Rearrangement from azides

Saxitoxin is a small tricyclic structure isolated from oceanic red tides it has attracted much interest for its peculiar structure and toxicity as a paralytic agent. The core structure that is related to a l-iminooctahydropyrrolo[l,2-f]-pyrimidine nucleus was prepared by rearrangement after oxidation of a double bond contained in a medium-size guanidine ring. This key intermediate in the synthesis was prepared from azide 376 with a judicious use of Mbs... 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

Scheme 2 Preparation of gem-Diaminoalkyl Derivatives by Curtius or Hofmann Rearrangement from Acyl Azides or Acyl Amides...

Compound 44 has the presumed Z configuration, since it is obtained by a sterically controlled hydrolysis of the diester 43. The E configuration of 46 then follows from rearrangement of azide to isocyanate 45, which occurs with retention of configuration. 

A key step in a synthesis of the carbazole alkaloid murraya-quinone-B (132) is the concomitant indole ring formation and regio-selective Claisen rearrangement from the azide (129), which on... 

Acyl halides react with TMSA to give trimethylsilyl halides and the corresponding isocyanates in a range of 83-98% yields, which are rearranged from the acyl azides via the Curtius degradation (eq 2). However, a reaction of aroyl chlorides with TMSA in the presence of zinc iodide at 0 °C gives the corresponding azides in 85-96% yields (eq 3). ... 

It should be obvious from the foregoing remarks that the rearrangement of azides in the complete absence of a solvent is highly hazardous however, it has sometimes been accomplished successfully. Catalystf... 

Preparation of Isocyanates. Isocyanates are prepared by rearrang-ii azides in inert solvents such as ethers, chloroform, benzene and its homologs, malonic ester, mid ligroin. If the isocyanate is to be isolated, the solvent is removed by distillation, or, if the isocyanate is the lower boiling, it is distilled directly. In this operation, a safety shield is advisable to guard against a possible explosion of yet undecomposed azide. Isocyanates can be converted to sym-ureas by reaction with water, to urethans by reaction with alcohols, to os-ureas by reaction with amines, or to acylamines by reaction with anhydrous acids or acid anhydrides, or they can be hydrolyzed directly to amines. Acylamines can also be obtained. from isocyanates by reaction with Grignard re-... 

Although the ethyl urethans have been the ones most commonly prepared from azides, almost any urethan can be prepared with the appropriate alcohol. Rearrangement in methanol usually succeeds as well as in ethanol, but occasionally, because the decomposition temperature of the azide may be above the boiling point of methanol, the azide is recovered unchanged or is converted to the methyl ester. ... 

Irradiation (s. a. under CFfiOOH) Azomethines from azides with rearrangement... 

Thermal decomposition of ( >-azidophenylthio)uracil (299) furnishes a 2 1 mixture of the dihydro-5-thia- (300) and dihydro-10-thia-isoalloxazines (301). The formation of the former product is analogous to the preparation of pheno-thiazines from o-azidodiphenyl sulphides, and presumably involves rearrangement via a Spiro-intermediate. However, the direct insertion of the nitrene intermediate derived from azide (299) into the uracil ring to give the 1,4-benzothiazine system (301) is unique. More surprising is the production of the unrearranged 10-thiaisoalloxazine (301) (70%) as the only product from the photolysis of (299) in methanol solution. 

Benzofuran isocyanate was prepared by Curtins rearrangement from 2-benzo-furoyl azide with acid hydrazide under microwave irradiation (Wang et al., 2006). A series of asymmetric semicarbazides was synthesized by reactions of 2-benzofuran isocyanate. This method gives high yield under mild conditions compared to the conventional method. 

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). 

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

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