- Methylation with Dimethyl Carbonate/Dimethyl Sulfide Mixtures: An Integrated Process without Addition of Acid/Base and Formation of Residual Salts
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Dimethyl sulfide, a major byproduct of the Kraft pulping process, was used as an inexpensive and sustainable catalyst/co-reagent (methyl donor) for various methylations with dimethyl carbonate (as both reagent and solvent), which afforded excellent yields of O-methylated phenols and benzoic acids, and mono-C-methylated arylacetonitriles. Furthermore, these products could be isolated using a remarkably straightforward workup and purification procedure, realized by dimethyl sulfide‘s neutral and distillable nature and the absence of residual salts. The likely mechanisms of these methylations were elucidated using experimental and theoretical methods, which revealed that the key step involves the generation of a highly reactive trimethylsulfonium methylcarbonate intermediate. The phenol methylation process represents a rare example of a Williamson-type reaction that occurs without the addition of a Br?nsted base.
- Chan, Bun,Lui, Matthew Y.,Lui, Yuen Wai
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- Rationalizing the Unprecedented Stereochemistry of an Enzymatic Nitrile Synthesis through a Combined Computational and Experimental Approach
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In this contribution, the unique and unprecedented stereochemical phenomenon of an aldoxime dehydratase-catalyzed enantioselective dehydration of racemic E- and Z-aldoximes with selective formation of both enantiomeric forms of a chiral nitrile is rationalized by means of molecular modelling, comprising in silico mutations and docking studies. This theoretical investigation gave detailed insight into why with the same enzyme the use of racemic E- and Z-aldoximes leads to opposite forms of the chiral nitrile. The calculated mutants with a larger or smaller cavity in the active site were then prepared and used in biotransformations, showing the theoretically predicted decrease and increase of the enantioselectivities in these nitrile syntheses. This validated model also enabled the rational design of mutants with a smaller cavity, which gave superior enantioselectivities compared to the known wild-type enzyme, with excellent E-values of up to E>200 when the mutant OxdRE-Leu145Phe was utilized.
- Yavuzer, Hilmi,Asano, Yasuhisa,Gr?ger, Harald
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supporting information
p. 19162 - 19168
(2021/07/26)
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- Rhenium(I)-Catalyzed C-Methylation of Ketones, Indoles, and Arylacetonitriles Using Methanol
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A ReCl(CO)5/MeC(CH2PPh2)3 (L2) system was developed for the C-methylation reactions utilizing methanol and base, following the borrowing hydrogen strategy. Diverse ketones, indoles, and arylacetonitriles underwent mono-and dimethylation selectively up to 99% yield. Remarkably, tandem multiple methylations were also achieved by employing this catalytic system.
- Shee, Sujan,Kundu, Sabuj
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p. 6943 - 6951
(2021/05/29)
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- Preparation method of alkyl nitrile compound
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The invention discloses a preparation method of an alkyl nitrile compound. Specifically, the preparation method comprises the following step: in an organic solvent, in the presence of a protective gasand under the action of a catalyst, carrying out a reduction reaction as shown in the specification on olefin as shown in a formula I, a cyanation reagent and water, wherein the alkyl nitrile compound 1 is a compound II and/or a compound III. The preparation method provided by the invention is mild in condition, can realize hydrocyanation of olefin more safely and efficiently, and has good substrate universality and functional group compatibility.
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-
Paragraph 0130-0132; 0156-0158
(2020/08/18)
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- Overcoming Selectivity Issues in Reversible Catalysis: A Transfer Hydrocyanation Exhibiting High Kinetic Control
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Reversible catalytic reactions operate under thermodynamic control, and thus, establishing a selective catalytic system poses a considerable challenge. Herein, we report a reversible transfer hydrocyanation protocol that exhibits high selectivity for the thermodynamically less favorable branched isomer. Selectivity is achieved by exploiting the lower barrier for C-CN oxidative addition and reductive elimination at benzylic positions in the absence of a cocatalytic Lewis acid. Through the design of a novel type of HCN donor, a practical, branched-selective, HCN-free transfer hydrocyanation was realized. The synthetically useful resolution of a mixture of branched and linear nitrile isomers was also demonstrated to underline the value of reversible and selective transfer reactions. In a broader context, this work demonstrates that high kinetic selectivity can be achieved in reversible transfer reactions, thus opening new horizons for their synthetic applications.
- Bhawal, Benjamin N.,Ehinger, Christian,Morandi, Bill,Reisenbauer, Julia C.
