(1R,3S)-N-Benzhydryl-2-benzyl-6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinoline-3-carbothio­amide

Tricia Naicker; Thavendran Govender; Hendrick G Kruger; Glenn E M Maguire

doi:10.1107/S1600536811049324

. 2011 Nov 25;67(Pt 12):o3441. doi: 10.1107/S1600536811049324

(1R,3S)-N-Benzhydryl-2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carbothioamide

Tricia Naicker ^a, Thavendran Govender ^a, Hendrick G Kruger ^b, Glenn E M Maguire ^b,^*

PMCID: PMC3239074 PMID: 22199922

Abstract

The title compound, C₃₈H₃₆N₂O₂S, has a heterocyclic ring that assumes a half-chair conformation. The phenyl rings of neighbouring molecules align forming alternating chains parallel to [100] within the crystal packing. The absolute stereochemistry of the crystal was confirmed to be R,S at the 1- and 3-positions, respectively, by proton NMR spectroscopy. A single intramolecular N—H⋯N hydrogen bond is observed.

Related literature

For background to chiral organocatalysts bearing a tetrahydroisoquinoline framework and for related structures, see: Naicker et al. (2010 ▶, 2011a ▶,b ▶).

Experimental

Crystal data

C₃₈H₃₆N₂O₂S
M _r = 584.75
Orthorhombic,
a = 9.0463 (1) Å
b = 17.6687 (2) Å
c = 19.6178 (2) Å
V = 3135.64 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.14 mm⁻¹
T = 173 K
0.34 × 0.32 × 0.30 mm

Data collection

Nonius KappaCCD diffractometer
7464 measured reflections
7464 independent reflections
6545 reflections with I > 2σ(I)
R _int = 0.013

Refinement

R[F ² > 2σ(F ²)] = 0.033
wR(F ²) = 0.090
S = 1.06
7464 reflections
394 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.19 e Å⁻³
Δρ_min = −0.25 e Å⁻³
Absolute structure: Flack (1983 ▶), 3271 Friedel pairs
Flack parameter: −0.07 (5)

Data collection: COLLECT (Nonius, 2000 ▶); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997 ▶); data reduction: DENZO-SMN; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomov et al., 2009) ▶; software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536811049324/hg5134sup1.cif

e-67-o3441-sup1.cif^{(28KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811049324/hg5134Isup2.hkl

e-67-o3441-Isup2.hkl^{(365.2KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811049324/hg5134Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H1N⋯N1	0.903 (17)	2.139 (16)	2.6548 (15)	115.4 (12)

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Acknowledgments

The authors wish to thank Dr Hong Su from the Chemistry Department of the University of Cape Town for her assistance with the crystallographic data collection and refinement.

supplementary crystallographic information

Comment

Chiral organocatalysts bearing a tetrahydroisoquinoline (TIQ) framework have proven to be very successful by our research group (Naicker et al., 2010 and 2011a). The title compound (Fig. 1) is a precursor in the synthesis of these novel chiral organocatalysts. The crystal structure contains a thioamide moiety at the C10 position making it the first example in this class to be reported.

The absolute stereochemistry of the molecule was confirmed to be R,S at C1 and C9 positions respectively by proton NMR spectroscopy.

The N-containing six membered ring assumes a half chair conformation [Q=0.5212 (12) Å, θ= 50.52 (14)° and φ=325.8 (18)°] similar to an analogous structure which has a methyl ester at the C10 position (Naicker et al., 2011b). This heterocyclic ring shape affects the position of the thioamide moiety relative to the phenyl ring at the C1 position. The torsion angle for C1—N1—C9—C10 is -157.6 (1)°. Also, in the analogous structure the torsion angle between C8—N1—C9—C10 is 44.1 (2)° while in the title structure this angle is -18.3 (2)°. This is probably due to the C═S bond which adopts a more planar orientation relative to the TIQ backbone as compared to the C═O bond orientation previously reported in this family of molecules (Naicker et al., 2011b). In addition, the N-benzyl and phenyl ring at C1 exist in a trans orientation along the N1—C9 bond with a dihedral angle of -153.3 (1)°.

The title compound contains four phenyl rings however, no intermolecular C—H···π or π···π interactions are evident. A single intramolecular hydrogen bond between atoms N2—H1N···N1 can be observed. The molecules within the crystal structure line up such that the phenyl rings face each other, this forms alternating chains parallel to the [100] plane (Fig. 2).

Experimental

To a solution of (1R,3S)-N-benzhydryl-2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (0.1 g, 0.02 mmol) in dry THF (20 ml), Lawssons reagent (0.06 g, 0.15 mmol) was added. The mixture was allowed to stir at 50 °C for 16 h under a nitrogen atmosphere. Thereafter the solvent was evaporated in vacuo and the residue purified using silica column chromatography (hexane: ethyl acetate, 50:50, R_f = 0.8) to yield the pure product (0.1 g, 90%) as a yellow solid. M.p. = 458 K

Recrystallization from ethyl acetate at room temperature afforded crystals suitable for X-ray analysis.