2,8-Dihydr­oxy-1-(3-methyl­but-2-en­yl)-9H-carbazole-3-carbaldehyde

The title naturally occurring carbazole compound, C₁₈H₁₇NO₃, known as hepta­zoline, was isolated from Micromelum minutum. The carbazole ring system is essentially planar. The hydr­oxy and aldehyde substituent groups lie in the plane of the benzene ring, while the 3-methyl-2-butenyl group is anti­clinal, with a dihedral angle of 70.26 (7)° between it and the mean plane of the carbazole. In the crystal structure, an intra­molecular O—H...O inter­action generates an S(6) ring motif, while an inter­molecular O—H...O inter­action forms dimers that link into chains along the [401] direction. The structure is further stabilized by weak intra­molecular C—H...O inter­actions and π–π inter­actions [centroid-to-centroid distances 3.5901 (8) and 3.5899 (8) Å].

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.044
• wR factor = 0.116
• Data-to-parameter ratio = 14.2

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?
PLAT420_ALERT_2_C D-H Without Acceptor       N1     -   H1N1   ...          ?
PLAT432_ALERT_2_C Short Inter X...Y Contact  O3     ..  C18     ..       3.01 Ang.
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          3

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

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

---

S1. Comment

Plants of the genus Micromelum (Rutaceae) are known to be rich sources of alkaloids (Nakahara et al., 2002), coumarins (Rahmani et al., 2003; Ito et al., 2000; Tantishaiyakul et al., 1986; Tantivatana et al., 1983) and flavonoids (Das et al., 1984; Sohrab et al., 2004). Some of these compounds show anti-cancer activity (Tantishaiyakul et al., 1986; Tantivatana et al., 1983). Micromelum minutum known locally in Thailand as "Hat-Sa-Khun", is a small to medium-sized tree or shrub found widespread in South-East Asian countries. The leaves of this plant are traditionally used in the treatment of fever and giddiness and a poultice of the boiled roots is used for ague (Rahmani et al., 2003). In our search for bioactive compounds from Thai medicinal plant, we herein report the crystal structure of the title compound, which was isolated from the stem barks of M. minutum collected from Nongkhai province in the northeasthern of Thailand.

In the structure of the title compound (Fig. 1), the carbazole ring system (C1–C12/N1) is essentially planar with the maximum deviation of -0.013 (1) Å for atom N1. The hydroxy and aldehyde substituent groups lie in the plane of the benzene ring and an intramolecular O1—H1O1···O2 hydrogen bond between the aldehyde and one of the hydroxy groups helps maintain the planarity of the structure. The orientation of the 3-methyl-2-butenyl substituent group with respect to the C1–C6 benzene ring is indicated by the torsion angle C2/C1/C13/C14 of 130.72 (13)°, showing an anti-clinal conformation. The dihedral angle between the 3-methyl-2-butenyl group and the mean plane of carbazole is 70.26 (7) Å. Bond lengths and angles in the title compound are within normal ranges (Allen et al., 1987) and comparable to related structures (Duan et al., 2005; Huang et al., 2005; Li et al., 2006). An O1—H1O1···O2 intramolecular interaction generates S(6) ring motif (Bernstein et al., 1995). In addition, the weak C13—H13B···O1 intramolecular interaction generates S(5) ring motif. O3—H1O3···O2 intermolecular interactions connect the molecules into dimers (Fig. 2). These dimers form chains along the [401] direction (Fig. 2). The crystal is stabilized by O—H···O hydrogen bonds and weak C—H···O intramolecular interaction. π–π interactions were also observed with the Cg₁···Cg₂ distances of 3.5901 (8) Å (symmetry code; 1 + x, y, z) and 3.5899 (8) Å (symmetry code; -1 + x, y, z), Cg₁ and Cg₂ are the centroids of C1–C6 and C6–C5–C12–C7–N1 rings.

Related literature

For background to the biological activity of alkaloids, flavonoids and coumarins, see, for example: Das et al. (1984); Ito et al. (2000); Nakahara et al. (2002); Rahmani et al. (2003); Sohrab et al. (2004); Tantishaiyakul et al. (1986); Tantivatana et al. (1983). For related structures, see, for example: Duan et al. (2005); Huang et al. (2005); Li et al. (2006). Bernstein et al. (1995) provide information on hydrogen bond motifs, and for reference structural data, see Allen et al. (1987).

