(S)-(+)-4-(Oxiran-2-ylmeth­oxy)-9H-carbazole

Lu, D.-Q.; Chen, J.; Wu, W.-Y.; Ling, X.-Q.; Chang, Y.-J.

doi:10.1107/S1600536810038900

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 66| Part 11| November 2010| Page o2785

https://doi.org/10.1107/S1600536810038900

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(S)-(+)-4-(Oxiran-2-ylmethoxy)-9H-carbazole

Ding-Qiang Lu,^a ^* Jia Chen,^a Wen-Yuan Wu,^b Xiu-Quan Ling ^a and Ya-Jun Chang ^a

^aCollege of Pharmaceutical Sciences, Nanjing University of Technolgy, Nanjing 210009, People's Republic of China, and ^bCollege of Science, Nanjing University of Technolgy, Nanjing 210009, People's Republic of China
^*Correspondence e-mail: ludingqiang@njut.edu.cn

(Received 12 July 2010; accepted 29 September 2010; online 9 October 2010)

In the title compound, C₁₅H₁₃NO₂, all atoms of the carbazole group are coplanar (r.m.s. deviation = 0.005 Å), and the dihedral angle between this plane and C—O—C plane of oxane group is 57.1 (4)°. The crystal packing is stabilized by an N—H⋯O hydrogen bond, resulting in infinite supramolecular chains along [001].

Related literature

For general background to the target product, see: Hildesheim et al. (2002 ); Morgan (1994 ). For other intermediates with similar structures, see: Herbert et al. (1987 ). For assignment of the absolute structure based on the synthesis, see: Rao et al. (2007 )

Experimental

Crystal data

C₁₅H₁₃NO₂
M_r = 239.26
Orthorhombic, P 2₁ 2₁ 2₁
a = 7.6140 (15) Å
b = 9.5870 (19) Å
c = 16.628 (3) Å
V = 1213.8 (4) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 293 K
0.30 × 0.10 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (North et al., 1968 ) T_min = 0.974, T_max = 0.991
2198 measured reflections
1298 independent reflections
834 reflections with I > 2σ(I)
R_int = 0.061
3 standard reflections every 200 reflections intensity decay: none

Refinement

R[F² > 2σ(F²)] = 0.058
wR(F²) = 0.124
S = 1.05
1298 reflections
163 parameters
H-atom parameters constrained
Δρ_max = 0.18 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O2ⁱ	0.86	2.09	2.948 (5)	172
Symmetry code: (i) $[-x+{\script{3\over 2}}, -y+2, z+{\script{1\over 2}}]$ .

Data collection: CAD-4 Software (Enraf–Nonius, 1989 ); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms & Wocadlo, 1995 ); program(s) used to solve structure: SHELXTL (Sheldrick, 2008 ); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536810038900/fl2309sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536810038900/fl2309Isup2.hkl

checkCIF report

Comment top

4-(2,3-epoxypropoxy)carbazole is used as a starting agent for the synthesis of 1-(carbazol-4-yloxy-3-[[2-(O-methoxyphenoxy)ethyl]amino]-2-propranol (Herbert & Heppenheim, 1987; Hildesheim et al., 2002), which is a commercial drug (carvedilol) with α- and β₁– receptor blocking activity that has been approved for the treatment of congestive heart failure (CHF). However carvedilol is actually a racemic mixture of the R and S enantiomers, and the β-receptor blocking activity of the S-enantiomer is about 200 times higher than that of R-carvedilol (Morgan, 1994).

We have now synthesized the title compound (CAS:67843–74-7), (I), as an intermediate in the synthesis of the target molecule, S-carvedilol, and report its structure here. The optically pure (R)-(-)-epichlorohydrin (CAS: 51594–55-9) was used as the starting agent, and during the reaction, an inversion of the chiral C atom occurred to give the final product (I) (Rao et al., 2007).

Both the carbazole group and oxane group are planar, and the dihedral angle between them is 57.1 (4). The molecules are stacked along the a axis, and linked by N–H..O hydrogen bonds to form infinite chains along the [001] direction,

Related literature top

For general background, see: Hildesheim et al. (2002); Morgan (1994); Rao et al. (2007). For other intermediates with similar structures, see: Herbert et al. (1987).

Experimental top

For the preparation of the title compound, K₂CO₃ (20.73 g, 0.15 mol) and (R)-(-)-epichlorohydrin (7 ml, 0.09 mol) were added to an IPA (60 ml) solution containing 4-hydroxycarbazole (10.98 g, 0.06 mol). Then the reaction mixture was refluxed for 5 h at 355 K. The crude product was purified by recrystallization from ethyl acetate to provide colourless crystals suitable for X-ray analysis.

Structure description top

For general background, see: Hildesheim et al. (2002); Morgan (1994); Rao et al. (2007). For other intermediates with similar structures, see: Herbert et al. (1987).

