The title compound, C17H13ClN4O2, displays profound and selective activity against Mycobacterium tuberculosis. In the crystal structure, there are two independent molecules in the asymmetric unit. Intermolecular hydrogen bonding between a CH group of the purine ring and the O atom of the furan ring, and also π–π stacking in another direction, builds the three-dimensional network.
Supporting information
CCDC reference: 649081
The title compound was synthesized as described by Bakkestuen et al.
(2005). Crystals of (I) suitable for X-ray diffraction studies were obtained
by dissolving the compound (50 mg) in deuterated dichloromethane (0.6 ml) by
heating, followed by slow evaporation of the solvent in a refrigerator.
Friedel pairs were not merged and the absolute structure has been determined
reliably. H atoms were positioned geometrically and allowed to ride and rotate
(for the CH3 group) on their carrier atoms, with C—H = 0.95 (aromatic
C—H), 0.99 (CH2) or 0.98 Å (CH3), and with Uiso(H) =
1.2Ueq(C) for CH2 and aromatic C—H, or 1.5Ueq(C) for
CH3.
Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1998); data reduction: SAINT (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Version 1.08; Farrugia, 1997) and
POV-RAY for Windows (Cason, 2004); software used to prepare material for publication: SHELXL97 and WinGX (Farrugia, 1999).
2-Chloro-6-(2-furyl)-9-(4-methoxybenzyl)-9
H-purine
top
Crystal data top
C17H13ClN4O2 | Dx = 1.477 Mg m−3 |
Mr = 340.76 | Melting point: 188 K |
Orthorhombic, Pca21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2c -2ac | Cell parameters from 7767 reflections |
a = 8.6963 (4) Å | θ = 2.5–39.7° |
b = 24.5966 (11) Å | µ = 0.27 mm−1 |
c = 14.3247 (7) Å | T = 105 K |
V = 3064.0 (2) Å3 | Plate, colourless |
Z = 8 | 0.4 × 0.3 × 0.02 mm |
F(000) = 1408 | |
Data collection top
Siemens SMART CCD area-detector diffractometer | 12073 reflections with I > 2σ(I) |
Sets of exposures each taken over 0.3° ω rotation scans | Rint = 0.039 |
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 1996) | θmax = 40.2°, θmin = 1.7° |
Tmin = 0.83, Tmax = 0.995 | h = −14→15 |
49273 measured reflections | k = −44→40 |
17784 independent reflections | l = −23→25 |
Refinement top
Refinement on F2 | H-atom parameters constrained |
Least-squares matrix: full | w = 1/[σ2(Fo2) + (0.0472P)2] where P = (Fo2 + 2Fc2)/3 |
R[F2 > 2σ(F2)] = 0.039 | (Δ/σ)max = 0.002 |
wR(F2) = 0.088 | Δρmax = 0.46 e Å−3 |
S = 0.89 | Δρmin = −0.30 e Å−3 |
17784 reflections | Absolute structure: Flack (1983), with 8178 Friedel pairs |
435 parameters | Absolute structure parameter: −0.01 (3) |
1 restraint | |
Crystal data top
C17H13ClN4O2 | V = 3064.0 (2) Å3 |
Mr = 340.76 | Z = 8 |
Orthorhombic, Pca21 | Mo Kα radiation |
a = 8.6963 (4) Å | µ = 0.27 mm−1 |
b = 24.5966 (11) Å | T = 105 K |
c = 14.3247 (7) Å | 0.4 × 0.3 × 0.02 mm |
Data collection top
Siemens SMART CCD area-detector diffractometer | 17784 independent reflections |
Absorption correction: empirical (using intensity measurements) (SADABS; Sheldrick, 1996) | 12073 reflections with I > 2σ(I) |
Tmin = 0.83, Tmax = 0.995 | Rint = 0.039 |
49273 measured reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.039 | H-atom parameters constrained |
wR(F2) = 0.088 | Δρmax = 0.46 e Å−3 |
S = 0.89 | Δρmin = −0.30 e Å−3 |
17784 reflections | Absolute structure: Flack (1983), with 8178 Friedel pairs |
435 parameters | Absolute structure parameter: −0.01 (3) |
1 restraint | |
