The gradient‐optimized geometry of haloperidol at the 4‐21G level

The molecular structure of haloperidol as free base in its C(13)—C(14) trans form is optimized using Pulay's gradient method and a 4‐21G basis set without any geometrical constraints. The resulting structure is compared with the experimental structure of the free base in the C(13)—C(14) gauche form and with the experimental structure of the HBr salt of haloperidol in the C(13)—C(14) trans form. Apart from the obvious differences, the two rotameric forms of the free base show many similarities. This, together with the manner in which the differences of the two experimental structures are distributed over the haloperidol molecule, leads to the conclusion that the conspicuous differences between the experimental structures are caused by inaccuracies in the X‐ray determination of the HBr salt. Deviations of phenyl ring geometries from D 6h symmetry and the asymmetry of the conformation around C(1)—C(9) could be rationalized by intramolecular effects.