RESOLUTION, ABSOLUTE STEREOCHEMISTRY AND ENANTIOSPECIFICITY OF OMOPHENYL)-2-METHYL-1,2,3,4-TETRAHYDROISOQUINOLINE - THE CRYSTAL AND MOLECULAR-STRUCTURES OF THE RACEMIC AND 4R-ENANTIOMERIC HYDROCHLORIDE SALT FORMS

The crystal structures and absolute stereochemistry of the (+/-)-racem ic and (-)-enantiomeric hydrochlorides of mophenyl)-2-methyl-1,2,3,4-t etrahydrolisoquinoline have been determined by single-crystal X-ray di ffraction methods. Crystal data: I. (+/-)-(4RS)-4. monoclinic, P2(1)/n , a = 10.754(3), b = 11.271(2), c = 12.459(3) angstrom. Beta = 104.33( 2)-degrees, Z = 4. R = 0.030 for 1921 reflections. II. (-)-(4R)-4, ort horhombic, P2(1)2(1)2(1), a = 10.988(2), b = 11.566(1), c = 11.892(2) angstrom. Z = 4, R = 0.035 for 1043 reflections. X-Ray intensity measu rements of anomalously scattered reflections established the absolute configuration of the (-)-enantiomer to be 4R. Only small conformationa l differences between the two crystal forms examined were observed. Th e intramolecular bond lengths and angles have expected values, and the Br-phenyl planes, in both structures. are almost perpendicular to the isoquinoline ring. In the solid state there are no intermolecular hyd rogen bonds except N-H...Cl salt bridge interactions, while the remain ing intermolecular forces are of normal or weak van der Waals' charact er. In the crystal structure of the racemic form, the molecules are mo re closely packed than in the optically active 4R form. In both isomer s the conformation of the piperidine ring is best described as a half- chair with the Br-phenyl group and N-methyl substituent equatorially p ositioned. The chiral hydrogen, H(4) and the N-methyl proton, H(2) are both axially oriented. Examination of the racemic and resolved isomer s in the inhibition of stress-induced stomach ulcers reveals a high de gree of enantiospecificity. The activity resides mainly in the S form.