Aniline substitution sites

The same differential behavior can be observed with amine nucleophiles. For example, calcium triflate promotes the aminolysis of propene oxide 84 with benzylamine to give 1-(A -benzyl)amino-2-propanol 85, the result of attack at the less substituted site <03T2435>, and which is also seen in the solventless reaction of epoxides with heterocyclic amines under the catalysis of ytterbium(III) triflate <03SC2989>. Conversely, zinc chloride directs the attack of aniline on styrene oxide 34 at the more substituted carbon center <03TL6026>. A ruthenium catalyst in the presence of tin chloride also results in an SNl-type substitution behavior with aniline derivatives (e.g., 88), but further provides for subsequent cyclization of the intermediate amino alcohol, thus representing an interesting synthesis of 2-substituted indoles (e.g., 89) <03TL2975>. 

The chemical information available through LFER is primarily the reaction constant p, but this value depends upon the substituent constants selected for the construction of the LFER. The u values available are ct, ct", ct" or and Ui, these quantities are listed, for many substituents, in Tables 7-1, 7-3, 7-4, 7-6, and 7-7. A reasonable approach is to plot log k against the substituent constant defined by a standard reaction that is expected to be most like the reaction under study. It is also reasonable to plot log k against several of the ct quantities, seeking the best correlation. [In choosing between two types of substituent constants, it is necessary to make use of substituents for which the two scales (say ct and rr, for example) are not themselves correlated, for otherwise both LFERs will be acceptable. ] The ct or o constants should be applicable to reactions that do not combine reaction sites and para substituents of the + and — type (push-pull systems capable of through resonance) for example, one would not expect ct" or o to provide good correlations for reactions of phenols or anilines substituted with nitro or cyano or for reactions of benzoic acids substituted with amino or methoxy. 

The effect of pH is rarely of use for pK measurement it is more often of use in identifying the site of protonation/deprotonation when several basic or acidic sites are present. Knowing the incremental substitutent effects Z of amino and ammonium groups on benzene ring shifts in aniline and in the anilinium ion (40), one can decide which of the nitrogen atoms is protonated in procaine hydrochloride (problem 24). 

Tables XXVIII and XXIX, respectively. Excellent correlations were obtained for all three sets. The stereochemistry of the sy -methyl ketoximes is discussed by Charton and Charton (73). The values of pj obtained for the trans-heterovinylene sets are not in good agreement with each other. Two sets gave values of 54 and 55, respectively, and the third set gave a value of 35. The difference in pj values cannot be accounted for. A value of 54 to 55 for pj suggests the possibility of some exaltation between substituent and reaction site such as that which occurs in para-substituted phenols and anilines. To demonstrate this with certainty requires that the value of pj be determined for a set of imines bearing a reaction site on the nitrogen which will not interact strongly with substituents. No such set of data is extant in the literature at the present time.

Tetra(o-aminophenyl)porphyrin, H-Co-Nl TPP, can for the purpose of electrochemical polymerization be simplistically viewed as four aniline molecules with a common porphyrin substituent, and one expects that their oxidation should form a "poly(aniline)" matrix with embedded porphyrin sites. The pattern of cyclic voltammetric oxidative ECP (1) of this functionalized metal complex is shown in Fig. 2A. The growing current-potential envelope represents accumulation of a polymer film that is electroactive and conducts electrons at the potentials needed to continuously oxidize fresh monomer that diffuses in from the bulk solution. If the film were not fully electroactive at this potential, since the film is a dense membrane barrier that prevents monomer from reaching the electrode, film growth would soon cease and the electrode would become passified. This was the case for the phenolically substituted porphyrin in Fig. 1. 

The hydrogenation of para-substituted anilines over rhodium catalysts has been investigated. An antipathetic metal crystallite size effect was observed for the hydrogenation of /Moluidinc suggesting that terrace sites favour the reaction. Limited evidence was found for catalyst deactivation by the product amines. Catalysts with pore diameters less than 13.2 nm showed evidence of diffusion control on the rate of reaction but not the cis trans ratio of the product. 

As a result of these substituent-induced polarizations, the complementary conjugative interactions at each ring site become somewhat imbalanced (so that, e.g., the donor-acceptor interaction from C3—C4 to C5—C(, is 23.1 kcal mol-1, but that in the opposite direction is only 16.4 kcal mol-1). From the polarization pattern in (3.133) one can recognize that excess pi density is accumulated at the ortho (C2, C6) and para (C4) positions, and thus that the reactivity of these sites should increase with respect to electrophilic attack. This is in accord with the well-known o, /(-directing effect of amino substitution in electrophilic aromatic substitution reactions. Although the localized NBO analysis has been carried out for the specific Kckule structure of aniline shown in Fig. 3.40, it is easy to verify that exactly the same physical conclusions are drawn if one starts from the alternative Kekule structure. 

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],... 

One solution for this problem, the most optimistic, suggested the existence of three independent sets of o--constants. The first set, the Hammett constants, would be applicable to side-chain reactions in which resonance interactions between the substituent and the side-chain were either small or insignificant. The second set, the w-constants, would apply to side-chain reactions of phenols and anilines and nucleophilic aromatic substitution reactions in which a negative charge was introduced in the aromatic nucleus (Miller, 1956). A third set, the c7+-constants, would apply to electrophilic substitution and electrophilic side-chain reactions for which resonance interactions between the reaction site and the substituent were important. 

Monotrifluoroacetylated diaminopyrazole was first reacted with the free Kemp s triacid to produce the imide, followed by N-Boc protection and amide-coupling with a m-substituted aniline derivative. Final Boc-deprotection occurred on the chromatography column leading directly to the new receptor modules. The recognition site X was chosen to be ethyl as a neutral reference, acetyl for polar side-chains, nitro for electron-rich aromatic residues and carboxylate for basic amino acids (Figure 2.4.4). 

Fig. 2.2S. A comparison of the potential dependence for the electrochemical oxidation of NADH at a poly(aniline)/poly(vinylsulfonate)-coated electrode. (fccu,[site]Ds /AwM). and the second-order rate constant for the homogeneous oxidation of NADH by a range of two-electron mediators, k2- The open symbols correspond to homogeneous oxidation by ortho. , and para, O, substituted quinones and diaminobenzenes. the filled triangles. , are the...

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