1-Ethyl-1H,6H-pyrrolo[2,3-c]azepine-4,8(5H,7H)-dione

Li, D.D.; Tang, G.H.; Zeng, X.C.; Xu, X.Y.; Huang, G.

doi:10.1107/S1600536809027378

organic compounds

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ISSN: 2056-9890

Volume 65| Part 8| August 2009| Page o1928

doi:10.1107/S1600536809027378

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1-Ethyl-1H,6H-pyrrolo[2,3-c]azepine-4,8(5H,7H)-dione

Dong Dong Li,^a Gui Hong Tang,^a Xiang Chao Zeng,^a ^* Xing Yan Xu ^a and Gang Huang ^a

^aDepartment of Chemistry, Jinan University, Guangzhou, Guangdong 510632, People's Republic of China
^*Correspondence e-mail: xczeng@126.com

(Received 2 July 2009; accepted 12 July 2009; online 18 July 2009)

The title compound, C₁₀H₁₂N₂O₂, was synthesized by cyclization of 3-(1-ethylpyrrole-2-carboxamido)propanoic acid in the presence of polyphosphoric acid and diphosphorus pentoxide. In the crystal structure, adjacent molecules are linked by N—H⋯O hydrogen bonds, forming chains extending along the b axis.

Related literature

For pyrroles sourced from marine organisms, see: Liu et al. (2005 ). For the bioactivity of pyrrole derivatives, see: Banwell et al. (2006 ); Sosa et al. (2002 ). For related structures, see: Zeng (2006 ); Zeng et al. (2005 ).

Experimental

Crystal data

C₁₀H₁₂N₂O₂
M_r = 192.22
Monoclinic, P 2₁ /c
a = 11.703 (2) Å
b = 7.7863 (13) Å
c = 11.0004 (19) Å
β = 113.878 (3)°
V = 916.6 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 173 K
0.46 × 0.45 × 0.30 mm

Data collection

Bruker SMART 1K CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ) T_min = 0.956, T_max = 0.971
4523 measured reflections
1984 independent reflections
1661 reflections with I > 2σ(I)
R_int = 0.021

Refinement

R[F² > 2σ(F²)] = 0.037
wR(F²) = 0.104
S = 1.07
1984 reflections
128 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.21 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2A⋯O1ⁱ	0.88	2.12	2.9043 (14)	148
Symmetry code: (i) $[-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}]$ .

Data collection: SMART (Bruker,1999 ); cell refinement: SAINT-Plus (Bruker, 1999); data reduction: SAINT-Plus; 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: 10.1107/S1600536809027378/jh2089sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809027378/jh2089Isup2.hkl

checkCIF report

Comment top

Pyrrole derivatives are well known in many marine organisms (Liu et al., 2005), some show important bioactivities, such as antitumor activity (Banwell et al., 2006) and protein kinase inhibiting activity (Sosa et al., 2002). This is the reason they have attracted our interest. This study is related to our previous structural investigations of 1-Methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione (Zeng et al.,2005) and 3-bromo-1-methyl-6,7- dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione (Zeng, 2006). In the crystal structure, molecules of the title compound are linked through N2—H2A···O1 hydrogen bonds to form chains extending to the b axis (shown in Fig. 2).

Related literature top

For pyrroles sourced from marine organisms, see: Liu et al. (2005). For the bioactivity of pyrrole derivatives, see: Banwell et al. (2006); Sosa et al. (2002). For related structures, see: Zeng (2006); Zeng et al. (2005).

Experimental top

3-(1-Ethylpyrrole-2-carboxamido)propanoic acid (0.84 g, 4 mmol) was added to polyphosphoric acid (13 g) to which diphosphorus pentoxide (0.7 g, 5 mmol) had been added, and the mixture magnetically stirred at about 393 K for 0.5 h, and was then poured into ice-water and neutralized with NaOH solution. After filtration, the aqueous solution was extracted four times with ethyl acetate (15 ml). The organic phase was dried with sodium sulfate overnight. The solvent was removed by distillation under reduced pressure, and the pale-yellow solid residue was collected. The crude product was dissolved in the mixture of ethyl acetate (60%) and petroleum ether (40%), colorless monoclinic crystals suitable for X-ray analysis (m.p. 428 K, yield 65.3%) were obtained when the solution was exposed to air at room temperature for 5 d.

