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

Abstract

Two polymorphic crystals (α and β) of 4-hydroxy-1-methylpiperidine betaine hydrochloride, HO-MPBH +·Cl −, 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 α-polymorph is in the axial position, while in the β-polymorph it is in the equatorial one. The CH 2COOH group in both polymorphs is in the equatorial position. Crystals of α-HO-MPBH +·Cl − (ax–eq) are monoclinic with the space group P2 1/ n. The molecules are linked by COOH⋯Cl⋯HO hydrogen bonds of 2.988(2) and 3.158(3) Å into infinite chains antiparallel to each other. Crystals of β-HO-MPBH +·Cl − (eq–eq) are orthorhombic with the space group Pca2 1. There are two non-equivalent chains in the unit cell, formed by β(1) and β(2) molecules, which contain different COOH⋯Cl⋯HO hydrogen bonds; 2.974(2) and 3.147(3) Å in β(1) and 3.011(2) and 3.147(3) Å in β(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 α-polymorph, the H-bonded proton is closer to the chloride atom and the O C–O·H unit is cis, while in the β-polymorph the betaine is protonated with the trans O C–O–H unit. In consequence, the β-polymorph is ca. 9.7 kcal/mol more stable than the α-one. From eight optimized structures of HO-MPBH + cations the most stable is ax–eq- cis conformer and the less stable is eq–eq- trans.