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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o1850.
Published online 2009 July 15. doi:  10.1107/S1600536809026300
PMCID: PMC2977456

N,N′-[(2,3,5,6-Tetra­methyl-p-phenyl­ene)dimethyl­ene]bis­[2-chloro-N-(2-chloro­ethyl)ethanamine]

Abstract

The title mol­ecule, C20H32Cl4N2, lies on an inversion center. A weak intra­molecular C—H(...)N hydrogen bond may, in part, influence the conformation of the mol­ecule.

Related literature

For a related crystal structure, see: Yin et al. (2006 [triangle]). For general background to the pharmacological activity of nitro­gen mustards, see: Rachid et al. (2007 [triangle]); Duan et al. (2008 [triangle]); Zhou et al. (2009 [triangle]); Zhuang et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1850-scheme1.jpg

Experimental

Crystal data

  • C20H32Cl4N2
  • M r = 442.29
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1850-efi1.jpg
  • a = 13.6694 (14) Å
  • b = 9.751 (1) Å
  • c = 8.3997 (8) Å
  • β = 93.695 (2)°
  • V = 1117.27 (19) Å3
  • Z = 2
  • Mo Kα radiation
  • μ = 0.54 mm−1
  • T = 298 K
  • 0.16 × 0.12 × 0.10 mm

Data collection

  • Bruker SMART CCD diffractometer
  • Absorption correction: multi-scan (SADABS; Sheldrick,1996 [triangle]) T min = 0.919, T max = 0.948
  • 13369 measured reflections
  • 2732 independent reflections
  • 2283 reflections with I > 2σ(I)
  • R int = 0.031

Refinement

  • R[F 2 > 2σ(F 2)] = 0.048
  • wR(F 2) = 0.134
  • S = 1.04
  • 2732 reflections
  • 120 parameters
  • H-atom parameters constrained
  • Δρmax = 0.46 e Å−3
  • Δρmin = −0.25 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809026300/lh2858sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809026300/lh2858Isup2.hkl

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

Acknowledgments

We thank Southwest University (SWUB2006018, XSGX0602) and the Natural Science Foundation of Chongqing (2007BB5369) for financial support.

supplementary crystallographic information

Comment

Nitrogen mustards such as chlorambucil and melphalan are cytotoxic chemotherapy agents, which are widely used in the treatment of a variety of malignant diseases. As bifunctional DNA-alkylating agents, nitrogen mustards are able to crosslink cellular DNA and thereby interfere with the DNA replication (Rachid et al., 2007; Duan et al., 2008; Zhuang et al., 2008; Zhou et al., 2009). The title compound (I), was obtained by the chlorination of the corresponding diol. Here we present the crystal structure of (I) (Fig. 1).

The title molecule lies on an inversion center. A weak intramolecular C—H···N hydrogen bond may, in part, influence the conformation of the molecule.

Experimental

To a stirred solution of 1,4-bis(bromomethyl)-2,3,5,6-tetramethylbenzene (6.40g, 20mmol) in absolute alcohol (30mL) at 348K potassium carbonate (5.53g, 40mmol) and 2,2'-azanediyldiethanol (4.21g, 40mmol) were added. The progress of the reaction was monitored by TLC. The mixture was filtered to remove the inorganic salts, the solvent was concentrated under reduced pressure and recrystallization from absolute alcohol gave the intermediate2,2',2'',2'''-(2,3,5,6-tetramethyl-p-phenylene)bis (methylene) bis (azanetriyl)tetraethanol (Yield: 5.23g, 71.0%; white solid; Mp., 417-418K). Sulfonyl chloride (40mL) was added dropwise to the intermediate (3.68g, 10mmol) in an ice-salt bath and then the mixture was stirred slowly at gentle reflux for three hours. Sulfonyl chloride was removed under reduced pressure, after cooling, water was added cautiously, and then the mixture was neutralized with NaHCO3. The suspension was filtered and washed with chloroform. The organic layer was washed with water, dried over anhydrous Na2SO4 and the solvent was removed in vacuo. The resulting residue was recrystallized from chloroform to give the title compound (Yield: 3.83g, 86.7%; white solid; Mp. 389-340K).

Refinement

Hydrogen atoms were placed in calculated positions with C—H = 0.93Å (aromatic), 0.97Å (methylene) and 0.96Å (methyl) with Uiso(H) = 1.2Ueq(C) (aromatic and methylene C) or 1.5Ueq(C) (methyl C).

Figures

Fig. 1.
The molecular structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level [symmetry code: (a) -x, -y, -z+1].

