- Biocatalytic Reduction of 2-Monosubstituted 3-Thiazolines Using Imine Reductases
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The application of a straightforward biocatalytic technology for the reduction of racemic 2-monosubstituted 3-thiazolines, which are easily prepared via Asinger-multicomponent reaction, is reported. The biocatalytic reduction yields racemic 2-monosubstituted 3-thiazolidines, which are difficult to be prepared by means of classic chemical routes, in moderate to high yields. Moreover, our study clarifies the stereochemical reaction course of the biocatalytic reduction. Furthermore, the efficiency of this biocatalytic technology is demonstrated in an experiment at an elevated substrate concentration of 60?mM leading to 96% conversion.
- Zumbr?gel, Nadine,Wagner, Karla,Wei?ing, Nils,Gr?ger, Harald
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p. 788 - 794
(2019/01/24)
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- PROCESS FOR THE PREPARATION OF 2,2-DIMETHYLPIPERAZINE
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This invention relates to a novel chemical process for the synthesis of 2,2-dimethylpiperazine and the further transformation of 2,2-dimethylpiperazine into ferf-butyl-3,3-dimethylpiperazine-l- carboxylate-hemi-DL-tartrate.
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Page/Page column 10; 11; 12
(2019/10/29)
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- Synthesis and low temperature spectroscopic observation of 1,3,5-trioxane-2,4,6-trione: The cyclic trimer of carbon dioxide
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1,3,5-Trioxane-2,4,6-trione (cyclic trimer of CO2) is the product of a four-step synthesis: chlorination of isobutyraldehyde; cyclotrimerization of 2-chloro-2-methylpropanal; dehydochlorination of 2,4,6-tris(2-chloropropan)-2-yl-1,3,5-trioxane; ozonolysis at -80 °C of 2,4,6-tri(propan-2-ylidene)-1,3,5-trioxane. This trioxane-trione is detected in solution at temperatures between -80 to -40 °C, and its conversion to CO2 is monitored by 13C NMR and FTIR. The CO2 trimer has a half-life of approximately 40 min at -40 °C.
- Rodig, Michael J.,Snow, Arthur W.,Scholl, Paul,Rea, Simon
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p. 5354 - 5361
(2016/07/13)
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- INHIBITORS OF BETA-SECRETASE
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The present invention relates to spirocyclic acylguanidines and their use as inhibitors of the β-secretase enzyme (BACE1) activity, pharmaceutical compositions containing the same, and methods of using the same as therapeutic agents in the treatment of neurodegenerative disorders, disorders characterized by cognitive decline, cognitive impairment, dementia and diseases characterized by production of β-amyloid aggregates.
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Paragraph 0199-0200
(2014/03/24)
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- Stereocontrolled 1,3-phosphatyloxy and 1,3-halogen migration relay toward highly functionalized 1,3-dienes
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A double migratory cascade reaction of α-halogen-substituted propargylic phosphates to produce highly functionalized 1,3-dienes has been developed. This transformation features 1,3-phosphatyloxy group migration followed by 1,3-shifts of bromine and chlorine as well as the unprecedented 1,3-migration of iodine. The reaction is stereodivergent: (Z)-1,3-dienes are formed in the presence of a copper catalyst, whereas gold-catalyzed reactions exhibit inverted stereoselectivity, producing the corresponding E products.
- Kazem Shiroodi, Roohollah,Dudnik, Alexander S.,Gevorgyan, Vladimir
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supporting information; experimental part
p. 6928 - 6931
(2012/06/15)
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- 2'-O-AMINOOXYMETHYL NUCLEOSIDE DERIVATIVES FOR USE IN THE SYNTHESIS AND MODIFICATION OF NUCLEOSIDES, NUCLEOTIDES AND OLIGONUCLEOTIDES
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Disclosed are O-protected compounds of the formula (I):wherein B is an optionally protected nucleobase, and R1-R3 are as described herein, a method of preparing such compounds, and a method of preparing oligonucleotides such as RNA starting from such compounds. The O-protected compounds have one or more advantages, for example, the 2'-O-protected compound is stable during the various reaction steps involved in oligonucleotide synthesis; the protecting group can be easily removed after the synthesis of the oligonucleotide, for example, by reaction with tetrabutylammonium fluoride; and/or the O-protected groups do not generate DNA/RNA alkylating side products, which have been reported during removal of 2'-O-(2-cyanoethyl)oxymethyl or 2'-O-[2-(4-tolylsulfonyl)ethoxymethyl groups under similar conditions.
