Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807028176/fj2027sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807028176/fj2027Isup2.hkl |
CCDC reference: 654931
Key indicators
- Single-crystal X-ray study
- T = 298 K
- Mean (C-C) = 0.003 Å
- R factor = 0.042
- wR factor = 0.120
- Data-to-parameter ratio = 11.0
checkCIF/PLATON results
No syntax errors found
Alert level C PLAT480_ALERT_4_C Long H...A H-Bond Reported H2 .. O2 .. 2.64 Ang. PLAT480_ALERT_4_C Long H...A H-Bond Reported H12 .. O2 .. 2.64 Ang. PLAT480_ALERT_4_C Long H...A H-Bond Reported H8B .. O1 .. 2.63 Ang. PLAT480_ALERT_4_C Long H...A H-Bond Reported H8A .. O3 .. 2.72 Ang.
Alert level G REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is correct. If it is not, please give the correct count in the _publ_section_exptl_refinement section of the submitted CIF. From the CIF: _diffrn_reflns_theta_max 29.56 From the CIF: _reflns_number_total 1409 Count of symmetry unique reflns 1445 Completeness (_total/calc) 97.51% TEST3: Check Friedels for noncentro structure Estimate of Friedel pairs measured 0 Fraction of Friedel pairs measured 0.000 Are heavy atom types Z>Si present no PLAT791_ALERT_1_G Confirm the Absolute Configuration of C12 = . S
0 ALERT level A = In general: serious problem 0 ALERT level B = Potentially serious problem 4 ALERT level C = Check and explain 2 ALERT level G = General alerts; check 1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data 0 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 5 ALERT type 4 Improvement, methodology, query or suggestion 0 ALERT type 5 Informative message, check
(S)-Glutamic acid was condensed with 3-furaldehyde to give a Schiff base, which upon treatment with sodium borohydride gave the crude (S)—N-(furylmethyl)-glutamic acid (Marchalín et al., 1998). Cyclization of acid into oxoproline was performed in refluxing ethanol in good yield (75%). This amino acid was conveniently converted to acid chloride by the action of thionyl chloride in dichloromethane. The resulting acid chloride under Friedel-Crafts cyclization conditions using aluminium trichloride of high quality as a catalyst gave the expected ketone in moderate yield (72%); mp 433–435 K.
All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances in the range 0.93 - 0.98 Å and Uiso set at 1.2Ueq of the parent atom. The absolute configuration could not be reliably determined for this compound using Mo radiation, and has been assigned according to the synthesis; Friedel pairs have been merged.
Indolizine derivatives are an important class of heterocyclic bioactive compounds which have a wide range of applications, such as pharmaceutical drugs, potential central nervous system depressants, calcium entry blockers, cardiovascular agents, spectral sensitizers and novel dyes (Gubin et al., 1992; Poty et al., 1994; Hema et al., 2003). Several polyhydroxylated indolizines are interesting as inhibitors of glycosides (Hempel et al., 1993; Brandi et al., 1995). Indolizines have also been tested as antimycobacterial agents against mycobacterial tuberculosis (Gundersen et al., 2003), for the treatment of angina pectoris (Rosseels et al., 1982) and as testosterone 5&-reductase inhibitors (Okada et al., 1993). Due to the diverse properties of indolizine derivatives, the structure of the title compound, (I), has been determined as part of our study of the conformational changes caused by different substituents at various positions on the indolizine ring system. The absolute configuration is known from the synthesis and is depicted in the scheme and figure. The bond lengths and bond angles in the molecule are comparable with those in related structures (Camus et al., 2000; Vrábel et al., 2004). The central N-heterocyclic ring is not planar and adopts a chair conformation (Nardelli, 1983). A calculation of least-squares planes shows that this ring is puckered in such a manner that the five atoms C4, C10, C11, C9 and C12 are coplanar to within 0.020 (2) Å, while atom N5 is displaced from this plane with out-of-plane displacement of 0.452 (2) Å. The oxopyrrolidine ring is distorted towards a flat-envelope conformation, with atom C8 on the flap. The deviation of atom C8 from the mean plane of the remaining four atoms is 0.263 (3) Å. The fused furan ring is planar (mean deviation 0.006 (2) Å). The N5—C4 and N5—C12 bonds are approximately equivalent and both are much longer than the N5—C6 bond. Moreover, the N5 atom is sp2 hybridized, as evidenced by the sum of the valence angles around it [360.0 (1)°]. These data are consistent with conjugation of the lone-pair electrons on N5 with the adjacent carbonyl and agree with literature values for simple amides (Brown & Corbridge, 1954; Pedersen, 1967). The bond lengths of the carbonyl groups C9=O2 and C6=O3 are 1.216 (3) and 1.221 (3) Å, respectively, are somewhat longer than typical carbonyl bonds. This may be due to the fact that atoms O2 and O3 participate in intermolecular van der Waals forces.
