2-Chloro-6-methyl­pyrimidin-4-amine

Abstract

In the crystal structure of the title compound, C₅H₆ClN₃, mol­ecules are linked by pairs of N—H⋯N hydrogen bonds, forming inversion dimers. These dimers are linked via N—H⋯N hydrogen bonds, forming a two-dimensional network lying parallel to (100). Inversion-related mol­ecules are also linked via a slipped π–π inter­action, with a centroid–centroid distance of 3.5259 (11) Å, a normal separation of 3.4365 (7) Å and a slippage of 0.789 Å.

Related literature  

The title compound is an important organic inter­mediate which has been used to synthesise a drug that has shown promising activity against, for example, inflammatory bowel disease. For the synthetic procedure, see: Graceffa et al. (2010 ▶). For bond-length data, see: Allen et al. (1987 ▶).

Experimental  

Crystal data  

• C₅H₆ClN₃

• M _r = 143.58

• Monoclinic,

• a = 7.1256 (8) Å

• b = 7.8537 (8) Å

• c = 13.0769 (15) Å

• β = 115.678 (1)°

• V = 659.54 (13) ų

• Z = 4

• Mo Kα radiation

• μ = 0.48 mm⁻¹

• T = 296 K

• 0.14 × 0.12 × 0.12 mm

Data collection  

• Enraf–Nonius CAD-4 diffractometer

• Absorption correction: ψ scan (North et al., 1968 ▶) T _min = 0.935, T _max = 0.944

• 5910 measured reflections

• 1157 independent reflections

• 1103 reflections with I > 2σ(I)

• R _int = 0.077

• 3 standard reflections every 200 reflections intensity decay: 1%

Refinement  

• R[F ² > 2σ(F ²)] = 0.057

• wR(F ²) = 0.143

• S = 1.17

• 1157 reflections

• 83 parameters

• H-atom parameters constrained

• Δρ_max = 0.36 e Å⁻³

• Δρ_min = −0.76 e Å⁻³

Data collection: CAD-4 Software (Enraf–Nonius, 1985 ▶); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo,1995 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Supplementary Material

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3A⋯N2i	0.86	2.24	3.090 (3)	170
N3—H3B⋯N1ii	0.86	2.26	3.045 (2)	152

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

Comment

The title compound is an important organic intermediate which has been used to synthesis drugs which have show promising activity against diseases, such as asthma, inflammatory bowel disease, and Crohn's disease (Graceffa et al., 2010). Herein we report on the crystal structure of the title compound.

The molecular structure of the title molecule is shown in Fig. 1. The bond lengths (Allen et al., 1987) and angles are within normal ranges.

In the crystal, molecules are linked by pairs of N-H···N hydrogen bonds forming inversion dimers. These dimers are linked via N-H···N hydrogen bonds forming a two-dimensional network lying parallel to plane (100). See Table 1 and Fig. 2 for details. Inversion related molecules are also linked via a slipped π-π interaction with a centroid-to-centroid distance of 3.5259 (11) Å ; a normal separation of 3.4365 (7) Å; slippage of 0.789 Å (Cg1···Cg1ⁱ where Cg1 is the N1/C1/N2/C4/C3/C2 ring; symmetry code: (i) -x+2, -y+1, -z+1).

Experimental

The title compound was prepared by the method reported in the literature (Graceffa et al., 2010). A solution of 2-chloro-4-methyl-6-nitropyrimidine (5 g, 15.77 mmol) in dichloromethane (50 ml) was added slowly to a solution of iron powder and hydrochloric acid (10 g, 178 mmol). After being stirred for 6 h at room temperature, the solution was filtered and the organic phase was evaporated on a rotary evaporator and gave the title compound. Block-like colourless crystals were obtained by slow evaporation of a solution of the title compound (0.5 g, 3.5 mmol) in ethanol (25 ml), at room temperature after ca. 7 d.

Refinement

All H atoms were positioned geometrically and refined using a riding model: N-H = 0.86 Å, C—H = 0.93 and 0.96 Å for aromatic and CH₃ H atoms, respectively, with U_iso(H) = k × U_eq(N,C), where k = 1.5 for CH₃ H atoms and = 1.2 for other H atoms.

Figures

Fig. 1.

The molecular structure of the title compound, with the atom numbering. Displacement ellipsoids are drawn at the 50% probability level.

Fig. 2.

A view of the crystal packing of the title compound. The N—H···N hydrogen bonds are shown as dashed lines (see Table 1 for details).

