9-(2-Phenyl­ethyl)-6-(2-thienyl)-9H-purine

In the title compound [alternative name: 9-benzyl-6-(2-thienyl)-9H-purine], C₁₆H₁₂N₄S, the purine system is not strictly planar and the dihedral angle between the fused rings is 1.46°. The packing of the mol­ecules is influenced by hydro­phobic and hydro­philic interactions.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.047
• wR factor = 0.130
• Data-to-parameter ratio = 14.4

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           28.00
         From the CIF: _reflns_number_total               3364
         From the CIF: _diffrn_reflns_limit_ max hkl   14.   12.   22.
         From the CIF: _diffrn_reflns_limit_ min hkl  -14.  -11.    0.
         TEST1: Expected hkl limits for theta max
         Calculated maximum hkl   13.   11.   20.
         Calculated minimum hkl  -13.  -11.  -20.
          ALERT: Expected hkl max differ from CIF values

---

S1. Comment

Tuberculosis (TB) is the major cause of death, from a single infectious agent, among adults in developing countries and there has been an unfortunate revival of TB in the industrialized world. There are ca 8 million new cases of TB each year and it has been estimated that ca 30 million people will die from tuberculosis within about 10 years (Duncan, 1997). Thus, there is an urgent need for new antimycobacterial agents and various 9-benzylpurines, including the title compound, (I), have shown high inhibitory activity against Mycobacterium tuberculosis (Bakkestuen et al., 2000). Hence, we undertook the present study to examine the effect of the thiophene substituent at the 6-position.

The molecular geometry is illustrated in Fig. 1 and the bond lengths and angles are listed in Table 1. The values are in agreement with those found in other structures containing the purine ring system (Stewart & Jensen, 1964; Lai & Marsh, 1972; Wilson et al., 1986; Low et al., 1987; Flensburg, 1994).

The benzene ring is inclined at an angle of 64.03 (5)° to the purine ring system and at an angle of 60.23 (6)° to the thiophene ring at the 6-position. The thiophene ring is nearly coplanar with the purine ring, the dihedral angle being only 6.39 (4)°. The base is not exactly planar; the two rings are rotated by 1.46 (6)° about the C4—C5 bond.

The bond distance N9—C10 [1.469 (2) Å] is longer than that found in the case of adenin-9-ylacetate [1.451 (1) Å] and the C8—N9—C10—C11 torsion angle of -94.6 (2)° also differs from the value of 104.65 (13)° reported by Flensburg (1994). The bond distances and angles in the thiophene ring are, by and large, normal. The bond angles C5—C6—C17 [123.89 (15)°] and N1—C6—C17 [118.13 (14)°] are comparable to corresponding angles of 124.21 (10)° and 118.29 (10)° in the case of NH₂ substitution at the 6-position, indicating that the thiophene ring has no great effect on the bond angles.

The N1—C6 bond distance of 1.352 (2) Å is slightly greater than a C═N distance of 1.282 (2) Å in 2-[(4-hydroxyphenyl)iminomethyl]thiophene (Kazak et al., 2000) due to the aromaticity of the purine ring system. However, the C6—C17 bond distance of 1.449 (2) Å is not affected.

As is evident from Fig. 2, a hydrophobic region is created due to interactions between the benzene rings. The molecular packing is stabilize d by segregation of alternate hydrophobic and hydrophilic zones.

S2. Experimental

The title compound was synthesized as described by Gundersen et al. (1994). Crystals suitable for X-ray diffraction studies were obtained by slow evaporation at room temperature from a mixture of ethanol, acetone and chloroform (1:1:1).

S3. Refinement

All H atoms, except for H21, were located from a difference Fourier synthesis and refined isotropically. H21, attached to C21, was positioned geometrically and not refined. Bond distances to H atoms range from 0.90 to 1.00 Å.

Computing details

Data collection: COLLECT (Nonius, 1997); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 1999); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. Plot showing the atomic numbering scheme for (I). Displacement ellipsoids of non-H atoms are drawn at the 50% probability level.
	Fig. 2. A view of the packing of the molecules in the unit cell.

