2-[Carbamothioyl(2-hydroxyethyl)amino]ethyl benzoate: crystal structure, Hirshfeld surface analysis and computational study

The title di-substituted thiourea has hydroxylethyl and ethyl benzoate substituents bound to the same amine-N atom; overall the molecule is twisted. Supramolecular layers are formed in the crystal, with the molecules connected by O—H⋯S and N—H⋯O(carbonyl, hydroxyl) hydrogen bonds.

The title di-substituted thiourea, C 12 H 16 N 2 O 3 S, has the hydroxylethyl and ethyl benzoate substituents bound to the same amine-N atom, and is twisted, having a (+)syn-clinal conformation with the N amine -C-C-O (hydroxyl, carbonyl) torsion angles of 49.39 (13) and 59.09 (12) , respectively; the dihedral angle between the almost planar CN 2 S core and the pendent benzene ring is 69.26 (4) . In the crystal, supramolecular layers propagating in the ac plane are formed via a combination of hydroxyl-O-HÁ Á ÁS(thione), amine-N-HÁ Á ÁO(hydroxyl, carbonyl) hydrogen-bonds. The layers stack along the b axis with inter-digitation of the benzene rings allowing the formation ofstacking [inter-centroid separation = 3.8722 (7) Å ] and parallel C OÁ Á Á interactions. A computational chemistry study shows the conventional hydrogen bonding in the crystal leads to significant electrostatic stabilization but dispersion terms are also apparent, notably through the interactions involving the benzene residue.

Chemical context
The title compound, (I), was characterized crystallographically in a continuation of recent structural studies of tri-substituted thiourea derivatives formulated as (HOCH 2 CH 2 ) 2 NC( S)-N(H)C( O)C 6 H 4 -R-4 for R = Me (Tan, Azizan et al., 2019) and R = NO 2 (Tan et al., 2020): these molecules are known for their various applications including biological activity (Saeed et al., 2014). A convenient synthesis for these molecules is via the reaction of NH 4 (NCS), R 2 NH and ArC( O)Cl to yield R 2 NC( S)N(H)C( O)Ar. In an experiment with R = CH 2 CH 2 OH and Ar = C 6 H 5 , the solution was also heated resulting in an apparent rearrangement with deprotonation of one hydroxyethyl group followed by nucleophilic attachment at the carbonyl-C atom along with protonation of the primary amine and cleavage of the original N-C( O) bond to yield (I), formulated as H 2 NC( S)N(CH 2 CH 2 OH)CH 2 CH 2 O-C( O)C 6 H 5 . The molecular structure of (I) was determined by X-ray crystallography and the supramolecular association investigated by Hirshfeld surface analysis and computational chemistry. ISSN 2056-9890

Structural commentary
The molecule of (I) is shown in Fig. 1 and comprises a disubstituted thiourea molecule with both substitutions occurring at the same amine atom. The CN 2 S atoms of the thiourea core are almost planar, exhibiting a r.m.s. deviation = 0.0054 Å , with the appended C2 and C4 atoms lying 0.0236 (18) and 0.0216 (16) Å to either side of the plane. The conformation of the C2-hydroxylethyl residue is (+)syn-clinal as indicated by the N2-C2-C3-O1 torsion angle of 49.39 (13) . The CO 2 residue is close to co-planar with the (C7-C12)-benzene ring to which it is connected, forming a dihedral angle of 4.83 (9) . The dihedral angle between the least-squares planes through the CN 2 S core and the benzene ring is 69.26 (4) , indicating the molecule is highly twisted. Finally, the N2-C4-C5-O2 torsion angle of 59.09 (12) is indicative of a (+)syn-clinal configuration about the C-C bond, thereby confirming the twisted nature of the molecule.

Supramolecular features
As anticipated, hydrogen bonding plays a key role in the supramolecular assembly of (I); see Table 1 for geometrical data. The combination of hydroxyl-O-HÁ Á ÁS(thione) and amine-N-HÁ Á ÁO(hydroxyl) hydrogen bonds connect molecules into a supramolecular tape propagating along the a-axis direction, Fig. 2 Table 1 Hydrogen-bond geometry (Å , ).

Figure 2
Molecular packing in the crystal of (I): (a) supramolecular tape along the a axis mediated by hydroxyl-O-HÁ Á ÁS(thione) and amine-N-HÁ Á ÁO(hydroxyl) hydrogen bonding shown as orange and blue dashed lines, respectively, (b) supramolecular layer where the tapes of (a) are connected by amine-N-HÁ Á ÁO(carbonyl) hydrogen bonds shown as green dashed lines, (c) detail of C-OÁ Á Á(benzene) interactions shown as red dashed lines and (d) a view of the unit-cell contents down the b axis with (benzene)-(benzene) interactions shown as purple dashed lines.

