Syntheses and conformational analyses of new naphth[1,2-e][1,3]oxazino[3,2-c]quinazolin-13-ones

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• 作者：Rená ; ta Csü ; t&ouml ; rt&ouml ; ki^a ; Istvá ; n Szatmá ; ri^a ; Andreas Koch^b ; Matthias Heydenreich^b ; Erich Kleinpeter^b ; ^{ekleinp@uni-potsdam.de} ; Ferenc Fü ; l&ouml ; p^a ; ^{fulop@pharm.u-szeged.hu}
• 关键词：Naphthoxazinoquinazolinones ; Aminonaphthols ; NMR spectroscopy ; Conformational analysis ; Theoretical calculations ; Ring current effect
• 刊名：Tetrahedron
• 出版年：2012
• 期刊代码：107_00404020
• 类别：ch
• 出版时间：17 June, 2012
• 卷：68
• 期：24
• 页码：4600-4608
• 文件大小：885 K

摘要

The syntheses of naphth[1,2-e][1,3]oxazino[3,2-c]quinazolin-13-one derivatives (3a-f) were achieved by the solvent-free heating of benzyloxycarbonyl-protected intermediates (2a-f) with MeONa. For intermediates 2a-f, prepared by the reactions of substituted aminonaphthols with benzyl N-(2-formylphenyl)carbamate, not only the expected trans ring form B and chain form A¹, but also the rearranged chain form A² as a new tautomer were detected in DMSO at room temperature. The quantity of A² in the tautomeric mixture was changed with time.

Conformational analyses of the target heterocycles 3a-f by NMR spectroscopy and accompanying theoretical calculations at the DFT level of theory revealed that the oxazine ring preferred a twisted chair conformation and the quinazolone ring was planar. Besides the conformations, both the configurations at C-7a and C-15 and the preferred rotamers of the 1-naphthyl substituent at C-15 were assigned, which allowed evaluation of the aryl substituent-dependent steric hindrance in this part of the molecules. Configurational assignments were corroborated by quantifying the ring current effect of 15-aryl in terms of spatial NICS.