Aryl anilines

Illustrative examples of the acylation of support-bound amines with carbodiimides as coupling agents are listed in Table 13.3. Difficulties are usually encountered in the acylation of a-alkylamino acid derivatives (which are significantly less nucleophilic than simple secondary amines Entries 3 and 4) and Al-alkyl (Entries 5 and 6) or iV-aryl anilines. Acylations with haloacetic or related acids containing a leaving group prone to nucleophilic displacement should not be performed with the aid of HOBt and bases because O-alkylation of HOBt by the product occurs readily. 

C-H activation can be used to generate carbazoles from N-aryl anilines by palladium catalyzed oxidative coupling (Scheme 3) [12]. Although this is a powerful method, it is ultimately limited by the fact that more heavily substituted N-aryl anilines may not couple selectively, leading to the formation of more than one product. 

The majority of TICT compounds investigated up to now contain (substituted) amino groups. In some cases, these are directly TICT-active (i.e. the bond linking the amino group twists). In other cases, the amino group merely helps to enhance the donor character of the donor moiety, and twisting occurs around a different (usually C-C) bond. The first set of compounds will be grouped under aromatic amines , the second one under aryl-anilines (Sect 4.2). 

Alkyl or aryl anilines etc. Derivatives formed by the introduction of alkyl or aryl radicals into the amino group. 

III. ARYLATED ANILINES AND RELATED SPECIES A. Amino Derivatives of Polynuclear Aromatic Hydrocarbons... 

Although not strictly an arylated aniline but rather a benzannelated species, the two isomeric naphthylamines are the simplest polynuclear aromatic hydrocarbon counterparts of aniline. Unfortunately, they are the only such examples with enthalpy of formation data known to the authors. No less than five sets of measurements23,44 - 47 with a range of 29 kJmol-1 have been reported for the enthalpy of combustion, and thus of formation, of 1-naphthylamine. Likewise, for the enthalpy of combustion of 2-naphthylamine... 

Scheme 2.21 Suzuki-Miyaura cross-coupling reactions of aryl anilines.

To a solution of substituted aryl aniline (2 1.0 equiv) and substituted 3-ethoxycyclobutanone (1 2.0 equiv) in anhydrous dichloromethane in a flame-dried round bottom flask was added Bp3-OEt2 (0.5-1.0 equiv). Then the reaction mixture was stirred at room temperature under atmosphere of argon for 6-18 h. After completion of the reaction as monitored by TLC and LC-MS, EtsN was added to quench the reaction. The reaction mixture was diluted with dichloromethane, and washed successively with saturated aqueous NaHC03 and water. Then organic layer was dried over MgS04 and concentrated under reduced pressure. Finally the residue was purified by silica gel column chromatography to afford 2-alkyl quinoline 3 with 43-97% yield. All the products were characterized by spectral studies. 

Aryl ether and aryl aniline derivatives as potent H3 antagonists... 

Arylation of Anilines. It was demonstrated that la, as well as other diphenyliodonium salts with other non-nucleophiUc counterions, can efficiently arylate aniline to AliV-diphenylamine (2) (eq 1). Salts Ig-i bearing halide counterions were found to be completely ineffective. A similar copper-catalyzed Buchwald-Hartwig-type phenylation of both alkyl and aryl amines using [Ph2l]BF4 (If) and its analogs has been reported. ... 

The diazonium salts 145 are another source of arylpalladium com-plexes[114]. They are the most reactive source of arylpalladium species and the reaction can be carried out at room temperature. In addition, they can be used for alkene insertion in the absence of a phosphine ligand using Pd2(dba)3 as a catalyst. This reaction consists of the indirect substitution reaction of an aromatic nitro group with an alkene. The use of diazonium salts is more convenient and synthetically useful than the use of aryl halides, because many aryl halides are prepared from diazonium salts. Diazotization of the aniline derivative 146 in aqueous solution and subsequent insertion of acrylate catalyzed by Pd(OAc)2 by the addition of MeOH are carried out as a one-pot reaction, affording the cinnamate 147 in good yield[115]. The A-nitroso-jV-arylacetamide 148 is prepared from acetanilides and used as another precursor of arylpalladium intermediate. It is more reactive than aryl iodides and bromides and reacts with alkenes at 40 °C without addition of a phosphine ligandfl 16]. 

A Pd-cataly2ed reaction of amines with halides is expected, but actually little is known about the reaction. The CDE ring system of lavendamycin (805) has been constructed by the intramolecular reaction of aryl bromide with aniline derivative in 804, but 1.2 equiv, of Pd(Ph3P)4 is required[679]. 

Important analogs of aniline include the toluidines, xyUdines, anisidines, phenetidines, and its chloro-, nitro-. A/-acetyl. A/-alkyl. A/-aryl. A/-acyl, and sulfonic acid derivatives. 

The N,]S -dialkyl-/)-PDAs are manufactured by reductively alkylating -PDA with ketones. Alternatively, these compounds can be prepared from the ketone and -lutroaruline with catalytic hydrogenation. The /V-alkyl-/V-aryl- -PDAs are made by reductively alkylating -nitro-, -nitroso-, or /)-aminodipheny1 amine with ketones. The AijAT-dialkyl- PDAs are made by condensing various anilines with hydroquinone in the presence of an acid catalyst (see Amines-aromatic,phenylenediamines). 

