Acyloxymethyl derivatives of secondary and tertiary amides undergo hydrolysis via acid-catalysed, base-catalysed and pH-independent processes. The pH-independent pathway involves rate-limiting iminium ion formation and is characterised by the following: a Hammett p value for the substituent in the benzamide moiety of ca. -1.2 for both types of substrate; the absence of general-base or nucleophilic catalysis; a common benzoate ion effect; a solvent deuterium isotope effect, k:&!/kEg:, of ca. 1.6; ASs values of -4 and -12 J K-l mol-l for secondary and tertiary substrates respectively; and higher reactivity of the tertiary amides over their secondary counterparts. The acidcatalysed process involves protonation of the substrate followed by iminium ion formation, and is characterised by the following: a Hammett p value of ca. -1.5 for the substituent effect of the benzamide moiety; a solvent deuterium isotope effect of ca. 0.4; a monotonic rise in the pseudofirst-order rate constant kobs with increasing [H, SO,];

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Kinetic measurements for the acid-catalysed decomposition of N-nitroso-2-arylimidazolines are reported. Reactions are first-order in both [substrate] and [H+]. Two products are formed; an oxazoline, which is the product of hydrolysis of the amidine moiety, and the parent imidazoline formed by denitrosation of the substrate. These products arise from two competing pathways both of which are acid catalysed. The solvent isotope effects for the denitrosation, k&/k$, and amidine hydrolysis, kE'/ki ', are 3.1 and 3.5, respectively. The denitrosation pathway, but not amidine hydrolysis, is catalysed by nucleophilic anions, and a value of 1.7 for the Swain-Scott constant, s, is obtained. In the absence of nucleophilic anions, amidine hydrolysis is preferred over denitrosation, k i t being twice as large as k:;) at 25°C. Substitutents in the 2-aryl ring affect the rate of decomposition giving Hammett p values of 0.7 for denitrosation and 1.0 for amidine hydrolysis, which reflect the proximity of the reacting centres to the substituents. Values of the activation parameters are AHRo 74 kJ mol-', AH1 74 kJ mot-', Asko -48 J K-l mol-' and A S i -43 J K-l mol-l. The data are interpreted in terms of a fast equilibrium protonation of the substrate, followed by competitive attack at the protonated substrate, either of water or nucleophilic anions at the nitroso nitrogen atom, or of water at the amidine carbon atom. Protonation is required to activate the substrate, the substrate being recovered from neutral or alkaline solutions unchanged. The mechanism is discussed with reference to the analogous reactions of N-nitrosoamines and Nn it rosoam ides.Imidazolines [ e g . (l)] are cyclic amidines that have a variety of biological effects.' For example, fenmetozole (2) and dazadrol (3) are examples of antidepressive imidazolines, whereas tolazoline (4) and phentolamine (5) are known vasodilator^.'-^ Many

Nitrosation of clonidine has been studied kinetically both in acid medium (with nitrous acid) and in basic medium (with 2.2-dichloroethyl nitrite). The reactive form in acid medium was found t o be the protonated clonidine (pK, 8.18). The absence of catalysis by halides or thiocyanate, the existence of general base catalysis, and the measured solvent isotope effect all indicate that the reaction mechanism is different from that for the N-nitrosation of amines. Specifically, kinetic results indicate that the attack of the nitrosating agent on the substrate is not the rate determining step of the process, and suggest a mechanism that shows parallels with that found for ureas. However, in slightly basic medium, the reaction of clonidine with the alkyl nitrite occurs through the free base form of clonidine, as shown by the influence of acidity upon the reaction rate. In this case, the kinetic behaviour is similar to that exhibited by amines.