Amines, aryl reaction

Nielsen DJ, Cavell KJ (2006) Pd-NHC complexes as catalysts in telomerization and aryl amination reactions. In Nolan SP (ed) N-Heterocyclic carbenes in synthesis. WUey-VCH, Weinheim, pp 73-102... 

The tricyclic core of duocarmycin has been produced by a novel copper-mediated aryl amination reaction, which cleanly gives the cyclized product under exceptionally mild conditions <2003JA6630>. Selective /) tw-bromination of indoline with T-bromosuccinimide (NBS) in DMF followed by aryl amination using 2 equiv of copper iodide quantitatively provides the indolinone (Equation 71). 

Scheme 24 Aryl amination reaction mediated by [(NHC)PdCl2]2...

Other efficient catalysts for the aryl amination reaction include the (NHC)-Pd(allyl)Cl series that bear the same metal/ligand ratio of 1 1 and allow excellent conversions to products at temperatures as low as room temperature [78]. Alkoxide bases lacking p-hydrogens (amylates and terf-butoxide) have a dual action in this system as they activate the catalyst through nucleophilic attack on the palladium allyl moiety and act as an efficient base for the catalytic process. The complexes were successfully used in the key step of a Cryptocarya alkaloid synthesis [79]. 

Although the active participation of Pd(IV) intermediates in catalysis is currently well established [21, 22], it has been shown that the catalytic activity of paUadacycles is usually due to Pd nanoparticles or soluble Pd(0) species arising from partial or complete decomposition processes. Hartwig and Louie [23] showed that paUadacycles of type 1 are reduced by amines (in aryl amination reactions) or stan-nanes (in the Stille coupling) to afford Pd(0) phosphine complexes. Furthermore,... 

The first demonstration of palladium catalysis in an aryl amination reaction was reported in 1983 by Kosugi and co-workers. In this reaction, an aminostannane is coupled to an aryl halide in a transformation analogous to a Stille cross-coupling. 

The dba ligand appears to play an innocent role in aryl amination reactions as the base, amine, or a combination of both, may react with it (1,4-addition), thereby reducing the overall dba concentration and its potential interference with Pd(0) and the catalytic cycle. However, some other alkene ligand effects are observed in aryl amination. ... 

Boufatah N, Gellis A, Maldonado J, Vanelle P (2004) Efficient microwave-assisted synthesis of new sulfonylbenzimidazoIe-4,7-diones heterocyclic quinones with potential antitumor activity. Tetrahedron 60(41) 9131-9137. doi 10.1016/j.tet.2004.07.070 Brain CT, Brunton SA (2002) An intramolecular palladium-catalysed aryl amination reaction to produce benzimidazoles. Tetrahedron Lett 43(10) 1893-1895. doi 10.1016/80040-4039(02) 00132-6... 

The first application of the single-step procedure to the synthesis of azacafix-arenes was laimched by Ito et al., who prepared a series of azacafix[ ]arenes 4a-f with different ring sizes (w = 3 to 8) [16,17]. As shown in Scheme 2, starting from the N-methylation of 3-bromoaniline (2) in 3 steps, the resultant 3-bromo-N-methylaniline (3) was subjected to the Buchwald-Hartwig aryl amination reaction to yield azacaUxarenes 4a-f, which were isolated by medium-pressure liquid chromatography. 

Scheme 1 Catalytic cyde of Buchwald-Hartwig aryl amination reaction of aromatic halide with N-alkylanUine [12]...

Another application of the single-step procedure tvas made by Miyazaki et al, who utilized the Buchwald-Hartwig aryl amination reaction for the preparation of azacalix[6]pyridine 7d [18], in which all the benzene rings of the above azacalix[6]arene 4d were replaced by pyridine rings (Scheme 3). Azacalix[ ]pyridines 8a-f (n = 3-8) with tolyl groups on the nitrogen bridges... 

Friedel-Crafts reactions are normally not successful when attempted on an aryl amine but can be carried out readily once the ammo group is protected... 

Phosgene reacts with a multitude of nitrogen, oxygen, sulfur, and carbon centers. Reaction with primary alkyl and aryl amines yield carbamoyl chlorides which are readily dehydrohalogenated to isocyanates. Secondary amines also form carbamoyl chlorides. 

