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Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2543–o2544.
Published online 2009 September 26. doi:  10.1107/S1600536809038185
PMCID: PMC2970185

tert-Butyl N-[N,N-bis­(2-chloro­ethyl)sulfamo­yl]-N-(2-chloro­ethyl)carbamate

Abstract

The title compound, C11H21Cl3N2O4S, was produced as part of a development programme of a new synthetic route to chloro­ethyl­nitro­sosulfamides (CENS) with three chloro­ethyl moieties. These compounds possess structural features that confer potential biological activity and act as alkyl­ating agents. The packing is governed by four weak C—H(...)O inter­actions, forming an infinite three-dimensional network.

Related literature

For the potential biological activity, pharmaceutical utility and cytotoxic activity of chloro­ethyl­nitro­sosulfamides, see: Abdaoui et al. (1996 [triangle], 2000 [triangle]); Dokhane et al. (2002 [triangle]); Galešić et al. (1987 [triangle]); Gnewuch & Sosnovsky (1997 [triangle]); Ishiguro et al. (2006 [triangle]); Jonnalagadda et al. (2007 [triangle]); Passagne et al. (2003 [triangle]); Seridi et al. (2006 [triangle]); Skinner & Scharts (1972 [triangle]); Voutsinas et al. (1993 [triangle]); Winum et al. (2003 [triangle]). For the synthetic procedure, see: Mitsunobu (1981 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2543-scheme1.jpg

Experimental

Crystal data

  • C11H21Cl3N2O4S
  • M r = 383.71
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2543-efi1.jpg
  • a = 9.6132 (5) Å
  • b = 17.1282 (9) Å
  • c = 10.6763 (5) Å
  • β = 93.868 (3)°
  • V = 1753.92 (15) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.66 mm−1
  • T = 100 K
  • 0.15 × 0.12 × 0.1 mm

Data collection

  • Bruker APEXII diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick, 2002 [triangle]) T min = 0.862, T max = 0.937
  • 17775 measured reflections
  • 3982 independent reflections
  • 3662 reflections with I > 2σ(I)
  • R int = 0.037

Refinement

  • R[F 2 > 2σ(F 2)] = 0.026
  • wR(F 2) = 0.068
  • S = 1.03
  • 3982 reflections
  • 193 parameters
  • H-atom parameters constrained
  • Δρmax = 0.37 e Å−3
  • Δρmin = −0.39 e Å−3

Data collection: SMART (Bruker, 2006 [triangle]); cell refinement: SAINT (Bruker, 2006 [triangle]); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 [triangle]); software used to prepare material for publication: WinGX (Farrugia, 1999 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809038185/dn2489sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809038185/dn2489Isup2.hkl

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

Acknowledgments

Dr T. Roisnel is acknowledged for his assistance during the data measurement. The authors are grateful to the Université de Rennes 1 for access to the Centre de Diffractométrie X, CDIFX, available at the Laboratoire des Sciences Chimiques de Rennes. The authors are also indebted to the Université du 20 Août 1955 – Skikda (Algeria) for financial support.

supplementary crystallographic information

Comment

Compounds with one or more N-(2-chloroethyl) moieties show many pharmacological activities (Galešić et al., 1987). They are cytotoxic (Ishiguro et al., 2006), mutagenic (Voutsinas et al., 1993), and immuno-suppressive (Skinner & Scharts, 1972). Many of them include Mechlorethamine, Chlorambucil, Melphalan,Cyclophosmamide, Ifosfamide, are used for the treatment of wide variety of cancers (Jonnalagadda et al., 2007). Among others, N-(2-chloroethyl) nitrososulfamides (CENS) are promising antitumoral agents which have been developed as new family of alkylating agents structurally related to 2-chloroethylnitrosoureas (CENU) (Abdaoui et al., 1996). A certain number of these derivatives exhibited interesting cytotoxic activity and among them, some prouved to be considerably more potent than the parent nitrosourea (Abdaoui et al., 2000; Gnewuch & Sosnovsky, 1997; Passagne et al., 2003; Seridi et al., 2006; Winum et al., 2003).

In order to extend our knowledge about such sulfamides derivatives with three N-(2-chloroethyl) moieties the crystal structure of the title compound is presented.

