nucleophilic acyl substitution

MS 934 - Carey and Giuliano 8th Ed. CH 19 Submitted by Matt on August 7, 2011.

Textbook and Chapter: Carey and Giuliano 8th Ed. (2010), Chapter 19

Keyword: nucleophilic acyl substitution

Description: Goes over carboxylic acid derivatives and the nucleophilic acyl substitution mechanism. Includes synthesis problems.

Total Problems: 6

MS 919 - Nucleophilic Acyl Substitution and Addition Submitted by Matt on August 6, 2011.

Textbook and Chapters: Carey and Giuliano 8th Ed. (2010), Chapters 17, 18, 19

Keywords: carbonyl hydrates, nucleophilic acyl addition, nucleophilic acyl substitution

Description: The most important mechanism in second semester organic chemistry. Goes over carbonyl addition/substitution mechanisms under both acidic and basic conditions.

Total Problems: 6

Problem # 743

Enolates are nucleophiles and react with a variety of electrophiles.

Carbonyls are electrophiles. But aldehydes/ketones and  esters/acid chlorides often form different products.


Use curved arrows to draw a mechanism for each reaction below. How do the two products differ?

Problem # 729

The ester below was dissolved in a solution of water, a small amount of which was isotopically labeled with O-18, denoted with an asterisk.

After a few hours, some isotopically labeled oxygen was found in the ester. Where was it found in the ester? Can you explain why?

Problem # 728

The acyl group is a protecting group for amines. Amines can be acylated using acetic anhydride, and deacylated with base.

Propose a mechanism for each reaction.

Problem # 727

Show how the ester below can be prepared from propene.

Problem # 726

Show two esters that would yield the two alcohols below after treatment with lithium aluminum hydride.

Problem # 725

A chemist carried out a Fischer esterification using methanol that was isotopically labeled with 18O (indicated with an asterisk).

Which one of the esters below (A-D) was formed?

Problem # 724

Use curved arrows to show the formation of the tetrahedral intermediate of a Fischer esterification reaction (shown below). There are three steps in total.

Problem # 708

The overall mechanism for Fischer esterification is shown below. This isn't a real mechanism, just an outline.

Methanol (the nucleophile) attacks the carbonyl carbon, forming a tetrahedral intermediate, which then loses a water to reform the carbonyl. This mechanism is called nucleophilic acyl substitution.


Use curved arrows to draw a full mechanism for this reaction. I've included structures for you to use as a guide.

This reaction takes place under acidic conditions, so the mechanism you draw will be similar to those in problem 706.