- Photoredox-Induced Radical Relay toward Functionalized β-Amino Alcohol Derivatives
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A radical relay strategy is described to synthesize functionalized β-amino alcohols. This strategy is enabled by photoredox-catalyzed and nitrogen-centered radical-triggered cascade reactions of styrenes (or phenylacetylenes), enol derivatives, and O-acyl hydroxylamines in DMSO. The broad synthetic application of this method is demonstrated by the reaction of structurally diverse reaction components, including complex molecular scaffolds. Multiple functional groups of the resultant highly functionalized β-amino alcohol derivatives facilitate their further transformations.
- An, Xiao-De,Jiao, Yan-Yan,Zhang, Hao,Gao, Yuxiang,Yu, Shouyun
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supporting information
p. 401 - 404
(2018/01/28)
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- Cu(II)-promoted methanolysis of N, N -bis(2-picolyl)carbamates: Rate-limiting metal ion delivery of coordinated alcoholate nucleophile followed by fast partitioning of a tetrahedral intermediate
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Five O-aryl/alkyl N,N-bis(2-picolyl)carbamates were prepared with the O-aryl/alkyl portions being p-nitrophenoxy, m-nitrophenoxy, trifluoroethoxy, methoxy, and isopropoxy (4a,b,c,d,e, respectively) and the kinetics and reaction products of their methanolysis reactions in the presence of Cu(O3SCF3)2 determined. The catalyzed reactions have maximal rates for each substrate at a 1:1 ratio of [4]:[Cu2+] at sspH 7.9, where the active forms are Cu(II):4:(-OCH3). The reactions are fast, that for the complex of 4a having a t1/2 of 30 s. The products of the reaction with 4a and 4b arise exclusively from C-OAr cleavage: those with 4d and 4e arise exclusively from C-N cleavage. With 4c, products from both C-O and C-N cleavage are observed in a 2.17:1 ratio. The common mechanism involves rate-limiting delivery of a Cu(II)-coordinated methoxide to the C=O unit to form a tetrahedral intermediate followed by fast partitioning to products by two pathways with relative barriers dependent on the sspKaHOAr/HOR. The data allow one to predict an effective sspKa of ~15.6 for the sspKaNH of Cu(II):bis(2-picolyl)amine.
- Neverov, Alexei A.,Cimpean, Luana,Chiykowski, Valerie,Vance, Tyler,Brown, R. Stan
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p. 1357 - 1364
(2015/02/19)
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- Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors
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A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, 1H, 13C and 19F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.
- Imramovsky, Ale?,Pejchal, Vladimír,?těpánková, ?árka,Vor?áková, Katarína,Jampílek, Josef,Van?o, Ján,?im?nek, Petr,Královec, Karel,Br??ková, Lenka,Mandíková, Jana,Trejtnar, Franti?ek
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p. 1735 - 1748
(2013/05/08)
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- Synthesis and properties of di(polyfluoroalkyl) peroxydicarbonates
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Synthesis of di(polyfluoroalkyl)peroxydicarbonates [X(CF2) nCH2OC(O)O]2, where X = H, F; n = 1, 2, 4, 6 (yield 80%) involves the step of the chloroformate formation (yield up to 93%) via the phosgenation of polyfluorinated alcohols followed by the reaction with sodium peroxide. The rate constant of monomolecular decomposition k term was found to decrease as the polyfluoroalkyl groups were incorporated into the peroxide: it equaled 3.30 and 3.10 s-1 for X = H, n = 2 and 4, respectively, and 7.36 s-1 for di-n- butylperoxydicarbonate. The new peroxides are a source of the polyfluoroalkoxy radicals and nano-modifiers of the polymers to improve their heat resistance and light stability. Pleiades Publishing, Ltd., 2011.
- Rakhimov,Butkovskaya
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experimental part
p. 884 - 889
(2011/09/14)
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- A facile synthesis of unsymmetrical ureas
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A facile and versatile method for the synthesis of unsymmetrical ureas from readily available reagents is reported. In the first step trifluoroethylchloroformate is reacted with a stoichiometric amount of a primary amine to give an intermediate trifluoroethyl carbamate. The addition of a second amine (primary or secondary) to the trifluoroethyl carbamate furnishes corresponding unsymmetrical ureas in 75-85% yield. A simple workup procedure, the high yields obtained, and the purity of the isolated products are suitable for the parallel synthesis of combinatorial libraries of unsymmetrical ureas with high structural and functional diversity.
