organic compounds
Ethyl 27-oxo-15-oxa-2,20-diazahexacyclo[18.6.1.01,8.02,6.09,14.021,26]heptacosa-9,11,13,21,23,25-hexaene-7-carboxylate
aCentre of Advanced Study in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai 600 025, India, and bDepartment of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
*Correspondence e-mail: shirai2011@gmail.com
In the title compound, C27H30N2O4, the pyrrolidine ring adopts a twisted conformation. The indoline ring system is almost perpendicular to the mean plane of the pyrrolidine ring, making a dihedral angle of 81.7 (8)°. In the crystal, molecules are linked into centrosymmetric dimers with graph-set motif R22(16) via pairs of C—H⋯O hydrogen bonds. The terminal ethyl group of the ester group is disordered over two sets of sites, with a site-occupancy ratio of 0.587 (11):0.413 (11).
Related literature
For the biological activity of spiro-pyrrolidine derivatives, see: Obniska et al. (2003); Peddi et al. (2004); Christoph et al. (2011); Stylianakis et al. (2003); Waldmann (1995); Suzuki et al. (1994); Huryn et al. (1991). For a related structure, see: Ganesh et al. (2012). For puckering parameters, see: Cremer & Pople (1975) and for asymmetry parameters, see: Nardelli et al. (1983).
Experimental
Crystal data
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Refinement
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Data collection: APEX2 (Bruker, 2008); cell SAINT (Bruker, 2008); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009).
Supporting information
https://doi.org/10.1107/S1600536812049082/bt6853sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812049082/bt6853Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536812049082/bt6853Isup3.cml
A solution of (E)-ethyl 3-(2-(4-(2,3-dioxoindolin-1-yl)butoxy)phenyl)acrylate (200 mg, 0.5 mmol) and L-proline (70 mg, 0.61 mmol) was refluxed in dry toluene under N2 atmosphere for 8hrs under Dean-Stark apparatus. After the completion of reaction as indicated by TLC, toluene was evaporated under reduced pressure. The crude product was washed with water and extracted with dichloromethane (4x20mL). The combined organic layers were dried (MgSO4) and filtered, concentrated in vacuum. The crude product was purified by
using hexane: EtOAc (8:2) as eluent.Atoms C1 and C2 are disordered over two positions (C1A/C1B & C2A/C2B) with refined occupancies of 0.587 (11):0.413 (11). The O-C and C-C distances of the disordered atoms were restrained to be equal. The displacement parameters of the disordered atoms were restrained to be equal for bonded atoms. All H atoms were fixed geometrically and allowed to ride on their parent C atoms, with C—H distances fixed in the range 0.93–0.97 Å with Uiso(H) = 1.5Ueq(C) for methyl H, 1.2Ueq(C) for other H atoms.
Spiro-pyrrolidine derivatives are unique tetracyclic 5-HT(2 A) receptor antagonists (Obniska et al., 2003; Peddi et al., 2004). These derivatives possess anticancer (Christoph et al., 2011) and anti-influenza virus (Stylianakis et al., 2003) activities. Highly functionalized pyrrolidines have gained much interest in the past few years as they constitute the main structural element of many natural and synthetic pharmacologically active compounds (Waldmann, 1995). Optically active pyrrolidines have been used as intermediates, chiral ligands or auxiliaries in controlled
(Suzuki et al., 1994; Huryn et al., 1991). In view of these importance and in continuation of our work on the analysis of spiro-pyrrolidine derivatives, the of the title compound has been carried out and the results are presented here.X-Ray analysis confirms the molecular structure and atom connectivity as illustrated in Fig. 1. The bond lengths and angles are within normal ranges and comparable to those found in related structures (Ganesh et al., 2012). Terminal atoms C1 & C2 is substituted at propanate group, which is disordered over two positions [C1A/C1B & C2A/C2B] with a site-occupancy ratio of 0.604 (5):0.396 (5). The sum of the angles at N1 & N2 [339 (1)° & 348.7 (1)°] of the pyrrolidine and indole rings are in accordance with sp3 hybridization.
The indoline ring system is essentially planar, with maximum deviation of 0.038 (2) Å for atom C16. The pyrrolidine ring system makes dihedral angle of 81.7 (8)° with the indoline ring system, it clearly shows that both the rings are perpendicular to each other. The propanate group assumes an extended conformation which can be seen from the torsion angle [C4/C3/O2/C2= 179.3 (2)°].
The dihedral angle of the pyrrolidine ring and the benzene ring (C21—C26) is 36.5 (1)°. The atom O4 deviates by 0.102 (1) Å from the leastsquares plane of the indole ring. The pyrrolidine ring adopts twisted conformation [it is twisted about C1—C2], with the puckering parameters q2 and φ (Cremer & Pople, 1975) and the smallest displacement asymmetric parameter, Δs, (Nardelli et al., 1983) as follows: q2=0.4071 (2) Å, φ=82.0 (8)°, Δs(C4)=7.61 (2). The crystal packing is stabilized by C—H···O interactions.
