Hydroxide as a leaving group

The leaving group should become neutral when it leaves. Do not expel hydroxide as a leaving group rather, it should first be protonated so that it can leave as water. 

The elimination of alkyl halides is done under basic conditions, the elimination of alcohols is done under acid conditions. Under basic conditions, an E2 elimination would require the loss of a hydroxide ion as a leaving group. Since the hydroxide ion is a strong base, it is not a good leaving group and so the elimination of alcohols under basic conditions is difficult to achieve. 

The product is not stable, because hydroxide can be lost from the oxygen atom that was the nucleophile. Hydroxide is fine as a leaving group here— after all, hydroxide is lost from enolates in ElcB eliminations, and here the bond breaking is a weak 0-0 bond. The product is an epoxide. 

A poorer mechanistic option would show hydroxide as the leaving group ... 

Example 3.10. Under some conditions, hydroxide can act as a leaving group. 

If the electrophile and the nitrile are in the same molecule and the spacing between them is appropriate, then intramolecular alkylation entails cyclization to form rings. The preparation of a cyclopropane is shown using sodium hydroxide as the base and chloride as a leaving group. With an intramolecular alkylation, the base and the electrophile necessarily have to be present together, but the cyclization is so fast that competing 5 2 substitution of Cl" by HO" is not a problem. 

STRATEGY AND ANSWER The strongly basic HO ion (hydroxide ion) virtually never acts as a leaving group, something this reaction would require. This reaction would be feasible under acidic conditions, in which case the leaving group would be a water molecule. 

When acid derivative 2 reacts with sulfuric acid, the oxygen atom is the base and the conjugate acid product of this acid-base reaction is oxocarbenium ion 3, which is resonance stabilized. When 2 is an acid chloride, anhydride, ester, or amide, a heteroatom is attached to the positive carbon in 3. As in Chapter 18 (Section 18.1), the acid-base reaction of the carbonyl unit in 2 to give 3 facilitates reactions with nucleophiles. The reaction of intermediate 3 with a nucleophile ( Y) gives tetrahedral intermediate 4 contrary to acyl addition, reaction 4 contains an X group that can function as a leaving group. Loss of X leads to the final product of this reaction 5. If the nucleophile ( Y) is hydroxide, compormd 5 is the carboxylic acid (X = OH). If the nucleophile Y is an alcohol, the product 5 is an ester, and if Y is an amine, the product 5 is an amide. This first reaction is therefore the acid-catalyzed acyl substitution reaction of acid derivatives. 

Hydroxide departure as a leaving group followed by deprotonation of the ketone a-hydrogen... 

You may be wondering, "Why doesn t a hydroxide act as a leaving group from // " Note that structure Hi is a "twisted amide". It does not have the planar structure that imparts the stabilization normally associated with amides. Hence, compound Hi is very reactive, and in water it immediatel v converts to ii. 

Now identify the nucleophile and the substrate. Bromobutane is the substrate and hydroxide is the nucleophile. When hydroxide attacks, it will eject the bromide ion as a leaving group. The net result is that the Br will be replaced with an OH group ... 

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