- Palladium catalysed asymmetric alkylation of benzophenone Schiff base glycine esters in ionic liquids
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Asymmetric alkyl substitution of various benzophenone Schiff base substrates under biphasic conditions proceeded using optically active Palladium(II) complexes. The corresponding products were obtained in high yields but with moderate enantiomeric excess (ee) . Addition of specific ionic liquids to the reaction medium enhanced reactivity and selectivity for phase transfer catalytic (PTC) glycine alkylation. It has been found that there is an anionic influence of the ionic liquids that modify the steric environment around the enolate ion. A computer-assisted molecular design of enantioselective phase-transfer catalysis with the palladium complex and the ionic liquid has been done. Indian Academy of Sciences.
- Kim, Dae Hyun,Im, Jin Kyu,Kim, Dae Won,Cheong, Minserk,Kim, Hoon Sik,Mukherjee, Deb Kumar
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Read Online
- Efficient solvent-free synthesis of N-unsubstituted ketimines from ketones and ammonia on porous solid acids
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We quantitatively synthesized N-unsubstituted (N–H) diphenylketimine from benzophenone and ammonia without solvent under ambient conditions on some solid acids, especially the proton-exchanged Y-type zeolite (H-Y), by a simple procedure. Similarly, other N-unsubstituted ketimines were also obtained in high yields by the reaction of alkyl aryl ketones or a dialkyl ketone having α-acidic hydrogens with a large excess of ammonia gas at 1 atm. without a solvent with the aid of the zeolite's high dehydration ability and stabilization effects.
- Shibata, Shintaro,Masui, Yoichi,Onaka, Makoto
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- 1,2-Radical Rearrangements of Aryl, Furanyl and Thiophenyl Groups from Carbon to Nitrogen
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1,2-Radical rearrangements of aryl, furanyl and thiophenyl groups from carbon to nitrogen using azido groups as radical precursors are observed for the first time; the 1,2-aryl rearrangement is applied to the synthesis of phenanthridine derivatives from 6-fluorenyl azides.
- Kim, Sunggak,Do, Jung Yun
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Read Online
- FORMATION OF ARYL RADICALS FROM NITROSOARENES BY THE REACTION WITH DIPHENYLMETHYLENEAMINO RADICALS
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By the reaction between nitrosoarenes and diphenylmethyleneamino radicals at 60 - 70 deg C aryl radicals are generated together with nitrogen and benzophenone.
- Suehiro, Tadashi,Masuda, Seiichi,Motoyama, Noboyuki,Sasaki, Masaru
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Read Online
- Reactivity of benzophenone O-vinyloxime
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Benzophenone O-vinyloxime readily takes up bromine and hydrogen chloride to give benzophenone O-(1,2-dibromoethyl)oxime and benzophenone O-(1-chloroethyl)oxime, respectively. Its reactions with methanol, trifluoroacetic acid, and acetic acid lead to formation of the corresponding O-(1-methoxyethyl), O-(1-trifluoroacetoxyethyl), and O-(1-acetoxyethyl) derivatives. Slow heating of the title compound induces its decomposition with formation of benzophenone as the major product; fast heating leads to a complex mixture of products containing benzophenone, benzophenone imine, and acetaldehyde.
- Zaitsev,Shmidt,Vasil'tsov,Mikhaleva,Morozova,Ushakov,Afonin,Il'icheva
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- REACTIONS OF PHENYLYTTERBIUM ? COMPLEX WITH CARBONYL COMPOUNDS: A NEW GRIGNARD-TYPE REAGENT HAVING UNUSUAL REACTIVITY TOWARD ESTERS AND KETONES
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Phenylytterbium iodide has been found to react with ketones, aldehydes, esters, and nitriles to give alcohols and/or ketones.The reactions with esters at low temperature give ketones as main products, and the reactivity of esters to Ph-Yb-I is higher than that of ketones in contrast to the Grignard reaction.
