6-(2-Hydro­xy­benzoyl)-5-(pyrrol-2-yl)-3H-pyrrolizine

The title compound, 2-hydroxy­phenyl 5-(pyrrol-2-yl)-3H-pyrrolizin-6-yl ketone, C₁₈H₁₄N₂O₂, was isolated from the base-catalyzed 1:2 condensation of 2-hydroxy­aceto­phenone with pyrrole-2-carbaldehyde. The pyrrole N-H and hydroxy­benzoyl O-H groups are hydrogen bonded to the benzoyl O atom. The allyl­ic C=C double bond of the 3H-pyrrolizine system is located between ring positions 1 and 2, the C atom at position 3 (adjacent to the N atom) being single bonded.

S1. Comment

The base-catalyzed Claisen–Schmidt reaction between equimolar quantities of 2-hydroxyacetophenone and benzaldehyde is among the most common synthetic routes to 2-hydroxychalcone, a compound that is useful in the synthesis of flavonoid compounds (Geissman, 1962; Harborne et al., 1975; Mallik et al., 1989, 1992). It has also been found that base-catalyzed 1:2 condensations between 2-hydroxyacetophenones and p-nitrobenzaldehyde in aqueous methanol gave trans-2,3-dimethoxy-3-(p-formylphenylamino)-4'-nitroflavanones as interesting novel products (Mallik et al., 1992). This encouraged us to study similar 1:2 condensations between phenyl methyl ketones and pyrrole-2-aldehyde, from which we obtained mixtures containing the usual (E)-1-acyl-3-(pyrrol-2-yl)-2-propen-1-ones together with 6-acyl-5-(pyrrol-2-yl)-3H-pyrrolizines as unexpected novel products (Mallik et al., 2002). Pyrrolizines and their derivatives are of condsiderable interest in view of both their occurrence as natural products and their potential biological activities.

Although the basic structural features of the new compounds could be established by detailed NMR studies (Mallik et al., 2002), there remained some ambiguity with respect to the exact position of the allylic C═C double bond in the 3H-pyrrolizine system, for which there exist two conceivable alternatives: either between ring positions 1 and 2 or between the C atoms located at sites 2 and 3 (Jones, 1984). The X-ray structure analysis carried out for the 1:2 condensation product (I), formed from 2-hydroxyacetophenone and pyrrole-2-aldehyde, showed the allylic C═C bond to be located between atoms C1 and C2 [1.327 (3) Å], atoms C2 and C3 of the 3H-pyrrolizine system being connected by a single bond [1.493 (3) Å]. The interatomic distances within the C≐N≐C units of the unsaturated bis(pyrrolyl) part of the 5-(pyrrol-2-yl)-3H-pyrrolizine moiety, viz. C4—N1—C7 and C8—N2—C11, span the relatively small range 1.351 (3)–1.380(2 Å, which is about 0.14 Å longer than calculated for a C═N double bond but ~0.10 Å shorter than the value of 1.459 (2) Å determined for the C—N single bond between C3 and N1. The substantial degree of π-electron delocalization evidenced from these bond lengths is also mirrored by the C—C distances within the two unsaturated five-membered rings, amounting to 1.422 (3), 1.432 (3) and 1.357 (3) Å for C4≐C5≐C6≐C7 and to 1.381 (3), 1.397 (3) and 1.360 (3) Å for C8≐C9≐C10≐C11, respectively (Table 1).

The formation of two intramolecular hydrogen bonds, O1)—H1···O2 and N2—H2···O2 (Table 2) results in a slightly skewed overall geometry of (I), which is best described by the torsion angles given in Table 1 or by the angles 〈 (1–2) = 5.42 (11)°, 〈 (1–3) = 46.15 (5)°, and 〈 (2–3) = 46.52 (7)°, between the least-squares planes through the 3H-pyrrolizine system (1), the pyrrole ring (2), and the o-hydroxybenzoyl building block (3).

S2. Experimental

20% aqueous ethanolic KOH (10 ml) was added dropwise to a mixture of 2-hydroxyacetophenone (1 mmol) and pyrrole-2-aldehyde (2 mmol) in ethanol (10 ml). After 4 d under ambient conditions, the mixture was diluted with water (20 ml), carefully acidified by dropwise addition of 1 M HCl at 278 K, and subsequently extracted with chloroform. Concentration of the chloroform extract followed by chromatography of the concentrate over silica gel allowed the red condensation product (I) to be separated from orange (E)-1-(2-hydroxyphenyl)-3-(pyrrol-2-yl)-2-propen-1-one, resulting from a usual 1:1 Claisen–Schmidt condensation reaction (Mallik et al., 2002). Single crystals were grown by slow evaporation of a chloroform–petroleum solvent mixture.

