Aniline 1

Aniline
Thomas Kahl, BASF AG, Ludwigshafen, Germany (Chaps. 1 – 7)
Kai-Wilfrid Schröder, BASF AG, Ludwigshafen, Germany (Chaps. 1 – 7)
F. R. Lawrence, E. I. du Pont de Nemours & Co., Deepwater, New Jersey 08023, United States (Chap. 8)
W. J. Marshall, E. I. du Pont de Nemours & Co., Deepwater, New Jersey 08023, United States (Chap. 8)
Hartmut Höke, Weinheim, Germany (Chaps. 9, 10)
Rudolf Jäckh, BASF AG, Ludwigshafen, Germany (Chaps. 9, 10)

1. Introduction . . . . . . . . . . . . . . 1 6.1. Methylene Diphenylene Iso-

2. Physical and Chemical Properties 1 cyanate (MDI) . . . . . . . . . . . . . 7
3. Production . . . . . . . . . . . . . . . 3 6.2. Rubber Processing Chemicals . . 7
3.1. Raw Materials . . . . . . . . . . . . . 3 6.3. Dyes and Pigments . . . . . . . . . . 8
3.2. Processes . . . . . . . . . . . . . . . . 3 6.4. Agricultural Chemicals . . . . . . . 8
3.2.1. Catalytic Hydrogenation of Ni- 6.5. Pharmaceuticals . . . . . . . . . . . 8
trobenzene . . . . . . . . . . . . . . . . 4 6.6. Cyclohexylamine/Dicyclohexyl-
3.2.1.1. Catalytic Vapor-Phase Hydrogena- amine . . . . . . . . . . . . . . . . . . 8
tion . . . . . . . . . . . . . . . . . . . . 4 6.7. Miscellaneous . . . . . . . . . . . . . 8
3.2.1.2. Catalytic Liquid-Phase Hydrogena-
7. Economic Aspects . . . . . . . . . . 8
tion . . . . . . . . . . . . . . . . . . . . 5
8. Derivatives . . . . . . . . . . . . . . . 9
3.2.2. Reduction of Nitrobenzene with Iron
and Iron Salts . . . . . . . . . . . . . . 5 9. Toxicology . . . . . . . . . . . . . . . 12
3.2.3. Amination of Phenol . . . . . . . . . 6 9.1. Toxicokinetic Properties and
4. Quality Specifications . . . . . . . . 6 Metabolism . . . . . . . . . . . . . . . 12
5. Handling, Storage and Trans- 9.2. Toxicological Properties . . . . . . 13
portation . . . . . . . . . . . . . . . . 6 10. Occupational Health . . . . . . . . 14
6. Uses . . . . . . . . . . . . . . . . . . . 7 11. References . . . . . . . . . . . . . . . 14

1. Introduction cessing chemicals, dyes and pigments, agricul-

tural chemicals and pharmaceuticals.
Aniline is the parent molecule of the family of
aromatic amines (→ Amines, Aromatic). First
isolated in the early 19th century (O. Unver- 2. Physical and Chemical Properties
dorben 1826, F. Runge 1834, C. J. Fritzsche
and N. N. Zinin 1841), the structure of the sub- Physical Properties. Aniline [62-53-3],
stance was finally proven in 1843 by A. W. von C6 H5 NH2 , aminobenzene, benzamine (CAS
Hofmann, who was able to obtain aniline by the name), phenylamine, aminophen when freshly
reduction of nitrobenzene. distilled, is a colorless oily liquid with a char-
The first technically applicable process acteristic sweet aminelike odor. Aniline turns
(Bechamp process, see Chap. 3.2.2) for the pro- to brown on exposure to air and light. Aniline
duction of aniline was developed as early as is partially soluble in water and miscible with
1854. most organic solvents (e.g. ethanol, acetone,
Over the last 145 years aniline has become and benzene). Important physical properties of
one of the hundred most important building aniline are as follows [1]:
blocks in chemistry. Aniline is used as an in-
Molecular mass (M r ) 93.13
termediate in many different fields of applica- Boiling point (101.3 kPa) 184.4 ◦ C
tion as, for example, isocyanates, rubber pro- (4.4 kPa) 92 ◦ C
(1.2 kPa) 71 ◦ C

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

10.1002/14356007.a02 303
2 Aniline

Solidification point − 6.2 ◦ C

Flash point (DIN 51758) 76 ◦ C
Explosion limits
Lower 1.2 vol %
Upper 11.0 vol %
Ignition temperature (DIN 51758) 540 ◦ C
Vapor pressure (20 ◦ C) 0.05 kPa
(100 ◦ C) 7.0 kPa
Saturation concentration (air, 20 ◦ C) 390 mL/m3
(air, 30 ◦ C) 880 mL/m3
Odor threshold 0.5 mL/m3
Density vapor (at bp, air = 1) 3.2
Density liquid (20 ◦ C) 1.022 g/cm3
(60 ◦ C) 0.990 g/cm3
Refractive index n20D 1.5863
Viscosity (20 ◦ C) 4.35 mPa s
◦
(60 C) 1.62 mPa s
Solubility (20 ◦ C)
Aniline in water 3.6 %
Water in aniline 5.5 %
pH value (3.6 g aniline per liter, 20 ◦ C) 8.8
log pow (distrib. coeff. n-octanol/water) 0.91
Specific heat (25 ◦ C) 2.1 Jg−1 K−1
Heat of vaporization (at bp) 478.6 J/g
Heat of combustion 36.4 kJ/g
Critical temperature 425.6 ◦ C
Critical pressure 5.30 MPa
Dielectric constant (25 ◦ C) 6.89

Figure 2. Reactions of the aromatic ring

Chemical Properties. The chemistry of ani-
line is determined by the primary amino group
(Fig. 1) and by the activated benzene nucleus
(Fig. 2) [2].
Figure 1. Reactions of the amino group
The lone electron pair on the nitrogen of
the amino group is partially delocalized to the
aromatic ring system [3]. Therefore aniline is
only a weak base (pK a = 4.60) as compared
with aliphatic amines such as cyclohexylamine
(pK a = 10.64). Nevertheless aniline forms sta-
ble, water-soluble salts with strong mineral acids
(e.g., hydrochloric or sulfuric acid). The forma-
tion of aniline sulfate can be used to protect the
amino group of aniline against oxidation during
subsequent synthesis steps.
Various alkylating agents (like alcohols,
alkylhalides, alkylsulfates, and olefins) alkylate
the amino group to form N-alkyl and N,N-di-
alkylaniline in Lewis acid catalyzed reactions
at elevated temperature and pressure. The re-
action of aniline with chloroform in a caus-
tic potash solution produces phenylisocyanide.
N,N-Diphenylthiourea is the product of the reac-
tion of aniline and carbon disulfide in an alkaline
alcohol solution. A characteristic reaction of pri-
mary aromatic amines like aniline is the forma-
tion of diazonium salts with nitrous acid. Aniline
undergoes condensation reactions with alky-
laldehydes. The most important reaction is the
formation of 4,4 -methylenedianiline (MDA) by
condensation of aniline with formaldehyde in
the presence of hydrochloric acid. Aniline re-
acts with organic acids and acid derivatives to

