Ethyl 2,4-dimethyl­pyrido[1,2-a]benz­imidazole-3-carboxyl­ate

Zhu, A.G.; Ma, Z.M.; Li, L.J.; Wei, T.T.; Ge, Y.Q.

doi:10.1107/S1600536812040299

organic compounds

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 68| Part 10| October 2012| Page o3032

https://doi.org/10.1107/S1600536812040299

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Ethyl 2,4-dimethylpyrido[1,2-a]benzimidazole-3-carboxylate

Ai Guo Zhu,^a Zhuo Ming Ma,^a Lin Jie Li,^a Tian Tian Wei ^a and Yan Qing Ge ^a ^*

^aSchool of Chemistry and Chemical Engineering, Taishan Medical University, Tai an 271016, People's Republic of China
^*Correspondence e-mail: yqge@yahoo.cn

(Received 12 September 2012; accepted 23 September 2012; online 29 September 2012)

The title compound, C₁₆H₁₆N₂O₂, was synthesized using a novel tandem annulation reaction between 1-(1H-benzo[d]imidazol-2-yl)ethanone and ethyl (E)-4-bromobut-2-enoate under mild conditions. The dihedral angles formed by the mean plane of the five-membered imidazole ring with the dihydropyridin and benzene rings are 1.54 (9) and 1.85 (9)°, respectively.

Related literature

For the synthesis and characterization of pyrido[1,2-a]benzimidazole derivatives, see: Ge et al. (2009 , 2011 ). For pharmaceutical applications of nitrogen-containing heterocyclic compounds, see: Badawey & Kappe (1999 ).

Experimental

Crystal data

C₁₆H₁₆N₂O₂
M_r = 268.31
Monoclinic, P 2₁ /c
a = 7.671 (4) Å
b = 13.174 (7) Å
c = 13.807 (7) Å
β = 102.680 (7)°
V = 1361.3 (12) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 273 K
0.32 × 0.28 × 0.26 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2005 ) T_min = 0.973, T_max = 0.978
6894 measured reflections
2389 independent reflections
2056 reflections with I > 2σ(I)
R_int = 0.086

Refinement

R[F² > 2σ(F²)] = 0.047
wR(F²) = 0.134
S = 1.05
2389 reflections
184 parameters
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL.

Supporting information

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S1600536812040299/rz5006sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812040299/rz5006Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S1600536812040299/rz5006Isup3.cml

checkCIF report

Comment top

The synthesis of nitrogen-containing heterocyclic compounds has been a subject of great interest due to the wide application in pharmaceutical fields (Ge et al., 2009; Ge et al., 2011). Some pyrido[1,2-a]benzimidazole derivatives have been of interest for their biological activities, such as antineoplastic activity and central GABA-A receptor modulators for the treatment of anxiety (Badawey et al.; 1999).

The fused-ring system of the title compound (Fig. 1) is approximately planar, the dihedral angles formed by the mean planes through the imidazole ring with the dihydropyridine and benzene rings being 1.54 (9) and 1.85 (9)°, respectively. The mean plane defined by the carboxylate group (C3/C4/O1/O2) is tilted by 60.38 (5)° with respect to the plane of the benzene ring. The crystal structure is stabilized only by van der Waals interactions.

Related literature top

For the synthesis and characterization of pyrido[1,2-a]benzimidazole derivatives, see: Ge et al. (2009, 2011). For pharmaceutical applications of nitrogen-containing heterocyclic compounds, see: Badawey & Kappe (1999).

Experimental top

To a 50 ml round-bottomed flask were added 1-(1H-benzo[d]imidazol-2-yl)ethanone (1.00 mmol), (E)-ethyl 4-bromobut-2-enoate (2.00 mmol), potassium carbonate (0.28 g, 2.05 mmol) and dry DMF (10 ml). The mixture was stirred at room temperature for 6 h. The solvent was removed under reduced pressure and the product was isolated by column chromatography on silica gel (yield 70%). Crystals of the title compound suitable for X-ray diffraction were obtained by allowing a refluxed solution of the product in ethyl acetate to cool slowly to room temperature (without temperature control) and allowing the solvent to slowly evaporate for 2 d.

Structure description top

For the synthesis and characterization of pyrido[1,2-a]benzimidazole derivatives, see: Ge et al. (2009, 2011). For pharmaceutical applications of nitrogen-containing heterocyclic compounds, see: Badawey & Kappe (1999).

