Propose a suitable synthesis to accomplish the following
The Correct Answer and Explanation is:
To accomplish the given transformation from 2-Bromo-benzamide to 1-(2-Bromo-phenyl)-2-bromo-ethene, a Hofmann rearrangement followed by a bromination step is suitable. The following is a step-by-step synthesis pathway:
Step 1: Hofmann Rearrangement
- React the 2-bromo-benzamide with bromine (Br₂) and a strong base such as sodium hydroxide (NaOH).
- This reaction converts the amide group to an amine with the loss of the carbonyl carbon, forming 2-bromoaniline.
Reaction:
2-Bromo-benzamide → 2-Bromoaniline
Conditions:
Br₂, NaOH, heat
Step 2: Formation of the Desired Vinyl Bromide via Sandmeyer Reaction and Subsequent Bromination
- The amino group of 2-bromoaniline can be diazotized using sodium nitrite (NaNO₂) and hydrochloric acid (HCl) at 0–5°C to form the diazonium salt.
- The diazonium group is then replaced with a vinyl group using a palladium-catalyzed Heck reaction with vinyl bromide, resulting in the formation of the target molecule.
Alternatively, to directly introduce the vinyl bromide side chain:
- Convert the diazonium salt to a bromide intermediate using CuBr (Sandmeyer reaction).
- Then perform a lithium-halogen exchange using n-BuLi, followed by reaction with ethylene oxide, giving a hydroxyl ethyl derivative.
- Finally, convert the hydroxyl group to a bromide using phosphorus tribromide (PBr₃), followed by elimination to form the vinyl bromide side chain.
Final Product:
The overall sequence yields the target compound 1-(2-bromophenyl)-2-bromo-ethene.
Explanation:
The key transformation begins with the Hofmann rearrangement, which effectively shortens the carbon chain by one carbon and introduces an amine functionality. The amine group is versatile and can be transformed via diazotization to a reactive diazonium intermediate, enabling substitution reactions such as Sandmeyer or Heck coupling. The introduction of the vinyl bromide side chain completes the synthesis, providing the desired structure. This synthetic route is efficient and commonly employed for such aromatic transformations.
