Green synthesis of building blocks, drug candidates and fine chemicals by barochemistry: application of high pressure in organic synthesis.

While there are many areas of green chemistry that affect contemporary synthesis, the development of non-traditional activation methods, such as microwaves, ultrasound, mechanochemistry or high hydrostatic pressure (HHP) is considered as one the most important contributors to the development of green synthetic processes. Among these methods HHP, which, by analogy with the other methods, sonochemistry or mechanochemistry, can be referred to as barochemistry, is well-suited for industrial production; the large scale instrumentation is broadly available, at this time focusing on food processing applications. HHP instruments are safe and easy to handle, robust, and are a good fit for batch and (stopped)-flow operations. The same instruments could be used for large scale chemical synthesis as well, however, the high pressure synthesis of organic compounds, including Active Pharmaceutical Ingredients (APIs), is still in its infancy with extensive developments expected in the near future. HHP applies mechanical compression force to initiate transformations, such as the inactivation of pathogens and enzymes, or activation of chemical reactions. The pressure range of these reactions (2-20 kbar) significantly exceeds that of the typical chemistry using pressurized gases (0.01-0.1 kbar), such as hydrogenations. This tutorial review provides a succinct introduction to the theory and use of barochemistry, with particular emphasis on its current applications and great potential in green synthesis.