Current Organocatalysis - Volume 11, Issue 3, 2024

An efficient, 5-Sulphosalicylic acid (5-SSA) catalysed green protocol for the synthesis of Indenopyrazolones and its derivatives is reported under metal-free conditions in an ethyl lactate system. The main advantages of this procedure include the use of an organocatalyst, ethyl lactate as a recyclable promoting media, practical simplicity, high yields, shorter reaction times, atom economy, and ease of isolation of the product. These results showed that aromatic aldehydes with electron- withdrawing groups reacted faster than aldehydes with electron-releasing groups as expected. According to these observations, aromatic aldehydes with electron-withdrawing groups reacted more quickly than aldehydes with electron-releasing groups.

Background: Epoxides are widely useful in various fields such as pharmaceuticals, pesticides, cosmetics, polymer synthesis, fragrance compounds, and food additives. However, the synthesis of epoxides involves heavy metal catalysts and toxic, unstable organic catalysts which causes serious environmental and safety concerns. In recent years, biocatalysts have received a great deal of interest in the synthesis of olefin-derived epoxides due to their mild reaction conditions, environmental friendliness, good selectivity, and sustainability. This study focuses on catalases as a biocatalyst for potential epoxidation reactions of olefins. Objective: To determine the possibility of using biocatalyst catalase from a novel source Sechium edule (squash) for epoxidation of olefins in the presence of H2O22. Methods: UV-Vis spectrophotometer was used to monitor the formation of epoxide from substrates- cyclohexene, cinnamic acid, cinnamaldehyde, furfural in acetonitrile solvent and a suitable aliquot of the enzyme solution in the presence of H2O22. The products formed were analyzed using FTIR and GC-MS. For the immobilized enzyme, chitosan beads activated with TPP were used in place of the enzyme and a similar procedure was followed for the analysis. Results: Four different olefin substrates (cyclohexene, cinnamic acid, cinnamaldehyde, and furfural) were selected to study the catalysis reaction of epoxidation by the catalase enzyme. The course of the epoxidation was monitored by UV-Vis, FTIR, and GC-MS methods. However, under optimized reaction conditions and spectral analysis, further confirmed by GC-MS, data showed only epoxide formation from cyclohexene. CAT completely catalyzed other olefins like furfural, cinnamic acid, and cinnamaldehyde into its degraded products biochemically. Therefore, cyclohexene was selected for further immobilization studies and the identified metabolites of olefins and their degradation mechanism. Major biodegradation products of cinnamic acid were found to be styrene( m/z 104.0) and benzaldehyde(m/z 105.0). GC-MS data of biotransformation of cinnamaldehyde, identified 2,4 dimethyl benzaldehyde(m/z 133) as the main product. The catalytic biotransformation of furfural investigated by GC-MS data identified 2,5 dimethyl benzaldehyde (m/z 133), dodecanol (m/z 181) and Pentanoic acid, 5 hydroxy, 2,4 dibutyl phenyl ester(m/z 306) as the major product. Three major oxidized products were detected in GC-MS data from the epoxidation of cyclohexene viz., cyclohexane diol(m/z 116), cyclohexene epoxide-1-ol(m/z 110), cyclohexene epoxide-1-one(m/z 110). Conclusion: In this investigation, catalase purified from Sechium edule(squash) was developed as an efficient catalytic tool for the biotransformation of olefins and selective epoxidation of cyclohexene. Under optimized conditions, the experimental results revealed the main products found in cinnamaldehyde as benzaldehyde (m/z 133.0) and cinnamic acid as benzaldehyde (m/z 133), styrene (m/z 104.0) and benzoic acid (m/z 122.0), while the data from furfural oxidation could not be justified from previous studies. The optimal concentration of CH3CN solvent for cyclohexene epoxidation was found to be 4 mM. Enzymatic characterization of free and immobilized catalase on chitosan was investigated using cyclohexene as a variable substrate and found to be 0.017 mM, 83.33 μmol/min for Km and Vmax values, pH 6.8 and 30#154;C for free CAT and 0.03 mM, 200 μmol/min, pH 7.6 and 35#154;C for immobilized one. Immobilization increases the thermal stability of the CAT and changes the pH to alkalinity. The possible oxidation of cyclohexene was deduced as the radical chain mechanism for the generation of epoxide with the key products obtained as cyclohexane diol(m/z 116), cyclohexene epoxide-1-ol(m/z 110) and cyclohexene epoxide-1-one(m/z 110). The reusability of the biocatalytic tool opens up the opportunity to reduce the cost of various catalytic reactions. Further studies can focus on the separation and advancement of epoxide yields, improved immobilization strategy for maximum repetitive cycles, and chemo-enzymatic epoxidation on biological olefins.

