Formaldehyde

(A) Mannich-Type Synthesis of Propargylamines: Bieber and da Silva reported a mild, easy, and efficient synthesis of propargylamines by copper I) iodide catalyzed Mannich reaction of terminal alkynes with aqueous formaldehyde and secondary amines. The aminomethylation was conducted in DMSO and high to quantitative yields were obtained.(B) Synthesis of Mannich Bases Related to Gramine: Indoles have potent biological activity and are one of the most important subjects in heterocyclic chemical research. The preparation of several gramines by Mannich reaction of paraformaldehyde, a secondary amine and indole/N-methylindole was reported by Dai et al. Using zinc(II) chloride as mediator, the indoles were obtained in 58-98% yields.(C) Piperazines by Ugi Four-Component Condensation: Giovenzana et al. described the preparation of diamines by modified Ugi four-component reaction of several isocyanides, paraformaldehyde carboxylic acids, and diamines. The method was particularly useful in the preparation of piperazines in methanolic solution, and good to quantitative yields were achieved. In addition, the authors extended the applicability of the Ugi multicomponent reaction in synthetic and medicinal chemistry research.(D) Solvent-Free, Microwave-Assisted Synthesis of Phosphono- and Phosphinoxidomethylated N-Heterocycles: Keglevich and co-workers prepared N-phosphono and N-phosphinoxi derivatives from the condensation of paraformaldehyde, Nheterocycles and diethylphosphite or diphenylphosphine. The reactions were conducted in environmentally friendly manner under solvent-free, microwave-assisted conditions, representing a green alternative to traditional techniques. A variety of N-phospho derivatives was swiftly synthesized in high yields (70-92%) with excellent purity levels.(E) Diastereoselective Synthesis of Pyrrolidines by Horner-Wadsworth-Emmons Olefination: In the reported synthesis, oxoalkanoates undergo reaction with hexyl- or benzylamines to yield phosphorylpyrrolidinones. The Horner-Wadsworth-Emmons olefination of these intermediates with paraformaldehyde yields 60-95% of pyrrolidinones with excellent diastereoselectivity.(F) Synthesis of 1,3-Dioxanes via Prins Reaction: 1,3- ioxanes are important compounds in drug discovery, displaying potent biological activity. Recently, Yadav et al. reported a new eco-friendly method for the preparation of 1,3-dioxane derivatives using molecular iodine as catalyst. The Prins reaction of a variety of alkyl- or aryl-substituted alkenes with paraformaldehyde afforded a library of these compounds in excellent yields.(G) Glycosyls via Diels-Alder Reaction: Vankar and co-orker described the synthesis of C-glycosyl aminoacids via Diels-Alder reaction of methyl nitroacetate and formaldehyde generating in situ a-nitro methyl acrylate, with glucal dienes. Single-pot reduction and acetylation of the resulting cycloadducts afforded the glycosyls in good yields with considerable stereoselectivity (85:15). This class of compounds is target of extensive research in drug discovery due to its biological properties.