Formation of amides from acid chlorides and amines

by James

Description: Addition of primary or secondary amines (or ammonia) to acid chlorides results in amides.
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Notes: Note that HCl is a byproduct in this reaction, although in practice excess amine is often used that will react with the HCl. (Trivia: this reaction is sometimes referred to as the Schotten-Baumann reaction).

This reaction works because Cl(–) is a better leaving group (i.e. weaker base) than the amine.

Examples:

Notes: Acid (HCl) is a byproduct of the reactions shown here.

Mechanism: Addition of the amine to the acid chloride (Step 1, arrows A and B) results in a tetrahedral intermediate, which undergoes 1,2-elimination (Step 2, arrows C and D). Finally the nitrogen is deprotonated (Step 3, arrows E and F) to give the neutral amide.

Notes: Although Cl is shown as the base in step 3, the starting amine is a considerably stronger base and will probably be the base here.

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{ 2 comments… read them below or add one }

manoj

How acid chloride of amino acid synthezed.

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james

For an amino acid like leucine or alanine with non-reactive sidechains, I think you’d need to di-protect the amine as a phthalimide or similar reagent, and then convert it into an acid chloride with SOCl2 or oxalyl chloride. you have to be careful, however – racemization is very facile.

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