Carboxylic Acids

Carboxylic acids and their Derivatives (chapter 36)

Structure

O

-I effect

R C O-H

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

Formation of RCOOH • • • •

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

Possible reactions Carbonyl group property

O R C

Acidic property

O H

Decarboxylation

Alkanolic property

Acidity

O R C extra +ve

Greater polarization of this bond

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 O H

H:-

R C H:-

H+

O

H R C OH H

H R C OH

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

O R

C

R C

NH2

O

Amide

R C O

O R

C

O

C

Acid Anhydride

R

Ester

O H

O R’

O R C

Cl

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 R C σ+

O

O

O R

Cl

C

σ+

O σ-

C

R

σ-

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

Reactions of acyl halides and acid anhydrides O:R C BH+

O R C

Z

Z

HB:

-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

Cl

C

RCOOH + HCl

O

O R

H2O:

O

H2O:

C

R

2 RCOOH

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 AlH3-

O AlH R C OR’

4

LiAlH4

O R C H

RCH2O-AlH3-

O R C OR’ H

+ R’O-AlH3H3O+

H3O+

RCH2OH

R’OH

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) LiAlH4 H3O+

RCONH2 →

→ RCH2NH2

Mechanism (Hofmann) O

O

R C NH + Br- + H2O

R C NH2 + OH- + Br2 O

OH

-

R C N

Br

H R-N=C=O + H2O

Br

O R C N-

Br

O R-NH-C-OH

-Br-

R-N=C=O

RNH2 + CO2

Mechanism (reduction) O

O- Li+

R C NH2 :H-

R C NH2 :HH LiAlH4

RCH2NH2 + Li2O