Computing details top

Data collection: SMART (Bruker,1999); cell refinement: SAINT-Plus (Bruker, 1999); data reduction: SAINT-Plus (Bruker, 1999); 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, with the atom-numbering scheme. Displacement ellipsoids are drawn at the 30% probability level.
	Fig. 2. Crystal packing of (I) showing the chain formed by hydrogen bonds (dashed lines).

1-Ethyl-1H,6H-pyrrolo[2,3-c]azepine-4,8(5H,7H)-dione top

Crystal data top

C₁₀H₁₂N₂O₂	D_x = 1.393 Mg m⁻³
M_r = 192.22	Melting point: 428 K
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.703 (2) Å	Cell parameters from 2801 reflections
b = 7.7863 (13) Å	θ = 3.2–27.0°
c = 11.0004 (19) Å	µ = 0.10 mm⁻¹
β = 113.878 (3)°	T = 173 K
V = 916.6 (3) Å³	Block, colourless
Z = 4	0.46 × 0.45 × 0.30 mm
F(000) = 408

Data collection top

Bruker SMART 1K CCD area-detector diffractometer	1984 independent reflections
Radiation source: fine-focus sealed tube	1661 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.021
ϕ and ω scans	θ_max = 27.0°, θ_min = 1.9°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −14→10
T_min = 0.956, T_max = 0.971	k = −9→6
4523 measured reflections	l = −11→14

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)] = 0.037	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.104	H-atom parameters constrained
S = 1.07	w = 1/[σ²(F_o²) + (0.0534P)² + 0.2795P] where P = (F_o² + 2F_c²)/3
1984 reflections	(Δ/σ)_max = 0.001
128 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.21 e Å⁻³

Crystal data top

C₁₀H₁₂N₂O₂	V = 916.6 (3) Å³
M_r = 192.22	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.703 (2) Å	µ = 0.10 mm⁻¹
b = 7.7863 (13) Å	T = 173 K
c = 11.0004 (19) Å	0.46 × 0.45 × 0.30 mm
β = 113.878 (3)°

Data collection top

Bruker SMART 1K CCD area-detector diffractometer	1984 independent reflections
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	1661 reflections with I > 2σ(I)
T_min = 0.956, T_max = 0.971	R_int = 0.021
4523 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.037	0 restraints
wR(F²) = 0.104	H-atom parameters constrained
S = 1.07	Δρ_max = 0.28 e Å⁻³
1984 reflections	Δρ_min = −0.21 e Å⁻³
128 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
O2	0.07477 (9)	0.05619 (12)	0.30383 (10)	0.0317 (3)
O1	0.47580 (8)	0.04303 (12)	0.16872 (9)	0.0277 (2)
N2	0.35948 (10)	0.26744 (13)	0.18305 (11)	0.0239 (3)
H2A	0.4269	0.3322	0.2129	0.029*
N1	0.24341 (10)	−0.13996 (13)	0.02340 (10)	0.0222 (3)
C5	0.37313 (11)	0.10354 (16)	0.15418 (12)	0.0210 (3)
C1	0.14174 (12)	−0.23379 (16)	0.01642 (13)	0.0255 (3)
H1	0.1100	−0.3328	−0.0372	0.031*
C4	0.25889 (11)	−0.00413 (15)	0.10751 (12)	0.0201 (3)
C7	0.19395 (13)	0.28160 (17)	0.26984 (14)	0.0276 (3)
H7A	0.2634	0.2860	0.3591	0.033*
H7B	0.1283	0.3613	0.2705	0.033*
C3	0.16546 (11)	−0.01426 (15)	0.15559 (12)	0.0212 (3)
C8	0.14076 (11)	0.10147 (16)	0.24709 (12)	0.0231 (3)
C2	0.09348 (12)	−0.16271 (16)	0.09844 (13)	0.0247 (3)
H2	0.0246	−0.2046	0.1144	0.030*
C9	0.31226 (13)	−0.17678 (16)	−0.05965 (13)	0.0257 (3)
H9A	0.3682	−0.0790	−0.0542	0.031*
H9B	0.2521	−0.1882	−0.1534	0.031*
C10	0.38929 (13)	−0.33927 (18)	−0.01768 (14)	0.0312 (3)
H10A	0.4517	−0.3265	0.0737	0.047*
H10B	0.4315	−0.3600	−0.0771	0.047*
H10C	0.3345	−0.4365	−0.0225	0.047*
C6	0.24223 (12)	0.34703 (16)	0.16897 (13)	0.0243 (3)
H6A	0.1785	0.3245	0.0783	0.029*
H6B	0.2543	0.4729	0.1793	0.029*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O2	0.0380 (6)	0.0290 (5)	0.0366 (5)	0.0024 (4)	0.0237 (5)	0.0032 (4)
O1	0.0232 (5)	0.0257 (5)	0.0347 (5)	0.0027 (4)	0.0123 (4)	0.0015 (4)
N2	0.0223 (5)	0.0189 (5)	0.0302 (6)	−0.0029 (4)	0.0102 (4)	−0.0020 (4)
N1	0.0253 (5)	0.0184 (5)	0.0222 (5)	0.0012 (4)	0.0090 (4)	−0.0004 (4)
C5	0.0232 (6)	0.0204 (6)	0.0199 (6)	0.0015 (5)	0.0091 (5)	0.0027 (5)
C1	0.0263 (7)	0.0192 (6)	0.0271 (6)	−0.0014 (5)	0.0068 (5)	−0.0011 (5)
C4	0.0237 (6)	0.0163 (5)	0.0191 (6)	0.0025 (5)	0.0075 (5)	0.0017 (4)
C7	0.0320 (7)	0.0230 (6)	0.0315 (7)	−0.0004 (5)	0.0168 (6)	−0.0045 (5)
C3	0.0215 (6)	0.0188 (6)	0.0217 (6)	0.0026 (5)	0.0072 (5)	0.0033 (5)
C8	0.0231 (6)	0.0231 (6)	0.0224 (6)	0.0043 (5)	0.0086 (5)	0.0034 (5)
C2	0.0228 (6)	0.0210 (6)	0.0287 (6)	−0.0011 (5)	0.0089 (5)	0.0031 (5)
C9	0.0320 (7)	0.0237 (6)	0.0235 (6)	0.0030 (5)	0.0135 (5)	−0.0007 (5)
C10	0.0341 (8)	0.0283 (7)	0.0308 (7)	0.0077 (6)	0.0128 (6)	−0.0025 (6)
C6	0.0276 (7)	0.0170 (6)	0.0283 (6)	0.0023 (5)	0.0114 (5)	−0.0002 (5)

