The crystal structure of (RS)-7-chloro-2-(2,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one: two hydrogen bonds generate an elegant three-dimensional framework structure

Two independent N—H⋯O hydrogen bonds link all of the molecules into a continuous three-dimensional framework structure. The quinazoline ring adopts an envelope conformation with the 2,5-dimethoxyphenylunit occupying a quasi-axial site.

In the title compound, C 61 H 15 ClN 2 O 3 , the heterocyclic ring adopts an envelope conformation, folded across the NÁ Á ÁN line, with the 2,5-dimethoxyphenyl unit occupying a quasi-axial site. There are two N-HÁ Á ÁO hydrogen bonds in the structure: one hydrogen bond links molecules related by a 4 1 screw axis to form a C(6) chain, and the other links inversion-related pairs of molecules to form an R 2 2 (8) ring. The ring motif links all of the chains into a continuous threedimensional framework structure. Comparisons are made with the structures of some related compounds.

Structural commentary
The molecule of compound (I) contains a stereogenic centre at atom C2, and the reference molecule was selected as one having the R configuration at this atom: the centrosymmetric space group confirms that compound (I) has crystallized as a racemic mixture. The heterocyclic ring in compound (I) adopts a conformation close to the envelope form, in which this ring is folded across the line N1Á Á ÁN3 (Fig. 1). The ring-puckering parameters, calculated for the atom sequence (N1,C2,N3,C4,C4A,C8A) in the R-enantiomer are Q = 0.258 (2) Å , = 121.8 (4) and ' = 219.3 (6) . For the ideal envelope form, the puckering angles take the values = 54.7 (equivalent to 125.3 ) and ' = (60k) , where k represents an integer (Boeyens, 1978). The r.m.s. deviation of the atoms N1, N3, C4, C4A, C8A from their mean plane is only 0.035 Å , with a maximum deviation of 0.0403 (11) Å for atom N3. However, atom C2 is displaced from this plane by 0.355 (3) Å . The 2,5dimethoxyphenyl substituent occupies the quasi-axial site at atom C2. Within this unit, the two methoxy C atoms are almost coplanar with the aryl ring: the deviations from the mean plane of this ring are 0.020 (5) Å for atom C221 and 0.101 (5) Å for atom C251. Associated with this planarity, the two exocyclic C-C-O angles at atoms C22 and C25 are significantly different, by 11.9 at C22 and by 8.2 at atoms C25, as previously observed in planar or near-planar alkoxyarenes (Seip & Seip, 1973;Ferguson et al., 1996).

Supramolecular features
The structure of compound (I) contains just two N-HÁ Á ÁO hydrogen bonds (Table 1) but these are sufficient to link all of the molecules into a three-dimensional framework structure, whose formation is readily analysed in terms of the actions of the two individual hydrogen bonds. The hydrogen bond having atom N1 as the donor links molecules related by the 4 1 screw axis along (0.25, 0.5, z) into a C(6) chain (Etter, 1990;Etter et al., 1990;Bernstein et al., 1995) running parallel to the [001] direction (Fig. 2). Four chains of this type pass through each unit cell. The hydrogen bond having atom N3 as the donor links inversion-related pairs of molecules to form a cyclic dimer characterized by an R 2 2 (8) motif (Fig. 3). This interaction directly links the C(6) chain around the 4 1 screw axis ( 1 4 , 1 2 , z) with four similar chains around the screw axes along ( 3 4 , 1 2 , z), (À 1 4 , 1 2 , z), ( 1 4 , 0, z) and ( 1 4 , 1, z) (Fig. 4). Propagation of these hydrogen bonds by the space-group symmetry operations links all of the C(6) chains, so linking all of the molecules into a very elegant three-dimensional structure generated by only two hydrogen bonds. Symmetry codes: (i) Ày þ 3 4 ; x þ 1 4 ; z þ 1 4 ; (ii) Àx þ 1 2 ; Ày þ 1 2 ; Àz þ 1 2 .

Figure 1
The molecular structure of compound (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
Part of the crystal structure of compound (I) showing the formation of a hydrogen-bonded C(6) chain running parallel to [001]. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.