Crystal data

C20H32Cl4N2F(000) = 468
Mr = 442.29Dx = 1.315 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 4998 reflections
a = 13.6694 (14) Åθ = 2.6–28.0°
b = 9.751 (1) ŵ = 0.54 mm1
c = 8.3997 (8) ÅT = 298 K
β = 93.695 (2)°Block, white
V = 1117.27 (19) Å30.16 × 0.12 × 0.10 mm
Z = 2

Data collection

Bruker SMART CCD diffractometer2732 independent reflections
Radiation source: fine-focus sealed tube2283 reflections with I > 2σ(I)
graphiteRint = 0.031
[var phi] and ω scansθmax = 28.3°, θmin = 2.6°
Absorption correction: multi-scan (SADABS; Sheldrick,1996)h = −17→17
Tmin = 0.919, Tmax = 0.948k = −12→12
13369 measured reflectionsl = −11→11

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)] = 0.048Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.134H-atom parameters constrained
S = 1.04w = 1/[σ2(Fo2) + (0.0809P)2 + 0.1826P] where P = (Fo2 + 2Fc2)/3
2732 reflections(Δ/σ)max = 0.001
120 parametersΔρmax = 0.46 e Å3
0 restraintsΔρmin = −0.25 e Å3

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 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
C10.12764 (15)0.2248 (2)0.6112 (3)0.0550 (5)
H1A0.10260.26500.70460.083*
H1B0.12960.29300.52900.083*
H1C0.19260.19060.63660.083*
C20.06149 (12)0.10771 (19)0.5531 (2)0.0396 (4)
C3−0.03006 (12)0.13651 (18)0.4753 (2)0.0400 (4)
C4−0.06146 (16)0.2853 (2)0.4533 (3)0.0578 (5)
H4A−0.04190.33640.54770.087*
H4B−0.13140.28970.43450.087*
H4C−0.03090.32370.36370.087*
C50.09103 (12)−0.02818 (19)0.57881 (19)0.0380 (4)
C60.18937 (12)−0.0575 (2)0.6671 (2)0.0426 (4)
H6A0.1939−0.00560.76580.051*
H6B0.1927−0.15410.69440.051*
C70.27229 (13)−0.08753 (18)0.4172 (2)0.0381 (4)
H7A0.2054−0.10960.38030.046*
H7B0.3099−0.17200.42380.046*
C80.31611 (16)0.0100 (2)0.3029 (2)0.0476 (4)
H8A0.38210.03420.34250.057*
H8B0.27740.09340.29520.057*
C90.36606 (12)−0.04271 (19)0.6687 (2)0.0403 (4)
H9A0.4158−0.07150.59860.048*
H9B0.3577−0.11590.74480.048*
C100.40134 (13)0.0836 (2)0.7575 (2)0.0454 (4)
H10A0.45510.05920.83320.055*
H10B0.34870.11990.81710.055*
N10.27367 (9)−0.02246 (15)0.57401 (16)0.0353 (3)
Cl10.31962 (4)−0.06609 (6)0.10972 (6)0.0624 (2)
Cl20.44162 (4)0.21356 (5)0.62479 (7)0.05813 (19)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0412 (10)0.0543 (12)0.0691 (14)−0.0048 (8)0.0002 (9)−0.0143 (10)
C20.0307 (8)0.0500 (10)0.0387 (9)−0.0023 (7)0.0059 (6)−0.0025 (7)
C30.0325 (8)0.0471 (10)0.0412 (9)0.0009 (7)0.0081 (7)0.0014 (7)
C40.0443 (11)0.0506 (11)0.0779 (15)0.0040 (8)0.0004 (10)0.0066 (10)
C50.0279 (8)0.0535 (10)0.0329 (8)0.0005 (7)0.0044 (6)0.0014 (7)
C60.0319 (8)0.0623 (11)0.0336 (8)−0.0002 (7)0.0028 (6)0.0061 (8)
C70.0364 (8)0.0440 (9)0.0341 (8)−0.0054 (7)0.0033 (6)−0.0018 (7)
C80.0630 (12)0.0471 (10)0.0329 (9)−0.0063 (9)0.0049 (8)−0.0025 (8)
C90.0309 (8)0.0485 (10)0.0410 (9)0.0037 (7)−0.0019 (7)0.0027 (7)
C100.0373 (9)0.0608 (12)0.0376 (9)−0.0038 (8)−0.0024 (7)−0.0015 (8)
N10.0272 (6)0.0470 (8)0.0316 (7)−0.0005 (5)0.0007 (5)−0.0014 (6)
Cl10.0788 (4)0.0759 (4)0.0331 (3)−0.0251 (3)0.0084 (2)−0.0071 (2)
Cl20.0622 (3)0.0514 (3)0.0611 (3)−0.0097 (2)0.0064 (2)−0.0031 (2)

