organic compounds
(S)-Ethyl 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylate
aSchool of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Mail Box 40, 103 Wenhua Road, Shenhe District, Shenyang 110016, People's Republic of China, and bJinZhou JiuTai Pharmaceutical Co.,Ltd, Taianli, Taihe District, Jinzhou 121012, People's Republic of China
*Correspondence e-mail: mscheng@syphu.edu.cn
The title chiral compound, C14H16N2O2, was prepared by esterification of (S)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-carboxylic acid in the presence of HCl/EtOH. In the molecule, the quinazoline ring is non-planar and exhibits a distorted half-chair conformation, while the five-membered ring shows a typical Intermolecular C—H⋯N hydrogen bonding helps to stabilize the crystal structure.
Experimental
Crystal data
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Data collection
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Refinement
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Data collection: SMART (Bruker, 1997); cell SAINT (Bruker, 1999); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL-Plus (Sheldrick, 2008); software used to prepare material for publication: SHELXL97.
Supporting information
10.1107/S1600536808008908/xu2409sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: 10.1107/S1600536808008908/xu2409Isup2.hkl
A rapid stream of hydrogen chloride was passed for 3 h into absolute ethanol (200 ml) in an icebath. To this solution was added (S)-1,2,3,9-tetrahydro-pyrrolo(2,1 - b)quinazolin-1-carboxylic acid (4.32 g, 20 mmol), and this solution was refluxed for 3 h. The ethanol was removed under vacuum. The pure product was obtained through silica gel
(eluant: petroleum ether/ethyl acetate, 1:10). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a of the title compound in ethyl acetate at room temperature.All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H = 0.95, 0.99, 0.98 and 1.00 Å for phenyl, methylene, methyl and tertiary H atoms, respectively, with Uiso(H) = xUeq(C), where x=1.5 for methyl H, and x=1.2 for all other H atoms. Based on known
of the equivalent atom in the starting material, the S at C11 was assigned. Friedel pairs were merged.Data collection: SMART (Bruker, 1997); cell
SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL-Plus (Sheldrick, 2008); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008).Fig. 1. The structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme. | |
Fig. 2. The molecular packing of the title compound. |
C14H16N2O2 | F(000) = 260 |
Mr = 244.29 | Dx = 1.273 Mg m−3 |
Monoclinic, P21 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2yb | Cell parameters from 1588 reflections |
a = 6.0545 (8) Å | θ = 2.9–25.0° |
b = 9.1438 (13) Å | µ = 0.09 mm−1 |
c = 11.5228 (16) Å | T = 187 K |
β = 92.905 (2)° | Block, colorless |
V = 637.10 (15) Å3 | 0.29 × 0.22 × 0.19 mm |
Z = 2 |
Bruker SMART APEX CCD area-detector diffractometer | 1166 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.016 |
Graphite monochromator | θmax = 25.4°, θmin = 1.8° |
ϕ and ω scans | h = −7→7 |
3430 measured reflections | k = −11→5 |
1246 independent reflections | l = −13→13 |
