In this lesson we will get a brief overview of amides and survey some of the more important reactions involving this very important organic functional group.
How Important Are Amides?
Did you know that without the amide functional group, life would not be possible? That’s right, we need amides to live. You see, proteins are made up of amino acid building blocks, and actually an amide bond is what links different amino acids together to make the different proteins in all living systems! Let’s now take a few minutes to explore how amides behave in terms of their electronic nature and the reactions they undergo!
One of the most interesting aspects of amides is that unlike other carbonyl-containing compounds (meaning compounds containing a carbon-oxygen double bond), they don’t usually undergo addition of nucleophiles to the carbonyl carbon. Why might this be the case? The answer lies in the resonance structure that we can draw for any amide. Because we can delocalize the lone pair on nitrogen, this destroys most of the electrophilic nature of the carbonyl, which ultimately explains why it doesn’t react with nucleophiles.
In addition to amides being non-electrophilic, the nitrogen atom isn’t all that basic at all, with again the delocalization of the lone pair on nitrogen being the contributing factor.
Classification of Amides
Amides are commonly classified based on the number of hydrogen atoms the nitrogen has attached to it. A primary amide has two hydrogens bonded to nitrogen, a secondary has one, and a tertiary amide has none.
Reactions of Amides
How to Make an Amide
One of the most common methods to make an amide is to take a carboxylic acid and convert it to an acid chloride by using thionyl chloride (SOCl2). An acid chloride is a very reactive building block and just exposing them to aqueous ammonia solution will trigger formation of our amide!
If we want to make a secondary or a tertiary amide, we only need to adjust our reaction to incorporate various organic amines in the place of ammonia to provide these substitution products.
Acid-Promoted Hydrolysis of Amides
Amides can undergo hydrolysis in the presence of aqueous acid, however the reaction is usually VERY sluggish and requires high temperatures in order to proceed. The products are always a carboxylic acid and an ammonium salt.
Base-Promoted Hydrolysis of Amides
Amides can also be hydrolyzed under basic conditions, such as with sodium hydroxide, to give carboxylate salts and ammonia. This is just like in the acid case, often forcing conditions are required such as high temperatures.
Reduction of an Amide
Amides can be reduced to amines, but a very strong reducing agent like lithium aluminum hydride is needed.
In this reaction, the carbon-oxygen bond is broken and replaced with two carbon-hydrogen bonds to give an amine product.
Amides as a Gateway to Nitriles
If we take an amide and react it with thionyl chloride (SOCl2), the organic product is a nitrile (carbon-nitrogen triple bond).
We also get sulfur dioxide gas and HCl gas as by-products and for this reason, this reaction must always be carried out in a fume hood to limit exposure to these toxic substances.
What are they Good for?
As we mentioned at the beginning of this lesson, amides play a vital role in biological systems as building blocks for proteins. Amides also find wide utility in the field of pharmaceuticals, especially antibiotics such as penicillin and ampicillin.
Amides represent a very important functional group in organic chemistry and find a wide variety of use, especially in living systems and medicines that many people depend on; when it’s an amide bond, it’s what links different amino acids together to make the different proteins in all living systems. Let’s recap what we learned:
- Amides are both unreactive to nucleophilic addition to the carbonyl carbon and non-basic because of the delocalization of the lone pair of electrons on the nitrogen atom.
- Amides are classified as primary, secondary, or tertiary depending on how many hydrogens are attached to the nitrogen atom; primary contain two, secondary contain one, and tertiary contain none at all.
- Amides can be hydrolyzed under both acidic and basic conditions, but high temperatures are usually required.
- Amides can be prepared from an acid chloride, and depending on the substitution pattern desired (i.
e. primary, secondary, or tertiary) different amines can be used.
- Amides can be reduced to amines if reacted with lithium aluminum hydride (a strong reducing agent, such as lithium aluminum hydride).
- Nitriles like HCl and NaOH can be made from amides when reacted with thionyl chloride (SOCl2).