Tag Archives: Synthetic methods

Belated publication of the week, number 12a, 7th February 2014

The chemistry from the group of Prof. Ley at the University of Cambridge, UK, is flowing again. Together with C. Battilocchio and J. Hawkins they discuss the “Mild and Selective Heterogeneous Catalytic Hydration of Nitriles to Amides by Flowing through Manganese Dioxide”.

Now you may think this is a trivial problem, but it’s not. The usual methods, acid or base hydrolysis often require relatively harsh conditions leading to side product formation. The use of catalysts is also not without problems, for example, low catalyst lifetime, catalyst leaching, cost and so on, so there is still plenty of room for improvement for this simplest of reactions. The Ley group has been investigating flow chemistry for some time now and has come up with some ingenious solutions to (no pun intended) to some complicated chemistry and I refer you to the Group’s web site for a literature listing. This latest offering is really simple to operate and all one needs to do is ” pass an aqueous solution of the nitrile through a column containing commercially available amorphous manganese dioxide, and one obtains the product  by concentration of the output stream without any other workup steps. The protocol described is rapid, robust, reliable, and scalable.”

The paper lists about 36 examples of nitriles belonging to a large variety of structural classes both aromatic and aliphatic, from simple (a) to complex (b) and heterocyclic (c):

examplesThe yields are excellent to awe inspiring (94-99%) and with no work-up except concentration is a tribute to the efficiency of flow chemistry. Manganese (IV) oxide is a cheap reagent for many reactions, but is not without its problems, usually it can be very messy and ridding glassware and reactors of residues is time-consuming. In this case it is simply packed inside a column, the column plugged with celite and a water/acetone solution of the nitrile passed through at 0.1 mL/minute at a temperature between 30°C and 110°C. The amount of manganese in the product was very low, <0.1ppm and a variety of functionality is tolerated. More importantly the same catalyst can be re-used, up to 100 times is mentioned. Steve really went to town on the scope of this flow system, even water insoluble nitriles were solubilised and hydrolysed without problem. One selectivity check catches the eye, namely when this is carried out in the presence of benzyl alcohol NO benzylic oxidation was observed.

So this is simple easy chemistry (depending on your substrate of course) that I hope will find universal application, especially in industry. Congratulations to the Group and keep it flowing and may your columns never block-up.

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