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)] = 0.031 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.076 | H-atom parameters constrained |
S = 1.08 | w = 1/[σ2(Fo2) + (0.0381P)2 + 0.082P] where P = (Fo2 + 2Fc2)/3 |
1246 reflections | (Δ/σ)max = 0.001 |
164 parameters | Δρmax = 0.11 e Å−3 |
1 restraint | Δρmin = −0.14 e Å−3 |
C14H16N2O2 | V = 637.10 (15) Å3 |
Mr = 244.29 | Z = 2 |
Monoclinic, P21 | Mo Kα radiation |
a = 6.0545 (8) Å | µ = 0.09 mm−1 |
b = 9.1438 (13) Å | T = 187 K |
c = 11.5228 (16) Å | 0.29 × 0.22 × 0.19 mm |
β = 92.905 (2)° |
Bruker SMART APEX CCD area-detector diffractometer | 1166 reflections with I > 2σ(I) |
3430 measured reflections | Rint = 0.016 |
1246 independent reflections |
R[F2 > 2σ(F2)] = 0.031 | 1 restraint |
wR(F2) = 0.076 | H-atom parameters constrained |
S = 1.08 | Δρmax = 0.11 e Å−3 |
1246 reflections | Δρmin = −0.14 e Å−3 |
164 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 | ||
C1 | 0.8935 (4) | 0.4244 (2) | 0.24523 (19) | 0.0343 (5) | |
H1A | 0.9134 | 0.4636 | 0.3252 | 0.041* | |
H1B | 0.7364 | 0.4369 | 0.2188 | 0.041* | |
C2 | 1.0401 (3) | 0.5062 (2) | 0.16534 (17) | 0.0301 (5) | |
C3 | 0.9824 (4) | 0.6432 (3) | 0.12309 (18) | 0.0360 (5) | |
H3 | 0.8452 | 0.6850 | 0.1421 | 0.043* | |
C4 | 1.1216 (4) | 0.7206 (3) | 0.05344 (18) | 0.0403 (5) | |
H4 | 1.0813 | 0.8155 | 0.0263 | 0.048* | |
C5 | 1.3199 (4) | 0.6585 (3) | 0.02377 (18) | 0.0385 (5) | |
H5 | 1.4157 | 0.7105 | −0.0244 | 0.046* | |
C6 | 1.3781 (4) | 0.5209 (3) | 0.06430 (18) | 0.0348 (5) | |
H6 | 1.5135 | 0.4786 | 0.0430 | 0.042* | |
C7 | 1.2412 (3) | 0.4433 (2) | 0.13602 (16) | 0.0295 (5) | |
C8 | 1.1581 (3) | 0.2248 (3) | 0.22061 (16) | 0.0309 (5) | |
C9 | 1.1809 (4) | 0.0669 (3) | 0.2550 (2) | 0.0413 (6) | |
H9A | 1.2678 | 0.0565 | 0.3297 | 0.050* | |
H9B | 1.2532 | 0.0098 | 0.1946 | 0.050* | |
C10 | 0.9409 (4) | 0.0170 (3) | 0.2667 (2) | 0.0428 (6) | |
H10A | 0.9307 | −0.0560 | 0.3297 | 0.051* | |
H10B | 0.8795 | −0.0261 | 0.1931 | 0.051* | |
C11 | 0.8183 (3) | 0.1590 (3) | 0.29605 (17) | 0.0351 (5) | |
H11 | 0.6653 | 0.1587 | 0.2590 | 0.042* | |
C12 | 0.8108 (4) | 0.1795 (3) | 0.42708 (19) | 0.0387 (6) | |
C13 | 0.6211 (4) | 0.1044 (4) | 0.5926 (2) | 0.0562 (8) | |
H13A | 0.7692 | 0.1147 | 0.6322 | 0.067* | |
H13B | 0.5573 | 0.0102 | 0.6169 | 0.067* | |
C14 | 0.4776 (5) | 0.2258 (4) | 0.6279 (2) | 0.0595 (7) | |
H14A | 0.3311 | 0.2158 | 0.5886 | 0.089* | |
H14B | 0.5433 | 0.3193 | 0.6063 | 0.089* | |
H14C | 0.4636 | 0.2228 | 0.7123 | 0.089* | |
N1 | 0.9521 (3) | 0.2705 (2) | 0.24410 (14) | 0.0315 (4) | |
N2 | 1.3078 (3) | 0.3013 (2) | 0.17238 (15) | 0.0328 (4) | |
O1 | 0.6431 (3) | 0.1034 (2) | 0.46705 (14) | 0.0454 (4) | |
O2 | 0.9396 (3) | 0.2508 (3) | 0.48572 (14) | 0.0652 (6) |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0276 (11) | 0.0351 (13) | 0.0405 (11) | 0.0037 (10) | 0.0048 (9) | −0.0020 (10) |
C2 | 0.0287 (10) | 0.0315 (12) | 0.0298 (10) | −0.0010 (9) | −0.0006 (8) | −0.0023 (9) |
C3 | 0.0340 (11) | 0.0361 (12) | 0.0380 (11) | 0.0045 (10) | 0.0007 (9) | −0.0005 (10) |
C4 | 0.0511 (14) | 0.0309 (12) | 0.0383 (11) | 0.0021 (11) | −0.0026 (10) | 0.0044 (11) |
