Sodium nitrite acyl azides

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. 

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. 

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... 

---