Search

An unprecedented union of multi-component reactions to construct pyrazole- and pyranopyrazole-adorned 4H-chromene from simple reactants in water at ambient temperature is reported. This innovative tactic has integrated two distinct four-component reactions (4CRs) that occur transiently to form four new heterocycles via ten covalent bonds in a single step.

An unprecedented union of multi-component reactions to construct pyrazole- and pyranopyrazole-adorned 4

An oxindole decorated 4H-chromene scaffold has been synthesized in water under catalyst-free reaction conditions at ambient temperature in good yields with moderate to high diastereoselectivities by implementing an ingenious methodology by integrating the guiding principles of Diversity Oriented Synthesis (DOS) and green chemistry.

6-Amino-5-cyano-2-oxo-N-(pyridin-2-yl)-4-(p-tolyl)-2H-[1,2′-bipyridine]-3-carboxamide and 6-amino-5-cyano-4-(4-fluorophenyl)-2-oxo-N-(pyridin-2-yl)-2H-[1,2′-bipyridine]-3-carboxamide were synthesized through three-component reaction between N1,N3-di(pyridin-2-yl)-malonamide, aldehyde and malononitrile in water using triethylamine as a base at room temperature. Synthesized compounds were characterized by using different techniques (FT-IR, NMR and X-ray diffraction). Additionally, the mentioned compounds were investigated by computational chemistry methods. Obtained results were supported with calculated results. Additionally, NLO properties and molecular docking analyses of related compounds were examined in detail. The binding modes of the compounds 4a and 4b were explored with the colchicine binding site of tubulin, from molecular docking studies, remarkable interactions have been observed for 4a and 4b near to the colchicines binding site of tubulin that may contribute to the inhibition of tubulin polymerization and anticancer activity.

The crystal structure of the potential active 2-amino-4-(4-hydroxy-3-methoxyphenyl)-7, 9-dimethyl-5-oxo-4, 5, 6, 7- tetrahydropyrano [2, 3-d] pyrazolo [3, 4-b] pyridine-3-carbonitrile (C21H22N5O6S) has been determined from single crystal X-ray diffraction data. In the title compound crystallizes in the monoclinic space group P-1 with unit cell dimension a=8.1201(9)A, b=12.2684(4)A and c= 12.387(2)A [α=69.573o, β= 12.168o and γ=76.060o]. In the structure the pyrazole, pyridine and pyran are almost coplanar each other. The crystal packing is stabilized by intermolecular C-H...O and NH... O hydrogen bond interaction.

Synthesis of the 2-aza analogues of pyrrolizidine and spirooxindole-2-azapyrrolizidine hybrid, a spiro-tetracyclic scaffold possessing multiple contiguous stereocenters, by an exclusive regio-, chemo-, and diastereoselective multicomponent reaction in water is reported. This logical and didactical tactic has integrated the principles of an ideal organic synthesis, privileged substructure-based diversity-oriented synthesis, and biology-oriented synthesis to access hybrid heterocyclic scaffolds.

Reactions of pyrazolone ketene dithioacetals with various binucleophiles afforded 4-heterocyclic substituted pyrazolone compounds as ketene N,N-, N,O-acetals in the absence of any acid/base catalyst in good yields. The products 3a–i formed by the direct displacement of dithioacetals exhibited high regioselectivity towards binucleophiles. All the synthesized compounds were characterized by IR, 1H, 13C, 2D NMR and X-ray diffraction techniques. Optimized geometry of compound 3e has been computed by Density Functional Theory (DFT) method in B3LYP 6-31G∗∗ level basis set. The title compounds 3d–f were crystallized in monoclinic space group Pc, P21/n, P21/c with cell parameters: a = 7.6647(3), b = 26.7020(8), c = 12.8364(5) Ǻ, β = 102.842(4)°, V = 2561.42(16) Ǻ3, Z = 9 (for 3d), a = 13.448(5), b = 7.539(5), c = 14.832(5) Ǻ, β = 94.747(5)°, V = 1498.6(12) Ǻ3, Z = 4 (for 3e) and a = 13.6468(17), b = 15.905(2), c = 7.9029(9) Ǻ, β = 100.774(9)°, V = 1685.1(4) Ǻ3, Z = 4 (for 3f) respectively. The spectral and crystal studies revealed that the compounds 3a–i exist in amine-one tautomeric form in solid state and the optimized structure T5 of the compound 3e exhibit good agreement with X-ray diffraction data.