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C2A | 0.59897 (12) | 0.84526 (4) | 0.52085 (8) | 0.01752 (18) | |
C4A | 0.83104 (11) | 0.81416 (4) | 0.54569 (7) | 0.01716 (18) | |
C8A | 1.01781 (12) | 0.75989 (5) | 0.58759 (8) | 0.0250 (2) | |
H8A | 1.1192 | 0.7471 | 0.5989 | 0.03* | |
C5A | 0.77394 (11) | 0.76467 (4) | 0.57984 (7) | 0.01752 (18) | |
C6A | 0.61351 (11) | 0.75903 (4) | 0.58149 (7) | 0.01573 (18) | |
C17A | 0.53788 (12) | 0.71070 (4) | 0.61642 (8) | 0.01779 (18) | |
C21A | 0.59340 (15) | 0.66286 (5) | 0.65138 (8) | 0.0237 (2) | |
H21A | 0.6984 | 0.6529 | 0.6576 | 0.028* | |
C20A | 0.46366 (17) | 0.63099 (5) | 0.67652 (9) | 0.0290 (3) | |
H20A | 0.4646 | 0.5956 | 0.7031 | 0.035* | |
C19A | 0.33829 (15) | 0.66115 (5) | 0.65499 (9) | 0.0285 (3) | |
H19A | 0.2351 | 0.6497 | 0.6645 | 0.034* | |
C10A | 1.10090 (13) | 0.85253 (5) | 0.52522 (9) | 0.0256 (2) | |
H10A | 1.0683 | 0.8704 | 0.4665 | 0.031* | |
H10B | 1.2023 | 0.8354 | 0.5142 | 0.031* | |
C11A | 1.11604 (12) | 0.89488 (5) | 0.60126 (8) | 0.02070 (19) | |
C12A | 1.03108 (14) | 0.94304 (5) | 0.59850 (9) | 0.0280 (2) | |
H12A | 0.9655 | 0.95 | 0.5468 | 0.034* | |
C13A | 1.04119 (15) | 0.98076 (5) | 0.67015 (10) | 0.0297 (3) | |
H13A | 0.983 | 1.0134 | 0.6673 | 0.036* | |
C14A | 1.13697 (12) | 0.97078 (5) | 0.74650 (9) | 0.0230 (2) | |
C15A | 1.22258 (12) | 0.92301 (5) | 0.75040 (9) | 0.0225 (2) | |
H15A | 1.2879 | 0.916 | 0.8022 | 0.027* | |
C16A | 1.21174 (12) | 0.88559 (5) | 0.67772 (9) | 0.0219 (2) | |
H16A | 1.2707 | 0.8531 | 0.6803 | 0.026* | |
C23A | 1.25094 (17) | 1.00705 (6) | 0.88609 (10) | 0.0321 (3) | |
H23B | 1.2512 | 1.041 | 0.9219 | 0.048* | |
H23C | 1.3523 | 1.0015 | 0.8578 | 0.048* | |
H23A | 1.2273 | 0.9766 | 0.9278 | 0.048* | |
N3A | 0.74811 (11) | 0.85633 (4) | 0.51483 (7) | 0.01807 (17) | |
N9A | 0.98807 (10) | 0.81022 (4) | 0.55052 (7) | 0.02054 (18) | |
N7A | 0.89430 (11) | 0.73066 (4) | 0.60624 (7) | 0.02257 (18) | |
N1A | 0.52548 (10) | 0.80099 (4) | 0.55050 (6) | 0.01702 (15) | |
O18A | 0.37981 (9) | 0.71026 (3) | 0.61765 (6) | 0.02229 (16) | |
O22A | 1.13690 (10) | 1.01013 (4) | 0.81416 (7) | 0.0317 (2) | |
Cl2A | 0.47867 (3) | 0.897752 (11) | 0.48363 (2) | 0.02667 (6) | |
C2B | 0.59777 (11) | 0.65406 (4) | 0.91328 (7) | 0.01713 (18) | |
C4B | 0.36619 (11) | 0.68669 (4) | 0.89193 (7) | 0.01730 (18) | |
C8B | 0.18027 (13) | 0.74230 (5) | 0.85371 (9) | 0.0241 (2) | |
H8B | 0.0791 | 0.7559 | 0.8444 | 0.029* | |
C5B | 0.42413 (12) | 0.73578 (4) | 0.85669 (7) | 0.01761 (18) | |
C6B | 0.58461 (11) | 0.74013 (4) | 0.85200 (7) | 0.01574 (17) | |
C17B | 0.66089 (12) | 0.78842 (4) | 0.81701 (7) | 0.01702 (17) | |
C21B | 0.60471 (14) | 0.83552 (5) | 0.77956 (8) | 0.0228 (2) | |
H21B | 0.4996 | 0.8448 | 0.771 | 0.027* | |
C20B | 0.73467 (16) | 0.86798 (5) | 0.75591 (9) | 0.0267 (2) | |
H20B | 0.7335 | 0.9031 | 0.7283 | 0.032* | |
C19B | 0.85975 (14) | 0.83884 (5) | 0.78059 (9) | 0.0263 (2) | |
H19B | 0.9628 | 0.8508 | 0.7728 | 0.032* | |
C10B | 0.09460 (13) | 0.64895 (5) | 0.91101 (9) | 0.0242 (2) | |
H10D | −0.0084 | 0.6658 | 0.9168 | 0.029* | |
H10E | 0.1204 | 0.6319 | 0.9716 | 0.029* | |
C11B | 0.09010 (12) | 0.60563 (5) | 0.83611 (8) | 0.02013 (19) | |
C12B | 0.18216 (13) | 0.55933 (5) | 0.84251 (8) | 0.0236 (2) | |
H12B | 0.2447 | 0.554 | 0.8961 | 0.028* | |
C13B | 0.18361 (13) | 0.52089 (5) | 0.77144 (9) | 0.0241 (2) | |
H13B | 0.2459 | 0.4893 | 0.7768 | 0.029* | |
C14B | 0.09293 (12) | 0.52888 (4) | 0.69193 (8) | 0.01968 (19) | |
C15B | −0.00166 (13) | 0.57468 (4) | 0.68475 (8) | 0.02012 (19) | |
