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20.5: Acid Anhydride Chemistry

  • Page ID
    183125
  • Synthesis of Acid Anhydrides

    Acid chlorides react with carboxylic acids to form anhydrides as shown in the reaction below.

    Sny1.jpg

    Some cyclic anhydrides can be synthesized from the corresponding dicarboxylic acid with gentle heating.  The example below shows the reaction of glutaric acid to form a cyclic anhydride.

    Example:  Acid Anhydride Synthesis

    ch 22 sect 5 example.png

    Acid Anhydride Reactivity

    Acid anhydrides undergo hydrolysis and  nucleophilic acyl substitution reactions.

    ch 22 sect 5 anhydride rxn map.png

    Acid Anhydride Hydrolysis

    Acid anhydrides readily hydrolyze to carboxylic acids.  In many cases, this reaction is an unwanted side reaction and steps will be taken in the lab to keep the system "dry" (aka water free).  The presence of pyridine facilitates proton transfers during the reaction.  The hydrolysis reaction for benzoic anhydride is shown below.

    ch 22 sect 5 anhydride hydrolysis updated.png

    The mechanism is analogous to the mechanism for ester synthesis from acid anhydrides and is shown below is detail.

    Nuclephilic Acyl Substitution Reactions from Acid Anhydrides

    Carboxylic acid derivatives can be synthesized from acid anhydrides via the nucleophilic acyl substitution mechanism previously discussed.

    Ester Synthesis

    Acid anhydrides react with alcohols to produce esters as shown in the reaction below.  The reactions of anhydrides frequently use pyridine as a solvent.

    2a.jpg

    A carboxylic acid is also produced, but is not considered a synthetic product.  The ester is considered the "product of interest". 

    The synthesis of methyl benzoate from benzoic anhydride and methanol is shown in the example.

    Example:  Ester Sythesis

    3a.jpg

    The mechanism follows the nucleophililc acyl substitution mechanism as previously discussed and reviewed below.

    1) Nucleophilic Alcohol reacts with Electrophilic Carbonyl

    4a.jpg

    2) Deprotonation by pyridine

    5a.jpg

    3) Leaving group removal

    6a.jpg

    4) Protonation of the carboxylate

    7a.jpg

    Amide Synthesis

    Acid Anhydrides react with amines to form amides.  As seen with acid halide reactions, a second equivalent of the amine must be present for the reaction to proceed.

    1.jpg

    Example: Amide Synthesis

    2.jpg

    The mechanism for amide synthesis is analogous to the mechanism for ester formation.  The only minor difference is that a second equivalent of the amine or ammonia is used instead of the pyridine.

    1) Nucleophilic Amine reacts with Electrophilic Carbonyl

    3.jpg

    2) Deprotonation by the amine

    4.jpg

    3) Leaving group removal

    5.jpg

    Exercise

    6. Draw out the mechanism for the following reaction.

    7.  Draw the product of the reaction between these two molecules.

     

    Answer

    6.

    7.

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