8-MEMBERED RING CONFORMATIONS - THE INTERCONVERSION OF THE SOLID-STATE CONFORMATIONS OF RETRONEFOPAM HYDROCHLORIDE AND DEOXYNEFOPAM HYDROCHLORIDE INTO THOSE EXHIBITED BY NEFOPAM HYDROCHLORIDE, A NONNARCOTIC ANALGESIC DRUG

The solid-state structures of (+/-)-retronefopam hydrochloride l-1-phe nyl-1,2,3,4-tetrahydro-6H-5,2-benzoxazocine hydrochloride], in which t he N-methyl and oxygen moieties are interchanged from their octagonal- ring positions in the non-narcotic analgesic drug nefopam hydrochlorid e, and of (+/-)-deoxynefopam hydrochloride thyl-6-phenyl-1,2,3,4,5,6-h exahydro-2-benzazocine] hydrochloride] were determined by single cryst al X-ray diffraction analysis. (+/-)-Retronefopam hydrochloride gave c rystals belonging to the triclinic space group P1BAR, and at ambient t emperature: a = 6.9503(7), b = 8.9500(9), c = 13.8988(12) angstrom, al pha = 102.590(8), beta = 94.527(8), gamma = 109.288(8)-degrees, V = 78 5.7(1) angstrom3, Z = 2, R(F) = 0.051, R(W)(F) = 0.049. (+/-)-Deoxynef opam hydrochloride gave crystals belonging to the monoclinic space gro up P2(1)1a, and at ambient temperature: a = 14.0901(7), b = 7.5958(5), c = 16.0560(9) angstrom, beta = 107.549(5)-degrees, V = 1638.4(2) ang strom3, Z = 4 R(F) = 0.064, R(W)(F) = 0.046. Both molecules have simil ar boat-chair molecular conformations [one benzo C(ipso) atom occupies a position at the junction of the boat and chair regions while the ot her resides in an adjacent position in the boat region, the N-methyl g roup is quasi-equatorial [retronefopam] or equatorial [deoxynefopam], while the phenyl group in both molecules occupies the middle of the bo at-fragment and shows an exo-orientation. The geometrical factors infl uencing the octagonal-ring boat-chair conformation were compared with those for the boat-boat of nefopam hydrochloride, and for the twist-ch air-flattened chair of (1S,3R,5S)-3-methylnefopam hydrochloride. Synpe riplanar torsion angle containing octagonal rings show a boat-chair co nformational preference unless the ring-substitution pattern is such t hat two cyclooctane type endo...endo transannular non-bonded interacti ons can be removed (or reduced in intensity) upon bending the ring int o the boat-boat conformation as is observed in the nefopam series.