For the biological activity of spiro-pyrrolidine derivatives, see: Obniska et al. (2003); Peddi et al. (2004); Christoph et al. (2011); Stylianakis et al. (2003); Waldmann (1995); Suzuki et al. (1994); Huryn et al. (1991). For a related structure, see: Ganesh et al. (2012). For puckering parameters, see: Cremer & Pople (1975) and for asymmetry parameters, see: Nardelli et al. (1983).
Data collection: APEX2 (Bruker, 2008); cell
SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).C27H30N2O4 | Z = 2 |
Mr = 446.53 | F(000) = 476 |
Triclinic, P1 | Dx = 1.305 Mg m−3 |
Hall symbol: -P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 8.9327 (5) Å | Cell parameters from 5603 reflections |
b = 10.0068 (5) Å | θ = 1.5–28.3° |
c = 14.6379 (11) Å | µ = 0.09 mm−1 |
α = 103.988 (4)° | T = 293 K |
β = 95.023 (4)° | Block, white crystalline |
γ = 113.775 (3)° | 0.30 × 0.30 × 0.25 mm |
V = 1136.41 (13) Å3 |
Bruker APEXII CCD area-detector diffractometer | 5603 independent reflections |
Radiation source: fine-focus sealed tube | 4378 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.025 |
ω and φ scans | θmax = 28.3°, θmin = 1.5° |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | h = −11→11 |
Tmin = 0.974, Tmax = 0.978 | k = −13→13 |
20472 measured reflections | l = −18→19 |
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)] = 0.045 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.125 | H-atom parameters constrained |
S = 1.08 | w = 1/[σ2(Fo2) + (0.0559P)2 + 0.215P] where P = (Fo2 + 2Fc2)/3 |
5603 reflections | (Δ/σ)max = 0.002 |
319 parameters | Δρmax = 0.23 e Å−3 |
40 restraints | Δρmin = −0.22 e Å−3 |
C27H30N2O4 | γ = 113.775 (3)° |
Mr = 446.53 | V = 1136.41 (13) Å3 |
Triclinic, P1 | Z = 2 |
a = 8.9327 (5) Å | Mo Kα radiation |
b = 10.0068 (5) Å | µ = 0.09 mm−1 |
c = 14.6379 (11) Å | T = 293 K |
α = 103.988 (4)° | 0.30 × 0.30 × 0.25 mm |
β = 95.023 (4)° |
Bruker APEXII CCD area-detector diffractometer | 5603 independent reflections |
Absorption correction: multi-scan (SADABS; Bruker, 2008) | 4378 reflections with I > 2σ(I) |
Tmin = 0.974, Tmax = 0.978 | Rint = 0.025 |
20472 measured reflections |
R[F2 > 2σ(F2)] = 0.045 | 40 restraints |
wR(F2) = 0.125 | H-atom parameters constrained |
S = 1.08 | Δρmax = 0.23 e Å−3 |
5603 reflections | Δρmin = −0.22 e Å−3 |
319 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. |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
C1A | −0.0430 (10) | 1.0338 (8) | 0.2839 (4) | 0.0877 (18) | 0.587 (11) |
H1A1 | 0.0125 | 1.0358 | 0.2306 | 0.132* | 0.587 (11) |
H1A2 | −0.0730 | 1.1174 | 0.2975 | 0.132* | 0.587 (11) |
H1A3 | −0.1420 | 0.9386 | 0.2680 | 0.132* | 0.587 (11) |
C2A | 0.0677 (12) | 1.0483 (8) | 0.3675 (6) | 0.089 (3) | 0.587 (11) |
H2A1 | 0.0188 | 1.0599 | 0.4238 | 0.106* | 0.587 (11) |
H2A2 | 0.1740 | 1.1376 | 0.3795 | 0.106* | 0.587 (11) |
C1B | 0.0656 (17) | 1.0966 (9) | 0.2980 (6) | 0.088 (3) | 0.413 (11) |
H1B1 | 0.1845 | 1.1562 | 0.3183 | 0.131* | 0.413 (11) |
H1B2 | 0.0130 | 1.1639 | 0.3003 | 0.131* | 0.413 (11) |
