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The title compound, C14H11Cl3N4O2, consists of two planar fragments which are nearly perpendicular to one another. The crystal packing is controlled by intra- and intermolecular C—H...O hydrogen bonds, and Cl...phenyl-ring-centroid and weak stacking interactions.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270104023133/av1201sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270104023133/av1201Isup2.hkl
Contains datablock I

CCDC reference: 263070

Comment top

The presence of an ortho-halogen-substituted phenyl ring in purine systems is characteristic of many marketed (e.g. Adipiodone, Guanfacine or Loviride) or emerging drugs in a wide area of pharmacology. Knowledge of their three-dimensional structures forms the basis for understanding the mechanism of their pharmaceutical action, and it is also necessary for the modeling of dockimg, in the study of the biological activity of these compounds. Against this background, we present here the crystal structure of the title compound, (I).

The molecular structure of (I) (Fig. 1) is characterized by two planar fragments, one formed by the heterocyclic system (N1/C2/N3/C4–C6/N7/C8/N9/C14) and the other based on the benzyl substituent (C14–C20). The dihedral angle between these planes is 86.75 (4)°. A search of the Cambridge Structural Database (CSD, Version 5.25; Allen, 2002) indicates that there are 126 derivatives of 7H-purine-2,6-dione. The bond lengths and angles of (I) have values which are characteristic of these compounds and are freely available in the archived CIF.

The molecular packing of (I) (Fig. 2) is characterized by two C—H···O hydrogen bonds, one intramolecular and the other intermolecular; details are given in Table 1. The intramolecular C—H···O bond corresponds to a moderate hydrogen bond (Gilli, 2002). Due to this hydrogen bond, an additional five-membered ring is formed in the molecule, coplanar with the purine system; because of this hydrogen bond, the C8—N7—C14—C15 torsion angle is 58.3 (2)°. The formation of the hydrogen bond is promoted by electron-acceptor substituents at C14. Most probably, the same type of hydrogen bond also occurs in the molecule of 7-(2,6-dichlorobenzyl)-8-(3-oxocyclopentyl)-1,3-dipropyl-7H-purine-2,6-dione (Bolte, 1996).

An estimate of the hydrogen-bond energy has been undertaken by the quantum-chemical AM1 method (MOPAC7; Stewart, 1993), which is suitable for systems with hydrogen bonds (Dewar et al., 1985). The AM1 heat of formation for (I) is 96.78 kJ mol−1 and the hydrogen bond order is 0.0048. For a virtual molecule (I) with a C8—N7—C14—C15 torsion angle of 90°, where a hydrogen bond is impossible, the heat of formation is 105.94 kJ mol−1. Thus, the energy of the intramolecular hydrogen bond in (I) can be estimated to be 9.16 kJ mol−1. This is a relatively high value, especially for a C—H···O bond. The theoretically calculated geometry of the hydrogen bond for an isolated molecule (I) [C···O = 3.115 Å, H···O = 2.24 Å and C—H···O = 133°] differs slightly from that obtained by our X-ray analysis (Table 1).

As shown in Fig. 2, inversion-related molecules [at (x, y, z) and (1 − x, 1 − y, 1 − z)] are linked by a pair of bifurcated C—H···O hydrogen bonds involving O13 and C14—H14B. These dimers are then linked by chlorine···ring-centroid interactions to generate ribbons which extend in the [100] direction; Cl1 is 3.258 Å from the centroid of the phenyl ring at (1 + x, y, z) and the C16—Cl1···Cg1ii angle (Fig. 2) is 162° Analogous interactions are observed in the crystal structure of 3-(2,6-dichlorobenzyl)-N,N-dimethyladenine (Mishnev et al., 1991), where the distance between the Cl atom and the plane of the six-membered ring is 3.25 Å. The only other significant intermolecular interaction in the crystal structure is between pairs of inversion related phenyl rings [at (x, y, z) and (1 − x, 1 − y, 1 − z)]; the centroids of these rings are separated by 4.261 Å, but the shortest atom–atom contact is C19···C19(1 − x, 1 − y, 1 − z) of 3.392 (3) Å.