Geometric parameters (Å, º) top

O2—C8	1.2250 (15)	C7—H7A	0.9900
O1—C5	1.2393 (15)	C7—H7B	0.9900
N2—C5	1.3402 (16)	C3—C2	1.4185 (17)
N2—C6	1.4556 (16)	C3—C8	1.4643 (18)
N2—H2A	0.8800	C2—H2	0.9500
N1—C4	1.3681 (16)	C9—C10	1.5131 (18)
N1—C1	1.3716 (16)	C9—H9A	0.9900
N1—C9	1.4704 (16)	C9—H9B	0.9900
C5—C4	1.4826 (17)	C10—H10A	0.9800
C1—C2	1.3609 (19)	C10—H10B	0.9800
C1—H1	0.9500	C10—H10C	0.9800
C4—C3	1.3964 (17)	C6—H6A	0.9900
C7—C8	1.5137 (18)	C6—H6B	0.9900
C7—C6	1.5223 (18)

C5—N2—C6	125.30 (11)	O2—C8—C3	120.92 (12)
C5—N2—H2A	117.4	O2—C8—C7	118.97 (11)
C6—N2—H2A	117.4	C3—C8—C7	120.09 (11)
C4—N1—C1	108.91 (10)	C1—C2—C3	107.09 (11)
C4—N1—C9	127.96 (11)	C1—C2—H2	126.5
C1—N1—C9	122.85 (11)	C3—C2—H2	126.5
O1—C5—N2	122.26 (12)	N1—C9—C10	112.47 (11)
O1—C5—C4	121.40 (11)	N1—C9—H9A	109.1
N2—C5—C4	116.31 (11)	C10—C9—H9A	109.1
C2—C1—N1	109.25 (11)	N1—C9—H9B	109.1
C2—C1—H1	125.4	C10—C9—H9B	109.1
N1—C1—H1	125.4	H9A—C9—H9B	107.8
N1—C4—C3	107.63 (11)	C9—C10—H10A	109.5
N1—C4—C5	121.69 (11)	C9—C10—H10B	109.5
C3—C4—C5	129.45 (11)	H10A—C10—H10B	109.5
C8—C7—C6	116.02 (11)	C9—C10—H10C	109.5
C8—C7—H7A	108.3	H10A—C10—H10C	109.5
C6—C7—H7A	108.3	H10B—C10—H10C	109.5
C8—C7—H7B	108.3	N2—C6—C7	113.08 (11)
C6—C7—H7B	108.3	N2—C6—H6A	109.0
H7A—C7—H7B	107.4	C7—C6—H6A	109.0
C4—C3—C2	107.08 (11)	N2—C6—H6B	109.0
C4—C3—C8	128.93 (11)	C7—C6—H6B	109.0
C2—C3—C8	123.99 (12)	H6A—C6—H6B	107.8

