5,6,7,8-Tetra­hydro-[1,2,4]triazolo[5,1-b]quinazolin-9(4H)-one

The triazole ring in the title mol­ecule is not quite coplanar with the six-membered ring to which it is fused, the dihedral angle between the two least-squares planes being 2.52 (6)°. In the crystal, a layer structure is formed by N—H⋯N and C—H⋯O hydrogen bonds plus slipped π-stacking inter­actions, with the fused cyclo­hexene rings projecting to either side.

Abstract

The triazole ring in the title mol­ecule, C₉H₁₀N₄O, is not quite coplanar with the six-membered ring to which it is fused, the dihedral angle between the two least-squares planes being 2.52 (6)°. In the crystal, a layered structure is formed by N—H⋯N and C—H⋯O hydrogen bonds plus slipped π-stacking inter­actions, with the fused cyclo­hexene rings projecting to either side.

Structure description

Compounds containing nitro­gen heterocycles make up a significant portion (approximately 60%) of small drug mol­ecules that have been approved by the FDA (Ramli & Essassi, 2015 ▸; Martins et al., 2015 ▸). Quinazoline is a frequently occurring structural feature in natural products and pharmaceutically active mol­ecules., which possess a range of useful biological properties, including anti-SARS-CoV-2 (e.g. Karan et al., 2021 ▸), anti­cancer (e.g. Zhao et al., 2021 ▸), anti­viral (e.g. El-Shershaby et al., 2021 ▸), anti­microbial, anti-inflammatory (e.g. Zhang et al., 2020 ▸), and anti­fungal activities (e.g. Ibrahim et al., 2021 ▸).

A puckering analysis of the C2–C7 ring of the title compound (Fig. 1 ▸) gave the parameters Q = 0.4922 (12) Å, θ = 129.71 (14)° and φ = 326.36 (18)°. This conformation is quite similar to a half-chair form. The C8/N2/C9/N3/N4 ring is closer to planarity than is the C1/C2/C7/N1/C8/N4 ring (r.m.s. deviations of the fitted atoms are 0.0128 and 0.0042 Å, respectively) and the dihedral angle between their mean planes is 2.52 (6)°. In the crystal, N1—H1⋯N3 hydrogen bonds (Table 1 ▸) form chains of mol­ecules extending along the c-axis direction, which are linked into layers parallel to the bc plane by weak C—H⋯O hydrogen bonds (Table 1 ▸ and Fig. 2 ▸). The layer formation is assisted by slipped π-stacking inter­actions between inversion-related C1/C2/C7/N1/C8/N4 rings [centroid–centroid distance = 3.4033 (6) Å, slippage = 0.96 Å]. The layers pack along the a-axis direction with van der Waals contacts between them (Fig. 3 ▸).

Figure 1.

The title mol­ecule with labeling scheme and 50% probability ellipsoids.

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

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N3i	0.919 (15)	1.907 (15)	2.8208 (12)	173.1 (13)
C9—H9⋯O1ii	0.95	2.57	3.3282 (12)	137

Symmetry codes: (i) ; (ii) .

Figure 2.

A portion of one layer viewed along the a-axis direction with N—H⋯N and C—H⋯O hydrogen bonds depicted by blue and black dashed lines, respectively. The slipped π-stacking inter­actions are depicted by orange dashed lines and non-inter­acting hydrogen atoms are omitted for clarity.

Figure 3.

Packing viewed along the c-axis direction giving edge views of portions of three layers. Inter­molecular inter­actions are depicted as in Fig. 2 ▸ and non-inter­acting hydrogen atoms are omitted for clarity.

Synthesis and crystallization

1H-1,2,4-Triazol-5-amine (0.5 g, 5.95 mmol) and ethyl 2-oxo-cyclo­hexa­necarboxyl­ate (0.951 ml, 5.95 mmol) were combined and heated under reflux in 10 ml of acetic acid for 1 h. The solid product obtained was recrystallized from ethanol solution to afford colorless crystals.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸.