H15B | −0.0645 | 0.5799 | 0.6313 | 0.024* | |
C16B | −0.00234 (12) | 0.61272 (5) | 0.75761 (9) | 0.0208 (2) | |
H16B | −0.0668 | 0.6438 | 0.7534 | 0.025* | |
C23B | 0.00844 (15) | 0.49465 (6) | 0.54469 (10) | 0.0294 (3) | |
H23D | 0.0258 | 0.4639 | 0.5026 | 0.044* | |
H23E | 0.0332 | 0.5286 | 0.5123 | 0.044* | |
H23F | −0.0996 | 0.4952 | 0.5641 | 0.044* | |
N3B | 0.44816 (10) | 0.64404 (4) | 0.92208 (7) | 0.01877 (17) | |
N9B | 0.20869 (10) | 0.69148 (4) | 0.88961 (7) | 0.02083 (18) | |
N7B | 0.30427 (11) | 0.77080 (4) | 0.83311 (8) | 0.02383 (19) | |
N1B | 0.67202 (10) | 0.69786 (4) | 0.88118 (6) | 0.01698 (15) | |
O18B | 0.81862 (9) | 0.78974 (3) | 0.81841 (6) | 0.02123 (15) | |
O22B | 0.10456 (10) | 0.48920 (3) | 0.62503 (6) | 0.02652 (17) | |
Cl2B | 0.71778 (3) | 0.601047 (11) | 0.94872 (2) | 0.02462 (6) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C2A | 0.0144 (4) | 0.0203 (5) | 0.0178 (4) | 0.0004 (3) | 0.0019 (3) | 0.0009 (4) |
C4A | 0.0122 (4) | 0.0236 (5) | 0.0157 (4) | −0.0009 (3) | 0.0008 (3) | −0.0050 (3) |
C8A | 0.0154 (4) | 0.0325 (6) | 0.0271 (6) | 0.0059 (4) | −0.0031 (4) | −0.0088 (5) |
C5A | 0.0153 (4) | 0.0205 (4) | 0.0168 (4) | 0.0016 (3) | −0.0011 (4) | −0.0039 (3) |
C6A | 0.0152 (4) | 0.0176 (5) | 0.0144 (5) | 0.0000 (3) | 0.0003 (4) | −0.0023 (3) |
C17A | 0.0181 (4) | 0.0185 (4) | 0.0167 (5) | −0.0011 (3) | 0.0005 (4) | −0.0016 (3) |
C21A | 0.0327 (6) | 0.0174 (5) | 0.0209 (5) | 0.0021 (4) | −0.0012 (4) | −0.0004 (4) |
C20A | 0.0467 (7) | 0.0193 (5) | 0.0211 (6) | −0.0064 (5) | 0.0041 (5) | 0.0001 (4) |
C19A | 0.0342 (6) | 0.0246 (6) | 0.0269 (6) | −0.0117 (5) | 0.0105 (5) | −0.0016 (4) |
C10A | 0.0148 (4) | 0.0387 (6) | 0.0234 (5) | −0.0071 (4) | 0.0034 (4) | −0.0086 (5) |
C11A | 0.0133 (4) | 0.0283 (5) | 0.0205 (5) | −0.0037 (3) | 0.0024 (4) | −0.0036 (4) |
C12A | 0.0215 (5) | 0.0344 (6) | 0.0283 (6) | 0.0010 (4) | −0.0062 (5) | 0.0020 (5) |
C13A | 0.0250 (6) | 0.0259 (6) | 0.0383 (7) | 0.0029 (4) | −0.0031 (5) | −0.0026 (5) |
C14A | 0.0185 (4) | 0.0231 (5) | 0.0274 (5) | −0.0051 (4) | 0.0031 (4) | −0.0039 (4) |
C15A | 0.0200 (5) | 0.0240 (5) | 0.0236 (5) | −0.0025 (4) | −0.0021 (4) | −0.0029 (4) |
C16A | 0.0176 (5) | 0.0241 (5) | 0.0239 (5) | 0.0009 (4) | −0.0010 (4) | −0.0033 (4) |
C23A | 0.0318 (6) | 0.0353 (7) | 0.0292 (7) | −0.0138 (5) | 0.0059 (5) | −0.0111 (5) |
N3A | 0.0153 (4) | 0.0212 (4) | 0.0178 (4) | −0.0016 (3) | 0.0021 (3) | −0.0006 (3) |
N9A | 0.0120 (3) | 0.0279 (5) | 0.0217 (4) | −0.0005 (3) | 0.0005 (3) | −0.0069 (4) |
N7A | 0.0179 (4) | 0.0254 (5) | 0.0244 (5) | 0.0058 (3) | −0.0036 (3) | −0.0043 (4) |
N1A | 0.0141 (4) | 0.0200 (4) | 0.0170 (4) | −0.0007 (3) | 0.0007 (3) | 0.0007 (3) |
O18A | 0.0192 (3) | 0.0217 (4) | 0.0260 (4) | −0.0036 (3) | 0.0047 (3) | 0.0008 (3) |
O22A | 0.0281 (4) | 0.0271 (4) | 0.0398 (5) | −0.0024 (3) | −0.0005 (4) | −0.0140 (4) |
Cl2A | 0.01891 (11) | 0.02432 (12) | 0.03677 (15) | 0.00315 (9) | 0.00297 (10) | 0.01145 (11) |
C2B | 0.0151 (4) | 0.0188 (5) | 0.0175 (4) | −0.0012 (3) | −0.0012 (4) | −0.0002 (3) |
C4B | 0.0125 (4) | 0.0232 (5) | 0.0161 (4) | −0.0021 (3) | −0.0001 (3) | −0.0039 (4) |
C8B | 0.0169 (5) | 0.0285 (6) | 0.0269 (6) | 0.0049 (4) | −0.0019 (4) | −0.0047 (5) |
C5B | 0.0156 (4) | 0.0199 (5) | 0.0174 (5) | 0.0006 (3) | −0.0004 (3) | −0.0034 (3) |
C6B | 0.0155 (4) | 0.0172 (4) | 0.0145 (4) | −0.0013 (3) | 0.0001 (3) | −0.0023 (3) |
C17B | 0.0169 (4) | 0.0190 (4) | 0.0152 (4) | −0.0007 (3) | 0.0008 (4) | −0.0016 (3) |