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Page/Page column 45
(2012/10/18)
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- Effects of sulphur nutrition during potato cultivation on the formation of acrylamide and aroma compounds during cooking
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Lack of sulphur nutrition during potato cultivation has been shown to have profound effects on tuber composition, affecting in particular the concentrations of free asparagine, other amino acids and sugars. This is important because free asparagine and sugars react at high temperatures to form acrylamide, a suspect carcinogen. Free amino acids and sugars also form a variety of other compounds associated with colour and flavour. In this study the volatile aroma compounds formed in potato flour heated at 180 °C for 20 min were compared for three varieties of potato grown, with and without sulphur fertiliser. Approximately 50 compounds were quantified in the headspace extracts of the heated flour, of which over 40 were affected by sulphur fertilisation and/or variety. Many of the 41 compounds found at higher concentrations in the sulphur-deficient flour were Strecker aldehydes and compounds formed from their condensation, whereas only one compound, benzaldehyde, behaved in the same way as did acrylamide and was found at higher concentrations in the sulphur-sufficient flour. The reasons for these effects are discussed.
- Elmore,Dodson,Muttucumaru,Halford,Parry,Mottram
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body text
p. 753 - 760
(2011/11/14)
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- Oxidation of alcohols by chlorine dioxide in organic solvents
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The kinetics of oxidation of a series of alcohols (propan-2-ol, 2-methylpropan-1-ol, butan-1-ol, butan-2-ol, 3-methylpentan-1-ol, heptan-4-ol, decan-2-ol, cyclohexanol, borneol) by chlorine dioxide in organic solvents was studied using spectrophotometry. The reaction is described by the second-order rate equation w = k[ROH][ClO2]. The rate constants were measured in the range of 10-60 °C, and the activation parameters of the processes were calculated. The products were identified, and the yields were determined.
- Ganieva,Ganiev,Grabovskiy,Kabalnova
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body text
p. 2328 - 2331
(2010/02/15)
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- Rearrangement of 4-(1-haloalkyl)- and 4-(2-haloalkyl)-2-azetidinones into methyl ω-alkylaminopentenoates via transient aziridines and azetidines
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The synthesis of 4-(1-haloalkyl)-2-azetidinones and 4-(2-haloalkyl)-2- azetidinones was investigated with use of the Staudinger reaction between in situ generated ketenes and α-haloimines or β-haloimines. This new class of functionalized 2-azetidinones was further evaluated for its potential use as intermediates in the synthesis of highly functionalized compounds. The reaction of 4-(1-haloalkyl)-2-azetidinones and 4-(2-haloalkyl)-2-azetidinones with sodium methoxide in methanol yielded ring-opened products, i.e., methyl 2-alkoxy-4-(alkylamino)pentenoate and methyl 5-(alkyl-amino)pentenoate, respectively. Further attention was paid in detail to the reaction mechanism involved in this peculiar transformation. It was proven that these reactions proceeded via intermediate aziridines or azetidines.
