- METHOD OF MANUFACTURING BIS(TRIFLUOROMEHTYL)BIPHENYL COMPOUND
-
A process for preparing a bis biphenyl compound according to example embodiments of the present invention is reacting a triflouromethylaniline compound with an alkali metal halide to form a halotrifluoride methylbenzene compound. The halotriflouromethylbenzene compound is subjected to coupling reaction under copper catalyst conditions. The productivity of bis biphenyl compounds can be improved.
- -
-
Paragraph 0076-0078
(2021/09/21)
-
- Lipshutz-type bis(amido)argentates for directed: Ortho argentation
-
Bis(amido)argentate (TMP)2Ag(CN)Li2 (3, TMP-Ag-ate; TMP = 2,2,6,6-tetramethylpiperidido) was designed as a tool for chemoselective aromatic functionalization via unprecedented directed ortho argentation (DoAg). X-Ray crystallographic analysis showed that 3 takes a structure analogous to that of the corresponding Lipshutz cuprate. DoAg with this TMP-Ag-ate afforded multifunctional aromatics in high yields in processes that exhibited high chemoselectivity and compatibility with a wide range of functional groups. These included organometallics- A nd transition metal-susceptible substituents such as methyl ester, aldehyde, vinyl, iodo, (trifluoromethanesulfonyl)oxy and nitro groups. The arylargentates displayed good reactivity with various electrophiles. Chalcogen (S, Se, and Te) installation and azo coupling reactions also proceeded efficiently.
- Tezuka, Noriyuki,Hirano, Keiichi,Peel, Andrew J.,Wheatley, Andrew E. H.,Miyamoto, Kazunori,Uchiyama, Masanobu
-
p. 1855 - 1861
(2020/03/03)
-
- Cathodic C-H Trifluoromethylation of Arenes and Heteroarenes Enabled by an in Situ-Generated Triflyltriethylammonium Complex
-
While several trifluoromethylation reactions involving the electrochemical generation of CF3 radicals via anodic oxidation have been reported, the alternative cathodic, reductive radical generation has remained elusive. Herein, the first cathodic trifluoromethylation of arenes and heteroarenes is reported. The method is based on the electrochemical reduction of an unstable triflyltriethylammonium complex generated in situ from inexpensive triflyl chloride and triethylamine, which produces CF3 radicals that are trapped by the arenes on the cathode surface.
- Cantillo, David,Jud, Wolfgang,Kappe, C. Oliver,Maljuric, Snjezana
-
supporting information
(2019/10/08)
-
- The ortho-Difluoroalkylation of Aryliodanes with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect
-
Presented herein is an intriguing effect of fluorine, and it allows difluoroenol silyl ethers to couple with aryliodanes in a redox-neutral manner to afford ortho-iodo difluoroalkylated arenes. The remaining iodide group provides a versatile platform for converting the products into various valuable difluoroalkylated arenes. The reaction shows excellent functional-group compatibility and broad substrate scope. A DFT mechanistic study suggests that the fluorine effect facilitates a subtle nucleophilic attack of the oxygen atom of enol silyl ethers onto aryliodanes, therefore leading to a rearrangement.
- Huang, Xin,Zhang, Yage,Zhang, Chaoshen,Zhang, Lei,Xu, Ying,Kong, Lichun,Wang, Zhi-Xiang,Peng, Bo
-
p. 5956 - 5961
(2019/04/03)
-
- Aryl iodine compound containing carboxydifluoromethylene at ortho-position and preparation method thereof
-
The invention discloses a preparation method of an aryl iodine compound containing carboxydifluoromethylene at ortho-position. The preparation method is characterized by including: at the presence oftrimethylsilyl trifluoromethanesulfonate, allowing aryl iodine diacetate shown as a structural formula (I) and pentafluoroacetone enol silicon ether shown as a structural formula (II) to be in rearrangement reaction, and hydrolyzing under strong base to obtain the aryl iodine compound containing methylene difluoroacetate and shown as a structural formula (III), wherein R1 is selected from hydrogen, halogen, alkyl, alkoxy, carbalkoxy, halogenated alkyl, halogenated alkoxy, carbalkoxy substituted alkyl, amino substituted alkyl, carbalkoxy and amino substituted alkyl, cyano or nitro, and Ar is selected from benzene ring, naphthalene ring and thiophene ring. The preparation method has the advantages of being mild in reaction condition, high in selectivity and yield, easy-to-separate in productand simple in operation.
