[(1R,3S)-6,7-Dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinolin-3-yl]methanol 2.33-hydrate

Abstract

The title compound, C₁₈H₂₁NO₃·2.33H₂O, is the fourth reported member in a series of (1R,3S)-6,7-dimeth­oxy-1-phenyl-1,2,3,4-tetra­hydro­isoquinoline derivatives used in catalysis as ligands (or their precursors). The N-heterocycle in the structure adopts a half-chair conformation. The dihedral angle between the benzene rings is 77.29 (13)°. There are three ill-resolved water molecules of crystallization in the structure (one of them rotationally disordered about a threefold axis) involved in short contacts probably due to hydrogen bonding.

Related literature

For the synthesis of the ligand, see: Chakka et al. (2009 ▶). For the Henry reaction, see: Kawthekar et al. (2010 ▶). For similar structures, see: Naicker et al. (2009 ▶, 2010a ▶,b ▶); Chakka et al. (2010 ▶).

Experimental

Crystal data

• C₁₈H₂₁NO₃·2.33H₂O

• M _r = 341.39

• Trigonal,

• a = 27.950 (2) Å

• c = 5.8035 (5) Å

• V = 3926 (2) ų

• Z = 9

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 173 K

• 0.13 × 0.12 × 0.09 mm

Data collection

• Bruker Kappa DUO APEXII CCD diffractometer

• 10224 measured reflections

• 4340 independent reflections

• 3707 reflections with I > 2σ(I)

• R _int = 0.022

Refinement

• R[F ² > 2σ(F ²)] = 0.056

• wR(F ²) = 0.162

• S = 1.06

• 4340 reflections

• 226 parameters

• 3 restraints

• H atoms treated by a mixture of independent and constrained refinement

• Δρ_max = 0.60 e Å⁻³

• Δρ_min = −0.30 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; 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

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
O3—H3O⋯O1W	0.99 (4)	1.95 (4)	2.917 (6)	164 (5)

supplementary crystallographic information

Comment

Heterocyclic rings play key roles in a number of areas of organic and inorganic chemistry. As part of an ongoing study employing (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline based metal complexes as catalysts in asymmetric hydride transfer reactions (Chakka et al., 2009) and the Henry reaction (Kawthekar et al., 2010) we synthesized the title compound. The absolute sterochemistry of the diastereomer was confirmed by NMR studies as R,S at C1 and C9. The primary alcohol group displays hydrogen bonding (O3—H3O···O1W)(2.917 (6) A) (Fig 1.).

The first (1R,3S)-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline structure we reported (Naicker et al., 2009) had an ester functionality at the C9 position and its N-heterocycle revealed a half boat conformation. For the title compound the N-heterocycle adopts a half chair conformation, as it does in the remaining two related structures that we have communicated (Naicker et al., 2010a; Naicker et al., 2010b).

There are in the structure of the title compound a number of short O···O contacts involving the crystal water molecules (one of them, O1W, rotationally disordered on a three fold axis), probably due to hydrogen bonding but which could not be considered in detail because of the impossibility to find the water H atoms.

Experimental

A solution of amino ester (0.5 g, 1.5 mmol) in dry THF (20 ml) (Chakka et al., 2009) was added dropwise to a suspension of LiAlH₄ (0.18, 4.5 mmol) in dry THF (20 ml) under N₂ atmosphere at 0 °C. The mixture was stirred at 0 °C for 2 h, and the reaction was monitored with TLC in hexane/ethyl acetate (50/50, R_f = 1/2). Excess lithium aluminium hydride was quenched with saturated sodium sulfate solution at 0 °C. The reaction mixture was filtered and the solid was washed with THF (20 ml). The solvent was evaporated to dryness, ethyl acetate (20 ml) was added, washed with water (2 × 5 ml), the organic layer was separated and dried over anhydrous MgSO₄ to afford the crude amino alcohol. This was purified by gradient column chromatography; solvent A: 10:90 saturated ammonia in MeOH:DCM and solvent B: 2:98 MeOH:DCM to yield 0.33 g (70% yield) of the pale yellow target compound. m.p.= 388–390 K Crystals apt for x-ray diffraction were grown in methanol, at room temperature. The water molecules in the crystal were probably due to contamination of the solvent.

