(1S,3S)-Methyl 6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinoline-3-carboxyl­ate

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

doi:10.1107/S1600536811018782

. 2011 May 25;67(Pt 6):o1501. doi: 10.1107/S1600536811018782

(1S,3S)-Methyl 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

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

PMCID: PMC3120575 PMID: 21754868

Abstract

In the title compound, C₁₉H₂₁NO₄, an organocatalyst with a tetrahydroisoquinoline backbone, the heterocyclic ring assumes a half-boat conformation. The dihedral angle between the aromatic rings is 82.93 (8)°. In the crystal, molecules are linked via N—H⋯O and C—H⋯O hydrogen bonds, forming a layer parallel to (10 Inline graphic ).

Related literature

For related structures, see: Naicker et al. (2010 ▶, 2011 ▶).

Experimental

Crystal data

C₁₉H₂₁NO₄
M _r = 327.37
Monoclinic,
a = 9.3841 (3) Å
b = 6.3453 (2) Å
c = 14.2048 (4) Å
β = 94.475 (2)°
V = 843.25 (4) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 173 K
0.90 × 0.07 × 0.06 mm

Data collection

Nonius KappaCCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.923, T _max = 0.995
4184 measured reflections
2275 independent reflections
2138 reflections with I > 2σ(I)
R _int = 0.010

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.082
S = 1.05
2275 reflections
222 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.13 e Å⁻³

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 (Dolomanov et al., 2009) ▶; software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811018782/is2714sup1.cif

e-67-o1501-sup1.cif^{(20.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811018782/is2714Isup2.hkl

e-67-o1501-Isup2.hkl^{(111.8KB, hkl)}

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
N1—H1N⋯O3ⁱ	0.91 (2)	2.27 (1)	3.0918 (17)	149 (2)
C1—H1⋯O3ⁱⁱ	1.00	2.55	3.503 (2)	160
C19—H19B⋯O2ⁱⁱⁱ	0.98	2.53	3.270 (2)	132

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

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.

supplementary crystallographic information

Comment

The title compound is a novel chiral organocatalyst containing a tetrahydroisoquinoline (TIQ) framework. We have recently reported the use of similar TIQ derivatives as organocatalysts in the Diels-Alder cycloaddition between alpha, beta-unsaturated aldehydes and cyclopentadiene (Naicker et al., 2010).

Diastereomers formed during the synthesis of the title compound were easily separated using column chromatography to yield the TIQ derivative with the stereochemistry as illustrated in Fig. 1. The absolute stereochemistry was confirmed to be S,S at the C1 and C9 positions, respectively, by proton NMR spectroscopy.

The N-containing six-membered ring assumes a half-boat conformation [Q = 0.5537 (16) Å, θ = 53.94 (16)° and φ = 335.3 (2)°]. This observation is similar to a related structure that we recently reported (Naicker et al., 2011). The molecules are linked through N1— H1N···O3ⁱ and C1—H1···O3ⁱⁱ hydrogen bonds (Table 1) into a column stacked along the b axis. The columns are further connected by C19—H19B···O2ⁱⁱⁱ hydrogen bonds, forming a layer parallel to the (101) plane (Fig. 2).

Experimental

To a stirred solution of 1:1 methanol: methylene chloride (6.0 ml) with 4 Å molecular sieves, (S)-methyl 2-amino-3-(3,4-dimethoxyphenyl)propanoate (1.0 g, 4.2 mmol) and benzaldehdye (1.1 eq.) was added under an inert atmosphere. The reaction mixture was allowed to stir for 1.5 h. Thereafter the reaction mixture was filtered and the solvents was removed in vacuo to yield the intermediate imine which was left on a high vacuum pump to remove any residual water for 2 h. The residue was then dissolved in trifluoroacetic acid (20 ml) and refluxed for 3 h. The reaction mixture was then neutralized with a saturated sodium bicarbonate solution and extracted with ethylacetate (4 × 20 ml). The organic extracts were combined and dried over anhydrous Na₂SO₄ and the solvent was removed in vacuo. The crude product (diastereomers) was purified by column chromatography (50:50 EtOAc/Hexane, R_f 1/2) to afford the product 1.20 g (88%) as a white solid. Melting point 370–372 K. IR (neat): 2928, 2600, 1746, 1516, 1250, 1123, 727 cm^-1 [α]²⁰_D = +15.38 (c 0.26 in CHCl₃) ¹H NMR (400 MHz, CDCl₃) δ 7.33 – 7.11 (m, 5H), 6.57 (s, 1H), 6.10 (s, 1H), 5.02 (s, 1H), 3.79 (s, 4H), 3.70 (s, 3H), 3.52 (s, 3H), 3.01 (s, 2H). ¹³C NMR (101 MHz, CDCl₃) δ 172.96, 147.76, 147.41, 143.87, 130.22, 129.04, 128.59, 127.84, 126.07, 111.31, 110.56, 62.85, 56.54, 55.89, 55.84, 52.18, 32.22.

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