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organic compounds
Monoclinic polymorph of 3,7-dimethyl-1-(5-oxohexyl)-3,7-dihydro-1H-purine-2,6-dione
aLatvian Institute of Organic Synthesis, 21 Aizkraukles Street, Riga, LV-1006, Latvia
*Correspondence e-mail: mishnevs@osi.lv
The structure of the title compound, pentoxifylline, C13H18N4O3, has been previously characterized as a triclinic polymorph [Pavelčík et al. (1989). Acta Cryst. C45, 836–837]. We have discovered the monoclinic form. There are no strong hydrogen bonds in the rather, moderate C—H⋯O hydrogen bonds are present, which serve to stabilize the three-dimensional architecture.
Related literature
For general background to pentoxifylline, see Dettelbach & Aviado (1985). For the structure and the nature of the hydrogen bonding in the triclinic polymorph, see: Pavelčík et al. (1989
); Gilli (2002
).
Experimental
Crystal data
|
Data collection
|
Refinement
|
|
Data collection: KappaCCD Server Software (Nonius, 1997); cell HKL SCALEPACK (Otwinovski & Minor, 1997
); data reduction: HKL DENZO (Otwinovski & Minor, 1997
) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008
); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008
); molecular graphics: ORTEP-3 (Farrugia, 1997
); software used to prepare material for publication: SHELXL97.
Supporting information
10.1107/S1600536811040232/tk2793sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536811040232/tk2793Isup2.hkl
Supporting information file. DOI: 10.1107/S1600536811040232/tk2793Isup3.cml
Title compound was obtained by recrystallization of Trental tablets, produced by Sanofi-Aventis Deutschland GmbH. Crystals were grown by slow evaporation from dichloromethane at temperature range 308–315 K.
All hydrogen atoms were positioned geometrically with C—H distances ranging from 0.93 to 0.97 Å and refined as riding on their parent atoms with Uiso (H) = 1.5Ueq (C) for methyl groups and Uiso (H) = 1.2Ueq (C) for others.
Data collection: KappaCCD Server Software (Nonius, 1997); cell
HKL SCALEPACK (Otwinovski & Minor, 1997); data reduction: HKL DENZO and SCALEPACK (Otwinovski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008). ![]() | Fig. 1. The molecular structure of the title compound, II, showing 50% probability ellipsoids and hydrogen atoms are shown as small spheres of arbitrary radii. |
C13H18N4O3 | Dx = 1.370 Mg m−3 |
Mr = 278.31 | Melting point: 365 K |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 9.743 (6) Å | Cell parameters from 6273 reflections |
b = 17.410 (8) Å | θ = 1.0–27.5° |
c = 7.956 (3) Å | µ = 0.10 mm−1 |
β = 90.89 (2)° | T = 190 K |
V = 1349.4 (12) Å3 | Plate, colourless |
Z = 4 | 0.4 × 0.3 × 0.05 mm |
F(000) = 592 |
Nonius KappaCCD diffractometer | 1817 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.053 |
