Synthesis and crystal structure of N-(4-chloro­phen­yl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-amine

Repich, H.; Orysyk, S.; Savytskyi, P.; Pekhnyo, V.

doi:10.1107/S2056989016019629

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Volume 73| Part 1| January 2017| Pages 35-37

https://doi.org/10.1107/S2056989016019629

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Synthesis and crystal structure of N-(4-chlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-amine

Hlib Repich,^a ^* Svitlana Orysyk,^a Pavlo Savytskyi ^b and Vasyl Pekhnyo ^a

^aVernadsky Institute of General and Inorganic Chemistry of the Ukrainian National Academy of Sciences, Palladin av. 32/34, 03142 Kyiv, Ukraine, and ^bThe Institute of Molecular Biology and Genetics of the Ukrainian National Academy of Sciences, Zabolotnogo Str. 150, 03680 Kyiv, Ukraine
^*Correspondence e-mail: glebrepich@gmail.com

Edited by A. J. Lough, University of Toronto, Canada (Received 14 November 2016; accepted 8 December 2016; online 1 January 2017)

The title compound, C₁₃H₁₂ClN₅, was synthesized by the cyclization of 1-(4,6-dimethylpyrimidin-2-yl)-4-phenylthiosemicarbazide in the presence of Ni(NO₃)₂. The molecular structure of the compound is essentially planar. In the crystal, molecules form dimers via pairs of N—H⋯N hydrogen bonds between the H atom of the exocyclic amino group and the N atom at the 4-position of the triazole ring. The resulting dimers are packed into layers which are connected by π-stacking interactions between the aromatic systems of the pyrimidine and benzene nuclei, and between the triazole cores.

Keywords: crystal structure; thiosemicarbazide cyclization; triazolopyrimidines; Dimroth rearrangement.

CCDC reference: 1521445

1. Chemical context

It is well known that thermal cyclization of 1-(pyrymidin-2-yl)thiosemicarbazides leads to the formation of mercapto derivatives of triazolopyrimidine (Babichev & Kovtunenko, 1977 ; Kottke & Kuhmshtedt, 1978 ). In contrast to this, it has been shown that analogous substrates can be converted into the corresponding 2-R-amino-5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidines by cyclization in the presence of methyl iodide and sodium acetate in boiling ethanol solution. Such processes undergo alcylation of a sulfur atom with the formation of the S-methyl derivative, which then undergoes intramolecular cyclization with elimination of a methanethiol molecule and the formation of the unstable intermediate A. The subsequent Dimroth rearrangement of intermediate A gives the final product B (Fig. 1) (Vas'kevich et al., 2006 ). In the present work we show that an analogous cyclization followed by Dimroth rearrangement can proceed in mild conditions in the presence of Ni²⁺ ions (Fig. 1).

Figure 1
Scheme showing the formation of related compounds (a) according to the literature and (b) in the present work.

2. Structural commentary

The molecular structure of the title compound is almost planar. The molecule consists of two flat fragments: the [1,2,4]triazolo[1,5-a]pyrimidine moiety, and the 4-chlorophenyl group. The mean deviation from the N1/C2/C3/C4/N2/C6/N3/C7/N4 plane is 0.010 Å while that from the C8–C13 plane is 0.006 Å. The dihedral angle between these planes is 6.23 (5)°. The sum of the C7—N5—C8, C7—N5—H1 and C8—N5—H1 angles is 359.86°, indicating sp² hybridization of atom N5.

3. Supramolecular features

In the crystal, molecules form inversion dimers via pairs of N5—H1⋯N3ⁱ hydrogen bonds (Table 1, Fig. 2). The resulting dimers are packed into layers parallel to the bc plane. These layers are connected by π-stacking interactions between the aromatic systems of the pyrimidine and benzene rings, and between triazole cores (Figs. 3 and 4). The centroid–centroid distance between the benzene ring of the 4-chlorophenyl group (C8–C13) and the pyrimidine ring (N1/C2/C3/C4/N2/C6) of symmetry-related molecules is 3.513 (1) Å. These overlapping rings have a slip angle of 16.3°. The centroid–centroid distance between five-membered (N1/N4/C7/N3/C6) triazole rings is 3.824 (1) Å with a slip angle of 29.0°.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N5—H1⋯N3ⁱ	0.870 (18)	2.109 (18)	2.9748 (14)	173.5 (16)
Symmetry code: (i) -x+1, -y, -z+2.