C21B | 0.0284 (5) | 0.0202 (5) | 0.0198 (5) | 0.0017 (4) | −0.0019 (4) | −0.0013 (4) |
C20B | 0.0413 (7) | 0.0178 (5) | 0.0211 (5) | −0.0047 (4) | 0.0035 (5) | 0.0002 (4) |
C19B | 0.0295 (6) | 0.0256 (6) | 0.0238 (6) | −0.0101 (4) | 0.0058 (5) | −0.0014 (4) |
C10B | 0.0160 (4) | 0.0351 (6) | 0.0216 (5) | −0.0066 (4) | 0.0054 (4) | −0.0076 (4) |
C11B | 0.0143 (4) | 0.0264 (5) | 0.0197 (5) | −0.0049 (4) | 0.0019 (4) | −0.0020 (4) |
C12B | 0.0183 (4) | 0.0318 (6) | 0.0207 (5) | −0.0025 (4) | −0.0033 (4) | 0.0024 (4) |
C13B | 0.0211 (5) | 0.0233 (5) | 0.0279 (6) | 0.0031 (4) | −0.0026 (4) | 0.0021 (4) |
C14B | 0.0175 (4) | 0.0195 (4) | 0.0221 (5) | −0.0014 (3) | 0.0014 (4) | −0.0014 (4) |
C15B | 0.0183 (4) | 0.0222 (5) | 0.0199 (5) | −0.0004 (3) | −0.0035 (4) | −0.0014 (4) |
C16B | 0.0160 (4) | 0.0225 (5) | 0.0239 (5) | 0.0002 (3) | −0.0004 (4) | −0.0032 (4) |
C23B | 0.0278 (6) | 0.0334 (6) | 0.0269 (6) | 0.0043 (5) | −0.0034 (5) | −0.0097 (5) |
N3B | 0.0152 (4) | 0.0235 (4) | 0.0176 (4) | −0.0033 (3) | −0.0001 (3) | −0.0013 (3) |
N9B | 0.0131 (4) | 0.0279 (5) | 0.0215 (4) | −0.0012 (3) | 0.0017 (3) | −0.0062 (4) |
N7B | 0.0184 (4) | 0.0256 (5) | 0.0274 (5) | 0.0035 (3) | −0.0007 (4) | −0.0035 (4) |
N1B | 0.0148 (3) | 0.0184 (4) | 0.0178 (4) | −0.0015 (3) | 0.0000 (3) | 0.0000 (3) |
O18B | 0.0177 (3) | 0.0219 (4) | 0.0241 (4) | −0.0044 (3) | 0.0030 (3) | 0.0007 (3) |
O22B | 0.0268 (4) | 0.0230 (4) | 0.0297 (4) | 0.0047 (3) | −0.0048 (3) | −0.0076 (3) |
Cl2B | 0.01861 (11) | 0.02191 (12) | 0.03336 (14) | 0.00040 (8) | −0.00054 (10) | 0.00709 (11) |
Geometric parameters (Å, º) top
C2A—N3A | 1.3280 (14) | C2B—N3B | 1.3302 (13) |
C2A—N1A | 1.3320 (13) | C2B—N1B | 1.3377 (14) |
C2A—Cl2A | 1.7453 (11) | C2B—Cl2B | 1.7455 (11) |
C4A—N3A | 1.3385 (14) | C4B—N3B | 1.3398 (14) |
C4A—N9A | 1.3708 (13) | C4B—N9B | 1.3752 (13) |
C4A—C5A | 1.4027 (15) | C4B—C5B | 1.4024 (15) |
C8A—N7A | 1.3198 (15) | C8B—N7B | 1.3196 (16) |
C8A—N9A | 1.3717 (16) | C8B—N9B | 1.3740 (16) |
C8A—H8A | 0.95 | C8B—H8B | 0.95 |
C5A—N7A | 1.3922 (13) | C5B—N7B | 1.3938 (14) |
C5A—C6A | 1.4022 (14) | C5B—C6B | 1.4013 (14) |
C6A—N1A | 1.3595 (13) | C6B—N1B | 1.3540 (14) |
C6A—C17A | 1.4479 (15) | C6B—C17B | 1.4497 (15) |
C17A—C21A | 1.3670 (16) | C17B—C21B | 1.3670 (15) |
C17A—O18A | 1.3748 (13) | C17B—O18B | 1.3722 (12) |
C21A—C20A | 1.4202 (18) | C21B—C20B | 1.4247 (17) |
C21A—H21A | 0.95 | C21B—H21B | 0.95 |
C20A—C19A | 1.354 (2) | C20B—C19B | 1.3500 (19) |
C20A—H20A | 0.95 | C20B—H20B | 0.95 |
C19A—O18A | 1.3696 (14) | C19B—O18B | 1.3710 (14) |
C19A—H19A | 0.95 | C19B—H19B | 0.95 |
C10A—N9A | 1.4755 (15) | C10B—N9B | 1.4740 (15) |
C10A—C11A | 1.5128 (16) | C10B—C11B | 1.5127 (16) |
C10A—H10A | 0.99 | C10B—H10D | 0.99 |
C10A—H10B | 0.99 | C10B—H10E | 0.99 |
C11A—C12A | 1.3968 (17) | C11B—C16B | 1.3932 (16) |
C11A—C16A | 1.3944 (17) | C11B—C12B | 1.3950 (16) |
C12A—C13A | 1.3863 (19) | C12B—C13B | 1.3895 (17) |
C12A—H12A | 0.95 | C12B—H12B | 0.95 |
C13A—C14A | 1.3966 (18) | C13B—C14B | 1.3992 (17) |
C13A—H13A | 0.95 | C13B—H13B | 0.95 |
C14A—O22A | 1.3698 (15) | C14B—O22B | 1.3715 (13) |
C14A—C15A | 1.3920 (16) | C14B—C15B | 1.3987 (15) |
C15A—C16A | 1.3929 (16) | C15B—C16B | 1.4017 (16) |
C15A—H15A | 0.95 | C15B—H15B | 0.95 |
C16A—H16A | 0.95 | C16B—H16B | 0.95 |
C23A—O22A | 1.4322 (18) | C23B—O22B | 1.4286 (16) |
C23A—H23B | 0.98 | C23B—H23D | 0.98 |
C23A—H23C | 0.98 | C23B—H23E | 0.98 |
C23A—H23A | 0.98 | C23B—H23F | 0.98 |
| | | |
N3A—C2A—N1A | 131.07 (10) | N3B—C2B—N1B | 130.83 (10) |