Table 2. Experimental details.

Crystal data
Chemical formula	C9H10N4O
M r	190.21
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	150
a, b, c (Å)	9.7925 (3), 7.9648 (3), 11.8039 (4)
β (°)	113.553 (1)
V (Å3)	843.95 (5)
Z	4
Radiation type	Cu Kα
μ (mm−1)	0.86
Crystal size (mm)	0.36 × 0.15 × 0.12
Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 3 CPAD
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T min, T max	0.84, 0.91
No. of measured, independent and observed [I > 2σ(I)] reflections	18079, 1657, 1626
R int	0.021
(sin θ/λ)max (Å−1)	0.618
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.030, 0.080, 1.07
No. of reflections	1657
No. of parameters	131
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.24, −0.19

Computer programs: APEX4 and SAINT (Bruker, 2021 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL2018/1 (Sheldrick, 2015b ▸), DIAMOND (Brandenburg & Putz, 2012 ▸) and SHELXTL (Sheldrick, 2008 ▸).

Supplementary Material

CCDC reference: 2259950

Additional supporting information: crystallographic information; 3D view; checkCIF report

full crystallographic data

Crystal data

C9H10N4O	F(000) = 400
Mr = 190.21	Dx = 1.497 Mg m−3
Monoclinic, P21/c	Cu Kα radiation, λ = 1.54178 Å
a = 9.7925 (3) Å	Cell parameters from 9958 reflections
b = 7.9648 (3) Å	θ = 4.1–72.3°
c = 11.8039 (4) Å	µ = 0.86 mm−1
β = 113.553 (1)°	T = 150 K
V = 843.95 (5) Å3	Column, colourless
Z = 4	0.36 × 0.15 × 0.12 mm

Data collection

Bruker D8 VENTURE PHOTON 3 CPAD diffractometer	1657 independent reflections
Radiation source: INCOATEC IµS micro—-focus source	1626 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.021
Detector resolution: 7.3910 pixels mm-1	θmax = 72.4°, θmin = 7.4°
φ and ω scans	h = −12→12
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −9→9
Tmin = 0.84, Tmax = 0.91	l = −14→14
18079 measured reflections

Refinement

Refinement on F2	Primary atom site location: dual
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.030	Hydrogen site location: mixed
wR(F2) = 0.080	H atoms treated by a mixture of independent and constrained refinement
S = 1.07	w = 1/[σ2(Fo2) + (0.0413P)2 + 0.2836P] where P = (Fo2 + 2Fc2)/3
1657 reflections	(Δ/σ)max = 0.001
131 parameters	Δρmax = 0.24 e Å−3
0 restraints	Δρmin = −0.19 e Å−3

Special details

Experimental. The diffraction data were obtained from 18 sets of frames, each of width 0.5° in ω or φ, collected with scan parameters determined by the "strategy" routine in APEX4. The scan time was θ-dependent and ranged from 4 to 15 sec/frame.

