



Supporting information
![]() | Crystallographic Information File (CIF) https://doi.org/10.1107/S2056989015008786/hb7417sup1.cif |
![]() | Structure factor file (CIF format) https://doi.org/10.1107/S2056989015008786/hb7417Isup2.hkl |
![]() | Chemdraw file https://doi.org/10.1107/S2056989015008786/hb7417Isup3.cdx |
![]() | Chemical Markup Language (CML) file https://doi.org/10.1107/S2056989015008786/hb7417Isup4.cml |
CCDC reference: 1063387
Key indicators
- Single-crystal X-ray study
- T = 100 K
- Mean
(C-C)= 0.001 Å
- R factor = 0.038
- wR factor = 0.119
- Data-to-parameter ratio = 31.6
checkCIF/PLATON results
No syntax errors found No errors found in this datablock
Indole skeleton is an aromatic heterocycle possessing a benzene ring fused to a pyrrole ring which exhibits a wide range of biological and pharmacological activities. Compounds presenting this moiety have been successfully synthesized and used in medicinal chemistry (Xu et al., 2012). In spite of the number of developed methods for the preparation of indoles (Xu et al., 2012; Humphrey and Kuethe, 2006), our interest to use Morita–Baylis–Hillman adducts as building blocks for organic synthesis resulted in a successful stereoselective strategy to obtain compounds of this class.
\ The synthesis of 3-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydrocyclopenta[b]indole-2-\ carboxylic acid started with a mixture of 1 mmol of (±)-methyl 2-[hydroxy(3,4,5-trimethoxyphenyl)-methyl]acrylate (the Morita–Baylis–Hillman adduct), 1.2 mmol of indole and 1 mmol of 2-iodoxybenzoic acid, in acetonitrile (5 mL). This mixture was kept under reflux to give 1,3-dicarbonyl compound, which was further reduced by sodium tetrahydroborate, resulting in the corresponding β-hydroxy-carbonyl.
This was then treated with trifluoromethanesulfonic acid and submitted to basic hydrolysis. The cyclopenta[b]indole, obtained with excellent diastereoselectivity (>99:1) and overall yield of 70%, was purified by flash chromatography (hexane/ethyl acetate (60:40)). 3-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydrocyclopenta[b]indole-2-\ carboxylic acid was dissolved in 10:1 (v/v) chloroform/methanol mixture and kept in the freezer to allow slowly formation of irregular colorless single crystals.
The positions of hydrogen atoms bound to carbon atoms were idealized and calculated by riding model, with C—H bond lengths of 0.95, 0.98 and 0.99 Å for phenyl, methyl and methylene, respectively. The isotropic displacement parameters values (Uiso(H)) were fixed at 1.5Ueq(C) for methyl H atoms and 1.2Ueq(C) for all other attached H atoms.
The molecules of the title compound present a trimethoxyphenyl ring bonded to a system of three rings, in which an indole skeleton unit is fused to a five-membered ring possessing a carboxylic unit (Fig. 1). It crystallized in P1 space group and has a conformational structure determined by intra and intermolecular nonclassical (C—H—O) and intermolecular (O—H—O and N—H—O) bonding (Table 1, Fig. 2).
All of the rings in the structure are almost planar, with r.m.s. of 0.010, 0.066, 0.006 and 0.006 Å for trimethoxyphenyl, five-membered, pyrrole and benzene rings, respectively. The three rings fused system is essentially planar (r.m.s. deviation of 0.057 Å) and make a plane-plane angle of 113.35° with the trimethoxyphenyl ring.
With respect to the pyrrole ring, the benzene ring and the five-membered ring make dihedral angles C14—C13—N1—C5 = 176.67 (7)° and C3—C4—C16—C17 = -175.72 (8)°, respectively. The dihedral angle between the five-membered ring and its trimethoxyphenyl substituent (C5—C6—C7—C8) is -164.79 (16)°, while that between the five-membered ring and the carboxylic unit (C16—C17—C18—O4) is -56.30 (8)°, which is consistent with the expected trans relative configuration of this isomer.
Data collection: APEX2 (Bruker, 2010); cell refinement: SAINT (Bruker, 2010); data reduction: SAINT (Bruker, 2010); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXLE (Hübschle et al., 2011); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2003) and publCIF (Westrip, 2010).
