Palladium catalyzed coupling of arylamines with arylhalides

Abstract

In view of tremendous importance of substituted arylamines for their synthesis in the field of biological and medicinal chemistry, and metal mediated approaches still remain scarce, it was planned to develop a simple and efficient method for the synthesis of substituted secondary arylamines through palladium catalyzed reactions of 4-substituted iodobenzene with 4- Substituted arylamines/2-Iodo 4-substituted arylamines as shown in the Scheme-1. Here a convenient method for the synthesis of substituted secondary arylamines derivatives through palladium catalyzed cross-coupling reaction is reported. In this purpose, 4-substituted iodobenzene 5-7 were synthesized by the diazotization of their parent 4-sustituted anilines 1-4 using NaNO2, H2SO4, KI in water and 2-iodo-4-substituted anilines 9 were synthesized by KI, KIO3, HCl, CH3OH in water. Another synthetic approach was used for the preparation of 4- Methyl iodobenzene 10 by using NaHCO3, I2 and water. The cross-coupling reaction of 4- substituted iodobenzene 4-7, 10 with 2-iodo-4-substituted-anilines 9 / 4-substituted aniline 9- 14 were carried out in the presence of Pd(OAc)3, Ph3P and KOt-Bu in THF at 80-85°C for 12 ~ 48 hrs and produced the compound 15-17. In addition to comparative study was done by (2- biphenyl)di-tert-butyl phosphine/DPPF as phosphine ligand instead of Ph3P in toluene and gave the product 18-21.----------------------------------------