Crystal structure and Hirshfeld surface analysis of 2-methyl­quinazolin-4(3H)-one hydro­chloride

Davlatboev, M.; Allabergenova, S.; Zulpanov, F.; Yakubov, U.; Tojiboev, A.; Sattarov, T.

doi:10.1107/S2056989025000258

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ISSN: 2056-9890

Volume 81| Part 2| February 2025| Pages 144-147

https://doi.org/10.1107/S2056989025000258

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Crystal structure and Hirshfeld surface analysis of 2-methylquinazolin-4(3H)-one hydrochloride

Muzaffar Davlatboev,^a ^* Sevara Allabergenova,^b Fazliddin Zulpanov,^b Ubaydullo Yakubov,^b Akmaljon Tojiboev ^c and Tulkinjon Sattarov ^a

^aNamangan State University, Boburshoh str. 161, Namangan, 160107, Uzbekistan, ^bInstitute of the Chemistry of Plant Substances, Uzbekistan Academy of Sciences, Mirzo Ulugbek Str. 77, Tashkent 100170, Uzbekistan, and ^cUniversity of Geological Sciences, Olimlar Str. 64, Tashkent 100170, Uzbekistan
^*Correspondence e-mail: davlatboyev.muzaffar@mail.ru

Edited by M. Weil, Vienna University of Technology, Austria (Received 14 November 2024; accepted 10 January 2025; online 17 January 2025)

The title salt (systematic name: 2-methyl-4-oxo-3,4-dihydroquinazolin-1-ium chloride), C₉H₉N₂O⁺·Cl⁻, has orthorhombic (Pbcm) symmetry. Except for two methyl H atoms, all atoms of the molecular cation are located about a mirror plane, making the quinazolinium moiety exactly planar. Individual molecules are arranged in (001) layers in the crystal. Supramolecular features include N—H⋯Cl hydrogen-bonding interactions, leading to zigzag chains along [010] with D₁¹(2) and C₁²(6) graph-set motifs. Additionally, weak π–π stacking interactions occur between benzene rings in adjacent layers. Hirshfeld surface analysis revealed that the most important contributions to the surface contacts are from H⋯H (36.1%), H⋯C/C⋯H (25.8%), and H⋯O/O⋯H (17.7%) interactions.

Keywords: quinazolin-4-one; crystal structure; hydrogen-bonding; intermolecular interactions; organic salt.

CCDC reference: 2416982

1. Chemical context

Syntheses based on pyrimidines (quinazolines) condensed with a benzene ring are widely used in agricultural and medical practice (Zayed, 2023 ). In particular, drugs based on compounds of this class are used against viruses, microbes, colds and cancer (Li et al., 2021 ; Arachchige & Yi, 2019 ) as well as stimulants and pesticides (Alsibaee et al., 2023 ). Examples of such types of drugs that have been used successfully against various types of cancer in recent years are imatinib, erlotinib, lapatinib and afatinib. Therefore, targeted syntheses of biologically active compounds containing this pharmacophore (i.e. the quinazoline ring), are important to determine their physical, chemical and biological properties. In this context, we report here the molecular and crystal structures of 2-methyl quinazolin-4(3H)-one hydrochloride (I) and its Hirshfeld surface analysis.

2. Structural commentary

The asymmetric unit of (I) consists of a quinazolinium cation and a Cl⁻ anion (Fig. 1). Except for methyl H atom H11b and its symmetry-related counterpart, all atoms are located on a mirror plane, making the benzene and pyrimidine rings in the cation exactly planar (Fig. 2). The basic heteroatom N1 of the pyrimidine ring is protonated, and the resulting positive charge is delocalized within the –N—C—N– moiety in the ring, making the C2—N1 and C2—N3 bonds shorter than the C4—N3 and C9—N1 bonds. Similar differences were observed in related compounds reported in the literature (Sharma et al., 1993 ; Turgunov et al., 2003 ; Tozhiboev et al., 2005 , Tojiboev et al., 2021 ).

Figure 1
The asymmetric unit of (I) with displacement ellipsoids drawn at the 50% probability level. The dotted turquoise line represents an N—H⋯Cl hydrogen bond.

Figure 2
Packing of (I) (a) along the a axis and (b) along the b axis, showing the π–π interactions.

3. Supramolecular features

In the crystal of (I), the cationic molecules are arranged in flat (001) layers. Individual molecules are linked to Cl⁻ anions through N—H⋯Cl hydrogen-bonding interactions (Table 1) into zigzag chains extending parallel to [010] (Fig. 3), generating D₁¹(2) and C₂¹(6) graph-set motifs (Bernstein et al., 1995 ). In addition, weak highly slipped π–π stacking interactions (Fig. 2) occur between benzene (centroid Cg2) rings in adjacent layers and involve contact distances Cg2⋯Cg2(1 − x, 1 − y, 1 − z) of 4.987 (14) Å (slippage 3.280 Å).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯Cl1	0.86	2.19	3.052 (2)	176
N3—H3⋯Cl1ⁱ	0.86	2.25	3.108 (3)	175
Symmetry code: (i) $[-x, -y, z+{\script{1\over 2}}]$ .

