Communications - The ortho-Alkylation of Aromatic Amines

Ecke, George G.; Napolitano, John P.; Kolka, Alfred J.

doi:10.1021/jo01112a620

Cited by 16 publications

(6 citation statements)

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“…80–82 °C (lit. [74] m.p. 81–83 °C); 1 H-NMR (CDCl 3 ): δ 7.45 (1H, bs, NH), 7.30–7.23 (2H, m, H4–H5), 6.99 (1H, d, J = 8.0 Hz, H2), 6.69 (1 H, dd, J = 2.1, 8.1 Hz, H6), 3.82 (3H, s, OMe), 2.20 (3H, s, CH 3 ).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

et al. 2016

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Identification of the novel (E)-N 1 -((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio) propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G 1 cell cycle arrest, as well as upregulation of the p27 kip1 cell cycle regulating protein.

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Section: Methodsmentioning

confidence: 99%

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

et al. 2016

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“…3 On the other hand, the alkylation of aniline with ethylene has been reported using basic aluminium anilide as catalyst under drastic conditions (40-60 bar; 330°C). 4,5 In addition, the reaction of aniline with styrene, leading to the formation of ortho-Cand N-alkylation products is possible when using aluminium phenoxide or zeolites as catalysts. 6 However, these catalysts always produce a mixture of regioisomers (o-, palkylated aniline).…”

Section: Methodsmentioning

confidence: 99%

“…5,6 The six-membered cyclic intermediate is more favourable, this accounts for the formation of 1a -5a as the main reaction products. The beneficial effect of the rhodium catalyst is explained via a coordination to the arene ring of styrene which results in an activation of styrene towards nucleophiles.…”

Section: Methodsmentioning

confidence: 99%

“…Although it is too early to give a detailed mechanistic explanation for the new rhodium/acid-catalyzed alkylation of aniline we propose that the reaction involves the key intermediates shown in Scheme 2. 5,6 The six-membered cyclic intermediate is more favourable, this accounts for the formation of 1a -5a as the main reaction products. The beneficial effect of the rhodium catalyst is explained via a coordination to the arene ring of styrene which results in an activation of styrene towards nucleophiles.…”

Section: Methodsmentioning

confidence: 99%

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Catalytic Alkylation of Aromatic Amines with Styrene in the Presence of Cationic Rhodium Complexes and Acid

Beller

Thiel

Trauthwein

1999

Synlett

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The first transition metal-catalyzed Friedel-Crafts alkylation of aromatic amines with styrene is reported. ortho-Alkylation of anilines occurs using catalytic amounts of [Rh(cod) 2 ]BF 4 / 4 PPh 3 and HBF 4 .There has been much effort in recent years towards the development of catalytic electrophilic aromatic substitution reactions. 1 Of special importance are methods, e.g. Friedel-Crafts reactions, which enable the introduction of carbon substituents onto aromatic rings. Although these reactions work best for electron-rich aromatic compounds, frequently the observed selectivities (ortho vs. para) are low and the reactions proceed only in the presence of stoichiometric amounts of Lewis acids. Scheme 1Unlike typical Friedel-Crafts processes of substituted benzenes, electrophilic carbon-carbon bond forming reactions of aromatic amines are more problematic. 2 This is due to the coordination of the Lewis acid to the aromatic nitrogen atom which leads to a deactivation of the aromatic ring and side reactions. Hence, few examples of alkylations of anilines with olefins under Friedel-Crafts conditions have been described. 3 On the other hand, the alkylation of aniline with ethylene has been reported using basic aluminium anilide as catalyst under drastic conditions (40-60 bar; 330°C). 4,5 In addition, the reaction of aniline with styrene, leading to the formation of ortho-Cand N-alkylation products is possible when using aluminium phenoxide or zeolites as catalysts. 6 However, these catalysts always produce a mixture of regioisomers (o-, palkylated aniline). To the best of our knowledge the only known transition metal-catalyzed alkylation of anilines was previously observed by J. J. Brunet et al. for the conversion of norbornene with aniline. 7,8 Using [(PEt 3 ) 2 RhCl] 2 / PhNHLi as catalyst the ortho-C-alkylation product (30 %) and the N-alkylation product (15 %) was obtained after 12 days at 70 °C. When applying the same catalyst to the reaction of styrene with aniline no Calkylation product was detected. 9Based on our recent investigations on the regioselective amination of aromatic olefins with aliphatic amines, 10 we became interested in the reaction of styrene with various substituted anilines in the presence of cationic rhodium complexes. Herein, we demonstrate for the first time that anilines afford alkylated anilines in the presence of catalytic amounts of HBF 4 ◊OEt 2 and a cationic rhodium species. Often high regioselectivities for the ortho-alkylated aniline 1a -5a are obtained.Recently, we described the first catalytic anti-Markovnikov hydroamination of styrene with aliphatic amines 11 using a catalyst system consisting of HBF 4 ◊OEt 2 and a cationic rhodium complex. Now, we used this catalyst system for the reaction of substituted anilines with styrene. In general, the experiments were performed in Acepressure tubes at 140 °C in the presence of 2.5 mol% [Rh(cod) 2 ]BF 4 / 4 mol% PPh 3 and 20 mol% HBF 4 ◊OEt 2 using toluene as solvent (Table 1).

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“…Alkali-metal and alkaline-earth-metal compounds of aromatic amines bring about N-alkylation [64]. The same reaction with the same catalysts was found at about the same time by American workers [65].…”

Section: E the Alkylation Of Aromatic Aminesmentioning

confidence: 60%

The Alkylation of Aromatic Compounds With Olefins

Asinger¹

1968

Mono-Olefins

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Communications - The ortho-Alkylation of Aromatic Amines

Cited by 16 publications

References 0 publications

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

Catalytic Alkylation of Aromatic Amines with Styrene in the Presence of Cationic Rhodium Complexes and Acid

The Alkylation of Aromatic Compounds With Olefins

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