Nucleophilic aromatic substitution aniline derivatives

For example, acetylation reactions of alcohols and carbohydrates have been performed in [Bmim]-derived ionic liquids.If the dicyanamide anion [N(CN)2] is incorporated into the liquid, mild acetylations of carbohydrates can be performed at room temperature, in good yields, without any added catalyst.In this example, it was shown that the RTIL was not only an effective solvent but also an active base catalyst. In a recent study, Welton and co-workers performed calculations on the gas phase basicity of the conjugate acids of possible anions from which to construct their liquid.Using these data, they were able to choose the optimum RTIL in which to conduct a nucleophilic aromatic substitution reaction of an activated aniline with an activated arylhalide. Given the enormous number of possible anions and cations from which to build up an ionic liquid, the role of computation in experimental design such as this will become increasingly important. 

Aniline reacts with nitrous acid to give benzenediazonium salts, which react with a variety of reagents via a substitution reaction. These reagents include cuprous salts, aqueous acid, iodide, hypophosphorous acid, and activated benzene derivatives. Nucleophilic substitution at the sp carbon of a halo-benzene derivative does not occur unless high heat and pressure are used. Electron-withdrawing substituents on the benzene ring significantly lower the temperature required for the reaction. Nucleophiles for this nucleophilic aromatic substitution reaction include water, hydroxide, alkoxide, and amines. 

It has been observed that in basic media aromatic hydrocarbons and benzylmethyl ethers bound to -Cr(CO)3 are easily nitrosated at the benzylic position. A review type article discusses the stereoselective manipulation of acetals derived from o-substituted benzaldehyde chromium tricarbonyls. The diastereoselective synthesis of a range of substituted cyclohexadienes has been reported from enandomerically pure (2-phenyl-4,S-dibydroxazole)chromium tiicaibonyl complexes. Aromatic nucleophilic substitution on halaogenoarene tricarbonylchromium complexes gives rise to a series of complexed aniline derivatives. The diastereoselective 1,4-addition of organocuprates to o-substituted-phenyI-(E)-enone chromium carbonyl conq)lexes provides a new method for remote stereocontrol at the 1,3, and S-positimis of the side chains. ... 

Since the publication of these works, the concept of LUMO-lowering activation of a,p-unsaturated aldehydes has been extended to a broad number of transformations. As examples we can cite the utihzation of a-branched aldehydes [7], intramolecular reactions [44—46], and the use of anilines derivatives as nucleophilic aromatic systems [47, 48]. Diarylprohnol silyl ether analogs were also successfully used in such approaches. An example with 4,7-dihydroindoles, which after oxidation afford 2-substituted indole derivatives, is illustrated in Scheme 35.2 [11]. 

Illustrative examples of cleavage reactions of /V-arylbenzylaminc derivatives are listed in Table 3.25. Aromatic amines can be immobilized as /V-bcnzylanilincs by reductive amination of resin-bound aldehydes or by nucleophilic substitution of resin-bound benzyl halides (Chapter 10). The attachment of the amino group of 5-aminoin-doles to 2-chlorotrityl chloride resin has been reported [486]. Anilines have also been linked to resin-bound dihydropyran as aminals [487]. 

Small hydrogen isotope effects have been found in a nucleophilic substitution of an aromatic heterocycle, the reaction of cyanuric chloride with aniline-N,N-d2 in benzene solution (Zollinger, 1961a). As the effects are small (5%), it is difficult to draw definite mechanistic conclusions. The reactions of cyanuric chloride and other halogenated triazine derivatives are subject to bifunctional catalysis (e.g. by carboxylic acids and by a -pyridone) and to catalysis by monofunctional bases like pyridine (Bitter and Zollinger, 1961). Reinheimer et al. (1962) measured the solvent isotope effect in the hydrolysis of 2-chloro-5-nitro-pyridine (A h,o/ d.o = 2 36). The result makes it probable, but... 

The synthesis of nitro dyes is relatively simple, a feature that accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 6.39 and 6.40, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of Cl Disperse Yellow 14, 6.39, involves the reaction of aniline with l-chloro-2,4-dinitroani-line while compound 6.40 is prepared by reacting aniline (2 moles) with the chlorosulfonyl derivative 6.42 (1 mole). 

There has been a major review of substitution by the radical-chain 5rn1 mechanism. It has been shown that reaction by the SrnI pathway of the enolate anions of 2- and 3-acetyl-l-methylpyrrole may yield a-substituted acetylpyrroles. The dichotomy of reactions of halonitrobenzenes with nucleophiles has been nicely summarized major pathways include reduction via radical pathways and. SnAt substitution of halogen. EPR spectroscopy has been used to detect radical species produced in the reactions of some aromatic nitro compounds with nucleophiles however, whether these species are on the substitution pathway is questionable. The reaction of some 4-substimted N,N-dimethylanilines with secondary anilines occurs on activation by thallium triacetate to yield diphenylamine derivatives radical cation intermediates are proposed. ... 

In 1996 it was found that condensing carboi lic acids and amines under azeotropic conditions in the presence of substituted benzeneboronic acid derivatives yielded the desired amides. Under these conditions, water was removed and non polar solvents disfavoured salt formation, resulting in amide formation. It was reported that these commercially available catalysts presented a more water and air stable method of catalysing amide bond formation reactions. Secondaiy amines and aromatic substrates also showed reactivity in the presence of catalytic trifluorobenzeneboronic acid. However, less nucleophilic amines such as aniline required an increase in temperature with a consequent change in reaction solvent to mesitylene. 

Aromatic n or /values derived from meta and para substituents tend to be identical, but ortho substituents often give outlying values, e.g., when they permit internal hydrogen bonding, lipophilicity is increased. Apart from this, these n and / values are very sensitive to polar environments. For example, n for chlorine substituted in benzene is 0.71, but this becomes (insertion is in all cases, meta) 0.61 in nitrobenzene, 0.68 in phenylacetic acid, 0.83 in benzoic acid (all ionizable substances are corrected for ionization), 0.98 in aniline, and 1.04 in phenol. This difference of 0.43 between extremes is increased to 0.90 when nitro-group replaces chlorine in the same nuclei (Hansch, Leo et aLy 1973). Two highly polar substituents, particularly if both are nucleophilic, show enhanced lipophilicity (often 0.8) if separated by only one carbon atom, and about half this enhancement if separated by two carbons (Leo, Hansch, and Elkins, 1971 Rekker, 1977, pp. 49y 98, 293). 

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