S3. Refinement

With the exception of the hydroxy O—H and pyrrole N—H atoms H1 and H2, which were allowed to refine freely, all H atoms were refined in geometrically idealized positions employing a riding model with isotropic displacement parameters constrained to 1.2 times U_eq of their respective carrier atoms.

Computing details

Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1994); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

Fig. 1. View of (I), with ellipsoids at the 50% probability level.

(I)

Crystal data

C18H14N2O2	F(000) = 608
Mr = 290.31	Dx = 1.37 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 25 reflections
a = 8.6868 (7) Å	θ = 8.4–12.7°
b = 22.0328 (13) Å	µ = 0.09 mm^−1
c = 7.592 (3) Å	T = 293 K
β = 104.407 (16)°	Block, red
V = 1407.4 (6) Å^3	0.4 × 0.15 × 0.15 mm
Z = 4

Data collection

Nonius MACH3 diffractometer	θmax = 25.2°, θmin = 2.4°
non–profiled ω scans	h = −10→0
2666 measured reflections	k = −26→0
2499 independent reflections	l = −8→9
1796 reflections with I > 2σ(I)	3 standard reflections every 60 min
Rint = 0.022	intensity decay: 1%

Refinement

Refinement on F^2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ^2(Fo^2) + (0.0518P)^2 + 0.2924P] where P = (Fo^2 + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.043	(Δ/σ)max < 0.001
wR(F^2) = 0.113	Δρmax = 0.15 e Å^−3
S = 1.03	Δρmin = −0.15 e Å^−3
2499 reflections	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
208 parameters	Extinction coefficient: 0.0134 (19)
0 restraints

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.2536 (2)	0.50797 (7)	0.7283 (2)	0.0690 (5)
H1	0.161 (3)	0.5270 (12)	0.647 (4)	0.091 (9)*
O2	0.07854 (17)	0.58247 (6)	0.5012 (2)	0.0661 (5)
N1	0.06924 (18)	0.77490 (7)	0.4304 (2)	0.0422 (4)
N2	−0.1586 (2)	0.63674 (8)	0.2532 (2)	0.0499 (4)
H2	−0.095 (3)	0.6067 (10)	0.316 (3)	0.071 (7)*
C1	0.2415 (3)	0.84817 (9)	0.5684 (3)	0.0533 (5)
H1A	0.3316	0.8669	0.6397	0.064*
C2	0.1133 (3)	0.87640 (9)	0.4716 (3)	0.0561 (6)
H2A	0.1012	0.9183	0.4662	0.067*
C3	−0.0092 (2)	0.83267 (8)	0.3725 (3)	0.0479 (5)
H3A	−0.1078	0.8365	0.4096	0.058*
H3B	−0.0303	0.8379	0.2418	0.058*
C4	0.0345 (2)	0.71511 (8)	0.4028 (3)	0.0404 (4)
C5	0.1710 (2)	0.68353 (8)	0.5034 (3)	0.0429 (5)
C6	0.2843 (2)	0.72810 (9)	0.5914 (3)	0.0468 (5)
H6	0.3845	0.7205	0.6665	0.056*
C7	0.2181 (2)	0.78346 (8)	0.5448 (3)	0.0450 (5)
C8	−0.1146 (2)	0.69644 (8)	0.2830 (3)	0.0418 (5)
