By using a greater reaction space afforded by a flow reactor, commercially available Au/TiO2 can be used for highly selective direct alkylation of amines by alcohols, without the need for an inert atmosphere or base. A brief survey of substrates includes the alkylation of aromatic, aliphatic and chiral amines by a number of primary and secondary alcohols, in high yield and selectivity. The synthesis of Piribedil, a drug used in the treatment of Parkinson's disease, can be achieved in a single synthetic operation without the need for column chromatography. Mechanistic aspects of the reaction were revealed through modelling of reaction profiles, and the origin of selectivity is attributed to the accessibility of high temperature. The presence of water was found to be crucial for catalyst activity.
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