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supporting information
p. 10914 - 10920
(2020/07/13)
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- Luminescent tungsten(vi) complexes as photocatalysts for light-driven C-C and C-B bond formation reactions
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The realization of photocatalysis for practical synthetic application hinges on the development of inexpensive photocatalysts which can be prepared on a large scale. Herein an air-stable, visible-light-absorbing photoluminescent tungsten(vi) complex which can be conveniently prepared at the gram-scale is described. This complex could catalyse photochemical organic transformation reactions including borylation of aryl halides, such as aryl chloride, reductive coupling of benzyl bromides for C-C bond formation, reductive coupling of phenacyl bromides, and decarboxylative coupling of redox-active esters of alkyl carboxylic acid with high product yields and broad functional group tolerance.
- Chan, Kaai-Tung,Che, Chi-Ming,Du, Lili,Liu, Yungen,Phillips, David Lee,To, Wai-Pong,Tong, Glenna So Ming,Wu, Liang-Liang,Yu, Daohong
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p. 6370 - 6382
(2020/07/15)
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- Ni-Catalyzed hydrocyanation of alkenes with formamide as the cyano source
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CN generation from formamide dehydration! A novel Ni-catalyzed hydrocyanation of various alkenes to provide aliphatic nitriles is developed by generating hydrocyanic acid in situ from safe and readily available formamide. Excellent linear or branched regio-selectivity, wide substrate scope, cheap and stable nickel salt as a pre-catalyst, a safe cyano source, slow generation of CN to obviate catalyst deactivation and convenient experimental operation would render this hydrocyanation attactive for laboratory synthesis of aliphatic nitriles.
- Shu, Xiao,Jiang, Yuan-Yuan,Kang, Lei,Yang, Luo
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supporting information
p. 2734 - 2738
(2020/06/17)
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- Nickel-Catalyzed Markovnikov Transfer Hydrocyanation in the Absence of Lewis Acid
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Hydrocyanation in the absence of toxic HCN gas is highly desirable. Addressing that challenge, transition-metal-catalyzed transfer hydrocyanation using safe HCN precursors has been developed, but these reagents generally require a Lewis acid for activation, and the control of regioselectivity often remains problematic. In this Letter, a Ni-catalyzed highly Markovnikov-selective transfer hydrocyanation that operates in the absence of any Lewis acid is reported. The readily prepared pro-aromatic 1-isopropylcyclohexa-2,5-diene-1-carbonitrile is used as the HCN source, and the reaction shows a broad substrate scope and high functional group tolerance. Terminal styrene derivatives, dienes, and internal alkynes are converted with good to excellent selectivities. Mechanistic studies provide insights into the origin of the regioselectivity.
- Frye, Nils L.,Bhunia, Anup,Studer, Armido
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supporting information
p. 4456 - 4460
(2020/06/03)
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- α-Methylation of 2-Arylacetonitrile by a Trimethylamine-Borane/CO2 System
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A highly selective monomethylation of 2-arylacetonitrile using CO2 is described. The utilization of trimethylamine-borane facilitates the six-electron reduction of CO2. This reaction is the first selective six-electron reductive functionalization of CO2 faciliated by C(sp3)-H bonds. A variety of 2-arylpropionitrile was obtained in good yields. The reaction could also be applied at the gram scale.
- Zhang, Xiaowei,Wang, Sheng,Xi, Chanjuan
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p. 9744 - 9749
(2019/08/16)
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- NOVEL COMPOUNDS
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The invention relates to compounds of Formula (I) and their use in therapy, for example in the treatment of mycobacterial infections or in the treatment of diseases caused by mycobacterium, such as tuberculosis
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Page/Page column 46
(2019/03/05)
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- Selective α-Monomethylation by an Amine-Borane/N,N-Dimethylformamide System as the Methyl Source
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A new and practical α-monomethylation strategy using an amine-borane/N,N-dimethylformamide (R3N-BH3/DMF) system as the methyl source was developed. This protocol has been found to be effective in the α-monomethylation of arylacetonitriles and arylacetamides. Mechanistic studies revealed that the formyl group of DMF delivered the carbon and one hydrogen atoms of the methyl group, and R3N-BH3 donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH2-, CD2H-, and CD3- units using Me2NH-BH3/d7-DMF, Me3N-BD3/DMF and Me3N-BD3/d7-DMF systems, respectively. Further application of this method to the facile synthesis of anti-inflammatory flurbiprofen and its varied deuterium-labeled derivatives was demonstrated.