In all essential details, the molecular geometry in terms of bond distances and angles is in good agreement with related structure (Dokhane et al. 2002). In the molecular geometry (Fig.1), the sulfamide moiety N1—S—N2 exhibit an asymmetry of S—N bond distance, with values of 1.688 (1) and 1.615 (1) Å respectively. The molecules are linked by four C—H···O intermolecular interactions involving sulfonamide (oxygen atoms O1 and O2) and carbonyl (oxygen atom O3) functions (table 1). Thus, these interactions lead to an infinite three-dimensional network.

Experimental

The synthetic pathway used for the preparation of the title compound is outlined in Fig. 2. First the formation of tert-butylN-(2-chloroethyl)sulfamoylcarbamate which is performed in dried dichloromethane with successive addition of tBuOH, and Chloroethylamine/TEA into CSI. After purification, the carbamate was recovered at (yield 80%). The second step is carried out according to the Mitsunobu procedure (Mitsunobu, 1981) in anhydrous THF as a solvent. The mixture of DEAD (diethyl azodicarboxylate) and tert-butylN-(2-chloroethyl)sulfamoylcarbamate is added to a solution of excess of chloroethanol and PPh3. The product was recrystallized in pure ethanol.

Refinement

H atoms bonded to C atoms were positioned geometrically and refined isotropically using a riding model (including free rotation about the ethanol C—C bond), with C—H = 0.97 Å (methylene) or 0.96Å (methyl) and with Uiso(H) = 1.2 (1.5 for methyl groups) times Ueq(C).

Figures

Fig. 1.
(Farrugia, 1997) The molecule of the title compound in the crystal. Ellipsoids correspond to 50% probability levels and H atoms are shown as small spheres of arbitrary radii.
Fig. 2.
Synthesis of the title compound.

Crystal data

C11H21Cl3N2O4SF(000) = 800
Mr = 383.71Dx = 1.453 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 9788 reflections
a = 9.6132 (5) Åθ = 2.4–27.4°
b = 17.1282 (9) ŵ = 0.66 mm1
c = 10.6763 (5) ÅT = 100 K
β = 93.868 (3)°Prism, colourless
V = 1753.92 (15) Å30.15 × 0.12 × 0.1 mm
Z = 4

Data collection

Bruker APEXII diffractometer3982 independent reflections
Radiation source: APEXII, Bruker-AXS3662 reflections with I > 2σ(I)
graphiteRint = 0.037
CCD rotation images, thick slices scansθmax = 27.4°, θmin = 2.1°
Absorption correction: multi-scan (SADABS; Sheldrick, 2002)h = −12→11
Tmin = 0.862, Tmax = 0.937k = −22→21
17775 measured reflectionsl = −13→13

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.026Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.068H-atom parameters constrained
S = 1.03w = 1/[σ2(Fo2) + (0.0272P)2 + 0.8873P] where P = (Fo2 + 2Fc2)/3
3982 reflections(Δ/σ)max = 0.001
193 parametersΔρmax = 0.37 e Å3
0 restraintsΔρmin = −0.39 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 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 (Å2)

