Monosubstituted anilines

Other derivatives of pyrrole that are of interest as coupling components are indole (12.39) and substituted indoles. Indole may be considered as a pyrrole with a benzo ring fused to it, or as a cyclized derivative of an 7V-monosubstituted aniline. For an aniline compound one expects either a C-coupling in the 5-position or an TV-cou-... 

When p-ethylaminobenzoate and N,N-dimethyl-p-phenylene diamine sulfate were similarly treated with the dibromosulfone (I) for 2 h, the yield was only 32% and 15% respectively (Figure 1). A possible explanation is that the nucleophilicity of these monosubstituted anilines is weaker than that of aniline while a Na2C03 1,4-HBr elimination reaction could be competing with the substitution reaction, leading to the lower yield (18). 

Figure 1. Reaction of 3,4-Bis(bromomethyl)-2,5-Dihydrothiophene-l, i-Dioxide with Monosubstituted Aniline.

The main problem encountered during electrophilic substitution reactions of aromatic amines is that of their veiy high reactivity. Substitution tends to occur at ortho- and para-positions. If we have to prepare monosubstituted aniline derivative, how can the activating effect of -NH group be controlled This can be done by protecting the -NH group by acetylation with acetic anhydride, then carrying out the desired substitution followed by hydrolysis of the substituted amide to the substituted amine. 

As an example, we consider the oxidation of a series of monosubstituted anilines by Mn02 in batch systems. In this case, quite a good correlation between log kK (expressed relative to R of 4-chloroaniline) and E]/2(ArX ) is obtained (Fig. 14.20). The slope of -0.54 indicates that, similar to what we have postulated for the reduction of NACs by surface-bound Fe(II) (see Fig. 14.10 /), the overall reaction rate is determined not solely by the actual electron transfer but also by other steps such as precursor complex formation. Comparable results (slopes of between-0.5 and -0.6) were obtained for the reaction of Mn02 at pH 4 with a series of substituted anilines (Laha and Luthy, 1990), and with a series of substituted phenols at pH 4.4 (Stone, 1987). In all these cases, only initial pseudo-first-order rate constants determined with clean Mn02 were considered. In the presence of solutes such as Mn2+ that may adsorb to the oxide surface, much slower reaction rates and much... 

Proton affinity (PA) is the negative of the enthalpy change defined at 298 K for the protonation reaction (equation 2)6. As seen from the values of representative monosubstituted anilines (Table 1), PA values of anilines are quite high. 

Table 9. Values of monosubstituted anilines in aqueous solution...

The introduction of substituents in the positions meta and para to the amino group of aniline leads to marked changes in the piT value which reveal clearly the two effects (inductive and mesomeric) which are operative in the molecules concerned. The effects of ortho substituents are more complicated and therefore they will be discussed separately. The pJfa values for a range of monosubstituted anilines are shown in Table 9. 

V-Alkylation can also be carried out with the appropriate alkyl haUde or alkyl sulfate. Reaction of aniline with ethylene, in the presence of metallic sodium supported on an inert carrier such as carbon or alumina, at high temperature and pressure yields V/-ethyl- or /V,/V-diethylaniline (11). At pressures below 10 MPa (100 atm), the monosubstituted product predominates. 

Monosubstitution can occur at any one of the six equivalent carbons of the ring. Most of the monosubstituted benzenes have common names such as toluene (methylbenzene), phenol (hydroxybenzene), and aniline (aminobenzene). 

Finally we mention in this section the non-catalytic selective bromination of aniline by the application of a zeolite pre-loaded with Bt2 as a slow release reagent (ref. 27). Aniline, dissolved in CCI4 was treated with Br2 adsorbed onto various zeolites and zeolite CaA was found to be most selective for monosubstitution (92%). The addition of organic bases improved the performance, probably due to scavenging of HBr. Also the toluidines could be monobrominated with this system with >95% selectivity. 

Retention volumes of monosubstituted benzenes, benzoic acid, phenols, and anilines have been measured in RPLC [76]. Buffered acetonitrile/water and tetrahydrofuran/water eluents were used with an octadecylsilica adsorbent. From the net retention volumes, a substituent interaction effect was calculated and described with the linear free energy relationship developed by Taft. The data was interpreted in terms of hydrogen bonding between the solutes and the eluent. 

