Figure 2. Melting points of primary amines
amine derivatives.
26 Amines, Aliphatic
Table 2. Mixture composition of primary fatty amines (mass fraction in %) [157]

Number of carbon atoms in alkyl chain

Saturated alkyl Unsaturated alkyl ∗

6 8 10 12 14 15 16 17 18 14 16 18 18 Other

Amine
Coco 0.5 8 7 50 18 8 1.5 6 1
Hydrogenated-tallow 1 4 0.5 30 1.5 60 0.5 0.5 2
Tallow 1 3 0.5 29 1 23 1 3 37 1.5
Oleyl 0.5 3.5 0.5 4 1 5 1.5 5 76 3
Soya 0.5 1 16 15 1 49.5 13 4

∗A single prime indicates one double bond; a double prime, two double bonds.

Table 4. Physical properties of fatty amines [159–162]

Formula Mr mp, ◦ C bp ∗, ◦ C Hydrochloride Acetate mp,

decomp. temp., ◦ C ◦
C

Pure primary amines

Octylamine C8 H17 NH2 129.25 −0.1 180.0 198
Decylamine C10 H21 NH2 157.30 15.9 221.8 194
Dodecylamine C12 H25 NH2 185.35 28.2 259.1 179 – 181 56.0 – 56.3
Tetradecylamine C14 H29 NH2 213.41 38.0 292.3 150 – 167 66.0 – 66.8
Hexadecylamine C16 H33 NH2 241.46 46.0 321.9 148 – 166 74.0 – 74.2
Octadecylamine C18 H37 NH2 269.52 53.1 348.5 158 – 161 79.8 – 80.0
Eicosylamine C20 H41 NH2 297.57 59.5 372.5 151 – 154 85.0 – 85.2
Docosylamine C22 H45 NH2 325.63 65.3 394.6 150 – 153 88.8 – 89.0
Commercial mixtures of primary amines
Coco amine 12 – 17 130 – 227 ca. 50
Oleylamine 200 – 210
Tallow amine 32 – 40 200 – 230 ca. 55
Hydrogenated-tallow amine 48 – 56 ca. 60
Soya amine 27 – 30

∗ At 101.3 kPa for pure compounds, at 3.6 kPa for mixtures

Table 5. Physical properties of secondary and tertiary fatty amines

Formula Mr mp, ◦ C bp, ◦ C ( p,Pa)

Secondary amines (α) (β)

Dioctylamine (C3 H17 )2 NH 241.46 14.8 26.5 115 (133)
Didecylamine (C10 H21 )2 NH 297.57 33.6 41.4 152 (133)
Didodecylamine (C12 H25 )2 NH 353.68 47.2 51.0 183 (133)
Ditetradecylamine (C14 H29 )2 NH 409.79 58.1 58.8 209 (133)
Dihexadecylamine (C16 H33 )2 NH 465.90 67.0 231 (133)
Dioctadecylamine (C18 H37 )2 NH 522.01 74.7 250 (133)
Dicoco amine 40 – 47
Dihydrogenated-tallow amine 60 – 65
Tertiary amines
N-Methyldioctadecylamine (C18 H37 )2 NCH3 536.03 40 252 – 259 (6.7)
N,N-Dimethyldodecylamine C12 H25 N(CH3 )2 213.41 −20.5 135 (1333)
N,N-Dimethyloctadecylamine C18 H37 N(CH3 )2 287.49 22.5 202 (1333)

Almost all amines derived from natural
sources have an even number of carbon
atoms. Diamines and 2-(alkylimino)diethanols
[N,N-bis(2-hydroxyethyl)alkylamines] are low-
melting pasty solids. Unsaturation decreases
the melting points of the amines relative to
the fully saturated compounds. Fatty amines
and their derivatives are cationic surfactants
(→ Surfactants) and show strong substantiv-
ity to the negatively charged surface of most
solids, e.g., cotton, minerals, and metals, and
thus change the physical properties of the sub-
strates [163], [164].
Chemical Properties. Fatty amines, like
short-chain amines, are stronger bases than am-

monia. Their ionization constants [165] do not
change significantly with chain length (see Ta-
ble 6), and their reactions are similar to those
known from the lower homologues.
Table 6. pK b Values of amines in water at 25◦ C ∗
R RNH2 R2 NH
Methyl 3.38 3.29
Ethyl 3.37 3.02
Octyl 3.35 3.00
Octadecyl 3.40 3.00
∗ The pK b of NH3 in water at 25 ◦ C is 4.79.
The following are industrially important re-
actions:
1) Salt formation with inorganic and organic
acids. The hydrochlorides are slightly more
soluble and the acetates considerably more
soluble in water than the free amines. Ac-
etates and salts of higher fatty acids are read-
ily soluble in organic solvents [158]. The
melting points of the salts are higher than
those of the free amines.
2) Conversion into N-alkyl carboxamides with
carboxylic acids or their derivatives.
3) Reaction with carbon dioxide to give carba-
mates, which are formed as contaminants in
amines exposed to air.
4) Alkylation with excess of strong nucle-
ophiles, such as methyl chloride, benzyl
chloride, or dimethyl sulfate, leading even-
tually to quaternary ammonium compounds.
This reaction is normally carried out in aque-
ous alcohol as the solvent and in the presence
of alkali as the proton acceptor [166], [167].
5) Oxyalkylationwith ethylene oxide, a more
selective reaction than alkylation. The un-
catalyzed reaction with primary amines
at 150 – 200 ◦ C yields almost exclu-
sively 2-(alkylimino)diethanols (N,N-bis(2-
hydroxyethyl) fatty amines). Base catalysis
even at temperatures as low as 100 ◦ C leads
to bis(polyoxyethyl) amines [168]. Under
mild conditions (80 ◦ C, 350 Pa) and in the
presence of water or acids, secondary and
tertiary amines react readily with ethylene
oxide to form the corresponding bis- or
mono(2-hydroxyethyl) quaternary ammo-
nium salts [169–171]. Long-chain epoxides
undergo a similar reaction [172], but prod-
Amines, Aliphatic 27
ucts from ethylene and propylene oxide are
the only important commercial products.
6) Reaction of fatty amines with halogenated
carboxylic acids or with lactones to give am-
photeric compounds (betaines).
7) Michael addition to activated double
R3 N bonds. For example, the important 1,3-pro-
panediamines are synthesized by the reac-
4.24
tion of a primary fatty amine with acryloni-
trile followed by hydrogenation of the inter-
mediate 2-(alkylimino)ethanenitrile [173].
8) Mannich reactions with formaldehyde and
nucleophiles, such as aldehydes, nitroparaf-
fins, or phenols, to form polyfunctional
derivatives [174–176].
9) Reaction with phosgene to form isocyanates
and ureas.
10) Oxidation by hydrogen peroxide, perox-
oacids, or ozone to give amine oxides. In-
dustrially, oxidation of tertiary amines to
amine oxides by hydrogen peroxide is very
impotant since the products find use as sur-
factants.
7.2. Production
Fatty amines can be produced from natural fats
and oils or from synthetic raw materials [177].
Production from Fatty Nitriles. The most
important source of fatty amines is still fatty
nitriles, which are themselves formed from
fatty carboxylic acids and ammonia over op-
tional dehydrating catalysts (Al2 O3 , SiO2 , ZnO,
bauxite, or salts of Ti, Fe, Mn, or Co) in
batch liquid-phase reactors or continuous liquid-
and vapor-phase reactors at 160 – 430 ◦ C and
0.03 – 0.7 MPa. The principal raw materials are
coconut oil, palm kernel oil, and tallow.
Depending on the process, the nitriles are pu-
rified by distillation or used as such. The fatty
acid feedstocks may be fractionated beforehand
as well. Hydrogenation of nitriles can lead to
all three types of amine, depending on reaction
conditions. Hydrogenation may be batch or con-
tinuous and is sensitive to catalyst poisons from
the natural feedstock.
Primary amines are formed by hydrogena-
tion of fatty nitriles, typically at 80 – 140 ◦ C
and 1 – 4 MPa, over nickel or cobalt catalysts.
Raney cobalt or copper chromite catalysts are
28 Amines, Aliphatic
used to obtain unsaturated amines [178–180].
To avoid formation of secondary amines, ammo-
nia is commonly used as a suppressant; a solvent
may also be used.
Secondary Amines. If ammonia is continu-
ously or periodically vented from the reactor
and temperatures of 150 – 210 ◦ C and pressures
of 5 – 20 MPa are maintained, saturated and un-
saturated secondary amines can be obtained in
yields of > 90 % [181], [182]. Catalysts mainly
used are nickel, cobalt, and copper chromite.
Tertiary Amines. Symmetrical trialky-
lamines are obtained similarly to the secondary
amines, but usually mixtures of primary, sec-
ondary, and tertiary amines result. Tertiary
amines may also be produced from nitriles via
the imine RCH=NH and Schiff base RCH=N–
CH2 R by using supported nickel catalysts at
230 ◦ C and 0.7 MPa hydrogen partial pressure
[183].
More important are the N-alkyl-
N-methylalkylamines and the N,N-di-
methylalkylamines, which can be synthesized
by the Leuckart reaction of primary or secondary
amines [184], [185]:
R2 NH + CH2 O + HCOOH −→ R2 NCH3 + CO2 +
H2 O
RNH2 + 2 CH2 O + 2 HCOOH −→ RN(CH3 )2 + 2 CO2 + 2 H2 O processes starting from fatty alcohols and with
Industrially, the reduction of the formaldehyde
may be achieved with hydrogen and a nickel cat-
alyst, e.g.:
RNH2 + 2 CH2 O + 2 H2 −→ RN(CH3 )2 + 2 H2 O
N,N-dimethylalkylamines can also be produced
from fatty nitriles and dimethylamine [186].
Both types of methyl-substituted tertiary amines
are accessible also from primary alcohols [187],
[188], and this route is used almost exclusively.
Efforts to use methanol or hexamethy-
lenetetramine to methylate the nitriles
with different catalysts to obtain N,N-di-
methylalkylamines or N-methyldialkylamines
are descibed in [189].
Production from Alcohols or Carbonyl
Compounds. Fatty amines are produced by re-
ductive alkylation of ammonia or substituted
amines with primary linear alcohols (C8 – C18 )
at 90 – 190 ◦ C under low pressure (atmospheric
up to 0.7 MPa) in the presence of a Raney nickel
catalyst. If water is continuously removed from
the reactor, only secondary and tertiary amines
are obtained [190–192]. Similarly, aldehydes
can be converted into primary amines by re-
ductive amination at 110 – 120 ◦ C and 1.5 MPa
with rare earth-promoted cobalt catalysts [193].
Oxo aldehydes react with methylamine to form
imines, which are then hydrogenated to give N-
methylalkylamines at 115 ◦ C and 3 MPa with a
Raney nickel catalyst [194]. Similarly, both al-
cohols and aldehydes can be converted into N,N-
dimethyl tertiary amines with dimethylamine.
Alcohols are converted into amines at 230 ◦ C
at atmospheric pressure with copper chromite
catalysts, whereas fatty aldehydes require no-
ble metal, copper chelate, or copper carboxylate
catalysts [195–198].
The widely used fatty alkyl dimethylamines
are nowadays almost exclusively produced from
long-chain natural, oxo, or Ziegler fatty alcohols
(C12 – C18 ). Conversion is achieved by reacting
dimethylamine with the fatty alcohol at elevated
temperatures and pressures with copper, copper
chromite, or nickel catalysts. Alternatively, the
fatty alcohol can initially be converted to the pri-
mary fatty amine by using ammonia and a nickel
catalyst and subsequently treated with formalde-
hyde as described above. Some other two-stage
sodium alkyl sulfates or chlorides as intermedi-
ates have been described, but direct conversion
with dimethylamine is the most attractive.
Production from Olefins. α-Olefins can be
converted to 1-bromoalkanes by radical addition
(anti-Markovnikov) of hydrogen bromide [199].
Reaction with ammonia furnishes primary fatty
amines, and using dimethylamine results in ter-
tiary fatty amines. A higher amount of branched
chain isomers is likely for the α-olefin route as
compared with the alcohol route.
Under hydrocarbonylation conditions, α-
olefins and dimethylamine form N,N-di-
methylalkylamines directly if highly selective
noble metal catalysts are used [200]. Use of the
less specific tributylphosphinecobalt catalysts
leads to mixtures of amines and alcohols [201].
In a Ritter reaction, α-olefins react with
hydrogen cyanide or acetonitrile in concen-
trated sulfuric acid or aqueous hydrogen fluo-
ride, via the intermediate 2-acylaminoalkane, to

