1,3,4-Oxadiazoles Subject

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. 

Derivatives of 5-alkyl-2-(l,3,4-oxadiazol-2-yl)thiophenes 168 were synthesized and their photochromic and fluorescent properties studied. A solution of the photochrome was subjected to irradiation over a wide range, including the lines of the mercury spectrum at 313, 365, 405, 436, 546, and 578 nm. It was discovered that the open form of compounds 168 showed strong fluorescence <2002CHE165>. 

Dioximes of a-diketones such as benzil on oxidation with IBTA are converted into 1,2,5-oxadiazole-A-oxides (furoxans) in high yields (75S445) (Eq. 35). Benzo- (Scheme 46) and pyrido-oxadiazoles (Eq. 36) are formed when o-nitroaniline and 3-amino-2-nitropyridine are subjected to similar oxidation. 

The chemistry of the 1,2,3-oxadiazole ring system is confined almost entirely to the mesoionic sydnones and related compounds. Sydnones are sensitive to hydrolysis, especially in basic media where they are rapidly cleaved. Nevertheless a range of useful reactions of sydnones, involving both ring cleavage and substitution with retention of the ring system, is known. Many of the publications that have appeared in the period 1982-1995 represent modifications or extensions to known reactions of sydnones. The subjects covered include the following. 

The 1,2,5-oxadiazole ring system has been the subject of intensive investigation since the first examples were reported in the 1850s. While much of the early work involved structure elucidation, particularly for the iV-oxides, current interest centers mainly on their reactivity and synthetic applications of their chemistry. 

Examples of the many oxadiazolinones which show herbicidal activity (weed killers) are (118e), (118f), and oxadiazon (118g), which is the subject of many regular reports in the literature. Insecticidal activity is shown by oxadiazolinones (118h), (1181), (the latter is an aphicide), and oxadiazole (117h). 

In a subsequent study, the impact of replacing one or both of the amide bonds with either a diacylhydrazine or a 1,3,4-oxadiazole was explored [36]. (fi)-Bromoallyl ethers were employed in the PI and Pi positions and similarly subjected to Suzuki conditions using the two aryl boronic acids that gave the most potent inhibitors in the previous study. Potent plasmepsin inhibitors were produced however, no real improvements in activity compared to the parent compound were observed (Scheme 5). The use of the preligand, [(f-Bu3)PH]BF4 [37], in combination with barium hydroxide was found beneficial although the yields were very low in these reactions. 

The oxadiazole ring has little aromatic character. Both C—N bond distances suggest conjugated double bond character in the only oxadiazole (90) that appears to have been subjected to X-ray analysis (79AX(B)2256). The C—N bond lengths in the aminopyridine... 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

The seventh volume of Advances in Heterocyclic Chemistry includes surveys of four groups of heterocyclic compounds furans (P. Bosshard and C. H. Eugster), dithiolium salts (H. Prinzbach and E. Futterer), 1,3,4-oxadiazoles (A. Hetzheim and K. Mockel), and diquinolylme-thanes (G. Scheibe and E. Daltrozzo). Further chapters deal with applications of mass spectrometry to heterocycles (G. Spiteller), an area which has expanded very rapidly of late, and the halogenation of heterocycles (J. J. Eisch). Finally, a summary is given of reviews in the heterocyclic field, classified by subject (A. R. Katritzky and S. M. Weeds), which it is hoped may be of assistance in literature surveys. 

Although not particularly well known, nitrosoimidazoles appear to be quite stable compounds. The nitroso function can be reduced to amino, or oxidized to nitro. When 5-nitroso-2,4-diphenylimidazole is subjected to dropwise treatment with phenylhydrazine there is some reduction, but ring modification with the formation of the oxadiazole (224) accompanies this reaction (Scheme 123) (60G831). The nitroso function is able to take part in condensation reactions with compounds which possess active methylene groups, and related species (B-76MI40701). 

