Crystal packing analysis of in situ cryocrystallized 2,2,2-trifluoroacetophenone

In this present study, the crystal structure of 2,2,2-trifluoroacetophenone (TFAP) is determined using in situ cryocrystallization techniques. The main objective of this work is to study its crystal packing associated with the various intermolecular interactions, along with a detailed comparison with the features of substituted analogs. It is interesting to note how the chemical substitution of different functional groups influences the crystal packing, the electronic environment of the molecule and the nature of the various intermolecular interactions.


Chemical context
The use of green, efficient, metal-free and inexpensive catalysts is the desire of every synthetic laboratory. The importance of metal-free catalysts is well known among synthetic chemists. In this class of catalysts, 2,2,2-trifluoroacetophenone (TFAP) is well known, because it is cheap and commercially available.
Research work in recent years has shown that TFAP can be used as a green organocatalyst in synthetic procedures, e.g. for the epoxidation of alkenes (Limnios & Kokotos, 2014a), the oxidation of allyloximes to form isoxazoline (Triandafillidi & Kokotos, 2017), the oxidation of aliphatic tertiary amines and azines (Limnios & Kokotos, 2014b) and for the synthesis of substituted tetra-hydrofurans (Theodorou & Kokotos, 2017a), indolines and pyrrolidines (Theodorou & Kokotos, 2017b), besides being used for the synthesis of fluorinated polymers (Guzmá n-Gutié rrez et al., 2008). Interestingly, TFAP has been also used for probing intermolecular interactions involved in the bi-molecular complexes formed on Pt(111) surfaces (Goubert et al., 2011). In fact, TFAP is also an excellent example to study the enantioselective hydrogenation on Pt surfaces (Cakl et al., 2011). Keeping in mind both the important applications of this molecule and our work on intermolecular interactions involving organic fluorine, we decided to determine the crystal structure of this compound. It is worth noting that since TFAP is a liquid at room temperature, a crystal structure determination using conventional methods is not feasible; hence, this class of compounds needs special experimental settings. The method for obtaining crystals of these compounds is called the in situ cryocrystallization technique (Boese et al., 2003;Choudhury et al., 2005). In the recent past, we have employed this technique to obtain crystal structures of both organic (Dey et al., 2016a,b) and organometallic liquids (Sirohiwal et al., 2017a). We believe that this study delineates the importance of fluorine-based interactions, in addition to other weak interactions, which play a role in the crystal packing of TFAP.

Computational methodology
All the calculations were performed at the crystal geometry, where hydrogen-atom positions are fixed to their respective neutron values (Allen, 1986). The lattice and intermolecular interaction energies were computed using the PIXELC module of the CLP program (Version 12.5.2014;Gavezzotti, 2003Gavezzotti, , 2011, which partitions the total energy into Coulombic, polarization, dispersion and repulsion energies. For the same purpose, the molecular electron density was computed at the MP2/6-31G (d, p) level of theory using Gaussian09 (Frisch et al., 2009).

Structural commentary and supramolecular features
The single-crystal X-ray diffraction analysis reveals that the title compound crystallizes in the space group C2/c, and confirms the presence of one -COCF 3 functional group attached to the phenyl ring (see Fig. 1). The backbone of the molecule formed by the atoms O1/C1-C8 is essentially planar, with a maximum deviation from the plane of 0.053 (1) Å for C8. In the molecule, two intramolecular C-HÁ Á ÁF interactions are present, involving C6-H6 and the atoms F1 and F3 (C6-H6Á Á ÁF1, 2.48 Å and 115 ; C6-H6Á Á ÁF3, 2.55 Å and 116 ; Table 1). A total of seven molecular pairs are extracted from the crystal packing based on their stabilizing contribution towards the total lattice energy. Their detailed energy decomposition analysis is listed in Table 2. These molecular pairs are associated through various intermolecular interactions involving aromatic C-H groups as donors and C-F and C O moieties as acceptors. The crystal packing is further 608 Dey et al.  Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) x; y; z À 1; (ii) x; Ày þ 1; z À 1 2 ; (iii) x; Ày; z À 1 2 .

