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

Ettahiri, W.; Dalbouha, A.; Baouid, A.; Alsubari, A.; Mague, J.T.; Taleb, M.; Ramli, Y.

doi:10.1107/S2414314623004091

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 8| Part 5| May 2023| x230409

https://doi.org/10.1107/S2414314623004091

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

Walid Ettahiri,^a,^b Amal Dalbouha,^a Abdesselam Baouid,^b Abdulsalam Alsubari,^c ^* Joel T. Mague,^d Mustapha Taleb ^a and Youssef Ramli ^e,^f ^*

^aLaboratory of Engineering, Electrochemistry, Modeling and Environment, Faculty of Sciences, Sidi Mohamed Ben Abdellah University, Fez, Morocco, ^bLaboratory of Molecular Chemistry, Faculty of Sciences Semlalia, Cadi Ayyad University, Marrakech, Morocco, ^cLaboratory of Medicinal Chemistry, Faculty of Clinical Pharmacy, 21 September University, Yemen, ^dDepartment of Chemistry, Tulane University, New Orleans, LA 70118, USA, ^eLaboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Morocco, and ^fMohammed VI Center for Research and Innovation (CM6), Rabat 10000, Morocco
^*Correspondence e-mail: alsubaripharmaco@21umas.edu.ye, y.ramli@um5r.ac.ma

Edited by E. R. T. Tiekink, Sunway University, Malaysia (Received 3 May 2023; accepted 9 May 2023; online 12 May 2023)

This article is part of a collection of articles to commemorate the founding of the African Crystallographic Association and the 75th anniversary of the IUCr.

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.

Keywords: crystal structure; π-stacking; hydrogen bonding; triazole; tetrahydroquinazoline.

CCDC reference: 2259950

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).

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) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ ; (ii) $[-x+1, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ .

Figure 1
The title molecule with labeling scheme and 50% probability ellipsoids.

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[F² > 2σ(F²)], wR(F²), 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
Δρ_max, Δρ_min (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 ).

Structural data

CCDC reference: 2259950

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2414314623004091/tk4091sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314623004091/tk4091Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314623004091/tk4091Isup3.cml

checkCIF report

Computing details top

Data collection: APEX4 (Bruker, 2021); cell refinement: SAINT (Bruker, 2021); data reduction: SAINT (Bruker, 2021); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/1 (Sheldrick, 2015b); molecular graphics: DIAMOND (Brandenburg & Putz, 2012); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

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

Crystal data top

C₉H₁₀N₄O	F(000) = 400
M_r = 190.21	D_x = 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 top

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	R_int = 0.021
Detector resolution: 7.3910 pixels mm^-1	θ_max = 72.4°, θ_min = 7.4°
φ and ω scans	h = −12→12
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −9→9
T_min = 0.84, T_max = 0.91	l = −14→14
18079 measured reflections

Refinement top

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(F_o²) + (0.0413P)² + 0.2836P] where P = (F_o² + 2F_c²)/3
1657 reflections	(Δ/σ)_max = 0.001
131 parameters	Δρ_max = 0.24 e Å⁻³
0 restraints	Δρ_min = −0.19 e Å⁻³

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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) top

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) top

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.

Acknowledgements

The support of NSF-MRI Grant #1228232 for the purchase of the diffractometer and Tulane University for support of the Tulane Crystallography Laboratory are gratefully acknowledged. Author contributions are as follows. Conceptualization, MT and AB; methodology, WE and AB; investigation, WE, AD; writing (original draft), JTM and YR; writing (review and editing of the manuscript), YR; formal analysis, YR; supervision, YR and MT; crystal-structure determination and validation, JTM.

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