cis-(9S,10S)-Methyl 1-propyl-1,2,3,4-tetra­hydro-β-carboline-3-carboxyl­ate

Abstract

The title compound, C₁₆H₂₀N₂O₂, was synthesized from (S)-tryptophan methyl ester hydro­chloride and butyraldehyde. The absolute configuration 9S,10S was assigned on the basis of the unchanging chirality of the C9 centre. The NH group of the indole ring is involved in inter­molecular N—H⋯O hydrogen bonding, while the NH group of the six-membered ring is not. This latter ring has a half-chair conformation.

Related literature

For related literature, see: Agurell et al. (1969 ▶); Bein (1953 ▶); Herraiz (2000 ▶); Johnson et al. (1963 ▶); Petter & Engelmann (1974 ▶). For synthetic details, see: Greenstein & Winiz (1961 ▶); Snyder et al. (1948 ▶).

Experimental

Crystal data

• C₁₆H₂₀N₂O₂

• M _r = 272.34

• Tetragonal,

• a = 9.3410 (11) Å

• c = 36.125 (5) Å

• V = 3152.1 (7) ų

• Z = 8

• Mo Kα radiation

• μ = 0.08 mm⁻¹

• T = 298 K

• 0.30 × 0.30 × 0.30 mm

Data collection

• Bruker–Nonius KappaCCD diffractometer

• Absorption correction: none

• 10764 measured reflections

• 1778 independent reflections

• 1285 reflections with I > 2σ(I)

• R _int = 0.043

Refinement

• R[F ² > 2σ(F ²)] = 0.048

• wR(F ²) = 0.116

• S = 1.08

• 1778 reflections

• 189 parameters

• 2 restraints

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

• Δρ_max = 0.18 e Å⁻³

• Δρ_min = −0.14 e Å⁻³

Data collection: COLLECT (Nonius, 1999 ▶); cell refinement: DIRAX (Duisenberg, 1992 ▶); data reduction: EVALCCD (Duisenberg et al., 2003 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997 ▶); molecular graphics: DIAMOND (Brandenburg, 2007 ▶); software used to prepare material for publication: publCIF (Westrip, 2008 ▶).

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
N1—H1N⋯O1i	0.84 (3)	2.20 (3)	3.037 (3)	177 (3)

Symmetry code: (i) .

supplementary crystallographic information

Comment

Keeping in mind the diverse biological activities of alkaloids containing an indole or indoline nucleus (Agurell et al., 1969; Bein, 1953; Johnson et al., 1963; Herraiz, 2000), we have designed and synthesized some optically active compounds containing the tetrahydro-β-carboline nucleus. We report here the crystal structure of the title compound.

Experimental

The title compound was prepared by condensation of (S)-tryptophan methyl ester hydrochloride with an aldehyde under polar protic conditions (Greenstein & Winiz, 1961; Snyder et al., 1948). (S)-tryptophan methyl ester hydrochloride (1.5 g, 0.0059 mol) and butyraldehyde (1.50 ml, 0.0059 mol) were dissolved in methanol/water solution (50 ml, 75/25%, v/v). The mixture was refluxed for 48 h, cooled and the solvent evaporated under vacuum. The residue was dissolved in 14% ammonium hydroxide, extracted with chloroform and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to yield an oily residue which was subjected to column chromatography. The purified oil was crystallized from benzene/pet. ether (b.p. 373–393 K) to give the title compound: yield 1.2 g, 74.8%, m.p. 413 K, R_f 0.84 methanol / chloroform (3:7). [a]_D²⁸-132.8 (c = 0.00348, acetonitrile). The product after purification was subjected to different spectroscopic techniques. This data together with the result of elemental analysis confirmed the formation of a pure stereoisomer.

Refinement

In the absence of significant anomalous scattering effects, Friedel pairs were merged prior to refinement. All C-bonded H atoms were placed at calculated positions. The two N-bonded H atoms were located from the Fourier map and were refined with the restraint N—H = 0.89 (1) Å. The isotropic displacement parameters of the H atoms were fixed at U_iso(H) = 1.2U_eq(C/N) (1.5U_eq(C) for the methyl groups).