For related literature, see: Brandi et al. (1995); Brown & Corbridge (1954); Camus et al. (2000); Gubin et al. (1992); Gundersen et al. (2003); Hema et al. (2003); Hempel et al. (1993); Marchalín et al. (1998); Nardelli (1983); Okada et al. (1993); Pedersen (1967); Poty et al. (1994); Rosseels et al. (1982); Vrábel et al. (2004).
Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis RED (Oxford Diffraction, 2006); data reduction: CrysAlis RED; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: DIAMOND (Brandenburg, 2002); software used to prepare material for publication: SHELXL97.
Fig. 1. Molecular structure of (I) with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. |
C10H9NO3 | F(000) = 400 |
Mr = 191.18 | Dx = 1.443 Mg m−3 |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 16436 reflections |
a = 6.8771 (1) Å | θ = 3.0–29.5° |
b = 7.2198 (1) Å | µ = 0.11 mm−1 |
c = 17.7271 (2) Å | T = 298 K |
V = 880.17 (2) Å3 | Block, yellow |
Z = 4 | 0.51 × 0.25 × 0.07 mm |
Oxford Diffraction Gemini R CCD diffractometer | 1409 independent reflections |
Radiation source: fine-focus sealed tube | 1110 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.027 |
Detector resolution: 10.4340 pixels mm-1 | θmax = 29.6°, θmin = 2.3° |
Rotation method data acquisition using ω and φ scans | h = −9→9 |
Absorption correction: analytical (Clark & Reid, 1995) | k = −9→9 |
Tmin = 0.943, Tmax = 0.993 | l = −24→24 |
35953 measured reflections |
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.042 | H-atom parameters constrained |
wR(F2) = 0.120 | w = 1/[σ2(Fo2) + (0.0618P)2 + 0.1705P] where P = (Fo2 + 2Fc2)/3 |
S = 1.03 | (Δ/σ)max < 0.001 |
1409 reflections | Δρmax = 0.14 e Å−3 |
128 parameters | Δρmin = −0.15 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.021 (5) |
C10H9NO3 | V = 880.17 (2) Å3 |
Mr = 191.18 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 6.8771 (1) Å | µ = 0.11 mm−1 |
b = 7.2198 (1) Å | T = 298 K |
c = 17.7271 (2) Å | 0.51 × 0.25 × 0.07 mm |
Oxford Diffraction Gemini R CCD diffractometer | 1409 independent reflections |
Absorption correction: analytical (Clark & Reid, 1995) | 1110 reflections with I > 2σ(I) |
Tmin = 0.943, Tmax = 0.993 | Rint = 0.027 |
35953 measured reflections |
R[F2 > 2σ(F2)] = 0.042 | 0 restraints |
wR(F2) = 0.120 | H-atom parameters constrained |
S = 1.03 | Δρmax = 0.14 e Å−3 |
1409 reflections | Δρmin = −0.15 e Å−3 |
128 parameters |
x | y | z | Uiso*/Ueq | ||
C2 | 1.4392 (4) | 0.3530 (4) | 0.82976 (16) | 0.0655 (7) | |
H2 | 1.5569 | 0.2958 | 0.8186 | 0.079* | |
C3 | 1.2944 (4) | 0.2720 (3) | 0.86888 (14) | 0.0592 (6) | |
H3 | 1.2938 | 0.1531 | 0.8890 | 0.071* | |
C4 | 0.9445 (3) | 0.3977 (3) | 0.90620 (12) | 0.0491 (5) | |
H4A | 0.8649 | 0.3109 | 0.8781 | 0.059* | |
H4B | 0.9515 | 0.3557 | 0.9581 | 0.059* | |
C6 | 0.7399 (4) | 0.6480 (4) | 0.95687 (13) | 0.0611 (7) | |
C7 | 0.6811 (5) | 0.8412 (4) | 0.93494 (16) | 0.0798 (9) | |
