Hydrazides acyl, reaction with nitrous acid

The Cunius degradation of acyl azides prepared either by treatment of acyl halides with sodium azide or trimethylsilyl azide [47] or by treatment of acyl hydrazides with nitrous acid [f J yields pnmarily alkyl isocyanates, which can be isolated when the reaction is earned out in aptotic solvents If alcohols are used as solvents, urethanes are formed Hydrolysis of the isocyanates and the urethanes yields primary amines. 

As described earlier (Section 4.4.1.1), the intermediates of the Curtius reaction are acyl azides, which themially rearrange to isocyanates. One of the classical procedures for the preparation of acyl azides consists of the formation of hydrazides from esters and hydrazine, followed by treatment of the hydrazides with nitrous acid, generated from sodium nitrite and acetic, hydrochloric or sulfuric acid. Acyl azides are commonly used in the crude state or in solution since they are thermally unstable and potentially explosive. 

Hydrazides. Acyl halides, esters, and amides react with hydrazine to form hydrazides which are themselves useful synthetic intermediates. Treatment of the hydrazide with nitrous acid yields the acyl azide which, upon heating, gives isocyanates (Curtius rearrangement). Di- or trichlorides are obtained upon reaction with Phosphorus(V) Chloride Crotonate and other esters have been cleaved with hydrazine to liberate the free alcohol (eq 10). ... 

Nevertheless, satisfactory results were often obtained in cyclizations through the azide. The method rests on the large difference in the rate of conversion of the hydrazide to the azide and that of deamination of the (protonated) N-ter-minal residue by nitrous acid. Hence, with the calculated amount of sodium nitrite (or alkyl nitrite) rapid conversion of the hydrazide to the azide can take place without significant deamination at the N-terminus. Cyclization occurs on addition of base that deprotonates the amino group and thus permits its acylation. This addition, however, should be preceded by dilution to decrease the extent of intermolecular reactions... 

Protection of amino groups from nitrous acid by acylation is not always successful, for deacylation may occur during treatment of the esters with hydrazine. Ethyl 2,6-dibenzamidoisonicotinate when treated with hydrazine gives 2,6-diMmnoisonicotinyl hydrazide the ethyl ester of phthalylglycine is similarly cleaved to gly(yl hydrazide and phthalhydrazide, a gener reaction for phthalimides (see p. 381). 

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