6-(2-Thienyl)-9-(2-phenylethyl)-9H-purine

Crystal data

C16H12N4S	F(000) = 608
Mr = 292.36	Dx = 1.388 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71070 Å
a = 10.1130 (4) Å	Cell parameters from 7690 reflections
b = 8.9101 (2) Å	θ = 3.2–28°
c = 15.6434 (7) Å	µ = 0.23 mm^−1
β = 96.8550 (17)°	T = 293 K
V = 1399.52 (9) Å^3	Trigonal prism, pale yellow
Z = 4	0.48 × 0.43 × 0.12 mm

Data collection

Nonius KappaCCD area-detector diffractometer	2745 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.024
Graphite monochromator	θmax = 28.0°, θmin = 3.2°
ϕ and ω scans	h = −14→14
7690 measured reflections	k = −11→12
3364 independent reflections	l = 0→22

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.047	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.130	w = 1/[σ^2(Fo^2) + (0.055P)^2 + 0.536P] where P = (Fo^2 + 2Fc^2)/3
S = 1.09	(Δ/σ)max = 0.001
3364 reflections	Δρmax = 0.26 e Å^−3
234 parameters	Δρmin = −0.45 e Å^−3
0 restraints

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 (Ų)

	x	y	z	Uiso*/Ueq
N1	0.01986 (15)	0.27529 (16)	0.09057 (9)	0.0391 (3)
C2	0.11782 (18)	0.3725 (2)	0.08096 (11)	0.0420 (4)
N3	0.16244 (14)	0.41884 (16)	0.00861 (9)	0.0396 (3)
C4	0.09648 (15)	0.35270 (18)	−0.06002 (10)	0.0340 (3)
C5	−0.00681 (15)	0.24882 (18)	−0.06038 (10)	0.0333 (3)
C6	−0.04605 (16)	0.21114 (17)	0.01955 (10)	0.0336 (3)
N7	−0.05253 (14)	0.20673 (18)	−0.14425 (9)	0.0433 (4)
C8	0.02187 (18)	0.2851 (2)	−0.19068 (11)	0.0450 (4)
N9	0.11296 (13)	0.37573 (17)	−0.14485 (9)	0.0385 (3)
C10	0.20579 (19)	0.4814 (2)	−0.17829 (14)	0.0466 (4)
C11	0.34095 (16)	0.41421 (18)	−0.18361 (11)	0.0374 (4)
C12	0.4409 (2)	0.4256 (3)	−0.11572 (14)	0.0551 (5)
C13	0.5655 (2)	0.3646 (3)	−0.12139 (18)	0.0679 (6)
C14	0.5904 (2)	0.2905 (3)	−0.19447 (18)	0.0666 (6)
C15	0.4923 (3)	0.2775 (3)	−0.26193 (16)	0.0659 (6)
C16	0.3678 (2)	0.3392 (2)	−0.25677 (13)	0.0497 (4)
C17	−0.15485 (16)	0.10996 (18)	0.03064 (11)	0.0367 (4)
S18	−0.20660 (6)	0.08415 (6)	0.13018 (3)	0.05740 (19)
C19	−0.3269 (2)	−0.0386 (2)	0.08988 (16)	0.0593 (5)
C20	−0.3277 (2)	−0.0602 (2)	0.00512 (16)	0.0586 (5)
C21	−0.23094 (18)	0.0247 (2)	−0.03142 (12)	0.0445 (4)
