Substituted acetic acids anilines

Isopropylidene and benzylidene hydrazones of the selenazoles w hich are unsubstituted in the 5-position react with p-nitrosodiethyl-and p-nitrosodimethyl-aniline in organic solvents on heating and the addition of acetic acid or pyridine. - Thus result crystalline, deeply colored, 2-hydrazono-5-(p-dialkylaminophenylimino)selenazoles (correspondingly substituted in the 4-position), details are given in Table VII. The presence of an aromatic residue in the 4-position of the selenazole ring appears to be needed to obtain crystalline compounds. 

Azcpincs under acid conditions reportedly117-225 yield aniline derivatives although ring contraction to pyridines is more usual. Thus, highly substituted 3//-azepines, e.g. 28, with a vacant 7-position, formed by cycloaddition of 2//-azirines with cyclopentadienones, on heating in acetic acid isomerize rapidly to the correspondingly substituted anilines 29.117... 

Bifunctional catalysis in nucleophilic aromatic substitution was first observed by Bitter and Zollinger34, who studied the reaction of cyanuric chloride with aniline in benzene. This reaction was not accelerated by phenols or y-pyridone but was catalyzed by triethylamine and pyridine and by bifunctional catalysts such as a-pyridone and carboxylic acids. The carboxylic acids did not function as purely electrophilic reagents, since there was no relationship between catalytic efficiency and acid strength, acetic acid being more effective than chloracetic acid, which in turn was a more efficient catalyst than trichloroacetic acid. For catalysis by the carboxylic acids Bitter and Zollinger proposed the transition state depicted by H. 

Pr)4, " borohydride-exchange resin,and formic acid. When the last is used, the process is called the Wallach reaction. Conjugated aldehydes are converted to alkenyl-amines with the amine/silica gel followed by reduction with zinc borohydride.In the particular case where primary or secondary amines are reductively methylated with formaldehyde and formic acid, the method is called the Esch-weiler-Clarke procedure. It is possible to use ammonium (or amine) salts of formic acid, " or formamides, as a substitute for the Wallach conditions. This method is called the Leuckart reaction,and in this case the products obtained are often the N-formyl derivatives of the amines instead of the free amines. Primary and secondary amines can be iV-ethylated (e.g., ArNHR ArNREt) by treatment with NaBH4 in acetic acid. Aldehydes react with aniline in the presence of Mont-morillonite KIO clay and microwaves to give the amine. Formaldehyde with formic acid converts secondary amines to the N-methyl derivative with microwave irradiation. 

Although aryl halides are the substrates of choice for Heck transformations, dia-zonium salts have also gained great interest, due mainly to reasons of economy [478]. With this in mind, the group of Beller explored a domino diazotization/Heck sequence of substituted anilines 2-935 with ethylene (Scheme 2.209) [479]. The reaction proceeds best in the presence of Pd(OAc)2 and tBuONO as diazotization reagent in a mixture of acetic acid and CH2C12. Using these conditions, the desired styrenes 2-936 were isolated in yields up to 72 %. 

The reaction of the O-alkylated cyclohexan-l,3-diones 73 with p-substituted anilines in the presence of acetic acid is influenced by the nature of R in 73, yielding 4-anilinoxanthones 74 when R = H, but the condensed y-lactams 75 when R = Me (Scheme 51) <00T5947>. 

The kinetics of oxidation of several para-substituted anilines and aliphatic acetals by peroxomonosulfate in aqueous acetic acid have been investigated. In the oxidation of sulfides to sulfoxides by peroxymonosulfate (Oxone), the observed increase in second-order rate constants with increasing concentration of H2SO4 has been shown to be due to the increasing polarity of the medium, rather than to acid catalysis. Similar conclusions were arrived at for the oxidation of aryl thiobenzoates and thiol-phosphorus(V) esters. 

In acetic acid it is possible to measure separately the equilibrium constant of proton transfer to form an ion pair and the constant for dissociation of ion pairs to form free ions. [I. M. Kolthoff and S. Bruckenstein, J. Amer. Chem. Soc., 78, I (1956) S. Bruckenstein and I. M. Kolthoff, J. Amer. Chem. Soc., 78, 10 (1956)]. G. W. Geska and E. Grunwald, J. Amer. Chem. Soc., 89, 1371, 1377 (1967) applied this technique to a number of substituted anilines and concluded that the equilibrium constant of the ionization step, rather than the overall acid dissociation constant, is the quantity that should be considered in discussions of effects of structural changes on acidity. 

