7-(4-Fluoro­benzyl­amino)-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amine methanol disolvate

Anton V Dolzhenko; Geok Kheng Tan; Lip Lin Koh; Anna V Dolzhenko; Wai Keung Chui

doi:10.1107/S1600536811014176

. 2011 Apr 22;67(Pt 5):o1183–o1184. doi: 10.1107/S1600536811014176

7-(4-Fluorobenzylamino)-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amine methanol disolvate¹

Anton V Dolzhenko ^a,^*,^‡, Geok Kheng Tan ^b, Lip Lin Koh ^b, Anna V Dolzhenko ^c, Wai Keung Chui ^d

PMCID: PMC3089080 PMID: 21754486

Abstract

The 1,2,4-triazolo[1,5-a][1,3,5]triazine system in the title compound, C₁₇H₁₄FN₇·2CH₃OH, is essentially planar, with an r.m.s. deviation of 0.0215 Å. The attached phenyl ring lies almost in the mean plane of the heterocyclic core [dihedral angle = 3.56 (4)°]. In the crystal, centrosymmetric inversion dimers connected via intermolecular N—H⋯N hydrogen bonds between H atom of the primary amino group and the triazine N atom [R ₂ ²(8) graph-set motif] form sheets parallel to (010). A second set of dimers connected via N—H⋯F hydrogen bonds between the other H atom of the primary amino group and the F atom forms an R ₂ ²(24) graph-set motif linking the sheets. Methanol solvent molecules are packed in channels running along the [010] direction.

Related literature

For a review of the synthesis and biological activity of 1,2,4-triazolo[1,5-a][1,3,5]triazines, see: Dolzhenko et al. (2006 ▶). For our work on the synthesis and biological activity of 1,2,4-triazolo[1,5-a][1,3,5]triazines, see: Dolzhenko et al. (2007a ▶,b ▶, 2008a ▶,b ▶, 2011a ▶). For the crystal structures of similar 1,2,4-triazolo[1,5-a][1,3,5]triazines, see: Dolzhenko et al. (2007c ▶,d ▶, 2008c ▶, 2011b ▶); Gilardi (1973 ▶); Khankischpur et al. (2010 ▶). For a review on the graph-set analysis of hydrogen bonding, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₇H₁₄FN₇·2CH₄O
M _r = 399.44
Monoclinic,
a = 27.516 (3) Å
b = 7.0091 (8) Å
c = 20.778 (3) Å
β = 104.380 (3)°
V = 3881.7 (8) Å³
Z = 8
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.56 × 0.18 × 0.02 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 2001 ▶) T _min = 0.946, T _max = 0.998
11861 measured reflections
3820 independent reflections
2876 reflections with I > 2σ(I)
R _int = 0.066

Refinement

R[F ² > 2σ(F ²)] = 0.084
wR(F ²) = 0.183
S = 1.20
3820 reflections
275 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: SMART (Bruker, 2001 ▶); cell refinement: SAINT (Bruker, 2001 ▶); data reduction: SAINT; 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

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811014176/sj5125sup1.cif

e-67-o1183-sup1.cif^{(21.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811014176/sj5125Isup2.hkl

e-67-o1183-Isup2.hkl^{(187.4KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811014176/sj5125Isup3.cdx

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
N6—H6B⋯O2Sⁱ	0.87 (2)	2.52 (3)	3.033 (4)	118 (3)
N6—H6B⋯F1ⁱⁱ	0.87 (2)	2.48 (2)	3.307 (3)	159 (3)
N6—H6A⋯N5ⁱ	0.90 (2)	2.13 (2)	3.025 (4)	178 (3)
N7—H7N⋯O1Sⁱⁱⁱ	0.88 (2)	1.96 (2)	2.797 (4)	158 (3)
O1S—H1S⋯O2S	0.84	1.86	2.690 (3)	169
O2S—H2S⋯N2	0.84	1.91	2.731 (4)	166

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported by the School of Pharmacy, Curtin University of Technology, and the National Medical Research Council, Singapore (NMRC/NIG/0019/2008).

supplementary crystallographic information

Comment

The 1,2,4-triazolo[1,5-a]triazine heterocyclic system has been well recognized as a promising scaffold for the construction of compounds with diverse biological effects (Dolzhenko et al., 2006). In our search for potential therapeutic agents in this class of compounds we devised a number of effective methods for the preparation of 1,2,4-triazolo[1,5-a]triazines (Dolzhenko et al., 2007a,b; Dolzhenko et al., 2008a,b). The structural investigations of 1,2,4-triazolo[1,5-a]triazines include an earlier report (Gilardi, 1973) of the 5,7-bis(dimethylamino)-2-methylthio-1,2,4-triazolo[1,5-a]triazine structure, our publications regarding structures of various amino substituted 1,2,4-triazolo[1,5-a]triazines (Dolzhenko et al., 2007c,d; Dolzhenko et al., 2008c; Dolzhenko et al., 2011b), and a recent paper (Khankischpur et al., 2010) mentioning the 2-amino-5-(2-phenylethyl)[1,2,4]triazolo[1,5-a] [1,3,5]triazin-7(6H)-one structure. In continuation of our program on the synthesis and structural investigation of potentially bioactive 1,2,4-triazolo[1,5-a]triazines, we synthesized 7-(4-fluorobenzylamino)-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazine-5-amine using a recently developed method (Dolzhenko et al., 2008a) and report herein its molecular and crystal structure.

7-(4-Fluorobenzylamino)-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazine-5-amine crystallizes together with two methanol molecules (Fig. 1 & 2). The closely similar 7-dimethylamino-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amine reported earlier (Dolzhenko et al., 2008c) also crystallized in the form of a methanol solvate. The 1,2,4-triazolo[1,5-a][1,3,5]triazine heterocyclic system is essentially planar with an r.m.s. deviation of 0.0215 Å. The phenyl ring mean plane C5—C10 makes a small dihedral angle of 3.56 (4)° with the mean plane of the 1,2,4-triazolo[1,5-a][1,3,5]triazine system. The amino group nitrogen atoms N6 and N7 are located practically in the plane of the heterocyclic core with slight deviations of 0.0861 (41) Å above and 0.0663 (41) Å below the mean plane, correspondingly. The molecule is twisted at the aminomethyl bridge N7—C11 [C3—N7—C11—C12 torsion angle is 100.38 (36)°].

In the crystal, molecules of 7-(4-fluorobenzylamino)-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazine-5-amine form two types of centrosymmetric inversion dimers (Fig. 2). The triazine N5 atom is connected with amino group N6—H6A of a neighbouring molecule by intermolecular N–H···N hydrogen bond making R²₂(8) graph-set motif (Bernstein et al., 1995) arranging the molecules in sheets parallel to the (010) plane. A second set of dimers connected via N–H···F hydrogen bonding between the N6—H6A amino group and the F1 atom of an adjacent molecule forms a R²₂(24) graph-set motif linking the sheets. The methanol molecules are packed in channels running along the [010] direction and also participate in linking the sheets via O–H···N and N–H···O contacts.

Experimental

The title compound was prepared according to the previously reported general method (Dolzhenko et al., 2008a). 2-Phenyl-7-trichloromethyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amine (0.66 g, 2.0 mmol) was added to a solution of 4-fluorobenzylamine (0.28 ml, 2.5 mmol) in DMF (5 ml) and the mixture was heated at 70–80 °C with stirring for 3 h. After cooling, ice-cold water (40 ml) was added and the product was filtered and recrystallized from methanol.