Upenn Organic Chemistry Lab Report 8

Multi-step Organic Synthesis: Aniline to 1-bromo-3-chloro-5-iodobenzene

Andrew Fang

Undergraduate Organic Chemistry Laboratory, University of Pennsylvania

Philadelphia, Pennsylvania 19104

andfang@seas.upenn.edu

The six-step organic synthesis of aniline to 1-bromo-3-chloro-5-iodobenzene is an example of multi-step organic chemistry. The synthesis is protected by conversion of the aniline to an amide side group, followed by a series of three electrophilic aromatic substitutions to halogenate the acetaniline. The free amine is regenerated and the amino group is removed in the final step to yield the desired product.

Introduction

Multi-step organic synthesis is an important undergraduate application of laboratory organic chemistry synthesis. The steps involve a sequence of electrophilic aromatic substitutions in an attempt to synthesis 1-bromo-3-chloro-5-iodobenzene. It illustrates two important strategies in synthesis: first protecting functionality to prevent undesired side reactions and using substituents to control the reactivity of the electrophilic aromatic substitution. Of particular note is the fact that activators generally active ortho and para, while halogens are deactivators of ortho and para positions as well.

The chemical structure of aniline (1) acts as a nucleophile in attacking the acetic anhydride (Scheme 1) to ultimately form acetanilide (2) and acetic acid. The amino group is very reactive and any attempts to brominate the ring would tribrominate the aniline at the ortho and para positions. The functional group is then acetylated to decrease ring reactivity to that the bromination only occurs at the para position of the aromatic ring. The amino attacks the carbonyl of the anhydride, pushing the double bond on the oxygen up to the atom, where the nitrogen is deprotonated by the acetic acid and the acetyl pops off forming the carbonyl. Acetic acid and acetanilide (2) are then generated.

SCHEME 1

1...