2,6-Dichloro-7-isopropyl-7H-purine

Hloušková, N.; Rouchal, M.; Nečas, M.; Vícha, R.

doi:10.1107/S160053681201879X

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 68| Part 6| June 2012| Page o1585

doi:10.1107/S160053681201879X

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2,6-Dichloro-7-isopropyl-7H-purine

Nikola Hloušková,^a Michal Rouchal,^a Marek Nečas ^b and Robert Vícha ^a ^*

^aDepartment of Chemistry, Faculty of Technology, Tomas Bata University in Zlin, Nám. T. G. Masaryka 275, Zlín, 762 72, Czech Republic, and ^bDepartment of Chemistry, Faculty of Science, Masaryk University, Kamenice 5, Brno-Bohunice, 625 00, Czech Republic
^*Correspondence e-mail: rvicha@ft.utb.cz

(Received 16 April 2012; accepted 26 April 2012; online 2 May 2012)

In the title molecule, C₈H₈Cl₂N₄, the essentially planar imidazole and pyrimidine rings [maximum deviations of 0.0030 (15) and 0.0111 (15) Å, respectively] make a dihedral angle of 1.32 (8)°. In the crystal, the fused-ring systems are stacked approximately parallel to the bc plane, with a centroid–centroid distance between inversion-related pyrimidine rings of 3.5189 (9) Å.

Related literature

For the synthesis, see: Oumata et al. (2008 ). For biological activity of some purine derivatives, see: Legraverend & Grierson (2006 ). For the selective synthesis of N7-substituted purines, see: Kotek et al. (2010 ). For related structures, see: Rouchal et al. (2009a ,b , 2010 ).

Experimental

Crystal data

C₈H₈Cl₂N₄
M_r = 231.08
Triclinic, $[P \overline 1]$
a = 7.0146 (5) Å
b = 8.2862 (6) Å
c = 8.9686 (7) Å
α = 70.499 (7)°
β = 83.820 (6)°
γ = 74.204 (6)°
V = 472.75 (7) Å³
Z = 2
Mo Kα radiation
μ = 0.65 mm⁻¹
T = 120 K
0.40 × 0.40 × 0.20 mm

Data collection

Oxford Diffraction Xcalibur Sapphire2 diffractometer
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009 $[Oxford Diffraction (2009). CrysAlis RED and CrysAlis CCD. Oxford Diffraction Ltd, Yarnton, England.]$ ) T_min = 0.933, T_max = 1.000
2825 measured reflections
1656 independent reflections
1419 reflections with I > 2σ(I)
R_int = 0.011

Refinement

R[F² > 2σ(F²)] = 0.023
wR(F²) = 0.061
S = 1.05
1656 reflections
129 parameters
H-atom parameters constrained
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.24 e Å⁻³

Data collection: CrysAlis CCD (Oxford Diffraction, 2009 $[Oxford Diffraction (2009). CrysAlis RED and CrysAlis CCD. Oxford Diffraction Ltd, Yarnton, England.]$ ); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2009 $[Oxford Diffraction (2009). CrysAlis RED and CrysAlis CCD. Oxford Diffraction Ltd, Yarnton, England.]$ ); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997 ) and Mercury (Macrae et al., 2008 ); software used to prepare material for publication: SHELXL97.

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053681201879X/lh5458sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S160053681201879X/lh5458Isup2.hkl

Supporting information file. DOI: 10.1107/S160053681201879X/lh5458Isup3.cml

checkCIF report

Comment top

Purines represent a class of compounds with wide range of biological activities. The most of biologically active purines are di-, tri- or tetrasubstituted, usually on the C(2), C(6), C(8) and/or N(9) centers. Moreover, interesting biological properties were also described for some N7-substituted purines (Legraverend & Grierson, 2006). Owing to the relatively small portions of N7 isomer originating within the direct alkylation of purine bases, the selective synthesis of N7-substituted purines was recently described (Kotek et al., 2010). The title molecule was isolated as a side product forming during the synthesis of novel 2,6,9-trisubstituted purine series.

