Anhydrides Curtius reactions, sodium azide

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 Curtius rearrangement has been extensively utilized for the synthesis of numerous cyclo-propylamines 4 from cyclopropanecarboxylic acids 1. The necessary acyl azides 2 are most conveniently obtained by reaction of sodium azide with the mixed anhydride of the cyclopropanecarboxylic acid and ethyl chloroformate. ... 

Scheme 9.134. A representation of the formation of phenyiisocyanate from the reaction between the acid anhydride of benzenecarboxylic acid [benzoic anhydride, (QH5C0)20] and sodium azide (NaNs) foiiowed by rearrangement of the benzoylazide (a Curtius-type reaction, vide supra).

The mechanism proposed for the Curtius degradation starts with the activation of carboxylic acid 119 by the (Boc)20, catalyzed by Zn(OTf )2, to generate carbonic anhydride 120, which is attacked by the azide ion to provide the unstable acyl azide 121 and sodium t-butoxide as a byproduct (Scheme 26). Next, isocyanate 122 is obtained by the decomposition of intermediate 121 with extrusion of N2. Reaction with sodium t-butoxide provides the desired carbamate 112. 

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