Crystal Structure of Polymorph II and the Pressure-Temperature Phase Diagram of the Dimorphic Anesthetic Butamben

The crystal structure of the low-temperature form II of butamben has been solved in a P2(1)/c space group very similar to that of form I. Form II possesses virtually the same packing as that of the high-temperature form I, and the dimorphism is mainly represented by a small discontinuous change in the size of the unit cell and by a difference in the enthalpy. Because of the small enthalpy difference between the two polymorphs of 375 J.mol(-)(1), it will be difficult to predict the change in the stability hierarchy by computer-aided methods. The pressure-temperature phase diagram, constructed using volume and enthalpy differences between the two phases at ordinary pressure, corresponds to a case of overall enantiotropy, as the I-II and I-L equilibrium lines diverge with increasing pressure. This conclusion is confirmed by the experimental pressure-temperature phase diagram obtained with differential thermal analysis measurements under pressure.