Nucleophilic reactions anilines

The nucleophilic reaction with the solvent is of crucial importance. Monomers with lower oxidation potentials (aniline and pyrrole) can easily be polymerized even in aqueous electrolytes. For monomers with higher oxidation potentials, aprotic solvents must be used, such as acetonitrile... 

Ar-Acyl oxy- A -a 1 k oxyamides have been found to undergo SN2 reactions with a number of organic and inorganic nucleophiles including anilines, thiols, hydroxide and azide anions. Reaction products from all of these processes are themselves reactive anomeric amides and outcomes have uncovered novel chemistry of this unusual class of compounds. 

Recently, the synthesis and evaluation of a new pyrazinone class of tryptase inhibitors has been reported. One step in the preparation of these compounds involved regioselective chloride displacements from a dichloropyrazinone scaffold using amines and anilines as nucleophiles. The aniline reactions required the use of microwave-assisted heating for 12 min at 120 °C, as illustrated in Scheme 23 [84]. Although the aniline-derived compounds (e.g., 50) were modest inhibitors, other compounds from this study, synthesized by classical heating methods, were shown to be highly potent tryptase inhibitors. 

As is shown in Figure 3 the highest occupied energy level is found to parallel well the oxidation potential in aniline and p-phenylenediamine derivatives. To elucidate the existence of the optimum oxidation potentials for antioxidation and antiozonization, the reactivity indices Sr and S for radical and nucleophilic reactions have been used. These are ... 

The structure of the TS for the nucleophilic reaction of aniline at secondary cycloalkyl carbon centers depends on the size of the cycloalkyl group53. We note in Table 4 that although the rate is fastest with the cyclopentyl and slower with the cyclohexyl compound, the TS shifts successively to a later position along the reaction coordinate (more... 

TABLE 3. Rates and selectivity parameters for the nucleophilic reactions of anilines at secondary alkyl carbon centers (R1R2CH0S02C6H4X) in MeCN at 65.0 °C51,52... 

Occasionally, electron transfer is a nuisance and competes with or overshadows a desired nucleophilic reaction. For example, reaction of thianthrene cation radical perchlorate with aniline leads to benzidine (among other products) instead of nucleophilic substitution in thianthrene (Shine and Kim, 1974). 

Another example of a single-pot-type reaction involved replacement of the carbon nucleophile with aniline 76, thus affording the a,P-unsaturated imine 77. Both aromatic and alkyl amines afford the desired imine in good-to-excellent yields. The use of triethylsilanes afforded greater Z E ratios in 77.f l... 

Theoretically, the condensation of aniline with formaldehyde proceeds in the same way. In this case, the aromatic ring acts as a suitable nucleophilic reaction partner in acid media cross-linked polymers can arise because of the substitution possible in two o and one p positions, and also because of the bifunctionality of the amino group. The monomeric unit here can be represented schematically as... 

It is interesting that the OSAR for nitrobenzenes and anilines shows no dependence of log (1/LC50) on log P. A similar finding was made by Mermens et al. (1985) for electrophilic halogen compounds. This may provide insights about the site of the electrophile/nucleophile reaction. 

While yields are good to excellent in most cases, lower yield is obtained as a result of steric hindrance (entries 4,9). Also, as a result of the lower nucleophilicity of aniline, the self-dehydrogenative coupling of the alcohol becomes competitive, leading to some ester formation. Noteworthy, no reaction took place with dibenzy-lamine, indicating that the reaction is limited to primary amines. Diamines react normally, leading to bis-amides (Table 3). Diethylenetriamine reacts only at the primary sites, requiring no protection of the secondary amine functionality. 

Two modified sigma constants have been formulated for situations in which the substituent enters into resonance with the reaction center in an electron-demanding transition state (cr+) or for an electron-rich transition state (cr ). cr constants give better correlations in reactions involving phenols, anilines, and pyridines and in nucleophilic substitutions. Values of some modified sigma constants are given in Table 9.4. 

Nucleophilic Reagents. In contrast to electrophilic reactions, nucleophiles attack positively charged, even carbons ia the chain. The reactions lead to the exchanging of substituents or terminal residues. Thus, SR and OR groups, or halogen atoms can be exchanged by other suitable nucleophiles (4,69,70), for example, by aniline ... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

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