Introduction: A simple and efficient one-pot synthesis of quinazolinone derivatives has been developed via a multicomponent reaction (MCR) involving the condensation of dimedone, benzaldehyde, and 2-aminobenzimidazole/2-aminobenzothiazole. Method: In this work, glucose water is used as a green, reusable, environmentally benign organocatalytic solvent system to synthesize desired products. Result: The main benefits of this one-pot method include its excellent yields, less time, cost-effectiveness, atom economy, environment benign, and easy workup. Conclusion: In conclusion, we successfully developed a green protocol for the environmentally benign synthesis of benzimidazo/benzothiazolo quinazolinones using glucose water as an organocatalytic medium.

Background: Multistranded foldamers mimic biopolymer architecture, through the assembly and folding of intrinsically flexible polymeric chains attached to polyol core have been synthesised here. The synthesised dendritic motifs possess helical cavities with properly arranged active sites. As these cavities are large enough to accommodate guest molecules, their application as synthetic foldamer catalyst were investigated in Knoevenagel and Mannich reactions. Methods: It is presumed to be the potentiality of dendritic foldamers to form reverse micelle in the interior of helical motif containing many reactive sites. Results: Inside the dendritic foldamer, the substrates are adequately concentrated, work together in cooperation for ligand-binding, and stabilize the transition state as in enzymes that helps to accelerate the reaction rate many times greater than in bulk solution. Conclusion: An unrivalled reaction rate and high yield of products were obtained within a short time in both Knoevenagel and Mannich reactions by using dendritic foldamers as catalysts.

Background: A simple, convenient and environmentally benign green protocol has been developed for the one-pot synthesis of 4-substituted-1,5-benzodiazepines through three-component reaction of 1,2-diamine, 1,3-cyclic diketone with an aldehyde catalyzed by water extract of onion. The reaction conditions were optimized and the scope of the reaction was extended to various 1,2- diamines, 1,3-cyclic diketones and aldehydes. The main advantages of this method are good to excellent yields, easy workup, simple experimental procedure, and an ability to tolerate a variety of functional groups which gives cost-effective as well as green rewards. The structure of compound 5f was confirmed by single crystal X-ray analysis. Objective: A methodology developed for the synthesizing of 4-substituted 1,5-Benzodiazepine derivatives via enaminones intermediates using 1,2-diamine, 1,3-cyclic diketone and aldehyde in environmentally friendly ethanol as medium. Methods: As a more environmentally friendly catalyst for producing products containing benzodiazepines using aqueous extract of onion. The devised method was proven reliable, non-toxic and greener solvent with quick work-up to produce the intended product. Results: Here, using a one-pot, three-component reaction with a dimedone, 1,2-diamine and range of aldehyde while using water extract of onion as a catalyst. The acquired experimental results showed that the employed synthesis methodology is a straightforward procedure that offers various benefits, including sustainability, easy separtion from the reaction medium. Conclusion: We have developed a sustainble approach for synthesizing benzodiazepine from radily available precursors under mild reaction conditions.

Aims: We aimed to conduct an L-Pipecolic acid-catalyzed synthesis of 2,4,5-trisubstituted imidazoles and N-cycloalkyl-2,4,5- trisubstituted imidazoles to develop a novel synthetic route followed by the synthesis of novel series of compounds. Background: A rapid, highly efficient, and greener approach for the synthesis of a series of 2,4,5- trisubstituted imidazoles and N-cycloalkyl-2,4,5- trisubstituted imidazoles were developed via onepot multicomponent reaction (MCRs). Objective: The objective of the current study was to discover a new and highly efficient organocatalyzed synthetic route for the synthesis of 2,4,5-trisubstituted imidazoles and 1,2,4,5-tetrasubstituted imidazoles followed by the synthesis of novel series of compounds. Method: L-Pipecolic acid was used as a bifunctional catalyst in one-pot multicomponent reaction (MCRs) for the cyclo-condensation of 1,2-dicarbonyl compounds, substituted aromatic aldehydes, cycloalkyl amines, and ammonium acetate in ethanol at moderate temperature. Purification of compounds was performed through a non-chromatographic method. Physical and spectral data analysis was carried out to characterize the products. Result: Employing our newly developed L-Pipecolic acid-catalyzed synthetic route, a series of total twenty-three compounds incorporating 2,4,5-trisubstituted imidazoles (3a-n) and N-cycloalkyl- 2,4,5- trisubstituted imidazoles (4a-i) were synthesized successfully, and a plausible reaction mechanism is proposed based on the results of the experiment. Conclusion: All the derivatives were afforded high purity and excellent yields (92–97%) in a short reaction time (45–90 min). The newly developed synthetic route is rapid and robust and could be applicable for the synthesis of pharmaceutically active compounds.