An improved and scale-up synthesis
Received: 14 August 2015 / Accepted: 21 September 2015 / Published online: 26 September 2015
Ó Springer Science+Business Media Dordrecht 2015
Abstract An optimized process for the preparation of 6-hydroxybenzofuran is
described. This process consists of three steps: the reaction of 2-hydroxy-4-
methoxybenzaldehyde with chloroacetic acid, the formation of the 6-methoxyben-
zofuran in acetic anhydride, and the demethylation with sodium 1-dodecanethiolate
to afford the desired product. The entire process is safe, cost effective, environ-
mentally benign, and scalable. A production scale of over 2.6 kg product was
achieved in good overall yield.
Keywords 6-Hydroxybenzofuran Á 6-Methoxybenzofuran Á Sodium
Benzofuran is one of the most widely distributed structures and compounds
containing this structure have demonstrated a variety of biological activities [1–4].
Among them, 6-hydroxybenzofuran (6-HBF) is the most frequently occurring
scaffold in many natural and pharmaceutical products, such as moracins A–Z ,
furochromones , psoralen and related analogs .
Many methods have been developed for the synthesis of benzofuran derivatives
[6, 7]. For the particular compound of 6-HBF and its closely related structures, there
are a few synthetic methods reported in the literature (Scheme 1), including the
Electronic supplementary material The online version of this article (doi:10.1007/s11164-015-2288-
7) contains supplementary material, which is available to authorized users.
& Yun-Sheng Huang
Guangdong Medical College School of Pharmacy, 1 Xincheng Ave, Songshan Lake
Technology Park, Dongguan 523808, China
Res Chem Intermed (2016) 42:4433–4442