Meta-substituted Anilines Research Articles

Solvent hydrogen bonding and structural effects on nucleophilic aromatic substitution reactions. Part-2 : Reaction of benzenesulphonyl chloride with anilines in propan-2-ol/2-methylpropan-2-ol mixtures

Substitution reactions of fourteen para- and meta-substituted anilines with benzenesulphonyl chloride in different mole fractions of propan-2-ol in 2-methylpropan-2-ol have been investigated conductometrically. The second order rate constants correlates satisfactorily with pK a values of the anilines and also with the Hammett's substituent constant. The para-substituted anilines shows a satisfactory correlation with Charton's LDR equation. The results of these correlations indicate the formation of an electron deficient transition state. The rate data correlate satisfactorily with macroscopic solvent parameters such as relative permittivity, e r and polarity, E T N . Multiple correlation analysis of the rate data via Kamlet-Taft's solvatochromic parameters reveals that the solvent dipolarity/polarizability plays a dominant role in governing the reactivity.

Indole Synthesis via Rhodium Catalyzed Oxidative Coupling of Acetanilides and Internal Alkynes

The oxidative synthesis of highly functionalized indoles from simple anilines and internal alkynes mediated by a rhodium(III) catalyst is described. Good yields are obtained for a variety of aniline substrates, and good regioselectivity is obtained for the more sterically accessible position when meta-substituted anilines are used. Symmetrical and unsymmetrical alkynes react efficiently with high (>40:1) C2/C3 regioselectivity when aryl/alkyl substituted alkynes are used.

Design and synthesis of a series of meta aniline-based LFA-1 ICAM inhibitors

A series of meta-substituted anilines were designed and synthesized to inhibit the interaction of LFA-1 with ICAM for the treatment of autoimmune disease. Design of these molecules was performed by utilizing a co-crystal structure for structure-based drug design. The resulting molecules were found to be potent and to possess favorable pharmaceutical properties.

Synthesis of enantiomerically pure analogues of the meta-substituted aniline antibiotics

A practical route is described for the preparation of enantiomerically pure analogues of the meta-substituted aniline antibiotics. Starting with enantiomerically pure anilinide, photooxygenation, reduction and diastereoselective Weitz-Scheffer epoxidation protocols provide enantiomerically pure analogues of the meta-substituted aniline antibiotics in three steps.

Substituent and Solvent Effects on the Electrochemical Oxidation of para- and meta-Substituted Anilines

Electrochemical oxidation of fifteen para- and meta-substituted anilines in different mole fractions of acetic acid in water has been investigated in the presence of 0.1 M sulphuric acid as supporting electrolyte. The oxidation potential data of anilines correlates well with Hammett’s and Brown- Okamoto’s substituent constants affording negative reaction constants. The effect of para- and metasubstituents on the oxidation potential conforms to Swain’s F and R parameters, affording negative reaction constants. The oxidation potential values correlate well with macroscopic solvent parameters such as relative permittivity, εr, and polarity, ET N. Multiple correlation analysis also shows an excellent correlation with the oxidation potential values.

Effect of solvent on the rate of oxidation of substituted anilines with nicotinium dichromate in aqueous-acetic acid media

Mechanistic studies on the oxidation of 15 para- and meta-substituted anilines by nicotinium dichromate in water-acetic acid medium of varying mole fractions have been performed. The reaction can be characterized by the experimental rate equation, -d[oxidizing agent] Kk [substrate] [HCrO - 4 ] dt (1 + K [substrate]) The addition of p-toluenesulfonic acid enhances the reaction. The oxidation substituted anilines at 299-322 K complies with the isokinetic relationship but not to any of the linear free energy relationships, the isokinetic temperature lies within the experimental range. Correlation of rate data with Kamlet-Taft solvatochromic parameters (a, β, π*) suggests that the specific solute-solvent interactions play a major role in governing the reactivity.

Scope and mechanistic study of the ruthenium-catalyzed ortho-C-H bond activation and cyclization reactions of arylamines with terminal alkynes.