N3A—C2A—Cl2A | 114.44 (8) | N3B—C2B—Cl2B | 114.77 (8) |
N1A—C2A—Cl2A | 114.49 (8) | N1B—C2B—Cl2B | 114.40 (8) |
N3A—C4A—N9A | 127.45 (10) | N3B—C4B—N9B | 127.21 (10) |
N3A—C4A—C5A | 126.66 (9) | N3B—C4B—C5B | 126.80 (9) |
N9A—C4A—C5A | 105.89 (9) | N9B—C4B—C5B | 105.98 (9) |
N7A—C8A—N9A | 114.61 (9) | N7B—C8B—N9B | 114.84 (10) |
N7A—C8A—H8A | 122.7 | N7B—C8B—H8B | 122.6 |
N9A—C8A—H8A | 122.7 | N9B—C8B—H8B | 122.6 |
N7A—C5A—C4A | 110.49 (9) | N7B—C5B—C4B | 110.53 (9) |
N7A—C5A—C6A | 133.16 (10) | N7B—C5B—C6B | 133.31 (10) |
C4A—C5A—C6A | 116.35 (9) | C6B—C5B—C4B | 116.16 (10) |
N1A—C6A—C5A | 118.67 (10) | N1B—C6B—C5B | 119.06 (10) |
N1A—C6A—C17A | 118.71 (9) | N1B—C6B—C17B | 118.61 (9) |
C5A—C6A—C17A | 122.61 (10) | C5B—C6B—C17B | 122.34 (10) |
C21A—C17A—O18A | 109.99 (9) | C21B—C17B—O18B | 110.05 (9) |
C21A—C17A—C6A | 132.30 (10) | C21B—C17B—C6B | 131.79 (10) |
O18A—C17A—C6A | 117.71 (9) | O18B—C17B—C6B | 118.15 (9) |
C17A—C21A—C20A | 106.70 (11) | C17B—C21B—C20B | 106.55 (11) |
C17A—C21A—H21A | 126.7 | C17B—C21B—H21B | 126.7 |
C20A—C21A—H21A | 126.7 | C20B—C21B—H21B | 126.7 |
C19A—C20A—C21A | 106.23 (11) | C19B—C20B—C21B | 106.21 (10) |
C19A—C20A—H20A | 126.9 | C19B—C20B—H20B | 126.9 |
C21A—C20A—H20A | 126.9 | C21B—C20B—H20B | 126.9 |
C20A—C19A—O18A | 111.09 (11) | C20B—C19B—O18B | 111.17 (10) |
C20A—C19A—H19A | 124.5 | C20B—C19B—H19B | 124.4 |
O18A—C19A—H19A | 124.5 | O18B—C19B—H19B | 124.4 |
N9A—C10A—C11A | 111.50 (9) | N9B—C10B—C11B | 111.70 (9) |
N9A—C10A—H10A | 109.3 | N9B—C10B—H10D | 109.3 |
C11A—C10A—H10A | 109.3 | C11B—C10B—H10D | 109.3 |
N9A—C10A—H10B | 109.3 | N9B—C10B—H10E | 109.3 |
C11A—C10A—H10B | 109.3 | C11B—C10B—H10E | 109.3 |
H10A—C10A—H10B | 108 | H10D—C10B—H10E | 107.9 |
C12A—C11A—C16A | 118.48 (11) | C16B—C11B—C12B | 119.10 (10) |
C12A—C11A—C10A | 121.17 (11) | C12B—C11B—C10B | 120.90 (10) |
C16A—C11A—C10A | 120.31 (11) | C16B—C11B—C10B | 119.96 (10) |
C13A—C12A—C11A | 120.88 (11) | C13B—C12B—C11B | 120.84 (10) |
C13A—C12A—H12A | 119.6 | C13B—C12B—H12B | 119.6 |
C11A—C12A—H12A | 119.6 | C11B—C12B—H12B | 119.6 |
C12A—C13A—C14A | 119.99 (11) | C12B—C13B—C14B | 119.71 (10) |
C12A—C13A—H13A | 120 | C12B—C13B—H13B | 120.1 |
C14A—C13A—H13A | 120 | C14B—C13B—H13B | 120.1 |
O22A—C14A—C15A | 124.63 (11) | O22B—C14B—C15B | 124.41 (10) |
O22A—C14A—C13A | 115.44 (11) | O22B—C14B—C13B | 115.29 (10) |
C15A—C14A—C13A | 119.92 (11) | C13B—C14B—C15B | 120.30 (10) |
C16A—C15A—C14A | 119.45 (11) | C14B—C15B—C16B | 119.03 (11) |
C16A—C15A—H15A | 120.3 | C14B—C15B—H15B | 120.5 |
C14A—C15A—H15A | 120.3 | C16B—C15B—H15B | 120.5 |
C15A—C16A—C11A | 121.28 (11) | C11B—C16B—C15B | 121.00 (10) |
C15A—C16A—H16A | 119.4 | C11B—C16B—H16B | 119.5 |
C11A—C16A—H16A | 119.4 | C15B—C16B—H16B | 119.5 |
O22A—C23A—H23B | 109.5 | O22B—C23B—H23D | 109.5 |
O22A—C23A—H23C | 109.5 | O22B—C23B—H23E | 109.5 |
H23B—C23A—H23C | 109.5 | H23D—C23B—H23E | 109.5 |
O22A—C23A—H23A | 109.5 | O22B—C23B—H23F | 109.5 |
H23B—C23A—H23A | 109.5 | H23D—C23B—H23F | 109.5 |
H23C—C23A—H23A | 109.5 | H23E—C23B—H23F | 109.5 |
C2A—N3A—C4A | 110.22 (9) | C2B—N3B—C4B | 110.17 (9) |
C4A—N9A—C8A | 105.73 (9) | C8B—N9B—C4B | 105.44 (9) |
C4A—N9A—C10A | 126.89 (10) | C8B—N9B—C10B | 127.04 (10) |
C8A—N9A—C10A | 127.32 (9) | C4B—N9B—C10B | 127.20 (10) |
C8A—N7A—C5A | 103.27 (9) | C8B—N7B—C5B | 103.21 (10) |
C2A—N1A—C6A | 117.03 (9) | C2B—N1B—C6B | 116.98 (9) |
C19A—O18A—C17A | 105.99 (9) | C19B—O18B—C17B | 106.02 (9) |
C14A—O22A—C23A | 118.12 (10) | C14B—O22B—C23B | 116.93 (9) |
| | | |
