Pinacol rearrangement of adrenaline - first try

This week, Alicia, James and Brett started in the lab. Their first task was to generate the catechol aldehyde using an amino-pinacol type rearrangement of adrenaline. As mentioned previously, we want to avoid using perchloric acid so we tried using sulfuric acid in a mixture of water and methanol.

The adrenaline free base proved to be practically insoluble in water, methanol or methylene chloride but dissolved readily in 1M aqueous sulfuric acid. Thus, 25 mg of adrenaline free base was dissovled in 5 mL of 1M aqueous sulfuric acid to give a clear solution. 20 mL of methanol were added and the solution was refluxed for 2 hours in open air and remained clear.

Samples taken a 0, 30, 60 and 120 minutes were run on TLC both directly and after treatment with sodium bicarbonate powder. As show in the TLC plates below, there was no change after 2 hours of reflux. The spots did not migrate in 4:1 hexanes/methylene chloride or pure methylene chloride. Streaks were obtained in pure methanol, with the samples treated with bicarbonate migrating less.

I suggest that we increase the sulfuric acid concentration tenfold and try again.


From left to right TLC's run in methanol from the reaction at 0, 30, 60 and 120 minutes. On each slide, the left spot is the untreated solution and the spot on the right is after treatment with excess sodium bicarbonate powder.