21.2 Nucleophilic Acyl Substitution Reactions
2 min read•may 7, 2024
is all about swapping out parts of molecules. It's like a game of musical chairs, where nucleophiles kick out leaving groups from . The reaction happens in two steps: addition and elimination.
Different play the game differently. are the party animals, ready to react with anything. are the wallflowers, needing a lot of convincing to join in. The products depend on which crashes the party.
Nucleophilic Acyl Substitution Reactions
Mechanism of nucleophilic acyl substitution
Top images from around the web for Mechanism of nucleophilic acyl substitution
Nucleophilic acyl substitution - Wikipedia View original
Is this image relevant?
6.5. Lewis acids & bases, electrophiles & nucleophiles | Organic Chemistry 1: An open textbook View original
Is this image relevant?
22.1. Introduction | Organic Chemistry II View original
Is this image relevant?
Nucleophilic acyl substitution - Wikipedia View original
Is this image relevant?
6.5. Lewis acids & bases, electrophiles & nucleophiles | Organic Chemistry 1: An open textbook View original
Is this image relevant?
1 of 3
Top images from around the web for Mechanism of nucleophilic acyl substitution
Nucleophilic acyl substitution - Wikipedia View original
Is this image relevant?
6.5. Lewis acids & bases, electrophiles & nucleophiles | Organic Chemistry 1: An open textbook View original
Is this image relevant?
22.1. Introduction | Organic Chemistry II View original
Is this image relevant?
Nucleophilic acyl substitution - Wikipedia View original
Is this image relevant?
6.5. Lewis acids & bases, electrophiles & nucleophiles | Organic Chemistry 1: An open textbook View original
Is this image relevant?
1 of 3
- Nucleophilic acyl substitution reactions replace the on a carboxylic acid derivative (, amides, acid chlorides, ) with a nucleophile
- Follows an :
- Addition step: nucleophile attacks the electrophilic carbonyl carbon forming a
- Tetrahedral intermediate has a negatively charged oxygen and the nucleophile bonded to the carbonyl carbon
- Elimination step: tetrahedral intermediate collapses reforming the carbonyl group and ejecting the
- Addition step: nucleophile attacks the electrophilic carbonyl carbon forming a
- Rate-determining step is typically the addition step where the nucleophile attacks the carbonyl carbon
Reactivity of carboxylic acid derivatives
- Reactivity order: acid chlorides > anhydrides > esters > amides
- Electronic factors affecting reactivity:
- Electron-withdrawing groups on the carbonyl carbon increase reactivity by making it more electrophilic (acid chlorides)
- stabilization of the leaving group increases reactivity by stabilizing the developing negative charge during elimination (anhydrides)
- Steric factors affecting reactivity:
- Bulky substituents near the carbonyl group decrease reactivity by hindering nucleophile approach (amides)
- Acid chlorides are most reactive due to excellent leaving group ability of the chloride ion and lack of resonance stabilization
- Amides are least reactive due to strong resonance stabilization of the amide bond and poor leaving group ability of nitrogen
Products of acyl substitution reactions
- Reactions with water ():
- Esters + water → carboxylic acids + alcohols
- Amides + water → carboxylic acids + amines (harsh conditions)
- Acid chlorides + water → carboxylic acids + HCl
- Anhydrides + water → carboxylic acids
- Reactions with alcohols ():
- Esters + alcohol → new ester + alcohol ()
- Amides + alcohol → esters + amines (harsh conditions)
- Acid chlorides + alcohol → esters + HCl
- Anhydrides + alcohol → esters + carboxylic acids
- Reactions with amines ():
- Esters + amine → amides + alcohol
- Acid chlorides + amine → amides + HCl
- Anhydrides + amine → amides + carboxylic acids
Key concepts in nucleophilic acyl substitution
- : The functional group consisting of a carbonyl group bonded to an alkyl or aryl substituent
- : A class of organic compounds containing a carbonyl group (C=O)
- : In these reactions, the carbonyl carbon acts as the electrophile, attracting nucleophiles
- Resonance: Contributes to the stability of certain carboxylic acid derivatives, affecting their reactivity
- : The process of introducing an into a molecule through nucleophilic acyl substitution
Key Terms to Review (24)
Acid anhydrides: Acid anhydrides are organic compounds formed by the removal of water between two carboxylic acid molecules. They play a significant role in nucleophilic acyl substitution reactions, where they act as electrophiles ready to react with nucleophiles.
Acid Chlorides: Acid chlorides, also known as acyl chlorides, are a class of organic compounds derived from carboxylic acids. They are characterized by the presence of a carbonyl carbon bonded to a chlorine atom, making them highly reactive and versatile in organic synthesis.
Acyl group: An acyl group is a functional group derived from a carboxylic acid by removal of a hydroxyl group (OH), represented as RCO-, where R can be any alkyl or aryl group. It plays a crucial role in the acylation reactions, including the synthesis of ketones and aldehydes through electrophilic aromatic substitution.
Acyl Group: An acyl group is a functional group with the general formula R-C(=O)-, where R represents an alkyl or aryl group. It is a key structural component in many organic compounds, particularly those involved in nucleophilic acyl substitution reactions and the chemistry of acid halides.
Acylation: Acylation is a chemical reaction in which an acyl group (such as an acetyl or benzoyl group) is introduced into a molecule, typically by the reaction of a carboxylic acid or its derivative with another compound. This process is central to the preparation of carboxylic acids, nucleophilic acyl substitution reactions, the chemistry of thioesters and acyl phosphates, and the reactions of amines.
