How difficult are anion-molecule SNAr reactions of unactivated arenes in the gas phase, dimethyl sulfoxide, and methanol solvents?


Nucleophilic substitution on the aromatic ring (SNAr) is a very important reaction for organic transformations. This kind of reaction is usually difficult to take place, requiring organometallic catalysis or activation of the ring by electron withdrawing groups to turn the nucleophilic attack possible. In this work, the relative importance of intrinsic gas phase barrier and the solvent effect on several SNAr reactions using theoretical calculations were investigated. The reactions of the anions OH, CN, and CH3O and the enolates CH3COCH2 and CH3COCHCOCH3 with bromobenzene and (o, m, p)-methoxy bromobenzene in methanol and dimethyl sulfoxide as solvents were considered. The OH and CH3O ions are highly reactive in the gas phase. However, the solvent effect induces a high activation barrier in solution, turning the reaction difficult, although feasible. The CN and CH3COCHCOCH3 ions have high activation barriers even in the gas phase. The interesting CH3COCH2 ion has a moderate barrier in the gas phase, although the free energy barrier in DMSO solution reaches 33 kcal mol−1. Our analysis suggests that decreasing the solvent effect, arylation of enolates with unactivated arenes could become possible.

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The authors thank the support of the agencies CNPq, FAPEMIG, and CAPES.

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Correspondence to Josefredo R. Pliego Jr..

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Silva, D.R., Pliego, J.R. How difficult are anion-molecule SNAr reactions of unactivated arenes in the gas phase, dimethyl sulfoxide, and methanol solvents?. Struct Chem 30, 75–83 (2019).

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  • Aromatic nucleophilic substitution
  • Formation of carbon-carbon bond
  • Solvent effect
  • Regioselectivity
  • Enolate