Ring-opening hydrolysis of spiro-epoxyoxindoles using a reusable sulfonic acid functionalized nitrogen rich carbon catalyst.

Controlling the product selectivity of a ring-opening hydrolysis reaction remains a great challenge with mineral acids and to an extent with homogeneous catalysts. In addition, even trace amounts of metal impurities in a bioactive product hinder the reaction progress. This has necessitated the development of robust and metal-free catalysts to offer an alternative sustainable route. We report a nitrogen-rich sulfonated carbon as a catalyst derived from an inexpensive precursor for the synthesis of bioactive vicinal diols of spiro-oxindole derivatives. The well-characterized catalyst shows wide generality with different electronic and steric substituents in the substrates under mild reaction conditions. Hot filtration test confirms no leaching of the acid moiety and the catalyst could be reused for four cycles with retention of activities.

Cycloaddition of CO2 with an Epoxide-Bearing Oxindole Scaffold by a Metal-Organic Framework-Based Heterogeneous Catalyst under Ambient Conditions.

The synthesis and characterization of a mixed ligand metal-organic framework (MOF) with good thermal and chemical stability, {[Co(BDC)(L)·2H2O]·xG}n (CoMOF-2), involving an aromatic dicarboxylate (H2BDC = 1,4-benzenedicarboxylic acid) and an acyl-decorated N-donor linker [L = (E)-N'-(pyridin-4-ylmethylene) isonicotinohydrazide] by various physicochemical techniques, including Single crystal X-Ray Diffraction (SXRD), are reported. The MOF showed a good affinity for CO2 capture, and Grand Canonical Monte Carlo simulation studies exposed strong interactions of CO2 with the functionalized N-donor ligand of the framework. CoMOF-2 and KI act as an efficient binary catalyst for the sustainable utilization of CO2 with spiro-epoxy oxindole to spirocyclic carbonate under ambient conditions. Notably, herein we report MOF-based catalysis for the cycloaddition of oxindole-based epoxides with CO2 for harvesting new spirocyclic carbonates. Interestingly, we could isolate and crystallize six of the spirocyclic carbonate products, and the structure of the newly synthesized molecules has been established by SXRD analysis. We present a plausible proposed catalytic mechanism through activation of the epoxide ring by the Lewis acidic/basic sites present on the framework surface that is validated by molecular modeling.

Hydrogenation of Furfural with Nickel Nanoparticles Stabilized on Nitrogen-Rich Carbon Core-Shell and Its Transformations for the Synthesis of γ-Valerolactone in Aqueous Conditions.

In this article, we report the synthesis of nitrogen-rich carbon layer-encapsulated Ni(0) nanoparticles as a core-shell structure (Ni@N/C-g-800) for the catalytic hydrogenation of furfural to furfuryl alcohol. The nickel nanoparticles were stabilized by the nitrogen-rich graphitic framework, which formed during the agitation of nickel acetate-impregnated cucurbit[6]uril surface in a reducing atmosphere. Furthermore, the catalyst was characterized using various physicochemical methods such as powder X-ray diffraction, Raman, field emission-scanning electron microscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, Brunauer-Emmett-Teller surface area, CO2-temperature-programmed desorption, inductive coupled plasma, and CHN analyses. The nitrogen-rich environment of the solid support with metallic Ni nanoparticles was found to be active and selective for the catalytic hydrogenation of furfural with molecular H2 in an aqueous medium at 100 °C. To understand the reaction mechanism, the diffuse reflectance infrared Fourier transform study was performed, which revealed that the C═O bond is activated in the presence of a catalyst. In addition, we have extended our methodology toward the synthesis of "levulinic acid" and "γ-valerolactone", by successive hydrolysis and hydrogenation of furfuryl alcohol and levulinic acid, respectively, in an aqueous medium. Moreover, the heterogeneous catalysts used in all of the three consecutive steps help in recovery and recycling of the catalyst and easy separation of products.

Sustainable Heterogeneous Catalysts for CO2 Utilization by Using Dual Ligand ZnII /CdII Metal-Organic Frameworks.

