A new polymorph and two pseudopolymorphs of pyrimethamine

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, C12H13ClN4, (I), and two pseudopolymorphs, pyrimethamine dimethyl sulfoxide monosolvate, C12H13ClN4 center dot C2H6OS, (Ia), and pyrimethamine N-methylpyrrolidin-2-one monosolvate, C12H13ClN4 center dot C5H9NO, (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 center dot center dot center dot N hydrogen bonds. However, the packing arrangements are completely different. In (I), the dimers are connected by two additional N-H center dot center dot center dot N hydrogen bonds to form ribbons and further connected into a two-dimensional network parallel to (100), while layers containing N-H center dot center dot center dot 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-3(2)(8) interactions involving two N-H center dot center dot center dot O hydrogen bonds. These arrangements are connected to form zigzag chains by N-H center dot center dot center dot Cl interactions in (Ia) and to form ribbons by NH center dot center dot center dot 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), C22H27ClN6O2, (II). In the packing of (II), the pyrimethamine derivatives are N-H center dot center dot center dot O hydrogen bonded to form ribbons. A database study was carried out to compare the molecular conformations and hydrogen-bonding interactions of pyrimethamine.