Characterization and Synthesis of a 6-Substituted Benzo[b]thiophene.
An impurity observed during the synthesis of zileuton (Zyflo) has been isolated and characterized as a benzo[b]thiophene derivative that has undergone electrophilic substitution in the 6 position (4). A nine-step synthesis confirms the structural assignment. Key steps in the synthesis include a regioselective Friedel-Crafts coupling between 2-hydroxythioanisole, 8, and 1-(benzo[b]thien-2-yl)ethanol, 1, and formation of a benzo[b]thiophene from an o-methylthiobenzaldehyde, 14, and chloroacetone. The synthesis provides a potentially general route to substituted benzo[b]thiophenes.
Haight
Anthony R.
AR
Chemical Process Research, D54P, and Structural Chemistry, D-418, Abbott Laboratories, North Chicago, Illinois 60064.
Wayne
Gregory S.
GS
Lannoye
Gregory S.
GS
Parekh
Shyamal I.
SI
Zhang
Weijiang
W
Copp
Richard R.
RR
Hollis
L. Steven
LS