give branched alkyl primary amines (β-amines).
The reaction is not specific, and positional iso-
mers are also formed [202], [203].
Aluminum alkoxides, as formed in the Ziegler
process, can be used to convert secondary
amines into tertiary amines [204].
Production from Alkane Derivatives. Ni-
troalkanes with a statistical distribution of nitro
groups can be hydrogenated over Pd/C at 190 ◦ C
and 3.9 MPa to form secondary alkyl primary
amines in yields of up to 93 % [205]. Nickel cat-
alysts can also be used. Selectively chlorinated
alkanes react with dimethylamine to yield up to
65 % terminal tertiary amine [206].
Production from Other Starting Mate-
rials. Glycerides and methyl esters of fatty
acids can be converted into fatty nitriles
at 220 – 300 ◦ C provided ammonia is vented
rapidly. Yields of nitrile and glycerine in ex-
cess of 80 % were reported with zinc carbox-
ylate or aryl sulfate catalysts [207]. Under hy-
drogenation conditions over Zn – Al catalysts at
high pressures (10 – 30 MPa) and temperatures
(200 – 350 ◦ C), coconut glycerides can be con-
verted into primary coco amine. Glycerine, how-
ever, decomposes completely under these con-
ditions [208].
Primary fatty amides can be converted in high
yields into odd-chain primary amines by Hof-
mann degradation of the chloroamide interme-
diate [209]:
These fatty amines have an uneven number
of carbon atoms and are hence distinct from the
more common primary amines from the nitrile
route.
N-Alkyl-1,3-propanediamines. These so
called fatty diamines are obtained by acry-
lonitrile addition to fatty amines followed by
hydrogenation in the presence of ammonia:
RNH2 + CH2 =CHCN −→ RNH(CH2 )2 CN
RNH(CH2 )2 CN + 2 H2 −→ RNH(CH2 )3 NH2
Amines, Aliphatic 29
Acrylonitrile addition may be catalyzed by the
presence of methanol and is conducted at tem-
peratures between 30 and 90 ◦ C. Hydrogenation
is performed under the same conditions as for the
fatty nitrile hydrogenations above. Polyamines
may also be obtained similarly.
7.3. Analysis and Quality Control
Because of their relatively high basicity, fatty
amines can be titrated easily with acids. Most
of the amines are insoluble in water; therefore,
organic solvents, such as isopropyl alcohol, are
commonly used. End points are determined col-
orimetrically (bromophenol blue) or potentio-
metrically. In the second case, perchloric acid
and glacial acetic acid are preferred as titrant
and solvent, respectively.
Industrial mixtures of amines normally con-
tain up to 90 % of the main compound. These
mixtures are analyzed by stepwise titrations with
acid. The total basicity is determined first. Pri-
mary amines then are removed with salicylalde-
hyde, and primary and secondary amines can
be removed with phenylisothiocyanate or acetic
acid, so that the remaining free amine can be
titrated with acid. Unsaturated amines are deter-
mined by means of the iodine number. Because
amine groups also consume iodine, the original
Wijs method must be slightly modified by using
acetic acid as the solvent. The resulting amine
salt absorbs the halide at a much slower rate than
the double bonds.
Quaternary ammonium compounds usually
are determined by solvent partition titration with
anionic surfactants or sodium tetraphenylboron
[210]. Iodine numbers of quaternary ammonium
compounds are obtained in sodium lauryl sulfate
containing chloroform to prevent the free iodine
from being retained by the nonaqueous phase. A
summary of approved wet chemical test meth-
ods (AOCS, ASTM) is given in [211].
Chain-length distribution and hydrocarbon
content of fatty amines are determined by gas
chromatography [212–216]; nitrile and amide
impurities are determined by IR spectroscopy
[217], [218].
More recently, NMR spectroscopy has been
used for determination of quaternary ammonium
compounds in the presence of free amines [219]
and also for establishing the relative amounts of
30 Amines, Aliphatic
primary, secondary, and tertiary amines in mix-
tures [220].
Fatty amines can be stored in carbon steel
containers; aluminum, copper or their alloys are
to be avoided. Quaternary amines are more cor-
rosive and thus require lined drums or stainless
steel. With water hydrates are formed by pri-
mary and secondary amines and carbamates with
CO2 .
7.4. Uses
Fabric Softeners. By far the largest use of
fatty amines and in particular their quaternary
derivatives used to be in fabric softening. Prior to
the early 1950s, fabric softeners were not needed
because most detergents were based on tallow-
derived soap formulations and some of the active
detergent remained on the textile and resulted
in a softer dried fabric. However, the advent of
synthetic detergents created the market for fab-
ric softeners in home care and institutional laun-
dries.
Most of these softeners are used in rinse cy-
cles where a 3 – 8 % formulated aqueous dis-
persion is added leaving 0.1 – 0.2 % active qua-
ternary ammonium compound on the surface of
the clothes. Since the 1980s, concentrates have
been developed, which contain up to 50 % ac-
tive ingredients. In another usage, a quaternary
fabric softener is applied to a substrate, such as
paper, to woven or nonwoven cloth, or to a foam
and then added to the drying cycle. The formu-
lation contains a quaternary ammonium com-
pound and a transfer agent that allows the active
ingredient to be transferred to the cloth during
the drying cycle. The prevention of static build-
up is actually more important than the softening
action in this application. A third area of appli-
cation are wash cycle softeners, in which qua-
ternaries are combined with other detergents to
achieve both cleaning and softening.
The fatty quaternary ammonium compounds
used were formerly mainly dimethyl dihydro-
genated tallow ammonium chloride, but this
compound was replaced in many countries
by other surfactants because of its lack of
biodegradability and potential aquatic toxicity.
Nowadays the most widely used quaternaries
are ester quats, which are not derived from fatty
amines but from fatty acids, alcoholamines (e.g.,
triethanolamine), and methylating agents.
Amine ethoxylates, mainly derived from pri-
mary tallow, hydrogenated tallow and coconut
amines, are also used in large amounts for tex-
tiles.
Flotation. One of the first commercial uses
of primary fatty amines was in the beneficiation
of potash [221]. In this process, fatty amine salts
adhere to the surface of potassium chloride, al-
lowing it to be removed by froth flotation and
leaving the sodium chloride in the tailings. The
technique spread to other mineral beneficiation
processes [222], the most important of which are
phosphate rock, precious metals, lead, zinc, cop-
per, molybdenum, tin, fluorspar, feldspar, mag-
nesite, limestone, mica, manganese, silica, and
coal. In general, any negatively charged surface
can be removed from a system with an amine
salt. Ore flotation accounts for the largest direct
use of primary fatty amines. Other fatty amines
used for mining are quaternary componds and
some diamines, but these are less important.
Corrosion Inhibition. Large quantities of
amines are used in corrosion inhibition. The
cationic amino group adheres to the surface
of metals and prevents attack by corrosive liq-
uids and gases. Primary amines and N-alkyl-
1,3-propanediamines are used most frequently
for this purpose. The amines may be neutral-
ized with oleic, naphthenic, and acetic acids to
adjust their solubility. A typical oil-soluble in-
hibitor formulation contains N-tallow-1,3-pro-
panediamine dioleate.
Asphalt Emulsification. The cationic na-
ture of fatty amines makes them useful as emul-
sifiers for asphalt. Primary amines, diamines,
polyamines, alkoxylated amines, and fatty qua-
ternary ammonium compounds can be used in
this application. The formulation used depends
on the properties of the emulsion desired. The
cationic emulsion can be rapid, medium, or slow
set. In all cases a cationic emulsifier is used at
a low concentration (0.2 – 2.0 wt % of the emul-
sion). When the cationic emulsion is mixed with
the negatively charged aggregate, for instance
limestone, the emulsion breaks, thereby setting
the road-covering formulation. Fatty amines, be-
cause of their positive charge, also increase the

adherence of the asphalt to the aggregate. For
di- and polyamines, asphalt emulsification is by
far the largest application and they are also the
most important surfactants for this purpose.
Other Applications. Significant amounts of
primary amines are used as fertilizer anticak-
ing agents. Frequently, fatty amine salts are also
added to other mineral products to prevent cak-
ing of the powdered mineral.
There are many other applications for fatty
amines in agriculture as emulsifiers, adjuvants,
and intermediates in pesticide production. Much
of their usefulness relies on the controllable lipid
solubility, which aids penetration or absorption
of many active pesticides. Among the emulsi-
fiers used are ethoxylated amines and quaternary
ammonium compounds. Some of the surfactants
also can act as foaming agents or foam stabiliz-
ers [223].
Neutralization of various herbicidal acids
with fatty amines enhances their activity because
the corresponding salts are more soluble in oil
and less volatile than the free amines [224–227].
In some cases, the N,N-dimethylalkylamines
were found to control the growth of suckers
or unwanted leaves, thereby producing a better
grade of product, for example, in tobacco [228].
The reaction of dodecylamine and cyanamide
leads to dodecylguanidine (Dodine from ACC,
Agrimont, Chemolimpex, and Drexel), which is
an excellent fungicide for fruit trees.
Many fatty alkylamine derivatives are used
as additives in plastic formulations. For exam-
ple, bis(2-hydroxyethyl)alkylamines are added
to polypropylene or polyethylene as internal an-
tistatic agents, either as 100 % amines or as a
75 % solid masterbatch to prevent static charge
buildup at low humidities.
Fatty amines, diamines, and ethoxylated
amines also can be used as pigment-grinding
aids and as dispersants for pigments in
paints, coatings, and magnetic tape. The most
widely used compound is N-tallow-1,3-pro-
panediammonium dioleate. The amine com-
pound coats the pigment particle, making it more
readily and evenly dispersible in the formula-
tion.
The organo-clay market also is a very large
user of quaternary fatty amines. Most of this
market is satisfied with methyl or benzyl qua-
ternary ammonium chlorides produced from
Amines, Aliphatic 31
mono- or dihydrogenated tallow amine. In ei-
ther case, the cations of the quaternary ammo-
nium chloride are exchanged with those of the
clay, mostly bentonite, to produce clay platelets
separated with a hydrophobic compound. These
organo-clay products are used as thickening
agents, mainly in drilling muds and oil-based
coatings, but also in the paint industry.
Some primary amines, amine salts, di- and
polyamines, e.g., lauryl and tallow amines,
posess biocidal properties; monoalkyl quater-
nary amines with a C10 – C18 chain act as germi-
cides and antiseptics and therefore have a wide
range of biocidal applications, for example, in
households, swimming pools, and oil fields.
Primary amines are also important lubricants
since their polar nitrogen end attaches to met-
als while the nonpolar chains form an oily
film above the surface. They are also used as
petroleum additives. Secondary amines have few
direct uses and are mainly used as interme-
diates for ethoxylation or quaternization. Ter-
tiary amines with three long chains are of mi-
nor commercial significance, but can be used,
for instance, as deicers for motor fuels. The
fatty alkyldimethylamines are used almost ex-
clusively as intermediates for alkyl betaines,
amine oxides, and quaternary ammonium salts.
7.5. Economic Aspects
The economics of fatty amines production gen-
erally depend on the worldwide fat and oil mar-
ket process. Most of the fatty amine products are
made from tallow and coconut oils; others are
made from oils such as soybean, palm, and cot-
tonseed. Minor amounts of tall oil acids are used.
When pure chain lengths are required, these can
be obtained by fractionating the acid mixture
found in the initial triglyceride. Pure fractions
are much more expensive than mixtures. Pri-
mary and secondary amines have a much larger
market than tertiary amines.
The nitrile route, which is mainly used for the
production of primary and secondary amines,
accounted for 300 000 t/a world capacity in 1996
for all alkylamines and their derivatives and
has decreased since the early 1990s from about
370 000 t/a due to declining demand for the
poorly biodegradable dihydrogenated tallow di-
methyl ammonium salts for fabric softeners. The
32 Amines, Aliphatic

fatty alcohol and α-olefin route, which is mainly Flash point 39.4 ◦ C
used for the production of alkyldimethylamines Ignition temperature 390 ◦ C
and their derivatives, is less important but is ex- (class T2)
Explosion limits in 2.7 and 16.6 vol %
pected to surpass the nitrile route in the long air (corresponding to
run. In Europe, the largest producers employing 67.4 and 415 g/m3 )
the nitrile route are Akzo Nobel, Clariant, Ceca, 3.41 J g−1 K−1 (at 100 ◦ C)
Specific heat capacity 3.45 J g−1 K−1 (at 110 ◦ C)
and Olefina, in North America Witco and Akzo 3.50 J g−1 K−1 (at 120 ◦ C)
Nobel, in South America Akzo Nobel, Clariant, Heat of vaporization
636.4 J/g (at 0.1 MPa)
and Quimi Kao, in Asia Kao and Lion-Akzo. 660 J/g (at 40 kPa)

The most important producers of N,N-di-

methyl fatty amines are Procter & Gamble, Vapor pressures, thermodynamic data, densi-
Albemarle, and Lonza in the United States, ties, and viscosities have been shown in graphi-
Clariant, Albright & Wilson, and Kao in Eu- cal form [230]. Diaminoethane is infinitely mis-
rope, and Kao and Lion-Akzo in Asia. World- cible with water, methanol, diethyl ether, ace-
wide demand was estimated at about 100 000 t/a tone, and benzene but is only slightly soluble in
in 1998. In 1988 it was only ca. 75 000 t/a. North lower hydrocarbons. It reacts, however, with car-
America accounts for 59 % of the installed ca- bon tetrachloride or methylene chloride. It forms
pacity, Europe for 28 %, and Asia for 8 %. binary azeotropes with water, several alcohols,
Because most fatty amines offered commer- or toluene [231].
cially contain mixed alkyl chain lengths, trade Chemical Properties. As a primary diamine,
names are common; a comprehensive list can be diaminoethane forms stable mono- and diacid
found in [229]. In Europe, about 20 000 t were salts. The free base can be liberated from
sold in 1996 as the underivatized primary, sec- these salts by inorganic alkali solutions. The
ondary or tertiary amines. mononitrate and dinitrate are highly explosive
in the dry state. The reaction of diaminoethane
with chloroacetic acid or with formalde-
8. Diamines and Polyamines hyde and hydrogen cyanide or an alkali-metal
cyanide to give ethylenediaminetetraacetic
acid or its salts is particularly important
8.1. Diamines (→ Ethylenediaminetetraacetic Acid and Re-
lated Chelating Agents). Diaminoethane forms
8.1.1. 1,2-Diaminoethane (Ethylenediamine)
complex salts with salts of copper, manganese,
cobalt, and other transition elements.
(For triethylenediamine, see page 23)
If diaminoethane is heated with a fatty acid
Physical Properties. 1,2-diaminoethane
under conditions favoring dehydration, the prod-
[107-15-3], EDA, C2 H8 N2 , M r 60.10, is a color-
uct is a mono- or diamide, which can be con-
less liquid, mp 10.9 ◦ C, bp 117 ◦ C (at 101.3 kPa),
verted into an imidazoline by cyclization. At
d 20 20
4 0.8978, nD 1.4571. high temperatures and pressures and in the pres-
ence of a catalyst, ammonia is eliminated from
diaminoethane, and the resulting product un-
dergoes cyclization to give piperazine. Diami-
noethane reacts with aldehydes and ketones to
Viscosity
give Schiff bases, which in turn can be hydro-
t, ◦ C 25 60 100 genated to give secondary amines. The Schiff
η, mPa · s 1.35 0.7 0.4 base can also cyclize to afford imidazolidines.
Condensation with 1,2-diketones results in the
elimination of water to give the corresponding
Vapor pressure
2,3-dihydropyrazines, which can be readily de-
t, ◦ C 20 40 60 80 100 hydrogenated to pyrazines [232]. Phosgene re-
p, kPa 1.21 3.87 11.13 26.53 55.99
acts with diaminoethane to give the hydrochlo-
ride of N,N
-ethyleneurea (2-imidazolidone)
[233]. One mole of diaminoethane reacts with

