pyrimidinones and 2-amino-6-methylpyrimidin-4-one

It is well known that pyrimidin-4-one derivatives are able to adopt either the 1H- or the 3H-tautomeric form in (co)crystals, depending on the coformer. As part of ongoing research to investigate the preferred hydrogen-bonding patterns of active pharmaceutical ingredients and their model systems, 2-amino-6-chloropyrimidin-4-one and 2-amino-5-bromo-6-methylpyrimidin-4-one have been cocrystallized with several coformers and with each other. Since Cl and Br atoms both have versatile possibilities to interact with the coformers, such as via hydrogen or halogen bonds, their behaviour within the crystal packing was also of interest. The experiments yielded five crystal structures, namely 2-aminopyridin-1-ium 2-amino-6-chloro-4-oxo-4H-pyrimidin-3-ide-2-amino-6-chloropyrimidin-4(3H)-one (1/3), C5H7N2(+)·C4H3ClN3O(-)·3C4H4ClN3O, (Ia), 2-aminopyridin-1-ium 2-amino-6-chloro-4-oxo-4H-pyrimidin-3-ide-2-amino-6-chloropyrimidin-4(3H)-one-2-aminopyridine (2/10/1), 2C5H7N2(+)·2C4H3ClN3O(-)·10C4H4ClN3O·C5H6N2, (Ib), the solvent-free cocrystal 2-amino-5-bromo-6-methylpyrimidin-4(3H)-one-2-amino-5-bromo-6-methylpyrimidin-4(1H)-one (1/1), C5H6BrN3O·C5H6BrN3O, (II), the solvate 2-amino-5-bromo-6-methylpyrimidin-4(3H)-one-2-amino-5-bromo-6-methylpyrimidin-4(1H)-one-N-methylpyrrolidin-2-one (1/1/1), C5H6BrN3O·C5H6BrN3O·C5H9NO, (III), and the partial cocrystal 2-amino-5-bromo-6-methylpyrimidin-4(3H)-one-2-amino-5-bromo-6-methylpyrimidin-4(1H)-one-2-amino-6-chloropyrimidin-4(3H)-one (0.635/1/0.365), C5H6BrN3O·C5H6BrN3O·C4H4ClN3O, (IV). All five structures show R2(2)(8) hydrogen-bond-based patterns, either by synthon 2 or by synthon 3, which are related to the Watson-Crick base pairs.

Topics: Base Pairing; Crystallography, X-Ray; Cytosine; Hydrogen Bonding; Molecular Structure; Pyrimidinones

The derivatives of pyrimidin-4-one can adopt either a 1H- or a 3H-tautomeric form, which affects the hydrogen-bonding interactions in cocrystals with compounds containing complementary functional groups. In order to study their tautomeric preferences, we crystallized 2,6-diaminopyrimidin-4-one and 2-amino-6-methylpyrimidin-4-one. During various crystallization attempts, four structures of 2,6-diaminopyrimidin-4-one were obtained, namely solvent-free 2,6-diaminopyrimidin-4-one, C(4)H(6)N(4)O, (I), 2,6-diaminopyrimidin-4-one-dimethylformamide-water (3/4/1), C(4)H(6)N(4)O·1.33C(3)H(7)NO·0.33H(2)O, (Ia), 2,6-diaminopyrimidin-4-one dimethylacetamide monosolvate, C(4)H(6)N(4)O·C(4)H(9)NO, (Ib), and 2,6-diaminopyrimidin-4-one-N-methylpyrrolidin-2-one (3/2), C(4)H(6)N(4)O·1.5C(5)H(9)NO, (Ic). The 2,6-diaminopyrimidin-4-one molecules exist only as 3H-tautomers. They form ribbons characterized by R(2)(2)(8) hydrogen-bonding interactions, which are further connected to form three-dimensional networks. An intermolecular N-H···N interaction between amine groups is observed only in (I). This might be the reason for the pyramidalization of the amine group. Crystallization experiments on 2-amino-6-methylpyrimidin-4-one yielded two isostructural pseudopolymorphs, namely 2-amino-6-methylpyrimidin-4(3H)-one-2-amino-6-methylpyrimidin-4(1H)-one-dimethylacetamide (1/1/1), C(5)H(7)N(3)O·C(5)H(7)N(3)O·C(4)H(9)NO, (IIa), and 2-amino-6-methylpyrimidin-4(3H)-one-2-amino-6-methylpyrimidin-4(1H)-one-N-methylpyrrolidin-2-one (1/1/1), C(5)H(7)N(3)O·C(5)H(7)N(3)O·C(5)H(9)NO, (IIb). In both structures, a 1:1 mixture of 1H- and 3H-tautomers is present, which are linked by three hydrogen bonds similar to a Watson-Crick C-G base pair.

Topics: Crystallization; Crystallography, X-Ray; Hydrogen Bonding; Ions; Isomerism; Molecular Structure; Pyrimidinones