H1B3 | 0.0393 | 1.0304 | 0.2334 | 0.131* | 0.413 (11) |
C2B | 0.0054 (13) | 1.0057 (11) | 0.3611 (9) | 0.072 (3) | 0.413 (11) |
H2B1 | −0.1149 | 0.9451 | 0.3426 | 0.086* | 0.413 (11) |
H2B2 | 0.0346 | 1.0696 | 0.4274 | 0.086* | 0.413 (11) |
C3 | 0.21727 (18) | 0.92280 (15) | 0.41102 (10) | 0.0423 (3) | |
C4 | 0.26073 (15) | 0.78973 (13) | 0.38728 (9) | 0.0328 (3) | |
H4 | 0.3792 | 0.8281 | 0.4159 | 0.039* | |
C5 | 0.15967 (15) | 0.66458 (14) | 0.43037 (9) | 0.0346 (3) | |
H5 | 0.0410 | 0.6419 | 0.4175 | 0.042* | |
C6 | 0.22279 (18) | 0.69639 (17) | 0.53715 (10) | 0.0466 (3) | |
H6A | 0.2708 | 0.8051 | 0.5713 | 0.056* | |
H6B | 0.1334 | 0.6416 | 0.5664 | 0.056* | |
C7 | 0.3552 (2) | 0.63749 (19) | 0.53718 (11) | 0.0550 (4) | |
H7A | 0.4601 | 0.7115 | 0.5293 | 0.066* | |
H7B | 0.3743 | 0.6130 | 0.5960 | 0.066* | |
C8 | 0.2771 (2) | 0.49510 (18) | 0.45101 (11) | 0.0503 (4) | |
H8A | 0.3628 | 0.4711 | 0.4251 | 0.060* | |
H8B | 0.2022 | 0.4082 | 0.4687 | 0.060* | |
C9 | 0.24212 (14) | 0.55059 (13) | 0.28972 (9) | 0.0314 (2) | |
C10 | 0.40719 (14) | 0.54634 (14) | 0.28034 (9) | 0.0335 (3) | |
C11 | 0.56843 (16) | 0.64768 (16) | 0.32716 (11) | 0.0433 (3) | |
H11 | 0.5907 | 0.7389 | 0.3736 | 0.052* | |
C12 | 0.69804 (17) | 0.6109 (2) | 0.30370 (12) | 0.0531 (4) | |
H12 | 0.8079 | 0.6793 | 0.3342 | 0.064* | |
C13 | 0.66598 (19) | 0.4754 (2) | 0.23631 (12) | 0.0552 (4) | |
H13 | 0.7541 | 0.4521 | 0.2231 | 0.066* | |
C14 | 0.50416 (19) | 0.37281 (19) | 0.18772 (11) | 0.0491 (4) | |
H14 | 0.4821 | 0.2810 | 0.1419 | 0.059* | |
C15 | 0.37664 (16) | 0.41162 (15) | 0.20968 (9) | 0.0373 (3) | |
C16 | 0.11869 (15) | 0.40657 (14) | 0.20770 (9) | 0.0362 (3) | |
C17 | 0.1341 (2) | 0.19559 (16) | 0.08382 (11) | 0.0528 (4) | |
H17A | 0.0135 | 0.1469 | 0.0769 | 0.063* | |
H17B | 0.1753 | 0.1226 | 0.0927 | 0.063* | |
C18 | 0.1747 (2) | 0.23314 (18) | −0.00835 (11) | 0.0552 (4) | |
H18A | 0.1372 | 0.1376 | −0.0597 | 0.066* | |
H18B | 0.2953 | 0.2869 | 0.0004 | 0.066* | |
C19 | 0.0979 (2) | 0.33016 (19) | −0.04075 (11) | 0.0568 (4) | |
H19A | 0.0621 | 0.2915 | −0.1103 | 0.068* | |
H19B | −0.0013 | 0.3154 | −0.0142 | 0.068* | |
C20 | 0.2087 (2) | 0.49895 (18) | −0.01325 (10) | 0.0531 (4) | |
H20A | 0.3192 | 0.5157 | −0.0248 | 0.064* | |
H20B | 0.1635 | 0.5445 | −0.0528 | 0.064* | |
C21 | 0.33250 (17) | 0.72236 (15) | 0.12529 (10) | 0.0396 (3) | |
C22 | 0.4290 (2) | 0.80905 (19) | 0.07220 (11) | 0.0536 (4) | |
H22 | 0.4166 | 0.7651 | 0.0066 | 0.064* | |
C23 | 0.5431 (2) | 0.95975 (19) | 0.11637 (12) | 0.0592 (4) | |
H23 | 0.6082 | 1.0165 | 0.0806 | 0.071* | |
C24 | 0.5606 (2) | 1.02605 (18) | 0.21268 (12) | 0.0565 (4) | |
H24 | 0.6379 | 1.1274 | 0.2427 | 0.068* | |
C25 | 0.46165 (18) | 0.94020 (16) | 0.26501 (11) | 0.0473 (3) | |
H25 | 0.4736 | 0.9863 | 0.3302 | 0.057* | |
C26 | 0.34589 (15) | 0.78868 (14) | 0.22383 (9) | 0.0350 (3) | |
C27 | 0.23201 (14) | 0.69994 (13) | 0.28114 (8) | 0.0314 (2) | |
H27 | 0.1165 | 0.6710 | 0.2510 | 0.038* | |
N1 | 0.18398 (13) | 0.53096 (12) | 0.37981 (7) | 0.0361 (2) | |