- Bogolubsky, Andrey V.,Ryabukhin, Sergey V.,Pipko, Sergey E.,Lukin, Oleg,Shivanyuk, Alexander,Mykytenko, Dmytro,Tolmachev, Andrey
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experimental part
p. 3619 - 3623
(2011/06/21)
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- Cyclization-Activated Prodrugs: N-(Substituted 2-hydroxyphenyl and 2-hydroxypropyl)carbamates Based on Ring-Opened Derivatives of Active Benzoxazolones and Oxazolidinones as Mutual Prodrugs of Acetaminophen
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N-(Substituted 2-hydroxyphenyl)- and N-(substituted 2-hydroxypropyl)carbamates based on masked active benzoxazolones (model A) and oxazolidinones (model B), respectively, were synthesized and evaluated as potential drug delivery systems.A series of alkyl and aryl N-(5-chloro-2-hydroxyphenyl)carbamates 1 related to model A was prepared.These are open drugs of the skeletal muscle relaxant chlorzoxazone.The corresponding 4-acetamidophenyl ester named chloracetamol is a mutual prodrug of chloroxazone and acetaminophen.Chlorzacetamol and two other mutual prodrugs of active bezoxazolones and acetaminophen were obtained in a two-step process via condensation of 4-acetamidophenyl 1,2,2,2-tetrachloroethyl carbonate with the appropiate anilines.Based on model B, two mutual prodrugs of acetaminophen and active oxazolidinones (metaxalone and mephenoxalone) were similarly obtained using the appropiate amines.All the carbamate prodrugs prepared were found to release the parent drugs in aqueous (pH 6-11) and plasma (pH 7.4) media.The detailed mechanistic study of prodrugs 1 carried out in aqueous medium at 37 deg C shows a change in the Broensted-type relationship log t1/2 vs pKa of the leaving groups ROH: log t1/2 = 0.46pKa - 3.55 for aryl and trihalogenoethyl esters and log t1/2 = 1.46pKa - 16.03 for alkyl esters.This change is consistent with a cyclization mechanism involving a change in the rate-limiting step from formation of a cyclic tetrahedral intermediate (step k1) to departure of the leaving group ROH (step k2) when the leaving group ability decreases.This mechanism occurs for all the prodrugs related to model A.Regeneration of the parent drugs from mutual prodrugs related to model B takes place by means of a rate-limiting elimination-addition reaction (E1cB mechanism).This affords acetaminophen and the corresponding 2-hydroxypropyl isocyanate intermediates which cyclize at any pH to the corresponding oxazolidinone drugs.As opposed to model A, the rates of hydrolysis of mutual prodrugs of model B clearly exhibit a catalytic role of the plasma.It is concluded from the plasma studies that the carbamate substrates can be enzymatically transformed into potent electrophiles, i.e., isocyanates.In the case of the present study, the prodrugs are 2-hydroxycarbamates for which the propinquity of the hydroxyl residue and the isocyanate group enforces a cyclization reaction.This mechanistic particularity precludes their potential toxicity in terms of potent electrophiles capable of modifying critical macromolecules.
- Vigroux, Alain,Bergon, Michel,Zedde, Chantal
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p. 3983 - 3994
(2007/10/03)
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- Unsymmetrical polynitrocarbonates and methods of preparation
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Unsymmetrical carbonates of the formula STR1 are prepared by the following reaction sequence STR2 where R and R' can each be --CH2 C(NO2)3, CH2 CF(NO..2)2, --CH2 CF2 (NO2), --CH2 CCl(NO2)2, --CH2 CF3, --CH2 CCl3, --CH2 C(NO2)2 CH3, or --CH2 CF2 CF2 H, provided that R≠R' and wherein R" is a lower alkyl group of from 1 to 6 carbon atoms. Also included are symmetrical 1,3-bis(halo- and nitroalkyl carbonyldioxy)-2,2-dinitropropanes of the formula STR3 which are synthesis by the following reaction sequence STR4 wherein R and R" are as defined above. The carbonates of this invention are useful as energetic additives to propellants and explosive.
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- Herbicidal fluorinated carbonates
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Fluorinated carbonates are described which are useful as miticides. These carbonates often possess herbicidal, insecticidal, and/or fungicidal properties. Examples of the fluorinated carbonates are 2',4'-dinitro-6'-sec-butylphenyl-2,2,2-trifluoroethyl carbonate; 2',4'-dinitro-6'-sec-butylphenyl-2,2,3,3-tetrafluoropropyl carbonate and 2',4'-dinitro-6'-cyclohexylphenyl 2,2,3,3-tetrafluoropropyl carbonate.
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