Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807045072/ci2460sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807045072/ci2460Isup2.hkl |
CCDC reference: 653171
A solution of (1E,4E,6Z)-1,7-bis(methylthiazol-5-yl)-4-[(4-methylthiazol -5yl)methylene]hepta-1,6-diene-3,5-dione (1 mmol), isatin (1 mmol) and L-proline (1 mmol) in aqueous methonal (20 ml) was refluxed until the disappearence of starting materials as evidenced by TLC. The solvent was removed under reduced pressure and the crude product was purified by column-chromatography using petroleum ether/ethyl acetate (5:1) as eluent. The final product was recrystallized in ethanol and chloroform (2:8).
H atoms were positioned geometrically (N—H = 0.86 Å and C—H = 0.93–0.98 Å) and allowed to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C) or 1.5Ueq(methyl C). PLATON (Spek, 2003) detected a solvent accessible void of approximately 75 Å3 including the position of this peak. This void could have initially contained solvent molecules but these molecules have since evaporated from the structure without degradation of the crystal.
The spiro ring system is a frequently encountered structural motif in many pharmacologically relevant alkaloids. Synthetic spiro-pyrrolidine derivatives have activity against aldose reductase enzyme which controls influenza (Stylianakis et al., 2003). The pyrrolizidine alkaloids are well documented for their mutagenic, antineoplastic, carcinogenic, hepatoxic, and many pharmacological activities (Usha, Selvanayagam, Velmurugan, Ravikumar, Durga & Raghunathan, 2005); Usha, Selvanayagam, Velmurugan, Ravikumar & Poornachandran, 2005). Thiazole derivatives possess anti-inflammatory properties (Köysal et al., 2004) and thiazole napthyridine derivatives exibit good antibactrial activity (Kondo et al., 1990). A series of thiazole[3,4–9]benzimidazole derivatives have been evaluated in vitro as antitumor agents against 60 human tumor cell-lines (Chimirri et al., 1994). Indole, being an integral part of many natural products of therapeutic importance, possesses potentially reactive sites for a variety of chemical reactions to generate molecular diversity (Farhanullah et al., 2004). In view of this biological importance, the crystal structure of the title compound has been determined and the results are presented here.
In the molecule of the title compound (Fig.1), the C—C and C—N bond lengths in the pyrrolizine ring system are slightly longer than the values reported for similar structures (Seshadri et al., 2003). This may be due to steric forces caused by the bulky substituents on the pyrrolizine ring system. The sum of angles at N1 of the pyrrolizine ring system (341.9°) is in accordance with sp3 hybridization (Beddoes et al., 1986), and the sum of the angles at N15 of the indole moiety (359.9°) is in accordance with sp2 hybridization.
In the pyrrolizine ring system, the pyrrolidine ring A adopts an envelope conformation whereas the ring B adopts a twist conformation. The puckering parameters (q2 and φ; Cremer & Pople, 1975) and the smallest displacement asymmetry parameter (Δ; Nardelli, 1983) are, for the ring A, q2 = 0.371 (2) Å, φ = 79.0 (3)° and Δs(C6) = 4.6 (2)°; for the ring B, q2 = 0.334 (3) Å, φ = 241.9 (4)°, Δ2(C5)=6.7 (3)° and Δs(C3) = 8.5 (3)°. The pyrrolizine ring system is folded about the bridging N1—C5 bond, as observed in related structures (Usha, Selvanayagam, Velmurugan, Ravikumar, Durga & Raghunathan, 2005); Usha, Selvanayagam, Velmurugan, Ravikumar & Poornachandran, 2005). The five-membered ring C in the indolone ring system adopts a twist conformation, with puckering parameters q2 = 0.074 (2) Å, φ = 133.5 (2)°, Δ2(C14) = 2.4 (2)° and Δs(C16) = 1.0 (2)°.
The molecular structure is stabilized by intramolecular C—H···O interactions and the crystal packing is stabilized by C—H···O and N—H···N intermolecular hydrogen bonds. The molecules at (x, y, z) and (1 - x, 2 - y, 1 - z) are linked by N15—H15···N22 hydrogen bonds into cyclic centrosymmetric R22(22) dimers. The dimers are cross-linked via C—H···π interactions involving the S1/C25/C26/N27/C28 ring (centroid Cg).
For general background, see: Chimirri et al. (1994); Farhanullah et al. (2004); Köysal et al. (2004); Kondo et al. (1990); Stylianakis et al. (2003). For ring conformations, see: Cremer & Pople (1975); Nardelli (1983). For related structures, see: Beddoes et al. (1986); Seshadri et al. (2003); Usha, Selvanayagam, Velmurugan, Ravikumar, Durga & Raghunathan (2005); Usha, Selvanayagam, Velmurugan, Ravikumar & Poornachandran (2005).