- Dejaegher, Yves,De Kimpe, Norbert
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p. 5974 - 5985
(2007/10/03)
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- Oxidation of benzylic alcohols and ethers to carbonyl derivatives by nitric acid in dichloromethane
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Nitric acid in dichloromethane may be successfully employed for the oxidation of benzylic alcohols and ethers to the corresponding carbonyl compounds. The proposed method proved to be of general applicability, affording very good yields of aldehydes and ketones and showing interesting chemoselectivity in many instances, allowing competitive aromatic nitration to be avoided, as well as - in the case of aldehydes - any further oxidation to carboxylic acids. The reaction probably proceeds by a radical mechanism, the active species in the oxidation process being NO2. Competitive formation of nitro esters was observed in some cases, whereas poor results were obtained with allylic and non-benzylic substrates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Strazzolini, Paolo,Runcio, Antonio
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p. 526 - 536
(2007/10/03)
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- Oxidation of Isopropylcyclopropane by Chromyl Chloride: Ring-Opened Products Support a Hydrogen Atom Abstraction Mechanism
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Chromyl chloride (CrO2Cl2) reacts with neat isopropylcyclopropane at 65 °C to give a dark precipitate along with at least 20 organic products. Both cyclopropyl products and ring-opened products are observed: 2-cyclopropyl-2-chloropropane (1,0.4% yield based on chromium), 2-cyclopropyl-2-propanol (2, 0.2%), 5-chloro-2-methyl-2-pentene (3, 0.3%), and 4-methyl-3-penten-1-ol (4, 0.5%) as well as other ring-opened products. Authentic samples of 1-4 were synthesized, and their GC and GC/ MS data were compared with the reaction mixture. Other organic products (5-10) were tentatively assigned by GC/MS on the basis of their m / z and fragmentation patterns. The ratio of (1 + 2) vs (3 + 4) increases by a factor of 2 when the initial concentration of CrO2Cl2 increases from 0.3 to 1.12 M. The reaction was also carried out in the gas phase, and essentially all the products from the liquid phase reaction were observed. The products are explained by a mechanism involving initial hydrogen atom abstraction from the substrate. The resulting dimethylcyclopropylcarbinyl radical can either be trapped by CrO2Cl2 (to form 1 and 2) or ring-open to give 4-methyl-3-pentenyl radical, which reacts with CrO2Cl2 to form 3 and 4 as well as further oxidized products. The oxidation of isopropylcyclopropane by MnO4- in pyridine was also examined. Acetone, an expected ring-opened product, was the only product observed by our analytical techniques. Me2C18O is produced from 18O-labeled MnO4-. These results suggest that the reactions of CrO2Cl2 and MnO4- with isopropylcyclopropane proceed by hydrogen atom transfer to form organic radical intermediates.
- Wang, Kun,Mayer, James M.
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p. 4248 - 4252
(2007/10/03)
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- 12-hetero substituted 6,11-ethano-6,11-dihydrobenzo (b) quinolizinium salts and compositions and method of use thereof
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1-Hetero substituted 6,11-ethano-6,11-dihydrobenzo[b]quinolizinium salts, pharmaceutical compositions containing them, and methods for the treatment or prevention of neurodegenerative disorders or neurotoxic injuries utilizing them.
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- C-H bond activation by metal oxo species: Chromyl chloride oxidations of cyclooctane, isobutane, and toluene
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Chromyl chloride, CrO2Cl2, oxidizes cyclooctane, isobutane, and toluene under mild conditions (25-60 °C). The reactions give chlorinated products (chlorocyclooctane, tert-butyl chloride, and benzyl chloride) and a dark chromium-containing precipitate. Hydrolysis of the precipitate yields oxygenated products, such as ketones, aldehydes, chloro ketones, epoxides, and alcohols. Kinetic data show that all of the reactions are first order in CrO2Cl2 and first order in substrate, with no sign of an induction period. Primary isotope effects have been observed for t-d1-isobutane and d8-toluene. The kinetic and mechanistic data indicate that the reactions proceed by initial hydrogen atom transfer from the substrate to CrO2Cl2 The rates of hydrogen atom abstraction by CrO2Cl2 vary in the order cyclohexane ? and ΔS?, indicating a common mechanism for the four substrates. The pathways leading from the initially formed alkyl radicals to the observed products are described. The ability of CrO2Cl2 to abstract a hydrogen atom from alkanes is remarkable, as it is a closed-shell, diamagnetic species, not a radical. It is proposed that the hydrogen atom abstracting ability derives from the strong O-H bond formed on hydrogen atom transfer, in [Cl2(O)Cr(OH)]. The rates of the CrO2Cl2 reactions correlate with rates of hydrogen atom abstraction by oxygen radicals, assuming a CrO-H bond strength of 83 kcal/mol (similar to that in HMnO4-). The implications of this perspective for transition metal mediated hydrogen atom transfer reactions are discussed.
