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

Yang, Yanchun a Guo, Yuhua b Zhu, Changjin a * [a ] Department of Applied Chemistry, Beijing Institute of Technology, Zhongguancun South Street, 100081 Beijing, People’s Republic of China [b ] Department of Chemistry and Environmental Engineering, Anyang Institute of Technology, Henan 455000, People’s Republic of China

Abstract

In the mol­ecule of the title compound, C 16H 12ClF 3N 2O 4S, 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 ). e-68-o1363-scheme1.jpg

Experimental  

Crystal data  

  • C 16H 12ClF 3N 2O 4S

  • M r = 420.79

  • Monoclinic, e-68-o1363-efi1.jpg

  • a = 9.3628 (2) Å

  • b = 12.3134 (2) Å

  • c = 15.5597 (3) Å

  • β = 105.996 (1)°

  • V = 1724.39 (6) Å 3

  • 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

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

e-68-o1363-Isup2.hkl

Supplementary material file. DOI: 10.1107/S1600536812014468/rz2722Isup3.cml

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

Notes

[1] Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: RZ2722).

Acknowledgements

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).

Appendices

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 R 2 2(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)-2 H-benzo[ e][1,2,4]thiadiazin-4(3 H)-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 MgSO 4 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%).

Refinement

H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93–0.97 Å, O—H = 0.82 Å and with U iso(H) = 1.2 U eq(C) or 1.5 U eq(O).

Figures

Fig. 1.

The molecular structure of the title compound, with 30% probability displacement ellipsoids.

The molecular structure of the title compound, with 30% probability displacement ellipsoids.

Crystal data

C 16H 12ClF 3N 2O 4S F(000) = 856
M r = 420.79 D x = 1.621 Mg m 3
Monoclinic, P2 1/ c Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc Cell parameters from 4599 reflections
a = 9.3628 (2) Å θ = 2.8–28.3°
b = 12.3134 (2) Å µ = 0.40 mm 1
c = 15.5597 (3) Å T = 296 K
β = 105.996 (1)° Block, colourless
V = 1724.39 (6) Å 3 0.20 × 0.20 × 0.20 mm
Z = 4

Data collection

Bruker APEXII CCD diffractometer 3302 reflections with I > 2σ( I)
Radiation source: fine-focus sealed tube R int = 0.027
Graphite monochromator θ max = 28.3°, θ min = 2.1°
φ and ω scans h = −12→12
15140 measured reflections k = −16→15
4293 independent reflections l = −20→20

Refinement

Refinement on F 2 Primary atom site location: structure-invariant direct methods
Least-squares matrix: full Secondary atom site location: difference Fourier map
R[ F 2 > 2σ( F 2)] = 0.047 Hydrogen site location: inferred from neighbouring sites
wR( F 2) = 0.131 H-atom parameters constrained
S = 1.04 w = 1/[σ 2( F o 2) + (0.0571 P) 2 + 1.0199 P] where P = ( F o 2 + 2 F c 2)/3
4293 reflections (Δ/σ) max < 0.001
245 parameters Δρ max = 0.73 e Å 3
0 restraints Δρ min = −0.82 e Å 3

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2, conventional R-factors R are based on F, with F set to zero for negative F 2. The threshold expression of F 2 > σ( F 2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2)

