Novel Biopolymer-Based Catalyst for the Multicomponent Synthesis of N-aryl-4-aryl-Substituted Dihydropyridines Derived from Simple and Complex Anilines.

Although Hantzsch synthesis has been an established multicomponent reaction method for more than a decade, its derivative, whereby an aniline replaces ammonium acetate as the nitrogen source, has not been explored at great length. Recent studies have shown that the products of such a reaction, N-aryl-4-aryldihydropyridines (DHPs), have significant anticancer activity. In this study, we successfully managed to synthesize a wide range of DHPs (18 examples, 8 of which were novel) using a metal-free, mild, inexpensive, recoverable, and biopolymer-based heterogeneous catalyst, known as piperazine, which was supported in agar-agar gel. In addition, 8 further examples (3 novel) of such dihydropyridines were synthesized using isatin instead of aldehyde as a reactant, producing spiro-linked structures. Lastly, this catalyst managed to afford an unprecedented product that was derived using an innovative technique-a combination of multicomponent reactions. Essentially, the product of our previously reported aza-Friedel-Crafts multicomponent reaction could itself be used as a reactant instead of aniline in the synthesis of more complex dihydropyridines.

Correction: One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity.

[This corrects the article DOI: 10.3762/bjoc.16.235.].

Efficient One-Pot Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones via a Three-Component Biginelli Reaction.

Multicomponent reactions are considered to be of increasing importance as time progresses due to the economic and environmental advantages such strategies entail. The three-component Biginelli reaction involves the combination of an aldehyde, a ß-ketoester and urea to produce 3,4-dihydropyrimidin-2(1H)-ones, also known as DHPMs. The synthesis of these products is highly important due to their myriad of medicinal properties, amongst them acting as calcium channel blockers and antihypertensive and anti-inflammatory agents. In this study, silicotungstic acid supported on Ambelyst-15 was used as a heterogeneous catalyst for the Biginelli reaction under solventless conditions. Electron-poor aromatic aldehydes gave the best results. Sterically hindered ß-ketoesters resulted in lower reaction yields. The reaction was carried out under heterogeneous catalysis to allow easy recovery of the product from the reaction mixture and recycling of the catalyst. The heterogeneity of the reaction was confirmed by carrying out a hot filtration test.

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity.

A rapid route for obtaining unsymmetrical 1,2-dihydropyridines (1,2-DHPs) as opposed to 1,4-dihydropyridines (1,4-DHPs) has been achieved via a one-pot multicomponent Hantzsch reaction. A benign protocol has been developed for the preparation of various 1,2-dihydropyridine derivatives using heterogenized phosphotungstic acid on alumina support (40 wt %). High yields of over 75% have been accomplished in just 2-3.5 h after screening several heterogeneous catalysts and investigating the optimal reaction conditions. The catalyst chosen has passed the heterogeneity test and was shown to have the potential of being reused for up to 8 consecutive cycles before having a significant loss in activity. In addition, aromatic aldehydes gave the aforementioned regioisomer while the classical 1,4-DHPs were obtained when carrying out the reaction using aliphatic aldehydes. The preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range.

One-pot multicomponent nitro-Mannich reaction using a heterogeneous catalyst under solvent-free conditions.

An environmentally-friendly, one-pot multicomponent reaction of various aldehydes, amines and nitroalkanes for the synthesis of ß-nitroamines is here described. Amberlyst A-21 supported CuI was found to be a highly efficient novel heterogeneous catalyst for the three-component nitro-Mannich reaction between aldehydes, amines and nitroalkanes. The developed protocol is performed in a solvent-free medium to produce a variety of ß-nitroamines in good to excellent yields within short reaction times. The catalyst can be easily prepared and recovered. It has been tested up to eight times with only a minor activity loss.

Aza-Michael Mono-addition Using Acidic Alumina under Solventless Conditions.

Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although others such as acrylonitrile, methyl acrylate and acrylamide were also utilized successfully. Bi-functional amines also gave the mono-adducts in good to excellent yields. Such compounds can serve as intermediates for the synthesis of anti-cancer and antibiotic drugs.

Addition of organocerium reagents to morpholine amides: synthesis of important pheromone components of Achaea janata.

Readily preparable morpholine amides hitch in good yields with organocerium reagents to produce ketones. Even in the presence of substrates and reagents with high steric hindrance, the organometallic compounds prepared from dry cerium(III) chloride and organomagnesium or organolithium compounds at -78 degrees C add cleanly to morpholine amides. The low cost of starting materials makes this new scheme of synthesis very interesting for the preparation of biologically important pheromones.