Geometric parameters (Å, °)

C1—C21.518 (3)C6—H6B0.9700
C1—H1A0.9600C7—N11.461 (2)
C1—H1B0.9600C7—C81.504 (2)
C1—H1C0.9600C7—H7A0.9700
C2—C51.398 (3)C7—H7B0.9700
C2—C31.402 (2)C8—Cl11.7874 (19)
C3—C5i1.403 (2)C8—H8A0.9700
C3—C41.521 (3)C8—H8B0.9700
C4—H4A0.9600C9—N11.462 (2)
C4—H4B0.9600C9—C101.503 (3)
C4—H4C0.9600C9—H9A0.9700
C5—C3i1.403 (2)C9—H9B0.9700
C5—C61.520 (2)C10—Cl21.798 (2)
C6—N11.473 (2)C10—H10A0.9700
C6—H6A0.9700C10—H10B0.9700
C2—C1—H1A109.5N1—C7—C8108.58 (14)
C2—C1—H1B109.5N1—C7—H7A110.0
H1A—C1—H1B109.5C8—C7—H7A110.0
C2—C1—H1C109.5N1—C7—H7B110.0
H1A—C1—H1C109.5C8—C7—H7B110.0
H1B—C1—H1C109.5H7A—C7—H7B108.4
C5—C2—C3120.14 (16)C7—C8—Cl1110.64 (13)
C5—C2—C1120.23 (16)C7—C8—H8A109.5
C3—C2—C1119.63 (17)Cl1—C8—H8A109.5
C2—C3—C5i119.59 (16)C7—C8—H8B109.5
C2—C3—C4118.96 (16)Cl1—C8—H8B109.5
C5i—C3—C4121.45 (16)H8A—C8—H8B108.1
C3—C4—H4A109.5N1—C9—C10113.44 (14)
C3—C4—H4B109.5N1—C9—H9A108.9
H4A—C4—H4B109.5C10—C9—H9A108.9
C3—C4—H4C109.5N1—C9—H9B108.9
H4A—C4—H4C109.5C10—C9—H9B108.9
H4B—C4—H4C109.5H9A—C9—H9B107.7
C2—C5—C3i120.26 (15)C9—C10—Cl2111.79 (13)
C2—C5—C6119.41 (16)C9—C10—H10A109.3
C3i—C5—C6120.33 (16)Cl2—C10—H10A109.3
N1—C6—C5113.28 (14)C9—C10—H10B109.3
N1—C6—H6A108.9Cl2—C10—H10B109.3
C5—C6—H6A108.9H10A—C10—H10B107.9
N1—C6—H6B108.9C7—N1—C9113.11 (13)
C5—C6—H6B108.9C7—N1—C6114.36 (13)
H6A—C6—H6B107.7C9—N1—C6110.96 (13)
C5—C2—C3—C5i−1.1 (3)C3i—C5—C6—N1110.03 (18)
C1—C2—C3—C5i179.79 (17)N1—C7—C8—Cl1178.35 (12)
C5—C2—C3—C4178.23 (17)N1—C9—C10—Cl2−69.96 (18)
C1—C2—C3—C4−0.9 (3)C8—C7—N1—C9−86.20 (18)
C3—C2—C5—C3i1.1 (3)C8—C7—N1—C6145.47 (16)
C1—C2—C5—C3i−179.79 (17)C10—C9—N1—C7138.52 (16)
C3—C2—C5—C6−178.45 (15)C10—C9—N1—C6−91.42 (19)
C1—C2—C5—C60.7 (3)C5—C6—N1—C7−54.9 (2)
C2—C5—C6—N1−70.5 (2)C5—C6—N1—C9175.66 (15)

Symmetry codes: (i) −x, −y, −z+1.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C1—H1C···N10.962.433.159 (3)133

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH2858).

References

  • Bruker (2001). SAINT-Plus and SMART Bruker AXS Inc., Madison, Wisconsin, USA.
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  • Rachid, Z., Brahimi, F., Qiu, Q., Williams, C., Hartley, J. M., Hartley, J. A. & Jean-Claude, B. J. (2007). J. Med. Chem 50, 2605–2608. [PubMed]
  • Sheldrick, G. M. (1996). SADABS Bruker AXS Inc., Madison, Wisconsin, USA.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Yin, L.-N., Liu, Q.-X., Wu, X.-M., Cheng, F.-J. & Guo, J.-H. (2006). Acta Cryst. E62, o2510–o2511.
  • Zhou, C. H., Gan, L. L., Zhang, F. F., Zhang, Y. Y., Wang, G. Z., Jin, L. & Geng, R. X. (2009). Sci. China Ser. Chem 52, 415–458.
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