The Schmidt reaction or rearrangement

The conversion of a carboxylic acid into an amine by treatment with hydrazoic acid in concentrated sulphuric acid is known as the Schmidt reaction or rearrangement  

Other carbonyl compounds are within the scope of the reaction ketones give amides, and aldehydes yield nitriles and formyl derivatives of amines  

The reaction is illustrated by the conversion of 3 5-dinitrobenzoic acid into 3 5-dinitroaniline, and of acetophenone into acetaniUde  

When consideriug the mechanism of the reaction, it must be realised that hydrazoic acid is best formulated as a resonance hybrid 

The conjugate acid (II) may also be formed by the addition of hydrazoic acid to an acyUum (carbonium) ion  

In the alkyl aryl ketones, the aryl groups migrate preferentially, yielding V-aryl amides. 

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Reactions which insert an O or NH group next to a carbonyl can be used to form heterocycles (Scheme 23). The Schmidt reaction or the Beckmann rearrangement can accomplish this for nitrogen, the Baeyer-Villiger oxidation does it for oxygen. For example, cyclohexanone is converted in this way into 2-azepinone and into 2-oxepinone cycloheptanone yields the corresponding eight-membered heterocycles. 

By application of the Schmidt reaction, the conversion of a carboxylic acid into an amine that has one carbon atom less than the carboxylic acid, can be achieved in one step. This may be of advantage when compared to the Curtius reaction or the Hofmann rearrangement, however the reaction conditions are more drastic. With long-chain, aliphatic carboxylic acids yields are generally good, while with aryl derivatives yields are often low. 

Thienobenzazocine 179 is formed regioselectively in 65-93% yield when the rearrangement is carried out in PPA or PPA in xylene. The use of H2SO4 or PCI5 gives a mixture of regioisomers 179 180 in ratios from 90 10 to 60 40. The Schmidt reaction forms only thienobenzazocine 179 in 25-65% yield from benzo[4,3]-cyclohepta[l,2- 7]thiophen-4-one 181 (Scheme 50). 

Of equal importance to the Beckmann rearrangement for the preparation of azepines and azepinones is the Schmidt reaction of ketones. Again, however, with unsymmetrically substituted cyclohexanones or with bicyclic ketones such as a-tetralone, two azepines are possible, a -Substituted cyclohexanones invariably yield the product of attack by azide ion at the least hindered side of the protonated ketone as exemplified in Scheme 19 (B-67MI51600). 

Substituted salicylaldehydes react with hydrazoic acid in sulfuric acid to give indoxazenes 50,51 up to 15% of the corresponding 2-aminobenzoxazole (32) may be obtained as a by-product. The reaction is a variant of the Schmidt reaction, in which the intermediate nitre-nium ion may cyclize at once to the indoxazene, or rearrange and react with more hydrazoic acid, ultimately providing the benzoxazole. 

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