Click chemistry approach: regioselective one-pot synthesis of some new 8-trifluoromethylquinoline based 1,2,3-triazoles as potent antimicrobial agents.

Three series of 8-trifluoromethylquinoline based 1,2,3-triazoles derivatives (5a-c, 6a-d and 7a-c) were synthesized by multi-step reactions by click chemistry approach. Synthesized compounds were characterized by spectral studies and X-ray analysis. The final compounds were screened for their in-vitro antimicrobial activity by well plate method (zone of inhibition). Compounds 5c, 6b, 8b, 11 and 12 were found to be active against tested microbial strains. The results are summarized in Tables 5 and 6.

Design and regioselective synthesis of trifluoromethylquinolone derivatives as potent antimicrobial agents.

Three series of new trifluoromethyl substituted quinolone derivatives were synthesized (4a-f, 6a-f and 8a-f) from corresponding substituted anilines by multi-step reactions. The regioselective alkylation with different alkyl halides were carried out by approaching two different routes to get the final products in good yield. Newly synthesized compounds were characterized by spectral study and also by C, H, N analyses. Three dimensional structure of 2b and 4b were also confirmed by single crystal X-ray studies. The final compounds (4a-f, 6a-f and 8a-f) were screened for their in-vitro antibacterial and antifungal activity by well plate method (zone of inhibition). The results revealed that, compounds 4a, 6b, 6c and 8e showed significant antibacterial activity as compared to the standard drug Ciprofloxacin. The compound 8a was found to be a potent antifungal agent.

2,4-Dichloro-benzyl 2-meth-oxy-benzoate.

In the title compound, C15H12Cl2O3, the aromatic rings make a dihedral angle of 10.78 (4)°. In the molecule, there is a short C-H⋯O contact. In the crystal, C-H⋯O contacts connect the mol-ecules into C(7)C(8) chains along the b axis. The shortest inter-centroid distance between two benzoic acid aromatic systems is 3.7416 (8) Å.

2-(4-Chloro-phen-yl)-2-oxoethyl naphthalene-1-carboxyl-ate.

In the title compound, C19H13ClO3, an ester of 1-naphthoic acid with an aromatic alcohol, the least-squares planes defined by the C atoms of the respective aromatic systems enclose an angle of 77.16 (3)°. In the crystal, C-H⋯O contacts connect the mol-ecules into undulating sheets parallel to the bc plane.

Ethyl 4-{[1-(2,4-dichloro-benz-yl)-1H-1,2,3-triazol-4-yl]meth-oxy}-8-(trifluoro-meth-yl)quinoline-3-carboxyl-ate.

In the title compound, C(23)H(17)Cl(2)F(3)N(4)O(3), the triazole ring makes dihedral angles of 50.27 (6) and 82.78 (7)° with the quinoline ring system and the dichloro-substituted benzene ring. The dihedral angle between the quinoline and dichloro-substituted benzene rings is 38.17 (4)°. In the crystal, mol-ecules are linked via C-H⋯N, C-H⋯F and C-H⋯O hydrogen bonds into a three-dimensional network. The crystal is further consolidated by C-H⋯π contacts to the triazole ring and inversion-related π-π inter-actions between the benzene and pyridine rings of quinoline systems [centroid-centroid distance = 3.7037 (7) Å].

Dimethyl 4-[3-(4-meth-oxy-phen-yl)-1-phenyl-1H-pyrazol-4-yl]-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxyl-ate dihydrate.

In the title compound, C(27)H(27)N(3)O(5)·2H(2)O, the dihydro-pyridine ring adopts a flattened boat conformation. The central pyrazole ring is essentially planar [maximum deviation of 0.003 (1) Å] and makes dihedral angles of 50.42 (6) and 26.44 (6)° with the benzene rings. In the crystal, mol-ecules are linked via N-H⋯O, O-H⋯O, O-H⋯N and C-H⋯O hydrogen bonds into two-dimensional networks parallel to the bc plane. The crystal structure is further consolidated by weak C-H⋯π inter-actions.

2-(4-Bromo-phen-yl)-2-oxoethyl anthracene-9-carboxyl-ate.

