Nucleophilic Substitutionin Acyl Chlorides

General Mechanism for Nucleophilic Acyl Substitutioninvolves formation and dissociation of a tetrahedral intermediateHY-HX

Preparation of Acyl Chloridesfrom carboxylic acids and thionyl chloride SOCl2heat+SO2+HCl(90%)

Reactions of Acyl Chlorides

Reactions of Acyl Chlorides++HClAcyl chlorides react with carboxylic acids to give acid anhydrides:

Reactions of Acyl Chlorides++HClAcyl chlorides react with carboxylic acids to give acid anhydrides:via:

Example+pyridine(78-83%)

Reactions of Acyl Chlorides++HClAcyl chlorides react with alcohols to give esters:R'OH

Reactions of Acyl Chlorides++HClAcyl chlorides react with alcohols to give esters:R'OHvia:

Example+(CH3)3COHpyridine(80%)

Reactions of Acyl Chlorides++H2OAcyl chlorides react with ammonia and amines to give amides:R'2NH+ HO+Cl

Reactions of Acyl Chlorides++H2OAcyl chlorides react with ammonia and amines to give amides:R'2NH+ HO+Clvia:

Example+NaOH(87-91%)H2O

Reactions of Acyl Chlorides++HClAcyl chlorides react with water to give carboxylic acids (carboxylate ion in base):H2O++Cl2HO+H2O

Reactions of Acyl Chlorides++HClAcyl chlorides react with water to give carboxylic acids (carboxylate ion in base):H2Ovia:

Example+H2O+HCl

ReactivityAcyl chlorides undergo nucleophilic substitution much faster than alkyl chlorides.C6H5CH2ClRelative rates of hydrolysis (25C)1,0001

Preparation ofCarboxylic Acid AnhydridesAnhydrides can be prepared from acyl chlorides

Some anhydrides are industrial chemicalsAcetic anhydridePhthalic anhydrideMaleic anhydride

From dicarboxylic acidsCyclic anhydrides with 5- and 6-membered rings can be prepared by dehydration of dicarboxylic acids(89%)+ H2O

Reactions ofCarboxylic Acid Anhydrides

Reactions of Anhydrides

Reactions of Acid Anhydridesnormally, symmetrical anhydrides are used (both R groups the same)reaction can be carried out in presence of pyridine (a base) or it can be catalyzed by acids++Carboxylic acid anhydrides react with alcohols to give esters:R'OH

Reactions of Acid Anhydrides++Carboxylic acid anhydrides react with alcohols to give esters:R'OHvia:

Example(60%)H2SO4

Reactions of Acid Anhydrides++Acid anhydrides react with ammonia and amines to give amides:2R'2NH

Reactions of Acid Anhydrides++Acid anhydrides react with ammonia and amines to give amides:2R'2NHvia:

Example(98%)+

Reactions of Acid Anhydrides+2RCOHAcid anhydrides react with water to give carboxylic acids (carboxylate ion in base):H2O+2RCO+2HOH2O

Reactions of Acid Anhydrides+2RCOHAcid anhydrides react with water to give carboxylic acids (carboxylate ion in base):H2O

Example+H2O

31 41 74444444444444434434444444444