Data collection: APEX2 (Bruker, 2004); cell refinement: APEX2 (Bruker, 2004); data reduction: SAINT (Bruker, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ZORTEP (Zsolnai, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and PLATON (Spek, 2003).
C25H24N4O2S2 | F(000) = 1000 |
Mr = 476.60 | Dx = 1.315 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 2850 reflections |
a = 10.8362 (3) Å | θ = 2.0–25.5° |
b = 9.0056 (2) Å | µ = 0.25 mm−1 |
c = 24.7698 (5) Å | T = 293 K |
β = 95.272 (1)° | Block, colourless |
V = 2406.97 (10) Å3 | 0.26 × 0.21 × 0.17 mm |
Z = 4 |
Bruker APEXII CCD area-detector diffractometer | 6839 independent reflections |
Radiation source: fine-focus sealed tube | 4872 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.027 |
ω scans | θmax = 29.8°, θmin = 1.7° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2001) | h = −15→15 |
Tmin = 0.939, Tmax = 0.958 | k = −12→11 |
29274 measured reflections | l = −34→34 |
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)] = 0.051 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.160 | H-atom parameters constrained |
S = 1.01 | w = 1/[σ2(Fo2) + (0.0799P)2 + 0.9857P] where P = (Fo2 + 2Fc2)/3 |
6839 reflections | (Δ/σ)max = 0.005 |
300 parameters | Δρmax = 0.56 e Å−3 |
0 restraints | Δρmin = −0.53 e Å−3 |
C25H24N4O2S2 | V = 2406.97 (10) Å3 |
Mr = 476.60 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 10.8362 (3) Å | µ = 0.25 mm−1 |
b = 9.0056 (2) Å | T = 293 K |
c = 24.7698 (5) Å | 0.26 × 0.21 × 0.17 mm |
β = 95.272 (1)° |
Bruker APEXII CCD area-detector diffractometer | 6839 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2001) | 4872 reflections with I > 2σ(I) |
Tmin = 0.939, Tmax = 0.958 | Rint = 0.027 |
29274 measured reflections |
R[F2 > 2σ(F2)] = 0.051 | 0 restraints |
wR(F2) = 0.160 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.56 e Å−3 |
6839 reflections | Δρmin = −0.53 e Å−3 |
300 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 | ||
S1 | 0.40437 (6) | 0.92038 (8) | 0.18158 (2) | 0.0692 (2) | |
S2 | 0.25147 (6) | 1.26490 (8) | 0.44224 (2) | 0.0696 (2) | |
O1 | 0.48783 (12) | 0.74268 (16) | 0.36378 (6) | 0.0506 (3) | |
O2 | 0.08715 (13) | 0.96110 (17) | 0.26782 (6) | 0.0546 (4) | |
N1 | 0.30422 (15) | 0.55545 (16) | 0.29597 (6) | 0.0408 (3) | |
C2 | 0.2387 (3) | 0.4160 (3) | 0.30022 (10) | 0.0762 (8) | |
H2A | 0.1512 | 0.4330 | 0.3031 | 0.091* | |
H2B | 0.2725 | 0.3601 | 0.3316 | 0.091* | |
C3 | 0.2585 (3) | 0.3356 (3) | 0.24902 (10) | 0.0665 (6) | |
H3A | 0.3374 | 0.2838 | 0.2523 | 0.080* | |
H3B | 0.1927 | 0.2645 | 0.2399 | 0.080* | |
C4 | 0.2573 (3) | 0.4542 (3) | 0.20783 (9) | 0.0723 (8) | |
H4A | 0.1736 | 0.4726 | 0.1919 | 0.087* | |