- -
-
Paragraph 0107; 0108; 0109
(2019/06/30)
-
- Silver-Mediated Trifluoromethylthiolation-Iodination of Arynes
-
(Chemical Equation Presented). A one-pot trifluoromethylthiolation-iodination of arynes with trifluoromethylthiosilver (AgSCF3) and 1-iodophenylacetylene is described. This protocol allows rapid construction of o-trifluoromethylthiolated arene building blocks in moderate yields. These products were found to be excellent precursors for Yagupolskii-Umemoto-type electrophilic trifluoromethylation reagents.
- Zeng, Yuwen,Hu, Jinbo
-
supporting information
p. 856 - 859
(2016/03/04)
-
- Using Anilines as Masked Cross-Coupling Partners: Design of a Telescoped Three-Step Flow Diazotization, Iododediazotization, Cross-Coupling Process
-
The conversion of commercially available anilines into biaryl and biarylacetylene products was realized by using a telescoped, three-reactor flow diazotization/iododediazotization/cross-coupling process. The segmented flow stream created by off-gassing during the Sandmeyer sequence was restored to a continuous column of reaction solution by using a specially designed continuous-flow unit controlled by custom software created in-house. The resultant aryl iodide was then combined with a stream of cross-coupling solution that fed into the final reactor. The system proved versatile as modifications to the diazotization/iododediazotization sequence could be made rapidly to account for any substrate specificity (e.g., solubility problems), leading to a wide substrate scope of Suzuki–Miyaura and Sonogashira cross-coupled products.
- Teci, Matthieu,Tilley, Michael,McGuire, Michael A.,Organ, Michael G.
-
supporting information
p. 17407 - 17415
(2016/11/23)
-
- Study on the degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF3)
-
Degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF3), which can only be generated in situ with mixing PhI(OAc)2 and TMSCF3 in the presence of CsF, was studied by ESI-MS and GC-MS combined with 19F-NMR. The important transient intermediate PhICF3+ was determined by ESI-MS, and the major volatile products containing CF3 were identified with the authentic compounds by using GC-MS, such as trifluoromethylbenzene, 2-iodobenzotrifluoride, 3-iodobenzotrifluoride, 4-iodobenzotrifluoride. Meanwhile, more evidences obtained with 19F-NMR were given for such degradation reaction. A possible rapid CF3 radical transfer reaction pathway was proposed to clarify such degradation progress based on the experimental results. Therefore, this study may be helpful in elucidating the intrinsic reactivity of PhI(OAc)(CF3) and the possible competing side reactions caused by such self-degradation pathway. Degradation of the highly reactive hypervalent trifluoromethylation iodine reagent PhI(OAc)(CF3), which can only be generated in situ with mixing PhI(OAc)2 and TMSCF3 in the presence of CsF, was studied by ESI-MS and GC-MS combined with 19F-NMR. The important transient intermediate PhICF3+ was determined by ESI-MS, and the major volatile products containing CF3 were identified with the authentic compounds by using GC-MS, such as trifluoromethylbenzene, 2-iodobenzotrifluoride, 3-iodobenzotrifluoride, 4-iodobenzotrifluoride. Meanwhile, more evidences obtained with 19F-NMR were given for such degradation reaction. A possible rapid CF3 radical transfer reaction pathway was proposed to clarify such degradation progress based on the experimental results. Therefore, this study may be helpful in elucidating the intrinsic reactivity of PhI(OAc)(CF3) and the possible competing side reactions caused by such self-degradation pathway.
- Zhu, Hui,Zhang, Shusheng,Wang, Haoyang,Xu, Bin,Guo, Yinlong
-
supporting information
p. 1365 - 1370
(2016/02/18)
-
- Silver-Catalyzed C-H Trifluoromethylation of Arenes Using Trifluoroacetic Acid as the Trifluoromethylating Reagent
-
Direct trifluoromethylation of arenes using TFA as the trifluoromethylating reagent was achieved with Ag as the catalyst. This reaction not only provides a new protocol for aryl C-H trifluoromethylation, but the generation of CF3· from TFA may prove useful in other contexts and could potentially be extended to other trifluoromethylation reactions. (Chemical Equation Presented).
