3-Ethyl 1-methyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxyl­ate

In the mol­ecular structure of the title compound, C₁₇H₁₅NO₄, the pyrrolo[2,1-a]isoquinoline unit is planar. The crystal structure is stabilized by weak intra- and inter­molecular C—H...O inter­actions, and also by π–π inter­actions with centroid–centroid distances of 3.5680–3.6683 Å.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.038
• wR factor = 0.101
• Data-to-parameter ratio = 18.0

checkCIF/PLATON results

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Alert level C
PLAT066_ALERT_1_C Predicted and Reported Transmissions Identical .          ?

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           37.50
           From the CIF: _reflns_number_total               3627
           Count of symmetry unique reflns         3627
           Completeness (_total/calc)            100.00%
           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
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          2

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
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   1 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
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S1. Comment

Indolizines are found in several naturally occurring alkaloids with important biological activities and are important synthetic targets (Saeva & Luss, 1988). As an extension of our research on the direct one-pot syntheses of indolizine derivatives (Liu et al., 2007), we have recently researched a general and versatile synthesis of indolizines and obtained the title compound, as one of the products. An x-ray crystallographic analysis was undertaken to elucidate its three-dimensional molecular and crystal structures.

The bond lengths and angles in the structure of the title compound (I) are within normal ranges (Allen et al., 1987), and comparable with those in related structures (Usman et al., 2002; Shen et al., 2006; Wang, 2006a; 2006b; Liu et al., 2007). In the title structure (Fig. 1), the pyrrolo[2,1-a]isoquinoline ring system [N1/C1–C12] is planar with the mean deviation of 0.006 (1) Å. The methoxycarbonyl group (O1/O2/C16/C17) is almost coplanar with the pyrrolo[2,1-a]isoquinoline ring. The plane of the methoxycarbonyl group is twisted about the C2—C16 bond by an angle of 8.00 (7)°. The ethoxycarbonyl group (O3/O4/C13–C15) is co-planarly attached at atom C12 of the pyrrole ring, as indicated by the torsion angles N1–C12–C13–O3 = -178.13 (10)° and C13–O3–C14–C15 = 179.39 (10)°. The planarity of the molecule is influenced by weak intramolecular C5—H5A···O2 and C11—H11A···O4 interactions (Fig. 1) which generate S(7) and S(6) ring motifs, respectively (Bernstein et al., 1995). The dihedral angle between the planes of two carboxylate groups is 8.33 (6)°.

In the crystal packing of (I) in Fig. 2, the molecules are arranged into molecular sheets parallel to the ac plane and these molecular sheets are stacked along the b axis. π···π interactions are also presented in the crystal with the distances of Cg₁···Cg₂ = 3.6683 (7) Å, Cg₁···Cg₃ = 3.5680 (7)Å and Cg₂···Cg₃ = 3.6514 (7)Å [symmetry codes; x, -1 + y, z and x, 1 + y, z for all π···π interactions]; Cg₁, Cg₂ and Cg₃ are the centroids of N1/C1–C3/C12, N1/C3–C4/C9–C11 and C4–C9 rings, respectively. The crystal is stabilized by weak intramolecular and intermolecular C—H···O interactions (Table 1) and further stabilized by π···π interactions.

Related literature

For reference values of bond lengths, see: Allen et al. (1987). For related literature on ring motifs, see: Bernstein et al. (1995). For examples of related structures, see: Usman et al. (2002); Shen et al. (2006); Wang (2006a,b); Liu et al. (2007). For related literature on indolizine derivatives and activities, see, for example: Basketter & Plunkett (1971); Saeva & Luss (1988); Tominaga et al. (1990); Gundersen et al. (2007).

