Nucleophilic aliphatic phase-transfer catalysis

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]. 

Most reactions in two-phase systems occur in a liquid phase following the transfer of a reactant across an interface these are commonly known as extractive reactions. If the transfer is facilitated by a catalyst, it is known as phase-transfer catalysis [2]. Unusually, reactions may actually occur at an interface (interfacial reactions) examples include solvolysis and nucleophilic substitution reactions of aliphatic acid chlorides [3 ] and the extraction of cupric ion from aqueous solution using oxime ligands insoluble in water [4], see Section 5.2.1.3(ii). 

The phase transfer catalysis process has also been extended to synthesize the alkyl and aryl esters (170) of N-aryl sulphamic acids212 (equation 23). If the ratio of aliphatic alcohol (169) to sulphamoyl chloride (168) is increased from 1 1 to 2 1, then N-alkyl-iV-arylsulphamate esters (171) with similar alkyl groups are obtained together with considerable amounts of iV-arylsulphamic acid esters (170). The exclusive formation of the iV-alkyl-iV-arylsulphamate esters (171) can be achieved by employing longer reaction times. A second approach to the synthesis of 171 would be to react the iV-methyl-iV-phenyl sulphamoyl chloride (172) with the alcohol. This was attempted, but the ester failed to form even under forcing conditions. The corresponding AT-alkyl iV-arylsulphamate ion (173) was isolated (equation 24) hydrolysis to the acid was considered to occur as opposed to nucleophilic displacement of the chloride by the methanol. 

Solid-liquid phase transfer catalyst 2 for aliphatic and aromatic nucleophilic substitution synergistic effect with Cu in Ullmann synthesis as ligand in homogeneous hydrogenation catalysis (see 1st edition). 

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