Basicity alkoxide ions

Special interactions of the charged reagent with the substrate can lead to kinetic complications and to exceptional substrate reactivity. For example, the strongly basic alkoxide ion promotes ionization of... 

As described in a previous section, the imidazole group of a histidyl residue is involved in a most direct fashion in the catalytic action of hydrolytic enzymes (see Table 2—1). This fact attracted mudi attention among phyrical organic chemists, and imidazole and imidazole compounds became the first organic bases to have been established as catalysts for ester hydrolysis. Since the weakly basic imidazolyl group is not capable of directly displacing the much mtxe basic alkoxide ions from normal esters, most studies have dealt with the catalysis of the hydrolysis of activated esters, such as phenyl acetates and thiol esters ... 

Hie basic alkoxide ion tmermediate abstracts a proton frQm water to yield gem diol product and regenerate hydroxide Ion catalyst. 

Such a reaction occurs much more readily than displacement of the strongly basic alkoxide ion from the neutral ether. 

As in alkaline hydrolysis, there is almost certainly a tetrahedral intermediate —or, rather, several of them. The existence of more than one intermediate is required by, among other things, the reversible nature of the reaction. Looking only at hydrolysis, intermediate II is likely, since it permits separation of the weakly basic alcohol molecule instead of the strongly basic alkoxide ion but consideration of esterification shows that H almost certainly must be involved, since it is the product of attack by alcohol on the protonated acid. 

The highly basic alkoxide ion then immediately reacts with phenol to regenerate phenoxide to repeat the cycle (Reaction 26), and at the same time to exclude the possibility of side reactions taking place ... 

The available data appear to be consistent with the notion that removal of one of the three water molecules from a basic alkoxide ion is necessary to make an electron pair available for nucleophilic attack. The requirement for this removal decreases the observed rate constants and Pnuc for basic oxygen anions that are solvated by three water molecules. This concept implies that partial solvation can be retained in the transition state. A somewhat similar situation has been calculated by Jorgensen and co-workers (2) for the attack of Cl- on methyl chloride in water. With the less basic phenoxide ions, less solvation occurs initially and nucleophilic attack can occur with little or no loss of solvation energy. 

There are at least two factors that are likely to contribute to this difference in the intrinsic rate constants for the two pathways. One is that in the ki k-i pathway the nucleophile is a strongly basic alkoxide ion. The strong solvation of such oxyanions is known to reduce their kinetic activity. This reduction is a classic... 

The key step is nucleophilic addition to the carbonyl group (step 1). The reaction proceeds via a tetrahedral intermediate, but the reactant and the product are trigonal. Saponification is not reversible in the final step (3), the strongly basic alkoxide ion removes a proton from the acid to form a carboxylate ion and an alcohol molecule—a step that proceeds completely in the forward direction. 

If the reaction of benzylpenicillin with alkoxide ions proceeded with rate-limiting attack, basic alkoxide ions would be expected to show a negative deviation from the Bronsted plot which is usually curved for such reactions (Hupe and Jencks, 1977 Jencks et al., 1982). 

Breakdown of alkoxide and thiolate ion adducts (10) of benzylidene Meldrum s acid (9a), methoxybenzylidene Meldrum s acid (9b), and thiomethoxybenzylidene Meldmm s acid (9c) is subject to weak general acid catalysis eliminative expulsion of RO or RS is in competition with protonation of a-carbon or enolate oxygen. Thiolate ion departure is much less sensitive to catalysis by H+ than is departure of the more basic alkoxide ion, and the positive Pig values for RO and RS departure imply an imbalanced transition state where proton transfer from H3O+ to the departing group is ahead of C-O or C-S bond cleavage. 

The dioxetane rearranges to an epoxide that has a strongly basic alkoxide ion called a vitamin K base. 

The highly basic alkoxide ion then immediately reacts with phenol according to reaction (80) to regenerate the phenoxide ion. The phenoxide ion, so formed, repeats the reaction cycle and thereby eliminates the side reaction. 

Esters (Claisen reaction). The Claisen reaction probably involves an ionic mechanism similar to that shown for the aldehydes and ketones. The first step is the displacement of the ester anion by the basic alkoxide ion ... 

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