Thermal and structural characterization of two polymorphs of the bronchodilator tulobuterol

Two polymorphs of the bronchodilator tulobuterol (2-chloro-α-(1,1-dimethylethyl)- amino]-methyl]benzenemethanol) with melting points differing by ~10 K were isolated and characterized by thermal analysis (HSM, TG, DSC), as well as powder and single crystal X-ray diffraction. Analysis of melting data for Forms 1 and 2 revealed a monotropic relationship, with ΔG ₀, the Gibbs free energy difference at the melting temperature of the lower melting form, less than 1 kJ mol^-1. This small difference is reconciled with known structural features in the crystals of the two forms. The hydrogen bonding capacity of the tulobuterol molecule is fully utilised in both polymorphs in forming a common trimeric unit via three strong O-H···N interactions. Consequently only weak intermolecular forces characterize the packing of the trimers in the monoclinic polymorph (Form 1, P2₁/n, Z =12) and the triclinic polymorph (Form 2, P(-1),Z =6). This revised version was published online in July 2006 with corrections to the Cover Date.