- Xia, Hui-Min,Zhang, Feng-Lian,Ye, Tian,Wang, Yi-Feng
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supporting information
p. 11770 - 11775
(2018/09/10)
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- Ex situ generation of stoichiometric HCN and its application in the Pd-catalysed cyanation of aryl bromides: Evidence for a transmetallation step between two oxidative addition Pd-complexes
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A protocol for the Pd-catalysed cyanation of aryl bromides using near stoichiometric and gaseous hydrogen cyanide is reported for the first time. A two-chamber reactor was adopted for the safe liberation of ex situ generated HCN in a closed environment, which proved highly efficient in the Ni-catalysed hydrocyanation as the test reaction. Subsequently, this setup was exploited for converting a range of aryl and heteroaryl bromides (28 examples) directly into the corresponding benzonitriles in high yields, without the need for cyanide salts. Cyanation was achieved employing the Pd(0) precatalyst, P(tBu)3-Pd-G3 and a weak base, potassium acetate, in a dioxane-water solvent mixture. The methodology was also suitable for the synthesis of 13C-labelled benzonitriles with ex situ generated 13C-hydrogen cyanide. Stoichiometric studies with the metal complexes were undertaken to delineate the mechanism for this catalytic transformation. Treatment of Pd(P(tBu)3)2 with H13CN in THF provided two Pd-hydride complexes, (P(tBu)3)2Pd(H)(13CN), and [(P(tBu)3)Pd(H)]2Pd(13CN)4, both of which were isolated and characterised by NMR spectroscopy and X-ray crystal structure analysis. When the same reaction was performed in a THF : water mixture in the presence of KOAc, only (P(tBu)3)2Pd(H)(13CN) was formed. Subjection of this cyano hydride metal complex with the oxidative addition complex (P(tBu)3)Pd(Ph)(Br) in a 1 : 1 ratio in THF led to a transmetallation step with the formation of (P(tBu)3)2Pd(H)(Br) and 13C-benzonitrile from a reductive elimination step. These experiments suggest the possibility of a catalytic cycle involving initially the formation of two Pd(ii)-species from the oxidative addition of LnPd(0) into HCN and an aryl bromide followed by a transmetallation step to LnPd(Ar)(CN) and LnPd(H)(Br), which both reductively eliminate, the latter in the presence of KOAc, to generate the benzonitrile and LnPd(0).
- Kristensen, Steffan K.,Eikeland, Espen Z.,Taarning, Esben,Lindhardt, Anders T.,Skrydstrup, Troels
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p. 8094 - 8105
(2017/11/27)
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- Cyanide-Free and Broadly Applicable Enantioselective Synthetic Platform for Chiral Nitriles through a Biocatalytic Approach
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A cyanide-free platform technology for the synthesis of chiral nitriles by biocatalytic enantioselective dehydration of a wide range of aldoximes is reported. The nitriles were obtained with high enantiomeric excess of >90 % ee (and up to 99 % ee) in many cases, and a “privileged substrate structure” with respect to high enantioselectivity was identified. Furthermore, a surprising phenomenon was observed for the enantiospecificity that is usually not observed in enzyme catalysis. Depending on whether the E or Z isomer of the racemic aldoxime substrate was employed, one or the other enantiomer of the corresponding nitrile was formed preferentially with the same enzyme.
- Betke, Tobias,Rommelmann, Philipp,Oike, Keiko,Asano, Yasuhisa,Gr?ger, Harald
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supporting information
p. 12361 - 12366
(2017/09/06)
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- Process for the Catalytic Reversible Alkene-Nitrile Interconversion
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The present invention refers to processes for catalytic reversible alkene-nitrile interconversion through controllable HCN-free transfer hydrocyanation.
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Page/Page column 20; 21
(2017/09/02)
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- Copper-Catalyzed Cyanation of N-Tosylhydrazones with Thiocyanate Salt as the "cN" Source
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A novel protocol for the synthesis of α-aryl nitriles has been successfully achieved via a copper-catalyzed cyanation of N-tosylhydrazones employing thiocyanate as the source of cyanide. The features of this method include a convenient operation, readily available substrates, low-toxicity thiocyanate salts, and a broad substrate scope.