Experimental top

The title compound was prepared for synthesis of a series of 7,8-disubstituted theophyllines as referred by Dolman et al. (1965). The compound was recrystallized from ether. The colourless crystals thus obtained were filtered off and dried in air.

Refinement top

All H atoms were revealed in difference maps and then allowed for in the refinement as riding atoms, with C—H = 0.93–0.97 Å, and Uiso(H) = 1.2Ueq(CH or CH2) and 1.5Ueq(C-methyl).

Computing details top

Data collection: KappaCCD (Nonius, 1999); cell refinement: SCALEPACK (Otwinowski & Minor 1997); data reduction: DENZO (Otwinowski & Minor, 1997) and SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. Perspective view of the molecular packing in (I), showing the C—H···O and Cl···centroid interactions as dashed lines. [Symmetry codes: (i) 1 − x, 1 − y, 1 − z; (ii) 1 + x, y, z.]
8-Chloro-7-(2,6-dichlorobenzyl)-1,3-dimethyl-7H-purine-2,6(1H,3H)-dione top
Crystal data top
C14H11Cl3N4O2Z = 2
Mr = 373.63F(000) = 380
Triclinic, P1Dx = 1.612 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.4073 (2) ÅCell parameters from 11449 reflections
b = 8.6544 (3) Åθ = 1.0–30.0°
c = 11.8014 (4) ŵ = 0.61 mm1
α = 71.8140 (14)°T = 293 K
β = 70.7538 (13)°Prism, colourless
γ = 82.343 (2)°0.39 × 0.28 × 0.26 mm
V = 769.74 (4) Å3
Data collection top
Nonius KappaCCD
diffractometer
3637 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.070
ϕ and ω scansθmax = 30.0°, θmin = 1.9°
Absorption correction: integration
By Gaussian integration based on twelve indexed crystal faces (NUMABS; Coppens, 1970)
h = 1111
Tmin = 0.838, Tmax = 0.905k = 1212
10330 measured reflectionsl = 1516
4339 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049H-atom parameters constrained
wR(F2) = 0.130 w = 1/[σ2(Fo2) + (0.0524P)2 + 0.2719P]
where P = (Fo2 + 2Fc2)/3
S = 1.02(Δ/σ)max = 0.002
4339 reflectionsΔρmax = 0.39 e Å3
211 parametersΔρmin = 0.36 e Å3
0 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.009 (2)
Crystal data top
C14H11Cl3N4O2γ = 82.343 (2)°
Mr = 373.63V = 769.74 (4) Å3
Triclinic, P1Z = 2
a = 8.4073 (2) ÅMo Kα radiation
b = 8.6544 (3) ŵ = 0.61 mm1
c = 11.8014 (4) ÅT = 293 K
α = 71.8140 (14)°0.39 × 0.28 × 0.26 mm
β = 70.7538 (13)°
Data collection top
Nonius KappaCCD
diffractometer
4339 independent reflections
Absorption correction: integration
By Gaussian integration based on twelve indexed crystal faces (NUMABS; Coppens, 1970)
3637 reflections with I > 2σ(I)
Tmin = 0.838, Tmax = 0.905Rint = 0.070
10330 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0490 restraints
wR(F2) = 0.130H-atom parameters constrained
S = 1.02Δρmax = 0.39 e Å3
4339 reflectionsΔρmin = 0.36 e Å3
211 parameters
Special details top

