S<sub>N</sub>Ar catalysis enhanced by an aromatic donor–acceptor interaction; facile access to chlorinated polyfluoroarenes

Senaweera, Sameera; Weaver, Jimmie D.

doi:10.1039/c7cc03996d

Cited by 24 publications

(16 citation statements)

References 26 publications

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“…Interestingly, clear inhibition was observed for every example, which indicates that these reactions are at least partially radical in nature. Alternatively, it is possible that galvinoxyl may disrupt CTC formation, which can theoretically facilitate both polar 19 and open-shell reactivity. In this regard, it should also be noted that the formation of strongly coloured reaction mixtures was observed for almost every substrate described in Table 2 , which suggests that CTC formation with oxime reagent 9d could be a general process.…”

Section: Resultsmentioning

confidence: 99%

Radical–anion coupling through reagent design: hydroxylation of aryl halides

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Radical–anion coupling through reagent design: hydroxylation of aryl halides

et al. 2021

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“…LiF has a much lower solubility in this solvent, and its precipitation provides a driving force for the reaction. Weaver recently showed that stoichiometric Me 3 SiCl can also promote the reverse halex reaction of pentafluoropyridine with added chloride ion through a donor–acceptor mechanism . We postulated that this could allow recycle of unwanted 3,4,5,6 -F 4 to intermediates that could be recycled for halex reactions to give 4,5,6 -F 3 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 6-Aryl-5-fluoropicolinate Herbicides via Halex Reaction of Tetrachloropicolinonitrile

Whiteker

Froese

Arndt

et al. 2019

Org. Process Res. Dev.

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The development of a new synthesis of 6-aryl-5-fluoropicolinate herbicides is described. This general route employs the halogen exchange (halex) reaction of tetrachloropicolinonitrile to give a mixture of chlorofluoropicolinonitriles. It was found that the isomeric purity of the trifluorochloropicolinonitrile fraction increased, with eventual conversion to tetrafluoropicolinonitrile. The desired product of this reaction, 3-chloro-4,5,6-trifluoropicolinonitrile, reacted with NH 3 regioselectively at the 4-position. Introduction of the aryl substituent was accomplished by initial conversion of the 6-fluoro substituent to 6-bromo using HBr in acetic acid followed by Pd-catalyzed Suzuki−Miyaura cross-coupling. The moderate regioselectivity of the halex reaction of tetrachloropicolinonitrile was studied computationally using a modified G3MP2B3* ab initio method. These computations were in agreement with the observed regioselectivity of the reaction. Recycle of the main byproduct, tetrafluoropicolinonitrile, was shown to be possible by two routes. The reverse halex reaction of tetrafluoropicolinonitrile using LiCl in DMSO gave a mixture of chlorofluoro products. In addition, scrambling of halogens between tetrafluoropicolinonitrile and tetrachloropicolinonitrile using catalytic n-Bu 4 PCl gave a mixture of chlorofluoropicolinonitriles that could be resubjected to halex conditions to give additional 4,5,6-trifluoro-3-chloropicolinonitrile.

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“…The perfluorination effect in hexafluorobenzene is experimentally well documented, with one of the more striking examples of the effect being the formation of a solid from the 1:1 mixture of hexafluorobenzene with mesitylene, both of which are liquids at room temperature [15]. Other work has also shed light on the perfluorination effect in perfluoropyridine and how it enables significant non-covalent interactions, which was recently shown to enhance the S N Ar substitution of perfluoropyridine [16,17]. The theoretical study of how these interactions affect chemical reaction outcomes and transition state geometries during the S N Ar substitution of perfluoroaromatics remains sparse.…”

Section: Introductionmentioning

confidence: 99%

Theoretical Prediction and Explanation of Reaction Site Selectivity in the Addition of a Phenoxy Group to Perfluoropyrimidine, Perfluoropyridazine, and Perfluoropyrazine

et al. 2021

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Perfluoroaromatics, such as perfluoropyridine and perfluorobenzene, are privileged synthetic scaffolds in organofluorine methodology, undergoing a series of regioselective substitution reactions with a variety of nucleophiles. This unique chemical behavior allows for the synthesis of many perfluoroaromatic derived molecules with unique and diverse architectures. Recently, it has been demonstrated that perfluoropyridine and perfluorobenzene can be utilized as precursors for a variety of materials, ranging from high performance polyaryl ethers to promising drug scaffolds. In this work, using density functional theory, we investigate the possibility of perfluoropyrimidine, perfluoropyridazine, and perfluoropyrazine participating in similar substitution reactions. We have found that the first nucleophilic addition of a phenoxide group substitution on perfluoropyrimidine and on perfluoropyridazine would happen at a site para to one of the nitrogen atoms. While previous literature points to mesomeric effects as the primary cause of this phenomenon, our work demonstrates that this effect is enhanced by the fact that the transition states for these reactions result in bond angles that allow the phenoxide to π-complex with the electron-deficient diazine ring. The second substitution on perfluoropyrimidine and on perfluoropyridazine is most likely to happen at the site para to the other nitrogen. The second substitution on perfluoropyrazine is most likely to happen at the site para to the first substitution. The activation energies for these reactions are in line with those reported for perfluoropyridine and suggest that these platforms may also be worth investigation in the lab as possible monomers for high performance polymers.

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S_NAr catalysis enhanced by an aromatic donor–acceptor interaction; facile access to chlorinated polyfluoroarenes

Cited by 24 publications

References 26 publications

Radical–anion coupling through reagent design: hydroxylation of aryl halides

Radical–anion coupling through reagent design: hydroxylation of aryl halides

Synthesis of 6-Aryl-5-fluoropicolinate Herbicides via Halex Reaction of Tetrachloropicolinonitrile

Theoretical Prediction and Explanation of Reaction Site Selectivity in the Addition of a Phenoxy Group to Perfluoropyrimidine, Perfluoropyridazine, and Perfluoropyrazine

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SNAr catalysis enhanced by an aromatic donor–acceptor interaction; facile access to chlorinated polyfluoroarenes

Cited by 24 publications

References 26 publications

Radical–anion coupling through reagent design: hydroxylation of aryl halides

Radical–anion coupling through reagent design: hydroxylation of aryl halides

Synthesis of 6-Aryl-5-fluoropicolinate Herbicides via Halex Reaction of Tetrachloropicolinonitrile

Theoretical Prediction and Explanation of Reaction Site Selectivity in the Addition of a Phenoxy Group to Perfluoropyrimidine, Perfluoropyridazine, and Perfluoropyrazine

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S_NAr catalysis enhanced by an aromatic donor–acceptor interaction; facile access to chlorinated polyfluoroarenes