7.6 Amides and Nitriles

7.6 Amides and Nitriles

  • We have said before that a carboxylic acid derivative can be prepared from any other carboxylic acid derivative that is more reactive.
  • We can make amides from any carboxylic acid derivatives that are higher on the chart since they are the least reactive.
    • Amides can be made from acid halides, anhydrides, or esters.
  • Acid halides and anhydrides are more reactive than es.
    • We have to use a trick to get the reaction to happen.
    • We can't use acid or base because an acid would make the attacking amine useless, and a base would cause other side reactions that we will learn in the next chapter.
    • We use brute force and patience.
  • The carbonyl group is re- formed by expelling RO-.
  • We have said this many times before.
    • It is possible for the amine to leave.
    • It happens all the time.
    • The amine gets expelled after it attacks.
    • There is no change to observe when this happens.
    • Something else can happen every once in a while.
    • As shown in the mechanism above, RO- can be expelled and immediately protonated.
    • When re-forming a carbonyl group, we are allowed to expel RO- because it is so high in energy.
  • The process of making amides is very slow and not really a synthetic technique.
  • If possible, you should not use this reaction in a synthesis.
    • A better way to make amides is to use a more reactive carboxylic acid derivative.
  • We have seen that we can make amides from both acid anhydride and acid halides.
    • Now that we know how to make amides, let's look at some important reactions.
    • Under basic and acidic conditions, we will explore the hydrolysis of amides.
    • Much of biochemistry is dependent on when and why amides will undergo hydrolysis.
  • Let's start with acid-catalyzed conditions.
    • The other acid-catalyzed reactions we have seen are not different.
  • This pattern is common among the acid-catalyzed reactions that we have seen so far.
  • We have not yet seen one of the last carboxylic acid derivatives.
  • nitriles are considered to be carboxylic acid derivatives.
    • The other carboxylic acid derivatives look similar to a nitrile.
    • To understand this, we need to consider oxidation states.
  • The carbon atom of the carbonyl group has two bonds with oxygen and one with Z, and it also has one more bond with some other atoms.
    • There are three bonds to the Heteroatoms.
    • The carbon atom of a group has three bonds.
    • The oxidation level of nitriles is the same as that of the other carboxylic acid derivatives.
  • You can only use this method with primary or secondary alkyl halides, because it's an S 2 process.
  • There are more than one way to make nitriles.
    • If you are responsible for knowing any other ways to make nitriles, you should look through your textbook and lecture notes.
  • Under basic conditions hydration can occur.
  • The core steps of the mechanisms we have seen in this chapter are slightly different than the core steps of acid-catalyzed hydration.
    • No leaving group is ejected when it comes to hydration of nitriles.
  • The only other steps in the mechanism are protons.
    • It greatly simplifies the mechanism when you think of it this way.
    • The formation of a strong base is not possible under acidic conditions.
  • The mechanism is very similar to the one above.
  • The rest of the mechanism is just a bunch of steps.
    • Staying consistent with the conditions is a must if you want to draw the proton transfers properly.
    • The formation of a strong base is not advisable in acidic conditions.
    • The formation of a strong acid can be avoided in basic conditions.
  • To see if you can draw a plausible mechanism for the hydration of a nitrile under basic conditions, complete the following exercise.
  • There is only one core step in attacking the cyano group.
    • The rest of the steps are just proton transfers.
    • You can use the space below to record your answer.
    • If you got it right, you can look in the back of the book to see if it was correct.
  • An amine is being used in this reaction.
    • These conditions have been seen before.
  • The carbonyl group is not protonsated because a source of protons has not been indicated.
  • There is a plausible mechanism for each of the transformations.
  • We looked at the starting material to see if we could have a reaction, because we weren't given any reagents.
    • There are two functional groups in our starting compound.
    • An amine can react with an amine.