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 > 2sigma(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. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.98 Å) and included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms. That attached to nitrogen was placed in a location derived from a difference map and was refined independently.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.26314 (8)	0.43095 (10)	0.61185 (6)	0.0244 (2)
N1	0.41264 (9)	0.32811 (10)	0.34454 (7)	0.0175 (2)
H1	0.4489 (16)	0.3032 (18)	0.2857 (14)	0.034 (4)*
N2	0.59918 (9)	0.16425 (10)	0.50516 (7)	0.0183 (2)
N3	0.51360 (9)	0.22338 (11)	0.65438 (7)	0.0189 (2)
N4	0.42719 (9)	0.30291 (10)	0.54577 (7)	0.0168 (2)
C1	0.30105 (11)	0.40365 (12)	0.52669 (9)	0.0180 (2)
C2	0.22902 (11)	0.46080 (12)	0.40036 (9)	0.0180 (2)
C3	0.08681 (11)	0.55964 (13)	0.36710 (10)	0.0227 (2)
H3A	0.111393	0.675596	0.398974	0.027*
H3B	0.025843	0.507898	0.407433	0.027*
C4	−0.00393 (12)	0.56563 (14)	0.22750 (10)	0.0245 (3)
H4A	−0.050592	0.454782	0.198573	0.029*
H4B	−0.084433	0.649834	0.208425	0.029*
C5	0.09473 (12)	0.61123 (13)	0.15965 (9)	0.0236 (2)
H5A	0.142182	0.721576	0.189077	0.028*
H5B	0.032941	0.620358	0.069973	0.028*
C6	0.21483 (11)	0.47830 (13)	0.18183 (9)	0.0215 (2)
H6A	0.169975	0.379239	0.129506	0.026*
H6B	0.292459	0.523786	0.156502	0.026*
C7	0.28651 (11)	0.42377 (12)	0.31498 (9)	0.0172 (2)
C8	0.48158 (10)	0.26443 (12)	0.45921 (8)	0.0160 (2)
C9	0.61124 (11)	0.14311 (12)	0.62317 (9)	0.0185 (2)
H9	0.686309	0.073934	0.680293	0.022*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0287 (4)	0.0296 (4)	0.0208 (4)	0.0032 (3)	0.0161 (3)	−0.0006 (3)
N1	0.0201 (4)	0.0205 (4)	0.0139 (4)	0.0001 (3)	0.0089 (3)	−0.0007 (3)
N2	0.0187 (4)	0.0190 (4)	0.0178 (4)	−0.0010 (3)	0.0079 (3)	−0.0009 (3)
N3	0.0206 (4)	0.0212 (4)	0.0143 (4)	−0.0004 (3)	0.0063 (3)	0.0019 (3)
N4	0.0188 (4)	0.0193 (4)	0.0133 (4)	−0.0007 (3)	0.0076 (3)	0.0002 (3)
C1	0.0195 (5)	0.0171 (5)	0.0196 (5)	−0.0020 (4)	0.0102 (4)	−0.0016 (4)
C2	0.0190 (5)	0.0170 (5)	0.0186 (5)	−0.0019 (4)	0.0083 (4)	−0.0008 (4)
C3	0.0218 (5)	0.0230 (5)	0.0254 (5)	0.0030 (4)	0.0115 (4)	0.0009 (4)
C4	0.0194 (5)	0.0222 (5)	0.0283 (6)	0.0025 (4)	0.0057 (4)	−0.0001 (4)
C5	0.0258 (5)	0.0211 (5)	0.0189 (5)	0.0010 (4)	0.0037 (4)	0.0013 (4)
C6	0.0239 (5)	0.0240 (5)	0.0157 (5)	0.0000 (4)	0.0069 (4)	0.0004 (4)
C7	0.0178 (5)	0.0161 (5)	0.0175 (5)	−0.0030 (3)	0.0067 (4)	−0.0011 (4)
C8	0.0182 (4)	0.0164 (5)	0.0152 (4)	−0.0036 (3)	0.0087 (4)	−0.0025 (3)
C9	0.0182 (5)	0.0188 (5)	0.0176 (5)	−0.0015 (4)	0.0063 (4)	0.0006 (4)

Geometric parameters (Å, º)