Computing details top

Data collection: APEX2 (Bruker, 2005); cell refinement: SAINT (Bruker, 2005); data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top

Fig. 1. The molecular structure of the title compound, showing displacement ellipsoids drawn at the 50% probability level.

Ethyl 2,4-dimethylpyrido[1,2-a]benzimidazole-3-carboxylate top

Crystal data top

C₁₆H₁₆N₂O₂	F(000) = 568
M_r = 268.31	D_x = 1.309 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4261 reflections
a = 7.671 (4) Å	θ = 3.0–28.2°
b = 13.174 (7) Å	µ = 0.09 mm⁻¹
c = 13.807 (7) Å	T = 273 K
β = 102.680 (7)°	Block, colourless
V = 1361.3 (12) Å³	0.32 × 0.28 × 0.26 mm
Z = 4

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	2389 independent reflections
Radiation source: fine-focus sealed tube	2056 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.086
phi and ω scans	θ_max = 25.0°, θ_min = 2.2°
Absorption correction: multi-scan (SADABS; Bruker, 2005)	h = −5→9
T_min = 0.973, T_max = 0.978	k = −15→14
6894 measured reflections	l = −16→16

Refinement top

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)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.134	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.075P)² + 0.2415P] where P = (F_o² + 2F_c²)/3
2389 reflections	(Δ/σ)_max = 0.052
184 parameters	Δρ_max = 0.23 e Å⁻³
0 restraints	Δρ_min = −0.26 e Å⁻³

Crystal data top

C₁₆H₁₆N₂O₂	V = 1361.3 (12) Å³
M_r = 268.31	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 7.671 (4) Å	µ = 0.09 mm⁻¹
b = 13.174 (7) Å	T = 273 K
c = 13.807 (7) Å	0.32 × 0.28 × 0.26 mm
β = 102.680 (7)°

Data collection top

Bruker SMART APEXII CCD area-detector diffractometer	2389 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2005)	2056 reflections with I > 2σ(I)
T_min = 0.973, T_max = 0.978	R_int = 0.086
6894 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.047	0 restraints
wR(F²) = 0.134	H-atom parameters constrained
S = 1.05	Δρ_max = 0.23 e Å⁻³
2389 reflections	Δρ_min = −0.26 e Å⁻³
184 parameters

