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Background: Pyrazolones are traditionally synthesized by the reaction of β-keto esters with hydrazine and its derivatives. There are methods to synthesize β-keto esters from esters and aldehydes, but these methods have main limitation in varying the substituents. Often, there are a number of methods such as acylation of enolates in which a chelating effect has been employed to lock the enolate anion using lithium and magnesium salts; however, these methods suffer from inconsistent yields in the case of aliphatic acylation. There are methods to synthesize β-keto esters from ketones like caboxylation of ketone enolates using carbon dioxide and carbon monoxide sources in the presence of palladium or transition metal catalysts. Currently, the most general and simple method to synthesize β-keto ester is the reaction of dimethyl or ethyl carbonate with ketone in the presence of strong bases which also requires long reaction time, use of excessive amount of reagent and inconsistent yield. These factors lead us to develop a simple method to synthesize β-keto esters by changing the base and reagent., Results: A series of β-keto esters were synthesized from ketones and ethyl chloroformate in the presence of base which in turn are converted to pyrazolones and then subjected to cytotoxicity studies towards various cancer cell lines and antimicrobial activity studies towards various bacterial and fungal strains., Conclusion: The β-keto esters from ethyl chloroformate was successfully attempted, and the developed method is simple, fast and applicable to the ketones having the alkyl halogens, protecting groups like Boc and Cbz that were tolerated and proved to be useful in the synthesis of fused bicyclic and tricyclic pyrazolones efficiently using cyclic ketones. Since this method is successful for different ketones, it can be useful for the synthesis of pharmaceutically important pyrazolones also. The synthesized pyrazolones were subjected to antimicrobial, docking and cytotoxicity assay against ACHN (human renal cell carcinoma), Panc-1 (human pancreatic adenocarcinoma) and HCT-116 (human colon cancer) cell line, and lead molecules have been identified. Some of the compounds are found to have promising activity against different bacterial and fungal strains tested.

The title compound, C(6)H(10)N(2)O, is a zwitterionic pyrazole derivative. The crystal packing is predominantly governed by a three-center iminium-amine N(+)-H⋯O(-)⋯H-N inter-action, leading to an undulating sheet-like structure lying parallel to (100).

The asymmetric unit of the title compound, C(23)H(23)ClFN(5)O(2), contains two crystallographically independent mol-ecules. In one mol-ecule, the pyrazole ring makes dihedral angles of 43.93 (7) and 35.82 (7)°, respectively, with the fluoro- and chloro-substituted benzene rings, while the corresponding angles in the other mol-ecule are 52.26 (8) and 36.85 (7)°. The piperazine rings adopt chair conformations. In the crystal, adjacent mol-ecules are connected via inter-molecular N-H⋯O, C-H⋯F, C-H⋯N and C-H⋯O hydrogen bonds, forming a two-dimensional network parallel to the bc plane. The crystal structure is further stabilized by a weak π-π inter-action with a centroid-centroid distance of 3.6610 (8) Å and by C-H⋯π inter-actions.

In the title compound, C(11)H(12)N(2)OS, the pyrazole ring makes a dihedral angle of 85.40 (8)° with the phenyl ring. In the crystal, inter-molecular N-H⋯O and C-H⋯O hydrogen bonds link mol-ecules into a two-dimensional network parallel to the bc plane.

The asymmetric unit of the title compound, C(13)H(16)N(2)OS, contains two independent mol-ecules (A and B). The pyrazole ring [maximum deviations = 0.0049 (17) Å in mol-ecule A and 0.0112 (19) Å in mol-ecule B] makes a dihedral angle of 70.23 (11) and 73.18 (12)° with the phenyl ring in mol-ecules A and B, respectively. The isobutyl group in mol-ecule B is disordered over two sets of sites with a ratio of refined occupancies of 0.858 (5):0.142 (5). In the crystal, mol-ecules A and B are linked via a pair of inter-molecular N-H⋯O hydrogen bonds, generating an R(2) (2)(8) ring motif. These ring motifs are further linked into two-dimensional arrays parallel to the bc plane by inter-molecular N-H⋯O and weak C-H⋯S hydrogen bonds. The crystal is further stablized by weak π-π inter-actions [centroid-centroid distances = 3.5698 (13) and 3.5287 (12) Å].

