Acid Derivatives


  • nomenclature:
    suffix example
    Acid chlorides -oyl chloride ethanoyl chloride
    ethanoyl chloride
    Anhydrides -oic anhydride ethanoic anhydride
    ethanoic anhydride
    Amides -amide N-methyl ethanamide
    N-methyl ethanamide
    Esters -oate methyl ethanoate
    methyl ethanoate

  • physical properties
    • C=O bond is polar, so there are dipole-dipole interactions.
    • No hydrogen bond exists in acid chlorides, anhydrides, or esters unless there is an -OH group somewhere.
    • Amides can hydrogen bond because of the N-H group. In fact, hydrogen bonding involving the amide backbone of polypeptides form the secondary structure of proteins.
    • Amides have higher boiling points than the other acid derivatives.
    • Acid derivatives have high boiling points than alkanes because of the C=O dipole interactions.
  • infrared absorption
    • Acid chloride: the C=O will show up at greater than 1700 cm-1, pretty close to 1800 cm-1
    • Anhydride: the double C=O doesn't show up as a single band. Instead, 2 bands shows up between 1700 cm-1 and 1800 cm-1.
    • Amide: the N-H shows up around 3300 cm-1, the C=O shows up at 1700 cm-1
    • Ester: C=O group shows up at 1700 cm-1. The C-O ether stretch shows up around 1200 cm-1

Important reactions

  • preparation of acid derivatives
    • Carboxylic acid + SOCl2 → Acid chloride.
    • Carboxylic acid + carboxylic acid + heat → Anhydride.
    • Acid chloride + carboxylic acid + base → Anhydride.
    • Acid chloride + alcohol + base → Ester.
    • Acid chloride + amine → Amide.
    • Acid chloride + water → Carboxylic acid.
  • acid derivatives synthesis
  • nucleophilic substitution: Nucleophile attacks the carbon center of the C=O group.
  • nucleophilic substitution of acid derivatives
  • Hofmann rearrangement: Hofmann rearrangement takes away the C=O of an amide. The alkyl migration is basically how the -R group on the other side of the C=O migrates and attaches itself to the nitrogen atom. See figure below for detailed mechanism of the Hofmann degradation and how the aryl group migrates.
  • Hofmann degradation
  • transesterification: Ester + alcohol → new ester.
  • transesterification
  • hydrolysis of fats and glycerides (saponification): saponification is basically the hydrolysis of an ester in base.
  • saponification
  • hydrolysis of amides: the leaving group is not NR2-, it is the neutral amine.
  • amide hydrolysis

General principles

  • relative reactivity of acid derivatives: Acid chloride > Anhydride > Esters > Amides
    • Acid halides are the most reactive derivatives because halides are very good leaving groups.
    • Amides are the most stable derivatives because NR2- is a terrible leaving group. Also, the C-N bond has a partial double bond characteristic. Proteins are made of peptide bonds, and they are very stable.
  • steric effects: bulky groups around the C=O group helps protect the carbon center from nucleophilic attack.
  • electronic effects: groups that can redistribute and stabilize negative charges are good leaving groups. For example, the anhydride has a good leaving group - the carboxylate ion - because the COO- can redistribute the negative charge to both oxygens via resonance.
  • strain (e.g., beta-lactams)
    • Amides have a double bond characteristic between the carbon and nitrogen. This means that the C-N bond can not rotate.
    • Normally, the sigma bonds in a ring rotate as to achieve the most stable conformation, but this can't occur for the C-N bond if the ring contains an amide.
    • Because C-N bond in an amide can not rotate, rings that contain amides have higher strain.
    • An example of this is the beta-lactam, which is basically a 4 membered ring with 1 amide in it.