Current Organocatalysis - Volume 5, Issue 1, 2018

Background: A heterocyclic compound containing Nitrogen linkage attracts interest in its synthesis in which cyclization reaction is conducted using suitable linear compounds. These compounds reported having biological effects such as anti-tumor, antibacterial, antidepressant, analgesic and antiviral activities. An efficient One-Pot protocol for the synthesis of 5-amino-1H-pyrazole-4- carbonitrile and its derivative using aromatic aldehyde, malononitrile, phenylhydrazine and Mg-Fe hydrotalcite as a heterogeneous catalyst at ambient temperature. Hydrotalcite also known as layer double hydroxide has a layer structure in which anionic species such as carbonate and hydroxide located in the interlayer region, has been reported as drug delivery agent, ion - exchanger and catalyst. Methods: Catalyst synthesized by co-precipitation method and characterization of catalyst carried out using an analytical technique such as XRD, TGA and SEM. The catalyst is used for the synthesis of substituted 5-amino-1H-pyrazole-4-carbonitrile heterocyclic moieties. Molecules are characterized using 1H NMR and 13C NMR. Results: Hydrotalcite of the various molar ratio of Mg/Fe was synthesize and screen for reaction. Catalyst characterization was done using XRD and TGA matched with the reported literature. Solvent, catalyst quantity and catalyst reusability also screen for reaction. Basicity study was done as per literature survey (Hammet indicator method). One pot methodology of synthesis applies for all substituted organic molecules. Conclusion: The calcined Mg-Fe hydrotalcite with a molar ratio of 3:1 derived from calcinations was found to be the suitable catalyst that gives the highest basicity and best catalytic activity. This procedure offers several advantages over reported methods including shorter reaction time, high yield and simple work-up procedure. Calcined hydrotalcite was found to be an effective catalyst for the synthesis of 5-amino-1H-pyrazole-4-carbonitrile and its derivatives at room temperature conditions. The catalytic activities of the calcined hydrotalcite show a striking correlation with their corresponding basic properties. This process has an advantage over the other reported methodology such as Non-toxic, reusable catalyst, convenient and cost-effective.

Background: To investigate the multicomponent organic synthesis of the biologically important spiro-oxindoles, spiro-acenaphthoquinone and spirochromenes scaffolds by using Amberlite IRA-400 Cl resin as catalyst in an aqueous medium. Methods: Three-component synthesis of spiro components has been achieved by the reaction of isatin/ acenaphthoquinone/ninhydrin, activated methylenes, and 1,3-dicarbonyl compounds under catalytic amount of Amberlite IRA-400 Cl resin in an aqueous medium. This protocol is significant due to its environmentally benign nature, efficiency, and easy handling. Results: A large number of spiro heterocyclic compounds have been synthesized by using efficient and environmentally benign Amberlite IRA-400 Cl resin catalyst. The synthesized compounds have displayed considerable antimicrobial activities against human pathogenic bacteria and fungi. The in silico studies revealed that these compounds are good antimicrobial agents as it showed lower binding energy and higher binding affinity towards the active binding pocket in the receptors transglycosylase of bacteria and glucoamylase of fungi. Conclusion: A number of spirochromene, spiroacenaphthylene and spiro-oxindoles derivatives have been synthesized using Amberlite IRA-400 Cl resin as catalyst in water medium. Selective synthesized compounds 4h, 4j, 6d and 6g have been proved to be antimicrobial agent against the entire test pathogens compared to commercial agents. Molecular docking studies revealed that even at a low concentration with exhibit lower binding energies and higher binding affinity in order to maintain the stable protein-ligand binding complex with the enzymes transglycosylase of bacteria and glucoamylase of fungi proves the compounds are possess strong antimicrobial property.