S2. Experimental

Stem barks of M. minutum (12 kg) were extracted with hexane–EtOAc (1:1) over the period of 3 days at room temperature. The mixture was filtered and concentrated under reduced pressure to provide the crude extract (58.3 g). This crude extract was subjected to quick column chromatography (QCC) over silica gel and eluted with a gradient of EtOAc–hexane to afford 60 factions (A1–A60). Fractions A29–A30 (617 mg) was subjected to repeated CC using the gradient of CH₂Cl₂ (70% CH₂Cl₂ in hexane to 100% CH₂Cl₂) to give the title compound (15.2 mg). Colorless block-shaped single crystals of the title compound were obtained by recrystallization from CH₂Cl₂–hexane (2:1 v/v) solution, Mp 487–489 K.

S3. Refinement

All H atoms were located from the difference map and refined isotropically.

Computing details

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2 (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 1998); program(s) used to refine structure: SHELXTL (Sheldrick, 1998); molecular graphics: SHELXTL (Sheldrick, 1998); software used to prepare material for publication: SHELXTL (Sheldrick, 1998) and PLATON (Spek, 2003).

Figures

	Fig. 1. The asymmetric unit of the title compound, showing 50% probability displacement ellipsoids and the atomic numbering scheme.
	Fig. 2. Crystal packing of the title compound viewed approximately along the c axis. O—H···O hydrogen bonds are shown as dashed lines.

2,8-Dihydroxy-1-(3-methylbut-2-enyl)-9H-carbazole-3-carbaldehyde

Crystal data

C18H17NO3	F(000) = 624
Mr = 295.33	Dx = 1.374 Mg m^−3
Monoclinic, P21/c	Melting point = 487–489 K
Hall symbol: -P 2ybc	Mo Kα radiation, λ = 0.71073 Å
a = 4.7749 (1) Å	Cell parameters from 3795 reflections
b = 18.8511 (6) Å	θ = 1.7–29.0°
c = 16.0164 (5) Å	µ = 0.09 mm^−1
β = 97.931 (2)°	T = 100 K
V = 1427.88 (7) Å^3	Block, colourless
Z = 4	0.52 × 0.18 × 0.09 mm

Data collection

Bruker APEXII CCD area-detector diffractometer	3795 independent reflections
Radiation source: fine-focus sealed tube	2840 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.033
Detector resolution: 8.33 pixels mm^-1	θmax = 29.0°, θmin = 1.7°
ω scans	h = −6→6
Absorption correction: multi-scan (SADABS; Bruker, 2005)	k = −24→25
Tmin = 0.953, Tmax = 0.992	l = −21→21
15047 measured reflections

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)] = 0.044	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.116	All H-atom parameters refined
S = 1.10	w = 1/[σ^2(Fo^2) + (0.0537P)^2 + 0.2314P] where P = (Fo^2 + 2Fc^2)/3
3795 reflections	(Δ/σ)max < 0.001
267 parameters	Δρmax = 0.32 e Å^−3
0 restraints	Δρmin = −0.24 e Å^−3

Special details

Experimental. The low-temparture data was collected with the Oxford Cyrosystem Cobra low-temperature attachment.