In the title compound, C(23)H(15)BrO(3), the anthracene ring system is essentially planar [maximum deviation = 0.29 (2) Å] and makes a dihedral angle of 5.74 (8)° with the mean plane of the bromo-substituted benzene ring. An intra-molecular C-H⋯O hydrogen bond generates an S(9) ring motif. In the crystal, mol-ecules are linked by C-H⋯O inter-actions, forming a two-dimensional network parallel to the ac plane. π-π stacking inter-actions are observed between benzene rings [centroid-centroid distances = 3.5949 (14) and 3.5960 (13) Å].

Synthesis, characterization and antimicrobial studies of some new quinoline incorporated benzimidazole derivatives.

Two new series of quinoline incorporated benzimidazole derivatives (4a-i and 8a-f) were synthesized from substituted aniline and isatin through multi-step reaction. 6-substituted-4-carboxyquinolines (3a,b and 7) were synthesized by multi component one pot reactions (via Doebner reaction and Pfitzinger reaction respectively) and the targeted benzimidazole derivatives were obtained by the reaction of 6-substituted-4-carboxyquinolines (3a,b and 7) with substituted aromatic diamines in acidic media. All the newly synthesized compounds were characterized by IR, NMR mass spectral study and also by C, H, N analyses. The final compounds were screened for their in-vitro antibacterial and antifungal activity by well plate method (zone of inhibition). The results revealed that, compounds 4c, 4d, 8c and 8d showed significant antibacterial activity. The compound 8b was found to be potent antifungal agent. 4a, 8a and 8f showed moderate to good antimicrobial activity as compared to the standard drugs against all tested microbial strains.

Ethyl 1-(2,4-dichloro-benz-yl)-4-oxo-7-trifluoro-meth-yl-1,4-dihydro-quinoline-3-carboxyl-ate.

In the title compound, C(20)H(14)Cl(2)F(3)NO(3), the trifluromethyl group is disordered over two sets of sites in a 0.784 (10):0.216 (10) ratio. The quinoline ring system is essentially planar with a maximum deviation of 0.058 (2) Šfor the N atom and forms dihedral angles of 89.23 (11) and 8.13 (17)°, respectively with the mean planes of the benzene ring and the carboxyl-ate group. In the crystal, pairs of weak C-H⋯O and C-H⋯F hydrogen bonds link mol-ecules into centrosymmetric dimers. The crystal structure is further stabilized by weak π-π [centroid-centroid distance = 3.624 (2) Å] inter-actions.

2-(4-Fluoro-phen-yl)-2-oxoethyl 2-methoxy-benzoate.

In the title compound, C(16)H(13)FO(4), the aromatic rings enclose an angle of 73.68 (6)°. In the crystal, C-H⋯O and C-H⋯F contacts connect the mol-ecules into a three-dimensional network. The shortest inter-centroid distance between two aromatic π-systems is 3.6679 (7) Šand is apparent between the fluorinated phenyl groups.

Diethyl 2-{[2-(trifluoro-meth-yl)anil-ino]methyl-idene}propane-dioate.

The title compound, C(15)H(16)F(3)NO(4), is an N-substituted derivative of ortho-trifluoro-methyl-aniline featuring a twofold Michael system. The least-squares planes defined by the atoms of the phenyl ring and the atoms of the Michael system enclose an angle of 15.52 (5)°. Apart from classical intra-molecular N-H⋯O and N-H⋯F hydrogen bonds, inter-molecular C-H⋯O contacts are observed, the latter connecting the mol-ecules into chains along [110]. The shortest inter-centroid distance between two aromatic systems is 3.6875 (9) Å.

Ethyl 4-oxo-8-trifluoro-methyl-1,4-dihydro-quinoline-3-carboxyl-ate.

The asymmetric unit of the title compound, C13H10F3NO3, contains two independent mol-ecules with similar conformations. In the crystal, N-H⋯O hydrogen bonds link alternating independent mol-ecules into chains in [-110]. In the chain, the quinoline planes of the independent mol-ecules are almost perpendicular to each other, forming a dihedral angle of 89.8 (1)°. π-π inter-actions between the aromatic rings of quinoline bicycles related by inversion centres [for two independent centrosymmetric dimers, the shortest centroid-centroid distances are 3.495 (1) and 3.603 (1) Å] link the hydrogen-bonded chains into layers parallel to (110). Weak C-H⋯F and C-H⋯O inter-actions further consolidate the crystal packing.