Addition-Elimination Sequence: The addition-elimination sequence is a mechanistic pathway that describes the reaction of a nucleophile with an acyl compound, such as an acid chloride or ester, to form a new acyl compound. This sequence involves the initial addition of the nucleophile to the carbonyl carbon, followed by the elimination of a leaving group, resulting in the formation of a new acyl compound.
Alcoholysis: Alcoholysis is a type of nucleophilic acyl substitution reaction in which an alcohol replaces a group attached to a carbonyl carbon, typically resulting in the formation of an ester. This process is also relevant in the chemistry of acid anhydrides, where alcohols can react with anhydrides to produce esters and carboxylic acids.
Amides: Amides are a class of organic compounds that contain a carbonyl group (C=O) bonded to a nitrogen atom. They are derived from carboxylic acids and can be considered the result of replacing the hydroxyl group (-OH) of a carboxylic acid with an amino group (-NH2). Amides are important functional groups in many organic molecules, including proteins, and play a crucial role in various chemical reactions and processes.
Aminolysis: Aminolysis is a chemical reaction in which an amine (a compound containing a nitrogen atom with a lone pair of electrons) reacts with an acyl compound, such as an ester or an acid chloride, to form a new amide bond. This process is a key step in various organic reactions, particularly in the context of nucleophilic acyl substitution reactions.
Anhydrides: Anhydrides are organic compounds derived from carboxylic acids, characterized by a carbonyl-oxygen-carbonyl functional group. They play a crucial role in various reactions and transformations involving carboxylic acid derivatives, including naming, nucleophilic acyl substitution, and the chemistry of acid halides.
Carbonyl Compound: A carbonyl compound is a class of organic compounds that contain a carbonyl group, which is a carbon atom double-bonded to an oxygen atom. These compounds are fundamental in organic chemistry and play a crucial role in various reactions and transformations, including the topics of alcohols from carbonyl compounds, the Wolff-Kishner reduction, nucleophilic acyl substitution, enolate ion formation, alkylation of enolate ions, and intramolecular aldol reactions.
Carboxylic acid derivatives: Carboxylic acid derivatives are compounds that feature a functional group derived from the substitution of the hydroxyl (-OH) group in carboxylic acids with other atoms or groups of atoms. They retain the carbonyl (C=O) group but differ in the atom or group attached to the acyl moiety.
Carboxylic Acid Derivatives: Carboxylic acid derivatives are a class of organic compounds that are structurally related to carboxylic acids, but have a different functional group attached to the carbonyl carbon. These derivatives include esters, acyl halides, anhydrides, and amides, and they play crucial roles in various chemical reactions and biological processes.
Electrophile: An electrophile is a species that is attracted to electron-rich regions and seeks to form new bonds by accepting electron density. Electrophiles play a crucial role in many organic reactions, including polar reactions, electrophilic aromatic substitution, and nucleophilic acyl substitution, among others.
Esters: Esters are a class of organic compounds formed by the reaction between a carboxylic acid and an alcohol, resulting in the replacement of the hydroxyl group (-OH) of the acid with an alkoxy group (-OR). Esters are ubiquitous in nature and play a crucial role in various chemical processes and applications.
Hydrolysis: Hydrolysis is a chemical reaction in which a compound is cleaved into smaller molecules by the addition of water. This process involves the breaking of chemical bonds through the insertion of water molecules, often resulting in the formation of new functional groups or the decomposition of larger molecules.
Leaving group: A leaving group in organic chemistry is an atom or group that detaches from the parent molecule during a nucleophilic substitution (SN2) reaction, forming a lone pair or negative ion. The ease with which a leaving group departs affects the rate and success of the reaction.
Leaving Group: A leaving group is a functional group or atom that is displaced or removed from a molecule during a chemical reaction. It is a key component in many organic reactions, particularly substitution and elimination reactions, as it facilitates the formation of a new bond or the creation of a new product.
Nucleophile: A nucleophile is a species that donates a pair of electrons to form a covalent bond with another atom or molecule. Nucleophiles are central to understanding many organic reactions, including polar reactions, electrophilic addition reactions, and nucleophilic substitution reactions.
Nucleophilic Acyl Substitution: Nucleophilic acyl substitution is a type of organic reaction where a nucleophile attacks the carbonyl carbon of a carboxylic acid derivative, such as an acid chloride, anhydride, or ester, leading to the replacement of the leaving group with the nucleophile. This process is central to the reactivity and transformations of carboxylic acid derivatives.
Nucleophilic acyl substitution reaction: A nucleophilic acyl substitution reaction is a type of chemical reaction where a nucleophile replaces the leaving group in an acyl compound. This reaction is fundamental in organic chemistry for modifying carboxylic acid derivatives into other functional groups.
Resonance: Resonance is a fundamental concept in organic chemistry that describes the ability of certain molecules to exist in multiple equivalent structures or resonance forms. This phenomenon arises from the delocalization of electrons within the molecule, leading to the stabilization of the overall structure and the distribution of electron density across multiple atoms.
Tetrahedral Intermediate: A tetrahedral intermediate is a key reaction step that occurs in many organic chemistry reactions, where a trigonal planar carbonyl carbon temporarily becomes a tetrahedral carbon with four bonded atoms. This transient intermediate is crucial for understanding the mechanisms of various nucleophilic addition and substitution reactions.
Transesterification: Transesterification is a chemical reaction in which an ester is transformed into another ester through the interchange of the alkoxy moiety. This process is of great importance in the context of organic chemistry, particularly in the areas of functional groups, nucleophilic acyl substitution reactions, and the chemistry of esters.