In the title compound, C(17)H(15)FN(2)O(2), the essentially planar pyrazole ring [maximum deviation = 0.026 (1) Å] makes dihedral angles of 72.06 (7) and 33.05 (7)°, with the phenyl and fluoro-benzene rings, respectively. The dihedral angle between the two six-membered rings is 87.88 (7)°. In the crystal, inter-molecular N-H⋯O and C-H⋯F hydrogen bonds link the mol-ecules into layers lying parallel to the bc plane.

The asymmetric unit of the title compound, C(11)H(12)N(2)O, consists of two crystallographically independent mol-ecules (A and B) with similar geometries. Both mol-ecules exist in a keto form, the C=O bond length being 1.286 (2) Å in A and 1.283 (2) Å in B. The dihedral angles between the pyrazole ring and the attached phenyl ring are 43.28 (12) and 46.88 (11)°, respectively, for A and B. The ethyl unit in mol-ecule B is disordered over two positions with a site-occupancy ratio of 0.508 (5):0.492 (5). In the crystal, each of the independent mol-ecules forms a centrosymmetric dimer with an R(2) (2)(8) ring motif through a pair of N-H⋯O hydrogen bonds. These dimers are further connected into a three-dimensional network by inter-molecular N-H⋯O and C-H⋯O hydrogen bonds. Inter-molecular C-H⋯π inter-actions are also present.

The asymmetric unit of the title compound, C(10)H(10)N(2)O, contains two crystallographically independent mol-ecules with similar geometries, which exist in the keto form. The C=O bond lengths are 1.2878 (12) Å in mol-ecule A and 1.2890 (12) Å in mol-ecule B, indicating that the compound undergoes enol-to-keto tautomerism during the crystallization process. In mol-ecule A, the pyrazole ring is approximately planar [maximum deviation = 0.007 (1) Å] and forms a dihedral angle of 36.67 (6)° with the attached phenyl ring. In mol-ecule B, the dihedral angle formed between the pyrazole ring [maximum deviation = 0.017 (1) Å] and the phenyl ring is 41.19 (6)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds link neighbouring mol-ecules into dimers generating R(2) (2)(8) ring motifs. These dimers are linked into ribbons along [101] via inter-molecular N-H⋯O hydrogen bonds, forming R(4) (2)(10) ring motifs.

The address of three of the authors in the paper by Shahani et al. [Acta Cryst. (2010), E66, o3020-o3021] is corrected.[This corrects the article DOI: 10.1107/S1600536810043886.].

In the title compound, C(21)H(17)ClFN(3)O(2), the 1H-pyrazole ring makes dihedral angles of 36.73 (7), 18.73 (7) and 60.88 (8)°, respectively, with the mean planes of the chloro-phenyl, 4-oxo-piperidine and fluoro-phenyl rings. The mol-ecular structure is stabilized by an intra-molecular C-H⋯N hydrogen bond, which forms an S(6) ring motif. In the crystal, inter-molecular C-H⋯O hydrogen bonds link mol-ecules into chains along [101]. In addition, inter-molecular C-H⋯F hydrogen bonds with an R(2) (1)(7) ring motif connect neighbouring chains into layers parallel to the ac plane.

