2 Methyl 6,7 di­hydro­thia­zolo­[3,2 b][1,2,4]­thia­diazine 1,1 dioxide

organic papers

o362

Structure Reports Online

ISSN 1600-5368

2-Methyl-6,7-dihydrothiazolo[3,2-

b

][1,2,4]thiadiazine

1,1-dioxide

Michel Evain,a_{* Cyrille} Landreau,b _{David Deniaud,}b Alain Reliquetb_{and Jean Claude} Meslinb

a_{Institut des MateÂriaux Jean Rouxel, Laboratoire}

de Chimie des Solides, 2 rue de la HoussinieÁre, BP 32229, 44322 Nantes CEDEX 3, France, and

b_{Laboratoire de SyntheÁse, Organique UMR}

CNRS 6513, Faculte des Sciences et des Techniques, 2 rue de la HoussinieÁre, BP 92208, 44322 Nantes CEDEX 3, France

Correspondence e-mail: evain@cnrs-imn.fr

Key indicators

Single-crystal X-ray study

T= 298 K

Mean(C±C) = 0.002 AÊ

Rfactor = 0.045

wRfactor = 0.110

Data-to-parameter ratio = 33.9

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

#2002 International Union of Crystallography Printed in Great Britain ± all rights reserved

The title compound, C6H8N2O2S2, represents one of the ®rst

examples of a novel sulfonamide family. The molecule, which is roughly planar, is built up from two fused rings, viz. the thiadiazine 1,1-dioxide and thiazole rings.

Comment

Heterocyclic sulfonamides are interesting compounds because of their promising chemotherapeutic potential. Among these, 1,2,4-benzothiadiazine 1,1-dioxides are already known to possess diuretic and antihypertensive properties (Edwards & Weston, 1990). The bioisosteric replacement of the benzene ring with a pyridine ring (Neillet al., 1998; de Tullioet al., 1999; Kheliliet al., 1999; Pirotteet al., 2000) has led to the discovery of a new class of PCOs (potassium channel openers), namely the pyrido[4,3-e]- and [2,3-e][1,2,4]thiadiazine-1,1-dioxides. Furthermore, Arranz et al. (1998, 1999) have described the synthesis and antiviral activity (HIV-1) of derivatives fused to a thiophene nucleus. These thieno[3,4-e][1,2,4]thiadiazines represent a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Ever since, such compounds have also been assessed for their antihypertensive properties as voltage-dependent calcium channel blockers (Arranzet al., 2000). On the other hand, many condensed thiazoles display signi®cant biological activities. As a recent example, several 1-aryl-1H,3H-thiazolo[4,3-b]quinazolines have been found to possess antitumor properties (Grasso et al., 2000). These considera-tions led us to prepare 6,7-dihydrothiazolo[3,2-b ][1,2,4]thia-diazine 1,1-dioxides, in which both these heterocycles are combined. A full report of the synthesis, as well as of the physical and analytical data, will be presented separately (Landreauet al., 2002). To our knowledge, the title compound, (I), is one of the ®rst examples in this novel sulfonamide family. The molecule, shown in Fig. 1, is built up from fused thiadiazine 1,1-dioxide and thiazole rings. The fused-ring system is nearly planar, with deviations less than 0.1 AÊ, except for atom C6, which is 0.363 (3) AÊ from the plane.

Experimental

To a solution of N0_{-(4,5-dihydrothiazol-2-yl)-N,N}

-dimethylform-amidine (2 mmol) in dichloromethane (10 ml) was added ethane-sulfonyl chloride (2.4 mmol). The reaction mixture was then stirred at room temperature for 4 h. After cooling to 273 K, triethylamine (4.8 mmol) was added and the reaction mixture was further stirred at room temperature for 16 h, then concentratedin vacuo. The residue was diluted with dichloromethane and ®ltered through a short pad of silica gel using, as eluant, CH2Cl2/EtOAc (1:1). The mixture was then

treated with a solution of iodomethane (2 ml) in tetrahydrofuran (5 ml). After stirring at room temperature for 5 d, the reaction mixture was evaporated to dryness and a solution of triethylamine (1 ml) in dichloromethane (10 ml) was added to this. Stirring was continued at room temperature for 2 d and the solvent was removed. The resulting residue was diluted with dichloromethane and chro-matographed (CH2Cl2/EtOAc, 9:1). Single crystals suitable for X-ray

analysis were obtained by slow evaporation at room temperature from diethyl ether.

