13. FUNCTIONAL DERIVATIVES OF CARBOXYLIC ACIDS

							 13. FUNCTIONAL DERIVATIVES OF
     CARBOXYLIC ACIDS
 13.1 STRUCTURES AND NOMENCLATURE

  O      O   O                         O              O
  C Cl   C   C                         C              C
R      R   O   R’                  R       OR’ R          N-R’
                                                          R”
Acyl halide Carboxylic anhydride       Ester         Amide
            R, R', R" May be aliphatic or aromatic
 13.2 NOMENCLATURE
     CH3COCl                CH3CH2COCl          CH3              COCl
   Acetyl chloride        Propionyl chloride        p-Toluyl chloride
 (Ethanoyl chloride)     (Propanoyl chloride)   (4-Methylbenzoyl chloride)

  CH3COOCOCH3          CH3CH2CH2COOCOCH3              C6H5COOCOCH3
  Acetic anhydride     Acetic butyric anhydride    Acetic benzoic anhydride
(Ethanoic anhydride) (Butanoic ethanoic anhydride)   (Benzenecarboxylic
                                                      ethanoic anhydride)
 CH3COOCH2CH3          CH3CH2CH2COOCH3              C6H5COOCH2CH3
   Ethyl acetate          Methyl butyrat              Ethyl benzoate
 (Ethyl ethanoate)      (Methyl butanoate )     (Ethyl benzenecarboxylate)

      HCONHCH3              CH3CH2CH2CONH2              C6H5CONH2
   N-Methylformamide           Butyramide                Benzamide
 (N-Methylmethanamide)        (Butanamide )         (Benzenecarboxamide)
13.3 PHYSICAL PROPERTIES

     -Polar, insoluble in water

     -Moderate boiling point (except amides)

     -Conversion to carboxylic acids on hydrolysis

     -Acyl halides: less stable, react readily with H2O

     -Carboxylic anhydrides: slightly stable than acyl halides

     -Esters: more stable than anhydrides, volatile liquid

     -Amides: stable, solids or high boiling liquid
13.4 SOURCES AND USES
  Acyl halides & Carboxylic anhydrides: from synthesis e.g. Acetic
  anhydride from dehydration of acetic acid or oxidation of
  acetaldehyde
  -Mainly used as reagents for the preparation of esters, cellulose
  acetate, aspirin, amides, paracetamal
  Esters & Amides: from plants and animals e.g. fats and oils,
  perfume, polyester fibers, proteins, polyamides (Nylons), etc.
  Synthesis from carboxylic acid and alcohol by esterification, from
  acyl chloride or carboxylic anhydride by reaction with alcohols of
  ammonia or amines
  -Esters are used as food additives, as solvents, as drugs, lacquer
  thinners, and reagents, etc.
  -Amides are used as solvents, reagents, etc.
13.5 TYPICAL REACTIONS

 -Hydrolysis
 CH3CH2COCl + H2O       ⎯→ CH3CH2COOH + HCl
 CH3COOCOCH3 + H2O      ⎯→ 2 CH3COOH
 C6H5COOCH3 + H2O/H+    ⎯→ C6H5COOH + CH3OH
 CH3CONH2 + H2O/H+      ⎯→ CH3COOH + NH4+
 -Alcoholysis
 CH3CH2COCl + CH3OH/pyr. ⎯→ CH3CH2COOCH3
      OH                          OCOCH3

               + Ac2O/AcONa ⎯→

     NO2                           NO2
-Aminolysis

       COCl                          CONHCH3

              + 2CH3NH2 /PhH   ⎯→

(CH3CO)2 + 2NH3 ⎯→ CH3CONH2 + CH3COO-NH4+
C6H5COOCH3 + (CH3)2NH ⎯→ C6H5CON(CH3)2 + CH3OH

-Friedel-Crafts Acylation

OCH3                                 OCH3

       + CH3COCl + Tl(OAc)3/CS2 ⎯→      (80%)

                                     COCH3
  -Reaction with Organometallic Reagents
HCOOCH2CH3 + 2CH3(CH2)3MgBr/Et2O → [CH3(CH2)3]2CHOH
                                        (85%)
  -Reduction
Cl3CCOCl + LiAlH4/Et2O then H3O+ → Cl3CCH2OH (64%)

                    LiAlH4/Et2O
CH3CH=CHCH2COOCH3 ⎯⎯⎯⎯⎯→ CH3CH=CHCH2CH2OH
                     then H3O+
                  LiAlH4/Et2O
CH3(CH2)10CONHCH3 ⎯⎯⎯⎯⎯→ CH3(CH2)11NHCH3
                   then H2O

  -Hofmann Degradation of Amides

            NaOBr/H2O
CH3CH2CONH2 ⎯⎯⎯⎯⎯→ CH3CH2NH2 + CO2 + NaBr
-Reaction with Carbanions

             1) NaOEt/EtOH
CH3COOCH2CH3 ⎯⎯⎯⎯⎯⎯→ CH3COCH2COOCH2CH3
               2) aq.AcOH

-Electrophilic Aromatic Substitution
                                 COCl

PhCOCl + Cl2/FeCl3 ⎯→
                                        Cl

                                       COOCH3

PhCOOPh + HNO3/H2SO4 ⎯→
                                             NO2
13.6 PREPARATIONS OF FUNCTIONAL DERIVATIVES OF
  ARBOXYLIC ACIDS

 CH3CH2CH2COOH + SOCl2/reflux ⎯→ CH3CH2CH2COCl

 CH3CH2COOH + CH3OH-H2SO4/reflux → CH3CH2COOCH3

 CH2=C=O + CH3COOH ⎯→ (CH3CO)2O

 C6H5COOH + NH3/heat ⎯→ C6H5CONH2
                                                 O
          COOH      200oC [-H2O]                 C
                    ⎯⎯⎯⎯⎯⎯→                          O
          COOH                                   C
                                                 O

13.7 ANALYSIS OF FUNCTIONAL DERIVATIVES OF
  CARBOXYLIC ACIDS
    -Hydrolysis back to its original components and analyze each
 component accordingly
    -Acyl chloride will give HCl
    -Carboxylic anhydride will yield only carboxylic acids
    -Ester will afford carboxylic acid and alcohol
    -Amide will end up with carboxylic acid and amine or ammonia