Synthesis and conformational study of some r(2), c(4)-bis(isopropoxycarbonyl)- t(3)-aryl- c(5)-hydroxy- t(5)-methylcyclohexanones using NMR spectra

Abstract

Seven r(2), c(4)-bis(isopropoxycarbonyl)- t(3)-aryl- c(5)-hydroxy- t(5)-methylcyclohexanones 7– 13 (aryl = C 6H 5, p-ClC 6H 4, p-FC 6H 4, p-OMeC 6H 4, p-Me 2NC 6H 4, m-O 2NC 6H 4 and m-C 6H 5OC 6H 4) have been synthesized by condensing isopropyl acetoacetate with aromatic aldehydes in the presence of methylamine. For all these compounds 1H and 13C NMR spectra have been recorded. For 7, HOMOCOSY, NOESY, HSQC and HMBC spectra also have been recorded. The spectral data suggest that compounds 7– 13 exist in chair conformation with axial orientation of the hydroxy group and equatorial orientations of all the other substituents. Long range coupling is observed between OH proton and H(6a) in all cases suggesting that OH group is anti to C(5) C(6) bond. In all cases four distinct doublets are observed for the methyl protons of the two isopropyl groups. In 7 and 13 four separate, closely spaced signals are observed for the methyl carbons of the two isopropyl groups. All signals could be assigned unambiguously in the case of 7. The protons of one methyl group of the isopropoxycarbonyl group at C-4 seems to be highly shielded. This suggests that these protons lie above the plane of the aryl group at C(3). This conclusion is in accordance with the structure of 7, determined by X-ray crystallography. MOPAC calculations on 7 suggest that the chair conformation with OH group anti to C(5) C(6) bond is more stable than the chair conformation with OH bond anti to C(5) CH 3 bond by 1.5 kcal mol −1.