form amides. Aniline undergoes a variety of ox-
idation reactions, depending on the oxidizing
agent and the conditions. Mononuclear prod-
ucts like p-benzoquinone (MnO2 , H2 SO4 ), bi-
molecular compounds such as azobenzene (air)
or polymeric substances like aniline black (Cu
or V, Na2 Cr2 O7 or NaClO3 ) may be formed (see
Fig. 2).
The aromatic ring of aniline is catalytically
hydrogenated to give cyclohexylamine and/or
dicyclohexylamine at elevated temperature and
pressure, depending on conditions and type of
catalyst. The presence of the amino group acti-
vates the ortho and para positions of the aromatic
ring and, as a result, aniline reacts readily with
electrophilic substances. For example, the bro-
mation of aniline yields 1,3,5-tribromoaniline
under mild conditions. The reaction with sul-
furic acid at high temperature forms almost
exclusively 4-aminobenzene sulfonic acid (4-
sulfanilic acid). Nitration of aniline (after pro-
tecting the amino group against oxidation by the
formation of acetanilide) forms the 4-nitro com-
pound. Numerous N-heterocyclic compounds
can be obtained from aniline. For example
quinoline is produced in the Skraup synthesis
by condensation of aniline with glycerol or acry-
laldehyde (acrolein) in nitrobenzene.
3. Production
3.1. Raw Materials
Most commercially used synthesis of aniline
start from benzene. There is some literature
about direct amination of benzene, but the high
temperature and pressure required and the need
to use an extreme excess of ammonia never al-
lowed the development of an economic process
[4]. DuPont and Mitsui Toatsu examined the ox-
idative amination process of benzene forming
water as a byproduct [5].
Up to now, all technically applied aniline syn-
theses use an indirect way to produce aniline
from benzene. In all cases a kind of derivatiza-
tion is included as an intermediate step. In this
step one of the two direct precursors of aniline
is formed: nitrobenzene or phenol.
Nitrobenzene (→ Nitro Compounds, Aro-
matic). Nitrobenzene is manufactured commer-
Aniline 3
cially by the direct nitration of benzene in liq-
uid phase using a mixture of nitric and sulfuric
acid (mixed acid, nitrating acid). There are basi-
cally two thermodynamic ways for the nitration
of benzene:
isothermal reaction
adiabatic reaction
In the isothermal process the nitration of ben-
zene takes part in a reaction cascade of reactors
(stirred cylindrical reactor or tubular reactor) at
a temperature of 50 to 100 ◦ C and ambient pres-
sure. The temperature is maintained by internal
and/or external cooling with cooling water. An
advantage of the isothermal process, caused by
the low reaction temperature, is the very low for-
mation rate of byproducts (nitrophenols, picric
acid) [6]. The nitrating acid is a mixture of fum-
ing sulfuric acid (oleum) and concentrated nitric
acid. In the adiabatic process the nitration of ben-
zene takes part in a cascade of stirred reactors or
a jet impingement reactor [7] at a temperature of
90 to 190 ◦ C and ambient pressure. As nitrating
acid a large volume of 65 to 85 % sulfuric acid
and concentrated nitric acid are used. An advan-
tage of the adiabatic process is that the reaction
heat of the nitration, heating up the reaction mix-
ture, is used to reconcentrated the spent sulfuric
acid. This is done by azeotropic distillation of
water/benzene, by stripping water with an inert
gas, or distillation of the spent acid under re-
duced pressure.
Phenol (→ Phenol). The cumene oxidation
(Hock process) process is the most important
commercial process to synthesize phenol.
Cumene is prepared by alkylation benzene
with propene using a carrier catalyst containing
absorbed phosphoric acid, at temperature of ca.
230 ◦ C and at a pressure of 3500 kPa [8]. An-
other process is the toluene oxidation route via
benzoic acid.
3.2. Processes
Nitrobenzene is used as raw material for ani-
line production by all world producers with the
exception of Mitsui Petrochemicals Ind. (Japan)
who additionally uses phenol as starting material
and Aristech Chemical Corp. (United States),
who only uses the phenol route [9].
4 Aniline
3.2.1. Catalytic Hydrogenation of
Nitrobenzene
The highly exothermic catalytic hydrogenation
(∆H = − 544 kJ/mol at 200 ◦ C) of nitrobenzene
is performed both in the vapor and in the liq-
uid phase in commercially used processes (see
Fig. 3).
The exchange and utilization of the heat of
reaction is a crucial point for all processes using
nitrobenzene as a raw material [10].
Figure 3. Simplified flow sheet of the reaction route nitro-
benzene to aniline
a) Hydrogenation; b) Separation; c) Dewatering; d) Recti-
fication
3.2.1.1. Catalytic Vapor-Phase
Hydrogenation
Nitrobenzene is hydrogenated to aniline, usu-
ally in more than 99 % yield, using fixed-bed or
fluidized-bed vapor-phase processes. The most
effective catalysts for the gas-phase hydrogena-
tion of nitrobenzene seem to be copper or palla-
dium on activated carbon or an oxidic support, in
combination with other metals (Pb, V, P, Cr) as
modifiers or promoters in order to achieve high
activity and selectivity.
In the Lonza process, which is operated by
First Chemical Corp., a homogenized feed of hy-
drogen and nitrobenzene is passed over a fixed-
bed catalyst of copper on pumice with an inlet
temperature of about 200 ◦ C (example: 215 ◦ C).
The homogenization is done by spraying the
nitrobenzene with the help of the fresh hydrogen
feed into the heated (example: 240 ◦ C) circulat-
ing gas stream at a fixed position. The molar
ratio of nitrobenzene feed to total hydrogen is
about 1 : 100 at the reactor inlet. The reaction
products leave the reactor with a temperature of
more than 300 ◦ C (example: 325 ◦ C). The heat
of hydrogenation is used for steam production
and for heating up the recycle gas stream. The
reactor outlet is cooled down further in a con-
denser; excess hydrogen, crude aniline and water
are separated. Aniline is purified by distillation
[11, 12, 14].
Bayer operates conventional fixed-bed reac-
tors using a palladium catalyst on a alumina sup-
port, modified in its activity by the addition of
vanadium and lead [13] and claims the adiabatic
hydrogenation of nitrobenzene over a fixed-bed
catalyst of 1.5 to 4 wt % palladium on coke
with 0.1 to 2 wt % lead as a modifier to reduce
aromatic ring hydrogenation. At a pressure of
100 – 700 kPa a mixture of vaporized nitroben-
zene and hydrogen in a molar ratio of 1 : 120
to 1 : 200 is fed to the adiabatic reactor with an
inlet temperature of 250 – 350 ◦ C. The height of
the catalysts’ bed in the reactor is 0.1 to 1. 0 m
The reaction products leave the reactor without
cooling at a maximum temperature of 460 ◦ C.
After leaving the reactor, the heat of reaction is
used for the production of high pressure steam.
A production unit can be built of several serial
and/or parallel adiabatic reactors. After cooling
down to 140 to 180 ◦ C, the outlet of the final
reactor is fed to a separation unit, where after
further cooling crude aniline, crude wastewater,
and the recycled hydrogen are separated under
pressure. The crude aniline is purified by distil-
lation [15–18].
BASF operates a vapor-phase, fluidized-bed
process [19]. Nitrobenzene is partially evapo-
rated by atomizing it with the aid of a hot stream
of gas consisting substantially of hydrogen. The
stream of gas is circulated in the presence of a
fluidized catalyst, the reaction products are con-
densed, and aniline is separated from the iso-
lated crude reaction products. One type of pre-
ferred catalyst is copper (≈ 15 wt %) on a silica
support promoted with chromium, zinc, and bar-
ium. The two phase mixture of nitrobenzene and
hydrogen is injected through nozzles located at
several heights in the fluidized bed and the hy-
drogenation is carried out at 250 – 300 ◦ C and
400 – 1000 kPa in the presence of excess hydro-
gen. The hot product gas is cooled by passing
it through a heat exchanger, and aniline is iso-