S2. Experimental

A mixture of N-(carboxyethyl)quinolinium bromide (1 mmol), methyl acrylate (3 mmol), TPCD (1.6 mmol) and sodium carbonate (2.5 mmol) in DMF (15 ml) was heated at 363 K for 4 h with magnetic stirring. The title compound (I) was isolated by column chromatography of the reaction mixture on silica gel in 60% yield. Single crystals of the title compound in colorless block shape were obtained by slow evaporation of a solution in petroleum ether/ethyl acetate (3:1, V/V), m.p. 404–406 K. Compound (I) has been reported before. [Basketter & Plunkett (1971); Tominaga et al., (1990)]. However there is no x-ray structure published yet. We prepared (I) with the same starting materials as in Tominaga et al., 1990, but under different reaction conditions and with the better yield. The spectroscopic and analytical data of (I) was found to be the same as the published data (Tominaga et al., 1990).

S3. Refinement

All H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H distances in the range 0.93–0.97 Å. The U_iso values were constrained to be 1.5U_eq of the carrier atom for methyl H atoms and 1.2U_eq for the remaining H atoms. A rotating group model was used for the methyl groups. 3573 Friedel pairs were merged as there is no significant anomalous dispersion to determine the absolute structure. The highest residual peak is located 0.68 Å from O2 and the deepest hole is located 0.67 Å from O2.

Computing details

Data collection: APEX2 (Bruker, 2005); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 1998); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.

Figures

	Fig. 1. The asymmetric unit of (I), showing 50% probability displacement ellipsoids and the atomic numbering. Weak C—H···O intramolecular interactions were shown as dash lines.
	Fig. 2. The crystal packing of (I), viewed along the b axis. C—H···O weak interactions were shown as dash lines.

3-ethyl 1-methyl pyrrolo[2,1-a]isoquinoline-1,3-dicarboxylate

Crystal data

C17H15NO4	F(000) = 624
Mr = 297.30	Dx = 1.436 Mg m^−3
Monoclinic, Cc	Melting point = 404–406 K
Hall symbol: C -2yc	Mo Kα radiation, λ = 0.71073 Å
a = 20.5388 (4) Å	Cell parameters from 3627 reflections
b = 4.4550 (1) Å	θ = 2.2–37.5°
c = 16.5764 (5) Å	µ = 0.10 mm^−1
β = 114.955 (2)°	T = 100 K
V = 1375.14 (6) Å^3	Block, colourless
Z = 4	0.53 × 0.27 × 0.15 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer	3627 independent reflections
Radiation source: fine-focus sealed tube	3404 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.044
Detector resolution: 8.33 pixels mm^-1	θmax = 37.5°, θmin = 2.2°
ω scans	h = −34→34
Absorption correction: multi-scan (SADABS; Bruker, 2005)	k = −7→7
Tmin = 0.948, Tmax = 0.985	l = −28→28
23077 measured reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.038	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.101	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0691P)^2 + 0.0494P] where P = (Fo^2 + 2Fc^2)/3
3627 reflections	(Δ/σ)max < 0.001
201 parameters	Δρmax = 0.42 e Å^−3
2 restraints	Δρmin = −0.28 e Å^−3

Special details

Experimental. The data was collected with the Oxford Cyrosystem Cobra low-temperature attachment.

