Enammonium ions

Important for the hydrolysis is the observation (10) that protonation of enamines with hydrogen chloride does not immediately lead to immonium salts, but in most, if not all, cases first to the formation of the corresponding enammonium ions, which afterward rearrange more or less rapidly to the more stable immonium ions [Eq. (1)] ... 

Even though enammonium ions have been shown to be eventually transformed into iminium ions38-40, the steps that determine the protonation of enamines are highly sensitive to the reaction conditions, so that they can be accelerated or decelerated in order to preferentially direct the attack at the carbon or the nitrogen site of the enamine. 

In principle, a solvent may favour protonation at the N site over the C site through solvating effects in fact, —NH3 sites are known to be more readily solvated than —CHJ sites6,45 so that enammonium ions will also be easier to solvate than will iminium cations. Bearing in mind that many enamines are nitrogen bases in the gas phase, it is not very surprising that a number of enamines are initially protonated in solution at the nitrogen, not only by kinetic but also by thermodynamic control. 

The acceleration of the 3-aza-Cope rearrangement of A-allylenamines through formation of a cationic quaternary nitrogen center (enammonium salt) has obvious advantages. However, direct allylation of enamines in order to form the enammonium ions is unsatisfactory, and difficult. Moreover, the rearrangement-hydrolysis product is often contaminated by the C-allylated product when an unsymmetrical allyl halide is employed... 

Already at pH 10 and continuing down to pH 6, compounds 12 (X = H), 13 and 14 show a sharp decrease in k/s-1. Reaction is not buffer-catalyzed in this region, hence this is not due to rate-controlling protonation, by water, of a minority of enamine in equilibrium with its enammonium ion (equations 14 and 15). Nor can C-protonation by H30+ be rate-controlling since one would observe either an upward slope in the pH-rate profile (when [E] > [NH+]) or a plateau (when [NH+] > [E]). Although such characteristics in the rate profile were observed for compounds 1-3, they were not observed for the propiophenone enamines. Rather, a switch to rate-controlling nucleophilic attack on the iminium ion is indicated (equation 16) for which rate-law equation 22 is appropriate. 

Equation 44 is essentially the same as equation 20 except that, in equation 20, the equilibrium constant factor, A H+, refers to the unreactive enammonium ion of a simple enamine. In equation 44 the unreactive protonated form is proposed to be the O-protonated conjugate acid. This conjugate acid is, of course, potentially reactive toward nucleophilic water, but such a reaction (equation 45, corresponding to equations 38 and 39 of Scheme 2) destroys the conjugated enaminone n system, while the observed reaction (equation 43) leaves it intact. It is quite possible that all or part of reaction 45 occurs, and represents an unproductive, but rapidly established, equilibrium. If this were correct, then the equilibrium constant identified as K%H+ in equation 44 would refer to equilibrium between the starting enamine and all three of the species in equation 45. 

We return now to a point raised above regarding the levelling-off of the pH-rate profiles, which occurs below pH 1, for series 10 and 11. Mechanistically this plateau is ambiguous. In fact we have already seen that such a plateau could be due to ratecontrolling C-protonation (in a pH domain where the enammonium ion is dominant), or it could represent rate-controlling nucleophilic attack by water (equation 16, enammonium and/or iminium ions predominant in the reactant mixture). Compounds 1-3 exhibited the first type of behavior (at higher pH) while 5 (X = H) and 12 (X = H), 13 and 14 showed the second, If C-protonation is rate-controlling, the rate law, a simplification of equation 20, is equation 29. If nucleophilic attack by water controls the rate, then the rate law is equation 30, a modification of equation 21 for the case where A-basicity and C-basicity are both important . Coward and Bruice report values of k + and which combine to produce the observed... 

The reactions of enamines with electrophiles follow a similar course and are also of OE t type. Enamines are isoconjugate with enolate ions and can likewise react with electrophiles in two different ways, either on nitrogen to form an enammonium ion or on carbon to form a methyleneammonium ion. As in the case of enolate ions, protonation takes place more rapidly on the heteroatom (here nitrogen) rather than carbon while allyl halides, e.g., methyl iodide, give C-alkylated products e.g.. 

Methyleneammonium ions [e.g. (137)] are more stable than the isomeric enammonium ions [e.g., (136)], just as simple ketones are more stable than the corresponding enols, because the sum of the C=N and C—C bond energies in, e.g., (137) is greater than that of the C—N and C=C bond energies in, e.g., (136). The heat of reaction for attack on carbon will be correspondingly more negative than that for attack on nitrogen by an amount dE which will be independent of the electrophile ... 

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