Two polymorphs of 4-hydroxy-1-methylpiperidine betaine hydrochloride studied by X-ray and DFT methods

Two polymorphic crystals (a and b) of 4-hydroxy-1-methylpiperidine betaine hydrochloride, HO-MPBHC$ClK, have been synthesized and their structures solved by the X-ray diffraction methods. The piperidine ring adopts the chair conformation and the hydroxy group at C(4) in the a-polymorph is in the axial position, while in the b-polymorph it is in the equatorial one. The CH2COOH group in both polymorphs is in the equatorial position. Crystals of a-HO-MPBHC$ClK (ax–eq) are monoclinic with the space group P21/n. The molecules are linked by COOH/Cl/HO hydrogen bonds of 2.988(2) and 3.158(3) A ° into infinite chains antiparallel to each other. Crystals of b-HO-MPBHC$ClK (eq–eq) are orthorhombic with the space group Pca21. There are two non-equivalent chains in the unit cell, formed by b(1) and b(2) molecules, which contain different COOH/Cl/HO hydrogen bonds; 2.974(2) and 3.147(3) A ° in b(1) and 3.011(2) and 3.147(3) A ° in b(2). These chains are linked by C–H/Cl and van der Waals contacts into polar ribbons. The optimized bond lengths and bond angles at the B3LYP/6-31G(d,p) level of theory are in good agreement with the X-ray data, except position of the hydrogen bonded proton and conformation of the carboxylate group. In the a-polymorph, the H-bonded proton is closer to the chloride atom and the OaC–O$H unit is cis, while in the b-polymorph the betaine is protonated with the trans OaC–O–H unit. In consequence, the b-polymorph is ca. 9.7 kcal/mol more stable than the a-one. From eight optimized structures of HO-MPBHC cations the most stable is ax–eq-cis conformer and the less stable is eq–eq-trans. q 2005 Elsevier B.V. All rights reserved