2-(4-Amino­benzene­sulfonamido)-4,6-dimethyl­pyrimidin-1-ium 2-carb­oxy-4,6-dinitro­phenolate

Graham Smith; Urs D Wermuth

doi:10.1107/S1600536813005631

. 2013 Mar 2;69(Pt 4):o472. doi: 10.1107/S1600536813005631

2-(4-Aminobenzenesulfonamido)-4,6-dimethylpyrimidin-1-ium 2-carboxy-4,6-dinitrophenolate

Graham Smith ^a,^*, Urs D Wermuth ^a

PMCID: PMC3629512 PMID: 23634030

Abstract

In the structure of the phenolate salt of the sulfa drug sulfamethazine with 3,5-dinitrosalicylic acid, C₁₂H₁₅N₄O₂S⁺·C₇H₃N₂O₇ ⁻, the dihedral angle between the pyrimidine and benzene rings of the cation is 59.70 (17)°. In the crystal, cation–anion hydrogen-bonding interactions involving pyrimidine–carboxy N⁺—H⋯O and amine–carboxy N—H⋯O pairs give a cyclic R ₂ ²(8) motif while secondary N—H⋯O hydrogen bonds between the aniline group and both sulfone and nitro O-atom acceptors give a two-dimensional structure extending in (001).

Related literature

For background to sulfamethazine and its co-crystals, see: O’Neil (2001 ▶); Caira (2007 ▶); Ghosh et al. (2011 ▶). For similar structures, see: Caira (1991 ▶); Lynch et al. (2000 ▶); Smith & Wermuth (2013 ▶). For structures of 3,5-dinitrosalicylic acid salts, see: Smith et al. (2003 ▶). For graph-set analysis, see: Bernstein et al. (1995 ▶). graphic file with name e-69-0o472-scheme1.jpg

Experimental

Crystal data

C₁₂H₁₅N₄O₂S⁺·C₇H₃N₂O₇ ⁻
M _r = 506.46
Monoclinic,
a = 8.1691 (3) Å
b = 32.0736 (9) Å
c = 8.9869 (3) Å
β = 112.258 (5)°
V = 2179.23 (15) Å³
Z = 4
Mo Kα radiation
μ = 0.22 mm⁻¹
T = 200 K
0.40 × 0.35 × 0.20 mm

Data collection

Oxford Diffraction Gemini-S CCD-detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012 ▶) T _min = 0.918, T _max = 0.980
14977 measured reflections
4264 independent reflections
3645 reflections with I > \2s(I)
R _int = 0.039

Refinement

R[F ² > 2σ(F ²)] = 0.070
wR(F ²) = 0.158
S = 1.10
4264 reflections
318 parameters
H-atom parameters constrained
Δρ_max = 0.87 e Å⁻³
Δρ_min = −0.51 e Å⁻³

Data collection: CrysAlis PRO (Agilent, 2012 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SIR92 (Altomare et al., 1993 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶) within WinGX (Farrugia, 2012 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Click here for additional data file.^{(30.3KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813005631/nk2201sup1.cif

e-69-0o472-sup1.cif^{(30.3KB, cif)}

Click here for additional data file.^{(209KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813005631/nk2201Isup2.hkl

e-69-0o472-Isup2.hkl^{(209KB, hkl)}

Click here for additional data file.^{(8.5KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813005631/nk2201Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1A—H1A⋯O11	0.88	1.75	2.617 (4)	168
N2A—H2A⋯O12	0.78	1.95	2.729 (4)	170
O12—H12⋯O2	0.96	1.52	2.416 (5)	154
N41A—H41A⋯O51ⁱ	0.81	2.50	3.248 (5)	153
N41A—H42A⋯O12A ⁱⁱ	0.81	2.46	3.202 (4)	152

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

The authors acknowledge financial support from the Australian Reseach Council, the Science and Engineering Faculty and the University Library, Queensland University of Technology.

supplementary crystallographic information

Comment

The drug sulfamethazine (or sulfadimidine) [4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide] (O'Neil, 2001) has been used as a model for co-crystal formation (Caira, 2007; Ghosh et al., 2011), commonly forming 1:1 adducts with carboxylic acids, predominently the benzoic analogues but including some amides. The structures of a number of these have been reported, e.g. anthranilic acid and 4-aminobenzoic acid (Caira, 1991), 2,4-dinitrobenzoic acid (Lynch et al., 2000), as well as benzamide, 4-hydroxybenzamide and picolinamide (Ghosh et al., 2011). In all of these co-crystals, heterodimers are formed through a cyclic intermolecular hydrogen-bonding motif [graph set R²₂(8) (Bernstein et al., 1995)], involving amine N—H···O_carboxyl and carboxylic acid O—H···N_pyrimidine pairs.

However, there are no examples of the structures of proton-transfer salts of sulfamethazine with carboxylic acids so we looked at the products from the 1:1 stoichiometric reactions with some strong acids. Crystalline materials were obtained from the 5-nitrosalicylic acid and picric acid reactions, namely the anhydrous (1:1) carboxylate and picrate salts, respectively (Smith & Wermuth, 2013). With 3,5-dinitrosalicylic acid (DNSA), the poorly-formed anhydrous 1:1 salt of the title compound, C₁₂H₁₅N₄O₂S⁺ C₇H₃N₂O₇^-, was obtained, and the structure is reported herein. DNSA has been particularly useful in providing crystalline proton-transfer salts with both aliphatic and aromatic amines, the majority of which have been picrates, in which an anti-related acidic proton is retained on the carboxylic acid group rather than on the phenolic group (Smith et al., 2003).

With the title salt, the phenolate anion is found (Fig. 1), providing a variant of the R²₂(8) cation–anion hydrogen-bonding interaction as found in the non-transfer co-crystal structures, the difference arising from the presence of the transferred acid proton on the pyrimidine nitrogen (N1A). The slight asymmetry in the N1A···O and N2A···O hydrogen bond distances [2.622 (5) and 2.732 (4) Å] (Table 1) is comparable with those in the non-transfer co-crystals. In the DNSA anion, the anti-related acid proton forms the usual intramolecular hydrogen bond with the phenolate O-atom (Smith et al., 2003). Both H-atoms of the aniline group of the cation participate in intermolecular N—H···O hydrogen-bonding interactions with both sulfone and nitro O-atom acceptors, giving extensions along the a and b axes respectively, giving a two-dimensional structure lying along (001) (Fig. 2).

In the sulfamethazine cation, the dihedral angle between the pyrimidinium and phenyl rings is 59.70 (17)°, similar to that found in the picrate salt [58.18 (7)°] (Smith & Wermuth, 2013), but significantly smaller than commonly found with the adduct structures, e.g. 70.3 (4)° in the 2,4-dinitrobenzoic acid co-crystal (Lynch et al., 2000). The two interacting pyrimidine–DNSA moieties are close to coplanar [inter-ring dihedral angle 12.2 (2)°].

Experimental

The title compound was prepared by the reaction of 1 mmol quantities of 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (sulfamethazine) with 3,5-dinitrosalicylic in 50 ml of 50% ethanol–water with 10 min refluxing. Partial evaporation of the solvent gave poorly-formed yellow crystal plates (m.p. 457–458 K) from which a specimen was cleaved for the X-ray analysis.