On the stability of 2-aminoselenophene-3-carboxylates: potential dual-acting selenium-containing allosteric enhancers of A1 adenosine receptor binding

Ethyl-2-amino-4,5,6,7-tetrahydro-1-benzoselenophene-3-carboxylate (4), has been prepared as a potential dual-acting selenium-containing allosteric enhancer of adenosine A(1)A receptor binding utilising a modified Gewald reaction. While preliminary testing indicated that 4 is a superior enhancer of A(1)AR binding than its thiophene counterpart, its instability under mildly acidic conditions is cause for concern. X-Ray crystallography, together with DFT calculations, provide evidence that the decomposition of 4 involves the ring-opening of selenophenium ion (12b) followed by the loss of elemental selenium through a radical chain process.