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The alkylation of heteroaryl chlorides through a homolytic aromatic substitution (HAS) mechanism was achieved by the use of alkyl formates as alkylating agents in the presence of a tert-butoxy radi...

The coupling reaction of aryl iodides with arenes was found to proceed under mild conditions to give biaryls through a homolytic aromatic substitution mechanism, using potassium tert-butoxide and di-tert-butyl hyponitrite as a stoichiometric promoter and a radical initiator, respectively.

We succeeded in synthesizing edge-brominated zeolite-templated carbon (ZTC-Br) as the key intermediate of edge-functionalization of ZTC via an electrophilic aromatic substitution reaction using dib...

Density functional theory (DFT) calculations of nitrogen-directed intramolecular electrophilic borylation reaction of arenes, which is widely used for construction of functional molecules, indicate...

The synthesis and properties of a novel type of α,α-bis(heteroazulen-3-yl)-1,4-benzoquinonemethides 11a–f are studied. The synthetic method was based on a TFA-catalyzed electrophilic aromatic substitution on the heteroazulenes with 4-hydroxybenzaldehyde to afford the corresponding methane derivatives, followed by oxidative hydrogen abstraction with DDQ, and subsequent exchange of the counter-anion by using aq. HBF4 or aq. HPF6 and neutralization. The polarization of 11a–f was evaluated by their 13C NMR and UV–vis spectral data. The thermodynamic stability of the conjugated acid of 11a–f was evaluated to be in the order 11a < 11b < 11c and in the order 11d < 11e < 11f based on their pKa values (

4′,4′′(5′′)-Di-tert-butyldibenzo-18-crown-6 (DTBB18C6) was synthesized by improving the electrophilic aromatic substitution of dibenzo-18-crown-6 (DB18C6) using tert-butyl alcohol (TBA) as alkylati...

Nucleophilic vinylic substitutions of (Z)-(β-halovinyl)phenyliodonium salts with tetrabutylammonium halides proceed in a stereoselective manner with retention of configuration yielding vicinal (Z)-...

A general approach is established for the synthesis of phenolic compounds having terpenoid side chains: (1) protection of the phenolic hydroxyls in the aromatic precursor by ether formation, (2) coupling the aromatic part with a terpenoid bromide, and (3) deprotection to regenerate the hydroxyl groups. This strategy was successfully applied to the synthesis of colletochlorins B and D and grifolin. Some of the colletochlorin derivatives were found to inhibit the cell growth of P388.

The reaction of p-chloronitrobenzene with N-methylpyrrolidine under high pressure gave demethylation product and ring opening products through quaternary ammonium chloride intermediate formed by the SNAr reaction. On the other hand, the reactions with N-methylpiperidine and N-methylmorpholine gave only demethylation products. The reactions of o-chloronitrobenzene and 2,4-dichloronitrobenzene with above amines gave similar results.

Photoreactions of 1,2- and 1,4-dicyanobenzenes (o- and p-DCB) with allylic silanes, germanes, and stannanes in acetonitrile were studied under various conditions. In these photoreactions, one of cyano groups of o- and p-DCB was replaced by allylic groups. With trimethyl(3-methyl-2-butenyl)silane, -germane, and -stannane, the photosubstitution occurred at both α- and γ-positions of the allylic moiety in a constant ratio, regardless of the kinds of metals. 1,3-Dicyanobenzene (m-DCB) was less reactive to the photosubstitution reaction. The reactivity of group 14 organometallic compounds increased in the order: Si- < Ge- < Sn-compounds. The photoreactions were sensitized by aromatic hydrocarbons such as phenanthrene and triphenylene, and also accelerated by adding Mg (ClO4)2 and alkylbenzenes. Quantum yields for the formation of the substitution products increased with decreasing oxidation potentials of group 14 organometallic compounds. A key step for the photoreactions is the reaction of radical anions of d...

A new diselenide dication salt, 1,5-diselenoniabicyclo[3.3.0]octane bis(hexafluorophosphate) was reacted with several aromatics to afford either the substitution or redox products. The reaction mode depends on the oxidation potential of aromatics.

The Friedel–Crafts-type carboxylation of arenes has been achieved by activating CO2 with silylium borates. The reaction exhibits broader substrate applicability than does our previously reported Al...

Methyl 2-methoxybenzoate undergoes facile nuclear-methoxyl displacement by treatment with sodium butoxide or isopropoxide in dimethylformamide.