H4B | 0.3086 | 0.4273 | 0.1793 | 0.087* | |
C5 | 0.30954 (19) | 0.5913 (2) | 0.23858 (7) | 0.0445 (4) | |
H5 | 0.3960 | 0.6064 | 0.2312 | 0.053* | |
C6 | 0.23813 (16) | 0.73706 (19) | 0.23011 (6) | 0.0344 (3) | |
H6 | 0.1492 | 0.7148 | 0.2264 | 0.041* | |
C7 | 0.26998 (14) | 0.81582 (18) | 0.28429 (6) | 0.0316 (3) | |
H7 | 0.3536 | 0.8572 | 0.2843 | 0.038* | |
C8 | 0.27434 (15) | 0.68763 (18) | 0.32670 (6) | 0.0330 (3) | |
C9 | 0.16479 (16) | 0.6752 (2) | 0.35981 (7) | 0.0375 (4) | |
C10 | 0.03935 (18) | 0.6653 (3) | 0.34481 (9) | 0.0525 (5) | |
H10 | 0.0095 | 0.6637 | 0.3084 | 0.063* | |
C11 | −0.0415 (2) | 0.6579 (3) | 0.38492 (12) | 0.0742 (7) | |
H11 | −0.1265 | 0.6532 | 0.3755 | 0.089* | |
C12 | 0.0038 (3) | 0.6573 (4) | 0.43879 (12) | 0.0817 (8) | |
H12 | −0.0518 | 0.6503 | 0.4652 | 0.098* | |
C13 | 0.1288 (3) | 0.6668 (3) | 0.45480 (9) | 0.0674 (7) | |
H13 | 0.1584 | 0.6659 | 0.4912 | 0.081* | |
C14 | 0.20798 (19) | 0.6779 (2) | 0.41451 (7) | 0.0441 (4) | |
N15 | 0.33653 (16) | 0.69457 (19) | 0.42016 (6) | 0.0472 (4) | |
H15 | 0.3812 | 0.6932 | 0.4507 | 0.057* | |
C16 | 0.38215 (16) | 0.71317 (19) | 0.37152 (7) | 0.0379 (4) | |
C17 | 0.18303 (16) | 0.94061 (19) | 0.29627 (6) | 0.0358 (3) | |
C18 | 0.21351 (17) | 1.0351 (2) | 0.34393 (7) | 0.0415 (4) | |
H18 | 0.1489 | 1.0887 | 0.3568 | 0.050* | |
C19 | 0.32534 (17) | 1.05114 (19) | 0.37045 (7) | 0.0391 (4) | |
H19 | 0.3895 | 0.9957 | 0.3581 | 0.047* | |
C20 | 0.35632 (18) | 1.1463 (2) | 0.41653 (7) | 0.0423 (4) | |
C21 | 0.3649 (3) | 1.3260 (3) | 0.48850 (9) | 0.0733 (7) | |
H21 | 0.3506 | 1.3987 | 0.5139 | 0.088* | |
N22 | 0.47284 (19) | 1.2656 (2) | 0.48645 (7) | 0.0596 (5) | |
C23 | 0.46987 (19) | 1.1618 (2) | 0.44532 (7) | 0.0450 (4) | |
C24 | 0.5839 (2) | 1.0779 (3) | 0.43622 (11) | 0.0623 (6) | |
H24A | 0.5622 | 0.9784 | 0.4252 | 0.093* | |
H24B | 0.6378 | 1.0753 | 0.4692 | 0.093* | |
H24C | 0.6255 | 1.1258 | 0.4084 | 0.093* | |
C25 | 0.26903 (16) | 0.8213 (2) | 0.18115 (6) | 0.0374 (4) | |
C26 | 0.20859 (17) | 0.8262 (2) | 0.13094 (7) | 0.0416 (4) | |
N27 | 0.26748 (17) | 0.9047 (2) | 0.09272 (6) | 0.0494 (4) | |
C28 | 0.3701 (2) | 0.9577 (3) | 0.11439 (8) | 0.0604 (6) | |
H28 | 0.4227 | 1.0132 | 0.0947 | 0.073* | |
C29 | 0.0868 (2) | 0.7560 (4) | 0.11396 (10) | 0.0760 (8) | |
H29A | 0.0998 | 0.6660 | 0.0945 | 0.114* | |
H29B | 0.0373 | 0.8230 | 0.0910 | 0.114* | |
H29C | 0.0448 | 0.7336 | 0.1455 | 0.114* |
U11 | U22 | U33 | U12 | U13 | U23 | |
S1 | 0.0752 (4) | 0.0939 (5) | 0.0364 (2) | −0.0519 (3) | −0.0055 (2) | 0.0098 (3) |
S2 | 0.0681 (4) | 0.0850 (5) | 0.0526 (3) | 0.0197 (3) | −0.0103 (3) | −0.0331 (3) |
O1 | 0.0369 (7) | 0.0500 (8) | 0.0625 (9) | 0.0037 (6) | −0.0084 (6) | −0.0038 (6) |
