KINETICS AND MECHANISM OF NITROSATION OF CLONIDINE - A BRIDGE BETWEENNITROSATION OF AMINES AND UREAS

Nitrosation of clonidine has been studied kinetically both in acid med ium (with nitrous acid) and in basic medium (with 2,2-dichloroethyl ni trite). The reactive form in acid medium was found to be the protonate d clonidine (pK(a) 8.18). The absence of catalysis by halides or thioc yanate, the existence of general base catalysis, and the measured solv ent isotope effect all indicate that the reaction mechanism is differe nt from that for the N-nitrosation of amines. Specifically, kinetic re sults indicate that the attack of the nitrosating agent on the substra te is not the rate determining step of the process, and suggest a mech anism that shows parallels with that found for ureas. However, in slig htly basic medium, the reaction of clonidine with the alkyl nitrite oc curs through the free base form of clonidine, as shown by the influenc e of acidity upon the reaction rate. In this case, the kinetic behavio ur is similar to that exhibited by amines.