Objective:
Aminomethylphenol molecules have wider applications in pharmaceuticals, agrochemicals, plant
protection and promising functional materials. The development of an efficient and practical method to prepare this class of
compound is highly desirable from both environmental and economical points of views.
Materials and Methods:
In order to establish an effective synthetic method for preparing aminomethylphenol derivatives,
the Petasis borono-Mannich reaction of salicylaldehyde, phenylboronic acid and 1,2,3,4-tetrahydroisoquinoline was selected
as a model reaction. A variety of reaction conditions are investigated including solvent and temperature. The generality and
limitation of the established method were also evaluated.
Results and Discussion:
It was found that model reaction can be carried out in cyclopentyl methyl ether at 80 oC under
catalyst-free condition. This protocol with a broad substrate applicability, the reaction of various arylboronic acid, secondary
amine and salicylaldehyde proceeded smoothly under optimal reaction conditions to afforded various aminomethylphenol
derivatives in high yields. A practical, scalable, and high-yielding synthesis of aminomethylphenol derivatives was
successfully accomplished.
Conclusion:
A catalyst-free practical method for the synthesis of minomethylphenol derivatives based on Petasis borono–
Mannich (PBM) reaction of various arylboronic acid, secondary amine and salicylaldehyde in cyclopentyl methyl ether has
been developed. The salient features of this protocol are avoidance of any additive/catalyst and toxic organic solvents, use
cyclopentyl methyl ether as the reaction medium, clean reaction profiles, easy operation, and high to excellent yield.
