Meta-substituted anilines

FrielA,nderSynthesis. The methods cited thus far all suffer from the mixtures which usually result with meta-substituted anilines. The use of an ortho-disubstituted benzene for the subsequent constmction of the quinoline avoids the problem. In the FrieWider synthesis (52) a starting material like 2-aminoben2aldehyde reacts with an CX-methyleneketone ia the presence of base. The difficulty of preparing the required anilines is a limitation ia this approach, but 2-nitrocarbonyl compounds and the subsequent reduction of the nitro group present a usehil modification (53). 

Diethyl acetylmalonate was reacted with anilines in benzene in the presence of a catalytic amount of concentrated hydrochloric acid at 65-70°C for 16 hr. Then, after evaporation, the residues were heated at 195-220°C for 5-15 min to give 2-methylquinoline-3-carboxylates (666) in 36-80% yields (83KGS 1521). Meta-substituted anilines (R = Me, Cl) gave 7-substituted 2-methylquinoline-3-carboxylates. 

Generally meta-substituted anilines give rise to a mixture of 4- and 6-substituted isatins9,13,19,33-37 although 4-trifluoromethyl,15,33,35,36 4-nitro,13 4-amino,13 4-hydroxy,13 4-carboxy,13 6-methoxy,35 and 6-bromo 4 isatins have been reported without the other isomer. 

Somewhat lower yields are obtained with use of aniline plus acetic anhydride followed by PCBN. Substituted anilines can also be used far higher yields are obtained from meta-substituted anilines than the corresponding para-isomers many ortho-derivatives give no aryne adduct. 

The 3-dimethylamino-2-phenyl-allylideneaniIines (225a-e) cyclize to 3-phenyl-quinolines (227) and as expected (225 c-e) derived from meta-substituted anilines, yield mixtures of the 5- and 7-substituted quinolines (227c-e) ... 

In general, meta-substituted anilines show the usual inductive effects, already discussed in connexion with aromatic carboxylic acids (p. 83). These effects usually inlluence the magnitude of the pKy of aniline even more than they iniluence that of phenol (Table 8.4). In the para position, these inductive effects are reinforced by any mesomcric effect of which the substituent is capable, as explained on p. 83. The halogens and the methoxy-group show the usual resultant of (-1) and (+M) effects. 

Other Type B Syntheses.—The prolonged interaction of 2-picoline with meta-substituted anilines in the presence of sulphur at 170 °C under Wiligerodt-Kindler conditions gives, apart from the thioanilides (18), only one of the two possible isomers, namely 5-substituted benzothiazoles (19), the structure of which was confirmed by their unequivocal synthesis from (20). In contrast, both isomers (19) and (21) are obtained by the oxidative cyclization of the thioanilides (18) by the modified Jacobson reaction the two reactions clearly occur by distinct mechanisms. ... 

Good yields of 10-aryl-3,6-dinitroacridones were obtained merely by heating 2,2, 4,4 -tetranitrobenzophenone (419) with an excess of the corresponding aryl amines at 125°C. For example, aniline provided 420 in 80% yield (Eq. 38). The reaction is fairly general for meta- and para-substituted anilines, though it proceeds less readily with orf/io-substituted compounds (79JCS(P1)1364). A method of isolation of the intermediate diarylamine in the synthesis of certain 10-aryl-3,6-dinitroacridones from 2,2, 4,4 -tetranitrobenzophenone has also been described (93JCR(M)2779). 

Substituted arylamines can be either more basic or less basic than aniline, depending on the substituent. Electron-donating substituents, such as — CH3, -NH2, and -OCH3, which increase the reactivity of an aromatic ring toward electrophilic substitution (Section 16.4), also increase the basicity of the corresponding arylamine. Electron-withdrawing substituents, such as —Cl, -NO2, and -CN, which decrease ring reactivity toward electrophilic substitution, also decrease arylamine basicity. Table 24.2 considers only -substituted anilines, but similar trends are observed for ortho and meta derivatives. 