H21	−0.2195	0.0237	−0.0895	0.050*
H2	0.159 (2)	0.415 (2)	0.1349 (14)	0.053 (6)*
H8	0.018 (2)	0.283 (2)	−0.2517 (15)	0.053 (6)*
H10A	0.165 (2)	0.511 (3)	−0.2339 (16)	0.063 (6)*
H10B	0.214 (2)	0.568 (3)	−0.1370 (14)	0.055 (6)*
H12	0.420 (2)	0.483 (3)	−0.0655 (17)	0.076 (8)*
H13	0.633 (3)	0.377 (3)	−0.0774 (19)	0.096 (9)*
H14	0.679 (3)	0.249 (3)	−0.1960 (18)	0.088 (8)*
H15	0.510 (3)	0.225 (3)	−0.3129 (19)	0.087 (9)*
H16	0.297 (2)	0.326 (3)	−0.3025 (16)	0.063 (6)*
H19	−0.384 (3)	−0.082 (3)	0.1281 (18)	0.085 (8)*
H20	−0.386 (2)	−0.123 (3)	−0.0251 (16)	0.071 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N1	0.0448 (8)	0.0444 (8)	0.0282 (7)	0.0016 (6)	0.0051 (6)	0.0000 (6)
C2	0.0451 (9)	0.0482 (9)	0.0320 (8)	−0.0008 (7)	0.0019 (7)	−0.0030 (7)
N3	0.0393 (8)	0.0433 (8)	0.0362 (7)	−0.0004 (6)	0.0042 (6)	−0.0009 (6)
C4	0.0323 (8)	0.0390 (8)	0.0311 (8)	0.0077 (6)	0.0055 (6)	0.0030 (6)
C5	0.0300 (7)	0.0413 (8)	0.0286 (8)	0.0054 (6)	0.0033 (6)	0.0001 (6)
C6	0.0340 (8)	0.0370 (8)	0.0301 (8)	0.0069 (6)	0.0050 (6)	0.0011 (6)
N7	0.0381 (8)	0.0630 (10)	0.0287 (7)	0.0002 (7)	0.0033 (6)	−0.0032 (6)
C8	0.0401 (9)	0.0685 (12)	0.0264 (8)	0.0056 (8)	0.0044 (7)	0.0014 (8)
N9	0.0344 (7)	0.0518 (8)	0.0305 (7)	0.0060 (6)	0.0082 (5)	0.0074 (6)
C10	0.0476 (10)	0.0481 (10)	0.0470 (10)	0.0085 (8)	0.0172 (8)	0.0146 (9)
C11	0.0374 (8)	0.0384 (8)	0.0381 (9)	−0.0018 (6)	0.0116 (7)	0.0069 (7)
C12	0.0513 (11)	0.0642 (12)	0.0494 (11)	−0.0023 (9)	0.0043 (9)	−0.0105 (10)
C13	0.0420 (11)	0.0836 (16)	0.0751 (16)	−0.0032 (11)	−0.0055 (11)	0.0019 (13)
C14	0.0442 (12)	0.0749 (15)	0.0845 (17)	0.0106 (10)	0.0234 (11)	0.0164 (13)
C15	0.0719 (15)	0.0709 (14)	0.0603 (14)	0.0184 (11)	0.0294 (12)	−0.0001 (11)
C16	0.0516 (11)	0.0588 (11)	0.0393 (10)	0.0043 (9)	0.0081 (8)	−0.0001 (8)
C17	0.0375 (8)	0.0387 (8)	0.0348 (8)	0.0063 (6)	0.0082 (6)	0.0039 (7)
S18	0.0642 (4)	0.0670 (4)	0.0442 (3)	−0.0131 (2)	0.0195 (2)	0.0027 (2)
C19	0.0536 (12)	0.0560 (12)	0.0716 (15)	−0.0071 (9)	0.0206 (11)	0.0122 (11)
C20	0.0494 (11)	0.0527 (11)	0.0725 (15)	−0.0097 (9)	0.0024 (10)	0.0007 (10)
C21	0.0422 (9)	0.0461 (9)	0.0458 (10)	−0.0021 (7)	0.0074 (8)	−0.0001 (8)