two moles of carbon disulfide in the presence
of a basic catalyst to give ethylene bisdithio-
carbamate [234]. With only one mole of carbon
disulfide, ethylenethiourea is formed. Similarly,
ethyleneurea is obtained from carbon dioxide.
With two moles of acrylonitrile, diaminoethane
undergoes a smooth cyanoethylation reaction
[235].
Production. 1,2-Diaminoethane is mainly
produced by treating ethylene dichloride (EDC)
with aqueous or liquid ammonia at about 100 ◦ C
in the liquid phase [236]. This so-called EDC
process has been modified frequently [237];
the reactant ratio, product recycle, pH, reac-
tor geometry, temperature, and pressure con-
trol the product mix. Byproducts include the
higher oligomers diethylenetriamine (DETA),
triethylenetetramine (TETA), and tetraethyl-
enenpentamine (TEPA). An unavoidable co-
product of the EDC process is the amine hy-
drochloride, which must be neutralized with
caustic soda, lime, or other bases to form, e.g.,
sodium or calcium chloride. Ethylenediamine
is either extracted or distilled from the aque-
ous stream after neutralization. If deemed nec-
essary, the higher amines can be recycled to op-
timize EDA production and vice versa. About
two-thirds of the installed ethylenediamine ca-
pacity still relies on the EDC process.
A second process is the reaction of mo-
noethanolamine with ammonia and hydrogen
over a nickel or cobalt catalyst at 20 MPa and
150 – 230 ◦ C [238]. The yield of 1,2-diami-
noethane is 74 %, based on an ethanolamine
conversion of 93 %. Byproducts are mainly
DETA and piperazine, but also aminoethyl-
piperazine (AEP) and hydroxyethylpiperazine
(HEP). The monoethanolamine process has cost
advantages over the ethylene dichloride process,
circumvents chloride disposal, and prevents the
formation of chlorinated hydrocarbons. Lower
amines can be recycled to increase the amount
of higher ethanolamines; cyclic products are
much more abundant than in the EDC pro-
cess. Product distribution is dependent on reac-
tant ratio, temperature, pressure, and conversion.
Nickel – rhenium catalysts have often been em-
ployed [239], but many other nickel catalysts
with different promoters have also been sug-
gested, for instance, Ni – Re – B supported on
alumina [240] or Ni – Co – Cu – Re – B on silica
[241].
Amines, Aliphatic 33
A third important and very cost effective pro-
duction process is the reaction of ethylene oxide
with ammonia [242], as developed by Berol
(now Akzo) in Sweden. Among the byprod-
ucts of this process are DETA, piperazine and
di- and triethanolamine. Union Carbide has re-
cently brought a similar process into operation.
The production of diaminoethane by the reaction
of formaldehyde with hydrocyanic acid, ammo-
nia, and hydrogen [243], of chloroacetyl chlo-
ride with ammonia [244], and by hydrogenation
of aminoacetonitrile [245] are of lesser impor-
tance.
Quality, Analysis, and Storage. The purity of
diaminoethane, determined by titration and gas
chromatography, is usually above 99 %. For stor-
age, containers made of stainless steel and alu-
minum are preferred to avoid deterioration of the
color number when the product is stored for long
periods. Because it is corrosive, EDA should not
be stored in containers made of copper, cop-
per alloys, or uncoated iron. Frequently contain-
ers made of iron coated with plastics, such as
Lupolen (BASF) or phenolic resins, are used for
shipping and storing diaminoethane. Tin-lined
drums can also be employed. Because the amine
is hygroscopic and reacts with carbon dioxide in
the air, tanks must be flushed with nitrogen be-
fore use. This also avoids discoloration during
storage.
Uses. Diaminoethane is mainly used in de-
tergents, resins, crop protection agents, pa-
per chemicals, lubricants, and pharmaceuticals.
The chelating agent ethylenediaminetetraacetic
acid (EDTA) and its salts are important prod-
ucts, in particular in the United States. They
are made by reaction of EDA with formalde-
hyde and hydrogen cyanide or sodium cyanide
together with an excess of sodium hydrox-
ide. Tetraacetylethylenediamine (TAED), which
is obtained from EDA, is used in the de-
tergent industry as a cold-bleach activator. It
has become the fasted-growing EDA product
in the last years. Hydroxyethylethylenediamine
is also converted into chelating agents. Sev-
eral nitrogen-containing surfactants are pro-
duced from fatty acids and EDA or amino-
ethylethanolamine, available from EDA and eth-
ylene oxide. Nonreactive polyamide resins pro-
duced from EDA and diacids also consume large
amounts of EDA. They find use as adhesives and
for printing inks.
34 Amines, Aliphatic
The zinc and manganese salts of ethylene-
bisdithiocarbamic acid, obtained from EDA, are
used as fungicides (maneb, mancozeb, zineb or
metiram) and have a significant market. Other
fungicides based on EDA are known, e.g., those
of the imidazoline type.
The EDA-derivative N,N-ethylene
bis(stearamide) (EBS) has lubricating proper-
ties and is used as a mold-release agent, for
the processing of thermoplastic resins, in pa-
per coating, wire production, etc. EDA is also
used for gasoline and lubricant additives and for
surfactant production.
Diaminoethane – polyester condensates
that are hydroxymethylated with formalde-
hyde can be used as plasticizers for
phenol – formaldehyde resins [246]. The use
of condensates of diaminoethane, epoxides, and
urea as nitrogen-containing polyol components
for the production of polyurethane foams is pro-
posed in [247]. The addition of EDA to viscose
fiber spinning baths is said to improve the tensile
strength of the fiber [248]. In the wet spinning of
polyurethane fibers, diaminoethane is a rapid-
action curing agent [249]. The incorporation
of diaminoethane into diisocyanate – polyester
prepolymers results in useful polymers for the
production of elastic polyurethane fibers [250].
Ethyleneurea derivatives prepared from diami-
noethane are used for textile finishing. Diami-
noethane is employed as a stabilizer for rubber
latex. In the mineral oil industry, diaminoethane
can act as a stabilizer for halogen-containing
high-pressure lubricating oils [251] and, in the
form of Schiff bases with ketones, is also used
as a metal deactivator [252].
Economic Aspects. Ethylenediamine and its
homologues are large-scale chemical products.
The global demand for ethyleneamines in 1998
was estimated at 250 000 t [253]; capacities are
around 340 000 t/a. The European market is ca.
100 000 t/a with an annual growth rate of 3 – 4 %
[254]; the U.S. market has a similar size, and
the Japanese is ca. 15 000 t/a. Major producers
are Union Carbide, Dow, Akzo Nobel, Tosoh,
BASF, and Bayer. In the United States and Japan,
the ethylenediamine market is smaller than that
of the higher ethyleneamines, and vice versa in
Europe.
8.1.2. Diaminopropanes
In the past few years, the demand for diami-
nopropanes and in particular for N-substituted
1,3-diaminopropanes has increased sharply in a
large variety of fields.
1,2-Diaminopropane [78-90-0], propyl-
ene-1,2-diamine, C3 H10 N2 , M r 74.13, mp
− 36.6 ◦ C, bp 120.9 ◦ C (at 101.3 kPa), d 20 4
0.872, n20 ◦
D 1.446, η 1.6 mPa · s (at 20 C), flash
point 33 ◦ C, is a colorless liquid that is very
hygroscopic and miscible with water and most
organic solvents. It forms azeotropes with bu-
tanol, 2-methylpropanol, and toluene and has a
strong ammoniacal odor.
Because 1,2-dichloropropane does not react
smoothly with ammonia, 1,2-diaminopropane
is usually prepared by aminating a mixture of
2-amino-1-propanol and 1-amino-2-propanol,
which is obtained from propylene oxide and am-
monia [255]. The process differs from corre-
sponding processes for the production of diami-
noethane in that the temperature in the catalytic
amination is higher (190 – 230 ◦ C). Producers of
1,2-diaminopropane include Bayer and BASF.
1,2-Diaminopropane is used as an interme-
diate for crop-protection agents, e.g., Basfun-
gin (BASF). Analogous to the ethylenediamine
derivatives, the zinc dithiocarbamate propineb
(Bayer) acts as a fungicide. Especially in the
United States, derivatives of the amine are used
as fuel and lubricant additives.
1,3-Diaminopropane [109-76-2], propyl-
ene-1,3-diamine, trimethylenediamine, pro-
panediamine, C3 H10 N2 , M r 74.13, mp
− 11.8 ◦ C, bp 136 ◦ C (at 101.3 kPa), d 20
4 0.8834,
n20 ◦
D 1.459, η 2.0 mPa · s (at 20 C), flash point
48 ◦ C. 1,3-Diaminopropane is a colorless liquid
that is miscible with water and most organic
solvents.
1,3-Diaminopropane is produced in a two-
stage continuous process, under a pressure of
 Amines, Aliphatic 35

10 – 20 MPa. In a first reactor, acrylonitrile re-

acts with excess ammonia at 70 – 100 ◦ C to give
2-aminopropionitrile and bis(cyanoethyl)amine.
The mixture of aminonitriles is then hydro-
genated in a downstream reactor over a fixed-
bed catalyst (cobalt or nickel) at 60 – 120 ◦ C
to give 1,3-diaminopropane and bis(aminopro-
pyl)amine [256]. The yield of 1,3-diaminopro-
pane can be increased by adding a polar solvent
and water or by using a large excess of ammo-
nia. Most of the 1,3-diaminopropane produced
is converted into the textile-finishing agent 1,3-
dihydroxymethylhexahydropyrimid-2-one. 1,3-
Diaminopropane is also utilized for the produc-
tion of a chelating agent used in the photo indus-
try and for anticorrosion agents.
N-Substituted Diaminopropanes. N-
Substituted 1,3-diaminopropanes can be pre-
pared from acrylonitrile and an amine, also
with such a two-stage procedure. It is usu-
ally more efficient to produce the substituted
aminopropionitrile batchwise and then hydro-
genate it continuously in the presence of am-
monia [257]. In some cases, hydrogenation
also can be carried out batchwise over Raney
nickel or Raney cobalt. A primary amine or
ammonia reacts with acrylonitrile in a molar
ratio of about 1/2 to give (after subsequent
hydrogenation) alkylbis(aminopropyl)amine,
1-Amino-3-dimethylaminopropane
[109-55-7], 3-dimethylamino-1-propylamine,
DMAPA, N,N-dimethyl-1,3-diaminopropane,
C5 H14 N2 , M r 102.18, mp < – 60 ◦ C, bp 133 ◦ C
(at 101.3 kPa), d 204 0.8112, n20
D 1.4350, η
1.6 mPa · s (at 20 C), flash point 32 ◦ C, ignition
◦
temperature 305 ◦ C (class T2), is a colorless
liquid and a lachrymator.
It is produced by addition of dimethylamine
to acrylonitrile and subsequent hydrogenation in
the presence of ammonia. DMAPA is used pri-
marily for the synthesis of betaines which are
employed as personal care products and for dish
washing. Of minor importance is the consump-
tion for the production of flocculants and ion
exchangers.
1-Amino-3-diethylaminopropane [104-78-9],
N,N-diethyl-1,3-propanediamine, N,N-diethyl-
1,3-diaminopropane, N,N-diethylaminopropyl-
amine, C6 H18 N2 , M r 130.2, mp − 60 ◦ C, bp
169 ◦ C (at 101.3 kPa), d 20 20
4 0.829, nD 1.4424, η
1.4 mPa · s (at 20 C), flash point 53 ◦ C is made
◦

