5-Alkyl and 5,5-Dialkyl Meldrum’s Acids

Abstract

This feature focuses on a reagent chosen by a postgraduate, highlighting the uses and preparation of the reagent in current research spotlight Introduction 5-Alkyl and 5,5-dialkyl Meldrum's acids (1 and 2, respectively) are used in total synthesis. 1 Monoalkylated derivatives 1 are synthesized from Meldrum's acid 3 by condensation with aldehyde 2 (or by acylation 3 ) followed by hydrogenation. 5-Alkyl and 5,5-Dialkyl Meldrum's Acids5,5-Dialkyl Meldrum's acids 2 can be obtained by alkylation of Meldrum's acid 3 or its monoalkylated derivatives 1 (Scheme 1). 4 Herein, reactions of Meldrum's acids 1 and 2 proceeding with destruction of 1,3-dioxane cycle are reviewed.(A) Hydrolysis of Meldrum's acid 2 leads to malonic or acetic acid derivatives. 5 Radical reduction of compound 2 with SmI 2 and H 2 O forms 3-hydroxypropanoic acids 4 selectively. The first step is activation of Meldrum's acid via coordination of SmI 2 to the carbonyl group, followed by electron transfer. 6 (B) Detz et al. 7 have reported that dimethyl malonate 5 can be obtained from propargylic derivative 2. The authors propose that the first step of the reaction cascade is copper-mediated addition of Meldrum's acid 2 to the triple bond and sequential methanolysis of the dioxane cycle forming lactone 6, which is further cleaved with methoxide leading to compound 5.(C) β-Substituted aldehydes 7 can be synthesized by Lewis base promoted hydrosilylation of Meldrum's acids 1 with phenylsilane, followed by hydrolysis. In situ treatment of aldehyde 7 with an amine and sequential hydrogenation of the formed imine with H 2 in the presence of Pd/C or with NaBH(OAc) 3 gives γ-substituted amines 8. 8 (D) 5-Alkyl Meldrum's acids 1 are used for the rapid synthesis of 2-alkyl acrylates 9 via Mannich-type reactions. The advantage of the method is the clean conversion into products due to the formation of volatile by-products -acetone, carbon dioxide, and dimethylamine. 9

Novel type of carbon‐centered antioxidants arylmethyl Meldrum's acids − inhibit free radicals

“…Contrary to the most of the previously mentioned 1,3‐dicarbonyl type antioxidants Meldrum's acid mainly exist in the keto‐form − more than 99.99% in water solution . Mono‐ and disubstituted Meldrum's acids are attractive building blocks in organic synthesis . However, despite the unique physico‐chemical properties of Meldrum's acid, less attention has been devoted to the studies of biological activity of the substituted 1,3‐dioxane‐4,6‐diones.…”

Crystal structure of 5-[4-(diethylamino)benzylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione

“…Mohite & Bhat, 2013). Arylidene Meldrum's acids can be easily converted to arylmethyl Meldrum's acids [for a description of a typical procedure, see Mierina et al (2015)], which serve as starting compounds for the synthesis of various valuable compounds [for a mini-review, see Mierina (2014)]. Apart from their wide application in syntheses, these derivatives of Meldrum's acid have been studied as platelet aggregation inhibitors (El Maatougui et al, 2012), antimalarial agents and anti-oxidants (Sandhu et al, 2010) and photostable UV-filters for cosmetic applications (Habeck & Krause, 1999).…”