An efficient and practical method for the preparation of 4-nitrogen-substituted benzoic acids is described. Our method consists of the aromatic substitution of 2,2,2,4′-tetrafluoroacetophenone with...

An efficient and mild method for the halogenation of aromatic compounds using N-chloro-, N-bromo-, and N-iodosuccinimide in the presence of NH4NO3 or FeCl3 in acetonitrile was developed.

A new type of electrophilic aromatic substitution without using organic halides has been realized by using Mo(CO)6 catalyst.

Treatment of N-methoxyamides with hypervalent iodine compounds generates electron deficient nitrogen species which react intra- or intermolecularly with an aromatic group to give N-aryl-N-methoxyamides in good yields.

We tried to explain the electrophilicity of radical reagents such as H and OH radicals in the aromatic substitution reaction by using the molecular orbital theory. The delocalization energy of π electrons was decomposed into two parts: one is the energy due to the delocalization from a substrate to a reagent and another is that from a reagent to a substrate. The former was considered to be a measure of the electrophilicity and the latter of the nucleophilicity. The decomposition of the delocalization energy into two parts was carried out by modifying the relevant core resonance integrals as appropriate. The result indicated that the delocalization energy for the electrophilicity was much larger than that for the nucleophilicity for both radicals. Thus, H and OH radicals should be electrophilic in nature, in good agreement with the experimental facts. Finally, the origin of the electrophilicity was discussed in connection with the height of the relevant energy levels by following a perturbational approach.

The oxazinyl and oxazolinyl substituents on an F-benzene ring facilitated the substitution of fluorine ortho to the heterocyclic functional groups by carbon and nitrogen nucleophiles. Alkylmagnesium halides and alkyllithium compounds were employed as the carbon nucleophile, and lithium N-methylanilide and N-methylanilinomagnesium halide as the nitrogen nucleophile. The selective ortho-substitution was accomplished by the complexing interaction between the ring-membered nitrogen on the functional substituents and the anionic nucleophile through the interposing metal cation. Effects of the substituents in the orientations and rates of the reactions depended upon the polarity of the reaction solvent and the kinds of anionic nucleophile and counter metal cation.

The kinetics of the reactions of 2-(acetylamino)ethyl 2,6-dinitrophenyl ether (Smiles rearrangement) and N-acetyl-N-(2-hydroxyethyl)-2,6-dinitroaniline with sodium isopropoxide in the DMSO–2-propanol mixture (20 : 80 v/v) was studied. Both reactions were found to rapidly produce the same spiro anionic σ complex, giving N-(2-acetoxyethyl)-2,6-dinitroaniline. Although the rates for formation of the complex were different in both reactions, the rates for rearrangement were the same.

The chlorination of 3-methyl-2-butenyl phenyl sulfone with either hexachloroethane or 1,1-dichloro-3-methyl-2-butenyl phenyl sulfone in basic medium gives rise to 1-chloro-3-methyl-2-butenyl phenyl sulfone which in turn reacts in situ with electrophilic compounds to give a variety of products in good yields.

In the gas-phase radiolysis of a C3H8(100 mm)–C6H6 mm)–C6D6(5 mm) mixture, it has been shown that isopropylbenzene (IPB) formed by the attack of i-C3H7+ ions to benzene consists of IPB-d1, -d2, -d3, and -d4 as well as IPB-d0 and -d5, indicating that a proton exchange between an intermediate complex and benzene molecules has occurred.

Oxazoles substituted in their 2-positions with 2-methoxy-, 2-fluoro-, or 2,6-difluorophenyl groups, and in their 4,5-positions with methyls or phenyls, were treated with ArMgBr or ArLi to give substituted biphenyl or terphenyl products. The oxazole groups were subsequently converted to esters, acids, or amides. These reactions provide a new unsymmetrical aryl-aryl coupling synthon.

Electrophilic nitration of dibenzofuran with nitric acid by a charge-transfer mechanism occurs exclusively at the 3-position and on the other hand, substitution at the 2-position predominates in the acylation, in which a classical σ-complex mechanism is important.

Irradiation of dicyanoxylenes and dicyanodurene in acetonitrile in the presence of triethylamine gave mainly substitution and reduction products respectively, whereas a photochemical reaction of 1,2,4,5-tetracyanobenzene in the presence of N-methylpyrrolidine or nicotine gave tricyanoaniline, an amination product, as well as substitution products.