Graphite monochromator | θmax = 27.5°, θmin = 2.4° |
CCD scans | h = −12→12 |
5073 measured reflections | k = −22→19 |
3065 independent reflections | l = −10→10 |
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)] = 0.066 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.150 | H-atom parameters constrained |
S = 1.02 | w = 1/[σ2(Fo2) + (0.0525P)2 + 0.5672P] where P = (Fo2 + 2Fc2)/3 |
3065 reflections | (Δ/σ)max = 0.004 |
184 parameters | Δρmax = 0.24 e Å−3 |
0 restraints | Δρmin = −0.20 e Å−3 |
C13H18N4O3 | V = 1349.4 (12) Å3 |
Mr = 278.31 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 9.743 (6) Å | µ = 0.10 mm−1 |
b = 17.410 (8) Å | T = 190 K |
c = 7.956 (3) Å | 0.4 × 0.3 × 0.05 mm |
β = 90.89 (2)° |
Nonius KappaCCD diffractometer | 1817 reflections with I > 2σ(I) |
5073 measured reflections | Rint = 0.053 |
3065 independent reflections |
R[F2 > 2σ(F2)] = 0.066 | 0 restraints |
wR(F2) = 0.150 | H-atom parameters constrained |
S = 1.02 | Δρmax = 0.24 e Å−3 |
3065 reflections | Δρmin = −0.20 e Å−3 |
184 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 | ||
O19 | −0.79244 (18) | 0.03718 (9) | −0.4841 (2) | 0.0407 (5) | |
O18 | −0.54702 (19) | −0.15692 (9) | −0.2345 (2) | 0.0431 (5) | |
N7 | −0.6688 (2) | −0.05902 (10) | −0.3550 (2) | 0.0314 (5) | |
O20 | −1.1444 (2) | −0.31616 (11) | −0.4130 (3) | 0.0550 (6) | |
N1 | −0.5641 (2) | 0.14522 (11) | −0.3470 (2) | 0.0337 (5) | |
N5 | −0.4583 (2) | −0.03670 (11) | −0.2089 (2) | 0.0350 (5) | |
C9 | −0.5831 (2) | 0.06649 (13) | −0.3380 (3) | 0.0304 (5) | |
N3 | −0.3878 (2) | 0.09676 (12) | −0.1963 (3) | 0.0380 (5) | |
C4 | −0.4742 (2) | 0.04006 (13) | −0.2463 (3) | 0.0319 (6) | |
C10 | −0.7740 (3) | −0.11505 (13) | −0.4085 (3) | 0.0351 (6) | |
H10A | −0.7303 | −0.1639 | −0.4317 | 0.042* | |
H10B | −0.8180 | −0.0973 | −0.5116 | 0.042* | |
C6 | −0.5568 (3) | −0.08839 (14) | −0.2631 (3) | 0.0331 (6) | |
C13 | −0.9288 (3) | −0.26965 (13) | −0.3170 (3) | 0.0323 (6) | |
H13A | −0.8532 | −0.2731 | −0.3946 | 0.039* | |
H13B | −0.8920 | −0.2790 | −0.2049 | 0.039* | |
C14 | −1.0310 (3) | −0.33177 (14) | −0.3593 (3) | 0.0326 (6) | |
C12 | −0.9861 (2) | −0.18878 (13) | −0.3236 (3) | 0.0361 (6) | |
H12A | −1.0633 | −0.1856 | −0.2484 | 0.043* | |
H12B | −1.0203 | −0.1787 | −0.4366 | 0.043* | |
C15 | −0.9876 (3) | −0.41325 (14) | −0.3319 (3) | 0.0412 (6) | |
H15A | −1.0331 | −0.4457 | −0.4128 | 0.062* | |
H15B | −1.0117 | −0.4290 | −0.2206 | 0.062* | |
H15C | −0.8900 | −0.4173 | −0.3446 | 0.062* | |
C17 | −0.3361 (3) | −0.06489 (15) | −0.1159 (3) | 0.0427 (6) | |
H17A | −0.2675 | −0.0805 | −0.1942 | 0.064* | |
H17B | −0.3612 | −0.1079 | −0.0474 | 0.064* | |
H17C | −0.3002 | −0.0246 | −0.0456 | 0.064* | |
C8 | −0.6905 (3) | 0.01842 (13) | −0.4012 (3) | 0.0324 (6) | |
C11 | −0.8821 (3) | −0.12644 (14) | −0.2754 (3) | 0.0388 (6) | |
