Oxazolo [2,3-a]isoindol-5-one derivatives exhibit anticonvulsant and anti-inflammatory activities. 1 The chemistry and reactivity of isoindolinone ring system is an area of interest because of its biological activity. 2 Recently Allin and coworkers 3 have reported a new synthesis of non-racemic isoindolinone targets through application of oxazolo-[2,3-a]isoindolinones as N-acyl iminium ion precursors in reactions with carbon and hydride nucleophiles. We had earlier reported the formation of a novel 10 membered chiral ring system 4 while attempting to synthesise oxazolo-[2,3-a]isoindol-5(9bH)-one using (R) or (S)-2-amino-1butanol via Meyers methodology 5 involving reduction of the imide and cyclisation using trifluoro acetic acid. The phenyl group was introduced by the addition of phenyl magnesium bromide (c) to (R) or (S)-2-(1-hydroxy)phthalimides 3a or 3b. These were derived from phthalic anhydride 1 and (R)-(-)-2amino-1-butanol 2a or (S)-(+)-2-amino-1-butanol 2b. The resulting dihydroxy compounds 4a or 4b were not isolated, but were directly subjected to acid-catalysed cyclisation to furnish the 9b-phenyl substituted oxazolo[2,3a] isoindolinones 10a or 10b in 40-50% yields. In a similar fashion the addition of p-fluoro(d), p-chloro(e), p-methoxy(f) and p-methyl(g) substituted phenyl magnesium bromides furnished the corresponding 9b-substituted-phenyl substituted oxazolo[2,3a] isoindolinones 11a-14a or 11b-14b respectively (Scheme 1).Compound 10b was subjected to a single crystal X-ray diffraction analysis 6 and its structure was solved and refined by SHELX 97 program 7 (Fig. 1). The absolute configuration of the phenyl substituted oxazolo[2,3-a]isoindolin-5-one was found to be (3S, 9bR).
Oxazole derivativesOxazole derivatives R 0220
Synthesis of Phenyl and Substituted Phenyl 3-Ethyl-2,3,5,9b-tetrahydro[1,3]oxazolo[2,3-a]isoindol-5-ones. -(NAIR, D. S.; PAURANIK, V.; SHAH*, A. C.;
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