Preparation and structure of 4-(dimethylamino)thiopivalophenone – intermolecular interactions in the crystal

1 Introduction

Quite a number of thioketones have been studied by X-ray diffraction analyses. However, crystal structures of only three tert-alkyl aryl thioketones, the cyclohexane derivative 1 [1], the β-arylethyl derivative 2 [2], and a complex tricyclic benzocyclopentenethion [3], are found in the Cambridge Structural Database [4].

We were particularly interested in the electronic structure of this type of thioketones, which would depend on the geometry of the molecule, for instance on the torsion angle between the arene ring and the thiocarbonyl moiety. This, on the other hand, should be significantly influenced by the mesomeric effect of a substituent at the arene ring. In this communication we present our experimental single-crystal X-ray diffraction and quantum chemical results on 4-(dimethylamino)thiopivalophenone 3 which exhibits the para-dimethylamino group as a strong electron donor substituent.

2 Results and discussion

We have prepared tert-butyl 4-dimethylaminophenyl thioketone (4-dimethylamino-thiopivalophenone) (3) from 4-dimethylaminophenyllithium, pivalonitrile and carbon disulfide by use of the Ahmed-Lwowski method [5] (Scheme 1), which we had also successfully applied for the synthesis of the related tert-butyl 4-tert-butylphenyl thioketone [6].

Scheme 1:

(1) n-BuLi, (2) Me₃C–CN, (3) CS₂, (4) heating to T=60–70°C.

The thioketone 3 was obtained as red-violet crystals which were suitable for X-ray diffraction. An Ortep plot of the compound is shown in Fig. 1. Selected bond lengths, bond angles and torsion angles of 3 are compiled in Table 1.

Fig. 1:

Ortep plot of 3. Displacement ellipsoids are drawn at the 40% probability level. Hydrogen atoms are omitted for clarity.

Table 1:

Selected experimental (X-ray diffraction), semi-empirical (PM7), and theoretical (DFT) bond distances, angles and dihedral angles for 3 as a single molecule and in the crystal.

Bond lengths (pm)					Bond angles (deg)
	X-ray	PM7	DFTa	DFTb		X-ray	PM7	DFTa	DFTb
C7–S1	164.8(6)	160.5	168.9	166.8	S1–C7–C8	118.1(4)	125.4	120.7	119.7
C7–C8	154.3(8)	151.8	160.0	155.2	S1–C7–C1	120.0(5)	118.6	118.5	119.5
C1–C7	143.4(8)	146.8	150.7	146.9	C1–C7–C8	121.9(5)	116.0	120.8	120.9
C4–N1	134.6(7)	140.4	141.1	136.9	C2–C1–C6	114.0(5)	119.2	115.6	115.4
C1–C2	140.6(8)	139.6	143.5	141.8	C3–C4–C5	115.1(5)	118.4	116.3	116.7
C2–C3	137.2(9)	138.7	141.0	138.5	C1–C6–C5	124.1(6)	120.5	122.7	122.9
C3–C4	140.6(8)	140.9	144.1	142.0	C4–C5–C6	121.6(6)	120.4	121.4	121.1
C4–C5	141.5(8)	141.2	144.3	142.3	C1–C2–C3	122.8(6)	120.6	122.5	122.6
C5–C6	135.6(9)	138.6	140.6	138.1	C2–C3–C4	122.3(6)	120.5	121.5	121.2
C6–C1	140.6(8)	139.9	143.7	141.8	Torsion angles (deg)
N1–C12	145.6(9)	147.3	149.2	145.9
N1–C13	1144.9(8)	147.4	149.3	145.7	S1–C7–C1–C6	−27.3	−82.1	−39.4	−25.9
					C8–C7–C1–C2	−28.6	−82.1	−42.4	−27.9
					C3–C4–N1–C12	0.3	−2.0	−8.3	0.4
					C5–C4–N1–C13	3.7	49.4	11.6	1.5

1. ^aSingle molecule (gas phase), CP2K^QZV2PD3BJ. ^bMean values of the four molecules in the unit cell, CP2K^QZV2PD3BJ, see text and Supporting Information. QZV2PD3BJ=Basis set notation with Grimme’s D3 correction and Becke-Johnson damping.

Inspection of the data in Table 1 and comparison with literature data of related thioketones compiled in Table 2 shows that 3 exhibits peculiar structural features.

Its geometry deviates significantly from the expected standard geometry. The C=S bond is elongated whereas the C_ar–C(S) single bond is shortened compared with 1 and 2, and the C–NMe₂ bond is shortened compared with the dimethylaminobenzenes 4 [7] and 5 [8] (Scheme 2) which do not exhibit a substituent with –m effect in the para-position.

Scheme 2:

Compounds comparable with 3.

Even the six C–C bonds in the phenyl ring of 3 are not equally long as emphasized by bold italic types in Table 2. Thus, the six-membered cycle is not perfectly aromatic but exhibits considerable quinodimethane character. Furthermore, the torsion angle Θ₁ between the thioketone plane and the arene plane is only 28° compared with 48° for 1 and 77° for 2, and the dimethylamino group of 3 is nearly coplanar (Θ₂=2°) with the arene ring as compared to Θ₂ values of up to 20.8° for the various dimethylamino groups of 5 [8].

This indicates a distinct contribution of the dipolar resonance formula 3a to the structure of the thioketone, which can thus be considered as a phenylogous thioamide (Scheme 3).

Scheme 3:

Resonance of the thioketone 3.