Database survey
It is of interest briefly to compare the molecular and supramolecular structure of (I) reported here with those of some related structures. In (RS)-2-(2-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (Li & Feng, 2009), the heterocyclic ring has a screw-boat conformation, as opposed to the envelope form in (I). As in (I), the structure contains two N-HÁ Á ÁO hydrogen bonds, and these were described in the original report as generating a polymer along b, but without further specification. However, examination of the published atomic coordinates shows clearly that the molecules are linked into a chain of centrosymmetric, edge-fused rings running parallel to the [100] direction, in which R 2 2 (8) rings centred at (n, 1, 0) alternate with R 2 4 (12) rings centred at (n + 1 2 , 1, 0), where n represents an integer in each case (Fig. 5).
In 5-chloro-3-hydroxy-2,2-dimethyl-2,3-dihydroquinazolin-4(1H)-one (Vembu et al., 2006), the heterocyclic ring again adopts the screw-boat conformation, and a combination of N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds links the molecules into complex sheets, within which rings of S(5), R 2 2 (4) A projection along [001] of part of the crystal structure of compound (I) showing the linking of the C(6) chains by the R 2 2 (8) rings. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, only the heterocyclic ring, along with its hydrogen-bond acceptors and donors, is shown for each molecule.

Figure 5
Part of the crystal structure of (RS)-2-(2-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one showing the formation of a hydrogen-bonded chain of edge-fused rings along [100]. The published atomic coordinates (Li & Feng, 2009) have been used. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the H atoms bonded to C atoms have been omitted.

Figure 3
Part of the crystal structure of compound (I) showing the formation of a cyclic hydrogen-bonded dimer. Hydrogen bonds are drawn as dashed lines and, for the sake of clarity, the unit-cell outline and the H atoms bonded to C atoms have been omitted. The atoms marked with an asterisk (*) are at the symmetry position ( 1 2 À x, 1 2 À y, 1 2 À z).
Finally, we note the structures of a number of 2,3-dihydroquinazolin-4(1H)-ones in which there is a substituent at atom N3 (Butcher et al., 2007;Toze et al., 2018;Zaytsev et al., 2018). In each of these examples, the molecules are linked by a single N-HÁ Á ÁO hydrogen bond to form a C(6) chain. However, when the substituent at atom N3 is an arylmethylamino group, the heterocyclic ring adopts a screw-boat conformation (Butcher et al., 2007), but in five examples where this substituent is either a benzyl group or a furanylmethyl unit, the heterocyclic ring adopts an envelope conformation,

Synthesis and crystallization
A sample of compound (I) was prepared using a recently published general procedure (Narasimhamurthy et al., 2014). Potassium tert-butoxide (3.3 mmol) was added to a suspension of 2-(dibromomethyl)-1,4-dimethoxybenzene (3.3 mmol) and 2-amino-4-chlorobenzamide (3.5 mmol) in a pyridine-dimethylformamide mixture (3:1, v/v). The resulting mixture was heated at 313 K for 4 h, with TLC monitoring. When the reaction was judged to be complete, an excess of water was added, followed by extraction with ethyl acetate (2 Â 20 ml). The combined organic extract was washed with brine and then dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the crude product was purified by column chromatography using silica gel mesh 60-120, with 30% ethyl acetate in hexane as eluent, to give the product (I) in 79% yield. Crystals suitable for single crystal X-ray diffraction were grown by slow evaporation, at ambient temperature and in the presence of air, of a solution in dimethylsulfoxide: m.p. 481-483 K.

Refinement
Crystal data, data collection and structure refinement details are given in Table 2. In the setting of space group I4 1 /a, No. 88, employed here the origin is located at a centre of inversion. All H atoms were located in difference maps. The H atoms bonded to C atoms were then treated as riding atoms in geometrically idealized position with C-H 0.93 Å (aromatic), 0.96 Å (CH 3 ) or 0.98 Å (aliphatic C-H), and with U iso (H) = kU eq (C), where k = 1.5 for the methyl groups, which were permitted to rotate but not to tilt, and 1.2 for all other H atoms bonded to C atoms. For the H atoms bonded to N atoms, the atomic coordinates were refined with U iso (H) = 1.2U eq (N), giving the N-H distances shown in Table 1  Computer programs: APEX2 and SAINT (Bruker, 2015), SHELXS97 (Sheldrick, 2008), SHELXL2014 (Sheldrick, 2015) and PLATON (Spek, 2009 The crystal structure of (RS)-7-chloro-2-(2,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one: two hydrogen bonds generate an elegant threedimensional framework structure Kereyagalahally H. Narasimhamurthy, Chandra, Belakavadi K. Sagar, Kanchugarakoppal S.

(RS)-7-Chloro-2-(2,5-dimethoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one
Crystal data Special details 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.