Carboxylic acid and derivatives

Structure of Carboxylic acid

O C R
H
124o 125o

O C
111
o

RCOOH
OH

106o

H O

Geometry : approximately planar

C : sp2 hybridised, nearly trigonal bond angles

OH is also in this plane eclipsed with C=O

Carboxylic acid and derivatives

Resonance of carboxylic acid

major

very minor

minor

Carboxylic acid and derivatives

Properties of carboxylic acid

1. Bp :

* higher than ROH, RCOR, RCHO of similar MW

2. Mp :

* > 8 C atoms are generally solids * Double bonds lower the mp

3. Solubility :

* very soluble in ROH / quite soluble in non-polar solvents * 1-4 C atoms are miscible with water * RCOO-Na+ quite soluble in water (ionic)

Carboxylic acid and derivatives

4. Acidity

* * * *
H Cl H
chloroacetic acid pKa = 2.86

weaker acid than mineral acids more acidic than ROH Electronegative substituent increases the acidity substituent effect depends on the number & distance from C=O
O H O Cl
dichloroacetic acid pKa = 1.26

H C C H Cl C C O H

O Cl

Cl C Cl

O C O H

acetic acid pKa = 4.74

trichloroacetic acid pKa = 0.64

Cl H CH3

Cl CH CH2

O C O H CH3 CH2

Cl

O CH C O
2-chlorobutanoic acid pKa = 2.86

CH2 CH2

CH2

4-chlorobutanoic acid pKa = 4.52

3-chlorobutanoic acid pKa = 4.05

Carboxylic acid and derivatives

Some important carboxylic acid

Acetic acid - vinegar and other foods, solvent, catalyst & reagent for synthesis

Fatty acids - fats and oils

Benzoic acid - drugs, preservatives

Adipic acid - to make nylon 66

Phthalic acid - to make polyesters

Carboxylic acid and derivatives

Synthesis of carboxylic acid

1. Oxidation of primary ROH and RCHO

2. Oxidative cleavage of alkenes and alkynes

3. Oxidation of substituted alkylbenzenes

[O] : hot KMnO4 ; hot chromic acid

R COOH

[O] H2O, 95C

Carboxylic acid and derivatives

4. Hydrolysis

a) Nitriles

b) Acid chloride d) Ester

c) Acid anhydride e) Amide

5. Carboxylation of Grignard reagents

i. CO2 ii. H3O+
R O OH

RMgX

Carboxylic acid and derivatives

Reaction of carboxylic acids

nucleophilic acyl substitution

one nucleophile replaces another on the acyl carbon

takes place under basic or acidic conditions

i. addition

ii. elimination

O R C Nuc Y

Nuc:

O R

O C Nuc + :Y

Carboxylic acid and derivatives

1. Conversion to ester
O R C OH

1. NaOH 2. R'X R'OH HCl

R

React with alcohols Eliminated water acid catalyse Fisher Esterification

O C OR'

OR'

Limited to primary alkyl halide (SN2)

Limited to simple alcohol

Carboxylic acid and derivatives

2. Conversion to Amides (direct synthesis to amide)

O heat >100 C amide
o

O NH 2
R NH + R' C

OH

+ R

H2O

3. Conversion to Acid Halides

O

SOCl2

Cl

OH

PBr3

Br

Carboxylic acid and derivatives

4. Conversion to Acid Anhydrides

O

R O O

OH

R'

Cl

800C

R'

OH

R'

R'

Carboxylic acid and derivatives

5. Reduction of carboxylic acids

i. LiAlH4 primary alcohol : strong reducing agent (non-selective)

O C ii) H3O
+

CH2

OH

i) LiAlH4

CH2 CH2 OH

ii. BH3 - primary alcohol (gives selectivity)

O C OH (or B2H6) BH3.THF CH3 O C CH2OH

CH3

Carboxylic acid and derivatives

Carboxylic acid derivatives

Derivatives : compounds with FGs that can be converted to carboxylic acids by simple acidic or basic hydrolysis

Acyl group is bonded to electronegative atom (heteroatoms)

O O R' R C OR' R R C O O O C NH2

Cl

Acid chloride Acid anhydride

Ester

Amide

reaction type nucleophilic acyl substitution

Carboxylic acid and derivatives

Acid chloride
O R C X

O O Acid anhydride R C O C R'

Ester
R C

O OR'

Amide
R

O C NH2

reactivity of the derivatives decreases as the LG becomes more basic

Carboxylic acid and derivatives

Acid chloride
:
see RCOOH reaction

Synthesis :
O C NR'2 R' O C NHR'

Reaction

1. hydrolysis 2. alcoholysis 3. aminolysis

NH2

R'

R'2NH R'NH2
R'

4. reduction

R'

OR'

R'OH
O C R Cl

NH3
O H H

Py

H2O

1. LiAlH4 2. H3O
+

1. LiAlH4
C R' H

R'

OH

2. H3O

C R' OH

Carboxylic acid and derivatives

5. Reaction with organometallic reagents

Grignard reagent
O

RMgX 1. RMgX
R R

OH

Cl

ether 2. H3O

R R R

Gilman reagent
O C R Cu R' R' R O C R'

Cl

Li+R'2Cu Ether

+ R'Cu Ketone

6. Conversion to acid anhydride (See RCOOH reaction)

Carboxylic acid and derivatives

Acid anhydride
:
see RCOOH reaction

Synthesis :
O R' C NH2

Reaction

alcoholysis

aminolysis

R'

OR'

R'OH NH3
O O C R' O R C

H H

R'

H2O

OH

[R] LiAlH4

hydrolysis

H3O

R'

LiAlH4
H

H3O+

R'

OH

Carboxylic acid and derivatives

Ester
:
see RCOOH and ROCl reaction

Synthesis :
O R' C NH2

Reaction

hydrolysis

R'

aminolysis

OH

H2O NH3
O C OR

H+ / OH[R]

O
+

H R' C

R'

LiAlH4 H3O

LiAlH4
H

H3O+

R'

OH

Carboxylic acid and derivatives

Amide
: see RCOOH, ROCl, RCOOCOR and RCOOR reaction :
H
hydrolysis

Synthesis

Reaction

O R'
-

R'

OH

C H

NH 2

H / OH
O R' C

H2O

LiAlH 4
[R]

NH 2

Nitrile

O R
C : sp hybridised Geometry : planar C-N : polar bond undergo nucleophilic addition reactions

RCN
C N R C OH

NuR

Nu C

+ -

Products Imine anion

Nitrile

Synthesis

1. From 1 alkyl halide

RCH2Br SN2

Na+ CN-

RCH2CN

2. Dehydration of 1 amide

SOCl2 or
NH2

R POCl3

CN

Nitrile

Reaction
H R H NH2

reduction
H3O+

LiAlH4 H2O
R NH2 O

H2O
H+ / OHR

O OH

H+ / OHhydrolysis O R R'

* See preparation of RCOOH

1. R'MgX 2. H3O+

Grignard reagent

Nitrile

N R R N C H

LiAlH4,
H C
2-

LiAlH4, ether H2O

ether Dianion Imine anion

H R C

H NH2

R R C R'

R'MgX

H2O
R O C R'

+ NH3