N3A—C4A—C5A—N7A | −179.53 (10) | N3B—C4B—C5B—N7B | −179.42 (10) |
N9A—C4A—C5A—N7A | 0.50 (12) | N9B—C4B—C5B—N7B | 0.26 (12) |
N3A—C4A—C5A—C6A | 0.11 (16) | N3B—C4B—C5B—C6B | 0.63 (16) |
N9A—C4A—C5A—C6A | −179.87 (9) | N9B—C4B—C5B—C6B | −179.70 (9) |
N7A—C5A—C6A—N1A | 179.57 (11) | N7B—C5B—C6B—N1B | 179.91 (11) |
C4A—C5A—C6A—N1A | 0.04 (15) | C4B—C5B—C6B—N1B | −0.15 (14) |
N7A—C5A—C6A—C17A | 0.69 (19) | N7B—C5B—C6B—C17B | −0.02 (18) |
C4A—C5A—C6A—C17A | −178.84 (10) | C4B—C5B—C6B—C17B | 179.92 (10) |
N1A—C6A—C17A—C21A | 179.86 (12) | N1B—C6B—C17B—C21B | 176.61 (11) |
C5A—C6A—C17A—C21A | −1.25 (19) | C5B—C6B—C17B—C21B | −3.46 (18) |
N1A—C6A—C17A—O18A | −1.00 (15) | N1B—C6B—C17B—O18B | −2.39 (14) |
C5A—C6A—C17A—O18A | 177.89 (9) | C5B—C6B—C17B—O18B | 177.54 (9) |
O18A—C17A—C21A—C20A | −0.50 (13) | O18B—C17B—C21B—C20B | 0.24 (13) |
C6A—C17A—C21A—C20A | 178.70 (12) | C6B—C17B—C21B—C20B | −178.83 (11) |
C17A—C21A—C20A—C19A | 0.28 (14) | C17B—C21B—C20B—C19B | −0.20 (14) |
C21A—C20A—C19A—O18A | 0.03 (14) | C21B—C20B—C19B—O18B | 0.10 (14) |
N9A—C10A—C11A—C12A | −94.59 (14) | N9B—C10B—C11B—C12B | 91.21 (13) |
N9A—C10A—C11A—C16A | 83.09 (13) | N9B—C10B—C11B—C16B | −86.23 (13) |
C16A—C11A—C12A—C13A | −0.14 (18) | C16B—C11B—C12B—C13B | 0.68 (17) |
C10A—C11A—C12A—C13A | 177.58 (12) | C10B—C11B—C12B—C13B | −176.78 (10) |
C11A—C12A—C13A—C14A | −0.2 (2) | C11B—C12B—C13B—C14B | 0.69 (18) |
C12A—C13A—C14A—O22A | −179.00 (12) | C12B—C13B—C14B—O22B | 178.80 (11) |
C12A—C13A—C14A—C15A | 0.21 (19) | C12B—C13B—C14B—C15B | −1.52 (17) |
O22A—C14A—C15A—C16A | 179.18 (11) | O22B—C14B—C15B—C16B | −179.37 (11) |
C13A—C14A—C15A—C16A | 0.05 (17) | C13B—C14B—C15B—C16B | 0.97 (17) |
C12A—C11A—C16A—C15A | 0.41 (17) | C12B—C11B—C16B—C15B | −1.23 (17) |
C10A—C11A—C16A—C15A | −177.33 (10) | C10B—C11B—C16B—C15B | 176.25 (10) |
C14A—C15A—C16A—C11A | −0.37 (17) | C14B—C15B—C16B—C11B | 0.41 (17) |
N1A—C2A—N3A—C4A | −0.59 (17) | N1B—C2B—N3B—C4B | 0.37 (17) |
Cl2A—C2A—N3A—C4A | 179.34 (8) | Cl2B—C2B—N3B—C4B | −179.11 (8) |
N9A—C4A—N3A—C2A | −179.91 (11) | N9B—C4B—N3B—C2B | 179.70 (10) |
C5A—C4A—N3A—C2A | 0.12 (15) | C5B—C4B—N3B—C2B | −0.69 (15) |
N7A—C8A—N9A—C4A | 0.70 (13) | N7B—C8B—N9B—C4B | −0.32 (14) |
N7A—C8A—N9A—C10A | 178.04 (11) | N7B—C8B—N9B—C10B | −174.12 (11) |
N3A—C4A—N9A—C8A | 179.34 (11) | N3B—C4B—N9B—C8B | 179.70 (11) |
C5A—C4A—N9A—C8A | −0.69 (12) | C5B—C4B—N9B—C8B | 0.02 (12) |
N3A—C4A—N9A—C10A | 1.99 (18) | N3B—C4B—N9B—C10B | −6.51 (18) |
C5A—C4A—N9A—C10A | −178.03 (10) | C5B—C4B—N9B—C10B | 173.81 (10) |
C11A—C10A—N9A—C4A | 78.72 (15) | C11B—C10B—N9B—C4B | −70.99 (15) |
C11A—C10A—N9A—C8A | −98.07 (13) | C11B—C10B—N9B—C8B | 101.50 (13) |
N9A—C8A—N7A—C5A | −0.38 (13) | N9B—C8B—N7B—C5B | 0.46 (14) |
C6A—C5A—N7A—C8A | −179.63 (12) | C6B—C5B—N7B—C8B | 179.51 (12) |
C4A—C5A—N7A—C8A | −0.08 (12) | C4B—C5B—N7B—C8B | −0.43 (13) |
N3A—C2A—N1A—C6A | 0.77 (18) | N3B—C2B—N1B—C6B | 0.02 (18) |
Cl2A—C2A—N1A—C6A | −179.16 (8) | Cl2B—C2B—N1B—C6B | 179.50 (7) |
C5A—C6A—N1A—C2A | −0.41 (15) | C5B—C6B—N1B—C2B | −0.13 (14) |
C17A—C6A—N1A—C2A | 178.52 (10) | C17B—C6B—N1B—C2B | 179.80 (9) |
C20A—C19A—O18A—C17A | −0.33 (13) | C20B—C19B—O18B—C17B | 0.04 (13) |
C21A—C17A—O18A—C19A | 0.51 (12) | C21B—C17B—O18B—C19B | −0.17 (12) |
C6A—C17A—O18A—C19A | −178.81 (10) | C6B—C17B—O18B—C19B | 179.03 (9) |
C15A—C14A—O22A—C23A | 11.24 (17) | C15B—C14B—O22B—C23B | −2.45 (17) |
C13A—C14A—O22A—C23A | −169.59 (11) | C13B—C14B—O22B—C23B | 177.22 (11) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C8A—H8A···O18Ai | 0.95 | 2.46 | 3.4037 (13) | 176 |
