There are many situations in organic synthesis where it is desirable to bring about reaction between reactants present in two (or more) immiscible phases. Agents known as phase-transfer catalysts are used for this purpose. Their role in initiating or accelerating such reactions has been proven extensively since the early seventies, and the principles of their operation are being increasingly understood [see Weber and Gokel, 1977; Reuben and Sjoberg, 1981; Frechet, 1984; Freedman, 1986; Goldberg, 1992 (English translation); Dehmlow and Dehmlow, 1993; Starks et al., 1994; Yufit, 1995; Sasson and Neumann, 1997; Naik and Doraiswamy, 1998]. To date, an estimated 500 different commercial chemical processes (mostly for small volume chemicals) using about 5-25 million pounds per annum of phase-transfer catalysts have been reported (Starks et al., 1994), and well over 6,500 compounds have been synthesized in the laboratory using PTC (Keller, 1979, 1986). A large number of industrial applications of phase-transfer catalysis are found in the pharmaceutical, agrochemical, and fine chemicals industries. Additionally, it is now being increasingly used in processes related to the environment, in process modifications for eliminating the use of solvents, and in reactions related to the treatment of poisonous effluents. Not surprisingly, then, there has been a constant stream of publications and patents every year. Phase-transfer catalysis (PTC) is an area that has largely been the province of the preparatory organic chemist (defined broadly to include organometallic and polymer chemists). It is only since the early eighties that the engineering aspects of phase-transfer catalysis are being explored, including such traditional features as mass and heat transfer and reactor design. Our main objective is to present a brief but coherent engineering analysis of PTC, following an introduction to its basic principles. When two reactants are present in two different, immiscible liquid phases (usually one aqueous and the other organic), they can often be brought together by addition of a solvent that is both water-like and organic-like (e.g., ethanol, which derives its hydrophilic nature from its hydroxyl group and its lipophilicity from the ethyl group). However, the rate enhancement tends to be limited due to excessive solvation of the nucleophile.
Chiral Phase-Transfer Catalysts with Hydrogen Bond: A Powerful Tool in the Asymmetric Synthesis