Phase Transfer and Ammonium Salt Catalyzed Reactions

10 Phase Transfer and Ammonium Salt Catalyzed Reactions 

Charles A. Eckert, Charles L. Liotta, Christy W. Culp, and David R. Lamb 

Phase transfer catalysis (PTC) is an important industrial method for carrying out reactions between two or more reactants which would normally be immiscible [1-6], Traditionally, polar aprotic solvents have been used to dissolve the reactants into a single phase where reactions may be carried out homogeneously. However, these solvents are frequently expensive, environmentally undesirable, and difficult to remove from the reaction products. PTC eliminates the need for these solvents and replaces them with less exotic media. With a less polar organic solvent, there are two phases present and a phase transfer catalyst is employed to transfer one of the reacting species from one phase into a second phase where reaction can occur. 

The special properties of supercritical fluid (SCF) solvents [7,8] for PTC reactions bring substantial environmental and econonric advantages. First, they permit the use of totally benign solvents, especially CO2, and the solvent separation from product becomes quite facile. Moreover, since PTC processes always involve mass transfer, the lower viscosity and higher diffusivity of SCFs significantly enhance transport. 

With the recent growth of research in this area, the general understanding of PTC systems is becoming well-defined. One result of the collaboration between chemists and engineers has been the realization that PTC can occur at the interface between a solid and an SCF this combination of techniques is a new frontier in chemistry and its potential has yet to be realized. 

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In 2000, Benaglia and coworkers reported preparation of MeO-PEG supported quaternary ammonium salt (10) and examined the catalytic efficiency in a series of phase-transfer reactions (Fig. 5.3) [69]. The reactions occurred at lower temperatures and with shorter reaction times than with comparable insoluble 2% cross-linked polystyrene-supported quaternary ammonium salts, although yields varied with respect to classical solution phase quaternary ammonium salt catalyzed reactions. It was observed that yields dropped with a shorter linker, and that PEG alone was not responsible for the extent of phase-transfer catalysis. While the catalyst was recovered in good yield by precipitation, it contained an undetermined amount of sodium hydroxide, although the presence of this byproduct was found to have no effect on the recyclability of the catalyst... 

Quaternary ammonium salts catalyze the reaction between an anion and an organic substrate by transferring the anion from the aqueous phase, where it cannot contact the substrate, to the organic phase. In the example just cited, the first step occurs in the... 

The asymmetric Darzens condensation, which involves both carbon-carbon and carbon-oxygen bond constructions, was realized by use of the chiral azacrown ether 75als2,s ,ss and the quaternary ammonium salts derived from cinchona alka-loids159"621 under phase transfer catalyzed conditions. The a,p-epoxy ketone 80 (R=Ph) was obtained with reasonable enantioselectivity by the reaction of... 

A slow non-competing liquid/liquid reaction with no catalyst present gave only 78 % O-alkylation. Thus the active site of the lipophilic phosphonium ion catalysts appears to be aprotic, just as in analogous phase transfer catalyzed alkylations with soluble quaternary ammonium salts 60), Regen 78) argued that the onium ion sites of both the 17% and the 52% RS tri-n-butylphosphonium ion catalysts 1 are hydrated, on the basis of measurements of water contents of the resins in chloride form. Mon-tanari has reported measurements that showed only 3.0-3.8 mols of water per chloride ion in similar 25 % RS catalysts 74). He argued that such small hydration levels do not constitute an aqueous environment for the displacement reactions. No measurements of the water content of catalysts containing phenoxide or 2-naphthoxide ions have been reported. 

As pointed out earlier, the lack of a common solvent, for aqueous and certain organic substrates, may result in a slow reaction rate and poor selectivity. This serious limitation has been circumvented with the aid of phase transfer catalysis, a well known technique in organic synthesis [55]. It consists in the transfer of a water soluble oxidant species into the immiscible organic phase, as a quaternary ammonium or phosphonium salt. Two main results are achieved by this technique. The reaction rate is increased, due to higher concentration of the oxidant species in the organic phase. Acid catalyzed side reactions are decreased, by keeping the products in the organic phase. 

The first reaction scheme pre.scnted by Starks [ 1 ] was for the reaction of aqueous sodium cyanide and organic 1-chlorooctane as in Eqs (I) and (2). No apparent reaction occurred after 24 h in the absence of catalyst. However, the cyanide displacement reaction took place rapidly with only 1% of the quaternary ammonium salt (C6Hi3)4N Cr added, and achieving near 100% yield of 1-cyanooctane product in 2-3 h [1]. The reaction scheme for the phase-transfer catalyzed cyanide displacement reaction in aqueous-organic pha.scs is shown as follows ... 

While PEGS can themselves serve as phase-transfer catalysts [86], onium salts are generally more effective as catalysts. Using the chemistry shown in Eq. 18, a methoxy-PEG5ooo derivative 47 was first treated with the Cs salt of 4-hydroxybenzyl alcohol to form the alcohol 48. Conversion of the alcohol to the bromide followed by reaction with tributylamine produced a quaternary ammonium salt 49. This salt was as active as low molecular weight salts in typical phase-transfer catalyzed reactions like those of alkyl halides with KI, KCN, phenol, and pyrrole [88]. Yields were often in the >90% range. Reactions were typically carried out at <40 °C and could be performed either with water or without solvent. Control experiments showed that the ammonium group of 49 was necessary as the simple alcoholic PEG derivative 48 was much less effec-... 

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