C9	−0.2356 (2)	0.73019 (9)	0.1742 (3)	0.0520 (5)
H9	−0.2395	0.7723	0.1656	0.062*
C10	−0.3511 (2)	0.68993 (10)	0.0794 (3)	0.0563 (6)
H10	−0.4453	0.7004	−0.0038	0.068*
C11	−0.3007 (2)	0.63267 (10)	0.1309 (3)	0.0574 (6)
H11	−0.3547	0.597	0.0891	0.069*
C12	0.3772 (3)	0.53855 (9)	0.6903 (3)	0.0531 (5)
C13	0.5280 (3)	0.51433 (10)	0.7530 (3)	0.0656 (7)
H13	0.5428	0.4798	0.8258	0.079*
C14	0.6553 (3)	0.54105 (11)	0.7084 (4)	0.0702 (7)
H14	0.7559	0.5241	0.7496	0.084*
C15	0.6363 (3)	0.59277 (11)	0.6029 (3)	0.0622 (6)
H15	0.7228	0.6099	0.5696	0.075*
C16	0.4879 (2)	0.61888 (9)	0.5472 (3)	0.0527 (5)
H16	0.4756	0.6543	0.4785	0.063*
C17	0.3557 (2)	0.59318 (9)	0.5919 (3)	0.0469 (5)
C18	0.1938 (2)	0.61877 (9)	0.5279 (3)	0.0482 (5)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0723 (11)	0.0491 (9)	0.0871 (12)	0.0096 (8)	0.0226 (10)	0.0193 (8)
O2	0.0513 (9)	0.0455 (8)	0.0948 (12)	−0.0042 (7)	0.0058 (8)	0.0167 (8)
N1	0.0416 (9)	0.0385 (9)	0.0475 (9)	0.0015 (7)	0.0127 (7)	0.0011 (7)
N2	0.0442 (10)	0.0449 (10)	0.0591 (11)	−0.0044 (8)	0.0104 (8)	0.0034 (9)
C1	0.0545 (13)	0.0473 (12)	0.0582 (13)	−0.0072 (10)	0.0142 (10)	−0.0064 (10)
C2	0.0646 (14)	0.0378 (11)	0.0673 (14)	−0.0023 (10)	0.0190 (12)	−0.0009 (10)
C3	0.0506 (12)	0.0406 (11)	0.0553 (12)	0.0071 (9)	0.0183 (10)	0.0054 (9)
C4	0.0419 (10)	0.0378 (10)	0.0444 (11)	−0.0008 (8)	0.0161 (8)	0.0013 (8)
C5	0.0420 (10)	0.0414 (11)	0.0455 (11)	0.0007 (8)	0.0113 (9)	0.0026 (8)
C6	0.0424 (11)	0.0473 (11)	0.0478 (11)	0.0017 (9)	0.0060 (9)	0.0035 (9)
C7	0.0439 (11)	0.0450 (11)	0.0463 (11)	−0.0040 (9)	0.0115 (9)	−0.0023 (9)
C8	0.0399 (10)	0.0419 (10)	0.0461 (11)	0.0002 (8)	0.0153 (9)	−0.0004 (9)
C9	0.0468 (12)	0.0464 (11)	0.0611 (13)	0.0041 (10)	0.0104 (10)	0.0009 (10)
C10	0.0403 (11)	0.0655 (14)	0.0598 (13)	−0.0003 (10)	0.0060 (10)	0.0012 (11)
C11	0.0458 (12)	0.0579 (14)	0.0670 (14)	−0.0125 (10)	0.0110 (11)	−0.0025 (11)
C12	0.0605 (13)	0.0419 (11)	0.0560 (13)	0.0055 (10)	0.0128 (11)	−0.0022 (10)
C13	0.0672 (15)	0.0509 (14)	0.0707 (15)	0.0159 (11)	0.0021 (12)	−0.0008 (11)
C14	0.0555 (14)	0.0653 (15)	0.0797 (17)	0.0151 (12)	−0.0022 (13)	−0.0176 (13)
C15	0.0506 (13)	0.0636 (15)	0.0706 (15)	−0.0013 (11)	0.0114 (11)	−0.0209 (12)
C16	0.0540 (12)	0.0503 (12)	0.0525 (12)	−0.0013 (10)	0.0106 (10)	−0.0080 (10)
C17	0.0504 (12)	0.0408 (11)	0.0478 (12)	0.0039 (9)	0.0088 (9)	−0.0032 (9)
C18	0.0489 (12)	0.0442 (11)	0.0511 (12)	0.0008 (10)	0.0118 (9)	0.0030 (9)