C5 | 0.0450 (12) | 0.0389 (13) | 0.0316 (11) | −0.0062 (11) | 0.0036 (9) | 0.0033 (10) |
C6 | 0.0296 (10) | 0.0399 (13) | 0.0351 (11) | −0.0049 (10) | 0.0042 (9) | −0.0039 (11) |
C7 | 0.0276 (10) | 0.0320 (12) | 0.0285 (10) | 0.0003 (9) | −0.0014 (8) | −0.0011 (9) |
C8 | 0.0282 (10) | 0.0337 (11) | 0.0307 (10) | 0.0034 (10) | 0.0013 (8) | −0.0002 (9) |
C9 | 0.0376 (12) | 0.0370 (14) | 0.0495 (14) | 0.0034 (11) | 0.0055 (10) | 0.0055 (10) |
C10 | 0.0451 (14) | 0.0366 (13) | 0.0471 (13) | −0.0041 (11) | 0.0065 (11) | 0.0043 (11) |
C11 | 0.0279 (10) | 0.0412 (13) | 0.0361 (11) | −0.0061 (10) | 0.0011 (8) | 0.0062 (10) |
C12 | 0.0308 (11) | 0.0479 (15) | 0.0372 (11) | 0.0032 (10) | 0.0001 (9) | 0.0092 (10) |
C13 | 0.0580 (16) | 0.073 (2) | 0.0391 (13) | 0.0063 (16) | 0.0170 (12) | 0.0200 (14) |
C14 | 0.0631 (16) | 0.0670 (18) | 0.0495 (14) | −0.0021 (16) | 0.0120 (12) | −0.0016 (15) |
N1 | 0.0274 (9) | 0.0328 (11) | 0.0347 (9) | 0.0008 (8) | 0.0050 (7) | 0.0042 (8) |
N2 | 0.0260 (9) | 0.0347 (11) | 0.0380 (9) | 0.0017 (8) | 0.0046 (7) | 0.0019 (8) |
O1 | 0.0442 (9) | 0.0514 (11) | 0.0418 (9) | −0.0038 (8) | 0.0140 (7) | 0.0093 (8) |
O2 | 0.0519 (11) | 0.1046 (18) | 0.0385 (9) | −0.0257 (12) | −0.0036 (8) | 0.0003 (11) |
C1—N1 | 1.452 (3) | C9—C10 | 1.536 (3) |
C1—C2 | 1.509 (3) | C9—H9A | 0.9900 |
C1—H1A | 0.9900 | C9—H9B | 0.9900 |
C1—H1B | 0.9900 | C10—C11 | 1.541 (4) |
C2—C3 | 1.383 (3) | C10—H10A | 0.9900 |
C2—C7 | 1.403 (3) | C10—H10B | 0.9900 |
C3—C4 | 1.387 (3) | C11—N1 | 1.450 (3) |
C3—H3 | 0.9500 | C11—C12 | 1.524 (3) |
C4—C5 | 1.387 (3) | C11—H11 | 1.0000 |
C4—H4 | 0.9500 | C12—O2 | 1.199 (3) |
C5—C6 | 1.381 (3) | C12—O1 | 1.332 (3) |
C5—H5 | 0.9500 | C13—O1 | 1.459 (3) |
C6—C7 | 1.394 (3) | C13—C14 | 1.480 (4) |
C6—H6 | 0.9500 | C13—H13A | 0.9900 |
C7—N2 | 1.416 (3) | C13—H13B | 0.9900 |
C8—N2 | 1.293 (3) | C14—H14A | 0.9800 |
C8—N1 | 1.355 (3) | C14—H14B | 0.9800 |
C8—C9 | 1.502 (3) | C14—H14C | 0.9800 |
N1—C1—C2 | 108.86 (17) | C9—C10—C11 | 103.7 (2) |
N1—C1—H1A | 109.9 | C9—C10—H10A | 111.0 |
C2—C1—H1A | 109.9 | C11—C10—H10A | 111.0 |
N1—C1—H1B | 109.9 | C9—C10—H10B | 111.0 |
C2—C1—H1B | 109.9 | C11—C10—H10B | 111.0 |
H1A—C1—H1B | 108.3 | H10A—C10—H10B | 109.0 |
C3—C2—C7 | 119.57 (19) | N1—C11—C12 | 111.57 (19) |
C3—C2—C1 | 121.18 (19) | N1—C11—C10 | 102.49 (17) |
C7—C2—C1 | 119.23 (18) | C12—C11—C10 | 111.05 (18) |
C2—C3—C4 | 121.1 (2) | N1—C11—H11 | 110.5 |
C2—C3—H3 | 119.5 | C12—C11—H11 | 110.5 |
C4—C3—H3 | 119.5 | C10—C11—H11 | 110.5 |
C5—C4—C3 | 119.5 (2) | O2—C12—O1 | 125.1 (2) |
C5—C4—H4 | 120.2 | O2—C12—C11 | 125.0 (2) |
C3—C4—H4 | 120.2 | O1—C12—C11 | 109.86 (19) |
C6—C5—C4 | 119.9 (2) | O1—C13—C14 | 111.2 (2) |
C6—C5—H5 | 120.0 | O1—C13—H13A | 109.4 |
C4—C5—H5 | 120.0 | C14—C13—H13A | 109.4 |
C5—C6—C7 | 121.0 (2) | O1—C13—H13B | 109.4 |
C5—C6—H6 | 119.5 | C14—C13—H13B | 109.4 |
C7—C6—H6 | 119.5 | H13A—C13—H13B | 108.0 |
C6—C7—C2 | 118.89 (19) | C13—C14—H14A | 109.5 |
C6—C7—N2 | 118.26 (19) | C13—C14—H14B | 109.5 |
C2—C7—N2 | 122.80 (18) | H14A—C14—H14B | 109.5 |
N2—C8—N1 | 126.3 (2) | C13—C14—H14C | 109.5 |
N2—C8—C9 | 125.2 (2) | H14A—C14—H14C | 109.5 |
N1—C8—C9 | 108.43 (19) | H14B—C14—H14C | 109.5 |
