2,6-Di-chloro-9-(2',3',5'-tri-O-acetyl-β-d-ribo-furanos-yl)-9H-purine.

The title synthetic analog of purine nucleosides, C16H16Cl2N4O7, has its acetyl-ated β-furan-ose ring in a 3'β-envelope conformation, with the corresponding C atom deviating by 0.602 (5) Å from the rest of the ring. The planar part of the furan-ose ring forms a dihedral angle of 65.0 (1)° with the mean plane of the purine bicycle. In the crystal, mol-ecules form a three-dimensional network through multiple C-H⋯O and C-H⋯N hydrogen bonds and C-H⋯π interactions.

Related literature

For applications of 9-(2′,3′,5′-tri-O-acetyl-β-d-ribo­furanos­yl)-2,6-di­chloro-9H-purine in synthesis, see: Caner & Vilarrasa (2010 ▶); Korboukh et al. (2012 ▶). For the synthesis, see: Vorbrüggen (1995 ▶); Robins & Uznański (1981 ▶); Nair & Richardson (1982 ▶); Francom et al. (2002 ▶); Francom & Robins (2003 ▶); Gerster & Robins (1966 ▶). The conditions were improved by using our previous studies (Kovalovs et al., 2013 ▶; Novosjolova et al., 2013 ▶). For the biological activity of purine nucleosides, their anti­cancer and anti­viral activity and use as agonists and antagonists of adenosine receptors, see: Lech-Maranda et al. (2006 ▶); Robak et al. (2009 ▶); Gumina et al. (2003 ▶); Fredholm et al. (2011 ▶); Elzein & Zablocki (2008 ▶). For the structure of another 2,6-di­chloro­purine ribonucleoside, 9-(2′-de­oxy-3′,5′-di-O-4-meth­oxy­benzoyl-β-d-ribo­furanos­yl)-2,6-di­chloro-9H-purine, see:Yang et al. (2012 ▶). The purine heterocycle is known to form π–π stacking inter­actions in related structures, see: Sternglanz & Bugg (1975 ▶). For standard bond lengths, see: Allen et al. (1987 ▶). The nature of hydrogen bonding is described by Gilli (2002 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶).

Experimental

Crystal data

C16H16Cl2N4O7

M = 447.23

Monoclinic,

a = 10.1324 (2) Å

b = 9.6887 (3) Å

c = 10.5399 (2) Å

β = 106.537 (2)°

V = 991.90 (4) Å3

Z = 2

Mo Kα radiation

μ = 0.37 mm−1

T = 296 K

0.38 × 0.32 × 0.15 mm

Data collection

Nonius KappaCCD diffractometer

3898 measured reflections

3898 independent reflections

2846 reflections with I > 2σ(I)

Refinement

R[F 2 > 2σ(F 2)] = 0.046

wR(F 2) = 0.107

S = 1.02

3898 reflections

265 parameters

H-atom parameters constrained

Δρmax = 0.22 e Å−3

Δρmin = −0.20 e Å−3

Absolute structure: Flack (1983 ▶), 1518 Friedel pairs

Absolute structure parameter: 0.00 (7)

Data collection: KappaCCD Server Software (Nonius, 1997 ▶); cell refinement: SCALEPACK (Otwinovski & Minor, 1997 ▶); data reduction: 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 for Windows (Farrugia, 2012 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97, PLATON (Spek, 2009 ▶) and publCIF (Westrip, 2010 ▶).

Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536813034521/ld2116sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813034521/ld2116Isup2.hkl

CCDC reference:

Additional supporting information: crystallographic information; 3D view; checkCIF report

C16H16Cl2N4O7	F(000) = 460
Mr = 447.23	Dx = 1.497 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 17407 reflections
a = 10.1324 (2) Å	θ = 1.0–27.5°
b = 9.6887 (3) Å	µ = 0.37 mm−1
c = 10.5399 (2) Å	T = 296 K
β = 106.537 (2)°	Prism, colorless
V = 991.90 (4) Å3	0.38 × 0.32 × 0.15 mm
Z = 2

Nonius KappaCCD diffractometer	2846 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.000
Graphite monochromator	θmax = 27.5°, θmin = 2.0°
CCD scans	h = −13→13
3898 measured reflections	k = −11→12
3898 independent reflections	l = −13→13

