1.2.4- Oxadiazoles, 3-acylamino rearrangements

Aminoethyl)-l,2,4-oxadiazoles (606 R = alkyl or aryl) readily isomerize to 3-acylamino-2-pyrazolines (607) on heating. Treatment of the salt (608) with triethylamine yields the transient ylide (609), which decomposes to methyl-phenylcarbodi-imide (610). 2,3-Diphenyl-l,2,4-oxadiazolin-5-one (611) rearranges photochemically to a mixture of the oxadiazolinones (612) and (613) pyrolysis gives 2-phenylbenzimidazole with extrusion of carbon dioxide. The oxadiazole (614) rearranges thermally to the indazole (615). ... 

The reaction is illustrated by the conversion of the 1,2,4-oxadiazole oxime (504) into the 3-acylamino-l,2,5-oxadiazole (505). This irreversible rearrangement occurred on heating (504) in hydrochloric acid (81AHC(29)l4l). Isoxazoles also undergo this rearrangement and these are discussed in Chapter 4.16. 

Several 3-acylamino-l,2-benzisoxazoles such as (278) underwent rearrangement to 3-(o-hydroxyphenyl)-l,2,4-oxadiazoles (279) on heating with base. It has been questioned whether the same mechanism is operative in these last rearrangements (8lAHC(29)l4l, p. 150). 

A series of 3-amino (or 3-N-substituted amino)-l,2,4-oxadiazoles 108 can be obtained in moderate to high yields by the photoinduced rearrangement of 3-acylamino-l,2,5-oxadiazoles (furazans) 106 irradiated in the presence of an excess of ammonia or aliphatic amines [64—66]. The reaction follows a fragmentation-cycloaddition route, with the initial formation of a nitrile and a nitrile-oxide the latter is attacked by a nitrogen nucleophilic reagent (ZH in Scheme 12.29), and the open-chain interme-... 

Buscemi, S., Vivona, N. and Caronna, T. (1995) Photoinduced molecular rearrangements. Some investigations of the photochemical behaviour of 3-acylamino-l,2,5-oxadiazoles (furazans). Journal of Organic Chemistry, 60 (13), 4096—4101. 

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

Some patents36 have described the rearrangement of a 3-acylamino-5-methylisoxazole (30) into 5-substituted 3-acetonyl-l,2,4-oxadiazole 31. The treatment of 30 with sodium methoxide produced an mhr as well as a ring expansion furnishing 31 which, in turn, by methylation followed by treatment with triethylamine, gave 32, with a 1,2,4-oxadiazole - isoxazole conversion (see Section II,C,1). 

Examples of this rearrangement that involve hydrazone as well as hy-drazide side-chain units have been reported, Some arylhydrazones of 5-substituted 3-aroyl-l,2,4-oxadiazoles (43) (see Table II) rearrange by heating at their melting point, or by refluxing with bases or acids, to 4-acylamino-2,5-di-aryl-1,2,3-triazoles (44) 41 44... 

The more reactive 5-substituted 3-arylformamidino-l,2,4-oxadiazoles (65) were rearranged to 3-acylamino-l,2,4-triazoles (66) both by melting and by the action of sodium hydroxide in ethanol at 20°C. The same ring transformation is achieved by heating the 3-ethoxyformylamino-l,2,4-oxa-diazoles (67) with anilines.52... 

Attempts55,56 to synthesize 5-substituted 3-phenylthioureido-l,2,4-oxadi-azoles (77) by reaction of 3-amino-l,2,4-oxadiazoles (76) with phenylisothio-cyanate directly furnished 3-acylamino-5-anilino-l,2,4-thiadiazoles (78), the rearrangement products derived from 77 which underwent a fast mhr55,56 under the experimental conditions. 

The 5-substituted 3-amino-l,2,4-oxadiazole (76) condensed with -di-ketones and /Fketoesters, giving the corresponding 3-enaminones (91). These compounds did not rearrange on melting, but with sodium ethoxide in DMF (a dipolar aprotic solvent which increased the nucleophilic power of anion 93) at 110°C they were converted into the 4-substituted 2-acylamino-5-acylimidazoles (92).60,61... 

Around this time, Spinelli et al.12 commenced research into the mechanism of mhrs using as substrates the arylhydrazones of 5-substituted 3-benzoyl-1,2,4-oxadiazoles (43) which rearranged to the 2-aryl-5-phenyl-4-acylamino-... 

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