organic compounds
N,N′-[(2,3,5,6-Tetramethyl-p-phenylene)dimethylene]bis[2-chloro-N-(2-chloroethyl)ethanamine]
aLaboratory of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China
*Correspondence e-mail: zhouch@swu.edu.cn
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 et al. (2006). For general background to the pharmacological activity of nitrogen mustards, see: Rachid et al. (2007); Duan et al. (2008); Zhou et al. (2009); Zhuang et al. (2008).
see: YinExperimental
Crystal data
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Refinement
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Data collection: SMART (Bruker, 2001); cell 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.
Supporting information
10.1107/S1600536809026300/lh2858sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536809026300/lh2858Isup2.hkl
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).
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).
Data collection: SMART (Bruker, 2001); cell
SAINT-Plus (Bruker, 2001); data reduction: SAINT-Plus (Bruker, 2001); 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 (Sheldrick, 2008).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]. |
C20H32Cl4N2 | F(000) = 468 |
Mr = 442.29 | Dx = 1.315 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 4998 reflections |
a = 13.6694 (14) Å | θ = 2.6–28.0° |
b = 9.751 (1) Å | µ = 0.54 mm−1 |
c = 8.3997 (8) Å | T = 298 K |
β = 93.695 (2)° | Block, white |
V = 1117.27 (19) Å3 | 0.16 × 0.12 × 0.10 mm |
Z = 2 |
Bruker SMART CCD diffractometer | 2732 independent reflections |
Radiation source: fine-focus sealed tube | 2283 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.031 |
ϕ and ω scans | θmax = 28.3°, θmin = 2.6° |
Absorption correction: multi-scan (SADABS; Sheldrick,1996) | h = −17→17 |
Tmin = 0.919, Tmax = 0.948 | k = −12→12 |
13369 measured reflections | l = −11→11 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.048 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.134 | H-atom parameters constrained |
S = 1.04 | w = 1/[σ2(Fo2) + (0.0809P)2 + 0.1826P] where P = (Fo2 + 2Fc2)/3 |
2732 reflections | (Δ/σ)max = 0.001 |
120 parameters | Δρmax = 0.46 e Å−3 |
0 restraints | Δρmin = −0.25 e Å−3 |
C20H32Cl4N2 | V = 1117.27 (19) Å3 |
Mr = 442.29 | Z = 2 |
Monoclinic, P21/c | Mo Kα radiation |
a = 13.6694 (14) Å | µ = 0.54 mm−1 |
b = 9.751 (1) Å | T = 298 K |
c = 8.3997 (8) Å | 0.16 × 0.12 × 0.10 mm |
β = 93.695 (2)° |
Bruker SMART CCD diffractometer | 2732 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick,1996) | 2283 reflections with I > 2σ(I) |
Tmin = 0.919, Tmax = 0.948 | Rint = 0.031 |
13369 measured reflections |
R[F2 > 2σ(F2)] = 0.048 | 0 restraints |
wR(F2) = 0.134 | H-atom parameters constrained |
S = 1.04 | Δρmax = 0.46 e Å−3 |
2732 reflections | Δρmin = −0.25 e Å−3 |
120 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.12764 (15) | 0.2248 (2) | 0.6112 (3) | 0.0550 (5) | |
H1A | 0.1026 | 0.2650 | 0.7046 | 0.083* | |
