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Acta Crystallogr Sect E Struct Rep Online. 2008 July 1; 64(Pt 7): o1207.
Published online 2008 June 7. doi:  10.1107/S1600536808016498
PMCID: PMC2961774

7,8,9,10-Tetra­hydro-2-methyl­cyclo­hepta­[b]indol-6(5H)-one

Abstract

The title compound, C14H15NO, was synthesized from 2-hydroxy­methyl­enecyclo­hepta­none via a Japp–Klingemann acid-catalyzed cyclization. The seven-membered ring exhibits a slightly distorted envelope conformation. N—H(...)O hydrogen bonds form a centrosymmetric dimer; C—H(...)O hydrogen bonds and π–π stacking inter­actions (the centers of the atoms involved in the stacking interaction are separated by 3.504 Å) give rise to another type of centrosymmetric dimer. In combination, these inter­actions create a stair-like chain of mol­ecules that inter­acts only loosely with neighboring chains via van der Waals inter­actions and weak C—H(...)π contacts.

Related literature

For related literature on the synthesis, structure, anti­cancer and anti­depressant activities, and toxicity of functionalized cyclo­hept[b]indoles, see: Cornec et al. (1998 [triangle]); Joseph et al. (1999 [triangle]); Kinnick et al. (2006 [triangle]); Humphrey & Kuethe (2006 [triangle], and references therein); Benoit et al. (2000 [triangle]); Kavitha & Rajendra Prasad (1999 [triangle], and references therein). Brameld et al. (2008 [triangle]) describe small-mol­ecule conformational preferences derived from crystal structure data. Bernstein et al. (1995 [triangle]) present the use of the versatile graph-set analysis for the description of hydrogen bonds.

An external file that holds a picture, illustration, etc.
Object name is e-64-o1207-scheme1.jpg

Experimental

Crystal data

  • C14H15NO
  • M r = 213.27
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-64-o1207-efi1.jpg
  • a = 11.461 (3) Å
  • b = 6.5062 (19) Å
  • c = 14.459 (4) Å
  • β = 92.310 (4)°
  • V = 1077.3 (6) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.08 mm−1
  • T = 100 (2) K
  • 0.48 × 0.10 × 0.08 mm

Data collection

  • Bruker SMART APEX CCD diffractometer
  • Absorption correction: multi-scan (SADABS as implemented in APEX2; Bruker, 2008 [triangle]) T min = 0.731, T max = 0.993
  • 9984 measured reflections
  • 2652 independent reflections
  • 1581 reflections with I > 2σ(I)
  • R int = 0.081

Refinement

  • R[F 2 > 2σ(F 2)] = 0.056
  • wR(F 2) = 0.135
  • S = 1.00
  • 2652 reflections
  • 146 parameters
  • H-atom parameters constrained
  • Δρmax = 0.19 e Å−3
  • Δρmin = −0.28 e Å−3

Data collection: APEX2 (Bruker, 2008 [triangle]); cell refinement: APEX2; data reduction: APEX2; program(s) used to solve structure: SHELXTL (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and Mercury (Macrae et al., 2006 [triangle]); software used to prepare material for publication: SHELXTL and Mercury.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536808016498/fl2202sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808016498/fl2202Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Acknowledgments

We acknowledge UGC, New Delhi, India, for the award of Major Research Project grant No. F. 31–122/2005. MS thanks UGC, New Delhi, for the award of a research fellowship. The diffractometer was funded by NSF grant 0087210, by Ohio Board of Regents grant CAP-491, and by YSU.

supplementary crystallographic information

Comment

Development of new methods towards the synthesis of functionalized cyclohept[b]indoles is currently attractive to organic chemists due to the discovery of anti-cancer and anti-depressant activities associated with this system (Cornec et al., 1998; Joseph et al. 1999). Synthetic studies on the large family of indoles have been documented extensively because of their structural diversity and association with their wide spectrum of pharmacological potential. Synthetic approaches to prepare cyclohept[b]indoles have been described in the literature and examined for central nervous system activity and reported to be active as antidepressants (Kinnick et al., 2006; Humphrey & Kuethe, 2006, and references therein). The design of molecules that spontaneously organize into a helical architecture is of considerable interest because of their fascinating structural features as well as their potential applications. Benoit et al. (2000) have reported the toxicity and structure activity relationship of benzocyclohept[b]indoles and these were found to be potent anti-inflammatory and anti-cancer agents. Therefore, much effort has been directed towards the development of efficient methodologies for the construction of heterocyclo-fused cyclohept[b]indoles. Based on the interesting features of these compounds we reported the synthesis and utility of cyclohept[b]indoles and their substituted analogs (Kavitha & Rajendra Prasad 1999, and references therein).