An oxindole decorated 4H-chromene scaffold has been synthesized in water under catalyst-free reaction conditions at ambient temperature in good yields with moderate to high diastereoselectivities by implementing an ingenious methodology by integrating the guiding principles of Diversity Oriented Synthesis (DOS) and green chemistry.

Libraries of skeletally diverse potential bioactive polycyclic/spirocyclic heterocyclic compounds; 2-amino-7,9-dimethyl-5-oxo-4-aryl-4,5,6,7-tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridine-3-carbonitrile, 2′-amino-7′,9′-dimethyl-2,5′-dioxo-6′,7′-dihydro-5′H-spiro[indoline-3,4′-pyrano[2,3-d]pyrazolo[3,4-b]pyridine]-3′-carbonitrile, and 5,5′-(arylmethylene)bis(4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one) have been synthesized through a multi-component reaction using novel heterocyclic active methylene compound 4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6(7H)-one as one of the building blocks. This protocol can be considered to be an efficient and eco-friendly strategy for diversity oriented synthesis.

Aerobic oxidative coupling of 2-naphthol to 1,1'-binaphthyl-2,2'-diol has been achieved using chiral/achiral copper salen complexes as catalyst. Moderate enantioselectivity was obtained for the reaction of 2-napthol with a coordinating substituent with a chiral salen complex. Unsubstituted 2-naphthol resulted in racemic 1,1'-binaphthyl-2,2'-diol only with all chiral complexes. Electron paramagnetic resonance spectroscopy has been used to understand the factors influencing the asymmetric induction.

Synthesis, characterization, and antimicrobial activity of tridentate Schiffbase ligands containing pyrazolone moiety (3a and 3b) and their transition metal complexes of VO(II), Cu(II), Fe(III), and Co(II) 4a–h have been investigated. The complexes show enhanced antibacterial activity against S. aureus, E. coli, and S. typhi and antifungal activity against C. albicans, Rhizopus sp., and A. niger compared to the ligands.

Checkpoint-1 kinase plays an important role in the G(2)M cell cycle control, therefore its inhibition by small molecules is of great therapeutic interest in oncology. In this paper, we have reported the virtual screening of an in-house library of 2499 pyranopyrazole derivatives against the ATP-binding site of Chk1 kinase using Glide 5.0 program, which resulted in six hits. All these ligands were docked into the site forming most crucial interactions with Cys87, Glu91 and Leu15 residues. From the observed results these ligands are suggested to be potent inhibitors of Chk1 kinase with sufficient scope for further elaboration.

Synthesis of the 2-aza analogues of the pyrrolizidine alkaloid motif with two contiguous stereocenters has been achieved with high regio-, chemo-, and diastereoselectivity by an innovative multicomponent reaction in water. This elegant tactic has integrated the principles of privileged substructure-based Diversity Oriented Synthesis (pDOS) and Biology Oriented Synthesis (BIOS) to access a biologically relevant scaffold.

An environmentally benign four-component reaction in aqueous medium at room temperature has been developed for the synthesis of 6-amino-5-cyano-3-methyl-4-aryl/heteroaryl-2H,4H-dihydropyrano[2,3-c]pyrazoles.

The 1H and 13C NMR spectra of 4-substituted phenylthiol acetates, benzoates and cinnamates and the 17O NMR spectra of a few thiol acetates were measured. The 13C chemical shifts of C-1 of the thiol esters when correlated with appropriate substituent-induced chemical shifts (SCS) of monosubstituted benzenes reveal an enhancement of substituent effect at C-1. Several good dual substituent parameter (DSP) correlations of 13C chemical shifts with σ1 and σR parameters were obtained for the carbons para to the substituent and the carbonyl carbons of all the three series of thiol esters display inverse substituent effects, indicating π-polarization of the thiol ester functionality by the dipole of the substituent. © John Wiley & Sons Ltd.

The reaction is highly regio- and chemoselective and only one diastereomer is formed (24 examples).

Libraries of skeletally diverse potential bioactive polycyclic/spirocyclic heterocyclic compounds; 2-amino-7,9-dimethyl-5-oxo-4-aryl-4,5,6,7-tetrahydropyrano[2,3-d]pyrazolo[3,4-b]pyridine-3-carbonitrile, 2′-amino-7′,9′-dimethyl-2,5′-dioxo-6′,7′-dihydro-5′H-spiro[indoline-3,4′-pyrano[2,3-d]pyrazolo[3,4-b]pyridine]-3′-carbonitrile, and 5,5′-(arylmethylene)bis(4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one) have been synthesized through a multi-component reaction using novel heterocyclic active methylene compound 4-hydroxy-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-6(7H)-one as one of the building blocks. This protocol can be considered to be an efficient and eco-friendly strategy for diversity oriented synthesis.

