WWU-Chemistry The Amides

WWU-Chemistry Carboxylic acids can be converted directly to the corresponding amides by the reaction of an acid with the appropriate amine. The amine used in this reaction can be ammonia, a primary amine, or a secondary amine, depending on the degree of nitrogen substitution expected.

WWU-Chemistry Preparation of Amides (“C+ Method”) While this is not the best method of preparing amides, it has the advantage of being simple. It also serves to introduce the amides as a class of compounds.

WWU-Chemistry Preparation of Amides (“A Method”)

WWU-Chemistry REMEMBER: The previous image neglects to account for the H-Cl produced in the reaction. In each of the previous reactions, two equivalents of amine are required -- one to act as nucleophile and the second to act as a base. The second equivalent of amine reacts with the H-Cl to form the corresponding amine hydrochloride.

WWU-Chemistry Peptides and Proteins

WWU-Chemistry Amino acids have the general structure: The correct Fischer projection for naturally- occurring amino acids is shown here. The R group is variable.

WWU-Chemistry As can be seen, the amino acids possess both functional groups required to form an amide. Each amino acid is both a carboxylic acid and an amine simultaneously. Therefore, it should be possible to link amino acids together through the formation of amides.

WWU-Chemistry Peptide bond (an amide linkage)

WWU-Chemistry Peptides When amino acids are linked together by amide linkages (biochemists call these “peptide bonds”), the resulting molecule is called a peptide. A peptide is a polymer formed from individual amino acid units.

WWU-Chemistry Peptides Peptides are named according to the number of amino acids that are linked: –dipeptide: two amino acids –tripeptide: three amino acids –tetrapeptide: four amino acids –etc. The term oligopeptide refers an amino acid polymer with a moderate number of repeating amino acid units.

WWU-Chemistry Peptides and Proteins When a peptide grows to a length of about 70 amino acid units (molecular weight = approximately 10,000), the molecule begins to coil onto itself and assume a particular secondary structure. At this point, we no longer refer to the molecule as a “peptide”; we begin to call it a protein.

WWU-Chemistry alpha-Helix

WWU-Chemistry Chateau de Chambord

WWU-Chemistry Chambord – Double Staircase by Leonardo DaVinci

WWU-Chemistry Other Amide Polymers NYLON!!!

WWU-Chemistry Hydrolysis of Amides The most important reaction of amides is hydrolysis. The products of amide hydrolysis are the carboxylic acid and the amine.

WWU-Chemistry Hydrolysis of Amides This reaction can also be run under basic conditions.

WWU-Chemistry Hydrolysis of Amides In living organisms, the hydrolysis of peptides is accomplished through catalysis by enzymes. The enzyme-catalyzed hydrolysis of peptides and proteins is what happens to protein when we eat it. The protein is hydrolyzed into individual amino acids, which are then used to build new proteins.

WWU-Chemistry Example

Reduction of Amides If either R 1 or R 2 is hydrogen in the amide, the corresponding R groups will be hydrogen in the amine product. Notice that the carbonyl group is reduced to a methylene group. NaBH 4 cannot reduce amides

WWU-Chemistry Examples

Nitriles

Formation of Nitriles This is an S N 2 reaction. It works best with primary alkyl halides.

WWU-Chemistry Hydrolysis of Nitriles The reaction can be conducted in either acidic or basic solution.

WWU-Chemistry Example

Example

Base-Promoted Hydrolysis of a Nitrile (Part One)

WWU-Chemistry Base-Promoted Hydrolysis of a Nitrile (Part Two)

WWU-Chemistry Acid-catalyzed Hydrolysis of a Nitrile (Part One)

WWU-Chemistry Acid-catalyzed Hydrolysis of a Nitrile (Part Two)

WWU-Chemistry Reduction of Nitriles NaBH 4 does not reduce nitriles.

WWU-Chemistry Also: CAUTION!!!

WWU-Chemistry Example

Example

Reduction of a Nitrile to an Aldehyde