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An efficient one-pot synthesis of novel pyrazolo[3,4-b][1,8]naphthyridine and pyrazolo[3,4-d]pyrimido[1,2-a]pyrimidine derivatives has been investigated from the reaction of 2-amino (pyrimidine or pyridine), aromatic aldehydes and 3-methyl-1-phenyl-2-pyrazolin-5-one. All synthesized compounds were evaluated for in vivo anti-inflammatory activity using carrageenan-induced rat paw edema assay. Compounds 4a, 4e, 4g, 5a, 5b (80%) and 5c (86%) showed good to excellent results when compared with the anti-inflammatory active standard drug diclofenac Na (93%). On the basis of the structure–activity relationship, the anti-inflammatory activity of pyrazolo[3,4-d]pyrimido[1,2-a]pyrimidine derivatives has been found to be much better than pyrazolo[3,4-b][1,8]naphthyridine derivatives.

The present study describes the synthesis and in vitro anticancer activity of novel piritrexim analogs against human breast cancer cell line MCF-7 and a normal Vero monkey cell line. The scheme involves the formation of 3-(4-nitrophenyl)-4-phenyl-1,8-naphthyridin-2-amine accomplished by the condensation reaction of 4-nitrophenyl acetonitrile, aromatic aldehyde, and 2-aminopyridine using acetic acid as a catalyst. The selected synthesized compounds have been screened against a human breast cancer cell line MCF-7 and a normal Vero monkey cell line, out of which the compounds 4b, 4e, 4f exhibited higher potency (GI50 [

An efficient green protocol has been investigated for the synthesis of pyrimido[4,5-b]quinolines derivatives via one-pot three-component condensation of 4-chloro aniline, aromatic aldehyde and barbituric acid using low transition temperature mixtures as new generation and sustainable solvents. The process was accomplished with the use of greener and recyclable reaction media, simple methodology, easy workup procedures and no chromatographic purification with high yield. This new approach is expected to discover some significance in combinatorial synthesis of biologically active scaffolds.

A series of novel 7-phenyl-7,12-dihydrobenzo(h)pyrido[2,3-b]naphthydrin-6(5H)-one were synthesized by a one-pot three-component condensation of 2,4-dihydroxyquinoline, 2-amino pyridine and various aromatic aldehydes with sulfamic acid as an enviro-economic catalyst. The salient features of this method consist of high atom economy and yields, short reaction time, non-carcinogenic solvents, and chromatography-free work-up procedure. Fascinatingly, the catalyst can be reused for up to four cycles giving good to excellent yields. By employing this method, a series of 14 pyrido[2,3-b]naphthydrin compounds were synthesized. This procedure is projected as a green avenue in the combinatorial synthesis of biologically active naphthydrin derivatives.

A proficient and meticulously designed diasterioselective, multicomponent, one-pot synthesis of densely substituted piperidine derivatives has been elaborated using polystyrene sulfonic acid catalyst via tandem reactions of 1,3-dicarbonyl compounds, aromatic aldehydes and various amines. Shorter reaction times, high yields and a polymer-supported inexpensive catalyst are the noteworthy aspects of the scaffold.

A simple methodology has been developed for the synthesis of diverse members of multifunctionalized 4-hydroxy-2-methyl-6-(phenyl)pyrimidine-5-carbonitrile derivatives via multicomponent reaction of aromatic aldehydes, ethyl cyanoacetate, and acetamidine hydrochloride using a quantitative amount of NaOH in dry DMF at 80 °C in a single procedural step. The carbon skeleton of synthesized compounds resembles the bacimethrin, an antibiotic active against several yeast and bacteria. The anti-inflammatory activities of all the synthesized compounds were assessed on Wistar rats using diclofenac sodium as a standard reference. The compound AC1, 2, 5, 9, and AC10 showed promising anti-inflammatory activity (80–83 %) in comparison with diclofenac sodium (85 %) in the carrageenan-induced rat paw edema assay, which is the key finding of this article. The synthesized 4-hydroxy-2-methyl-6-(phenyl)pyrimidine-5-carbonitrile derivatives shown promising anti-inflammatory activity (80–83 %) in comparison with diclofenac sodium (85 %) in the carrageenan-induced rat paw edema assay.