C8B—H8B···O18Bii | 0.95 | 2.44 | 3.3924 (14) | 179 |
C19A—H19A···Cg1B | 0.95 | 2.78 | 3.5261 (14) | 136 |
C19B—H19B···Cg1A | 0.95 | 2.85 | 3.6163 (13) | 139 |
Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z. |
Experimental details
Crystal data |
Chemical formula | C17H13ClN4O2 |
Mr | 340.76 |
Crystal system, space group | Orthorhombic, Pca21 |
Temperature (K) | 105 |
a, b, c (Å) | 8.6963 (4), 24.5966 (11), 14.3247 (7) |
V (Å3) | 3064.0 (2) |
Z | 8 |
Radiation type | Mo Kα |
µ (mm−1) | 0.27 |
Crystal size (mm) | 0.4 × 0.3 × 0.02 |
|
Data collection |
Diffractometer | Siemens SMART CCD area-detector diffractometer |
Absorption correction | Empirical (using intensity measurements) (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.83, 0.995 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 49273, 17784, 12073 |
Rint | 0.039 |
(sin θ/λ)max (Å−1) | 0.908 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.039, 0.088, 0.89 |
No. of reflections | 17784 |
No. of parameters | 435 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.46, −0.30 |
Absolute structure | Flack (1983), with 8178 Friedel pairs |
Absolute structure parameter | −0.01 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
C8A—H8A···O18Ai | 0.95 | 2.46 | 3.4037 (13) | 176 |
C8B—H8B···O18Bii | 0.95 | 2.44 | 3.3924 (14) | 179 |
C19A—H19A···Cg1B | 0.95 | 2.78 | 3.5261 (14) | 136 |
C19B—H19B···Cg1A | 0.95 | 2.85 | 3.6163 (13) | 139 |
Symmetry codes: (i) x+1, y, z; (ii) x−1, y, z. |
Table 1. A comparison of selected geometric parameters (Å, °) of
molecules A and B in (I) and compound (II). top | Molecule A in (I)a | Molecule B in (I)a | Compound (II)b |
C6—C17 | 1.4479 (15) | 1.4497 (15) | 1.449 (2) |
C10—N9 | 1.4755 (15) | 1.4740 (15) | 1.469 (2) |
C10—C11 | 1.5128 (16) | 1.5127 (16) | 1.504 (2) |
C14—O22—C23 | 118.12 (10) | 116.93 (9) | c |
C15—C14—O22—C23 | 11.24 (17) | -2.45 (17) | c |
C4—N9—C10—C11 | 78.72 (15) | -70.99 (15) | 88.3 (2) |
N9—C10—C11—C12 | -94.59 (14) | 91.21 (13) | -91.0 (2) |
Notes: (a) this work; (b) Mazumdar et al. (2001);
(c) Compound (II) does not contain the methoxy group. |
Tuberculosis (TB) claims ca 2 million lives every year, and infection with multidrug-resistant strains is an increasing problem, but nevertheless, no new drugs have been launched to treat TB for approximately 40 years (Dye, 2006; Tripathi et al., 2005). We have previously reported that certain 6,9-disubstituted purines are potent inhibitors of Mycobacterium tuberculosis (Mtb) in vitro. Our antimycobacterial purines display several properties which make them highly interesting as potential drugs against tuberculosis. These properties include high selectivity towards Mtb compared with other micro-organisms, activity against several drug-resistant strains of Mtb, generally low toxicity towards mammalian cells, and an ability to affect Mtb inside macrophages (Bakkestuen et al., 2000, 2005; Gundersen et al., 2002; Braendvang & Gundersen 2005). Our most active 6,9-disubstituted purine identified to date is 2-chloro-6-(2-furanyl)-9-[(4-methoxyphenyl)methyl]-9H-purine, which displays an MIC against Mtb of 0.39 µg ml-1 (Bakkestuen et al., 2005) (MIC is defined as the minimum concentration of compound required to give 90% inhibition of bacterial growth. MIC for the currently used drug, rifampicin, is 0.25 µg ml-1). The present work reports the X-ray crystallographic study of the potent antimycobacterial title compound, (I).