Refinement

There is one main molecule and two and one-third water molecules in the asymmetric unit. Water molecule O1W is disordered on a site of higher rotational (threefold) symmetry than its own (twofold). It has accordingly a high temperature factor (U_iso = 0.0959), for what it was refined isotropically. All hydrogen atoms attached to carbon were positioned geometrically with C—H = 0.95 - 1.00 Å and refined as riding on their parent atoms. The hydrogen atoms H3O and H1N were located in a difference electron density map and refined with simple bond length constraints. In all cases U_iso (H) = 1.2 - 1.5 U_eq (Host). In spite of the low temperature data, the hydrogen atoms on the three water molecules could not be found and therefore were excluded from the final model.

Figures

Fig. 1.

Molecular structure of (I) showing numbering scheme. All non-hydrogen atoms except O1W are shown as ellipsoids with probability level of 30%.

Crystal data

C18H21NO3·2.33H2O	Dx = 1.299 Mg m−3
Mr = 341.39	Mo Kα radiation, λ = 0.71073 Å
Trigonal, R3	Cell parameters from 10224 reflections
Hall symbol: R 3	θ = 2.5–28.3°
a = 27.950 (2) Å	µ = 0.10 mm−1
c = 5.8035 (5) Å	T = 173 K
V = 3926 (2) Å3	Needle, colourless
Z = 9	0.13 × 0.12 × 0.09 mm
F(000) = 1650

Data collection

Bruker Kappa DUO APEXII CCD diffractometer	3707 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.022
graphite	θmax = 28.3°, θmin = 2.5°
0.5° φ scans and ω	h = −37→37
10224 measured reflections	k = −31→37
4340 independent reflections	l = −7→7

Refinement

Refinement on F2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.056	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.162	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	w = 1/[σ2(Fo2) + (0.0985P)2 + 2.1271P] where P = (Fo2 + 2Fc2)/3
4340 reflections	(Δ/σ)max < 0.001
226 parameters	Δρmax = 0.60 e Å−3
3 restraints	Δρmin = −0.30 e Å−3

Special details

Experimental. Half sphere of data collected using SAINT strategy (Bruker, 2006). Crystal to detector distance = 50 mm; combination of φ and ω scans of 0.5°, 60 s per °, 2 iterations.