Two-dimensional ZnII /CdII -based dual ligand metal-organic frameworks (MOFs) {[M(CHDC)(L)]⋅H2 O}n involving 4-pyridyl carboxaldehyde isonicotinoylhydrazone (L) in combination with flexible 1,4-cyclohexanedicarboxylic acid (H2 CHDC) as linkers have been synthesized by adaptable synthetic protocols including a green mechanochemical (grinding) method. Characterization, chemical/thermal stability, phase purity, and solid-state luminescent properties of both MOFs have been established by various analytical methods. Structural analysis revealed dimeric metal clusters composed of [M2 (CHDC)2 ]n loops doubly pillared with L, generating a 2D framework. Both MOFs can be used as highly active solvent-free binary catalysts for CO2 cycloaddition with epoxides in the presence of the co-catalyst tetrabutylammonium bromide (TBAB) with good catalytic conversion in up to six catalytic cycles without significant loss of activity. The present investigation demonstrates the application of MOFs as efficient heterogeneous catalysts for CO2 utilization under moderate reaction conditions. Based on the single-crystal X-ray data, a probable mechanism for the cycloaddition reaction has also been proposed.

Amine-functionalized Zn(ii) MOF as an efficient multifunctional catalyst for CO2 utilization and sulfoxidation reaction.

Herein, a zinc(ii)-based 3D mixed ligand metal organic framework (MOF) was synthesized via versatile routes including green mechanochemical synthesis. The MOF {[Zn(ATA)(L)·H2O]}n (ZnMOF-1-NH2) has been characterized by various physico-chemical techniques, including SCXRD, and composed of the bipyridyl-based Schiff base (E)-N'-(pyridin-4-ylmethylene)isonicotinohydrazide (L) and 2-aminoterephthalic acid (H2ATA) ligands as linkers. The MOF material has been explored as a multifunctional heterogeneous catalyst for the cycloaddition of alkyl and aryl epoxides with CO2 and sulfoxidation reactions of aryl sulfides. The influence of various reaction parameters is examined to optimize the performance of the catalytic reactions. It is found that solvent-free catalytic reaction conditions offer good catalytic conversion in the case of cyclic carbonates, and for sulfoxide, good conversion and selectivity are achieved in the presence of DCM as a solvent medium under ambient reaction conditions. The chemical and thermal stability of the catalyst are excellent and it is active for up to four catalytic cycles without significant loss in activity. Furthermore, based on the catalytic activity and structural evidence, a plausible mechanism for both catalytic reactions is proposed.

Self-Supported Chiral Polymeric MnIII Salen Complexes as Highly Active and Recyclable Catalysts for Epoxidation of Nonfunctionalized Olefins.

A series of self-supported chiral polymeric MnIII N,N'-ethylenebis(salicylimine) (salen) complexes were synthesized through metalation of the corresponding salen ligands obtained by condensation of several bis/tris-aldehydes with (1R,2R)-1,2-diaminocyclohexane. Upon employment in the asymmetric epoxidation reaction of nonfunctionalized olefins, all complexes showed enhanced activity and enantioselectivity relative to the classical Jacobsen's monomeric salen complex. However, 1,3,5-triazole-based polymeric MnIII salen complex 7 was noticeably preferred over others owing to its ability to render higher enantioselectivity at the expense of lower catalyst loading. Furthermore, complex 7 was recycled and reused in eight recycling experiments with marginal loss in catalytic activity.

Synthesis and characterization of new chiral Cu(ii)-N4 complexes and their application in the asymmetric aza-Henry reaction.