Cyclization of 2-hydroxymethylenecycloheptanone under Japp-Klingemann conditions using acetic acid and HCl in a 4:1 ratio (Kent's reagent) as the catalyst furnished the title compound (Fig. 1). Details of the synthesis of the title compound were reported by Kavitha & Rajendra Prasad (1999). An ORTEP style representation of the title compound is given in Fig 2.

The sp2 hybridized section of the molecule is essentially planar with an r.m.s. deviation from the mean plane of only 0.052 Å. Of the methylene carbon atoms C3 is deviates the most (0.786 (3) Å ) from this plane. Deviations for C2 and C4 are 0.252 (2) and -0.157 (3) Å, respectively. The seven membered ring thus is best described as having a slightly distorted envelope conformation (Brameld et al. 2008). All bond distances and angles in the structure of the title compound are in the expected ranges.

Via a pair of N—H···O hydrogen bonds the molecules form centrosymmetric dimers with an R22(10) graph set motif (Bernstein et al., 1995) in the solid state (Table 1, Fig. 3). The keto oxygen atom also acts as acceptor for a weaker C—H···O hydrogen bond from another neighboring molecule. The same neighboring molecule also acts as a partner for a π-π stacking interaction across an inversion center. The π moieties of these thus formed π-stacked dimers are slipped against each other and only the atoms C1, C6, C7 and C13 and their inversion symmetry related counterparts in the neighboring molecule are involved in the interaction of the π systems with a distance of about 3.5 Å between the planes (Fig. 3). Distances between the slipped centroids of the pyrrole rings are given in table 1. The main planes of the molecules are connected via the N—H···O and C—H···O hydrogen bonds and the π-π stacking interactions are all aligned roughly in parallel to each other. The two types of dimers created by the N—H···O and C—H···O interactions do each share one molecule, which extends the molecules held together via these strong to medium interactions into a flight of stairs like chain of molecules. Neighboring chains are only loosly connected via van der Waals interactions and weak C—H···π contacts (Table 1, Fig. 4).

Experimental

A solution of 2-(2-(4-methylphenyl)hydrazono)cycloheptanone (0.230 g, 0.001 mol) in a mixture of acetic acid (20 ml) and concentrated hydrochloric acid (5 ml) was heated to reflux on an oil bath pre-heated to 398–403 K for 2 h. The reaction was monitored by TLC. After completion of the reaction the contents were cooled and poured into icewater with stirring. The separated brown solid was filtered and purified by passing through a column of silica gel and eluting with a petroleum ether-ethyl acetate mixture (95:5) to yieldthe title compound (171 mg, 80%). The product thus obtained was recrystallized using ethanol, m.p. 451–453 K.

Refinement

All hydrogen atoms were added in calculated positions with a C—H bond distances of 0.99 (methylene), 0.95 (aromatic) and 0.98 Å (methyl) and an N—H distance of 0.88 Å. They were refined with isotropic displacement parameteres Uiso of 1.5 (methyl) or 1.2 times Ueq (all others) of the adjacent carbon or nitrogen atom. The s.u. values of the cell parameters are taken from the software recognizing that the values are unreasonably small.

Figures

Fig. 1.
Synthesis of the title compound
Fig. 2.
Thermal ellipsoid plot of one of the N—H···O bonded dimers with the atom labeling scheme. Displacement ellipsoids are shown at the 50% probability level, hydrogen atoms are shown as capped sticks.
Fig. 3.
Thermal ellipsoid plot of one of the π-stacked dimers. Red spheres are centers of π bonds involved in the π-stacking interactions, green dotted lines represent π···π contacts. Atom and bond ...
Fig. 4.
Packing view of the title crystal. Blue dotted lines represent N—H···O, C—H···O and C—H···π interactions. Green dotted lines are π···π ...

Crystal data

C14H15NOF(000) = 456
Mr = 213.27Dx = 1.315 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
a = 11.461 (3) ÅCell parameters from 1265 reflections
b = 6.5062 (19) Åθ = 2.3–24.5°
c = 14.459 (4) ŵ = 0.08 mm1
β = 92.310 (4)°T = 100 K
V = 1077.3 (6) Å3Plate, colourless
Z = 40.48 × 0.10 × 0.08 mm

Data collection

Bruker SMART APEX CCD diffractometer2652 independent reflections
Radiation source: fine-focus sealed tube1581 reflections with I > 2σ(I)
graphiteRint = 0.081
ω scansθmax = 28.3°, θmin = 2.2°
Absorption correction: multi-scan (SADABS as implemented in APEX2; Bruker, 2008)h = −15→15
Tmin = 0.731, Tmax = 0.993k = −8→8
9984 measured reflectionsl = −19→19