x y z U iso*/ U eq
S1 0.45256 (6) 0.88685 (5) 0.08722 (3) 0.04077 (16)
Cl1 −0.00328 (10) 0.62773 (8) 0.09172 (6) 0.0872 (3)
C11 0.8849 (2) 0.89923 (18) 0.16523 (14) 0.0394 (5)
C5 0.3729 (2) 0.79827 (17) 0.14930 (12) 0.0350 (4)
N2 0.62050 (19) 0.90503 (15) 0.15259 (11) 0.0387 (4)
F2 1.26561 (18) 1.08588 (15) 0.23239 (13) 0.0768 (5)
O1 0.46125 (19) 0.83390 (17) 0.00742 (10) 0.0607 (5)
F3 1.0586 (2) 1.12091 (14) 0.07690 (12) 0.0729 (5)
C12 0.9947 (3) 0.88393 (19) 0.24347 (15) 0.0458 (5)
C6 0.2388 (2) 0.75123 (19) 0.10327 (14) 0.0449 (5)
H6 0.1985 0.7648 0.0426 0.054*
N1 0.5746 (2) 0.82433 (15) 0.28393 (11) 0.0392 (4)
F1 0.97529 (19) 0.80656 (14) 0.30117 (11) 0.0714 (5)
O2 0.37472 (19) 0.98763 (15) 0.07985 (13) 0.0597 (5)
C4 0.4382 (2) 0.77835 (16) 0.24064 (12) 0.0341 (4)
C7 0.6157 (2) 0.92240 (18) 0.24459 (13) 0.0400 (5)
H7A 0.7126 0.9466 0.2802 0.048*
H7B 0.5445 0.9792 0.2456 0.048*
C3 0.3601 (3) 0.70893 (18) 0.28347 (14) 0.0435 (5)
H3 0.3996 0.6932 0.3438 0.052*
C2 0.2264 (3) 0.66393 (19) 0.23789 (16) 0.0484 (5)
H2 0.1761 0.6192 0.2679 0.058*
C1 0.1662 (3) 0.6843 (2) 0.14823 (16) 0.0489 (5)
C9 0.5751 (3) 0.8936 (2) 0.43292 (13) 0.0447 (5)
C8 0.6382 (3) 0.8131 (2) 0.37949 (13) 0.0462 (5)
H8A 0.7449 0.8232 0.3935 0.055*
H8B 0.6200 0.7400 0.3972 0.055*
C19 0.7430 (2) 0.8351 (2) 0.14144 (16) 0.0468 (5)
H19A 0.7213 0.8102 0.0800 0.056*
H19B 0.7531 0.7720 0.1800 0.056*
C16 0.9087 (2) 0.98074 (19) 0.10813 (15) 0.0442 (5)
H16 0.8376 0.9939 0.0542 0.053*
C15 1.0367 (3) 1.0414 (2) 0.13140 (16) 0.0482 (5)
C14 1.1431 (3) 1.0230 (2) 0.21047 (18) 0.0506 (6)
C13 1.1245 (3) 0.9440 (2) 0.26747 (17) 0.0527 (6)
H13 1.1968 0.9307 0.3209 0.063*
O4 0.6474 (2) 0.89659 (17) 0.51717 (10) 0.0651 (6)
H4 0.6053 0.9380 0.5435 0.098*
O3 0.4682 (2) 0.95079 (17) 0.39943 (11) 0.0645 (6)

Atomic displacement parameters (Å 2)

