Current Organocatalysis - Volume 10, Issue 1, 2023

Background: In this study, a heterogeneous catalyst containing MIL-101(Cr) functionalized TEDA-BAIL was used to carry out an efficient four-component reaction between aromatic aldehydes, barbituric acid, dimedone, and aryl amines, resulting in the synthesis of a new class of pyrimido[4,5-b]quinolinetrione derivatives. Methods: Pyrimido[4,5-b]quinolinetrione derivatives were synthesized through a one-pot fourcomponent reaction between aromatic aldehydes, barbituric acid, dimedone, and aryl amines, in the presence of triethylenediamine-based ionic liquid@MIL-101(Cr) composite as a catalyst under reflux conditions. The TEDA-BAIL@MIL-101(Cr), which is a recyclable catalyst, was fully characterized by Fourier transform infrared spectrophotometry (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) and Transmission electron microscopy (TEM). Results: Four-component synthesis of pyrimido[4,5-b]quinolinetriones was catalyzed by TEDABAIL@ MIL-101(Cr) with aromatic aldehydes, barbituric acid, dimedone, and aryl amines under reflux conditions. The obtained experimental results revealed that the employed synthesis approach is a simple method that offers several advantages, including sustainability, facile separation from the reaction medium, and reusability of the catalyst after six consecutive runs without loss of activity. Conclusion: The presented method is an efficient synthesis route for the synthesis of pyrimido[4,5- b]quinolinetriones in the presence of TEDA-BAIL@MIL-101(Cr) under reflux conditions. This procedure provides multiple advantages, such as ease of execution, high yield, clean reaction conditions, shorter reaction time, and catalyst sustainability.

Background: The synthesis of 2-azapyrrolizidine scaffolds has fascinated scientists due to their potential biological activities. Objective: An efficient and environmentally sustainable synthetic method has been presented to synthesize structurally various 2-azapyrrolizidines via a three-component reaction. Methods: The condensation of aldehydes, hydantoin, and malononitrile in the presence of green and sustainable sulfamic acid as catalyst in mild conditions has been achieved. Results: The present protocol leads, in most cases, to the desired products in high yields. Conclusion: The synthetic efficiency and operational simplicity make the present procedure cost effective, time efficient and eco-friendly for the synthesis of substituted 2-azapyrrolizidines.

The synthesis of Proline-2-triethyl-ethylamide hexafluorophosphate (ILPA-PF6) (with 96% yield) and further the application during the synthesis of (R)-9-Methyl-5(10)-octaline-1,6-dione (Wieland-Miescher ketone molecule) are defined in this manuscript. The suggested protocol signifies one of the most efficient methods for the synthesis of these flexible chiral building blocks in good yield. The evident solubility of ionic liquids allows straightforward isolation of the (R)-9-Methyl- 5(10)-octaline-1,6-dione product from reaction mass. Additionally, six times catalyst recycling was considered the main conclusion of this proposed procedure. Background: The synthesis of WMK starts with the Michael Addition step, where the α, β- unsaturated ketone reacts with 2-methyl-1,3-cyclohexanedione followed by the nucleophilic attack and produces the triketone. Further, the isolated triketone goes to intramolecular Aldol Condensation, (in the Robinson Annulation reaction cascade) to get an enolate. Later, followed by the dehydrogenation reaction of enolate (to expel hydroxide ion) the desired product Wieland Miescher Ketone was isolated in good yield. The above conventional method suffers from several drawbacks like a slow reaction rate, the requirement of high boiling point solvent systems, and low reaction yield. Objective: To prepare ionic liquid-supported organocatalysts for the synthesis of stereoselective (R)- 9-Methyl-5(10)-octaline-1,6-dione Methods: This report summarizes the synthesis and its application of triethyl salt-supported prolinebased organocatalysts as recyclable and highly efficient for the asymmetric Wieland-Miescher ketone ((R)-9-Methyl-5(10)-octaline-1,6-dione). An ionic liquid-supported proline (as a catalyst) is equipped with basic proline and a significantly acidic amide moiety to promote the reaction rate, and synchronously having a specialty of ionic liquid could be easy to separate and recycle. Results: The report simply defined the WMK molecule in good yield and enantioselectivity followed by minimal ether washing. During the reaction, low catalyst loading i.e., 0.5 g of catalyst was found enough to attain the maximum yield and enantioselectivity in 2 hours. Furthermore, catalyst recycling was observed 6 times as a significant element of the suggested catalytic method. Conclusion: The synthesis of an extremely dynamic and enantioselective ILPA-PF6 catalytic approach is demonstrated in the report. The ILPA-PF6 catalyst was further modified after its characterization for use in the synthesis of the WMK molecule and the subsequent intramolecular aldol reaction of triketone. The WMK molecule was isolated with good yield and enantioselectivity followed by minimal ether washing. During the reaction, low catalyst loading i.e., 0.5 g of catalyst was found enough to get the maximum yield and enantioselectivity in 2 hours. Additionally, catalyst recycling was observed 6 times as a significant element of the suggested catalytic method.