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.45336 (5)	−0.2384 (3)	0.04828 (6)	0.0244 (2)
O2	0.49888 (5)	0.0351 (4)	0.17187 (8)	0.0383 (3)
O3	0.19014 (4)	−0.5425 (2)	−0.07101 (6)	0.01815 (15)
O4	0.12973 (5)	−0.3018 (2)	−0.00418 (6)	0.02089 (16)
N1	0.26700 (5)	−0.0079 (2)	0.11014 (6)	0.01466 (15)
C1	0.31898 (5)	−0.2445 (2)	0.03391 (7)	0.01531 (16)
H1A	0.3262	−0.3652	−0.0074	0.018*
C2	0.37166 (5)	−0.0660 (3)	0.09913 (7)	0.01470 (16)
C3	0.33828 (5)	0.0848 (2)	0.14737 (7)	0.01413 (16)
C4	0.36033 (5)	0.2977 (3)	0.21988 (7)	0.01494 (16)
C5	0.43085 (6)	0.4134 (3)	0.26242 (7)	0.01794 (18)
H5A	0.4656	0.3528	0.2437	0.022*
C6	0.44863 (6)	0.6159 (3)	0.33164 (8)	0.0202 (2)
H6A	0.4953	0.6901	0.3588	0.024*
C7	0.39770 (7)	0.7114 (3)	0.36171 (8)	0.0213 (2)
H7A	0.4105	0.8472	0.4085	0.026*
C8	0.32840 (7)	0.6021 (3)	0.32128 (8)	0.0201 (2)
H8A	0.2944	0.6646	0.3411	0.024*
C9	0.30869 (6)	0.3964 (3)	0.25012 (7)	0.01647 (17)
C10	0.23655 (6)	0.2863 (3)	0.20788 (8)	0.01857 (18)
H10A	0.2028	0.3514	0.2277	0.022*
C11	0.21679 (6)	0.0901 (3)	0.13991 (8)	0.01766 (18)
H11A	0.1697	0.0206	0.1130	0.021*
C12	0.25490 (5)	−0.2107 (2)	0.04127 (7)	0.01502 (17)
C13	0.18567 (5)	−0.3499 (3)	−0.01099 (7)	0.01573 (17)
C14	0.12267 (6)	−0.6880 (3)	−0.12763 (8)	0.01850 (18)
H14A	0.0869	−0.5390	−0.1607	0.022*
H14B	0.1047	−0.8042	−0.0918	0.022*
C15	0.13787 (7)	−0.8902 (3)	−0.19044 (8)	0.0207 (2)
H15A	0.0969	−1.0153	−0.2220	0.031*
H15B	0.1788	−1.0139	−0.1572	0.031*
H15C	0.1477	−0.7704	−0.2322	0.031*
C16	0.44691 (6)	−0.0746 (3)	0.11232 (7)	0.01717 (18)
C17	0.52569 (7)	−0.2785 (4)	0.05696 (9)	0.0269 (3)
H17A	0.5248	−0.3920	0.0073	0.040*
H17B	0.5534	−0.3843	0.1111	0.040*
H17C	0.5471	−0.0859	0.0583	0.040*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0118 (3)	0.0404 (6)	0.0210 (4)	−0.0009 (3)	0.0068 (3)	−0.0103 (4)
O2	0.0145 (4)	0.0634 (9)	0.0361 (6)	−0.0096 (4)	0.0099 (4)	−0.0281 (6)
O3	0.0124 (3)	0.0199 (4)	0.0192 (3)	−0.0015 (3)	0.0037 (2)	−0.0022 (3)
O4	0.0123 (3)	0.0260 (4)	0.0239 (4)	−0.0014 (3)	0.0072 (3)	−0.0017 (3)
N1	0.0110 (3)	0.0175 (4)	0.0152 (3)	0.0005 (3)	0.0052 (3)	0.0006 (3)
C1	0.0116 (3)	0.0187 (4)	0.0144 (4)	−0.0003 (3)	0.0043 (3)	0.0001 (3)
C2	0.0111 (3)	0.0183 (4)	0.0137 (4)	−0.0006 (3)	0.0043 (3)	−0.0002 (3)
C3	0.0116 (3)	0.0161 (4)	0.0142 (4)	0.0006 (3)	0.0049 (3)	0.0014 (3)
C4	0.0136 (4)	0.0162 (4)	0.0138 (4)	0.0006 (3)	0.0047 (3)	0.0005 (3)
C5	0.0157 (4)	0.0196 (5)	0.0164 (4)	−0.0008 (3)	0.0048 (3)	−0.0006 (3)
C6	0.0186 (4)	0.0216 (5)	0.0162 (4)	−0.0012 (4)	0.0034 (3)	−0.0018 (3)
C7	0.0240 (5)	0.0215 (5)	0.0161 (4)	0.0015 (4)	0.0062 (4)	−0.0016 (4)
C8	0.0223 (5)	0.0204 (5)	0.0173 (4)	0.0028 (4)	0.0081 (4)	0.0001 (3)
C9	0.0168 (4)	0.0169 (4)	0.0158 (4)	0.0016 (3)	0.0070 (3)	0.0015 (3)
C10	0.0162 (4)	0.0202 (5)	0.0209 (4)	0.0016 (3)	0.0094 (4)	−0.0004 (4)
C11	0.0136 (4)	0.0202 (5)	0.0204 (5)	0.0011 (3)	0.0084 (3)	0.0001 (3)
C12	0.0111 (3)	0.0175 (4)	0.0149 (4)	−0.0004 (3)	0.0040 (3)	0.0003 (3)
C13	0.0124 (4)	0.0169 (4)	0.0157 (4)	0.0001 (3)	0.0038 (3)	0.0018 (3)
C14	0.0133 (4)	0.0192 (5)	0.0194 (4)	−0.0029 (3)	0.0033 (3)	−0.0013 (3)
C15	0.0199 (4)	0.0212 (5)	0.0189 (5)	−0.0027 (4)	0.0062 (4)	−0.0011 (4)
C16	0.0120 (3)	0.0241 (5)	0.0152 (4)	−0.0010 (3)	0.0056 (3)	−0.0017 (3)
C17	0.0137 (4)	0.0451 (8)	0.0230 (5)	0.0001 (4)	0.0089 (4)	−0.0068 (5)

