Structural studies on benzothiazoles. Crystal and molecular structure of 5,6-dimethoxy-2-(4-methoxyphenyl)-benzothiazole and molecular orbital calculations on related compounds.

Article abstract of DOI:10.1016/S0040-4020(01)86576-5

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 P2₁/c, a=17.142(1), b=11.165(1), c=7.683(2) A, β=101.34(1)°. 2307 Reflections were refined to R=0.039. The inter-ring twist angle is 21°, greater than in 2-(o-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.