Sodium azide with mixed carboxylic-carbonic

Sodium, with l-bromo-3-chloro-cyclobutane to give bicyclo [l.l.O]butane, 51, 55 Sodium amalgam, 50, 50, 51 Sodium amide, with 2,4-pentane-dione and diphenyliodonium chloride to give l-phenyl-2, 4-pentanedione, 51, 128 Sodium azide, 50, 107 with mixed carboxylic-carbonic anhydrides, 51, 49 Sodium borohydride, reduction of erythro-3-methanesulfony-loxy-2-butyl cyclobutanecar-boxylate, 51, 12 reduction of 2-(1-phenylcyclo-pentyl)-4,4,6-trimethyl-5,6-dihydro-1,3(4H)-oxazine to 2-(1-phenylcyclopentyl)-4,4, 6-trimethyltetrahydro-l,3-oxazine, 51, 25 Sodium cyanoborohydride, used... 

The usual procedure of preparing acid azides, which involves treating an acid chloride with sodium azide,8,9 suffers from the disadvantage that it is often difficult to obtain pure acid chlorides in good yields from acids which either decompose or undergo isomerization in the presence of mineral acids.7 Synthesis of the azide by way of the ester and hydrazide10 has been used to circumvent this difficulty but is much less convenient. The present procedure permits ready formation of acid azides in excellent yields from mixed carboxylic-carbonic anhydrides and sodium azide under very mild conditions. 

The acyl azides required for Curtius rearrangement can be prepared under mild conditions via mixed carboxylic-carbonic anhydrides. The original 1961 report detailed preparation of racemic c/5-2-phenylcyclopropylamine. Treatment of carboxylic acid 58 with ethyl chloroformate and base in aqueous acetone provided the mixed anhydride, which was treated in situ with sodium azide. The crude acyl azide was isolated by extractive workup and underwent Curtius rearrangement, followed by acid hydrolysis. After raising the pH, the free base 59 was obtained in good overall yield. 

Another synthetic approach to acyl azides was reported by Weinstock one decade earlier. In this methodology, acyl azides are prepared via carboxylic-carbonic anhydrides. Generally, carboxylic acids are treated with ethyl chloroformate, generating mixed anhydrides which are trapped in situ by sodium azide. This sinple strategy was applied recently in the synthesis of ( )-spisulosine fScheme 4.21 After only 5 min in the presence of ethyl chloroformate, the appropriate carboxylic acid 58 was next treated with sodium azide. The intermediate ene-isocyanate 59 was obtained after heating, and this latter is finally hydrolyzed by water. The corresponding methyl ketone 60 was isolated in 40% overall yield. 

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