- Shi, Guangfa,Shao, Changdong,Pan, Shulei,Yu, Jingxun,Zhang, Yanghui
-
supporting information
p. 38 - 41
(2015/07/28)
-
- Potassium-alkyl magnesiates: Synthesis, structures and Mg-H exchange applications of aromatic and heterocyclic substrates
-
Using structurally well-defined dipotassium-tetra(alkyl)magnesiates, a new straightforward methodology to promote regioselective Mg-H exchange reactions of a wide range of aromatic and heteroaromatic substrates is disclosed. Contacted ion pair intermediates are likely to be involved, with K being the key to facilitate the magnesiation processes. This journal is
- Baillie, Sharon E.,Bluemke, Tobias D.,Clegg, William,Kennedy, Alan R.,Klett, Jan,Russo, Luca,De Tullio, Marco,Hevia, Eva
-
supporting information
p. 12859 - 12862
(2014/12/11)
-
- Trifluoromethylation of arenediazonium salts with fluoroform-derived CuCF3 in aqueous media
-
A new protocol has been developed for trifluoromethylation of arenediazonium salts with moisture-sensitive CuCF3 (from fluoroform) in aqueous media. The reaction is governed by a radical mechanism, tolerates a broad variety of functional groups, and is applicable to the synthesis of complex, polyfunctionalized molecules. This journal is the Partner Organisations 2014.
- Lishchynskyi, Anton,Berthon, Guillaume,Grushin, Vladimir V.
-
supporting information
p. 10237 - 10240
(2014/08/18)
-
- Silver-catalyzed formal insertion of arynes into Rf-I bonds
-
An unprecedented silver-catalyzed formal insertion of arynes into R f-I (Rf=CF3, C2F5) bonds has been developed. This protocol provides easy access to various ortho-perfluoroalkyl iodoarenes under mild conditions. In this insertion reaction, an ionic atom-transfer reaction of RfI occurs, and a silver-mediated metathesis process is involved in the efficient transfer of the electropositive iodine atom.
- Zeng, Yuwen,Hu, Jinbo
-
p. 6866 - 6870
(2014/06/09)
-
- Donor-activated lithiation and sodiation of trifluoromethylbenzene: Structural, spectroscopic, and theoretical insights
-
Aiming to shed new light on the stability and constitution of the organometallic intermediates involved in direct ortho-metalation processes, using trifluoromethylbenzene (1) as a case study, this paper investigates the deprotonation of 1 using group 1 alkyl bases tBuLi and nBuNa in the presence of the Lewis donors TMEDA (N,N,N′, N′-tetramethylethylenediamine), THF, and PMDETA (N,N,N′,N″, N″-pentamethyldiethylenetriamine). A systematic and comprehensive study combining structural, spectroscopic, and theoretical studies reveals that these donors strongly influence the final outcome of the reactions, not only by activating the alkali-metal bases and facilitating deprotonation of 1 but also by tuning the regioselectivity of the reaction. Thus, while using tBuLi/TMEDA, ortho-metalation of 1 is preferred, switching to THF gives a complex mixture of products with the meta-regioisomer being the major species crystallizing from hexane solution. This donor effect is significantly reduced when nBuNa is employed, as ortho-regioselectivity is observed almost exclusively using THF, TMEDA, or PMDETA. DFT calculations computing the relative energies of the ortho-, meta-, and para-regioisomers obtained from these metalating systems have also been carried out. Reinforcing the experimental findings, these theoretical studies show that although in all cases the product of ortho-metalation is the most thermodynamically preferred, the energy difference between the three possible modeled regioisomers is much larger for the Na systems than for the Li ones. The structures of key reaction intermediates [(TMEDA)·Li(C6H4-CF 3)]2 (2), [(TMEDA)·Na(C6H 4-CF3)]2 (3), and [(PMDETA)·Na(C 6H4-CF3)]2 (4) have been elucidated by X-ray crystallographic studies. All compounds exhibit a similar dimeric arrangement with a four-atom core constituting a {MCMC} ring. Interestingly for Na derivatives 3 and 4 unusual Na···F dative interactions are found, which appear to contribute to the overall stability of these compounds, therefore favoring ortho-metalation of 1, as the meta or para structures do not contain these additional interactions.
- Garden, Jennifer A.,Armstrong, David R.,Clegg, William,Garcia-Alvarez, Joaquin,Hevia, Eva,Kennedy, Alan R.,Mulvey, Robert E.,Robertson, Stuart D.,Russo, Luca
-
p. 5481 - 5490
(2013/11/06)
-
- Palladium-catalyzed trifluoromethylation of aromatic C-H bond directed by an acetamino group
-
The first palladium-catalyzed ortho-trifluoromethylation of the aromatic C-H bond directed by an acetamino group is reported. This method provides an efficient and green approach to synthesize the highly biological potential key structure of ortho-CF3 acetanilides and anilines.