Figure 1
The molecular structure of (I) showing the atom-labelling scheme and displacement ellipsoids at the 70% probability level.
formation of 12-membered {Á Á ÁHOÁ Á ÁHNCS} 2 and 14membered {Á Á ÁOC 2 NCNH} 2 synthons, each disposed about a centre of inversion, and linked via the edges defined by the amine-N-HÁ Á ÁO(hydroxyl) hydrogen bonds. The tape has a step-ladder topology and projecting laterally to either side of the tape are the remaining amine-H and carbonyl-O atoms, which form the donors and acceptors of amine-N-HÁ Á ÁO(carbonyl) hydrogen bonds to link the tapes into a layer in the ac plane, Fig. 2(b). The directional links between layers are twofold, namelystacking between the centrosymmetrically related benzene rings [inter-centroid separation = 3.8722 (7) for symmetry operation 2 À x, 1 À y, 1 À z] and parallel C OÁ Á Á interactions, Table 1 and Fig. 2(c). These interactions are possible owing to the inter-digitation of the benzene rings along the b-axis direction, as highlighted in Fig. 2(d).

Hirshfeld surface analysis
Structure (I) was subjected to a Hirshfeld surface analysis in order to gain further understanding into the molecular interactions existing within the crystal. This was achieved through Crystal Explorer 17 (Turner et al., 2017) using established methods . A list of d norm contact distances for all identified interactions is given in Table 2. As noted from Fig. 3, several red spots of variable intensity were identified on the Hirshfeld surface of (I), being indicative of close interactions with contact distances shorter than the sum of the respective van der Waals (vdW) radii (Spackman & Jayatilaka, 2009). In particular, the most intense red spot is observed for the amine-N1-H2NÁ Á ÁO1(hydroxyl) hydrogen bond with a d norm distance of 1.92 Å , which is significantly shorter, by 0.69 Å [= Á|(d norm -AEvdW) HÁ Á ÁO | in Table 2], than the vdW value of 2.61 Å (adjusted to neutron values). Other prominent features are due to the hydroxyl-O1-H1OÁ Á ÁS1(thione) and amine-N1-H1NÁ Á ÁO3(carbonyl) hydrogen bonds. Less intense features on the d norm maps of Fig. 3 are due to benzene-C9-H9Á Á ÁC1(thione) and methylene-C3-H3BÁ Á ÁH8(benzene) interactions, and the diminutive spots arise from weaker methylene-C5Á Á ÁO3(carbonyl), methylene-C2-H2AÁ Á ÁS1(thione) and benzene-C9-H9Á Á ÁS1(thione) contacts at distances just shorter or approximately equivalent to the values of the respective AEvdW radii. Apart from the conventional hydrogen bonds and other interactions involving hydrogen, several interactions involving the aromatic ring are apparent.