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SHELXTL Sheldrick, 2008); program(s) used to refine structure: SHELXTL Sheldrick, 2008); molecular graphics: SHELXTL Sheldrick, 2008); software used to prepare material for publication: SHELXTL Sheldrick, 2008).

Figures top

	Fig. 1. The molecular structure of (I), with atom labels and 30% probability displacement ellipsoids for non-H atoms.
	Fig. 2. Supramolecular chains along the [010] direction by N–H···O hydrogen bonds (dashed lines).

(S)-(+)-4-(Oxiran-2-ylmethoxy)-9H-carbazole top

Crystal data top

C₁₅H₁₃NO₂	F(000) = 504
M_r = 239.26	D_x = 1.309 Mg m⁻³
Orthorhombic, P2₁2₁2₁	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 25 reflections
a = 7.6140 (15) Å	θ = 9–13°
b = 9.5870 (19) Å	µ = 0.09 mm⁻¹
c = 16.628 (3) Å	T = 293 K
V = 1213.8 (4) Å³	Prism, colourless
Z = 4	0.30 × 0.10 × 0.10 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	834 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.061
Graphite monochromator	θ_max = 25.4°, θ_min = 2.5°
ω/2θ scans	h = −9→9
Absorption correction: ψ scan (North et al., 1968)	k = 0→11
T_min = 0.974, T_max = 0.991	l = 0→19
2198 measured reflections	3 standard reflections every 200 reflections
1298 independent reflections	intensity decay: none

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)] = 0.058	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.124	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0341P)² + 0.3329P] where P = (F_o² + 2F_c²)/3
1298 reflections	(Δ/σ)_max < 0.001
163 parameters	Δρ_max = 0.18 e Å⁻³
0 restraints	Δρ_min = −0.17 e Å⁻³