H7A | 0.7059 | 0.9271 | 0.9759 | 0.096* | |
H7B | 0.5439 | 0.8457 | 0.9224 | 0.096* | |
C8 | 0.8023 (4) | 0.8888 (3) | 0.86777 (14) | 0.0644 (7) | |
H8A | 0.9054 | 0.9738 | 0.8817 | 0.077* | |
H8B | 0.7231 | 0.9461 | 0.8290 | 0.077* | |
C9 | 1.0983 (4) | 0.7184 (3) | 0.81577 (11) | 0.0492 (5) | |
C10 | 1.1434 (3) | 0.4052 (3) | 0.87314 (11) | 0.0438 (5) | |
C11 | 1.2078 (3) | 0.5567 (3) | 0.83589 (11) | 0.0453 (5) | |
C12 | 0.8871 (3) | 0.7060 (3) | 0.83954 (11) | 0.0441 (5) | |
H12 | 0.8097 | 0.6622 | 0.7967 | 0.053* | |
N5 | 0.8583 (3) | 0.5804 (2) | 0.90326 (9) | 0.0456 (4) | |
O1 | 1.3924 (2) | 0.5282 (3) | 0.80864 (9) | 0.0597 (5) | |
O2 | 1.1586 (3) | 0.8488 (3) | 0.77918 (11) | 0.0746 (6) | |
O3 | 0.6908 (3) | 0.5644 (4) | 1.01363 (11) | 0.0947 (8) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C2 | 0.0502 (12) | 0.0705 (16) | 0.0759 (16) | 0.0132 (12) | −0.0061 (12) | −0.0105 (14) |
C3 | 0.0586 (14) | 0.0518 (12) | 0.0672 (13) | 0.0101 (11) | −0.0137 (12) | −0.0030 (11) |
C4 | 0.0516 (11) | 0.0418 (10) | 0.0541 (11) | −0.0032 (9) | 0.0020 (10) | 0.0062 (9) |
C6 | 0.0565 (13) | 0.0784 (16) | 0.0484 (11) | 0.0122 (13) | 0.0075 (11) | 0.0048 (11) |
C7 | 0.081 (2) | 0.0815 (19) | 0.0646 (15) | 0.0381 (19) | 0.0129 (14) | −0.0037 (14) |
C8 | 0.0811 (17) | 0.0496 (12) | 0.0625 (13) | 0.0199 (13) | 0.0040 (14) | −0.0008 (11) |
C9 | 0.0604 (13) | 0.0456 (11) | 0.0415 (9) | −0.0035 (10) | 0.0061 (10) | 0.0043 (8) |
C10 | 0.0481 (10) | 0.0413 (9) | 0.0420 (9) | 0.0004 (9) | −0.0081 (8) | −0.0026 (8) |
C11 | 0.0440 (10) | 0.0484 (11) | 0.0436 (9) | −0.0031 (9) | 0.0023 (9) | −0.0021 (9) |
C12 | 0.0544 (11) | 0.0406 (10) | 0.0372 (8) | 0.0033 (9) | −0.0016 (9) | 0.0013 (8) |
N5 | 0.0492 (9) | 0.0447 (9) | 0.0430 (8) | 0.0020 (8) | 0.0062 (8) | 0.0037 (7) |
O1 | 0.0457 (9) | 0.0710 (11) | 0.0623 (9) | −0.0015 (8) | 0.0059 (7) | 0.0000 (8) |
O2 | 0.0819 (13) | 0.0620 (10) | 0.0798 (11) | −0.0041 (11) | 0.0174 (11) | 0.0295 (9) |
O3 | 0.0900 (15) | 0.1256 (19) | 0.0685 (11) | 0.0293 (15) | 0.0361 (11) | 0.0327 (13) |
C2—C3 | 1.347 (4) | C7—H7A | 0.9700 |
C2—O1 | 1.358 (3) | C7—H7B | 0.9700 |
C2—H2 | 0.9300 | C8—C12 | 1.527 (3) |
C3—C10 | 1.417 (3) | C8—H8A | 0.9700 |
C3—H3 | 0.9300 | C8—H8B | 0.9700 |
C4—N5 | 1.447 (3) | C9—O2 | 1.216 (3) |
C4—C10 | 1.489 (3) | C9—C11 | 1.434 (3) |
C4—H4A | 0.9700 | C9—C12 | 1.515 (3) |
C4—H4B | 0.9700 | C10—C11 | 1.353 (3) |
C6—O3 | 1.221 (3) | C11—O1 | 1.374 (3) |
C6—N5 | 1.343 (3) | C12—N5 | 1.462 (2) |
C6—C7 | 1.504 (4) | C12—H12 | 0.9800 |
C7—C8 | 1.493 (4) | ||
C3—C2—O1 | 111.8 (2) | C12—C8—H8A | 110.5 |
C3—C2—H2 | 124.1 | C7—C8—H8B | 110.5 |
O1—C2—H2 | 124.1 | C12—C8—H8B | 110.5 |
C2—C3—C10 | 106.0 (2) | H8A—C8—H8B | 108.7 |
C2—C3—H3 | 127.0 | O2—C9—C11 | 125.7 (2) |
C10—C3—H3 | 127.0 | O2—C9—C12 | 121.4 (2) |
N5—C4—C10 | 109.22 (17) | C11—C9—C12 | 112.72 (18) |
N5—C4—H4A | 109.8 | C11—C10—C3 | 106.4 (2) |
C10—C4—H4A | 109.8 | C11—C10—C4 | 121.50 (19) |
N5—C4—H4B | 109.8 | C3—C10—C4 | 132.0 (2) |
