6.8.2 Halogenation

The carboxylic acids can be halogenated in α-position by treating with red phosphorus and halogens (Scheme 9). This is usually called Hell-Vollhard-Zelinsky reaction, which is an important process from the perspective of synthetic chemistry.

Scheme 9

The reaction is believed to proceed by an acyl halide intermediate (Scheme 10). The role of phosphorus is to ultimately convert a little of the acid to acid chloride which then undergoes halogenation at α-position.

Scheme 10

The α-haloacids so generated may be used as intermediates for the preparation of α-amino acids, α-hydroxy acids and α,β-unsaturated acids (Scheme 11).

Scheme 11

6.8.3 Arndt Eistert Synthesis

In order to go up by one carbon in the linear chain of a carboxylic acid, a protocol called Arndt Eistert synthesis may be employed (Scheme 12 ). In this protocol the homologation of a carboxylic acid is achieved by first converting the acid to acyl chloride which is then treated with diazomethane. The diazoketene so formed is treated with moist silver oxide to form a ketene which can be easily hydrolyzed to obtain the next higher carboxylic acid.

Scheme 12

6.8.4 Hoffman Rearrangement

An important reaction for the amides is the so called Hoffman reaction (Scheme 13). In this reaction, an amide is converted to an amine containing one less carbon. The reaction is carried out by treating the amide with an alkaline solution of sodium hypobromite.

Scheme 13

The isocyanate formed in this reaction is the key intermediate and can be found in other related rearrangement reactions of carboxylic acid and its derivatives. This isocyanate intermediate undergoes addition of water to form a hydroxamic acid which decomposes under the reaction conditions to give an amine. This reaction involves a concerted step of the removal of the bromide along with the migration of the R group which migrates with retention of configuration.

6.8.5 Lossen, Curtius and Schimdt Rearrangements

The Lossen rearrangement involves treatment of O-acyl derivatives of hydroxamic acids with base causing the departure of R¹CO_2^- as leaving group (Scheme 14). The other related reactions, Curtius and Schmidt reactions involve acid hydrazides and carboxylic acids as the starting point. In both cases, nitrogen is the leaving group from the intermediate azide

Scheme 14