Fate of the Tetrahedral Intermediate

(for aldehyde example click here)

What we mostly need to know about carbonyl chemistry for the entire semester can be summarized by the few concepts on this page. The following three rules are true for all carbonyl compounds:

1. the carbonyl oxygen is basic, and will give electrons to Lewis acids

2. the carbonyl carbon is electrophilic, and accepts electrons from and forms bonds with all sorts of nucleophiles

3. Addition of a nucleophile to a carbonyl will give a tetrahedral intermediate, and predicting what happens next is the same as predicting the carbonyl’s chemistry. The reaction may reverse, stop there, or collapse to a new carbonyl compound (which may or may not go on to react again).

Addition to a carbonyl always gives a tetrahedral intermediate:

What happens to the tetrahedral intermediate next? There are four possible outcomes, and each is described below.

The reaction may reverse back to starting materials:

The reaction may stop after one addition:

The tetrahedral intermediate may collapse to a new unreactive carbonyl compound:

The tetrahedral intermediate may collapse to a new carbonyl compound which reacts with the nucleophile:

As the ability of the group X (the X in the above structures) to donate electron density into the carbonyl through resonance or hyperconjugation increases:

1. the carbonyl oxygen will become more basic

2. the carbonyl carbon becomes less electrophilic and less reactive towards nucleophiles

The reactivity trends of aldehydes, ketones, acids, acid chlorides, esters and amides can be explained by understanding how X increases or decreases reactivity. Seeing these models of the functional groups may help you understand their reactivity. (Here’s a smaller pdf file of the same thing.) Here’s a pKa table expressing the same ideas in a more precise manner.

To predict carbonyl chemistry you must consider:

1. the strength of the nucleophile

2. the ability of X to serve as a leaving group

3. the ability of X to donate electron density into the carbonyl (see discussion and models given immediately above)

4. the reaction conditions

5. the stability of the proposed product under the reaction conditions

Here’s an example with an aldehyde.