Figure 21. Conversion of substituted anilines (OT, MT, and PT are respective ortho-, meta-, and para-toluidine, PA = p-anisidine, and PAA = p-aminoacetophenone), corresponding mono-N-methylated anilines selectivity and yield obtained on Cu0.5Zn0.5Fe204 at 300oC with methanol. Only in the case of PAA, feed with CH30H PAA = 6 was employed to avoid solubility problem, and in all other cases a CH30H Sub. Amline H20 = 3 1 1 was maintained. Reprinted from Applied Catalysis A General, 320, Vijayaraj M., et al., 2007, 64-68 with permission from Elsevier.

Very interesting results were obtained from the reaction of magnesium alkylidene carbenoids with mefa-substituted arylamines (Table 8) . The reaction of magnesium alkylidene carbenoids 157 and 161 with three mefa-substituted anilines was carried out and the results are summarized in Table 8. The reaction of 157 with meta-anisidine gave two products 163 and 164 (in a 30 13 ratio) in 43% yield. The main product was found to have the alkenyl group at the more hindered position (163). As shown in the Table, all the other meto-substituted aniline derivatives also gave the more hindered alkenylated compounds as the main product in variable ratio. 

The rate of reaction of 2-bromo-3,5-dinitrothiophene (470) with meta and para substituted anilines has been determined (76JOC968). The kinetic data are accommodated by the Ingold-Yukawa-Tsuno equation (1). 

Correlation with Hammett substituent constants alone was not satisfactory. The reaction has been extended to ortho substituted anilines also the results have been treated by the Fujita-Nishioka method. Combining these with the previous data for meta and para substituted anilines, a multiparameter regression equation (2) has been developed (79JCS(P2)219>. 

The oxidation of meta- and para-substituted anilines with imidazolium fluorochro-mate (IFC)18 and nicotinium dichromate (NDC),19 in several organic solvents, in the presence of p-toluenesulfonic acid (TsOH) is first order in the oxidant and TsOH and is zero order with respect to substrate. A correlation of rate data in different solvents with Kamlet-Taft solvatochromic parameters suggests that the specific solute-solvent interactions play a major role in governing the reactivity, and the observed solvent effects have been explained on the basis of solute-solvent complexation. The oxidation rates with NDC exhibited negative reaction constants, while the oxidation with IFC did not correlate well with any linear free energy relationships. 

In the rabbit, phenol gives rise to catechol and quinol. Hydroxyquinol is a minor metabolite of catechol but not of quinol, and neither quinol nor resorcinol is further oxidized to trihydric phenols.126 Aniline and its derivatives do not undergo meta substitution, but give rise to ortho- and para-directed hydroxylation products only.122... 

Derivatives of Biphenyl. By coupling diazo compounds and N-nitrosoacetyl derivatives obtained from substituted anilines with benzene, a large variety of biphenyl derivatives can be prepared in which only one of the rings is substituted. In this manner, the isomeric monosubstituted biphenyls, RCel CeHs, have been prepared in which R = Br, Cl, CH3, OCH3, NO2, CN, etc. The meta derivatives, such as 3-brQmobiphenyl (I), 3-nitrobiphenyl (II), and 3-cyanobiphenyl (III), are of particular interest because they cannot be prepared readily from biphenyl. The usefulness of the methods for the preparation of compounds of definite... 

Bis(trifluoromethyl)phenyl derivatives with meta substitution of the trifluoromethyl groups can be converted into phosphanes via regioselective lithiation. Thus, Af,fV-dimethyl-3,5-bis(tri-fluoromethyl)aniline (9) can be treated with butyllithium/W,Af,Af. .V -tctramcthylethylene-diamine or with methyllithium alone to yield isomers 10 or 11, respectively. ... 

Although protonation of the amine leads to the anilinium salt which is a deactivating substituent, nitration of aniline in nitric acid sulfuric acid yields 60% para and 34% meta substitution, whilst nitration of acetanilide gives 79% para and 19% ortho nitroacetanilides. 

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