Figure 2
The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

Figure 3
Packing diagram of the title compound with N—H⋯N hydrogen bonds shown as dashed lines. The projection is shown along [001] and the atoms labelled with suffix A are related by an inversion centre (symmetry code 1 − x, −y, 2 − z).

Figure 4
Packing diagram of the title compound with π–π interactions between aromatic systems represented by dashed lines. The projection is shown along [100]. H atoms have been omitted for clarity.

In general, the crystal structure of the title compound is very similar to that of 5,7-dimethyl-2-phenylamino-1,2,4-triazolo[1,5-a]pyrimidine (Vas'kevich et al., 2006).

4. Synthesis and crystallization

A warm solution of Ni(NO₃)₂ (0.0364 g, 0.125 mmol in 15 ml of ethanol) was added dropwise under vigorous stirring to a warm solution of 1-(4,6-dimethylpyrimidin-2-yl)-4-phenylthiosemicarbazide (0.0767 g, 0.25 mmol in 20 ml of ethanol), prepared according to a known procedure (Vas'kevich et al., 2006). An orange precipitate of the Ni²⁺ complex (M:L = 1:2) was formed. The resulting mixture was left for a few days. Detailed analysis of the obtained compound showed the presence of a significant amount of colourless plate-shaped crystals of the title compound, which were used for X-ray analysis.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. All H atoms bonded to C atoms were placed in geometrically idealized positions according to hybridization and constrained to ride on their parent C atoms, with C—H bonds for the aromatic rings and methyl groups of 0.95 and 0.98 Å, respectively, with U_iso(H_aromatic) = 1.2U_eq(C) and U_iso(H_methyl) = 1.5U_eq(C). The methyl groups were allowed to rotate freely about the C—C bonds. The H atom bonded to the N atom was located in a difference map and refined without any restraints.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₃H₁₂ClN₅
M_r	273.73
Crystal system, space group	Monoclinic, P2₁/n
Temperature (K)	100
a, b, c (Å)	7.0640 (1), 25.2362 (4), 7.6494 (1)
β (°)	113.243 (1)
V (Å³)	1252.97 (3)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.30
Crystal size (mm)	0.40 × 0.30 × 0.05

Data collection
Diffractometer	Bruker APEXII CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2001 )
T_min, T_max	0.874, 0.985
No. of measured, independent and observed [I > 2σ(I)] reflections	11572, 3837, 3347
R_int	0.018
(sin θ/λ)_max (Å⁻¹)	0.716

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.039, 0.100, 1.04
No. of reflections	3837
No. of parameters	178
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.47, −0.33
Computer programs: APEX2 and SAINT (Bruker, 2007 ), SHELXS97 and SHELXTL (Sheldrick, 2008 ), SHELXL2014 (Sheldrick, 2015 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 1521445

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989016019629/lh5830sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016019629/lh5830Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989016019629/lh5830Isup3.cml

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and publCIF (Westrip, 2010).

N-(4-Chlorophenyl)-5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidin-2-amine top

Crystal data top

C₁₃H₁₂ClN₅	F(000) = 568
M_r = 273.73	D_x = 1.451 Mg m⁻³
Monoclinic, P2₁/n	Mo Kα radiation, λ = 0.71073 Å
a = 7.0640 (1) Å	Cell parameters from 5527 reflections
b = 25.2362 (4) Å	θ = 3.0–30.5°
c = 7.6494 (1) Å	µ = 0.30 mm⁻¹
β = 113.243 (1)°	T = 100 K
V = 1252.97 (3) Å³	Plate, colorless
Z = 4	0.40 × 0.30 × 0.05 mm

