Acid hydrazides, Curtius rearrangement, acyl

Goodman and Chorev 75 found that the required a-aminoacyl azides 14 are best prepared by reaction of the mixed anhydride of the amino acid with sodium azide. This method led to slightly better yields than the nitrosylation of TV-formylaminoacyl hydrazide. Curtius rearrangement of the a-aminoacyl azide 14 yielded the isocyanate 16, which was subsequently trapped as 17 or 18 as shown in Scheme 2. Comparable yields were obtained by nitrosylation with tert-butyl nitrite. 76 Other methods of acyl azide formation have rarely been employed for PMRI-peptide synthesis. Only Fincham et al. 11 reported the use of trimethylsilyl azide to synthesize an acyl azide en route to a PMRI-peptide. 

The thermal decomposition of acyl azides into isocyanate intermediates is known as Curtius rearrangement reaction (Scheme 5.2) [27, 28]. Conventionally used general methods to synthesize aroyl azides are limited to diazotization of hydrazides and reactions of NaNs with acid chlorides, mixed anhydrides, and Al-acyl benzotriazoles [35-38]. However, these procedures involve highly reactive chemicals which put significant limitations on functionalities of the substrate. The development of methodologically new, highly functional-group tolerant, catalytic routes to aroyl azides is particularly desirable. 

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). ... 

A closely related reaction of general applicability is the Curtius rearrangement222 of acyl azides. The rearranging species in the Schmidt reaction (see p. 898) is in fact also a protonated acyl azide these azides are readily prepared by the action of nitrous acid on acyl hydrazides which are themselves formed from esters and hydrazine (Section 9.6.17, p. 1269). On heating in aprotic solvents the acyl azides decompose to yield the corresponding isocyanates in good yield. 

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. 

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