The title compound, C(13)H(16)N(2)O(3)S, consists of two crystallographically independent mol-ecules with similar geometries and exists in a keto form, the C=O bond lengths being 1.267 (2) and 1.254 (2) Å. In both mol-ecules, the pyrazole rings are approximately planar, with maximum deviations of 0.017 (2) and 0.010 (2) Å, and the dihedral angles between the pyrazole and phenyl rings are 83.63 (11) and 70.07 (12)°. In one mol-ecule, an intra-molecular C-H⋯O hydrogen bond with an S(6) ring motif is observed. In the crystal, inter-molecular N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into two-dimensional networks parallel to the ab plane.

The title compound, C(9)H(14)N(2)O, exists in the zwitterionic form in the crystal. The cyclo-octane ring adopts a twisted boat-chair conformation. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into sheets lying parallel to bc. The structure is also stabilized by π-π inter-actions, with a centroid-to-centroid distance of 3.5684 (8) Å.

In the title 1:1 adduct, C(6)H(12)N(2)O(2)·C(9)H(10)N(2)O(2), the maximum deviations from the 1H-pyrazole-5-ol and furan rings are 0.014 (1) and 0.003 (1) Å, respectively. The dihedral angle formed between the 1H-pyrazol-5-ol and 2,5-dimethyl-furan rings is 21.07 (5)°. In the crystal, pairs of inter-molecular O-H⋯N hydrogen bonds form inversion dimers of the 3-(2,5-dimethyl-furan-3-yl)-1H-pyrazol-5-ol species, generating R(2) (2)(8) ring motifs. Mol-ecules are further linked by inter-molecular N-H⋯O, N-H⋯N and C-H⋯O hydrogen bonds to form ribbons along the [010] direction containing bifurcated R(1) (2)(5) and R(2) (1)(7) ring motifs. Further stablization of the packing is provided by weak π-π [centroid-centroid distance = 3.5686 (15) Å] and C-H⋯π inter-actions.

In the title compound, C(22)H(17)ClFN(3)O(2)S, the pyrazole ring is approximately planar with a maximum deviation of 0.001 (4) Å and makes dihedral angles of 4.95 (19), 35.78 (18) and 54.73 (18)° with the thia-zole, fluoro-benzene and chloro-benzene rings, respectively. In the crystal, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into chains along the a axis.

The title compound, C(16)H(13)FN(2)OS, has undergone enol-to-keto tautomerism during the crystallization process. The 1H-pyrazole-5-one ring [maximum deviation = 0.0198 (11) Å] is inclined at angles of 33.10 (5) and 79.57 (5)° with respect to the fluoro-phenyl [maximum deviation = 0.0090 (12) Å] and phenyl-thiol [maximum deviation = 0.0229 (3) Å] rings attached to it. In the crystal, neighbouring mol-ecules are linked into inversion dimers, generating R(2) (2)(8) ring motifs. These dimers are further linked into two-dimensional arrays parallel to the bc plane via inter-molecular N-H⋯O, C-H⋯F and C-H⋯O hydrogen bonds. The crystal is further stabilized by weak π-π [centroid-centroid distance = 3.6921 (7) Å] and C-H⋯π inter-actions.

In the title compound, C(10)H(16)N(2)O·H(2)O, the cyclo-hexane ring is in a chair conformation and its least-squares plane makes a dihedral angle of 53.68 (5)° with the approximately planar pyrazole ring [maximum deviation = 0.034 (1) Å]. Pairs of inter-molecular N-H⋯O hydrogen bonds form inversion dimers between neighbouring pyrazolone mol-ecules, generating R(2) (2)(8) ring motifs. The pyrazolone and water mol-ecules are further linked by inter-molecular N-H⋯O, C-H⋯O and O-H⋯O hydrogen bonds into two-dimensional sheets parallel to the bc plane.