Cu(ii) Schiff base complexes Cu(ii)- and Cu(ii)- based on 2-acetyl pyridine with both (1R,2R)-1,2-diaminocyclohexane and (1S,2S)-1,2-diaminocyclohexane were synthesized in a single step. Subsequent reduction of ligands and with NaBH4 followed by complexation with Cu(OTf)2 resulted in generation of two more additional chiral centers in complexes Cu(ii)- and Cu(ii)-. The ligands and their corresponding complexes were well characterized by several spectral techniques like (1)H-NMR, (13)C-NMR, LC-MS, CD, UV-Vis spectroscopy and microanalysis. The respective Cu(ii) complexes derived from ligands and were investigated using both the solution and solid state EPR spectra. The particular orientation of the reduced complex with Cu(OTf)2 was confirmed by the X-ray crystal structure of the corresponding complex. All the catalytic protocols were applied in the asymmetric aza-Henry reaction to evaluate the catalytic properties of the Cu(ii) complexes in the present study.

Unravelling a new class of chiral organocatalyst for asymmetric ring-opening reaction of meso epoxides with anilines.

Chiral sulfinamide based organocatalyst 11 was synthesized from readily available starting materials and used for the asymmetric ring-opening (ARO) reaction of meso epoxides with anilines. A high yield (up to 95%) of chiral ß-amino alcohols with excellent enantioselectivity (ee up to 99%) was achieved in 24-30 h at rt under optimized reaction conditions. A probable mechanism for the catalytic ARO reaction is envisaged by (1)H and (13)C NMR experiments.

Oxazoline-based organocatalyst for enantioselective strecker reactions: a protocol for the synthesis of levamisole.

A chiral oxazoline-based organocatalyst has been found to efficiently catalyze asymmetric Strecker reactions of various aromatic and aliphatic N-benzhydrylimines with trimethylsilyl cyanide (TMSCN) as a cyanide source at -20 °C to give α-aminonitriles in high yield (96 %) with excellent chiral induction (up to 98 % ee). DFT calculations have been performed to rationalize the enantioselective formation of the product with the organocatalyst in these reactions. The organocatalyst has been characterized by single-crystal X-ray diffraction analysis, as well as by other analytical methods. This protocol has been extended to the synthesis of the pharmaceutically important drug molecule levamisole in high yield and with high enantioselectivity.

Asymmetric aminolytic kinetic resolution of racemic epoxides using recyclable chiral polymeric Co(III)-salen complexes: a protocol for total utilization of racemic epoxide in the synthesis of (R)-Naftopidil and (S)-Propranolol.

Chiral polymeric Co(III) salen complexes with chiral ((R)/(S)-BINOL, diethyl tartrate) and achiral (piperazine and trigol) linkers with varying stereogenic centers were synthesized for the first time and used as catalysts for aminolytic kinetic resolution (AKR) of a variety of terminal epoxides and glycidyl ethers to get enantio-pure epoxides (ee, 99%) and N-protected ß-amino alcohols (ee, 99%) with quantitative yield in 16 h at RT under optimized reaction conditions. This protocol was also used for the synthesis of two enantiomerically pure drug molecules (R)-Naftopidil (α1-blocker) and (S)-Propranolol (ß-blocker) as a key step via AKR of single racemic naphthylglycidyl ether with Boc-protected isoproylamine with 100% epoxide utilization at 1 g level. The catalyst 1 was successfully recycled for a number of times.

Synthetically amenable amide derivatives of tosylated-amino acids as organocatalysts for enantioselective allylation of aldehydes: computational rationale for enantioselectivity.

A phenylalanine derived chiral amide is developed that serves as an effective organocatalyst for the reaction of allyltrichlorosilane with aryl, hetero-aryl and α,ß-unsaturated aldehydes to afford the desired homoallylic alcohols in good yield (up to 90%) and high enantioselectivity (up to 99%). The experimental results and DFT calculations suggest that para substituted aromatic aldehydes as substrate show higher ee in the product than their ortho/meta counterparts. The (1)H and (13)C NMR spectra study corroborated the calculated results. The chiral organocatalyst can be easily synthesized from optically pure phenylalanine in two simple steps with 90% overall yield.

DNA binding, antioxidant activity, and DNA damage protection of chiral macrocyclic Mn(III) salen complexes.

