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Acta Cryst. (2008). E64, o815    [ doi:10.1107/S1600536808008908 ]

(S)-Ethyl 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylate

C. Ma, G.-J. Du, Y. Tian, Y. Sha and M.-S. Cheng

Abstract top

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 envelope conformation. Intermolecular C-H...N hydrogen bonding helps to stabilize the crystal structure.

Comment top

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.

Related literature top

For general background, see: Cheng et al. (2006); Hua et al. (2002).

Experimental top

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 chromatography (eluant: petroleum ether/ethyl acetate, 1:10). Single crystals suitable for X-ray diffraction were obtained by slow evaporation of a dilute solution of the title compound in ethyl acetate at room temperature.

Refinement top

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 chirality of the equivalent atom in the starting material, the S chirality at C11 was assigned. Friedel pairs were merged.

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: 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).

Figures top
[Figure 1] Fig. 1. The structure of the title compound, showing 30% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The molecular packing of the title compound.
(S)-Ethyl 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylate top
Crystal data top
C14H16N2O2F000 = 260
Mr = 244.29Dx = 1.273 Mg m−3
Monoclinic, P21Mo Kα radiation
λ = 0.71073 Å
Hall symbol: P 2ybCell parameters from 1588 reflections
a = 6.0545 (8) Åθ = 2.9–25.0º
b = 9.1438 (13) ŵ = 0.09 mm−1
c = 11.5228 (16) ÅT = 187 (2) K
β = 92.905 (2)ºBlock, colorless
V = 637.10 (15) Å30.29 × 0.22 × 0.19 mm
Z = 2
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer		1166 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.016
Monochromator: graphiteθmax = 25.4º
T = 187(2) Kθmin = 1.8º
φ and ω scansh = −7→7
Absorption correction: nonek = −11→5
3430 measured reflectionsl = −13→13
1246 independent reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.031H-atom parameters constrained
wR(F2) = 0.076  w = 1/[σ2(Fo2) + (0.0381P)2 + 0.082P]
where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max = 0.001
1246 reflectionsΔρmax = 0.11 e Å−3
164 parametersΔρmin = −0.14 e Å−3
1 restraintExtinction correction: none
Primary atom site location: structure-invariant direct methods
Crystal data top
C14H16N2O2V = 637.10 (15) Å3
Mr = 244.29Z = 2
Monoclinic, P21Mo Kα
a = 6.0545 (8) ŵ = 0.09 mm−1
b = 9.1438 (13) ÅT = 187 (2) K
c = 11.5228 (16) Å0.29 × 0.22 × 0.19 mm
β = 92.905 (2)º
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer		1246 independent reflections
Absorption correction: none1166 reflections with I > 2σ(I)
3430 measured reflectionsRint = 0.016
Refinement top
R[F2 > 2σ(F2)] = 0.031H-atom parameters constrained
wR(F2) = 0.076Δρmax = 0.11 e Å−3
S = 1.08Δρmin = −0.14 e Å−3
1246 reflectionsAbsolute structure: ?
164 parametersFlack parameter: ?
1 restraintRogers parameter: ?
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.8935 (4)0.4244 (2)0.24523 (19)0.0343 (5)
H1A0.91340.46360.32520.041*
H1B0.73640.43690.21880.041*
C21.0401 (3)0.5062 (2)0.16534 (17)0.0301 (5)
C30.9824 (4)0.6432 (3)0.12309 (18)0.0360 (5)
H30.84520.68500.14210.043*
C41.1216 (4)0.7206 (3)0.05344 (18)0.0403 (5)
H41.08130.81550.02630.048*
C51.3199 (4)0.6585 (3)0.02377 (18)0.0385 (5)
H51.41570.7105−0.02440.046*
C61.3781 (4)0.5209 (3)0.06430 (18)0.0348 (5)
H61.51350.47860.04300.042*
C71.2412 (3)0.4433 (2)0.13602 (16)0.0295 (5)
C81.1581 (3)0.2248 (3)0.22061 (16)0.0309 (5)
C91.1809 (4)0.0669 (3)0.2550 (2)0.0413 (6)
H9A1.26780.05650.32970.050*
H9B1.25320.00980.19460.050*
C100.9409 (4)0.0170 (3)0.2667 (2)0.0428 (6)
H10A0.9307−0.05600.32970.051*
H10B0.8795−0.02610.19310.051*
C110.8183 (3)0.1590 (3)0.29605 (17)0.0351 (5)
H110.66530.15870.25900.042*
C120.8108 (4)0.1795 (3)0.42708 (19)0.0387 (6)