Table 2
Stabilization energies (in kJ mol À1 ) of the individual molecular pairs.  stabilized by the presence ofstacking and of different types of atom-atom contacts, such as intermolecular FÁ Á ÁF, FÁ Á ÁO, and HÁ Á ÁH contacts. The strongest molecular pair I ( Fig. 2a), with an interaction energy of À18.8 kJ mol À1 , is formed via molecular stacking interactions and intermolecular type I FÁ Á ÁF contacts [F3Á Á ÁF3, 2.8743 (1) Å and C8-F3Á Á ÁF3 139 ]. In this case, the dispersion contribution (78%) is more significant in comparison to the electrostatic contribution towards the total stabilization of the dimer. The centrosymmetric molecular pair II (Fig. 2b), which is also formed due tostacking, and to intermolecular F1Á Á ÁC4 interactions, shows an interaction energy of À14.5 kJ mol À1 (18% electrostatic and 82% dispersion contribution). Motif III (involving O1 with F1 and F2), with an interaction energy of À12.7 kJ mol À1 , is stabilized via intermolecular bifurcated FÁ Á ÁO interactions with individual distances of 3.1436 (1) and 3.0457 Å (Fig. 2c). This shows how intermolecular FÁ Á ÁO contacts provide a significant contribution towards the stabilization of the crystal packing, as already investigated in our recent study in terms of the associated nature and energetics (Sirohiwal et al., 2017b).
The overall molecular arrangement shows the formation of a molecular sheet parallel to the bc plane (Fig. 3a). This sheet is constructed via the molecular pairs IV (À10.0 kJ mol À1 ), V (À6.9 KJ mol À1 ) and VI (À6.0 kJ mol À1 ). It is interesting to note the dominance of the electrostatic (54%) over the dispersion (46%) contribution in case of motif IV, which is not to be found in other motifs. A molecular dimeric chain, associated with motif IV, is formed along the crystallographic c-axis direction, involving intermolecular C4-H4Á Á ÁO1 and C5-H5Á Á ÁF2 interactions (Table 1). Such dimeric chains are interlinked alternatively along the b-axis direction either via molecular pairs V (involving C4-H4Á Á ÁO1 interactions and HÁ Á ÁH contacts) or VI (involving bifurcated C-HÁ Á ÁF interactions and FÁ Á ÁF contacts) related by c-glide symmetry. Finally, these parallel molecular sheets are stacked along the a-axis direction (Fig. 3b)

Database survey
Most of the substituted TFAPs are also liquid at room temperature and were crystallized via in situ cryocrystallization methods in the absence of OHCD. In particular, the crystal and molecular structures of 4-fluoro TFAP (SIDMAU), 4-chloro TFAP (SIDLUN), 4-bromo TFAP (SIDLOH), 3-bromo TFAP (SIDLEX), and 3-nitro TFAP (SIDLIB) have been obtained and reported (Chopra et al., 2007). Fig. 4 highlights the similarities and differences of the molecular assemblies for these structures in comparison to unsubstituted TFAP. Interestingly, in most of the cases, the molecular sheets are stacked on each other. The supramolecular assemblies are mainly stabilized via various weak C-HÁ Á ÁO/F/Cl/Br/N interactions and FÁ Á ÁF, FÁ Á ÁO, BrÁ Á ÁO, BrÁ Á ÁF contacts without the presence of any strong interactions. Upon substitution with F, Cl, Br and -NO 2 groups, a molecular chain associated with FÁ Á ÁF contacts is observed. In particular, in the case of the para-substituted chloro and bromo analogs, the FÁ Á ÁF chain is quite similar, wherein in the case of the para-substituted fluoro compound, bifurcated FÁ Á ÁF contacts are present. Finally, in the case of the m-nitro and bromo derivatives, a centrosymmetric, dimeric FÁ Á ÁF chain is observed.

Hirshfeld surface analysis
The Hirshfeld surface analysis was performed using Crystal-Explorer3.3 (Turner et al., 2017) to obtain two-dimensional fingerprint maps (Spackman et al., 2002;McKinnon et al., 2007), which help us to understand the crystalline environment in terms of the contributions of various interatomic contacts present in the crystal packing. The 2D fingerprint plots and the decomposed contributions for different atom- atom contacts in unsubstituted TFAP are shown in Fig. 5. It is observed that the contributions for HÁ Á ÁF (37.4%) and HÁ Á ÁH (19.0%) contacts is relatively high in comparison to the other interatomic contacts. Interestingly, in this case, the fluorine atoms present in the -CF 3 group are more involved in the formation of C-HÁ Á ÁF interactions rather than the formation of FÁÁF (6.9%) contacts. The other contacts, namely CÁ Á ÁH (7.6%), HÁ Á ÁO (8.4%) and FÁ Á ÁO (4.0%) also contribute to the overall crystal packing.

Crystallization, data collection and structure refinement
The compound TFAP was purchased from Sigma-Aldrich and used for the in situ crystallization experiment without any further purification. The detailed procedure of the crystal-lization process is already discussed in one of our previous reports (Dey et al., 2016a). Good quality crystals (Fig. 6a) were obtained at 200 K using a CO 2 laser scan utilizing an OHCD apparatus. Fig. 6b and c depict the crystal at 110 (2) K inside the Lindemann glass capillary and the corresponding diffraction image, respectively. The crystal data, data collection and details on structure refinement are summarized in Table 3. All non-hydrogen atoms were refined anisotropically and the aromatic hydrogen atoms bonded to C atoms were positioned geometrically and refined using a riding model with U iso (H) =1.2U eq (C) and C-H distances of 0.95 Å . Two-dimensional fingerprint plots for TFAP, decomposed into contributions from specific atom-atom contacts.   program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL2016/6 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: CIFTAB (Sheldrick, 2008) and PLATON (Spek, 2009).

2,2,2-Trifluoroacetophenone
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.
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )