Structural, Hirshfeld surface and three-dimensional interaction energy studies of 2-(6-iodo-4-oxo-3,4-dihydroquinazolin-3-yl)ethanesulfonyl fluoride

In the crystal, molecules of the title compound are connected through C—H⋯N and C—H⋯O hydrogen bonds, I⋯O halogen bonds, π–π stacking interactions between the benzene and pyrimidine rings, and edge-to-edge electrostatic interactions, as shown by the analysis of the Hirshfeld surface and two-dimensional fingerprint plots, as well as intermolecular interaction energies.


Figure 2
Intermolecular hydrogen (see Table 1) and halogen bonds in the structure of (I).

Figure 3
stacking in the structure of (I).

Figure 1
Molecular structure of (I). The atomic displacement ellipsoids are drawn at the 50% probability level.

Three-dimensional framework analysis of interaction energies
Quantification of intermolecular interactions energies is important for molecular recognition, protein modelling and drug design (Volkov & Coppens, 2004). We computed these energies for (I) with the HF/3-21G(d,p) electron-density model (Grimme, 2006), using CrystalExplorer17.5 software. Eleven molecules surrounding the original one with shortest intermolecular atom-atom distances of 3.8 Å or less were included in the calculations. The total interaction energy (E tot ) between each pair of molecules comprises coloumbic (E ele ), dispersion (E dis ), polarization (E pol ) and exchange-repulsion interaction energies (E rep ) (Turner et al., 2015(Turner et al., , 2017. The E ele , E dis and E tot intermolecular energy frameworks for (I) are shown graphically in Fig. 6 and numerically in Fig. 7. The molecular stacks (   Different aspects of the three-dimensional Hirshfeld surface of (I) mapped over d norm . Red spots indicate shortened contacts, revealing intermolecular hydrogen and halogen bonds

Figure 6
Intermolecular energy frameworks of (a) E ele , (b) E dis and (c) E tot in the structure of (I), viewed down the b axis.
together mostly by dispersion (van der Waals) interactions, supported by the shortest C-HÁ Á ÁO hydrogen bonds, while edge-to-edge intermolecular contacts (lines 5 to 8) have larger contributions of electrostatic interactions. The interaction between halogen-bonded molecules (line 3) is smaller than the above in absolute terms (10.8 kJ mol À1 ), but is remarkable given that only one pair of atoms is actually in contact.

Synthesis and crystallization
To an ice-cooled stirred suspension of NaH (60% suspension in mineral oil; 125 mg, 2.0 mmol, 2.0 equiv) and 6-iodoquinazolin-4(3H)-one (1.0 mmol, 1.0 equiv) in DMF (2 mL), a solution of 2-bromoethanesulfonyl fluoride (350 mg, 1.0 mmol, 1.0 equiv) in DMF (1 mL) was added, under an N 2 atmosphere. The reaction was heated at 353 K for 4 h under an N 2 atmosphere (monitored by TLC). After the complete conversion of the reactants as confirmed from TLC analysis, the reaction mixture was quenched with saturated NH 4 Cl solution (25 mL), extracted with EtOAc (25 mL) and the collected organic layer was further washed with water (25 mL) and brine (25 mL), then dried over anhydrous Na 2 SO 4 and concentrated under vacuum. Compound (I) was isolated by silica gel chromatography (using chloroform and methanol as mobile phase) and recrystallized from DMF.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen atoms were placed in idealized positions and refined using a riding model with C-H 0.93 Å for sp 2 and 0.97 Å for sp 3 C atoms, with U iso (H) = 1.2U eq (C) for both.

Figure 7
Intermolecular energies (in kJ mol À1 ) and their components in the structure of (I). N is the number of molecules in a group, Symop is the symmetry operator, R is the distance between molecular centroids in Å .

2-(6-Iodo-4-oxo-3,4-dihydroquinazolin-3-yl)ethanesulfonyl fluoride
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.