lated in a liquid – gas separator. The reaction heat
is used for steam production. For catalyst re-
generation, after flushing the whole system with
nitrogen, the organic material deposited on the
catalyst surface is burned off at 200 to 250 ◦ C
with air. After completion of the regeneration
and subsequent replacement of the air in the sys-
tem with nitrogen, the catalyst is activated again
by reducing the copper oxide to copper with hy-
drogen at 200 to 300 ◦ C [20], [21].
3.2.1.2. Catalytic Liquid-Phase
Hydrogenation
The industrial aniline processes of ICI and
DuPont involve hydrogenation in the liquid
phase. Liquid-phase hydrogenation processes
are operated at 90 – 200 ◦ C and 100 – 600 kPa.
The liquid phase reaction may be carried out in
slurry or in fluidized-bed reactors. Conversion of
nitrobenzene is normally complete after a single
reactor pass with yields of 98 to 99 %.
In the 1960s, ICI developed a continuous, liq-
uid phase hydrogenation process, that used ani-
line as the solvent in a proportion > 95 wt %
of the liquid phase. By operating at or near the
boiling point of the solvent (usually at pressures
< 100 kPa), some or all of the heat of the reaction
is dissipated by allowing the reaction mixture
to evaporate. Water is removed with the efflu-
ent vapors and sufficient aniline is returned to
the reaction vessel to maintain steady state con-
ditions. One preferred catalyst is finely divided
nickel on kieselguhr [22].
DuPont hydrogenates nitrobenzene in liquid
phase using a platinum – palladium catalyst on a
carbon support with iron as modifier. The mod-
ifier provides good catalyst life, high activity,
and protection against hydrogenation of the aro-
matic ring. The continuous process uses a plug-
flow reactor that achieves essentially quantita-
tive yields, and the product exiting the reactor is
virtually free of nitrobenzene [23], [24].
A comparison of the catalytic liquid-phase
and vapor-phase hydrogenation of nitrobenzene
shows virtually no differences in yield and prod-
uct quality for both processes. The liquid-phase
process has the advantage of a higher space-time
yield and no need for a recycle gas loop (lower
energy requirement), the vapor-phase process
has the advantage of a very effective utilization
Aniline 5
of the heat of reaction (steam production), no
need for a product-catalyst separation and longer
catalyst live.
3.2.2. Reduction of Nitrobenzene with Iron
and Iron Salts
A historical variation of the nitrobenzene route
is the Béchamp process, which uses iron and
iron(II) chloride for the reduction.
This process is more than one hundred years
old, but still used in two Bayer aniline plants.
Nowadays the product of interest is no longer the
aniline, but the colored iron oxide pigments, that
are formed as byproducts. In the Béchamp pro-
cess nitrobenzene is reduced in an agitated re-
action vessel with iron(II) chloride solution and
ground iron fillings. The reactor is filled with the
total amount of water required for the reaction
(aniline water from aniline distillation), 20 %
of the iron, the total amount of catalyst needed,
and about 5 % to 10 % of the total nitrobenzene
feed. Under intense agitation the reactor con-
tent is heated up to reflux. After the reduction
has started the remaining nitrobenzene and iron
are added slowly to avoid excessive temperature
and pressure buildup. For the completion of the
reduction the vessel is heated up to 100 ◦ C for
two more hours after the end of the iron/nitro-
benzene addition. The reaction is completed in
about 8 to 10 h [25].
The reaction mixture is neutralized with lime;
it is then transferred to a separator, and the or-
ganic phase containing the aniline is withdrawn.
Aniline is recovered from the organic phase by
water stripping and distillation. Residual aniline
is recovered from the material remaining in the
separator before the iron oxide powder slurry is
processed into a fine particle, colored pigment.
The color of the iron oxide byproduct can be
controlled by additives to the reaction medium,
by the use of different types of iron, and by sub-
sequent calcination conditions [26].
6 Aniline
3.2.3. Amination of Phenol
In the commercial phenol route developed
by Halcon, phenol is aminated in the vapor
phase using ammonia in the presence of a
silica – alumina catalyst.
The reaction is mildly exothermic
(∆H = − 8.4 kJ/mol) and reversible, so high
conversion is obtained only by the use of ex-
cess ammonia (mole ratio of 20 : 1) and a low
reaction temperature, which also reduces the
dissociation of ammonia. Byproduct impurities
include diphenylamine, triphenylamine and car-
bazole. Their formation is also inhibited by the
use of excess ammonia. Yields based on phenol
and ammonia are
96 % and 80 %, respectively
[28].
In the process (Fig. 4) phenol and fresh
and recycle ammonia are vaporized separately
(to prevent yield losses) and combined in the
fixed bed amination reactor (a) containing the
silica – alumina catalyst. After the reaction at
370 ◦ C and 1.7 MPa, the gas is cooled, partly
condensed and the excess ammonia is recov-
ered in a separation column (b), compressed and
recycled. The condensation product is passed
through a drying column to remove water and
then through a finishing column to separate ani-
line from residual phenol and impurities in vac-
uum (less than 80 kPa). The phenol, containing
some aniline (azeotropic mixture) is recycled
[29], [30].
Figure 4. Simplified flow sheet of the reaction route phenol
to aniline
a) Amination; b) Ammonia recovery; c) Dewatering; d) Rec-
tification
Comparison of the phenol route to the nitro-
benzene route, both starting from benzene,
shows four steps for the former (cumene to
phenol involves two steps via the intermediate
cumene hydroperoxide) versus two for the latter.
The nitrobenzene route has an overall advantage
in yield and lower total energy requirements. The
phenol route has an advantage in prolonged cat-
alyst life and product quality. It is the preferred
method if low cost phenol is available (phenol
producers).
4. Quality Specifications
The common standard specification of
commercial-grade aniline is listed below:
Aniline min. 99.9 %
Nitrobenzene max. 2 ppm
Water max. 500 ppm
Color max. 100 APHA
For special applications the concentra-
tion of trace impurities like cyclohexylamine,
cyclohexanol, cyclohexanone, toluidines, phe-
nol, phenylcyclohexylamines, and dicyclo-
hexylamine may be specified as well.
The analysis of the specified organic impuri-
ties is normally carried out by gas chromatog-
raphy using a nonpolar stationary phase (di-
methylpolysiloxane) and a flame ionization de-
tector.
The water concentration in aniline is deter-
mined with the coulometric Karl-Fischer titra-
tion.
The color of the aniline is determined spec-
trophotometrically. Freshly distilled aniline is a
colorless liquid (< 10 APHA) which becomes
brownish by exposure to light and air.
5. Handling, Storage and
Transportation
Aniline is slightly corrosive to some types of
metal. So all amphoteric materials such as alu-
minum, copper, tin, zinc, and alloys containing
one of these metals (brass, bronze) are not suit-
able for the handling of aniline, as they are cor-
roded by it. For normal applications carbon steel
or cast iron are appropriate materials for the ani-
line handling or storage. Only if discoloration
 Aniline 7

