A Convenient Synthesis of N‐Aryl Benzamides by Rhodium‐Catalyzed ortho‐Amidation and Decarboxylation of Benzoic Acids

The rhodium‐catalyzed amidation of substituted benzoic acids with isocyanates by directed C?H functionalization followed by decarboxylation to afford the corresponding N‐aryl benzamides is demonstrated, in which the carboxylate serves as a unique, removable directing group. Notably, less common meta‐substituted N‐aryl benzamides are generated readily from more accessible para‐ or ortho‐substituted groups by employing this strategy.     

A LFER Kinetic Study of The Reaction of 5‐Substituted Orotic Acids with Diazodiphenylmethane

Linear free energy relationships (LFER) were applied to the kinetic data for the reaction of 5‐substituted orotic acids, series 1 , with diazodiphenylmethane (DDM) in N,N–dimethylformamide and compared with results obtained for 2‐substituted benzoic acids, series 2 . The correlation analysis of the kinetic data with σ substituent parameters was carried out using SSP (single substituent parameter) methods. From the sign and value of proportinality constant ρ, lower sensitivity to the substituent effect was obtained in series 1 , 0.876, than in the series 2 , 1.877. Evaluation of substituent “ortho‐effect” was performed using the Charton model, which includes the steric substituent parameter, and Fujita and Nishioka's model, which describes the total ortho‐effect as contribution of ordinary polar effect, the ortho‐steric and ortho‐polar effects. Results of correlations, obtained by using the Charton model, showed highest contribution of the polar effect, 0.861 vs. 2.101, whereas the steric effect is of lowest significance, 0.117 vs. 0.055, for series 1 and 2 , respectively. Also, a low negative value of coefficient with the steric effect, –0.08, obtained from the Fujita–Nishioka model indicated low steric effect, influencing a decrease of the reaction rate in series 1 . The structural and substituent effects were also studied by using the density functional theory method, and together with kinetic data, it gave a better insight into the influence of the effect of both geometry and substituent on the π?electron density shift induced reactivity of investigated acids.     

Direct CH Amidation of Benzoic Acids to Introduce meta‐ and para‐Amino Groups by Tandem Decarboxylation

The Ir‐catalyzed mild C?H amidation of benzoic acids with sulfonyl azides was developed to give reactions with high efficiency and functional‐group compatibility. Subsequent protodecarboxylation of ortho‐amidated benzoic acid products afforded meta‐ or para‐substituted (N‐sulfonyl)aniline derivatives, the latter being inaccessible by other C?H functionalization approaches. The decarboxylation step was compatible with the amidation conditions, enabling a convenient one‐pot, two‐step process.     

Iron‐Promoted ortho‐ and/or ipso‐Hydroxylation of Benzoic Acids with H2O2

Regioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [Fe^II(BPMEN)(CH₃CN)₂](ClO₄)₂ ( 1 ) and [Fe^II(TPA)(CH₃CN)₂](OTf)₂ ( 2 ), where BPMEN=N,N′‐dimethyl‐N,N′‐bis(2‐pyridylmethyl)‐1,2‐ethylenediamine, TPA=tris‐(2‐pyridylmethyl)amine. Two cis‐sites, which are occupied by labile acetonitrile molecules in 1 and 2 , are available for coordination of H₂O₂ and substituted benzoic acids. The hydroxylation of the aromatic ring occurs exclusively in the vicinity of the anchoring carboxylate functional group: ortho‐hydroxylation affords salicylates, whereas ipso‐hydroxylation with concomitant decarboxylation yields phenolates. The outcome of the substituent‐directed hydroxylation depends on the electronic properties and the position of substituents in the molecules of substrates: 3‐substituted benzoic acids are preferentially ortho‐hydroxylated, whereas 2‐ and, to a lesser extent, 4‐substituted substrates tend to undergo ipso‐hydroxylation/decarboxylation. These two pathways are not mutually exclusive and likely proceed via a common intermediate. Electron‐withdrawing substituents on the aromatic ring of the carboxylic acids disfavor hydroxylation, indicating an electrophilic nature for the active oxidant. Complexes 1 and 2 exhibit similar reactivity patterns, but 1 generates a more powerful oxidant than 2 . Spectroscopic and labeling studies exclude acylperoxoiron(III) and Fe^IV?O species as potential reaction intermediates, but strongly indicate the involvement of an Fe^III? OOH intermediate that undergoes intramolecular acid‐promoted heterolytic O? O bond cleavage, producing a transient iron(V) oxidant.     