The asymmetric unit of the title compound consists of a single purine molecule (Fig. 1). Both imidazole and pyrimidine rings are essentially planar with maximum deviations from the best plane being 0.0030 (15) Å for C4 (imidazole ring) and 0.0111 (15) Å for C3 (pyrimidine ring). The dihedral angle between the two rings is 1.32 (8)°. In the crystal packing (Fig .2), molecules are stacked parallel to the bc-plane. The distance between purine ring atoms (-x, 1 - y, -z) and best plane of adjacent purine ring (x, y, z) varies from -3.4111 (15) Å for N4 to -3.3728 (15) Å for C3. We have already published the structures of some related compounds (Rouchal et al., 2009a,b; Rouchal et al., 2010).

Related literature top

For the synthesis, see: Oumata et al. (2008). For biological activity of some purine derivatives, see: Legraverend & Grierson (2006). For the selective synthesis of N7-substituted purines, see: Kotek et al. (2010). For related structures, see: Rouchal et al. (2009a,b, 2010).

Experimental top

The title compound was prepared following modified literature procedure (Oumata et al., 2008). To a well stirred solution of 2,6-dichloro-9H-purine (4.5 g, 23.8 mmol) in DMSO (50 cm³), potassium carbonate (9.9 g, 71.4 mmol) and 2-iodopropane (11.9 cm³, 119.0 mmol) were added. The reaction mixture was stirred at 288–291K for 8 h. After that, the mixture was diluted with water (50 cm³) and extracted with ether (7 × 15 cm³). Collected organic layers were washed with brine (2 × 10 cm³), dried over sodium sulfate and evaporated in vacuo. Both N7 and N9 isomers were separated from the crude material using column chromatography (silicagel; petroleum ether/ethyl acetate, 1/1, v/v). 2,6-Dichloro-7-isopropyl-7H-purine was obtained as a pale yellow crystalline powder (mp 425–427 K) in minor fraction. The crystal used for data collection was grown by spontaneous evaporation from deuterochloroform at room temperature.

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2009); cell refinement: CrysAlis CCD (Oxford Diffraction, 2009); data reduction: CrysAlis RED (Oxford Diffraction, 2009); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure with 50% probability ellipsoids. H-atoms are shown as small spheres at arbitrary radii.
	Fig. 2. Molecules of title compound stacked along the a-axis. H-atoms have been omitted for clarity.

2,6-Dichloro-7-isopropyl-7H-purine top

Crystal data top

C₈H₈Cl₂N₄	Z = 2
M_r = 231.08	F(000) = 236
Triclinic, P1	D_x = 1.623 Mg m⁻³
Hall symbol: -P 1	Melting point: 426 K
a = 7.0146 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 8.2862 (6) Å	Cell parameters from 2034 reflections
c = 8.9686 (7) Å	θ = 3.0–27.7°
α = 70.499 (7)°	µ = 0.65 mm⁻¹
β = 83.820 (6)°	T = 120 K
γ = 74.204 (6)°	Block, colourless
V = 472.75 (7) Å³	0.40 × 0.40 × 0.20 mm

Data collection top

Oxford Diffraction Xcalibur Sapphire2 diffractometer	1656 independent reflections
Radiation source: Enhance (Mo) X-ray Source	1419 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.011
Detector resolution: 8.4353 pixels mm^-1	θ_max = 25.0°, θ_min = 3.5°
ω scan	h = −8→8
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009)	k = −9→9
T_min = 0.933, T_max = 1.000	l = −10→10
2825 measured reflections

Refinement top

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)] = 0.023	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.061	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0323P)² + 0.0416P] where P = (F_o² + 2F_c²)/3
1656 reflections	(Δ/σ)_max < 0.001
129 parameters	Δρ_max = 0.26 e Å⁻³
0 restraints	Δρ_min = −0.24 e Å⁻³

Crystal data top

C₈H₈Cl₂N₄	γ = 74.204 (6)°
M_r = 231.08	V = 472.75 (7) Å³
Triclinic, P1	Z = 2
a = 7.0146 (5) Å	Mo Kα radiation
b = 8.2862 (6) Å	µ = 0.65 mm⁻¹
c = 8.9686 (7) Å	T = 120 K
α = 70.499 (7)°	0.40 × 0.40 × 0.20 mm
β = 83.820 (6)°

