3.2.5- Disubstituted 1,4-oxadiazoles

In line with its importance in characterization, this section has been expanded and updated and includes a more detailed analysis than that in CHEC-II(1996) and CHEC(1984), which contain, nonetheless, important data on proton NMR shifts of C-3- and C-5-unsubstituted fully conjugated 1,2,4-oxadiazoles. A major advance since CHEC-II(1996) is the appearance of a large amount of fully assigned 13C data for C-3/C-5-disubstituted fully conjugated 1,2,4-oxadiazoles <1996JHC1583,... 

The inclusion complexes of 3-R 4-R2-disubstituted l,2,5-oxadiazole-2-oxide with polycyclic derivatives of gluco-pyranose were prepared by heating an aqueous ethanolic solution of /3-cyclodedextrin with the corresponding furazan... 

The well-known method of furazan formation is based on nitrosation of alkenes. Thus, several NO donor 3,4-disubstituted 1,2,5-oxadiazole 2-oxide derivatives and the related 1,2,5-oxadiazoles, containing methylsulfonylphe-nyl, phenylsulfonyl, sulfonylamidophenyl, and phenylsulfonylamido groups were synthesized by nitration of... 

The applications of 1,2,5-oxadiazole iV-oxide and benzo[c][l,2,5]oxadiazole iV-oxide derivatives as compounds which have herbicidal activity are known. For example, the most active compound, butylcarbamoylbenzoL] 1,2,5-oxadiazole iV-oxide, displayed herbicidal activity at concentrations as low as 24 gha-1 <2000JFA2995>. The preparation of 5,7-disubstituted 4,6-dinitrobenzofuroxane derivatives (2-chlorophenylamino, 2,5-dichlorophenyl-amino, 2-hydroxyphenylamino, or 4-bromophenylamino), which are useful as agricultural arachnicides and bactericides, was described <2005RUP2255935>. 

Electron ionization (El) mass spectra of 1,3,4-oxadiazole itself and its 2-mono- and 2,5-disubstituted derivatives, including the proposed main fragmentation pathways have already been discussed in CHEC(1984) and CHEC-11(1996) <1984CHEC(6)427, 1996CHEC-II(4)268>. Molecular ions of the compounds are usually of high intensity and the most important fragmentation pathways of the molecular ions involve loss of respective HCN, RCN molecules, or RCO cations. Loss of HNCO is significant in the spectra of 2-amino derivatives. 

Substituted tetrazoles reacting in the mass spectrometer with acyl ions afforded 2,5-disubstituted 1,3,4-oxadiazoles with nitrogen loss. Tandem mass spectrometry allowed for the collision-induced dissociation of the products. Chemical ionization was the better method to make the transformation. A scheme for the transformation of 5-substituted tetrazoles into 2,5-disubstituted 1,3,4-oxadiazoles was proposed (Scheme 1) <2001JMP1069>. The fragmentation patterns of monocyclic l,3,4-oxadiazolium-2-thiolates have been proposed by Ollis and Ramsden <1974J(P1)645>. 

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. 

A one-pot synthesis of 2,5-disubstituted 1,3,4-oxadiazoles from acids and acyl hydrazides has recently been reported. The method involves an activation of an acid with carbonyl diimidazole followed by the addition of benzoyl hydrazide and then the addition of CBr4 and Ph3P. Under the conditions, the dehydration proceeds smoothly to provide the desired oxadiazoles in high yields <2006TL4827>. 

The synthesis and properties of heat-resistant polyazomethines containing 2,5-disubstituted oxadiazole fragments, being insulators convertible into semiconductors by doping with iodine, have been described. The radical copolymerization of alkenes with the fluorescent co-monomer 2-/-butyl-5-(4 -vinyl-4-biphenylyl)-l,3,4-oxadiazole has resulted in useful macromolecular scintillators. Anionic polymerization of 2-phenyl-l,3,4-oxadiazolin-5-one has produced a nylon-type product <1996CHEC-II(4)268>. 

The cyclocondensation of 3-acyl/3-aroyl-5-aryl[l,3,4]oxadiazol-2(3//)-ones 98 with hydrazine hydrate gives the corresponding 3,6-disubstituted-[l,2,4]triazolo[3,4- ][l,3,4]oxadiazoles 99 (Equation 26) <1991H(32)237>. 

In a related study, it has been shown that several aldehyde N-acylhydra-zones undergo oxidative cyclization with IBD in methanolic sodium acetate to give 2,5-disubstituted 1,3,4-oxadiazoles (Eq. 32). The oxidation of ketone N-acylhydrazones by IBD in methanol or ethanol affords the corresponding 2-alkoxy-A -l,3,4-oxadiazolines in excellent yields (Eq. 33), while oxidative cyclization of acetone 4-phenylsemicarbazone provides 2-(A -phenylimino)-A -l,3,4-oxadiazoline in 93% yield (Eq. 34) (93JOC3381). 

Scheme 27 The synthesis of disubstituted 1,2,4-oxadiazoles in a microreactor setup [60]...

Adib M, Jahromi AH, Tavoosi N et al (2006) Microwave-assisted efficient, one-pot, three-component synthesis of 3, 5-disubstituted 1, 2, 4-oxadiazoles under solvent-free conditions. Tetrahedron Lett 47(17) 2965-2967... 

Thermolysis of tetrazole oximes (478) in a suitable hydrocarbon solvent, or pyrolysis without it, produces 3,5-disubstituted 1,2,4-oxadiazoles (480) (Scheme 75) (81BSB193 87BSB675 91MIP137367). in the case of 5-unsubstituted tetrazoles (478 R = H), the reaction goes by two concomitant pathways, which imply elimination of hydrazoic acid or nitrogen. 

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