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.056Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.135H-atom parameters constrained
S = 1.00w = 1/[σ2(Fo2) + (0.0596P)2] where P = (Fo2 + 2Fc2)/3
2652 reflections(Δ/σ)max < 0.001
146 parametersΔρmax = 0.19 e Å3
0 restraintsΔρmin = −0.28 e Å3

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 (Å2)

xyzUiso*/Ueq
C10.13517 (16)0.2801 (3)1.08139 (13)0.0251 (4)
C20.21105 (17)0.3796 (3)1.15581 (13)0.0284 (5)
H2A0.25320.26881.19010.034*
H2B0.15890.44631.19980.034*
C30.30146 (17)0.5391 (3)1.12828 (14)0.0283 (5)
H3A0.34910.57861.18410.034*
H3B0.35440.47501.08410.034*
C40.24910 (17)0.7329 (3)1.08433 (13)0.0280 (5)
H4A0.17350.76181.11250.034*
H4B0.30180.85001.09880.034*
C50.22933 (17)0.7184 (3)0.97993 (13)0.0272 (5)
H5A0.18740.84380.95860.033*
H5B0.30660.71940.95160.033*
C60.16294 (15)0.5361 (3)0.94335 (13)0.0241 (4)
C70.12670 (16)0.3572 (3)0.98660 (13)0.0243 (4)
C80.06994 (16)0.3237 (3)0.83704 (13)0.0244 (4)
C90.02351 (16)0.2566 (3)0.75210 (13)0.0274 (5)
H9−0.01260.12570.74550.033*
C100.03204 (16)0.3877 (3)0.67779 (14)0.0287 (5)
H10−0.00030.34630.61920.034*
C110.08746 (17)0.5823 (3)0.68576 (13)0.0275 (5)
C120.13502 (16)0.6455 (3)0.77013 (14)0.0271 (5)
H120.17340.77460.77590.032*
C130.12601 (16)0.5160 (3)0.84787 (13)0.0245 (4)
C140.09470 (18)0.7160 (3)0.60049 (14)0.0339 (5)
H14A0.12110.85390.61870.051*
H14B0.01750.72500.56910.051*
H14C0.15020.65550.55840.051*
N10.07063 (13)0.2311 (2)0.92167 (10)0.0253 (4)
H10.04020.11010.93320.030*
O10.07986 (11)0.1233 (2)1.10088 (9)0.0300 (4)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0207 (10)0.0302 (10)0.0251 (11)0.0036 (8)0.0076 (8)0.0000 (8)
C20.0258 (10)0.0348 (11)0.0248 (11)0.0005 (9)0.0034 (9)0.0010 (9)
C30.0240 (10)0.0350 (11)0.0258 (11)0.0028 (9)0.0002 (8)−0.0005 (9)
C40.0233 (10)0.0321 (11)0.0286 (11)0.0013 (9)0.0017 (9)−0.0010 (9)
C50.0260 (10)0.0312 (11)0.0246 (11)−0.0014 (9)0.0036 (9)0.0008 (9)
C60.0183 (9)0.0305 (10)0.0237 (10)0.0030 (8)0.0032 (8)−0.0015 (8)
C70.0196 (10)0.0294 (10)0.0241 (11)0.0012 (8)0.0037 (8)−0.0021 (8)
C80.0182 (10)0.0309 (10)0.0245 (11)0.0007 (8)0.0050 (8)0.0007 (9)
C90.0228 (10)0.0337 (11)0.0260 (11)−0.0034 (9)0.0049 (8)−0.0016 (9)
C100.0206 (10)0.0429 (12)0.0230 (11)−0.0005 (9)0.0051 (8)−0.0025 (9)
C110.0210 (10)0.0380 (12)0.0239 (11)−0.0015 (9)0.0048 (8)0.0009 (9)
C120.0204 (10)0.0327 (11)0.0284 (11)0.0000 (9)0.0060 (8)0.0019 (9)
C130.0170 (9)0.0321 (11)0.0246 (11)0.0008 (8)0.0044 (8)−0.0013 (9)
C140.0297 (12)0.0439 (13)0.0284 (12)−0.0028 (10)0.0067 (9)0.0052 (10)
N10.0226 (9)0.0292 (9)0.0243 (9)−0.0015 (7)0.0035 (7)0.0008 (7)
O10.0311 (8)0.0309 (8)0.0283 (8)−0.0012 (6)0.0070 (6)0.0028 (6)

Geometric parameters (Å, °)