must be kept to minimum, aniline should be
stored and transported in stainless steel equip-
ment with proper nitrogen blanketing. Suitable
gasket materials include for example graphite,
polytetrafluoroethylene or poly(vinylidene flu-
oride), best reinforced with glass fiber.
Aniline is transported in drums, containers
for the transportation on rail, water and street,
railway tank cars and tank trucks as well as in
tanks of ships for river and sea transportation.
Aniline is classified as a hazardous chemical
substance for transportation (UN no. 1547). Be-
cause of its chemical properties it is classified as
a poisonous liquid (class 6.1 12 b) class b (dan-
gerous substance). Therefore, aniline must be
transported following the Hazardous Materials
Transportation Act regulations regarding load-
ing, handling, and labeling.
6. Uses
In 1996 aniline was known to be used in more
than 300 different end products (see Table 1).
Thereof the polyurethane building block 4,4-
methylene-di-paraphenylene isocyanate (MDI),
accounting for 2/3 of the total demand, was
of paramount importance. With an expected
growth well above the increase of the average
global gross domestic product, MDI in future
will extent its position as dominating outlet for
aniline even further.
Table 1. Worldwide consumption of aniline by application
Application Percentage of consumption
insulation. Due to the wide spectrum of tradi-
tional end uses and new fields of application
MDI-PU will continue to show a strong growth
especially in emerging markets.
Worldwide production capacity for MDI in
1996 was 2.35 × 106 t. Biggest producer was
Bayer (capacity: 580 × 103 t), followed by ICI,
BASF, and, Dow. Whereas ICI and BASF are
fully back-integrated (i.e., self-sufficient), Bayer
and Dow to a certain extent depend on aniline
supplies from third parties.
After double digit growth rates in the mid
1990s, future use of aniline for MDI is projected
to grow at a more modest rate of 6 – 8 % per year.
A typical MDI process used by commercial
producers is as follows:
A mixture of polymeric methy-
lenephenylamines is prepared by condensing
aniline with formaldehyde in the presence of
HCl. The reaction involves intermediate for-
mation of amine hydrochlorides, which subse-
quently are neutralized with caustic soda. The
reaction usually is run with an excess of aniline
at subatmospheric pressure and temperatures
between 70 and 105 ◦ C. The yield is about 96 %.
The polyamine product is converted to a
crude mixture of isocyanates by reaction with
phosgene in a solvent. Reaction temperature is
about 120 ◦ C, pressure is 345 kPa, and yield ca.
97 %. Chlorobenzene is removed by distillation.
The crude is separated by vacuum distillation
into pure MDI and polymeric MDI. Hydrogen
chloride is produced as a byproduct of the reac-
tion.

MDI
Rubber processing chemicals
Dyes and pigments
Agricultural chemicals
Pharmaceuticals
Cyclohexylamine/dicyclohexyl-
amine
Miscellaneous
6.1. Methylene Diphenylene Isocyanate
(MDI)
MDI is one of the principal isocyanates that
is reacted with alcohols such as polyols and
polyetherols to produce polyurethanes (PU).
MDI based PU systems are mainly used in
construction, furniture, automotive industry, and
65 %
18 %
5% 6.2. Rubber Processing Chemicals
4%
2%
2%
In the first decade of this century pure aniline
was used as a vulcanization accelerator. The call
4% for higher effectiveness and safer handling led to
the development of aniline based mercaptothia-
zole and sulfenic amide accelerators (→ Rubber,
4. Chemicals and Additives, Chap. 2.3.1.) which
at present account for ca. 80 % of all vulcaniza-
tion accelerators used worldwide.
Of even bigger importance for aniline
within the rubber processing chemicals sector
are antidegradants (i.e., antioxidants, antiozo-
nants) such as paraphenylenediamines (PPD),
quinolines, and diphenylamine (→ Rubber,
8 Aniline
4. Chemicals and Additives, Chap. 3.2.1.). Ani-
line is feedstock to roughly 70 % of all an-
tidegradants consumed worldwide.
Future use of aniline in the rubber industry
is forecasted to increase by 2 – 3 % per year,
equivalent to the worldwide growth in demand
for synthetic and natural rubber.
6.3. Dyes and Pigments
Intermediates for dyes and pigments cover more
than 50 % of all known formulations using ani-
line as a raw material, albeit most of them are
of minor importance. The largest classes are
the mono-, di-, and triazo compounds. Produc-
tion of dyes and pigments has shifted toward
Asian countries, such as China and India. How-
ever, some world-scale dyes and pigments plants
in Europe and NAFTA (United States, Canada,
Mexico) are still using aniline, e.g., for the pro-
duction of indigo. Since the industrial realiza-
tion of the chemical indigo syntheses at the end
of the 19th century by BASF, indigo (→ Indigo
and Indigo Colorants) is the most important dye
based on aniline.
Worldwide growth for this application is ex-
pected to be at a low rate of 1 – 2 % per year.
6.4. Agricultural Chemicals
More than 40 active substances for pesticides
(herbicides, fungicides, and insecticides) use
aniline as raw material. Most important are
amide and urea herbicides. NAFTA-located
companies stand for more than 50 % of the
world s aniline consumption for agricultural
chemicals. Aniline-based active substances are
predominantly in the later stage of their life cy-
cle and are about to be substituted. Global con-
sumption therefore is forecasted to decrease by
1 – 2 % per year.
6.5. Pharmaceuticals
As a stable, although small outlet, aniline is
mainly used for preparation of analgesics, an-
tipyretics, antiallergics, and vitamins. A certain
growth in demand for drugs is expected for the
next five years, counterbalanced by a decreasing
aniline consumption for production of vitamins
where the aniline route is being abandoned in
favor of fermentation technology.
6.6. Cyclohexylamine/Dicyclohexylamine
In the 1990s aniline became the raw material
of choice for the production of these amines.
Both are predominantly used as intermediates
for sulfenamide vulcanization accelerators. Cy-
clohexylamine is also used in large quantities
as corrosion inhibitor and feedstock for cycla-
mates.
Whereas the usage of these amines in accel-
erators and water treatment is expected to grow
at a rate of ca. 3 – 4 % per year, the consump-
tion of cyclohexylamine for production of cycla-
mates has fluctuated considerably and is difficult
to predict. A boost in demand can be expected
should the FDA lift the ban on the usage of cy-
clamates as artificial sweeteners in the United
States.
6.7. Miscellaneous
Among various other applications (production
of alkylanilines, optical brighteners, sulfonic
acids, etc.) the consumption of aniline for syn-
thesis of aramid fibers is worth mentioning.
Aramids are suitable for a wide spectrum of ap-
plications, mainly as substitutes for steel, show-
ing equivalent reinforcement characteristics at
far lower weight. Because of additional use in
other applications, e.g., the replacement of as-
bestos in brake linings, healthy growth rates for
aramids can be expected.
7. Economic Aspects
A breakdown of aniline consumption by region
is given in Table 2.
Table 2. Aniline consumption by region
Region Percentage of consumption
Europe 39 %
Americas 34 %
Asia 27 %
 Aniline 9

