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. 




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
* dIstill 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](http://dx.doi.org/10.1039/B701677H)) on the topic.


 6

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.


![enter image description here](https://i.stack.imgur.com/QtQrq.gif) (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>.


 4