everyone. In the following reaction, what is it that causes NaOH to attack either bond A or B over all the other bonds available? Subsequently, why does NaOH not continue with bond B once bond A has been reacted with? Thanks! enter image description here

  • $\begingroup$ I believe this is a matter of manipulating the stoichiometry and concentrations of the reactants such that only one of them reacts. Note that bonds A and B are equivalent actually. To make only one of them break, I suppose the concentration of the base could be limited. $\endgroup$ – Tan Yong Boon Jun 17 at 15:13
  • $\begingroup$ Imide carbonyl groups are more reactive toward nucleophiles than amides. That is why hydrazine is used in the removal of the phthaloylimide moiety in the Gabriel amine synthesis. The second bond, the amide bond, is cleaved intramolecularly by the hydrazide formed in the intiial hydrazine nucleophilic attack on the imide. $\endgroup$ – user55119 Jun 17 at 16:35

The above reaction is a modification of Gabriel phtahlimide synthesis from here:

This procedure, known as the Gabriel synthesis, can be used to advantage in aminating bromomalonic esters.Since the phthalimide substituted malonic ester has an acidic hydrogen (colored orange), activated by the two ester groups, this intermediate may be converted to an ambident anion and alkylated. Finally, base catalyzed hydrolysis of the phthalimide moiety and the esters.enter image description here

The reaction you show is base catalyzed hydrolysis of the phthalimide shown in the link.

The mechanism of this reaction is shown below:

enter image description here

Both amide bonds(2 to 3 and 5 to 6) cleaves.


  1. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Map%3A_Organic_Chemistry_(Vollhardt_and_Schore)/26%3A_Amino_Acids%2C_Peptides%2C_Proteins%2C_and_Nucleic_Acids%3A_Nitrogen-Containing_Polymers_in_Nature/26.02%3A_Synthesis_of_Amino__Acids%3A_A_Combination_of_Amine__and_Carboxylic_Acid__Chemistry

  2. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Amines/Synthesis_of_Amines/Gabriel_Synthesis

  • $\begingroup$ Yes, but why that particular bond (either A or B)? Why does the reaction happen at one of those two bonds than, say, at one of the carboxylate esters, for example? What makes the resulting intermediate more stable at A or B than anywhere else? $\endgroup$ – edmund shelto Jun 17 at 15:36
  • $\begingroup$ The esters are hydrolyzed also, in your reaction scheme. The scheme shows both esters being cleaved, along with one of the amide bonds. Your question is really about why is one amide bond cleaved in the imide, rather than both $\endgroup$ – Withnail Jun 17 at 15:40

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