Crystal data

C6H8N2O2S2

Mr= 204.3

Monoclinic, P21=c

a= 8.3906 (8) AÊ

b= 8.4339 (8) AÊ

c= 12.0900 (11) AÊ = 98.036 (12)

V= 847.15 (14) AÊ3

Z= 4

Dx= 1.601 Mg mÿ3

MoKradiation Cell parameters from 8000

re¯ections = 12.7±27.8

= 0.59 mmÿ1

T= 298 K Block, colourless 0.350.280.22 mm

Data collection

Nonius CAD-4 and Stoe IPDS diffractometers

/2and!scans

Absorption correction: Gaussian (JANA2000; Petricek & Dusek, 2000)

Tmin= 0.885,Tmax= 0.909

25270 measured re¯ections 3729 independent re¯ections

2287 re¯ections withI> 2(I)

Rint= 0.061

max= 35.1

h=ÿ13!13

k=ÿ13!13

l=ÿ19!15 3 standard re¯ections

frequency: 60 min intensity decay: 1.0%

Re®nement

Re®nement onF2

R[F2_{> 2(F}2_{)] = 0.045}

wR(F2_{) = 0.110}

S= 1.42 3729 re¯ections 110 parameters

H-atom parameters constrained

w= 1/[2_{(I) + 0.0016I}2_]

(/)max= 0.001 max= 0.71 e AÊÿ3 min=ÿ0.46 e AÊÿ3

Extinction correction: B±C type 1 Lorentzian isotropic (Becker & Coppens, 1974)

Extinction coef®cient: 0.93 (6)

CAD-4 and IPDS data sets (11575 and 13695 re¯ections, respectively) were scaled on the basis of 5421 common re¯ections withI> 10(I) [scale factor: 0.0354 (1)]. The CH3group was located

in a difference Fourier map. All H atoms were then ®xed at calculated positions. Riding isotropic displacement parameters were used for all H atoms.

Data collection: CAD-4-PC Software (Enraf±Nonius, 1993) and

EXPOSE (Stoe & Cie, 1997); cell re®nement:CELL(Stoe & Cie, 1997); data reduction: JANA2000 (Petricek & Dusek, 2000); program(s) used to solve structure: SHELXTL (Sheldrick, 1995); program(s) used to re®ne structure:JANA2000; molecular graphics:

DIAMOND (Brandenburg & Berndt, 1999); software used to prepare material for publication:JANA2000.

The authors gratefully acknowledge ®nancial support by the French Ministry of Education and CNRS.

References

Arranz, E., DõÂaz, J. A., Ingate, S. T., Witvrouw, M., Pannecouque, C., Balzarini, J., De Clercq, E. & Vega, S. (1998).J. Med. Chem.41, 4109±4117. Arranz, E., DõÂaz, J. A., Ingate, S. T., Witvrouw, M., Pannecouque, C., Balzarini,

J., De Clercq, E. & Vega, S. (1999).Bioorg. Med. Chem.7, 2811±2822. Arranz, E., DõÂaz, J. A., Vega, S., Campos-Toimil, M., Orallo, F., CardeluÂs, I.,

Llenas, J. & FernaÂndez, A. G. (2000).Eur. J. Med. Chem.35, 751±759. Becker, P. J. & Coppens, P. (1974).Acta Cryst.A30, 129±153.

Brandenburg, K. & Berndt, M. (1999).DIAMOND. Crystal Impact GbR, Bonn, Germany.

Edwards, G. & Weston, A. H. (1990).Trends Pharmacol. Sci.11, 417±422. Enraf±Nonius (1993).CAD-4-PC Software. Enraf±Nonius, Delft, The

Nether-lands.

Grasso, S., Micale, N., Monforte, A.-M., Monforte, P., Polimeni, S. & ZappalaÁ, M. (2000).Eur. J. Med. Chem.35, 1115±1119.