Much of the growth in demand for aniline in flash point 90 ◦ C, bp 208 ◦ C, fp − 2.3 ◦ C. o-
recent years has originated in Asia, where ex- Chloroaniline is used as an intermediate for rub-
tensive use of MDI based polyurethanes in con- ber chemicals, pigments, pesticides, and dyes.
struction and consumer goods was the driver for Production is by low-pressure hydrogenation of
the entire urethanes sector. A substantial part of 2-chloronitrobenzene with noble metal and/or
Asia s demand for urethanes and urethane raw noble metal sulfide catalysts at temperatures of
materials, however, was imported from Europe ca. 50 – 100 ◦ C in inert organic solvents. The
and the United States. It is safe to say that Asia yield is almost quantitative.
will see stronger growth in demand for aniline
because major MDI producers are pushing ahead m-Chloroaniline [108-42-9], 1-amino-3-
with plans to build large plants in the region. chlorobenzene, ClC6 H4 NH2 , is a water-white to
World aniline production capacity was esti- light-amber liquid, M r 127.6, flash point (TOC)
mated at ca. 2.3 × 106 t for 1996. Capacity by 90 ◦ C, bp 230 ◦ C, fp − 10.5 ◦ C. This compound
geographic area in 103 t was: is used as an intermediate for pesticides, phar-
maceuticals, and dyes. It is produced by low-
Europe 960
Americas 820 pressure hydrogenation of 3-chloronitrobenzene
Japan 270 in the liquid phase with noble metal and/or noble
Asia exc. Japan 250 metal sulfide catalysts. The addition of metal ox-
Africa 7
ides to the reaction helps avoid dehalogenation.
The yield is approximately 98 %.
In 1996 worldwide more than 40 compa-
nies produced aniline. The leading manufactur- p-Chloroaniline [106-47-8], 1-amino-4-
ers were (capacity in 103 t): chlorobenzene, ClC6 H4 NH2 , is a white to light
ICI incl. joint ventures 460 amber, crystalline solid at room temperature,
Bayer 345 M r 127.6, bp 230 ◦ C, mp 70 ◦ C. It is used as
BASF incl. joint ventures 305
Mitsui 125
an intermediate for pesticides, pharmaceuticals,
DuPont 118 pigments, and dyes. Production is similar to that
First Chemical Corp. 131 of m-chloroaniline [31].
Aristech 91
MCHZ 75
Anilina de Portugal 60 3,4-Dichloroaniline [95-76-1], 1-amino-
3,4- dichlorobenzene, Cl2 C6 H3 NH2 , is a gray
BASF was the sole company with production to dark-brown crystalline solid at room temper-
facilities in Europe, the United States, and Asia. ature, M r 162.0, fp 66 – 71 ◦ C, bp 272 ◦ C. It is
Besides ICI and Bayer with sites in Europe and used as an intermediate for pesticides and dyes
the United States all other companies were re- and is produced by catalytic hydrogenation of
stricted to one region or one site only. 3,4-dichloronitrobenzene with noble metal cat-
Expansions that have taken place since 1996 alysts under pressure. Various types of additives
and formally announced projects taken into ac- prevent dehalogenation during production and
count, annual world capacity will grow to more reactors must be fabricated with special steel
than 3.50 × 106 t until 2005, with ICI and BASF alloys to inhibit corrosion [31], [32].
leading the competition by a wide margin.
N,N-Dimethylaniline [121-69-7], N,N-di-
methylphenylamine, (H3 C)2 NC6 H5 , is a light
8. Derivatives yellow (straw colored) to brown oily liquid,
freezing to a crystalline solid at low tempera-
Table 3 shows substituted anilines, their proper- tures, M r 121.2, fp 2.1 ◦ C, flash point, Tagliabue
ties, and their uses. closed cup (TCC) 63 ◦ C, bp 193 ◦ C. It is used as
a polymerization catalyst and as an intermediate
for pharmaceuticals and dyes. Dimethylaniline
o-Chloroaniline [95-51-2], 1-amino-2-
is produced from aniline and methanol under
chlorobenzene, ClC6 H4 NH2 , is a water-white to
pressure in the presence of acidic catalysts or by
tan liquid, M r 127.6, Tagliabue open cup (TOC)
passing dimethyl ether and aniline vapor over
Table 3. Substituted anilines

10
b b
Class and name Formula CAS regis- Mr Appear- mp, ◦ C bp, ◦ C d 20
4 n20
D Solubility a Use c
try number ance a

Salts
Aniline hydrochloride C6 H5 NH2 HCl [142-04-1] 129.60 w. cr. 198 245 1.22154 s. w, alc
Aniline sulfate (C6 H5 NH2 )2 H2 SO4 [542-16-5] 284.34 w. cr. dec. 1.3774 s. w
Chloro

Aniline
o-Chloroaniline ClC6 H4 NH2 [95-51-2] 127.58 c. liq. −14 209 1.2125 1.5881 s. alc, eth, be, ace (1)
m-Chloroaniline [108-42-9] 127.58 c. liq. −10 230 1.2161 1.5941 s. alc, eth, be (1)
p-Chloroaniline [106-47-8] 127.58 c. cr. 72.5 232 1.42919 1.554687 s. hot w, alc, eth, ace (1) (8)
2,3-Dichloroaniline Cl2 C6 H3 NH2 [608-27-5] 162.02 cr. 24 252 1.38325 s. alc, eth, ace, be
2,4-Dichloroaniline [554-00-7] 162.02 cr. 63 245 1.567 s.s. w; s. alc, eth
2,5-Dichloroaniline [95-82-9] 162.02 cr. 50 251 s. alc, eth, be (1)
2,6-Dichloroaniline [608-31-1] 162.02 cr. 39 s. alc, eth
3,4-Dichloroaniline [95-76-1] 162.02 w. cr. 72 272 1.3380 s. alc, eth (1) (8)
3,5-Dichloroaniline [626-43-7] 162.02 cr. 51 260 s. alc, eth, be
2,4,5-Trichloroaniline Cl3 C6 H2 NH2 [636-30-6] 196.46 cr. 97 270 s. alc, eth
Alkyl
o-Toluidine H3 CC6 H4 NH2 [95-53-4] 107.17 y. liq. −16.4 200 0.9994 1.5725 s.s. w; s. alc, eth (1)
m-Toluidine [108-44-1] 107.17 c. liq. −30 203 0.9889 1.568122 s.s. w; s. alc, eth, ace, be (1)
p-Toluidine [106-49-0] 107.17 w. cr. 44 – 45 200.6 0.9619 1.5636 s.s. w; s. alc, eth, ace, be (1)
2,3-Xylidine (H3 C)2 C6 H3 NH2 [87-59-2] 121.20 liq. <−15 221 – 222 0.9931 1.5684 s. alc, eth
2,4-Xylidine [95-68-1] 121.20 liq. −14 215 0.9723 1.5569 s. alc, eth, be
2,5-Xylidine [95-78-3] 121.20 oily liq. 16 214 0.979021 1.5593 s. eth (1)
2,6-Xylidine [87-62-7] 121.20 liq. 11 216 0.9842 1.5610 s. alc, eth (1)
3,4-Xylidine [95-64-7] 121.20 cr. 51 226 1.07618 s. eth (4)
3,5-Xylidine [108-69-0] 121.20 oily liq. 9.8 220 – 221 0.9706 1.5581 s. eth (1)
Alkoxy
o-Anisidine H3 COC6 H4 NH2 [90-04-0] 123.17 y. liq. 6.2 225 1.0923 1.5793 s. alc, eth, ace, be; s.s. w (1)
m-Anisidine [536-90-3] 123.17 oily liq. <−12 251 1.096 1.5794 s. alc, eth, ace, be; s.s. w
p-Anisidine [104-94-9] 123.17 w. cr. 57.2 243 1.060567 1.555967 s. alc, eth, ace, be; s.s. w (1)
o-Phenetidine H5 C2 OC6 H4 NH2 [94-70-2] 137.20 oily liq. <−21 232 1.5560 s. alc, eth, (1) (2) (3)
p-Phenetidine [156-43-4] 137.20 liq. 2–3 254 1.065215 1.5528 s. alc, eth; s.s. w (1)
p-Cresidine H3 CO(CH3 )−C6 H3 NH2 [120-71-8] 137.20 w. cr. 52 235 s. alc, eth, ace, be; s.s. w. (1)
N-Alkyl, N-Aryl
Table 3. (Continued)

b b
Class and name Formula CAS regis- Mr Appear- mp, ◦ C bp, ◦ C d 20
4 n20
D Solubility a Use c
try number ance a

