A Novel Cyclisation

Many years ago, one of my tasks at a pharmaceutical research establishment was to see if it were possible to make 2-ethyloxazoline cheaper than it cost the company to buy it. The route chosen was shown below. Here, ethanolamine treated with ethanoic anhydride to produce N-(2-hydroxyethyl) - propanamide. This was possible because the amino group of ethanolamine was far more nucleophilic than the hydroxyl group. N-(2-hydroxyethyl)-propanamide 2-ethyloxazoline The real purpose of the research was to examine the next step: the cyclisation of the intermediate to 2-ethyloxazoline. This was achieved by refluxing the non-cyclic precursor in the presence of a catalyst and distilling off the water as it formed. The aim of the research was to reduce costs as far as possible - including energy costs. Various transition metal compounds and lanthanides, even actinides, were tried. In certain cases, when using cobalt compounds and nickel compounds for example cobalt(ll) chloride and nickel(ll) sulfate, I noticed that little whiskers of metal were found on the magnetic follower following extensive heating. Although I never followed this up (it being beyond my present remit) it was clear that extensive reducing conditions existed, and that the metal catalysts were being reduced to the parent metal in the zero oxidation state. I never discovered the reasons behind this reduction process, but it seemed novel and worthy of further work. Maybe this could be useful material for an extended investigation by a sixth-former or undergraduate.