O2 | 0.0535 (8) | 0.0560 (9) | 0.0501 (8) | 0.0122 (7) | −0.0174 (6) | −0.0026 (6) |
N1 | 0.0555 (9) | 0.0313 (7) | 0.0350 (7) | 0.0002 (6) | 0.0006 (6) | −0.0035 (6) |
C2 | 0.144 (3) | 0.0380 (12) | 0.0490 (12) | −0.0259 (14) | 0.0224 (14) | −0.0036 (9) |
C3 | 0.0973 (18) | 0.0446 (12) | 0.0562 (13) | −0.0152 (12) | −0.0011 (12) | −0.0089 (10) |
C4 | 0.135 (2) | 0.0408 (12) | 0.0410 (10) | −0.0058 (13) | 0.0063 (13) | −0.0106 (9) |
C5 | 0.0597 (11) | 0.0361 (9) | 0.0395 (9) | −0.0037 (8) | 0.0139 (8) | −0.0043 (7) |
C6 | 0.0407 (8) | 0.0358 (9) | 0.0265 (7) | −0.0085 (6) | 0.0022 (6) | −0.0019 (6) |
C7 | 0.0360 (7) | 0.0313 (8) | 0.0267 (7) | −0.0039 (6) | −0.0012 (5) | −0.0002 (6) |
C8 | 0.0382 (8) | 0.0319 (8) | 0.0277 (7) | −0.0008 (6) | −0.0026 (6) | 0.0000 (6) |
C9 | 0.0433 (9) | 0.0366 (9) | 0.0322 (8) | −0.0021 (7) | 0.0009 (6) | 0.0048 (6) |
C10 | 0.0453 (10) | 0.0609 (13) | 0.0509 (11) | −0.0075 (9) | 0.0009 (8) | 0.0108 (9) |
C11 | 0.0484 (12) | 0.091 (2) | 0.0858 (19) | −0.0083 (12) | 0.0182 (12) | 0.0186 (15) |
C12 | 0.0846 (19) | 0.097 (2) | 0.0703 (17) | −0.0054 (16) | 0.0413 (15) | 0.0091 (15) |
C13 | 0.0881 (18) | 0.0782 (17) | 0.0384 (10) | −0.0047 (14) | 0.0195 (11) | 0.0017 (10) |
C14 | 0.0579 (11) | 0.0431 (10) | 0.0311 (8) | 0.0001 (8) | 0.0029 (7) | 0.0014 (7) |
N15 | 0.0570 (9) | 0.0519 (10) | 0.0297 (7) | 0.0009 (7) | −0.0119 (6) | −0.0001 (6) |
C16 | 0.0428 (9) | 0.0313 (8) | 0.0372 (8) | 0.0062 (7) | −0.0082 (7) | −0.0017 (6) |
C17 | 0.0416 (8) | 0.0331 (8) | 0.0316 (7) | −0.0004 (6) | −0.0030 (6) | 0.0020 (6) |
C18 | 0.0472 (9) | 0.0393 (9) | 0.0371 (8) | 0.0074 (7) | −0.0012 (7) | −0.0059 (7) |
C19 | 0.0495 (9) | 0.0327 (9) | 0.0343 (8) | 0.0018 (7) | −0.0009 (7) | −0.0015 (6) |
C20 | 0.0539 (10) | 0.0396 (10) | 0.0321 (8) | 0.0018 (8) | −0.0024 (7) | −0.0027 (7) |
C21 | 0.0852 (18) | 0.0872 (19) | 0.0449 (11) | 0.0044 (15) | −0.0087 (11) | −0.0311 (12) |
N22 | 0.0730 (12) | 0.0670 (12) | 0.0359 (8) | −0.0090 (10) | −0.0105 (8) | −0.0081 (8) |
C23 | 0.0558 (10) | 0.0442 (10) | 0.0337 (8) | −0.0071 (8) | −0.0035 (7) | 0.0028 (7) |
C24 | 0.0506 (12) | 0.0630 (14) | 0.0715 (14) | −0.0059 (10) | −0.0036 (10) | 0.0011 (11) |
C25 | 0.0436 (9) | 0.0387 (9) | 0.0298 (7) | −0.0099 (7) | 0.0026 (6) | −0.0010 (6) |
C26 | 0.0438 (9) | 0.0488 (11) | 0.0318 (8) | −0.0044 (8) | 0.0012 (6) | 0.0007 (7) |
N27 | 0.0607 (10) | 0.0569 (10) | 0.0304 (7) | −0.0069 (8) | 0.0038 (7) | 0.0047 (7) |
C28 | 0.0780 (15) | 0.0678 (14) | 0.0359 (9) | −0.0287 (12) | 0.0075 (9) | 0.0076 (9) |
C29 | 0.0569 (13) | 0.118 (2) | 0.0493 (12) | −0.0302 (14) | −0.0145 (10) | 0.0133 (13) |
S1—C28 | 1.705 (2) | C11—H11 | 0.93 |
S1—C25 | 1.7157 (17) | C12—C13 | 1.379 (4) |