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

	x	y	z	U_iso*/U_eq
N1	0.75792 (18)	−0.01609 (10)	0.27023 (9)	0.0440 (4)
N2	0.72152 (15)	−0.05514 (9)	0.10717 (9)	0.0351 (3)
O1	1.03253 (17)	0.23943 (10)	−0.01104 (10)	0.0594 (4)
O2	0.80757 (16)	0.30461 (8)	0.04828 (9)	0.0487 (3)
C1	0.7586 (4)	0.47805 (16)	0.07813 (19)	0.0802 (7)
H1A	0.6335	0.4681	0.0505	0.120*
H1B	0.7907	0.5467	0.0664	0.120*
H1C	0.7830	0.4654	0.1483	0.120*
C2	0.8641 (3)	0.40713 (12)	0.03063 (14)	0.0531 (5)
H2A	0.8429	0.4204	−0.0401	0.064*
H2B	0.9906	0.4155	0.0590	0.064*
C3	0.9069 (2)	0.22855 (11)	0.02743 (11)	0.0400 (4)
C4	0.84263 (19)	0.12847 (11)	0.05743 (10)	0.0365 (4)
C5	0.78468 (19)	0.05213 (11)	−0.01807 (10)	0.0360 (4)
C6	0.72718 (19)	−0.03754 (12)	0.00956 (10)	0.0373 (4)
H6	0.6910	−0.0881	−0.0376	0.045*
C7	0.77753 (19)	0.01635 (11)	0.18186 (10)	0.0358 (3)
C8	0.84377 (19)	0.11132 (11)	0.15597 (11)	0.0376 (4)
C9	0.9153 (2)	0.18433 (13)	0.23890 (12)	0.0505 (4)
H9A	1.0014	0.2284	0.2196	0.076*
H9B	0.9714	0.1471	0.2972	0.076*
H9C	0.8189	0.2241	0.2529	0.076*
C10	0.7900 (2)	0.07044 (13)	−0.12539 (11)	0.0460 (4)
H10A	0.7427	0.0123	−0.1643	0.069*
H10B	0.9113	0.0816	−0.1306	0.069*
H10C	0.7194	0.1291	−0.1495	0.069*
C11	0.66408 (19)	−0.13957 (11)	0.15187 (11)	0.0377 (4)
C12	0.6866 (2)	−0.11231 (12)	0.25233 (11)	0.0410 (4)
C13	0.6335 (2)	−0.18090 (14)	0.31784 (13)	0.0527 (5)
H13	0.6463	−0.1652	0.3847	0.063*
C14	0.5616 (2)	−0.27222 (14)	0.28027 (14)	0.0566 (5)
H14	0.5252	−0.3183	0.3229	0.068*
C15	0.5415 (2)	−0.29809 (13)	0.17999 (14)	0.0551 (5)
H15	0.4928	−0.3607	0.1577	0.066*
C16	0.5929 (2)	−0.23193 (12)	0.11366 (13)	0.0473 (4)
H16	0.5805	−0.2484	0.0470	0.057*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
N1	0.0471 (8)	0.0517 (8)	0.0327 (7)	−0.0038 (6)	0.0078 (5)	0.0015 (6)
N2	0.0331 (6)	0.0393 (7)	0.0329 (6)	0.0012 (5)	0.0070 (5)	−0.0004 (5)
O1	0.0582 (8)	0.0569 (7)	0.0723 (9)	−0.0017 (6)	0.0340 (7)	0.0058 (6)
O2	0.0493 (7)	0.0397 (6)	0.0601 (7)	0.0010 (5)	0.0186 (5)	0.0031 (5)
C1	0.0948 (17)	0.0504 (11)	0.1022 (18)	0.0057 (11)	0.0363 (14)	−0.0058 (11)
C2	0.0638 (11)	0.0409 (9)	0.0546 (10)	−0.0031 (8)	0.0126 (8)	0.0046 (8)
C3	0.0396 (8)	0.0440 (9)	0.0363 (8)	0.0011 (7)	0.0080 (6)	0.0016 (6)
C4	0.0319 (7)	0.0413 (8)	0.0366 (8)	0.0036 (6)	0.0085 (6)	0.0005 (6)
C5	0.0321 (7)	0.0438 (8)	0.0324 (7)	0.0057 (6)	0.0074 (6)	0.0000 (6)
C6	0.0366 (8)	0.0432 (8)	0.0314 (7)	0.0027 (6)	0.0055 (6)	−0.0043 (6)
C7	0.0333 (7)	0.0421 (8)	0.0318 (7)	0.0019 (6)	0.0064 (6)	−0.0017 (6)
C8	0.0355 (8)	0.0409 (8)	0.0360 (8)	0.0017 (6)	0.0069 (6)	−0.0024 (6)
C9	0.0584 (10)	0.0523 (10)	0.0397 (9)	−0.0096 (8)	0.0084 (7)	−0.0069 (7)
C10	0.0473 (9)	0.0566 (10)	0.0345 (8)	0.0042 (7)	0.0097 (7)	0.0030 (7)
C11	0.0311 (7)	0.0401 (8)	0.0419 (8)	0.0032 (6)	0.0081 (6)	0.0046 (6)
C12	0.0352 (8)	0.0488 (9)	0.0380 (8)	0.0030 (6)	0.0057 (6)	0.0067 (6)
C13	0.0480 (10)	0.0654 (11)	0.0432 (9)	−0.0023 (8)	0.0067 (7)	0.0143 (8)
C14	0.0476 (10)	0.0582 (11)	0.0622 (11)	−0.0028 (8)	0.0085 (8)	0.0237 (9)
C15	0.0480 (10)	0.0450 (9)	0.0711 (12)	−0.0029 (7)	0.0105 (8)	0.0066 (8)
C16	0.0449 (9)	0.0444 (9)	0.0534 (10)	−0.0003 (7)	0.0124 (7)	−0.0015 (7)

Geometric parameters (Å, º) top

N1—C7	1.332 (2)	C6—H6	0.9300
N1—C12	1.381 (2)	C7—C8	1.425 (2)
N2—C6	1.3775 (19)	C8—C9	1.504 (2)
N2—C11	1.3899 (19)	C9—H9A	0.9600
N2—C7	1.393 (2)	C9—H9B	0.9600
O1—C3	1.2065 (19)	C9—H9C	0.9600
O2—C3	1.3283 (19)	C10—H10A	0.9600
O2—C2	1.455 (2)	C10—H10B	0.9600
C1—C2	1.480 (3)	C10—H10C	0.9600
C1—H1A	0.9600	C11—C16	1.389 (2)
C1—H1B	0.9600	C11—C12	1.406 (2)
C1—H1C	0.9600	C12—C13	1.401 (2)
C2—H2A	0.9700	C13—C14	1.377 (3)
C2—H2B	0.9700	C13—H13	0.9300
C3—C4	1.498 (2)	C14—C15	1.401 (3)
C4—C8	1.377 (2)	C14—H14	0.9300
C4—C5	1.446 (2)	C15—C16	1.383 (2)
C5—C6	1.345 (2)	C15—H15	0.9300
C5—C10	1.511 (2)	C16—H16	0.9300