Background: L-proline organocatalyst was supported on graphene oxide/Fe3O4 nanocomposite by using non-covalent immobilization technique. Methods: The mixture of the dried GO/Fe3O4 (1 g) and L-proline (0.5 g) was sonicated in deionized water for 0.5 h and further stirred at room temperature for 24 h. The prepared GO/Fe3O4/L-proline nano hybrid was separated by an external permanent magnet and dried under vacuum. Results: Hydrogen bonding interactions between L-proline and graphene oxide support made the organocatalyst to be easily recoverable using an external magnet. The prepared heterogeneous catalyst was well characterized using FTIR, TGA, DTG, XRD, TEM, SEM and elemental analysis techniques. Gaussian statistics measuring was used to calculate the median size of Fe3O4 nanoparticles.This novel superparamagnetic graphene oxide/Fe3O4/L-proline efficiently catalyzed the synthesis of 3,3′- diaryloxindoles derivatives in the reaction of indole and isatin and good to excellent yields were obtained in ethanol under reflux condition. Conclusion: This method improves the thermal stability of L-proline organocatalyst. The results showed that immobilized L-proline on GO/Fe3O4 nanocomposite has better catalytic activity than pristine L-prolin at the same weight ratios. GO/Fe3O4/l-proline catalyst can be recovered simply by applying an external magnet and reused at least for eight runs for the one-pot pseudo three-component synthesis of 3,3′-diaryloxindoles derivatives.

Background: Biphenyl derivatives are an important component of many natural products and used in the treatment of conditions such as anxiety disorders, infections, and insomnia. In addition, the synthesis of these molecules is very important due to their kinase inhibitory effect as well as their antibacterial and antifungal effects. In this study, highly efficient and reusable Pd/AlO(OH) Nanoparticles (NPs) were used as an alternative heterogeneous catalysts system for the coupling reactions. Methods: Pd/AlO(OH) Nanoparticles (NPs) was characterized by SEM, XRD and TEM. Later, Pd/AlO(OH) nanoparticles were performed for coupling reactions. At the end of the reaction, the main products were checked with GC and the GC yield calculated. The desired biaryl products were successfully obtained within 2 h with good yields in the presence of Pd/AlO(OH) nanoparticles. Results: The morphologies of the Pd/AlO(OH) NPs were characterized by scanning electron microscopy (SEM) and x-ray diffraction (XRD). The determination of the appropriate reaction conditions for the desired biaryl products is of crucial importance for successful synthesis. For this purpose, optimization of the conditions for conversion of iodobenzene to biphenyl.was carried out in detail. The reusability of the PdAlO(OH) NPs was also examined for Suzuki Cross-Coupling Reaction. On the other hand, the high temperature and type of catalyst are the factors that make it easier to reach the activation energy. For this reason, the comparison of the designed catalytic system with recently published works are given for Suzuki cross-coupling of bromobenzene with aryl boronic acid. Last but not least, the reaction mechanism of the Suzuki cross-coupling reaction has been entirely identified in the presence of PdAlO(OH) NPs. Conclusion: A novel method was developed for the synthesis of biphenyl derivatives in a short time with high yields by the help of Pd/AlO(OH) NPs at room temperature. As starting materials, neither phenylboronic acid, nor aryl halide derivatives are water soluble, so it was desirable to conduct the reactions in water/isopropyl alcohol as an eco-friendly solvent. Thus, the developed method is both ecofriendly and economical and can be considered as a viable alternative to prior methods appearing in the literature.

