title: 6-Chloroisocytosine and 5-bromo-6-methylisocytosine: again, one or two tautomers present in the same crystal?
abstract: 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.
authors.affiliation: Institut für Organische Chemie und Chemische Biologie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
authors.forename: Valeska
authors.initials: V
authors.lastname: Gerhardt
authors.affiliation: Institut für Anorganische und Analytische Chemie, Goethe-Universität Frankfurt, Max-von-Laue-Strasse 7, 60438 Frankfurt am Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bolte
mesh_terms: D020029:Base Pairing; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006860:Hydrogen Bonding; D015394:Molecular Structure; D011744:Pyrimidinones / Q000737:chemistry*
chemical_list: C559652:2-amino-6-methylpyrimidin-4-one; C000608089:5-bromo-6-methylisocytosine; C000608058:6-chloroisocytosine; D011744:Pyrimidinones; D003596:Cytosine
keywords: 2-amino-4-chloro-6-methylpyrimidine; 2-aminopyridine; 5-bromo-6-methylisocytosine; 6-chloroisocytosine; Watson–Crick base pairs; active pharmaceutical ingredients; crystal structure; halogen bond; hydrogen bond