1860-47-5

Usage

Synthesis Reference(s)

Tetrahedron, 52, p. 4637, 1996 DOI: 10.1016/0040-4020(96)00168-8

InChI:InChI=1/C6H5FN2O2/c1-4-5(9(10)11)2-3-6(7)8-4/h2-3H,1H3

Upstream product

• 512778-41-5 1-trifluoromethyl-3-(4-methylphenylamino)prop-2-en-1-one 
• 106-49-0 p-toluidine 
• 239437-47-9 3,3,4,4,4-Pentafluoro-butyraldehyde 
• 1382715-78-7 Br^(1-)*C₁₈H₁₈NO⁽¹⁺⁾ 
• 91-62-3 6-methylquinoline 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 887144-94-7 Togni's reagent II 
• 1195931-68-0 6-methyl-2-(trifluoromethyl)-quinolin-4-yl trifluoromethanesulfonate 
• 1548899-28-0 1-phenylimino-3-phenoxy-3-trifluoromethylprop-2-ene 
• 100-01-6 4-nitro-aniline 
• 95-53-4 o-toluidine 
• 2923-16-2 potassium trifluoroacetate 
• 1233947-65-3 (Z,Z)-N,N'-bis(4,4,4-trifluoro-3-oxo-1-buten-1-yl)-1,3-phenylenediamine 
• 123638-04-0 6‐methyl‐2‐(trifluoromethyl)‐quinolin‐4(1H)‐one 

Relevant academic research and scientific papers

Nucleophilic trifluoromethylation of azinium salts with Zn(CF3)2·bpy

(Trifluoromethyl)zinc complexes have been widely used in metal-mediated trifluoromethylation reactions. However, direct nucleophilic addition with a (trifluoromethyl)zinc complex is rare. In this article, we describe an unprecedented trifluoromethylation of azinium salts using Zn(CF3)2·bpy as CF3 source, giving 1-(4-methoxybenzyl)-2-(trifluoromethyl)-1,2-dihydroquinolines as products. The latter species were further transformed to 2-trifluoromethylquinolines under oxidative conditions. This work also shows that ligands play an important role in tuning the reactivity of (trifluoromethyl)zinc complexes.

2-Position-Selective C-H Perfluoroalkylation of Quinoline Derivatives

We developed 2-position-selective, direct C-H trifluoromethylation, pentafluoroethylation, and heptafluoropropylation of quinoline derivatives. Regioselective transformation was achieved without derivatization of the quinolines. The reaction proceeded at room temperature with high functional group tolerance, even in gram scale. Notably, the reaction was applicable to substrates containing a functional group sensitive to oxidation and a drug molecule.

Coupling Radical Homoallylic Expansions with C-C Fragmentations for the Synthesis of Heteroaromatics: Quinolines from Reactions of o-Alkenylarylisonitriles with Aryl, Alkyl, and Perfluoroalkyl Radicals

Selective addition of radicals to isonitriles can be harnessed for initiating reaction cascades designed to overcome the stereoelectronic restrictions on homoallylic ring expansion in alkyne reactions and to develop a new general route for the preparation of N-heteroaromatics. This method utilizes alkenes as synthetic equivalents of alkynes by coupling homoallylic ring expansion to yield the formal "6-endo" products with aromatization via stereoelectronically assisted C-C bond scission. Computational analysis of the homoallyic expansion potential energy surface reveals that the indirect 5-exo/3-exo/retro-3-exo path is faster than the direct 6-endo-trig closure, revealing the general exo-preference for the cyclization processes.

A Fluorinated Ligand Enables Room-Temperature and Regioselective Pd-Catalyzed Fluorination of Aryl Triflates and Bromides

A new biaryl monophosphine ligand (AlPhos, L1) allows for the room-temperature Pd-catalyzed fluorination of a variety of activated (hetero)aryl triflates. Furthermore, aryl triflates and bromides that are prone to give mixtures of regioisomeric aryl fluorides with Pd-catalysis can now be converted to the desired aryl fluorides with high regioselectivity. Analysis of the solid-state structures of several Pd(II) complexes, as well as density functional theory (DFT) calculations, shed light on the origin of the enhanced reactivity observed with L1.