Background: In recent times sustainable organic transformations are the challenge for the chemist in areas like environment, health, social sector and to overcome these troubles, it is planned to develop simple and facile methods to carry organic reaction under benign media. Literature survey revealed nano magnetite supported heterogeneous catalysis is a growing field in catalytic science with huge application in organic synthesis. So in this present article our focus is on the synthesis of nanomagnetite supported cysteine organocatalyst and their application in organic synthesis. Methods: Nanocat-ferrite-L-cysteine was prepared by simple stirring technique in aqueous media followed by dehydration technique. The prepared catalyst is well characterized by some analytical system like FT-IR, TEM and FEG-SEM-EDS spectroscopy. This functionalised nanocat-Fe-Cys was employed in the synthesis of bis(indolyl) methanes under solvent-free conditions. The % conversion of products was checked by thin layer chromatography and the synthesized compounds were further confirmed by NMR techniques. Results: To check the competency of synthesized nanocat-Fe-Cys for bis(indolyl) methanes reaction, a benign one step transformation reported under microwave irradiation method superiorly over conventional oil bath method. The products were obtained in very clean & noticeably higher yield (80- 94%). The catalyst ferrite cysteine was found to be recyclable for ten times without any remarkable damage in catalytic activity. Conclusion: In present research article, the synthesis of highly active, recyclable & versatile organo nanocatlyst ferrite-cysteine reported using easily available precursor via the simple impregnation method. The MNPs was found to be stable under investigated conditions & highly effective in the synthesis of bis(indolyl) methanes derivatives. The simple eco-friendly method, mild reaction conditions, economically affordable and good product yields concentrate this attractive sustainable protocol.

Introduction: 4H-furo[3,4-b]pyran, 4H-benzo[g]chromene and1H-benzo[b]xanthene derivatives have been efficiently synthesized in water using glycine as organocatalyst. Methods and Results: The key aspects of the present method are (1) The use glycine as organcatalyst which is metal free and in expensive (2) The synthesis was performed in water which is an ecofriendly solvent. Conclusion: Our reported protocol has several advantages like environmentally benign reaction conditions, operational simplicity, high atom economy, cost effectiveness and excellent yield.

Background: A facile, effective and green methodology has been developed for the synthesis of 1,2-dihydropyridine-3,5-dicarbonitriles (3a-h) and ethyl 4H-pyran-2-carboxylates (5a-d) through one-pot, two or three-component condensation reactions consisting of aromatic aldehydes, malononitrile and cyanoacetic acid hydrazide or ethyl benzoylpyruvate in the presence of 1,4-diazabicyclo [2.2.2]octane, DABCO, in aqueous ethanol at room temperature. This work consistently has advantages as high yields, short reaction times, mild reaction condition, simple procedure and low toxicity. Methods: To a solution of arylaldehydes (1.0 mmol) and malononitrile (1.0 mmol) DABCO (20 mol%) H2O/EtOH (1:1, 10 mL) were added. The mixture was stirred for 15 min then cyanoacetic acid hydrazide or ethyl benzoylpyruvate (1.0 mmol) was added to the mixture. The mixture was stirred at ambient temperature for 90-120 min (the progress of the reaction being monitored by TLC and using hexane/AcOEt 1:1 as an eluent). The resulting solid was filtered, washed with cold H2O for removal of the catalyst, then crystallized from EtOH. All of the resulting structures were confirmed by their physical constant, IR, 1H NMR, 13C NMR spectroscopy and elemental analyses. Results: Convenient and practical protocols to 1,2-dihydropyridine-3,5-dicarbonitriles (3a-h) and 4Hpyran- 2-carboxylates (5a-d) from aromatic aldehydes, malononitrile and cyanoacetic acid hydrazide or ethyl benzoylpyruvate using DABCO as an efficient catalyst are described. Conclusion: In conclusion, we have presented DABCO as a mild and efficient catalyst for the synthesis of the corresponding 1,2-dihydropyridine-3,5-dicarbonitriles (3a-h) and 4H-pyran-2-carboxylates (5a-d). DABCO is inexpensive, nontoxic, easy to handle, and can act as a green medium. Simple work-up procedure, short reaction times, excellent yields of product with better purity, green solvent and mild condition are advantages of this protocol.

