Crystalline-state conformational analysis of M alpha NP esters, powerful resolution and chiral H-1 NMR anisotropy tools

摘要

To compare the crystalline-state conformations of M alpha Np acid esters with those existing in the solution state, X-ray crystallographic analyses of 22 M alpha NP esters and two M alpha NP acids were carried out. It was found that all 27 conformers observed in the solid state have structures in which the 2-CH3 group and the 2'-H of the naphthyl group are syriperiplanar and are almost always located in the same plane. In addition, the CH3-O7-C2-C1 moiety in all cases has an antiperiplanar structure within the M alpha NP plane. From further analyses, 22 conformers adopt the so-called syn structure, in which the O7-C2-C1-O6 moiety is syriperiplanar. On the other hand, the remaining five conformers have the so-called anti structure. With regard to the rotational conformation around C1 ''-O5, all conformers have structures similar to the synperiplanar conformation. In the so-called syn conformers, the interatomic distance d(H8'-O6) is distributed between 2.48 angstrom and 2.96 angstrom, while the distance d(H8'-O7) varies between 2.26 angstrom and 2.56 angstrom, indicating the weak bifurcated hydrogen bond between O6-H8'-O7 as the intramolecular stabilizing force. The crystalline-state conformations of M alpha NP esters are thus similar to those in solution as determined by H-1 NMR spectroscopy, implying that the intramolecular forces make a dominant contribution to the conformations of M alpha NP esters. The X-ray crystallographic analyses of M alpha NP acids indicated that the O6-H(acid)-O7 bifurcated hydrogen bond also serves as an intermolecular force to stabilize the so-called syn conformation. A similar bifurcated hydrogen bond [O6-H(alcohol)-O7] was observed in a M alpha NP ester containing a tertiary alcohol group. It should be emphasized that despite the existence of the so-called syn and anti conformations in the crystalline state, the absolute configurations of all M alpha NP esters determined here by X-ray crystallography all agree with those obtained by the H-1 NMR anisotropy method. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).