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

We report a new synthesis and our study of the mechanism of formation of substituted 1-trifluoromethyl and 1-perfluoroalkyl-3-(phenylamino)prop-2-en-1- one starting from 3-(R-phenoxy)-3-perfluoroalkyl-prop-2-enals and arylamines. Reactivity study of the intermediates confirmed that 3-perfluoroalkyl-N, N′-diphenyl-1,5-diazapentadienes are the synthetic intermediates of the synthesis of 2-perfluoroalkylquinolines. The mechanism of the reaction of 1-trifluoromethyl and 1-perfluoroalkyl-3-(phenylamino)prop-2-en-1-one with POCl3 was studied. To our knowledge this is the first detection and isolation of N,N′-diaryldiazapentadiene derivatives as intermediates in the Combes F-alkyl substituted quinoline synthesis starting from enaminoketones. Finally, we succeeded isolating and identifying unsymmetrically substituted 2-perfluorolakyldiazapentadiene.

Rapid and efficient trifluoromethylation of aromatic and heteroaromatic compounds using potassium trifluoroacetate enabled by a flow system

Going to the source: The trifluoromethylation of aryl/heteroaryl iodides has been demonstrated using a flow system, thus enabling a rapid rate of reaction. A broad spectrum of trifluoromethylated compounds was prepared in good to excellent yields using CF3CO2K as the trifluoromethyl source. The process has the advantage of short reaction times and uses convenient [CF3] sources. Copyright

Simultaneous regioselective synthesis of trifluoromethyl-containing 1,7-phenanthrolines and quinolines form cyclocondensation reaction of N,N′-bis(oxotrifluoroalkenyl)-1,3-phenylenediamines

This paper reports interesting results of the conventional synthesis of a new series of 2,10-dialkyl(aryl)-4,8-bis(trifluoromethyl)-1,7-phenanthrolines, in 22-40percent yields, form cyclization reactions of N,N′- bis(oxotrifluoroalkenyl)-1,3-phenylenediamines [1,3-C6H 4-(NHCR=CHC(O)CF3)2] in a strongly acidic medium (PPA) and absence of solvent. The synthetic route also allowed the isolation of a new series of 2-alkyl(aryl/heteroaryl)-4-trifluoromethyl-7- aminoquinolines, in 20-73percent yields, simultaneously. The enaminone precursors were obtained form the reaction of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones [CF 3C(O)CH=C(R)OR1, where R = H, Me, Ph, 4-MePh, 4-OMePh, 4-ClPh, 4-FPh, 4-BrPh, 4-NO2Ph, 2-furyl and R1 = Me, Et] with 1,3-phenylenediamine under mild conditions, in 47-91percent yields.

New regiospecific synthesis of 2-trifluoromethyl-1,5 diazapentadiene compounds and of 2-trifluoromethylquinolines, their cyclization products

2-Trifluoromethylquinolines 5 are synthesized in high yields using a perfluoroalkylated gemiodoacetoxy derivative 3 and arylamines 4. The intermediate of this reaction, 2-trifluoromethyl-1,5-diazapentadiene compound 6, was isolated. The procedures are eas

Selective and efficient structural elaboration of 2-(trifluoromethyl)quinolinones

The acid-catalyzed cyclization-condensation between anilines and ethyl 4,4,4-trifluoroacetoacetate affords 1,4-dihydro-2-trifluoromethyl-4H-4-quinolinones (1), which can easily be converted into 4-bromo-2-(trifluoromethyl)quinolines. These undergo halogen/metal exchange, generating 2-trifluoromethyl-4-quinolyllithiums, when treated with butyllithium, and hydrogen/metal exchange, generating 4-bromo-2-trifluoromethyl-3-quinolyllithiums, when treated with lithium diisopropylamide. Trapping of the latter intermediates provides 3-functionalized products that may be further elaborated by electrophilic substitution of the bromine atom. A few unexpected findings resulted from these investigations, the most noteworthy being an unprecedented buttressing effect and a counterintuitive halogen reactivity. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

A novel synthesis of 2-fluoroalkyl quinolines

2-Fluoroalkyl quinolines are prepared by reacting aniline with α-fluoroalkyl aldehydes or α-fluoroalkyl cyclohexanones in the presence of acetic acid. Under the same reaction condition, 2-aminophenol gives the corresponding 2-fluoroalkyl-8-quinolinols; in some cases, 2-fluoroalkyl benzoxazoles are also formed as minor products.