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) top
xyzUiso*/Ueq
Cl10.98523 (5)0.31640 (6)0.22929 (6)0.05765 (16)
Cl20.30121 (6)0.38943 (7)0.35749 (6)0.06179 (17)
Cl30.75631 (6)0.38277 (7)0.00409 (5)0.05783 (16)
O110.01392 (19)0.0921 (2)0.19921 (16)0.0605 (4)
O130.32874 (17)0.04897 (16)0.43853 (11)0.0475 (3)
N10.17535 (17)0.07179 (17)0.31570 (13)0.0393 (3)
N30.24486 (18)0.06248 (19)0.09908 (13)0.0419 (3)
N70.54906 (16)0.18439 (16)0.19603 (12)0.0353 (3)
N90.48998 (19)0.23064 (19)0.01492 (13)0.0438 (3)
C20.1380 (2)0.0369 (2)0.20289 (17)0.0418 (3)
C40.3777 (2)0.12715 (19)0.10982 (15)0.0367 (3)
C50.40950 (18)0.09403 (18)0.22202 (14)0.0341 (3)
C60.30841 (19)0.01100 (18)0.33537 (15)0.0353 (3)
C80.5892 (2)0.2602 (2)0.07194 (15)0.0406 (3)
C100.0560 (3)0.1767 (3)0.4255 (2)0.0542 (5)
H10A0.08080.17960.50000.081*
H10B0.06620.28480.41730.081*
H10C0.05680.13410.43090.081*
C120.2088 (3)0.1095 (3)0.0202 (2)0.0573 (5)
H12A0.30880.14950.08730.086*
H12B0.12150.19320.02010.086*
H12C0.17220.01660.03180.086*
C140.6326 (2)0.18867 (19)0.28687 (16)0.0370 (3)
H14A0.74600.14210.26340.044*
H14B0.57190.12090.36890.044*
C150.64267 (18)0.35755 (18)0.29604 (14)0.0347 (3)
C160.7970 (2)0.4218 (2)0.27699 (15)0.0393 (3)
C170.8086 (3)0.5710 (2)0.29424 (19)0.0495 (4)
H170.91320.60980.28070.059*
C180.6635 (3)0.6607 (2)0.3316 (2)0.0550 (5)
H180.67020.76020.34430.066*
C190.5077 (3)0.6040 (2)0.3505 (2)0.0523 (4)
H190.40970.66500.37500.063*
C200.5002 (2)0.4544 (2)0.33209 (17)0.0415 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0313 (2)0.0611 (3)0.0814 (4)0.00555 (18)0.0153 (2)0.0222 (2)
Cl20.0318 (2)0.0691 (3)0.0903 (4)0.00055 (19)0.0110 (2)0.0397 (3)
Cl30.0492 (3)0.0636 (3)0.0508 (3)0.0241 (2)0.00283 (19)0.0070 (2)
O110.0521 (8)0.0692 (9)0.0742 (9)0.0198 (7)0.0293 (7)0.0218 (7)
O130.0514 (7)0.0518 (7)0.0402 (6)0.0149 (6)0.0181 (5)0.0046 (5)
N10.0334 (6)0.0405 (7)0.0454 (7)0.0096 (5)0.0113 (5)0.0114 (5)
N30.0390 (7)0.0513 (8)0.0439 (7)0.0025 (6)0.0188 (6)0.0185 (6)
N70.0315 (6)0.0382 (6)0.0383 (6)0.0069 (5)0.0103 (5)0.0120 (5)
N90.0422 (7)0.0514 (8)0.0364 (7)0.0053 (6)0.0103 (6)0.0109 (6)
C20.0381 (8)0.0430 (8)0.0527 (9)0.0039 (6)0.0190 (7)0.0188 (7)
C40.0350 (7)0.0409 (7)0.0377 (7)0.0017 (6)0.0131 (6)0.0140 (6)
C50.0312 (6)0.0365 (7)0.0377 (7)0.0058 (5)0.0116 (5)0.0119 (6)
C60.0335 (7)0.0340 (7)0.0414 (7)0.0052 (5)0.0125 (6)0.0119 (6)
C80.0355 (7)0.0426 (8)0.0402 (8)0.0067 (6)0.0063 (6)0.0104 (6)