Functionalization of Hexa‐peri‐hexabenzocoronenes: Investigation of the Substituent Effects on a Superbenzene

We have demonstrated that the iridium‐catalyzed direct borylation of hexa‐peri‐hexabenzocoronene (HBC) enables regioselective introduction of boryl groups to the para‐, ortho‐, and meta‐substituted HBCs in high yields. The boryl groups have been transformed into various functionalities such as hydroxy, cyano, ethynyl, and amino groups. We have elucidated that the substituents significantly influence the photophysical properties of HBCs to enhance fluorescence quantum yields. DFT calculations revealed that the origin of the substituent effect is the lift in degeneracy in the frontier orbitals by an interaction with electron‐donating and electron‐withdrawing substituents at the para‐ and ortho‐positions. The change in molecular orbitals results in an increase of the transition probability from the S₀→S₁ states. In addition, the two‐photon absorption cross‐section values of para‐substituted HBCs are significantly larger than those of ortho‐ and meta‐substituted HBCs.     

Palladium‐Catalyzed ortho‐Selective CH Deuteration of Arenes: Evidence for Superior Reactivity of Weakly Coordinated Palladacycles

We disclose a protocol for the palladium‐catalyzed ortho‐selective C? H deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho‐deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.     

Structure–Reactivity Relationships in Negishi Cross‐Coupling Reactions

Competition experiments have been performed to determine the relative reactivities of substituted bromobenzenes and of different arylzinc reagents in the [Pd(PPh₃)₄]‐catalyzed Negishi cross‐coupling reaction in THF at 25 °C. The cross‐coupling reactions are accelerated by electron acceptors in the bromobenzenes, the effect of which increases in the order ortho <meta <para. On the other hand, electron acceptors in the arylzinc halides diminish the reaction rates. Hammett correlations show that substituent variations in the bromobenzenes (ρ=+2.5) have a larger effect than substituent variations in the arylzinc halides (ρ=?0.98).     

Hydrogen migrations in mass spectrometry. VI—the chemical ionization mass spectra of substituted benzoic acids and benzyl alcohols

The H₂ and CH₄ chemical ionization mass spectra of a series of series of substituted benzoic acids and substituted benzyl alcohols have been determined. For the benzoic acids the major fragmentation reactions of the protonated molecule involve elimination of H₂O or elimination of CO₂, the latter reaction involving migration of the carboxylic hydrogen to the aromatic ring. For the benzyl alcohols the major fragmentation reactions of [MH]⁺ involve loss of H₂O or CH₂O, analogous to the CO₂ elimination reaction for the benzoic acids. It is shown that the CO₂ and CH₂O elimination reactions occur only when a conjugated aromatic ring system is present, and that for the carboxylic acid systems, methyl groups and, to a lesser extent, phenyl groups are capable of migrating. The only discernible effect of substituents on the fragmentation of [MH]⁺ is an enhancement of the H₂O loss reaction in the benzoic acid system when an amino, hydroxyl, or halogen substituent is ortho to the carboxyl function. This ‘ortho’ effect, which differs in scope from that observed in electron impact mass spectra, is attributed to an intramolecular catalysis by the ortho substituent of the 1,3 hydrogen migration in the carbonyl protonated acid followed by H₂O elimination. Apparently, this route is favoured over the direct elimination of H₂O from the carbonyl protonated acid, since the latter has a high activation energy barrier because of unfavourable orbital symmetry restrictions.     