- Zhang, Li-Sheng,Chen, Kang,Chen, Guihua,Li, Bi-Jie,Luo, Shuang,Guo, Qing-Yun,Wei, Jiang-Bo,Shi, Zhang-Jie
-
-
- Silver-mediated trifluoromethylation-iodination of arynes
-
An unprecedented silver-mediated vicinal trifluoromethylation-iodination of arynes that quickly introduces CF3 and I groups onto aromatic rings in a single step to give o-trifluoromethyl iodoarenes has been developed. A new reactivity of AgCF3 has been revealed, and 2,2,6,6-tetramethylpiperidine plays an important role in this difunctionalization reaction.
- Zeng, Yuwen,Zhang, Laijun,Zhao, Yanchuan,Ni, Chuanfa,Zhao, Jingwei,Hu, Jinbo
-
p. 2955 - 2958
(2013/04/10)
-
- Silver-mediated trifluoromethylation of arenes using TMSCF3
-
The silver-mediated C-H trifluoromethylation of aromatic substrates using TMSCF3 is described. The development, optimization, and scope of these transformations are reported. AgCF3 intermediates are proposed.
- Ye, Yingda,Lee, Shin Hee,Sanford, Melanie S.
-
supporting information; experimental part
p. 5464 - 5467
(2011/12/05)
-
- Design and Synthesis of Novel Cyclooxygenase-1 Inhibitors as Analgesics: 5-Amino-2-ethoxy-N-(substituted-phenyl)benzamides
-
We previously found that N-(4-aminophenyl)-4-trifluoromethylbenzamide (TFAP), a COX-1 inhibitor, exhibits an analgesic effect without causing gastric damage. Unfortunately, TFAP causes reddish purple coloration of urine, and its analgesic effect is less potent than that of indomethacin. Herein we describe our study focusing on the development of 4- and 5-amino-2-alkoxy-N-phenylbenzamide scaffolds, designed on the basis of the structures of TFAP and parsalmide, another known COX-1 inhibitory analgesic agent. 5-Amino-2-ethoxy-N-(2- or 3-substituted phenyl)benzamide derivatives exhibited analgesic activity in a murine acetic acid induced writhing test. Among these compounds, 5-amino-2-ethoxy-N-(2-methoxyphenyl)benzamide (9v) possesses potent COX-1 inhibitory and analgesic activities, similar to those of indomethacin. In addition, 5-amino-2-ethoxy-N-(3-trifluoromethylphenyl)benzamide (9g) showed a more potent analgesic effect than indomethacin or 9v without causing apparent gastric damage or coloration of urine, although its COX-1 inhibitory activity was weaker than that of indomethacin or 9v. Thus, 9g and 9v appear to be promising candidates for analgesic agents and are attractive lead compounds for further development of COX-1 inhibitors.
- Fukai, Ryosuke,Zheng, Xiaoxia,Motoshima, Kazunori,Tai, Akihiro,Yazama, Futoshi,Kakuta, Hiroki
-
experimental part
p. 550 - 560
(2011/12/22)
-
- An aluminum ate base: Its design, structure, function, and reaction mechanism
-
An aluminum ate base, i-Bu3Al(TMP)Li, has been designed and developed for regio- and chemoselective direct generation of functionalized aromatic aluminum compounds. Direct alumination followed by electrophilic trapping with I2, Cu/Pd-catalyzed C-C bond formation, or direct oxidation with molecular O2 proved to be a powerful tool for the preparation of 1,2- or 1,2,3-multisubstituted aromatic compounds. This deprotonative alumination using i-Bu3Al(TMP)Li was found to be effective in aliphatic chemistry as well, enabling regio- and chemoselective addition of functionalized allylic ethers and carbamates to aliphatic and aromatic aldehydes. A combined multinuclear NMR spectroscopy, X-ray crystallography, and theoretical study showed that the aluminum ate base is a Li/Al bimetallic complex bridged by the nitrogen atom of TMP and the α-carbon of an i-Bu ligand and that the Li exclusively serves as a recognition point for electronegative functional groups or coordinative solvents. The mechanism of directed ortho alumination reaction of functionalized aromatic compounds has been studied by NMR and in situ FT-IR spectroscopy, X-ray analysis, and DFT calculation. It has been found that the reaction proceeds with facile formation of an initial adduct of the base and aromatic, followed by deprotonative formation of the functionalized aromatic aluminum compound. Deprotonation by the TMP ligand rather than the isobutyl ligand was suggested and reasoned by means of spectroscopic and theoretical study. The remarkable regioselectivity of the ortho alumination reaction was explained by a coordinative approximation effect between the functional groups and the counter Li+ ion, enabling stable initial complex formation and creation of a less strained transition state structure.