N-Methylaniline C6 H5 NHCH3 [100-61-8] 107.17 y. liq. −57 196 0.9891 1.5684 s. alc; s.s. w
N,N-Dimethylaniline C6 H5 N(CH3 )2 [121-69-7] 121.20 y. liq. 2 194 0.9557 1.5582 s. alc, eth, ace, be (1)
N-Ethylaniline C6 H5 NHC2 H5 [103-69-5] 121.20 liq. −63.5 205 0.9625 1.5559 s. alc, eth, ace, be (1) (5)
N,N-Diethylaniline C6 H5 N(C2 H5 )2 [91-66-7] 149.26 y. liq. −38.8 216 0.9351 1.5409 s.s. alc, eth, ace (1)
N-Ethyl-N-benzylaniline C6 H5 N(C2 H5 )−CH2 C6 H5 [92-59-1] 211.20 y. liq. 314 1.034 s. alc, eth (1)
N,N-Diphenylamine C6 H5 NHC6 H5 [122-39-4] 169.24 w. cr. 54 – 55 302 1.159 s. alc, eth, ace, be (3)
N-Acyl
Formanilide C6 H5 NHCOH [103-70-8] 121.15 w. cr. 50 271 1.143717 s. alc; s.s. w (1) (6)
Acetanilide C6 H5 NHCOCH3 [103-84-4] 135.18 cr. 114 304 1.21915 s. alc, eth, ace, be, hot w (1) (3) (6)
Acetoacetanilide C6 H5 NHCOCH2 COCH3 [102-01-2] 177.22 w. cr. 86 s. alc, eth, ace, be (1)
Nitro
o-Nitroaniline O2 NC6 H4 NH2 [88-74-4] 138.14 y. cr. 71 – 72 284 1.44215 s. alc, eth, ace, be, hot w (1)
m-Nitroaniline [99-09-2] 138.14 y. cr. 114 306 s. alc, eth, ace; s.s. w (1)
p-Nitroaniline [100-01-6] 138.14 y. cr. 148 – 149 332 1.424 s.s. alc (1) (3)
2,4-Dinitroaniline (O2 N)2 C6 H3 NH2 [97-02-9] 183.14 y. cr. 187 – 188 1.61514 (1)
2,4,6-Trinitroaniline (O2 N)3 C6 H2 NH2 [489-98-5] 228.12 y. cr. 192 – 195 1.76212 (7)
Sulfonated
Orthanilic acid (o) H2 NC6 H4 SO3 H [88-21-1] 173.9 cr. >320 (1)
Methanilic acid (m) [121-47-1] 173.9 w. cr. dec. s.s. alc, w (1)
Sulfanilic acid (p) [121-57-3] 173.9 w. cr. 288 1.48525 s.s. w (1) (6)
a
c. = colorless; w. = white; y. = yellow; liq. = liquid; cr. = crystals; dec. = decomposes; s. = soluble; s.s. = slightly soluble; w = water; alc = alcohol; eth = ether; ace = acetone; be = benzene
b
Density and refractive index superscripts refer to temperature (◦ C)
c
(1) dyes, pigments; (2) synthetic sweetener; (3) rubber antioxidant, accelerator; (4) vitamin B2 (riboflavin); (5) explosive stabilizer; (6) medication (analgesic), pharmaceuticals; (7) explosive; (8)
agricultural chemicals
Aniline
11
12 Aniline
highly activated aluminum oxide at 230 – 295 ◦ C
[33].
N,N-Diethylaniline [91-66-7], N-phenyl-
diethylamine, (H5 C2 )2 NC6 H5 , is a yellow to
brown, oily liquid, M r 149.2, flash point (TOC)
85 ◦ C, bp 216 ◦ C. Uses are similar to those for
the dimethyl analogue. Its production is analo-
gous to methods used for dimethylaniline pro-
duction except that ethanol instead of methanol
is reacted with aniline.
N-Phenylacetamide [103-84-4], acet-
anilide, acetylaniline, C6 H5 NHCOCH3 , is a
colorless, glossy, crystalline material, M r 135.2,
fp 114 ◦ C, bp 304 ◦ C. It is used as a dye inter-
mediate, plasticizer and stabilizer for cellulose
esters, and as an intermediate for the synthesis
of sulfonamides. It is produced by heating ani-
line with acetic acid, acetic anhydride, or acetyl
chloride [34].
2,4-Xylidine [95-68-1], m-xylidine, 2,4-di-
methylaniline, (H3 C)2 C6 H3 NH2 , is a colorless
to tan, oily liquid, M r 121.2, flash point (TCC)
> 93 ◦ C, bp 213 ◦ C. It is used as an intermedi-
ate for photographic chemicals, pesticides, and
dyes. It is produced by the catalytic hydrogena-
tion of the corresponding nitro derivative.
2,6-Xylidine [87-62-7], 2,6-dimethylaniline,
H2 NC6 H3 (CH3 )2 , is a colorless to reddish-
yellow, clear liquid, M r 121.2, flash point (TCC)
> 94 ◦ C, bp 217 ◦ C. This compound is used as
an intermediate for dyes, pesticides, and phar-
maceuticals. Production is by the catalytic hy-
drogenation of the corresponding nitro deriva-
tive [35].
N-Phenylaminobenzene [122-39-4], di-
phenylamine, C6 H5 NHC6 H5 , is isolated in the
form of colorless leaflets, M r 212.2, flash point
(TCC) 153 ◦ C, bp 302 ◦ C, mp 53 ◦ C. Dipheny-
lamine is used as a stabilizer for elastomers,
nitrocellulose, and nitroglycerine and as an in-
termediate for dyes. It is produced by passing
aniline over various types of acidic catalysts at
elevated temperatures and pressures [36].
9. Toxicology
9.1. Toxicokinetic Properties and
Metabolism
Aniline, a weakly alkaline liquid, is readily ab-
sorbed into the circulation after oral ingestion,
inhalation and dermal contact. In human volun-
teers, more than 90 % of the inhaled aniline va-
pors (5 – 30 mg/m3 ) were absorbed in the state of
rest [37–39]. The percutaneous uptake from the
vapor phase accounted for 25 – 30 % of the total
incorporation in normally dressed individuals at
25 ◦ C and 35 % relative air humidity (estimated
absorption rate: 0.2 – 0.4 µg cm−2 h−1 ), but in-
creased by 21 and 29 % when the temperature
was elevated by 5 ◦ C and the humidity from 35 to
75 %, respectively [38]. Likewise, when applied
as liquid to human skin from a drained gauze
(concentration 10 mg/cm2 ), skin absorption of
aniline was between 0.2 and 0.7 mg cm−2 h−1
but could reach up to 3.5 mg cm−2 h−1 on highly
moistened skin [38], [39], also temperature ap-
peared to be a factor.
Aniline undergoes rapid oxidation, mainly in
the liver, but also in other organs like the intestine
and erythrocytes. Three primary transformation
reactions compete with each other and are ex-
pressed to varying degree in different species
and individuals:
1) N-Hydroxylation
2) (Ring) hydroxylation
3) N-Acetylation followed by p-(ring) hydroxy-
lation
In secondary steps, the hydroxyl intermedi-
ates are rapidly conjugated, largely to sulfate and
glucuronic acid and excreted, mainly in the urine
[40–43]. In humans, the half-life of aniline is ca.
3.5 h [39].
The primary conversion products, mainly
phenylhydroxylamine and p-aminophenol as
well as their oxidized forms nitrosobenzene
and p-iminoquinone, resulting from reactions
1 and 2, are regarded as toxification steps
to biologically active compounds (see below),
whereas N-acetylation may be considered as
a detoxification step, which is followed by p-
hydroxylation to N-acetyl-p-aminophenol. N-
Acetyl transferase is congenitally expressed to
varying extent in humans (“strong and weak