An uncatalyzed efficient synthesis of bioactive pyridine derivatives has been investigated for the first time by a three-component sequential multicomponent reaction tackled with aromatic aldehydes, malononitrile, and 1,3-indandione via Knoevenagel condensation followed by Michael addition. The difference between the domino multicomponent and sequential multicomponent reaction is emphasized by this methodology. The reaction proceeds at ambient temperature without frequently useful N-source like ammonium salt for the construction of N-heterocycles, which makes this protocol a novel synthetic route for the preparation of the indenopyridine skeleton.

A series of novel 18-crown-6 ether functionalized bis-benzimidazole derivatives (3a–g) have been synthesized by reacting various substituted ortho-phenylene diamines and pyridine diamines with 4,4′-diformyl dibenzo-18-crown-6 ether (1). The required starting material 4,4′-diformyl dibenzo-18-crown-6 ether (1) was prepared by Duff formylation method. All synthesized novel molecules have been identified on the basis of infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, mass spectroscopy (MS), and elemental analyses. The title compounds (3a–g) were tested for antifungal activity against Aspergillus niger, Trichothecium sp., Rhizopus sp., and Sclerotium rolfsii fungi species using agar well diffusion method, showing mild to good results.

The quest to develop an environmentally friendly, sustainable protocol for immensely bioactive spirooxindole derivatives has encouraged to explore oxalic acid dihydrate: proline low transition temperature mixture as a new designer solvent for the said synthesis at room temperature. It has been successfully applied for the three component reaction of isatin, malononitrile or ethyl cyanoacetate and 1,3–dicarbonyl compounds for the first time. Moderate to good yield of the products, shorter reaction time, energy efficiency, chromatography-free purification process, recyclability and high atom economy are the captivating feature of this protocol which will find applications in multi-component, diversity-oriented synthesis.

Protic ionic liquids (PILs), which are easily produced through the combination of a Bronsted acid and Bronsted base, such as [Mim]Ac and 1,4-diazabicyclo[2.2.2]octane (DABCO):AcOH:H2O (1:1:3), were found to be lucid, tunable tool for synthesis of various heterocyclic motifs such as phthalazinediones, quinoxalines and benzopyrans. These PILs were found to be efficient for synthesis of diverse heterocyclic derivatives, along with demonstrating noteworthy aspects such as high yields, isolation of pure products without column chromatography and recyclable reaction media.

An innovatively designed novel crown ether functionalized imidazolium-based reusable acidic ionic liquid [crown ether MIm] [HSO4] has been efficiently implemented for the synthesis of pyrazole derivatives using various substituted enaminones, hydrazine hydrate and phenyl hydrazine under solvent-free conditions. Structural novelty and task efficiency of the catalyst, high yields of desired products, greener approach attributing high atom economy and solvent-free conditions render this protocol suitable to cope with the current demand in contemporary organic chemistry. The inventive idea of utilizing crown ether functionalized ionic liquid as a catalyst was for the first time demonstrated in this protocol.

A novel, highly efficient and recyclable Bronsted acidic ionic liquid ([CMIM][CF3COO]) has been successfully implemented for the synthesis of acridinediones in aqueous media. Recyclability of novel catalyst, high yields, use of environmentally benign aqueous media as solvent, simple product isolation, high atom economy and sidestep to column chromatography are the noteworthy features of this protocol. This protocol is competent for producing wide library of acridinediones in good to excellent yields. Furthermore, molecular structure and relative stereochemistry of 4c and 4s derivatives were confirmed by single-crystal X-ray diffraction.

A convenient, eco-friendly and economic method for Knoevenagel condensation of aromatic aldehydes with active methylene compounds using calcined eggshell (CES) as an efficient natural catalyst in aqueous medium has been reported. CES is a new, ecologically safe and inexpensive green catalyst obtained from renewable resources.

(±)-Camphor-10-sulfonic acid is used for the synthesis of triazolo[1,2-a]indazole-triones and spiro triazolo[1,2-a]indazole-tetraones by condensation reaction of dimedone, urazole and aromatic aldehydes or isatin. The noteworthy aspects of this new method are high yields, high atom efficiency, use of non-toxic solvent, mild conditions, simple workup and synthesis of complex molecules using an eco-friendly, inexpensive catalyst.

S-alkylation of 3-aryl-2-thioquinazolin-4(3H)-one (1) with chloroacetone gave 2-(propanonyl thio)-3-arylquinazol-4(3H)ones (2). Further, the treatment of compound (2) with hydroxylamine hydrochloride gave the corresponding oximes (3) which on reaction with phenyl isocyanate in THF yielded corresponding oxime carbamates 4. The synthesized compounds have been confirmed using IR and 1H NMR, mass spectral data together with elemental analysis. All newly synthesized compounds have been tested for their antibacterial and antifungal activities.

