Crystal structures of 6-nitroquinazolin-4(3H)-one, 6-aminoquinazolin-4(3H)-one and 4-aminoquinazoline hemihydrochloride dihydrate

6-Nitroquinazolin-4(3H)-one (C8H5N3O3), 6-aminoquinazolin-4(3H)-one (C8H7N3O) and 4-aminoquinazoline hemihydrochloride dihydrate (C16H19N6O2) were synthesized and their structures were determined by single-crystal X-ray analysis.

In line with this, we synthesized 6-nitroquinazolin-4(3H)one (I), 6-aminoquinazolin-4(3H)-one (II) and 4-aminoquinazoline hemihydrochloride dihydrate (III), which are important intermediates in drug synthesis, and their crystal structures were determined. The hemi-protonated structures may be useful for the preparation of materials important to ISSN 2056-9890 various branches of science, ranging from biology to nanodevice fabrication and to pharmaceuticals (Perumalla et al., 2013).

Structural commentary
Compound I crystallizes in the triclinic space group P1 with one molecule in the asymmetric unit. As a whole, the molecule is nearly planar. The nitro group is rotated slightly with respect to the quinazoline ring system, the C5-C6-N9-O3 and C7-C6-N9-O2 torsion angles being 6.0 (3) and 4.9 (4) , respectively. All bond lengths and angles are normal and in good agreement with those reported previously (Liao et al., 2018;Yong et al., 2008). Fig. 1 shows the molecular structure of I in the solid state. Selected geometric parameters are listed in Table 1.
Compound II crystallizes in the orthorhombic space group Pca2 1 with two crystallographically independent molecules, A and B, in the asymmetric unit (Fig. 2). All the atoms of the molecule (except the amino-group hydrogens) lie in the same plane. The nitrogen atom of the amino group is somewhere between the sp 2 and sp 3 hybridized states, the sum of the valence angles at the nitrogen atom being 349 and 342 in molecules A and B, respectively. All bond lengths and angles  The molecular structure of 6-aminoquinazolin-4(3H)-one (II), showing the two independent molecules, with displacement ellipsoids drawn at the 50% probability level.

Figure 3
The asymmetric unit of compound III with displacement ellipsoids drawn at the 50% probability level.

Figure 1
The molecular structure of 6-nitroquinazolin-4(3H)-one (I), with displacement ellipsoids drawn at the 50% probability level. Table 1 Selected bond lengths (Å ) for I.   In the case of compound III, there are protonated (A) and unprotonated (B) 4-aminoquinazoline molecules (Fig. 3) in the asymmetric unit and they both have a planar structure. Molecule A is protonated at the N1 nitrogen atom and this leads to an elongation of the N1-C2 and N3-C4 bonds and a shortening of the C2-N3 and C4-N9 bonds with respect to the unprotonated molecule B. In both A and B, the nitrogen atom of the amino group is in an sp 2 hybridized state. The sum of the valence angles around the nitrogen atoms in molecules A and B are 360 and 359 , respectively, and the carbon-toamino group nitrogen bond lengths C4-N9 are shorter than the bond lengths observed in compound II (Table 3).
The two independent molecules of compound II are related by a pseudo-center of symmetry and are linked by two N-HÁ Á ÁO hydrogen bonds, forming an R 2 2 (8) motif. An N-HÁ Á ÁN hydrogen bond generates a three-dimensional network ( Table 5, Fig. 5).
The packing analysis of III shows that the protonated and unprotonated 4-aminoquinazoline molecules are linked by intermolecular N-HÁ Á ÁN hydrogen bonds, forming pseudocentrosymmetric dimers characterized by a donor-acceptor distance of 2.786 (3) Å . Other N-HÁ Á ÁN hydrogen bonds form centrosymmetric R 2 2 (8) ring motifs. The chloride anion and water molecules form hydrogen-bonded chains consisting of fused five-membered rings with the participation of two chloride anions and three water molecules. A chain of rings runs through the twofold screw axis parallel to the [010] direction (Fig. 6). The protonated and unprotonated quinazoline molecules link to the chain via N-HÁ Á ÁCl and N-HÁ Á ÁOw hydrogen bonds from the lower and upper side ( Table 6, Fig. 6). The chain direction corresponds to the smallest unit-cell edge and such self-assembly of molecules has also been observed in other quinazoline hydrochloride crystals Hydrogen bonding in the crystal of 6-aminoquinazolin-4(3H)-one (II).

Synthesis and crystallization
Compound I: In a three-necked flask equipped with a mechanical stirrer and reflux condenser, quinazolin-4(3H)one (22.5 g, 0.15 mol) was dissolved in 78 ml of concentrated sulfuric acid at 303 K for 1 h. Then a nitrating mixture (21 ml of nitric acid and 18 ml of concentrated sulfuric acid) was added to the flask under vigorous stirring of the mixture. The reaction mixture was stirred for another hour, maintaining a temperature not higher than 303 K, and then for another hour at room temperature. At room temperature, 45 ml of nitric acid were added dropwise to the reaction mixture over a period of 1 h. The reaction mixture was left at room temperature for 10 h. The contents of the flask were poured into a dish containing ice, the resulting precipitate was filtered off, washed with water and dried and recrystallized from ethanol to obtain 25.7 g of pure compound I as single crystals in 87.4% yield, m.p. 560-562 K.
Compound II: In a three-necked flask equipped with a mechanical stirrer and reflux condenser, 12.6 g (56 mmol) of tin (II) chloride dihydrate (SnCl 2 Á2H 2 O) were cooled in an ice bath and 16.98 ml of concentrated (36%) HCl were added, then 3 g (16 mmol) of quinazolin-4-one as a suspension in 20 ml of ethanol and 7 ml of HCl (36%) were added portionwise with stirring of the mixture. The reaction was carried out for 10-15 minutes at $273 K, 30 min at room temperature and 2 h in a water bath ($363 K). The reaction mixture was left overnight at room temperature, diluted with water, and brought to a strongly alkaline medium (pH = 10-11) with 10% of sodium hydroxide, in which the expected 6amino-3N-quinazoline-4-one was dissolved, so that the chloride was brought to a neutral medium in the presence of acid, and precipitated when converted to an alkaline medium with ammonia. The precipitate was filtered, washed with water until it reached a neutral medium, and dried at room temperature. The precipitate was recrystallized from ethanol and 6.67 g of pure compound II were obtained representing an 88.1% yield, m.p. 589-591 K.
Compound III: Crystals of compound III were obtained as a minor additional product in the reaction of 4-chloroquinazoline with ammonia.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 7. C-bound H atoms were placed in calculated positions and refined to ride on their parent atoms: C-H = 0.93 Å with U iso (H) = 1.2U eq (C). Hydrogen atoms of the water molecules and those bonded to nitrogen atoms were located in electron density difference maps and were freely refined. Table 6 Hydrogen-bond geometry (Å , ) for III.

Figure 6
Part of the crystal structure of III showing the hydrogen-bonding scheme.

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.

6-Aminoquinazolin-4(3H)-one (II)
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.   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.