Acylamidines 1,2,4-oxadiazoles

In comparison to N—S bond formation, O—N bond formation by essentially oxidative procedures has found few applications in the synthesis of five-membered heterocycles. The 1,2,4-oxadiazole system (278) was prepared by the action of sodium hypochlorite on A(-acylamidines (277) (76S268). The A -benzoylamidino compounds (279) were also converted into the 1,2,4-oxadiazoles (280) by the action of r-butyl hypochlorite followed by base. In both cyclizations A -chloro compounds are thought to be intermediates (76BCJ3607). 

In a related approach, the reaction of the acylamidine 201 (Scheme 29) with hydroxylamine results in loss of dimethylamine to give intermediate 202 which undergoes cyclization to give the 1,2,4-oxadiazole 203 <1999JME2218>. 

The intermediate acylamidine 244 functions as the three-atom component in reaction with hydroxylamine to give the [l,2,4-oxadiazol-5-yl]pyrazole 245, where the intermediate acylamidine 244 was obtained in good yield from reaction of the corresponding amide 243 with dimethylacetamide-dimethyl acetal (Scheme 37) <1999JME2218>. 

In 4,5-dihydro-1,2,4-oxadiazoles (82) the N—O bond breaks on irradiation to give A-acylamidines (83) (Equation (18)) <70JHC151, 88T4917>. Therefore, oxadiazolines (82) are sensitive to diffuse daylight. For R = t-butyl, elimination of RH occurs in preference to ring cleavage. 

Substituted acylamidines, such as (119), have been cyclized to oxadiazoles with hydroxylamine-0-sulfonic acid (Scheme 51) <9UMC1086>. Mechanistically related reactions include formations of oxadiazoles from oxazinium salts (120) (Scheme 52) <92KGS540>, and other oxadiazole-forming ring transformations <94H(38)ii3>, such as (121) (122) (Scheme 53) <89CB1107>. 

N—O bond formation by oxidative procedures has found less application. However, the 1,2,4-oxadiazole system (450) can be prepared by the action of sodium hypochlorite on N-acylamidines (449) (76S268). 

Oxadiazoles can also be prepared from amides via acylamidines, ° or via the cycloaddition of nitrile oxides to nitriles, as illustrated. "" 3-Alkylamino-l,2,4-oxadiazoles result from the reaction of N-acyl-l-benzotriazolyl-l-carboximidamides with hydroxylamine. " ... 

Oxadiazoles can be prepared by acylation of amidoximes or from amides via acylamidines. ... 

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