SnAt reactions, solvent effects

The use of DMSO as a mechanistic tool is not restricted to rate variation effects (Section 4). Advantage can also be taken of its unique molecular properties which enable it to stabilize certain types of structures, such as the anionic intermediates in SnAt reactions. Moreover, as a consequence of its influence on ion association constants, it is found to affect the product distribution and the stereochemical course of bimolecular olefin-forming eliminations. These two illustrative systems which have been chosen for discussion are intended to demonstrate the versality of this solvent in mechanistic studies and may suggest other avenues of investigation. 

For the nucleophilic aromatic substitution reaction (SnAt) it has been discussed whether the addition of the nucleophile, the elimination of the leaving group is the rate limiting step or if this depends on the solvent. Taking the SnAt reaction between azide ion and 4-fluoronitrobenzene as an example, QM/MM calculations indicate that solvation effects cause the highest barrier for the elimination step. As a function of the solvent the experimental free energies of activation for these reactions are (values are given in kcal/mol) H2O 28.1/MeOH 27.5/MeCN ... 

Sun and DiMagno demonstrated the rapid generation of Af-methyl-5-fluoro-4-nitroimidazole from the corresponding chloride using anhydrous TBAF that was generated in situ from KF by fluoride relay (Scheme 60) [75]. hi fluoride relay, the reaction of KF with 2,6-dicyano-tetrachlorobenzene transfers the fluoride to the arene that finally produces the activated anhydrous tetrabutylammonium fluoride (TBAF) upon the addition of tetrabutylammonium cyanide (>60 % yield from KF). Other polar aprotic solvents, such as THF and acetonitrile, are also effective for this SnAt fluorination reaction. 

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