Current Organocatalysis - Volume 7, Issue 2, 2020

Background: Quinoline is a type of N-based organic heterocyclic biologically active compound. Quinolines have grasped the interest of scientists because of their wide scope of applications. Several methods have been developed for the synthesis of quinoline and its derivatives. In this study, a new, efficient, simple, one-pot synthesis of the substituted quinolines was developed by using palladium nanoparticles as a catalyst. Methods: Catalyst synthesized by algal extract of green alga Botryococcus braunii and palladium acetate solution, and characterized by different instrumental techniques like FTIR, SEM, and XRD. The synthesized palladium nanoparticles explored for the catalytic activity in the synthesis of quinoline derivatives by the use of 2-aminobenzyl alcohol in toluene with acetyl derivatives followed by the addition of potassium hydroxide. The formation of the product was confirmed by 1HNMR, 13C NMR, and electron ionization mass spectra. Results: The formation of palladium nanoparticles characterized by visual observation means the color change from light pale yellow to dark brown indicates the reduction of palladium ions into palladium nanoparticles. Synthesized palladium nanoparticles characterized by FTIR spectrum of the algal extract of green algae B. braunii for the presence of proteins, lipids, carbohydrates, carotenoids, vitamins and other secondary metabolites in algal extract, which function as active components for bioreduction. The morphology of the catalyst was confirmed by SEM and X-ray diffraction measurements for shape, crystalline nature and size. The synthesized palladium nanoparticles explored for the catalytic activity in the synthesis of quinoline derivatives by use of 2-aminobenzyl alcohol in toluene and added acetyl derivatives followed by the addition of potassium hydroxide. In order to establish the optimum heating method, a comparative study between conventional and microwave heating method was carried out in the presence of palladium nanoparticles as a catalyst. Conclusion: This protocol provides a convenient and practical procedure for the preparation of quinoline derivatives from 2-aminobenzyl alcohol, acetyl derivatives, potassium hydroxide and palladium nanoparticles as a catalyst. This protocol will be helpful in synthesizing other quinoline derivatives and several organic heterocycles which are used in different fields such as biological, industrial, pharmaceutical, chemical, medical, etc.

Background: Phase transfer catalysis technique is recognized as an attractive method for synthesizing several organic compounds under heterogeneous reaction. Methods: In this study, the effect of Multi-site Phase-Transfer Catalyst (MPTC) was tested during the synthesis of 1-(4-nitrophenyl)-1-indole from 1-chloro-4-nitrobenzene (CNB) and indole in a heterogeneous solid-liquid condition using sodium hydroxide at 50°C. Results: In a synergetic condition, in the presence of MPTC the conversion of 1-chloro-4- nitrobenzeneyield was increased, which is proved the efficacy of this catalyst. In addition, the rate of this reaction was also enhanced by the change in volume of water. Conclusion: The apparent reaction rate was found to be of pseudo-first-order kinetics. MPTC is a promising tool for many organic reactions. Therefore, increase the rate constant can be achieved by various parameters, such as temperature, MPTC, sodium hydroxide, and stirring speed.

Introduction: The N-heterocyclic compounds have been extensively studied in pharmaceutical industries. Furthermore, syntheses of such compounds employing organo-catalyst have been associated with sustainable technology. Methods: The synthesis of new, stable ionic liquids and their catalytic applications in one-pot multicomponent Biginelli reaction is presented. The method provides broad substrate scope, yielding the corresponding 3,4-dihydropyrimidin-2(1H)-ones and 3,4-dihydropyrimidin-2(1H)-thiones, in good to excellent yields, respectively. Results and Conclusion: The developed reactions are associated with certain advantages, short reaction time and sustainable conditions. The protocol has advantages eco-friendly procedure, recovery and reusability of catalyst, which showed consistent activity.

Background: N-Heterocyclic Carbenes (NHCs) have emerged as ubiquitous species having applications in a broad range of fields, including organocatalysis and organometallic chemistry. Since Arduengo and co-workers first isolated a bottlable NHC, namely imidazol-2-ylidene derivative, these nucleophilic species have attained a prominent place in synthetic organic chemistry. The NHC-induced non-asymmetric catalysis has turned out to be a really fruitful area of research in recent years. Methods and Results: The quantitative aspects of the experimental and theoretical investigation of isomerization of dimethyl maleate to dimethyl fumarate catalyzed by an N-heterocyclic carbene (NHC), namely 3-benzylbenzothiazolylidene are being reported for the first time. Dimethyl maleate on treating with 3-benzylbenzothiazolylidene carbene (10 mol%), generated in situ from the reaction of 3- benzylbenzothiazolium bromide with triethylamine in diethyl ether at room temperature under nitrogen atmosphere isomerizes quantitatively to dimethyl fumarate. Theoretical investigation of a model reaction scheme at the wB97XD/6-31+G(d) level reveals that initial attack of the carbene, which is the ratedetermining step, is followed by rotation about the C-C bond in preference to a higher activation free energy path involving proton abstraction. The species so formed splits off the carbene to yield dimethyl fumarate. Eyring equation has been used to rationalize the effect of temperature on the isomerization rate. Conclusions and Perspective: 3-Benzylbenzothiazolylidene carbene catalyzes the isomerization of dimethyl maleate to its trans-isomer. This carbene can be used in other catalytic reactions, such as acyloin condensation and Stetter reaction.