Khelili, S., de Tullio, P., Lebrun, P., Fillet, M., Antoine, M.-H., Ouedraogo, R., Dupont, L., Fontaine, J., Felekidis, A., Leclerc, G., Delarge, J. & Pirotte, B. (1999).Bioorg. Med. Chem.7, 1513±1520.

Landreau, C., Deniaud, D., Reliquet, A. & Meslin, J. C. (2002).Tetrahedron Lett.In the press.

Neill, C. G., Preston, P. N. & Wightman, R. H. (1998).Tetrahedron,54, 13645± 13654.

Petricek, V. & Dusek, M. (2000).JANA2000. Institute of Physics, Praha, Czech Republic.

Pirotte, B., Ouedraogo, R., de Tullio, P., Khelili, S., Somers, F., Boverie, S., Dupont, L., Fontaine, J., Damas, J. & Lebrun, P. (2000).J. Med. Chem.43, 1456±1466.

Sheldrick, G. M. (1995). SHELXTL.Version 5.0. Analytical X-ray Instru-ments Inc., Madison, Wisconsin, USA.

Stoe & Cie (1997).EXPOSEandCELLin Stoe IPDS. Stoe & Cie GmbH, Darmstadt, Germany.

Tullio, P. de, Ouedraogo, R., Dupont, L., Somers, F., Boverie, S., DogneÂ, J.-M., Delarge, J. & Pirotte, B. (1999).Tetrahedron,55, 5419±5432.

Figure 1

supporting information

sup-1

Acta Cryst. (2002). E58, o362–o363

supporting information

Acta Cryst. (2002). E58, o362–o363 [https://doi.org/10.1107/S1600536802003987]

2-Methyl-6,7-dihydrothiazolo[3,2-

b

][1,2,4]thiadiazine 1,1-dioxide

Michel Evain, Cyrille Landreau, David Deniaud, Alain Reliquet and Jean Claude Meslin

(I)

Crystal data

C6H8N2O2S2 Mr = 204.3

Monoclinic, P21/c

Hall symbol: -P 2ybc

a = 8.3906 (8) Å

b = 8.4339 (8) Å

c = 12.0900 (11) Å

β = 98.036 (12)°

V = 847.15 (14) Å3

Z = 4

F(000) = 424

Dx = 1.601 Mg m−3

Mo Kα radiation, λ = 0.71069 Å Cell parameters from 8000 reflections

θ = 12.7–27.8°

µ = 0.59 mm−1 T = 298 K Block, colourless 0.35 × 0.28 × 0.22 mm

Data collection

Nonius CAD-4 and Stoe IPDS diffractometer

Radiation source: X-ray tube Graphite monochromator

θ/2θ and ω scans

Absorption correction: gaussian (JANA2000; Petricek & Dusek, 2000)

Tmin = 0.885, Tmax = 0.909

25270 measured reflections 3729 independent reflections 2287 reflections with I > 2σ(I)

Rint = 0.061

θmax = 35.1°, θmin = 2.5° h = −13→13

k = −13→13

l = −19→15

Refinement

Refinement on F2 R[F > 3σ(F)] = 0.045

wR(F) = 0.110

S = 1.42 3729 reflections 110 parameters

H-atom parameters constrained

Weighting scheme based on measured s.u.'s w = 1/[σ2_{(I) + 0.0016I}2_]

(Δ/σ)max = 0.001

Δρmax = 0.71 e Å−3

Δρmin = −0.46 e Å−3

Extinction correction: B-C type 1 Lorentzian isotropic (Becker & Coppens, 1974) Extinction coefficient: 0.93 (6)

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2₎

x y z Uiso*/Ueq

S5 0.41100 (6) 0.18039 (5) 0.48260 (4) 0.05554 (15) C6 0.3601 (2) 0.1577 (2) 0.33408 (15) 0.0576 (6) C7 0.3272 (3) 0.3168 (2) 0.28742 (15) 0.0680 (7) N8 0.27029 (16) 0.41489 (15) 0.37505 (10) 0.0415 (4) C9 0.0806 (3) 0.8175 (2) 0.46962 (18) 0.0631 (6) O1 0.04106 (15) 0.56498 (18) 0.26999 (11) 0.0670 (5) O2 0.30443 (16) 0.68336 (15) 0.29325 (11) 0.0651 (5) H9a −0.0269 0.8101 0.4261 0.084* H9b 0.1441 0.8968 0.4358 0.084* H9c 0.0709 0.8486 0.5464 0.084*

