Cocrystals of 6-methyl-2-thiouracil: presence of the acceptor–donor–acceptor/donor–acceptor–donor synthon

Abstract

The results of seven cocrystallization experiments of the antithyroid drug 6-methyl-2-thiouracil (MTU), C5H6N2OS, with 2,4-diaminopyrimidine, 2,4,6-triaminopyrimidine and 6-amino-3H-isocytosine (viz.2,6-diamino-3H-pyrimidin-4-one) are reported. MTU features anADA(A= acceptor andD= donor) hydrogen-bonding site, while the three coformers show complementaryDADhydrogen-bonding sites and therefore should be capable of forming anADA/DADN—H...O/N—H...N/N—H...S synthon with MTU. The experiments yielded one cocrystal and six cocrystal solvates, namely 6-methyl-2-thiouracil–2,4-diaminopyrimidine–1-methylpyrrolidin-2-one (1/1/2), C5H6N2OS·C4H6N4·2C5H9NO, (I), 6-methyl-2-thiouracil–2,4-diaminopyrimidine (1/1), C5H6N2OS·C4H6N4, (II), 6-methyl-2-thiouracil–2,4-diaminopyrimidine–N,N-dimethylacetamide (2/1/2), 2C5H6N2OS·C4H6N4·2C4H9NO, (III), 6-methyl-2-thiouracil–2,4-diaminopyrimidine–N,N-dimethylformamide (2/1/2), C5H6N2OS·0.5C4H6N4·C3H7NO, (IV), 2,4,6-triaminopyrimidinium 6-methyl-2-thiouracilate–6-methyl-2-thiouracil–N,N-dimethylformamide (1/1/2), C4H8N5+·C5H5N2OS−·C5H6N2OS·2C3H7NO, (V), 6-methyl-2-thiouracil–6-amino-3H-isocytosine–N,N-dimethylformamide (1/1/1), C5H6N2OS·C4H6N4O·C3H7NO, (VI), and 6-methyl-2-thiouracil–6-amino-3H-isocytosine–dimethyl sulfoxide (1/1/1), C5H6N2OS·C4H6N4O·C2H6OS, (VII). Whereas in cocrystal (I) anR22(8) interaction similar to the Watson–Crick adenine/uracil base pair is formed and a two-dimensional hydrogen-bonding network is observed, the cocrystals (II)–(VII) contain the triply hydrogen-bondedADA/DADN—H...O/N—H...N/N—H...S synthon and show a one-dimensional hydrogen-bonding network. Although 2,4-diaminopyrimidine possesses only oneDADhydrogen-bonding site, it is, due to orientational disorder, triply connected to two MTU molecules in (III) and (IV).