amide

Examples of amide in the following topics:

• Related Carbonyl Derivatives

  • As in the case of amines, amides are classified as 1º, 2º or 3º, depending on the number of alkyl groups bonded to the nitrogen.
  • Most of the functions are amides or esters, cantharidin being a rare example of a natural anhydride.
  • Cyclic esters are called lactones, and cyclic amides are referred to as lactams.
  • Penicillin G has two amide functions, one of which is a β-lactam.
  • The Greek letter locates the nitrogen relative to the carbonyl group of the amide.

• Important Reagent Bases

  • Most base reagents are alkoxide salts, amines or amide salts.
  • Since alcohols are much stronger acids than amines, their conjugate bases are weaker than amide bases, and fill the gap in base strength between amines and amide salts.
  • Finally, the two amide bases see widespread use in generating enolate bases from carbonyl compounds and other weak carbon acids.

• Other Reactions

  • When electrophiles bond to an amide, they do so at the oxygen atom in preference to the nitrogen.
  • One practical application of this behavior lies in the dehydration of 1º-amides to nitriles by treatment with thionyl chloride.

• Peptide Bonding between Amino Acids

  • The peptide bond is an amide bond which links amino acids together to form proteins.
  • The amide bond can only be broken by amide hydrolysis, where the bonds are cleaved with the addition of a water molecule.
  • The amide group has three resonance forms, which confer important properties.
  • Peptide bonds are amide bonds, characterized by the presence of a carbonyl group attached to an amine.

• Background and Properties

  • Similar hydrogen bonding occurs between molecules of 1º and 2º-amides (amides having at least one N–H bond), and the first three compounds in the table serve as hydrogen bonding examples.
  • The relatively high boiling points of equivalent 3º-amides and nitriles are probably due to the high polarity of these functions.

• Directed ortho-Metalation

  • The strongly deactivating sulfonic acid substituent is easily converted to a DMG by amide formation.
  • The third diagram above shows the DoM of such an amide.
  • Direct electrophilic substitution would normally occur at the meta position, so the action of the amide DMG is particularly noteworthy.
  • A similar amide derivative of a carboxylic acid substituent may be used for DoM, as shown in the following diagram.

• Nomenclature

  • Amides: The name of the related acid is used first and the oic acid or ic acid suffix is replaced by amide (only for 1º-amides). e.g.
  • CH3CONH2 is ethanamide (or acetamide). 2º & 3º-amides have alkyl substituents on the nitrogen atom.
  • Cyclic amides are called lactams.

• Acyl Group Substitution

  • Reactivity: acyl halides > anhydrides >> esters ≈ acids >> amides
  • An interesting exception to the low reactivity of amides is found in beta-lactams such as penicillin G.
  • Although amines are among the most reactive nucleophiles, only 1º and 2º-amines give stable amide products.
  • This explains why reactions #2 & 3 do not give amide products.
  • No acylation reactions of amides were shown in these problems.

• Peptides & Proteins

  • If the amine and carboxylic acid functional groups in amino acids join together to form amide bonds, a chain of amino acid units, called a peptide, is formed.
  • This restriction is due to the rigid nature of the amide (peptide) bond.

• Elimination

  • Chloro and bromobenzene reacted with the very strong base sodium amide (NaNH2 at low temperature (-33 ºC in liquid ammonia) to give good yields of aniline (aminobenzene).
  • The steric bulk of the methoxy group and the ability of its ether oxygen to stabilize an adjacent anion result in a substantial bias in the addition of amide anion or ammonia.