Activation for amide formation
Carboxylic acids or activated acid derivatives connect to amide-bond formation.
- Reagents
- amine plus a specified coupling or activating reagent
- Conditions
- anhydrous; reagent-specific
- Reaction class
- amide formation
- Equation
- activated R-CO2H derivative + R'-NH2 -> R-CONHR' + by-products
Overview
Carboxylic acids or activated acid derivatives connect to amide-bond formation.
Transformation
Carboxylic acids → Amide chemistry
- Equation
- activated R-CO2H derivative + R'-NH2 -> R-CONHR' + by-products
- Reagents
- amine plus a specified coupling or activating reagent
- Environment
- anhydrous; reagent-specific
- Reaction class
- amide formation
- Mechanism
- acyl substitution / condensation
- Evidence level
- curated extension
Scope and limitations
- Scope
- A carboxylic acid must be activated, converted to a reactive derivative, or used with a defined coupling process before an amine forms an amide efficiently.
- Limitations
- Simply mixing a carboxylic acid and an amine normally gives an ammonium carboxylate salt, not a preparative amide reaction. This record is a synthesis bridge rather than a single experimental procedure.
Related reactions
- Oxidation: Alcohols → Carboxylic acids
Full oxidation of a primary alcohol gives a carboxylic acid.
- Complete oxidation: Primary alcohols → Carboxylic acids
Full oxidation of a primary alcohol gives a carboxylic acid.
- Reduction: Carboxylic acids → Primary alcohols
Reduction of a carboxylic acid gives a primary alcohol.
- Oxidation: Aldehydes → Carboxylic acids
Oxidation of an aldehyde gives a carboxylic acid.
- Hydrolysis: Nitriles → Carboxylic acids
Nitriles can be hydrolysed to carboxylic acids, splitting the old aggregate nitrile-to-amide route into a single functional-group conversion.
- Polycondensation: Amide chemistry → Polyamide-related materials
Repeated amide bond formation gives polyamide-related materials such as nylon-family fibres and engineering plastics.
- Esterification: Carboxylic acids → Esters
Carboxylic acids react with alcohols to form esters.
- Hydrolysis: Esters → Carboxylic acids
Hydrolysis converts esters back into carboxylic acid products.
- Chlorination: Carboxylic acids → Acyl chlorides
PCl5 converts carboxylic acids into acyl chlorides.
- Chlorination with thionyl chloride: Carboxylic acids → Acyl chlorides
Thionyl chloride converts carboxylic acids into acyl chlorides with sulfur dioxide and hydrogen chloride as by-products.
- Hydrolysis: Acyl chlorides → Carboxylic acids
Water hydrolyses acyl chlorides to carboxylic acids, releasing hydrogen chloride.
- Carboxylation: Grignard reagents → Carboxylic acids
Grignard carboxylation gives carboxylic acids after acidic work-up.
- Grignard carboxylation co reactant: Carbon dioxide → Carboxylic acids
Carbon dioxide plus a Grignard reagent gives a carboxylic acid after acidic work-up.
- Salt formation: Carboxylic acids → Carboxylate salts
Carboxylic acids react with bases, carbonates and reactive metals to form carboxylate salts.
- Anhydride hydrolysis: Acid anhydrides → Carboxylic acids
Water attacks an anhydride carbonyl, and collapse of the tetrahedral intermediate breaks the acyl-oxygen linkage. Proton transfer gives carboxylic-acid products; a mixed anhydride yields two different acids.
References
- Hydrogenation of Adiponitrile to Hexamethylenediamine over Raney Ni and Co CatalystsYounghyun Lee; Sung Woo Lee; Hyung Ju Kim; Yong Tae Kim; Kun-Yi Andrew Lin; Jechan Lee · Applied Sciences · 2020
Supports adiponitrile hydrogenation to hexamethylenediamine, a nylon-6,6 monomer route.