H11A | −0.9303 | −0.0784 | −0.2583 | 0.047* | |
H11B | −0.8373 | −0.1403 | −0.1700 | 0.047* | |
C16 | −0.6522 (3) | 0.20142 (14) | −0.4321 (3) | 0.0420 (6) | |
H16A | −0.6097 | 0.2511 | −0.4268 | 0.063* | |
H16B | −0.7394 | 0.2034 | −0.3778 | 0.063* | |
H16C | −0.6653 | 0.1867 | −0.5475 | 0.063* | |
C2 | −0.4478 (3) | 0.15899 (15) | −0.2608 (3) | 0.0386 (6) | |
H2 | −0.4118 | 0.2081 | −0.2469 | 0.046* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O19 | 0.0381 (11) | 0.0348 (10) | 0.0490 (10) | −0.0019 (8) | −0.0061 (8) | 0.0061 (8) |
O18 | 0.0530 (12) | 0.0232 (9) | 0.0530 (11) | 0.0008 (8) | −0.0011 (8) | 0.0021 (8) |
N7 | 0.0359 (12) | 0.0224 (10) | 0.0358 (11) | −0.0046 (9) | 0.0003 (8) | −0.0003 (8) |
O20 | 0.0438 (13) | 0.0385 (11) | 0.0818 (14) | −0.0051 (9) | −0.0226 (10) | −0.0014 (10) |
N1 | 0.0327 (12) | 0.0231 (10) | 0.0452 (12) | 0.0017 (9) | 0.0017 (9) | 0.0010 (8) |
N5 | 0.0334 (12) | 0.0288 (11) | 0.0428 (12) | 0.0007 (9) | −0.0018 (9) | 0.0033 (9) |
C9 | 0.0322 (13) | 0.0217 (11) | 0.0374 (13) | −0.0010 (10) | 0.0039 (10) | 0.0004 (10) |
N3 | 0.0362 (12) | 0.0304 (11) | 0.0473 (12) | −0.0030 (10) | −0.0003 (9) | −0.0037 (9) |
C4 | 0.0313 (14) | 0.0261 (12) | 0.0384 (13) | 0.0001 (11) | 0.0032 (10) | −0.0009 (10) |
C10 | 0.0425 (15) | 0.0245 (12) | 0.0383 (13) | −0.0080 (11) | 0.0011 (11) | −0.0020 (10) |
C6 | 0.0370 (14) | 0.0279 (13) | 0.0346 (13) | 0.0003 (11) | 0.0044 (10) | −0.0021 (10) |
C13 | 0.0356 (14) | 0.0267 (12) | 0.0345 (12) | −0.0052 (10) | −0.0001 (10) | 0.0001 (10) |
C14 | 0.0366 (15) | 0.0322 (13) | 0.0290 (12) | −0.0029 (11) | −0.0008 (10) | −0.0002 (10) |
C12 | 0.0335 (14) | 0.0284 (13) | 0.0465 (14) | −0.0009 (11) | 0.0060 (11) | −0.0015 (11) |
C15 | 0.0443 (16) | 0.0282 (13) | 0.0510 (15) | −0.0050 (12) | −0.0026 (12) | 0.0002 (11) |
C17 | 0.0404 (16) | 0.0372 (14) | 0.0503 (16) | 0.0079 (12) | −0.0051 (12) | 0.0051 (12) |
C8 | 0.0332 (14) | 0.0294 (13) | 0.0347 (13) | 0.0002 (11) | 0.0061 (11) | 0.0011 (10) |
C11 | 0.0453 (16) | 0.0253 (12) | 0.0459 (15) | −0.0048 (11) | 0.0095 (11) | −0.0065 (11) |
C16 | 0.0392 (15) | 0.0289 (14) | 0.0578 (16) | 0.0077 (11) | −0.0040 (12) | 0.0066 (11) |
C2 | 0.0322 (15) | 0.0328 (14) | 0.0509 (15) | −0.0039 (11) | −0.0013 (11) | −0.0039 (12) |
O19—C8 | 1.228 (3) | C13—C12 | 1.515 (3) |
O18—C6 | 1.218 (3) | C13—H13A | 0.9700 |
N7—C6 | 1.401 (3) | C13—H13B | 0.9700 |
N7—C8 | 1.413 (3) | C14—C15 | 1.495 (3) |
N7—C10 | 1.473 (3) | C12—C11 | 1.530 (3) |
O20—C14 | 1.209 (3) | C12—H12A | 0.9700 |
N1—C2 | 1.337 (3) | C12—H12B | 0.9700 |
N1—C9 | 1.385 (3) | C15—H15A | 0.9600 |
N1—C16 | 1.461 (3) | C15—H15B | 0.9600 |
N5—C4 | 1.377 (3) | C15—H15C | 0.9600 |
N5—C6 | 1.380 (3) | C17—H17A | 0.9600 |
N5—C17 | 1.476 (3) | C17—H17B | 0.9600 |
C9—C4 | 1.359 (3) | C17—H17C | 0.9600 |
