p-nitroaniline Synthesis: Electrophilic Aromatic Substitution & Amino Group Protection, Study notes of Organic Chemistry

Download p-nitroaniline Synthesis: Electrophilic Aromatic Substitution & Amino Group Protection and more Study notes Organic Chemistry in PDF only on Docsity! NH2 O O O H2N O O O HN O H O O HN O OHO2N S O O OHOH OH2O2 + S O O OHO N OO + H2O Electrophile Chem 2364 Synthesis of p-nitroaniline p-nitroaniline is an important chemical for the synthesis of dyes. Its synthesis involves an electrophilic aromatic substitution (EAS). This type of reaction is very important in synthetic organic chemistry. An electrophile and an aromatic ring are the principal actors (a catalyst is often needed). When an EAS is performed on benzene it’s relatively easy to predict the product. However, when the aromatic ring has substituents different isomers can be obtained. As a general rule, if the substituent is an electron donating group (EDG) it will favor EAS and will orient it to the o - and p - positions. On the other hand, if the susbtituent is an electron withdrawing group (EWG) it will hinder EAS. If more than one substituent is present, the one that “wants” EAS the most is the one that will govern the reaction. For example, if the aromatic ring has an EDG and an EWG, the one that will govern orientation is the EDG because it favors the reaction i.e. “wants” the reaction to occur. In the case of the synthesis of p-nitroaniline one could think that since the amino (-NH2) group is already an EDG, a simple EAS with the appropriate electrophile would give the product. However, the electrophile needs acid to be generated and this protonates the amino group. The protonation of the amino group yields an ammonium group (-NH3+) which is an EWG. For this reason is that the reaction is carried out in three steps: 1st Protection of the amino group (synthesis of acetanilide) 2nd EAS between the protected amino group and nitronium ion (synthesis of p-nitroacetanilide) 3rd Deprotection of the amino group (hydrolysis of p-nitroaniline → p-nitroaniline) The protection of the amino group with acetic anhydride yields acetanilide which is still an activating group but since it’s neutral it does not get protonated. Protection EAS (nitration) ES