Room‐Temperature Nucleophilic Aromatic Fluorination: Experimental and Theoretical Studies

Sun, Haoran; DiMagno, Stephen G.

doi:10.1002/ange.200504555

Cited by 44 publications

(20 citation statements)

References 28 publications

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“…Experimental results (Scheme 3) show that a nucleophilic fluorination reaction only occurs for those chlorobenzenes with strong electron withdrawing substituents (e.g., CN) on the para-position. 55,56 Chlorobenzenes without electron-withdrawing substituents or with electron-donating substituents (e.g., NH 2 ) do not undergo nucleophilic aromatic fluorination even with the most active nucleophilic fluorinating reagent, anhydrous tetrabutylammonium fluoride (TBAF anh ). 56 The ESP maps in Figure 4 clearly show the electron density difference at the ipso carbon with NO 2 -substituted chlorobenzene displaying the least negative charge and the ipso carbon with NH 2 -substituted chlorobenzene displaying the most negative charge.…”

Section: Applications To Nucleophilic Aromatic Substitution Reactionsmentioning

confidence: 99%

Electrostatic Potential Maps and Natural Bond Orbital Analysis: Visualization and Conceptualization of Reactivity in Sanger’s Reagent

et al. 2015

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Frederick Sanger's early work on protein sequencing through the use of colorimetric labeling combined with liquid chromatography involves an important nucleophilic aromatic substitution (S N Ar) reaction in which the N-terminus of a protein is tagged with Sanger's reagent. Understanding the inherent differences between this S N Ar reaction and other nucleophilic substitution reactions (S N 1 and S N 2) can be challenging for students learning organic chemistry. Here, both electrostatic potential (ESP) maps and natural bond orbital (NBO) analyses are employed to visualize and conceptualize Sanger's key observation of the difference in reactivity between 2,4-dinitrochlorobenzene and 2,4-dinitrofluorobenzene. The utility of this method is extended to compare the reactivity of a series of halobenzenes for S N Ar fluorination, a widely used reaction in pharmaceutical and medicinal fields. In combination with experimental results from the literature, the ESP maps and NBO analyses are consistent with and provide excellent corroboration with the reactivity of different substrates toward S N Ar reactions.

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Section: Applications To Nucleophilic Aromatic Substitution Reactionsmentioning

confidence: 99%

Electrostatic Potential Maps and Natural Bond Orbital Analysis: Visualization and Conceptualization of Reactivity in Sanger’s Reagent

et al. 2015

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“…[28,29] By using high-pressure mass spectrometry, gas-phase thermochemical data for the equilibria involving the addition of anions to substituted benzenes have been obtained. Information is thus provided on the stabilities of the complexes, though not directly on their structures.…”

Section: Introductionmentioning

confidence: 99%

Molecular Complexes of Simple Anions with Electron‐Deficient Arenes: Spectroscopic Evidence for Two Types of Structural Motifs for Anion–Arene Interactions

Chiavarino

Crestoni

Fornarini

et al. 2009

Chemistry A European J

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Anion-pi interactions between a pi-acidic aromatic system and an anion are gaining increasing recognition in chemistry and biology. Herein, the binding features of an electron-deficient aromatic system (1,3,5-trinitrobenzene (TNB)) and selected anions (OH-, Br-, and I-) are examined in the gas phase by using the combined information derived from collision-induced dissociation experiments at variable energy, infrared multiple-photon dissociation spectroscopy, and quantum chemical calculations. We provide spectroscopic evidence for two different structural motifs of anion-arene complexes depending on the nature of the anion. The TNB-OR- complexes (R=H, or alkyl groups which were studied earlier) adopt an anionic sigma-complex structure whereby RO- attacks the aromatic ring with covalent bond formation, and develops a tetrahedral ring carbon bound to H and OR. The halide complexes rather conform to a structure in which the TNB moiety is hardly altered, and the halogen is placed on an unsubstituted carbon atom over the periphery of the ring at a C-X distance that is appreciably longer than a typical covalent bond length. The ensuing structural motif, previously characterized in the solid state and named weak sigma interaction, is now confirmed by an IR spectroscopic assay in the gas phase, in which the sampled species are unperturbed by crystal packing or solvation effects.

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“…122 Sun and DiMagno also used 1-(4-fluorobenzyl)-2-chlorobenzimidazole as a substrate for studying their recently developed anhydrous TBAF and reported a >90% conversion to the 2-fluoro derivative in 30 min at room temperature. 123 The milder conditions reveal again the reactivity of anhydrous TBAF. .…”

Section: Fluorinated Purines and Benzimidazolesmentioning

confidence: 99%

Fluorinated Five‐Membered Nitrogen‐Containing Heterocycles

Kirk¹

2009

Fluorinated Heterocyclic Compounds

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Room‐Temperature Nucleophilic Aromatic Fluorination: Experimental and Theoretical Studies

Cited by 44 publications

References 28 publications

Electrostatic Potential Maps and Natural Bond Orbital Analysis: Visualization and Conceptualization of Reactivity in Sanger’s Reagent

Electrostatic Potential Maps and Natural Bond Orbital Analysis: Visualization and Conceptualization of Reactivity in Sanger’s Reagent

Molecular Complexes of Simple Anions with Electron‐Deficient Arenes: Spectroscopic Evidence for Two Types of Structural Motifs for Anion–Arene Interactions

Fluorinated Five‐Membered Nitrogen‐Containing Heterocycles

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