Organic Synthesis under High Pressure

This article is dedicated to the use of hydrostatic pressure (2-20 kbar) in organic synthesis. This technique, whose mode of action can be described as "physical catalysis", is presented because, on the one hand, it enables many reactions in organic chemistry to be carried out under "gentle" conditions that respect fragile reagents or products, and, on the other, it is energy-efficient (no energy input during chemical transformation).

These techniques can be expected to make a wide range of contributions to fine chemistry. Indeed, compared with conventional thermal or catalytic techniques, hyperbaric methods sometimes make possible reactions that would be impossible due to large molecular congestion, thus offering synthetic shortcuts that can be invaluable in the multi-step elaboration of complex molecules with high added value. Furthermore, the quantities of solvent to be used can be very low, as reactions are carried out at high concentration, or even in the absence of solvent, thus minimizing recycling and environmental contamination problems. The absence of a chemical catalyst and/or lower temperature reduces degradation (e.g. in the case of acid catalysts), thereby facilitating purification, as the medium is generally cleaner at the end of the process. Processing times are also reduced, as the kinetics of typical organic chemistry reactions can be dramatically accelerated. It should be noted, however, that the use of this type of process is still rare and has not yet found large-scale application in organic synthesis (vide infra).

We present here :

• firstly, the technical aspects of high pressure, limiting ourselves to the elements necessary for the implementation of this activation in organic chemistry;

  • the basic physico-chemical concepts to be considered when pressure varies and the usual parameters that are most influenced by it;

  • then, briefly, the equipment most commonly used in the useful pressure range in organic chemistry, in particular "piston-cylinder" type equipment, which allows access to very high pressures while maintaining "reasonable" useful volumes for the synthetic chemist;

  • a few selected examples, and some recent ones, to represent the major classes of reactions that are positively influenced by pressure.