An Efficient One-Pot Green Protocol for the Synthesis of 5-Unsubstituted 3,4-Dihydropyrimidin-2(1H)-Ones Using Recyclable Amberlyst 15 DRY as a Heterogeneous Catalyst via Three-Component Biginelli-Like Reaction
An environmentally benign green protocol for the synthesis of 5-unsubstituted 3,4-dihydropyrimidin-2(1H)-ones using Amberlyst 15 DRY as a recyclable catalyst has been developed. The use of resinous, nontoxic, thermally stable, and inexpensive Amberlyst 15 DRY, as a recyclable heterogeneous catalyst, makes the process simple with negligible chemical waste. Among the various solid acid catalysts Amberlyst 15 DRY was found to be the most efficient catalyst with regard to reaction time, yield, and ease of work-up procedure. 1. Introduction Replacement of conventional, toxic, and polluting Bronsted and Lewis acid catalysts with ecofriendly reusable solid acid heterogeneous catalysts like acidic zeolites, clays, sulfated zirconia, and ion exchange resins is an area of current interest [1, 2]. The use of solid acid catalyst instead of liquids includes many advantages, such as reduced equipment corrosion, ease of product separation, recycling of the catalyst, and environmental acceptability. In the recent past ion exchange resins in general and styrene-DVB matrix resin sulfonic acid (Amberlyst 15 DRY) in particular, which are strongly acidic and chemically as well as thermally stable, have been found to be excellent catalysts for a variety of the major organic reactions like esterification, alkylation, acylation, and condensation [3–8]. Pyrimidinones or dihydropyrimidinones (DHPMs) are well known for their wide range of bioactivities. Their applications in the field of drug research have stimulated the development of a wide range of synthetic methods for their preparation and chemical transformations. Out of the five major bases in nucleic acids three are pyrimidine derivatives which comprise of cytosine (1) which is found in DNA and RNA, uracil (2) in RNA and thymine, and (3) in DNA. Because of their involvement as bases in DNA and RNA, they have become very important in the world of synthetic organic chemistry. Aryl-substituted 3,4-dihydropyrimidin-2(1H)-one and their derivatives are an important class of substances in organic and medicinal chemistry (see Figure 1). Figure 1 4-Aryl-1,4-dihydropyridines (DHPMs) of the Nifedipine type (4) [9] were first introduced into clinical medicine in 1975 and are still the most potent group of calcium channel modulators available for the treatment of cardiovascular diseases [10]. Dihydropyrimidines of type (5) show a very similar pharmacological profile, and in recent years, several related compounds were developed (5) that are equal in potency and duration of antihypertensive activity to classical and second-generation
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