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.046	H-atom parameters constrained
wR(F2) = 0.107	w = 1/[σ2(Fo2) + (0.0352P)2 + 0.3514P] where P = (Fo2 + 2Fc2)/3
S = 1.02	(Δ/σ)max < 0.001
3898 reflections	Δρmax = 0.22 e Å−3
265 parameters	Δρmin = −0.20 e Å−3
0 restraints	Absolute structure: Flack (1983), 1518 Friedel pairs
0 constraints	Absolute structure parameter: 0.00 (7)
Primary atom site location: structure-invariant direct methods

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
N1	1.0850 (3)	0.1139 (3)	0.4785 (3)	0.0535 (8)
C2	0.9650 (4)	0.1787 (4)	0.4602 (3)	0.0508 (9)
N3	0.9178 (3)	0.2553 (3)	0.5399 (2)	0.0458 (6)
C4	1.0170 (3)	0.2704 (3)	0.6574 (3)	0.0404 (7)
C5	1.1477 (3)	0.2135 (4)	0.6915 (3)	0.0429 (8)
C6	1.1761 (4)	0.1309 (4)	0.5952 (3)	0.0510 (9)
N7	1.2211 (3)	0.2508 (3)	0.8196 (3)	0.0506 (7)
C8	1.1331 (3)	0.3266 (4)	0.8596 (3)	0.0473 (8)
H8	1.1540	0.3671	0.9430	0.057*
N9	1.0071 (2)	0.3404 (3)	0.7669 (2)	0.0405 (6)
Cl10	1.32958 (12)	0.04548 (15)	0.62312 (11)	0.0892 (4)
Cl11	0.85038 (11)	0.15549 (12)	0.30379 (9)	0.0733 (3)
C1'	0.8877 (3)	0.4205 (4)	0.7769 (3)	0.0409 (7)
H1	0.8574	0.4827	0.7008	0.049*
C2'	0.7695 (3)	0.3282 (4)	0.7845 (3)	0.0397 (7)
H2	0.7642	0.2421	0.7344	0.048*
C3'	0.8034 (3)	0.3062 (3)	0.9343 (3)	0.0385 (7)
H3	0.8772	0.2380	0.9639	0.046*
C4'	0.8537 (3)	0.4472 (3)	0.9862 (3)	0.0382 (7)
H4	0.7733	0.5063	0.9786	0.046*
C5'	0.9455 (3)	0.4570 (4)	1.1251 (3)	0.0432 (8)
H5A	0.9788	0.5509	1.1437	0.052*
H5B	0.8946	0.4325	1.1870	0.052*
O6'	0.9264 (2)	0.4982 (2)	0.89486 (18)	0.0402 (5)
O7'	0.6460 (2)	0.4081 (2)	0.74576 (19)	0.0490 (6)
C8'	0.5479 (3)	0.3728 (4)	0.6337 (3)	0.0520 (9)
C9'	0.4297 (4)	0.4704 (5)	0.6096 (4)	0.0696 (12)
H9A	0.4616	0.5627	0.6031	0.104*
H9C	0.3895	0.4651	0.6816	0.104*
H9B	0.3620	0.4462	0.5285	0.104*
O10'	0.5636 (3)	0.2809 (4)	0.5649 (3)	0.0967 (11)
O11'	0.6883 (2)	0.2701 (2)	0.9804 (2)	0.0458 (6)
C12'	0.6474 (4)	0.1370 (4)	0.9636 (3)	0.0504 (9)
C13'	0.5286 (4)	0.1098 (5)	1.0189 (5)	0.0826 (15)
H13A	0.5188	0.0122	1.0288	0.124*
H13B	0.4456	0.1462	0.9597	0.124*
H13C	0.5455	0.1538	1.1037	0.124*
O14'	0.7012 (3)	0.0544 (3)	0.9110 (3)	0.0775 (8)
O15'	1.0599 (2)	0.3644 (2)	1.13994 (18)	0.0441 (5)
C16'	1.1551 (3)	0.3677 (4)	1.2595 (3)	0.0499 (8)
C17'	1.2746 (4)	0.2794 (4)	1.2628 (3)	0.0618 (10)
H17A	1.3570	0.3342	1.2865	0.093*
H17B	1.2630	0.2393	1.1770	0.093*
H17C	1.2816	0.2075	1.3270	0.093*
O18'	1.1385 (3)	0.4370 (4)	1.3478 (2)	0.0909 (10)

