1766-14-9Relevant academic research and scientific papers
Identifying the potential of pulsed LED irradiation in synthesis: Copper-photocatalysed C-F functionalisation
Nicholls, Thomas P.,Robertson, Johnathon C.,Gardiner, Michael G.,Bissember, Alex C.
, p. 4589 - 4592 (2018)
It has been reported that pulsed irradiation can improve photosynthetic activity and phytochemical production in plants. Intrigued and inspired by these observations, we postulated that pulsed irradiation strategies may have broader implications in organic synthesis. We report here the results of a proof-of-concept study demonstrating that pulsed LED irradiation enhances the efficiency of a visible light-mediated photoredox-catalysed reaction. The design and construction of an inexpensive multiphase circuit (～US$5) enabling power and pulse frequency modulation, which is connected to light-emitting diodes (LEDs), provides a source of pulsed visible light. This technology was then utilised to establish a novel copper-photocatalysed dual α-amino C-H/C-F functionalisation reaction. Pulsed blue LED irradiation was shown to be crucial for facilitating a much more efficient process and increasing the rate of product formation. Our results suggest that pulsed irradiation strategies have the potential to contribute to enhancing the synthetic utility and extending the scope of first row transition metal-based photoredox catalysts. We also anticipate that this approach will find wider applications in synthesis.
Activation of C-F bonds in ionic liquids catalyzed by nickel complex compounds
Prikhod'Kv,Adonin, N. Yu.,Parmon
, p. 33 - 38 (2013/11/19)
A nickel complex-catalyzed hydrodefluorination of acet(pentafluoroanilide) with zinc in ionic liquids resulted in the corresponding 2,3,4,5-tetrafluoro, 3,4,5-trifluoro, and 3,4-difluoro derivatives. The influence of the ionic liquid nature and the reaction conditions on its selectivity were studied, a possibility of the multiple reuse of the ionic liquids as the reaction media was demonstrated.
Hydrodefluorination of N-acetylheptafluoro-2-naphthylamine by zinc in aqueous ammonia: Synthetic outcomes and mechanistic considerations
Reshetov, Alexey V.,Selivanova, Galina A.,Politanskaya, Larisa V.,Beregovaya, Irina V.,Shchegoleva, Lyudmila N.,Vasil'eva, Nadezhda V.,Bagryanskaya, Irina Yu.,Shteingarts, Vitalij D.
experimental part, p. 242 - 262 (2011/10/09)
Reduction of the N-acetyl derivatives of heptafluoro-2-naphthylamine and its less fluorinated analogues by zinc in aqueous NH3 has been investigated as a possible general and concise route to partially fluorinated N-(2-naphthyl)acetamides and, accordingly, 2-naphthylamines inaccessible by other ways. Quantum chemical calculations and CV measurement results have been used to discuss and justify the suggested reaction mechanism including two competing routes: fragmentation of a substrate radical anion and its complex with a zinc cation. ARKAT-USA, Inc.
Discovery of [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl] acetic acids as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications
Van Zandt, Michael C.,Doan, Brian,Sawicki, Diane R.,Sredy, Janet,Podjarny, Alberto D.
supporting information; experimental part, p. 2006 - 2008 (2009/11/30)
Efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl] acetic acid aldose reductase inhibitors. The lead candidate, [6-methyl-3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyri din-1-yl]acetic acid example 16, inhibits aldose reductase with an IC50 of 8 nM, while being inactive against aldehyde reductase (IC50 > 100 μM), a related enzyme involved in the detoxification of reactive aldehydes.
N-acetylation as a means to activate polyfluoroarylamines for selective ortho-hydrodefluorination by zinc in aqueous ammonia: A concise route to polyfluorobenzo azaheterocycles
Laev, Sergey S.,Gurskaya, Larisa Yu.,Selivanova, Galina A.,Beregovaya, Irina V.,Shchegoleva, Lyudmila N.,Vasil'eva, Nadezhda V.,Shakirov, Makhmut M.,Shteingarts, Vitalij D.