Crystal data

C5H6ClN3	F(000) = 296
Mr = 143.58	Dx = 1.446 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 5910 reflections
a = 7.1256 (8) Å	θ = 3.2–25.0°
b = 7.8537 (8) Å	µ = 0.48 mm−1
c = 13.0769 (15) Å	T = 296 K
β = 115.678 (1)°	Block, colourless
V = 659.54 (13) Å3	0.14 × 0.12 × 0.12 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer	1103 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.077
Graphite monochromator	θmax = 25.0°, θmin = 3.2°
ω/2θ scans	h = −8→8
Absorption correction: ψ scan (North et al., 1968)	k = −8→9
Tmin = 0.935, Tmax = 0.944	l = −15→15
5910 measured reflections	3 standard reflections every 200 reflections
1157 independent reflections	intensity decay: 1%

Refinement

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)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.143	H-atom parameters constrained
S = 1.17	w = 1/[σ2(Fo2) + (0.0881P)2 + 0.2103P] where P = (Fo2 + 2Fc2)/3
1157 reflections	(Δ/σ)max = 0.004
83 parameters	Δρmax = 0.36 e Å−3
0 restraints	Δρmin = −0.76 e Å−3

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
C1	0.6937 (3)	0.4212 (2)	0.33622 (15)	0.0279 (4)
C2	0.9835 (3)	0.2642 (2)	0.42236 (17)	0.0304 (5)
C3	0.9496 (3)	0.2568 (2)	0.51731 (17)	0.0336 (5)
H3	1.0404	0.1980	0.5814	0.040*
C4	0.7729 (3)	0.3408 (2)	0.51565 (15)	0.0286 (4)
C5	1.1670 (3)	0.1823 (3)	0.4147 (2)	0.0463 (6)
H5A	1.2551	0.1315	0.4863	0.069*
H5B	1.2442	0.2669	0.3958	0.069*
H5C	1.1193	0.0961	0.3569	0.069*
Cl1	0.51828 (9)	0.52705 (8)	0.21459 (4)	0.0494 (3)
N1	0.8510 (2)	0.34779 (19)	0.32654 (13)	0.0305 (4)
N2	0.6439 (2)	0.42741 (19)	0.42172 (13)	0.0288 (4)
N3	0.7236 (3)	0.3407 (3)	0.60284 (15)	0.0416 (5)
H3A	0.6144	0.3939	0.5978	0.050*
H3B	0.8009	0.2874	0.6642	0.050*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0323 (9)	0.0294 (9)	0.0252 (9)	−0.0011 (7)	0.0154 (7)	−0.0003 (7)
C2	0.0321 (9)	0.0291 (9)	0.0321 (11)	−0.0023 (7)	0.0158 (7)	−0.0051 (7)
C3	0.0348 (10)	0.0346 (10)	0.0300 (10)	0.0008 (7)	0.0126 (8)	0.0023 (7)
C4	0.0340 (9)	0.0300 (9)	0.0250 (9)	−0.0042 (7)	0.0159 (7)	−0.0013 (7)
C5	0.0422 (11)	0.0513 (13)	0.0525 (14)	0.0096 (10)	0.0271 (10)	−0.0002 (10)
Cl1	0.0559 (5)	0.0652 (5)	0.0326 (4)	0.0224 (3)	0.0245 (3)	0.0176 (2)
N1	0.0348 (8)	0.0331 (8)	0.0289 (9)	−0.0021 (6)	0.0187 (7)	−0.0044 (6)
N2	0.0332 (8)	0.0315 (8)	0.0267 (8)	−0.0006 (6)	0.0177 (7)	−0.0003 (6)
N3	0.0466 (10)	0.0571 (11)	0.0284 (9)	0.0088 (8)	0.0232 (8)	0.0095 (8)

Geometric parameters (Å, º)

C1—N2	1.313 (3)	C4—N3	1.331 (3)
C1—N1	1.315 (2)	C4—N2	1.356 (2)
C1—Cl1	1.7494 (18)	C5—H5A	0.9600
C2—N1	1.366 (3)	C5—H5B	0.9600
C2—C3	1.365 (3)	C5—H5C	0.9600
C2—C5	1.499 (3)	N3—H3A	0.8600
C3—C4	1.413 (3)	N3—H3B	0.8600
C3—H3	0.9300
N2—C1—N1	130.94 (17)	C2—C5—H5A	109.5
N2—C1—Cl1	113.97 (13)	C2—C5—H5B	109.5
N1—C1—Cl1	115.09 (14)	H5A—C5—H5B	109.5
N1—C2—C3	122.03 (16)	C2—C5—H5C	109.5
N1—C2—C5	114.88 (18)	H5A—C5—H5C	109.5
C3—C2—C5	123.09 (19)	H5B—C5—H5C	109.5
C2—C3—C4	118.28 (17)	C1—N1—C2	113.67 (16)
C2—C3—H3	120.9	C1—N2—C4	115.17 (16)
C4—C3—H3	120.9	C4—N3—H3A	120.0
N3—C4—N2	116.70 (17)	C4—N3—H3B	120.0
N3—C4—C3	123.43 (18)	H3A—N3—H3B	120.0
N2—C4—C3	119.88 (17)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3A···N2i	0.86	2.24	3.090 (3)	170
N3—H3B···N1ii	0.86	2.26	3.045 (2)	152

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) x, −y+1/2, z+1/2.