Synthesis of 2- (2, 4-dimethyl pyrrolyl) benzothiazole by chemical means and molecular structure by X-ray crystallographic techniques is reported. The compound crystallizes in the orthorhombic crystal system with space group Pbca and unit cell parameters: a = 12.161(9), b = 0.787(1), c = 16.792(2) Ǻ, V = 2202.8(4) Ǻ3 and Z = 8. The final reliability index is 0.073 for 7,959 observed reflections. The benzothiazole and pyrrole rings exist in planar conformations. The dihedral angle between the least-squares planes of both these moieties is 13.31°. There exists an isolated C4–H4···N1 intermolecular interaction, besides two C–H···S and C–H···N intermolecular interactions. The presence of C–H···S and C–H···N intramolecular interactions make the present molecule look like a virtual two-six-membered and three-five-membered ring structure. Synthesis of 2- (2, 4-dimethyl pyrrolyl) benzothiazole by chemical means and molecular structure by X-ray crystallographic techniques is reported. The compound crystallizes in the orthorhombic crystal system with space group Pbca and unit cell parameters: a = 12.161(9), b = 0.787(1), c = 16.792(2) Ǻ, V = 2202.8(4) Ǻ3 and Z = 8. The final reliability index is 0.073 for 7,959 observed reflections. The benzothiazole and pyrrole rings exist in planar conformations. The dihedral angle between the least-squares planes of both these moieties is 13.31°. There exists an isolated C4–H4···N1 intermolecular interaction, besides two C–H···S and C–H···N intermolecular interactions. The presence of C–H···S and C–H···N intramolecular interactions make the present molecule look like a virtual two-six-membered and three-five-membered ring structure.

The sorption and leaching behavior of kresoxim-methyl was explored in four different soils, viz., clay, sandy loam, loamy sand, and sandy loam (saline), representing vegetables and fruits growing regions of India. Adsorption of kresoxim-methyl in all the soils reached equilibrium within 48 h. The rate constants for adsorption and desorption at two different temperatures were obtained from the Lindstrom model, which simultaneously evaluated adsorption and desorption kinetics. The data for rate constants, activation energies, enthalpy of activation, entropy of activation, and free energy indicated physical adsorption of kresoxim-methyl on soil. The relative adsorptivity of the test soils could be attributed to different organic matter and clay contents of the soils. A good fit to the linear and Freundlich isotherms was observed for both adsorption as well as desorption. The groundwater ubiquity score (GUS) for different soils varied between 0 and 2.26. The GUS and leaching study indicated moderately low leaching potential of kresoxim-methyl. The adsorption on four soil types largely depended on the soil physicochemical properties such as organic carbon content, cation-exchange capacity, and texture of the soil.

The synthesis, X-ray structure and role of intermolecular interactions have been studied in case of 1,3-diphenyl-urea, owing to its medicinal importance. The compound crystallizes in orthorhombic crystal system (space group,Pna2 1)with unit cell parameters,a = 9.118(3), b = 10.558(2),c = 11.780(3) A and Z = 4. The structure has been solved by direct methods and refined to a final R-value of 00316. The oxygen atom of the carbonyl group is responsible for the existence of two N—H…O intermolecular interactions.

The crystal structure of the title compound has been determined by X-ray diffraction methods. It crystallizes in the monoclinic space group P21/n with cell parameters a = 7.097(1) A, b = 19.257(1) A, c = 10.893(1) A, β = 106.17(2)∘, V = 1429.8(3) A3 and Z = 4. The final reliability index is 0.059 for 2419 observed reflections. The molecule comprises of two six- membered rings which are abridged together through a network of C–N, N–N and C–N bonds. There are three keto functional groups and two methyl groups at various locations of the molecule. The C9 atom of methyl group and O2 of the keto group are deviated significantly from the mean plane of the molecule. Both the six-membered rings are planar and it is evident from the magnitude of their exocyclic torsion angles. The molecular structure is stabilized by few intra and intermolecular hydrogen bonds.

The title compound crystallizes in the monoclinic space group P21/n with unit cell parameters a = 10.842(9), b = 5.750(7), c = 12.964(6) A, β = 110.13(6)∘, V = 758.8(11) A3 and Z = 4. The final reliability index is 0.060 for 1034 observed reflections. The five-membered heterocyclic thiazole ring is coplanar with its fused benzene ring. The crystal structure is stabilized by two intermolecular N=H ⋅s N hydrogen bonded interactions.

