N 3-[(E)-Morpholin-4-yl­methyl­idene]-1-phenyl-1H-1,2,4-triazole-3,5-diamine monohydrate

V M Chernyshev; A V Astakhov; V V Ivanov; Z A Starikova

doi:10.1107/S160053681004729X

. 2010 Nov 20;66(Pt 12):o3247–o3248. doi: 10.1107/S160053681004729X

N ³-[(E)-Morpholin-4-ylmethylidene]-1-phenyl-1H-1,2,4-triazole-3,5-diamine monohydrate

V M Chernyshev ^a,^*, A V Astakhov ^a, V V Ivanov ^a, Z A Starikova ^b

PMCID: PMC3011646 PMID: 21589534

Abstract

In the title compound, C₁₃H₁₆N₆O·H₂O, the mean planes of the benzene and 1,2,4-triazole rings form a dihedral angle of 54.80 (5)°. The N atom of the amino group adopts a trigonal–pyramidal configuration. Conjugation in the amidine N=C—N fragment results in sufficient shortening of the formal single bond. In the crystal, intermolecular N—H⋯O and O—H⋯N hydrogen bonds link molecules into double layers parallel to the bc plane.

Related literature

The title compound was synthesized according to Astakhov & Chernyshev (2010 ▶). The synthesis of 3,5-diamino-1-phenyl-1,2,4-triazole is described by Steck et al. (1958 ▶). Intramolecular reactions of N-substituted aminomethylene malonates accompanied by nucleophilic substitution of malonic ester were described by Sunder & Peet (1980 ▶); Yamazaki et al. (1988 ▶); Selic et al. (1998 ▶, 2000 ▶); Tkachev et al. (2007 ▶). Analogous intermolecular reaction affording substituted formamidines was described by Rajappa et al. (1970 ▶); Bao et al. (2008 ▶). For examples of the use of the triazolyl-substituted amidines in the synthesis of annulated heterocycles, see: Dolzhenko et al. (2007 ▶, 2008a ▶,b ▶). For crystal structures of substituted 3,5-diamino-1,2,4-triazoles, see: Ried et al. (1983 ▶); Dunstan et al. (1998 ▶); Chernyshev et al. (2006 ▶, 2007 ▶, 2009 ▶). For crystal structures of hetaryl substituted amidines, see: Ryng & Glowiak (1998 ▶); Kurbatov et al. (2006 ▶); Xie et al. (2007 ▶); Lyakhov et al. (2008 ▶); Quiroga et al. (2010 ▶). The synthesis of mesoionic [1,2,4]triazolo[4,3-a]pyrimidines from N-(5-amino-1-R-1,2,4-triazol-3-yl)-substituted enaminoesters was described by Chernyshev et al. (2010 ▶). For a description of the Cambridge Structural Database, see: Allen (2002 ▶). For values of bond lengths in organic compounds, see: Allen et al. (1987 ▶). For the correlation of bond lengths with bond orders between sp ² hybridized C and N atoms, see: Burke-Laing & Laing (1976 ▶).

Experimental

Crystal data

C₁₃H₁₆N₆O·H₂O
M _r = 290.33
Triclinic,
a = 8.7886 (7) Å
b = 9.0100 (7) Å
c = 9.4373 (7) Å
α = 99.938 (1)°
β = 105.933 (1)°
γ = 95.331 (1)°
V = 700.00 (9) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.55 × 0.30 × 0.25 mm

Data collection

Bruker APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2004 ▶) T _min = 0.948, T _max = 0.976
5231 measured reflections
2724 independent reflections
2510 reflections with I > 2σ(I)
R _int = 0.015

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.088
S = 1.00
2724 reflections
206 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.29 e Å⁻³

Data collection: APEX2 (Bruker, 2004 ▶); cell refinement: SAINT (Bruker, 2004 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXTL (Sheldrick, 2008 ▶), publCIF (Westrip, 2010 ▶) and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053681004729X/cv2798sup1.cif

e-66-o3247-sup1.cif^{(18.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S160053681004729X/cv2798Isup2.hkl

e-66-o3247-Isup2.hkl^{(133.7KB, hkl)}

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
N5—H5A⋯O1ⁱ	0.89 (2)	2.08 (2)	2.929 (2)	159 (1)
N5—H5B⋯O2ⁱⁱ	0.89 (2)	2.04 (2)	2.906 (2)	164 (1)
O2—H2A⋯N3	0.89 (2)	2.07 (2)	2.929 (2)	164 (1)
O2—H2B⋯N4ⁱⁱⁱ	0.91 (2)	2.01 (2)	2.916 (2)	172 (1)

