Chapter 28. Reactions of Interest in Medicinal Chemistry

Abstract

Publisher Summary This chapter presents reactions that are of interest in medicinal such as oxidation and reduction aldehydes and ketones; preparation of organometallic reagents; and preparation of amines and nitriles. It also discusses crown ethers and their synthetic applications. Aldehydes and ketones are reduced by alkylsilanes to alcohols in aqueous acid media; in carboxylic acid as solvent, carboxylate esters and symmetrical ethers are formed. In organometallic reagents, phenylselen bromide and acetate undergo electrophilic trans-1, 2 addition to olefins. The adducts solvolyze in acetic acid or alcohols and oxidation of the resulting products affords allylic acetates and ethers in high overall yield. Crown ethers, a class of macrocyclic polyethers, which have a remarkable ability to solubilize alkali metals in non-polar aprotic solvents have found new and useful synthetic applications. For instance, poor nucleophiles such as fluorides, solubilized as the potassium salt in CH 3 CN or benzene containing 1, 4, 7, 10, 13, 16-hexaoxacyclooctadecane becomes sufficiently nucleophilic to react smoothly and quantitatively, at room temperature, with a variety of organic substrates. This naked fluoride reagent, thus, provides a facile and efficient means of obtaining organic fluorine compounds in high yield. In a similar fashion, the naked acetate and cyanide are excellent reagents for preparing organic acetates and nitriles, respectively.