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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.91196 (8)	0.15356 (9)	0.2897 (4)	0.0468 (5)
O2	0.95248 (8)	0.22297 (9)	0.6202 (3)	0.0484 (5)
O3	0.67745 (12)	0.27007 (15)	0.4378 (6)	0.0809 (9)
H3O	0.675 (2)	0.287 (2)	0.291 (5)	0.097*
O1W	0.6667	0.3333	0.0620 (11)	0.0959 (17)*
O2W	0.82161 (9)	0.36012 (8)	0.0053 (3)	0.0477 (5)
O3W	0.76609 (13)	0.41438 (12)	−0.0962 (6)	0.0806 (8)
N1	0.75539 (10)	0.24710 (8)	0.1792 (4)	0.0370 (5)
H1N	0.7216 (8)	0.2411 (13)	0.108 (5)	0.043*
C1	0.76741 (9)	0.20211 (9)	0.1292 (4)	0.0285 (4)
H1	0.7785	0.2059	−0.0366	0.034*
C2	0.81654 (9)	0.20906 (9)	0.2690 (4)	0.0299 (4)
C3	0.84111 (9)	0.17779 (10)	0.2090 (4)	0.0327 (5)
H3	0.8270	0.1529	0.0825	0.039*
C4	0.88544 (10)	0.18267 (10)	0.3311 (4)	0.0348 (5)
C5	0.90748 (11)	0.22030 (11)	0.5167 (4)	0.0369 (5)
C6	0.88280 (12)	0.25024 (10)	0.5776 (4)	0.0375 (5)
H6	0.8969	0.2749	0.7045	0.045*
C7	0.83662 (10)	0.24501 (9)	0.4548 (4)	0.0314 (5)
C8	0.81126 (12)	0.27861 (10)	0.5265 (4)	0.0399 (6)
H8A	0.8346	0.3171	0.4722	0.048*
H8B	0.8096	0.2793	0.6968	0.048*
C9	0.75403 (13)	0.25544 (11)	0.4300 (4)	0.0411 (6)
H9	0.7287	0.2193	0.5058	0.049*
C10	0.73288 (16)	0.29565 (15)	0.4714 (7)	0.0594 (8)
H10A	0.7417	0.3100	0.6310	0.071*
H10B	0.7516	0.3274	0.3646	0.071*
C11	0.71644 (9)	0.14513 (9)	0.1564 (4)	0.0280 (4)
C12	0.70780 (10)	0.11199 (10)	0.3506 (4)	0.0337 (5)
H12	0.7343	0.1252	0.4715	0.040*
C13	0.66148 (12)	0.06060 (11)	0.3683 (5)	0.0433 (6)
H13	0.6562	0.0387	0.5013	0.052*
C14	0.62243 (11)	0.04056 (11)	0.1934 (6)	0.0463 (7)
H14	0.5909	0.0047	0.2051	0.056*
C15	0.62937 (11)	0.07295 (11)	0.0015 (5)	0.0451 (6)
H15	0.6024	0.0597	−0.1175	0.054*
C16	0.67646 (10)	0.12540 (10)	−0.0156 (4)	0.0374 (5)
H16	0.6811	0.1478	−0.1464	0.045*
C17	0.88839 (12)	0.11055 (14)	0.1231 (6)	0.0509 (7)
H17A	0.9112	0.0931	0.1098	0.076*
H17B	0.8868	0.1260	−0.0264	0.076*
H17C	0.8510	0.0829	0.1711	0.076*
C18	0.97424 (13)	0.25805 (14)	0.8174 (5)	0.0533 (8)
