O and N Alkylation Reactions

The O-alkylation reactions of hindered phenols are normally sluggish reactions and attempts to improve reactivity have received considerable attention from synthetic organic chemists. Ultrasonic irradiation has been used to greatly enhance the rate of alkylation of 2,6-dimethylphenol with several different primary halides under heterogeneous conditions using KjCOj in N-methylpyrrolidinone (NMP) (Eq. 3.26) [126]. 

This methodology was found to be highly successful when applied to the O-alkyla-tion of 5-hydroxychromones, reactions that are normally very difficult to perform due to electronic hindrance to the OH group caused by hydrogen bonding between it and the carbonyl group [127]. For example the alkylation of5-hydroxy-2-carboxyethyl-4H-l-benzopyran-4-one with 1-iodopropane at 65 °C in NMP is only 28% complete after 1.5 h (Eq. 3.27) whereas under ultrasonic irradiation complete reaction was obtained in this time period. 

Nitrogen alkylation occurs easily under sonochemical conditions [128], Indole and carbazole undergo N-alkylation with increased rates and yields under sonication in the presence of polyethylene glycol methyl ether as PTC. No reaction occurs in the absence of the PTC (Eq. 3.28). 

A synthetically important N-acylation reaction is the formation of Boc protected amines [129]. A rapid and simple method has been reported using sonication which allows this reaction to be effected in the absence of water using solid sodium hydrogen carbonate as the base in a methanol suspension (Eq. 3.29). 

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Microwave irradiation and phase transfer catalysis in C-, O- and N-alkylation reactions 13COS751. 

G. Keglevich, A. Griin, E. Balint, Microwave irradiation and phase transfer catalysis in C-, O- and N-alkylation reactions, Gurr. Org. Synth. 10 (2013) 751-763. 

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