Two benzyl ether is an important hydroxyl protecting group. It has been widely used in the multi-step synthesis of natural products and their analogues. In addition, two benzyl ether is also an important pharmacophore, and compounds containing two benzyl ether structure have shown good antiviral activity. In view of this, methods for the synthesis of two benzyl ethers have also been extensively studied
The reported methods for preparing two benzene methyl ether mainly has the following 3 types: 1) in the catalytic organic alkali, benzyl chloride two or two benzene methyl bromide and alcohol nucleophilic substitution reaction; 2) consists of two benzene methanol active phosphate as two benzene methyl phenyl phosphate and alcohol - two have affinity substitution reaction; 3) Lew is acid in catalytic amount, two benzene methanol and other alcohol direct nucleophilic substitution reaction.
The method (1) need to use stoichiometric organic alkali, organic salts to produce an equivalent in the reaction process; and (2) to the first of two benzene methanol (preact IV at ion pre activation), generating active ester, to nucleophilic substitution reaction; in contrast, the use of methods (3) a catalytic amount of Lew acid is reaction process, the only byproduct is water, and does not require the two benzyl alcohol by pre activation, so the method (3) more in line with the atom economy principle.