Oxadiazole ring opening

Thus quaternized thiazoles (170) consume two equivalents of OH on titration because the pseudo bases (171) ring open to (172), which form anions (173). Quaternized oxazoles (174) are readily attacked by hydroxide to give open-chain products such as (175) (74AHC(17)99), and quaternized 1,3,4-oxadiazoles behave similarly. Quaternary isothiazoles (e.g. 176) are cleaved by hydroxide (72AHC(l4)l), as are 1,2,4-thiadiazolium salts (177 178). 

Amino-l,3,4-oxadiazoles (423) ring-open and the products immediately recyclize to triazolinones (424) (66AHC(7)183). 

Simple 1,2,3-oxadiazoles are unknown (spontaneous ring opening to give diazoketones) and hence 4-hydroxy- 147 and 5-hydroxy-l,2,3-oxadiazoles 148 are not studied (Scheme 55). For 2-hydroxy-l,3,4-oxadiazoles, the oxo tautomers 149b are usually considered the major forms [84CHEC-I(6)427, 96CHEC-II(4)267]. 

The 3-oxidotriazolopyridinium zwitterions 245 fail to react with DMAD unless magnesium bromide is present, when ring opening occurs (2000H(53 265) (Section IV.F). The thiol 268 adds methyl acrylate as expected the resulting ester is converted via the acid hydrazide, to an oxadiazole (89IJC(B)170). 

The mesoionic tetrazole dehydrodithizone is transformed by iron penta-carbonyl into 4-phenyl-2-phenylazo-A2-l,3,4-thiadiazolin-5-one, presumably by a mechanism of ring opening, complexation, carbonyl insertion and subsequent ring closure (Scheme 128).193 Unfortunately, analogous processes do not occur on other mesoionic compounds in the 1,2,3-oxadiazole, s-triazole or tetrazole series, and the scope of this unusual carbonylation is probably limited. 

The reduction of the Wang resin-bound 1,2,4-oxadiazole 107 (Equation 15) with LiAlH4 resulted in reductive cleavage from the resin and a reductive ring opening of the 1,2,4-oxadiazole to furnish the amidoxime 108 <1999BML2101>. 

The 1,2,4-oxadiazole dioxolanes 144 react with hydroxylamine and hydrazines to form the 5-pyrazole- and isoxazole-substituted 1,2,4-oxadiazoles 146 via the dioxolane ring-opened intermediates 145 (Scheme 17). Reaction of compounds 144 with amidine or guanidine salts allows access to pyrimidine substituted analogues 147, via intermediate 145 (X = C(NH)R1), albeit in lower yield <1996JHC1943, 1998JHC161>. 

The tautomerism of furoxan (l,2,5-oxadiazole-2-oxide) has been investigated by different computational methods comprising modern density functions as well as single-reference and multi-reference ab initio methods. The ring-opening process to 1,2-dinitrosoethylene is the most critical step of the reaction and cannot be treated reliably by low-level computations (Scheme 2). The existence of cis-cis-trans- 1,2-dinitrosoethylene as a stable intermediate is advocated by perturbational methods, but high-level coupled-cluster calculations identify this as an artifact <2001JA7326>. 

Most of the cyclically conjugated 1,3,4-oxadiazoles are thermally stable, and very high temperatures are required to induce ring cleavage. In 3-alkyl-5-phenyl-2-oxadiazolidinones, the rings open up at 700 °C losing carbon dioxide < 1996CHEC-II(4)268>. 

A number of ring systems have been converted into 1,2,4-thiadiazole derivatives. The most common include 5-imino-1,2,4-dithiazolidines, isoxazoles, oxadiazoles, and 5-imino-l,2,3,4-thiatriazolines. In general, a ring-opening reaction is followed by rotation and ring closure, or the heterocyclic ring may act as a masked 1,3-dipole which reacts with a suitable dipolarophile. 

The retro-1,3-dipolar cycloaddition of imidazo[l,5- ][l,2,4]oxadiazoles 40, promoted by reaction with triphenylphos-phine at reflux in THF, gives the cyclic nitrones 187 (unreported yields) (Equation 15) <1997T13873>. The ring opening of compounds 40 leading to heterocycles 187 (Equation 15) can also be achieved thermally in the condensed phase under vacuum <1997TL2299>. 

Compounds 190 on heating with ethanol/HCl convert to 4//[l,2,4]oxadiazole-5-thiones 191 (Equation 17) as a result of the ring opening in acid media <2003PS(178)881>. 

A development in the synthesis of macromolecular scintillators is the radical co-polymerization of alkenes with the fluorescent co-monomer 2-t-butyl-5-(4 -vinyl-4-biphenylyl)-l,3,4-oxadiazole <89MI 406-04). Basic initiators cause ring opening of 2-phenyl-l,3,4-oxadiazolin-5-one with subsequent anionic polymerisation to form A-benzamido-1-nylon [-N(NHCOPh)CO-] <90PB583>. 

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