Azides acyl, isocyanates from

A violent explosion occurred during vacuum distillation of 4-chlorophenyl isocyanate, prepared by Curtius reaction from the azide. It was found by IR spectroscopy that this isocyanate (as well as others prepared analogously) contained some unchanged azide, to which the explosion was attributed. The use of IR spectroscopy to check for absence of azides in isocyanates is recommended before distillation [1], Subsequently, the explosion was attributed to free hydrogen azide, produced by hydrolysis of the unchanged acyl azide [2],... 

One principal access to 1,2,4-oxadiazoles consists of N—O bond formation by electrocyclic ring closure of nitrenoids N—CR —N—CR =0. For instance, heating acyl isocyanates (159) with trimethylsilyl azide alfords high yields of 1,2,4-oxadiazoles (Scheme 68) <79JCS(P1)185,80JOC5130). Similarly, elimination of HCl from A -chloroamidines (160) (Scheme 69) <84BCJ1I6> and ther-... 

Tributylstannyl azide (51), prepared from tributylstannyl chloride and sodium azide, is also useful for the direct conversion of acyl chlorides to isocyanates (equation 32). In addition, succinic anhydride... 

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"). 

Alkyl isocyanates, like n-butyl isocyanate, do not react with different alkyl azides and aryl azides respectively. In contrast, aryl isocyanates 131 react with alkyl azides 130 like n-butyl azide or cyclohexyl azide to yield 1-alkyl-4-aryl-A -tetrazoline-5-ones 132, however, aryl isocyanates do not react with aryl azides. The reactions take place within some hours and up to several days at elevated temperatures, ranging from 55 to 130 °C, and are performed in benzene or without solvent (Scheme 29A). The addition of aryl azides to acyl isocyanates, such as benzoyl isocyanate or carboalkoxy isocyanates like chloroacetyl isocyanate and trichloroacetyl isocyanate, was unsuccessfully attempted at different reaction conditions [107]. 

The classic Curtius route to isocyanates from carboxylic acids via the acyl azides involves three separate synthetic steps, two of which are potentially explosive. 

Acyl azides may loose N2 on heating and rearrange to isocyanates (Curtius rearrangement), which may be solvolyzed. Some of the possibilities of classical carboxyl conversions are exemplified in the schemes below, which are taken from a triquinacene synthesis (R. Russo, 1971 C. Merder, 1973) and the ergotamine synthesis of A. Hofmann (1963). 

Special reactions of hydrazides and azides are illustrated by the conversion of the hydrazide (205) into the azide (206) by nitrous acid (60JOC1950) and thence into the urethane (207) by ethanol (64FES(19)105Q) the conversion of the same azide (206) into the N-alkylamide (208) by ethylamine the formation of the hydrazone (209) from acetaldehyde and the hydrazide (205) and the IV-acylation of the hydrazide (205) to give, for example, the formylhydrazide (210) (65FES(20)259). It is evident that there is an isocyanate intermediate between (206) and (207) such compounds have been isolated sometimes, e.g. (211). Several of the above reactions are involved in some Curtius degradations. 

A third approach to 3-amino-/3-lactams is by Curtius rearrangement of the corresponding acyl azides. These are readily prepared from r-butyl carbazides, available via photochemical ring contraction of 3-diazopyrrolidine-2,4-diones in the presence of f-butyl carbazate (c/. Section 5.09.3.3.2). Thus treatment of (201) with trifluoroacetic acid followed by diazotiz-ation gives the acyl azide (202) which, in thermolysis in benzene and subsequent interception of the resulting isocyanate with r-butanol, yields the protected 3-amino-/3-lactam (203) (73JCS(P1)2907). 

The Curtius rearrangement can be catalyzed by Lewis acids or protic acids, but good yields are often obtained also without a catalyst. From reaction in an inert solvent (e.g. benzene, chloroform) in the absence of water, the isocyanate can be isolated, while in aqueous solution the amine is formed. Highly reactive acyl azides may suffer loss of nitrogen and rearrange already during preparation in aqueous solution. The isocyanate then cannot be isolated because it immediately reacts with water to yield the corresponding amine. 

Section A of Scheme 10.15 contains a number of examples of Curtius rearrangements. Entry 1 is an example carried out in a nonnucleophilic solvent, permitting isolation of the isocyanate. Entries 2 and 3 involve isolation of the amine after hydrolysis of the isocyanate. In Entry 2, the dihydrazide intermediate is isolated as a solid and diazotized in aqueous solution, from which the amine is isolated as the dihydrochloride. Entry 3 is an example of the mixed anhydride procedure (see p. 948). The first stage of the reaction is carried out in acetone and the thermolysis of the acyl azide is done in refluxing toluene. The crude isocyanate is then hydrolyzed in acidic water. Entry 4 is a reaction that demonstrates the retention of configuration during rearrangement. 

The pyrido[l,2-tf][l,3,5]triazine-2,4(3//)-dione derivative 89 was obtained in a cycloaddition reaction of diphenyl-methyl isocyanate 90 with 2-pyridyl isocyanate 91 derived from the corresponding acyl azide via Curtius rearrangement <2002ARK438>. Compound 89 was also synthesized by the reaction of diphenylacetyl chloride 118 and picolinyl azide 116a in the presence of triethylamine (Scheme 11) <2002ARK438>. ... 

Gerardin, P., Maurin, E. and Loubinoux, B. (1995). Reaction of wood with isocyanates generated in situ from acyl azides. Holzforschung, 49(4), 379-381. 

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