Figure 3
Packing of (I) along the c axis. Hydrogen bonding between N1—H1⋯Cl and N3—H3⋯Cl is shown as blue dotted lines.

4. Hirshfeld surface analysis

A Hirshfeld surface analysis (Hirshfeld, 1977 ) was carried out using CrystalExplorer (Spackman et al., 2021 ) to visualize non-covalent interactions in the crystal packing of (I). The Hirshfeld surface mapped over d_norm is represented in Fig. 4. The white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colours indicate distances shorter or longer than the van der Waals radii, respectively. The bright-red spot near N1 indicates its role as a hydrogen-bond donor towards Cl1.

Figure 4
Three-dimensional Hirshfeld surface of (I) mapped over d_norm.

The most important contributions to the Hirshfeld surface arise from H⋯H contacts at 36.1% (Fig. 5b). C⋯H/H⋯C and O⋯H/H⋯O interactions follow with contributions of 25.8% and 17.7%, respectively (Fig. 5c,d). The classical N—H⋯Cl hydrogen bonds correspond to H⋯Cl/Cl⋯H contacts (10.3% contribution) and show up as a spike (Fig. 5e). Minor contributors are due to C⋯Cl/Cl⋯C (3.3%), N⋯H/H⋯N (2.4%), N⋯Cl/Cl⋯N (2.2%) and C⋯C (1.8%) interactions.

Figure 5
Two-dimensional fingerprint plots for the title compound, showing (a) all interactions, and decomposed into (b) H⋯H, (c) C⋯H/H⋯C, (d) O⋯H/H⋯O, (e) Cl⋯H/H⋯Cl interactions. Values for d_i and d_e represent the closest internal and external distances (in Å) from given points on the Hirshfeld surface.

5. Database survey

A search of the Cambridge Structural Database (CSD, Version 5.43, last update November 2022; Groom et al., 2016 ) for the 2-methylquinazolin-4(3H)-one moiety resulted in twelve hits with a similar planar conformation: ACANLC10 (Etter et al., 1983 ), AWIYIR (Kalogirou et al., 2021a ), BIHJUA and BIHKAH (Liao et al., 2018 ), BOLGAK (Etter et al., 1983) and BOYMAD (Chadwick & Easton, 1983 ), DILFEL (Rybarczyk-Pirek et al., 2013 ), RUGTEV (Kalogirou et al., 2020 ), UQOGAL (Kalogirou et al., 2021b ) and YILLEM (Moghimi et al., 2013 ). The main difference with respect to the molecular structures of these compounds is that the C2—N1 bond in the pyrimidine ring of (I) is slightly longer due to the protonation of the N atom.

6. Synthesis and crystallization

30 g (0.2 mol) of N-acetylanthranilic acid and 76.53 g (1.4 mol) of ammonium chloride were placed in a 250 ml round-bottom flask. The mixture was heated in a sand bath at 498–503 K for 4 h. Then the reaction mixture was cooled and treated with boiling water. The mixture was filtered and brought to pH 7–9, and then was left at room temperature. The precipitate was filtered off, washed with distilled water and dried. Recrystallization from ethanol yielded 20.4 g (76%) of 2-methylquinazolin-4(3H)-one; m.p. 511–513 K, R_f = 0.28. In order to get 2-methylquinazolin-4(3H)-one hydrochloride crystals, the latter was dissolved in a mixture of ethanol and methanol (9:1 v:v) to which 10 drops of 30%_wt HCl solution were added and stirred on a magnetic stirrer for 2 h. Crystal growth was carried out in a drying oven at 303 K. Colourless single crystals suitable for X-ray diffraction analysis were obtained after 5 d.

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms were positioned geometrically (aromatic C—H = 0.93 Å, N—H = 0.86 Å and methyl C—H = 0.96 Å) and treated as riding atoms, with U_iso(H) = 1.2U_eq(aromatic C, N) or 1.5U_eq(methyl C).