The cationic ruthenium hydride complex [(PCy(3))(2)(CO)(CH(3)CN)(2)RuH](+)BF(4)(-) was found to be a highly effective catalyst for the C-H bond activation reaction of arylamines and terminal alkynes. The regioselective catalytic synthesis of substituted quinoline and quinoxaline derivatives was achieved from the ortho-C-H bond activation reaction of arylamines and terminal alkynes by using the catalyst Ru(3)(CO)(12)/HBF(4).OEt(2). The normal isotope effect (k(CH)/k(CD) = 2.5) was observed for the reaction of C(6)H(5)NH(2) and C(6)D(5)NH(2) with propyne. A highly negative Hammett value (rho = -4.4) was obtained from the correlation of the relative rates from a series of meta-substituted anilines, m-XC(6)H(4)NH(2), with sigma(p) in the presence of Ru(3)(CO)(12)/HBF(4).OEt(2) (3 mol % Ru, 1:3 molar ratio). The deuterium labeling studies from the reactions of both indoline and acyclic arylamines with DCCPh showed that the alkyne C-H bond activation step is reversible. The crossover experiment from the reaction of 1-(2-amino-1-phenyl)pyrrole with DCCPh and HCCC(6)H(4)-p-OMe led to preferential deuterium incorporation to the phenyl-substituted quinoline product. A mechanism involving rate-determining ortho-C-H bond activation and intramolecular C-N bond formation steps via an unsaturated cationic ruthenium acetylide complex has been proposed.

Direct alkenylation of arylamines at the ortho-position with magnesium alkylidene carbenoids and some theoretical studies of the reactions

1-Chlorovinyl p-tolyl sulfoxides were synthesized from ketones and chloromethyl p-tolyl sulfoxide in high yields. Treatment of the sulfoxides with isopropylmagnesium chloride at −78 °C in toluene gave magnesium alkylidene carbenoids (α-chloro alkenylmagnesium chlorides), which were treated with N-lithio arylamines to afford ortho-alkenylated arylamines in moderate yields. The reaction, in some cases, proceeded in a highly stereospecific manner at the carbon bearing the chlorine and the sulfinyl group. The structures of the α-chloro alkenylmagnesium chlorides and the reactivity of the N-lithio meta-substituted anilines were studied at the B3LYP and MP2 levels of theory with the 6-31(+)G* basis set. This reaction offers a quite novel and direct alkenylation of arylamines at the ortho-position of the aromatic ring.

Meta-Substituted aniline- N-salicylidenes as corrosion inhibitors of zinc in sulphuric acid

The corrosion of zinc in sulphuric acid containing different m-substituted aniline- N-salicylidenes has been studied with respect to inhibitor and acid concentration, period of exposure and temperature. 99% inhibitor efficiencies have been observed. It appears that the salicylidene part of the inhibitor including the iminic group in the molecule plays a dominant role in the inhibition. As far as the effect of exposure period and temperature is concerned, m-CNS has turned out to be the best one. For all the five inhibitors, the heats of adsorption and free energies of adsorption are negative, while the entropies of adsorption are positive. The free energies of adsorption are more negative in the case of very good inhibitors like m-TNS and m-CNS, indicating a strong interaction of the inhibitor molecules with the metal surface. The activation energies in the presence of these inhibitors are higher than that in plain acid. The adsorption of these inhibitors follows Langmuir adsorption isotherm. The conjoint effect of external cathodic current and the inhibitor is observed to be either synergistic or additive. Galvanostatic polarization studies indicate that these are mixed type inhibitors with predominant action on the local cathodes. Mechanism of the action of inhibitors has been provided.

Spectroscopic investigation of oxidation products of ortho- or meta-substituted aniline derivatives in acetonitrile using an electron-transfer stopped-flow method

The absorption spectra of the oxidation products of ortho- or meta-toluidine or anisidine in acetonitrile (AN) were observed using a stopped-flow technique by mixing with AN solutions of the tris( p-bromophenyl)amine (TBPA) cation radical. During the oxidation of o-toluidine in AN, the dynamic transformation of absorption spectra could be observed in the visible region, which was assigned to the oxidized states of the benzidine dimer, o-tolidine, formed via the C para –C para coupling of the o-toluidine monomer. Because a decrease in the absorption of the oxidized dimer was observed in the presence of the monomers, it is inferred that the monomer contributed to the consecutive reactions of the oxidized states of the benzidine dimer in AN. In contrast, during the oxidation of o-anisidine, the formation of a similar C para –C para coupling dimer was hardly observed in the visible absorption spectra, while some transformations of the absorption spectra could be recorded. This indicates that the changes in the reaction sites in the case of o-anisidine are due to the substitutents. Furthermore, during the oxidation of m-toluidine or m-anisidine, no remarkable absorption was observed in the visible region, which indicated the high reactivity of the cation radicals of m-toluidine and m-anisidine.