Data collection top

Oxford Diffraction Xcalibur Sapphire2 diffractometer	1656 independent reflections
Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2009)	1419 reflections with I > 2σ(I)
T_min = 0.933, T_max = 1.000	R_int = 0.011
2825 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.023	0 restraints
wR(F²) = 0.061	H-atom parameters constrained
S = 1.05	Δρ_max = 0.26 e Å⁻³
1656 reflections	Δρ_min = −0.24 e Å⁻³
129 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 > 2σ(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

	x	y	z	U_iso*/U_eq
Cl1	0.22677 (6)	0.42378 (6)	−0.21906 (5)	0.02126 (13)
Cl2	0.31193 (6)	0.39565 (5)	0.35468 (5)	0.02020 (13)
N1	0.2261 (2)	0.71202 (18)	−0.16073 (15)	0.0172 (3)
N2	0.26395 (19)	0.44137 (17)	0.05831 (15)	0.0160 (3)
N3	0.27132 (19)	0.83054 (17)	0.17303 (15)	0.0150 (3)
N4	0.2361 (2)	0.96725 (18)	−0.09060 (15)	0.0175 (3)
C1	0.2390 (2)	0.5421 (2)	−0.09346 (19)	0.0160 (4)
C2	0.2758 (2)	0.5246 (2)	0.15927 (18)	0.0153 (4)
C3	0.2616 (2)	0.7041 (2)	0.10815 (18)	0.0139 (3)
C4	0.2541 (2)	0.9822 (2)	0.04869 (19)	0.0177 (4)
H4	0.2549	1.0914	0.0613	0.021*
C5	0.2397 (2)	0.7924 (2)	−0.05616 (18)	0.0153 (4)
C6	0.2741 (2)	0.8107 (2)	0.34377 (18)	0.0165 (4)
H6	0.3683	0.6952	0.3972	0.020*
C7	0.3474 (3)	0.9569 (2)	0.3651 (2)	0.0245 (4)
H7A	0.4765	0.9589	0.3115	0.037*
H7B	0.3608	0.9358	0.4782	0.037*
H7C	0.2525	1.0708	0.3195	0.037*
C8	0.0694 (2)	0.8061 (2)	0.41748 (19)	0.0203 (4)
H8A	−0.0253	0.9186	0.3670	0.030*
H8B	0.0733	0.7879	0.5310	0.030*
H8C	0.0282	0.7090	0.4020	0.030*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0217 (2)	0.0247 (2)	0.0217 (2)	−0.00501 (18)	−0.00236 (17)	−0.01289 (18)
Cl2	0.0284 (3)	0.0158 (2)	0.0155 (2)	−0.00685 (18)	−0.00177 (17)	−0.00235 (17)
N1	0.0152 (7)	0.0196 (8)	0.0164 (7)	−0.0033 (6)	−0.0005 (6)	−0.0062 (6)
N2	0.0136 (7)	0.0170 (8)	0.0182 (7)	−0.0040 (6)	−0.0006 (6)	−0.0064 (6)
N3	0.0158 (7)	0.0140 (7)	0.0155 (7)	−0.0047 (6)	−0.0004 (6)	−0.0041 (6)
N4	0.0188 (8)	0.0152 (8)	0.0177 (7)	−0.0045 (6)	−0.0003 (6)	−0.0038 (6)
C1	0.0109 (8)	0.0211 (9)	0.0188 (8)	−0.0034 (7)	0.0003 (7)	−0.0105 (7)
C2	0.0109 (8)	0.0182 (9)	0.0152 (8)	−0.0035 (7)	0.0004 (6)	−0.0036 (7)
C3	0.0094 (8)	0.0166 (9)	0.0162 (8)	−0.0030 (7)	0.0005 (6)	−0.0062 (7)
C4	0.0161 (9)	0.0137 (8)	0.0220 (9)	−0.0045 (7)	−0.0003 (7)	−0.0038 (7)
C5	0.0103 (8)	0.0184 (9)	0.0162 (8)	−0.0030 (7)	0.0005 (6)	−0.0050 (7)
C6	0.0185 (9)	0.0166 (9)	0.0145 (8)	−0.0036 (7)	−0.0017 (7)	−0.0053 (7)
C7	0.0301 (11)	0.0255 (10)	0.0230 (9)	−0.0119 (8)	−0.0007 (8)	−0.0104 (8)
C8	0.0227 (10)	0.0233 (10)	0.0159 (8)	−0.0066 (8)	0.0016 (7)	−0.0077 (7)