	U11	U22	U33	U12	U13	U23
N1	0.063 (2)	0.055 (2)	0.0498 (17)	0.0015 (15)	0.0270 (14)	−0.0050 (14)
C2	0.064 (2)	0.052 (2)	0.0376 (17)	−0.0083 (19)	0.0173 (14)	−0.0028 (16)
N3	0.0551 (17)	0.0437 (17)	0.0444 (15)	0.0010 (13)	0.0239 (12)	0.0023 (13)
C4	0.0511 (19)	0.0378 (19)	0.0362 (16)	−0.0014 (15)	0.0189 (13)	0.0051 (14)
C5	0.0451 (19)	0.046 (2)	0.0406 (16)	0.0016 (15)	0.0166 (13)	0.0040 (15)
C6	0.057 (2)	0.050 (2)	0.0533 (19)	0.0053 (17)	0.0275 (16)	0.0000 (17)
N7	0.0465 (16)	0.0552 (19)	0.0495 (15)	0.0014 (14)	0.0126 (12)	−0.0009 (14)
C8	0.050 (2)	0.048 (2)	0.0437 (17)	−0.0015 (16)	0.0143 (14)	−0.0012 (15)
N9	0.0450 (15)	0.0425 (16)	0.0363 (13)	0.0033 (12)	0.0154 (11)	0.0016 (12)
Cl10	0.0712 (7)	0.1099 (11)	0.0907 (7)	0.0324 (7)	0.0299 (6)	−0.0156 (7)
Cl11	0.0824 (7)	0.0903 (9)	0.0433 (5)	−0.0046 (6)	0.0118 (4)	−0.0139 (5)
C1'	0.0501 (18)	0.0420 (19)	0.0319 (14)	0.0100 (15)	0.0137 (12)	0.0040 (14)
C2'	0.0413 (17)	0.0406 (19)	0.0364 (15)	0.0043 (14)	0.0096 (12)	−0.0049 (14)
C3'	0.0383 (16)	0.0419 (19)	0.0366 (15)	0.0032 (14)	0.0130 (12)	−0.0013 (14)
C4'	0.0405 (16)	0.0397 (19)	0.0357 (14)	0.0054 (14)	0.0129 (12)	−0.0043 (14)
C5'	0.0492 (18)	0.044 (2)	0.0364 (15)	0.0030 (15)	0.0116 (13)	−0.0055 (14)
O6'	0.0493 (12)	0.0367 (13)	0.0371 (11)	−0.0013 (10)	0.0162 (9)	−0.0035 (9)
O7'	0.0426 (12)	0.0597 (17)	0.0380 (11)	0.0133 (11)	0.0005 (9)	−0.0104 (10)
C8'	0.044 (2)	0.060 (3)	0.0451 (18)	−0.0044 (17)	0.0028 (14)	−0.0038 (18)
C9'	0.047 (2)	0.084 (3)	0.065 (2)	0.011 (2)	−0.0044 (16)	−0.006 (2)
O10'	0.079 (2)	0.096 (3)	0.089 (2)	0.0098 (18)	−0.0174 (16)	−0.048 (2)
O11'	0.0382 (12)	0.0531 (16)	0.0492 (12)	−0.0009 (11)	0.0174 (9)	0.0004 (11)
C12'	0.044 (2)	0.054 (2)	0.0484 (18)	−0.0001 (18)	0.0050 (14)	0.0148 (18)
C13'	0.053 (3)	0.109 (4)	0.087 (3)	−0.016 (2)	0.022 (2)	0.027 (3)
O14'	0.0762 (19)	0.0504 (18)	0.112 (2)	−0.0012 (16)	0.0364 (17)	0.0004 (17)
O15'	0.0455 (12)	0.0469 (14)	0.0356 (10)	0.0033 (10)	0.0049 (9)	−0.0040 (10)
C16'	0.051 (2)	0.048 (2)	0.0401 (18)	−0.0036 (17)	−0.0029 (14)	−0.0044 (17)
C17'	0.056 (2)	0.062 (3)	0.057 (2)	0.006 (2)	0.0006 (16)	0.0030 (19)
O18'	0.087 (2)	0.120 (3)	0.0482 (14)	0.026 (2)	−0.0101 (13)	−0.0346 (18)

