Zinc-Catalyzed Alkylation of Aromatic Amines in Continuous Flow

Abstract

A practical approach to the synthesis of antioxidant 4,4′-dicumyldiphenylamine (DCDPA) and its derivatives by Friedel−Crafts alkylation of aromatic amines was developed under continuous flow conditions. Because of the enhanced mass and heat transfer features of the microreactor, the reaction time was significantly reduced in contrast to a batch mode. The reaction was carried out using a 1:6 v/v ethanol/Cl(CH 2 ) 2 Cl cosolvent system with ZnCl 2 as the catalyst to achieve satisfactory yields. This is an effective method for the synthesis of DCDPA and its derivatives with excellent para selectivity that has the merits of shorter reaction time, easy operation, and straightforward scale-up.

H2O ⋅ B(C6F5)3‐Catalyzed para‐Alkylation of Anilines with Alkenes Applied to Late‐Stage Functionalization of Non‐Steroidal Anti‐Inflammatory Drugs

“…Dialkylated aniline 3 al is an efficient antioxidant for polymeric materials [1a] . We were pleased to find that dialkylated products 3 al and 3 aj , and novel dialkylated anilines 3 ak , 3 am and 3 ay (Scheme 2 and 3) were formed from the corresponding diaryl amines using the H 2 O ⋅ B(C 6 F 5 ) 3 catalyzed procedure.…”

Reactor design and selection for effective continuous manufacturing of pharmaceuticals

“…There are other publications that report on reactions performed in PFRs [23,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63], which are not discussed in detail here.…”