Carboxylic acids and their Derivatives

(chapter 36)

Structure
Two functional groups adjacent to each other C=O and –OH groups modify each other and shows different properties.

O

-I effect

R C O-H

Formation of RCOOH
• • • • Halides → nitriles → acids Oxidation of 1o R-OH and R-CHO Oxidation of Alkylbenzene Iodoform reaction

Possible reactions
Carbonyl group property Acidic property

O R C

O H

Alkanolic property

Decarboxylation

Acidity
Greater polarization of this bond

O R C
extra +ve

O H
Polarization of this bond is increased, O-H bond is weakened. (Acidic)

Acidity

O R C .. O

OR C O

..

-ve charge is spreaded over the –C=O group and stabilize the anion RCOO-

Acid strength
RCOOH  RCOO- + H+
Acid HCOOH CH3COOH CH3CH2COOH CH3CH3CH2COOH pKa 3.8 4.8 4.9 4.8

All are weak acids, <1% ionized in water

Question
Explain the following order of acid strength a. RCOOH > C6H5OH > R-OH b. CCl3COOH > CHCl2COOH > CH2ClCOOH > CH3COOH

Formation of salts
Formation of salts by reacting with 2. Metals 3. Carbonates 4. Hydroxides

Reaction of the C=O group

RCOOH
NaBH4 No reaction

1. LiAlH4/ether 2. H3O+ H2/Ni No reaction

RCH2OH

Reduction mechanism
O R C
H:H+

H O H R C
H:-

O

H R C OH

H R C OH H

Nucleophilic substitution
Nucleophilic substitution • C-OH bond as attractor of Nu: (HBr, PBr3, SOCl2) • C=O play background role in enhancing the reactivity of C-OH bond by attracting Nu:

Acid Derivatives
O R C
Amide

O
NH2

R C O R C O H
Ester

O R’

O R C O

O C R

O R C Cl

Acid Anhydride

Acid Chloride

Conversion to Acid Derivatives
1. To Acyl chlorides PCl5/SOCl2 RCOOH → RCOCl

1. To Ester H+ R’COOH + ROH  R’COOR + H2O

Conversion to Acid Derivatives
1. To acid anhydride RCOOH + R’COCl →RCOOCOR’ + HCl 1. To amide RCOOH + NH3 → RCOO-NH4+
excess RCOOH

RCONH2 + H2O

reflux (excess RCOOH is used to repress the hydrolysis of amide)

Reactions of acyl halides and acid anhydrides
O R C
σ+

O R
σ-

O O
σ-

C

Cl

σ+

C

R

C=O provides extra polarity to activate the C-X, C-O bonds

Reactions of acyl halides and acid anhydrides
O R C
HB:

Z

O:R C BH+ Z
-Z-

O R C B

-H+

O R C BH+

Reactivity: -Cl > -OCOR > -OR > -NH2 (base strength: NH2->OR->OCOR->Cl-)

pKa HCl -2.2 RCOOH 4~5 ROH 16~19 NH3 34

Reaction with water
O R C
O R C O

Cl

H2O:

RCOOH + HCl

O C R

2 RCOOH

H2O:

Reaction with R-OH
CH3COCl + R-OH → CH3COOR + HCl
COOH OH + (CH3CO)2O COOH OCOCH3 + CH3COOH (Aspirin)

Reaction with ammonia and amine
CH3COCl + 2NH3 → CH3CONH2 + NH4Cl CH3COCl + NH(CH3)2 → CH3CON(CH3)2 + HCl (CH3CO)2O + 2NH3 → CH3CONH2 + NH4+CH3COO(CH3CO)2O + 2RNH2 → CH3CONHR + RNH3+CH3COO-

Reactions of esters
1. Hydrolysis H3O+, reflux RCOOR’ + H2O  RCOOH + R’OH OHRCOOR’ + H2O  RCOO- + R’OH • Reduction with LiAlH4 1. LiAlH4/ether RCOOR’ → RCH2OH + R’OH 2. H3O+

Mechanism of reduction
O AlH R C OR’
4

O R C OR’ H

AlH3-

LiAlH4

O R C H

+ R’O-AlH3H3O+

RCH2O-AlH3-

H3O+

R’OH

RCH2OH

Reactions of amides
1. Hydrolysis
reflux

RCONH2 + H3O+  RCOOH + NH4+
reflux

RCONH2 + OH-  RCOO- + NH3 1. Dehydration
P2O5, heat

C6H5CONH2

C6H5C≡N + H2O

Reactions of amides
1. Hofmann degradation CH3CH2CONH2 + 4KOH + Br2 → CH3CH2NH2 + K2CO3 + 2KBr + 2H2O (one carbon atom less) • Reduction (LiAlH4) RCONH2 →
LiAlH4 H3O+

→ RCH2NH2

Mechanism (Hofmann)
O R C NH2 + OH- + Br2 O R C N H R-N=C=O + H2O Br OH
-

O R C NH + Br- + H2O O R C NBr Br -BrR-N=C=O

O R-NH-C-OH

RNH2 + CO2

Mechanism (reduction)
O R C NH2 :HO- Li+ R C NH2 :HH
LiAlH4

RCH2NH2 + Li2O