N2 | 0.20527 (14) | 0.32851 (12) | 0.16915 (8) | 0.0398 (3) | |
O1 | 0.28603 (18) | 1.03033 (14) | 0.48165 (9) | 0.0743 (4) | |
O2 | 0.09278 (16) | 0.90670 (14) | 0.34755 (9) | 0.0684 (3) | |
O3 | 0.22133 (12) | 0.57163 (11) | 0.08703 (6) | 0.0447 (2) | |
O4 | −0.03046 (11) | 0.36456 (11) | 0.18380 (7) | 0.0494 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1A | 0.106 (4) | 0.079 (3) | 0.104 (3) | 0.063 (3) | 0.008 (3) | 0.038 (3) |
C2A | 0.119 (6) | 0.077 (4) | 0.087 (4) | 0.078 (4) | −0.009 (4) | 0.002 (3) |
C1B | 0.131 (7) | 0.069 (4) | 0.074 (4) | 0.046 (4) | 0.027 (4) | 0.032 (3) |
C2B | 0.092 (5) | 0.072 (4) | 0.087 (6) | 0.058 (4) | 0.041 (5) | 0.038 (4) |
C3 | 0.0498 (7) | 0.0370 (7) | 0.0411 (8) | 0.0205 (6) | 0.0135 (6) | 0.0094 (6) |
C4 | 0.0343 (6) | 0.0329 (6) | 0.0297 (6) | 0.0152 (5) | 0.0065 (5) | 0.0064 (5) |
C5 | 0.0346 (6) | 0.0354 (6) | 0.0328 (6) | 0.0155 (5) | 0.0097 (5) | 0.0072 (5) |
C6 | 0.0565 (8) | 0.0451 (8) | 0.0320 (7) | 0.0163 (6) | 0.0131 (6) | 0.0103 (6) |
C7 | 0.0570 (9) | 0.0661 (10) | 0.0420 (8) | 0.0227 (8) | 0.0038 (7) | 0.0265 (7) |
C8 | 0.0655 (9) | 0.0601 (9) | 0.0476 (9) | 0.0391 (8) | 0.0218 (7) | 0.0304 (7) |
C9 | 0.0315 (5) | 0.0331 (6) | 0.0300 (6) | 0.0157 (5) | 0.0067 (5) | 0.0075 (5) |
C10 | 0.0341 (6) | 0.0377 (6) | 0.0340 (6) | 0.0193 (5) | 0.0086 (5) | 0.0128 (5) |
C11 | 0.0360 (6) | 0.0470 (8) | 0.0474 (8) | 0.0183 (6) | 0.0062 (6) | 0.0162 (6) |
C12 | 0.0349 (7) | 0.0702 (10) | 0.0638 (10) | 0.0254 (7) | 0.0118 (7) | 0.0319 (9) |
C13 | 0.0528 (8) | 0.0895 (12) | 0.0568 (10) | 0.0507 (9) | 0.0274 (7) | 0.0396 (9) |
C14 | 0.0629 (9) | 0.0646 (9) | 0.0431 (8) | 0.0460 (8) | 0.0218 (7) | 0.0208 (7) |
C15 | 0.0433 (7) | 0.0437 (7) | 0.0347 (7) | 0.0255 (6) | 0.0126 (5) | 0.0156 (5) |
C16 | 0.0379 (6) | 0.0353 (6) | 0.0342 (7) | 0.0161 (5) | 0.0082 (5) | 0.0081 (5) |
C17 | 0.0673 (9) | 0.0375 (7) | 0.0460 (9) | 0.0239 (7) | 0.0076 (7) | −0.0002 (6) |
C18 | 0.0703 (10) | 0.0500 (9) | 0.0403 (8) | 0.0310 (8) | 0.0085 (7) | −0.0018 (7) |
C19 | 0.0667 (10) | 0.0619 (10) | 0.0342 (8) | 0.0330 (8) | −0.0024 (7) | −0.0020 (7) |
C20 | 0.0743 (10) | 0.0599 (9) | 0.0305 (7) | 0.0375 (8) | 0.0112 (7) | 0.0090 (6) |
C21 | 0.0473 (7) | 0.0439 (7) | 0.0353 (7) | 0.0260 (6) | 0.0094 (6) | 0.0148 (6) |
C22 | 0.0738 (10) | 0.0600 (9) | 0.0394 (8) | 0.0345 (8) | 0.0225 (7) | 0.0230 (7) |
C23 | 0.0705 (10) | 0.0612 (10) | 0.0576 (10) | 0.0276 (8) | 0.0278 (8) | 0.0351 (8) |
C24 | 0.0612 (9) | 0.0471 (8) | 0.0554 (10) | 0.0138 (7) | 0.0143 (8) | 0.0226 (7) |
C25 | 0.0530 (8) | 0.0448 (8) | 0.0388 (8) | 0.0155 (6) | 0.0103 (6) | 0.0140 (6) |
C26 | 0.0392 (6) | 0.0386 (6) | 0.0322 (6) | 0.0201 (5) | 0.0081 (5) | 0.0134 (5) |
C27 | 0.0331 (6) | 0.0327 (6) | 0.0287 (6) | 0.0164 (5) | 0.0046 (5) | 0.0072 (5) |
N1 | 0.0436 (6) | 0.0373 (6) | 0.0323 (6) | 0.0210 (5) | 0.0125 (4) | 0.0115 (4) |
N2 | 0.0451 (6) | 0.0357 (6) | 0.0365 (6) | 0.0207 (5) | 0.0071 (5) | 0.0024 (4) |