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	−0.1526 (2)	0.39677 (5)	0.42061 (6)	0.0216 (2)
H1O1	−0.288 (4)	0.3808 (11)	0.3755 (13)	0.057 (6)*
O2	−0.43458 (19)	0.31436 (5)	0.30620 (6)	0.0224 (2)
O3	1.1123 (2)	0.23309 (6)	0.69986 (6)	0.0229 (2)
H1O3	1.265 (5)	0.2095 (11)	0.7341 (13)	0.059 (6)*
N1	0.6366 (2)	0.28325 (6)	0.58847 (7)	0.0174 (2)
H1N1	0.695 (4)	0.3170 (10)	0.6218 (11)	0.035 (5)*
C1	0.2402 (3)	0.34865 (7)	0.50719 (8)	0.0167 (3)
C2	0.0161 (3)	0.33985 (7)	0.44266 (8)	0.0167 (3)
C3	−0.0384 (3)	0.27355 (7)	0.40085 (8)	0.0174 (3)
C4	0.1316 (3)	0.21427 (7)	0.42481 (8)	0.0173 (3)
H4A	0.093 (3)	0.1682 (8)	0.3955 (10)	0.021 (4)*
C5	0.3561 (3)	0.22080 (7)	0.48859 (7)	0.0164 (3)
C6	0.4046 (3)	0.28848 (7)	0.52797 (7)	0.0162 (3)
C7	0.7370 (3)	0.21414 (7)	0.59080 (8)	0.0175 (3)
C8	0.9687 (3)	0.18691 (8)	0.64334 (8)	0.0189 (3)
C9	1.0343 (3)	0.11657 (8)	0.63314 (8)	0.0218 (3)
H9A	1.198 (3)	0.0965 (8)	0.6684 (10)	0.025 (4)*
C10	0.8714 (3)	0.07462 (8)	0.57257 (9)	0.0230 (3)
H10A	0.923 (3)	0.0249 (9)	0.5670 (10)	0.026 (4)*
C11	0.6392 (3)	0.10177 (8)	0.52068 (8)	0.0202 (3)
H11A	0.524 (3)	0.0717 (8)	0.4791 (9)	0.021 (4)*
C12	0.5716 (3)	0.17311 (7)	0.52989 (8)	0.0174 (3)
C13	0.3057 (3)	0.41821 (8)	0.55191 (8)	0.0211 (3)
H13A	0.480 (3)	0.4407 (8)	0.5317 (10)	0.027 (4)*
H13B	0.147 (3)	0.4527 (9)	0.5336 (10)	0.030 (4)*
C14	0.3473 (3)	0.41179 (8)	0.64689 (8)	0.0213 (3)
H14A	0.218 (3)	0.3766 (9)	0.6707 (10)	0.027 (4)*
C15	0.5236 (3)	0.44972 (8)	0.70103 (8)	0.0210 (3)
C16	0.5300 (4)	0.44116 (10)	0.79470 (9)	0.0302 (4)
H16A	0.462 (4)	0.4849 (10)	0.8203 (11)	0.036 (5)*
H16B	0.399 (3)	0.4005 (9)	0.8061 (10)	0.029 (4)*
H16C	0.730 (4)	0.4325 (10)	0.8242 (12)	0.046 (5)*
C17	0.7187 (3)	0.50577 (9)	0.67578 (9)	0.0258 (3)
H17A	0.727 (4)	0.5072 (9)	0.6130 (12)	0.041 (5)*
H17B	0.652 (4)	0.5541 (10)	0.6914 (11)	0.037 (5)*
H17C	0.913 (4)	0.4996 (10)	0.7068 (11)	0.044 (5)*
C18	−0.2709 (3)	0.26594 (8)	0.33395 (8)	0.0200 (3)
H18A	−0.292 (3)	0.2171 (8)	0.3105 (9)	0.020 (4)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0183 (5)	0.0200 (5)	0.0242 (5)	0.0030 (4)	−0.0051 (4)	0.0011 (4)
O2	0.0174 (5)	0.0263 (6)	0.0214 (5)	0.0001 (4)	−0.0044 (4)	0.0024 (4)
O3	0.0193 (5)	0.0265 (6)	0.0202 (5)	0.0007 (4)	−0.0066 (4)	0.0016 (4)
N1	0.0158 (5)	0.0189 (6)	0.0161 (5)	0.0002 (5)	−0.0026 (4)	−0.0003 (5)
C1	0.0151 (6)	0.0187 (7)	0.0156 (6)	−0.0006 (5)	−0.0002 (5)	0.0012 (5)
C2	0.0146 (6)	0.0180 (7)	0.0171 (6)	0.0010 (5)	0.0009 (5)	0.0029 (5)
C3	0.0141 (6)	0.0228 (7)	0.0147 (6)	−0.0022 (5)	−0.0001 (5)	0.0014 (5)
C4	0.0167 (6)	0.0188 (7)	0.0161 (6)	−0.0023 (5)	0.0013 (5)	−0.0005 (5)
C5	0.0152 (6)	0.0190 (7)	0.0150 (6)	−0.0001 (5)	0.0016 (5)	0.0010 (5)
C6	0.0142 (6)	0.0209 (7)	0.0133 (5)	−0.0015 (5)	0.0008 (5)	0.0010 (5)
C7	0.0160 (6)	0.0203 (7)	0.0164 (6)	0.0007 (5)	0.0029 (5)	0.0022 (5)
C8	0.0162 (6)	0.0252 (8)	0.0148 (6)	0.0001 (5)	0.0003 (5)	0.0024 (5)
C9	0.0188 (7)	0.0268 (8)	0.0194 (6)	0.0057 (6)	0.0018 (5)	0.0063 (6)
C10	0.0266 (7)	0.0204 (8)	0.0224 (6)	0.0057 (6)	0.0052 (6)	0.0024 (6)
C11	0.0215 (7)	0.0212 (8)	0.0176 (6)	0.0008 (6)	0.0021 (5)	0.0007 (5)
C12	0.0150 (6)	0.0218 (7)	0.0152 (5)	0.0007 (5)	0.0017 (5)	0.0025 (5)
C13	0.0234 (7)	0.0194 (8)	0.0190 (6)	0.0003 (6)	−0.0028 (5)	0.0000 (5)
C14	0.0227 (7)	0.0200 (8)	0.0209 (6)	0.0008 (6)	0.0021 (5)	0.0002 (5)
C15	0.0229 (7)	0.0206 (8)	0.0187 (6)	0.0038 (6)	−0.0004 (5)	−0.0017 (5)
C16	0.0418 (10)	0.0292 (9)	0.0188 (7)	−0.0012 (8)	0.0013 (6)	−0.0026 (6)
C17	0.0265 (8)	0.0260 (9)	0.0232 (7)	−0.0029 (6)	−0.0027 (6)	−0.0025 (6)
C18	0.0179 (7)	0.0228 (8)	0.0189 (6)	−0.0032 (6)	0.0011 (5)	0.0009 (5)