Azulene and guaiazulene react with nitroethene to form substitution products having 2-nitroethyl, 2,4-dinitrobutyl, or 2-nitroethenyl groups at the 1(3)-position in low yields. The presence of formic acid prevented the formation of the dinitrobutyl compound, and increased the yield of the 2-nitroethyl derivative. A reaction course leading to these products is proposed. Reduction of 1-(2-nitroethyl)azulene and 1-(2-nitroethyl)guaiazulene gave the corresponding amine compounds in good yields. This two-step process provides a new, improved route to 2-(1-azulenyl)ethanamines having a primary amino group. The amine products, like related biogenic amines, inhibited the contraction of smooth muscle.

SNAr reactions of 1,2,3,5-tetranitrobenzene or 2,4,6-trinitrofluorobenzene with aromatic amines were studied in aprotic solvents by means of stopped-flow kinetic measurements. Base catalysis and negative activation enthalpy were observed in nonpolar solvents, which were ascribed to an intermediate encounter complex.

Treatment of p-dinitrobenzene with active methylene compounds of rather weak acidity in the presence of t-BuOK in liq NH3 at −70 °C leads to nucleophilic substitution of a nitro group, giving p-substituted nitrobenzenes in generally good yields.

Disulfide dication was found to react with several aromatics to give either the substitution or redox products. The reaction mode depends remarkably on the oxidation potential of the aromatics.

For rationalization of regioselectivities observed in nucleophilic aromatic photosubstitutions, two rules discriminating orientation-controlling MO’s, based on reaction mechanisms and frontier orbital theory, are proposed.

Irradiation of benzophenone O-acetyloxime, O-phenylacetyloxime, O-benzoyloxime, and O-(p-chlorobenzoyl)oxime in benzene, toluene, chlorobenzene, or o-xylene effected aromatic substitution on the solvent molecules by diphenylmethaniminyl radicals to give N-diphenylmethylenearylamines only when benzoxyl or p-chlorobenzoxyl radicals were generated concurrently. A mechanism involving a participation of the sufficiently long-lived acyloxyl radicals is proposed for the iminylation reaction on the basis of the reactivity patterns in this substitution reaction. o-Phenylbenzophenone O-benzoyloxime was also photolyzed in benzene to give 9-phenylphenanthridine, the intramolecular cyclization product of 2-biphenylylphenylmethaniminyl radicals.

The reaction of 2,6-dimethyl-4-methoxybenzyl alcohols, ethyl ethers, and acetates, possessing electrondonating and -withdrawing groups at the benzylic position, with bromine water was studied at different temperatures. The reaction was strongly affected by the electronegativity of a benzyl substituent to afford bromination products of aromatic nuclei and 2,4-dibromo-3,5-dimethylmethoxybenzene along with 2,4,6-tribromo derivatives formed by the cleavage of C–C bond.

The propagator method is applied to the study of solvent effects on reactivities of aromatic substitution reactions. We obtain the following set of results: (1) The influence of nonpolar solvent on...

Intramolecular aromatic substitution by a N-chloro-N-methoxyamide group to a suitably situated aromatic ring in the molecule is performed by using anhydrous zinc acetate and nitromethane as solvent to give nitrogen heterocycles in good yield.

The mechanism of the aromatic substitution was studied on the basis of the energy level diagrams determined for both the aromatic molecule and the reagent. From the consideration of the relative heights of the highest occupied and lowest vacant orbitals of the former to those of the latter, it was deduced that a large electron transfer occurs at some stage of the reaction from the aromatic molecule towards the reagent for the electrophilic substitution and in the reverse direction for the nucleophilic substitution. In connection with this electron transfer mechanism, it was expected that the orientation rule observed with the aromatic substitution can be explained by free valency values of the aromatic cation, neutral molecule and anion for the electrophilic, radical and nucleophilic substitutions respectively. It was shown that this expectation is fully satisfied for various aromatic substitutions.

N-Nitroso-p-chloro(36Cl)acetanilide has been decomposed in mixtures of benzene and mono-substituted benzene C6H5X (X=NO2, Cl, OCH3, and CH3), and the reaction products have been analyzed for 4-chlorobiphenyl and isomeric 4-ClC6H4C6H4X by the isotope dilution method. On the basis of these results, the partial rate factors for the p-chlorophenylation have been calculated to be, for nitrobenzene: o, 4.35; m, 0.61; p, 6.18; for chlorobenzene: o, 2.70; m, 0.87; p, 1.33; for anisole: o, 3.93; m, 0.94; p, 1.54 and for toluene: o, 2.97; m, 1.07; p, 1.32. The values of the partial rate factor for the meta position give a satisfactory Hammett plot with a slope of −0.27. This fact demonstrates that the p-chlorophenyl radical shows a measure of electrophilic character in the homolytic aromatic substitution.