N1—C6	1.321 (4)	C4'—C5'	1.497 (4)
N1—C2	1.333 (4)	C4'—H4	0.9800
C2—N3	1.308 (4)	C5'—O15'	1.439 (4)
C2—Cl11	1.740 (3)	C5'—H5A	0.9700
N3—C4	1.363 (4)	C5'—H5B	0.9700
C4—N9	1.367 (4)	O7'—C8'	1.354 (4)
C4—C5	1.384 (4)	C8'—O10'	1.187 (4)
C5—C6	1.386 (4)	C8'—C9'	1.489 (5)
C5—N7	1.391 (4)	C9'—H9A	0.9600
C6—Cl10	1.712 (4)	C9'—H9C	0.9600
N7—C8	1.314 (4)	C9'—H9B	0.9600
C8—N9	1.376 (4)	O11'—C12'	1.351 (5)
C8—H8	0.9300	C12'—O14'	1.190 (4)
N9—C1'	1.466 (4)	C12'—C13'	1.502 (5)
C1'—O6'	1.409 (4)	C13'—H13A	0.9600
C1'—C2'	1.515 (5)	C13'—H13B	0.9600
C1'—H1	0.9800	C13'—H13C	0.9600
C2'—O7'	1.429 (4)	O15'—C16'	1.352 (3)
C2'—C3'	1.532 (4)	C16'—O18'	1.198 (4)
C2'—H2	0.9800	C16'—C17'	1.475 (5)
C3'—O11'	1.429 (3)	C17'—H17A	0.9600
C3'—C4'	1.505 (5)	C17'—H17B	0.9600
C3'—H3	0.9800	C17'—H17C	0.9600
C4'—O6'	1.455 (3)
C6—N1—C2	116.3 (3)	C5'—C4'—C3'	117.7 (3)
N3—C2—N1	131.2 (3)	O6'—C4'—H4	108.3
N3—C2—Cl11	114.5 (3)	C5'—C4'—H4	108.3
N1—C2—Cl11	114.3 (2)	C3'—C4'—H4	108.3
C2—N3—C4	109.5 (3)	O15'—C5'—C4'	108.9 (2)
N3—C4—N9	127.5 (3)	O15'—C5'—H5A	109.9
N3—C4—C5	126.6 (3)	C4'—C5'—H5A	109.9
N9—C4—C5	105.9 (3)	O15'—C5'—H5B	109.9
C4—C5—C6	115.0 (3)	C4'—C5'—H5B	109.9
C4—C5—N7	110.9 (3)	H5A—C5'—H5B	108.3
C6—C5—N7	134.1 (3)	C1'—O6'—C4'	109.7 (2)
N1—C6—C5	121.2 (3)	C8'—O7'—C2'	118.5 (3)
N1—C6—Cl10	117.4 (2)	O10'—C8'—O7'	122.0 (3)
C5—C6—Cl10	121.4 (3)	O10'—C8'—C9'	127.8 (3)
C8—N7—C5	103.5 (3)	O7'—C8'—C9'	110.1 (3)
N7—C8—N9	113.8 (3)	C8'—C9'—H9A	109.5
N7—C8—H8	123.1	C8'—C9'—H9C	109.5
N9—C8—H8	123.1	H9A—C9'—H9C	109.5
C4—N9—C8	105.9 (3)	C8'—C9'—H9B	109.5
C4—N9—C1'	125.7 (2)	H9A—C9'—H9B	109.5
C8—N9—C1'	128.2 (3)	H9C—C9'—H9B	109.5
O6'—C1'—N9	108.5 (2)	C12'—O11'—C3'	116.1 (3)
O6'—C1'—C2'	107.2 (2)	O14'—C12'—O11'	122.6 (3)
N9—C1'—C2'	111.8 (3)	O14'—C12'—C13'	126.0 (4)
O6'—C1'—H1	109.8	O11'—C12'—C13'	111.5 (4)
N9—C1'—H1	109.8	C12'—C13'—H13A	109.5
C2'—C1'—H1	109.8	C12'—C13'—H13B	109.5
O7'—C2'—C1'	107.8 (3)	H13A—C13'—H13B	109.5
O7'—C2'—C3'	106.9 (2)	C12'—C13'—H13C	109.5
C1'—C2'—C3'	100.8 (2)	H13A—C13'—H13C	109.5
O7'—C2'—H2	113.5	H13B—C13'—H13C	109.5
C1'—C2'—H2	113.5	C16'—O15'—C5'	115.2 (2)
C3'—C2'—H2	113.5	O18'—C16'—O15'	121.1 (3)
O11'—C3'—C4'	108.8 (2)	O18'—C16'—C17'	127.1 (3)
O11'—C3'—C2'	114.8 (2)	O15'—C16'—C17'	111.8 (3)
C4'—C3'—C2'	101.7 (2)	C16'—C17'—H17A	109.5
O11'—C3'—H3	110.4	C16'—C17'—H17B	109.5
