(S)-4-Phenyl-2-(1,2,3,4-tetrahydroisoquinolin-3-yl)-1,3-thiazole

In the title compound, C18H16N2S, the N-containing ring adopts a half-chair configuration. The crystal packing features C—H⋯N contacts. There is no π–π stacking within the crystal structure.


Related literature
The title compound is a potential ligand for the asymmetric Henry reaction. For the application of these ligands as catalysts, see: Chakka et al.   Table 1 Hydrogen-bond geometry (Å , ).

Comment
Tetrahydroisoquinoline is a core structure in various natural and pharmaceutically active compounds, displaying a broad spectrum of activity. Molecules with a C 1 -symmetric tetrahydroisoquinoline backbone have been studied for various catalytic reactions such as allylic alkylation (Blanc et al.,2003), Henry reactions (Kawthekar et al., 2010), asymmetric hydrogenation reactions (Chakka et al.,2010;Peters et al., 2010) and Diels-Alder reactions (Naicker et al.,2010). The title compound is one of the ligands used for asymmetric Henry reaction, its' catalytic activity is currently under investigation. The chiral carbon (C9) has been assigned an S configuration from two-dimensional NMR measurements.

Experimental
The N-protected thiazole (3 mmol) was dissolved in THF (15 ml), to this 12 M HCl (15 ml) was added slowly and the reaction mixture was stirred at room temperature for 2 h. THF was evaporated under vacuum. The reaction was monitored by TLC using EtOAc/Hexane (20:80, R f = 0.5). The reaction mixture was slowly poured into aqueous saturated NaHCO 3 solution, the mixture was then extracted with CH 2 Cl 2 (3 x 30 ml). The combined organic layer was dried over MgSO 4 . The solvent was evaporated under reduced pressure, the residue was purified by column chromatography on silica gel (deactivated with 5% Et 3 N) with Et 3 N/EtOAc/Hexane (5/8/100) as the eluent to afford the thiazole as a yellow solid (0.27 g, yield 95%).

M.p. = 357-360 K.
Recrystallization from tetrahydrofuran at room temperature afforded colourless crystals suitable for X-ray analysis.

Refinement
All non-hydrogen atoms were refined anisotropically. All hydrogen atoms, except H1N, were positioned geometrically with C-H distances ranging from 0.95 Å to 1.00 Å and refined as riding on their parent atoms with U iso (H) = 1.2 -1.5 U eq (C).