Many 3-substituted indoles have also been prepared with the use of a-alkyl or a-aryl-p-keto sulfides. Thus indolization of aniline 5 with 3-methylthio-2-butanone 27 furnished indolenine 28, presumably via the same mechanism discussed earlier. The indolenine 28 was relatively unstable and reduced to the indole 29 without purification. Tetrahydrocarbazole 32 was prepared in 58% overall yield. Smith et al. made excellent use of the Gassman process in the total synthesis of (-i-)-paspalicine and (+)-paspalinine. ... 

The Zincke reaction is an overall amine exchange process that converts N- 2,A-dinitrophenyl)pyridinium salts (e.g, 1), known as Zincke salts, to iV-aryl or iV-alkyl pyridiniums 2 upon treatment with the appropriate aniline or alkyl amine. The Zincke salts are produced by reaction of pyridine or its derivatives with 2,4-dinitrochlorobenzene. This venerable reaction, first reported in 1904 and independently explored by Konig, proceeds via nucleophilic addition, ring opening, amine exchange, and electrocyclic reclosure, a sequence that also requires a series of proton transfers. By... 

General Conditions for each step and selectivity of m-substituted anilines As previously mentioned, Hauser and Reynolds reported on factors governing the first step of the Conrad-Limpach reaction but they tvere by no means exhaustive. Other than the conditions reported above for the first step, HClAleOH, CHCI3 or CHCI2 (neat or with acid catalyst), PhMe or PhH with removal of water with or without acid catalyst, or EtOH/AcOH/CaS04 were reported to provide the desired enamino-ester from an aryl amine and 3-keto-ester. Hauser and Reynolds also noted that o-nitroaniline and o-nitro-p-methoxyaniline failed to form the desired enamino-ester under conditions which they reported. 

In 1883, Bottinger described the reaction of aniline and pyruvic acid to yield a methylquinolinecarboxylic acid. He found that the compound decarboxylated and resulted in a methylquinoline, but made no effort to determine the position of either the carboxylic acid or methyl group. Four years later, Doebner established the first product as 2-methylquinoline-4-carboxylic acid (8) and the second product as 2- methylquinoline (9). Under the reaction conditions (refluxing ethanol), pyruvic acid partially decarboxylates to provide the required acetaldehyde in situ. By adding other aldehydes at the beginning of the reaction, Doebner found he was able to synthesize a variety of 2-substituted quinolines. While the Doebner reaction is most commonly associated with the preparation of 2-aryl quinolines, in this primary communication Doebner reported the successful use of several alkyl aldehydes in the quinoline synthesis. 

A variety of aryl systems have been explored as substrates in the Knorr quinoline synthesis. Most notable examples are included in the work of Knorr himself who has demonstrated the high compatibility of substituted anilines as nucleophilic participants in that reaction. In the case of heteroaromatic substrates however, the ease of cyclization is dependent on the nature and relative position of the substituents on the aromatic ring." For example, 3-aminopyridines do not participate in ring closure after forming the anilide... 

Heating arylamines with carbon dioxide at 200 C (8500 atm) gives good yields of 3-aryl derivatives of 2,4-dihydroxyquinazoline ° (see 5e). The method is unsatisfactory when riitro, halo, and phenolic anilines and a- or p-naphthylamines are used. 

Good yields of 10-aryl-3,6-dinitroacridones were obtained merely by heating 2,2, 4,4 -tetranitrobenzophenone (419) with an excess of the corresponding aryl amines at 125°C. For example, aniline provided 420 in 80% yield (Eq. 38). The reaction is fairly general for meta- and para-substituted anilines, though it proceeds less readily with orf/io-substituted compounds (79JCS(P1)1364). A method of isolation of the intermediate diarylamine in the synthesis of certain 10-aryl-3,6-dinitroacridones from 2,2, 4,4 -tetranitrobenzophenone has also been described (93JCR(M)2779). 

Arenediazonium ions are relatively weak electrophiles, and therefore react only with electron-rich aromatic substrates like aryl amines and phenols. Aromatic compounds like anisole, mesitylene, acylated anilines or phenolic esters are ordinarily not reactive enough to be suitable substrates however they may be coupled... 

The preparation of an aryl fluoride—e.g. fluorobenzene 3—starting from an aryl amine—e.g. aniline 1—via an intermediate arenediazonium tetrafluoroborate 2, is called the Schiemann reaction (also called the Balz-Schiemann reaction) The diazotization of aniline 1 in the presence of tetrafluoroborate leads to formation of a benzenediazonium tetrafluoroborate 2 that can be converted into fluorobenzene 3 by thermolysis. 

Treatment of aniline 1 with nitric acid in the presence of tetrafluoroboric acid leads to a relatively stable benzenediazonium tetrafluoroborate 2 by the usual diazotization mechanism. There are several variants for the experimental procedure. Subsequent thermal decomposition generates an aryl cation species 4, which reacts with fluoroborate anion to yield fluorobenzene 3 " ... 

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