Data collection top

Bruker APEXII CCD diffractometer	3347 reflections with I > 2σ(I)
Radiation source: sealed tube	R_int = 0.018
φ and ω scans	θ_max = 30.6°, θ_min = 1.6°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −10→8
T_min = 0.874, T_max = 0.985	k = −36→33
11572 measured reflections	l = −6→10
3837 independent 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)] = 0.039	Hydrogen site location: mixed
wR(F²) = 0.100	H atoms treated by a mixture of independent and constrained refinement
S = 1.04	w = 1/[σ²(F_o²) + (0.047P)² + 0.6408P] where P = (F_o² + 2F_c²)/3
3837 reflections	(Δ/σ)_max = 0.001
178 parameters	Δρ_max = 0.47 e Å⁻³
0 restraints	Δρ_min = −0.33 e Å⁻³

Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 (Å²) top

	x	y	z	U_iso*/U_eq
C1	−0.39001 (18)	−0.06515 (5)	0.47760 (19)	0.0212 (2)
H1A	−0.4039	−0.0542	0.5949	0.032*
H1B	−0.4903	−0.0931	0.4153	0.032*
H1C	−0.4154	−0.0347	0.3919	0.032*
C2	−0.17835 (18)	−0.08555 (5)	0.52419 (16)	0.0163 (2)
C3	−0.12544 (19)	−0.13199 (5)	0.46223 (17)	0.0176 (2)
H3	−0.2303	−0.1544	0.3786	0.021*
C4	0.08323 (19)	−0.14699 (5)	0.52120 (17)	0.0171 (2)
C5	0.1395 (2)	−0.19827 (5)	0.45558 (19)	0.0212 (2)
H5C	0.2813	−0.1962	0.4637	0.032*
H5B	0.0457	−0.2050	0.3235	0.032*
H5A	0.1285	−0.2272	0.5366	0.032*
C6	0.18434 (17)	−0.07241 (4)	0.69865 (16)	0.0154 (2)
C7	0.17125 (17)	0.00081 (4)	0.82697 (16)	0.0152 (2)
C8	0.13730 (18)	0.08741 (4)	0.96620 (16)	0.0156 (2)
C9	−0.07753 (18)	0.08999 (5)	0.89705 (17)	0.0179 (2)
H9	−0.1590	0.0613	0.8262	0.022*
C10	−0.17128 (19)	0.13482 (5)	0.93266 (18)	0.0203 (2)
H10	−0.3172	0.1366	0.8871	0.024*
C11	−0.0532 (2)	0.17674 (5)	1.03401 (17)	0.0199 (2)
C12	0.1601 (2)	0.17448 (5)	1.10631 (18)	0.0202 (2)
H12	0.2404	0.2031	1.1785	0.024*
C13	0.25465 (19)	0.12990 (5)	1.07201 (17)	0.0184 (2)