xyzUiso*/Ueq
C10.30088 (13)−0.00247 (8)0.74767 (12)0.0142 (3)
H1A0.3977−0.01550.73750.017*
H1B0.2483−0.01200.66840.017*
C20.24504 (14)−0.05402 (8)0.84875 (13)0.0166 (3)
H2A0.1511−0.03810.86490.020*
H2B0.3033−0.04890.92610.020*
C30.16945 (13)0.12486 (8)0.74993 (12)0.0141 (3)
C4−0.07329 (14)0.11154 (9)0.66503 (14)0.0212 (3)
C5−0.15279 (16)0.03860 (10)0.62057 (17)0.0332 (4)
H5A−0.10900.01620.55080.050*
H5B−0.24730.05230.59500.050*
H5C−0.15210.00140.68780.050*
C6−0.05995 (16)0.16890 (10)0.55745 (15)0.0281 (3)
H6A−0.01280.21510.58850.042*
H6B−0.15110.18250.52200.042*
H6C−0.00750.14520.49410.042*
C7−0.13690 (15)0.14725 (10)0.77813 (15)0.0285 (3)
H7A−0.13750.10920.84420.043*
H7B−0.23070.16350.75500.043*
H7C−0.08270.19160.80680.043*
C80.38802 (13)0.13068 (8)1.08849 (12)0.0150 (3)
H8A0.45970.15231.14680.018*
H8B0.41150.07651.07410.018*
C90.24946 (14)0.13378 (8)1.14857 (13)0.0184 (3)
H910.22390.18791.16090.022*
H920.25940.10901.23040.022*
C100.36795 (13)0.25857 (8)0.96777 (12)0.0139 (3)
H10A0.31440.27311.03790.017*
H10B0.31460.27330.89100.017*
C110.50586 (14)0.30294 (8)0.97652 (12)0.0158 (3)
H11A0.55930.29040.90530.019*
H11B0.56050.28881.05280.019*
Cl10.24477 (4)−0.15386 (2)0.79617 (4)0.02567 (9)
Cl20.11302 (3)0.08604 (2)1.05440 (3)0.02616 (10)
Cl30.46514 (4)0.40555 (2)0.97723 (3)0.02271 (9)
N10.29004 (10)0.08109 (6)0.78128 (10)0.0123 (2)
N20.38924 (11)0.17329 (6)0.96878 (9)0.0121 (2)
O10.52796 (9)0.06756 (6)0.87615 (9)0.01627 (19)
O20.46793 (9)0.18884 (6)0.75688 (8)0.0161 (2)
O30.16339 (9)0.19465 (6)0.76460 (9)0.0177 (2)
O40.06748 (9)0.07794 (6)0.70365 (9)0.0181 (2)
S10.43157 (3)0.129314 (19)0.84310 (3)0.01123 (8)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0159 (6)0.0112 (7)0.0153 (6)0.0002 (5)−0.0004 (4)−0.0037 (5)
C20.0169 (6)0.0110 (7)0.0219 (7)−0.0006 (5)0.0011 (5)−0.0016 (5)
C30.0131 (6)0.0153 (7)0.0136 (6)−0.0015 (5)−0.0015 (4)0.0027 (5)
C40.0122 (6)0.0221 (8)0.0283 (7)−0.0004 (5)−0.0076 (5)0.0057 (6)
C50.0238 (8)0.0296 (9)0.0438 (10)−0.0088 (6)−0.0159 (7)0.0055 (7)
C60.0227 (7)0.0311 (9)0.0292 (8)−0.0003 (6)−0.0074 (6)0.0102 (7)
C70.0161 (7)0.0343 (9)0.0347 (9)0.0020 (6)0.0001 (6)0.0067 (7)
C80.0183 (6)0.0143 (7)0.0120 (6)−0.0011 (5)−0.0008 (5)0.0028 (5)
C90.0248 (7)0.0161 (7)0.0149 (6)−0.0041 (5)0.0052 (5)−0.0016 (5)
C100.0165 (6)0.0094 (6)0.0158 (6)−0.0009 (5)0.0008 (5)0.0000 (5)
C110.0197 (6)0.0114 (7)0.0166 (6)−0.0031 (5)0.0027 (5)−0.0008 (5)
Cl10.02584 (18)0.01139 (18)0.0396 (2)−0.00249 (13)0.00118 (14)−0.00252 (14)
Cl20.01773 (16)0.0387 (2)0.02252 (18)−0.00801 (14)0.00518 (12)−0.00232 (15)
Cl30.03418 (19)0.01075 (17)0.02329 (18)−0.00579 (13)0.00268 (13)0.00063 (12)
N10.0116 (5)0.0097 (6)0.0153 (5)−0.0015 (4)−0.0014 (4)−0.0013 (4)
N20.0158 (5)0.0093 (5)0.0112 (5)−0.0010 (4)0.0014 (4)−0.0002 (4)
O10.0130 (4)0.0164 (5)0.0190 (5)0.0027 (4)−0.0014 (3)−0.0026 (4)
O20.0182 (4)0.0162 (5)0.0139 (4)−0.0048 (4)0.0031 (3)0.0001 (4)
O30.0164 (4)0.0112 (5)0.0247 (5)0.0001 (3)−0.0037 (4)0.0019 (4)
O40.0138 (4)0.0142 (5)0.0251 (5)−0.0013 (4)−0.0071 (4)0.0017 (4)
S10.01039 (14)0.01148 (17)0.01178 (15)−0.00120 (11)0.00045 (10)−0.00080 (11)