C7—N1—C12	104.51 (12)	C4—C8—C9	124.71 (14)
C6—N2—C11	130.57 (13)	C7—C8—C9	117.46 (13)
C6—N2—C7	122.66 (13)	C8—C9—H9A	109.5
C11—N2—C7	106.78 (12)	C8—C9—H9B	109.5
C3—O2—C2	117.24 (13)	H9A—C9—H9B	109.5
C2—C1—H1A	109.5	C8—C9—H9C	109.5
C2—C1—H1B	109.5	H9A—C9—H9C	109.5
H1A—C1—H1B	109.5	H9B—C9—H9C	109.5
C2—C1—H1C	109.5	C5—C10—H10A	109.5
H1A—C1—H1C	109.5	C5—C10—H10B	109.5
H1B—C1—H1C	109.5	H10A—C10—H10B	109.5
O2—C2—C1	107.44 (15)	C5—C10—H10C	109.5
O2—C2—H2A	110.2	H10A—C10—H10C	109.5
C1—C2—H2A	110.2	H10B—C10—H10C	109.5
O2—C2—H2B	110.2	C16—C11—N2	131.97 (15)
C1—C2—H2B	110.2	C16—C11—C12	123.44 (14)
H2A—C2—H2B	108.5	N2—C11—C12	104.56 (13)
O1—C3—O2	123.88 (14)	N1—C12—C13	129.53 (15)
O1—C3—C4	124.72 (14)	N1—C12—C11	111.65 (13)
O2—C3—C4	111.39 (13)	C13—C12—C11	118.81 (15)
C8—C4—C5	122.15 (14)	C14—C13—C12	118.01 (17)
C8—C4—C3	119.11 (13)	C14—C13—H13	121.0
C5—C4—C3	118.72 (13)	C12—C13—H13	121.0
C6—C5—C4	118.31 (14)	C13—C14—C15	122.22 (16)
C6—C5—C10	119.97 (14)	C13—C14—H14	118.9
C4—C5—C10	121.71 (14)	C15—C14—H14	118.9
C5—C6—N2	120.53 (13)	C16—C15—C14	121.04 (17)
C5—C6—H6	119.7	C16—C15—H15	119.5
N2—C6—H6	119.7	C14—C15—H15	119.5
N1—C7—N2	112.50 (13)	C15—C16—C11	116.48 (16)
N1—C7—C8	129.02 (14)	C15—C16—H16	121.8
N2—C7—C8	118.48 (13)	C11—C16—H16	121.8
C4—C8—C7	117.80 (13)

Experimental details

Crystal data
Chemical formula	C₁₆H₁₆N₂O₂
M_r	268.31
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	273
a, b, c (Å)	7.671 (4), 13.174 (7), 13.807 (7)
β (°)	102.680 (7)
V (Å³)	1361.3 (12)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.09
Crystal size (mm)	0.32 × 0.28 × 0.26

Data collection
Diffractometer	Bruker SMART APEXII CCD area-detector
Absorption correction	Multi-scan (SADABS; Bruker, 2005)
T_min, T_max	0.973, 0.978
No. of measured, independent and observed [I > 2σ(I)] reflections	6894, 2389, 2056
R_int	0.086
(sin θ/λ)_max (Å⁻¹)	0.595

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.047, 0.134, 1.05
No. of reflections	2389
No. of parameters	184
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.23, −0.26

Computer programs: APEX2 (Bruker, 2005), SAINT (Bruker, 2005), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Acknowledgements

This study was supported by the Natural Science Foundation of Shandong Province (No. ZR2012BL04).

References

Badawey, E. S. A. M. & Kappe, T. (1999). Eur. J. Med. Chem. 34, 663–667. Web of Science PubMed CAS Google Scholar
Bruker (2005). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Ge, Y. Q., Jia, J., Li, Y., Yin, L. & Wang, J. W. (2009). Heterocycles, 78, 197–206. CAS Google Scholar
Ge, Y. Q., Jia, J., Yang, H., Tao, X. T. & Wang, J. W. (2011). Dyes Pigm. 88, 344–349. Web of Science CSD CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar