4-Amino-N-(4,6-dimethyl­pyrimidin-2-yl)benzene­sulfonamide–2-nitro­benzoic acid (1/1)

Graham Smith; Urs D Wermuth

doi:10.1107/S1600536813000779

. 2013 Jan 12;69(Pt 2):o234. doi: 10.1107/S1600536813000779

4-Amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide–2-nitrobenzoic acid (1/1)

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

PMCID: PMC3569767 PMID: 23424513

Abstract

In the asymmetric unit of the title co-crystal, C₁₂H₁₄N₄O₂S·C₇H₅NO₄, the sulfamethazine and 2-nitrobenzoic acid molecules form a heterodimer through intermolecular amide–carboxylic acid N—H⋯O and carboxylic acid–pyrimidine O—H⋯N hydrogen-bond pairs, giving a cyclic motif [graph set R ₂ ²(8)]. The dihedral angle between the two aromatic ring systems in the sulfamethazine molecule is 88.96 (18)° and the nitro group of the acid is 50% rotationally disordered. Secondary aniline N—H⋯O_sulfone hydrogen-bonding associations give a two-dimensional structure lying parallel to the ab plane.

Related literature

For background to sulfamethazole as a model for co-crystal formation, see: Caira (2007 ▶); Ghosh et al. (2011 ▶). For structures of 1:1 adducts of sulfamethazine with nitrobenzoic acid analogues, see: Lynch et al. (2000 ▶); Smith & Wermuth (2012 ▶). For graph-set analysis, see: Etter et al. (1990 ▶).

Experimental

Crystal data

C₁₂H₁₄N₄O₂S·C₇H₅NO₄
M _r = 445.46
Orthorhombic,
a = 14.2945 (4) Å
b = 8.0115 (3) Å
c = 19.0962 (5) Å
V = 2186.91 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 200 K
0.30 × 0.21 × 0.12 mm

Data collection

Oxford Diffraction Gemini-S CCD-detector diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012 ▶) T _min = 0.964, T _max = 0.980
5541 measured reflections
2777 independent reflections
2587 reflections with I > 2σ(I)
R _int = 0.023

Refinement

R[F ² > 2σ(F ²)] = 0.040
wR(F ²) = 0.099
S = 1.04
2777 reflections
286 parameters
29 restraints
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.21 e Å⁻³
Absolute structure: Flack (1983 ▶), 565 Friedel pairs
Flack parameter: 0.08 (9)

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.^{(29.5KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813000779/gg2106sup1.cif

e-69-0o234-sup1.cif^{(29.5KB, cif)}

Click here for additional data file.^{(136.4KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813000779/gg2106Isup2.hkl

e-69-0o234-Isup2.hkl^{(136.4KB, hkl)}

Click here for additional data file.^{(7.8KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813000779/gg2106Isup3.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
O12—H12⋯N1A	0.90	1.77	2.671 (4)	180
N2A—H2A⋯O11	0.90	2.01	2.862 (4)	158
N41A—H41A⋯O11A ⁱ	0.92	2.18	2.990 (3)	147
N41A—H42A⋯O12A ⁱⁱ	0.83	2.24	2.973 (3)	146

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

Acknowledgments

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

supplementary crystallographic information

Comment

The drug sulfamethazine [4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide] has been used as a model for co-crystal formation (Caira, 2007; Ghosh et al., 2011)), commonly forming 1:1 adducts with carboxylic acids and amides, particularly the benzoic acid analogues. The structures of a number of these are known, including those with 4-nitrobenzoic acid (Smith & Wermuth, 2012) and 2,4-dinitrobenzoic acid (Lynch et al., 2000). In these co-crystals, and in sulfamethazine adducts generally a common structural feature is the cyclic heterodimeric hydrogen-bonding association involving amide N—H···O_carboxyl–carboxylic acid O—H···N_pyrimidine pairs [graph set R²₂(8) (Etter et al., 1990)].

Our 1:1 stoichiometric interaction of sulfamethazine with 2-nitrobenzoic acid gave the co-crystalline adduct C₁₂H₁₄N₄O₂S. C₇H₅NO₄, the title compound and the structure is reported herein. In the sulfamethazine component (Fig. 1) the dihedral angle between the pyrimidine ring and the phenyl ring is 89.98 (18)° which compares with 82.33 (9)° and 78.77 (8)° for the two independent molecules in the 4-nitrobenzoic acid analogue (Smith & Wermuth, 2012). The angles between these two rings and the phenyl ring of the 2-nitrobenzoic acid molecule are 9.65 (19) and 88.22 (19)°, respectively. In the crystal the sulfamethazine and 2-nitrobenzoic acid molecules interact as previously described, giving cyclic R²₂(8) hydrogen-bonded heterodimers (Table 1, Fig. 1).

Intermolecular amine N—H···O_sulfone hydrogen-bonding interactions link the heterodimer units along a (Fig. 2) as well as down b, forming two-dimensional sheet structures which extend along [110]. Unlike the isomeric 4-nitrobenzoic acid adduct there are no π–π interactions present in the structure but there are 52.2 Å³ potential solvent accessible voids present. The oxygen atoms of the nitro group of the adduct acid molecule are rotationally disordered over four 50% occupancy sites [O21, O22 and O23, O24]. In the absence of chirality in the molecules, the Flack absolute structure parameter [0.08 (9)] is of no structural significance.

Experimental

The title compound was formed in the interaction of 1 mmol quantities of 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (sulfamethazine) and 2-nitrobenzoic acid in 50 ml of 50% ethanol–water with 10 min refluxing. Partial evaporation of the solvent gave a pale yellow solid which gave crystal plates suitable for the X-ray analysis after recrystallization from ethanol.