Electrophilic fluorination of aromatic compounds with NF type reagents: kinetic isotope effects and mechanism

Borodkin, G. I.; Zaikin, Pavel A.; Shubin, V. G.

doi:10.1016/j.tetlet.2006.02.016

Cited by 25 publications

(13 citation statements)

References 13 publications

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“…The bonds broken overall are N-O and C-C pi and aromatic C-H while C-N, C-C and O-H bonds are formed; the extent of these changes in the rate-limiting step could be probed via primary kinetic isotope effect 21. Overall hybridization (geometry) changes, potentially detectable through secondary H/D kinetic isotope effects,22 include sp --> sp2 at the alkyne carbons, while a sp2 --> sp3 --> sp2 change could intervene at the ortho aromatic carbon in a step-wise addition/tautomerization process.…”

Section: Resultsmentioning

confidence: 99%

On the Mechanism of Nitrosoarene−Alkyne Cycloaddition

et al. 2008

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The thermal reaction between nitrosoarenes and alkynes produces N-hydroxyindoles as the major products. The mechanism of these novel reactions has been probed using a combination of experimental and computational methods. The reaction of nitrosobenzene (NB) with an excess of phenyl acetylene (PA) is determined to be first order in each reactant in benzene at 75° C. The reaction rates have been determined for reactions between phenyl acetylene with a set of p-substituted nitrosoarenes, 4-X-C 6 H 4 NO, and of 4-O 2 N-C 6 H 4 NO with a set of p-substituted arylalkynes, 4-Y-C 6 H 4 C≡CH. The former reactions are accelerated by electron-withdrawing X-groups (ρ = + 0.4), while the latter are faster with electron-donating Y groups (ρ = − 0.9). The kinetic isotope effect for the reaction of C 6 H 5 NO/C 6 D 5 NO with PhC≡CH is found to be 1.1 (± 0.1) while that between PhC≡CH/PhC≡CD with PhNO is also 1.1 (± 0.1). The reaction between nitrosobenzene and the radical clock probe cyclopropylacetylene affords 3-cyclopropyl indole in low yield. In addition to 3-carbomethoxy-N-hydroxyindole, the reaction between PA and o-carbomethoxy-nitrosobenzene also affords a tricyclic indole derivative 3, likely derived from trapping of an intermediate indoline nitrone with PA and subsequent rearrangement. Computational studies of the reaction mechanism were carried out with density functional theory at the (U)B3LYP/6-31+G(d) level. The lowest energy pathway of the reaction of PhNO with alkynes was found to be stepwise; the N-C bond between nitrosoarene and acetylene is formed first, the resulting vinyl diradical undergoes cis-trans isomerization, and then the C-C bond forms. Conjugating substituents Z on the alkyne, Z-C≡CH, lower the calculated (and observed) activation barrier, Z=-H (19 kcal/mol), -Ph (15.8 kcal/mol) and -C(O)H (13 kcal/mol). The regioselectivity of the reaction, with formation of the 3-substituted indole, was reproduced by the calculations of PhNO + PhC≡CH; the rate-limiting step for formation of the 2-substituted indole is higher in energy by 11.6 kcal/mol. The effects of -NO 2 , -CN, -Cl, -Br, -Me, and -OMe substituents were computed for the reactions of p-X-C 6 H 4 NO with PhC≡CH and of PhNO and/or p-NO 2 -C 6 H 4 NO with p-Y-C 6 H 4 C≡CH. The activation energies for the set of p-XC 6 H 4 NO vary by 4.3 kcal/mol and follow the trend found experimentally, with electron withdrawing X-groups accelerating the reactions. The range of barriers for the p-Y-C 6 H 4 C≡CH reactions is smaller, about 1.5 kcal/mol and 1.8 kcal/mol in the cases of PhNO and p-NO 2 -PhNO, respectively. In agreement with the experiments, electron donating Y-groups on the alkyne accelerate the reactions with p-NO 2 -C 6 H 4 NO, while both ED and EW groups are predicted to facilitate the reaction. The calculated kinetic isotope effect for the reaction of C 6 H 5 NO/C 6 D 5 NO with PhC≡CH is negligible (as found experimentally) while that for PhC≡CH/PhC≡CD with PhNO (0.7) differs somewhat from the experiment (1.1). Taken together the experimen...