Geometric parameters (Å, º) top

Cl1—C1	1.7437 (16)	C3—C5	1.414 (2)
Cl2—C2	1.7249 (16)	C4—H4	0.9500
N1—C1	1.315 (2)	C6—C7	1.511 (2)
N1—C5	1.343 (2)	C6—C8	1.519 (2)
N2—C2	1.3289 (19)	C6—H6	1.0000
N2—C1	1.339 (2)	C7—H7A	0.9800
N3—C4	1.360 (2)	C7—H7B	0.9800
N3—C3	1.3770 (19)	C7—H7C	0.9800
N3—C6	1.486 (2)	C8—H8A	0.9800
N4—C4	1.318 (2)	C8—H8B	0.9800
N4—C5	1.371 (2)	C8—H8C	0.9800
C2—C3	1.381 (2)

C1—N1—C5	112.46 (14)	N4—C5—C3	110.38 (14)
C2—N2—C1	115.85 (14)	N3—C6—C7	110.35 (13)
C4—N3—C3	105.08 (13)	N3—C6—C8	109.77 (12)
C4—N3—C6	127.26 (14)	C7—C6—C8	112.12 (14)
C3—N3—C6	127.25 (13)	N3—C6—H6	108.2
C4—N4—C5	103.55 (13)	C7—C6—H6	108.2
N1—C1—N2	130.38 (15)	C8—C6—H6	108.2
N1—C1—Cl1	116.32 (12)	C6—C7—H7A	109.5
N2—C1—Cl1	113.29 (12)	C6—C7—H7B	109.5
N2—C2—C3	121.08 (14)	H7A—C7—H7B	109.5
N2—C2—Cl2	116.30 (12)	C6—C7—H7C	109.5
C3—C2—Cl2	122.62 (13)	H7A—C7—H7C	109.5
N3—C3—C2	137.57 (15)	H7B—C7—H7C	109.5
N3—C3—C5	105.65 (13)	C6—C8—H8A	109.5
C2—C3—C5	116.70 (15)	C6—C8—H8B	109.5
N4—C4—N3	115.34 (15)	H8A—C8—H8B	109.5
N4—C4—H4	122.3	C6—C8—H8C	109.5
N3—C4—H4	122.3	H8A—C8—H8C	109.5
N1—C5—N4	126.13 (14)	H8B—C8—H8C	109.5
N1—C5—C3	123.49 (15)

Experimental details

Crystal data
Chemical formula	C₈H₈Cl₂N₄
M_r	231.08
Crystal system, space group	Triclinic, P1
Temperature (K)	120
a, b, c (Å)	7.0146 (5), 8.2862 (6), 8.9686 (7)
α, β, γ (°)	70.499 (7), 83.820 (6), 74.204 (6)
V (Å³)	472.75 (7)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.65
Crystal size (mm)	0.40 × 0.40 × 0.20

Data collection
Diffractometer	Oxford Diffraction Xcalibur Sapphire2 diffractometer
Absorption correction	Multi-scan (CrysAlis RED; Oxford Diffraction, 2009)
T_min, T_max	0.933, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	2825, 1656, 1419
R_int	0.011
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.023, 0.061, 1.05
No. of reflections	1656
No. of parameters	129
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.26, −0.24

Computer programs: CrysAlis CCD (Oxford Diffraction, 2009), CrysAlis RED (Oxford Diffraction, 2009), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 1997) and Mercury (Macrae et al., 2008).

Acknowledgements

The financial support of this work by the Internal Founding Agency of Tomas Bata University in Zlin (project No. IGA/FT/2012/016) is gratefully acknowledged.

References

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