Synthesis of substituted 1-trifluoromethyl and 1-perfluoroalkyl-3-(arylamino)prop-2-en-1-one: advances in the mechanism of Combes 2-trifluoromethyl and 2-perfluoroalkyl quinolines synthesis

Kharrat, Salem El; Laurent, Philippe; Blancou, H.

doi:10.1016/j.tet.2013.12.073

Cited by 26 publications

(11 citation statements)

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“…15 (in DCM at rt: 21a – l,o – o’ ; or refluxing: 21m–n’ ), the main reaction product was the intermediate 21 , the latter ( 21a – o’ ) have been isolated in fair yields then characterized by NMR and mass spectrometry (Scheme 6). All N , N’ -diaryl-2-(perfluoroalkyl)-1,5-diazapenta-1,3-dienes 21a – o’ were actually isolated as mixtures of E/Z -stereoisomers, as in our previous works [59,64,65].…”

Section: Resultsmentioning

confidence: 63%

“…In order to better understand the mechanism of this reaction, its evolution was monitored by 19 F-NMR spectroscopy, carried out on aliquots of the reaction medium diluted in CDCl 3 or DMSO- d 6 , then comparing the spectra of reaction mixtures with NMR data of compounds already investigated and characterized in the course of our previous studies on gem -iodoacetoxy related systems [59,60,61,62,63,64,65].…”

Section: Resultsmentioning

confidence: 99%

“…In previous articles [59,60,61,62,63,64,65] we have reported the synthesis of various perfluoroalkylated quinoline derivatives, by reacting perfluoroalkylated gem -iodoacyloxy derivatives 14 with substituted anilines 15 . Later we observed that the presence of a ketone in the medium leads to the formation of arylpyridiniums instead of quinolines; what suggested an interesting alternative to published synthetic methods, and led us to design a new and efficient synthesis of substituted 2-trifluoromethyl and 2-perfluoroalkyl- N -arylpyridinium derivatives 17 – 19 under mild reaction conditions and with very good yields.…”

Section: Introductionmentioning

confidence: 99%

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Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

et al. 2019

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We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N’-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson’s. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it.

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Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

et al. 2019

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“…1). [12][13][14] The synthesis of quinolines has been an active area for many years and as a result, a number of efficient synthetic methods have been developed, [15][16][17][18][19][20] such as the classical Skraup, [21][22][23] Combes, [24][25][26] Friedlander, [27][28][29] Gould-Jacobs, [30][31][32] and Doebner-von Miller reactions. [33][34][35][36] More recently, alternative strategies for the quinoline synthesis such as domino cycloadditions [37][38][39][40][41] and transition-metal mediated methods [42][43][44][45] have been introduced.…”

Section: Introductionmentioning

confidence: 99%

An efficient 3-acylquinoline synthesis from acetophenones and anthranilviaC(sp³)–H bond activation mediated by Selectfluor

Gao

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2019

RSC Adv.

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“…11 Interestingly, Kharrat has reported the synthesis of 2-(trifluoromethyl)quinoline with a fluorinated building block prepared from TFAA. 12 However, the systematic synthesis of various trifluoromethyl-containing heterocycles using trifluoroacetic acid derivatives has not been well developed.…”

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Synthesis of Trifluoromethyl Derivatives of Quinoline and Isoquinoline

Miyashita¹,

Fujisaka²,

Aomatsu³

et al. 2022

HETEROCYCLES

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Trifluoromethyl derivatives of quinoline and isoquinoline were synthesized using phosphonium salts with a trifluoroacetamide group in the presence of 1,8-diazabicyclo[5.4.0]-7-undecene. The quinoline skeleton was formed from a phenethylphosphonium salt with a trifluoroacetamide NH proton, whereas the isoquinoline formation required masking of the amide proton of trifluoroacetamide in the benzylphosphonium structure.Fluorinated aromatic compounds are found in various bioactive compounds, such as pharmaceuticals and pesticides. This is because the introduction of a fluorine group or a trifluoromethyl group into organic molecules causes significant changes in the chemical and pharmaceutical properties of the parent molecules. 1 Currently, the trifluoromethyl group is one of the most common fluorine-containing substituents found in commercial pharmaceuticals and agrochemicals. 2,3 Considerable efforts have been made developing synthetic strategies for introducing trifluoromethyl groups into organic skeletons. Two primary methods have been reported: (i) direct trifluoromethylating reactions using various trifluoromethylating reagents 4 and (ii) the use of pre-functionalized CF3 group-containing building blocks. 5 Various organofluorine compounds can be obtained by the first method using different types of trifluoromethylating reagents based on their electronic properties, such as radicality, 6 electrophilicity, 7 and nucleophilicity. 8 However, this method requires multi-step synthesis, and the trifluoromethylating reagents are sometimes difficult to handle, expensive, or both. Some studies used the second method with fluorinated building blocks, such as β-trifluoromethyl-α,β-unsaturated carbonyl compounds, which have attracted tremendous attention in recent years because of their availability and versatility. 9 By contrast, we have used trifluoroacetic acid derivatives, such as trifluoroacetic anhydride (TFAA), as a

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Synthesis of substituted 1-trifluoromethyl and 1-perfluoroalkyl-3-(arylamino)prop-2-en-1-one: advances in the mechanism of Combes 2-trifluoromethyl and 2-perfluoroalkyl quinolines synthesis

Cited by 26 publications

References 85 publications

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

An efficient 3-acylquinoline synthesis from acetophenones and anthranilviaC(sp³)–H bond activation mediated by Selectfluor

Synthesis of Trifluoromethyl Derivatives of Quinoline and Isoquinoline

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Synthesis of substituted 1-trifluoromethyl and 1-perfluoroalkyl-3-(arylamino)prop-2-en-1-one: advances in the mechanism of Combes 2-trifluoromethyl and 2-perfluoroalkyl quinolines synthesis

Cited by 26 publications

References 85 publications

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds—Mechanistic Insights

An efficient 3-acylquinoline synthesis from acetophenones and anthranilviaC(sp3)–H bond activation mediated by Selectfluor

Synthesis of Trifluoromethyl Derivatives of Quinoline and Isoquinoline

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An efficient 3-acylquinoline synthesis from acetophenones and anthranilviaC(sp³)–H bond activation mediated by Selectfluor