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

Acknowledgments

The authors thank the Ministry of Education and Science of the Russian Federation for the financial support of this work through the Federal Target Program "Research and Educational Personnel of Innovative Russia at 2009–2013 Years", State contract P302, project NK-109P/2.

supplementary crystallographic information

Comment

Recently, we have reported a simple method for the synthesis of mesoionic 3-amino-5-oxo-2-R-2,5-dihydro-[1,2,4]triazolo[4,3-a]pyrimidines by heating of N-(5-amino-1-R-1,2,4-triazol-3-yl)-substituted enaminoesters in alkaline alcoholic solutions (Chernyshev et al., 2010). In the analogous conditions, N-(5-amino-1-R-1,2,4-triazol-3-yl)-substituted aminomethylene malonates 1 (Fig. 1) furnished mesoionic 3-amino-6-(ethoxycarbonyl)-2-R-5-oxo-5H-[1,2,4]triazolo[4,3- a]pyrimidines 2 in high yield (Astakhov & Chernyshev, 2010). However, when the compounds 1 were heated with aliphatic amines in acetonitrile, nucleophilic substitution of malonic ester affording the amidines 3 was observed instead of the expected reactions of heterocyclization or amidation (Fig. 1). This reaction is analogous to the previously described intramolecular heterocyclizations of N-substituted aminomethylene malonates (Sunder & Peet, 1980;Yamazaki et al., 1988; Selic et al., 1998, 2000; Tkachev et al., 2007). However, we could find the intermolecular variant of the reaction in two publications (Rajappa et al., 1970; Bao et al., 2008), only. Good yields of the compounds 3 allow to expect that the reaction will be a useful tool for the selective synthesis of N-hetaryl substituted formamidines. Analogous compounds are valuable building blocks for the preparation of annulated heterocycles (Dolzhenko et al., 2007, 2008a,b).

For unambiguous confirmation of structure of the compounds 3 (Fig. 1), we performed an X-ray investigation of the title compound. In accordance with the X-ray diffraction data (Fig. 2), the benzene and triazole rings are not coplanar, the dihedral angle is 54.80 (5)°. Bond lengths and angles in the triazole cycle are within the normal ranges and are comparable with those found in the other substituted 3,5-diamino-1,2,4-triazoles (Ried et al., 1983; Dunstan et al., 1998; Chernyshev et al., 2006, 2007, 2009). The nitrogen atom of the amino group is in a trigonal pyramidal configuration (sum of valence angles is 349.8°) and deviates from the triazole plane by only 0.020 (2) Å. Conjugation between the unshared electron pair of N5 and the π system of the triazole fragment leads to a shortening of the N5—C5 bond (1.352 (2) Å) relative to the standard length of a purely single Nsp2-Csp2 bond (1.43–1.45 Å) (Burke-Laing & Laing,1976; Allen et al., 1987). The N3 atom deviates from the least-squares plane of the triazole cycle by 0.056 (2) Å. The dihedral angle between the planes of the triazole cycle and amidine fragment (H1/C1/N3/N6) of the molecule is 8.66 (7)°. The amidine fragment is in the E configuration, as in the majority of other (het)aryl substituted formamidines (Cambridge Structural Database, Version 5.31 of November 2009, including updates up to August 2010, Allen, 2002). Although the formally single bond N6—C1 (1.337 (2) Å) is longer than the double bond N3—C1 (1.297 (2) Å), it is sufficiently shorter than the purely single Nsp2-Csp2 bond (1.43–1.45 Å) (Burke-Laing & Laing,1976; Allen et al., 1987). Apparently, that is caused by conjugation of the N6 atom lone pair with the N3—C1 double bond, analogously to the other hetaryl substituted formamidines (Ryng & Glowiak, 1998; Kurbatov et al., 2006; Xie et al., 2007; Lyakhov et al., 2008; Quiroga et al., 2010). Atom N6 of morpholine cycle has a slightly pyramidalized trigonal configuration (sum of valence angles is 359.1°). The morpholine ring adopts the usual chair conformation.