![]() | Fig. 1. The molecular structure of the title compound with 50% probability displacement ellipsoids. |
![]() | Fig. 2. Crystal packing of the title compound, showing hydrogen-bonding interactions. |
C21H21NO5 | Z = 2 |
Mr = 367.39 | F(000) = 388 |
Triclinic, P1 | Dx = 1.372 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.203 (1) Å | Cell parameters from 9708 reflections |
b = 9.5844 (12) Å | θ = 2.6–38° |
c = 12.9957 (17) Å | µ = 0.10 mm−1 |
α = 91.939 (5)° | T = 100 K |
β = 97.198 (6)° | Irregular, colourless |
γ = 91.716 (5)° | 0.34 × 0.17 × 0.13 mm |
V = 889.1 (2) Å3 |
Bruker APEX CCD diffractometer | 7825 independent reflections |
Radiation source: fine-focus sealed tube | 6558 reflections with I > 2σ(I) |
Detector resolution: 8.3333 pixels mm-1 | Rint = 0.031 |
phi and ω scans | θmax = 35.0°, θmin = 1.6° |
Absorption correction: multi-scan (SADABS; Bruker, 2010) | h = −11→11 |
Tmin = 0.967, Tmax = 0.987 | k = −15→15 |
100846 measured reflections | l = −20→20 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.038 | H-atom parameters constrained |
wR(F2) = 0.119 | w = 1/[σ2(Fo2) + (0.079P)2 + 0.2107P] where P = (Fo2 + 2Fc2)/3 |
S = 0.94 | (Δ/σ)max < 0.001 |
7825 reflections | Δρmax = 0.58 e Å−3 |
248 parameters | Δρmin = −0.27 e Å−3 |
C21H21NO5 | γ = 91.716 (5)° |
Mr = 367.39 | V = 889.1 (2) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.203 (1) Å | Mo Kα radiation |
b = 9.5844 (12) Å | µ = 0.10 mm−1 |
c = 12.9957 (17) Å | T = 100 K |
α = 91.939 (5)° | 0.34 × 0.17 × 0.13 mm |
β = 97.198 (6)° |
Bruker APEX CCD diffractometer | 7825 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2010) | 6558 reflections with I > 2σ(I) |
Tmin = 0.967, Tmax = 0.987 | Rint = 0.031 |
100846 measured reflections |
R[F2 > 2σ(F2)] = 0.038 | 0 restraints |
wR(F2) = 0.119 | H-atom parameters constrained |
S = 0.94 | Δρmax = 0.58 e Å−3 |
7825 reflections | Δρmin = −0.27 e Å−3 |
248 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
O1 | 0.67935 (8) | 0.20458 (6) | 0.61432 (4) | 0.01701 (10) | |
O2 | 0.85593 (8) | 0.13066 (7) | 0.45301 (4) | 0.02026 (11) | |
O3 | 0.52886 (8) | 0.14039 (6) | 0.07684 (5) | 0.02004 (11) | |
O4 | 0.27178 (9) | 0.00009 (6) | 0.05008 (5) | 0.02346 (12) | |
H4 | 0.3380 | −0.0455 | 0.0131 | 0.035* | |
O5 | 0.36545 (8) | 0.34406 (6) | 0.59020 (4) | 0.01927 (11) | |
N1 | 0.20865 (9) | 0.57757 (6) | 0.22742 (5) | 0.01503 (10) | |
H1 | 0.2993 | 0.6285 | 0.2636 | 0.018* | |
C1 | −0.33636 (10) | 0.65445 (9) | 0.10853 (6) | 0.01960 (13) | |
H1A | −0.4633 | 0.6671 | 0.0816 | 0.024* | |
C2 | −0.25626 (10) | 0.52708 (8) | 0.09178 (6) | 0.01735 (12) | |
H2 | −0.3264 | 0.4538 | 0.0522 | 0.021* | |