Aromatic nitro compounds are often strongly colored. They frequently produce characteristic, colored, quinoid derivatives on reaction with alkali or compounds with reactive methylene groups. Reduction to primary aryl amines followed by diazotization and coupling with phenols yields azo dyestuffs. Aryl amines can also react with aldehydes with formation of Schiff s bases to yield azomethines. 

Protection of primary aryl amines as the triazene is accomplished by diazotiza-tion of the amine followed by reaction with pyrrolidine in aq. KOH. This group is stable to metalation of the aromatic ring by metal halogen exchange. The amine is recovered by reductive cleavage with Ni-Al alloy (aq. KOH, rt, 37-68% yield). ... 

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. 

Aryl amine 31 was found to react readily with acetylene dicarboxylate 32 to yield fumarate 33. Several similar reactions were reported and found to be general. The... 

The Knorr quinoline synthesis refers to the formation of a-hydroxyquinolines 4 from P-ketoesters 2 and aryl amines 1. The reaction usually requires heating well above 100°C. However, some cases do exist when the cyclization takes place in the presence of a catalytic amount of mineral acid at temperatures as low as -10 °C. The intermediate anilide 3 undergoes cyclization by dehydration with concentrated sulfuric acid. The reaction is conceptually close to the Doebner-Miller and Gould-Jacobs reactions. ... 

The first cyclization of acetanilide was carried out by Knorr in 1883 who subsequently demonstrated that the reaction was also applicable to acetoacylated aryl amines that have a vacant ortho position. ... 

Chapman and co-workershave shown that, in the reactions of nitro-2-chloropyridines with piperidine, aryl amines, or pyridine bases, a 5-nitro group activates more than a 3-nitro group (cf. Table VII, p. 276). 

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 1 can undergo a coupling reaction with electron-rich aromatic compounds 2 like aryl amines and phenols to yield azo compounds 3. The substitution reaction at the aromatic system 2 usually takes place para to the activating group probably for steric reasons. If the para position is already occupied by a substituent, the new substitution takes place ortho to the activating group. 

For aryl amines the reaction mixture should be slightly acidic or neutral, in order to have a high concentration of free amine as well as arenediazonium ions. Aryl ammonium species—ArNH3+—are unreactive. The coupling of the diazonium species with aromatic amines proceeds by an analogous mechanism ... 

With primary and secondary aryl amines a reaction at the amino nitrogen can occur, leading to formation of an aryl triazene 5 ... 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

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. 

Palladium-catalyzed aminations of aryl halides is now a well-documented process [86-88], Heo et al. showed that amino-substituted 2-pyridones 54 and 55 can be prepared in a two-step procedure via a microwave-assisted Buchwald-Hartwig amination reaction of 5- or 6-bromo-2-benzyloxypyri-dines 50 and 51 followed by a hydrogenolysis of the benzyl ether 52 and 53, as outlined in Fig. 9 [89]. The actual microwave-assisted Buchwald-Hartwig coupling was not performed directly at the 2-pyridone scaffold, but instead at the intermediate pyridine. Initially, the reaction was performed at 150 °C for 10 min with Pd2(dba)3 as the palladium source, which provided both the desired amino-pyridines (65% yield) as well as the debrominated pyridine. After improving the conditions, the best temperature and time to use proved... 

Independently, Caddick et al. reported microwave-assisted amination of aryl chlorides using a palladium-N-heterocyclic carbene complex as the catalyst (Scheme 99) [lOlj. Initial experiments in a domestic microwave oven (reflux conditions) revealed that the solvent is crucial for the reaction. The Pd source also proved very important, since Pd(OAc)2 at high power in DMF gave extensive catalyst decomposition and using it at medium and low power gave no reaction at all. Pd(dba)2/imidazohum salt (1 mol% catalyst loading) in DME with the addition of some DMF was found to be suitable. Oil bath experiments indicated that only thermal effects are governing the amination reactions. 

The reaction of amines with aryl halides requires a catalyst in most cases to initiate the reaction. There are several approaches that result in N-aryl amines. Treatment of cyclohexylamine with p-MeC6H4B(OH)2 and Cu(OAc)2 gave the N-aryl amide in 63% yield. Aryl halides react with amines in the presence of palladium... 

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