S2—C21 | 1.694 (2) | C12—H12 | 0.93 |
S2—C20 | 1.723 (2) | C13—C14 | 1.378 (3) |
O1—C16 | 1.208 (2) | C13—H13 | 0.93 |
O2—C17 | 1.215 (2) | C14—N15 | 1.395 (3) |
N1—C2 | 1.451 (3) | N15—C16 | 1.354 (2) |
N1—C5 | 1.464 (2) | N15—H15 | 0.86 |
N1—C8 | 1.465 (2) | C16—O1 | 1.208 (2) |
C2—C3 | 1.493 (3) | C16—O1 | 1.208 (2) |
C3—C4 | 1.476 (3) | C17—C18 | 1.468 (2) |
C3—H3A | 0.97 | C18—C19 | 1.332 (2) |
C3—H3B | 0.97 | C18—H18 | 0.93 |
C4—C5 | 1.532 (3) | C19—C20 | 1.442 (2) |
C4—H4A | 0.97 | C19—H19 | 0.93 |
C4—H4B | 0.97 | C20—C23 | 1.371 (3) |
C5—C6 | 1.529 (3) | C21—N22 | 1.295 (3) |
C5—H5 | 0.98 | C21—H21 | 0.93 |
C6—C25 | 1.494 (2) | N22—C23 | 1.381 (3) |
C6—C7 | 1.529 (2) | C23—C24 | 1.483 (3) |
C6—H6 | 0.98 | C24—H24A | 0.96 |
C7—C17 | 1.513 (2) | C24—H24B | 0.96 |
C7—C8 | 1.559 (2) | C24—H24C | 0.96 |
C7—H7 | 0.98 | C25—C26 | 1.352 (2) |
C8—C9 | 1.508 (2) | C26—N27 | 1.384 (2) |
C8—C16 | 1.553 (2) | C26—C29 | 1.489 (3) |
C9—C10 | 1.379 (3) | N27—C28 | 1.282 (3) |
C9—C14 | 1.392 (2) | C28—H28 | 0.93 |
C10—C11 | 1.386 (3) | C29—H29A | 0.96 |
C10—H10 | 0.93 | C29—H29B | 0.96 |
C11—C12 | 1.379 (4) | C29—H29C | 0.96 |
C28—S1—C25 | 89.25 (9) | C11—C12—H12 | 119.0 |
C21—S2—C20 | 89.37 (11) | C12—C13—C14 | 117.2 (2) |
C2—N1—C5 | 108.9 (2) | C12—C13—H13 | 121.4 |
C2—N1—C8 | 122.2 (2) | C14—C13—H13 | 121.4 |
C5—N1—C8 | 110.8 (1) | C13—C14—C9 | 121.8 (2) |
N1—C2—C3 | 104.38 (19) | C13—C14—N15 | 128.1 (2) |
N1—C2—H2A | 110.9 | C9—C14—N15 | 110.04 (16) |
C3—C2—H2A | 110.9 | C16—N15—C14 | 111.5 (1) |
N1—C2—H2B | 110.9 | C16—N15—H15 | 124.2 |
C3—C2—H2B | 110.9 | C14—N15—H15 | 124.2 |
H2A—C2—H2B | 108.9 | O1—C16—N15 | 126.69 (16) |
C4—C3—C2 | 104.09 (19) | O1—C16—N15 | 126.69 (16) |
C4—C3—H3A | 110.9 | O1—C16—N15 | 126.69 (16) |
C2—C3—H3A | 110.9 | O1—C16—C8 | 125.51 (16) |
C4—C3—H3B | 110.9 | O1—C16—C8 | 125.51 (16) |
C2—C3—H3B | 110.9 | O1—C16—C8 | 125.51 (16) |
H3A—C3—H3B | 109.0 | N15—C16—C8 | 107.80 (15) |
C3—C4—C5 | 105.07 (18) | O2—C17—C18 | 119.71 (16) |
C3—C4—H4A | 110.7 | O2—C17—C7 | 120.92 (15) |
C5—C4—H4A | 110.7 | C18—C17—C7 | 119.35 (14) |
C3—C4—H4B | 110.7 | C19—C18—C17 | 125.91 (17) |
C5—C4—H4B | 110.7 | C19—C18—H18 | 117.0 |
H4A—C4—H4B | 108.8 | C17—C18—H18 | 117.0 |
N1—C5—C6 | 104.95 (14) | C18—C19—C20 | 126.13 (18) |
N1—C5—C4 | 105.04 (15) | C18—C19—H19 | 116.9 |
C6—C5—C4 | 117.69 (18) | C20—C19—H19 | 116.9 |
N1—C5—H5 | 109.6 | C23—C20—C19 | 127.18 (18) |
C6—C5—H5 | 109.6 | C23—C20—S2 | 109.60 (14) |
C4—C5—H5 | 109.6 | C19—C20—S2 | 123.19 (14) |
C25—C6—C7 | 115.30 (14) | N22—C21—S2 | 116.02 (17) |
C25—C6—C5 | 113.53 (14) | N22—C21—H21 | 122.0 |
C7—C6—C5 | 101.96 (13) | S2—C21—H21 | 122.0 |
C25—C6—H6 | 108.6 | C21—N22—C23 | 110.71 (18) |