The transition-metal complexes with unsymmetrical binucleating ligands based on substituted azole moieties are of interest as subjects for mechanistic studies of oxidation. A good example is the oxadiazole-based ligand (71) that has been reported.103... 

Acyltetrazoles in solution are subject to dediazoniation at room temperature. However, the acyl nitrilimines cyclize immediately to give 1,3,4-oxadiazoles (HuiSGEN reaction) ... 

Reactivity towards nucleophilic reagents is not very high. 1,2,5-Oxadiazoles, and 1,2,3- and 1,2,4-thiadiazoles are subject to ring cleavage. Halogenated compounds such as 5-chloro-1,2,4-thiadiazole, 3(5)-chloro-1,2,4-triazole and 5-chlorotetrazole undergo nucleophilic substitution reactions. 

The reaction of diethyl 3,4-dimethylthieno[2,3-Z ]thiophene-2,5-dicarboxylate (117, R = Me, EWG = C02Et) with hydrazine hydrate afforded dihydrazide 231, which was subjected to various transformations. For example, the reactions with acetylacetone, ethyl acetoacetate or malononitrile (93BCJ2011) are accompanied by the closure of the exocyclic pyrazole ring to form the corresponding derivatives 232-234. The reaction of dihydrazide 231 with carbon disulfide in the presence of KOH followed by decomposition with dilute HCl or concentrated H2SO4 produces di(oxadiazole) (235) or di(thiadiazole) derivative (236). Condensation of di(oxadia-zolyl)thienothiophene 235 with hydrazine hydrate affords di(triazolyl)thienothio-phene 237. 

In blends of PVK with PBD and in random copolymers with carbaz-ole and oxadiazole groups attached as side chains, the active groups have different mobility, or are subjected to different topological constraints, respectively. In the blends, exciplexes emerge, and in the copolymers, electroplexes are effective. Both types of complexes shift the EL spectra to red in comparison to pure PVK homopolymer. The red-shift is significantly greater for the electroplex. 

Although a wide variety of heterocycle/side-chain combinations can be used in the Boulton-Katritzky rearrangement, among these, the most commonly used heterocycle has been the 1,2,4-oxadiazole. This is due to the relative ease with which it is synthesized as well as the fact that it has a very low index of aromaticity. Its heightened chemical reactivity has made it an important target for medicinal and materials chemists and the subject of multiple reviews in the last several years. ... 

N-C-N side chain was used by Cusmano and co-workers in the preparation of triazolo[l,5-a]quinolines and triazolo[l,5-a]pyridines. The base-catalyzed thermal rearrangement of 1,2,5-oxadiazole 22 afforded the desired triazolo[l,5-a]quinoline (E)-23 in good yield as a single stereoisomer. The expected Z-oxime products readily isomerize to the respective -oximes under the reaction conditions. When the phenyl-substituted 1,2,5-oxadiazole 24 was subjected to the reaction conditions, however, complete isomerization of the products was not observed and a mixture of stereoisomers (E)-25 and (Z)-25 was obtained. 

Synthesis.—The majority of 1,3,4-thiadiazole syntheses are based on cyclizations of thiosemicarbazidcs or compounds incorporating this basic structural pattern. Others involve ring-closures of dithiocarbazates, acyl hydrazines, or bithioureas, or interconversions of other ring systems, particularly oxadiazoles and dithiolethiones. Recent contributions to this subject have been numerous and are presented, as far as possible, in accordance with this classification. 

Pioneering work on this subject [8] reported the preparation of various perfluoro-alkylamidoxiines 11 (Rf=CF3, C2F5, C3F7, C7F15) and their acylation with perfluoro-acylchlorides (Rf COCI) followed by cyclodehydration to produce 3,5-bis(perfluoroalkyl)-l,2,4-oxadiazoles 12 either symmetrically (Rf=Rf ) or unsymmetrically substituted. By following the same methodology, bis-oxadiazoles 14 (n=3) could be obtained (Scheme 3) [8, 9],... 

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