Arylthallic acetate perchlorate monohydrates, Ar-Tl(OAc)(ClO4)·H2O, were obtained as the major products of the reaction between thallic acetate and aromatics in acetic acid containing perchloric acid. As the minor products, various types of oxidation products including oxidative coupling were obtained. Reactivity order of the aromatics and the isomer distributions in the products were the same as those in the usual electrophilic aromatic substitution. With thallic nitrate, sulfate, and chloride, no arylthallic compounds could be obtained.

m-Nitrobenzenesulfonyl peroxide has been photolyzed in nitrobenzene and benzonitrile. On the basis of the product analyses, the reactivity of the sulfonyloxy radical is discussed.

Photocycloaddition of thiobenzophenone to acetylenic compounds, R–C≡C–R′ (R=COOH, Ph, CH2OH, and CN; R′=H: R=COOMe; R′=COOMe), affords 1-phenyl-2-thia-1,2-dihydronaphthalene derivatives. The key step to the product is an intra-molecular aromatic substitution of the composite vinylic biradical 13. The difference in reactivity of acetylenic and olefinic compounds as well as that between thiobenzophenone and benzophenone are discussed. Ethoxyacetylene does not undergo the reaction. This is interpreted in terms of electronegativity of a radical center in 13. It is found that cyanoacetylene reacts with butanethiyl radical in contrast to its olefin analog, acrylonitrile.

The system, olefin-palladium chloride complex-silver nitrate has been shown to cause the oxidative coupling reaction of the aromatic compounds to afford biphenyl derivatives. The mechanism was also discussed in connection with the aromatic substitution of olefins by palladium salts.

In order to elucidate the nature of the chemisorption in the platinum-catalyzed exposure reaction with tritium, the effects of the substituents upon the hydrogen-tritium exchange of the aromatic ring and upon the tritium distribution in benzoic acid, salicylic acid and benzoylvaline have been investigated. All the substituents except the hydroxyl group decrease the hydrogen-tritium exchange of the aromatic ring, and the compounds carrying those substituents poison the catalyst for the tritium incorporation of benzene. This retardation effect of the substituents upon the hydrogen-tritium exchange of the aromatic nucleus may perhaps be attributed to the preferential adsorption of the substituents on the catalyst surface. The tritium distribution in benzoic acid and salicylic acid suggests that the hydrogen-tritium exchange in the aromatic ring may follow the substitution rule for electrophilic aromatic exchange. The relative hydrogen-tritium exchange rates of benzoylvaline show that the more readily a hydro...

Mass spectral decomposition process involving intramolecular aromatic substitution with the ejection of either the hydrogen or the substituent in the ortho position from the M+· ion is noticed in the eleven 5-(arylmethylene) barbituric acids studied. It has been generally noticed that for such a cyclization to occur, the presence of an α,β-unsaturated carbonyl function, in conjugation with the ring, is essential in aromatic systems.

The reaction of aryl bromides with methoxymethyltributyltin in the presence of a catalytic amount of dichlorobis(triphenylphosphine)palladium was found to give arylmethyl methyl ether. The reaction is a novel aromatic methoxymethylation.

In aromatic substitution of olefins, steric factor of o-alkyl substituents of styrene was investigated. The formation of arylated products was found to be decreased by introduction of alkyl groups to ortho position of styrene.

o-Bromo- and o-iodonitrobenzenes react with stable enolate anions in hot DMF in the presence of copper(I) iodide, to afford not the expected arylation products but the coupling products, 2,2′-dinitrobiphenyls.

Iodobenzene was obtained by a reaction of benzene with molecular iodine in trifluoromethanesulfonic acid in oxygen atmosphere in the presence of vanadium salt as a catalyst. The method affords a new aromatic iodination process in which benzene is iodinated directly with molecular iodine.

Naphthalene and tricarbonyl(η-cyclobutadiene)iron(0) have been found to react with styrene in the presence of palladium(II) acetate to give the styryl-substituted derivatives. This result shows that the present reaction possesses a high generality with which the reaction can be extended to such classes of the aromatic compounds.

The iodination of some electron-rich aromatic compounds, namely, three polymethylbenzenes, aniline, phenol, anisole, and phenetole, using iodine–copper(II) acetate in acetic acid, afforded the corr...