1.2.4- Oxadiazoles, phenyl-, nitration

Phenylisothiazole is nitrated predominantly in the meta position of the phenyl group, whereas 4-phenylisothiazole is nitrated ortho and para in the phenyl group <72AHC(14)1). Nitration of 3-phenyl-l,2,4-oxadiazole gives a mixture of m- and p-nitrophenyl derivatives <6301196). 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

Bromination of the phenyl group in 5-(4-nitrophenyl)-2-phenyl-l,3,4-oxadiazole in the presence of potassium bromate yielded o- (16%), m- (14%), and /)-bromo (26%) products, together with low yields of dibromo products <84JCR(S)382>. Similar results were obtained on nitration of 2,5-diphenyl-1,3,4-oxadiazole with fuming nitric acid to give dinitro products. The ratio of o- w-.-/ -nitration... 

The products of the thermolysis of 3-phenyl-5-(arylamino)-l,2,4-oxadiazoles and thiazoles have been accounted for by a radical mechanism.266 Flash vacuum pyrolysis of 1,3-dithiolane-1-oxides has led to thiocarbonyl compounds, but the transformation is not general.267 hi an ongoing study of silacyclobutane pyrolysis, CASSF(4,4), MR-CI and CASSCF(4,4)+MP2 calculations using the 3-21G and 6-31G basis sets have modelled the reaction between silenes and ethylene, suggesting a cyclic transition state from which silacyclobutane or a trcins-biradical are formed.268 An AMI study of the thermolysis of 1,3,3-trinitroazacyclobutane and its derivatives has identified gem-dinitro C—N bond homolysis as the initial reaction.269 Similar AMI analysis has determined the activation energy of die formation of NCh from methyl nitrate.270 Thermal decomposition of nitromethane in a shock tube (1050-1400 K, 0.2-40 atm) was studied spectrophotometrically, allowing determination of rate constants.271... 

The addition of amyl nitrate to a suspension of 2,4-diphenyl-5-nitro-soimidazole (37) in ether results in a mixture of 2,4-diphenyl-5-nitroim-idazole (38) and 3-benzoyl-5-phenyl-l, 2,4-oxadiazole (39), but a similar reaction using 4-phenyl-5-nitrosoimidazole gives only 3-benzoyl-1,2,4-oxadiazole (40) (60MI1). 

The nitration of 3-phenyl-1,2,4-oxadiazoles (45a-c) with mixed acid at -5 to 0°C gives a different orientation according to the substituent R. For the series 45a, meta products are obtained, for 45b both meta and para products are obtained, whereas for 45c only the 4-nitrophenyl product is obtained (63G1205). 

The relatively low electron density at carbon, coupled with the possibility of protonation at nitrogen, makes electrophilic substitution at carbon difficult. A further problem is acid-catalyzed ring cleavage, particularly with alkyloxadiazoles. No examples of nitration or sulfonation of the oxadiazole ring have been reported and attempted brominations were unsuccessful. A low yield of 2-(2-furoyl)-5-phenyl-l,3,4-oxadiazole is obtained when 2-phenyl-l,3,4-oxadiazole is treated with 2-furoyl chloride in the presence of triethylamine (77LA159). 

As a rule, oxadiazoles and thiadiazoles are not nitrated. Reports on the production of 2-nitro-5-amino-l,3,4-thiadiazole during the nitration of 2-amino-l,3,4-thiadiaz-ole [274] proved erroneous [275], The compound obtained in this case was 2-nit-ramino-l,3,4-thiadiazole [275], There is only a single paper on the nitration of derivatives of 1,3,4-oxa- and 1,3,4-thiadiazoles [276], 2-Dimethylamino-l,3,4-oxa-and 2-dimethylamino-l,3,4-thiadiazoles react with the nitrating mixture with the formation of 2-dimethylamino-5-nitro derivatives. Aryl-substituted oxadiazoles and thiadiazoles are nitrated in the phenyl ring [277, 278],... 

A 3 2 mixture of coned. H2SO2 and HNO3 (d. 1.52) added slowly at —5 to 0° to a soln. of 3-phenyl-5-acetamidomethyl-l,2,4-oxadiazole in coned. H2SO4, and the mixture dil. with ice 3-(m-nitrophenyl)-5-acetamidomethyl-l,2,4-oxadia-zole. Y 90%.—Nitration of the free aminomethyl derivative gave a mixture of m- and p-nitrophenyl isomers, whereas only the m-nitrophenyl derivative was obtained, when the amino group was acetylated or further removed from the ring. F. e. s. G. Palazzo and G. Cor si, G. 93, 1196 (1963). 

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