title: Eight salt forms of sulfadiazine.
abstract: Proton transfer to the sulfa drug sulfadiazine [systematic name: 4-amino-N-(pyrimidin-2-yl)benzenesulfonamide] gave eight salt forms. These are the monohydrate and methanol hemisolvate forms of the chloride (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride monohydrate, C(10)H(11)N(4)O(2)S(+) · Cl(-) · H2O, (I), and 2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium chloride methanol hemisolvate, C(10)H(11)N(4)O(2)S(+) · Cl(-) · (0.5)CH(3)OH, (II)); a bromide monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium bromide monohydrate, C(10)H(11)N(4)O(2)S(+) · Br(-) · H2O, (III)), which has a disordered water channel; a species containing the unusual tetraiodide dianion [bis(2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium) tetraiodide, 2C(10)H(11)N(4)O(2)S(+) · I4(2-), (IV)], where the [I4](2-) ion is located at a crystallographic inversion centre; a tetrafluoroborate monohydrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium tetrafluoroborate monohydrate, C(10)H(11)N(4)O(2)S(+) · BF(4)(-) · H2O, (V)); a nitrate (2-{[(4-azaniumylphenyl)sulfonyl]azanidyl}pyrimidin-1-ium nitrate, C(10)H(11)N(4)O(2)S(+) · NO(3)(-), (VI)); an ethanesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium ethanesulfonate, C(10)H(11)N(4)O(2)S(+) · C(2)H(5)SO(3)(-), (VII)}; and a dihydrate of the 4-hydroxybenzenesulfonate {4-[(pyrimidin-2-yl)sulfamoyl]anilinium 4-hydroxybenzenesulfonate dihydrate, C(10)H(11)N(4)O(2)S(+) · HOC(6)H(4)SO(3)(-) · 2H2O, (VIII)}. All these structures feature alternate layers of cations and of anions where any solvent is associated with the anion layers. The two sulfonate salts are protonated at the aniline N atom and the amide N atom of sulfadiazine, a tautomeric form of the sulfadiazine cation that has not been crystallographically described before. All the other salt forms are instead protonated at the aniline group and on one N atom of the pyrimidine ring. Whilst all eight species are based upon hydrogen-bonded centrosymetric dimers with graph set R2(2)(8), the two sulfonate structures also differ in that these dimers do not link into one-dimensional chains of cations through NH3-to-SO2 hydrogen-bonding interactions, whilst the other six species do. The chloride methanol hemisolvate and the tetraiodide are isostructural and a packing analysis of the cation positions shows that the chloride monohydrate structure is also closely related to these.
authors.affiliation: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Buist
authors.affiliation: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors.forename: Lynn
authors.initials: L
authors.lastname: Dennany
authors.affiliation: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Kennedy
authors.affiliation: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors.forename: Craig
authors.initials: C
authors.lastname: Manzie
authors.affiliation: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors.forename: Katherine
authors.initials: K
authors.lastname: McPhie
authors.affiliation: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors.forename: Brandon
authors.initials: B
authors.lastname: Walker
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry; D001557:Benzenesulfonates / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry; D015394:Molecular Structure; D009861:Onium Compounds / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012492:Salts / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013411:Sulfadiazine / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*; D000096926:Benzenesulfonamides
chemical_list: D000814:Aniline Compounds; D001557:Benzenesulfonates; D007477:Ions; D009861:Onium Compounds; D011743:Pyrimidines; D000644:Quaternary Ammonium Compounds; D012492:Salts; D012997:Solvents; D013411:Sulfadiazine; D013449:Sulfonamides; C000593297:2-(((4-azaniumylphenyl)sulfonyl)azanidyl)pyrimidin-1-ium chloride methanol; C000593298:4-((pyrimidin-2-yl)sulfamoyl)anilinium 4-hydroxybenzenesulfonate dihydrate; C000593296:4-amino-N-(pyrimidin-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C023650:aniline
keywords: active pharmaceutical ingredients (APIs); crystal structure; pharmaceutical compounds; salt forms; sulfa drugs; sulfadiazine; tautomerism; tetraiodide