Geometric parameters (Å, º)

O1—C16	1.3401 (14)	C6—H6A	0.9300
O1—C17	1.4419 (14)	C7—C8	1.3810 (18)
O2—C16	1.2097 (14)	C7—H7A	0.9300
O3—C13	1.3458 (14)	C8—C9	1.4114 (16)
O3—C14	1.4574 (13)	C8—H8A	0.9300
O4—C13	1.2199 (13)	C9—C10	1.4322 (16)
N1—C11	1.3882 (14)	C10—C11	1.3462 (17)
N1—C3	1.3900 (13)	C10—H10A	0.9300
N1—C12	1.3935 (14)	C11—H11A	0.9300
C1—C12	1.3803 (14)	C12—C13	1.4551 (15)
C1—C2	1.4088 (15)	C14—C15	1.5058 (17)
C1—H1A	0.9300	C14—H14A	0.9700
C2—C3	1.4224 (15)	C14—H14B	0.9700
C2—C16	1.4673 (14)	C15—H15A	0.9600
C3—C4	1.4457 (15)	C15—H15B	0.9600
C4—C5	1.4137 (15)	C15—H15C	0.9600
C4—C9	1.4207 (15)	C17—H17A	0.9600
C5—C6	1.3819 (16)	C17—H17B	0.9600
C5—H5A	0.9300	C17—H17C	0.9600
C6—C7	1.4014 (18)
C16—O1—C17	115.50 (9)	C11—C10—H10A	119.5
C13—O3—C14	114.63 (9)	C9—C10—H10A	119.5
C11—N1—C3	123.35 (9)	C10—C11—N1	119.67 (10)
C11—N1—C12	126.35 (9)	C10—C11—H11A	120.2
C3—N1—C12	110.29 (8)	N1—C11—H11A	120.2
C12—C1—C2	108.84 (10)	C1—C12—N1	107.21 (9)
C12—C1—H1A	125.6	C1—C12—C13	129.03 (10)
C2—C1—H1A	125.6	N1—C12—C13	123.76 (9)
C1—C2—C3	107.56 (9)	O4—C13—O3	122.75 (10)
C1—C2—C16	121.27 (10)	O4—C13—C12	126.30 (11)
C3—C2—C16	130.99 (10)	O3—C13—C12	110.94 (9)
N1—C3—C2	106.09 (9)	O3—C14—C15	107.05 (9)
N1—C3—C4	117.78 (9)	O3—C14—H14A	110.3
C2—C3—C4	136.13 (9)	C15—C14—H14A	110.3
C5—C4—C9	118.12 (10)	O3—C14—H14B	110.3
C5—C4—C3	123.35 (10)	C15—C14—H14B	110.3
C9—C4—C3	118.53 (9)	H14A—C14—H14B	108.6
C6—C5—C4	120.56 (11)	C14—C15—H15A	109.5
C6—C5—H5A	119.7	C14—C15—H15B	109.5
C4—C5—H5A	119.7	H15A—C15—H15B	109.5
C5—C6—C7	121.20 (11)	C14—C15—H15C	109.5
C5—C6—H6A	119.4	H15A—C15—H15C	109.5
C7—C6—H6A	119.4	H15B—C15—H15C	109.5
C8—C7—C6	119.44 (11)	O2—C16—O1	121.21 (10)
C8—C7—H7A	120.3	O2—C16—C2	128.49 (11)
C6—C7—H7A	120.3	O1—C16—C2	110.26 (9)