Table 2
A summary of short interatomic contacts (Å ) for (I) a .
complementary concave and convex shapes indicated by the red and blue regions around the centre of aromatic ring and ester-C6 atom, respectively, in Fig. 4(b). This suggests the interaction could involve a significant contribution from the C6 atom; the C6Á Á ÁCg(benzene) separation is 3.5026 (11) Å as opposed to the O3Á Á ÁCg(benzene) separation of 3.6604 (10) Å , Table 1. In order to confirm the above findings, particularly the short contacts as well as the interactions involving the aromatic ring, electrostatic potential (ESP) mapping was also performed on the Hirshfeld surface using the DFT-B3LYP quantum level of theory and 6-31G(d,p) basis set as available in Crystal Explorer 17 (Turner et al., 2017). The ESP charge for each Hatom donor and acceptor of the relevant close contacts are tabulated in Table 3. As expected for the conventional hydrogen bonds detected through PLATON (Spek, 2020), significant differences are observed in the electrostatic potentials of the hydrogen-bond donor and acceptor atoms, indicating a strong attraction. Similar observations are noted for the other identified contacts but with smaller differences with the notable exception of the methylene-C3-H3BÁ Á ÁH8(benzene) contact, for which both interacting hydrogen atoms exhibit a positive electrostatic potential signifying that the interaction is dispersive in nature. As for theinteraction, it has already been established that the 936 Tan and Tiekink C 12 H 16 N 2 O 3 S Acta Cryst. (2020). E76, 933-939 research communications Table 3 Electrostatic potential charge (V ESP ) for each hydrogen atom donor and acceptor in (I) participating in a close contact identified through Hirshfeld surface analysis.    The electrostatic potential mapped onto the Hirshfeld surface for (I) within the range À0.0672 to 0.0620 atomic units for (a) the upper side of the ester group (circled blue region) and -ring system (circled red region) and (b) the reverse sides of the ester group (circled faint-blue region) and -ring system (circled faint-red region). The images highlight the charge complementarity between the specified interactions.
contacts arise to charge complementarity between the rings. Concerning the C O3Á Á Á contact, occurring between benzene rings separated by an inter-centroid separation of 4.5890 (7) Å , the ester-C6 atom exhibits positive ESP of +0.0127 a.u. on one side to complement the negative ESP of À0.0114 a.u. at the centre of the aromatic ring it interacts with, Fig. 5(a). At the same time it has an ESP charge of +0.0223 a.u. on the reverse side that complements the other side of a symmetry related aromatic ring, involved in thecontact with an inter-centroid distance of 3.8722 (7) Å , with the ESP charge of À0.0091 a.u., Fig. 5(b). The close contacts were also investigated through fingerprint plot analysis, shown in the upper views of Fig. 6. The d norm -mapped Hirshfeld surfaces for the most prominent point-to-point interactions, giving rise to the most discernible peaks in the fingerprint plots, are shown in the lower views of Fig. 6. In general, (I) exhibits a paw-like, overall fingerprint profile, Fig. 6(a), which can be mainly delineated into HÁ Á ÁH (51.1%), HÁ Á ÁO/ OÁ Á ÁH (14.6%), HÁ Á ÁS/ SÁ Á ÁH (14.5%), HÁ Á ÁC/ CÁ Á ÁH (7.2%), CÁ Á ÁC (6.0%) contacts, Fig. 6(b)-(e), as well as other minor contacts which constitute about 6.0% of the remaining contacts. A further analysis on the respective fingerprint plots shows that the distribution for the (internal)-OÁ Á ÁH-(external), (internal)-SÁ Á ÁH-(external) and (internal)-CÁ Á ÁH-(external) are slightly more dominant than the (internal)-HÁ Á ÁX-(external) counterparts (X = O, S, and C), with the distribution being 8.0, 9.3 and 4.0% as against 6.6, 5.2 and 3.2%, respectively. These results tally with the fact that (I) has more hydrogen-bond acceptors than hydrogen-bond donor atoms. Nonetheless, both (internal)-XÁ Á ÁH-(external) and (internal)-HÁ Á ÁX-(external) exhibit equivalent contact distances that are tipped at the minimum d i + d e values, which correspond to the specified contacts in Table 2.
The crystal of (I) is mainly sustained by electrostatic forces owing to the presence of the relatively strong hydrogenbonding interactions, viz. amine-N1-H1NÁ Á ÁO3(carbonyl) that propagates along the c axis together with amine-N1-H2NÁ Á ÁO1(hydroxyl) and hydroxyl-O1-H1OÁ Á ÁS1(thione), which extend along the a axis, thereby forming a step-ladder framework as shown in Fig. 7(a). On the other hand, significant dispersion force is also present as evidenced from the wire mesh-like dispersion energy framework predominantly governed by theinteractions, with contributions from the interactions involving the benzene-C9 atom, Fig. 7(b). Overall, the combination of electrostatic and dispersion forces leads to a cuboid-like framework shown in Fig. 7(c).

Database survey
Crystal-structure determinations of organic molecules of the general formula R(R 0 )NC( S)NH 2 are comparatively rare with the simplest derivative being the R = R 0 = Me species, the almost planar molecule being first reported in 1994 (WIFKOL; Pathirana et al., 1994). Similarly, derivatives bearing hydroxyl groups are uncommon and include the relatively simple derivatives shown in Fig. 8, i.e. acyclic (II) (IYAYAJ; Griffiths et al., 2010) and cyclic imidazolidine-2-thione (III) (DOJSUT; Lee et al., 2018).

Synthesis and crystallization
Compound (I) was synthesized by gently heating an acetone mixture (30 ml) containing ammonium thiocyanate (Fisher, 1 mmol), benzoyl chloride (Acros, 1 mmol) and bis(hydroxy- Perspective views of the energy frameworks of (I), showing the (a) electrostatic force, (b) dispersion force and (c) total energy. The radii of the cylinders are proportional to the relative strength of the corresponding energies and were adjusted to the same scale factor of 100 with a cut-off value of 8 kJ mol À1 within a 2 Â 2 Â 2 unit cells.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 5. The carbon-bound H atoms were placed in calculated positions (C-H = 0.95-0.98 Å ) and were included in the refinement in the riding-model approximation, with U iso (H) set to 1.2U eq (C). The oxygen-and nitrogenbound H atoms were located from a difference-Fourier map and refined with O-H = 0.84AE0.01 Å and N-H = 0.88AE0.01 Å , and with U iso (H) set to 1.5U eq (O) or 1.2U eq (N). DIAMOND (Brandenburg, 2006); software used to prepare material for publication: publCIF (Westrip, 2010). 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.