, p. 306 - 316 (2007/10/03)
N-Acetylation of polyfluoroarylamines is proposed as a means to remove the amino group blocking effect of their hydrodefluorination by zinc in aqueous ammonia. With pentafluoroacetanilide, the Zn ion specific effect has been demonstrated to be responsible for ortho hydrodefluorination. This regiochemistry is accompanied by the removal of a fluorine atom from the para position, which occurs predominantly in the initial phase of the process in the absence of deliberately added zinc salt. The CuCl2 additive has been found to accelerate the reaction and to propel it to double defluorination. Quantum chemical calculations suggest a diminished electron affinity of pentafluoroaniline, which is responsible for its inertness in relation to the hydrodefluorination reaction. The pentafluoroaniline radical anion, which essentially has a nonplanar structure, is prone to easy fragmentation to give an aminotetrafluorophenyl radical. For pentafluoroacetanilide, CVA experiments and quantum chemical calculations predict that the pentafluorophenyl moiety serves as the electron receptor and that the acetamido group is twisted out of coplanarity with the benzene ring; thus, together with the electron-withdrawing effect of the acetyl group, the amino group blocking effect is suppressed. On this ground, the selective ortho hydrodefluorination of polyfluoroacetanilides is developed as an important protocol for the expeditious and general synthesis of polyfluorobenzo azaheterocycles via readily accessible polyfluoroarylamines from base polyfluoroarenes. Its applicability has been illustrated by preparing quinolines that possess a polyfluorinated benzene moiety by the Skraup synthesis utilizing crude polyfluoroacetanilide hydrodefluorination products as starting materials. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications
Van Zandt, Michael C.,Jones, Michael L.,Gunn, David E.,Geraci, Leo S.,Jones, J. Howard,Sawicki, Diane R.,Sredy, Janet,Jacot, Jorge L.,DiCioccio, A. Thomas,Petrova, Tatiana,Mitschler, Andre,Podjarny, Alberto D.
, p. 3141 - 3152 (2007/10/03)
Recent efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective 3-[(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors. The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat, 9) inhibits aldose reductase with an IC50 of 5 nM, while being 5400 times less active against aldehyde reductase, a related enzyme involved in the detoxification of reactive aldehydes. It lowers nerve and lens sorbitol levels with ED50's of 1.9 and 4.5 mg/kg/d po, respectively, in the 5-day STZ-induced diabetic rat model. In a 3-month diabetic intervention model (1 month of diabetes followed by 2 months of drug treatment at 5 mg/kg/d po), it normalizes polyols and reduces the motor nerve conduction velocity deficit by 59% relative to diabetic controls. It has a favorable pharmacokinetic profile (F, 82%; t1/2, 5.6 h; Vd, 0.694 L/kg) with good drug penetration in target tissues (Cmax in sciatic nerve and eye are 2.36 and 1.45 μg equiv/g, respectively, when dosed with [14C] lidorestat at 10 mg/kg po).
Substituted heteroarylalkanoic acids
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, (2008/06/13)
Disclosed are substituted heteroarylalkanoic acids acids of the following formula D-A-C(O)R′, where D, A, and R′ are defined herein. These compounds are useful in the treatment of chronic complications arising from diabetes mellitus. Also disclosed are pharmaceutical compositions containing the compounds and methods of treatment employing the compounds, as well as methods for their synthesis.
Methods of reducing serum glucose and triglyceride levels and for inhibiting angiogenesis using substituted indolealkanoic acids
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, (2008/06/13)
Disclosed are methods of reducing serum glucose and triglyceride levels and for inhibiting angiogenesis, the methods comprising administration of substituted indolealkanoic acids to patients in need of such treatment. Also disclosed are such compounds use
Substituted phenoxyacetic acids
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, (2008/06/13)
Disclosed are substituted phenoxyacetic acids useful in the treatment of chronic complications arising from diabetes mellitus. Also disclosed are pharmaceutical compositions containing the compounds, alone or in combination with other therapeutic agents, and methods of treatment employing the compounds and pharmaceutical compositions, as well as methods for their synthesis.
A new approach to polyfluoroaromatic amines with an unsubstituted position ortho to the amino group
Laev,Evtefeev,Shteingarts
, p. 43 - 46 (2007/10/03)
N-acetyl derivatives of polyfluoroaromatic amines have been found to be highly selectively defluorinated by zinc in aqueous ammonia at the position ortho to the acetamido group thus affording a new approach to potential building blocks for the synthesis o