Geometric parameters (Å, º)

O1—C2	1.3587 (16)	C9—C10	1.401 (2)
O1—H1O1	0.95 (2)	C9—H9A	0.974 (16)
O2—C18	1.2433 (17)	C10—C11	1.389 (2)
O3—C8	1.3698 (17)	C10—H10A	0.977 (17)
O3—H1O3	0.96 (2)	C11—C12	1.396 (2)
N1—C6	1.3707 (16)	C11—H11A	0.983 (15)
N1—C7	1.3870 (18)	C13—C14	1.5115 (18)
N1—H1N1	0.851 (18)	C13—H13A	1.027 (16)
C1—C2	1.3914 (17)	C13—H13B	1.010 (17)
C1—C6	1.3933 (18)	C14—C15	1.3305 (19)
C1—C13	1.5062 (19)	C14—H14A	1.015 (16)
C2—C3	1.4249 (19)	C15—C17	1.501 (2)
C3—C4	1.4034 (19)	C15—C16	1.5049 (19)
C3—C18	1.4396 (18)	C16—H16A	0.994 (18)
C4—C5	1.3803 (17)	C16—H16B	1.022 (17)
C4—H4A	0.993 (16)	C16—H16C	1.02 (2)
C5—C6	1.4279 (19)	C17—H17A	1.012 (18)
C5—C12	1.4550 (18)	C17—H17B	1.007 (19)
C7—C8	1.3922 (18)	C17—H17C	0.996 (19)
C7—C12	1.4005 (18)	C18—H18A	0.993 (16)
C8—C9	1.377 (2)
C2—O1—H1O1	105.3 (13)	C9—C10—H10A	118.7 (9)
C8—O3—H1O3	110.8 (12)	C10—C11—C12	117.98 (13)
C6—N1—C7	109.23 (11)	C10—C11—H11A	121.2 (9)
C6—N1—H1N1	123.5 (12)	C12—C11—H11A	120.8 (9)
C7—N1—H1N1	127.0 (12)	C11—C12—C7	119.30 (12)
C2—C1—C6	115.52 (12)	C11—C12—C5	134.97 (12)
C2—C1—C13	123.01 (12)	C7—C12—C5	105.72 (12)
C6—C1—C13	121.47 (11)	C1—C13—C14	113.50 (12)
O1—C2—C1	117.81 (12)	C1—C13—H13A	109.5 (9)
O1—C2—C3	120.49 (11)	C14—C13—H13A	110.5 (9)
C1—C2—C3	121.70 (12)	C1—C13—H13B	108.9 (9)
C4—C3—C2	120.58 (12)	C14—C13—H13B	109.4 (9)
C4—C3—C18	118.80 (12)	H13A—C13—H13B	104.6 (12)
C2—C3—C18	120.61 (12)	C15—C14—C13	126.62 (13)
C5—C4—C3	119.48 (12)	C15—C14—H14A	117.9 (9)
C5—C4—H4A	120.1 (9)	C13—C14—H14A	115.3 (9)
C3—C4—H4A	120.4 (9)	C14—C15—C17	124.27 (13)
C4—C5—C6	117.96 (12)	C14—C15—C16	121.07 (14)
C4—C5—C12	135.20 (13)	C17—C15—C16	114.60 (12)
C6—C5—C12	106.84 (11)	C15—C16—H16A	111.0 (10)
N1—C6—C1	126.95 (12)	C15—C16—H16B	109.2 (9)
N1—C6—C5	108.30 (11)	H16A—C16—H16B	107.9 (13)
C1—C6—C5	124.75 (12)	C15—C16—H16C	111.5 (11)
N1—C7—C8	127.28 (12)	H16A—C16—H16C	106.2 (15)