U 11 U 22 U 33 U 12 U 13 U 23
S1 0.0349 (3) 0.0559 (3) 0.0303 (2) −0.0079 (2) 0.00703 (18) 0.0092 (2)
Cl1 0.0666 (5) 0.1026 (7) 0.0868 (6) −0.0466 (5) 0.0117 (4) 0.0042 (5)
C11 0.0321 (10) 0.0454 (12) 0.0418 (11) 0.0012 (9) 0.0122 (8) −0.0088 (9)
C5 0.0337 (10) 0.0405 (11) 0.0317 (9) −0.0010 (8) 0.0107 (7) 0.0047 (8)
N2 0.0305 (8) 0.0499 (10) 0.0360 (8) −0.0045 (7) 0.0095 (7) −0.0032 (7)
F2 0.0449 (9) 0.0762 (11) 0.1085 (14) −0.0195 (8) 0.0196 (9) −0.0269 (10)
O1 0.0554 (10) 0.0992 (15) 0.0291 (7) −0.0253 (10) 0.0143 (7) −0.0050 (8)
F3 0.0804 (12) 0.0682 (11) 0.0810 (11) −0.0100 (9) 0.0403 (10) 0.0087 (8)
C12 0.0422 (12) 0.0479 (13) 0.0464 (12) 0.0040 (10) 0.0108 (9) 0.0000 (10)
C6 0.0404 (12) 0.0546 (14) 0.0376 (10) −0.0088 (10) 0.0072 (9) 0.0050 (9)
N1 0.0435 (10) 0.0441 (10) 0.0272 (8) 0.0020 (8) 0.0052 (7) −0.0012 (7)
F1 0.0715 (11) 0.0740 (11) 0.0638 (10) 0.0000 (9) 0.0101 (8) 0.0207 (8)
O2 0.0453 (10) 0.0598 (11) 0.0706 (11) 0.0027 (8) 0.0101 (8) 0.0289 (9)
C4 0.0403 (11) 0.0337 (10) 0.0292 (9) 0.0057 (8) 0.0110 (8) 0.0000 (7)
C7 0.0384 (11) 0.0444 (12) 0.0362 (10) −0.0029 (9) 0.0084 (8) −0.0067 (8)
C3 0.0597 (14) 0.0408 (12) 0.0341 (10) 0.0057 (10) 0.0195 (9) 0.0073 (8)
C2 0.0582 (14) 0.0397 (12) 0.0555 (13) −0.0028 (11) 0.0295 (11) 0.0075 (10)
C1 0.0440 (13) 0.0486 (13) 0.0552 (13) −0.0125 (10) 0.0154 (10) 0.0009 (10)
C9 0.0438 (12) 0.0551 (14) 0.0305 (9) 0.0077 (10) 0.0025 (8) −0.0027 (9)
C8 0.0468 (12) 0.0566 (14) 0.0310 (10) 0.0132 (11) 0.0036 (8) −0.0007 (9)
C19 0.0383 (12) 0.0501 (13) 0.0527 (13) −0.0044 (10) 0.0138 (9) −0.0133 (10)
C16 0.0386 (11) 0.0549 (14) 0.0402 (11) 0.0035 (10) 0.0124 (9) −0.0059 (9)
C15 0.0477 (13) 0.0486 (13) 0.0544 (13) 0.0009 (10) 0.0243 (11) −0.0043 (10)
C14 0.0335 (11) 0.0531 (14) 0.0666 (15) −0.0051 (10) 0.0160 (10) −0.0196 (12)
C13 0.0352 (12) 0.0634 (16) 0.0525 (13) 0.0073 (11) 0.0005 (9) −0.0104 (12)
O4 0.0648 (12) 0.0852 (14) 0.0333 (8) 0.0296 (10) −0.0066 (8) −0.0137 (8)
O3 0.0606 (11) 0.0843 (14) 0.0379 (8) 0.0325 (10) −0.0042 (7) −0.0133 (8)

Geometric parameters (Å, º)

S1—O1 1.4245 (17) C4—C3 1.407 (3)
S1—O2 1.4277 (19) C7—H7A 0.9700
S1—N2 1.6357 (18) C7—H7B 0.9700
S1—C5 1.7540 (19) C3—C2 1.374 (3)
Cl1—C1 1.734 (2) C3—H3 0.9300
C11—C12 1.373 (3) C2—C1 1.376 (3)
C11—C16 1.398 (3) C2—H2 0.9300
C11—C19 1.502 (3) C9—O3 1.217 (3)
C5—C6 1.389 (3) C9—O4 1.300 (2)
C5—C4 1.405 (3) C9—C8 1.514 (3)
N2—C7 1.460 (2) C8—H8A 0.9700
N2—C19 1.482 (3) C8—H8B 0.9700
F2—C14 1.347 (3) C19—H19A 0.9700
F3—C15 1.347 (3) C19—H19B 0.9700
C12—F1 1.355 (3) C16—C15 1.374 (3)
C12—C13 1.383 (3) C16—H16 0.9300
C6—C1 1.376 (3) C15—C14 1.372 (4)
C6—H6 0.9300 C14—C13 1.360 (4)
N1—C4 1.389 (3) C13—H13 0.9300
N1—C8 1.448 (2) O4—H4 0.8200
N1—C7 1.453 (3)
O1—S1—O2 118.58 (12) C4—C3—H3 119.4
O1—S1—N2 109.19 (10) C3—C2—C1 120.7 (2)
O2—S1—N2 108.23 (11) C3—C2—H2 119.7
O1—S1—C5 109.30 (11) C1—C2—H2 119.7
O2—S1—C5 107.43 (10) C6—C1—C2 120.2 (2)
N2—S1—C5 102.98 (9) C6—C1—Cl1 119.63 (19)
C12—C11—C16 116.8 (2) C2—C1—Cl1 120.18 (18)
C12—C11—C19 122.8 (2) O3—C9—O4 123.6 (2)
C16—C11—C19 120.4 (2) O3—C9—C8 122.87 (19)
C6—C5—C4 121.91 (19) O4—C9—C8 113.50 (19)
C6—C5—S1 115.88 (15) N1—C8—C9 112.90 (18)
C4—C5—S1 122.18 (16) N1—C8—H8A 109.0
C7—N2—C19 115.69 (18) C9—C8—H8A 109.0
C7—N2—S1 110.23 (13) N1—C8—H8B 109.0
C19—N2—S1 119.35 (14) C9—C8—H8B 109.0
F1—C12—C11 118.7 (2) H8A—C8—H8B 107.8
F1—C12—C13 117.7 (2) N2—C19—C11 109.07 (18)
C11—C12—C13 123.6 (2) N2—C19—H19A 109.9
C1—C6—C5 119.4 (2) C11—C19—H19A 109.9
C1—C6—H6 120.3 N2—C19—H19B 109.9
C5—C6—H6 120.3 C11—C19—H19B 109.9
C4—N1—C8 121.46 (18) H19A—C19—H19B 108.3
C4—N1—C7 116.70 (16) C15—C16—C11 120.2 (2)
C8—N1—C7 115.48 (18) C15—C16—H16 119.9
N1—C4—C5 120.34 (18) C11—C16—H16 119.9
N1—C4—C3 123.12 (18) F3—C15—C14 119.1 (2)
C5—C4—C3 116.53 (19) F3—C15—C16 120.2 (2)
N1—C7—N2 112.00 (17) C14—C15—C16 120.8 (2)
N1—C7—H7A 109.2 F2—C14—C13 120.0 (2)
N2—C7—H7A 109.2 F2—C14—C15 119.3 (2)
N1—C7—H7B 109.2 C13—C14—C15 120.7 (2)
N2—C7—H7B 109.2 C14—C13—C12 117.9 (2)
H7A—C7—H7B 107.9 C14—C13—H13 121.1
C2—C3—C4 121.29 (19) C12—C13—H13 121.1
C2—C3—H3 119.4 C9—O4—H4 109.5