C7—C6—H6 | 108.6 | C20—C23—N22 | 114.30 (19) |
C5—C6—H6 | 108.6 | C20—C23—C24 | 126.11 (18) |
C17—C7—C6 | 114.97 (13) | N22—C23—C24 | 119.58 (19) |
C17—C7—C8 | 113.49 (13) | C23—C24—H24A | 109.5 |
C6—C7—C8 | 103.79 (13) | C23—C24—H24B | 109.5 |
C17—C7—H7 | 108.1 | H24A—C24—H24B | 109.5 |
C6—C7—H7 | 108.1 | C23—C24—H24C | 109.5 |
C8—C7—H7 | 108.1 | H24A—C24—H24C | 109.5 |
N1—C8—C9 | 116.42 (14) | H24B—C24—H24C | 109.5 |
N1—C8—C16 | 107.70 (13) | C26—C25—C6 | 129.59 (16) |
C9—C8—C16 | 101.55 (13) | C26—C25—S1 | 109.29 (13) |
N1—C8—C7 | 104.24 (12) | C6—C25—S1 | 120.93 (12) |
C9—C8—C7 | 116.43 (14) | C25—C26—N27 | 115.54 (16) |
C16—C8—C7 | 110.26 (13) | C25—C26—C29 | 126.01 (18) |
C10—C9—C14 | 119.89 (17) | N27—C26—C29 | 118.44 (17) |
C10—C9—C8 | 131.62 (16) | C28—N27—C26 | 109.91 (16) |
C14—C9—C8 | 108.48 (15) | N27—C28—S1 | 115.99 (15) |
C9—C10—C11 | 118.9 (2) | N27—C28—H28 | 122.0 |
C9—C10—H10 | 120.6 | S1—C28—H28 | 122.0 |
C11—C10—H10 | 120.6 | C26—C29—H29A | 109.5 |
C12—C11—C10 | 120.1 (2) | C26—C29—H29B | 109.5 |
C12—C11—H11 | 119.9 | H29A—C29—H29B | 109.5 |
C10—C11—H11 | 119.9 | C26—C29—H29C | 109.5 |
C13—C12—C11 | 122.1 (2) | H29A—C29—H29C | 109.5 |
C13—C12—H12 | 119.0 | H29B—C29—H29C | 109.5 |
C5—N1—C2—C3 | 26.5 (3) | O1—O1—C16—N15 | 0.0 (2) |
C8—N1—C2—C3 | 157.8 (2) | O1—O1—C16—C8 | 0.0 (2) |
N1—C2—C3—C4 | −35.7 (3) | O1—O1—C16—C8 | 0.0 (2) |
C2—C3—C4—C5 | 31.2 (3) | C14—N15—C16—O1 | 173.29 (18) |
C2—N1—C5—C6 | 117.7 (2) | C14—N15—C16—O1 | 173.29 (18) |
C8—N1—C5—C6 | −19.43 (19) | C14—N15—C16—O1 | 173.29 (18) |
C2—N1—C5—C4 | −7.0 (3) | C14—N15—C16—C8 | −7.5 (2) |
C8—N1—C5—C4 | −144.16 (18) | N1—C8—C16—O1 | 64.1 (2) |
C3—C4—C5—N1 | −15.3 (3) | C9—C8—C16—O1 | −173.06 (17) |
C3—C4—C5—C6 | −131.6 (2) | C7—C8—C16—O1 | −49.0 (2) |
N1—C5—C6—C25 | 159.30 (14) | N1—C8—C16—O1 | 64.1 (2) |
C4—C5—C6—C25 | −84.4 (2) | C9—C8—C16—O1 | −173.06 (17) |
N1—C5—C6—C7 | 34.64 (17) | C7—C8—C16—O1 | −49.0 (2) |
C4—C5—C6—C7 | 150.96 (17) | N1—C8—C16—O1 | 64.1 (2) |
C25—C6—C7—C17 | 75.27 (19) | C9—C8—C16—O1 | −173.06 (17) |
C5—C6—C7—C17 | −161.26 (14) | C7—C8—C16—O1 | −49.0 (2) |
C25—C6—C7—C8 | −160.18 (14) | N1—C8—C16—N15 | −115.12 (15) |
C5—C6—C7—C8 | −36.71 (16) | C9—C8—C16—N15 | 7.70 (18) |
C2—N1—C8—C9 | −4.7 (3) | C7—C8—C16—N15 | 131.73 (15) |
C5—N1—C8—C9 | 125.79 (16) | C6—C7—C17—O2 | 9.2 (2) |
C2—N1—C8—C16 | 108.4 (2) | C8—C7—C17—O2 | −110.07 (18) |
C5—N1—C8—C16 | −121.05 (16) | C6—C7—C17—C18 | −172.64 (15) |
C2—N1—C8—C7 | −134.4 (2) | C8—C7—C17—C18 | 68.1 (2) |
C5—N1—C8—C7 | −3.91 (18) | O2—C17—C18—C19 | −162.21 (19) |
C17—C7—C8—N1 | 151.14 (13) | C7—C17—C18—C19 | 19.6 (3) |
C6—C7—C8—N1 | 25.64 (16) | C17—C18—C19—C20 | 178.51 (18) |
C17—C7—C8—C9 | 21.44 (19) | C18—C19—C20—C23 | 178.2 (2) |
