2-(3,5-Dimethyl-1,1-dioxo-2H-1λ6,2,6-thia­diazin-4-yl)benzoic acid

Nilay Bhatt; Pralav Bhatt; Thavendran Govender; Hendrik G Kruger; Glenn E M Maguire

doi:10.1107/S1600536812037026

. 2012 Sep 5;68(Pt 10):o2859. doi: 10.1107/S1600536812037026

2-(3,5-Dimethyl-1,1-dioxo-2H-1λ⁶,2,6-thiadiazin-4-yl)benzoic acid

Nilay Bhatt ^a, Pralav Bhatt ^b, Thavendran Govender ^c, Hendrik G Kruger ^b, Glenn E M Maguire ^b,^*

PMCID: PMC3470217 PMID: 23125661

Abstract

In the title molecule, C₁₂H₁₂N₂O₄S, the S atom of the thiadiazine ring deviates by 0.5104 (4) Å from the mean plane of the other five atoms [largest deviation = 0.0623 (15) Å] giving a slightly distorted sofa conformation. The carboxy H atom was refined as disordered over two sets of sites with refined occupancies of 0.58 (2) and 0.48 (2). This corresponds to rotational disorder of the C=O and O—H groups about the attached C—C bond. In the crystal, O—H⋯O and N—H⋯O hydrogen bonds connect the molecules into chains along [110].

Related literature

The title compound is a phenyl acid thiadiazine derivative. For synthetic background and applications of 1,2,6-thiadiazine-1,1-dioxide derivatives, see: Wright (1964 ▶); Breining et al. (1995 ▶). For a related structure, see: Bhatt et al. (2012 ▶)

Experimental

Crystal data

C₁₂H₁₂N₂O₄S
M _r = 280.30
Monoclinic,
a = 10.5048 (14) Å
b = 10.4254 (13) Å
c = 11.1294 (14) Å
β = 92.772 (4)°
V = 1217.4 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.28 mm⁻¹
T = 173 K
0.24 × 0.19 × 0.18 mm

Data collection

Bruker Kappa DUO APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.936, T _max = 0.952
5724 measured reflections
3030 independent reflections
2573 reflections with I > 2σ(I)
R _int = 0.020

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.103
S = 1.05
3030 reflections
187 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.37 e Å⁻³
Δρ_min = −0.42 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812037026/lh5507sup1.cif

e-68-o2859-sup1.cif^{(17.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812037026/lh5507Isup2.hkl

e-68-o2859-Isup2.hkl^{(148.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812037026/lh5507Isup3.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
N1—H1⋯O1ⁱ	0.97 (1)	2.09 (2)	2.9699 (18)	151 (2)
O4—H4⋯O3ⁱⁱ	0.97 (3)	1.64 (3)	2.6103 (19)	177 (3)
O3—H3⋯O4ⁱⁱ	0.97 (3)	1.67 (3)	2.6103 (19)	161 (5)

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

Acknowledgments

The authors wish to thank Dr Hong Su from the University of Cape Town for assistance with the data collection and refinement.

supplementary crystallographic information

Comment

The synthesis of 1,2,6-thiadiazine-1,1-dioxides derivatives was first reported using sulfamide with alpha and beta diketones (Wright, 1964). Anti-HIV-1 activity for this family of structures was also reported (Breining et al., 1995). For this reason we are interested in this class of compounds as potential agents in other diseases. The crystal structure of the title compound is described herein.

The molecular structure of the title compound is shown in Fig. 1. It is the second 3,5-dimethyl based structure reported with an aromatic ring at position 4 of the thiadiazine ring. Previously we have reported the phenyl ethyl and methyl ester (Bhatt et al., 2012). It is the first containing an acid functional group in the broader family of 1,2,6-thiadiazine-1,1-dioxides. The S atom of the thiadiazine ring deviates by 0.5104 (4) Å from the plane of the other five atoms [largest deviation 0.0623 (15) Å] giving a slightly distorted sofa conformation. The carboxylic acid H atom was refined as disordered over two sets of sites with refined occupancies 0.58 (2) and 0.48 (2). This corresponds to roational disorder of the C═O and O—H groups about the attached C—C bond. In the crystal, O—H···O and N—H···O hydrogen bonds connect molecules into chains along [110] (Fig. 2).

Experimental

2-(2, 4-dioxopentan-3-yl) benzoic acid (0.072 mol) and sulfamide (0.072 mol) were dissolved in methanol (70 ml). Anhydrous hydrogen chloride gas was bubbled into the mixture until the temperature increased to 323 K. The contents of the reaction were then refluxed for 3hrs. The reaction mixture was cooled, filtered and the filtrate was concentrated under reduced pressure. The residual solid was treated with NaOH (0.138 mol) in water (200 ml), the contents were heated at 343 K for 2.5 hrs. The reaction progress was monitored by TLC ethyl acetate/hexane (80:20 R_f = 1/2). The reaction mixture was cooled and acidified using concentrated HCl to get the crude acid as an oil. To this oily residue was added a solution of methanol/ethyl acetate (10 ml) (10/90) which yielded a white colourless solid (79%). M.p.= 523 K. Crystals suitable for X-ray analysis were grown in dioxane/water at room temprature.