STRUCTURAL STUDIES ON BENZOTHIAZOLES - CRYSTAL AND MOLECULAR-STRUCTURE OF 5,6-DIMETHOXY-2-(4-METHOXYPHENYL)-BENZOTHIAZOLE AND MOLECULAR-ORBITAL CALCULATIONS ON RELATED-COMPOUNDS

The benzothiazole derivatives reported here have structural similarities to the 2-phenylindole derivatives that are known to bind to oestrogen receptors. We report the synthesis of 5,6-dimethoxy-2-(4-methoxyphenyl)- benzothiazole together with the determination of its three dimensional crystal structure. Crystals are monoclinic, space group P2(1)/c, a = 17.142(1), b = 11.165(1), c = 7.683(2) angstrom, beta = 101.34(1)-degrees. 2307 Reflections were refined to R = 0.039. The inter-ring twist angle is 21-degrees, greater than in 2-(omicron-hydroxyphenyl)benzothiazole but similar to that in 2-(4'-bromophenyl)-4,6-dimethoxyindole. Molecular mechanics calculations predict a torsional barrier to inter-ring twist of 6.3 kcal mol-1 for unsubstituted benzothiazole. Molecular orbital calculations show that while hydrogen bonding can confer stability on substituted benzothiazoles, a greater number of non-hydrogen bonding groups as substituents can confer even greater stability.