Background: A convenient and efficient methodology for the synthesis of quinazolin- 4(3H)-ones from simple and readily available 2-amino benzamides and aromatic aldehydes in ethanol using Magnesium perchlorate are being reported in the present study. Good to excellent isolated yields (68-95%) of the corresponding 2-substituted quinazolinones were obtained under mild reaction conditions with excellent functional group tolerance. The affordability of the catalyst, the wide availability of the starting materials, transition metal free synthesis and the simplicity of the procedure renders the present methodology useful in organic synthesis. Objective: A maneuver methodology developed for the synthesis of quinazolin-4(3H)-ones via using Magnesium perchlorate from 2-amino benzamides and aromatic aldehydes in ethanol. Methods: 10% mol anhydrous Magnesium perchlorate in presence of ethanol give to simply rapid formation of Quinazolin-4(3H)-ones from 1 mole of 2-amino benzamides and 1 mole of aromatic aldehydes. Results: Screening results of Anti-leishmanial showed that out of the synthesized series of 12 compounds, compounds 3c, 3d, 3g, 3h and 3i showed significant antileishmanial activities (L. donavani) with IC50 values 8.39, 9.37, 9.43, 7.1 and 8.7 μM. Conclusion: In summary, we have developed convenient synthesis of quinazolin-4(3H)-one, from simple and easily available precursor employing anhydrous Mg(ClO4)2 under green conditions.

Background: Bis(indolyl) methanes (BIMs) have a wide spectrum of applications in biomedicine and agriculture as well as are present in natural products. These bisheterocyclic compounds possess vast pharmacological, including antifungal, antitubercular, anti-inflammatory, antibacterial, anticancer, anticonvulsant, antibiotic, antiviral, antimalarial, analgesic, and antidiabetic properties. BIMs scaffolds have also been employed as selective optical chemosensors for detection of some anions and cations with the naked eye. Because of the importance of these bisheterocycles, various methods have been reported for their synthesis through reaction of indole derivatives and aldehydes or ketones. Therefore, the synthesis of BIMs through different methodologies has received widespread attention in the field of organic synthesis and medicinal chemistry. Objective: In this study, the catalytic activity of phthalimide-N-sulfonic acid (PISA) as an efficient and safe solid acidic organocatalyst toward the synthesis of BIMs derivatives in ethanol is described. Methods: Indole derivatives (2 mmol), aryl/heteroaryl aldehydes (1 mmol), and PISA (10 mol%) were mixture in ethanol. The reaction mixture was stirred at room temperature for the appropriate times. After workup and separation of catalyst, the corresponding heterocyclic products were obtained through recrystallization from hot ethanol. Results: The BIMs derivatives were easily obtained via Bisindolization Reaction (BIR) of two indoles (2-methylindole and indole) with a series of aryl and heteroaryl aldehydes. The BIR was efficiently catalyzed at room temperature using PISA as an excellent organocatalyst under optimized reaction conditions. Conclusion: The reactions were implemented in simple manner and were completed within acceptable reaction times. The expected BIM products were obtained in satisfactory yields. The catalyst can be recovered and reused several times in the template reaction. This approach provides the benefits of convenience, simple operational procedure, no use of hazardous organic solvents, cheapness and ease of preparation of catalyst.

Background: A cheap and commercially available organocatalyst, 4-dimethylaminopyridine was successfully employed in the regioselective [3+2] cycloaddition of isatin-derived Morita-Baylis- Hillman carbonates with azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles in excellent yields under mild conditions. Methods: In the presence of 4-dimethylaminopyridine with a loading of 10 mol%, a series of isatinderived Morita-Baylis-Hillman carbonates reacted smoothly with azonaphthalenes in dichloromethane at room temperature to furnish 3-spiropyrazole-2-oxindoles in 72-98% yield. Results and Conclusion: In summary, we have developed reasonably cheap and commercially available 4-dimethylaminopyridine-mediated regioselective [3+2] annulations between isatin-derived Morita- Baylis-Hillman carbonates and azonaphthalenes for the construction of 3-spiropyrazole-2-oxindoles under mild conditions.