Geometric parameters (Å, º)

O1—C12	1.358 (3)	C6—C7	1.357 (3)
O1—H1	0.98 (3)	C6—H6	0.93
O2—C18	1.258 (2)	C8—C9	1.381 (3)
N1—C4	1.356 (2)	C9—C10	1.397 (3)
N1—C7	1.380 (2)	C9—H9	0.93
N1—C3	1.459 (2)	C10—C11	1.360 (3)
N2—C11	1.351 (3)	C10—H10	0.93
N2—C8	1.373 (2)	C11—H11	0.93
N2—H2	0.91 (2)	C12—C13	1.385 (3)
C1—C2	1.327 (3)	C12—C17	1.404 (3)
C1—C7	1.445 (3)	C13—C14	1.368 (3)
C1—H1A	0.93	C13—H13	0.93
C2—C3	1.493 (3)	C14—C15	1.379 (3)
C2—H2A	0.93	C14—H14	0.93
C3—H3A	0.97	C15—C16	1.378 (3)
C3—H3B	0.97	C15—H15	0.93
C4—C5	1.422 (3)	C16—C17	1.396 (3)
C4—C8	1.445 (3)	C16—H16	0.93
C5—C6	1.432 (3)	C17—C18	1.481 (3)
C5—C18	1.446 (3)
C12—O1—H1	102.9 (15)	N2—C8—C4	123.06 (17)
C4—N1—C7	111.59 (15)	C9—C8—C4	130.74 (18)
C4—N1—C3	137.01 (16)	C8—C9—C10	107.96 (18)
C7—N1—C3	111.40 (15)	C8—C9—H9	126
C11—N2—C8	110.24 (18)	C10—C9—H9	126
C11—N2—H2	129.6 (15)	C11—C10—C9	107.59 (19)
C8—N2—H2	120.1 (14)	C11—C10—H10	126.2
C2—C1—C7	108.72 (19)	C9—C10—H10	126.2
C2—C1—H1A	125.6	N2—C11—C10	108.04 (19)
C7—C1—H1A	125.6	N2—C11—H11	126
C1—C2—C3	111.82 (18)	C10—C11—H11	126
C1—C2—H2A	124.1	O1—C12—C13	117.8 (2)
C3—C2—H2A	124.1	O1—C12—C17	122.03 (18)
N1—C3—C2	100.95 (16)	C13—C12—C17	120.2 (2)
N1—C3—H3A	111.6	C14—C13—C12	120.2 (2)
C2—C3—H3A	111.6	C14—C13—H13	119.9
N1—C3—H3B	111.6	C12—C13—H13	119.9
C2—C3—H3B	111.6	C13—C14—C15	120.8 (2)
H3A—C3—H3B	109.4	C13—C14—H14	119.6
N1—C4—C5	105.56 (16)	C15—C14—H14	119.6
N1—C4—C8	120.28 (16)	C16—C15—C14	119.4 (2)
C5—C4—C8	134.09 (17)	C16—C15—H15	120.3
C4—C5—C6	107.42 (16)	C14—C15—H15	120.3
C4—C5—C18	128.38 (17)	C15—C16—C17	121.3 (2)
C6—C5—C18	124.08 (17)	C15—C16—H16	119.4
C7—C6—C5	107.30 (17)	C17—C16—H16	119.4
C7—C6—H6	126.3	C16—C17—C12	117.93 (19)
C5—C6—H6	126.3	C16—C17—C18	122.51 (18)
C6—C7—N1	108.12 (16)	C12—C17—C18	119.40 (18)
C6—C7—C1	144.8 (2)	O2—C18—C5	121.90 (18)
N1—C7—C1	107.09 (17)	O2—C18—C17	117.63 (17)
N2—C8—C9	106.17 (17)	C5—C18—C17	120.43 (17)
C7—C1—C2—C3	−0.2 (2)	N1—C4—C8—C9	4.2 (3)
C4—N1—C3—C2	178.4 (2)	C5—C4—C8—C9	−172.1 (2)
C7—N1—C3—C2	−1.0 (2)	N2—C8—C9—C10	−0.2 (2)
C1—C2—C3—N1	0.7 (2)	C4—C8—C9—C10	177.63 (19)
C7—N1—C4—C5	−1.1 (2)	C8—C9—C10—C11	0.2 (2)
C3—N1—C4—C5	179.5 (2)	C8—N2—C11—C10	0.0 (2)
C7—N1—C4—C8	−178.35 (16)	C9—C10—C11—N2	−0.1 (2)
C3—N1—C4—C8	2.2 (3)	O1—C12—C13—C14	175.6 (2)
N1—C4—C5—C6	0.7 (2)	C17—C12—C13—C14	−4.8 (3)
C8—C4—C5—C6	177.45 (19)	C12—C13—C14—C15	0.9 (4)
N1—C4—C5—C18	176.70 (19)	C13—C14—C15—C16	2.2 (3)
C8—C4—C5—C18	−6.6 (3)	C14—C15—C16—C17	−1.5 (3)
C4—C5—C6—C7	−0.1 (2)	C15—C16—C17—C12	−2.2 (3)
C18—C5—C6—C7	−176.33 (19)	C15—C16—C17—C18	−177.46 (19)
C5—C6—C7—N1	−0.5 (2)	O1—C12—C17—C16	−175.09 (18)
C5—C6—C7—C1	178.9 (3)	C13—C12—C17—C16	5.3 (3)
C4—N1—C7—C6	1.0 (2)	O1—C12—C17—C18	0.3 (3)
C3—N1—C7—C6	−179.39 (16)	C13—C12—C17—C18	−179.26 (19)
C4—N1—C7—C1	−178.63 (16)	C4—C5—C18—O2	−19.5 (3)
C3—N1—C7—C1	1.0 (2)	C6—C5—C18—O2	155.9 (2)
C2—C1—C7—C6	−179.9 (3)	C4—C5—C18—C17	162.63 (19)
C2—C1—C7—N1	−0.5 (2)	C6—C5—C18—C17	−22.0 (3)
C11—N2—C8—C9	0.1 (2)	C16—C17—C18—O2	148.9 (2)
C11—N2—C8—C4	−177.92 (18)	C12—C17—C18—O2	−26.3 (3)
N1—C4—C8—N2	−178.23 (17)	C16—C17—C18—C5	−33.1 (3)
C5—C4—C8—N2	5.4 (3)	C12—C17—C18—C5	151.64 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···O2	0.98 (3)	1.68 (3)	2.584 (2)	151 (2)
N2—H2···O2	0.91 (2)	1.87 (2)	2.699 (2)	150 (2)