C6—N2—C5—O1	−179.77 (11)	C5—C4—C3—C8	13.5 (2)
C6—N2—C5—C4	−1.61 (17)	C4—C3—C8—O2	−163.02 (12)
C4—N1—C1—C2	−1.80 (14)	C2—C3—C8—O2	17.16 (19)
C9—N1—C1—C2	−176.11 (11)	C4—C3—C8—C7	18.71 (19)
C1—N1—C4—C3	0.68 (13)	C2—C3—C8—C7	−161.10 (12)
C9—N1—C4—C3	174.62 (11)	C6—C7—C8—O2	−162.98 (12)
C1—N1—C4—C5	169.12 (11)	C6—C7—C8—C3	15.32 (17)
C9—N1—C4—C5	−16.93 (18)	N1—C1—C2—C3	2.15 (14)
O1—C5—C4—N1	−30.73 (17)	C4—C3—C2—C1	−1.71 (14)
N2—C5—C4—N1	151.09 (11)	C8—C3—C2—C1	178.14 (11)
O1—C5—C4—C3	134.95 (14)	C4—N1—C9—C10	114.79 (14)
N2—C5—C4—C3	−43.23 (18)	C1—N1—C9—C10	−72.04 (15)
N1—C4—C3—C2	0.63 (13)	C5—N2—C6—C7	69.94 (16)
C5—C4—C3—C2	−166.62 (12)	C8—C7—C6—N2	−72.98 (15)
N1—C4—C3—C8	−179.21 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1ⁱ	0.88	2.12	2.9043 (14)	148

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Experimental details

Crystal data
Chemical formula	C₁₀H₁₂N₂O₂
M_r	192.22
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	173
a, b, c (Å)	11.703 (2), 7.7863 (13), 11.0004 (19)
β (°)	113.878 (3)
V (Å³)	916.6 (3)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.10
Crystal size (mm)	0.46 × 0.45 × 0.30

Data collection
Diffractometer	Bruker SMART 1K CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Sheldrick, 1996)
T_min, T_max	0.956, 0.971
No. of measured, independent and observed [I > 2σ(I)] reflections	4523, 1984, 1661
R_int	0.021
(sin θ/λ)_max (Å⁻¹)	0.639

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.037, 0.104, 1.07
No. of reflections	1984
No. of parameters	128
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.21

Computer programs: SMART (Bruker,1999), SAINT-Plus (Bruker, 1999), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2A···O1ⁱ	0.88	2.12	2.9043 (14)	148.4

Symmetry code: (i) −x+1, y+1/2, −z+1/2.

Acknowledgements

We thank the Natural Science Foundation of Guangdong Province, China (No. 06300581) for generously supporting this study.

References

Banwell, M. G., Hamel, E., Hockless, D. C. R., Verdier-Pinard, P., Willis, A. C. & Wong, D. J. (2006). Bioorg. Med. Chem. 14, 4627–4638. Web of Science CrossRef PubMed CAS Google Scholar
Bruker (1999). SMART and SAINT-Plus. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Liu, J. F., Guo, S. P. & Jiang, B. (2005). Chin. J. Org. Chem. 25, 788–799. CAS Google Scholar
Sheldrick, G. M. (1996). SADABS. University of Göttingen, Germany. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sosa, A. C. B., Yakushijin, K. & Horne, D. A. (2002). J. Org. Chem. 67, 4498–4500. Web of Science CrossRef PubMed CAS Google Scholar
Zeng, X.-C. (2006). Acta Cryst. E62, o5505–o5507. Web of Science CSD CrossRef IUCr Journals Google Scholar
Zeng, X.-C., Xu, S.-H., Gu, J. & Deng, D.-S. (2005). Acta Cryst. E61, o795–o796. Web of Science CSD CrossRef IUCr Journals Google Scholar