- Huang, Yubing,Yu, Yue,Zhu, Zhongzhi,Zhu, Chuanle,Cen, Jinghe,Li, Xianwei,Wu, Wanqing,Jiang, Huanfeng
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p. 7621 - 7627
(2017/07/26)
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- Methylation of C(sp3)-H/C(sp2)-H bonds with methanol catalyzed by cobalt system
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A highly efficient Co-based catalytic system, composed of a commercially available Co salt, a tetradentate phosphine ligand P-(CH2CH2PPh2)3(PP3), and a base (denoted as [Co]/PP3/base), is developed for the methylation of C(sp3)-H and C(sp2)-H bonds using methanol as a methylating reagent. The Co(BF4)2.6H2O/PP3/K2CO3 catalytic system showed high catalytic activity for the methylation of C-H bonds in aryl alkyl ketones, aryl acetonitriles, and indoles, with wide substrate scope and good functional group tolerance, and methylsubstituted products were obtained in good to excellent yields at 100 °C. This cheap, readily available, and highly efficient Co-based catalytic system may have promising applications in methylation reaction using methanol.
- Liu, Zhenghui,Yang, Zhenzhen,Yu, Xiaoxiao,Zhang, Hongye,Yu, Bo,Zhao, Yanfei,Liu, Zhimin
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supporting information
p. 5228 - 5231
(2017/11/06)
-
- Efficient nickel-catalyzed hydrocyanation of alkenes using acetone cyanohydrin as a safer cyano source
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An active nickel catalyst prepared in situ from a Ni(II) compound, phosphine ligand, and zinc powder was found to be an efficient catalyst system for the hydrocyanation of various alkenes using acetone cyanohydrin as a safer cyano source. The combination of NiCl2·6H2O and 1,3-bis(diphenylphosphino)propane was the most efficient catalyst precursor in DMF. Under the optimized conditions, various styrenes, heterocyclic alkenes, and aliphatic alkenes were converted to their corresponding nitriles in excellent yields.
- Nemoto, Koji,Nagafuchi, Tsuyoshi,Tominaga, Ken-ichi,Sato, Kazuhiko
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p. 3199 - 3203
(2016/07/06)
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- TRIAZOLOPYRIDINE ETHER DERIVATIVES AND THEIR USE IN NEUROLOGICAL AND PYSCHIATRIC DISORDERS
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The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds modulate the mGluR2 receptor and may be useful for the treatment of various disorders of the central nervous system.
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Page/Page column 27
(2015/04/15)
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- S-IMINO-S-OXO IMINOTHIAZINE COMPOUNDS AS BACE INHIBITORS, COMPOSITIONS, AND THEIR USE
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In its many embodiments, the present invention provides provides certain S-imino-S-oxo iminothiazine compounds, including compounds Formula (I): or a tautomers and/or stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein RN, R1A, R1B, R2, R3, R4, ring A, RA, m, L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and may be useful for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.
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Page/Page column 72
(2014/10/04)
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- Activation of alcohols with carbon dioxide: Intermolecular allylation of weakly acidic pronucleophiles
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The direct coupling of allyl alcohols with nitroalkanes, nitriles, and aldehydes using catalytic Pd(PPh3)4 has been accomplished via activation of C-OH bonds with CO2. The in situ formation of carbonates from alcohols and CO2 facilitates oxidative addition to Pd to form reactive π-allylpalladium intermediates. In addition, the formation of a strong base activates nucleophiles toward the reaction with the π-allylpalladium electrophile. Overall, this atom economical reaction provides a new C-C bond without the use of an external base and generates water as the only byproduct.
- Lang, Simon B.,Locascio, Theresa M.,Tunge, Jon A.
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supporting information
p. 4308 - 4311
(2014/11/08)
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- Catalytic asymmetric protonation of silyl ketene imines
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An efficient catalytic and highly enantioselective protonation of silyl ketene imines is described. The reaction is catalyzed by the chiral phosphoric acids TRIP or STRIP in the presence of a stoichiometric amount of methanol as the proton source and silyl acceptor. A variety of substituted racemic silyl ketene imines have been transformed into highly enantioenriched nitriles.
- Guin, Joyram,Varseev, Georgy,List, Benjamin
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supporting information
p. 2100 - 2103
(2013/03/28)
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- β-Amination of saturated nitriles through palladium-catalyzed dehydrogenation, 1,4-addition, and re-dehydrogenation
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Amination at the β-position of 2-arylpropionitriles through catalytic dehydrogenation occurred by using [PdCl2(PMe3) 2] catalyst and bromobenzene. This is the first catalytic reaction involving the direct dehydrogenation of saturated nitriles.
