3,3′-Dimethyl-4,4′-(hexane-1,6-di­yl)bis­[1H-1,2,4-triazol-5(4H)-one]

Abstract

The title compound, C₁₂H₂₀N₆O₂, has a centre of symmetry. The mol­ecule consists of two triazole rings joined by an aliphatic –(CH₂)₆– chain. The crystal structure is stabilized by inter­molecular N—H⋯O hydrogen bonds and by π–π stacking inter­actions between the triazole rings of inversion-related mol­ecules [centroid–centroid distance = 3.277 (8) Å].

Related literature

For background information including pharmacological studies, see: Chiu & Huskey (1998 ▶); Clemons et al. (2004 ▶); Dalloul & Boyle (2006 ▶); Eliott et al. (1986 ▶); Griffin & Mannion (1986 ▶); Santen (2003 ▶); Tanaka (1974 ▶); Zamani et al. (2003 ▶). Related structures have been reported by Ustabaş et al. (2006 ▶, 2007 ▶, 2009 ▶); Ünver et al. (2008 ▶, 2009 ▶); Çoruh et al. (2003 ▶).

Experimental

Crystal data

• C₁₂H₂₀N₆O₂

• M _r = 280.34

• Triclinic,

• a = 6.3641 (2) Å

• b = 7.3034 (2) Å

• c = 7.7774 (2) Å

• α = 93.299 (2)°

• β = 109.578 (2)°

• γ = 94.707 (2)°

• V = 338.05 (2) ų

• Z = 1

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 101 K

• 0.40 × 0.16 × 0.12 mm

Data collection

• Bruker Kappa APEXII CCD area-detector diffractometer

• Absorption correction: multi-scan (SADABS; Bruker, 2007 ▶) T _min = 0.962, T _max = 0.988

• 6074 measured reflections

• 1673 independent reflections

• 1309 reflections with I > 2σ(I)

• R _int = 0.033

Refinement

• R[F ² > 2σ(F ²)] = 0.041

• wR(F ²) = 0.112

• S = 1.03

• 1673 reflections

• 131 parameters

• All H-atom parameters refined

• Δρ_max = 0.32 e Å⁻³

• Δρ_min = −0.28 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); 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 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶).

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—H3⋯O1i	0.90 (2)	1.89 (2)	2.7707 (15)	167 (2)

Symmetry code: (i) .

supplementary crystallographic information

Comment

The 1,2,4-triazole compounds possess important pharmacological activities that include antifungal and antiviral properties. Examples of compounds bearing the 1,2,4-triazole group are fluconazole, the powerful azole antifungal agent as well as the potent antiviral N– nucleoside ribavirin (Ünver et al., 2008; Ünver et al., 2009). Furthermore, various 1,2,4-triazole derivatives have been reported as fungicidal (Zamani et al., 2003), insecticidal (Tanaka, 1974), antimicrobial (Griffin & Mannion, 1986), and some showed antitumor activity as well as having anticonvulsant (Dalloul & Boyle, 2006), antidepressant (Chiu & Huskey, 1998) and plant growth regulator anticoagulant activity (Eliott et al., 1986). It was reported that compounds having triazole moieties, such as Vorozole, Anastrozole and Letrozole appear to be very effective aromatase inhibitors and can be useful for preventing breast cancer (Santen, 2003; Clemons et al., 2004).

The molecular structure of the compound is shown in Fig.1. The molecule consists of two triazole rings, joined by an aliphatic —(CH₂)₆— chain connected to nitrogen atoms of the rings. The molecule has an inversion center in the middle of the chain, that connects the triazole rings. The length of the N═C [N2═C5= 1.3031 (17) Å] bond in the triazole ring is close to the those similar structures in the literature [1.296 (3)Å in C₁₄H₁₆N₆O₂S (Ustabaş et al., 2007); 1.288 (2)Å in C₁₆H₂₈N₆O₂ (Çoruh et al., 2003)]. The bond length of O═C [O1═C1= 1.2421 (16) Å] is in conformity with the values mentioned before[1.218 (3)Å in C₁₆H₂₀N₆O₂S (Ustabaş et al., 2006); 1.220 (2)Å in C₂₄H₂₀N₄O₂S (Ustabaş et al., 2009)]. The triazole ring is very close to planarity, with a maximum deviation from the least-squares plane of -0.014 (13)Å for atom C1.

In the crystal structure of the compound, there is a strong intermolecular N3—H3···O1 hydrogen-bonding interaction (Table 1). The compound also exhibits π-π stacking interactions between triazole rings (Cg1···Cg1= 3.277 (8) Å; symmetry code: –X, 2-Y, –Z).

