1,3,4-Oxadiazoles, from acylhydrazones

Oxadiazoles from acylhydrazones Oxidative ring closure... 

The second most popular method of oxadiazole preparation starts from acylhydrazones 110, which undergo cyclization usually under the action of oxidizing agents (Br2, PhN02, HgO, iodobenzene diacetate). Also, the use of acetic anhydride can lead to cyclization of compound 110. The cyclization can be supported by microwave irradiation. In particular cases, heating is sufficient to accomplish the reaction. 

Table 2 Representative examples of the synthesis of oxadiazole derivatives 122 from acylhydrazones 110a...

The 1,3,4-oxadiazole 113 is formed from the azo compound 112 by the action of triphenylphosphine <96SL652>. A general synthesis of 1,3.4-oxadiazolines consists in boiling an acylhydrazone with an acid anhydride (e.g., Scheme 18) <95JHC1647>. 2-Alkoxy-2-amino-l,3,4-oxadiazolines are sources of alkoxy(amino)carbenes the spiro compound 114, for instance, decomposes in boiling benzene to nitrogen, acetone and the carbene 115, which was trapped as the phenyl ether 116 in the presence of phenol <96JA4214>. 

Oxidative cyclization of acylhydrazones 110a, derived from aldehydes or ketones, with the use of lead tetraacetate (LTA) has been developed into a useful route to several disubstituted and tetrasubstituted oxadiazole derivatives 122, being a convenient source of relatively stable carbenes, like N(0)C , S(0)C , 0(0)C , or S(S)C <2000J(P1)2161 >. Some representative recent examples of the syntheses are collected in Table 2. 

Nonoxidative cyclization of acylhydrazones in acetic anhydride yields 4-acetyloxadiazolines, as in the conversion of hydrazone (96f R = 2-benzthiazolyl) into oxadiazoline (90b) <89MI 406-03). Hydrazones derived from tetra-O-acetyl-D-arabinose cyclized (Ac20/ZnCl2) to oxadiazoles pos-... 

Substituted acylhydrazones (95), formally derivatives of 1,2-diacylhydrazines (75), also cyclize to oxadiazoles (76), with loss of HX. Imidol ethers (95a R2 = H), prepared from acylhydrazines R1CONHNH2 and ortho esters HC(OR)3, cyclize on heating to monosub-stituted oxadiazoles (76 R1 = H). This reaction is an important synthesis of monosubstituted... 

A mixture of benzoylhydrazine and 2 eqs. benzoic acid heated at 240° for 6 h - 2,5-diphenyl-1,3,4-oxadiazole. Y 51%. Reduced yields were obtained from reactants in equimolar amount, while heating at lower temp. (150 ) gave intermediate diacyl-hydrazines the method is simple, work-up is easy, and starting materials readily available. F.e., also from N-acylhydrazones by KMn04 oxidation, s. P.S.N. Reddy, P.P. Reddy, Indian J. Chem. 26B, 890-1 (1987). 

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