RN[(CH2 )3 NH2 ]2 , as the principal product, by addition of diethylamine to acrylonitrile and

whereas until the molar ratio exceeds 1/1, the subsequent hydrogenation. The market for this
principal product is a 1-amino-3-alkylaminopro- product is relatively small.
pane, RNH(CH2 )3 NH2 . Dialkylamines give 1-
amino-3-dialkylaminopropanes.
Major producers of diamines, oligoamines,
and polyamines of acrylonitrile include Hunts-
man and BASF.
1-Amino-3-cyclohexylaminopropane
The following liquid, water-miscible N-
[3312-60-5], N-cyclohexylpropylene-1,3-
substituted diaminopropanes are industrially im-
diamine, N-cyclohexyl-1,3-propanediamine,
portant. Their chief use is as components of
C9 H20 N2 , M r 156.27, mp − 16 ◦ C, bp 113 ◦ C (at
epoxy resins:
1.3 kPa), d 20 20
4 0.9154, nD 1.4810, η 9.4 mPa · s
1-Amino-3-methylaminopropane [6291-84-5],
(at 20 C), flash point 103 ◦ C, ignition temper-
◦
N-methyl-1,3-propanediamine, methylami-
ature 205 ◦ C (class T3) is made by addition of
nopropylamine, C4 H12 N2 , M r 88.15, bp
cyclohexylamine to acrylonitrile and subsequent
140 – 141 ◦ C (at 101.3 kPa), d 204 0.852, n20
D
◦ hydrogenation.
1.4479, flash point 35 C, is a byproduct of
the production of N-methyldipropylenetriamine
and results from addition of methylamine to
acrylonitrile followed by hydrogenation.
36 Amines, Aliphatic
N,N,N’,N’-Tetramethyl-1,3-propanediamine
[110-95-2], C7 H18 N2 , M r 130.23, mp < –70 ◦ C,
bp 145 – 146 ◦ C (at 1.3 kPa), d 19
4 0.7837, nD
20
◦
1.4234, flash point 31 C can be made by methy-
lation of 1,3-diaminopropane with formalde-
hyde or from dimethylaminopropionitrile and
dimethylamine and is an intermediate for cor-
rosion inhibitors, textile auxiliaries, flotation
agents, and emulgators. It is also employed as a
catalyst for polyurethanes and as a hardener for
epoxy resins.
8.1.3. Higher Diamines
1,3-Diaminobutane [590-88-5], C4 H12 N2 ,
M r 88.15, bp 138 – 141 ◦ C (at 101.3 kPa), d 20
4 dicyanohexane).
0.8536, n20
D 1.4449, can be produced from cro-
tonaldehyde by amination under hydrogenation
conditions [258].
Diamines with four to five carbon atoms
are important intermediates for pharmaceuti-
cals. However, the production of these diamines
is restricted by the fact that the starting materials
are difficult to obtain and that there is a strong
tendency for cyclization during preparation.
1,4-Diaminobutane [110-60-1], tetramethy-
lenediamine, putrescine, C4 H12 N2 , M r 88.15,
mp 27 – 28 ◦ C, bp 158 – 159 ◦ C (at 101.3 kPa),
d 25 20 ◦
4 0.8704, nD 1.4569, flash point 63 C, occurs
as colorless crystals that are soluble in water and
conventional organic solvents.
1,4-Diaminobutane can be produced from
1,4-dichloro-2-butene or 1,4-dihalobutane (ob-
tainable from the reaction of butadiene or
tetrahydrofuran with a halogen), preferably via
the phthalimido compounds. Alternatively, 1,4-
diaminobutane can be prepared by hydrogenat-
ing succinodinitrile [259].
1,5-Diaminopentane [462-94-2], penta-
methylenediamine, cadaverine, C5 H14 N2 , M r
102.18, mp 9 ◦ C, bp 178 – 180 ◦ C (at 101.3 kPa),
d 25 20
4 0.867, nD 1.4582, flash point 62 C, can
◦
be prepared by methods similar to those de-
scribed for 1,4-diaminobutane. The starting ma-
terials are 1,5-dichloropentane (obtainable from
tetrahydropyran), glutarodinitrile, or glutaralde-
hyde (e.g., Relugan, BASF). The compound is
hygroscopic and has a very bad odor.
1,8-Diaminooctane [373-44-4], octamethy-
lenediamine, C8 H20 N2 , M r 144.26, mp
52 – 53 ◦ C, bp 225 – 226 ◦ C (at 101.3 kPa),
flash point 165 ◦ C is hygroscopic. It is used
for the production of fungicides and is ob-
tained by hydrogenation of suberonitrile (1,6-
1,10-Diaminodecane [646-25-3],
decamethylenediamine, H2 N(CH2 )10 NH2 ,
C10 H24 N2 , M r 172.31, mp 61 – 62 ◦ C, bp
140 ◦ C (at 1.6 kPa).
1,12-Diaminododecane [2783-17-7],
H2 N(CH2 )12 NH2 , C12 H28 N2 , M r 200.37, mp
66 – 67 ◦ C, bp 304 ◦ C (at 101.3 kPa), flash point
155 ◦ C can be used as a spacer in affinity chro-
matography.
Diamines containing more than six carbon
atoms can be obtained readily by hydrogenating
the corresponding dinitriles over a Raney nickel
catalyst in a batch procedure under pressure at
up to 125 ◦ C. A five- to tenfold excess of liq-
uid ammonia is used, with or without methanol
solvent [260].
Higher diamines can be prepared contin-
uously, as described for the production of
hexamethylenediamine. For methods of prepar-
ing specific higher diamines, see [3].
2-(Diethylamino)ethylamine [100-36-7],
N,N-diethylethylenediamine, 1-amino-2-
(N,N-diethylamino)ethane, N,N-diethyl-1,2-
ethanediamine, diethylaminoethylamine,
 Amines, Aliphatic 37

C6 H16 N2 , M r 116.21, mp < – 70 ◦ C, bp 146 ◦ C This specialty diamine is produced by

(at 101.3 kPa), d 20 20
4 0.8222, nD 1.4360, flash Degussa-Hüls and BASF. It is made from
point 30 ◦ C. isophorone nitrile, ammonia, and hydrogen,
which leads to simultaneous imination and hy-
drogenation of the resulting imine and nitrile
groups [263]. Catalysts employed are mainly
cobalt or ruthenium. Isophorone diamine is em-
ployed as a hardener for epoxy resins and as
an intermediate for isophorone diisocyanate; its
1-Diethylamino-4-aminopentane [140-80-7], market is considerable. Very important for the
N,N-diethyl-1,4-pentanediamine, novol- applications is the cis/trans isomer ratio, which
diamine, C9 H22 N2 , M r 158.29, bp 191 ◦ C (at should be as high as possible, since the trans
101.3 kPa), d 20 20
4 0.821, nD 1.4442, flash point isomer reacts more sluggishly.
68 ◦ C, is a colorless liquid that is soluble in
water and the usual organic solvents. N,N,N
,N
-Tetramethyl-1,6-hexanediamine
[111-18-2], N,N,N
,N
-tetramethylhexamethy-
lenediamine, C10 H24 N2 , M r 172.31, bp
209 – 210 ◦ C (at 101.3 kPa), d 20 4 0.7981, nD
20

1.4363, flash point 73 ◦ C, can be made from

adipodinitrile and dimethylamine or from 1,6-
The diamine is produced by a conven- hexanediamine and formaldehyde and is used
tional method, for example, by aminating 1- for instance as a catalyst for polyurethanes and
diethylaminopentan-4-one under hydrogenation hardener for epoxy resins.
conditions, by hydrogenating the oxime, or by
aminating 1-diethylaminopentan-4-ol. The ke-
tone is obtained from 2-chloroethyldiethylamine
by synthesis of the acetoacetate, and 1-
diethylaminopentan-4-ol is obtained by Man-
nich condensation of diethylamine, formalde-
hyde, and 1-butyn-3-ol followed by hydrogena-
tion of the product, or is prepared from 1-
methyltetrahydrofuran [261], [262]. Producers 8.2. Oligoamines and Polyamines
of 1-diethylamino-4-aminopentane are BASF
and some Chinese producers. Derivatives of 1- 8.2.1. Physical Properties
diethylamino-4-aminopentane are particularly
important as antimalarial agents [262] (e.g., Diethylenetriamine [111-40-0], DETA,


chloroquine from Bayer). bis(2-aminoethyl)amine, 2,2 -diaminodiethyl-
amine, 3-azapentane-1,5-diamine, C4 H13 N3 ,
3-Aminomethyl-3,5,5-trimethylcyclo- M r 103.17, is a colorless liquid, mp − 39 ◦ C, bp
hexylamine [2855-13-2], isophorone diamine, 207 ◦ C (at 101.3 kPa), d 20 20
4 0.9542, nD 1.4859,
◦
IPDA, (5-amino-1,3,3-trimethyl-1-cyclo- η 7 mPa · s (at 20 C).
hexylmethyl)amine, 1-amino-3-aminomethyl-
3,5,5-trimethylcyclohexane, C10 H22 N2 , M r
170.30, mp 10 ◦ C, bp 247 ◦ C (at 101.3 kPa),
d 20 20 ◦
4 0.922, nD 1.4880, flash point 112 C.
Vapor pressure
t, ◦ C 20 89 174
p, kPa 0.049 1.333 40.0
38 Amines, Aliphatic

Flash point 102 ◦ C

101.3 kPa), d 20 20
4 0.9994, nD 1.505, η 96.2 mPa · s
◦
Ignition temperature 330 ◦ C (class T2) (at 20 C). Technical-grade TEPA may be avail-
3.44 J g−1 K−1 (at 190 ◦ C) able as a distillation cut that also contains
Specific heat capacity 3.48 J g−1 K−1 (at 200 ◦ C)
3.53 J g−1 K−1 (at 210 ◦ C)
branched isomers and cyclic compounds.
456.4 J/g (at 0.1 MPa)
Heat of vaporization
485.7 J/g (at 40 kPa)
Dissociation constant 7.07×10−5
43.8 mN/m (at 25 ◦ C)
Surface tension 40.8 mN/m (at 50 ◦ C)
Coefficient of expansion 9.1×10−4 (at 55 ◦ C).
Vapor pressure
t ◦C 20 195 300
The amine is infinitely miscible with water, p, kPa 0.0013 13.5 40
methanol, acetone, ether, and benzene, but insol-
uble in heptane. Because of its reactivity, CCl4 Dissociation constant 6.5×10−5
cannot be used as solvent. DETA is hygroscopic Flash point 163 ◦ C

and has a strong ammoniacal odor.

Tetraethylenepentamine is infinitely miscible
Triethylenetetramine [112-24-3], TETA, with water, methanol, acetone, benzene, and di-
N,N
-bis(2-aminoethyl)ethylenediamine, ethyl ether but is insoluble in heptane and reacts
1,8-diamino-3,6-diazaoctane, 1,4,7,10- violently with CCl4 .
tetraazadecane, C6 H18 N4 , M r 146.24, is a
colorless to yellowish oily viscous liquid, mp Pentaethylenehexamine [4067-16-7],
− 35 ◦ C, bp 277 ◦ C (at 101.3 kPa), d 20
4 0.9818, PEHA, C10 H28 N6 , M r 232.37, mp − 26 ◦ C,
n20 ◦
D 1.4986, η 26.7 mPa · s (at 20 C). bp 136 – 144 ◦ C (at 0.02 kPa), d 20
4 1.0020, flash
point 186 ◦ C, commercially is of minor impor-
tance. Technical-grade PEHA may be available
as a distillation cut that also contains branched
isomers and cyclic compounds.
Vapor pressure
t, ◦ C 20 144 240
p, kPa 0.001 1.33 40.0

Flash point 135 ◦ C Dipropylenetriamine [56-18-8], 1-amino-

374.7 J/g (at 0.1 MPa)
Heat of vaporization
397.8 J/g (at 40 kPa)
3-(3-aminopropyl)aminopropane, bis(ami-
Dissocation constant 6.7×10−5 nopropyl)amine, C6 H17 N3 , M r 131.22, mp
− 15.1 ◦ C, bp 238 ◦ C (at 101.3 kPa), d 20
4 0.9386,
TETA is hygroscopic, corrosive, and has a n20
D 1.4846, flash point 118 ◦
C, vapor pres-
strong ammoniacal odor. With water a crys- sure < 0.001 kPa at 20 ◦ C, dissociation constant
talline hydrate is formed. Like DETA, it is com- 3.96 × 10−4 , η 9.6 mPa · s (at 20 ◦ C), is miscible
pletely miscible with water and many polar or- with water, methanol, and conventional organic
ganic solvents, but less so with lipids; with CCl4 solvents.
a violent reaction occurs. Its four pK a values
are 3.32, 6.67, 9.20, and 9.92. Technical-grade
TETA is sometimes available as a distillation cut
that also contains branched isomers and cyclic
compounds. N-Methyldipropylenetriamine [105-83-9],
1-amino-3-N-methyl-N-(3-aminopropyl)-ami-
Tetraethylenepentamine [112-57-2], nopropane, C7 H19 N3 , M r 145.25, mp − 32 ◦ C,
TEPA, 1,4,7,10,13-pentaazatridecane, bp 234 ◦ C (at 101.3 kPa), d 20 4 0.9040, n20
D
◦
C8 H23 N5 , M r 189.30, is a slightly yellow- 1.4732, η 7.4 mPa · s (at 20 C), flash point
ish viscous liquid, mp − 40 ◦ C, bp 340 ◦ C (at 107 ◦ C, ignition temperature 250 ◦ C (class T3),