C3 | −0.07052 (9) | 0.50802 (7) | 0.13406 (5) | 0.01394 (11) | |
C4 | 0.05337 (9) | 0.39331 (7) | 0.13915 (5) | 0.01372 (11) | |
C5 | 0.21619 (9) | 0.43919 (7) | 0.19636 (5) | 0.01331 (11) | |
C6 | 0.36676 (9) | 0.33516 (7) | 0.20740 (5) | 0.01314 (11) | |
H6 | 0.4670 | 0.3624 | 0.1645 | 0.016* | |
C7 | 0.45411 (9) | 0.30909 (7) | 0.31710 (5) | 0.01289 (11) | |
C8 | 0.62291 (9) | 0.24015 (7) | 0.33130 (5) | 0.01407 (11) | |
H8 | 0.6873 | 0.2187 | 0.2736 | 0.017* | |
C9 | 0.69665 (9) | 0.20293 (7) | 0.43061 (5) | 0.01429 (11) | |
C10 | 0.60455 (9) | 0.23835 (7) | 0.51579 (5) | 0.01402 (11) | |
C11 | 0.58428 (11) | 0.08561 (8) | 0.65126 (6) | 0.02034 (13) | |
H11A | 0.4493 | 0.1005 | 0.6438 | 0.031* | |
H11B | 0.6302 | 0.0737 | 0.7246 | 0.031* | |
H11C | 0.6086 | 0.0016 | 0.6106 | 0.031* | |
C12 | 0.94999 (11) | 0.08870 (10) | 0.36769 (7) | 0.02528 (16) | |
H12A | 0.8643 | 0.0311 | 0.3179 | 0.038* | |
H12B | 1.0587 | 0.0345 | 0.3927 | 0.038* | |
H12C | 0.9918 | 0.1716 | 0.3337 | 0.038* | |
C13 | 0.03194 (10) | 0.62141 (7) | 0.19116 (5) | 0.01434 (11) | |
C14 | −0.04783 (11) | 0.75053 (8) | 0.20623 (6) | 0.01750 (12) | |
H14 | 0.0223 | 0.8256 | 0.2437 | 0.021* | |
C15 | −0.23267 (11) | 0.76525 (8) | 0.16470 (6) | 0.01940 (13) | |
H15 | −0.2905 | 0.8517 | 0.1743 | 0.023* | |
C16 | 0.06472 (10) | 0.24706 (7) | 0.09663 (5) | 0.01538 (12) | |
H16A | 0.0682 | 0.2448 | 0.0207 | 0.018* | |
H16B | −0.0415 | 0.1870 | 0.1125 | 0.018* | |
C17 | 0.25541 (9) | 0.20188 (7) | 0.15655 (5) | 0.01396 (11) | |
H17 | 0.2239 | 0.1432 | 0.2146 | 0.017* | |
C18 | 0.36696 (10) | 0.11304 (7) | 0.09044 (5) | 0.01515 (12) | |
C19 | 0.36205 (9) | 0.34551 (7) | 0.40179 (5) | 0.01444 (11) | |
H19 | 0.2477 | 0.3931 | 0.3918 | 0.017* | |
C20 | 0.43904 (10) | 0.31162 (7) | 0.50143 (5) | 0.01433 (11) | |
C21 | 0.19448 (12) | 0.41674 (9) | 0.58029 (6) | 0.02137 (14) | |
H21A | 0.2090 | 0.5011 | 0.5411 | 0.032* | |
H21B | 0.1631 | 0.4429 | 0.6494 | 0.032* | |
H21C | 0.0939 | 0.3561 | 0.5435 | 0.032* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0210 (2) | 0.0173 (2) | 0.0115 (2) | −0.00177 (18) | −0.00212 (16) | 0.00000 (16) |
O2 | 0.0164 (2) | 0.0267 (3) | 0.0175 (2) | 0.00815 (19) | 0.00017 (17) | −0.00044 (19) |
O3 | 0.0183 (2) | 0.0206 (3) | 0.0210 (2) | 0.00222 (19) | 0.00369 (18) | −0.00790 (19) |
O4 | 0.0243 (3) | 0.0181 (3) | 0.0283 (3) | −0.0019 (2) | 0.0082 (2) | −0.0119 (2) |
O5 | 0.0259 (3) | 0.0208 (3) | 0.0124 (2) | 0.0063 (2) | 0.00682 (18) | −0.00088 (18) |
N1 | 0.0170 (2) | 0.0125 (2) | 0.0146 (2) | 0.00230 (18) | −0.00148 (18) | −0.00317 (18) |
C1 | 0.0167 (3) | 0.0230 (3) | 0.0192 (3) | 0.0042 (2) | 0.0019 (2) | 0.0012 (2) |
C2 | 0.0155 (3) | 0.0197 (3) | 0.0166 (3) | 0.0007 (2) | 0.0015 (2) | 0.0002 (2) |
