O-Alkylation of phenols

O-Alkylation of phenols Phenol/cresols/catechols, alkyl halides/dimethyl sulphate/diethyl sulphate... 

Besides N-alkylation reactions, there are also reports in the literature concerning microwave-promoted O-alkylations. A mild method for the O-alkylation of phenols with alkyl bromides and chlorides has been developed by Wagner and coworkers (Scheme 6.117 a) [235], The protocol is applicable to substrates that are sensitive to strong bases or to hydrolysis, or are difficult to extract from an aqueous phase. The procedure uses methanol as a solvent and a stoichiometric amount of potassium carbonate as a weak base. Optimum yields were obtained by heating the phenol with 1.2 equivalents of the alkyl bromide (or 3 equivalents of the less reactive chloride) at 100-140 °C for 15-30 min. 

The methods that are known for introducing trifluoromethoxy groups into arenes are generally not effective. An interesting onc-pot O-alkylation of phenols followed by halogen exchange to form trifluoromethyl ethers 6 has been described227 (see also Houben-Weyl, Vol. E4, pp 626-627). 

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). 

Interestingly, it is possible to etherify hydroxybenzoic acids without the need to protect the carboxyl group (Scheme 6.19). The high charge delocalization of the car-boxylate obviously leads to a sufficient decrease of nucleophilicity to enable clean ether formation under certain conditions. During the planning of such reactions it should, however, be kept in mind that carboxylates can be O-alkylated under conditions similar to those required for the O-alkylation of phenols (see Section 6.9). 

Table 14.3 O-alkylation of phenols catalysed by LaPC>4, CS2HPO4...

Alkylation catalyst. KF or CsF impregnated on A1203 is an effective catalyst for O-alkylation of phenols and alcohols in CH3CN or DME. Both are preferable to Bu4NF/ A1203, because they are more easily handled as well as cheaper.2... 

Parrish, J. P., Sudaresan, B., Jung, K. W. Improved CsjCOj promoted O-alkylation of phenols. Synth. Common. 1999, 29,4423-4431. 

Numerous studies concerning O-alkylation of phenol were reported (refs. 3-9). Described catalysts belong to all the catalyst families oxides (ref. 3) phosphates (refs. 4, 5) metallosilicates (ref. 6) aluminophosphates (ref. 7) ion exchange resin (ref. 8). On the other hand, the selective mono-O-alkylation of diphenols was little reported and mainly in patent literature (ref. 9). The main studies deal with synthesis of guaiacol by methylation of 1-2-dihydroxybenzene 2 (catechol) (eqn. 1) catalyzed by boronphosphate eventually doped or supported (ref. 9). The main difficulties of this reaction consists in physical instability of the catalyst which is eluted in the reaction stream conducting to the formation of methylborate as a byproduct which has to be separated. It is then needed to add some new catalyst continuously. 

CATALYSIS BY RARE EARTH PHOSPHATE HI. CHARACTERISATION OF SAMARIUM PHOSPHATE AND SAMARIUM PHOSPHATE-CESIUM HYDROGENOPHOSPHATE AS KEY CATALYSTS FOR O-ALKYLATION OF PHENOLS... 

Samarium phosphates, impregnated or not by cesium hydrogenophosphate, selective catalysts for O-alkylation of phenols, have been characterised by various techniques. This study has shown that ... 

Sodium hydroxide sodium carbonate Partial and total O-alkylation of phenols... 

Scheme 8.12 The O-alkylation of phenols using alkyl halides in a sodium hydroxide/ dichloromethane biphasic media using TBAB as phase-transfer catalyst...

Hydrophenanthrene ring synthesis o-Alkylation of phenols Diketones... 

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