H1B | 0.1296 | 0.2930 | 0.5290 | 0.083* | |
H1C | 0.1926 | 0.1906 | 0.6366 | 0.083* | |
C2 | 0.06149 (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 | −0.0419 | 0.3364 | 0.5477 | 0.087* | |
H4B | −0.1314 | 0.2897 | 0.4345 | 0.087* | |
H4C | −0.0309 | 0.3237 | 0.3637 | 0.087* | |
C5 | 0.09103 (12) | −0.02818 (19) | 0.57881 (19) | 0.0380 (4) | |
C6 | 0.18937 (12) | −0.0575 (2) | 0.6671 (2) | 0.0426 (4) | |
H6A | 0.1939 | −0.0056 | 0.7658 | 0.051* | |
H6B | 0.1927 | −0.1541 | 0.6944 | 0.051* | |
C7 | 0.27229 (13) | −0.08753 (18) | 0.4172 (2) | 0.0381 (4) | |
H7A | 0.2054 | −0.1096 | 0.3803 | 0.046* | |
H7B | 0.3099 | −0.1720 | 0.4238 | 0.046* | |
C8 | 0.31611 (16) | 0.0100 (2) | 0.3029 (2) | 0.0476 (4) | |
H8A | 0.3821 | 0.0342 | 0.3425 | 0.057* | |
H8B | 0.2774 | 0.0934 | 0.2952 | 0.057* | |
C9 | 0.36606 (12) | −0.04271 (19) | 0.6687 (2) | 0.0403 (4) | |
H9A | 0.4158 | −0.0715 | 0.5986 | 0.048* | |
H9B | 0.3577 | −0.1159 | 0.7448 | 0.048* | |
C10 | 0.40134 (13) | 0.0836 (2) | 0.7575 (2) | 0.0454 (4) | |
H10A | 0.4551 | 0.0592 | 0.8332 | 0.055* | |
H10B | 0.3487 | 0.1199 | 0.8171 | 0.055* | |
N1 | 0.27367 (9) | −0.02246 (15) | 0.57401 (16) | 0.0353 (3) | |
Cl1 | 0.31962 (4) | −0.06609 (6) | 0.10972 (6) | 0.0624 (2) | |
Cl2 | 0.44162 (4) | 0.21356 (5) | 0.62479 (7) | 0.05813 (19) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0412 (10) | 0.0543 (12) | 0.0691 (14) | −0.0048 (8) | 0.0002 (9) | −0.0143 (10) |
C2 | 0.0307 (8) | 0.0500 (10) | 0.0387 (9) | −0.0023 (7) | 0.0059 (6) | −0.0025 (7) |
C3 | 0.0325 (8) | 0.0471 (10) | 0.0412 (9) | 0.0009 (7) | 0.0081 (7) | 0.0014 (7) |
C4 | 0.0443 (11) | 0.0506 (11) | 0.0779 (15) | 0.0040 (8) | 0.0004 (10) | 0.0066 (10) |
C5 | 0.0279 (8) | 0.0535 (10) | 0.0329 (8) | 0.0005 (7) | 0.0044 (6) | 0.0014 (7) |
C6 | 0.0319 (8) | 0.0623 (11) | 0.0336 (8) | −0.0002 (7) | 0.0028 (6) | 0.0061 (8) |
C7 | 0.0364 (8) | 0.0440 (9) | 0.0341 (8) | −0.0054 (7) | 0.0033 (6) | −0.0018 (7) |
C8 | 0.0630 (12) | 0.0471 (10) | 0.0329 (9) | −0.0063 (9) | 0.0049 (8) | −0.0025 (8) |
C9 | 0.0309 (8) | 0.0485 (10) | 0.0410 (9) | 0.0037 (7) | −0.0019 (7) | 0.0027 (7) |
C10 | 0.0373 (9) | 0.0608 (12) | 0.0376 (9) | −0.0038 (8) | −0.0024 (7) | −0.0015 (8) |
N1 | 0.0272 (6) | 0.0470 (8) | 0.0316 (7) | −0.0005 (5) | 0.0007 (5) | −0.0014 (6) |
Cl1 | 0.0788 (4) | 0.0759 (4) | 0.0331 (3) | −0.0251 (3) | 0.0084 (2) | −0.0071 (2) |
Cl2 | 0.0622 (3) | 0.0514 (3) | 0.0611 (3) | −0.0097 (2) | 0.0064 (2) | −0.0031 (2) |
C1—C2 | 1.518 (3) | C6—H6B | 0.9700 |
C1—H1A | 0.9600 | C7—N1 | 1.461 (2) |
C1—H1B | 0.9600 | C7—C8 | 1.504 (2) |
C1—H1C | 0.9600 | C7—H7A | 0.9700 |
C2—C5 | 1.398 (3) | C7—H7B | 0.9700 |
C2—C3 | 1.402 (2) | C8—Cl1 | 1.7874 (19) |
C3—C5i | 1.403 (2) | C8—H8A | 0.9700 |
C3—C4 | 1.521 (3) | C8—H8B | 0.9700 |
C4—H4A | 0.9600 | C9—N1 | 1.462 (2) |
C4—H4B | 0.9600 | C9—C10 | 1.503 (3) |
C4—H4C | 0.9600 | C9—H9A | 0.9700 |
C5—C3i | 1.403 (2) | C9—H9B | 0.9700 |