acetylators”; see below); this is a reason for dif-
ferent individual susceptibilities.
Certain metabolites, such as nitrosobenzene,
are coupled to thiols, especially glutathione; the
quantities of aniline-protein conjugates, espe-
cially aniline-Hb adducts in blood, are diagnos-
tic tools for the estimation of aniline exposure
and body burden [44], [45].
9.2. Toxicological Properties
Central Nervous System Effects. Aniline
may produce an euphoric state through its ac-
tion on the central nervous system. At very high
exposure, a narcotic effect may result and also
cardiac dysfunction, coma, convulsions, and
respiratory paralysis.
Methemoglobinemia and Hemolysis.
Methemoglobinemia and hemolysis are typi-
cal aniline-related effects; they are frequently
observed also with many other related aromatic
amines: Primary oxidation products (phenyl hy-
droxylamine, p-aminophenol) are regarded as
intermediate active agents and show in the pres-
ence of oxygen the propensity to compete with
redox cycles (for a review see [46]).
Cats and humans appear to be the most re-
sponsive species and more susceptible than rats
and mice [47–49]. In healthy adult humans, ca.
25 mg aniline per individual, orally ingested for
3 consecutive days, was found to be a critical
threshold dose which causes measurable eleva-
tion of metHb; the highest noneffective dose in
rats was reported as 20 mg/kg [50]. Up to ca.
15 % of metHb are normally tolerated in hu-
mans; doses of 65 mg per person may transiently
exceed the 15 % limit [50].
One sequel of metHb formation may be the
destruction and hemolysis of erythrocytes, as-
sociated with the formation of “Heinz bodies”
in red blood cells and a hemolytic anemia with
secondary effects on other organs.
A deficiency in oxygen supply follows the de-
pletion of normal Hb to metHb and causes, de-
pending on the dose, hypoxemia, anoxia, bluish
discoloration to pronounced cyanosis, headache,
weakness, drowsiness, shortness of breath, and
unconsciousness.
In one acute case, a massive suicidal dose
of 60 mL orally, the “hemolytic crisis” caused
Aniline 13
death by organ failure of heart, liver, kidney, and
lung [51].
Early reports say that 6-h expo-
sures to 40 – 53 mL/m3 of aniline vapors
(150 – 200 mg/m3 ) were tolerated by workers
without noticeable symptoms [52], but in other
cases slight discomfort or dysfunction were
produced already at 7 – 26 mL/m3 after several
hours; 105 – 160 mL/m3 were not tolerable for
more than 1 h without the health status being
severely disturbed [52].
The ratio of toxifying and detoxifying reac-
tions has implications for the individual suscep-
tibility: ca. 50 % of Europeans are congenitally
deficient in hepatic N-acyl transferase: in these
individuals, the formation of inactive acetanilide
is delayed in favor of phenylhydroxylamine and
nitrosobenzene. Even at the industrial limit con-
centration of 2 mL/m3 , the sensitive persons
show higher mean levels of metHb (1.5 versus
0.9 %) and of aniline-Hb adducts than similarly
exposed persons with a high acetylating capacity
[52, p. 7].
In general, methemoglobinemia will reverse
spontaneously when exposure ceases. Cyanosis,
however, needs medical treatment with support-
ive measures, e.g., oxygen inhalation and bed
rest. In most cases, normal body functions will
be restored after 3 weeks without irreversible
damage [53].
Genotoxicity/Carcinogenicity. Under spe-
cific activating test conditions, aniline may ex-
hibit certain forms of genotoxicity: standard
Ames assays are negative, unless the incuba-
tion mixture is coactivated with norharmane. In
mammalian cell assays for DNA damage, gene
mutation and clastogenicity, and also in vivo,
varying results were obtained. However, aniline
does not appear to be a potent genotoxic agent
[52].
In the early years of industrial production of
aniline-based dyes, an increased incidence of
urinary bladder cancer was ascribed to aniline
exposure [54], [46]. However, it was recognized
later that contaminations of β-naphthylamine or
benzidine probably were the active agents, ani-
line itself was mainly considered noncarcino-
genic.
Most early experimental investigations failed
to support carcinogenicity (for a detailed re-
view on early studies: see [59]. However,
14 Aniline
in more recent rodent long-term feeding
studies with aniline HCl, the incidence of
spleen sarcomas was significantly increased in
rats (100 – 300 mg kg−1 d−1 ); the lower levels
(10 – 30 mg kg−1 d−1 ) were still associated with
hemato- and splenotoxicity and few spleen tu-
mors [55–58]. It was therefore assumed that the
production of spleen sarcomas was a secondary
response, initiated by the hemolytic toxicity and
associated with the decay and phagocytosis of
damaged erythrocytes in spleen sinuses, includ-
ing an iron overload in this target organ. This
is supported by the fact that the spleen is a very
unique target organ for carcinogenic effects even
with strongly genotoxic compounds, whereas
spleen enlargement, hemosiderosis (iron de-
position) and splenic lipid peroxidation [47]
are typically induced by aniline-related methe-
moglobinemia. Tumorigenesis of typical geno-
toxic aromatic amines (→ Amines, Aromatic,
Chap. 5.1.) is usually seen at other tumor sites
than spleen [52].
Studies of individuals exposed to aniline and
not to other aromatic amines have shown little
evidence of increased tumor risk: among 1223
men producing or using aniline one bladder can-
cer was recorded vs. 0.83 expected from the gen-
eral population incidence [59].
Reproduction Toxicity. Although aniline
can pass the placental barrier, studies in rats
and mice failed to provide evidence for the
induction of malformations in the fetus. Slight
embryo retardations, fetal hematological effects,
and increased liver weights were recorded at the
highest dose of 100 mg kg−1 d−1 . Also maternal
effects occurred at that level. The no observed
effect level was 10 mg kg−1 d−1 [60–62].
10. Occupational Health
Based on absorption properties (see Chap. 9), a
TLV and a MAK value (maximal concentration
at the workplace) of 2 ppm (8 mg/m3 ) with a skin
notation (potential of toxicologically relevant
cutaneous absorption) were established in the
United States and Germany, respectively [63],
[52].
In Germany, because of the limited data base
for embryotoxicity, the MAK Commission has
allocated aniline to group D (no final conclusion
on the prenatal risk under MAK value condi-
tions) [52].
11. References
1. “Aniline” BASF Safety Data Sheet
(91/155/EWG).
2. D. Barton, W. D. Ollis: Comprehensive
Organic Chemistry, 1st ed., vol. 2, Pergamon
Press, Oxford 1979, pp. 131 – 184.
3. S. Patai: The Chemistry of the Amino Group,
1st ed., Interscience Publ., London 1968,
pp. 161 – 205.
4. DuPont, US 3 832 364, 1972.
5. DuPont, US 4 001 260, 1973.
6. Kirk-Othmer, 4th ed., vol. 17, pp. 133 – 152.
7. A. Guenkel, T. Maloney, ACS Symp. Ser. 623
(1996), pp. 223 – 233.
8. Kirk-Othmer, 4th ed., vol. 7, pp. 730 – 736.
9. Winnacker-Küchler Chemische Technologie,
4th ed., vol. 6, pp. 205 – 214.
10. D. N. Rihani, T. K. Narayanan, L. K.
Doraiswamy, I&EC Process. Des. Develop. 4
(1965) 403 – 410.
11. Lonza/First Chemical Co., Hydrocarbon
Process 59 (Nov. 1979) no. 11, 136.
12. Lonza, US 3 636 152, 1969.
13. Bayer, EP 011 090, 1979.
14. First Chem. Corp., US 4 740 621, 1986.
15. Bayer, US 5 304 525, 1990.
16. Bayer, EP 696 574, 1995; Bayer, EP 696 573,
1995.
17. Bayer, EP 748 790, 1996; Bayer, EP 748 789,
1996.
18. Chemopetrol, GB 1 452 466, 1975.
19. American Cyanamide, US 28 910 994, 1955.
20. BASF, US 3136818, 1961.
21. BASF, DE 4110457, 1991.
22. ICI, US 3270057, 1964.
23. DuPont, US 3 499 034, 1966.
24. DuPont, US 4 185 036, 1977.
25. Winnacker-Küchler Chemische Technologie,
4th ed., vol. 4, pp. 170 – 171.
26. F. A. Lowenheim, M. K. Moran: Industrial
Chemicals, 4th ed., J. Wiley & Sons, New
York 1975, pp. 109 – 111.
27. Halcon International, Inc., US 3272865, 1966
(R. S. Barker).
28. Halcon International, Inc., US 3860650, 1975
(M. Becker, S. Khoobiar).
29. Scientific Design, Hydrocarbon Process. 59
(1979) 137.