O1—C1	1.2222 (12)	C3—C4	1.5287 (14)
N1—C8	1.3471 (12)	C3—H3A	0.9900
N1—C7	1.3724 (13)	C3—H3B	0.9900
N1—H1	0.919 (15)	C4—C5	1.5247 (15)
N2—C8	1.3258 (13)	C4—H4A	0.9900
N2—C9	1.3605 (12)	C4—H4B	0.9900
N3—C9	1.3192 (13)	C5—C6	1.5253 (14)
N3—N4	1.3762 (11)	C5—H5A	0.9900
N4—C8	1.3625 (12)	C5—H5B	0.9900
N4—C1	1.4135 (13)	C6—C7	1.5066 (13)
C1—C2	1.4449 (14)	C6—H6A	0.9900
C2—C7	1.3687 (14)	C6—H6B	0.9900
C2—C3	1.5087 (13)	C9—H9	0.9500
C8—N1—C7	120.21 (8)	C3—C4—H4B	109.5
C8—N1—H1	119.2 (9)	H4A—C4—H4B	108.1
C7—N1—H1	120.5 (9)	C4—C5—C6	110.58 (8)
C8—N2—C9	101.49 (8)	C4—C5—H5A	109.5
C9—N3—N4	101.96 (7)	C6—C5—H5A	109.5
C8—N4—N3	108.42 (8)	C4—C5—H5B	109.5
C8—N4—C1	125.93 (8)	C6—C5—H5B	109.5
N3—N4—C1	125.63 (8)	H5A—C5—H5B	108.1
O1—C1—N4	120.21 (9)	C7—C6—C5	112.64 (8)
O1—C1—C2	127.54 (9)	C7—C6—H6A	109.1
N4—C1—C2	112.23 (8)	C5—C6—H6A	109.1
C7—C2—C1	121.15 (9)	C7—C6—H6B	109.1
C7—C2—C3	121.96 (9)	C5—C6—H6B	109.1
C1—C2—C3	116.88 (9)	H6A—C6—H6B	107.8
C2—C3—C4	112.04 (8)	C2—C7—N1	121.71 (9)
C2—C3—H3A	109.2	C2—C7—C6	123.29 (9)
C4—C3—H3A	109.2	N1—C7—C6	114.96 (8)
C2—C3—H3B	109.2	N2—C8—N1	129.96 (9)
C4—C3—H3B	109.2	N2—C8—N4	111.37 (8)
H3A—C3—H3B	107.9	N1—C8—N4	118.66 (9)
C5—C4—C3	110.87 (8)	N3—C9—N2	116.74 (9)
C5—C4—H4A	109.5	N3—C9—H9	121.6
C3—C4—H4A	109.5	N2—C9—H9	121.6
C5—C4—H4B	109.5
C9—N3—N4—C8	−0.54 (10)	C1—C2—C7—C6	179.19 (9)
C9—N3—N4—C1	177.90 (9)	C3—C2—C7—C6	0.39 (15)
C8—N4—C1—O1	−179.38 (9)	C8—N1—C7—C2	1.57 (14)
N3—N4—C1—O1	2.46 (15)	C8—N1—C7—C6	−176.34 (8)
C8—N4—C1—C2	1.78 (14)	C5—C6—C7—C2	13.45 (14)
N3—N4—C1—C2	−176.39 (8)	C5—C6—C7—N1	−168.67 (8)
O1—C1—C2—C7	178.33 (10)	C9—N2—C8—N1	−178.78 (10)
N4—C1—C2—C7	−2.93 (13)	C9—N2—C8—N4	0.72 (10)
O1—C1—C2—C3	−2.81 (15)	C7—N1—C8—N2	176.72 (9)
N4—C1—C2—C3	175.93 (8)	C7—N1—C8—N4	−2.74 (14)
C7—C2—C3—C4	16.83 (14)	N3—N4—C8—N2	−0.13 (11)
C1—C2—C3—C4	−162.02 (9)	C1—N4—C8—N2	−178.56 (8)
C2—C3—C4—C5	−47.48 (12)	N3—N4—C8—N1	179.43 (8)
C3—C4—C5—C6	62.20 (11)	C1—N4—C8—N1	1.00 (14)
C4—C5—C6—C7	−43.86 (11)	N4—N3—C9—N2	1.08 (11)
C1—C2—C7—N1	1.46 (15)	C8—N2—C9—N3	−1.16 (11)
C3—C2—C7—N1	−177.34 (9)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N3i	0.919 (15)	1.907 (15)	2.8208 (12)	173.1 (13)
C9—H9···O1ii	0.95	2.57	3.3282 (12)	137

Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) −x+1, y−1/2, −z+3/2.