is miscible with water and conventional organic
solvents.
3-(2-Aminoethyl)-aminopropylamine
[13531-52-7], N-(2-aminoethyl)-1,3-diami-
nopropane, C5 H15 N3 , M r 117.19, mp − 10 ◦ C,
bp 80 ◦ C (at 0.3 kPa), d 20 20
20 0.9401, nD 1.4805,
flash point 98 ◦ C.
N,N
-Bis(3-aminopropyl)-1,2-diami-
noethane [79554-59-9], N,N
-bis(3-ami-
nopropyl)ethylenediamine, C8 H22 N4 , M r
174.3, mp −1.5 ◦ C, bp 170 ◦ C (at 0.3 kPa).
H2 N(CH2 )3 NHCH2 CH2 NH(CH2 )3 NH2
8.2.2. Chemical Properties
Because they possess terminal primary amino
groups, condensates of 1,2-diaminoethane re-
act very much like 1,2-diaminoethane itself.
The higher condensates of 1,3-diaminopro-
pane have similar properties. Dibasic acids re-
act with oligoamines and polyamines to give
polyamides [264]. A number of urea compounds
can be obtained from oligoamines, e.g., diethyl-
enetriamine, or from polyamines [265]. These
amines react with aliphatic dihalides to give
water-soluble cationic products [266] and with
epichlorohydrin to give anionic polymers [267].
In a manner similar to diaminoethane,
diethylenetriamine reacts with formalde-
hyde and sodium cyanide to give dieth-
ylenetriaminepentaacetic acid, which also
has complex-forming properties. Diethyl-
enetriamine undergoes also a smooth cyanoethy-
lation reaction [235]. The oligoamines react
directly with formaldehyde to give permethyl-
ated products. At elevated temperatures, dieth-
ylenetriamine can be cyclized to piperazine; if
the temperature is about 400 ◦ C, the cyclization
reaction gives pyrazine directly [268].
Amines, Aliphatic 39
8.2.3. Production, Analysis, and Uses
Diethylenetriamine is obtained as a byproduct
in the synthesis of 1,2-diaminoethane from di-
chloroethane (ethylene dichloride, EDC), ethy-
lene oxide, or ethanolamine and ammonia.
Triethylenetetramine, tetraethylenepentamine,
and pentaethylenehexamine are other byprod-
ucts from the EDC process for 1,2-diami-
noethane. More selective production methods
have been described as well, in particular for
DETA, mostly starting with EDA [269].
A number of polyamines are obtained by cya-
noethylation of diaminoethane or a diaminopro-
pane with acrylonitrile, followed by hydrogena-
tion of the product [133]. For instance, dipro-
pylenetriamine is produced as byproduct by hy-
drogenation of the addition product of ammonia
and acrylonitrile [256]; it is used as curing agent
for epoxy resins. N-Methyldipropylenetriamine
is obtained from methylamine and acrylonitrile.
The regulations governing storage and trans-
portation of the oligoamines and polyamines are
the same as those for 1,2-diaminoethane. For
storage of DETA, TETA, and TEPA, plastic-
lined, stainless steel or aluminum containers
are best suited. Carbon steel leads to iron con-
tamination. A nitrogen atmosphere without car-
bon dioxide is necessary for DETA. TETA and
TEPA are sometimes stored under air, but nitro-
gen is superior. Purity is determined preferably
by titration, and analysis is performed by frac-
tional distillation. The oligoamines, e.g., dieth-
ylenetriamine, can be also analyzed by gas chro-
matography, but this method is unsuccessful for
the higher polyamines, owing to their low vapor
pressures.
Many uses of the higher acyclic ethyl-
eneamines are similar to those of EDA itself,
the most important being lubricant oil addi-
tives, polyamide resins, epoxy curing agents,
surfactants, and oil field chemicals [231]. Poly-
isobutenylsuccinimides derived from TETA,
TEPA, or PEHA are important motor oil addi-
tives. Polyamide resins produced from DETA
or TETA with adipic acid are treated with
epichlorohydrin and used as wet-strength addi-
tives in paper manufacture. Polyamine-modified
urea – formaldehyde resins are also used as wet-
strength additives for cellulose fibers. DETA and
40 Amines, Aliphatic
TETA or their ethoxylation products are used
as curing agents for epoxy resins. Polyamine
amides possessing terminal primary amino
groups, which are prepared from fatty acids and
polyamines, serve the same purpose.
Amidoamines obtained from the reaction
of a fatty acid and a polyamine, in particu-
lar DMAPA and DETA, have similar uses to
the more expensive fatty amines, e.g., as as-
phalt emulsifiers, flotation agents, and corro-
sion inhibitors. If the solid amidoamines are
further heated to 200 – 240 ◦ C, cyclization to
imidazoline derivatives is induced. Since these
are liquids they posses handling advantages
over the amidoamines; the uses are similar,
and the polyamines mostly used for produc-
tion are DETA and TETA. Polyamine deriva-
tives are also used for textile finishing. The
most important DETA applications are chelat-
ing agents (diethylenetrinitrilopentaacetic acid)
and wet-strength paper additives. The latter ap-
plication is increasing since the paper industry is
replacing melamine – formaldehyde resins with
polyamide – epichlorohydrin resins which oper-
ate under neutral pH conditions.
9. Chiral Amines
With the trend in modern pharmaceutical and
agricultural chemistry towards enantiomerically
pure compounds, amines, being important in-
termediates in both areas, came into demand in
their chiral forms. Some can be taken from the
chiral pool and others made from it, but a grow-
ing proportion of the market for these speciali-
ties is being synthesized. Although enantiomeric
syntheses or resolutions are sometimes available
[270], they tend to use very expensive reagents,
so that enzyme-catalyzed processes offer a sig-
nificant economic advantage. Enzymatic resolu-
tion of a racemic mixture affords a pure enan-
tiomer, albeit with loss of the other enantiomer.
Both enantiomers are obtained in pure form by
enantioselective acylation, after which the (R)-
amide and the unchanged (S)-amine are sepa-
rated by simple distillation [271], [272]. For-
mation of diastereomeric salts by neutralizing a
racemic amine with an optically active acid and
subsequent fractional crystallization can also be
used for optical resolution [273].
The chiral amines can be directly incor-
porated in pharmaceuticals or used as chi-
ral auxilaries in synthesis. For instance, (S)-1-
phenylethylamine has been used for the optical
resolution of the analgesic Naproxen [274].
10. Toxicology and Occupational
Health
10.1. General Aspects
The aliphatic amines are highly irritating or cor-
rosive. In their nonprotonated form they are
lipid soluble and therefore penetrate rapidly into
the lower layers of the exposed tissue. Even in
low concentration the vapors cause swelling and
damage in the mucous membranes of the eye and
the respiratory tract.
Acute Toxicity and Local Effects. Gener-
ally, the LD50 (rat, oral or dermal) is on the order
of 100 – 1.000 mg/kg [275]. The symptoms are
caused mainly by high penetrability, corrosion,
alkalosis, and, in some cases, by functional in-
terference with nerve-impulse conduction. The
LD50 values of the hydrochlorides are usually
higher because they do not cause corrosion and
alkalosis: 1600 – 3200 mg/kg (rat, oral) [275].
Acute toxic values, local effects on exposed skin
and eyes, and occupational exposure limits in
Germany [276] and the United States [277] are
compiled in Table 7.
Irritation and corrosion of the skin and mu-
cous membranes were observed frequently in
humans [275], [316], also on exposure to the
vapor [317]. Accidental inhalation of large
amounts can cause headache, nausea, excitation,
and short convulsions [275]. Some aliphatic
amines, especially di- and polyamines, can cause
sensitization of the skin and the respiratory tract
(allergies) [275], [318].
β-Chloroalkylamines have an alkylating po-
tential in addition to their corrosiveness. There-
fore, they are suspected carcinogens.
Systemic Toxicity. In neutral media the
amines are almost completely protonated to the
ammonium compounds. Therefore, interaction
with the cation channels of the nerve-cell mem-
branes is possible. This may result in a change
of permeability for physiologically important
Table 7. Survey of acute toxicological data and occupational exposure limits of aliphatic amines

d
Acute toxicological data Occup. exposure limits [276], [277]
a b 3 c 3
Substance CAS no. LD50 mg/kg Source LC50 (inhal.) g/m Source Local irritation Source MAK (1998), mL/m TLV (1997), mL/m3

Ethylamine [75-04-7] 400 – 800 (o, rt) [278], [279], [280] 12.6 (4 h, [281] c [282] 10 10
20 – 22 ◦ C, rt)
Diethylamine [109-89-7] 450 – 650 (o, rt, ms) [282], [283] 12.1 (4 h, [283], [284] c [283], [285], 5 5
20 – 22 ◦ C, rt) [286]
580 – 820 (d, rbt) [287], [288]
Triethylamine [204-44-8] 460 – 590 (o, rt, ms) [283], [288], [289], 10.9 (4 h) [291] c [292], [293] 1 1
[282], [290]
Dipropylamine [142-84-7] 200 – 690 (o, rt) [294], [282] ca. 4.2 (4 h) [294] c [295] n.e. n.e.
925 (d, rbt)
Isopropylamine [75-31-0] 120 – 820 (o, rt) [283], [296], [281] > 9.8 to < 19.6 [283], [296] c [283], [297] 5 5
(4 h)
Cyclohexylamine [108-91-8] 710 (o, rt) [298] > 16 (4 h) [299] c [275] 10 10
320 (d, rbt)
4,4’-Diaminodicy- [1761-71-3] 300 – 1000 (o, rt, [281], [300], [301] - c [281], [300], n.e. n.e.
clohexylmethane ms, rbt) [302]
Piperazine [110-85-0] ca. 2200 (o, rt) [281] no mortality (8 h, [281] c [281] n.e. 5 mg/m3 (as HCl)
satur.)
1-(2- [140-31-8] 1500 – 2100 (o, rt) [281], [294] no mortality (8 h, [281] c [281], [294] n.e. n.e.
Aminoethyl)pipera- satur.)
zine ca. 870 (d, rbt)
Pyrrolidine [123-75-1] 300 – 450 (o, rt) [303] > 4.5 – 11.7 (4 h, [281] c [304], [305] n.e. n.e.
rt)
5.9 (o, rt); 1.3 (2 h, [306]
ms)
Ethylenediamine [107-15-3] ca. 700 – 1400 (o, [275], [281] > 5 (6 h) [281] c [275], [281] 10 10
rt)
3-Aminopropyl [109-55-7] 930 – 1800 (o, rt) [307] > 4.3 (4 h) [281] c [281] n.e. n.e.
dimethylamine (irritating)
Diethylenetriamine [111-40-0] ≥ 1080 (o, rt) [275], [308], [281] no mortality (8 h, [281], [309] c [281] n.e. 1
satur.)
ca. 700 – 1000 (d, [309]
rbt)
Triethyl- [112-24-3] ca. 2800 – 4940 (o, [298], [310] no mortality (8 h, [310] c [310] n.e. n.e.
enetetramine rt) satur.)
550 – 820 (d, rbt)
Hexamethylene [111-49-9] ca. 350 (o, rt) [281] - - c [281] n.e. n.e.
imine
Amines, Aliphatic

Hexamethylene [100-97-0] 9200 (o, rt) [311] - - no, weak [312] n.e. n.e.
tetramine
1850 (o, ms)
Morpholine [110-91-8] 1050 – 1600 (o, rt) [313], [314] - - c [313], [314] 20 20
ca. 500 – 900 (o, [315] [315]
ms)
41

a
rt = rat, ms = mouse, rbt = rabbit, o = oral, d = dermal. b satur. = saturated atmosphere, rt = room temperature. c c = corrosive. d n.e. = not established
42 Amines, Aliphatic
cations and thus in inhibition of impulse con-
duction along the nerve fibers. The essential
structural element of most local anesthetics is
a tertiary amino group. If significant amounts of
these substances are present in the blood, effects
adverse to the impulse conduction of the heart
and especially to the inhibitory neurons of the
CNS result. The clinical symptoms range from
excitation to clonic convulsions. Consequently,
excitation of the CNS with increased blood pres-
sure and short spasms were observed along with
irritation and injury to the respiratory tract on ac-
cidental inhalation of large amounts of aliphatic
amines.
Long-chain mono- and dialkylamines are
potential histamine liberators and may pro-
duce reddening and edema of the skin
and mucous membranes, itching, decreased
blood pressure, tachycardia, and bronchio-
constriction [275], [319]; the maximum
effect occurs with C10 monoamines and
C14 diamines. Certain aliphatic di- and
polyamines, such as putrescine [110-60-1]
(H2 N(CH2 )4 NH2 ), spermidine [124-20-9]
(H2 N(CH2 )4 NH(CH2 )3 NH2 ), and spermine
[71-44-3] (H2 N(CH2 )3 NH(CH2 )4 NH(CH2 )3 -
NH2 ), are found characteristically in prolifer-
ating cells and are formed under the influence
of hormones, natural growth stimuli, specific
tumor promoters, and other factors. Their phys-
iological action is apparently involved in cell
division and tissue proliferation [320].
Metabolism. In many cases, little is known
about the metabolism of alkylamines. Gener-
ally, once absorbed, alkylamines do not accumu-
late and are rapidly released from the organism,
mostly into the urine, either unchanged (e.g.,
diethylamine, cyclohexylamine) or metaboli-
cally converted. Reactions catalyzed by the cy-
tochrome P450 system include the oxidative
deamination of primary alkylamines and N-
dealkylation of secondary and tertiary amines
[321]. This enzyme system competes with an un-
specific flavin-containing monooxygenase that
produces N-oxides from tertiary amines and
hydroxylamines from secondary amines. Fur-
thermore, N-methyltransferases may alkylate
mono-, di-, and trialkylamines [321]. In ad-
dition, by monoamine oxidase, primary, sec-
ondary, and tertiary amines can be oxidatively
dealkylated stepwise to aldehydes (or carboxylic
acids), ammonia, and hydrogen peroxide [321].
The oxidation rate increases with increasing
chain length; methylamine is not transformed by
monoamine oxidase [322], [323]. Short-chain
mono- and diamines are also oxidized by di-
amine oxidase (histaminase); those most readily
oxidized are 1,4-butanediamine and the C5 – C6
monoamines.
Secondary amines (including those with
cyclic structures), and to some extent tertiary
amines, can be chemically transformed into car-
cinogenic N-nitrosodialkylamines in the pres-
ence of nitrites or nitrates under reducing con-
ditions.
10.2. Toxicology of Specific Amines
10.2.1. Alkylamines, Cyclic Amines, and
Polyamines
Ethylamine [75-04-7], alkaline liquid, in
neat form gaseous at room temperature, is read-
ily absorbed through the skin and respiratory
tract [282], but easily excreted in the urine after
partial metabolism [324]. Exposure to the vapor
may transiently impair vision in humans (“blue
haze”) [325]. The odor threshold in air is ca.
0.027 – 0.27 mL/m3 (≤ 0.5 mg/m3 ) [326], [327].
In rabbits, inhalation of 50 mL/m3 (94 mg/m3 )
for 6 weeks resulted in local and systemic or-
gan lesions (corneal erosions and edemas, pneu-
monia, peribronchitis, focal muscular degener-
ation of the heart) [285]. Transient physiologi-
cal effects were seen after prolonged exposure
of rats to vapors (0.06 – 3.69 mg/m3 , 90 d) with
no effects at 0.015 mg/m3 . At the highest con-
centration, morphological changes in the lung
and cerebral neurons apparently were reversible
[326].
Diethylamine [109-89-7], alkaline liquid,
once absorbed, is rapidly excreted unchanged
in the urine [328]. Exposure to low vapor con-
centrations are reported to transiently impair
vision in humans (reduction of sensitivity to
light): no-effect threshold 0.022 – 0.028 mL/m3
(≤ 0.08 mg/m3 ) [326], [329]. The odor thresh-
old in air is ca. 0.02 – 0.3 mL/m3 (≤ 0.9 mg/m3 )
[329], [330]. Transient physiological effects in
rats after 90-d exposure to vapors were re-
ported to already be visible at 0.37 – 4.19 mg/m3

