Alkoxide leaving group ability

The concept of intrinsic barriers provides insight into the poor leaving group ability of alkoxides in other S 2 reactions as well. For instance, the methoxide exchange component of the intrinsic barrier to the reaction X + CH OCH XCH + OCHg is so large that, regardless of the nature of X, the reaction is predicted to be slow unless it is also extremely... 

The presence of four methyl groups at positions 4 and 5 of the dioxolan ring causes a larger decrease in 0- (Tables 12, 13) than in kH<. It is possible that in the hydroxide-ion catalysed reaction there is, superimposed on the steric effect, an electronic effect of the methyl groups which causes a decrease in the leaving group ability of the alkoxide ion due to their electronreleasing inductive effect. A similar effect is observed in the hydroxide-ion catalysed breakdown of benzaldehyde f-butyl and methyl hemiacetals for which / -( )/ -( ) = 37. 

The alkoxide formed by addition of a Grignard reagent to an aldehyde or ketone is stable. Tetrahedral intermediates are similarly formed by addition of a nucleophile to a carbonyl group, so why are they unstable . The answer is to do with leaving group ability. 

In acidic solution, the nitrogen is protonated and becomes a better leaving group and also loses its ability to assist in the elimination of the alkoxide. Under these circumstances, nitrogen eUmination is favored ... 

The principal difference hes in the poorer ability of amide ions to act as leaving groups, compared to alkoxides. As a result, protonation at nitrogen is required for breakdown of the tetrahedral intermediate. Also, exchange between the carbonyl oxygen and water is extensive because reversal of the tetrahedral intermediate to reactants is faster than its decomposition to products. 

The relief of strain can increase a group s leaving ability. For example, the reaction of epoxides with nucleophiles Nu- to give NuCH2CHRO proceeds readily, even though alkoxides are normally very bad leaving groups. 

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