Nucleophilic alkyl substitution phase-transfer catalysis

The preparation of mono- and di-tm-butylcyclopentadienes 1 and 2 starting from monomeric cyclopentadiene was reported first in 1963 [23]. It was noted that the nucleophilic attack of the cyclopentadienide anion on ferf-alkyl halide has to compete with elimination reaction giving isobutene. The yield of the di- and tri-fer/-butylcyclopentadienes 2 and 3 was therefore reported to be modest to low [23, 24], Recently an elegant improvement for this synthesis using phase transfer catalysis was presented (Eq. 1), but the availability of the tri-substituted derivative... 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Polymeric phosphonium salt-bound carboxylate, benzenesulphinate and phenoxide anions have been used in nucleophilic substitution reactions for the synthesis of carboxylic acid esters, sulphones and C/O alkylation of phenols from alkyl halides. The polymeric reagent seems to increase the nucleophilicity of the anions376 and the yields are higher than those for corresponding polymer phase-transfer catalysis (reaction 273). 

Nucleophilic Substitutions. 7V,7V-Dimethyldithiocarbamoyl-acetonitrile (1) serves as an active methylene compound, because its carbanion is stabilized by sulfur and cyano groups. It can be alkylated stepwise in aqueous sodium hydroxide under phase transfer catalysis (eq 1). The anion undergoes nucleophilic aromatic substitution to give nitroarenes, with elimination of the dithiocarbamate group (eq 2). Nucleophilic addition of (1) to phenyl isothiocyanate also occurs readily. ... 

Phase-transfer catalysis is a useful adjunct to the alkylation of benzyP and iodomethyl aryl sulphones. In the latter case, an tr-proton is substituted, rather than the halogen, and this same initial deprotonation has been proposed for the novel, quaintly-named, vicarious nucleophilic substitution of nitrobenzene by ClCHjSOjPh in the presence of NaOH (Scheme 19). The novel crketo-sulphones ArCOSOzAr are obtained by ozonolysis of the or-diazo- or cr-alkoxymethylene analogues. 

One of the most useful applications of phase transfer catalysis in nucleophilic substitution has been in the Williamson ether synthesis. The reaction of an alkoxide anion with an alkyl halide or sulfonate to give either symmetrical or unsymmetrical ethers (depending on reactants) shows significant improvement in convenience, reaction rate, and yield when conducted under phase transfer catalytic conditions. 

The use of anion-exchangers as the source of nucleophiles in nucleophilic substitution reactions has been referred to (Chapter 12). Brown and Jenkins (1976) and Regen (1975, 1976, 1977) have developed a triphase-catalysis method for carrying out such nucleophilic substitution reactions. The resin in these reactions acts as a polymer-bound phase-transfer catalyst. Quaternary ammonium groups that were introduced into the resin contained large alkyl groups to act as the linked phase-transit catalyst. 

The majority of research on catalysis by anion-exchange resins is devoted to the use of resins in interfacial catalysis reactions [38-43]. In this connection, quaternary ammonium or phosphonium, onium salts have been commonly obtained [44]. Crown-ethers, cryptands and linear polyesters supported on polymers also catalyze similar reactions dealing with the interfacial transfer of reagents. In the simplest case, the mechanism of interfacial catalysis represents a substitution reaction of Sf 2 type typical for the interaction of the nucleophile, T , present in the aqueous solution with the alkyl halogenide, RX, in the organic phase ... 

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