Acyl halide

Interchange among carboxylic acid derivatives, such as amides, esters, acyl phosphates, and thioesters, is a major theme in biochemistry. This makes reactions of carboxylic acid derivatives a major theme for MCAT review.

Carboxylic acid derivatives include the carboxylates, amides, and esters. Also anhydrides, acyl halides, thioesters and acyl phosphates. Of the latter group, anhydrides and acyl halides don't appear in biochemistry, so while they are important for general organic chemistry, the new MCAT in not be so interested in them. However, thioesters and acyl phosphates do figure prominently in biochemistry. In fact, having a high free energy, the status of thioesters and acyl phosphates as the prototypical activated acyl compounds in biochemistry makes them among the most important types of organic molecules to understand.

WikiPremed Resources



Acyl Compounds Mechanisms
Mechanisms and explanations from the Organic Mechanisms Pocketbook

Reactions of Carboxylic Acids and Derivatives Images
Image gallery for study with links to larger teaching JPEGs for classroom presentation

Question Drill for Carboxylic Acids and Derivatives
Conceptual Vocabulary Self-Test

Basic Terms Crossword Puzzle

Basic Puzzle Solution

Learning Goals

Proficiency 

Understand how resonance stabilization of the carboxylate anion promotes the acidity of carboxylic acids.

Understand the order of stability among carboxylic acid derivatives.

See nucleophilic acyl substitution mechanisms as recapitulations of a general mechanism involving formation and resolution of a tetrahedral intermediate: Acid Halide Formation, Fischer Esterification, Use of Carboxylate Anion Nucleophile to form Esters, Hydrolysis of Acid Halides, Reaction of Acyl Halide with Ammonia or Amine, Esterification of Acid Halides, Esterification of Acid Anhydrides, Saponification of Esters. Acyl substitution appears on many MCATs.

Understand the role acid catalysis plays in facilitating some acyl substitution mechanisms.

Be able to recognize and follow Claisen Condensation, Nitrile Hydrolysis, Nitrile Reduction or Hofmann Rearrangement if you were presented with the mechanism.

Suggested Assignments

Review the basic terms for reactions of aldehydes & ketones using the question server. Complete the fundamental terms crossword puzzle. Here is the solution to the puzzle.

Read pp. 90-95 in ExamKrackers Chemistry.

Review the web resources for reactions of carboxylic acids & derivatives.

Conceptual Vocabulary for Carboxylic Acids and Derivatives

Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of a carboxyl group.
Ester
Esters are a class of chemical compounds and functional groups which consist of an inorganic or organic acid in which at least one hydroxyl group has been replaced by an alkoxy group.
Nucleophilic acyl substitution
Nucleophilic acyl substitution describes the substitution reaction involving nucleophiles and carboxylic acid derivatives including esters, amides and acid halides.
Amide
Amides are a class of chemical compounds and functional groups in which a carbonyl group carbon is linked to a nitrogen atom.
Acyl halide
An acyl or acid halide is a chemical compound derived from an acid by replacing a hydroxyl group with a halide group.
Hydrolysis
Hydrolysis is a chemical reaction or process in which a chemical compound is broken down by reaction with water.
Condensation reaction
A condensation reaction is a chemical reaction in which two molecules or moieties combine to form one single molecule, together with the loss of a small molecule.
Acyl
An acyl group is a functional group derived by the removal of one or more hydroxyl group from an oxoacid.
Esterification
Esterification is the general name for a chemical reaction in which two chemicals, such as an alcohol and an acid, form an ester as the reaction product.
Acid anhydride
An acid anhydride is an organic compound which has two acyl groups bound to the same oxygen atom.
Fischer esterification
Fischer esterification is the process of forming an ester by refluxing a carboxylic acid and an alcohol in the presence of an acid catalyst.
Saponification
Saponification is the hydrolysis of an ester under basic conditions to form an alcohol and the salt of a carboxylic acid.
Acetylation
Acetylation or ethanoylation describes a reaction that introduces an acetyl functional group into an organic compound.
Aminolysis
Aminolysis is any chemical reaction in which a molecule is split into two parts by reacting with a molecule of ammonia or an amine.
Hell-Volhard-Zelinsky halogenation
The Hell-Volhard-Zelinsky halogenation reaction halogenates carboxylic acids at the alpha carbon.
Hofmann Rearrangement
The Hofmann rearrangement is the organic reaction of a primary amide to form a primary amine with one fewer carbon atom.
Malonic ester synthesis
In the malonic ester synthesis, diethyl malonate or a similar ester is alkylated at the carbon alpha to both carbonyl groups, and then converted to a substituted acetic acid.
Advanced terms that may appear in context in MCAT passages
Knoevenagel condensation
The Knoevenagel condensation reaction is a modification of the Aldol condensation in which nucleophilic addition occurs of an active hydrogen compound, which is a substance capable of adding hydrogens to an enolate anion, followed by an dehydration reaction.
Arndt-Eistert synthesis
The Arndt-Eistert synthesis is a series of chemical reactions designed to convert a carboxylic acid to a carboxylic acid homologue with one additional carbon atom.
Curtius rearrangement
The Curtius rearrangement is a chemical reaction that involves the rearrangement of an acyl azide to an isocyanate.
Schmidt reaction
The Schmidt reaction involves alkyl migration over the carbon to nitrogen chemical bond in an azide with expulsion of nitrogen.
Dakin-West reaction
The Dakin-West reaction is a chemical reaction that transforms an amino-acid into an amino-ketone using a acid anhydride and a base, typically pyridine.
Fries rearrangement
The Fries rearrangement is a rearrangement reaction of a phenyl ester to a hydroxy aryl ketone by catalysis of lewis acids.
Reformatskii reaction
The Reformatskii reaction is an organic reaction which condenses aldehydes or ketones with alpha-halo esters in the presence of metallic zinc to form beta-hydroxy-esters.