Synthesis and Crystal Structures of N-Substituted Pyrazolines

Four pyrazole compounds, 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde (1), 5-(4-bromophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazole-1-carbaldehyde (2), 1-[5-(4-chlorophenyl)-3-(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl]ethanone (3) and 1-[3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl]propan-1-one (4), have been prepared by condensing chalcones with hydrazine hydrate in the presence of aliphatic acids, namely formic acid, acetic acid and propionic acid. The structures were characterized by X-ray single crystal structure determination. The dihedral angles formed between the pyrazole and the fluoro-substituted rings are 4.64(7)° in 1, 5.3(4)° in 2 and 4.89(6)° in 3. In 4, the corresponding angles for molecules A and molecules B are 10.53(10)° and 9.78(10)°, respectively.


Introduction
The reaction of chalcones with hydrazine derivatives is one of the most extensively applied reactions in organic synthesis. Investigations revealed that in most cases the products formed are OPEN ACCESS pyrazoline derivatives [1][2][3][4]. However, the reactions may also produce pyrazole derivatives [5] and Schiff base hydrazones [6]. These reactions are usually carried out in an acidic medium.
In view of importance of pyrazolines and in continuation of our work on the synthesis and structure determination of various pyrazoline derivatives [12][13][14][15], we report the synthesis and crystal structures of four novel N-substituted pyrazolines.

Results and Discussion
One of the most convenient methods for the synthesis of pyrazolines is the reaction of α,β-unsaturated ketones with hydrazine hydrate and its derivatives. New N-substituted pyrazolines, 1-4 have been synthesized by the reaction of respective chalcone with hydrazine hydrate in the presence of different aliphatic acids as shown in Scheme 1. The crystallographic data for the four compounds are listed in Table 1.

Crystal Structure Description of Compound 1
The molecular structure of 1 is depicted in Figure 1a. The pyrazole ring (N1/N2/C7-C9) is almost planar with a r.m.s deviation of 0.0457Å. This ring forms a dihedral angle of 4.64(7)° with the fluoro-substituted benzene ring (C1-C6) and is almost perpendicular with the benzene ring (C10-C15), with a dihedral angle of 84.83(7)°. Bond lengths and angles are within the normal ranges [16]. In the crystal structure of 1, the molecules are linked into planes parallel to the ab-plane by intermolecular C-H•••O hydrogen bonds as shown in Figure 2a ( Table 2). These planes are further linked into a threedimensional network by intermolecular C-H•••F hydrogen bonds ( Figure 2b; Table 2).    (1), (2), (3) and (4).    Figure 1b shows the molecular structure of 2. The pyrazole ring (N1/N2/C7-C9) with r.m.s deviation of 0.0434Å is almost coplanar with the fluoro-substituted benzene ring (C1-C6) with a dihedral angle of 5.3(4)° and it is almost perpendicular with the bromo-substituted benzene ring (C10-C15) with a dihedral angle of 85.1(4)° which is identical to that of compound 1. Bond lengths and angles are within the normal ranges [16]. The crystal structure of 2 is shown in Figure 3

Materials and Method
X-ray diffraction studies were carried out using the Bruker SMART Apex II and Apex II Duo CCD diffractometers. Melting points were taken in open capillary tubes and were uncorrected. The purity of the compounds was confirmed by thin layer chromatography using Merck silica gel 60 F 254 coated aluminium plates. Elemental analyses were carried out by using VARIO EL-III (Elementar Analysensysteme GmBH, Hanau, Germany).

General Procedure for the Synthesis of N-Substituted Pyrazolines
A mixture of substituted chalcone (0.01 mol) and hydrazine hydrate (0.5 mL, 0.01 mol) in 25 mL formic or acetic or propionic acid was refluxed for 8 h. The reaction mixture was cooled and poured into 50 mL ice-cold water. The precipitate was collected by filtration and purified by recrystallization from ethanol. The crystals were grown by the slow evaporation method.

X-ray Crystallographic Analysis
Selected crystals were mounted on glass fibers and intensity data were collected using either Bruker SMART Apex II or Apex II Duo CCD diffractometer. The data for these compounds were processed with SAINT and corrected for absorption using SADABS. The structures of the compounds were solved by direct method using the program SHELXTL [18], and were refined by full-matrix least squares technique on F 2 using anisotropic displacement parameters. The non-hydrogen atoms were refined anisotropically. All the H atoms in these compounds were calculated geometrically with isotropic displacement parameters set to 1.2 (1.5 for methyl groups) times the equivalent isotropic U values of the parent carbon atoms. A rotating group model was applied to the methyl groups. Hydrogen bonding interactions are shown in Table 2. CCDC 895315 for (1), 895316 for (2), 895317 for (3) and 895318 for (4) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge at http://www.ccdccam.ac.uk/const/retrieving.html or from the Cambridge Crystallographic Data Centre (CCDC), 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk.