Page 271 - Advanced Organic Chemistry Part B - Reactions & Synthesis

among these derivatives are usually straightforward, involving such fundamental 243
reactions as ester saponification, formation of acyl chlorides, and the reactions of
amines with acid anhydrides or acyl chlorides to form amides. The mechanisms of SECTION 3.4
these reactions are discussed in Section 7.4 of Part A. Interconversion of
Carboxylic Acid
Derivatives
– OH
RCO CH 3 RCO 2 – + CH OH
3
2
H O
2
RCO H + SOCl 2 RCOCl + HCl + SO 2
2
RCOCl + R′ NH RCONR′ + HCl
2
2
When a multistep synthesis is being undertaken with other sensitive functional groups
present in the molecule, milder reagents and reaction conditions may be necessary. As
a result, many alternative methods for effecting interconversion of the carboxylic acid
derivatives have been developed and some of the most useful reactions are considered
in the succeeding sections.

3.4.1. Acylation of Alcohols
The traditional method for transforming carboxylic acids into reactive acylating
agents capable of converting alcohols to esters or amines to amides is by formation
of the acyl chloride. Molecules devoid of acid-sensitive functional groups can be
converted to acyl chlorides with thionyl chloride or phosphorus pentachloride. When
milder conditions are necessary, the reaction of the acid or its sodium salt with oxalyl
chloride provides the acyl chloride. When a salt is used, the reaction solution remains
essentially neutral.

O
O
CH 3 H CH H
ClCOCOCl 3
CH 3 CH
H 25°C 3 H
CO Na COCl Ref. 98
2
This reaction involves formation of a mixed anhydride-chloride of oxalic acid, which
then decomposes, generating both CO and CO.
2
O
Cl –
O O O
R + CO 2 + C O
R Cl
Cl O

Treatment of carboxylic acids with half an equivalent of oxalyl chloride can generate
anhydrides. 99
O O O O
2 RCO H + ClCCCl RCOCR + CO 2 + CO + 2 HCl
2
1–1.2 equiv
98 M. Miyano and C. R. Dorn, J. Org. Chem., 37, 268 (1972).
99
R. Adams and L. H. Urich, J. Am. Chem. Soc., 42, 599 (1920).