Palladium‐Catalyzed ortho‐Selective C?H Deuteration of Arenes: Evidence for Superior Reactivity of Weakly Coordinated Palladacycles

We disclose a protocol for the palladium‐catalyzed ortho‐selective C H deuteration of arenes. Phenylacetic acids and benzoic acids are suitable substrates for this reaction. This reaction offers a catalytic route to ortho‐deuterated phenylacetic acids and benzoic acids and demonstrates the sharp difference in reactivity of palladacycle intermediates held together by weak and strong coordination.     

Direct synthesis of γ‐substituted phthalides via ortho‐aryl benzoic acid mediated benzyl radical cyclization

Direct synthesis of γ‐substituted phthalids from related ortho‐aryl benzoic acids with 48–85% yield are covered. The direct oxidation in the presence of peroxydisulphate‐copper (II) chloride in aqueous medium was applied. The reaction is highly regioselective and leads exclusively to γ‐butyrolactone, through very stable benzylic radical intermediate.     

1-萘甲酰苯胺和2-萘甲酰苯胺的分子内电荷转移研究

A series of 1-naphthanilides (1) and 2-naphthanilides (2) with varied substituents at the para- or meta-position of anilino phenyl ring were prepared and their absorption and fluorescence spectra in a nonpolar solvent cyclohexane were investigated. An abnormal long wavelength emission assigned to the charge transfer (CT) state was found for all of the prepared naphthanilides in cyclohexane. A linear free energy correlation between the CT emission energies and the Hammett constants of the substituent was found within series 1 and 2. The value of the linear slope with 1 (0.42 eV) was higher than that with 2 (0.32 eV) being close to that of the substituted benzanilides 3 (0.31 eV) The higher slope value suggested higher charge separation extent in the CT state of 1 than that of 2. It was found that the corresponding linear slope of anilino-substituted benzanilides remained unchanged when para-, meta-, ortho-, or ortho, ortho-methyls were introduced into the anilino moiety, which ruled out the possible contribution of the difference in the steric effect and the electron accepting ability of the naphthoyl acceptor in 1 and 2. Compared with the early reported N-substituted-benzoyl-aminonaphthalene derivatives 4 and 5, it was considered that 1-naphthoyl enhanced the charge transfer in 1 and the proximity of its ^1La and ^1Lb states was suggested to be responsible. It was shown that 1- and/or 2-substituted naphthalene cores acting as either electron acceptor (naphthoyl) or electron donor (aminonaphthalene) were different in not only electron accepting (donating) ability but also shaping the charge transfer pathway.     

Ionic dehydration reactions: The effect of location of the activated complex on kinetic energy release

A broad range of kinetic energy release has been found for the 1,4 elimination of water in a series of ortho substituted benzyl alcohols and benzoic acids. It is suggested that the trend reflects, in part, the position of the activated complex on the reaction coordinate. More specifically, reactions which proceed via an ‘early’ transition state release only small quantities of energy, whereas those processes occurring ‘later’ release a larger fraction of the available energy. Consequently, the o- methyl derivatives give large kinetic energy release compared to o- amino or hydroxy substituted compounds. Father verification is obtained from the small kinetic energy release observed for the 1,4 ionic dehydration in simple,acyclic alcohols.     

