18.2: Consequences of Tautomerization

Last updated
Save as PDF

Page ID: 375467

\( \newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} } \) \( \newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}} \)\(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\) \(\newcommand{\id}{\mathrm{id}}\) \( \newcommand{\Span}{\mathrm{span}}\) \( \newcommand{\kernel}{\mathrm{null}\,}\) \( \newcommand{\range}{\mathrm{range}\,}\) \( \newcommand{\RealPart}{\mathrm{Re}}\) \( \newcommand{\ImaginaryPart}{\mathrm{Im}}\) \( \newcommand{\Argument}{\mathrm{Arg}}\) \( \newcommand{\norm}[1]{\| #1 \|}\) \( \newcommand{\inner}[2]{\langle #1, #2 \rangle}\) \( \newcommand{\Span}{\mathrm{span}}\)\(\newcommand{\AA}{\unicode[.8,0]{x212B}}\)

So, what are some of the consequences of keto-enol tautomerization?

1. \(α\)-epimerization – stereochemical equilibration of a stereogenic center (either under acidic or basic conditions)

Screen Shot 2023-01-04 at 9.53.48 AM.png

In the example above under acidic conditions, since the enol is achiral, reprotonation can occur from the opposite face, giving a racemic mixture. The same thing can happen under basic conditions:

Screen Shot 2023-01-04 at 9.53.56 AM.png

2. isomerization of nonconjugated enones into conjugated enones

Screen Shot 2023-01-04 at 9.54.01 AM.png

3. exchange of \(α\)-protons for deuterium

Screen Shot 2023-01-04 at 9.54.10 AM.png

4. enols are electron-rich alkenes that undergo electrophilic addition.

Screen Shot 2023-01-04 at 9.54.16 AM.png

Enols/enolates are nucleophiles that react through the (\(π\) bond (note the regiochemistry). The oxygen lone pairs increase the level of the HOMO (\(π\)_C_-C)

An example of the this type of reactivity is the \(α\)-halogenation of ketones. This reaction can be performed under both acidic and basic conditions, but the products that form are quite different.

a) acidic conditions

Screen Shot 2023-01-04 at 9.54.25 AM.png

In this reaction, bromine is electronegative, so it’s pulling electron density away from the carbonyl inductively, making the carbonyl lone pairs less basic and less likely to protonate and perform a second bromination. In other words, the monobrominated product is less reactive than the starting material, so the reaction stops at monobromination.

b) basic conditions

Screen Shot 2023-01-04 at 9.54.33 AM.png

Under these conditions, the product of monobromination is more reactive than the starting material. The a C-H bond is more acidic because of the inductively withdrawing bromine atom that has been incorporated, so the reaction continues. A second and third bromination can occur, and it is very difficult to stop the reaction. When methyl ketones are treated with NaOH and Br₂, an even different product forms:

Screen Shot 2023-01-04 at 9.54.45 AM.png

This is a good way of making carboxylic acids from ketones.