H13	0.4008	0.1281	1.1208	0.022*
Cl1	−0.17415 (6)	0.23384 (2)	1.06639 (5)	0.02889 (10)
H1	0.378 (3)	0.0447 (7)	1.006 (2)	0.023 (4)*
N1	−0.01741 (15)	−0.05610 (4)	0.64112 (14)	0.01484 (19)
N3	0.30697 (15)	−0.03648 (4)	0.81768 (15)	0.01627 (19)
N5	0.24606 (16)	0.04442 (4)	0.93749 (15)	0.0171 (2)
N4	−0.02837 (15)	−0.00828 (4)	0.72245 (14)	0.01575 (19)
N2	0.23744 (16)	−0.11766 (4)	0.63896 (15)	0.0173 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0139 (5)	0.0218 (6)	0.0243 (6)	−0.0013 (4)	0.0036 (5)	0.0008 (5)
C2	0.0154 (5)	0.0171 (5)	0.0145 (5)	−0.0025 (4)	0.0038 (4)	0.0020 (4)
C3	0.0183 (5)	0.0169 (5)	0.0161 (5)	−0.0041 (4)	0.0050 (4)	−0.0006 (4)
C4	0.0210 (5)	0.0155 (5)	0.0163 (5)	−0.0013 (4)	0.0090 (4)	0.0000 (4)
C5	0.0253 (6)	0.0178 (5)	0.0220 (6)	−0.0013 (4)	0.0109 (5)	−0.0046 (4)
C6	0.0144 (5)	0.0160 (5)	0.0161 (5)	−0.0008 (4)	0.0064 (4)	0.0012 (4)
C7	0.0153 (5)	0.0147 (5)	0.0156 (5)	−0.0002 (4)	0.0060 (4)	0.0006 (4)
C8	0.0176 (5)	0.0146 (5)	0.0144 (5)	0.0018 (4)	0.0063 (4)	0.0017 (4)
C9	0.0168 (5)	0.0180 (5)	0.0178 (5)	0.0006 (4)	0.0056 (4)	−0.0002 (4)
C10	0.0186 (5)	0.0223 (6)	0.0192 (6)	0.0053 (4)	0.0068 (5)	0.0024 (4)
C11	0.0271 (6)	0.0167 (5)	0.0166 (5)	0.0073 (4)	0.0092 (5)	0.0026 (4)
C12	0.0264 (6)	0.0156 (5)	0.0174 (5)	0.0003 (4)	0.0074 (5)	0.0006 (4)
C13	0.0189 (5)	0.0162 (5)	0.0184 (5)	0.0002 (4)	0.0056 (4)	0.0006 (4)
Cl1	0.03686 (19)	0.02176 (16)	0.02714 (18)	0.01310 (12)	0.01167 (14)	0.00019 (12)
N1	0.0142 (4)	0.0138 (4)	0.0160 (5)	−0.0005 (3)	0.0053 (4)	−0.0002 (3)
N3	0.0140 (4)	0.0153 (4)	0.0190 (5)	−0.0003 (3)	0.0061 (4)	−0.0019 (4)
N5	0.0128 (4)	0.0158 (4)	0.0203 (5)	0.0002 (3)	0.0040 (4)	−0.0031 (4)
N4	0.0149 (4)	0.0134 (4)	0.0175 (5)	−0.0003 (3)	0.0050 (4)	−0.0013 (3)
N2	0.0177 (5)	0.0161 (4)	0.0192 (5)	−0.0011 (4)	0.0084 (4)	−0.0015 (4)