Kinetics and mechanism of the oxidation of substituted benzaldehydes by hexamethylenetetramine‐bromine

The oxidation of thirty‐six monosubstituted benzaldehydes by hexa‐methylenetetramine‐bromine (HABR), in aqueous acetic acid solution, leads to the formation of the corresponding benzoic acids. The reaction is first order with respect to HABR. Michaelis‐Menten–type kinetics were observed with respect to aldehyde. The reaction failed to induce the polymerization of acrylonitrile. There is no effect of hexamethylenetetramine on the reaction rate. The oxidation of [²H]benzaldehyde (PhCDO) indicated the presence of a substantial kinetic isotope effect. The effect of solvent composition indicated that the reaction rate increases with an increase in the polarity of the solvent. The rates of oxidation of meta‐ and para‐substituted benzaldehydes showed excellent correlations in terms of Charton's triparametric LDR equation, whereas the oxidation of ortho‐substituted benzaldehydes correlated well with tetraparametric LDRS equation. The oxidation of para‐substituted benzaldehydes is more susceptible to the delocalization effect but the oxidation of ortho‐ and meta‐substituted compounds displayed a greater dependence on the field effect. The positive value of γ suggests the presence of an electron‐deficient reaction center in the rate‐determining step. The reaction is subjected to steric acceleration when ortho‐substituents are present. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 615–622, 2000     

Palladium‐Catalyzed [3+3] Annulation between Diarylamines and α,β‐Unsaturated Acids through CH Activation: Direct Access to 4‐Substituted 2‐Quinolinones

A C?H activation strategy has been successfully employed for the high‐yielding synthesis of a diverse array of 4‐substituted 2‐quinolinone species by a palladium‐catalyzed dehydrogenative coupling involving diarylamines. This intermolecular annulation approach incorporates readily available α,β‐unsaturated carboxylic acids as the coupling partner by suppressing the facile decarboxylation. Based on preliminary mechanistic studies, a reaction sequence is proposed, involving ortho palladation, π‐coordination, β‐migratory insertion, and β‐hydride elimination.     

Conformation of hydrogen‐bonded dimeric o‐methyl‐substituted benzoic acids

Molecules of 2,4‐dimethylbenzoic acid, C₉H₁₀O₂, form typical centrosymmetric hydrogen‐bonded dimers. The carboxyl group is twisted with respect to the benzene ring and the methyl group in the ortho position shows evasive in‐plane splaying. The relation between the in‐plane splaying and the twist angle of the carboxyl group for various ortho‐substituted dimeric derivatives of benzoic acid is presented. It shows how the steric strains are released depending on the numbers and positions of the substituents.     

Silver‐Catalyzed Arylation of (Hetero)arenes by Oxidative Decarboxylation of Aromatic Carboxylic Acids

A long‐standing challenge in Minisci reactions is achieving the arylation of heteroarenes by oxidative decarboxylation of aromatic carboxylic acids. To address this challenge, the silver‐catalyzed intermolecular Minisci reaction of aromatic carboxylic acids was developed. With an inexpensive silver salt as a catalyst, this new reaction enables a variety of aromatic carboxylic acids to undergo decarboxylative coupling with electron‐deficient arenes or heteroarenes regardless of the position of the substituents on the aromatic carboxylic acid, thus eliminating the need for ortho‐substituted aromatic carboxylic acids, which were a limitation of previously reported methods.     

Photocatalytic/Cu‐Promoted C−H Activations: Visible‐light‐Induced ortho‐Selective Perfluoroalkylation of Benzamides

A visible‐light‐induced and copper‐promoted perfluoroalkylation of benzamides was successfully developed under the assistance of an 8‐aminoquinoline directing group. It provides a straightforward method for the synthesis of ortho‐perfluoroalkyl‐substituted benzoic acid derivatives. The reaction employs a cheap organic dye eosin Y as the photoredox catalyst and is run under the irradiation of a 26 W fluorescent LED light bulb.     

