Nucleophilic catalysis, mechanisms

If this intermediate, in turn, is more n idly attacked by water or hydroxide ion than the original ester, the overall reaction will be faster in the presence of the nucleophile than in its absence. These are the requisite conditions for nucleophilic catalysis. Esters of relatively acidic alcohols (in particular, phenols) are hydrolyzed by the nucleophilic catalysis mechanism in the presence of imidazole ... 

The nucleophilic catalysis mechanism only operates when the alkoxy group being hydrolyzed is not much more basic than the nucleophilic catalyst. This relationship can be imderstood by considering the tetrahedral intermediate generated by attack of the potential catalyst on the ester ... 

The relative importance of the potential catalytic mechanisms depends on pH, which also determines the concentration of the other participating species such as water, hydronium ion, and hydroxide ion. At low pH, the general acid catalysis mechanism dominates, and comparison with analogous systems in which the intramolecular proton transfer is not available suggests that the intramolecular catalysis results in a 25- to 100-fold rate enhancement At neutral pH, the intramolecular general base catalysis mechanism begins to operate. It is estimated that the catalytic effect for this mechanism is a factor of about 10. Although the nucleophilic catalysis mechanism was not observed in the parent compound, it occurred in certain substituted derivatives. 

Another way to esterify a carboxylic acid is to treat it with an alcohol in the presence of a dehydrating agent. One of these is DCC, which is converted in the process to dicyclohexylurea (DHU). The mechanism has much in common with the nucleophilic catalysis mechanism the acid is converted to a compound with a better leaving group. However, the conversion is not by a tetrahedral mechanism (as it is in nucleophilic catalysis), since the C—O bond remains intact during this step ... 

General base (jSnuc = 0.19) and nucleophilic catalysis mechanisms have been established for the hydrolysis of benzenesulfonyl chloride. Two-parameter LFERs were found for each route and electronic effects were seen to be greater than steric.272... 

G3P) and D-sedoheptulose 7-P as illustrated in Scheme 5.53. In addition D-erythrose 4-phosphate can function as the ketol acceptor thus producing D-fructose-6-P and G3P (Scheme 5.53). The enzyme relies on two cofactors for activity — thiamin pyrophosphate (TPP) and Mg2+—and utilizes the nucleophilic catalysis mechanism outlined in (Scheme 5.54).83 When TPP is used as a cofactor for nucleophilic catalysis, an activated aldehyde intermediate is formed. This intermediate functions as a nucleophile, and thus TK employs a strategy that is similar to the umpolung strategy exploited in synthetic organic chemistry. 

Mechanism The experimental evidence supports the nucleophilic catalysis mechanism as discussed in Scheme 3.11. The amine is acting as a nucleophilic catalyst rather than a base... 

For less acidic alcohols, nucleophilic participation is ineffective because of the low tendency for such alcohols to function as leaving groups. The tetrahedral intermediate formed by intramolecular addition simply returns to starting material because the carboxylate is a much better leaving roup than the alkoxide. In contrast to aspirin itself, acetyl salicylates with electron-withdrawing groups (o- and p-nitro analogs) hydrolyze via the nucleophilic catalysis mechanism. ... 

The nucleophile catalysis mechanism for benzoate formation depieted in Scheme 10.2 involves a first step produeing an intermediate aeyl ammonium salt and a seeond step in whieh the salt reaets with the phenol to form the ester. As a general rule for the kinetie study of eomplex reactions, we can make some assumptions to... 

Hydroximoyl chlorides 1 and 2. Do they really Isomerba Ouough a nucleophile catalysis mechanism ... 

An important data in favor of the nucleophile catalysis mechanism is the result obtained for 1 in the presence of radioactive chloride ion ( CF). It was found fliat the label was incorporated into the hydroximoyl chloride at a rate equal of one half ot the isomerization rate, as indicated in Eq. 27.1. 

The calculations show that protonated hydroximoyl chlorides 4 and 5 have a rotation barrier considerably higher than the corresponding hydroximates 6 (differences of about 17 and 10 kcal mol , respectively). A higher energy rotation barrier in the iminium intermediate should disable the protonation-rotation pathway, favoring the alternative nucleophilic attack. This is in agreement with the nucleophile catalysis mechanism proposed previously for the E/Z isomerization of hydroximoyl chlorides 1 and 2 (Scheme 27.5). 

The ElZ isomerization of C=N bonds can oeeur either by a nucleophile catalysis mechanism or by iminium ion rotation. The electrophilicity and the barrier to rotation of the iminium ion formed during the first step of the reaction determine the isomerization pathway. Thus, hydroximoyl chlorides 1 and 2 isomerize only by the nucleophile catalysis mechanism whereas hydroximates 3 are capable of isom-erizing by iminium ion rotation. 

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