Hydrogen-bond geometry (Å, º)

D—H··· A D—H H··· A D··· A D—H··· A
O4—H4···O3 i 0.82 1.86 2.676 (2) 171
C3—H3···O1 ii 0.93 2.47 3.391 (3) 169
C16—H16···O2 iii 0.93 2.46 3.387 (2) 172
C13—H13···O3 iv 0.93 2.51 3.307 (3) 144

Symmetry codes: (i) − x+1, − y+2, − z+1; (ii) x, − y+3/2, z+1/2; (iii) − x+1, − y+2, − z; (iv) x+1, y, z.

References

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Bruker (2001). SAINT-Plus Bruker AXS Inc., Madison, Wisconsin, USA.

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Bruker (2005). APEX2 . Bruker AXS Inc., Madison, Wisconsin, USA.

4  

Buckheit, R. W. Jr, Fliakas-Boltz, V., Decker, W. D., Roberson, J. L., Pyle, C. A., White, E. L., Bowdon, B. J., McMahon, J. B., Boyd, M. R., Bader, J. P., Nickell, D. G., Barth, H. & Antonucci, T. K. (1994). Antivir. Res. 25, 43–56.

5  

Chen, X., Zhu, C. J., Guo, F., Qiu, X. W., Yang, Y. C., Zhang, S. Z., He, M. L., Parveen, S., Jing, C. J., Li, Y. & Ma, B. (2010). J. Med. Chem. 53, 8330–8344.

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Pirotte, B., Podona, T., Diouf, O., de Tullio, P., Lebrun, P., Dupont, L., Somers, F., Delarge, J., Morain, P., Lestage, P., Lepagnol, J. & Spedding, M. (1998). J. Med. Chem. 41, 2946–2959.

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Figures and Tables

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯ A D—H H⋯ A DA D—H⋯ A
O4—H4⋯O3 i 0.82 1.86 2.676 (2) 171
C3—H3⋯O1 ii 0.93 2.47 3.391 (3) 169
C16—H16⋯O2 iii 0.93 2.46 3.387 (2) 172
C13—H13⋯O3 iv 0.93 2.51 3.307 (3) 144

Symmetry codes: (i) e-68-o1363-efi2.jpg ; (ii) e-68-o1363-efi3.jpg ; (iii) e-68-o1363-efi4.jpg ; (iv) e-68-o1363-efi5.jpg .