H3 0.196 0.6306 0.6319 0.058*

H6a 0.4475 0.1143 0.2974 0.077* H6b 0.2617 0.0961 0.3119 0.077* H7a 0.2453 0.3112 0.2216 0.09*

H7b 0.4268 0.3618 0.266 0.09*

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

S1 0.0450 (2) 0.0451 (2) 0.02806 (17) 0.00496 (14) 0.00393 (13) 0.00669 (14) C2 0.0451 (7) 0.0363 (7) 0.0378 (7) −0.0020 (5) 0.0071 (6) −0.0013 (5) C3 0.0600 (9) 0.0430 (7) 0.0310 (7) 0.0044 (6) 0.0080 (6) −0.0049 (6) N4 0.0865 (10) 0.0518 (7) 0.0252 (6) 0.0205 (7) 0.0064 (6) 0.0014 (5) C4a 0.0457 (7) 0.0391 (6) 0.0288 (6) 0.0030 (6) 0.0054 (5) 0.0013 (5) S5 0.0758 (3) 0.0478 (2) 0.0414 (2) 0.0228 (2) 0.0022 (2) −0.00003 (17) C6 0.0742 (11) 0.0555 (9) 0.0441 (9) 0.0083 (8) 0.0122 (8) −0.0097 (8) C7 0.1083 (15) 0.0638 (11) 0.0331 (8) 0.0268 (10) 0.0144 (9) −0.0056 (8) N8 0.0577 (7) 0.0423 (6) 0.0250 (5) 0.0068 (5) 0.0078 (5) 0.0012 (5) C9 0.0850 (13) 0.0439 (9) 0.0603 (11) 0.0154 (8) 0.0102 (10) −0.0004 (8) O1 0.0575 (7) 0.0913 (10) 0.0463 (7) 0.0157 (6) −0.0133 (6) −0.0114 (7) O2 0.0800 (9) 0.0621 (8) 0.0592 (8) 0.0010 (6) 0.0307 (7) 0.0228 (6)

Geometric parameters (Å, º)

S1—C2 1.7166 (14) S5—C6 1.797 (2)

S1—N8 1.6519 (11) C6—C7 1.467 (2)

S1—O1 1.4260 (15) C6—H6a 0.98

S1—O2 1.4272 (17) C6—H6b 0.98

C2—C3 1.3380 (19) C7—N8 1.475 (2)

C2—C9 1.497 (3) C7—H7a 0.98

C3—N4 1.378 (2) C7—H7b 0.98

C3—H3 0.98 C9—H9a 0.98

N4—C4a 1.280 (2) C9—H9b 0.98

C4a—S5 1.7397 (17) C9—H9c 0.98

C4a—N8 1.3599 (17)

supporting information

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Acta Cryst. (2002). E58, o362–o363

C2—S1—O2 111.25 (8) C7—C6—H6b 105.85 N8—S1—O1 108.15 (8) H6a—C6—H6b 109.43 N8—S1—O2 108.57 (9) C6—C7—N8 107.40 (13) O1—S1—O2 114.89 (8) C6—C7—H7a 110.00 S1—C2—C3 120.92 (13) C6—C7—H7b 109.45 S1—C2—C9 114.79 (12) N8—C7—H7a 110.5 C3—C2—C9 124.27 (15) N8—C7—H7b 110.13 C2—C3—N4 128.46 (13) H7a—C7—H7b 109.32 C2—C3—H3 113.67 S1—N8—C4a 124.78 (10) N4—C3—H3 117.87 S1—N8—C7 118.98 (10) C3—N4—C4a 117.53 (13) C4a—N8—C7 115.14 (12) N4—C4a—S5 121.58 (12) C2—C9—H9a 109.5 N4—C4a—N8 127.44 (16) C2—C9—H9b 109.5 S5—C4a—N8 110.96 (10) C2—C9—H9c 109.5 C4a—S5—C6 92.40 (7) H9a—C9—H9b 109.5 S5—C6—C7 107.03 (12) H9a—C9—H9c 109.5