H18A	1.0064	0.2566	0.8759	0.080*
H18B	0.9458	0.2455	0.9375	0.080*
H18C	0.9854	0.2961	0.7738	0.080*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
O1	0.0351 (10)	0.0572 (12)	0.0562 (11)	0.0292 (9)	−0.0095 (8)	−0.0163 (9)
O2	0.0420 (10)	0.0542 (12)	0.0480 (11)	0.0233 (9)	−0.0183 (8)	−0.0117 (9)
O3	0.0626 (17)	0.092 (2)	0.095 (2)	0.0430 (15)	−0.0005 (15)	−0.0043 (17)
O2W	0.0541 (12)	0.0409 (10)	0.0489 (11)	0.0243 (9)	0.0054 (9)	0.0036 (8)
O3W	0.0695 (17)	0.0625 (16)	0.115 (2)	0.0372 (14)	−0.0191 (16)	−0.0032 (15)
N1	0.0478 (12)	0.0286 (10)	0.0405 (11)	0.0235 (9)	−0.0004 (9)	0.0020 (8)
C1	0.0311 (11)	0.0278 (10)	0.0258 (9)	0.0141 (9)	0.0038 (8)	0.0054 (8)
C2	0.0331 (11)	0.0253 (10)	0.0273 (10)	0.0117 (9)	0.0072 (8)	0.0055 (8)
C3	0.0296 (11)	0.0341 (11)	0.0305 (11)	0.0130 (9)	0.0028 (8)	−0.0035 (8)
C4	0.0294 (11)	0.0373 (12)	0.0332 (11)	0.0131 (10)	0.0024 (9)	−0.0009 (9)
C5	0.0372 (12)	0.0357 (12)	0.0328 (11)	0.0143 (10)	−0.0036 (9)	0.0022 (9)
C6	0.0500 (14)	0.0312 (11)	0.0271 (10)	0.0170 (11)	−0.0019 (10)	−0.0004 (9)
C7	0.0410 (12)	0.0218 (10)	0.0298 (10)	0.0145 (9)	0.0017 (9)	0.0031 (8)
C8	0.0631 (17)	0.0325 (12)	0.0303 (11)	0.0284 (12)	−0.0007 (11)	−0.0016 (9)
C9	0.0557 (16)	0.0351 (12)	0.0414 (13)	0.0295 (12)	0.0118 (11)	0.0061 (10)
C10	0.063 (2)	0.0548 (18)	0.072 (2)	0.0387 (17)	0.0177 (16)	0.0012 (15)
C11	0.0309 (11)	0.0252 (10)	0.0307 (10)	0.0162 (9)	0.0070 (8)	0.0024 (8)
C12	0.0377 (12)	0.0328 (11)	0.0374 (12)	0.0227 (10)	0.0091 (9)	0.0091 (9)
C13	0.0474 (14)	0.0320 (12)	0.0557 (15)	0.0237 (11)	0.0239 (12)	0.0150 (11)
C14	0.0347 (13)	0.0298 (12)	0.0675 (18)	0.0108 (10)	0.0190 (13)	−0.0014 (11)
C15	0.0336 (12)	0.0370 (13)	0.0546 (16)	0.0101 (11)	0.0033 (11)	−0.0077 (11)
C16	0.0375 (12)	0.0350 (12)	0.0374 (12)	0.0165 (10)	0.0038 (10)	0.0016 (10)
C17	0.0382 (14)	0.0600 (17)	0.0640 (19)	0.0317 (14)	−0.0060 (12)	−0.0230 (14)
C18	0.0462 (16)	0.0548 (17)	0.0419 (14)	0.0126 (13)	−0.0158 (12)	−0.0037 (12)