with no effects at 0.05 mg/m3 , but with mor-
phological, apparently reversible changes in the
lung and cerebral neurons at the highest con-
centration [326]. On the other hand, 50 mL/m3
(150 mg/m3 ) was the lowest concentration to
show mild, but significant effects in the lung and
liver of rabbits on prolonged inhalation [285].
There were no visible signs of toxicity follow-
ing exposure of rats to 25 mL/m3 (75 mg/m3 )
for 120 d, but a moderate, bronchiolar hyperpla-
sia of lymphoid cells [286]. It was assumed that
diethylamine may exert a certain neurotoxic ef-
fect, which, however, was not confirmed by oth-
ers [286].
Under experimental conditions, no sensi-
tizing potential was observed [331]. Diethy-
lamine itself showed no mutagenic potential. Al-
though the carcinogenic N-nitrosodiethylamine
is formed in the presence of nitrite, combined ad-
ministration in the feed and drinking water gave
no evidence of increased tumor incidence in a
lifelong study with rats [332].
Triethylamine 204-44-8, oily, alkaline liq-
uid, once absorbed, is rapidly excreted un-
changed or as its N-oxide in the urine [333],
[334]. Exposure to the vapor may transiently im-
pair vision in humans (“blue haze”): concentra-
tions without visual effect are in the range of
1.4 – 2.7 mL/m3 [293], [335]. Its exciting effect
on the CNS is more pronounced than that ex-
erted by the other lower ethyl homologues; ef-
fects on parasympathetically controlled muscu-
lature and inhibition of nerve pulse transmission
in sypmpathetic ganglia can be explained by in-
hibition of cerebral monoamine oxidase [292],
[335]; however, triethylamine does not inhibit
neuromuscular impulse transmission [292]. Un-
der experimental conditions and in humans, no
sensitizing potential was observed [335]. The
odor threshold in air is reported from < 0.09 to
1.4 mL/m3 (≥ 0.33 mg/m3 ) [326], [335].
Dipropylamine [142-84-7], alkaline liquid,
may cause headache, nausea, faintness, and lung
edema on inhalation. The odor threshold in air
is 0.02 – 0.1 mL/m3 (≤ 0.4 mg/m3 ) [295].
Isopropylamine [75-31-0], alkaline liquid:
Signs of respiratory irritation may occur at
about 24 mg/m3 and above (≥ 10 mL/m3 ) in hu-
mans [297]. In rats, a NOAEL was defined as
Amines, Aliphatic 43
100 mg/m3 for prolonged inhalation (1 month)
[336]. The substance was void of any terato-
genic effects after exposure of pregnant rats
to up to 1000 mg/m3 [337]. An odor threshold
in air is reported to be between 5 – 10 mL/m3
(≤ 24 mg/m3 ) [297].
Cyclohexylamine [108-91-8], alkaline liq-
uid, is readily absorbed by the oral and respira-
tory route, but only slowly through the skin, and
is rapidly excreted in the urine almost unchanged
[338]. It has a strong fishlike odor (odor thresh-
old ca. 2.5 mL/m3 = 10.4 mg/m3 ) [299], [338].
First signs of a sympathomimetic effect in hu-
mans (elevation of the arterial blood pressure)
are reported at a daily dose of 5 mg/kg [338].
Cyclohexylamine has been studied inten-
sively because it is a metabolite of the sweet-
ener saccharin. Intake of either up to 300 mg/kg
of the HCl salt daily in the feed of rats for two
years and lifelong [339–341] or of up to about
750 mg/kg daily in the feed of mice (0.3 and
0.5 % HCl salt) for ≥ 80 weeks [342], [343] did
not lead to higher incidence of tumors. Acceler-
ated basal metabolic rate and reduced spermato-
genesis were observed in rats after 90 d [344] at
daily doses of 2000 and 6000 ppm (HCl salt),
but no such symptoms were evident at 600 ppm
(ca. 20 mg amine per kilogram) daily intake. In
other long-term feeding studies, no convincing
evidence of toxicity was apparent at doses of 5
to ca. 20 mg kg−1 d−1 [299].
In a multigeneration study (two years,
150 mg/kg daily of cyclohexylammonium chlo-
ride), the fertility of rats was not affected ad-
versely in spite of slight atrophy of the testicles
[341]. Based on these and other results [345],
[346], it is concluded that no mutagenicity, car-
cinogenicity, or teratogenicity is suspected for
cyclohexylamine [347], [338].
4,4
-Diaminodicyclohexylmethane
[1761-71-3], alkaline solid, was shown to have
skin-sensitizing potential [302], [348]. On re-
sorption, predominant clinical signs of intoxi-
cation were hyperexcitability, excessive saliva-
tion, and convulsions in animals; repeated oral
dosing (50 – 100 mg kg−1 d−1 in rats and mice
for 10 and 16 d, respectively, 50 mg/kg in dogs
for up to 82 weeks) resulted in gastrointesti-
nal hemorrhagic inflammations, nephritis, and
fatty changes to the liver [281], [300], [348]. No
44 Amines, Aliphatic
changes in methemoglobin or in other hemato-
logical parameters were induced in cats on re-
peated doses of 50 and 100 mg kg−1 d−1 , given
twice per week over 2 months [281], [301].
Several in vitro [281], [349] and in vivo muta-
genicity studies [281], [301] gave no evidence
of a mutagenic or clastogenic potential.
Piperazine [110-85-0], alkaline solid, is al-
most completely absorbed from the intestinal
tract on oral ingestion. Acute intoxications occa-
sionally follow therapeutic treatment of animals
with piperazine salts (as anthelmintics), and
symptoms include adverse neurologic events
such as ataxia, muscle tremor, muscular weak-
ness, and vomiting [350]. In humans, headache,
nausea, coordination disorders, and exanthems
have been observed occasionally during re-
peated intake of piperazine salts in daily doses of
30 – 75 mg/kg [351]. Apparently, sensitizations
of the skin and also the respiratory tract can oc-
cur; these are also caused by the dihydrochloride
[352–354]. Based on several observations, es-
pecially in workers in Germany, piperazine was
included in the list of allergens which are also
suspected of inducing respiratory sensitization,
but no MAK value was established [355], [356].
Although experimental data suggest that
piperazine itself is unlikely to be mutagenic and
carcinogenic, there is strong evidence that the
combination with nitrite produces malignant tu-
mors in animals: for reviews, see [357], [358].
1-(2-Aminoethyl)piperazine [140-31-8],
alkaline liquid: Sensitization was observed in
animal experiments [359].
Pyrrolidine [123-75-1], alkaline liquid: As
with other amines, sympathomimetic action is
observed and results in increased blood pressure
and a tendency to convulsions [304]. In an in-
halation study on male rats [360], exposure to
2.6 mg/m3 for 6 months caused increasing ex-
citation of the nervous system, inhibition of di-
uresis and spermatogenesis without impairment
of spermatozoon mobility and fertility; however,
morphological alterations were evident from an
increase in the number of tubuli seminiferi with
desquamation of the seminiferous epithelium.
Experimental data suggest that pyrrolidine itself
is unlikely to be mutagenic [303] and carcino-
genic: in limited long-term studies in rats and
mice in the presence of nitrite in drinking water
to favor nitrosation, there was no evidence of a
carcinogenic effect [361], [362].
Ethylenediamine [107-15-3], alkaline liq-
uid: Dermatitis related to primary irritation and
also to sensitization occurs frequently [275].
Sensitization of the mucous membranes of
the respiratory tract with asthmatic symptoms
has also been described [363], [364]. After
oral administration in rats and mice at up to
1000 mg kg−1 d−1 of the dihydrochloride salt,
no teratogenic effects were produced [365–
367], and there was no evidence for an im-
pairment of reproduction in a two-generation
study [365]: 250 mg kg−1 d−1 dihydrochloride
salt (ca. 112 mg kg−1 d−1 base) can be consid-
ered the NOAEL [368]. Several in vitro tests
gave no evidence for a mutagenic potential
[369–371].
3-Dimethylamino-1-propylamine [109-55-7],
alkaline liquid: There are indications of contact
and possibly respiratory allergy in relation to
occupational exposure [307]. Less than 0.9 ppm
of 3-dimethylaminopropylamine in the work-
place air may adversely affect respiratory func-
tion [372]. The skin-sensitizing potential was
verified in an animal study. In an oral 28-d
study with rats (gavage, 7 times per week.),
clinical symptoms including pulmonary and
cardiac failure were noted at 250 mg kg−1 d−1 ,
but no treatment-related effects at a level of
50 mg kg−1 d−1 [307].
Diethylenetriamine [111-40-0], alkaline
liquid: sensitization of the skin and possibly
respiratory tract occurs frequently [275], [309].
Experience from occupational medicine sug-
gests that the latter has to be considered the
main adverse effect that may occur in humans
[309]. Following oral administration, diethyl-
enetriamine is readily absorbed and rapidly ex-
creted, mainly via the urine and feces [309].
In rats, no histopathological changes were ob-
served after 90-d feeding up to the highest di-
etary level of 15 g/kg (ca. 1200 mg kg−1 d−1 ),
[373] while in cats and rabbits, repeated oral
doses of ca. 200 mg kg−1 d−1 and above as base
or HCl salt resulted in severe gastritis, lung
edema or pneumonia, and kidney lesions [281],
[309].