Rapid and Efficient Microwave‐Assisted Amination of Electron‐Rich Aryl Halides Without a Transition‐Metal Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rapid and efficient microwave-assisted amination of electron-rich aryl halides without a transition-metal catalyst.

[reaction: see text] A rapid and direct amination of aryl halides has been developed in good to high yields under microwave irradiation without a transition-metal catalyst. This reaction is a particularly powerful method for the coupling of electron-rich aryl halides with various amines. In some cases, the excellent regioselectivity could be observed, which facilitated the preparation of meta-substituted anilines from ortho- or para-substituted phenylhalides. In addition, a mechanism via the interesting benzyne intermediate has been proposed.

Synthesis of 2,3-dihydroindoles, indoles, and anilines by transition metal-free amination of aryl chlorides.

Aliphatic and aromatic amines react with 2- and 3-chlorostyrene in the presence of potassium tert-butoxide to give N-substituted 2,3-dihydroindoles in good yields. The combination of this domino-amination protocol with a suitable dehydrogenation reaction gives access to pharmacologically interesting indoles in a one-pot procedure. Overall product yields of N-substituted indoles >50% are obtained by this method starting from commercially available substrates. In addition to the intramolecular base-promoted amination of aromatic C-Cl bonds, metal-free intermolecular aminations of aryl chlorides with primary and secondary amines are described. The use of potassium tert-butoxide as base allows the synthesis of various anilines in good to excellent yields. Due to the formation of aryne intermediates, either N-substituted anilines or meta-substituted anilines are produced with excellent selectivities.

Synthesis of Meta-substituted aniline derivatives by nucleophilic substitution

Substitution by amines of fluorobenzenes containing a meta-substituted electron withdrawing group (EWG), in DMSO at 100 °C over 60 h gave meta-substituted aniline derivatives in isolated yields of up to 98%. The scope of the reaction is explored in terms of reaction conditions and substrates. It is postulated that facile meta-substitutions are facilitated through field stabilisation of the intermediate anion by EWG substituents.

Comparison of brönsted acidities of neutral NH-acids in gas phase, dimethyl sulfoxide and water

The Brönsted acidities of several neutral NH-acids (substituted diphenylamine, substituted anilines and imides) were measured in the gas phase (pulsed FT ICR spectrometry), dimethyl sulfoxide and aqueous solution. Comparison of the Brönsted acidities of neutral NH-acids in the gas phase, dimethyl sulfoxide and water was also carried out. It was shown that substituent effects on the acidity of the studied compounds are significantly attenuated by the transfer of the reaction series of acidic dissociation of neutral acids from the gas phase into dimethyl sulfoxide and water. The strongest solvent-induced attenuation of the substituent effects is characteristic of the meta-substituted anilines whose sensitivity towards substituent effects decreases with transfer from the gas phase into DMSO by 2.83 times and with transfer into water by 4.13 times. At the same time, the reaction series of para and/or ortho-π-acceptor substituted anilines, amides, imides and substituted diphenylamines are less sensitive to a change in gas phase for DMSO or water. In the special case of para-acceptor substituted anilines it was demonstrated that the specific solvation induced an increase in the acidity of the para- and/or ortho-acceptor substituted anilines as compared with the behavior of the corresponding meta-substituted anilines by amounts up to 10 pK a units.

