Synthesis, crystal structure and Hirshfeld surface analysis of (1H-benzimidazol-2-yl)(morpholin-4-yl)methanethione

In the crystal of the title compound, molecules are linked by N—H⋯N hydrogen bonds into chains running parallel to the c axis.


Chemical context
Benzimidazole is a biologically important compound and a useful structural motif for designing molecules of biochemical and pharmacological relevance. Numerous studies have confirmed that these molecules are effective against various strains of microorganisms (El Ashry et al., 2016). Likewise, substituted benzimidazole derivatives possess various biological activities, including antibacterial (Kazimierczuk et al., 2002), antifungal (Ansari & Lal, 2009), antinematode (Mavrova et al., 2006), antiviral (Pandey & Shukla, 1999), anticancer (Hranjec et al., 2011) and antiprotozoal (Mavrova et al., 2010) properties. Similarly, the morpholine moiety is a versatile and readily accessible synthetic building block; it is easily introduced as an amine reagent or can be built according to a variety of available synthetic methodologies. This versatile scaffold, appropriately substituted, possesses a wide range of biological activities (Walia et al., 2011). Additionally, most drugs containing a morpholine moiety in their structure have been found to exhibit significant biological properties (Basavaraja et al., 2010).
In this context, the title compound with its bifunctional properties (benzimidazole and morpholine derivative, respectively) was synthesized and structurally characterized. The bifunctional properties predispose its potential biological activity, and the three nitrogen and one sulfur atoms can be used in reactions as electrophilic or nucleophilic sites for the formation of heterocyclic compounds.

Supramolecular features
In the crystal, molecules are linked by N2-H2Á Á ÁN1 hydrogen bonds into chains running parallel to the c axis (Table 1, Fig. 2).
Analysis and calculations of the Hirshfeld surface were carried out with CrystalExplorer17.5 (Spackman et al., 2021). The d norm plots were mapped with a colour scale between À0.182 a.u. (blue) and 1.195 a.u. (red) and are shown Fig. 3. The red spots indicate the contribution of N-HÁ Á ÁN hydrogen bonds.
The expanded two-dimensional fingerprint plots (Seth, 2014;McKinnon et al., 2007) are displayed in Fig. 4 where d e and d i are the respective distances to the nearest nuclei outside and inside the surface from the Hirshfeld surface. The most important contributions to the crystal packing originate from HÁ Á ÁH contacts (46.4%), followed by CÁ Á ÁH/HÁ Á ÁC contacts (21.0%) and SÁ Á ÁH/HÁ Á ÁS contacts (15.7%). Numerical data for other contributions are given in Fig. 4.  Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
A view of the crystal packing of the title compound along the a axis. Intermolecular N-HÁ Á ÁN hydrogen bonds are indicated by blue dotted lines. Only the major component of the disordered morpholide ring is shown.

Figure 1
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. Open bonds refer to the minor component of the disordered morpholide ring.

Figure 3
View of the three-dimensional Hirshfeld surface of the title compound plotted over d norm .
zoyl-thiocarbonate moiety, CSD refcode FUTSOF (Ranskiy et al., 2016). In the latter compound, the N and S atoms are bound to a Cu II cation. The corresponding N-C bond lengths within the benzimidazole ring exhibit little difference from those the of title compound, except that the C8-S1 bond length is slightly longer [1.708 (7)
Method (ii): 1.32 g (10 mmol) of 2-methylbenzimidazole, 0.92 ml (0.93 g, d = 1.01 g ml À1 , 11.0 mmol) of morpholine, 0.96 g (30 mmol) of sulfur, 0.11 g (0.46 mmol) Na 2 SÁ9H 2 O and 5 ml of DMSO were mixed and heated in an oil bath at 403-408 K for 10 h. The reaction mixture was cooled to 343 K and extracted three times with 30 ml of a 5% wt NaOH solution. The extracts were combined and filtered. The filtrate was adjusted to pH 5-6 with H 2 SO 4 . The precipitate was filtered off and dried, then recrystallized from benzene and dried again. Yield 1.91 g (77.0%). Melting point 513-515 K, R f = 0.25 (benzene:acetone 3:1 v:v). A single crystal suitable for X-ray diffraction was selected from crystals obtained by method (ii).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Refinement of the structure with an ordered model gave remaining electron difference peaks about 0.5, 0.26 and 0.24 e À Å À3 near the morpholide ring, resulting in R1[F o > 4(F o )] = 0.039. Introduction of a disorder model including split positions for C9, C10, C11 and C12 of the morpholide ring resulted in a occupancy ratio of 0.841 (11):0.159 (11) for the major and minor components (atoms of the minor component denoted by the B). For atom pair C10/C10B, the SHELXL command EADP was used. All C-bound H atoms were positioned geometrically, with C-H = 0.96 Å (for methylene H atoms) and C-H = 0.93 Å (for aromatic H atoms), and were refined with U iso (H) = 1.2U eq (C). The H atom bound to N2 was located in a difference-Fourier map, and its coordinates and isotropic displacement parameter refined freely.     (Rigaku OD, 2020); cell refinement: CrysAlis PRO (Rigaku OD, 2020); data reduction: CrysAlis PRO (Rigaku OD, 2020); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: XP (Siemens, 1994), Mercury (Macrae et al. 2020); software used to prepare material for publication: PLATON (Spek, 2020).

(1H-Benzimidazol-2-yl)(morpholin-4-yl)methanethione
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.