- Ueno, Satoshi,Maeda, Ryohei,Yasuoka, Shohei,Kuwano, Ryoichi
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supporting information
p. 40 - 42
(2013/02/25)
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- Self-assembled bidentate ligands for the nickel-catalyzed hydrocyanation of alkenes
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(Chemical Equation Presented) Well-stocked library: A catalyst with interesting activity, regioselectivity (rs), and functional-group tolerance could be identified from a 5x4 library of isoquinolone-or aminopyridine-derived self-assembled bidentate ligand
- De Greef, Michiel,Breit, Bernhard
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supporting information; experimental part
p. 551 - 554
(2009/04/14)
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- Selective Mono-methylation of Arylacetonitriles and Methyl Arylacetates by Dimethyl Carbonate
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Both arylacetonitriles and methyl arylacetates react with dimethyl carbonate (DMC) (20 molar excess) at 180 - 200 deg C in the presence of K2CO3 to produce monomethylated 2-arylpropionitriles and methyl 2-arylpropionates, respectively, with a selectivity >99.5percent.The reaction, with wide application, proceeds by DMC acting as a methoxycarbonylating agent towards the ArCH-X anion (X = CN, CO2Me) and as a methylating agent to ArC-(CO2Me)X.DMC also proved to be the best solvent for such reactions.
- Selva, Maurizio,Marques, Carlos Alberto,Tundo, Pietro
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p. 1323 - 1328
(2007/10/02)
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- Molecular Orbital and Experimental Studies on the Photoinduced Decarboxylation of Pyrethroid Model Esters
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A series of pyrethroid model esters with various substituents in the acid or alcohol moiety have been irradiated by u. v.-radiation (λ > 220 nm).The main reaction is decarboxylation, as evidenced by gas chromatographic (g. c.) and mass spectrometric (m. s.) analyses.In the photoinduced decarboxylation reaction, the substituent effect on the main transition, which occurs via carbonyl excitation, and on the reactivity of a radical intermediate have been examined by semiempirical molecular-orbital calculations (MNDO and CNDO/S).It has been found tha the change of benzyl carbon-oxygen bond strength in the excited states is one of the important factors in determining the yield of the decarboxylated product.
- Katagi, Toshiyuki,Mikami, Nobuyoshi,Matsuda, Tadashi,Miyamoto, Junshi
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p. 779 - 782
(2007/10/02)
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- Anti-protozoal α-aryl-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)-benzeneacetonitrile derivatives, pharmaceutical compositions, and method of use therefor
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The present invention is related with α-aryl-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)benzeneacetonitriles which are effective in destructing or preventing the growth of Protozoa in subjects suffering from such Protozoa.
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- 2-aryl-ethyl ether derivatives and insecticidal and acaricidal agents containing said derivatives
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The present invention relates to 2-arylethyl ether or thioether derivatives represented by the following general formula [I]: STR1 wherein Ar stands for an aryl group, R1 stands for straight or branched chain alkyl group of 1 to 6 carbons, R2 stands for a hydrogen atom, or a methyl or ethyl group, R3 stands for a halogen atom, or a methyl or methoxyl group, R4 stands for a hydrogen or halogen atom, or a lower alkyl or lower alkoxy group, and n is an integer of 1 or 2 with the proviso that when n is 2, the groups R4 may be the same or different, and Y stands for an oxygen or sulfur atom, and also to processes for the preparation of these ethers or thioethers and a use of these ethers or thioethers. These compounds of the present invention have excellent insecticidal and acaricidal activities while the toxicity of these compounds are very low.
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- 2-Arylpropyl ether or thioether derivatives and insecticidal and acaricidal agents containing said derivatives
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The present invention relates to 2-arylpropyl ether or thioether derivatives represented by the following general formula [I]: STR1 wherein Ar stands for an aryl group, R stands for a methyl or ethyl group, Y stands for an oxygen or sulfur atom, and B stands for a group represented by the following formula [II]: STR2 or the following general formula [III]: STR3 wherein Z stands for an oxygen or sulfur atom or a carbonyl or methylene group, R1 stands for a hydrogen or halogen atom or a lower alkyl group or a lower alkoxy group, and n is an integer of from 1 to 5 with the proviso that when n is 2 or more, the groups R1 may be the same or different, and also to processes for the preparation or these ethers of thioethers and a use of these ethers or thioethers. These compounds of the present invention have excellent insecticidal and acaricidal activities while the toxicity of these compounds are very low.
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