Experimental

The synthesis of 4,4'-(hexane-1,6-diyl)bis (5-ethyl-2H-1,2,4-triazol-3(4H)-one) to a solution of ethyl 2 (1-ethoxyethylidene)hydrazinecarboxylate (0.02 mol) in 50 ml water hexane-1,6-diamine (0.01 mol) was added. Having refluxed this mixture for 4 h the precipitate formed was filtered off. The solid product was washed with water and crystallized from ethanol/water (1/3)(yield 73.25%) to afford the desired compound.

Refinement

All H atoms were located in a difference synthesis and refined [N—H = 0.902 (19) Å; ethylene C—H = 0.945 (18) Å-1.017 (18) Å; and methylene C—H= 0.952 Å-1.00 (2) Å].

Figures

Fig. 1.

An ellipsoid plot of the title compound, with the atom numbering scheme. Atoms with primed labels are related via an inversion center (1-x, 1-y, 1-z). Displacement ellipsoids are drawn at the 50% probability level.

Fig. 2.

A packing diagram, viewed along b.

Crystal data

C12H20N6O2	Z = 1
Mr = 280.34	F(000) = 150
Triclinic, P1	Dx = 1.377 Mg m−3
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 6.3641 (2) Å	Cell parameters from 1309 reflections
b = 7.3034 (2) Å	θ = 2.8–28.3°
c = 7.7774 (2) Å	µ = 0.10 mm−1
α = 93.299 (2)°	T = 101 K
β = 109.578 (2)°	Rod-shaped, colorless
γ = 94.707 (2)°	0.40 × 0.16 × 0.12 mm
V = 338.05 (2) Å3

Data collection

Bruker Kappa APEXII CCD area-detector diffractometer	1673 independent reflections
Radiation source: fine-focus sealed tube	1309 reflections with I > 2σ(I)
graphite	Rint = 0.033
φ and ω scans	θmax = 28.3°, θmin = 2.8°
Absorption correction: multi-scan (SADABS; Bruker, 2007)	h = −8→8
Tmin = 0.962, Tmax = 0.988	k = −9→9
6074 measured reflections	l = −10→10

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)] = 0.041	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.112	All H-atom parameters refined
S = 1.03	w = 1/[σ2(Fo2) + (0.062P)2 + 0.0594P] where P = (Fo2 + 2Fc2)/3
1673 reflections	(Δ/σ)max < 0.001
131 parameters	Δρmax = 0.32 e Å−3
0 restraints	Δρmin = −0.28 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
O1	0.49741 (15)	0.02539 (13)	0.76514 (13)	0.0199 (3)
N1	0.84928 (18)	0.18555 (15)	0.81036 (15)	0.0159 (3)
N2	0.98018 (18)	0.22436 (15)	1.11442 (15)	0.0183 (3)
N3	0.76344 (18)	0.13460 (15)	1.04956 (15)	0.0173 (3)
C1	0.6815 (2)	0.10507 (17)	0.86549 (18)	0.0162 (3)
C2	0.8354 (2)	0.1878 (2)	0.61861 (18)	0.0189 (3)
C3	0.7642 (2)	0.36813 (19)	0.54057 (19)	0.0202 (3)
C4	0.5280 (2)	0.40487 (19)	0.53108 (19)	0.0193 (3)
C5	1.0248 (2)	0.25341 (17)	0.96590 (18)	0.0166 (3)
C6	1.2408 (2)	0.3456 (2)	0.9639 (2)	0.0207 (3)
H21	0.981 (3)	0.163 (2)	0.609 (2)	0.019 (4)*
H61	1.220 (3)	0.461 (3)	0.914 (2)	0.030 (4)*
H32	0.772 (3)	0.361 (2)	0.415 (2)	0.025 (4)*
H41	0.512 (3)	0.397 (2)	0.655 (2)	0.018 (4)*
H31	0.876 (3)	0.476 (2)	0.614 (2)	0.028 (4)*
H42	0.414 (3)	0.309 (2)	0.446 (2)	0.022 (4)*
H22	0.732 (3)	0.087 (2)	0.551 (2)	0.025 (4)*
H3	0.696 (3)	0.089 (2)	1.125 (3)	0.036 (5)*
H62	1.310 (3)	0.273 (3)	0.887 (3)	0.035 (5)*
H63	1.348 (3)	0.368 (3)	1.093 (3)	0.041 (5)*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0140 (5)	0.0240 (5)	0.0184 (5)	−0.0042 (4)	0.0030 (4)	0.0004 (4)
N1	0.0126 (6)	0.0162 (6)	0.0181 (6)	0.0005 (4)	0.0043 (5)	0.0024 (4)
N2	0.0123 (6)	0.0186 (6)	0.0213 (6)	−0.0005 (4)	0.0028 (5)	0.0012 (4)
N3	0.0127 (6)	0.0192 (6)	0.0183 (6)	−0.0006 (4)	0.0035 (5)	0.0026 (4)
C1	0.0134 (6)	0.0150 (6)	0.0197 (7)	0.0028 (5)	0.0047 (5)	0.0025 (5)
C2	0.0156 (7)	0.0230 (7)	0.0169 (7)	−0.0009 (6)	0.0049 (5)	−0.0001 (5)
C3	0.0163 (7)	0.0237 (7)	0.0202 (7)	−0.0017 (6)	0.0065 (6)	0.0039 (6)
C4	0.0160 (7)	0.0213 (7)	0.0184 (7)	−0.0029 (5)	0.0039 (6)	0.0035 (5)
C5	0.0130 (6)	0.0153 (6)	0.0198 (7)	0.0033 (5)	0.0028 (5)	0.0018 (5)
C6	0.0131 (7)	0.0208 (7)	0.0261 (8)	−0.0005 (5)	0.0045 (6)	0.0021 (6)