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Section: Resultsmentioning

confidence: 99%

On the Mechanism of Nitrosoarene−Alkyne Cycloaddition

et al. 2008

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“…Kinetic isotope effect studies of the fluorination of aromatic compounds with N-F-type reagents are consistent with a polar S E Ar mechanism where the decomposition of the Wheland intermediate is not rate limiting. 9 Studies of the fluorination of 1,3,5-trideuterobenzene demonstrated the occurrence of 1,2-hydrogen and deuterium migrations in the Wheland intermediates, the first time such a process has been demonstrated in electrophilic fluorination. The kinetics of the chlorination of phenol and 2-naphthol by 1,3-dichloro-5,5dimethylhydantoin (2) in aqueous acidic media have been interpreted 10 in terms of an initial rate-limiting formation of a charge-transfer complex between the substrate and the chlorinating agent.…”

Section: Halogenationmentioning

confidence: 99%

Electrophilic Aromatic Substitution

Coombes¹

2010

Organic Reaction Mechanisms · 2006

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GeneralThe wide scope of application of the electrophilicity index of Parr, Szentpály, and Liu has been reviewed. 1 Applications to electrophilic aromatic substitutions discussed are few. However, some alkylation and acylation reactions do correlate well with electrophilicity values. In the case of the nitration of toluene and chlorobenzene, correlation is not very good and it is suggested 2 that electrophilicity is a kinetic quantity with inherent thermodynamic information.A quantitative description of the reactivity of monosubstituted benzenes to electrophilic substitution based on considerations of inductive effect parameters and conjugative effect parameters from the 13 C chemical shifts of the aromatic compounds has been proposed. 3 MO calculations on the proton migration in the ipso adducts formed in the reaction of CH 3 + and SiH 3 + with benzene have been described. 4 With SiH 3 + the ipso adduct is the most stable of possible isomers, whereas for CH 3 + the para-protonated isomer is the most stable.A DFT study of the reactivity of pyridine and the diazabenzenes towards electrophilic substitution, assuming frontier orbital control of the reactions, predicts their low reactivity as the HOMOs of these substrates are not π -orbitals. 5 For pyridine-Noxide, however, the HOMO is an aromatic orbital. DFT studies giving Fukui indices predict 6 the preferred sites of electrophilic attack on pyrrole, furan, and thiophene and calculation of the local softness of the reactive sites rationalizes relative reactivities.2-Aminothiazole and its 4-methyl derivative react with the superelectrophilic 4,6dinitrobenzofuroxan at C(5) to form, for example, (1) in spite of them exhibiting higher nitrogen basicity than aniline. 7 In the case of 4,5-dimethyl-2-aminothiazole, however, attack did occur at nitrogen. 187

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“…refs. [14][15][16][17][18] ). Recently, we have studied promotional effect of ionic liquids in electrophilic fluorination of methylated uracils with Selectfluor TM in alcohols.…”

Section: Introductionmentioning

confidence: 99%

Promotional effect of ionic liquids in electrophilic fluorination of phenols

Borodkin¹,

Elanov²,

Shubin³

et al. 2017

Arkivoc

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The influence of a stoichiometric amount of ionic liquids (IL) on the fluorination of phenols in various solvents has been studied. The fluorination of phenol, 1-naphthol and resorcinol was carried out using 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (F-TEDA-BF 4 , Selectfluor™) with the formation of 2-fluoro-, 4-fluorophenol, 2-fluoro-, 4-fluoronaphthol and 4-fluoro-, 4,6-difluoro-benzene-1,3-diol as the main products. The use of a stoichiometric amount of ionic liquid as an additive results in acceleration of the reactions. The effect is most significant at low temperatures. It has been found that solvent polarity has an essential effect on the difference in yields of fluoroproducts obtained in the presence of IL and without it.

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Electrophilic fluorination of aromatic compounds with NF type reagents: kinetic isotope effects and mechanism

Cited by 25 publications

References 13 publications

On the Mechanism of Nitrosoarene−Alkyne Cycloaddition

On the Mechanism of Nitrosoarene−Alkyne Cycloaddition

Electrophilic Aromatic Substitution

Promotional effect of ionic liquids in electrophilic fluorination of phenols

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