Q70E - Organic Chemistry (Mcmurry)

Question

21-70 Treatment of a carboxylic acid with trifluoroacetic anhydride leads to anunsymmetrical anhydride that rapidly reacts with alcohol to give an ester.
  $\mathbf{\text{R}}\mathbf{-}\stackrel{\mathbf{\text{O}}}{\stackrel{\mathbf{\parallel }}{\mathbf{\text{C}}}}\mathbf{-}\mathbf{\text{OH }}\stackrel{{\mathbf{\left(}{\mathbf{\text{CF}}}_{\mathbf{\text{3}}}\mathbf{\text{CO}}\mathbf{\right)}}_{\mathbf{\text{2}}}\mathbf{\text{O}}}{\mathbf{\to }}\mathbf{\text{ R}}\mathbf{-}\stackrel{\mathbf{\text{O}}}{\stackrel{\mathbf{\parallel }}{\mathbf{\text{C}}}}\mathbf{-}\mathbf{\text{O}}\mathbf{-}\stackrel{\mathbf{\text{O}}}{\stackrel{\mathbf{\parallel }}{\mathbf{\text{C}}}}\mathbf{-}{\mathbf{\text{CF}}}_{\mathbf{\text{3}}}\stackrel{{\mathbf{\text{R}}}^{\mathbf{\text{'}}}\mathbf{\text{OH}}}{\mathbf{\to }}\mathbf{\text{ R}}\mathbf{-}\stackrel{\mathbf{\text{O}}}{\stackrel{\mathbf{\parallel }}{\mathbf{\text{C}}}}\mathbf{-}{\mathbf{\text{OR}}}^{\mathbf{\text{'}}}\mathbf{+}{\mathbf{\text{CF}}}_{\mathbf{\text{3}}}{\mathbf{\text{CO}}}_{\mathbf{\text{2}}}\mathbf{\text{H}}$
 (a) Propose a mechanism for the formation of the unsymmetrical anhydride.
 (b) Why is the unsymmetrical anhydride unusually reactive?
(c) Why does the unsymmetrical anhydride react as indicated ratherthan giving a trifluoroacetate ester plus carboxylic acid?

Step-by-Step Solution

Answer

a) The mechanism for the formation of the unsymmetrical anhydride

 

b) The reason for the unsymmetrical anhydride being unusually reactiveis because of the inductive electron removal by the,${\mathbf{\text{â€"CF}}}_{\mathbf{\text{3}}}\mathbf{\text{ group}}$ which makes the carbonyl carbon highly electrophilic.

c) The reaction proceeds as expected since trifluoroacetate is a better leaving group than other carboxylate anions

Step 1: Introduction to the Concept

The arrangement of chemical bonds between atoms in a molecule (in anion or radical with many atoms), particularly which atoms are chemically bound to which other atoms with what kind of chemical bond, as well as any geometric shape information needed to uniquely identify the type of molecule.

Step 2: Determination of mechanism for the formation of the unsymmetrical anhydride

a)

 The following diagram depicts the creation of the unsymmetrical anhydride

Step 3: Determination of reason for the unsymmetrical anhydride unusually reactive

b)

The inductive electron removal by the,${\mathbf{\text{â€"CF}}}_{\mathbf{\text{3}}}\mathbf{\text{ group}}$ which makes the carbonyl carbon highly electrophilic, makes the unsymmetrical anhydride extremely reactive.

Step 4: Determination of reason for unsymmetrical anhydride react as indicated

c)

Because trifluoroacetate is a better leaving group than other carboxylate anions, the reaction proceeds as expected.

As a result, the reaction pathway is heavily reliant on the strength of the bearing group's capacity, with a strong base requiring two weak bearing groups for the reaction to take place.