Background: Lemon peel powder was used as a natural catalyst for the synthesis of biscoumarins and 3,4-dihydropyrano[c]chromene derivatives. The catalyst is natural, biodegradable, environmentally benign and thus contributes a valuable addition to the existing sustainable methods for the synthesis of coumarin derivatives. Objective: Development of Green synthesis and use of Natural catalyst. Methods: Lemon peel powder was used as a natural, biodegradable, environmentally benign heterogenous catalyst for the synthesis of coumarin derivatives. Results: Natural lemon peel powder was successfully used as a heterogeneous catalyst for the synthesis of coumarin based heterocyclic compounds. Conclusion: In conclusion, an environmentally benign, green and one-pot multicomponent protocol has been developed for the synthesis of biscoumarins and 3,4-dihydropyrano[c]chromene derivatives using lemon peel powder as a natural and biodegradable catalyst. Lemon peel being natural, the present approach is sustainable and will highlight the emerging applications of natural resources for synthetic organic transformations. This protocol offers several advantages such as high yields, clean reaction conditions, and no pollution threat to the environment making it a useful and attractive process for the synthesis of coumarin derivatives.

Background: Present interest in catalytic bioconversions is concerned with 2 major environmental issues. (i) The replacement or substitution of oxidations which involves heavy metal salts and reagents by alternatives using H2O2 as the ecofriendly oxidant. (ii) The prominent issue is the increasing interest in the production of high chemoselectivity, regioselectivity and stereoselectivity of compounds in chemical reactions in order to achieve better byproducts. Keeping these points in view the work on peroxidases have been carried out which fullfills these two goals. Objective: To determine the enzyme activity in the available source to explore its catalytic efficiency in biotransformations of heavy metal compounds. Optimizing the effect of different oxidants for maximum activity of peroxidase and to study the nature of inhibition of peroxidase in presence of different metal ions. Methods: Enzyme extracted in large volume from Luffa aegyptiaca fruit. Peroxidase activity measured by spectrophotometric method. Peroxidase catalyzed rate of reaction was determined spectrophotometerically by making use of guaiacol as the substrate and in presence of H2O2, V2O5, VOSO4, VO(acac)2, (NH4)2(Ce(NO3)6), and (NH4)6Mo7.4H2O monitored at λmax = 470 nm. The haloperoxidase activity were assayed by monitoring the formation of halogen by UV/VIS spectra. The steady state velocity of the enzyme catalysed reaction was measured at different concentrations of metal ions like trivalent (Cr3+ and Al3+), divalent (Ca2+, Mg2+, Cd2+, Zn2+ and Ni2+) and monovalent (Na+ and K+) in the range of 0.0 mM to 100 mM at the fixed enzyme saturating concentration. Graph was plotted to determine the nature of enzyme activity inhibition. Results: Study of rate of reaction by steady state kinetics measurements confirmed peroxidase activity of order of 9.0 U in the fruit extract prepared. The oxidation potential required for the oxidation of guaiacol to tetraguaiacol is 0.575V and the reaction is irreversible. (NH4)2(Ce(NO3)6) and (NH4)6Mo7.4H2O oxidized guaiacol with the rate found to be 0.009 OD/sec in former substituent and the rate of formation of tetraguaiacol was much low in the later substituent found to be 0.003 OD/sec as compared to enzyme with rate 0.01 OD/sec. Enzyme peroxidase was able to oxidize Fe2+ and Mn2+ to Fe3+ and Mn3+ respectively in the reaction mixture. It is found that V2O5 is better oxidizing agent than H2O2 for catalytic oxidation of guaiacol as the substrate. Peroxidases in presence of H2O2 and KBr/KCl/KI act as a viable ecofriendly reagent for the halogenation reaction in organic synthesis. Nature of inhibition by Zn2+ and Ni2+ ions is competitive type. Enzyme activity is inhibited in presence of Cr3+ and Al3+ and the nature of inhibition is uncompetitive type. Conclusion: Luffa aegyptiaca is a better source of peroxidase having 9 U. UV-Visible spectrum analysis indicated that (NH4)2 (Ce(NO3)6 can substitute peroxidase enzyme under optimized conditions.( NH4)2(Ce(NO3)6 act as a cocatalyst by enhancing the activity twice. The enzyme with H2O2 and KBr/KCl/KI is a suitable environmentally suitable reagent for halogenation reaction in organic and inorganic synthesis. The rate of reaction is highest in presence of V2O5 as compared to other vanadium compounds. Thus V2O5 act as better oxidizing agent than H2O2. Chemical technology can be substituted by enzyme technology which should be developed to removal excess and toxic heavy metals. Salinity required for normal functioning of enzyme is 140mM NaCl and 90mM KCl. Enzyme activity enhanced in presence of Ca2+, Mg2+ and Cd2+ while inhibited in presence of Zn2+ and Ni2+. Nature of inhibition by Zn2+ and Ni2+ ions is competitive type. Enzyme activity is inhibited in presence of Cr3+ and Al3+ and the nature of inhibition is uncompetitive type. Extensive studies are needed to understand the mechanism of inhibition of manganese peroxidase activity by metal ions.