title: A new polymorph and two pseudopolymorphs of pyrimethamine.
abstract: Due to its donor-acceptor-donor site, the antimalarial drug pyrimethamine [systematic name: 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine] is a potential component of a supramolecular synthon. During a cocrystallization screen, one new polymorph of solvent-free pyrimethamine, C(12)H(13)ClN(4), (I), and two pseudopolymorphs, pyrimethamine dimethyl sulfoxide monosolvate, C(12)H(13)ClN(4)·C(2)H(6)OS, (Ia), and pyrimethamine N-methylpyrrolidin-2-one monosolvate, C(12)H(13)ClN(4)·C(5)H(9)NO, (Ib), were obtained. In (I), (Ia), (Ib) and the previously reported polymorph, the pyrimethamine molecules exhibit similar conformations and form R(2)(2)(8) dimers stabilized by a pair of N-H···N hydrogen bonds. However, the packing arrangements are completely different. In (I), the dimers are connected by two additional N-H···N hydrogen bonds to form ribbons and further connected into a two-dimensional network parallel to (100), while layers containing N-H···Cl hydrogen-bonded pyrimethamine ribbons are observed in the packing of the known polymorph. In the two pseudopolymorphs, two pyrimethamine molecules are linked to form R(2)(2)(8) dimers and the solvent molecules are connected to the dimers by R(2)(3)(8) interactions involving two N-H···O hydrogen bonds. These arrangements are connected to form zigzag chains by N-H···Cl interactions in (Ia) and to form ribbons by N-H...N interactions in (Ib). Unexpectedly, a reaction between pyrimethamine and N-methylpyrrolidin-2-one occurred during another cocrystallization experiment from a solvent mixture of N-methylpyrrolidin-2-one and dimethyl sulfoxide, yielding solvent-free 5,5'-{[5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diyl]bis(azanediyl)}bis(1-methylpyrrolidin-2-one), C(22)H(27)ClN(6)O(2), (II). In the packing of (II), the pyrimethamine derivatives are N-H···O hydrogen bonded to form ribbons. A database study was carried out to compare the molecular conformations and hydrogen-bonding interactions of pyrimethamine.
authors: Institut für Organische Chemie und Chemische Biologie, Goethe-Universität Frankfurt, Frankfurt am Main, Germany.
authors: Maya
authors: M
authors: Tutughamiarso
authors: Michael
authors: M
authors: Bolte
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D015394:Molecular Structure; D011739:Pyrimethamine / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*
chemical_list: D012997:Solvents; D011739:Pyrimethamine