O1 | 0.0918 (9) | 0.0525 (7) | 0.0627 (8) | 0.0368 (7) | 0.0019 (7) | −0.0139 (6) |
O2 | 0.0874 (8) | 0.0622 (7) | 0.0668 (8) | 0.0558 (7) | −0.0023 (6) | 0.0045 (6) |
O3 | 0.0589 (6) | 0.0458 (5) | 0.0286 (5) | 0.0243 (5) | 0.0090 (4) | 0.0078 (4) |
O4 | 0.0336 (5) | 0.0502 (6) | 0.0515 (6) | 0.0142 (4) | 0.0025 (4) | 0.0029 (5) |
C1A—C2A | 1.443 (6) | C11—C12 | 1.3947 (19) |
C1A—H1A1 | 0.9600 | C11—H11 | 0.9300 |
C1A—H1A2 | 0.9600 | C12—C13 | 1.373 (2) |
C1A—H1A3 | 0.9600 | C12—H12 | 0.9300 |
C2A—O2 | 1.487 (5) | C13—C14 | 1.385 (2) |
C2A—H2A1 | 0.9700 | C13—H13 | 0.9300 |
C2A—H2A2 | 0.9700 | C14—C15 | 1.3827 (18) |
C1B—C2B | 1.438 (7) | C14—H14 | 0.9300 |
C1B—H1B1 | 0.9600 | C15—N2 | 1.4011 (17) |
C1B—H1B2 | 0.9600 | C16—O4 | 1.2123 (15) |
C1B—H1B3 | 0.9600 | C16—N2 | 1.3701 (16) |
C2B—O2 | 1.478 (6) | C17—N2 | 1.4524 (18) |
C2B—H2B1 | 0.9700 | C17—C18 | 1.521 (2) |
C2B—H2B2 | 0.9700 | C17—H17A | 0.9700 |
C3—O1 | 1.1925 (18) | C17—H17B | 0.9700 |
C3—O2 | 1.3145 (18) | C18—C19 | 1.530 (2) |
C3—C4 | 1.5038 (17) | C18—H18A | 0.9700 |
C4—C5 | 1.5333 (16) | C18—H18B | 0.9700 |
C4—C27 | 1.5351 (17) | C19—C20 | 1.500 (2) |
C4—H4 | 0.9800 | C19—H19A | 0.9700 |
C5—N1 | 1.4720 (16) | C19—H19B | 0.9700 |
C5—C6 | 1.5241 (19) | C20—O3 | 1.4440 (16) |
C5—H5 | 0.9800 | C20—H20A | 0.9700 |
C6—C7 | 1.520 (2) | C20—H20B | 0.9700 |
C6—H6A | 0.9700 | C21—O3 | 1.3643 (16) |
C6—H6B | 0.9700 | C21—C22 | 1.3930 (19) |
C7—C8 | 1.511 (2) | C21—C26 | 1.4064 (18) |
C7—H7A | 0.9700 | C22—C23 | 1.380 (2) |
C7—H7B | 0.9700 | C22—H22 | 0.9300 |
C8—N1 | 1.4756 (17) | C23—C24 | 1.370 (2) |
C8—H8A | 0.9700 | C23—H23 | 0.9300 |
C8—H8B | 0.9700 | C24—C25 | 1.3896 (19) |
C9—N1 | 1.4867 (15) | C24—H24 | 0.9300 |
C9—C10 | 1.5093 (15) | C25—C26 | 1.3843 (19) |
C9—C16 | 1.5442 (17) | C25—H25 | 0.9300 |
C9—C27 | 1.5669 (16) | C26—C27 | 1.5194 (16) |
C10—C11 | 1.3734 (18) | C27—H27 | 0.9800 |
C10—C15 | 1.3934 (18) | ||
C1A—C2A—O2 | 107.4 (5) | C14—C13—H13 | 119.5 |
C1A—C2A—H2A1 | 110.2 | C15—C14—C13 | 117.71 (14) |
O2—C2A—H2A1 | 110.2 | C15—C14—H14 | 121.1 |
C1A—C2A—H2A2 | 110.2 | C13—C14—H14 | 121.1 |
O2—C2A—H2A2 | 110.2 | C14—C15—C10 | 121.80 (13) |
H2A1—C2A—H2A2 | 108.5 | C14—C15—N2 | 127.97 (13) |
C2B—C1B—H1B1 | 109.5 | C10—C15—N2 | 110.23 (10) |
C2B—C1B—H1B2 | 109.5 | O4—C16—N2 | 125.24 (12) |
H1B1—C1B—H1B2 | 109.5 | O4—C16—C9 | 126.60 (11) |
C2B—C1B—H1B3 | 109.5 | N2—C16—C9 | 108.07 (10) |
H1B1—C1B—H1B3 | 109.5 | N2—C17—C18 | 113.75 (12) |
H1B2—C1B—H1B3 | 109.5 | N2—C17—H17A | 108.8 |
C1B—C2B—O2 | 103.0 (6) | C18—C17—H17A | 108.8 |
C1B—C2B—H2B1 | 111.2 | N2—C17—H17B | 108.8 |
O2—C2B—H2B1 | 111.2 | C18—C17—H17B | 108.8 |
C1B—C2B—H2B2 | 111.2 | H17A—C17—H17B | 107.7 |
O2—C2B—H2B2 | 111.2 | C17—C18—C19 | 115.73 (13) |
H2B1—C2B—H2B2 | 109.1 | C17—C18—H18A | 108.3 |
O1—C3—O2 | 123.36 (13) | C19—C18—H18A | 108.3 |
O1—C3—C4 | 123.34 (14) | C17—C18—H18B | 108.3 |
O2—C3—C4 | 113.27 (12) | C19—C18—H18B | 108.3 |
C3—C4—C5 | 111.85 (10) | H18A—C18—H18B | 107.4 |
C3—C4—C27 | 118.71 (10) | C20—C19—C18 | 116.20 (14) |
C5—C4—C27 | 102.81 (9) | C20—C19—H19A | 108.2 |
