Phase-transfer catalysis. A general green methodology in organic synthesis*

Basic concept of phase-transfer catalysis (PTC), its field of applications and specific features as the most general, efficient, and environment-friendly green methodology of organic synthesis, particularly for industrial processes, is discussed. Organic synthesis is the principal way to produce chemical products of practical applications such as pharmaceuticals, plant protection agents, dyes, photographic chemicals, monomers, etc. Transformations of starting materials into desired final products usually require a number of chemical operations in which additional reagents, catalysts, solvents, etc. are used. Thus, in the course of synthesis, besides the desired products, many waste materials are produced because transformations of educts into products are not quantitative and selective processes, particularly due to the use of these additional components. These wastes should be regenerated, destroyed, and disposed, consuming much energy and creating heavy burden on the environment. It is therefore of great importance to develop and use synthetic methodologies that minimize these problems. Perhaps one of the most general and efficient methodologies that fulfill this requirement is phase-transfer catalysis (PTC) [1]. This methodology is applicable to a great variety of reactions in which inorganic and organic anions and also carbenes react with organic substrates. It consists in use of heterogeneous two-phase systems—one phase being a reservoir of reacting anions or base for generation of organic anions, whereas organic reactants and catalysts (source of lipophilic cations) are located in the second, organic phase. The reacting anions are continuously introduced into the organic phase in the form of lipophilic ionpairs with lipophilic cations supplied by the catalyst. Most often tetraalkylammonium cations serve this purpose. Reactions to which PTC is applicable can be divided into two major categories: 1. Reactions of anions that are available as salts, for example, sodium cyanide, sodium azide, sodium acetate, etc. 2. Reactions of anions that should be generated in situ, such as alkoxides, phenolates, N-anions of amides or heterocycles, etc. and particularly carbanions In the former case the salts are used as aqueous solutions or in the form of powdered solids, whereas the organic phase contains organic reactants neat (when liquid) or in appropriate solvents. Since the phases are mutually immiscible the reaction does not proceed unless the catalyst, usually a tetraalkylammonium salt, QX is present. The catalyst transfers continuously reacting anions into the organic phase in form of lipophilic ion-pairs produced according to the ion-exchange equilibrium (1a), where they react further, for example, with alkyl halides affording nucleophilic substitution (1b). A variety of other reactions with participation of inorganic anions such as addition, reduction, oxidation, etc. is efficiently executed using this methodology. Phase-transfer catalyzed reactions of organic anions are mechanistically more complicated. In these cases the inorganic phase contains base such as conc. aqueous or solid NaOH or KOH or solid K 2 CO 3 , whereas the organic phase contains the anion precursor, an electrophilic reactant and eventually