Deuterium exchange at the 7-methyl group in 6,7,8-trimethyl-lumazine [6,7,8-trimethylpteridine-2(1H),4(3H)-dione]. An unusual example of general acid–general base catalysis

Abstract

The rate of exchange of the hydrogen atoms in the 7-methyl group of 6,7,8-trimethyl-lumazine (I) at 34·5° has been followed by means of ¹H n.m.r. spectroscopy. The reaction is subject to both general acid and general base catalysis, with Brönsted coefficients α= 0·46 (12 acids) and β= 0·45 (14 bases). The rate of the spontaneous reaction is extremely low and there is no evidence of a product term, [HA][A^–], for the catalysis. The catalytic constants k_HA and k_A^– are approximately equal when the acid–base pair used as buffer has a pK_a of 2·8. The acid- and base-catalysed routes differ only by the presence of an extra proton in the former. This permits a comparison to be made of the ability [k_{(SH⁺+ A^–)}] of the buffer anion A^– to abstract a proton from the protonated substrate relative to its ability [k_{(S + A^–)}] to do so from the neutral substrate. The value of k_{(SH⁺+ A^–)}/k_{(S + A^–)} is 10² in the case of compound (I), and since α+β for this reaction is close to unity, is almost independent of the buffer used. Other prototropic reactions that are also subject to general acid–base catalysis are analysed in the same way and it is shown that the value of k_{(SH⁺+ A^–)}/k_{(S + A^–)} found in the present work is unusually low.