Geometric parameters (Å, °)

O1—C4	1.368 (3)	C8—H8B	0.9900
O1—C17	1.422 (3)	C9—C10	1.528 (4)
O2—C5	1.362 (3)	C9—H9	1.0000
O2—C18	1.430 (3)	C10—H10A	0.9900
O3—C10	1.357 (5)	C10—H10B	0.9900
O3—H3O	0.99 (4)	C11—C16	1.390 (3)
N1—C9	1.477 (3)	C11—C12	1.401 (3)
N1—C1	1.484 (3)	C12—C13	1.375 (4)
N1—H1N	0.97 (3)	C12—H12	0.9500
C1—C2	1.521 (3)	C13—C14	1.387 (5)
C1—C11	1.524 (3)	C13—H13	0.9500
C1—H1	1.0000	C14—C15	1.386 (4)
C2—C7	1.387 (3)	C14—H14	0.9500
C2—C3	1.399 (3)	C15—C16	1.401 (4)
C3—C4	1.374 (3)	C15—H15	0.9500
C3—H3	0.9500	C16—H16	0.9500
C4—C5	1.414 (3)	C17—H17A	0.9800
C5—C6	1.370 (4)	C17—H17B	0.9800
C6—C7	1.417 (4)	C17—H17C	0.9800
C6—H6	0.9500	C18—H18A	0.9800
C7—C8	1.491 (3)	C18—H18B	0.9800
C8—C9	1.502 (4)	C18—H18C	0.9800
C8—H8A	0.9900
C4—O1—C17	117.5 (2)	N1—C9—H9	109.6
C5—O2—C18	117.1 (2)	C8—C9—H9	109.6
C10—O3—H3O	102 (3)	C10—C9—H9	109.6
C9—N1—C1	111.16 (18)	O3—C10—C9	110.5 (3)
C9—N1—H1N	110 (2)	O3—C10—H10A	109.6
C1—N1—H1N	112.6 (19)	C9—C10—H10A	109.6
N1—C1—C2	111.10 (19)	O3—C10—H10B	109.6
N1—C1—C11	112.09 (18)	C9—C10—H10B	109.6
C2—C1—C11	113.00 (17)	H10A—C10—H10B	108.1
N1—C1—H1	106.7	C16—C11—C12	118.5 (2)
C2—C1—H1	106.7	C16—C11—C1	119.09 (19)
C11—C1—H1	106.7	C12—C11—C1	122.4 (2)
C7—C2—C3	119.9 (2)	C13—C12—C11	120.8 (3)
C7—C2—C1	121.3 (2)	C13—C12—H12	119.6
C3—C2—C1	118.74 (19)	C11—C12—H12	119.6
C4—C3—C2	120.6 (2)	C12—C13—C14	120.5 (2)
C4—C3—H3	119.7	C12—C13—H13	119.8
C2—C3—H3	119.7	C14—C13—H13	119.8
O1—C4—C3	125.5 (2)	C15—C14—C13	120.0 (2)
O1—C4—C5	114.3 (2)	C15—C14—H14	120.0
C3—C4—C5	120.2 (2)	C13—C14—H14	120.0
O2—C5—C6	125.9 (2)	C14—C15—C16	119.5 (3)
O2—C5—C4	115.1 (2)	C14—C15—H15	120.3
C6—C5—C4	119.1 (2)	C16—C15—H15	120.3
C5—C6—C7	121.2 (2)	C11—C16—C15	120.8 (2)
C5—C6—H6	119.4	C11—C16—H16	119.6
C7—C6—H6	119.4	C15—C16—H16	119.6
C2—C7—C6	118.9 (2)	O1—C17—H17A	109.5
C2—C7—C8	121.7 (2)	O1—C17—H17B	109.5
C6—C7—C8	119.4 (2)	H17A—C17—H17B	109.5
C7—C8—C9	111.3 (2)	O1—C17—H17C	109.5
C7—C8—H8A	109.4	H17A—C17—H17C	109.5
C9—C8—H8A	109.4	H17B—C17—H17C	109.5
C7—C8—H8B	109.4	O2—C18—H18A	109.5
C9—C8—H8B	109.4	O2—C18—H18B	109.5
H8A—C8—H8B	108.0	H18A—C18—H18B	109.5
N1—C9—C8	109.2 (2)	O2—C18—H18C	109.5
N1—C9—C10	108.7 (2)	H18A—C18—H18C	109.5
C8—C9—C10	110.2 (2)	H18B—C18—H18C	109.5
C9—N1—C1—C2	−48.0 (3)	C1—C2—C7—C8	−0.1 (3)
C9—N1—C1—C11	79.5 (3)	C5—C6—C7—C2	−0.4 (3)
N1—C1—C2—C7	14.4 (3)	C5—C6—C7—C8	−179.7 (2)
C11—C1—C2—C7	−112.6 (2)	C2—C7—C8—C9	18.5 (3)
N1—C1—C2—C3	−166.43 (19)	C6—C7—C8—C9	−162.2 (2)
C11—C1—C2—C3	66.6 (3)	C1—N1—C9—C8	68.4 (2)
C7—C2—C3—C4	−0.6 (3)	C1—N1—C9—C10	−171.4 (2)
C1—C2—C3—C4	−179.8 (2)	C7—C8—C9—N1	−51.1 (3)
C17—O1—C4—C3	−7.1 (4)	C7—C8—C9—C10	−170.5 (2)
C17—O1—C4—C5	173.1 (3)	N1—C9—C10—O3	75.4 (3)
C2—C3—C4—O1	178.9 (2)	C8—C9—C10—O3	−165.0 (3)
C2—C3—C4—C5	−1.2 (4)	N1—C1—C11—C16	76.9 (3)
C18—O2—C5—C6	3.4 (4)	C2—C1—C11—C16	−156.7 (2)
C18—O2—C5—C4	−176.4 (2)	N1—C1—C11—C12	−102.1 (2)
O1—C4—C5—O2	2.0 (3)	C2—C1—C11—C12	24.3 (3)
C3—C4—C5—O2	−177.9 (2)	C16—C11—C12—C13	1.5 (3)
O1—C4—C5—C6	−177.9 (2)	C1—C11—C12—C13	−179.5 (2)
C3—C4—C5—C6	2.3 (4)	C11—C12—C13—C14	0.1 (4)
O2—C5—C6—C7	178.7 (2)	C12—C13—C14—C15	−1.5 (4)
C4—C5—C6—C7	−1.5 (4)	C13—C14—C15—C16	1.2 (4)
C3—C2—C7—C6	1.4 (3)	C12—C11—C16—C15	−1.8 (4)
C1—C2—C7—C6	−179.4 (2)	C1—C11—C16—C15	179.2 (2)
C3—C2—C7—C8	−179.2 (2)	C14—C15—C16—C11	0.5 (4)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
O3—H3O···O1W	0.99 (4)	1.95 (4)	2.917 (6)	164 (5)