Geometric parameters (Å, º)

N1—C2	1.338 (2)	C11—C16	1.380 (3)
N1—C6	1.352 (2)	C12—C13	1.385 (3)
C2—N3	1.333 (2)	C12—H12	0.98 (3)
C2—H2	0.97 (2)	C13—C14	1.369 (4)
N3—C4	1.332 (2)	C13—H13	0.92 (3)
C4—N9	1.372 (2)	C14—C15	1.364 (4)
C4—C5	1.395 (2)	C14—H14	0.97 (3)
C5—N7	1.390 (2)	C15—C16	1.385 (3)
C5—C6	1.397 (2)	C15—H15	0.96 (3)
C6—C17	1.449 (2)	C16—H16	0.95 (2)
N7—C8	1.308 (2)	C17—C21	1.391 (3)
C8—N9	1.363 (2)	C17—S18	1.7164 (17)
C8—H8	0.95 (2)	S18—C19	1.700 (2)
N9—C10	1.469 (2)	C19—C20	1.339 (3)
C10—C11	1.504 (2)	C19—H19	0.96 (3)
C10—H10A	0.95 (2)	C20—C21	1.411 (3)
C10—H10B	1.01 (2)	C20—H20	0.91 (3)
C11—C12	1.380 (3)	C21—H21	0.9300
C2—N1—C6	118.71 (14)	C16—C11—C10	120.58 (17)
N3—C2—N1	128.76 (16)	C11—C12—C13	120.7 (2)
N3—C2—H2	117.6 (12)	C11—C12—H12	116.5 (14)
N1—C2—H2	113.6 (12)	C13—C12—H12	122.7 (14)
C4—N3—C2	111.09 (15)	C14—C13—C12	120.1 (2)
N3—C4—N9	127.33 (15)	C14—C13—H13	119.2 (19)
N3—C4—C5	126.83 (15)	C12—C13—H13	120.6 (19)
N9—C4—C5	105.82 (14)	C15—C14—C13	119.9 (2)
N7—C5—C4	110.33 (14)	C15—C14—H14	122.3 (17)
N7—C5—C6	133.00 (15)	C13—C14—H14	117.9 (17)
C4—C5—C6	116.64 (14)	C14—C15—C16	120.2 (2)
N1—C6—C5	117.96 (15)	C14—C15—H15	119.8 (17)
N1—C6—C17	118.13 (14)	C16—C15—H15	120.0 (17)
C5—C6—C17	123.89 (15)	C11—C16—C15	120.7 (2)
C8—N7—C5	103.39 (15)	C11—C16—H16	118.7 (14)
N7—C8—N9	114.93 (15)	C15—C16—H16	120.5 (14)
N7—C8—H8	126.1 (13)	C21—C17—C6	128.41 (15)
N9—C8—H8	119.0 (13)	C21—C17—S18	110.91 (13)
C8—N9—C4	105.52 (14)	C6—C17—S18	120.67 (13)
C8—N9—C10	127.80 (15)	C19—S18—C17	91.83 (10)
C4—N9—C10	126.63 (15)	C20—C19—S18	112.27 (16)
N9—C10—C11	112.85 (14)	C20—C19—H19	128.7 (17)
N9—C10—H10A	105.8 (14)	S18—C19—H19	119.0 (17)
C11—C10—H10A	111.0 (14)	C19—C20—C21	113.7 (2)
N9—C10—H10B	105.9 (12)	C19—C20—H20	122.1 (16)
C11—C10—H10B	109.6 (12)	C21—C20—H20	124.2 (16)
H10A—C10—H10B	111.7 (19)	C17—C21—C20	111.28 (18)
C12—C11—C16	118.39 (17)	C17—C21—H21	124.4
C12—C11—C10	121.03 (17)	C20—C21—H21	124.4
C6—N1—C2—N3	0.3 (3)	C8—N9—C10—C11	−94.6 (2)
N1—C2—N3—C4	−0.9 (3)	C4—N9—C10—C11	88.3 (2)
C2—N3—C4—N9	178.20 (15)	N9—C10—C11—C12	−91.0 (2)
C2—N3—C4—C5	0.4 (2)	N9—C10—C11—C16	88.9 (2)
N3—C4—C5—N7	178.93 (15)	C16—C11—C12—C13	0.7 (3)
N9—C4—C5—N7	0.73 (18)	C10—C11—C12—C13	−179.4 (2)
N3—C4—C5—C6	0.6 (2)	C11—C12—C13—C14	−0.8 (4)
N9—C4—C5—C6	−177.59 (13)	C12—C13—C14—C15	0.3 (4)
C2—N1—C6—C5	0.8 (2)	C13—C14—C15—C16	0.1 (4)
C2—N1—C6—C17	−177.95 (15)	C12—C11—C16—C15	−0.3 (3)
N7—C5—C6—N1	−179.02 (16)	C10—C11—C16—C15	179.84 (19)
C4—C5—C6—N1	−1.2 (2)	C14—C15—C16—C11	−0.1 (4)
N7—C5—C6—C17	−0.4 (3)	N1—C6—C17—C21	−175.69 (16)
C4—C5—C6—C17	177.47 (14)	C5—C6—C17—C21	5.7 (3)
C4—C5—N7—C8	−0.40 (19)	N1—C6—C17—S18	5.0 (2)
C6—C5—N7—C8	177.54 (17)	C5—C6—C17—S18	−173.64 (12)
C5—N7—C8—N9	−0.1 (2)	C21—C17—S18—C19	0.25 (15)
N7—C8—N9—C4	0.5 (2)	C6—C17—S18—C19	179.66 (14)
N7—C8—N9—C10	−177.00 (16)	C17—S18—C19—C20	0.36 (18)
N3—C4—N9—C8	−178.92 (16)	S18—C19—C20—C21	−0.9 (3)
C5—C4—N9—C8	−0.73 (17)	C6—C17—C21—C20	179.88 (17)
N3—C4—N9—C10	−1.3 (3)	S18—C17—C21—C20	−0.8 (2)
C5—C4—N9—C10	176.85 (15)	C19—C20—C21—C17	1.1 (3)