Elimination mechanisms in the anilinolysis of sulfamoyl chlorides in chloroform and acetonitrile

The kinetics of the reaction of various sulfamoyl chlorides, R1R2NSO2Cl (R1 = Ph, Me, c-C6H11, But, R2 = H and R1 = R2 = Me and R1 = R2 = PhCH2) with anilines in chloroform and acetonitrile have been studied. Reaction is first order in both chloride and aniline and pseudo first order and second order rate constants have been determined for various chlorides and para- and meta-substituted anilines. Hammett ρ values vary from –4.76 to –2.63 for varying XC6H4NH2 depending on the halide, X. Substituents in XC6H4NHSO2Cl have only small effects on the rates. There is a ca. 106-fold rate difference between PhNHSO2Cl and (PhCH2)2NSO2Cl reacting with p-anisidine in chloroform at 25 °C. This finding, coupled with the observation of hydrogen/deuterium isotope effects, supports the operation of an elimination mechanism involving an N-sulfonylamine, [PhNSO2], as a transient species. In chloroform an E2-type mechanism is suggested, while in acetonitrile the activation parameters (ΔH, ΔS) may indicate a more E1cB-like E2 mechanism.

ESR study of the free radical intermediates formed during the electrolytic process: III. Electrooxidation of substituted anilines

Active free radicals formed by the electrooxidation of substituted anilines RC6H4NH2 (R = H, p-Br, p-Cl, p-I, p-Me, p-COOH, p-MeCO, p-NO2, m-CO2H, and m-Cl) are trapped by spin trap 2-methyl-2-nitroso propane (MNP). A multiple ESR signal of the solution containing electrolytic aniline and MNP is identified with the spin adduct of MNP and radical cation 1 by theoretical simulation of observed spectrum. Furthermore, ESR spectra of para- or meta-substituted anilines give a reasonable explanation about spin adducts of MNP and the cation 2 or 3 by the same method.

Berechnung der Reaktionsenthalpie der Diazotierungsreaktion von aromatischen primÄren Aminen auf Grund der Hammettschen Gleichung

It has been assumed that Hammett's equation can be applied to the calculation of the enthalpy of diazotization of aromatic primary amines. To prove this, the correlation between the reaction enthalpy and substituents of the aromatic ring for the diazotization of some meta- and para-substituted anilines has been studied. On plotting the changes in reaction enthalpy occuring as the effect of the substituents, as a function of the Hammett substituent-constants, a straight line was obtained, whose slope is characteristic of the diazotization reaction. From a knowledge of the constants,δH r can be calculated to a good approximation for the diazotization of para- and meta-substituted anilines.

Studies on organosulfur compounds. XI. Selective cyclization to benzothiazole by the reaction between quinaldine and meta-substituted anilines (or nitro compounds) under the modified Willgerodt-Kindler reaction.

In order to clarify in more detail the cyclization mechanism of thioanilides to benzothiazoles under the modified Willgerodt-Kindler reaction condition, quinaldine (I) was heated with meta-substituted anilines (II) or meta-substituted nitrobenzenes (III) in the presence of sulfur. Further, in order to examine on solvent effects through these processes, dimethylformamide (DMF) was employed. Although the yields of these reactions were different, the reactions also gave similarly thioanilides and one of the two possible benzothiazoles. The latter was proved to have the structure of 5-substituted 2-(2-quinolyl) benzothiazoles (V) by independent synthesis. On the other hand, the expected two isomeric benzothiazoles (V and VI) were obtained from the oxidaitve cyclization of thioanilides (IV) by the modified Jacobson reaction. Moreover, the thioanilides obtained from I or 2-picoline were found to react with the corresponding II in the presence of sulfur in DMF at 160-170°to give the selective cyclization product, respectively.

Studies on the Proton Magnetic Resonance Spectra in Aromatic Systems. XVIII. Tris (dipivalomethanato) europium Induced Shift of para- and meta-Substituted Deuteroanilines

The S values, those are the paramagnetic shift parameters of deuterated and undeuterated and undeuterated para- and meta-substituted aniline derivatives induced by tris (dipivalomethanato) europium, were measured. The observed S values of compounds in the para-substituted series were linearly related with the substituent constants σπ, whereas those of the meta-substituted series were linearly related with σi. The following results were obtained for the magnitudes, Sh and Sd, and the slopes, ρh and ρd, of the undeuterated and deuterated compounds in the two series : Sd>Sh and ρd/ρh=1.35.