A catalyst-free combinatorial library of novel 2-amino-4-(5-hydroxy-3-methyl-1H-pyrazol-4-yl)-4H-chromene-3-carbonitrile derivatives has been developed by a four-component reaction between hydrazine hydrate (1), ethyl acetoacetate (2), 2-hydroxybenzaldehydes (3) and malononitrile (4) in water at ambient temperature.

The 1H, 13C and 17O NMR spectra of several 4,1-disubstituted naphthalenes, viz. 4-substituted 1- acetylnaphthalenes (series 1), 4-substituted 1-nitronaphthalenes (series 2), 4-substituted 1-methoxynaphthalenes (series 3) and 4-substituted 1-naphthyl methyl sulphides (series 4), were measured. The 17O and 13C chemical shifts of these 4,1-disubstituted naphthalenes were compared with those of the corresponding 4,1-disubstituted benzenes and analysed using the dual substituted parameter (DSP) equation. It is concluded that in series 1, 2 and 4 the substituent effects from the 4-substituent to the C-1 carbon and the side-chain atoms are transmitted more effectively than those in the corresponding 4,1-disubstituted benzenes, whereas the transmission in series 3 is almost equal to that in the analogous benzene series, viz. 4-substituted anisoles. The reverse substituent effects displayed by the H-8 chemical shifts of series 1 and 2 and the existence of linear relationships between the chemical shifts of H-8 and the 17O chemical shifts of the oxygen of both the acetyl and nitro groups in series 1 and 2, respectively, are ascribed mainly to changes in the electron densities on the oxygen of the carbonyl and nitro groups affecting the diamagnetic screening of the proton.

An environmentally benign four-component reaction in aqueous medium at room temperature has been developed for the synthesis of 6-amino-5-cyano-3-methyl-4-aryl/heteroaryl-2H,4H-dihydropyrano[2,3-c]pyrazoles.

The proton and carbon spectra of ten 4-X-l-acetylnaphthalenes have been assigned. Shift correlations have been made with benzene substituent-induced chemical shifts (SCS, Lynch plots) and with dual substituent parameters (DSP) in the manner successfully done for many series of 1,4-disubstituted benzenes. The results obtained are compared with those for 4-X-acetophenones and 1-X-naphthalenes. The main conclusions are (i) the carbon para to the variable substituent X is more sensitive to change of substituent in the naphthalenes than in the benzenes, (ii) of the carbons ortho to the variable substituent X, that at C-3 is more sensitive and that at C-4a is less sensitive, to change of substituent in the naphthalenes than in the benzenes, (iii) the effect of the 4-substituents on the shift of H-8 in 1-acetylnaphthalenes is due mainly to changes in the carbonyl dipole affecting the diamagnetic screening of the proton.

In the title compound, C15H14N4O, the pyrazole ring is aligned at 88.23 (4)° with respect to the aromatic ring and at 3.75 (4)° with respect to the pyran ring. In the crystal, N—H...N hydrogen bonds link adjacent molecules into a linear chain motif. C—H...N interactions are also observed.

In the title compound C14H17N3O2, the dihedral angle between the rings is 16.68 (13)°. Although the compound crystallizes in the keto form, the possibility of keto-enamine–enol-imine tautomerism is explained by a strong intramolecular N—H...O hydrogen bond.

In the title compound, C23H22N2O3, the pyran ring adopts a twisted boat conformation. The tolyl rings and carboxylate group are attached to the pyran ring with torsion angles of −77.1 (2), 59.5 (3) and 17.8 (3)°, respectively. The ethyl group is disordered over two orientations with a site-occupancy ratio of 0.508 (5):0.492 (5). In the crystal, molecules are linked by N—H...N and N—H...O hydrogen bonds, generating a chain running the a axis. Weak C—H...O, C—H...N and C—H...π interactions are also observed.

In he title compound, C13H16N4O3, the pyrazole ring is planar (r.m.s. deviation = 0.054 Å). The pyran ring is not planar; the mean plane makes a dihedral angle of 1.9 (1)° with the pyrazole ring. In the crystal structure, intermolecular N—H...N and N—H...O interactions lead to a linear chain motif.

A catalyst-free combinatorial library of novel 2-amino-4-(5-hydroxy-3-methyl-1H-pyrazol-4-yl)-4H-chromene-3-carbonitrile derivatives has been developed by a four-component reaction between hydrazine hydrate (1), ethyl acetoacetate (2), 2-hydroxybenzaldehydes (3) and malononitrile (4) in water at ambient temperature.