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Organic Chemistry Text Book (CHEM 3401 and 3402)

20.5.2 Substitution of the Hydroxyl Hydrogen

This reaction class could be termed electrophilic substitution at oxygen, and is defined as follows (E is an electrophile). Some examples of this substitution are provided in equations (1) through (4).

RCO2–H   +   E(+) RCO2–E  +  H(+)


If E is a strong electrophile, as in the first equation, it will attack the nucleophilic oxygen of the carboxylic acid directly, giving a positively charged intermediate which then loses a proton. If E is a weak electrophile, such as an alkyl halide, it is necessary to convert the carboxylic acid to the more nucleophilic carboxylate anion to facilitate the substitution. This is the procedure used in reactions 2 and 3. Equation 4 illustrates the use of the reagent diazomethane (CH2N2) for the preparation of methyl esters. This toxic and explosive gas is always used as an ether solution (bright yellow in color). The reaction is easily followed by the evolution of nitrogen gas and the disappearance of the reagent's color. This reaction is believed to proceed by the rapid bonding of a strong electrophile to a carboxylate anion.
The nature of SN2 reactions, as in equations 2 & 3, has been described elsewhere. The mechanisms of reactions 1 & 4 will be displayed by clicking the "Toggle Mechanism" button below the diagram.




Alkynes may also serve as electrophiles in substitution reactions of this kind, as illustrated by the synthesis of vinyl acetate from acetylene. Intramolecular carboxyl group additions to alkenes generate cyclic esters known as lactones. Five-membered (gamma) and six-membered (delta) lactones are most commonly formed. Electrophilic species such as acids or halogens are necessary initiators of lactonizations. Even the weak electrophile iodine initiates iodolactonization of γ,δ- and δ,ε-unsaturated acids. Examples of these reactions will be displayed by clicking the "Other Examples" button.