C3—C4—H4 | 107.6 | C18—C19—H19A | 108.2 |
C5—C4—H4 | 107.6 | C20—C19—H19B | 108.2 |
C27—C4—H4 | 107.6 | C18—C19—H19B | 108.2 |
N1—C5—C6 | 105.91 (10) | H19A—C19—H19B | 107.4 |
N1—C5—C4 | 103.94 (9) | O3—C20—C19 | 110.62 (13) |
C6—C5—C4 | 115.22 (11) | O3—C20—H20A | 109.5 |
N1—C5—H5 | 110.5 | C19—C20—H20A | 109.5 |
C6—C5—H5 | 110.5 | O3—C20—H20B | 109.5 |
C4—C5—H5 | 110.5 | C19—C20—H20B | 109.5 |
C7—C6—C5 | 103.05 (11) | H20A—C20—H20B | 108.1 |
C7—C6—H6A | 111.2 | O3—C21—C22 | 123.50 (13) |
C5—C6—H6A | 111.2 | O3—C21—C26 | 116.04 (11) |
C7—C6—H6B | 111.2 | C22—C21—C26 | 120.46 (13) |
C5—C6—H6B | 111.2 | C23—C22—C21 | 120.37 (14) |
H6A—C6—H6B | 109.1 | C23—C22—H22 | 119.8 |
C8—C7—C6 | 102.04 (12) | C21—C22—H22 | 119.8 |
C8—C7—H7A | 111.4 | C24—C23—C22 | 120.23 (14) |
C6—C7—H7A | 111.4 | C24—C23—H23 | 119.9 |
C8—C7—H7B | 111.4 | C22—C23—H23 | 119.9 |
C6—C7—H7B | 111.4 | C23—C24—C25 | 119.26 (15) |
H7A—C7—H7B | 109.2 | C23—C24—H24 | 120.4 |
N1—C8—C7 | 105.66 (11) | C25—C24—H24 | 120.4 |
N1—C8—H8A | 110.6 | C26—C25—C24 | 122.54 (14) |
C7—C8—H8A | 110.6 | C26—C25—H25 | 118.7 |
N1—C8—H8B | 110.6 | C24—C25—H25 | 118.7 |
C7—C8—H8B | 110.6 | C25—C26—C21 | 117.12 (12) |
H8A—C8—H8B | 108.7 | C25—C26—C27 | 121.56 (11) |
N1—C9—C10 | 116.46 (9) | C21—C26—C27 | 121.25 (11) |
N1—C9—C16 | 106.22 (9) | C26—C27—C4 | 114.73 (10) |
C10—C9—C16 | 101.89 (9) | C26—C27—C9 | 117.37 (9) |
N1—C9—C27 | 104.52 (9) | C4—C27—C9 | 101.60 (9) |
C10—C9—C27 | 115.18 (9) | C26—C27—H27 | 107.5 |
C16—C9—C27 | 112.44 (9) | C4—C27—H27 | 107.5 |
C11—C10—C15 | 119.80 (11) | C9—C27—H27 | 107.5 |
C11—C10—C9 | 131.67 (12) | C5—N1—C8 | 108.13 (10) |
C15—C10—C9 | 108.54 (10) | C5—N1—C9 | 110.23 (9) |
C10—C11—C12 | 118.65 (14) | C8—N1—C9 | 120.66 (10) |
C10—C11—H11 | 120.7 | C16—N2—C15 | 110.85 (10) |
C12—C11—H11 | 120.7 | C16—N2—C17 | 123.63 (11) |
C13—C12—C11 | 121.05 (14) | C15—N2—C17 | 124.23 (11) |
C13—C12—H12 | 119.5 | C3—O2—C2B | 124.6 (5) |
C11—C12—H12 | 119.5 | C3—O2—C2A | 111.3 (3) |
C12—C13—C14 | 120.93 (13) | C21—O3—C20 | 117.33 (11) |
C12—C13—H13 | 119.5 | ||
O1—C3—C4—C5 | 89.09 (17) | C22—C21—C26—C27 | 175.06 (12) |
O2—C3—C4—C5 | −89.09 (14) | C25—C26—C27—C4 | −2.05 (16) |
O1—C3—C4—C27 | −151.44 (14) | C21—C26—C27—C4 | −178.96 (10) |
O2—C3—C4—C27 | 30.38 (16) | C25—C26—C27—C9 | −121.25 (13) |
C3—C4—C5—N1 | 165.51 (10) | C21—C26—C27—C9 | 61.84 (15) |
C27—C4—C5—N1 | 37.05 (11) | C3—C4—C27—C26 | 67.92 (14) |
C3—C4—C5—C6 | −79.07 (14) | C5—C4—C27—C26 | −168.04 (9) |
C27—C4—C5—C6 | 152.47 (10) | C3—C4—C27—C9 | −164.39 (10) |
N1—C5—C6—C7 | 28.37 (13) | C5—C4—C27—C9 | −40.35 (11) |
C4—C5—C6—C7 | −85.91 (13) | N1—C9—C27—C26 | 155.06 (10) |
C5—C6—C7—C8 | −38.37 (13) | C10—C9—C27—C26 | 25.97 (15) |
C6—C7—C8—N1 | 34.89 (14) | C16—C9—C27—C26 | −90.16 (12) |
N1—C9—C10—C11 | −70.23 (17) | N1—C9—C27—C4 | 29.09 (11) |
C16—C9—C10—C11 | 174.70 (13) | C10—C9—C27—C4 | −99.99 (11) |
C27—C9—C10—C11 | 52.69 (18) | C16—C9—C27—C4 | 143.88 (10) |
N1—C9—C10—C15 | 110.05 (12) | C6—C5—N1—C8 | −6.82 (13) |
