From 1,2,4-oxadiazoles

From l,2A-oxadiazoles. The reaction of 5-substituted 3-amino-1,2,4-oxadiazoles 

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The removal of oxygen from 1,2,4-oxadiazole 4-oxides and polymer-supported analogues 187 can be achieved with triethyl- or trimethylphosphite, as the example in Equation (30) shows <2005JC0887>. 

All attempts to effect this rearrangement have failed.2,4 This observation agrees with the fact that the inverse reaction (from 1,2,4-oxadiazole to 1,2,5-oxadiazole) has been realized and found to be irreversible (see Section II,A,1). 

Mononuclear heterocyclic rearrangement Imidazoles from 1,2,4-oxadiazoles... 

UV irradiation of 2,5-diphenyloxadiazole (43) together with benzo[6]thiophene (42) yields an oxadiazepine (44) as the initial and major product, along with the 3-substituted benzo[6]thiophenes (45a) and (45b). These latter products are also obtained on photolysis of the oxadiazepine (Scheme 6). Prolonged irradiation gives products (45) and what is formally a trans [2 + 2] cycloadduct (46). This cycloadduct is also formed from oxadiazole (43) and benzo[6 jthiophene on irradiation with benzophenone as a sensitizer and the reaction presumably involves the triplet state of the oxadiazole. Somewhat similar photoreactions have been observed between oxadiazole (43) and methyIbenzo[6]thiophenes, indazoles, furan and indene (77BCJ3281). 

With suitably constructed oxazapyrrolidinones, new heterocycles can also be formed via the hydrogenolysis of the N—O bond followed by a reclosure sequence. The formation of pyrazinone 75 from isoxazolone indole 77 from oxadiazole and... 

Carboxylic acid hydiazides are prepared from aqueous hydrazine and tfie carboxylic acid, ester, amide, anhydride, or halide. The reaction usually goes poody with the free acid. Esters are generally satisfactory. Acyl halides are particularly reactive, even at room temperature, and form the diacyl derivatives (22), which easily undergo thermal dehydration to 1,3,4-oxadiazoles (23). Diesters give dihydtazides (24) and polyesters such as polyacrylates yield a polyhydrazide (25). The chemistry of carboxyhc hydrazides has been reviewed (83,84). 

Oxygen-containing azoles are readily reduced, usually with ring scission. Only acyclic products have been reported from the reductions with complex metal hydrides of oxazoles (e.g. 209 210), isoxazoles (e.g. 211 212), benzoxazoles (e.g. 213 214) and benzoxazolinones (e.g. 215, 216->214). Reductions of 1,2,4-oxadiazoles always involve ring scission. Lithium aluminum hydride breaks the C—O bond in the ring Scheme 19) 76AHC(20)65>. 

Acyltetrazoles lose nitrogen spontaneously to give oxadiazoles, and thiadiazoles can be prepared similarly from 2-thioacyltetrazoles (Scheme 63) (77AHC(21)323). 

A similar intramolecular trapping of the intermediate (511) from the photolysis of the corresponding methyl tetrazole-l,5-dicarboxylate (510) gave methyl 5-methoxy-l,2,4-oxadiazole-3-carboxylate (512). 

A study of the effect of substitution patterns in oxadiazoles and isoxazoles and their effect on the UV spectra in the lO -lO M concentration range was performed. Hypso-chromic effects and deviations from Beer s law were observed and were believed to be associated with antiparallel, sandwich-type self-association via dipole-dipole interactions. Beer s law is followed when the molecular dipole moments are small or when self-association is sterically hindered. 

The benzofuroxtin [benzofurazan oxide, 3,4-benzo-l,2,6-oxa-diazole-2-oxide, or 2,1,3-benzoxadiazole-l-oxide (1)] ring system has been reviewed briefly on several occasions, notably by Kaufman and Picard,Boyer, and Behr. The mqst recent of these covers the literature until 1959, and since that date there have been many advances in the subject. This, we feel, justifies the field being covered once more, and its separation from the monocyclic 1,2,5-oxadiazole oxides—the furoxans. We consider also other furoxano-fused compounds in this chapter, subject to the limitation that the ring adjacent to the furoxan is aromatic and six-membered. 

A mixture of 3-hydroxy-4-phenylfurazan and 1,2,4-oxadiazole 243 was prepared from a-phenyl-a-hydroximino hydroxamic acid by acylation and subsequent treatment with 15% aqueous NaOH (Scheme 164) (25G201). The reaction of tetraacetate 244 with sodium acetate hydrate in glacial acetic acid at 70°C gives 3,4-dihydroxyfurazan (9%) (92URP1752734). a-Hydroximino ester 245 reacts with hydroxylamine to form furazan 246 in 25% yield (Scheme 164) (79JHC689). 

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