C130.6211 (4)0.1044 (4)0.5926 (2)0.0562 (8)
H13A0.76920.11470.63220.067*
H13B0.55730.01020.61690.067*
C140.4776 (5)0.2258 (4)0.6279 (2)0.0595 (7)
H14A0.33110.21580.58860.089*
H14B0.54330.31930.60630.089*
H14C0.46360.22280.71230.089*
N10.9521 (3)0.2705 (2)0.24410 (14)0.0315 (4)
N21.3078 (3)0.3013 (2)0.17238 (15)0.0328 (4)
O10.6431 (3)0.1034 (2)0.46705 (14)0.0454 (4)
O20.9396 (3)0.2508 (3)0.48572 (14)0.0652 (6)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0276 (11)0.0351 (13)0.0405 (11)0.0037 (10)0.0048 (9)−0.0020 (10)
C20.0287 (10)0.0315 (12)0.0298 (10)−0.0010 (9)−0.0006 (8)−0.0023 (9)
C30.0340 (11)0.0361 (12)0.0380 (11)0.0045 (10)0.0007 (9)−0.0005 (10)
C40.0511 (14)0.0309 (12)0.0383 (11)0.0021 (11)−0.0026 (10)0.0044 (11)
C50.0450 (12)0.0389 (13)0.0316 (11)−0.0062 (11)0.0036 (9)0.0033 (10)
C60.0296 (10)0.0399 (13)0.0351 (11)−0.0049 (10)0.0042 (9)−0.0039 (11)
C70.0276 (10)0.0320 (12)0.0285 (10)0.0003 (9)−0.0014 (8)−0.0011 (9)
C80.0282 (10)0.0337 (11)0.0307 (10)0.0034 (10)0.0013 (8)−0.0002 (9)
C90.0376 (12)0.0370 (14)0.0495 (14)0.0034 (11)0.0055 (10)0.0055 (10)
C100.0451 (14)0.0366 (13)0.0471 (13)−0.0041 (11)0.0065 (11)0.0043 (11)
C110.0279 (10)0.0412 (13)0.0361 (11)−0.0061 (10)0.0011 (8)0.0062 (10)
C120.0308 (11)0.0479 (15)0.0372 (11)0.0032 (10)0.0001 (9)0.0092 (10)
C130.0580 (16)0.073 (2)0.0391 (13)0.0063 (16)0.0170 (12)0.0200 (14)
C140.0631 (16)0.0670 (18)0.0495 (14)−0.0021 (16)0.0120 (12)−0.0016 (15)
N10.0274 (9)0.0328 (11)0.0347 (9)0.0008 (8)0.0050 (7)0.0042 (8)
N20.0260 (9)0.0347 (11)0.0380 (9)0.0017 (8)0.0046 (7)0.0019 (8)
O10.0442 (9)0.0514 (11)0.0418 (9)−0.0038 (8)0.0140 (7)0.0093 (8)
O20.0519 (11)0.1046 (18)0.0385 (9)−0.0257 (12)−0.0036 (8)0.0003 (11)
Geometric parameters (Å, °) top
C1—N11.452 (3)C9—C101.536 (3)
C1—C21.509 (3)C9—H9A0.9900
C1—H1A0.9900C9—H9B0.9900
C1—H1B0.9900C10—C111.541 (4)
C2—C31.383 (3)C10—H10A0.9900
C2—C71.403 (3)C10—H10B0.9900
C3—C41.387 (3)C11—N11.450 (3)
C3—H30.9500C11—C121.524 (3)
C4—C51.387 (3)C11—H111.0000
C4—H40.9500C12—O21.199 (3)
C5—C61.381 (3)C12—O11.332 (3)
C5—H50.9500C13—O11.459 (3)
C6—C71.394 (3)C13—C141.480 (4)
C6—H60.9500C13—H13A0.9900
C7—N21.416 (3)C13—H13B0.9900
C8—N21.293 (3)C14—H14A0.9800
C8—N11.355 (3)C14—H14B0.9800
C8—C91.502 (3)C14—H14C0.9800
N1—C1—C2108.86 (17)C9—C10—C11103.7 (2)
N1—C1—H1A109.9C9—C10—H10A111.0
C2—C1—H1A109.9C11—C10—H10A111.0
N1—C1—H1B109.9C9—C10—H10B111.0
C2—C1—H1B109.9C11—C10—H10B111.0
H1A—C1—H1B108.3H10A—C10—H10B109.0
C3—C2—C7119.57 (19)N1—C11—C12111.57 (19)
C3—C2—C1121.18 (19)N1—C11—C10102.49 (17)
C7—C2—C1119.23 (18)C12—C11—C10111.05 (18)
C2—C3—C4121.1 (2)N1—C11—H11110.5
C2—C3—H3119.5C12—C11—H11110.5
C4—C3—H3119.5C10—C11—H11110.5
C5—C4—C3119.5 (2)O2—C12—O1125.1 (2)
C5—C4—H4120.2O2—C12—C11125.0 (2)
C3—C4—H4120.2O1—C12—C11109.86 (19)
C6—C5—C4119.9 (2)O1—C13—C14111.2 (2)
C6—C5—H5120.0O1—C13—H13A109.4
C4—C5—H5120.0C14—C13—H13A109.4
C5—C6—C7121.0 (2)O1—C13—H13B109.4
C5—C6—H6119.5C14—C13—H13B109.4
C7—C6—H6119.5H13A—C13—H13B108.0
C6—C7—C2118.89 (19)C13—C14—H14A109.5
C6—C7—N2118.26 (19)C13—C14—H14B109.5
C2—C7—N2122.80 (18)H14A—C14—H14B109.5
N2—C8—N1126.3 (2)C13—C14—H14C109.5
N2—C8—C9125.2 (2)H14A—C14—H14C109.5
N1—C8—C9108.43 (19)H14B—C14—H14C109.5
C8—C9—C10103.55 (19)C8—N1—C11113.89 (18)
C8—C9—H9A111.0C8—N1—C1121.87 (18)
C10—C9—H9A111.1C11—N1—C1122.40 (17)
C8—C9—H9B111.1C8—N2—C7115.34 (18)
C10—C9—H9B111.1C12—O1—C13116.7 (2)
H9A—C9—H9B109.0
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C5—H5···N2i0.952.593.523 (3)169
Symmetry codes: (i) −x+3, y+1/2, −z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
C5—H5···N2i0.952.593.523 (3)169
Symmetry codes: (i) −x+3, y+1/2, −z.
references
References top

Bruker (1997). SMART. Bruker AXS Inc., Madison, Wisconsin, USA.

Bruker (1999). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.

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.

Hua, H.-M., Cheng, M.-S., Li, X. & Pei, Y.-H. (2002). Chem. Pharm. Bull. 50, 1393–1394.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.