Ethyl 2-amino-1-(4-fluorophenyl)-5-oxo-4,5-dihydro-1H-pyrrole-3-carboxylate: crystal structure and Hirshfeld surface analysis

In the title molecule, the central pyrrole ring makes dihedral angles of 9.2 (3) and 67.6 (2)°, respectively, with the ethoxy carbonyl moiety and the fluorophenyl ring. Supramolecular aggregation is due to off-centric π–π stacking interactions involving screw-related pairs of molecules, which are further connected by N—H⋯O and C—H⋯O interactions, forming a sinusoidal pattern


Chemical context
Pyrrole, an electron-rich five-membered unsaturated ring, and its derivatives are widely used as intermediates in the synthesis of organic compounds, medicines, pharmaceuticals, agrochemicals, perfumes etc. Its derivatives possess a broad spectrum of biological activities. Substitution by a halogen (Cl, Br, F, I) is known to increase the activities of drug molecules and this group of molecules interact with receptors via halogen bonding. Organofluorine compounds display a variety of pharmacological and agro-chemical properties. Specific halogen-bonding interactions are responsible for the supramolecular architecture in halogen-substituted heterocycles. Bearing in mind the importance of pyrrole and the role of halogens, we have synthesized a series of halogen-substituted pyrrole derivatives. Bromo and methoxy derivatives of the title molecule have been reported earlier (Patel et al., 2012(Patel et al., , 2013. As a continuation of these studies, the title molecule, with fluorine as one of the substituents, was synthesized and characterized crystallographically and by Hirshfeld surface analysis.

Structural commentary
In the title compound, Fig. 1, the F atom is displaced by 0.014 (3) Å from the phenyl ring, facilitating it in to take part in a number of intermolecular interactions. The heterocyclic five-membered pyrrole ring is essentially planar with a maximum displacement of 0.022 (4) Å for atom C3 from its mean plane. The fluorophenyl ring forms a dihedral angle of 67.6 (2) whereas the mean plane of ethoxy carbonyl tail is inclined at 9.2 (3) to the central pyrrole ring. The terminal ethoxy carbonyl chain adopts a zigzag extended conformation, as is usually observed in analogous derivatives, with the carbonyl oxygen atom O19 on the same side as the methyl carbon atom C17 [C17-O16-C15-O19 = 5.0 (7) ] and the ethoxy carbon atom C18 in a trans [C15-O16-C17-C18 = 144.6 (5) ] conformation with respect to the pyrrole ring. Bond lengths in the phenyl ring vary from 1.365 (6) to 1.385 (6) Å and the endocyclic angle varies from 118.0 (4) to 122.9 (4) with an average value of 120.4 (4) , which coincides exactly with the theoretical value 120 for sp 2 hybridization.
The intramolecular N6-H61Á Á ÁO19 hydrogen bond involving the carbonyl oxygen atom O19 leads to the formation of a pseudo-six-membered ring with an S(6) graph-set motif.

Figure 1
ORTEP view of the title molecule with the atom-labelling scheme and displacement ellipsoids drawn at the 50% probability level.

Analysis of the Hirshfeld Surfaces
Crystal Explorer 3.1 (Wolff et al., 2012) was used to generate Hirshfeld surfaces mapped over d norm , d e and electrostatic potential for the title compound. The electrostatic potentials were calculated using TONTO (Spackman et al., 2008;Jayatilaka et al., 2005) as integrated in Crystal Explorer and are mapped on Hirshfeld surfaces using the STO-3G basis set at the Hartree-Fock level of theory over a range AE0.10 au as shown in Fig. 3. The positive electrostatic potential (blue region) over the surface indicates a hydrogen-bond donor, whereas the hydrogen-bond acceptors are represented by negative electrostatic potential (red region). The contact distances d i and d e from the Hirshfeld surface to the nearest atom inside and outside, respectively, enables the analysis of the intermolecular interactions through the mapping of d norm .

Synthesis and crystallization
In a 50 ml flat-bottom flask, a mixture of dry toluene (15 ml), potassium hydroxide (0.012 mol, 0.672 g) and 18-crown-6 (0.0005 mol, 0.132 g) were prepared. Ethyl cyanoacetate (0.006 mol, 0.6787 g) was then added to this stirred mixture, followed by the portionwise addition of N-(4-fluorophenyl)-2chloroacetamide (0.005 mol, 1.2425 g) after 5 min. The stirring was continued until the chloroacetamide derivative had been consumed (20 min), monitored TLC (hexane:ethyl acetate 7:3). On completion of the reaction, water (25 ml) was added to the reaction mixture and stirring continued for a further 5 min. This was then taken into a separating funnel and the aqueous phase was neutralized with glacial acetic acid (pH = 7). The phases were separated and the aqueous phase extracted with toluene (10 ml). The combined organic layers were dried over magnesium sulfate and the toluene removed    in vacuo to obtain a solid product. The crude product was crystallized from ethanol to obtain 1.42 g (87% yield) of 2-amino-1-(4-fluorophenyl)-oxo-4,5-dihydro-1H-pyrrole-3carboxylic acid ethyl ester, m.p. 783.24 K. It is more or less soluble in different solvents such as benzene, ethanol, DMF, DMSO, CH 2 CL 2 , CHCl 3 , ethyl acetate but diffraction quality crystal could be grown by the slow evaporation method at room temperature from ethyl acetate only after repeated trials.

Ethyl 2-amino-1-(4-fluorophenyl)-5-oxo-4,5-dihydro-1H-pyrrole-3-carboxylate:
Crystal data Special details Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles