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

Alam, S.; Hasan, M.; Saeed, S.; Fischer, A.; Khan, N.

doi:10.1107/S1600536807066020

organic compounds

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Volume 64| Part 2| February 2008| Page o361

doi:10.1107/S1600536807066020

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

Samina Alam,^a Mashooda Hasan,^a Sadaf Saeed,^a ^* Andreas Fischer ^b and Naeema Khan ^a

^aDepartment of Chemistry, Quaid-i-Azam University, Islamabad, Pakistan, and ^bInorganic Chemistry, School of Chemical Science and Engineering, Royal Institute of Technology (KTH), 10044 Stockholm, Sweden
^*Correspondence e-mail: sadaf03_2000@yahoo.com

(Received 26 October 2007; accepted 6 December 2007; online 4 January 2008)

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, P 4₃ 2₁ 2
a = 9.3410 (11) Å
c = 36.125 (5) Å
V = 3152.1 (7) Å³
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[F² > 2σ(F²)] = 0.048
wR(F²) = 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

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) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, -z+{\script{1\over 4}}]$ .

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 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536807066020/bi2260sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536807066020/bi2260Isup2.hkl

checkCIF report

Comment top

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.

Related literature top

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

Experimental top

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.

Computing details top

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).

Figures top

	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.

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

Crystal data top

C₁₆H₂₀N₂O₂	D_x = 1.148 Mg m⁻³
M_r = 272.34	Mo Kα radiation, λ = 0.71073 Å
Tetragonal, P4₃2₁2	Cell parameters from 87 reflections
Hall symbol: P 4nw 2abw	θ = 3.8–15.5°
a = 9.3410 (11) Å	µ = 0.08 mm⁻¹
c = 36.125 (5) Å	T = 298 K
V = 3152.1 (7) Å³	Block, colourless
Z = 8	0.30 × 0.30 × 0.30 mm
F(000) = 1168

Data collection top

Bruker–Nonius KappaCCD diffractometer	R_int = 0.043
Radiation source: fine-focus sealed tube	θ_max = 25.5°, θ_min = 4.5°
ϕ & ω scans	h = −10→11
10764 measured reflections	k = −10→11
1778 independent reflections	l = −42→43
1285 reflections with I > 2σ(I)

Refinement top

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(F_o²) + (0.0441P)² + 0.674P] where P = (F_o² + 2F_c²)/3
S = 1.08	(Δ/σ)_max < 0.001
1778 reflections	Δρ_max = 0.18 e Å⁻³
189 parameters	Δρ_min = −0.14 e Å⁻³
2 restraints

Crystal data top

C₁₆H₂₀N₂O₂	Z = 8
M_r = 272.34	Mo Kα radiation
Tetragonal, P4₃2₁2	µ = 0.08 mm⁻¹
a = 9.3410 (11) Å	T = 298 K
c = 36.125 (5) Å	0.30 × 0.30 × 0.30 mm
V = 3152.1 (7) Å³

Data collection top

Bruker–Nonius KappaCCD diffractometer	1285 reflections with I > 2σ(I)
10764 measured reflections	R_int = 0.043
1778 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.048	2 restraints
wR(F²) = 0.116	H atoms treated by a mixture of independent and constrained refinement
S = 1.08	Δρ_max = 0.18 e Å⁻³
1778 reflections	Δρ_min = −0.14 e Å⁻³
189 parameters

Special details top

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 (Å²) top

	x	y	z	U_iso*/U_eq
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 (Å²) top

	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, º) top

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, º) top

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) x+1/2, −y+3/2, −z+1/4.

Experimental details

Crystal data
Chemical formula	C₁₆H₂₀N₂O₂
M_r	272.34
Crystal system, space group	Tetragonal, P4₃2₁2
Temperature (K)	298
a, c (Å)	9.3410 (11), 36.125 (5)
V (Å³)	3152.1 (7)
Z	8
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.30 × 0.30 × 0.30

Data collection
Diffractometer	Bruker–Nonius KappaCCD diffractometer
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	10764, 1778, 1285
R_int	0.043
(sin θ/λ)_max (Å⁻¹)	0.606

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.048, 0.116, 1.08
No. of reflections	1778
No. of parameters	189
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.14

Computer programs: COLLECT (Nonius, 1999), DIRAX (Duisenberg, 1992), EVALCCD (Duisenberg et al., 2003), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), DIAMOND (Brandenburg, 2007), publCIF (Westrip, 2008).

Hydrogen-bond geometry (Å, º) top

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) x+1/2, −y+3/2, −z+1/4.

Acknowledgements

MH is grateful to the Alexander von Humboldt Foundation, Germany, and AF thanks the Swedish Research Council for financial assistance.

References

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