The three-dimensional molecular and crystal structure of 2-(2'-propanonylthio)3-(o-methyl phenyl)quinazol-4(3H)-one has been determined by X-ray crystallographic methods. This compound crystallizes in the orthorhombic space group Pbca with unit cell parameters: a=9.649(5), b=30.102(10), c=11.403(9)A. It has been solved by direct methods and refined to a residual index of 0.054. The magnitude of torsion along C16— C11— N3— C4 bond is 93.5(4)°. The dihedral angle between the plane comprising all the ring atoms of quinazoline moiety and the atoms of the methyl substituted phenyl ring is 94.12(1)°. The crystal structure is stabilized by one intramolecular C— H⋯sO interaction and three intermolecular C— H⋯sN contacts.

The molecular and crystal structure of 2-aniline benzo(2,3-b) cyclopentane-1,3-dione has been determined by X-ray crystallographic techniques. This compound crystallizes in the orthorhombic space groupP212121 with unit cell parameters:a = 5.467(1),b = 10.657(3),c = 19.602(6) A;V = 1142.01(5) A3,Z = 4. The crystal structure has been resolved up to anR-factor 0.050 for 1129 reflections. All the three rings in the structure are planar. However, the dihedral angle between the phenyl ring and the moiety comprising of a five-membered and six-membered ring is 92.4°. The oxygen atom O1 acts as a trifurcated acceptor and is involved in the formation of three intermolecular interactions.

The title compound crystallizes in the orthorhombic space group Fdd2 with unit cell parameters a = 10.848(1) A, b = 30.264(1) A and c = 10.577(1) A, V = 3472.47(2) A3, and Z = 4. The final reliability index is 0.030 for 700 observed reflections. Nitrogen of the amide group and carbon atom of the acid group deviate significantly below and above the plane of the phenyl ring. The crystal cohesion is accentuated by N—H⋅⋅⋅O and O—H⋅⋅⋅O hydrogen bonds.

The title compound belongs to acylal class of organic materials and it crystallizes in the monoclinic space group P21/c with unit cell parameters a = 7.643(2) A, b = 20.546(6) A, c = 7.783 A, β = 112.206(2)°, V = 1131.50(5) A3 and Z = 4. The structure has been solved by direct methods and the final R-factor is 0.0401 for 2579 unique reflections. The acetate groups are deviated significantly from the plane of phenyl ring atoms. There are two C–H···O intermolecular hydrogen bonds which gives rise to an antiparallel dimer pattern. The title compound belongs to acylal class of organic materials and it crystallizes in the monoclinic space group P21/c with unit cell parameters a = 7.643(2) A, b = 20.546(6) A, c = 7.783 A, β = 112.206(2)°, V = 1131.50(5) A3 and Z = 4. The structure has been solved by direct methods and the final R-factor is 0.0401 for 2579 unique reflections. The acetate groups are deviated significantly from the plane of phenyl ring atoms. There are two C–H···O intermolecular hydrogen bonds which gives rise to an antiparallel dimer pattern.

Treatment of 2-formyl-3-dimethylamino-propenenitrile (1a) and 2-ethoxycarbonyl-3-dimethylamino-propenenitrile (1b), resp., with substituted ureas led to the 2-cyano-3-ureidoacrylates2, which can be cyclized under alkaline conditions to give 5-formyl-5-cyano-, and 5-alkoxycarbonyl-2-oxopyrimidine derivatives3,6, and7. Reaction of3 with isopentylnitrite gave a mixture of the deaminated and oxidized product4 and the oxo derivative5, which was acetalized during the separation step. Similar reaction with the alkoxycarbonyl derivatives7 led to the formation of 1-alkyl-5-alkoxycarbonyl-pyrimidine-2,6-diones8a–d.

Oxidation of 3-amino-2-isobutylquinazoline-4-one (2) with lead tetraacetate at −20°C gave N-acetoxyamino-2-isobutylquinazolin-4-one (3), which selectively aziridinated olefinic esters to yield substituted 1-(2′-isobutylquinazolin-4′-one-3′-yl)-aziridine-2-carboxylates5a–q.

Treatment of 2-phenoxypropionic acid with polyphosphoric acid gave substituted benzofuran-3-ones (2a–h), which were converted into 2,3,4-trihydrodibenzofuran-3-ones (4a–h)via the compounds3a–h.Clemmensen reduction of the compounds4a–h gave the 2,3,4-trihydrodibenzofuranes (5a–h).