Protonated intermediates

The overall rate being measured is that of step 2, but there may be no means of directly measuring [ROH2+]. The concentration of the protonated intermediate ROH2+ can be expressed in terms of the concentration of the starting material by taking into consideration the equilibrium constant, which relates [ROH], [Br ], and [H+] ... 

Specific acid catalysis is observed when a reaction proceeds through a protonated intermediate that is in equilibrium with its conjugate base. Because the position of this equilibrium is a function of the concentration of solvated protons, only a single acid-dependent term appears in the kinetic expression. For example, in a two-step reaction involving rate-determining reaction of one reagent with the conjugate acid of a second, the kinetic expression will be as follows ... 

The protonated intermediate in Eq. (5) is very reactive and could not be observed spectroscopically under the reaction circumstances. Fast hydration to isobutyraldehyde and the secondary amine occurred (75). This mechanism is exactly analogous to that of the hydrolysis of enolate anions (79), as is to be expected. 

Figure 22.1 MECHANISM Mechanism of acid-catalyzed enol formation. The protonated intermediate can lose H+, either from the oxygen atom to regenerate the kelo tautomer or from the a carbon atom to yield an enol.

In the other pathway, the migrations are in the same direction. The actual mechanism of this pathway is not certain, but an epoxide (protonated) intermediate " is one possibility ... 

The acid initially, protonates the nitrosamine to give a charged intermediate having significant water solubility. When the agent is gaseous hydrogen chloride or concentrated hydrochloric acid, the protonated intermediate is rapidly... 

The symmetric edge- or side-on N2 attachment mode appears to favor initial complexation at Fe-Fe edges or faces in the M center. This mode is less able to explain how, or if, partially reduced and protonated intermediates migrate to the molybdenum atom for generation of ammonia. The asymmetric N2 attachment mode appears to involve the molybdenum atom of the M center but not the iron atoms except as possible electron providers. 

Scheme 6 depicts three possible hydrolysis mechanisms.140 The first (pathway (i)) is normal acid-catalysed ester hydrolysis in which attack of solvent (H20) upon the protonated intermediate is rate determining. The second (pathway (ii)) is the... 

Fig. 14 (a) Anomerically weakened NO bond in the protonated intermediate (b) transition state (c) products from AaiI reaction of iV-acyloxy-iV-alkoxyamides. 

The isopropoxy compound 25f reacts about an order of magnitude faster than 25a, 25c and 25g. A measurably larger AS is consistent with additional relief of steric compression in the transition state the protonated intermediate (Fig. 14a) would be sp3 hybridised at nitrogen while the alkoxynitrenium ion (Fig. 14c) would be sp2 hybridised at nitrogen. The isobutoxy compound 25g, in which the branching is one methylene removed from the oxygen atom has similar parameters to straight chain substrates 25a and 25c. 

In the presence of alcohols, the corresponding ethers are formed and added nucleophiles such as chloride ion40 or azide ion41 lead to the chloro- and azido-amine products, respectively. Rate constants are independent of the concentration of added nucleophile. Labelled 180 from the solvent is incorporated in the product42. All the evidence points to a reaction mechanism where water is lost from the O-protonated reactant to give a nitrenium ion-iminium ion intermediate which is rapidly trapped by a nucleophile (H2O in this case) to give the final product. This is shown in Scheme 7. Protonation at N- is likely to be more extensive, but there is no pathway to products from the N-protonated intermediate. 

The Birch reduction has been used by several generations of synthetic organic chemists for the conversion of readily available aromatic compounds to alicyclic synthetic intermediates. Birch reductions are carried out with an alkali metal in liquid NH3 solution usually with a co-solvent such as THF and always with an alcohol or related acid to protonate intermediate radical anions or related species. One of the most important applications of the Birch reduction is the conversion of aryl alkyl ethers to l-alkoxycyclohexa-l,4-dienes. These extremely valuable dienol ethers provide cyclohex-3-en-l-ones by mild acid hydrolysis or cyclohex-2-en-l-ones when stronger acids are used (Scheme 1). 

The tetrazole-catalysed alcoholysis of simple dialkylphosphoramidates (267) in THE to yield trialkylphosphites (268) occurs via nucleophilic catalysis (Scheme 29). The proposed mechanism sees tetrazole acting first as an acid catalyst to give the protonated intermediate (269), which then reacts with tetrazolide anion to yield the tetrazolylphosphite (270) alcoholysis of the latter (270) then yields the final product, the trialkylphosphite (268). ... 

Prior to 1967 acetal hydrolysis had been found to be a specific-acid catalysed reaction with the accepted mechanism [equation (46)] involving fast pre-equilibrium protonation of the acetal by hydronium ion, followed by unimolecular rate-determining decomposition of the protonated intermediate to an alcohol and a resonance stabilized carbonium ion (Cordes, 1967). An A-1 mechanism was supported by an extremely large body of evidence, but it appeared unlikely that such a mechanism could expledn the... 

The norbomyl system has been subjected to an analogous series of experiments with the results shown in Table 4. When exo-2-chloro-norbornane was solvolysed in the presence of a hydride donor good yields of norbornane were obtained. The product had not acquired any protons from the acid and thus an edge-protonated intermediate had not formed before reaction with the hydride donor occurred. 

Although protonation does not occur on nitrogen in an amide, protonation can occur on the carbonyl oxygen, because this still allows the same type of resonance stabilization. Accordingly, acid hydrolysis of amides proceeds through nucleophilic attack of water onto the protonated carbonyl, giving a tetrahedral protonated intermediate. 

Y = OMe, Ph, OPh), acid catalysis resulted in a concerted El decomposition of the protonated intermediate (117) and release of benzyl cation in the rate-determining step according to Scheme 21. 

It is important to distinguish these novel reactions, which take place between the individual sheet silicates and involve the intercalation of one or more of the reactants, from those catalysed by clay mineral surfaces. While details of the mechanism of reactions involving intercalation in sheet silicates are not fully understood, it is generally known that acid sites present in sheet silicates (Bronsted, as well as Lewis) are involved in the reactions. Protonated intermediates such as carbonium or oxonium ions play a crucial role in such reactions. 

It has been shown that /-butylation of acetanilide [10] gives the 1,4-isomer as the kinetic product which is then converted into the 1,3-isomer. The isomerization is a 1,2-alkyl migration within the C-protonated intermediate which has a perfect set-up of donor and acceptor sites, and the two substituents of 3-(/-butyl)acetanilide are conjoint in polarity. 

To probe the thermodynamics of amine encapsulation, the binding affinities for different protonated amines for 1 were investigated. By studying the stabilization of the protonated form of encapsulated amines, the feasibility of stabilizing protonated intermediates in chemical reactions could be assessed. The thermodynamic cycle for encapsulation of a hypothetical substrate (S) is shown in Scheme 7.5. The acid-base equilibrium of the substrate is defined by Ki and the binding constant of the protonated substrate in 1 is defined by K2. Previous work has shown that neutral substrates can enter 1 [94] however, the magnitude of this affinity (K4) remains unexplored. Although neutral encapsulated amines were not observable in the study of protonated substrates, the thermodynamic cycle can be completed with K3, which is essentially the acid-base equilibrium inside 1. 

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