Crystal data top

C₁₅H₁₃NO₂	V = 1213.8 (4) Å³
M_r = 239.26	Z = 4
Orthorhombic, P2₁2₁2₁	Mo Kα radiation
a = 7.6140 (15) Å	µ = 0.09 mm⁻¹
b = 9.5870 (19) Å	T = 293 K
c = 16.628 (3) Å	0.30 × 0.10 × 0.10 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	834 reflections with I > 2σ(I)
Absorption correction: ψ scan (North et al., 1968)	R_int = 0.061
T_min = 0.974, T_max = 0.991	3 standard reflections every 200 reflections
2198 measured reflections	intensity decay: none
1298 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.058	0 restraints
wR(F²) = 0.124	H-atom parameters constrained
S = 1.05	Δρ_max = 0.18 e Å⁻³
1298 reflections	Δρ_min = −0.17 e Å⁻³
163 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
N1	0.8591 (5)	1.1011 (4)	0.7894 (2)	0.0555 (11)
H1	0.9127	1.1158	0.8341	0.067*
O1	0.4664 (4)	0.9701 (4)	0.59614 (16)	0.0626 (10)
O2	0.4551 (4)	0.8193 (4)	0.43812 (17)	0.0717 (11)
C1	0.8311 (6)	1.1218 (5)	0.5757 (2)	0.0521 (12)
H1A	0.7493	1.0967	0.5367	0.063*
C2	0.9839 (7)	1.1859 (6)	0.5539 (3)	0.0659 (15)
H2A	1.0065	1.2022	0.4998	0.079*
C3	1.1059 (7)	1.2271 (6)	0.6109 (3)	0.0740 (16)
H3A	1.2082	1.2719	0.5946	0.089*
C4	1.0774 (6)	1.2024 (6)	0.6922 (3)	0.0652 (15)
H4A	1.1595	1.2291	0.7306	0.078*
C5	0.9233 (6)	1.1369 (5)	0.7139 (3)	0.0523 (12)
C6	0.7981 (6)	1.0942 (5)	0.6563 (2)	0.0441 (11)
C7	0.6551 (6)	1.0313 (5)	0.6998 (2)	0.0452 (11)
C8	0.6986 (6)	1.0394 (5)	0.7821 (3)	0.0520 (12)
C9	0.5853 (7)	0.9866 (5)	0.8409 (2)	0.0595 (14)
H9A	0.6131	0.9928	0.8953	0.071*
C10	0.4327 (7)	0.9258 (6)	0.8160 (3)	0.0648 (15)
H10A	0.3572	0.8893	0.8546	0.078*
C11	0.3850 (7)	0.9158 (6)	0.7348 (3)	0.0651 (15)
H11A	0.2803	0.8731	0.7198	0.078*
C12	0.4970 (6)	0.9709 (5)	0.6776 (2)	0.0501 (12)
C13	0.3242 (6)	0.8870 (6)	0.5679 (2)	0.0648 (15)
H13A	0.2137	0.9217	0.5890	0.078*
H13B	0.3387	0.7909	0.5849	0.078*
C14	0.3258 (7)	0.8962 (7)	0.4805 (3)	0.0706 (15)
H14A	0.3019	0.9894	0.4589	0.085*
C15	0.2734 (6)	0.7819 (6)	0.4288 (3)	0.0687 (16)
H15A	0.2331	0.6966	0.4541	0.082*
H15B	0.2164	0.8046	0.3783	0.082*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.057 (2)	0.073 (3)	0.0360 (19)	−0.006 (2)	−0.0127 (19)	−0.0015 (19)
O1	0.0521 (18)	0.092 (3)	0.0436 (17)	−0.012 (2)	−0.0062 (15)	−0.0092 (17)
O2	0.053 (2)	0.115 (3)	0.0468 (19)	−0.007 (2)	0.0064 (17)	−0.0009 (19)
C1	0.055 (3)	0.059 (3)	0.042 (2)	−0.002 (3)	−0.006 (2)	0.004 (2)
C2	0.068 (4)	0.090 (4)	0.040 (3)	−0.011 (4)	−0.003 (3)	0.005 (3)
C3	0.065 (3)	0.093 (4)	0.064 (3)	−0.025 (3)	0.002 (3)	−0.003 (3)
C4	0.061 (3)	0.080 (4)	0.055 (3)	−0.008 (3)	−0.012 (3)	−0.004 (3)
C5	0.053 (3)	0.061 (3)	0.043 (2)	0.000 (3)	−0.001 (2)	0.000 (2)
C6	0.045 (3)	0.050 (3)	0.037 (2)	0.004 (2)	−0.003 (2)	0.001 (2)
C7	0.058 (3)	0.042 (3)	0.035 (2)	0.007 (3)	−0.005 (2)	−0.004 (2)
C8	0.054 (3)	0.057 (3)	0.046 (2)	0.004 (3)	−0.005 (2)	−0.003 (2)
C9	0.071 (4)	0.070 (4)	0.037 (2)	0.005 (3)	0.004 (2)	0.002 (2)
C10	0.076 (4)	0.070 (4)	0.048 (3)	0.000 (3)	0.021 (3)	0.002 (3)
C11	0.059 (3)	0.079 (4)	0.058 (3)	−0.014 (3)	0.015 (3)	−0.005 (3)
C12	0.050 (3)	0.058 (3)	0.043 (2)	0.007 (3)	−0.004 (2)	−0.011 (2)
C13	0.045 (3)	0.092 (4)	0.057 (3)	−0.007 (3)	−0.002 (2)	−0.012 (3)
C14	0.058 (3)	0.093 (4)	0.060 (3)	−0.007 (3)	−0.011 (3)	−0.003 (3)
C15	0.056 (3)	0.084 (4)	0.066 (3)	−0.015 (3)	−0.003 (3)	−0.008 (3)

Geometric parameters (Å, º) top

N1—C8	1.363 (6)	C6—C7	1.439 (6)
N1—C5	1.389 (6)	C7—C12	1.386 (6)
N1—H1	0.8600	C7—C8	1.409 (5)
O1—C12	1.375 (4)	C8—C9	1.399 (6)
O1—C13	1.424 (5)	C9—C10	1.364 (7)
O2—C14	1.418 (6)	C9—H9A	0.9300
O2—C15	1.438 (6)	C10—C11	1.401 (6)
C1—C2	1.365 (7)	C10—H10A	0.9300
C1—C6	1.389 (5)	C11—C12	1.382 (6)
C1—H1A	0.9300	C11—H11A	0.9300
C2—C3	1.385 (6)	C13—C14	1.455 (6)
C2—H2A	0.9300	C13—H13A	0.9700
C3—C4	1.388 (6)	C13—H13B	0.9700
C3—H3A	0.9300	C14—C15	1.449 (7)
C4—C5	1.380 (6)	C14—H14A	0.9800
C4—H4A	0.9300	C15—H15A	0.9700
C5—C6	1.412 (6)	C15—H15B	0.9700

