Acid chlorides Curtius reactions, sodium azide

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. 

Scheme 9.129. A representation of the formation of phenyUsocyanate (CjHsNCO) from the reaction between the acid chloride of benzenecarboxyhc acid (benzoyl chloride, CeHsCOCl) and sodium azide (NaNs) followed by rearrangement of the benzoylazide (C6H5CON3) (the Curtius reaction). ...

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 ... 

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. 

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). 

A useful variant of die Curtius reaction comprises the reaction of acyl chlorides in dichloromethane with sodium azide under phase transfer conditions, followed by treatment of the dried dichloromethane solution, which contains acyl azides, with a slight excess of trifluoroacetic acid. The resulting trifluo-roacetamides can easily be cleaved with potassium carbonate in aqueous methanol at room temperature, giving the amines (equation 30). ... 

The sodium azide pathway (Pathway A), Figure 4, begins with a thionylchloride treatment of the free acid to form the acyl chloride. Subsequent treatment with sodium azide may involve a non-aqueous environment (1,2-dimethoxy ethane, "dry method"), or an aqueous medium ("wet method"). The organic azide is recovered from the reaction mixture and converted into the isocyanate by the Curtius rearrangement. This may be accomplished in solid form ("dry method"), or in a non-aqueous solvent like dioxane or DMF ("solution method"). 

Acid azides are obtainable by reaction of the respective hydrazides with nitrous acid or of acid chlorides with sodium azide.302 378 Curtius degradation of 2-phenyloxazole-4-carbonyl azide (236) in boiling xylene... 

Reaction of acid chlorides with sodium azide/ NaN3, yields acyl azides/ RCON3. When heated, these undergo the Curtius rearrangement to amines, RNH2, or, in a non-hydroxylie solvent, to isocyanates, RNCO. Using the structure... 

Chromone-2-carbonyl azide (67) may be prepared in excellent yield either by adding sodium azide to a solution of the acyl chloride (68) in dioxan, or by the action of nitrous acid on the hydrazide (69) [157], A Curtius reaction on the azide led to an interesting series of derivatives of 2-aminochrbmone (70, R = OEt, Me, CCI3, NEta and similar groups), whose reactions have been studied [175-179]. 

The Schmidt reaction cannot be used on acids unstable towards sulfuric acid or on acids containing aromatic rings that are readily sul-fonated. The Curtius reaction can be used on such compounds in one of its modifications (see p. 339), in which an acid chloride is treated with sodium azide in boiling benzene and thus transformed directly to the amine, " it is almost as direct as the Schmidt process. 

Acid azides are commonly prepared by treating acid hydrazides in cold, aqueous solution with nitrous acid. The required hydrazides are prepared from esters hy reaction with hydrazine. Acid azides can also be made by treatment of acid chlorides with sodium azide. In Curtius ... 

H)-Oxazolones are formed by the spontaneous cyclization of /3-oxo isocyanates (equation 134). Similarly, o-hydroxyphenyl isocyanate, produced by the Curtius rearrangement of the azide of salicylic acid or by the action of sodium hypochlorite on salicylamide, forms benzoxazolone (equation 135). An analogous reaction is the formation of IV-phenyl-benzoxazolone by the action of thionyl chloride on the hydroxamic acid shown in equation (136) (78TL2325). Pyrolysis of aryl azidoformates affords benzoxazolones by nitrene insertion (equation 137) (81CC241). 

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