[RhIII(Cp*)]‐Catalyzed ortho‐Selective Direct C(sp2)H Bond Amidation/Amination of Benzoic Acids by N‐Chlorocarbamates and N‐Chloromorpholines. A Versatile Synthesis of Functionalized Anthranilic Acids

A Rh^III‐catalyzed direct ortho‐C?H amidation/amination of benzoic acids with N‐chlorocarbamates/N‐chloromorpholines was achieved, giving anthranilic acids in up to 85 % yields with excellent ortho‐selectivity and functional‐group tolerance. Successful benzoic acid aminations were achieved with carbamates bearing various amide groups including NHCO₂Me, NHCbz, and NHTroc (Cbz=carbobenzyloxy; Troc=trichloroethylchloroformate), as well as secondary amines, such as morpholines, piperizines, and piperidines, furnishing highly functionalized anthranilic acids. A stoichiometric reaction of a cyclometallated rhodium(III) complex of benzo[h]quinoline with a silver salt of N‐chlorocarbamate afforded an amido–rhodium(III) complex, which was isolated and structurally characterized by X‐ray crystallography. This finding confirmed that the C?N bond formation results from the cross‐coupling of N‐chlorocarbamate with the aryl–rhodium(III) complex. Yet, the mechanistic details regarding the C?N bond formation remain unclear; pathways involving 1,2‐aryl migration and rhodium(V)– nitrene are plausible.     

Asymmetric anionic polymerizations of 7‐(o‐substituted phenyl)‐2,6‐dimethyl‐1,4‐benzoquinone methides: Electrostatic interaction and steric,inductive, and resonance effects of the ortho‐substituent on the optical activity

7‐(o‐Substituted phenyl)‐2,6‐dimethyl‐1,4‐benzoquinone methides which have an electron‐donating methoxy‐(o‐OMe, 2a ) and methyl‐ (o‐Me, 2b ) substituents or an electron‐withdrawing cyano‐ (o‐CN, 2c ) and trifluoromethyl‐ (o‐CF₃, 2d ) substituents at the ortho‐position of the aromatic ring and 7‐(m‐substituted phenyl)‐2,6‐dimethyl‐1,4‐benzoquinone methide with an electron‐withdrawing trifluoromethyl‐ (m‐CF₃, 2e ) substituent at the meta‐position of the aromatic ring were synthesized, and their asymmetric anionic polymerizations using the complex of lithium 4‐isopropylphenoxide with (?)‐sparteine were carried out in toluene at 0 °C. The polymers with negative optical activity were obtained for all of five monomers, and their specific rotation values largely changed depending upon the substituents of the monomers. On the basis of the comparison of various substituents effects, it was found that the specific rotation of obtained polymers is significantly affected by the electronic effects such as inductive and resonance effects rather than the steric and electrostatic effects of the substituent. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55 , 1048–1058     

Linear Free‐Energy Relationships Applied to the 13C NMR Chemical Shifts in 4‐Substituted N‐[1‐(Pyridine‐3‐ and ‐4‐yl)ethylidene]anilines

Two series of 4‐substituted N‐[1‐(pyridine‐3‐ and ‐4‐yl)ethylidene]anilines have been synthesized using different methods of conventional and microwave‐assisted synthesis, and linear free‐energy relationships have been applied to the ¹³C NMR chemical shifts of the carbon atoms of interest. The substituent‐induced chemical shifts have been analyzed using single substituent parameter and dual substituent parameter methods. The presented correlations describe satisfactorily the field and resonance substituent effects having similar contributions for C1 and the azomethine carbon, with exception of the carbon atom in para position to the substituent X. In both series, negative ρ values have been found for C1′ atom (reverse substituent effect). Quantum chemical calculations of the optimized geometries at MP2/6‐31G++(d,p) level, together with ¹³C NMR chemical shifts, give a better insight into the influence of the molecular conformation on the transmission of electronic substituent effects. The comparison of correlation results for different series of imines with phenyl, 4‐nitrophenyl, 2‐pyridyl, 3‐pyridyl, 4‐pyridyl group attached at the azomethine carbon with the results for 4‐substituted N‐[1‐(pyridine‐3‐ and ‐4‐yl)ethylidene]anilines for the same substituent set (X) indicates that a combination of the influences of electronic effects of the substituent X and the π₁‐unit can be described as a sensitive balance of different resonance structures.