Figures

Fig. 1.

The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level for non-H atoms.

Fig. 2.

The intermolecular N—H···O hydrogen bond (dashed line). H atoms not involved in hydrogen bonding are omitted.

Crystal data

C16H20N2O2	Z = 8
Mr = 272.34	F000 = 1168
Tetragonal, P43212	Dx = 1.148 Mg m−3
Hall symbol: P 4nw 2abw	Mo Kα radiation λ = 0.71073 Å
a = 9.3410 (11) Å	Cell parameters from 87 reflections
b = 9.3410 (11) Å	θ = 3.8–15.5º
c = 36.125 (5) Å	µ = 0.08 mm−1
α = 90º	T = 298 K
β = 90º	Block, colourless
γ = 90º	0.30 × 0.30 × 0.30 mm
V = 3152.1 (7) Å3

Data collection

Bruker–Nonius KappaCCD diffractometer	Rint = 0.043
Radiation source: fine-focus sealed tube	θmax = 25.5º
φ & ω scans	θmin = 4.5º
Absorption correction: none	h = −10→11
10764 measured reflections	k = −10→11
1778 independent reflections	l = −42→43
1285 reflections with I > 2σ(I)

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)] = 0.048	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.116	w = 1/[σ2(Fo2) + (0.0441P)2 + 0.674P] where P = (Fo2 + 2Fc2)/3
S = 1.08	(Δ/σ)max < 0.001
1778 reflections	Δρmax = 0.18 e Å−3
189 parameters	Δρmin = −0.14 e Å−3
2 restraints	Extinction correction: none

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 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
C1	1.0247 (3)	1.1462 (3)	0.13466 (8)	0.0614 (8)
C2	1.0963 (4)	1.2716 (4)	0.12461 (10)	0.0795 (10)
C3	1.0883 (4)	1.3850 (4)	0.14882 (13)	0.0947 (12)
C4	1.0138 (5)	1.3760 (4)	0.18233 (12)	0.0943 (12)
C5	0.9434 (4)	1.2512 (4)	0.19235 (10)	0.0787 (10)
C6	0.9480 (3)	1.1324 (3)	0.16848 (8)	0.0600 (8)
C7	0.8933 (3)	0.9871 (3)	0.16950 (7)	0.0570 (7)
C8	0.9361 (3)	0.9219 (3)	0.13770 (7)	0.0559 (7)
C9	0.9096 (3)	0.7685 (3)	0.12739 (8)	0.0618 (8)
C10	0.8291 (3)	0.7477 (3)	0.19244 (7)	0.0607 (8)
C11	0.8098 (4)	0.9089 (3)	0.19896 (7)	0.0654 (8)
C12	0.8563 (4)	0.7499 (3)	0.08743 (7)	0.0733 (9)
C13	0.8352 (5)	0.5956 (4)	0.07535 (9)	0.0947 (12)
C14	0.7879 (7)	0.5844 (6)	0.03549 (11)	0.156 (2)
C15	0.7327 (3)	0.6573 (4)	0.21666 (7)	0.0668 (8)
C16	0.6592 (6)	0.6136 (5)	0.27900 (9)	0.140 (2)
O1	0.6595 (3)	0.5587 (3)	0.20643 (5)	0.0843 (7)
O2	0.7402 (3)	0.6986 (3)	0.25177 (6)	0.1103 (10)
N1	1.0152 (3)	1.0167 (3)	0.11634 (7)	0.0639 (7)
N2	0.7998 (3)	0.7132 (3)	0.15343 (7)	0.0660 (7)
H2	1.1472	1.2781	0.1025	0.095*
H3	1.1339	1.4703	0.1427	0.114*
H4	1.0114	1.4547	0.1981	0.113*
H5	0.8936	1.2461	0.2146	0.094*
H9	0.9983	0.7139	0.1306	0.074*
H10	0.9288	0.7226	0.1979	0.073*
H11A	0.7093	0.9342	0.1975	0.078*
H11B	0.8449	0.9349	0.2233	0.078*
H12A	0.7660	0.8001	0.0848	0.088*
H12B	0.9245	0.7949	0.0709	0.088*
H13A	0.9244	0.5438	0.0785	0.114*
H13B	0.7640	0.5509	0.0911	0.114*
H14A	0.7047	0.6429	0.0317	0.235*
H14B	0.7653	0.4866	0.0298	0.235*
H14C	0.8637	0.6166	0.0196	0.235*
H16A	0.5589	0.6186	0.2734	0.211*
H16B	0.6757	0.6511	0.3034	0.211*
H16C	0.6903	0.5157	0.2780	0.211*
H1N	1.052 (3)	0.996 (3)	0.0958 (9)	0.077*
H2N	0.799 (3)	0.620 (4)	0.1515 (9)	0.079*

