CO7. What is a Good Nucleophile?

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CO7. What is a Nucleophile?

Lots of things can be nucleophiles. In principle, a nucleophile only needs a lone pair. However, some nucleophiles are better than others.

You already know something about nucleophiles if you know something about acidity and basicity. Nucleophiles are really Lewis bases. Some of the factors that account for basicity also account for nucleophilicity.

Halides are not very good nucleophiles for carbonyls. The negative charge on a halide is pretty stable, either because of electronegativity or polarizability. If a halide donates to a carbonyl, producing an oxygen anion, the reaction is uphill.

Hydroxide and alkoxide anions (such as CH₃O^-) are more reactive than halides. They are better nucleophiles. The sulfur analogues are similarly good nucleophiles (such as CH₃S^-). In addition, water, alcohols and thiols are nucleophilic, because they all have lone pairs that could be donated to an electrophile.

Nitrogen also has a lone pair in most compounds. That means amines are good nucleophiles, too.

Carbon does not normally have a lone pair, unless it is a carbanion. Carbanions are usually not very stable. As a result, they are not very common, except for cyanide (CN^-) and acetylides (RCC^-, in which R is a hydrogen or an alkyl group).

Problem CO7.1.

Carbanions such as CH₃^- (methyl anion) are very unstable and highly reactive. Explain why the following anions are more stable than a methyl anion.

Acetylide, HCC^-

cyanide, CN^-

Problem CO7.2.

Nucleophilicity is the degree of attraction of a nucleophile to a positive charge (or partial positive charge). It is related to basicity. Choose the most nucleophilic item from each of the following pairs, and explain your answer.

CH₃OK or CH₃OH

CH₃OH or CH₃NH₂

NaCN or NaCCH

c-C₆H₁₁ONa or c-C₆H₅ONa (c- in this case means "cyclo")

Problem CO7.3.

Carbonyl compounds such as aldehydes and ketones contain a very slightly acidic hydrogen next to the carbonyl. Some nucleophiles are basic enough to remove that proton instead of donating to the carbonyl. Show why the resulting anion is stable, using cyclopentanone as an example.

Problem CO7.4.

Accidental deprotonation (proton removal) alpha to a carbonyl (one carbon away from the carbonyl) can occur when a nucleophile is added to a ketone. In the following cases, explain which nucleophile is more likely to add to the carbonyl in cyclohexanone and which is more likely to deprotonate it.

Contributors

Chris P Schaller, Ph.D., (College of Saint Benedict / Saint John's University)