2-[7-Chloro-1,1-dioxo-2-(2,4,5-trifluoro­benz­yl)-3,4-dihydro-2H-1,2,4-benzothia­diazin-4-yl]acetic acid

Yanchun Yang; Yuhua Guo; Changjin Zhu

doi:10.1107/S1600536812014468

. 2012 Apr 13;68(Pt 5):o1363. doi: 10.1107/S1600536812014468

2-[7-Chloro-1,1-dioxo-2-(2,4,5-trifluorobenzyl)-3,4-dihydro-2H-1,2,4-benzothiadiazin-4-yl]acetic acid

Yanchun Yang ^a, Yuhua Guo ^b, Changjin Zhu ^a,^*

PMCID: PMC3344495 PMID: 22590257

Abstract

In the molecule of the title compound, C₁₆H₁₂ClF₃N₂O₄S, the thiadiazine ring adopts a half-chair conformation. The dihedral angle between the benzene ring of the benzothiadiazine ring system and trifluorophenyl group is 15.02 (7)°. In the crystal, centrosymmetrically related molecules are linked into dimers via pairs of O—H⋯O hydrogen bonds, generating R ₂ ²(8) ring motifs. The dimers are further connected into a three-dimensional network by C—H⋯O hydrogen bonds.

Related literature

For the pharmacological properties of benzothiadiazine derivatives, see: Longman & Hamilton (1992 ▶); Buckheit et al. (1994 ▶); Yamada & Tang (1993 ▶); Phillips et al. (2002 ▶); Braghiroli et al. (2002 ▶); Pirotte et al. (1998 ▶); Francotte et al. (2007 ▶). For the biological properties and synthetic details of the title compound, see: Chen et al. (2010 ▶).

Experimental

Crystal data

C₁₆H₁₂ClF₃N₂O₄S
M _r = 420.79
Monoclinic,
a = 9.3628 (2) Å
b = 12.3134 (2) Å
c = 15.5597 (3) Å
β = 105.996 (1)°
V = 1724.39 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.40 mm⁻¹
T = 296 K
0.20 × 0.20 × 0.20 mm

Data collection

Bruker APEXII CCD diffractometer
15140 measured reflections
4293 independent reflections
3302 reflections with I > 2σ(I)
R _int = 0.027

Refinement

R[F ² > 2σ(F ²)] = 0.047
wR(F ²) = 0.131
S = 1.04
4293 reflections
245 parameters
H-atom parameters constrained
Δρ_max = 0.73 e Å⁻³
Δρ_min = −0.82 e Å⁻³

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT-Plus (Bruker, 2001 ▶); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812014468/rz2722sup1.cif

e-68-o1363-sup1.cif^{(17.8KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812014468/rz2722Isup2.hkl

e-68-o1363-Isup2.hkl^{(210.4KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812014468/rz2722Isup3.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
O4—H4⋯O3ⁱ	0.82	1.86	2.676 (2)	171
C3—H3⋯O1ⁱⁱ	0.93	2.47	3.391 (3)	169
C16—H16⋯O2ⁱⁱⁱ	0.93	2.46	3.387 (2)	172
C13—H13⋯O3^iv	0.93	2.51	3.307 (3)	144

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

Acknowledgments

This work was supported by the Beijing Natural Science Foundation (No. 7102091) and the Research Fund for the Doctoral Program of Higher Education of China (No. 20111101110042).

supplementary crystallographic information

Comment

Benzothiadiazine derivatives have attracted considerable attention because they are endowed with a large spectrum of properties. Since the 1950's, various pharmacological investigations of newly synthesized benzothiadiazines demonstrated interesting pharmacological activities and showed great potential for the development of new medications for treating diseases (Longman & Hamilton, 1992; Buckheit et al., 1994; Yamada & Tang, 1993; Phillips et al., 2002; Braghiroli et al., 2002; Pirotte et al., 1998; Francotte et al., 2007). The title compound, whose structure is reported herein, was synthesized and used as an aldose reductase inhibitor (Chen et al., 2010).

In the molecule of the title compound (Fig. 1), the thiadiazine ring (C7/N1/C4/C5/S1/N2) adopts a half-chair conformation, with puckering parameters Q_T = 0.5164 (19) Å, θ = 47.5 (2)° and φ = -25.9 (3)°. The deviation of the S1, N1 and N2 atoms from the plane of the benzene ring of the benzothiadiazin ring system are -0.0726 (6), 0.0305 (19) and 0.2655 (18) Å, respectively. The dihedral angle formed by the two six-membered aromatic rings C1–C6 and C11–C16 is 15.02 (7)°. In the crystal, centrosymmetrically related molecules interact to form dimers through pairs of O—H···O hydrogen bonds (Table 1) generating a R²₂(8) ring motif. The dimers are further linked into a three-dimensional network by intermolecular C—H···O hydrogen bonds (Table 1).

Experimental

A mixture of methyl 2-(7-chloro-1,1-dioxido-2-(2,4,5-trifluorobenzyl)-2H-benzo[e][1,2,4]thiadiazin-4(3H)-yl)acetate (1 mmol), 1,4-dioxane (5 ml) and saturated aqueous sodium hydroxide (5 ml) was stirred at room temperature for 2 h. The alkaline suspension was adjusted to be acidic with 0.1 molar HCl and extracted with ethyl acetate (3 × 20 ml). The combined organic layers were dried over MgSO₄ and filtered. The filtrate was concentrated to dryness under reduced pressure. Crystals suitable for X-ray diffraction were obtained by slow evaporation of a methanol solution of the compound (yield: 76%).