Butaclamol: Absolute configuration, crystal and molecular conformation

Abstract

(−)-Butaclamol HCl, C₂₅H₃₁ONCl, crystallizes in the monoclinic space group P2₁ with cell dimensionsa=12.842(2),b=7.741(1),c=11.667(2)Å andβ=106.54(2)°,z=2. Refinement of nonhydrogen atoms with anisotropic thermal parameters and isotropic hydrogen atoms using 4381 observed reflections gaveR=5.4% for the (3R,4aR,13aR) enantiomorph, andR=6.6% for the other enantiomorph. The crystal structure shows that butaclamol has thetrans A conformer with respect to the rotation at C8-C9, as observed in other crystal structures of butaclamol and analogues. Conformational energy calculations were redone for butaclamol and isobutaclamol with the 1986 version of the MM2 program and parameter set with the result thattrans conformer A is now preferred for the protonated form of butaclamol, whereas thecis conformers continue to be preferred for the free base. The results for isobutaclamol are similar to those previously reported.