C7—C8—C9	120.53 (11)	O1—C17—H17A	109.5
C7—C8—H8A	119.7	O1—C17—H17B	109.5
C9—C8—H8A	119.7	H17A—C17—H17B	109.5
C8—C9—C4	120.15 (10)	O1—C17—H17C	109.5
C8—C9—C10	120.25 (10)	H17A—C17—H17C	109.5
C4—C9—C10	119.60 (10)	H17B—C17—H17C	109.5
C11—C10—C9	121.06 (10)
C12—C1—C2—C3	−0.68 (12)	C8—C9—C10—C11	179.98 (11)
C12—C1—C2—C16	174.97 (10)	C4—C9—C10—C11	0.09 (17)
C11—N1—C3—C2	179.63 (10)	C9—C10—C11—N1	0.08 (17)
C12—N1—C3—C2	0.30 (11)	C3—N1—C11—C10	0.38 (17)
C11—N1—C3—C4	−0.95 (15)	C12—N1—C11—C10	179.60 (11)
C12—N1—C3—C4	179.72 (9)	C2—C1—C12—N1	0.86 (12)
C1—C2—C3—N1	0.23 (12)	C2—C1—C12—C13	−179.75 (10)
C16—C2—C3—N1	−174.85 (11)	C11—N1—C12—C1	179.97 (10)
C1—C2—C3—C4	−179.03 (12)	C3—N1—C12—C1	−0.72 (12)
C16—C2—C3—C4	5.9 (2)	C11—N1—C12—C13	0.54 (17)
N1—C3—C4—C5	−178.91 (10)	C3—N1—C12—C13	179.84 (9)
C2—C3—C4—C5	0.29 (19)	C14—O3—C13—O4	0.30 (15)
N1—C3—C4—C9	1.06 (14)	C14—O3—C13—C12	−178.83 (9)
C2—C3—C4—C9	−179.74 (11)	C1—C12—C13—O4	−176.52 (12)
C9—C4—C5—C6	0.23 (16)	N1—C12—C13—O4	2.79 (18)
C3—C4—C5—C6	−179.79 (11)	C1—C12—C13—O3	2.57 (16)
C4—C5—C6—C7	0.17 (18)	N1—C12—C13—O3	−178.13 (10)
C5—C6—C7—C8	−0.23 (19)	C13—O3—C14—C15	179.39 (10)
C6—C7—C8—C9	−0.12 (18)	C17—O1—C16—O2	1.39 (19)
C7—C8—C9—C4	0.53 (17)	C17—O1—C16—C2	−176.48 (12)
C7—C8—C9—C10	−179.36 (11)	C1—C2—C16—O2	−169.91 (15)
C5—C4—C9—C8	−0.57 (15)	C3—C2—C16—O2	4.6 (2)
C3—C4—C9—C8	179.45 (10)	C1—C2—C16—O1	7.77 (15)
C5—C4—C9—C10	179.32 (10)	C3—C2—C16—O1	−177.72 (11)
C3—C4—C9—C10	−0.66 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C5—H5A···O2	0.93	2.14	2.9691 (19)	148
C11—H11A···O4	0.93	2.27	2.8891 (16)	123
C14—H14A···O2^i	0.97	2.60	3.2930 (17)	129
C14—H14B···O4^ii	0.97	2.58	3.3817 (16)	140

Symmetry codes: (i) x−1/2, −y−1/2, z−1/2; (ii) x, y−1, z.