Atomic displacement parameters (Ų)

	U11	U22	U33	U12	U13	U23
C1	0.0602 (19)	0.0582 (19)	0.0658 (18)	0.0029 (14)	−0.0028 (15)	0.0070 (15)
C2	0.084 (2)	0.067 (2)	0.087 (2)	−0.0118 (18)	−0.0036 (18)	0.0132 (19)
C3	0.094 (3)	0.068 (2)	0.121 (3)	−0.015 (2)	−0.010 (3)	0.017 (2)
C4	0.105 (3)	0.055 (2)	0.123 (3)	−0.001 (2)	−0.019 (3)	−0.012 (2)
C5	0.087 (3)	0.068 (2)	0.081 (2)	0.0092 (19)	−0.0023 (19)	−0.0071 (19)
C6	0.0579 (18)	0.0541 (17)	0.0679 (18)	0.0069 (14)	−0.0079 (15)	−0.0013 (15)
C7	0.0585 (18)	0.0534 (17)	0.0590 (16)	0.0006 (13)	0.0017 (13)	0.0011 (14)
C8	0.0575 (17)	0.0558 (17)	0.0542 (15)	−0.0043 (14)	0.0037 (14)	0.0027 (14)
C9	0.0640 (19)	0.0601 (18)	0.0614 (16)	−0.0018 (15)	0.0041 (14)	−0.0013 (14)
C10	0.0611 (19)	0.068 (2)	0.0535 (15)	−0.0128 (15)	−0.0004 (14)	0.0025 (14)
C11	0.072 (2)	0.069 (2)	0.0553 (16)	−0.0053 (16)	0.0071 (15)	−0.0030 (15)
C12	0.086 (2)	0.076 (2)	0.0581 (17)	−0.0049 (18)	0.0105 (17)	−0.0059 (16)
C13	0.122 (3)	0.084 (3)	0.078 (2)	−0.008 (2)	0.005 (2)	−0.018 (2)
C14	0.239 (7)	0.143 (5)	0.087 (3)	−0.011 (5)	−0.025 (4)	−0.042 (3)
C15	0.070 (2)	0.079 (2)	0.0511 (17)	−0.0185 (17)	−0.0037 (15)	0.0033 (16)
C16	0.208 (6)	0.148 (4)	0.065 (2)	−0.090 (4)	0.027 (3)	0.006 (2)
O1	0.0951 (17)	0.0920 (17)	0.0658 (13)	−0.0389 (15)	−0.0028 (12)	0.0037 (12)
O2	0.150 (2)	0.127 (2)	0.0542 (12)	−0.0739 (18)	0.0075 (14)	0.0014 (14)
N1	0.0699 (17)	0.0634 (16)	0.0583 (14)	−0.0033 (13)	0.0096 (13)	0.0024 (13)
N2	0.0749 (17)	0.0676 (17)	0.0555 (14)	−0.0187 (14)	0.0069 (12)	−0.0051 (13)

Geometric parameters (Å, °)