N1—C7—C12	109.89 (11)	H16B—C16—H16C	110.9 (14)
C8—C7—C12	122.83 (13)	C15—C17—H17A	113.4 (10)
O3—C8—C9	126.08 (12)	C15—C17—H17B	110.0 (10)
O3—C8—C7	116.65 (13)	H17A—C17—H17B	106.3 (14)
C9—C8—C7	117.26 (12)	C15—C17—H17C	110.7 (11)
C8—C9—C10	120.79 (13)	H17A—C17—H17C	109.7 (14)
C8—C9—H9A	118.8 (9)	H17B—C17—H17C	106.5 (14)
C10—C9—H9A	120.4 (9)	O2—C18—C3	125.11 (13)
C11—C10—C9	121.84 (14)	O2—C18—H18A	121.3 (9)
C11—C10—H10A	119.4 (9)	C3—C18—H18A	113.6 (9)
C6—C1—C2—O1	179.32 (11)	C12—C7—C8—O3	179.74 (11)
C13—C1—C2—O1	−1.14 (18)	N1—C7—C8—C9	−178.43 (12)
C6—C1—C2—C3	−0.31 (17)	C12—C7—C8—C9	0.49 (19)
C13—C1—C2—C3	179.23 (12)	O3—C8—C9—C10	−179.66 (12)
O1—C2—C3—C4	−178.56 (11)	C7—C8—C9—C10	−0.48 (19)
C1—C2—C3—C4	1.07 (19)	C8—C9—C10—C11	0.0 (2)
O1—C2—C3—C18	0.72 (18)	C9—C10—C11—C12	0.5 (2)
C1—C2—C3—C18	−179.66 (11)	C10—C11—C12—C7	−0.47 (18)
C2—C3—C4—C5	−1.02 (18)	C10—C11—C12—C5	178.79 (13)
C18—C3—C4—C5	179.70 (11)	N1—C7—C12—C11	179.07 (11)
C3—C4—C5—C6	0.25 (18)	C8—C7—C12—C11	−0.01 (19)
C3—C4—C5—C12	179.63 (13)	N1—C7—C12—C5	−0.38 (14)
C7—N1—C6—C1	178.76 (12)	C8—C7—C12—C5	−179.46 (11)
C7—N1—C6—C5	−1.12 (13)	C4—C5—C12—C11	1.0 (3)
C2—C1—C6—N1	179.65 (11)	C6—C5—C12—C11	−179.62 (14)
C13—C1—C6—N1	0.10 (19)	C4—C5—C12—C7	−179.72 (13)
C2—C1—C6—C5	−0.48 (18)	C6—C5—C12—C7	−0.30 (13)
C13—C1—C6—C5	179.97 (12)	C2—C1—C13—C14	130.72 (13)
C4—C5—C6—N1	−179.59 (10)	C6—C1—C13—C14	−49.76 (17)
C12—C5—C6—N1	0.87 (13)	C1—C13—C14—C15	146.11 (14)
C4—C5—C6—C1	0.52 (19)	C13—C14—C15—C17	−1.1 (2)
C12—C5—C6—C1	−179.02 (11)	C13—C14—C15—C16	175.88 (14)
C6—N1—C7—C8	179.98 (12)	C4—C3—C18—O2	−179.07 (12)
C6—N1—C7—C12	0.94 (14)	C2—C3—C18—O2	1.6 (2)
N1—C7—C8—O3	0.82 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O1···O2	0.95 (2)	1.75 (2)	2.6274 (13)	151.4 (18)
O3—H1O3···O2^i	0.96 (2)	1.77 (2)	2.7139 (14)	166.9 (19)
C13—H13B···O1	1.011 (16)	2.391 (16)	2.8469 (17)	106.4 (11)

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