Pd/PTABS: Low-Temperature Thioetherification of Chloro(hetero)arenes

The
thioetherification of heteroaryl chlorides is an essential
synthetic methodology that provides access to bioactive drugs and
agrochemicals. Due to their (actual or potential) industrial importance,
the development of efficient and low-temperature protocols for accessing
these compounds is a requirement for economic and ecologic reasons.
A particular highly effective catalytic protocol using the Pd/PTABS
system at only 50 °C was developed accordingly. The coupling
between chloroheteroarenes and a variety of less reactive arylthiols
and alkylthiols was carried out with a high efficiency. Heteroarenes
of commercial relevance such as purines and pyrimidines were also
found to be useful substrates for the reported transformation. The
commercial drug Imuran (azathioprine) was synthesized as an example,
and its preparation could be optimized. DFT studies were performed
to understand the electronic effects of the tested ligands on the
catalytic reaction.