Rapid formation of N-nitrosodimethylamine from gramine, a naturally occurring precursor in barley malt

The two tertiary amine alkaloids, hordenine and gramine, which are biosynthesized in malt during germination, were subjected to nitrosation under conditions typical for the study of tertiary amine nitrosation. At 65 degrees C in dilute aqueous acid (pH 4.4 or pH 6.4), nitrosation of both amines resulted in formation of N-nitrosodimethylamine (NDMA). At 24 degrees C in dilute acid (pH 3.4), the initial rate of NDMA formation from gramine was nearly equal to the initial rate of NDMA formation from dimethylamine. At the same temperature, the ratio of initial rates of formation of NDMA from gramine and trimethylamine was 6250:1. At 23 degrees C, the ratio of initial rates of formation of NDMA from gramine and hordenine was 5200:1. The rapid reaction of gramine with nitrous acid and the nature of the gramine nitrosation reaction products both indicated that gramine did not undergo nitrosation by the expected mechanism of nitrosative dealkylation. A new mechanism if proposed to explain the labile nature of the dimethylamino group of gramine and to account for the fact that NDMA is the only N-nitrosamine formed during the nitrosation of gramine.