C100.0453 (9)0.0561 (11)0.0577 (11)0.0211 (8)0.0117 (8)0.0081 (8)
C120.0568 (11)0.0783 (14)0.0492 (10)0.0023 (10)0.0291 (9)0.0217 (9)
C140.0340 (7)0.0353 (7)0.0471 (8)0.0045 (5)0.0184 (6)0.0113 (6)
C150.0324 (7)0.0354 (7)0.0379 (7)0.0057 (5)0.0113 (6)0.0102 (6)
C160.0354 (7)0.0406 (8)0.0435 (8)0.0089 (6)0.0136 (6)0.0095 (6)
C170.0535 (10)0.0448 (9)0.0554 (10)0.0180 (8)0.0195 (8)0.0118 (7)
C180.0734 (13)0.0387 (8)0.0589 (11)0.0127 (8)0.0211 (10)0.0166 (8)
C190.0569 (11)0.0424 (9)0.0587 (11)0.0030 (8)0.0148 (9)0.0211 (8)
C200.0375 (8)0.0411 (8)0.0473 (8)0.0044 (6)0.0117 (6)0.0147 (7)
Geometric parameters (Å, º) top
Cl1—C161.7323 (18)C10—H10A0.96
Cl2—C201.7375 (17)C10—H10B0.96
Cl3—C81.6963 (16)C10—H10C0.96
O11—C21.2226 (19)C12—H12A0.96
O13—C61.2213 (19)C12—H12B0.96
N1—C21.400 (2)C12—H12C0.96
N1—C61.4095 (18)C14—C151.514 (2)
N1—C101.470 (2)C14—H14A0.97
N3—C21.368 (2)C14—H14B0.97
N3—C41.3713 (19)C15—C201.392 (2)
N3—C121.460 (2)C15—C161.4018 (19)
N7—C81.350 (2)C16—C171.389 (2)
N7—C51.3928 (18)C17—C181.375 (3)
N7—C141.4738 (19)C17—H170.93
N9—C81.322 (2)C18—C191.385 (3)
N9—C41.360 (2)C18—H180.93
C4—C51.372 (2)C19—C201.390 (2)
C5—C61.427 (2)C19—H190.93
C2—N1—C6127.07 (14)N3—C12—H12A109.5
C2—N1—C10115.35 (14)N3—C12—H12B109.5
C6—N1—C10117.49 (14)H12A—C12—H12B109.5
C2—N3—C4119.75 (13)N3—C12—H12C109.5
C2—N3—C12119.67 (14)H12A—C12—H12C109.5
C4—N3—C12120.39 (16)H12B—C12—H12C109.5
C8—N7—C5104.62 (12)N7—C14—C15114.12 (12)
C8—N7—C14129.42 (13)N7—C14—H14A108.7
C5—N7—C14125.94 (13)C15—C14—H14A108.7
C8—N9—C4102.67 (13)N7—C14—H14B108.7
O11—C2—N3122.26 (16)C15—C14—H14B108.7
O11—C2—N1120.76 (17)H14A—C14—H14B107.6
N3—C2—N1116.98 (13)C20—C15—C16115.58 (14)
N9—C4—C5112.28 (13)C20—C15—C14122.66 (13)
N9—C4—N3125.54 (14)C16—C15—C14121.62 (14)
C5—C4—N3122.17 (15)C17—C16—C15122.74 (16)
C4—C5—N7105.23 (13)C17—C16—Cl1116.53 (13)
C4—C5—C6122.65 (13)C15—C16—Cl1120.74 (12)
N7—C5—C6132.10 (13)C18—C17—C16119.27 (16)
O13—C6—N1121.60 (14)C18—C17—H17120.4
O13—C6—C5127.07 (14)C16—C17—H17120.4
N1—C6—C5111.33 (13)C17—C18—C19120.43 (16)
N9—C8—N7115.18 (14)C17—C18—H18119.8
N9—C8—Cl3122.99 (13)C19—C18—H18119.8
N7—C8—Cl3121.82 (13)C18—C19—C20118.99 (18)
N1—C10—H10A109.5C18—C19—H19120.5
N1—C10—H10B109.5C20—C19—H19120.5
H10A—C10—H10B109.5C19—C20—C15122.97 (16)
N1—C10—H10C109.5C19—C20—Cl2116.90 (14)
H10A—C10—H10C109.5C15—C20—Cl2120.13 (12)
H10B—C10—H10C109.5
C4—N3—C2—O11176.93 (17)N7—C5—C6—O132.6 (3)
C12—N3—C2—O111.9 (3)C4—C5—C6—N10.6 (2)