C4'—C3'—H3	110.4	H17A—C17'—H17B	109.5
C2'—C3'—H3	110.4	C16'—C17'—H17C	109.5
O6'—C4'—C5'	109.5 (2)	H17A—C17'—H17C	109.5
O6'—C4'—C3'	104.5 (2)	H17B—C17'—H17C	109.5
C6—N1—C2—N3	−2.3 (6)	O6'—C1'—C2'—O7'	82.0 (3)
C6—N1—C2—Cl11	178.7 (3)	N9—C1'—C2'—O7'	−159.2 (2)
N1—C2—N3—C4	3.0 (5)	O6'—C1'—C2'—C3'	−29.8 (3)
Cl11—C2—N3—C4	−178.0 (2)	N9—C1'—C2'—C3'	89.0 (3)
C2—N3—C4—N9	−178.6 (3)	O7'—C2'—C3'—O11'	44.0 (4)
C2—N3—C4—C5	−0.9 (5)	C1'—C2'—C3'—O11'	156.5 (3)
N3—C4—C5—C6	−1.5 (5)	O7'—C2'—C3'—C4'	−73.3 (3)
N9—C4—C5—C6	176.6 (3)	C1'—C2'—C3'—C4'	39.2 (3)
N3—C4—C5—N7	180.0 (3)	O11'—C3'—C4'—O6'	−157.0 (2)
N9—C4—C5—N7	−1.9 (4)	C2'—C3'—C4'—O6'	−35.5 (3)
C2—N1—C6—C5	−0.8 (5)	O11'—C3'—C4'—C5'	81.3 (3)
C2—N1—C6—Cl10	178.4 (3)	C2'—C3'—C4'—C5'	−157.2 (2)
C4—C5—C6—N1	2.4 (5)	O6'—C4'—C5'—O15'	−65.6 (3)
N7—C5—C6—N1	−179.6 (4)	C3'—C4'—C5'—O15'	53.4 (3)
C4—C5—C6—Cl10	−176.8 (3)	N9—C1'—O6'—C4'	−112.7 (3)
N7—C5—C6—Cl10	1.2 (6)	C2'—C1'—O6'—C4'	8.2 (3)
C4—C5—N7—C8	0.9 (4)	C5'—C4'—O6'—C1'	144.5 (2)
C6—C5—N7—C8	−177.2 (4)	C3'—C4'—O6'—C1'	17.6 (3)
C5—N7—C8—N9	0.4 (4)	C1'—C2'—O7'—C8'	115.0 (3)
N3—C4—N9—C8	−179.9 (3)	C3'—C2'—O7'—C8'	−137.4 (3)
C5—C4—N9—C8	2.0 (3)	C2'—O7'—C8'—O10'	−2.6 (5)
N3—C4—N9—C1'	−3.4 (5)	C2'—O7'—C8'—C9'	−178.7 (3)
C5—C4—N9—C1'	178.5 (3)	C4'—C3'—O11'—C12'	−168.0 (2)
N7—C8—N9—C4	−1.6 (4)	C2'—C3'—O11'—C12'	78.9 (3)
N7—C8—N9—C1'	−177.9 (3)	C3'—O11'—C12'—O14'	−1.6 (5)
C4—N9—C1'—O6'	−168.8 (3)	C3'—O11'—C12'—C13'	178.4 (3)
C8—N9—C1'—O6'	6.9 (4)	C4'—C5'—O15'—C16'	176.9 (3)
C4—N9—C1'—C2'	73.2 (4)	C5'—O15'—C16'—O18'	4.7 (5)
C8—N9—C1'—C2'	−111.1 (3)	C5'—O15'—C16'—C17'	−174.8 (3)

D—H···A	D—H	H···A	D···A	D—H···A
C8—H8···O15′	0.93	2.52	3.265 (4)	137
C8—H8···O14′i	0.93	2.56	3.350 (4)	143
C1′—H1···N1ii	0.98	2.48	3.355 (5)	148
C9′—H9B···O18′iii	0.96	2.51	3.434 (4)	161
C13′—H13B···N7iv	0.96	2.54	3.502 (5)	175
C5′—H5A···Cgi	0.97	2.69	3.454	136

Table 1

Hydrogen-bond geometry (Å, °)

Cg is the centroid of the C4/C5/N7/C8/N9 imidazole ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H8⋯O15′	0.93	2.52	3.265 (4)	137
C8—H8⋯O14′i	0.93	2.56	3.350 (4)	143
C1′—H1⋯N1ii	0.98	2.48	3.355 (5)	148
C9′—H9B⋯O18′iii	0.96	2.51	3.434 (4)	161
C13′—H13B⋯N7iv	0.96	2.54	3.502 (5)	175
C5′—H5A⋯Cg i	0.97	2.69	3.454	136

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) .