86569-78-0Relevant articles and documents
Direct C–H Carboxylation Forming Polyfunctionalized Aromatic Carboxylic Acids by Combined Br?nsted Bases
Hanasaka, Kazuya,Izumi, Koki,Kondo, Yoshinori,Kwon, Eunsang,Nozawa-Kumada, Kanako,Shigeno, Masanori,Tohara, Itsuki,Yamakoshi, Hiroyuki
, p. 809 - 814 (2022/02/05)
CO2 fixation into electron-deficient aromatic C–H bonds proceeds with the combined Br?nsted bases LiO-t-Bu and LiO-t-Am/CsF/18-crown-6 (t-Am = CEtMe2) under a CO2 atmosphere to afford a variety of polyfunctionalized aromat
Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program
Zhang, Ting,Liu, Yong,Yang, Xianshu,Martin, Gary E.,Yao, Huifang,Shang, Jackie,Bugianesi, Randal M.,Ellsworth, Kenneth P.,Sonatore, Lisa M.,Nizner, Peter,Sherer, Edward C.,Hill, Susan E.,Knemeyer, Ian W.,Geissler, Wayne M.,Dandliker, Peter J.,Helmy, Roy,Wood, Harold B.
, p. 1818 - 1829 (2016/03/22)
A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure-activity relationships (SARs) and guide drug design via microisolation-structural characterization and ALIS capabilities.
Correlation of the rates of solvolysis of 3,4,5-trimethoxy- and 2,4,6-trichlorobenzoyl chlorides
Park, Kyoung-Ho,Kevill, Dennis N.
, p. 647 - 653,7 (2020/07/30)
The introduction of methoxy groups into the 3- and 5-positions of 4-methoxybenzoyl chloride leads to a reduction in specific rates of solvolysis. An extended Grunwald-Winstein equation correlation for the specific rates of solvolysis of 3,4,5-trimethoxybenzoyl chloride gives sensitivities towards changes in solvent nucleophilicity (l value) of 0.29 and towards changes in solvent ionising power (m value) of 0.54. The low m value allows specific rates to be determined in highly ionising fluoroalcohol-H2O mixtures. A parallel correlation of the specific rates of solvolysis of 2,4,6- trichlorobenzoyl chloride reveals that solvolyses in 100% and 90% ethanol or methanol do not appreciably follow the ionisation pathway indicated for solvolyses in the other solvents and it is proposed that, despite the two ortho-substituents, the addition-elimination pathway has become dominant.
A New Trifluoromethylating Agent: Synthesis of Polychlorinated (Trifluoromethyl)benzenes and 1,3-Bis(trifluoromethyl)benzenes and Conversion into Their Trichloromethyl Counterparts and Molecular Structure of Highly Strained Polychloro-m-xylenes
Castaner, J.,Riera, J.,Carilla, J.,Robert, A.,Molins, E.,Miravitlles, C.
, p. 103 - 110 (2007/10/02)
Mixtures of CCl3F and AlCl3 replace CF3 for H in polychlorobenzenes.Thus, by treatment of a solution of the suitable polychlorobenzene in CCl3F with AlCl3, the following compounds can be prepared: pentachloro- (2), 2,3,4,5-tetrachloro- (5), 2,3,4,6-tetrachloro- (8), 2,3,5,6-tetrachloro- (11), 2,3,4-trichloro- (14), 2,4,5-trichloro- (17), and 2,4,6-trichloro-1-(trifluoromethyl)benzene (20), as well as 4,5,6-trichloro- (31) and 2,4,6-trichloro-1,3-bis(trifluoromethyl)benzene (32).The reaction of the above-mentioned trifluoromethylated compounds with AlCl3 in CS2 yieldstheir trichloromethyl counterparts: 3, 6, 9, 12, 15, 18, 21, 34, and 36.The chlorination of 32 or 36 by means of Silberrad's reagent (SO2Cl2, AlCl3, and S2Cl2) affords perchloro-m-xylene (38), a new highly strained chlorocarbon whose synthesis was attempted repeatedly in the past. 9, 15, 17, and 21, when treated with oleum and then with water, are converted into 2,3,4,6-tetrachloro- (22), 2,3,4-trichloro- (23), 2,4,5-trichloro- (24), and 2,4,6-trichlorobenzoic acid (25), respectively; under similar treatment, 34, 36, and 38 give 4,5,6-trichloro- (33), 2,4,5-trichloro- (35), and tetrachloroisophthalic acid (39), respectively.The formation of the (trifluoromethyl)benzenes is discussed, and in this connection it has been found that CCl3F solutions of 3 and 18 in the presence of AlCl3 give back 2 and 17, respectively.Molecular structures of highly strained m-xylenes 36 and 38, as well as that of the much less strained 34, ascertained by X-ray analysis, are reported and commented.IR, UV, and NMR spectral data of the compounds synthesized are presented.The interesting UV spectrum of 21 is discussed.