C8—N1—C5	110.0 (4)	C10—C9—H9A	121.1
C8—N1—H1	125.0	C8—C9—H9A	121.1
C5—N1—H1	125.0	C9—C10—C11	122.9 (5)
C12—O1—C13	117.2 (4)	C9—C10—H10A	118.6
C14—O2—C15	61.0 (3)	C11—C10—H10A	118.6
C2—C1—C6	119.7 (4)	C12—C11—C10	118.4 (5)
C2—C1—H1A	120.1	C12—C11—H11A	120.8
C6—C1—H1A	120.1	C10—C11—H11A	120.8
C1—C2—C3	121.2 (4)	O1—C12—C11	124.9 (4)
C1—C2—H2A	119.4	O1—C12—C7	114.3 (4)
C3—C2—H2A	119.4	C11—C12—C7	120.8 (4)
C2—C3—C4	120.8 (5)	O1—C13—C14	106.8 (4)
C2—C3—H3A	119.6	O1—C13—H13A	110.4
C4—C3—H3A	119.6	C14—C13—H13A	110.4
C5—C4—C3	117.8 (4)	O1—C13—H13B	110.4
C5—C4—H4A	121.1	C14—C13—H13B	110.4
C3—C4—H4A	121.1	H13A—C13—H13B	108.6
C4—C5—N1	130.4 (4)	O2—C14—C15	60.2 (3)
C4—C5—C6	121.9 (4)	O2—C14—C13	118.1 (5)
N1—C5—C6	107.7 (4)	C15—C14—C13	123.0 (5)
C1—C6—C5	118.5 (4)	O2—C14—H14A	114.8
C1—C6—C7	134.5 (4)	C15—C14—H14A	114.8
C5—C6—C7	106.9 (3)	C13—C14—H14A	114.8
C12—C7—C8	119.0 (4)	O2—C15—C14	58.8 (3)
C12—C7—C6	134.3 (4)	O2—C15—H15A	117.9
C8—C7—C6	106.7 (4)	C14—C15—H15A	117.9
N1—C8—C9	130.3 (4)	O2—C15—H15B	117.9
N1—C8—C7	108.7 (4)	C14—C15—H15B	117.9
C9—C8—C7	121.0 (4)	H15A—C15—H15B	115.0
C10—C9—C8	117.8 (4)

C6—C1—C2—C3	−1.5 (8)	C6—C7—C8—N1	−0.9 (5)
C1—C2—C3—C4	1.0 (9)	C12—C7—C8—C9	0.5 (7)
C2—C3—C4—C5	−0.6 (9)	C6—C7—C8—C9	−180.0 (4)
C3—C4—C5—N1	−178.9 (5)	N1—C8—C9—C10	−178.0 (5)
C3—C4—C5—C6	0.7 (8)	C7—C8—C9—C10	0.7 (7)
C8—N1—C5—C4	179.0 (5)	C8—C9—C10—C11	−0.8 (8)
C8—N1—C5—C6	−0.7 (5)	C9—C10—C11—C12	−0.4 (8)
C2—C1—C6—C5	1.5 (7)	C13—O1—C12—C11	−10.7 (7)
C2—C1—C6—C7	179.4 (5)	C13—O1—C12—C7	168.4 (4)
C4—C5—C6—C1	−1.2 (7)	C10—C11—C12—O1	−179.3 (5)
N1—C5—C6—C1	178.5 (4)	C10—C11—C12—C7	1.7 (8)
C4—C5—C6—C7	−179.6 (4)	C8—C7—C12—O1	179.1 (4)
N1—C5—C6—C7	0.1 (5)	C6—C7—C12—O1	−0.3 (8)
C1—C6—C7—C12	1.9 (10)	C8—C7—C12—C11	−1.7 (8)
C5—C6—C7—C12	180.0 (5)	C6—C7—C12—C11	178.9 (5)
C1—C6—C7—C8	−177.6 (5)	C12—O1—C13—C14	−176.5 (4)
C5—C6—C7—C8	0.5 (5)	C15—O2—C14—C13	113.9 (6)
C5—N1—C8—C9	179.9 (5)	O1—C13—C14—O2	75.6 (6)
C5—N1—C8—C7	1.0 (5)	O1—C13—C14—C15	146.6 (5)
C12—C7—C8—N1	179.5 (4)	C13—C14—C15—O2	−106.0 (6)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.86	2.09	2.948 (5)	172

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

Experimental details

Crystal data
Chemical formula	C₁₅H₁₃NO₂
M_r	239.26
Crystal system, space group	Orthorhombic, P2₁2₁2₁
Temperature (K)	293
a, b, c (Å)	7.6140 (15), 9.5870 (19), 16.628 (3)
V (Å³)	1213.8 (4)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.30 × 0.10 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4
Absorption correction	ψ scan (North et al., 1968)
T_min, T_max	0.974, 0.991
No. of measured, independent and observed [I > 2σ(I)] reflections	2198, 1298, 834
R_int	0.061
(sin θ/λ)_max (Å⁻¹)	0.603

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.058, 0.124, 1.05
No. of reflections	1298
No. of parameters	163
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.18, −0.17

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), XCAD4 (Harms & Wocadlo, 1995), SHELXTL Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2ⁱ	0.86	2.09	2.948 (5)	172.0

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

Acknowledgements

The authors gratefully acknowledge Professor Hua-qin Wang of the Analysis Center, Nanjing University, for the data collection.

References

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