Geometric parameters (Å, º) top

C1—C2	1.4857 (16)	C7—N5	1.3612 (15)
C1—H1A	0.9800	C7—N3	1.3651 (14)
C1—H1B	0.9800	C8—N5	1.3960 (14)
C1—H1C	0.9800	C8—C9	1.3977 (16)
C2—N1	1.3574 (15)	C8—C13	1.4008 (16)
C2—C3	1.3702 (16)	C9—C10	1.3911 (16)
C3—C4	1.4124 (17)	C9—H9	0.9500
C3—H3	0.9500	C10—C11	1.3805 (18)
C4—N2	1.3309 (15)	C10—H10	0.9500
C4—C5	1.4976 (16)	C11—C12	1.3859 (18)
C5—H5C	0.9800	C11—Cl1	1.7423 (12)
C5—H5B	0.9800	C12—C13	1.3855 (16)
C5—H5A	0.9800	C12—H12	0.9500
C6—N3	1.3338 (15)	C13—H13	0.9500
C6—N2	1.3374 (15)	N1—N4	1.3737 (13)
C6—N1	1.3781 (15)	N5—H1	0.870 (18)
C7—N4	1.3381 (15)

C2—C1—H1A	109.5	N5—C8—C9	124.01 (11)
C2—C1—H1B	109.5	N5—C8—C13	116.67 (11)
H1A—C1—H1B	109.5	C9—C8—C13	119.32 (11)
C2—C1—H1C	109.5	C10—C9—C8	119.56 (11)
H1A—C1—H1C	109.5	C10—C9—H9	120.2
H1B—C1—H1C	109.5	C8—C9—H9	120.2
N1—C2—C3	115.11 (10)	C11—C10—C9	120.28 (11)
N1—C2—C1	118.05 (11)	C11—C10—H10	119.9
C3—C2—C1	126.84 (11)	C9—C10—H10	119.9
C2—C3—C4	120.77 (11)	C10—C11—C12	120.89 (11)
C2—C3—H3	119.6	C10—C11—Cl1	119.47 (10)
C4—C3—H3	119.6	C12—C11—Cl1	119.62 (10)
N2—C4—C3	122.65 (11)	C11—C12—C13	119.16 (11)
N2—C4—C5	116.91 (11)	C11—C12—H12	120.4
C3—C4—C5	120.42 (11)	C13—C12—H12	120.4
C4—C5—H5C	109.5	C12—C13—C8	120.76 (11)
C4—C5—H5B	109.5	C12—C13—H13	119.6
H5C—C5—H5B	109.5	C8—C13—H13	119.6
C4—C5—H5A	109.5	C2—N1—N4	126.67 (10)
H5C—C5—H5A	109.5	C2—N1—C6	122.58 (10)
H5B—C5—H5A	109.5	N4—N1—C6	110.72 (9)
N3—C6—N2	128.28 (11)	C6—N3—C7	102.94 (9)
N3—C6—N1	109.03 (10)	C7—N5—C8	128.56 (10)
N2—C6—N1	122.69 (10)	C7—N5—H1	116.2 (11)
N4—C7—N5	124.68 (10)	C8—N5—H1	115.1 (11)
N4—C7—N3	116.54 (10)	C7—N4—N1	100.77 (9)
N5—C7—N3	118.77 (10)	C4—N2—C6	116.17 (10)

N1—C2—C3—C4	0.80 (16)	N2—C6—N1—C2	2.19 (17)
C1—C2—C3—C4	−178.75 (11)	N3—C6—N1—N4	0.47 (13)
C2—C3—C4—N2	0.44 (18)	N2—C6—N1—N4	−179.62 (10)
C2—C3—C4—C5	178.90 (11)	N2—C6—N3—C7	−179.97 (12)
N5—C8—C9—C10	−179.67 (11)	N1—C6—N3—C7	−0.07 (12)
C13—C8—C9—C10	0.64 (17)	N4—C7—N3—C6	−0.38 (14)
C8—C9—C10—C11	0.64 (18)	N5—C7—N3—C6	−179.42 (10)
C9—C10—C11—C12	−1.73 (19)	N4—C7—N5—C8	0.2 (2)
C9—C10—C11—Cl1	176.72 (9)	N3—C7—N5—C8	179.17 (11)
C10—C11—C12—C13	1.50 (18)	C9—C8—N5—C7	6.89 (19)
Cl1—C11—C12—C13	−176.95 (9)	C13—C8—N5—C7	−173.41 (11)
C11—C12—C13—C8	−0.19 (18)	N5—C7—N4—N1	179.62 (11)
N5—C8—C13—C12	179.42 (11)	N3—C7—N4—N1	0.64 (13)
C9—C8—C13—C12	−0.87 (18)	C2—N1—N4—C7	177.46 (11)
C3—C2—N1—N4	−179.95 (10)	C6—N1—N4—C7	−0.64 (12)
C1—C2—N1—N4	−0.35 (17)	C3—C4—N2—C6	−0.44 (17)
C3—C2—N1—C6	−2.06 (16)	C5—C4—N2—C6	−178.96 (10)
C1—C2—N1—C6	177.54 (10)	N3—C6—N2—C4	179.07 (11)
N3—C6—N1—C2	−177.72 (10)	N1—C6—N2—C4	−0.82 (16)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N5—H1···N3ⁱ	0.870 (18)	2.109 (18)	2.9748 (14)	173.5 (16)

Symmetry code: (i) −x+1, −y, −z+2.

Acknowledgements

The authors thank the Ukrainian Academy of Sciences for financial support.

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