Geometric parameters (Å, °)

O1—C1	1.2421 (16)	C3—C4	1.5271 (19)
N1—C5	1.3751 (17)	C3—H32	0.991 (16)
N1—C1	1.3794 (16)	C3—H31	1.017 (18)
N1—C2	1.4653 (16)	C4—C4i	1.528 (3)
N2—C5	1.3031 (17)	C4—H41	1.007 (15)
N2—N3	1.3907 (15)	C4—H42	1.000 (17)
N3—C1	1.3467 (18)	C5—C6	1.4856 (19)
N3—H3	0.902 (19)	C6—H61	0.952 (18)
C2—C3	1.521 (2)	C6—H62	1.006 (18)
C2—H21	0.985 (15)	C6—H63	1.00 (2)
C2—H22	0.945 (18)
C5—N1—C1	107.39 (11)	C2—C3—H31	110.3 (10)
C5—N1—C2	128.60 (11)	C4—C3—H31	109.3 (9)
C1—N1—C2	123.98 (11)	H32—C3—H31	107.2 (13)
C5—N2—N3	103.79 (11)	C3—C4—C4i	112.27 (14)
C1—N3—N2	112.63 (11)	C3—C4—H41	110.2 (9)
C1—N3—H3	124.9 (12)	C4i—C4—H41	108.2 (8)
N2—N3—H3	122.0 (12)	C3—C4—H42	110.5 (9)
O1—C1—N3	128.98 (12)	C4i—C4—H42	109.0 (9)
O1—C1—N1	126.86 (12)	H41—C4—H42	106.5 (13)
N3—C1—N1	104.16 (11)	N2—C5—N1	111.99 (11)
N1—C2—C3	112.31 (11)	N2—C5—C6	124.26 (13)
N1—C2—H21	108.9 (9)	N1—C5—C6	123.74 (12)
C3—C2—H21	111.3 (9)	C5—C6—H61	110.6 (10)
N1—C2—H22	107.6 (10)	C5—C6—H62	113.5 (10)
C3—C2—H22	110.7 (10)	H61—C6—H62	105.9 (14)
H21—C2—H22	105.8 (13)	C5—C6—H63	108.9 (11)
C2—C3—C4	114.14 (11)	H61—C6—H63	108.3 (15)
C2—C3—H32	106.5 (9)	H62—C6—H63	109.6 (14)
C4—C3—H32	109.1 (9)
C5—N2—N3—C1	1.87 (14)	N1—C2—C3—C4	−64.04 (15)
N2—N3—C1—O1	178.11 (12)	C2—C3—C4—C4i	174.64 (14)
N2—N3—C1—N1	−2.33 (14)	N3—N2—C5—N1	−0.58 (14)
C5—N1—C1—O1	−178.57 (12)	N3—N2—C5—C6	−179.47 (12)
C2—N1—C1—O1	−0.5 (2)	C1—N1—C5—N2	−0.81 (15)
C5—N1—C1—N3	1.86 (13)	C2—N1—C5—N2	−178.77 (12)
C2—N1—C1—N3	179.93 (11)	C1—N1—C5—C6	178.09 (12)
C5—N1—C2—C3	−84.62 (16)	C2—N1—C5—C6	0.1 (2)
C1—N1—C2—C3	97.73 (14)

Symmetry codes: (i) −x+1, −y+1, −z+1.

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N3—H3···O1ii	0.90 (2)	1.89 (2)	2.7707 (15)	167 (2)

Symmetry codes: (ii) −x+1, −y, −z+2.