Curtius reactions, sodium azide

Formation of acyl azides from acyl chlorides is also a classical procedure - for the Curtius reaction. Sodium azide is used for the azidation under aqueous and anhydrous conditions, called the wet and dry methods respectively (equations 27 and 28 ). 

Unsaturated acids are converted to amines most satisfactorily by the Curtius reaction (sodium azide method). The Hofmann reaction is applicable with certainty only to a,/3-olefinic acid amides, since the olefin group in another position is likely to be halogenated by the reagent. The Schmidt reaction is applicable to all olefinic acids, although there is a possible danger of sulfonation at the site of unsaturation. 

Activation of the carboxylic acid as the acyl chloride permits direct reaction with azide anion to form the acyl azide substrates for Curtius rearrangement. Sodium azide is commonly used, and the reaction has been used on the process chemistry scale for the synthesis of benzyl-A-vinyl carbamate. Acryloyl chloride was combined with sodium azide in a biphasic system with phase-transfer catalysis (PTC), providing acyl azide 25. Upon heating, Curtius rearrangement provided vinyl isocyanate, which was distilled directly into benzyl alcohol containing phenothiazine (27) to inhibit polymerization of 26 and triethylamine to catalyze addition of the alcohol to the isocyanate. The vinyl carbamate product 28 was isolated by crystallization. As the autiior clearly pointed out, preparation and reaction of acyl azides, particularly on large scales, require appropriate safety precautions. 

N-benzylaniline with phosgene, and then with sodium azide to produce carbonyl azide 52. On heating, nitrogen is evolved and a separable mixture of nitrene insertion product 53 and the desired ketoindazole 54 results. The latter reaction appears to be a Curtius-type rearrangement to produce an N-isocyanate (54a), which then cyclizes. Alkylation of the enol of 54... 

The reaction of Curtius, which is especially to be preferred in the case of the higher members on account of the favourable solubilities of the intermediate products, involves as its first stage the preparation of the hydrazide from an ester (or acid chloride). The hydrazide is then converted, usually very readily, by the action of nitrous acid into the azide. In many cases it is more convenient to prepare the azide by treating an acid chloride with sodium azide previously activated with hydrazine hydrate.1 Azides easily undergo thermal decomposition, the two azo nitrogen atoms being eliminated as elementary nitrogen. In this way, however, the same radicle is formed as was invoked above to explain the Hofmann reaction ... 

A related reaction is the Curtius rearrangement, which replaces the cimide with an azide, RCO-N3. The azide can be formed by the reaction of an acyl chloride with sodium azide. 

Curtius and Rissom [41] prepared cupric azide by the action of an aqueous solution of sodium azide on an aqueous solution of cupric sulphate, obtaining the salt in a hydrated form. The anhydrous salt was prepared by Straumanis and Ciru-lis [125] in the form of dark brown, reddish sediment by reaction of lithium azide on cupric nitrate in an alcohol solution. Another method described by Curtius consists of reacting hydrazoic acid with metallic copper in an aqueous medium. 

Curtius rearrangement of the heteroaroyl azides, obtained from the reaction of the carboxylic acid chlorides with sodium azide, provides a route to the amino-pyrroles and -indoles (e.g. B-70MI30504, B-77MI30506, 78CPB1054), which, because of the ease of synthesis of the carboxylic acids, is frequently preferable to reduction of the nitro compounds. 

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. 

Arylsulfonylbenzimidoyl chlorides, with aminothiazoles, 50 Arylsulfonyl halides, 98, 115 Azide, with azothiazoles, 111 to carbamate, 16 Curtius rearrangement of, 15, 16 See also Sodium azide Azido thiazoles, 113 azidothiazole-thiazolotetrazole, 113 reactions of, 113... 

Earlier, Turrentine (Ref 4) obtained ferric azide in soln by electrolysis of a dil sodium azide soln using iron electrodes and later by Browne et al (Ref 6) on using iron electrodes in liq amm solns of ammonium azide, but the product was ammonolyzed to an Ammono-Basic Ferric Azide. Curtius et al (Refs 1 2), with ferric alum and NaN, obtained ferric azide in soln and they also repotted that iron dissolved in dil aq hydrazoic acid to form the azide, but the soln decompd on evapn giving either the basic azide or hydroxide. In 1934 Franklin (Ref 9) noted that aq hydrazoic acid reacts on iron to form ferric azide, nitrogen and ammonia together with a small amt of hydrazine. According to Franklin Ferrous Azide, Fe(Nj), is formed first and oxidizes to ferric azide when the soln is warmed with excess hydrazoic acid present. Ricca (Ref 11) studied the reactions of the ferric ion with hydrazoic acid on electrolysis of their solns and obtained results which would indicate that ferric azide has the structure [Fe(Nj)](Nj)2... 

Phthalein type dyes have been prepared from 2,3-dicarboxypyrazine by heating with phenols or aromatic amines and zinc chloride. For example, compound (25) was obtained with resorcinol (1353). Efforts to prepare 2,6-diaminopyrazine through a Curtius-Schmidt reaction on 2-acetamido-6-carboxypyrazine (with sodium azide, sulfuric acid, and trichloroacetic acid) proved unsuccessful (434). The preparation of bicyclic heterocyles from 2-amino-3-carboxypyrazines has been described in Section VIII. 1D(6). 

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