Pyromellitate - a little used counterion to add to the process chemist's tool box

19 January 2004

Process chemists are always on the lookout for simple practical tricks and tools to facilitate product crystallisation, purification and isolation. Furthermore, when it comes to active pharmaceutical ingredients, the desired physical properties may require tuning to suit the drug delivery system. Salt formation is the commonest way of tackling these challenges.

Typically used counterions for basic molecules include tosylate, mesylate, tartrate, succinate, oxalate, citrate and benzoate, as well as hydrochloride, hydrobromide, hydrosulfate etc, etc..

A counterion which may not be so familiar to many is pyromellitate (1,2,4,5-benzenetetracarboxylate), which was recently reported* by GlaxoSmithKline process chemists as being the only one of nearly 100 acids screened which gave the desired physical properties for the salt of a nucleoside analogue to be delivered by inhalation.

Perhaps pyromellitic acid could be the key to isolating or purifying your non-crystalline intermediate or product.....?

* P. Blatcher (GlaxoSmithKline, UK), "Highlights from the Development of Processes for the Synthesis of 2,6-Diaminopurine Nucleosides", Presentation given at the 8 th international conference on Organic Process Research and Development, Barcelona, 7-10 September 2003.