The crystal structure and Hirshfeld surface analysis of 1-(2,5-dimethoxyphenyl)-2,2,6,6-tetramethylpiperidine

The title compound, 1-(2,5-dimethoxyphenyl)-2,2,6,6-tetramethylpiperidine, was synthesized as a side-product during the synthesis of the intermediate, methyl 3,6-dimethoxy-2-(2-methoxy-2-oxoethyl)benzoate, necessary for the total synthesis of the isocoumarin 5,8-dimethoxy-3-methyl-1H-isochromen-1-one.


Chemical context
During research on phytotoxins produced by the Ceratocystis fimbriata species (Tiouabi, 2005), the pathogenic agents responsible for the infections of plane, coffee and elm trees, analytical and spectroscopic studies enabled the isolation of a number of isocoumarins in small quantities. In order to confirm their molecular structures and especially to study their phytotoxicity and pathogenicity it was necessary to develop efficient methods for the total syntheses of these various isocoumarins. The title compound (3) was synthesized as a side product during the synthesis of the intermediate, methyl 3,6dimethoxy-2-(2-methoxy-2-oxoethyl)benzoate (2) (see Fig. 1), necessary for the total synthesis of the isocoumarin 5,8dimethoxy-3-methyl-1H-isochromen-1-one (Tiouabi, 2005).

Supramolecular features
In the crystal of 3, molecules related by the glide plane are linked by C-HÁ Á ÁO hydrogen bonds, forming chains propagating along the c-axis direction ( Fig. 3 and Table 1). There are no other significant intermolecular interactions present in the crystal.

Hirshfeld surface analysis and two-dimensional fingerprint plots
The Hirshfeld surface analysis (Spackman & Jayatilaka, 2009) and the associated two-dimensional fingerprint plots (McKinnon et al., 2007) were performed with Crystal-Explorer17.5 (Turner et al., 2017). For an excellent explanation of the use of Hirshfeld surface analysis and other calculations, such as energy frameworks, to study the molecular packing see the recent article by Tiekink and collaborators (Tan et al., 2019). The Hirshfeld surface is colour-mapped with the normalized contact distance, d norm , from red (distances shorter than the sum of the van der Waals radii) through white to blue (distances longer than the sum of the van der Waals radii). The energy frameworks (Turner et al., 2015;Tan et al., 2019) are represented by cylinders joining the centroids of molecular pairs using red, green and blue colour codes for the E electrostatic , The molecular structure of compound 3, with atom labelling. Displacement ellipsoids are drawn at the 50% probability level.
E dispersion and E total energy components, respectively. The radius of the cylinder is proportional to the magnitude of the interaction energy. A view of the Hirshfeld surface of 3 mapped over d norm is shown in Fig. 4. The short interatomic OÁ Á ÁH/HÁ Á ÁO contacts are indicated by the faint red spots. A full list of short interatomic contacts in the crystal of 3 are given in Table 2. The most significant contacts, apart from HÁ Á ÁH contacts, are OÁ Á ÁH and CÁ Á ÁH contacts as confirmed by the two-dimensional fingerprint plots (Fig. 5). The principal intermolecular contacts for 3, are delineated into HÁ Á ÁH at 84.1% (Fig. 5b), OÁ Á ÁH/HÁ Á ÁO at 8.3% (Fig. 5c) and CÁ Á ÁH/HÁ Á ÁC at 7.6% ( Fig. 5d) contacts. The intermolecular contacts are therefore dominated by dispersion forces (HÁ Á ÁH at 84.1%; Fig. 5b). This is confirmed by the energy frameworks shown in Fig. 6. The energy frameworks were adjusted to the same scale factor of 80 with a cut-off value of 5 kJ mol À1 within 2 Â 2 Â 2 unit cells, and obtained using the wave function calculated at the HF/3-21G level of theory.

Synthesis and crystallization
The synthesis of compound 3 is illustrated in Fig. 1. It arises as a result of the condensation of 2-bromo-1,4-dimethoxybenzene (1) with tetramethylpiperidene (HTMP). It is a side product obtained during the synthesis of methyl 3,6-dimethoxy-2-(2-methoxy-2-oxoethyl)benzoate (2) (Tiouabi, 2005). Colourless rod-like crystals of 3 were obtained by slow evaporation at room temperature of a solution in acetone.There are no analytical or spectroscopic data available for compound 3.

Refinement details
Crystal data, data collection and structure refinement details are summarized in Table 3. The hydrogen atoms were fixed geometrically (C-H = 0.95-0.99 Å ) and allowed to ride on their parent atoms with U iso (H) = 1.5U eq (C-methyl) and 1.2U eq (C) for other H atoms.

Figure 6
The energy frameworks viewed down the b-axis direction comprising (a) electrostatic potential forces, (b) dispersion forces and (c) total energy for a cluster about a reference molecule of 3. The energy frameworks were adjusted to the same scale factor of 80 with a cut-off value of 5 kJ mol À1 within 2 Â 2 Â 2 unit cells.