Ethyl 4-({1-[2-(4-bromo-phen-yl)-2-oxo-eth-yl]-1H-1,2,3-triazol-4-yl}meth-oxy)-8-(trifluoro-meth-yl)quinoline-3-carboxyl-ate.

The title compound, C24H18BrF3N4O4, is a 1,2,3-triazole derivative featuring, among others, a quinoline-derived substituent. In the crystal, C-H⋯O, C-H⋯N and C-H⋯F contacts connect the mol-ecules into a three-dimensional network. The shortest centroid-centroid distance between two aromatic systems is 3.896 (2) Šand is found between the two different six-membered rings of the quinoline scaffold in neighbouring mol-ecules.

Ethyl 3-(2-eth-oxy-2-oxoeth-oxy)-6-(tri-fluoro-meth-yl)furo[3,2-c]quinoline-2-carboxyl-ate.

In the title compound, C19H16F3NO6, a quinoline derivative featuring an annealated furan substituent, the mean planes of the carb-oxy substituents are at an angle of 74.3 (2)°. In the crystal, C-H⋯O contacts result in undulating chains along [110]. C-H⋯F contacts also occur. The shortest centroid-centroid distance between rings is 3.3376 (7) Å, involving two furan rings of neighbouring mol-ecules.

3-(4-Chloro-phen-yl)-5-phenyl-4,5-di-hydro-1,3-oxazole.

In the title compound, C(15)H(12)ClNO, the isoxazoline ring adopts an envelope conformation with the C atom bearing an unsubstituted phenyl ring as the flap atom. The chlorinated phenyl group is nearly in-plane with the four coplanar atoms of the heterocycle and the corresponding mean planes enclosing an angle of 1.16 (7)°. The unsubstituted phenyl group attached to the envelope flap atom approaches a nearly perpendicular orientation relative to the isoxazoline ring with a dihedral angle of 74.93 (7)°. In the crystal, weak C-H⋯O, C-H⋯N and C-H⋯π inter-actions connect the mol-ecules into layers perpendicular to the a axis.

Ethyl (Z)-3-(4-methyl-anilino)-2-[(4-methyl-phen-yl)carbamo-yl]prop-2-enoate.

The title compound, C(20)H(22)N(2)O(3), is a secondary amine featuring an amide and an ester functionality in connection with a Michael system. The conformation about the C=C bond is E. Intra-molecular N-H⋯O hydrogen bonds occur. In the crystal, C-H⋯O contacts connect the mol-ecules into chains along the b-axis direction.

2-(4-Bromo-phen-yl)-2-oxoethyl 4-methyl-benzoate.

The title compound, C(16)H(13)BrO(3), consists of a toluene ring and a bromo-benzene ring which are linked together by a 2-oxopropyl acetate group. The dihedral angle formed between the toluene and bromo-benzene rings is 80.70 (7)°. In the crystal, inter-molecular C-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network.

2-(2,4-Dichloro-phen-yl)-2-oxoethyl 4-meth-oxy-benzoate.

In the title compound, C(16)H(12)Cl(2)O(4), the dihedral angle between the benzene rings is 70.11 (6)°. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds into a three-dimensional network. A C-H⋯π inter-action is also observed.

2-(4-Fluoro-phen-yl)-2-oxoethyl 4-meth-oxy-benzoate.

In the title compound, C(16)H(13)FO(4), the dihedral angle between the benzene rings is 84.28 (8)°. In the crystal, C-H⋯F and C-H⋯O hydrogen bonds link the mol-ecules to form a three-dimensional network. The crystal structure is consolidated by C-H⋯π inter-actions and short F⋯F contacts [2.7748 (14) Å] also occur.

2-(4-Chloro-phen-yl)-2-oxoethyl 4-hy-droxy-benzoate.

The title compound, C(15)H(11)ClO(4), consists of a chloro-benzene ring and a phenol ring which are linked together by a 1,4-dioxo-2-oxabutane-1,4-diyl group. The dihedral angle between the chloro-benzene and phenol rings is 65.70 (11)°. In the crystal, inter-molecular O-H⋯O hydrogen bonds link the mol-ecules into chains along [010].