C3 | 0.0151 (3) | 0.0150 (3) | 0.0116 (2) | 0.0016 (2) | 0.00173 (19) | −0.0009 (2) |
C4 | 0.0155 (3) | 0.0137 (3) | 0.0118 (2) | 0.0010 (2) | 0.00152 (19) | −0.00208 (19) |
C5 | 0.0160 (3) | 0.0121 (3) | 0.0115 (2) | 0.0017 (2) | 0.00085 (19) | −0.00173 (19) |
C6 | 0.0153 (2) | 0.0127 (3) | 0.0113 (2) | 0.0017 (2) | 0.00156 (19) | −0.00173 (19) |
C7 | 0.0147 (2) | 0.0127 (3) | 0.0111 (2) | 0.0013 (2) | 0.00167 (19) | −0.00187 (19) |
C8 | 0.0146 (2) | 0.0153 (3) | 0.0123 (2) | 0.0017 (2) | 0.00190 (19) | −0.0019 (2) |
C9 | 0.0136 (2) | 0.0149 (3) | 0.0139 (2) | 0.0015 (2) | 0.00027 (19) | −0.0019 (2) |
C10 | 0.0163 (3) | 0.0142 (3) | 0.0109 (2) | −0.0002 (2) | −0.00008 (19) | −0.00137 (19) |
C11 | 0.0230 (3) | 0.0187 (3) | 0.0195 (3) | 0.0007 (2) | 0.0022 (2) | 0.0047 (2) |
C12 | 0.0191 (3) | 0.0344 (4) | 0.0229 (3) | 0.0105 (3) | 0.0035 (3) | −0.0029 (3) |
C13 | 0.0168 (3) | 0.0141 (3) | 0.0120 (2) | 0.0029 (2) | 0.00133 (19) | −0.00108 (19) |
C14 | 0.0212 (3) | 0.0152 (3) | 0.0158 (3) | 0.0046 (2) | 0.0008 (2) | −0.0018 (2) |
C15 | 0.0206 (3) | 0.0199 (3) | 0.0181 (3) | 0.0071 (2) | 0.0024 (2) | 0.0002 (2) |
C16 | 0.0169 (3) | 0.0139 (3) | 0.0148 (3) | 0.0006 (2) | 0.0008 (2) | −0.0035 (2) |
C17 | 0.0176 (3) | 0.0124 (3) | 0.0119 (2) | 0.0016 (2) | 0.00258 (19) | −0.00245 (19) |
C18 | 0.0195 (3) | 0.0134 (3) | 0.0124 (2) | 0.0028 (2) | 0.0016 (2) | −0.0023 (2) |
C19 | 0.0163 (3) | 0.0156 (3) | 0.0117 (2) | 0.0032 (2) | 0.0025 (2) | −0.0011 (2) |
C20 | 0.0179 (3) | 0.0139 (3) | 0.0115 (2) | 0.0014 (2) | 0.0033 (2) | −0.00188 (19) |
C21 | 0.0257 (3) | 0.0198 (3) | 0.0208 (3) | 0.0062 (3) | 0.0110 (3) | −0.0001 (2) |
O1—C10 | 1.3785 (8) | C7—C8 | 1.3961 (9) |
O1—C11 | 1.4396 (10) | C8—C9 | 1.3949 (10) |
O2—C9 | 1.3632 (9) | C8—H8 | 0.9500 |
O2—C12 | 1.4229 (10) | C9—C10 | 1.3974 (9) |
O3—C18 | 1.2232 (9) | C10—C20 | 1.3973 (10) |
O4—C18 | 1.3206 (9) | C11—H11A | 0.9800 |
O4—H4 | 0.8400 | C11—H11B | 0.9800 |
O5—C20 | 1.3591 (8) | C11—H11C | 0.9800 |
O5—C21 | 1.4269 (10) | C12—H12A | 0.9800 |
N1—C5 | 1.3779 (9) | C12—H12B | 0.9800 |
N1—C13 | 1.3834 (9) | C12—H12C | 0.9800 |
N1—H1 | 0.8800 | C13—C14 | 1.3980 (10) |
C1—C2 | 1.3879 (11) | C14—C15 | 1.3857 (11) |
C1—C15 | 1.4078 (11) | C14—H14 | 0.9500 |
C1—H1A | 0.9500 | C15—H15 | 0.9500 |
C2—C3 | 1.4009 (10) | C16—C17 | 1.5719 (10) |
C2—H2 | 0.9500 | C16—H16A | 0.9900 |
C3—C13 | 1.4271 (10) | C16—H16B | 0.9900 |
C3—C4 | 1.4347 (9) | C17—C18 | 1.5078 (9) |
C4—C5 | 1.3601 (9) | C17—H17 | 1.0000 |
C4—C16 | 1.4975 (10) | C19—C20 | 1.3961 (9) |
C5—C6 | 1.4921 (9) | C19—H19 | 0.9500 |
C6—C7 | 1.5164 (9) | C21—H21A | 0.9800 |
C6—C17 | 1.5686 (10) | C21—H21B | 0.9800 |