- Naka, Hiroshi,Uchiyama, Masanobu,Matsumoto, Yotaro,Wheatley, Andrew E. H.,McPartlin, Mary,Morey, James V.,Kondo, Yoshinori
-
p. 1921 - 1930
(2007/10/03)
-
- Regio- and chemoselective direct generation of functionalized aromatic aluminum compounds using aluminum ate base
-
A regio- and chemoselective direct method for generation of functionalized aromatic aluminum compounds through deprotonative directed ortho-alumination using triisobutyl(tetramethylpiperidino)aluminate (iBu3Al(TMP)Li), prepared by mixing of triisobutylaluminum (iBu3Al) and lithium tetramethylpiperidide (LTMP) in THF, has been developed. Deprotonative alumination of various functionalized benzenes with the use of iBu3Al(TMP)Li proved effective for the direct generation of various ortho-functionalized aluminum aromatic and heteroaromatic derivatives, particularly those with electrophilic functional groups such as cyano, amide, and halogen. Direct alumination, followed by electrophilic trapping (with I2), provided a convenient preparative method for 1,2- or 1,2,3-multisubstituted aromatic compounds. The functionalized aromatic aluminate intermediate also was found to undergo copper- and palladium-catalyzed C-C bond-forming reactions very efficiently and highly regio- and chemoselectively. Copyright
- Uchiyama, Masanobu,Naka, Hiroshi,Matsumoto, Yotaro,Ohwada, Tomohiko
-
p. 10526 - 10527
(2007/10/03)
-
- TRIFLUORMETHYLIERUNGSREAKTIONEN VON Te(CF3)2 MIT HALOGENBENZOLEN UND METHYLBENZOLEN
-
Substituent effects on yields and regioselectivity of photochemical and thermal trifluoromethylation reactions of Te(CF3)2 with halogen benzenes and methyl benzenes are investigated under comparable conditions.All reactions lead to trifluoromethylated products.The yields of the thermal are always higher than those of the corresponding photochemical reactions.The reactivity of the halobenzenes increases in the series C6H5-F a sidereaction, but H-substitution is the primary reaction pathway.During the reactions with iodobenzene tellurium containing compounds are also formed.The reactions with methyl benzenes show an increase in reactivity in the series hexamethylbenzene mesitylene toluene p-xylene.In all cases only ring substituted products are detected.Reactions with toluene and p-xylene yield tellurium containing compounds as well as addition products.The 19F-n.m.r spectra of the products are given.
- Naumann, Dieter,Kischkewitz, Jurgen
-
p. 283 - 299
(2007/10/02)
-
- Nucleophilic Displacement in Polyhalogenoaromatic Compounds. Part 11. Kinetics of Protiodeiodination of Iodoarenes in Dimethyl Sulphoxide-Methanol
-
The rates of methoxide-ion induced protiodeiodination of a number of polychloroiodobenzenes and their derivatives have been measured in dimethyl sulphoxide-methanol (9:1 v/v; 323.2 K).The true reagent under these conditions appears to be the dimethyl sulphoxide anion, and the rates of reaction in some cases appear to approach that expected of a diffusion controlled process.This corresponds to a major decrease in the efficacy of further activating substituents in the aromatic system, altough deactivating groups such as p-OMe still show large effects.Chlorine promotes protiodeiodination in the order of efficiency o-Cl > m-Cl > p-Cl; the trifluoromethyl group activates displacement in the order o-CF3 > p-CF3 > m-CF3, although with much less difference between isomeric sites. o-Nitro-groups promote protiodeiodination whereas the p-nitro-group encourages methoxydeiodination.No evidence of methoxydeiodination was found in attack of the polychloroiodobenzenes, although the rates of methoxydechlorination of the corresponding polychlorobenzenes suggest that in some cases this might occur.Evidence rejecting the possible SRN1 mechanism and supporting nucleophilic attack by a carbanionic species upon iodine is presented.
- Bolton, Roger,Moore, Clive,Sandall, John P.B.
-
p. 1593 - 1598
(2007/10/02)
-