We are reporting the synthesis, characterization, and calf thymus DNA binding studies of novel chiral macrocyclic Mn(III) salen complexes S-1, R-1, S-2, and R-2. These chiral complexes showed ability to bind with DNA, where complex S-1 exhibits the highest DNA binding constant 1.20 × 10(6) M(-1). All the compounds were screened for superoxide and hydroxyl radical scavenging activities; among them, complex S-1 exhibited significant activity with IC(50) 1.36 and 2.37 µM, respectively. Further, comet assay was used to evaluate the DNA damage protection in white blood cells against the reactive oxygen species wherein complex S-1 was found effective in protecting the hydroxyl radicals mediated plasmid and white blood cells DNA damage.

Modified asymmetric Strecker reaction of aldehyde with secondary amine: a protocol for the synthesis of S-clopidogrel (an antiplatelet agent).

A first approach for catalytic asymmetric Strecker reaction of aldehydes with a secondary amine in the presence of sodium fluoride using hydroquinine as chiral catalyst was developed. The catalytic system gave α-aminonitriles in excellent yields (up to 95%) and high enantioselectivities (er up to 94:6). The efficacy of the chiral product was successfully fulfilled in the improved synthesis of (S)-clopidogrel (an antiplatelet agent).

C2-symmetric recyclable organocatalyst for enantioselective Strecker reaction for the synthesis of α-amino acid and chiral diamine--an intermediate for APN inhibitor.

Recyclable chiral amide-based organocatalyst 5 efficiently catalyzed asymmetric Strecker reaction of various aromatic and aliphatic N-benzhydrylimines with ethyl cyanoformate as cyanide source at -10 °C to give a high yield (95%) of α-aminonitriles with excellent chiral induction (ee, up to 99%) with the added advantage of recyclability. Based on experimental observations a probable mechanism was proposed for this reaction. This protocol with catalyst 5 was extended for the synthesis of (R)-phenylalanine and pharmaceutically important drug intermediate (R)-3-phenylpropane-1,2-diamine in high yield with high enantioselectivity.

Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic Co(III)-salen complexes: a practical strategy in the preparation of (R)-mexiletine and (S)-propranolol.

A chiral cobalt(III) complex (1e) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R-(-)-1,2-diaminocyclohexane with trigol bis-aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47% with respect to the epoxides, 53% with respect to the diols) and high enantioselectivity (ee>99% for the epoxides, up to 96% for the diols) were achieved in 2.5-16 h. The Co(III) macrocyclic salen complex (1e) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)-mexiletine and (S)-propranolol.

Influence of chirality of V(V) Schiff base complexes on DNA, BSA binding and cleavage activity.

New chiral V(V) Schiff base complexes (S)-[VO(OMe)L] and (R)-[VO(OMe)L] were synthesized and characterized by microanalysis, infrared (IR), UV-Visible, Circular dichroism (CD) spectroscopy and single crystal X-ray studies. The interaction of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA) protein showed chiral expression DNA/protein binding strength. The influence of chirality was also observed in cytotoxicity assay of Hep 2 cells. (R)-[VO(OMe)L] enantiomer exhibited higher binding constant (5 ± 1 × 10(5) M(-1)) as compared to (S)-[VO(OMe)L] (8 ± 1 × 10(4) M(-1)). The fluorescence quenching, thermal melting and viscosity data suggest DNA surface and/or groove binding nature of the complexes and electrophoresis studies also showed greater activity for (R)-[VO(OMe)L] in cleaving DNA and protein as against (S)-[VO(OMe)L].

Enantioselective desymmetrization of meso-epoxides with anilines catalyzed by polymeric and monomeric Ti(IV) salen complexes.