C1—O11.239 (2)C7—N11.385 (2)
C1—C71.459 (3)C8—N11.364 (2)
C1—C21.502 (3)C8—C91.389 (3)
C2—C31.531 (3)C8—C131.412 (3)
C2—H2A0.9900C9—C101.378 (3)
C2—H2B0.9900C9—H90.9500
C3—C41.524 (3)C10—C111.420 (3)
C3—H3A0.9900C10—H100.9500
C3—H3B0.9900C11—C121.379 (3)
C4—C51.520 (3)C11—C141.514 (3)
C4—H4A0.9900C12—C131.412 (3)
C4—H4B0.9900C12—H120.9500
C5—C61.494 (3)C14—H14A0.9800
C5—H5A0.9900C14—H14B0.9800
C5—H5B0.9900C14—H14C0.9800
C6—C71.393 (3)N1—H10.8800
C6—C131.434 (3)
O1—C1—C7118.77 (18)N1—C7—C6109.23 (17)
O1—C1—C2118.56 (17)N1—C7—C1116.39 (17)
C7—C1—C2122.64 (18)C6—C7—C1134.38 (18)
C1—C2—C3118.96 (16)N1—C8—C9130.00 (18)
C1—C2—H2A107.6N1—C8—C13107.80 (17)
C3—C2—H2A107.6C9—C8—C13122.19 (18)
C1—C2—H2B107.6C10—C9—C8117.27 (19)
C3—C2—H2B107.6C10—C9—H9121.4
H2A—C2—H2B107.0C8—C9—H9121.4
C4—C3—C2114.21 (16)C9—C10—C11122.29 (19)
C4—C3—H3A108.7C9—C10—H10118.9
C2—C3—H3A108.7C11—C10—H10118.9
C4—C3—H3B108.7C12—C11—C10119.84 (18)
C2—C3—H3B108.7C12—C11—C14121.11 (18)
H3A—C3—H3B107.6C10—C11—C14119.04 (18)
C5—C4—C3113.79 (16)C11—C12—C13119.17 (18)
C5—C4—H4A108.8C11—C12—H12120.4
C3—C4—H4A108.8C13—C12—H12120.4
C5—C4—H4B108.8C12—C13—C8119.21 (18)
C3—C4—H4B108.8C12—C13—C6133.15 (18)
H4A—C4—H4B107.7C8—C13—C6107.63 (16)
C6—C5—C4116.99 (16)C11—C14—H14A109.5
C6—C5—H5A108.1C11—C14—H14B109.5
C4—C5—H5A108.1H14A—C14—H14B109.5
C6—C5—H5B108.1C11—C14—H14C109.5
C4—C5—H5B108.1H14A—C14—H14C109.5
H5A—C5—H5B107.3H14B—C14—H14C109.5
C7—C6—C13105.92 (16)C8—N1—C7109.40 (16)
C7—C6—C5131.40 (17)C8—N1—H1125.3
C13—C6—C5122.66 (17)C7—N1—H1125.3
O1—C1—C2—C3165.37 (17)C9—C10—C11—C120.0 (3)
C7—C1—C2—C3−12.8 (3)C9—C10—C11—C14179.14 (17)
C1—C2—C3—C464.2 (2)C10—C11—C12—C13−1.0 (3)
C2—C3—C4—C5−88.3 (2)C14—C11—C12—C13179.88 (17)
C3—C4—C5—C651.7 (2)C11—C12—C13—C80.9 (3)
C4—C5—C6—C7−9.5 (3)C11—C12—C13—C6−178.67 (19)
C4—C5—C6—C13172.25 (17)N1—C8—C13—C12−178.80 (16)
C13—C6—C7—N10.32 (19)C9—C8—C13—C120.3 (3)
C5—C6—C7—N1−178.10 (18)N1—C8—C13—C60.8 (2)
C13—C6—C7—C1−179.5 (2)C9—C8—C13—C6179.93 (16)
C5—C6—C7—C12.0 (3)C7—C6—C13—C12178.9 (2)
O1—C1—C7—N1−9.3 (3)C5—C6—C13—C12−2.5 (3)
C2—C1—C7—N1168.83 (16)C7—C6—C13—C8−0.71 (19)
O1—C1—C7—C6170.51 (19)C5—C6—C13—C8177.89 (16)
C2—C1—C7—C6−11.3 (3)C9—C8—N1—C7−179.65 (18)
N1—C8—C9—C10177.61 (18)C13—C8—N1—C7−0.7 (2)
C13—C8—C9—C10−1.3 (3)C6—C7—N1—C80.2 (2)
C8—C9—C10—C111.1 (3)C1—C7—N1—C8−179.91 (15)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.882.092.890 (2)150.
C4—H4a···O1ii0.992.593.211 (3)121
C2—H2B···Cg1iii0.992.883.740 (2)146
C5—H5b···C10iv0.992.903.794 (2)151

Symmetry codes: (i) −x, −y, −z+2; (ii) x, y+1, z; (iii) −x, −y+1, −z+2; (iv) −x+1/2, y+1/2, −z+3/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FL2202).

References

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Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography