221313-10-6Relevant articles and documents
Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI
Liu, He,Wu, Jian,Jin, Yuxuan,Leng, Xuebing,Shen, Qilong
supporting information, p. 14367 - 14378 (2021/09/13)
The synthesis, characterization, and reactivity of key intermediates [Cu(CF3)(X)]-Q+ (X = CF3 or I, Q = PPh4) in copper-mediated trifluoromethylation of aryl halides were studied. Qualitative and quantitative studies showed [Cu(CF3)2]-Q+ and [Cu(CF3)(I)]-Q+ were not highly reactive. Instead, a much more reactive species, ligandless [CuCF3] or DMF-ligated species [(DMF)CuCF3], was generated in the presence of excess CuI. On the basis of these results, a general mechanistic map for CuI-promoted trifluoromethylation of aryl halides was proposed. Furthermore, on the basis of this mechanistic understanding, a HOAc-promoted protocol for trifluoromethylation of aryl halides with [Ph4P]+[Cu(CF3)2]- was developed.
TCDA: Practical Synthesis and Application in the Trifluoromethylation of Arenes and Heteroarenes
Wang, Jian,Zhang, Xiaomin,Wan, Zehong,Ren, Feng
, p. 836 - 839 (2016/05/19)
A practical synthesis of the reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported on 50 g scale. The trifluoromethylation with TCDA was optimized, and the reaction shows very broad scope with respect to electron-deficient, -neutral, -rich aryl/heteroaryl iodides, as well as excellent functional group tolerability, such as ester, amide, aldehyde, hydroxyl, and carboxylic acid. The reagent was also applied to the late-stage trifluoromethylation of three medicinally relevant compounds. Additionally, the building block trifluoromethylpyridine and one drug related molecule Boc-Fluoxetin were synthesized in 10 g scale by this method, demonstrating its practical applications in process chemistry.
New Reagent for Highly Efficient Synthesis of Trifluoromethyl-Substituted Arenes and Heteroarenes
Zhang, Xiaomin,Wang, Jian,Wan, Zehong
supporting information, p. 2086 - 2089 (2015/05/13)
A new reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported for the introduction of a -CF3 group to arenes and heteroarenes. Compared with current known reagents, TCDA shows very broad scope with respect to electron-deficient, -neutral, and -rich aryl/heteroaryl iodides as well as excellent functional group tolerance, including ester, amide, aldehyde, hydroxyl, and carboxylic acid. (Chemical Equation Presented).
NOVEL TRPV3 MODULATORS
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Paragraph 1570; 1571, (2013/06/04)
Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
NOVEL TRPV3 MODULATORS
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Paragraph 97; 98, (2013/05/21)
Disclosed herein are modulators of TRPV3 of formula (II): wherein G1, X1, X2, X3, X4, X5, G2, Ra, Rb, and u are as defined in the specification. Composition
Convergent asymmetric synthesis of two complex TRPV1 antagonists
Butcher, Kenneth J.,Denton, Steven M.,Field, Stuart E.,Gillmore, Adam T.,Harbottle, Gareth W.,Howard, Roger M.,Laity, Daniel A.,Ngono, Christian J.,Pibworth, Benjamin A.
experimental part, p. 1192 - 1200 (2011/12/16)
The convergent scale-up synthesis of two complex TRPV1 antagonists to support exploratory toxicology studies is described. Both compounds contain three chiral centers introduced by asymmetric synthesis with chiral control being critical for the success of the project. Preparation of the key cyclopropyl intermediate utilised an asymmetric cyclopropanation using thermally unstable ethyl diazoacetate. Ellman's auxiliary was used to synthesize the chiral α-methyl benzylamine fragments. This paper highlights some of the key synthetic challenges, processing issues, and safety aspects from the scale-up of this chemistry.
Synthesis of trifluoromethylated azines via nucleophilic oxidative substitution of hydrogen by trifluoromethyl carbanions
Loska, Rafal,Majcher, Monika,Makosza, Mieczyslaw
, p. 5574 - 5580 (2008/02/09)
(Chemical Equation Presented) A novel, three-step method of trifluoromethylation of azines via oxidative nucleophilic substitution of hydrogen in the heteroaromatic ring by a CF3- carbanion is presented. The key reaction of this proc
The direct metalation and subsequent functionalization of trifluoromethyl-substituted pyridines and quinolines
Schlosser, Manfred,Marull, Marc
, p. 1569 - 1575 (2007/10/03)
Depending on the choice of the reagent, 2-(trifluoromethyl)-pyridine can be selectively metalated and subsequently carboxylated of otherwise functionalized either at the 3- or at the 6-position. "Optional site selectivity" can also be achieved with 4-(trifluoromethyl)pyridine, which may be deprotonated either at the 2- or at the 3-position. In contrast, 3-(trifluoromethyl)pyridine undergoes nucleophilic addition and ensuing decomposition whatever the base. Depending on the reaction conditions, 2-(trifluoromethyl)quinoline displays reactivity toward lithium reagents at its 3-, 4-, or 8-positions, 3-(trifluoromethyl)quinolines at the 2- or 4-positions, and 4-(trifluoromethyl)quinoline at the 2- or 3-positions. It was therefore possible to prepare four trifluoromethyl-substituted pyridinecarboxylic acids (1, 4, 9, and 10) and six trifluoromethyl-substituted quinolinecarboxylic acids (11, 13, 14, 15, 17, and 18) regioisomerically uncontaminated and in a most straightforward way. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).
Herbicidal 2-azinyl-6-aryloxypyr (mi) dines
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, (2008/06/13)
The novel compounds of formula I: wherein A represents an optionally substituted aryl group or an optionally substituted 5- or 6-membered nitrogen- or sulfur-containing heteroaromatic group or a difluorobenzodioxolyl group; B represents an optionally substituted 6-membered nitrogen- containing heteroaromatic group; R represents a halogen atom or an optionally substituted alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, group or a haloalkyl, haloalkoxy, cyano, nitro group; or -S(O)p-R5, in which p is 0,1 or 2, and R5represents an alkyl or haloalkyl group; or -NR6R7, in which R6and R7each indepently represent a hydrogen atom, an alkyl, alkenyl, arakyl or aryl group, or R8O-CY-, in which R8represents an alkyl group, and Y represents O or S;X represents an oxygen or a sulfur atom, Z represents CH or N, and n represents an integer from 0 to 3, and herbicidal compositions containing such compounds as active ingredients.
