Mechanochemical Synthesis Method for Drugs Used in the Treatment of CNS Diseases under PTC Conditions

Abstract

Phase transfer catalysis (PTC) is an excellent possibility in the synthesis of organic compounds as it allows the reactions to be carried out under the conditions of green chemistry, while maintaining high yields and selectivity. The great advantage of these reactions is also the possibility of carrying out the reactions not only under conventional conditions, but also mechanochemically in solvent-free processes. Bearing this in mind, we decided to develop a new method for the synthesis of known biologically active compounds from the group of long-chain arylpiperazines (LCAPs). The first mortar trials were very promising and prompted us to carry out a series of ball mill reactions. One of the technological problems that we encountered while conducting reactions in the ball mill was the difficulty in extracting the post-reaction mixture. We tested the effects of additives improving the insulation of the product, such as, e.g., starch, zeolites, and silica. Research has proven that with appropriate process conditions using TBAB as a catalyst and in the presence of potassium carbonate and a small amount of Zeolite ZSM5 or silica, aripiprazole can be obtained with a yield of 90% in just five minutes. The obtained results are very promising and it is worth considering them as an alternative to the synthesis of other compounds from the LCAPS group.