The active catalysts for the enantioselective ring opening (ARO) of meso-stilbene oxide, cis-butene oxide, cyclohexene oxide, cyclopentene oxide, and cyclooctene oxide with various substituted anilines were generated in situ by the reaction of Ti(O(i)Pr)(4) with poly-[(R,R)-N,N'-bis-{3-(1,1-dimethylethyl)-5-methylene salicylidene} cyclohexane-1,2-diamine]-1 and (1R,2R)-N,N'-bis[3,5-di(tert-butyl)salicylidene] cyclohexane-1,2-diamine-2. These catalysts in the presence of nonracemic imine as an additive provided ß-amino alcohol in excellent yield (99%) and chiral purity (enantiomeric excess (ee) up to 99%) for the ARO of meso-stilbene oxide with aniline. The same protocol was less effective for the ARO of cyclic epoxides; however, when triphenylphosphine was used as an additive, there was a significant improvement in catalyst performance for the ARO of cyclohexene oxide (yield, 85-90%; ee, 63-67%). Both in situ generated polymeric and monomeric catalysts performed in a similar manner except that the polymeric catalyst Ti(IV)-1 was more active and recycled several times with retention of enantioselectivity when compared with the monomeric catalyst Ti(IV)-2, which was nonrecyclable.

Influence of chirality using Mn(III) salen complexes on DNA binding and antioxidant activity.

Chiral Mn(iii) salen complexes S-1, R-1, S-2, R-2, S-3 and R-3 derived from the respective chiral salen ligands, viz., (1S,2S)-N,N'-bis-[3-tert-butyl-5-chloromethyl-salicylidine]-1,2-cyclohexanediamine S-1'/(1R,2R)-N,N'-bis-[3-tert-butyl-5-chloromethyl-salicylidine]-1,2-cyclohexanediamine R-1'/(1S,2S)-N,N'-bis-[3-tert-butyl-5-N,N'N'triethylaminomethyl-salicylidine]-1,2-cyclohexanediamine dichloride S-2'/(1R,2R)-N,N'-bis-[3-tert-butyl-5-N,N'N'triethylaminomethyl-salicylidine]-1,2-cyclohexanediamine dichloride R-2'/(1S,2S)-N,N'-bis-[3,5-di-tert-butylsalicylidene]-1,2-cyclohexanediamine S-3' and (1R,2R)-N,N'-bis-[3,5-di-tert-butyl-salicylidene]-1,2-cyclohexanediamine R-3', were synthesized. Characterization of the complexes was done by microanalysis, IR, LC-MS, UV-vis. and circular dichroism (CD) spectroscopy. Binding of these complexes with calf thymus DNA (CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements, circular dichroism measurements, thermal denaturation study and observation of their different antioxidant activities. Among all the complexes used, the best result in terms of binding constant (intercalative) (130.4 x 10(4)) was achieved with the complex S-1 by spectroscopic titration. The complex S-1 showed strong antioxidant activity as well.

Heterogeneous chiral copper complexes of amino alcohol for asymmetric nitroaldol reaction.

Chiral amino alcohols supported on mesoporous silicas were synthesized and evaluated as a new class of chiral ligands in copper-catalyzed nitroaldol reaction under heterogeneous and mild reaction conditions. The activity and enantioselectivity of the present catalytic system is immensely influenced by the presence of achiral and chiral bases as an additive. The heterogenized chiral copper(II) complex of amino alcohol was found to be an effective recyclable catalyst for the nitroaldol reaction of different aldehydes such as aromatic, aliphatic, alicyclic, and α-ß unsaturated aldehydes to produce nitroaldol products with remarkably high enantioselectivity (≥99%) and yields.

Enantioselective cyanoformylation of aldehydes catalyzed with solid base mediated chiral V(V) salen complexes.

Polymeric and monomeric V(V) chiral salen complexes-catalyzed enantioselective ethyl cyanoformylation of aldehydes using ethyl cyanoformate as a source of cyanide was accomplished in the presence of several basic cocatalysts viz., NaOH, KOH, basic Al2O3 and hydrotalcite. Excellent yield (>95%) of chiral ethyl cyanohydrincarbonate with high enantioselectivity up to 94% was achieved in 24-36 h when hydrotalcite was used as an additive. The polymeric catalyst 1 is more reactive than the monomeric catalyst 2 to produce chiral ethyl cyanohydrincarbonate in high optical purity. The chiral polymeric catalyst 1 and cocatalysts hydrotalcite and basic alumina used in this study were recoverable and recyclable several times with retention of its performance.