C6—H6 | 1.0000 | C21—H21C | 0.9800 |
C7—C19 | 1.3942 (9) | ||
C10—O1—C11 | 112.48 (6) | H11A—C11—H11C | 109.5 |
C9—O2—C12 | 116.77 (6) | H11B—C11—H11C | 109.5 |
C18—O4—H4 | 109.5 | O2—C12—H12A | 109.5 |
C20—O5—C21 | 117.21 (6) | O2—C12—H12B | 109.5 |
C5—N1—C13 | 107.21 (6) | H12A—C12—H12B | 109.5 |
C5—N1—H1 | 126.4 | O2—C12—H12C | 109.5 |
C13—N1—H1 | 126.4 | H12A—C12—H12C | 109.5 |
C2—C1—C15 | 121.12 (7) | H12B—C12—H12C | 109.5 |
C2—C1—H1A | 119.4 | N1—C13—C14 | 129.41 (7) |
C15—C1—H1A | 119.4 | N1—C13—C3 | 108.66 (6) |
C1—C2—C3 | 119.10 (7) | C14—C13—C3 | 121.91 (6) |
C1—C2—H2 | 120.5 | C15—C14—C13 | 117.73 (7) |
C3—C2—H2 | 120.5 | C15—C14—H14 | 121.1 |
C2—C3—C13 | 118.90 (6) | C13—C14—H14 | 121.1 |
C2—C3—C4 | 135.29 (7) | C14—C15—C1 | 121.22 (7) |
C13—C3—C4 | 105.75 (6) | C14—C15—H15 | 119.4 |
C5—C4—C3 | 107.07 (6) | C1—C15—H15 | 119.4 |
C5—C4—C16 | 112.09 (6) | C4—C16—C17 | 101.36 (5) |
C3—C4—C16 | 140.65 (6) | C4—C16—H16A | 111.5 |
C4—C5—N1 | 111.28 (6) | C17—C16—H16A | 111.5 |
C4—C5—C6 | 115.13 (6) | C4—C16—H16B | 111.5 |
N1—C5—C6 | 133.48 (6) | C17—C16—H16B | 111.5 |
C5—C6—C7 | 116.44 (5) | H16A—C16—H16B | 109.3 |
C5—C6—C17 | 100.20 (5) | C18—C17—C6 | 113.56 (6) |
C7—C6—C17 | 111.15 (5) | C18—C17—C16 | 113.05 (5) |
C5—C6—H6 | 109.5 | C6—C17—C16 | 109.05 (5) |
C7—C6—H6 | 109.5 | C18—C17—H17 | 106.9 |
C17—C6—H6 | 109.5 | C6—C17—H17 | 106.9 |
C19—C7—C8 | 120.56 (6) | C16—C17—H17 | 106.9 |
C19—C7—C6 | 120.63 (6) | O3—C18—O4 | 123.34 (6) |
C8—C7—C6 | 118.70 (6) | O3—C18—C17 | 124.14 (6) |
C9—C8—C7 | 119.72 (6) | O4—C18—C17 | 112.51 (6) |
C9—C8—H8 | 120.1 | C7—C19—C20 | 119.54 (6) |
C7—C8—H8 | 120.1 | C7—C19—H19 | 120.2 |
O2—C9—C8 | 124.76 (6) | C20—C19—H19 | 120.2 |
O2—C9—C10 | 115.23 (6) | O5—C20—C19 | 125.19 (6) |
C8—C9—C10 | 120.01 (6) | O5—C20—C10 | 114.64 (6) |
O1—C10—C20 | 119.89 (6) | C19—C20—C10 | 120.17 (6) |
O1—C10—C9 | 120.14 (6) | O5—C21—H21A | 109.5 |
C20—C10—C9 | 119.94 (6) | O5—C21—H21B | 109.5 |
O1—C11—H11A | 109.5 | H21A—C21—H21B | 109.5 |
O1—C11—H11B | 109.5 | O5—C21—H21C | 109.5 |
H11A—C11—H11B | 109.5 | H21A—C21—H21C | 109.5 |
O1—C11—H11C | 109.5 | H21B—C21—H21C | 109.5 |
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H4···O3i | 0.84 | 1.84 | 2.6748 (8) | 176 |
N1—H1···O1ii | 0.88 | 2.20 | 2.9041 (8) | 136 |
C12—H12B···O2iii | 0.98 | 2.62 | 3.3905 (11) | 137 |
Symmetry codes: (i) −x+1, −y, −z; (ii) −x+1, −y+1, −z+1; (iii) −x+2, −y, −z+1. |
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H4···O3i | 0.84 | 1.84 | 2.6748 (8) | 176 |
N1—H1···O1ii | 0.88 | 2.20 | 2.9041 (8) | 136 |
C12—H12B···O2iii | 0.98 | 2.62 | 3.3905 (11) | 137 |
Symmetry codes: (i) −x+1, −y, −z; (ii) −x+1, −y+1, −z+1; (iii) −x+2, −y, −z+1. |