In the title pyrazole derivative, C(25)H(26)ClFN(4)O(3), both benzene rings are twisted out of the plane through the pyrazole ring, with dihedral angles of 67.62 (10) and 27.63 (10)° for the fluoro- and chloro-substituted rings, respectively. The dihedral angle between the two benzene rings is 64.54 (9)°. The piperazine ring (with a chair conformation) is linked to the pyrazole ring via a carbonyl spacer and is orientated to lie to one side of the pyrazole plane. In addition to an intra-molecular C-H⋯N contact, there are inter-molecular C-H⋯O inter-actions, which generate a supra-molecular chain with an undulating topology along the c axis that is sustained by alternating centrosymmetric ten-membered {⋯HCNCO}(2) and {⋯HC3O}(2) synthons.

In the title compound, C(28)H(22)ClFN(6)O(2), the piperazine ring adopts a chair conformation and the least-squares plane through the four coplanar atoms forms dihedral angles of 69.37 (13) and 56.56 (12)°, respectively, with the pyrazole and cyano-phenyl rings. The dihedral angles formed between the pyrazole and the attached fluoro- and chloro-phenyl rings are 34.16 (10) and 73.27 (12)°, respectively. In the crystal, inter-molecular N-H⋯O, C-H⋯N and C-H⋯O hydrogen bonds link the mol-ecules into sheets parallel to the ac plane.

The asymmetric unit of the title compound, C(25)H(14)ClFN(4)S, contains two independent mol-ecules (A and B). Each mol-ecule consists of five rings, namely chloro-phenyl, fluoro-phenyl, 1H-pyrazole, thia-zole and benzonitrile. In mol-ecule A, the 1H-pyrazole ring makes dihedral angles of 52.54 (8), 35.96 (8) and 15.43 (8)° with respect to the attached chloro-phenyl, fluoro-phenyl and thia-zole rings. The corresponding values in mol-ecule B are 51.65 (8), 37.26 (8) and 8.32 (8)°. In the crystal, mol-ecules are linked into dimers by C-H⋯N hydrogen bonds, generating R(2) (2)(10) ring motifs. These dimers are further linked into two-dimensional arrays parallel to the ab plane via inter-molecular weak C-H⋯N and C-H⋯F hydrogen bonds. The crystal structure is further stabilized by weak π-π inter-actions [with centroid-centroid distances of 3.4303 (9) and 3.6826 (9) Å] and weak C-H⋯π inter-actions.

The title compound, C(13)H(13)F(3)N(2)O(2), crystallizes with two independent mol-ecules in the asymmetric unit, with different conformations of their ethyl side chains. The dihedral angles formed between the 1H-pyrazole and benzene rings in the two mol-ecules are 79.44 (6) and 77.81 (6)°. In the crystal, mol-ecules are linked by O⋯H-N hydrogen bonds into chains propagating along [001] and the packing is further stabilized by π-π inter-actions [centroid-centroid separations = 3.5409 (10) and 3.6335 (10) Å].

The title compound, C(10)H(10)N(2)O, crystallizes with two independent mol-ecules in the asymmetric unit, having closely comparable geometries. The dihedral angles between the 1H-pyrazole and benzene rings in the two mol-ecules are 39.57 (14) and 41.95 (13)°. The two mol-ecules are each connected to neighbouring mol-ecules by pairs of inter-molecular O-H⋯N hydrogen bonds, forming dimers with R(2) (2)(8) ring motifs. These dimers are further linked into R(4) (4)(10) ring motifs by inter-molecular N-H⋯O hydrogen bonds, forming chains along [101]. The crystal structure is further stabilized by a C-H⋯π inter-action.

In the title compound, C(14)H(18)N(2)O(3)S, the 1H-pyrazole ring is approximately planar, with a maximum deviation of 0.005 (1) Å. The dihedral angle formed between the 1H-pyrazole and phenyl rings is 79.09 (5)°. Pairs of inter-molecular N-H⋯O and O⋯H⋯N hydrogen bonds form dimers between neighboring mol-ecules, generating R(2) (2)(10) ring motifs. These dimers are further linked by intermolecular N-H⋯O and O-H⋯N hydrogen bonds into two-dimensional arrays parallel to the ac plane. The crystal structure is also stabilized by C-H⋯π inter-actions.