Triethylenetetramine [112-24-3], alkaline
liquid: may induce lung edema on inhalation of
its vapors. The compound is also an effective
skin sensitizer [275]. Following repeated dosing
(ca. 50 mg each, 17 – 55 times) onto the skin of
pregnant and nonpregnant guinea pigs, signifi-
cant amounts were absorbed by the strongly irri-
tated skin, leading to toxic effects in the kidneys,
liver, brain, and placenta and causing abortion
[310], [374], [375]. Triethylenetetramine proved
to be a mutagen in vitro [376] but not in vivo
[310].
Hexamethyleneimine, hexahydro-1H-
azepine [111-49-9], for acute toxicity data: see
Table 7.
Hexamethylenetetramine [100-97-0],
HMTA, urotropin, is rapidly absorbed from
the gastrointestinal tract, and the majority is
excreted unchanged in the urine [311].
Irritation and Sensitization. In animals,
HMTA exhibited a skin-sensitizing potential
[377]. Several reports in industry [378–380]
suggest an association between HMTA expo-
sure and the increased occurrence of irritative,
allergic events among workers: this was often
encountered with hot processing in the rub-
ber and foundry industries. Sensitized persons
frequently showed positive responses on patch
testing, although the causative agent remained
obscure [379], [381]. They can suffer from asth-
matic or asthmalike attacks on inhaling HMTA
[382].
Systemic Toxicity. Experience from thera-
peutic use in the past, especially for the pre-
vention of recurrent urinary tract infections in
human patients, support the low toxicity on pro-
longed oral ingestion of up to 4 g/d per indi-
vidual. Some 1 – 7 % of the patients experi-
enced untoward events such as gastrointesti-
nal intolerance (nausea, vomiting, abdominal
cramps) and unspecific skin reactions (pruri-
tus, urticaria, erythematous eruptions) [383].
Chronic animal studies with HMTA adminis-
tered in the diet or drinking water did not reveal
any evidence of a carcinogenic potential and ac-
count for a high chronic NOAEL of more than
1000 mg kg−1 d−1 [384–386].
Mutagenicity. The majority of studies failed
to reveal any in vitro or in vivo genotoxic activ-
ity. At cytotoxic or sublethal doses (≤ 10 g/kg)
Amines, Aliphatic 45
[311], a weak mutagenic effect was found in
male mice [387], but there was no positive re-
sponse at up to 1500 mg/kg [388], while a cyto-
genetic assay after single oral and repeated doses
of one-third of the LD50 in mice was clearly
negative [389]. Furthermore, the compound is
described as mutagenic for larvae of Drosophila
(dose not specified) [382].
Teratogenicity and Reproduction. In several
multigeneration studies on rats, no treatment-
related abnormalities or developmental defects
in the offspring or reproductive defects in the
parental generation were seen following high
oral doses of up to more than 1500 mg kg−1 d−1
[311], [386]. In a study with female beagles
(600 and 1250 ppm of HMTA in the feed
(15 – 31 mg kg−1 d−1 ), from the 4th to 56th day
after mating), slight embryotoxic effects were
found at higher doses but no malformations
[390].
Morpholine [110-91-8], alkaline liquid, is
well absorbed by the oral, dermal, and inhalation
route, but rapidly excreted, mainly unchanged,
in the urine. Experimental evidence suggests that
morpholine is unlikely to induce skin sensitiza-
tion [314], [391].
Common signs of toxicity following repeated
dosing are local irritation and inflammations
of the stomach, respiratory tract, and eyes, as
well as systemic effects primarily on the liver
and kidneys. In rats, exposure to 250 mL/m3
(890 mg kg−1 d−1 , 6 h/d, 5 d/week, 90 d) [392]
and to up to 150 mL/m3 (543 mg/m3 , 6 h/d,
5 d/week, 104 weeks) [393], [313] produced
focal erosions and squamous-cell metaplasia
of the nasal cavities and turbinates and ocu-
lar irritation, but no hematological or organ ef-
fects; at 90 mg/m3 (25 mL/m3 , subchronic) and
36 mg/m3 (10 mL/m3 , chronic), no treatment-
related effects at all were identified. These data
may be taken as NOAELs, although one ear-
lier Russian publication [394] claimed that some
adverse effects were conspicuous on the spleen
and in the red and white blood counts in rats
and guinea pigs after four-month inhalation of
70 mg/m3 and less (see also [313]).
After oral application, no toxic signs were
found in mice receiving 70 – 140 mg kg−1 d−1
base in drinking water as morpholine oleate for
90 days [396].
46 Amines, Aliphatic
In a subacute feeding test (four weeks, rats), a
daily dose of 323 mg/kg led to increased weight
of the suprarenal gland accompanied by retarded
development of body weight; daily doses of 27
and 93 mg/kg were without effect [303], [313].
In isolated cases, morpholine showed a weak
mutagenic acticity; however, most of the ex-
perimental in vitro and in vivo data confirmed
that purified morpholine did not give any ev-
idence of a mutagenic potential [281], [313],
[314], [395]. Furthermore, longterm studies (in
rats and hamsters with feed containing 0.1 %
base [396], in mice with drinking water contain-
ing up to 0.24 % base [397], and inhalation of
up to 530 mg/m3 in rats [398]) failed to reveal
an inherent cancerogenic potential of morpho-
line [313], [314]. However, there is a possibility
of nitrosation in the presence of traces of ni-
trous acid or nitrogen oxides [303], [399]: N-
nitrosomorpholine is a potent carcinogen [313],
[395].
10.2.2. Fatty Amines
Skin and Eye Irritation. Fatty amines are lo-
cal irritants of eyes, skin, and mucous mem-
branes. Both the primary amines and the pro-
panediamines are generally regarded as severely
irritating and possibly corrosive. Even dilute so-
lutions (5 %) of fatty amines may cause irre-
versible damage to the eye; cornea inflamma-
tion caused by 1 % solutions heals without per-
manent effects. Concentrated solutions of salts
of fatty amines and quaternary ammonium com-
pounds are almost neutral but they have an irri-
tating potential similar to the free bases. Ethoxy-
lation of fatty amines reduces the irritating ef-
fects.
A small number of workers became sensi-
tized to selected fatty amines. Symptoms in-
cluded skin rash, dermatitis, eye swelling, and
a sensation of the skin, described as “crawl-
ing”. Appropriate skin and eye protection must
be worn when handling fatty amines.
Inhalation. At ambient temperatures only
the short-chain amines, especially if branched,
have sufficient vapor pressure to present
any hazard by inhalation. The LC100 of 2-
ethylhexylamine is 1.3 mg/L (rat, 4 h) [400],
whereas exposure to air saturated with N,N-di-
(tridecyl)tridecanamine for eight hours resulted
in no deaths [401].
Acute and Chronic Oral Toxicity. None of
the fatty amines are highly toxic by ingestion.
The more corrosive ones, such as coco-1,3-
diaminopropane, have oral LD50 values as low
as 147 mg/kg, whereas compounds of higher
molecular weight, such as di(hydrogenated-
tallow) dimethylammonium chloride, are rel-
atively nontoxic, with oral LD50 values of
7000 mg/kg and higher [402].
Chronic feeding studies have shown that rats
fed with 500 ppm of 1-octadecylamine in the
diet for two years showed no observable ad-
verse health effects, whereas dogs fed the same
level for twelve months showed mainly non-
pathologic irritant effects on the mucosa of the
gastrointestinal tract [403].
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G. R. Wilder); US 3 196 179, 1962 (R. M.
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et al.).
54. BASF, DE 1 543 377, 1966 (K. Adam, E.
Haarer); Inst. Cercetari, RO 63 243, 1975 (E.
Dutkay).
55. Halcon Internat., NL 6 401 010, 1964.
56. Inst. Français du Pétrole, GB 1 050 589, 1965
(B. Choffe, R. Stern); Quaker Oats,
FR 1 446 554, 1965 (A. P. Dunlop, D. G.
Manly); Mitsubishi Chem. Ind., JP 4 332, 1968
(R. Matsura, T. Otaki); Toa Gosei Chem. Ind.,
JP 19 897, 1970 (T. Kawaguchi, T. Matsubara);
JP 19 898, 1970 (T. Kawaguchi, T. Matsubara).
57. BASF, DE 3 045 719, 1980 (N. Goetz, P.
Jacobs, L. Hupfer, H. Trussaint, W. Reiss).
58. Dearborn Chem., US 2 956 889, 1956 (W. L.
Denman); Chem. Eng. (N.Y.) 62 (1955) no. 4,
140.
59. Monsanto, US 2 191 657, 1937 (M. W.
Harman).
60. US Rubber, GB 898 319, 1962.
61. Monsanto, US 2 731 338, 1951 (E. A. Fike,
H. L. Morrill).
62. Esso, GB 793 737, 1958 (J. Scott, R. J.
Westland).
63. BASF, DE 1 921 467, 1970 (W. Corr, W.
Friedrichsen).
64. W. S. Emerson, Org. React. (N.Y.) 4 (1948)
218.
48 Amines, Aliphatic
65. Shell Development, US 2 580 284, 1949 (T. J.
Deahl, F. H. Stross).
66. Goodyear, US 3 086 018, 1957 (A. F.
Hardman); Monsanto, US 2 930 777, 1955
(H. M. Leeper).
67. DuPont, US 3 376 341, 1964 (C. R. Bauer).
BASF, DE 851 189, 1944 (O. Stichnoth).
68. W. S. Emerson, Org. React. (N.Y.) 4 (1948)
174. BASF, DE 1 543 354, 1966 (H. Corr, E.
Haarer).
69. Bayer, DE 826 641, 1949 (E. Windemuth).
70. Bayer, DE 962 113, 1953 (F. Brochhagen,
A. Höchtlen).
71. Bayer, DE 946 173, 1953 (W. Bunge, K. H.
Mielke).
72. J. F. Norris, A. E. Bearse, J. Am. Chem. Soc.
62 (1940) 953.
73. BASF, DE 805 518, 1949 (O. Stichnoth).
Ugine Kuhlmann, FR 1 530 477, 1967.
74. Witco Chem., US 3 551 486, 1968 (J. M.
Solomon).
75. Abbott Lab., FR 1 333 693, 1963 (R. M.
Robinson).
76. Dow, US 2 571 016, 1949 (J. Dankert). Abbott
Lab., FR 1 34 3 391, 1963 (R. M. Robinson);
US 3 351 661, 1967 (F. H. Van Munster).
77. I. Garz, K. Schwabe, Werkst. Korros. 14
(1965) 842. Nagynyomasu Kiserleti Intezet,
HU 16 386, 1976 (J. Gemes).
78. R. Johannsen, Farbe Lack 70 (1964) 189.
79. S. Hünig, M. Kiessel, J. Prakt. Chem. 277
(1958) 224.
80. DuPont, DE 1 468 779, 1964 (L. D. Brake).
81. BASF, DE 1 272 919, 1966 (P. Raff, H. G.
Peine).
82. BASF, DE 2 036 502, 1970; DE 2 038 023,
1970 (K. Adam, H. Hoffmann).
83. R. Jacquier, H. Christol, Bull. Soc. Chim. Fr.
1954, 556.
84. L. Ruzicka, M. W. Goldberg, M. Hürbin, Helv.
Chim. Acta 16 (1933) 1339.
85. L. Schuster, Tetrahedron Lett. 1963,
2001. BASF, DE 1 178 846, 1964 (L.
Schuster).
86. BASF, FR 1 468 354, 1966 (K. Adam, E.
Haarer).
87. V. Prelog, M. Fausy El-Neweihy, O. Häfliger,
Helv. Chim. Acta 33 (1950) 365.
88. H. Meister, Justus Liebigs Ann. Chem. 679
(1964) 83.
89. L. Schuster, Tetrahedron Lett. 1963,
2001. BASF, NL 6 408 389, 1965.
90. BASF, FR 1 528 400, 1967.
91. J. M. Patterson, P. Drenchko, J. Org. Chem. 24
(1959) 878.
92. I. G. Farbenind., DE 701 825, 1938 (W.
Reppe).
93. DuPont, US 2 525 584, 1948 (C. A. Bordner).
94. J. Timmermans, J. Chim. Phys. Phys. Chim.
Biol. 34 (1937) 693.
95. S. A. G. Osborn, D. R. Douslin, J. Chem. Eng.
Data 13 (1968) 543.
96. A. G. Cook: Enamines, Marcel Dekker, New
York 1969.
97. I. Szmuszkovicz, Adv. Org. Chem. 4 (1963) 1.
98. K. Blàha, O. Cesvinka, Adv. Heterocycl.
Chem. 6 (1966) 147.
99. G. Laban, R. Bayer, Z. Chem. 8 (1968) 165.
100. K. Smeykal, K. K. Moll, Chem. Tech. (Leipzig)
19 (1967) 92.
101. A. A. Ponomarev, A. S. Ĉegolja, Khim.
Geterotsikl. Soedin. 1966, 239.
102. Celanese, DE 1 802 122, 1968 (D. R. Larkin).
103. Quaker Oats Co., US 3 163 652, 1962 (D. G.
Manly). Inst. of Petrochem. Synth.,
SU 2 478 887, 1977 (A. N. Bashkirov).
104. ICI, GB 971 187, 1962 (C. Gardner, G. A.
Silverstone).
105. Rhône-Poulenc, FR 1 475 961, 1966 (G.
Chichery, P. Perras).
106. ICI, NL 6 605 495, 1966.
107. Ciba, US 2 826 583, 1954 (K. Hoffmann, J.
Heer).
108. Phillips Petroleum, US 2 771 737, 1951 (C. R.
Scott, A. L. Ayers).
109. G. Jones, Org. React. (N.Y.) 15 (1967) 204.
110. A. T. Nielsen, W. J. Honlihan, Org. React.
(N.Y.) 16 (1968) 1.
111. G. B. Bachmann, M. T. Atwood, J. Am. Chem.
Soc. 78 (1956) 484.
112. E. N. Zilbermann, E. D. Skorikowa, Zh.
Obshch. Khim. 23 (1953) 1659.
113. Bayer, DE 738 448, 1941 (H. Raab).
114. BASF, DE 1 138 780, 1960 (A. Palm, H.
Stanger).
115. Artemev, GB 1 570 647, 1980 (D. M. Popov,
E. V. Genkina). BASF, DE 2 837 290, 1978 (W.
Schröder, W. Franzischka). Mitsubishi, JP
82 183 771, 1982.
116. Monsanto, US 3 635 952, 1969 (D. A. Tyssee).
117. Soc. Prod. Chim. Marles Kuhlmann, FR
1 583 461, 1969.
118. Houben-Weyl, vol. 11/1 (1957) 45, 129.
119. Wyandotte, DE 1 049 864, 1957 (W. K.
Langdon, E. Jaul).
120. Goodyear, DE 3 002 342, 1979 (K. J. Frech).
BASF, DE 3 125 662, 1981 (W. Schröder, W.
Lengsfeld, G. Heilen). Jefferson, US
3 155 657, 1961 (W. C. Bedoit).