C16—C9—C10—C15 | −5.02 (12) | C4—C5—N1—C8 | 115.00 (11) |
C27—C9—C10—C15 | −127.02 (11) | C6—C5—N1—C9 | −140.65 (10) |
C15—C10—C11—C12 | −1.28 (19) | C4—C5—N1—C9 | −18.83 (12) |
C9—C10—C11—C12 | 179.03 (12) | C7—C8—N1—C5 | −17.71 (14) |
C10—C11—C12—C13 | −1.0 (2) | C7—C8—N1—C9 | 110.39 (13) |
C11—C12—C13—C14 | 1.7 (2) | C10—C9—N1—C5 | 121.72 (11) |
C12—C13—C14—C15 | −0.2 (2) | C16—C9—N1—C5 | −125.67 (10) |
C13—C14—C15—C10 | −2.1 (2) | C27—C9—N1—C5 | −6.59 (12) |
C13—C14—C15—N2 | 178.71 (13) | C10—C9—N1—C8 | −5.43 (16) |
C11—C10—C15—C14 | 2.89 (19) | C16—C9—N1—C8 | 107.18 (12) |
C9—C10—C15—C14 | −177.35 (11) | C27—C9—N1—C8 | −133.74 (11) |
C11—C10—C15—N2 | −177.82 (11) | O4—C16—N2—C15 | 177.33 (12) |
C9—C10—C15—N2 | 1.94 (14) | C9—C16—N2—C15 | −5.83 (14) |
N1—C9—C16—O4 | 60.93 (16) | O4—C16—N2—C17 | 9.9 (2) |
C10—C9—C16—O4 | −176.69 (13) | C9—C16—N2—C17 | −173.31 (12) |
C27—C9—C16—O4 | −52.82 (17) | C14—C15—N2—C16 | −178.20 (13) |
N1—C9—C16—N2 | −115.86 (10) | C10—C15—N2—C16 | 2.56 (15) |
C10—C9—C16—N2 | 6.52 (12) | C14—C15—N2—C17 | −10.8 (2) |
C27—C9—C16—N2 | 130.40 (10) | C10—C15—N2—C17 | 169.95 (12) |
N2—C17—C18—C19 | −66.50 (18) | C18—C17—N2—C16 | 96.75 (16) |
C17—C18—C19—C20 | 97.32 (18) | C18—C17—N2—C15 | −69.06 (18) |
C18—C19—C20—O3 | −76.86 (17) | O1—C3—O2—C2B | −9.2 (4) |
O3—C21—C22—C23 | −177.87 (14) | C4—C3—O2—C2B | 169.0 (4) |
C26—C21—C22—C23 | 2.2 (2) | O1—C3—O2—C2A | 8.6 (5) |
C21—C22—C23—C24 | −0.9 (3) | C4—C3—O2—C2A | −173.2 (5) |
C22—C23—C24—C25 | −0.4 (3) | C1B—C2B—O2—C3 | 106.8 (10) |
C23—C24—C25—C26 | 0.6 (2) | C1B—C2B—O2—C2A | 52.4 (13) |
C24—C25—C26—C21 | 0.6 (2) | C1A—C2A—O2—C3 | 167.2 (7) |
C24—C25—C26—C27 | −176.39 (13) | C1A—C2A—O2—C2B | −58.7 (15) |
O3—C21—C26—C25 | 178.04 (12) | C22—C21—O3—C20 | 1.99 (19) |
C22—C21—C26—C25 | −1.99 (19) | C26—C21—O3—C20 | −178.03 (11) |
O3—C21—C26—C27 | −4.92 (17) | C19—C20—O3—C21 | 173.01 (12) |
D—H···A | D—H | H···A | D···A | D—H···A |
C11—H11···O1i | 0.93 | 2.49 | 3.3957 (19) | 164 |
C12—H12···O2ii | 0.93 | 2.59 | 3.446 (2) | 153 |
C13—H13···O4ii | 0.93 | 2.47 | 3.3986 (17) | 175 |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) x+1, y, z. |
Experimental details
Crystal data | |
Chemical formula | C27H30N2O4 |
Mr | 446.53 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 293 |
a, b, c (Å) | 8.9327 (5), 10.0068 (5), 14.6379 (11) |
α, β, γ (°) | 103.988 (4), 95.023 (4), 113.775 (3) |
V (Å3) | 1136.41 (13) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.30 × 0.30 × 0.25 |
Data collection | |
Diffractometer | Bruker APEXII CCD area-detector |
Absorption correction | Multi-scan (SADABS; Bruker, 2008) |
Tmin, Tmax | 0.974, 0.978 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 20472, 5603, 4378 |
Rint | 0.025 |
(sin θ/λ)max (Å−1) | 0.667 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.045, 0.125, 1.08 |
No. of reflections | 5603 |
No. of parameters | 319 |
No. of restraints | 40 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.23, −0.22 |