C4—N3—C2—N12.2 (2)N7—C5—C6—N1177.97 (16)
C12—N3—C2—N1177.27 (16)C4—N9—C8—N70.3 (2)
C6—N1—C2—O11176.75 (17)C4—N9—C8—Cl3179.22 (13)
C10—N1—C2—O110.2 (3)C5—N7—C8—N90.8 (2)
C6—N1—C2—N32.4 (3)C14—N7—C8—N9179.29 (15)
C10—N1—C2—N3179.00 (16)C5—N7—C8—Cl3178.68 (12)
C8—N9—C4—C50.43 (19)C14—N7—C8—Cl30.2 (2)
C8—N9—C4—N3178.68 (16)C8—N7—C14—C1558.3 (2)
C2—N3—C4—N9178.16 (16)C5—N7—C14—C15123.51 (16)
C12—N3—C4—N93.2 (3)N7—C14—C15—C2060.6 (2)
C2—N3—C4—C50.9 (2)N7—C14—C15—C16123.94 (16)
C12—N3—C4—C5175.86 (17)C20—C15—C16—C170.8 (2)
N9—C4—C5—N70.90 (18)C14—C15—C16—C17174.93 (16)
N3—C4—C5—N7178.24 (14)C20—C15—C16—Cl1178.88 (12)
N9—C4—C5—C6179.78 (15)C14—C15—C16—Cl15.4 (2)
N3—C4—C5—C60.6 (2)C15—C16—C17—C180.0 (3)
C8—N7—C5—C40.97 (17)Cl1—C16—C17—C18179.75 (15)
C14—N7—C5—C4179.53 (14)C16—C17—C18—C190.8 (3)
C8—N7—C5—C6179.70 (17)C17—C18—C19—C200.6 (3)
C14—N7—C5—C61.7 (3)C18—C19—C20—C150.4 (3)
C2—N1—C6—O13179.51 (16)C18—C19—C20—Cl2179.86 (16)
C10—N1—C6—O133.0 (2)C16—C15—C20—C191.0 (3)
C2—N1—C6—C51.0 (2)C14—C15—C20—C19174.68 (17)
C10—N1—C6—C5177.50 (15)C16—C15—C20—Cl2179.50 (12)
C4—C5—C6—O13178.89 (17)C14—C15—C20—Cl24.8 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C14—H14B···O130.972.443.170 (2)132
C14—H14B···O13i0.972.553.196 (2)124
Symmetry code: (i) x+1, y, z+1.

Experimental details

Crystal data
Chemical formulaC14H11Cl3N4O2
Mr373.63
Crystal system, space groupTriclinic, P1
Temperature (K)293
a, b, c (Å)8.4073 (2), 8.6544 (3), 11.8014 (4)
α, β, γ (°)71.8140 (14), 70.7538 (13), 82.343 (2)
V3)769.74 (4)
Z2
Radiation typeMo Kα
µ (mm1)0.61
Crystal size (mm)0.39 × 0.28 × 0.26
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correctionIntegration
By Gaussian integration based on twelve indexed crystal faces (NUMABS; Coppens, 1970)
Tmin, Tmax0.838, 0.905
No. of measured, independent and
observed [I > 2σ(I)] reflections
10330, 4339, 3637
Rint0.070
(sin θ/λ)max1)0.703
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.049, 0.130, 1.02
No. of reflections4339
No. of parameters211
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.39, 0.36

Computer programs: KappaCCD (Nonius, 1999), SCALEPACK (Otwinowski & Minor 1997), DENZO (Otwinowski & Minor, 1997) and SCALEPACK, SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C14—H14B···O130.972.443.170 (2)132
C14—H14B···O13i0.972.553.196 (2)124
Symmetry code: (i) x+1, y, z+1.
 

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