SNAr Reaction run neat

Mechanism + Description

As per N-based dipolar aprotic solvents

General comments

If one reagent is cheap and readily available, and can be used in excess, or if the reaction mixture forms a mobile liquid at reasonable temperature, there may be a possibility to run the reaction without solvent. This does somewhat detract from PMI metrics if the excess reagent is not recovered, and care needs to be taken regarding any potential exotherms and how they are handled with a diluent present. Neat reactions can be run at atmospheric or elevated pressure.

Phase transfer catalysts (PTC) are sometimes added to aid reaction –see section on PTC


Key references

Tetrahedron, 2010 vol. 66; nb. 35, p. 7112 – 7118 Superacid mediated reactions applied to 4-aminobenzofused sultams and fluorinated 4-aminobenzene sulfonamides synthesis

Eur. J. Org. Chem. 2015, 6932–6942 SNAr versus Buchwald–Hartwig Amination/Amidation in the Imidazo[2,1‐b][1,3,4]thiadiazole Series

Int. J. Mol. Sci. 2013, 14(9), 18850-18860 A Facile and Efficient Synthesis of Diaryl Amines or Ethers under Microwave Irradiation in Presence of KF/Al2O3 without Solvent


Relevant scale up examples solvents under pressure

Org. Process Res. Dev., 1997, 1, 106-116

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