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

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].

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.007 Å
• R factor = 0.058
• wR factor = 0.124
• Data-to-parameter ratio = 8.0

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT089_ALERT_3_C Poor Data / Parameter Ratio (Zmax .LT. 18) .....       7.96
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds (x 1000) Ang ..          7
PLAT912_ALERT_4_C Missing # of FCF Reflections Above STh/L=  0.600          5

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           25.38
           From the CIF: _reflns_number_total               1298
           Count of symmetry unique reflns         1304
           Completeness (_total/calc)             99.54%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported   _diffrn_ambient_temperature        293 K
PLAT791_ALERT_4_G Note: The Model has Chirality at C14    (Verify)          S

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   4 ALERT level G = General alerts; check

   2 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

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

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).

S2. Experimental

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.

S3. Refinement

H atoms were positioned geometrically [N–H = 0.86 Å, and C–H = 0.93, 0.97 and 0.98 Å for aromatic, methyne and methine H atoms, respectively] and constrained to ride on their parent atoms, with U_iso(H) = 1.2U_eq(C or N). In the absence of significant anomalous scattering effects, Friedel pairs were merged for the final cycles of refinement.

Computing details

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

	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

Crystal data

C15H13NO2	F(000) = 504
Mr = 239.26	Dx = 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) Å^3	Prism, colourless
Z = 4	0.30 × 0.10 × 0.10 mm

Data collection

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

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.058	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.124	H-atom parameters constrained
S = 1.05	w = 1/[σ^2(Fo^2) + (0.0341P)^2 + 0.3329P] where P = (Fo^2 + 2Fc^2)/3
1298 reflections	(Δ/σ)max < 0.001
163 parameters	Δρmax = 0.18 e Å^−3
0 restraints	Δρmin = −0.17 e Å^−3

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
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 (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
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)

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)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O2^i	0.86	2.09	2.948 (5)	172

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