The cyclization of the 0/7/fo-substituted aniline 487 with acetic acid and sodium nitrite affords 4,l,2-benzothiadiazin-3-carboxylate 4,4-dioxides 488 via diazonium salt intermediates (Scheme 255) <1996JHC347, CHEC-III(9.08.8.1)429>. 

It should be taken into consideration that the rhodanation of substituted anilines goes mainly to the position 4. The reported synthesis of 2-amino-4-nitrobenzothi-azole by rhodanation of ortho-nitroaniline [583] turned out to be incorrect. In fact, the authors obtained 2-nitro-4-rhodanylaniline of the same empirical formula [584, 585], 2,4-Dinitrophenylthiocyanate is reduced to 2-amino-5-nitrobenzothiazole in acetic acid by iron (Scheme 2.103) [407, 408],... 

Phenylazo-2-thiazolidinone-4-thione (107), when treated with aniline and sodium acetate in acetic acid under reflux for 20 minutes, is converted into 108 in 54% yield [Eq. (34)], whereas, with aniline in methanol at 60° for 1.5 hours, it is transformed by 4-substitution to 109.144 (Hydrazone tautomers, as shown, are likely for 107 -109.)... 

Intermolecular Nucleophilic Substitution with Heteroatom Nucleophiles. A patent issued in 1965 claims substitution for fluoride on fluorobenzene-Cr(CO)3 in dimethyl sulfoxide (DMSO) by a long list of nucleophiles including alkoxides (from simple alcohols, cholesterol, ethylene glycol, pinacol, and dihydroxyacetone), carboxylates, amines, and carbanions (from triphenyhnethane, indene, cyclohexanone, acetone, cyclopentadiene, phenylacetylene, acetic acid, and propiolic acid). In the reaction of methoxide with halobenzene-Cr(CO)3, the fluorobenzene complex is ca. 2000 times more reactive than the chlorobenzene complex. The difference is taken as evidence for a rate-limiting attack on the arene ligand followed by fast loss of halide the concentration of the cyclohexadienyl anion complex does not build up. In the reaction of fluorobenzene-Cr(CO)3 with amine nucleophiles, the coordinated aniline product appears rapidly at 25 °C, and a carefiil mechanistic study suggests that the loss of halide is now rate limiting. 

In other cases, the concentrations of the intermediates are much smaller. The intermediate in the acetate ion catalyzed hydrolysis of phenyl acetates is acetic anhydride. It can be chemically trapped by addition of aniline to the reacting solution, for acetanilide is formed much faster than acetic acid even at low aniline concentrations [264]. Nucleophilic catalysis is highly effective in these examples because phenoxy, substituted phenoxy and ethylthio are very good leaving groups and the intermediates are more reactive with respect to hydrolysis than the substrates. 

Rate coefficient for proton exchange in substituted anilines in acetic acid at 30 °C... 

The reduction of N-alkyl- -nitroanilines to the corresponding cyclo-hexanediamines has been carried out with hydrogen over cobalt-on-alumina and ruthenium catalysts. Sometimes a nuclear-substituted aniline is acetylated before reduction in order to avoid side reactions. Thus, catalytic hydrogenation of p-acetaminophenol and ethyl p-acetaminophenyl-acetate has been successfully accomplished with platinum catalyst at 50-60° in the presence of acetic acid. 

Condensation of aromatic nitroso compounds with primary amines is a satisfactory procedure for obtaining azo compounds. An example is the combination of nitrosobenzene and aniline in acetic acid, which results in a quantitative yield of azobenzene. Similarly, a series of methyl-substituted azobenzenes have been prepared, although the yields are poor in the case of the oriAo-substituted compounds. As an illustration of the versatility of the reaction, nitrosobenzene can be condensed with o-methoxyaniline (o-anisidine)," p-aminobenzoic acid, o-phenylene-diamine monobenzoate, and m-nitroaniline to form the corresponding substituted azobenzenes. 

The reactivity of the aniline may be modified by acetylation. Bromination of acetanilide with bromine in acetic acid gives 4-bro-moacetanilide (4.6). Under some conditions, bromination can take place first on the amide to give the A-bromo compound. This then undergoes a rearrangement known as the Orton rearrangement to give the para substituted product. 

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