Alkylation of amino acids and glutathione in water by o-quinone methide. Reactivity and selectivity

o-Quinone methide (1)has been produced in water both thermally:and photoche mically from (2- hydroxybenzyl)trimethylammonium iodide (2). Michael additi on reactions of 1 to various amines, and sulfides, including amino acids an d glutathione have been carried out, obtaining alkylated adducts (3-16) in fairly good to quantitative yields. The reaction rate and selectivity of 1 toward nitrogen and sulfur nucleophiles, in competition with the hydration reaction, have been investigated at different pH by laser flash photolysis technique. The observed reactivity: spans 7 orders of magnitude on passing from water (k(Nu) = 5.8 M-1 s(-1))to the most reactive :nucleophile (2.8 x 10(8) M-1 s(-1), 2-mercaptoethanol under alkaline conditions). These are th e first direct reaction rate measurements of nucleophilic addition to the p arent o-quinone methide (1). Competition experiments provided strong kineti c support to the involvement of free 1 as an intermediate in both thermal a nd photochemical reactions. Furthermore, several alkylation adducts regener ate 1 either by heating (9, 10, 13, and 14) or by irradiation(9, 11-13, 16) . Such a thermal and photochemical reversibility of the alkylation process opens anew perspective for the use and application of such adducts as o-QM molecular carriers.