C6—C7—C8—C9 | −104.06 (15) | C18—C19—C20—S2 | −4.0 (3) |
C17—C7—C8—C16 | −93.52 (16) | C21—S2—C20—C23 | 0.26 (18) |
C6—C7—C8—C16 | 140.98 (14) | C21—S2—C20—C19 | −177.86 (19) |
N1—C8—C9—C10 | −70.0 (3) | C20—S2—C21—N22 | −0.3 (2) |
C16—C8—C9—C10 | 173.3 (2) | S2—C21—N22—C23 | 0.2 (3) |
C7—C8—C9—C10 | 53.6 (3) | C19—C20—C23—N22 | 177.81 (19) |
N1—C8—C9—C14 | 111.27 (17) | S2—C20—C23—N22 | −0.2 (2) |
C16—C8—C9—C14 | −5.35 (18) | C19—C20—C23—C24 | −2.9 (3) |
C7—C8—C9—C14 | −125.11 (16) | S2—C20—C23—C24 | 179.10 (18) |
C14—C9—C10—C11 | −0.2 (3) | C21—N22—C23—C20 | 0.0 (3) |
C8—C9—C10—C11 | −178.7 (2) | C21—N22—C23—C24 | −179.3 (2) |
C9—C10—C11—C12 | −1.3 (4) | C7—C6—C25—C26 | −145.1 (2) |
C10—C11—C12—C13 | 1.3 (5) | C5—C6—C25—C26 | 97.8 (2) |
C11—C12—C13—C14 | 0.3 (5) | C7—C6—C25—S1 | 40.4 (2) |
C12—C13—C14—C9 | −1.9 (4) | C5—C6—C25—S1 | −76.68 (18) |
C12—C13—C14—N15 | 177.3 (2) | C28—S1—C25—C26 | −0.87 (17) |
C10—C9—C14—C13 | 1.8 (3) | C28—S1—C25—C6 | 174.65 (17) |
C8—C9—C14—C13 | −179.3 (2) | C6—C25—C26—N27 | −174.20 (18) |
C10—C9—C14—N15 | −177.48 (18) | S1—C25—C26—N27 | 0.8 (2) |
C8—C9—C14—N15 | 1.4 (2) | C6—C25—C26—C29 | 5.9 (4) |
C13—C14—N15—C16 | −175.2 (2) | S1—C25—C26—C29 | −179.1 (2) |
C9—C14—N15—C16 | 4.0 (2) | C25—C26—N27—C28 | −0.2 (3) |
O1—O1—C16—O1 | 0.0 (2) | C29—C26—N27—C28 | 179.7 (2) |
O1—O1—C16—O1 | 0.0 (2) | C26—N27—C28—S1 | −0.5 (3) |
O1—O1—C16—N15 | 0.0 (2) | C25—S1—C28—N27 | 0.8 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N15—H15···N22i | 0.86 | 2.15 | 2.978 (2) | 162 |
C7—H7···O1 | 0.98 | 2.56 | 3.005 (2) | 108 |
C19—H19···O1 | 0.93 | 2.51 | 3.301 (2) | 143 |
C28—H28···O1ii | 0.93 | 2.47 | 3.016 (3) | 118 |
C24—H24C···Cgii | 0.96 | 2.77 | 3.631 (3) | 149 |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1, y+1/2, −z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C25H24N4O2S2 |
Mr | 476.60 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 10.8362 (3), 9.0056 (2), 24.7698 (5) |
β (°) | 95.272 (1) |
V (Å3) | 2406.97 (10) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.25 |
Crystal size (mm) | 0.26 × 0.21 × 0.17 |
Data collection | |
Diffractometer | Bruker APEXII CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2001) |
Tmin, Tmax | 0.939, 0.958 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 29274, 6839, 4872 |
Rint | 0.027 |
(sin θ/λ)max (Å−1) | 0.699 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.051, 0.160, 1.01 |
No. of reflections | 6839 |
No. of parameters | 300 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.56, −0.53 |
Computer programs: APEX2 (Bruker, 2004), SAINT (Bruker, 2004), SHELXS97 (Sheldrick, 1997), ZORTEP (Zsolnai, 1997), SHELXL97 (Sheldrick, 1997) and PLATON (Spek, 2003).