In the title compound, C(6)H(10)N(2)O, the 2,3-dihydro-1H-pyrazole ring is approximately planar, with a maximum deviation of 0.013 (1) Å. Pairs of inter-molecular N-H⋯O hydrogen bonds link neighboring mol-ecules into dimers, generating R(2) (2)(8) ring motifs. These dimers are further linked into two-dimensional arrays parallel to the bc plane by inter-molecular N-H⋯O hydrogen bonds. The crystal structure is further stabilized by C-H⋯π inter-actions.

The asymmetric unit of the title compound, C(13)H(10)F(2)N(2)O, contains one and a half N,N'-bis-(4-fluoro-phen-yl)urea mol-ecules. One of the mol-ecules has crystallographic twofold rotation symmetry. The benzene rings are twisted from each other by dihedral angles of 29.69 (6)° for the mol-ecule in a general position and 89.83 (6)° for the symmetry-generated mol-ecule. In the crystal structure, a pair of inter-molecular N-H⋯O hydrogen bonds link symmetry-related mol-ecules into chains along the b axis, forming R(2) (1)(6) ring motifs.

Novel 1,5-diaryl pyrazole derivatives viz. 5-(4-chlorophenyl)-1-(4-fluorophenyl)-1H-pyrazole-3-carboxamides (2a-e, 3, 3a-f), 2-(5-(4-chlorophenyl)-1-(4-fluorophenyl)-1H-pyrazole-3-yl)thiazoles (6a-c,7, 8, 9a-c, 10, 11) were synthesized by varying the active part (amide group) of pyrazole, characterized using IR, (1)H NMR, mass spectral data and screened for their antibacterial activity against Escherichia coli (ATTC-25922), Staphylococcus aureus (ATTC-25923), Pseudomonas aeruginosa (ATTC-27853), Klebsiella pneumonia. Similarly all these compounds were screened for their antifungal activity against Aspergillus flavus (NCIM No. 524), Aspergillus fumigates (NCIM No. 902), Penicillium marneffei and Trichophyton mentagrophytes. Interestingly all the synthesized compounds exhibited good antibacterial (except 2a-c, 8, 9a) and antifungal activity (except 2a-c, 6a, 8, 9a)., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

In the title compound, C(27)H(22)ClNO(2), the phenyl substituent on the quinoline ring system is almost perpendicular to it [dihedral angle = 88.2 (1)°]. The quinoline ring system and the ethoxy-phenyl ring are oriented at dihedral angles of 79.5 (1) and 17.6 (3)°, respectively, with respect to the almost planar [r.m.s. deviation= 0.037 (3) Å] -C(=O)-C=C- linkage. In the crystal, the inversion-related mol-ecules exist as C-H⋯O hydrogen-bonded R(2) (2)(8) dimers.

In the title compound, C(11)H(17)N(3)O(3), the pyrazole ring is approximately planar, with a maximum deviation of 0.005 (2) Å, and forms a dihedral angle of 5.69 (13)° with the plane through the six atoms of the piperidine ring. In the crystal, pairs of inter-molecular N-H⋯O hydrogen bonds form dimers with neighbouring mol-ecules, generating R(2) (2)(8) ring motifs. These dimers are further linked into two-dimensional arrays parallel to the bc plane by inter-molecular N-H⋯O and C-H⋯O hydrogen bonds.

In the title compound, C(11)H(12)N(2)O(3), the pyrazole ring system is essentially planar [maximum deviation = 0.002 (2) Å] and forms a dihedral angle of 66.93 (9)° with the benzene ring. In the crystal packing, pairs of inter-molecular N-H⋯O and O-H⋯N hydrogen bonds connect neighbouring mol-ecules into dimers, generating R(2) (2)(10) and R(2) (2)(8) ring motifs, respectively. The crystal structure is further stabilized by C-H⋯π inter-actions.