In order to obtain complexes held together by hydrogen as well as halogen bonds, 6-chlorouracil [6-chloropyrimidin-2,4(1H,3H)-dione; 6CU] and its 3-methyl derivative [6-chloro-3-methylpyrimidin-2,4(1H,3H)-dione; M6CU] were cocrystallized with 2,4,6-triaminopyrimidine and the three triazine derivatives 2,4,6-triamino-1,3,5-triazine (melamine), 2,4-diamino-6-methyl-1,3,5-triazine and 2-chloro-4,6-diamino-1,3,5-triazine, which all offer complementary hydrogen-bonding sites. Three of these compounds form cocrystals with 6CU; however, melamine yielded only a new pseudopolymorph with 6CU, but formed a cocrystal with M6CU. All six cocrystals contain solvent molecules (N,N-dimethylformamide, N,N-dimethylacetamide or N-methylpyrrolidin-2-one), whose intermolecular interactions contribute significantly to the stabilization of the crystal packing. Each of these structures comprises chains, which are primarily formed by strong hydrogen bonds with a basic framework built by R2(2)(8) hydrogen bonds of either pure N-H...N or mixed patterns. Solvent molecules are aligned to the border of these chains via N-H...O hydrogen bonds. Two of the reported crystal structures containing 6CU show additional Cl...O halogen bonds, which connect the chains to two-dimensional layers, while one weak and one strong Cl...Cl interaction are observed in the two structures in which molecules of M6CU are present.
Hydantoin-5-acetic acid [2-(2,5-dioxoimidazolidin-4-yl)acetic acid] and orotic acid (2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid) each contain one rigid acceptor-donor-acceptor hydrogen-bonding site and a flexible side chain, which can adopt different conformations. Since both compounds may be used as coformers for supramolecular complexes, they have been crystallized in order to examine their conformational preferences, giving solvent-free hydantoin-5-acetic acid, C(5)H(6)N(2)O(4), (I), and three crystals containing orotic acid, namely, orotic acid dimethyl sulfoxide monosolvate, C(5)H(4)N(2)O(4)·C(2)H(6)OS, (IIa), dimethylammonium orotate-orotic acid (1/1), C(2)H(8)N(+)·C(5)H(3)N(2)O(4)(-)·C(5)H(4)N(2)O(4), (IIb), and dimethylammonium orotate-orotic acid (3/1), 3C(2)H(8)N(+)·3C(5)H(3)N(2)O(4)(-)·C(5)H(4)N(2)O(4), (IIc). The crystal structure of (I) shows a three-dimensional network, with the acid function located perpendicular to the ring. Interestingly, the hydroxy O atom acts as an acceptor, even though the carbonyl O atom is not involved in any hydrogen bonds. However, in (IIa), (IIb) and (IIc), the acid functions are only slightly twisted out of the ring planes. All H atoms of the acidic functions are directed away from the rings and, with respect to the carbonyl O atoms, they show an antiperiplanar conformation in (I) and synperiplanar conformations in (IIa), (IIb) and (IIc). Furthermore, in (IIa), (IIb) and (IIc), different conformations of the acid O=C-C-N torsion angle are observed, leading to different hydrogen-bonding arrangements depending on their conformation and composition.
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.
Since 6-aminouracil derivatives show diversified use in various fields of application, we crystallized 6-aminouracil to examine its preferred hydrogen-bonding frameworks. 6-Aminouracil shows two rigid hydrogen-bonding sites, viz. one acceptor-donor-acceptor (ADA) site and one donor-donor-acceptor (DDA) site. During various crystallization attempts, we obtained three structures, namely two dimethylacetamide monosolvates, C4H5N3O2·C4H9NO, and a 1-methylpyrrolidin-2-one monosolvate, C4H5N3O2·C5H9NO. In all three structures, R2(1)(6) N-H...O hydrogen-bonding patterns link the molecules to their respective solvent molecules. The formation of R2(2)(8) N-H...O hydrogen-bond motifs between 6-aminouracil molecules can only be found in two-dimensional frameworks, whereas R3(3)(14) N-H...O patterns are present when zigzag chzins of 6-aminouracil molecules are formed.
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.
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