C10—C4—H4B | 109.8 | O1—C11—C10 | 110.68 (19) |
H4A—C4—H4B | 108.3 | O1—C11—C9 | 121.3 (2) |
O3—C6—N5 | 124.9 (3) | C10—C11—C9 | 127.4 (2) |
O3—C6—C7 | 126.7 (3) | N5—C12—C9 | 112.43 (17) |
N5—C6—C7 | 108.5 (2) | N5—C12—C8 | 103.35 (16) |
C6—C7—C8 | 105.6 (2) | C9—C12—C8 | 114.0 (2) |
C6—C7—H7A | 110.6 | N5—C12—H12 | 109.0 |
C8—C7—H7A | 110.6 | C9—C12—H12 | 109.0 |
C6—C7—H7B | 110.6 | C8—C12—H12 | 109.0 |
C8—C7—H7B | 110.6 | C6—N5—C12 | 113.81 (19) |
H7A—C7—H7B | 108.7 | C6—N5—C4 | 123.63 (19) |
C7—C8—C12 | 106.0 (2) | C12—N5—C4 | 122.52 (16) |
C7—C8—H8A | 110.5 | C11—O1—C2 | 105.18 (19) |
O1—C2—C3—C10 | 0.0 (3) | O2—C9—C12—C8 | −42.4 (3) |
O3—C6—C7—C8 | 171.7 (3) | C11—C9—C12—C8 | 142.1 (2) |
N5—C6—C7—C8 | −8.0 (3) | C7—C8—C12—N5 | −16.2 (3) |
C6—C7—C8—C12 | 15.0 (3) | C7—C8—C12—C9 | −138.5 (2) |
C2—C3—C10—C11 | 0.3 (3) | O3—C6—N5—C12 | 177.5 (3) |
C2—C3—C10—C4 | 177.5 (2) | C7—C6—N5—C12 | −2.8 (3) |
N5—C4—C10—C11 | −10.1 (3) | O3—C6—N5—C4 | −0.3 (4) |
N5—C4—C10—C3 | 173.0 (2) | C7—C6—N5—C4 | 179.4 (2) |
C3—C10—C11—O1 | −0.5 (2) | C9—C12—N5—C6 | 135.4 (2) |
C4—C10—C11—O1 | −178.05 (17) | C8—C12—N5—C6 | 12.1 (3) |
C3—C10—C11—C9 | 170.8 (2) | C9—C12—N5—C4 | −46.8 (3) |
C4—C10—C11—C9 | −6.8 (3) | C8—C12—N5—C4 | −170.1 (2) |
O2—C9—C11—O1 | −6.0 (4) | C10—C4—N5—C6 | −144.5 (2) |
C12—C9—C11—O1 | 169.21 (18) | C10—C4—N5—C12 | 37.9 (3) |
O2—C9—C11—C10 | −176.4 (2) | C10—C11—O1—C2 | 0.5 (2) |
C12—C9—C11—C10 | −1.2 (3) | C9—C11—O1—C2 | −171.4 (2) |
O2—C9—C12—N5 | −159.6 (2) | C3—C2—O1—C11 | −0.3 (3) |
C11—C9—C12—N5 | 25.0 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
C3—H3···O3i | 0.93 | 2.44 | 3.278 (3) | 150 |
C2—H2···O2ii | 0.93 | 2.64 | 3.374 (3) | 136 |
C12—H12···O2iii | 0.98 | 2.64 | 3.344 (3) | 129 |
C8—H8B···O1iv | 0.97 | 2.63 | 3.547 (3) | 157 |
C8—H8A···O3v | 0.97 | 2.72 | 3.417 (4) | 130 |
Symmetry codes: (i) x+1/2, −y+1/2, −z+2; (ii) −x+3, y−1/2, −z+3/2; (iii) −x+2, y−1/2, −z+3/2; (iv) −x+2, y+1/2, −z+3/2; (v) x+1/2, −y+3/2, −z+2. |
Experimental details
Crystal data | |
Chemical formula | C10H9NO3 |
Mr | 191.18 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 298 |
a, b, c (Å) | 6.8771 (1), 7.2198 (1), 17.7271 (2) |
V (Å3) | 880.17 (2) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.51 × 0.25 × 0.07 |
Data collection | |
Diffractometer | Oxford Diffraction Gemini R CCD |
Absorption correction | Analytical (Clark & Reid, 1995) |
Tmin, Tmax | 0.943, 0.993 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 35953, 1409, 1110 |
Rint | 0.027 |
(sin θ/λ)max (Å−1) | 0.694 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.042, 0.120, 1.03 |
No. of reflections | 1409 |
No. of parameters | 128 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.14, −0.15 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2006), CrysAlis RED (Oxford Diffraction, 2006), CrysAlis RED, SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), DIAMOND (Brandenburg, 2002), SHELXL97.