Compound (I) crystallizes as two crystallographically independent molecules, A and B, and their molecular geometries are illustrated in Fig. 1. Selected bond lengths and angles are listed in Table 1. The conformations of molecules A and B are slightly different, as revealed by a molecular fit using the quaternion transformation method (Mackay, 1984). The overlay of all atoms in molecule A with those of molecule B, except the H atoms, gives r.m.s. bond and angle fits of 0.0034 Å and 0.32°, respectively. The differences are mainly in the orientations of the methoxy and benzyl groups (Table 1). The purine ring system (C1–N9) is almost perfectly planar; the displacements of the atoms from their mean planes do not exceed 0.007 (1) Å in molecule A and 0.006 (1) Å in molecule B.
The conformations of molecules A and B in (I) very much resemble that in the previously reported crystal structure of the related antimycobacterial 9-benzyl-6-(2-thienyl)-9H-purine, (II) (Mazumdar et al., 2001). The bond lengths from the purine ring atoms to the substituents are compared in Table 1. The 6-aryl group in the title compound is nearly coplanar with the purine ring. The angles between the mean plane of the purine ring system and that of the furyl group are 2.31 (6)° in molecule A and 2.79 (5)° in molecule B, compared with 6.39 (4)° in compound (II). This coplanarity has also been reported for other 6-hetroarylpurines (Mazumdar et al., 2001; Zhong et al., 2006). The positions of the benzyl groups are slightly different in compounds (I) and (II), as seen from the torsion angles C4—N9—C10—C11 and N9—C10—C11—C12 (Table 1). The benzene ring plane is inclined at an angle of 73.64 (5)° to the purine ring plane in molecule A and at 77.80 (4)° in molecule B. In compound (II), the angle between the corresponding planes is 64.03 (5)°.
Fig. 2 shows the crystal packing of molecules A and B in the unit cell. The molecular packing appears to be stabilized by segregation of alternate hydrophobic and hydrophilic zones. In the hydrophobic region, the conformation adopted by the benzene rings allows for C—H···π interactions, viz. C19A—H19A···Cg1B and C19B—H19B···Cg1A within the asymmetric unit (Fig. 3 and Table 2) (Cg1B and Cg1A are the centroids of the C11–C16 benzene rings in molecules B and A, respectively).
In the hydrophilic region, the conformation allows for π–π interactions between the heterocycles in the asymmetric unit and these occur between the furyl and pyrimidine rings (Fig. 3). The average interplanar distance between furyl ring C17A/O18A/C19A–C21A (molecule A) and pyrimidine ring N1B/C2B/N3B/C4B–C6B (molecule B) is 3.379 Å and the centroids of the two rings are slipped by 17.2° relative to their ring normals. The corresponding interaction between furyl ring C17B/C18B/C19B–C21B and pyrimidine ring N1A/C2A/N3A/C4A–C6A results in a distance of 3.332 Å with the two ring centroids slipped by 18.6° relative to their ring normals. The Cg2A···Cg3B and Cg2B···Cg3A distances are 3.5357 (7) and 3.5160 (7) Å, respectively (Cg2 and Cg3 are the centroids of the furyl rings and pyrimidine rings, respectively), while the mean angle between the purine ring planes is 2.04 (3)°.
The crystal packing (Fig. 2) gives further π–π interactions along the c axis between the imidazole ring (C4A/C5A/N7A/C8A/N9A) in molecule A and the pyrimidine ring (N1B/C2B/N3B/C4B–C6B) in molecule Biii [symmetry code: (iii) 3/2 - x, y, -1/2 + z]. Moving down the c axis, the ring centroid-to-centroid distance Cg4A···Cg3Biii is 3.4516 (6) Å (Cg4A is the centroid of the imidazole ring C4A/C5A/N7A/C8A/N9A). In this interaction, the average interplanar distance is 3.28 Å and the centroids of the two rings are slipped by 18.1° relative to their ring normals, while the mean angle between the purine ring planes is 0.58 (3)°.
Finally, moving along the a axis, the two molecules A and B separately build up their own infinite chains via C8A—H8A···O18Ai and C8B—H8B···O18Bii hydrogen bonds [Table 2 and Fig. 3; symmetry codes: (i) x + 1, y, z; (ii) x - 1, y, z]. These values are in agreement with C—H···O hydrogen bonding reported for the C-8 H atom in other purine ring systems (Trávníček & Popa, 2007).