# How do you Synthesise a Fatty Acid Amide?

How would you go about synthesising a fatty acid amide, preferably by means of a high-yield reaction. Please provide an explanation that I, as a grade 12 chemistry graduate, could understand.

I am familiar with:

• Fatty acids
• Carboxylic acid
• Equilibrium reactions & constants
• Amide groups
• Amines
• Alkanols
• Esterification

If you need to use terms I may be unfamiliar with, it would be nice if you could explain them or provide a link to an explanation.

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This is very similar to your other question on amide synthesis: chemistry.stackexchange.com/questions/2751/…. Could these be combined into one question? –  Ben Norris Dec 12 '12 at 0:16

## 2 Answers

You are perfectly right on that you need to convert the carboxylic acid to a more reactive species to eventually obtain the amide!

Playing with the pH will not help:

• under acidic conditions, the amine is protonated and therefore unreactive
• under alkaline conditions, the acid is deprotonated and the carboxylate won't react at all

The Schotten-Baumann reaction of fatty acids with $\ce{SOCl2}$ will probably work fine:

• reflux 1 mol of the acid with 1.5 mol of thionyl chloride
• destill the remaining thionyl chloride off
• purify the fatty acid chloride by distillation in vacuum. Note that the bp of stearoyl chloride is about 175 °C at 2 mm Hg!

This is quite some work to obtain a fatty acid derivative that eventually reacts with an amine!

Wouldn't it be much more convenient to form the amide in a one-pot reaction, possibly at room temperature, by activating the carboxylic acid in situ?

(In situ means: at the same spot, without isolating the reactive intermediate.)

There's a large number of coupling reagents available, such as

• carbodiimides like DCC (dicyclohexylcarbodiimide)
• $1H$-benzotriazoles
• chloro-substituted triazines

Eric Valeur and Mark Bradley published a critical review titled Amide bond formation: beyond the myth of coupling reagents, in Chem. Soc. Rev., 2009, 38, 606-631 (DOI) on the topic.

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## Schotten-Baumann Reaction

I found the solution to my question and it is the Schotten-Baumann reaction which takes an acyl chloride (which can be synthesised from a carboxylic acid via the methods detailed in the next section) and an amine to form an amide, a hydrogen chloride.

(1)

[Net reaction: $\ce{RCOCl+NH_2 R' \rightarrow RCONHR' + HCl}$]

## Synthesis of Acyl Chlorides

To create acyl chlorides from carboxylic acids the following three reactions will suffice:

$\ce{RCOOH (l) + PCl_5 (s) \rightarrow RCOCl (aq) + POCl_3 (aq) + HCl (g) }$

$\ce{3 RCOOH (l)+ PCl_3 (s) \rightarrow 3 RCOCl (aq) + H_2 PO_3 (aq)}$

$\ce{RCOOH (l) + SOCl_2 (s) \rightarrow RCOCl (aq) + SO_2 (g) + HCl (g)}$

(2)

## Reference List (APA style)

1. Schotten-Baumann Reaction Schotten-Baumann Conditions (n.d.). Retrieved December 22 2012 from http://www.organic-chemistry.org/namedreactions/schotten-baumann-reaction.shtm.
2. Clarke, J. (2004). CONVERTING CARBOXYLIC ACIDS INTO ACYL CHLORIDES (ACID CHLORIDES). Retrieved December 22 2012 from http://www.chemguide.co.uk/organicprops/acids/pcl5.html.
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