C9—C8 | 1.426 (3) | C11—H11A | 0.9700 |
N3—C2 | 1.330 (3) | C11—H11B | 0.9700 |
N3—C4 | 1.353 (3) | C16—H16A | 0.9600 |
C10—C11 | 1.518 (3) | C16—H16B | 0.9600 |
C10—H10A | 0.9700 | C16—H16C | 0.9600 |
C10—H10B | 0.9700 | C2—H2 | 0.9300 |
C13—C14 | 1.505 (3) | ||
C6—N7—C8 | 126.6 (2) | C13—C12—H12A | 108.7 |
C6—N7—C10 | 116.24 (19) | C11—C12—H12A | 108.7 |
C8—N7—C10 | 117.1 (2) | C13—C12—H12B | 108.7 |
C2—N1—C9 | 105.3 (2) | C11—C12—H12B | 108.7 |
C2—N1—C16 | 127.2 (2) | H12A—C12—H12B | 107.6 |
C9—N1—C16 | 127.5 (2) | C14—C15—H15A | 109.5 |
C4—N5—C6 | 119.3 (2) | C14—C15—H15B | 109.5 |
C4—N5—C17 | 121.2 (2) | H15A—C15—H15B | 109.5 |
C6—N5—C17 | 119.4 (2) | C14—C15—H15C | 109.5 |
C4—C9—N1 | 105.0 (2) | H15A—C15—H15C | 109.5 |
C4—C9—C8 | 123.6 (2) | H15B—C15—H15C | 109.5 |
N1—C9—C8 | 131.4 (2) | N5—C17—H17A | 109.5 |
C2—N3—C4 | 102.3 (2) | N5—C17—H17B | 109.5 |
N3—C4—C9 | 112.8 (2) | H17A—C17—H17B | 109.5 |
N3—C4—N5 | 125.2 (2) | N5—C17—H17C | 109.5 |
C9—C4—N5 | 121.9 (2) | H17A—C17—H17C | 109.5 |
N7—C10—C11 | 111.85 (19) | H17B—C17—H17C | 109.5 |
N7—C10—H10A | 109.2 | O19—C8—N7 | 120.7 (2) |
C11—C10—H10A | 109.2 | O19—C8—C9 | 128.1 (2) |
N7—C10—H10B | 109.2 | N7—C8—C9 | 111.2 (2) |
C11—C10—H10B | 109.2 | C10—C11—C12 | 112.4 (2) |
H10A—C10—H10B | 107.9 | C10—C11—H11A | 109.1 |
O18—C6—N5 | 121.9 (2) | C12—C11—H11A | 109.1 |
O18—C6—N7 | 120.9 (2) | C10—C11—H11B | 109.1 |
N5—C6—N7 | 117.2 (2) | C12—C11—H11B | 109.1 |
C14—C13—C12 | 114.7 (2) | H11A—C11—H11B | 107.8 |
C14—C13—H13A | 108.6 | N1—C16—H16A | 109.5 |
C12—C13—H13A | 108.6 | N1—C16—H16B | 109.5 |
C14—C13—H13B | 108.6 | H16A—C16—H16B | 109.5 |
C12—C13—H13B | 108.6 | N1—C16—H16C | 109.5 |
H13A—C13—H13B | 107.6 | H16A—C16—H16C | 109.5 |
O20—C14—C15 | 121.3 (2) | H16B—C16—H16C | 109.5 |
O20—C14—C13 | 121.0 (2) | N3—C2—N1 | 114.6 (2) |
C15—C14—C13 | 117.6 (2) | N3—C2—H2 | 122.7 |
C13—C12—C11 | 114.1 (2) | N1—C2—H2 | 122.7 |
C2—N1—C9—C4 | −0.3 (2) | C8—N7—C6—O18 | −177.9 (2) |
C16—N1—C9—C4 | 179.9 (2) | C10—N7—C6—O18 | 2.0 (3) |
C2—N1—C9—C8 | 177.9 (2) | C8—N7—C6—N5 | 1.3 (3) |
C16—N1—C9—C8 | −2.0 (4) | C10—N7—C6—N5 | −178.80 (19) |
C2—N3—C4—C9 | 0.1 (3) | C12—C13—C14—O20 | 8.2 (3) |
C2—N3—C4—N5 | −179.1 (2) | C12—C13—C14—C15 | −171.5 (2) |
N1—C9—C4—N3 | 0.1 (3) | C14—C13—C12—C11 | 178.31 (19) |
C8—C9—C4—N3 | −178.2 (2) | C6—N7—C8—O19 | 179.1 (2) |
N1—C9—C4—N5 | 179.3 (2) | C10—N7—C8—O19 | −0.8 (3) |
C8—C9—C4—N5 | 1.0 (4) | C6—N7—C8—C9 | −1.5 (3) |
C6—N5—C4—N3 | 177.8 (2) | C10—N7—C8—C9 | 178.54 (19) |
C17—N5—C4—N3 | −3.8 (4) | C4—C9—C8—O19 | 179.7 (2) |
C6—N5—C4—C9 | −1.3 (3) | N1—C9—C8—O19 | 1.8 (4) |
C17—N5—C4—C9 | 177.1 (2) | C4—C9—C8—N7 | 0.4 (3) |
C6—N7—C10—C11 | 87.7 (2) | N1—C9—C8—N7 | −177.5 (2) |
C8—N7—C10—C11 | −92.3 (2) | N7—C10—C11—C12 | −175.8 (2) |
C4—N5—C6—O18 | 179.4 (2) | C13—C12—C11—C10 | 71.4 (3) |
