(S)-Benzyl 3-phenylcarbamoyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

There are two independent molecules in the asymmetric unit of the title compound, C24H22N2O3. The heterocyclic ring assumes a twisted boat conformation and N—H⋯O interactions help to construct the three-dimensional network within the crystal packing.


M. Maguire Comment
The tetrahydroisoquinoline (TIQ) molecule and its derivatives have been widely investigated for their biological and pharmaceutical properties (Sridharan et al. 2011). Our research currently focuses on the evaluation of novel TIQ compounds for their potential biological activity and as a source of chirality in the synthesis of novel asymmetric catalysts.
The title compound is a precursor in the synthesis of novel asymmetric catalysts and containing a tetrahydroisoquinoline framework (Peters et al. 2010).
The title structure was derived from commercially available S-phenyl glycine and formaldehyde. The absolute stereochemistry was confirmed to be S at the C9 position from proton NMR spectroscopy (Peters et al. 2010).
The structure has two molecules in the asymmetric unit (Fig. 1). The molecules display intermolecular hydrogen bonding via the amide and carbamate carbonyl group. (Table 1). This bonding arrangement creates chains which link the molecules together resulting in layers parallel to the 100 plane. (Fig. 2).

Experimental
(S)-2-(Benzyloxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1.5 g, 4.8 mmol) was dissolved in DMF (15 ml) followed by addition of EDC.HCl (1.1 g, 5.8 mmol), HOBt (0.81 g, 5.3 mmol), a catalytic amount of DMAP and aniline (5.3 mmol). The reaction mixture was then stirred at room temperature until no more starting material could be detected by TLC analysis (approximately 1 h). The reaction mixture was poured into 30 volumes of chilled water; the mixture was then extracted twice with ethyl acetate. The extracts were combined, washed with 10% aqueous HCl to remove latent EDC urea, dried over anhydrous magnesium sulfate and then concentrated to dryness affording the crude product which was purified by column chromatography. (Hexane:EtOAc 60:40 R f 1/2).
Melting point = 410-412 K Recrystallization from ethyl acetate at room temperature afforded crystals suitable for X-ray analysis.

Refinement
All non-hydrogen atoms were refined anisotropically. The hydrogen atoms H2A and H2B were located in the difference density maps and refined with simple bond length constraints with d(N-H) = 0.970 (2) Å. The remaining hydrogen atoms could all be found in the difference electron density maps but were finally placed in idealized positions and refined in riding models with U iso set at 1.2 or 1.5 times those of their parent atoms. The Friedel pairs were merged. software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).

Figure 1
The molecular structure of the title compound with the atom numbering scheme. Displacement ellipsoids are drawn at the 40% probability level. Hydrogen atoms have been omitted for clarity.

Special details
Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.