Tertiary Amines from Alcohols without Oxidants, Reductants or Alkyl Halides

In order to make pharmaceutical drugs and related compounds, it is sometimes necessary to use toxic chemicals as starting materials in their synthesis and manufacture. One example of this is a class of compounds known as alkyl halides, which are often used to react with amines (nitrogen-containing compounds which are found in many pharmaceutical drugs). Alkyl halides are often toxic because they not only react with amines, but also with our own DNA. This alkylation of DNA means that alkyl halides are often mutagens and carcinogens. Not surprisingly, there is increasing legislation to ensure that these alkyl halides are not present in the final drug molecule, and that the manufacturing processes are carefully contained. The proposed research in this project involves replacing the alkyl halides with alcohols as alternatives for these reactions. Normally, the problem is that alcohols are very unreactive in comparison with alkyl halides and would be unsuccessful in achieving the desired reaction. However, using catalysts, we have designed a method that involves temporarily removing hydrogen from the alcohols to form much more reactive aldehydes as intermediates. The catalyst returns the hydrogen after the aldehyde has reacted with the amine. Overall, the same products are formed as with alkyl halides, but safer, cheaper alcohols are used in their place. The only byproduct from the reaction is water, making these processes clean and environmentally benign.In order to be appealing as a useful industrial process, we will demonstrate that it is possible to run these reactions on a larger scale. In order to do this, a collaboration between Chemistry and Chemical Engineering is proposed. The small scale reactions will be adapted to a larger scale using purpose built reactors that will model reactions that would be necessary for the manufacture of drug molecules on a large scale.