Computer programs: APEX2 (Bruker, 2008), SAINT (Bruker, 2008), SHELXS97 (Sheldrick, 2008), ORTEP-3 (Farrugia, 2012), SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).
D—H···A | D—H | H···A | D···A | D—H···A |
C11—H11···O1i | 0.93 | 2.49 | 3.3957 (19) | 164.0 |
C12—H12···O2ii | 0.93 | 2.59 | 3.446 (2) | 152.9 |
C13—H13···O4ii | 0.93 | 2.47 | 3.3986 (17) | 174.6 |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) x+1, y, z. |
Acknowledgements
The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection. SN thanks the University Grant Commission (UGC), Government of India, New Delhi, for a Meritorious Fellowship under the SAP programme.
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This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
Spiro-pyrrolidine derivatives are unique tetracyclic 5-HT(2 A) receptor antagonists (Obniska et al., 2003; Peddi et al., 2004). These derivatives possess anticancer (Christoph et al., 2011) and anti-influenza virus (Stylianakis et al., 2003) activities. Highly functionalized pyrrolidines have gained much interest in the past few years as they constitute the main structural element of many natural and synthetic pharmacologically active compounds (Waldmann, 1995). Optically active pyrrolidines have been used as intermediates, chiral ligands or auxiliaries in controlled asymmetric synthesis (Suzuki et al., 1994; Huryn et al., 1991). In view of these importance and in continuation of our work on the crystal structure analysis of spiro-pyrrolidine derivatives, the crystal structure of the title compound has been carried out and the results are presented here.
X-Ray analysis confirms the molecular structure and atom connectivity as illustrated in Fig. 1. The bond lengths and angles are within normal ranges and comparable to those found in related structures (Ganesh et al., 2012). Terminal atoms C1 & C2 is substituted at propanate group, which is disordered over two positions [C1A/C1B & C2A/C2B] with a site-occupancy ratio of 0.604 (5):0.396 (5). The sum of the angles at N1 & N2 [339 (1)° & 348.7 (1)°] of the pyrrolidine and indole rings are in accordance with sp3 hybridization.
The indoline ring system is essentially planar, with maximum deviation of 0.038 (2) Å for atom C16. The pyrrolidine ring system makes dihedral angle of 81.7 (8)° with the indoline ring system, it clearly shows that both the rings are perpendicular to each other. The propanate group assumes an extended conformation which can be seen from the torsion angle [C4/C3/O2/C2= 179.3 (2)°].
The dihedral angle of the pyrrolidine ring and the benzene ring (C21—C26) is 36.5 (1)°. The atom O4 deviates by 0.102 (1) Å from the leastsquares plane of the indole ring. The pyrrolidine ring adopts twisted conformation [it is twisted about C1—C2], with the puckering parameters q2 and φ (Cremer & Pople, 1975) and the smallest displacement asymmetric parameter, Δs, (Nardelli et al., 1983) as follows: q2=0.4071 (2) Å, φ=82.0 (8)°, Δs(C4)=7.61 (2). The crystal packing is stabilized by C—H···O interactions.