Drawbacks to overcome:
One type of solventless reaction is one where a liquid reactant is used neat, for instance the reaction of 1-bromonaphthalene with Lawesson's reagent is done with no added liquid solvent, but the 1-bromonaphthalene acts as a solvent.
A reaction which is closer to a true solventless reaction is a Knoevenagel condensation of ketones with (malononitrile) where a 1:1 mixture of the two reactants (and ammonium acetate) is irradated in a microwave oven.
Collin Raston's research group have been responsible for a number of new solvent free reactions In some of these reactions all the starting materials are solids, they are ground together with some sodium hydroxide to form a liquid, which turns into a paste which then hardens to a solid.
In another development the two components of an Aldol reaction are combined together with the asymmetric catalyst S-proline in a ball mill in a mechanosynthesis. The reaction product has 97% enantiomeric excess.
The reaction goes to completion in 5 minutes with immediate evaporation whereas the same reaction in solution after the same 5 minutes (dichloromethane) has only 70% conversion and even after 24 hours some of the aldehyde remains.