Crystal structure of 2-(2,5-dimethoxyphenyl)benzo[d]thiazole

The title compound was synthesized efficiently in the solid state by exploiting pepsin catalysis. The ring systems are nearly coplanar. A short intramolecular S⋯O=C contact is observed.


Chemical context
Although countless synthetic methods are widely available, new and more efficient procedures or approaches are always needed. Enzymes, as 'green' catalysts for modern organic synthesis, have attracted increased attention because they may provide alternative and sustainable processes, thus helping to minimize the release of hazardous substances into the environment (Witayakran & Ragauskas, 2009). Pepsin, a kind of hydrolase, belongs to the family of aspartic acid proteases and is involved in chemical digestion of protein (Cooper et al., 1990;Lin et al., 1989). Pepsin-catalysed aldol (and other) reactions have been developed (Li et al., 2010;He et al., 2016;Zongbo et al., 2017).
2-Aryl-benzothiazoles are a class of nitrogen-containing heterocyclic compounds that can be found in a variety of natural and synthetic compounds. In view of their biological and pharmacological characteristics, we are interested in developing synthetic strategies for heterocyclic ring systems containing a benzothiazole moiety; these have shown significant biological activity as novel antiviral and antimicrobial agents. (Azzam et al. 2017a(Azzam et al. ,b, 2020a(Azzam et al. ,b,c, 2021Elgemeie et al., 2000aElgemeie et al., ,b, 2020. The conventional synthesis of 2-aryl-benzothiazoles, which involves heating a mixture containing 2-aminothiophenol (1), is disadvantageous because 1 is extremely unstable in air and highly toxic. In a continuation of our recent research in developing 'green' and simple syntheses of novel heterocyclic compounds (Metwally et al., 2020(Metwally et al., , 2021a, we have now synthesized 2-(2,5-dimethoxyphenyl)benzo[d]thiazole (3) using pepsin as the 'green' catalytic reaction. Thus, a mixture of 1 and 2,5-dimethoxybenzaldehyde 2 was ground in a mortar with 0.05 g pepsin for 10 minutes, providing the desired product 3 in 97% yield. The nature of compound 3 was confirmed by spectroscopic analysis and by the single-crystal X-ray structure reported here.

Structural commentary
The structure of 3 is shown in Fig. 1. Molecular dimensions may be regarded as normal; a brief selection is presented in Table 1. Both ring systems are effectively planar (r.m.s. values of 0.01 Å for the benzothiazole and 0.004 Å for the phenyl ring, respectively), with an interplanar angle of 5.38 (2) . The approximate coplanarity leads to the short intramolecular contacts S1Á Á ÁO1 = 2.7082 (4) and H16Á Á ÁN3 = 2.48 Å ; the C16-H16Á Á ÁN3 angle is 101 .

Figure 2
Crystal packing of 3, viewed perpendicular to (100) in the region x ' 0.25. Dashed lines indicate 'weak' C-HÁ Á ÁO hydrogen bonds or C-HÁ Á Á contacts. Atom labels correspond to the asymmetric unit.

Figure 1
The molecule of 3 in the crystal. Ellipsoids represent 50% probability levels.

Synthesis and crystallization
A mixture of o-aminothiophenol 1 (0.01 mol), 2,5-dimethoxybenzaldehyde 2 (0.01 mol) and pepsin (0.05 g) was ground together at room temperature for 10 min. The viscous mixture was poured onto ice-water; the solid that formed was filtered off and recrystallized from ethanol to give pale-yellow crystals of 3 in 97% yield, m.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Methyl groups were refined as idealized rigid groups allowed to rotate but not tip (AFIX 137), with C-H = 0.98 Å , H-C-H = 109.5 . Other hydrogen atoms were included using a riding model starting from calculated positions (C-H aromatic = 0.95 Å ). The U(H) values were fixed at 1.5 or 1.2 Â U eq of the parent carbon atoms for methyl and aromatic hydrogens, respectively. CrysAlis PRO (Rigaku OD, 2021); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: XP (Siemens, 1994); software used to prepare material for publication: SHELXL2018/3 (Sheldrick, 2015b).

2-(2,5-Dimethoxyphenyl)benzo[d]thiazole
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. Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane) -0.2606 (0.0025) x + 11.3686 (0.0009) y -3.5208 (0.0006) z = 4.3561 (0.0009) * -0.0113 (0.0003) S1 * 0.0122 (