Convenient Method for the Preparation of the 2-Methyl Thiophen-3-yl Magnesium Bromide Lithium Chloride Complex and Its Application to the Synthesis of 3-Substituted 2-Methylthiophenes

Abstract

Lithium chloride was found to accelerate formation of the Grignard reagent from inactive 3-bromo-2-methylthiophene (1) and commercial magnesium metal. Based on this finding, a convenient and potentially scalable preparation of ethyl 2-methylthiophene-3-carboxylate (3) was achieved. In addition, this process has been found to provide a new, general approach to 3-substituted 2-methylthiophenes.

GRAPHICAL ABSTRACT

Keywords:

• Activator
• 3-bromo-2-methylthiophene
• Grignard reagent
• lithium chloride

Notes

^a Determined by HPLC analysis after conversion into 8.

^b Isolated yields (%) are given in parentheses.

^a Isolated yield after column chromatography.