Table 2
Experimental details

Crystal data
Chemical formula	C₉H₉N₂O⁺·Cl⁻
M_r	196.64
Crystal system, space group	Orthorhombic, Pbcm
Temperature (K)	295
a, b, c (Å)	10.1221 (5), 13.6533 (4), 6.6248 (3)
V (Å³)	915.55 (7)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	3.37
Crystal size (mm)	0.20 × 0.15 × 0.05

Data collection
Diffractometer	PhotonJet (Cu) X-ray Source
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2020 $[Rigaku OD (2020). CrysAlis PRO. Rigaku Oxford Diffraction, Wroclaw, Poland.]$ )
T_min, T_max	0.600, 1.000
No. of measured, independent and observed [I ≥ 2u(I)] reflections	7833, 977, 824
R_int	0.086
(sin θ/λ)_max (Å⁻¹)	0.616

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.133, 1.01
No. of reflections	977
No. of parameters	84
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.29, −0.35
Computer programs: CrysAlis PRO (Rigaku OD, 2020 $[Rigaku OD (2020). CrysAlis PRO. Rigaku Oxford Diffraction, Wroclaw, Poland.]$ ), SHELXT (Sheldrick, 2015 ), OLEX2-refine (Bourhis et al., 2015 ) and OLEX2 (Dolomanov et al., 2009 ).

Supporting information

CCDC reference: 2416982

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989025000258/wm5743sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989025000258/wm5743Isup2.hkl

checkCIF report

Computing details top

2-Methyl-4-oxo-3,4-dihydroquinazolin-1-ium chloride top

Crystal data top

C₉H₉N₂O⁺·Cl⁻	D_x = 1.427 Mg m⁻³
M_r = 196.64	Cu Kα radiation, λ = 1.54184 Å
Orthorhombic, Pbcm	Cell parameters from 2575 reflections
a = 10.1221 (5) Å	θ = 4.4–70.9°
b = 13.6533 (4) Å	µ = 3.37 mm⁻¹
c = 6.6248 (3) Å	T = 295 K
V = 915.55 (7) Å³	Prizm, colourless
Z = 4	0.20 × 0.15 × 0.05 mm
F(000) = 410.692

Data collection top

PhotonJet (Cu) X-ray Source diffractometer	824 reflections with I ≥ 2u(I)
Detector resolution: 10.0000 pixels mm^-1	R_int = 0.086
ω scans	θ_max = 71.7°, θ_min = 4.4°
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2020)	h = −12→12
T_min = 0.600, T_max = 1.000	k = −16→16
7833 measured reflections	l = −8→5
977 independent reflections

Refinement top

Refinement on F²	0 restraints
Least-squares matrix: full	14 constraints
R[F² > 2σ(F²)] = 0.043	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.133	w = 1/[σ²(F_o²) + (0.0787P)² + 0.2674P] where P = (F_o² + 2F_c²)/3
S = 1.01	(Δ/σ)_max = −0.0005
977 reflections	Δρ_max = 0.29 e Å⁻³
84 parameters	Δρ_min = −0.35 e Å⁻³

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
Cl1	0.15171 (8)	0.09775 (5)	0.75	0.0549 (3)
O1	0.2374 (3)	0.60927 (16)	0.75	0.0819 (9)
N1	0.1883 (2)	0.31959 (17)	0.75	0.0472 (6)
H1	0.1741 (2)	0.25748 (17)	0.75	0.0708 (9)*
C2	0.0870 (3)	0.3786 (2)	0.75	0.0463 (7)
N3	0.1070 (3)	0.47530 (17)	0.75	0.0502 (6)
H3	0.0384 (3)	0.51250 (17)	0.75	0.0753 (10)*
C4	0.2314 (3)	0.5209 (2)	0.75	0.0558 (8)
C5	0.4723 (3)	0.4864 (3)	0.75	0.0622 (9)
H5	0.4897 (3)	0.5532 (3)	0.75	0.0746 (10)*
C6	0.5757 (4)	0.4204 (3)	0.75	0.0679 (9)
H6	0.6625 (4)	0.4428 (3)	0.75	0.0814 (11)*
C7	0.5498 (4)	0.3204 (3)	0.75	0.0659 (9)
H7	0.6197 (4)	0.2762 (3)	0.75	0.0791 (11)*
C8	0.4220 (3)	0.2862 (2)	0.75	0.0584 (8)
H8	0.4052 (3)	0.2192 (2)	0.75	0.0701 (10)*
C9	0.3187 (3)	0.3528 (2)	0.75	0.0469 (7)
C10	0.3423 (3)	0.4534 (2)	0.75	0.0491 (7)
C11	−0.0492 (4)	0.3396 (3)	0.75	0.0610 (9)
H11a	−0.058 (4)	0.274 (4)	0.75	0.0914 (13)*
H11b	−0.090 (3)	0.360 (2)	0.869 (5)	0.0914 (13)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0623 (5)	0.0370 (4)	0.0655 (5)	−0.0071 (3)	−0.000000	0.000000
O1	0.0805 (18)	0.0339 (12)	0.131 (3)	−0.0025 (11)	−0.000000	0.000000
N1	0.0543 (14)	0.0323 (11)	0.0551 (14)	−0.0005 (10)	−0.000000	0.000000
C2	0.0531 (16)	0.0375 (13)	0.0483 (15)	0.0031 (12)	−0.000000	0.000000
N3	0.0558 (15)	0.0351 (12)	0.0597 (14)	0.0064 (11)	−0.000000	0.000000
C4	0.0652 (19)	0.0372 (15)	0.0651 (18)	−0.0022 (13)	−0.000000	0.000000
C5	0.065 (2)	0.0510 (18)	0.070 (2)	−0.0085 (16)	−0.000000	0.000000
C6	0.0526 (19)	0.071 (2)	0.080 (2)	−0.0055 (17)	−0.000000	0.000000
C7	0.0546 (19)	0.067 (2)	0.076 (2)	0.0093 (17)	−0.000000	0.000000
C8	0.0633 (19)	0.0425 (16)	0.069 (2)	0.0071 (14)	−0.000000	0.000000
C9	0.0555 (17)	0.0378 (14)	0.0474 (15)	0.0000 (13)	−0.000000	0.000000
C10	0.0566 (17)	0.0390 (14)	0.0518 (16)	−0.0038 (13)	−0.000000	0.000000
C11	0.0562 (19)	0.0480 (17)	0.079 (2)	0.0000 (15)	−0.000000	0.000000