Evaluation of the only appropriate Fukui function is required for investigating an intramolecular reaction, as local softness is merely scaling of Fukui function (as shown in Equation 12.7), and does not alter the intramolecular reactivity trend. For this type, one needs to evaluate the proper Fukui functions (/+ or / ) for the different potential sites of the substrate. For example, the Fukui function values for the C and O atoms of H2CO, shown above, predicts that O atom should be the preferred site for an electrophilic attack, whereas C atom will be open to a nucleophilic attack. Atomic Fukui function for electrophilic attack (fc ) for the ring carbon atoms has been used to study the directing ability of substituents in electrophilic substitution reaction of monosubstituted benzene [23]. In some cases, it was shown that relative electrophilicity (f+/f ) or nucleophilicity (/ /f+) indices provide better intramolecular reactivity trend [23]. For example, basicity of substituted anilines could be explained successfully using relative nucleophilicity index ( / /f 1) [23]. Note however that these parameters are not able to differentiate the preferred site of protonation in benzene derivatives, determined from the absolute proton affinities [24],... 

Witte, F., Urbanik, E., and Zetzsch, C. Temperature dependence of the rate constants for the addition of hydroxyl radical to benzene and to some monosubstituted aromatics (aniline, bromobenzene, and nitrobenzene) and the unimolecular decay of the adducts. Part 2. Kinetics into a quasi-equilibrium, J. Phys. Chem., 90(14) 3251-3259, 1986. 

Similar processes are observed for the monosubstituted aminobenzenes, as shown for aniline [Fig. 5(a)]. Such efficiency spectral curves were obtained also for methyl-, dimethyl-aniline, and benzylamine [Figs. 

Thiolate anions37 38 and oxime alkoxides38 react under phase transfer conditions to give aryl sulfides and O-aryl oximes, respectively the o-dichloro benzene complex can be converted selectively to the monosubstitution product (equation 9). The arylation of oximes leads to a simple process for benzofuran formation (equation 10). Simple primary and secondary amine nucleophiles react smoothly in the absence of added base, in a very general and efficient process for aniline derivatives.49... 

Monosubstitution of the free amine may be achieved by using a less reactive electrophile. Thus aniline and o-toluidine may be mono-iodinated (Expt 6.60) by treatment with iodine (in the presence of sodium hydrogen carbonate or calcium carbonate to remove the liberated hydrogen iodide), the substituent entering the position para to the amino group. Direct iodination can also be effected by using the more powerfully electrophilic reagent, iodine monochloride... 

Several reactive chloro compounds have been used to attempt to effect the controlled monochlorination of aromatic amines. One such reagent is N-chlorosuccinimide, with which the chlorination of aniline, for example, can be largely restricted to monosubstitution, although a mixture of isomers (orthopara, 1.9 1) is obtained.24 One approach to the achievement of specific ortho chlorination is illustrated by the synthesis of o-chlorobenzanilide (Expt 6.61), readily hydrolysable to o-chloroaniline. The anilide is formed, by a type of Swi mechanism indicated below, when AT-phenylhydroxylamine is benzoylated and the product is treated with thionyl chloride.25 The reaction has been successfully applied to several substituted JV-phenylhydroxylamines, prepared by the controlled reduction of the corresponding substituted nitro compounds (cf. Expt 6.87). 

The nomenclature of benzene derivatives is described in Sec. 4.6. Common names and structures to be memorized include those of toluene, styrene, phenol, aniline, and xylene. Monosubstituted benzenes are named as benzene derivatives (bromobenzene, nitrobenzene, and so on). Disubstituted benzenes are named as ortho- (1,2-), meta- (1,3-), or para- (1,4-), depending on the relative positions of the substituents on the ring. Two important groups are phenyl (C6H5-) and benzyl (C6H5CH2-). 

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... 

The monosubstitution of vinyl bromide (Truce et al., 1956b) probably occurs via elimination-addition owing to the low reactivity of the halo-olefin. Acetylene is the only product formed with alkoxide ions or aniline. 

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