- Cook, Gerald K.,Mayer, James M.
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p. 7139 - 7156
(2007/10/02)
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- Synthesis and Reactivity of 3-Oxazolines
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3-Oxazolines 1 have been prepared from α-hydroxy aldehydes, ammonia, water and a second oxo compound (aldehyde or ketone) in a one-pot reaction.Carboxylic acid chlorides add to the azomethine bond of 1 to yield 3-acyl-4-chlorooxazolidines 2. 4-Hydroxy and 4-alkoxyoxazolidines 3 are obtained from 2 upon treatment with aqueons sodium hydroxide or alkanol/triethyl amine, respectively.Some oxazolidines 3 are formed with high diastereoselectivity. Key Words: Oxazole, 2,5-dihydro- / Oxazolidine / Acyliminium ion
- Weber, Maya,Jakob, Juergen,Martens, Juergen
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- N-HALOAMIDINES.VI. REACTION OF N-CHLORO-N'-BENZENESULFONYLBENZAMIDINES WITH ENAMINES.
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The reaction between N-chloro-N'-benzenesulfonylbenzamidines and β,β-disubstituted enamines affords N-(benzenesulfonyl)-N'--benzamidines.When both β-substituents are methyl groups the open chain adducts have been isolated and characterized, whereas, when one of the two substituents is a phenyl group, they have been characterized only by PMR because of the easy cyclization to 1-benzenesulfonyl-4,5-dihydroimidazoles.
- Rossi, E.,Stradi, R.,Benedusi, A.
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p. 4785 - 4792
(2007/10/02)
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- The pKa values of simple aldehydes determined by kinetics of chlorination
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From the kinetics of chlorination of acetaldehyde and isobutyraldehyde we have been able to determine the pKa values of the free aldehydes (corrected for covalent hydration) as 16.9 +/- 0.5 and 15.7 +/- 0.5 respectively.These values are in resonable accord with other work and show that our kinetic method for ketone pKa's can be extended to aldehydes.For isobutyraldehyde tha transition from rate-determining halogenation to rate-determining enolization occurs at -> values around 10-3 M for hydroxide concentrations of 0.1 to 1.For acetaldehyde the transition would only occur at much higher ->.
- Guthrie, J.Peter,Cossar, John
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p. 2470 - 2474
(2007/10/02)
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- Process of preparing α-formyl sulfides and 2-hydrocarbylthioaldoximes therefrom
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An α-formyl sulfide is prepared by a process which comprises reacting in an aqueous medium an α-haloaldehyde of the formula EQU1 wherein R' and R" independently are hydrogen, hydrocarbon radicals of 1 to 18 carbon atoms selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl and aryl, or substituted hydrocarbon radicals of the above group, and X is a halogen selected from the group consisting of chlorine, bromine, and iodine, with a thiol salt of the formula R"'SM, wherein R"' is a hydrocarbon radical of 1 to 18 carbon atoms selected from the group consisting of alkyl, cycloalkyl, alkenyl, cycloalkenyl and aryl or a substituted hydrocarbon radical of the above group; and M is an alkali or alkaline earth metal, thereby forming an α-formyl sulfide of the formula EQU2 Also, 2-hydrocarbylthioaldoximes are prepared by oximating the above α-sulfides by reaction with a source of hydroxylamine. Additionally, 2-hydrocarbylthioaldoximes are prepared by a process which comprises halogenating an aldehyde having the formula EQU3 wherein R' and R" are defined as above, to form an α-haloaldehyde of the formula EQU4 wherein X is defined as above, reacting in an aqueous medium the α-haloaldehyde with a thiol salt of the formula R"'SM, wherein R"' and M are defined as above, to form an α-formyl sulfide of the formula EQU5 and oximating the α-formyl sulfide to form a 2-hydrocarbylthioaldoxime of the formula EQU6
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