‘On-Water’ Multicomponent Reaction for the Diastereoselective Synthesis of Functionalized Tetrahydropyridines and Mechanistic Insight

Abstract

An ecofriendly approach for the synthesis of highly substituted tetrahydropyridines by an 'on-water' multicomponent reaction has been demonstrated. The use of water as the reaction medium is essential under the catalytic influence of a surfactant. The use of a variety of anionic, cationic, and non-ionic surfactants in water was examined and the reaction was successfully catalyzed by anionic surfactants sodium dioctyl sulfosuccinate (SDOSS) and sodium dodecyl sulfate (SDS), with the former being superior. The use of an organic solvent together with a catalytic amount of sodium dioctyl sulfosuccinate to form homogeneous conditions afforded inferior yields and highlighted the specific role of water through the creation of microreactors at the water surfactant interface. A mechanistic insight for the five-component reaction leading to the formation of tetrahydropyridines is provided invoking a tandem inter-and intramolecular Mannich reaction pathway.

Diphenhydramine Hydrochloride–CuCl as a New Catalyst for the Synthesis of Tetrahydrocinnolin-5(1H)-ones

“… 23 , 24 High convergence and atom economy, environmentally favorable processes, mild reaction conditions, simple experimental procedure, and a one-pot character are outstanding advantages of these reactions over the classical stepwise methods. 25 − 30 Consequently, they provide a more efficient and convenient protocol for synthetic chemistry for the preparation of fine chemicals.…”

“…During recent years, multicomponent reactions (MCRs) have gained a great deal of attention in organic and medicinal chemistry owing to the generation of biologically active compounds with significant structural diversity and complex heterocyclic compounds. , High convergence and atom economy, environmentally favorable processes, mild reaction conditions, simple experimental procedure, and a one-pot character are outstanding advantages of these reactions over the classical stepwise methods. − Consequently, they provide a more efficient and convenient protocol for synthetic chemistry for the preparation of fine chemicals.…”

Green Synthesis of Novel Pyridines via One-Pot Multicomponent Reaction and Their Anti-Inflammatory Evaluation

“…Moreover, pyridine derivatives have appeared as a substantial scaffold in view of their prevalence in a considerable number of natural products and their application to biological and pharmaceutical chemistry. − In recent years, chemists have been interested in developing pyridine derivatives because of their great importance, whether in organic chemistry or in medical applications. − Moreover, they are interested to use modern techniques in organic synthesis. One-pot multicomponent reactions are the most increasing academic and ecological method because of the possibility of achieving high synthetic efficiency and reaction design. ,− In addition, it is known that multicomponent reactions (MCRs) possess many advantages, such as eco-friendly efficiency, atom economy, and reduced reaction times with increased yields, and these advantages are very important in synthetic organic chemistry, especially when the target compounds are studied in their biological evaluation. − …”

A Facile One‐Pot Solvent‐Free Synthesis, in Vitro and in Silico Studies of a Series of Tetrahydropyridine Derivatives as Breast Cancer Inhibitors

“…[9] THPs have also been comprehensively studied for their prospective pharmacological actions such as anticancer, [10][11] antidiabetic, [12] anti-neurotropic, [13] anti-tubercular, [14] bronchodilations, [15] larvicidal, [16] neuropeptide YY1 receptor antagonists, [17] neuroprotective, [18] platelet anti-aggregation, [19] anti-inflammatory, [20] mGluR1 antagonists, [21] antihypertensives, [22] antimicrobial, [23][24][25] antimycobacterial, [26] antifungal, [27] antimalarial [28] and anti-HIV [29] activities. Substituted tetrahydropyridines have been synthesized employing various catalysts like iodine, [30] bromodimethylsulfonium bromide, [31] glycolic acid, [32] vitamin B1, [33] lactic acid, [34] lanthanum nitrate, [35] nickel chloride hexahydrate, [36] sulfamic acid, [37] cyanuric chloride, [38] sodium dioctyl sulfosuccinate, [39] acetic acid, [40] tetrabutylammonium tribromide, [41] picric acid, [42] and thiourea dioxide. [43] These methods have one or more drawbacks: expensive catalysts or strongly acidic conditions, low yields, high temperatures; and tedious workup procedures.…”