C17—N5—C6—O18 | 1.0 (3) | C4—N3—C2—N1 | −0.3 (3) |
C4—N5—C6—N7 | 0.2 (3) | C9—N1—C2—N3 | 0.3 (3) |
C17—N5—C6—N7 | −178.2 (2) | C16—N1—C2—N3 | −179.8 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O18i | 0.93 | 2.39 | 3.206 (4) | 147 |
C15—H15B···O19ii | 0.96 | 2.60 | 3.439 (4) | 147 |
C16—H16A···O18i | 0.96 | 2.55 | 3.395 (4) | 148 |
Symmetry codes: (i) −x−1, y+1/2, −z−1/2; (ii) −x−2, y−1/2, −z−1/2. |
Experimental details
Crystal data | |
Chemical formula | C13H18N4O3 |
Mr | 278.31 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 190 |
a, b, c (Å) | 9.743 (6), 17.410 (8), 7.956 (3) |
β (°) | 90.89 (2) |
V (Å3) | 1349.4 (12) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.10 |
Crystal size (mm) | 0.4 × 0.3 × 0.05 |
Data collection | |
Diffractometer | Nonius KappaCCD diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5073, 3065, 1817 |
Rint | 0.053 |
(sin θ/λ)max (Å−1) | 0.650 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.066, 0.150, 1.02 |
No. of reflections | 3065 |
No. of parameters | 184 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.24, −0.20 |
Computer programs: KappaCCD Server Software (Nonius, 1997), HKL SCALEPACK (Otwinovski & Minor, 1997), HKL DENZO and SCALEPACK (Otwinovski & Minor, 1997), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997).
D—H···A | D—H | H···A | D···A | D—H···A |
C2—H2···O18i | 0.93 | 2.39 | 3.206 (4) | 147 |
C15—H15B···O19ii | 0.96 | 2.60 | 3.439 (4) | 147 |
C16—H16A···O18i | 0.96 | 2.55 | 3.395 (4) | 148 |
Symmetry codes: (i) −x−1, y+1/2, −z−1/2; (ii) −x−2, y−1/2, −z−1/2. |
Acknowledgements
This work was supported by the European Regional Development Fund (No. 2DP/ 2.1.1.1.0/10/APIA/VIAA/066).
References
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Otwinovski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York: Academic Press. Google Scholar
Pavelčík, F., Sivý, J., Havránek, E., Sivý, P., Komanová, E. & Nevýdal, J. (1989). Acta Cryst. C45, 836–837. CSD CrossRef Web of Science IUCr Journals Google Scholar
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The background to pentoxifylline has been summarized (Dettelbach & Aviado, 1985). The polymorph structure II differs from the known form I Pavelčík et al., 1989; Gilli, 2002) in their molecular conformation and the packing of the molecules in the lattice. The bond lengths of forms I and II are close to their standard values, but torsion angle N7—C10—C11—C12 (75.6 (3)° for I and 175.8 (2)° for II) and some bond angles significantly differ: N7—C10—C11 (114.2 (2)° for I and 111.9 (2)° for II), C10—C11—C12 (115.4 (2)° for I and 115.4 (2)° for II), C11—C12—C13 (111.0 (2)° for I and 114.1 (2)° for II). In the crystal structure of II, the molecules are connected by means of C—H···O hydrogen bonds, Table 1.