Chapter 20, Problem 20.44P

Interpretation Introduction

Interpretation:

In a Gabriel synthesis, the yield of the amine can be compromised when hydrolysis is carried out under conditions that are too basic. The problem, in particular, is with the second hydrolysis (Steps 6–8 in Equation 20-13), not the first (Steps 3–5). The reason for this is to be explained.

Concept introduction:

In the Gabriel synthesis, phthalimide is first treated with a strong base such as potassium hydroxide, followed by an alkyl halide. Subsequent hydrolysis using hydroxide then liberates the primary amine. In the mechanism shown in Equation 20-13, Step 1 is simply a proton transfer in which ${\text{HO}}^{\text{-}}$ deprotonates phthalimide at the N atom. The resulting anion is strongly nucleophilic at N, so an ${\text{S}}_{\text{N}}\text{2}$ reaction occurs when the alkyl halide is added in Step 2. Steps 3 through 8 make up two successive acyl substitutions. In step 6, the hydroxide acts as a nucleophile to add to the $\text{C=O}$ group of the amide.