121. M. F. Obrecht, Effluent Water Treat. J. 4
(1964) 279.
122. Chem. Werke Hüls, BE 642 387, 1964.
123. H. Koppers GmbH, US 3 555 782, 1968 (H.
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124. E. Cinelli, P. L. Girotti, R. Tesei, Hydrocarbon
Process. Pet. Refiner 42 (1963) no. 8, 141.
125. Wyandotte, US 3 167 551, 1961 (E. A.
Weipert). Agency Ind. Sci. Techn.,
JP 80 43 008, 1980 (Y. Sugi).
126. Jefferson, US 3 210 349, 1961 (N. B. Godfrey).
127. BASF, DE 1 793 380, 1968 (E. Fürst, H.
Toussaint).
128. Jefferson, US 3 087 928, 1961 (N. B. Godfrey).
129. Pennsalt Chem., US 3 155 656, 1960 (R. H.
Goshorn, R. Ferren).
130. Jefferson, US 3 151 113, 1962 (P. S. Advani,
G. P. Speranza). ICI, GB 1 106 084, 1964
(L. L. Dufty).
131. BASF, FR 1 575 059, 1968. Union Carbide,
US 3 112 318, 1957 (R. C. Lemmon, R. C.
Myerly).
132. DuPont, US 2 130 948, 1937 (W. H. Carothers).
133. M. M. Epstein, C. W. Hamilton, Mod. Plast.
37 (1960) 142.
134. Eastman Kodak, US 2 950 197, 1960 (C. F. H.
Allen, E. R. Webster). AGFA, DE 1 130 283,
1962 (W. Himmelmann, H. Ulrich).
135. J. R. Lindsay Smith, A. U. Smart, M. V. Twigg,
J. Chem. Soc., Perkin Trans. 2 1992, 939.
136. Air Products and Chemicals, US 4 362 886,
1981 (M. E. Ford, T. A. Johnson).
137. Air Products and Chemicals, US 3 166 558,
1961 (R. L. Mascioli).
138. Houdry Process Corp., US 2 937 176, 1956
(E. C. Herrick).
139. Air Products and Chemicals, EP 69 322, 1981
(J. E. Wells). Chem. Werke Hüls,
DE 1 445 578, 1963 (W. Thomas, H.
Steinbrink, M. zur Hansen). Bayer,
DE 2 846 813, 1978 (L. Imre, W. Horstmann,
H. G. Leopold).
140. Air Products and Chemicals, US 5 741 906,
1996 (J. N. Armor, J. G. Santiesteban, H. Li).
Air Products and Chemicals, EP 842 935, 1996
(J. N. Armor, J. G. Santiesteban, H. Li).
141. Houdry Process Corp., DE 1 120 691, 1958
(M. Orchin).
142. National Starch and Chem. Corp.,
DE 2 040 607, 1970 (H. H. Stockmann).
143. S. S. Chang, E. F. Westrum, J. Phys. Chem. 64
(1960) 1547.
144. A. Chentin, I. P. Mathieu, J. Chem. Phys. 53
(1956) 106.
Amines, Aliphatic 49
145. G. Klipping, I. N. Stranski, Z. Anorg. Allg.
Chem. 297 (1958) 23.
146. VEB Gärungschemie Dessau, DE 1 076 104,
1959 (H. Plischke, W. Zettl). H. Plischke, Z.
Chem. 1 (1961) 217.
147. Stachowski, PL 106 934, 1980. Celanese,
US 2 640 826, 1949 (A. F. Maclean, A. L.
Stautzenberger).
148. Bayer, DE 977 337, 1953 (R. Ludwig, F.
Halle).
149. Montecatini, BE 601 096, 1960. Soc. Belge de
l’Azote et des Prod. Chim., GB 962 925, 1962
(R. Englebert, A. Genkenne, A. Lefebre).
150. F. Meissner, E. Schwiedessen, D. F. Othmer,
Ind. Eng. Chem. 46 (1954) 724.
151. Tenneco, US 3 538 199, 1968 (S. Weiss, D. X.
Klein); BE 743 974, 1969 (S. Weiss).
152. Phillips Petroleum, US 3 547 597, 1967 (G. E.
Hayes).
153. Degussa, DE 1 104 967, 1961 (H. J. Mann).
BASF, US 2 912 435, 1957 (H. Scholz).
154. Degussa, DE 1 085 491, 1959 (A. Lehn).
155. Bayer, FR 895 645, 1962. Food Machinery and
Chem. Corp., US 2 833 656, 1953 (A. F.
Kalmar, H. F. Fitzpatrick).
156. Dow, GB 960 732, 1964; US 3 268 399, 1964
(R. R. Langner); US 3 524 854, 1968 (S. J.
Kuhn).
157. “Armeen Aliphatic Amines”, Armak Product
Data Bulletin 72-8 (1972).
158. Kirk-Othmer, 2nd ed., vol. 2, pp. 130, 132.
159. Melting points were calculated using
references [160][161] , and internal Armak
data converted into a polynomial. Vapor
pressures were correlated in a similar way
using the Antoine equation given in [162]
160. R. R. Dreisbach: “Physical Properties of
Chemical Compounds, III”, Adv. Chem. 1961,
no. 29. 1.
161. Selected Values of Properties of Chemical
Compounds, Thermodynamics Research
Center, Department of Chemistry, Texas A &
M University, June 30, 1971.
162. J. A. Dean: Lange’s Handbook of Chemistry,
11th ed., McGraw-Hill, New York 1973,
p. 10 – 31.
163. G. Tauber, A. May, Tenside Deterg. 19 (1982)
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164. A. Weiss, Tenside Deterg. 19 (1982) no 3, 157.
165. C. W. Hoerr, M. R. McCorkle, A. W. Ralston,
J. Am. Chem. Soc. 65 (1943) 328, 329.
166. Kao Soap Co., JP Kokai 7 616 603, 1976 (U.
Nishimoto, K. Okabe, M. Takaku).
167. Akzona Inc., US 4 237 064, 1980 (R. A. Reck).
50 Amines, Aliphatic
168. H. L. Sanders, J. B. Braunwarth, R. B.
McConnell, R. A. Swenson, J. Am. Oil Chem.
Soc. 46 (1969) no. 3, 167 – 170.
169. Henkel DE 2 117 427, 1972 (G. Demmering).
170. Armour, GB 1 223 730, 1967 (R. A. Reck).
171. Akzona Inc., US 4 368 127, 1983 (J. M.
Richmond).
172. Union Carbide, US 3 636 114, 1972 (E.
Tobler, D. J. Foster).
173. Armour, US 3 222 402, 1965 (M. C.
Cooperman).
174. R. S. Egly, Nitroparaffin Symposium,
Commercial Solvents Corp., Chicago, Jan. 25,
1956.
175. Akzona Inc., US 4 334 887, 1982 (D. Frank,
L. D. Metcalfe).
176. Akzona Inc., US 4 357 181, 1982 (D. Frank,
L. D. Metcalfe).
177. S. Billenstein, G. Blaschke, J. Am. Oil Chem.
Soc. 61 (1984) 353.
178. P. Jowett, GB 1 475 689, 1973.
179. W. R. Grace & Co., GB 1 388 053, 1975 (R. A.
Diffenbach).
180. Chemcell, US 3 574 754, 1971 (G. Specken).
181. Hoechst, DE 1 941 290, 1971 (H. Mueller, W.
Kuehn, G. Mueller-Schiedmayer, J. Strauss).
182. Hoechst, DE 1 280 243, 1968 (H. Oberrauch,
W. Froehlich, H. Lewinsky); Chem. Abstr. 70
(1969) 11 108.
183. Archer-Daniels-Midland Co., US 3 264 254,
1966 (E. J. Sawyer).
184. Armour, GB 860 922, 1961 (S. H. Shapiro, F.
Pilch).
185. Lion Fat and Oil, US 4 248 801, 1981 (S.
Tomidokoro, M. Sato, D. Saika).
186. Hoechst, US 3 444 205, 1969 (W. Froehlich, H.
Oberrauch, K. Fischer).
187. Kao Soap Co., JP Kokai 81 152 441, 1981.
188. BASF, DE 2 639 648, 1978 (H. Hoffmann, H.
Mueller, H. Toussaint, A. Wittwer).
189. L. Barrault, Y. Pouilloux, Catal. Today 37
(1997) 137.
190. Archer-Daniels-Midland Co., US 3 223 734,
1965 (H. T. Fallstad, A. E. Rheineck).
191. Gulf Research & Development Co., US
2 953 601, 1960 (A. C. Whitaker).
192. BASF, DE 2 645 712, 1978 (H. Hoffmann, H.
Mueller, H. Toussaint, A. Wittwer);
US 4 207 263, 1980.
193. Japan Catalytic Chem. Ind., JP Kokai
7 424 905, 1974 (H. Koike, N. Kurata, Y.
Okuda).
194. Imperial Chem. Ind., GB 2 048 866, 1979
(C. B. Hanson, G. E. B. Smith).
195. Gulf Research and Development Co., US
4 251 465, 1981 (H. E. Swift, R. A. Innes, P.
Adams).
196. UOP, DE 3 014 455, 1981.
197. Kao Soap Co., US 4 254 060, 1980 (H.
Kimura, K. Matsutani, S. Tsutsumi).
198. Kao Soap Co., US 4 210 605, 1980 (F.
Hoshino, H. Kimura, K. Matsutani).
199. Gulf Research and Development Co., US
3 742 060, 1973 (R. W. Lagally, G. D. Johann).
200. UOP, US 4 250 115, 1981 (T. Imai).
201. Shell Oil Co., US 3 234 283, 1966 (H. V. Finch,
R. E. Meeker).
202. M. R. McCorkle, P. L. Dubrow, B. E. Marsh, J.
Am. Oil Chem. Soc. 45 (1968) 10A.
203. Armour, US 3 338 967, 1966; US 3 530 153,
1966 (R. H. Potts, E. J. Miller, A. Mais).
204. Ethyl Corp., GB 1 115 238, 1968.
205. Texaco Development Corp., US 3 739 027,
1971.
206. Continental Oil Co., US 3 371 118, 1968 (A. J.
Lundeen, K. L. Motz).
207. Hoechst, US 4 234 509, 1980; DE 2 813 294,
1978; DE 2 737 607, 1979 (S. Billenstein, B.
Kukla, H. Stuehler).
208. Henkel, DE 1 288 595, 1969 (H. Rutzen);
US 3 579 585, 1971 (H. Rutzen).
209. SNIA Viscosa, US 4 198 348, 1980 (C. A.
Pauri).
210. C. Jungermann: Cationic Surfactants, Marcel
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211. L. D. Metcalfe, J. Am. Oil Chem. Soc. 56
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212. K. G. van Senden, Recl. Trav. Chim. Pays Bas
84 (1965) 1459.
213. DGF-Einheitsmethoden M-V-6 (57).
214. G. Grossi, J. Gas Chromatogr. 3 (1965) no. 5,
170.
215. L. D. Metcalfe, A. A. Schmitz, J. Gas
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216. L. D. Metcalfe, R. J. Martin, Anal. Chem. 44
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217. R. B. Stage, J. B. Stanley, P. B. Moseley, J. Am.
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218. G. F. Okunev, L. G. Morozova, E. M.
Shmeleva, Zavod. Org. Sint. 2 (1972) 173;
Chem. Abstr. 83 (1975) 178 196 v
219. A. E. Merbach, Mitt. Geb. Lebensmittelunters.
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220. F. Mozayeni, Appl. Spectrosc. 33 (1979) 520.
221. DuPont, US 2 088 325, 1937 (J. E. Kirby).
222. DuPont, US 2 132 902, 1938 (S. Lenhar).
223. L. L. Johnsen, Weeds 13 (1965) 123 – 130.
224. Armour, US 3 246 015, 1966 (H. L.
Lindaberry, W. W. Abramitis).

225. Akzona, US 3 506 433, 1970 (W. W.
Abramitis, R. A. Reck).
226. Sherwin-Williams, US 3 166 469, 1965 (H. A.
Pass, M. S. H. Nurse, B. J. Watt).
227. Armour, US 3 135 656, 1964 (W. W.
Abramitis, R. A. Reck).
228. Armour, US 3 223 517, 1965 (W. W.
Abramitis, R. A. Reck).
229. Kirk-Othmer, 4th ed., 2, 405.
230. R. W. Gallant, Hydrocarbon Process. 48
(1969) 143.
231. Kirk-Othmer, 4th ed., 8, p. 74.
232. I. Flament, M. Stoll, Helv. Chim. Acta 50
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233. N. Puschin, R. Mitič, Justus Liebigs Ann.
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234. Rohm & Haas, US 2 326 643, 1941 (W. F.
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235. H. Bruson, Org. React. (N.Y.) 5 (1949) 79.
236. IG Farbenind., BIOS Final Rep. no. 1154,
no. 5; Toyo Soda, JP 79 26288, 1979 (S.
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237. Simon Carves, GB 1 147 984, 1965 (J. G.
Blears, P. Simpson). Nippon Soda, JP 6325,
1965.
238. Dow, US 2 861 995, 1956 (G. F. Mac Kenzie).
BASF, DE 1 172 268, 1962 (S. Winderl, E.
Haarer). Union Carbide, US 3 112 318, 1957
(R. C. Lemon, R. C. Myerly).
239. Union Carbide, US 5 750 790, 1995 (S. W.
King).
240. Union Carbide, EP 737 514, 1995 (S. W.
King). Union Carbide, JP 08 2997 98, 1995
(S. W. King).
241. Dow, WO 96/38 226, 1995 (D. Chang, F. A.
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242. Eur. Chem. News 20 (1971) no. 495, 16.
243. Rohm & Haas, JP 1909, 1964.
244. Prod. Chim. Pechiney-St. Gobain,
US 3 281 471, 1963 (P. Chassaing, J. Coillard).
245. DuPont, US 2 429 876, 1944 (W. F. Gresham).
246. Monsanto, FR 1 426 289, 1964 (J. R.
Le Blanc).
247. Bayer, FR 1 411 269, 1964 (H. J. Hennig, G.
Braun).
248. Phrix, DE 1 185 331, 1959 (F. Kaiser, P.
Weber).
249. Thiocol Chem., GB 1 038 355, 1964.
250. Polythane, BE 633 253, 1963 (A. D. Schneider,
T. V. Peters).
251. Texas Corp., US 2 696 473, 1951 (S. J. Sokol).
252. Shell Dev., US 2 285 878, 1942 (E. R. White).
253. Chemical Market Reporter, Feb. 16, 1998.
254. Eur. Chem. News, Feb. 9 – 15, 1998.
Amines, Aliphatic 51
255. BASF, FR 1 347 648, 1963 (S. Winderl, E.
Haarer).
256. BASF, DE 1 034 184, 1957 (H. Scholz,
H. Günthert).
257. Houben-Weyl, vol. 11/1 (1957) 272, 565.
258. Houben-Weyl, vol. 11/1 (1957) 606.
259. Houben-Weyl, vol. 11/1 (1957) 92, 95, 558.
Nitto Chemical, JP 79 40524, 1979 (S. Tomita).
260. Houben-Weyl, vol. 11/1 (1957) 558, 567.
261. A. Wingler, Angew. Chem. 61 (1949) 52.
262. Houben-Weyl, vol. 11/1 (1957) 61, 72, 131,
498. E. Buse, Naturw. Rdsch. 50 (1997) 253.
263. Degussa, DE 4 343 890, 1993 (T. Haas, D.
Arntz, D. Most); Degussa, DE 4 343 891, 1993
(T. Haas, D. Arntz, D. Most); Degussa,
DE 195 40 191, 1995 (T. Haas, R. Burmeister,
D. Arntz, K.-L. Weber, M. Berweiler); BASF,
EP 449 089, 1990 (F. Merger, C.-U. Priester, T.
Witzel, G. Koppenhoefer, W. Harder); BASF,
DE 19 507 398, 1995 (G. Voit, T. Witzel, B.
Breitscheidel, W. Harder, H. Luyken, A. Paul,
K.-H. Roß, P. Wahl); BASF, EP 757 980, 1995
(T. Witzel, G. Voit).
264. Cyanamid, US 2 371 104, 1943 (R. H. Kienle).
265. Cyanamid, US 2 554 475, 1947 (T. J. Suen).
266. Talbott Dev. Assoc., US 2 694 633, 1950 (D. K.
Pattiloch).
267. Cyanamid, US 2 469 683, 1945 (J. R. Dudley).
268. Cyanamid, US 2 414 552, 1942 (H. F. Pfann).
269. US 5 410 086, 1991 (L. M. Burgess).
270. X. Verdaguer, U. E. W. Lange, S. L. Buchwald,
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271. Chem. Market Reporter, Dec. 8, 1997, p. 14.
272. Bayer, DE 19 621 686, 1996 (U. Stelzer).
273. Ajinomoto, EP 845 455, 1994 (T. Hijiya, T.
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274. Abermarle Corp., WO 97 47 572, 1996 (R. E.
Young, H. V. Phan, T. Manimarant, R. C.
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275. R. R. Beard, J. T. Noe: “Aliphatic and Alicyclic
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276. Deutsche Forschungsgemeinschaft (ed.):
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277. Am. Conf. of Governmental Industrial
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278. H. F. Smyth et al., Arch. Ind. Hyg. 10 (1954)
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279. G. Dura et al., Arch. Toxicol., Suppl. 8 (1985)
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52 Amines, Aliphatic
280. D. Fasset in C. D. Clayton, F. Clayton (eds.):
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281. BASF Aktiengesellschaft, unpublished results.
282. W. L. Sutton in F. A. Patty (ed.): Industrial
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283. H. F. Smyth et al., Arch. Ind. Hyg. 4 (1951)
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284. BIBRA (The British Industrial Biological
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286. D. W. Lynch et al., Fund. Appl. Toxic. 6
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287. E. Anderson, B. Irvholm, Arbete och Haelsa
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