Geometric parameters (Å, º) top

O1—C4	1.208 (3)	C5—C10	1.391 (5)
N1—H1	0.8600	C6—H6	0.9300
N1—C2	1.304 (4)	C6—C7	1.389 (5)
N1—C9	1.396 (4)	C7—H7	0.9300
C2—N3	1.335 (4)	C7—C8	1.375 (5)
C2—C11	1.478 (5)	C8—H8	0.9300
N3—H3	0.8600	C8—C9	1.386 (4)
N3—C4	1.404 (4)	C9—C10	1.394 (4)
C4—C10	1.452 (5)	C11—H11a	0.91 (5)
C5—H5	0.9300	C11—H11bⁱ	0.93 (3)
C5—C6	1.381 (5)	C11—H11b	0.93 (3)

C2—N1—H1	118.56 (17)	H7—C7—C6	119.6 (2)
C9—N1—H1	118.56 (15)	C8—C7—C6	120.8 (3)
C9—N1—C2	122.9 (2)	C8—C7—H7	119.6 (2)
N3—C2—N1	119.5 (3)	H8—C8—C7	120.4 (2)
C11—C2—N1	120.7 (3)	C9—C8—C7	119.1 (3)
C11—C2—N3	119.9 (3)	C9—C8—H8	120.43 (19)
H3—N3—C2	117.49 (17)	C8—C9—N1	120.1 (3)
C4—N3—C2	125.0 (3)	C10—C9—N1	118.8 (3)
C4—N3—H3	117.49 (16)	C10—C9—C8	121.1 (3)
N3—C4—O1	119.2 (3)	C5—C10—C4	121.7 (3)
C10—C4—O1	126.5 (3)	C9—C10—C4	119.5 (3)
C10—C4—N3	114.3 (2)	C9—C10—C5	118.7 (3)
C6—C5—H5	119.8 (2)	H11a—C11—C2	117 (3)
C10—C5—H5	119.8 (2)	H11b—C11—C2	107.9 (19)
C10—C5—C6	120.4 (3)	H11bⁱ—C11—C2	107.9 (19)
H6—C6—C5	120.1 (2)	H11bⁱ—C11—H11a	105 (2)
C7—C6—C5	119.8 (3)	H11b—C11—H11a	105 (2)
C7—C6—H6	120.1 (2)	H11b—C11—H11bⁱ	116 (4)

O1—C4—N3—C2	180.0	N3—C4—C10—C5	180.0
O1—C4—C10—C5	0.0	N3—C4—C10—C9	0.0
O1—C4—C10—C9	180.0	C4—C10—C5—C6	180.0
N1—C2—N3—C4	0.0	C4—C10—C9—C8	180.0
N1—C9—C8—C7	180.0	C5—C6—C7—C8	0.0
N1—C9—C10—C4	0.0	C5—C10—C9—C8	0.0
N1—C9—C10—C5	180.0	C6—C7—C8—C9	0.0
C2—N3—C4—C10	0.0	C7—C8—C9—C10	0.0

Symmetry code: (i) x, y, −z+3/2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···Cl1	0.86	2.19	3.052 (2)	176
N3—H3···Cl1ⁱⁱ	0.86	2.25	3.108 (3)	175

Symmetry code: (ii) −x, −y, z+1/2.

Acknowledgements

The authors thank the Institute of Bioorganic Chemistry of Academy Sciences of Uzbekistan, Tashkent, Uzbekistan for providing the single-crystal XRD facility.

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