Background: Several types of catalysts have been cited in the literature. However, the current work showed that a multi-component reaction involving aldehydes, malononitrile, and resorcinol or α/β-naphthol could produce 2-amino-4H-chromene in a more environmentally friendly manner. The reaction is optimized by both stirring and microwave methods, but the reaction carried out under microwave irradiation is found to be faster with easy separation of the product with high yield and purity. The catalyst is analyzed for the presence of elemental composition using Flame Photometry (FP) and SEM-EDX. The synthesis of 2-amino-4H-chromenes is catalyzed by the new, green catalyst HRSPLAE (Water Extract of Hibiscus Rosa Sinensis plant dry leaves ash) within 3-5 min. The final product is analyzed by FT-IR,¹H-, ¹³C-NMR, and mass spectrometry techniques and the product obtained is free from the use of chromatographic separation with isolation and yield of 80– 95%. Selected 2-amino-4H-chromene derivatives (4b and 4c) were screened for their anti-cancer and antimicrobial activity in vitro. Methods: The agro-waste sourced from Hibiscus rosa-sinensis plant dry leaves ash is utilized for the preparation of HRSPLAE catalyst, which is employed for the synthesis of 2-amino-4H-chromene derivatives under microwave irradiation. Results: 2-Amino-4H-chromene derivatives were obtained from aromatic aldehyde, malononitrile, and resorcinol or α/β naphthol catalyzed by HRSPLAE. They were comprehensively evaluated using flame emission spectrometry, SEM, and EDX. Conclusion: HRSPLAE outperforms expensive catalysts. An efficient simpler workup without column chromatography for increased yield through a new unique green method for the synthesis of 2- amino-4H-chromene derivatives has been developed.

Background: Ketone is one of the important functional groups in synthetic chemistry. For this reason, organic chemists focused on the synthesis of ketone starting from various functionalities since nineties. One of the method deals with the conversion of carboxylic acids to ketones in a one pot manner. We have recently reported a one pot transformation of carboxylic acid to ketone using TsCl or MsCl as an activator of carboxylc acid. In our previous reports, two equivalents of organometallic reagent have been used which may not be useful in medicinal chemistry. In this report, we have developed an alternative process for the transformation where only one equivalent of organometallic reagent has been employed. Objective: In present scenario, we are interested to develop a process for the transformation of carboxylic acid to ketone using one equivalent of an organometallic reagent. Methods: A carboxylic acid reacted with tosyl chloride in the presence of a sodium hydride to form a mixed anhydride. Here, the acidic proton was removed from the reaction mixture as hydrogen gas. This mixed anhydride was then treated with one equivalent of an organomagnesium reagent at -30°C to obtain the desired ketone. Results: Following the optimum conditions, a few commercially available carboxylic acids were treated with TsCl, followed by the treatment of phenyl magnesium and methyl magnesium bromide to obtain phenyl and methyl ketones, respectively, in good to excellent yields. Conclusion: A simple and modified one pot method for the conversion of carboxylic acids to ketone has been reported. In this developed process, one equivalent of the organomagnesium reagent has been used to obtain the desired ketone under the optimized reaction conditions.

Background: An efficient and green strategy for the synthesis of 2-arylbenzoxazoles using [Bmim]PF6 ionic liquid as a catalyst has been investigated via the condensation of oaminophenol with aldehydes. The microwave-assisted synthesis features some advantages such as good yield of products, broad substrate scope, short reaction time, and absence of metal catalyst and solvent. Furthermore, the synthesis could be conveniently expanded to a gram scale. Methods: 2-arylbenzoxazoles were obtained from o-aminophenol with aldehydes using [Bmim]PF6 ionic liquid as a catalyst under microwave irradiation at 80ºC, 120 W. Results: Twenty-three 2-arylbenzoxazole derivatives were furnished in good to excellent yields under optimized conditions. The structures of these compounds were confirmed by analysis of NMR data. In addition, the method could be conveniently expanded to gram scale. Conclusion: An efficient and straightforward protocol for the synthesis of 2-arylbenzoxazoles catalyzed by [Bmim]PF6 ionic liquid has been demonstrated. The synthesis delivers several advantages such as short reaction time, broad substrate scope, scalability, solvent-free conditions, and high efficiency. The reaction mechanism and applications of this synthesis are currently ongoing in our lab and will be reported in due course.