C1—N1	1.382 (4)	C16—O2	1.473 (4)
C1—C2	1.397 (4)	C2—H2	0.930
C1—C6	1.422 (4)	C3—H3	0.930
C2—C3	1.376 (5)	C4—H4	0.930
C3—C4	1.399 (5)	C5—H5	0.930
C4—C5	1.386 (5)	C9—H9	0.980
C5—C6	1.406 (4)	C10—H10	0.980
C6—C7	1.452 (4)	C11—H11A	0.970
C7—C8	1.360 (4)	C11—H11B	0.970
C7—C11	1.508 (4)	C12—H12A	0.970
C8—N1	1.388 (3)	C12—H12B	0.970
C8—C9	1.501 (4)	C13—H13A	0.970
C9—N2	1.484 (4)	C13—H13B	0.970
C9—C12	1.537 (4)	C14—H14A	0.960
C10—N2	1.471 (4)	C14—H14B	0.960
C10—C15	1.513 (4)	C14—H14C	0.960
C10—C11	1.535 (4)	C16—H16A	0.960
C12—C13	1.519 (5)	C16—H16B	0.960
C13—C14	1.510 (5)	C16—H16C	0.960
C15—O1	1.206 (3)	N1—H1N	0.84 (3)
C15—O2	1.327 (3)	N2—H2N	0.87 (3)
N1—C1—C2	129.8 (3)	C6—C5—H5	120.4
N1—C1—C6	107.5 (3)	N2—C9—H9	109.1
C2—C1—C6	122.7 (3)	C8—C9—H9	109.1
C3—C2—C1	117.0 (3)	C12—C9—H9	109.1
C2—C3—C4	122.0 (3)	N2—C10—H10	108.4
C5—C4—C3	120.9 (4)	C15—C10—H10	108.4
C4—C5—C6	119.2 (3)	C11—C10—H10	108.4
C5—C6—C1	118.1 (3)	C7—C11—H11A	110.1
C5—C6—C7	135.4 (3)	C10—C11—H11A	110.1
C1—C6—C7	106.5 (2)	C7—C11—H11B	110.1
C8—C7—C6	107.1 (2)	C10—C11—H11B	110.1
C8—C7—C11	122.1 (3)	H11A—C11—H11B	108.5
C6—C7—C11	130.8 (3)	C13—C12—H12A	108.6
C7—C8—N1	109.9 (3)	C9—C12—H12A	108.6
C7—C8—C9	126.0 (3)	C13—C12—H12B	108.6
N1—C8—C9	124.0 (2)	C9—C12—H12B	108.6
N2—C9—C8	106.8 (2)	H12A—C12—H12B	107.5
N2—C9—C12	109.4 (2)	C14—C13—H13A	109.2
C8—C9—C12	113.2 (3)	C12—C13—H13A	109.2
N2—C10—C15	108.7 (2)	C14—C13—H13B	109.2
N2—C10—C11	109.9 (2)	C12—C13—H13B	109.2
C15—C10—C11	112.9 (3)	H13A—C13—H13B	107.9
C7—C11—C10	107.8 (2)	C13—C14—H14A	109.5
C13—C12—C9	114.8 (3)	C13—C14—H14B	109.5
C14—C13—C12	112.2 (3)	H14A—C14—H14B	109.5
O1—C15—O2	123.0 (3)	C13—C14—H14C	109.5
O1—C15—C10	125.9 (3)	H14A—C14—H14C	109.5
O2—C15—C10	111.0 (3)	H14B—C14—H14C	109.5
C15—O2—C16	117.0 (3)	O2—C16—H16A	109.5
C1—N1—C8	109.1 (2)	O2—C16—H16B	109.5
C10—N2—C9	113.7 (2)	H16A—C16—H16B	109.5
C3—C2—H2	121.5	O2—C16—H16C	109.5
C1—C2—H2	121.5	H16A—C16—H16C	109.5
C2—C3—H3	119.0	H16B—C16—H16C	109.5
C4—C3—H3	119.0	C1—N1—H1N	127 (2)
C5—C4—H4	119.6	C8—N1—H1N	124 (2)
C3—C4—H4	119.6	C10—N2—H2N	107 (2)
C4—C5—H5	120.4	C9—N2—H2N	108 (2)

Hydrogen-bond geometry (Å, °)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1N···O1i	0.84 (3)	2.20 (3)	3.037 (3)	177 (3)

Symmetry codes: (i) x+1/2, −y+3/2, −z+1/4.