Geometric parameters (Å, °)

C1—N11.4809 (17)C7—H7B0.9600
C1—C21.5201 (18)C7—H7C0.9600
C1—H1A0.9700C8—N21.4725 (16)
C1—H1B0.9700C8—C91.5178 (18)
C2—Cl11.7997 (14)C8—H8A0.9700
C2—H2A0.9700C8—H8B0.9700
C2—H2B0.9700C9—Cl21.7950 (14)
C3—O31.2074 (17)C9—H910.9700
C3—O41.3364 (15)C9—H920.9700
C3—N11.4020 (16)C10—N21.4749 (17)
C4—O41.5024 (15)C10—C111.5255 (17)
C4—C71.519 (2)C10—H10A0.9700
C4—C61.523 (2)C10—H10B0.9700
C4—C51.524 (2)C11—Cl31.8007 (14)
C5—H5A0.9600C11—H11A0.9700
C5—H5B0.9600C11—H11B0.9700
C5—H5C0.9600N1—S11.6875 (10)
C6—H6A0.9600N2—S11.6147 (11)
C6—H6B0.9600O1—S11.4345 (10)
C6—H6C0.9600O2—S11.4326 (10)
C7—H7A0.9600
N1—C1—C2110.82 (10)H7B—C7—H7C109.5
N1—C1—H1A109.5N2—C8—C9114.08 (11)
C2—C1—H1A109.5N2—C8—H8A108.7
N1—C1—H1B109.5C9—C8—H8A108.7
C2—C1—H1B109.5N2—C8—H8B108.7
H1A—C1—H1B108.1C9—C8—H8B108.7
C1—C2—Cl1108.88 (9)H8A—C8—H8B107.6
C1—C2—H2A109.9C8—C9—Cl2112.10 (9)
Cl1—C2—H2A109.9C8—C9—H91109.2
C1—C2—H2B109.9Cl2—C9—H91109.2
Cl1—C2—H2B109.9C8—C9—H92109.2
H2A—C2—H2B108.3Cl2—C9—H92109.2
O3—C3—O4127.07 (12)H91—C9—H92107.9
O3—C3—N1123.01 (11)N2—C10—C11111.92 (10)
O4—C3—N1109.92 (11)N2—C10—H10A109.2
O4—C4—C7109.86 (11)C11—C10—H10A109.2
O4—C4—C6109.51 (11)N2—C10—H10B109.2
C7—C4—C6113.49 (13)C11—C10—H10B109.2
O4—C4—C5101.24 (11)H10A—C10—H10B107.9
C7—C4—C5110.95 (13)C10—C11—Cl3107.35 (9)
C6—C4—C5111.09 (13)C10—C11—H11A110.2
C4—C5—H5A109.5Cl3—C11—H11A110.2
C4—C5—H5B109.5C10—C11—H11B110.2
H5A—C5—H5B109.5Cl3—C11—H11B110.2
C4—C5—H5C109.5H11A—C11—H11B108.5
H5A—C5—H5C109.5C3—N1—C1121.97 (10)
H5B—C5—H5C109.5C3—N1—S1117.61 (9)
C4—C6—H6A109.5C1—N1—S1119.98 (8)
C4—C6—H6B109.5C8—N2—C10119.21 (10)
H6A—C6—H6B109.5C8—N2—S1120.48 (9)
C4—C6—H6C109.5C10—N2—S1119.90 (8)
H6A—C6—H6C109.5C3—O4—C4119.72 (11)
H6B—C6—H6C109.5O2—S1—O1120.08 (6)
C4—C7—H7A109.5O2—S1—N2106.74 (6)
C4—C7—H7B109.5O1—S1—N2109.53 (6)
H7A—C7—H7B109.5O2—S1—N1108.80 (5)
C4—C7—H7C109.5O1—S1—N1103.05 (5)
H7A—C7—H7C109.5N2—S1—N1108.16 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C2—H2B···O1i0.972.593.5465 (16)167
C8—H8B···O1i0.972.583.5047 (17)159
C9—H91···O3ii0.972.393.3156 (17)160
C11—H11B···O2ii0.972.443.0428 (16)120

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: DN2489).

References

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