D—H···A | D—H | H···A | D···A | D—H···A |
N15—H15···N22i | 0.86 | 2.15 | 2.978 (2) | 162 |
C7—H7···O1 | 0.98 | 2.56 | 3.005 (2) | 108 |
C19—H19···O1 | 0.93 | 2.51 | 3.301 (2) | 143 |
C28—H28···O1ii | 0.93 | 2.47 | 3.016 (3) | 118 |
C24—H24C···Cgii | 0.96 | 2.77 | 3.631 (3) | 149 |
Symmetry codes: (i) −x+1, −y+2, −z+1; (ii) −x+1, y+1/2, −z+1/2. |
The spiro ring system is a frequently encountered structural motif in many pharmacologically relevant alkaloids. Synthetic spiro-pyrrolidine derivatives have activity against aldose reductase enzyme which controls influenza (Stylianakis et al., 2003). The pyrrolizidine alkaloids are well documented for their mutagenic, antineoplastic, carcinogenic, hepatoxic, and many pharmacological activities (Usha, Selvanayagam, Velmurugan, Ravikumar, Durga & Raghunathan, 2005); Usha, Selvanayagam, Velmurugan, Ravikumar & Poornachandran, 2005). Thiazole derivatives possess anti-inflammatory properties (Köysal et al., 2004) and thiazole napthyridine derivatives exibit good antibactrial activity (Kondo et al., 1990). A series of thiazole[3,4–9]benzimidazole derivatives have been evaluated in vitro as antitumor agents against 60 human tumor cell-lines (Chimirri et al., 1994). Indole, being an integral part of many natural products of therapeutic importance, possesses potentially reactive sites for a variety of chemical reactions to generate molecular diversity (Farhanullah et al., 2004). In view of this biological importance, the crystal structure of the title compound has been determined and the results are presented here.
In the molecule of the title compound (Fig.1), the C—C and C—N bond lengths in the pyrrolizine ring system are slightly longer than the values reported for similar structures (Seshadri et al., 2003). This may be due to steric forces caused by the bulky substituents on the pyrrolizine ring system. The sum of angles at N1 of the pyrrolizine ring system (341.9°) is in accordance with sp3 hybridization (Beddoes et al., 1986), and the sum of the angles at N15 of the indole moiety (359.9°) is in accordance with sp2 hybridization.
In the pyrrolizine ring system, the pyrrolidine ring A adopts an envelope conformation whereas the ring B adopts a twist conformation. The puckering parameters (q2 and φ; Cremer & Pople, 1975) and the smallest displacement asymmetry parameter (Δ; Nardelli, 1983) are, for the ring A, q2 = 0.371 (2) Å, φ = 79.0 (3)° and Δs(C6) = 4.6 (2)°; for the ring B, q2 = 0.334 (3) Å, φ = 241.9 (4)°, Δ2(C5)=6.7 (3)° and Δs(C3) = 8.5 (3)°. The pyrrolizine ring system is folded about the bridging N1—C5 bond, as observed in related structures (Usha, Selvanayagam, Velmurugan, Ravikumar, Durga & Raghunathan, 2005); Usha, Selvanayagam, Velmurugan, Ravikumar & Poornachandran, 2005). The five-membered ring C in the indolone ring system adopts a twist conformation, with puckering parameters q2 = 0.074 (2) Å, φ = 133.5 (2)°, Δ2(C14) = 2.4 (2)° and Δs(C16) = 1.0 (2)°.
The molecular structure is stabilized by intramolecular C—H···O interactions and the crystal packing is stabilized by C—H···O and N—H···N intermolecular hydrogen bonds. The molecules at (x, y, z) and (1 - x, 2 - y, 1 - z) are linked by N15—H15···N22 hydrogen bonds into cyclic centrosymmetric R22(22) dimers. The dimers are cross-linked via C—H···π interactions involving the S1/C25/C26/N27/C28 ring (centroid Cg).