In the crystal, the molecules C₁₃H₁₆N₆O with the parallel oriented triazole and morpholine cycles form stacks along the a axis of the triclinic cell (Fig. 3). The nearest molecules in the stacks adopt inverse orientation, i. e. they are space related by the inversion centres with coordinates [0, 0, 0]. The pairs of the nearest inversely oriented molecules in the stacks are connected with two water molecules located between them by means of the hydrogen bonds O2—H2A···N3 and O2—H2B···N4 (Table 1). These stacks together with the water molecules form rows which are parallel to the (011) plane (Fig. 3). In these rows the inversely oriented molecules C₁₃H₁₆N₆O of the neighboring stacks are linked with each other by the chains of N5—H5A···O1 hydrogen bonds. The rows are connected with one another by the system of N5—H5B···O2 hydrogen bonds (Table 1). In the crystal, parallel to (100), one can see two types of molecular layers consisting of the molecules C₁₃H₁₆N₆O (Fig. 4). The adjacent layers are related by the inversion centres. In the each layer the nearest molecules C₁₃H₁₆N₆O are displaced from each other by the cell parameter along the b and c axes. The neighbouring layers from both sides of the (100) crystallographic planes are pairwise linked by the O2—H2A···N3, O2—H2B···N4 and N5—H5B···O2 hydrogen bonds. Thus, the crystal structure consists of the C₁₃H₁₆N₆O×H₂O molecular double layers in the direction of normal to the (100) plane.

Experimental

The crystals of N³-[(E)-morpholin-4-ylmethylidene]-1-phenyl-1H-1,2,4- triazole-3,5-diamine hydrate suitable for X-ray analysis were grown by slow evaporation from 1:9 water: acetonitrile mixture at room temperature. The title compound was prepared by the following procedure.

A mixture of diethyl 2-(((5-amino-1-phenyl-1H-1,2,4-triazol-3-yl)amino)methylene)malonate (1a, R¹ = Ph, 0.69 g, 2 mmol), morpholine (0.37 g, 4.2 mmol) and acetonitrile (5 ml) was refluxed for 5 h, then cooled to 0 °C. The precipitate formed was isolated by filtration, recrystallized from acetonitrile and dried at 130 °C to give 0.46 g (84% yield) of white powder, m. p. 208–208.5 °C. Spectrum ¹H NMR (300 MHz), δ: 3.42–3.61 (m, 8H, 4CH₂), 6.21 (s, 2H, NH₂), 7.25–7.53 (m, 5H, Ph), 8.26 (s, 1H, CH). Spectrum ¹³C NMR (125 MHz), δ: 42.52, 48.58, 65.44, 66.57, 121.68, 125.75, 129.16, 137.71, 153.59 (C5 of triazole), 155.03 (N—CH═N), 163.52 (C3 of triazole). MS (EI, 70 eV), m/z (%): 272 (M⁺, 100), 241 (25), 186 (17), 175 (17), 77 (27). Anal. Calcd for C₁₃H₁₆N₆O: C 57.34; H 5.92; N 30.86. Found: C 57.35; H 5.94; N 30.88.

For the preparation of compound 1a a solution of 3,5-diamino-1-phenyl-1,2,4-triazole (1.05 g, 6 mmol) and diethyl 2-(ethoxymethylene)malonate (1.56 g, 7.2 mmol) in EtOH (5 ml) was refluxed for 2 h, then water (5 ml) was added. After cooling to 20 °C, the precipitate formed was isolated by filtration and recrystallized from ethanol. Yield 2.07 g (97%) of white powder, m. p. 140–141 °C. Spectrum ¹H NMR (300 MHz) δ: 1.22 (t, J = 6.9 Hz, 3H, OCH₂CH₃), 1.24 (t, J = 6.9 Hz, 3H, OCH₂CH₃), 4.12 (q, J = 6.9 Hz, 2H, OCH₂CH₃), 4.20 (q, J = 6.9 Hz, 2H, OCH₂CH₃), 6.84 (s, 2H, NH₂), 7.33–7.54 (m, 5H, Ph), 8.53 (d, J=13.4 Hz, 1H, CH), 10.56 (d, J=13.4 Hz, 1H, NH). MS (EI, 70 eV), m/z (%): 345 (M⁺, 21), 254 (18), 253 (99), 186 (21), 119 (37), 105 (16), 91 (34), 77 (100). Anal. Calcd for C₁₆H₁₉N₅O₄: C, 55.64; H, 5.55; N, 20.28. Found: C, 55.81; H, 5.62; N, 20.04. Starting 3,5-diamino-1-phenyl-1,2,4-triazole was synthesized by known method (Steck, et al., 1958).