C8—C9—C10 | 103.55 (19) | C8—N1—C11 | 113.89 (18) |
C8—C9—H9A | 111.0 | C8—N1—C1 | 121.87 (18) |
C10—C9—H9A | 111.1 | C11—N1—C1 | 122.40 (17) |
C8—C9—H9B | 111.1 | C8—N2—C7 | 115.34 (18) |
C10—C9—H9B | 111.1 | C12—O1—C13 | 116.7 (2) |
H9A—C9—H9B | 109.0 |
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5···N2i | 0.95 | 2.59 | 3.523 (3) | 169 |
Symmetry code: (i) −x+3, y+1/2, −z. |
Experimental details
Crystal data | |
Chemical formula | C14H16N2O2 |
Mr | 244.29 |
Crystal system, space group | Monoclinic, P21 |
Temperature (K) | 187 |
a, b, c (Å) | 6.0545 (8), 9.1438 (13), 11.5228 (16) |
β (°) | 92.905 (2) |
V (Å3) | 637.10 (15) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.29 × 0.22 × 0.19 |
Data collection | |
Diffractometer | Bruker SMART APEX CCD area-detector diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3430, 1246, 1166 |
Rint | 0.016 |
(sin θ/λ)max (Å−1) | 0.602 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.031, 0.076, 1.08 |
No. of reflections | 1246 |
No. of parameters | 164 |
No. of restraints | 1 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.11, −0.14 |
Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1999), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL-Plus (Sheldrick, 2008).
D—H···A | D—H | H···A | D···A | D—H···A |
C5—H5···N2i | 0.95 | 2.59 | 3.523 (3) | 169 |
Symmetry code: (i) −x+3, y+1/2, −z. |
References
Bruker (1997). SMART. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (1999). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Cheng, M.-S., Li, Q., Lin, B., Sha, Y., Ren, J.-H., He, Y., Wang, Q.-H., Hua, H.-M. & Kenneth, R. (2006). Tetrahedron Asymmetry, 17, 179–183. Web of Science CSD CrossRef CAS Google Scholar
Hua, H.-M., Cheng, M.-S., Li, X. & Pei, Y.-H. (2002). Chem. Pharm. Bull. 50, 1393–1394. Web of Science CSD CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
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The title chiral compound is a derivate of (S)-1,2,3,9-tetrahydro-pyrrolo(2,1 - b)quinazolin-1-carboxylic acid (Linaria acid). Linaria acid is a nature compound, was isolated from the Linaria vulgaris (Hua et al., 2002). Linaria vulgaris is a grassy plant that occurs in northeast China. The plant is used in traditional folk medicine for the treatment of coughs and asthma and as an expectorant. As part of our search on new Linaria acid derivate compounds (Cheng et al., 2006), the title compound is recently synthesized and its crystal structure is reported here.
The molecular structure is shown in Fig. 1. The bond lengths and angles are within normal ranges. The quinazoline moiety is not planar, the central N-heterocyclic ring shows a distorted conformation, with atom N1 and C8 displaced by 0.420 Å and 0.257 Å from the mean plane defined by atoms C1/C2/C7/N2. The five-membered ring adopts an envelope conformation, with atom C10 deviating by 0.443 Å from the plane formed by the other atoms in the ring. Atom C11 of the title molecule is chiral, S configuration was assigned to this atom based on the known chirality of the equivalent atom in the starting material. An intermolecular C—H···N hydrogen bonding (Table 1) helps to stabilize the crystal structure.