D—H···A | D—H | H···A | D···A | D—H···A |
C3—H3···O3i | 0.93 | 2.44 | 3.278 (3) | 150 |
C2—H2···O2ii | 0.93 | 2.64 | 3.374 (3) | 136 |
C12—H12···O2iii | 0.98 | 2.64 | 3.344 (3) | 129 |
C8—H8B···O1iv | 0.97 | 2.63 | 3.547 (3) | 157 |
C8—H8A···O3v | 0.97 | 2.72 | 3.417 (4) | 130 |
Symmetry codes: (i) x+1/2, −y+1/2, −z+2; (ii) −x+3, y−1/2, −z+3/2; (iii) −x+2, y−1/2, −z+3/2; (iv) −x+2, y+1/2, −z+3/2; (v) x+1/2, −y+3/2, −z+2. |
Indolizine derivatives are an important class of heterocyclic bioactive compounds which have a wide range of applications, such as pharmaceutical drugs, potential central nervous system depressants, calcium entry blockers, cardiovascular agents, spectral sensitizers and novel dyes (Gubin et al., 1992; Poty et al., 1994; Hema et al., 2003). Several polyhydroxylated indolizines are interesting as inhibitors of glycosides (Hempel et al., 1993; Brandi et al., 1995). Indolizines have also been tested as antimycobacterial agents against mycobacterial tuberculosis (Gundersen et al., 2003), for the treatment of angina pectoris (Rosseels et al., 1982) and as testosterone 5&-reductase inhibitors (Okada et al., 1993). Due to the diverse properties of indolizine derivatives, the structure of the title compound, (I), has been determined as part of our study of the conformational changes caused by different substituents at various positions on the indolizine ring system. The absolute configuration is known from the synthesis and is depicted in the scheme and figure. The bond lengths and bond angles in the molecule are comparable with those in related structures (Camus et al., 2000; Vrábel et al., 2004). The central N-heterocyclic ring is not planar and adopts a chair conformation (Nardelli, 1983). A calculation of least-squares planes shows that this ring is puckered in such a manner that the five atoms C4, C10, C11, C9 and C12 are coplanar to within 0.020 (2) Å, while atom N5 is displaced from this plane with out-of-plane displacement of 0.452 (2) Å. The oxopyrrolidine ring is distorted towards a flat-envelope conformation, with atom C8 on the flap. The deviation of atom C8 from the mean plane of the remaining four atoms is 0.263 (3) Å. The fused furan ring is planar (mean deviation 0.006 (2) Å). The N5—C4 and N5—C12 bonds are approximately equivalent and both are much longer than the N5—C6 bond. Moreover, the N5 atom is sp2 hybridized, as evidenced by the sum of the valence angles around it [360.0 (1)°]. These data are consistent with conjugation of the lone-pair electrons on N5 with the adjacent carbonyl and agree with literature values for simple amides (Brown & Corbridge, 1954; Pedersen, 1967). The bond lengths of the carbonyl groups C9=O2 and C6=O3 are 1.216 (3) and 1.221 (3) Å, respectively, are somewhat longer than typical carbonyl bonds. This may be due to the fact that atoms O2 and O3 participate in intermolecular van der Waals forces.