SNAr Reaction in common molecular solvents under pressure
Mechanism + Description
As per N-based dipolar aprotic solvents
While many SNAr reactions will take place in solvents other than dipolar aprotics, the rates are often poor and too slow for practical application. One way to address this drawback is to use elevated temperatures with the solvent under pressure. This can often give reaction rates comparable with reaction in dipolar aprotic solvents. Heating in pressurized closed vessels is often associated with microwave heating, which can be used for smaller scale reactions. The use of continuous /flow chemistry with appropriate back pressure regulation can allow operation above a solvent's boiling point and somewhat negates issues with running closed pressurized batch reactions at scale.
Operation at higher temperature can also be effective when a particularly unreactive electrophile or nucleophile is being employed.
Chemistry Letters and Reviews 2012, Vol. 5, No. 4, 595-601 Efficient nucleophilic substitution of halopyridines using ethanol as solvent with microwave heating: synthesis of 2-aminoethylsulfanylpyridines
Relevant scale up examples solvents under pressure