30. J. A. Kent (ed.): Riegel’s Handbook of
Industrial Chemistry, 9th ed., van Nostrand
Reinhold, New York 1992, p. 1136.
31. DuPont, US 3 361 819, 1968 (J. R. Kosak, L.
Spiegler).
32. Dow, US 3 067 253, 1962 (A. J. Dietzler, T. R.
Kell).
33. Biller, Michaelis, US 2991311, 1961 (M.
Thoma).
34. British Industrial Solvents, US 2 462 221, 1949
(E. S. Pemberton).
35. Standard Oil Development, US 2 421 608,
1947; US 2481245, 1949.
36. Amer. Cyanamid, US 2 968 676, 1961 (A. G.
Potter, R. G. Weyker).
37. T. Dutkiewicz, Med. Pracy 12 (1961) 1.
38. T. Dutkiewicz, J. Piotrowski, Pure Appl.
Chem. 3 (1961) 319.
39. J. Piotrowski, Pracov. Lék. 24 (1972) 94.
40. J. Piotrowski, J. Hyg. Epidem. 1 (1957) 23.
41. J. Kao, J. Faulkner, J. W. Bridges, Drug Metab.
Dispos. 6 (1978) 549.
42. J. N. Smith, R. T. Williams, Biochem. J. 44
(1949) 242.
43. D. V. Parke, Biochem. J. 77 (1960) 493.
44. W. Albrecht, H.-G. Neumann, Arch. Toxicol.
57 (1985) 1.
45. G. Birner, H.-G. Neumann, Arch. Toxicol. 62
(1988) 110.
46. M. Kiese: Methemoglobinemia: A
Comprehensive Treatise, CRC Press, Inc.,
Cleveland 1974.
47. M. F. Khan et al., Toxicol. Lett. 92 (1997)
31 – 37.
48. D. Lester, J. Pharmacol. Exp. Ther. 77 (1943)
154.
49. Y. Henderson, H. W. Haggard, cited in: F.
Flury, F. Zernik: Schaedliche Gase,
Springer-Verlag, Berlin 1931.
50. F. P. Jenkins et al., Fd. Cosmet. Toxicol. 10
(1972) 671.
51. S. Janik-Kurylcio et al., Pol. Tyg. Lék. 28
(1973) 1241.
Anilinesulfonic Acids → Benzenesulfonic Acids and Their Derivatives
Animal Feeds → Foods, 1. Survey
Aniline 15
52. Deutsche Forschungsgemeinschaft (DFG)
(ed.): “Anilin”, in: Gesundheitsschädliche
Arbeitsstoffe.
Toxikologisch-Arbeitsmedizinische
Begründung von MAK-Werten, VCH
Verlagsgesellschaft, Weinheim 1992.
53. R. Hopmann, H. Bürschaper, Arch. Toxicol.
15 (1955) 340.
54. M. Mackenzie, Med. Tms. (London) 1 (1862)
239.
55. Chem. Ind. Inst. Toxicol. (CIIT): “Week
Chronic Toxicity Study in Rats: Aniline
Hydrochloride,” Final Rep. 104-Res. Triangle
Park, NC/USA (1982).
56. Nat. Cancer Inst. (NCI): NCI-Bioassay Report
No. 130, US-DHEW, Bethesda, MD/USA
(1978).
57. D. G. Goodman, J. M. Ward, W. D. Reichardt,
“Splenic Fibrosis and Sarcomas in F344 Rats
Fed Diets Containing Aniline Hydrochloride
p-Chloroaniline, Azobenzene, o-Toluidine
Hydrochloride, 4,4
-Sulfonyldianiline, or
D & C Red No. 9,”JNCI. 75 (1984) no. 1.
58. M. A. Weinberger, R. H. Albert, St. B.
Montgomery, “Splenotoxicity Associated With
Splenic Sarcomas in Rats Fed High Doses of
D & C Red No. 9 or Aniline Hydrochloride,”
JNCI. 75 (1985) no. 4.
59. IARC: “Aniline”, in: IARC Monographs on the
Evaluation of the Carcinogenic Risk of
Chemicals to Humans, vol. 27, Intern. Agency
for Res. on Cancer, Lyon 1982.
60. C. J. Price et al., Toxicol. Appl. Pharmacol. 77
(1985) 465.
61. V. J. Piccirillo et al., NTIS, PB83-257600,
Borriston Laboratories, Inc., MD/USA (1983)
62. B. D. Hardin et al., Teratog. Carcinog. Mutag.
7 (1987) 29.
63. Am. Conf. of Governmental Industrial
Hygienists (ACGIH, ed.): List of Threshold
Limit Values (TLV), Cincinnati, Ohio 1997.