Background: The catalytic asymmetric Michael addition of carbonyl compounds to nitrostyrenes is of interest because the reaction establishes two adjacent stereocenters in one step and the product γ-nitrocarbonyl compounds are synthetically useful intermediates. This reaction has been exhaustively investigated with β-nitrostyrenes as the Michael acceptors but the use of α-nitrostyrenes, for establishing nonadjacent stereocenters in the product, is not well studied. Objective: The aim of this study was to investigate the organocatalytic asymmetric, enamine mediated, Michael addition of cyclic ketones and α,α-disubstituted aldehydes to in situ generated α- nitrostyrenes and to optimize the diastereoselectivity and the enantioselectivity of the reaction. Method: The Michael addition reactions of a series of ketones and aldehydes with a variety of α- nitrostyrenes, that were generated in situ form nitroacetates, were conducted in a selection of solvents in the presence of chiral pyrrolidine catalysts and protic acid additives. Conditions that provided the highest asymmetric induction were identified. Results: Under optimized conditions, γ-nitroketones (up to 99% ee) and γ-nitroaldehydes (up to 79% ee) were obtained. The synthetic utility of the γ-nitroladehydes was demonstrated by converting a representative Michael adduct into a functionalized pyrrolidine. Conclusion: The enamine mediated Michael addition of cyclic ketones and α,α-disubstituted aldehydes to in situ generated α-nitrostyrenes proceeds with moderate to good levels of 1,3-asymmetric induction. The methodology complements the well-known Michael addition reactions of β- nitrostyrene, and provides access to enantiomerically enriched γ-aryl-γ-nitro ketones and γ-aryl-γ-nitro aldehydes.

Background: 2-Amino-4H-chromenes are associated with diverse biological properties, its synthesis has gained significant consideration. Two enantiomers of same compounds have different chemical properties, the two enantiomers of a molecule interact differently with a living organism. In this consideration researchers have started investigation for single enantiomer of chromen molecules. Many asymmetric reactions have been recorded using chiral organocatalysts. Theses catalysts help to provide stereo controlled organic reactions. The field of asymmetric synthesis of chromenes molecules is not much studied. This report describes asymmetric synthesis of chromenes molecules using organocatalysts. Methods: We have designed and synthesized various organocatalysts with different structural framework based on (S) -2-amino-N-[(1R, 2R) - 2 - (4-methylphenylsulfonamido) cyclohexyl] aryl / sulfon amide. The synthesized organocatalysts were studied in the model reaction between 5, 5- dimethylcyclohexane-1, 3-dione and 2-benzylidenemalononitrile to give 2-amino-5-oxo-4-phenyl-5, 6, 7, 8-tetrahydro-4H-chromene-3-carbonitrile as the product. The reaction was optimized and scope of the reaction was applied to various 2-arylidenemalononitriles to obtain enantiopure 2-Amino-4Hchromenes. Result: The efficiency of synthesized chiral bifunctional organocatalysts was tested in model reaction between 5, 5-dimethylcyclohexane-1, 3-dione and 2-benzylidenemalononitrile. Out of all synthesized catalysts, the organocatalyst (S) -2-amino-N-[(1R, 2R) - 2 - (4-methylphenylsulfonamido) cyclohexyl] butanamide was proved to be an efficient for the reaction. The reaction was also optimized in terms of solvent and catalytic loading. Optimized reaction conditions were used for different substrates to give corresponding products in excellent yields and good to moderate enantioselectivities. Conclusion: we have developed an efficient organocatlyzed route for asymmetric synthesis of 2- amino-4H-chromens using chiral organocatalyst and silica gel as an additive. We synthesized various organocatalysts with different structural framework based on (S) -2-amino-N-[(1R, 2R) - 2 - (4- methylphenylsulfonamido) cyclohexyl] aryl / sulfon amide and employed in the synthesis of 2-amino- 5-oxo-4-phenyl-5, 6, 7, 8-tetrahydro-4H-chromene-3-carbonitrile. The organocatalysts (S) -2-amino- N-[(1R, 2R) - 2 - (4-methylphenylsulfonamido) cyclohexyl] butanamide was proved to be ideal catalyst for the reaction and catalyzed broad range of substrates to give desired product at room temperature. In addition, some advantageous features of the method are mild reaction conditions, excellent yields with high enantioselectivities and easy work up of procedure.