C5—C6 | 1.520 (2) | C10—Cl2 | 1.798 (2) |
C6—N1 | 1.473 (2) | C10—H10A | 0.9700 |
C6—H6A | 0.9700 | C10—H10B | 0.9700 |
C2—C1—H1A | 109.5 | N1—C7—C8 | 108.58 (14) |
C2—C1—H1B | 109.5 | N1—C7—H7A | 110.0 |
H1A—C1—H1B | 109.5 | C8—C7—H7A | 110.0 |
C2—C1—H1C | 109.5 | N1—C7—H7B | 110.0 |
H1A—C1—H1C | 109.5 | C8—C7—H7B | 110.0 |
H1B—C1—H1C | 109.5 | H7A—C7—H7B | 108.4 |
C5—C2—C3 | 120.14 (16) | C7—C8—Cl1 | 110.64 (13) |
C5—C2—C1 | 120.23 (16) | C7—C8—H8A | 109.5 |
C3—C2—C1 | 119.63 (17) | Cl1—C8—H8A | 109.5 |
C2—C3—C5i | 119.59 (16) | C7—C8—H8B | 109.5 |
C2—C3—C4 | 118.96 (16) | Cl1—C8—H8B | 109.5 |
C5i—C3—C4 | 121.45 (16) | H8A—C8—H8B | 108.1 |
C3—C4—H4A | 109.5 | N1—C9—C10 | 113.44 (14) |
C3—C4—H4B | 109.5 | N1—C9—H9A | 108.9 |
H4A—C4—H4B | 109.5 | C10—C9—H9A | 108.9 |
C3—C4—H4C | 109.5 | N1—C9—H9B | 108.9 |
H4A—C4—H4C | 109.5 | C10—C9—H9B | 108.9 |
H4B—C4—H4C | 109.5 | H9A—C9—H9B | 107.7 |
C2—C5—C3i | 120.26 (15) | C9—C10—Cl2 | 111.79 (13) |
C2—C5—C6 | 119.41 (16) | C9—C10—H10A | 109.3 |
C3i—C5—C6 | 120.33 (16) | Cl2—C10—H10A | 109.3 |
N1—C6—C5 | 113.28 (14) | C9—C10—H10B | 109.3 |
N1—C6—H6A | 108.9 | Cl2—C10—H10B | 109.3 |
C5—C6—H6A | 108.9 | H10A—C10—H10B | 107.9 |
N1—C6—H6B | 108.9 | C7—N1—C9 | 113.11 (13) |
C5—C6—H6B | 108.9 | C7—N1—C6 | 114.36 (13) |
H6A—C6—H6B | 107.7 | C9—N1—C6 | 110.96 (13) |
C5—C2—C3—C5i | −1.1 (3) | C3i—C5—C6—N1 | 110.03 (18) |
C1—C2—C3—C5i | 179.79 (17) | N1—C7—C8—Cl1 | 178.35 (12) |
C5—C2—C3—C4 | 178.23 (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—C3i | 1.1 (3) | C8—C7—N1—C6 | 145.47 (16) |
C1—C2—C5—C3i | −179.79 (17) | C10—C9—N1—C7 | 138.52 (16) |
C3—C2—C5—C6 | −178.45 (15) | C10—C9—N1—C6 | −91.42 (19) |
C1—C2—C5—C6 | 0.7 (3) | C5—C6—N1—C7 | −54.9 (2) |
C2—C5—C6—N1 | −70.5 (2) | C5—C6—N1—C9 | 175.66 (15) |
Symmetry code: (i) −x, −y, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C20H32Cl4N2 |
Mr | 442.29 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 298 |
a, b, c (Å) | 13.6694 (14), 9.751 (1), 8.3997 (8) |
β (°) | 93.695 (2) |
V (Å3) | 1117.27 (19) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.54 |
Crystal size (mm) | 0.16 × 0.12 × 0.10 |
Data collection | |
Diffractometer | Bruker SMART CCD diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick,1996) |
Tmin, Tmax | 0.919, 0.948 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13369, 2732, 2283 |
Rint | 0.031 |
(sin θ/λ)max (Å−1) | 0.667 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.048, 0.134, 1.04 |
No. of reflections | 2732 |
No. of parameters | 120 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.46, −0.25 |
Computer programs: SMART (Bruker, 2001), SAINT-Plus (Bruker, 2001), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).
Acknowledgements
We thank Southwest University (SWUB2006018, XSGX0602) and the Natural Science Foundation of Chongqing (2007BB5369) for financial support.
References
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
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.