A similar effect is observed for the phenylogous thiourea 4,4′-bis(dimethylamino)thiobenzophenone 6 [9], cf. Table 2. The phenylogous amide character of 4-aminoacetophenone 7 [10], on the other hand, is less pronounced as compared with 3, cf. Table 2.

3 Computational results

Computations of molecular structures in the solid state have emerged tremendously during the last decade [11], [12], [13]. Particularly, significant improvements have been achieved with DFT-type calculations considering weak attractions between atoms and molecules known as London dispersion forces. Grimme and coworkers successfully introduced the atom pairwise dispersion correction with the Becke-Johnson damping scheme (D3BJ) [14], [15], [16], [17].

We chose two different approaches to compare the quantum chemical with the experimental results.

First, we performed calculations on a single gas phase molecule of 3. We applied the semi-empirical PM7 method [18] and DFT calculations particularly utilizing the PBE functional [19], [20] and Ahlrichs’ split valence basis set def2-tzvp [21], [22] by means of the Nwchem program package [23]. The considerably differing PM7 and DFT results are compiled in Table 2. The C=S bond length as calculated by the PM7 method is much too short while the DFT calculation results in a significantly too long C=S bond. Also, the C_Aryl–N and the C–C bond lengths of the phenyl ring are calculated too long compared with the corresponding crystal structure data. Considering the bond angles, the DFT results are closer to the experimental results as the PM7 values. Also the DFT torsion angles agree better with the experimental values as compared to the PM7 results.

Thus, the phenylogous thioamide structure of 3, as is evident from the X-ray diffraction structure is not fully sustained by the theoretical calculations on a single gas phase molecule.

Secondly, we calculated a unit cell consisting of four molecules of 3 to take the intermolecular interactions in the crystal into account, which surely should exhibit a significant impact on the structure. The experimental unit cell, as a reference, was constructed from the cif data deposited at CCDC by means of the program Avogadro [24]. To generate the theoretical unit cell on the basis of the X-ray cell parameters with Z=4, we used the CP2K code [25] developed by Hutter et al. with the Gaussian plane wave method [26] for the condensed phase of 3. Additionally, dispersion correction (D3BJ) was used for both types of DFT calculations, which led to nearly identical results. The differences between the respective distances and angles of the four molecules in the theoretical unit cell are virtually nil (cf. Table S1 and S2 in the Supporting Information available online). Mean values are therefore given in Table 1. Expectedly, the deviations from the single-molecule data are noticeable and the agreement of all bond lengths, bond angles and even the torsion angles as calculated for the unit cell, with the crystal structure, is significantly better (see Table 1).

The experimental (X-ray diffraction) and the calculated (DFT) unit cells are compared in Fig. 2.

Fig. 2:

Unit cell of 3, top: experimental (X-ray diffraction), bottom: theoretical (CP2K, QZV2P incl. D3BJ).

The agreement between the experimental and the theoretical unit cell is quite convincing. Not only the geometric parameters of the four molecules, but also their mutual orientations are exactly reproduced by the calculations as is demonstrated in Fig. 3.

Fig. 3:

Overlay representation of the experimental structure in the background (C atoms black) and the MD-simulated structure (NVE, 300 K, QZV2P basis) in the foreground (C atoms turquoise).

For the sake of a better understanding of the intermolecular forces, we additionally performed MD simulations at T=0, 300, 390 and 500 K (NVE ensemble, 0.5 fs integration step size, QZV2P basis). The resulting interaction energies E_I and dispersion energies E_D (Table 3) were calculated based on the averaged total electronic energy by use of equations (1) and (2), respectively.

These energies are assumed to represent an approximate measure for the binding forces in the crystal.

Increasing values of E indicate decreasing binding forces and contributions of the part of dispersion energy. At room temperature, the averaged interaction energy E_I is calculated as ca. 299 kJ mol⁻¹ whereas the long range contribution E_D (London dispersion) is computed as ca. −63 kJ mol⁻¹. These results appear to be reasonable compared with data published by Grimme’s [16] and Beran’s research groups [27].

Apparently, the attractive dispersion interactions between the numerous C–H entities of the tert-butyl and methyl groups together with the dipole interactions between the thiocarbonyl and the amino groups are decisive for the orientation of the thioketone molecules in the cell. This observed situation is obviously well reproduced by the DFT calculations under consideration of the dispersion forces.

4 Conclusions

4-(Dimethylamino)thiopivalophenone (3) was synthesized from pivalonitrile and 4-bromo-N,N-dimethylaniline according to the Ahmed and Lwowski [5] protocol.

Single crystals of 3 were studied by X-ray diffraction. The thioketone 3 exhibits typical structural features of a phenylogous thioamide.

This experimental result is corroborated by quantum chemical (DFT) calculations. In particular the bond lengths and bond and torsion angles are well reproduced by the calculations if dispersion effects are taken into consideration. Furthermore, this leads to the correct orientation of the four molecules observed in the unit cell.

5 Experimental section

Melting point (corrected): Electrothermal. ¹H NMR (CDCl₃, δ in ppm vs. Me₄Si): Varian EM 360. IR spectrum (KBr pellet): Perkin-Elmer 399. Column chromatography: Silica gel 60 (70–230 mesh, Merck).

6 Supporting information

The calculated bond distances, bond angles and torsion angles of the individual four molecules in the unit cell of 3 are given as Supplementary Material (Table S1 and S2) available online (DOI: 10.1515/znb-2019-0113).