- Fukagawa, Toshihiro,Fujiwara, Yuzo,Yokoo, Kazuhiro,Taniguchi, Hiroshi
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Read Online
- Preparation of 2-amino-2'-hydroxy-1,1'-binaphthyl and N-arylated 2- amino-1,1'-binaphthyl derivatives via palladium-catalyzed amination
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Palladium-catalyzed amination reactions were carried out with 2- triflato-2'-(4-methoxybenzyloxy)-1,1'-binaphthyl (5) and benzophenone imine followed by hydrolysis of the imine and hydrogenolysis of the benzyl protecting group to afford 2-amino-2'-hydroxy-1,1'-binaphthyl (1). Arylamines were also coupled successfully with 5 under similar conditions.
- Singer, Robert A.,Buchwald, Stephen L.
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Read Online
- Preparation method of sun-screening agent intermediate etocrilene
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The invention provides a preparation method of etocrilene. The method uses benzophenone imine and ethyl cyanoacetate as raw materials, wherein benzophenone imine is prepared through benzophenone and ammonia. The method has the advantages of mild reaction conditions, high purity of the prepared etocrilene product, high yield of the process method, less three wastes, simple operation and easy control. Industrialized production can be achieved easily.
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Paragraph 0087-0087
(2021/02/06)
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- Copper-Catalysed Electrophilic Amination of Aryl(alkenyl) Boronic Acids with Nitrogen-Containing Hypervalent Iodine (III) Reagent
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A copper-catalysed electrophilic N-imination of aryl(alkenyl) boronic acids with a stable hypervalent iodine(III) reagent containing a transferable (diarylmethylene)amino group is developed. The electrophilic C?N cross-coupling reaction proceeds smoothly at room temperature under oxidant-free and base-free conditions, which is further characterized by the broad functional group compatibility, thereof, extending the N-electrophile scope of electrophilic C?N cross-coupling outside the limitation of N?O and N?Cl reagents. (Figure presented.).
- Hu, Yuanyuan,Zheng, Songlin,Fan, Wu,Yuan, Weiming
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p. 4701 - 4707
(2021/08/23)
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- Scandium(III) Triflate Catalyzed Direct Synthesis of N-Unprotected Ketimines
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N-Unprotected ketimines are useful substrates and intermediates for synthesizing valuable nitrogen-containing compounds, but their potential applicability is limited by the available synthetic methods. To address this issue, we report a scandium(III) triflate catalyzed direct synthesis of N-unprotected ketimines. Using commercially available reagents and Lewis acid catalysts, ketones were directly transformed into the corresponding N-unprotected ketimines in high yields with broad functional group tolerance, even in multigram scales. The reactions were readily applicable for one-pot synthesis of important compounds such as a glycine Schiff base without isolation of N-unprotected ketimine intermediates. Preliminary mechanistic studies to clarify the reaction mechanism are also described.
- Hirazawa, Yoshinobu,Kadota, Tetsuya,Kondo, Yuta,Morimoto, Hiroyuki,Morisaki, Kazuhiro,Ohshima, Takashi
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supporting information
p. 120 - 125
(2020/02/20)
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- Copper-catalyzed [2+3]-annulation of N-H imines with vinyl azides: Access to polyaryl 2: H -imidazoles
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A practical method for the synthesis of 2H-imidazoles via a [2+3] annulation of N-H imines with vinyl azides using a copper catalyst is developed. In this conversion, environmentally friendly oxygen is used as the sole oxidant and N2 and H2O are the only by-products. The catalytic transformation, operating under mild conditions, is operationally simple and is considered as a readily available catalytic system having good substrate and functional compatibility with high atom-efficiency without the need for additional ligands or additives.
- Zhu, Zhongzhi,Lin, Hanze,Liang, Baihui,Huang, Junjie,Liang, Wanyi,Chen, Lu,Huang, Yubing,Chen, Xiuwen,Li, Yibiao
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supporting information
p. 5621 - 5624
(2020/06/19)
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- Concurrent Formation of N-H Imines and Carbonyl Compounds by Ruthenium-Catalyzed C-C Bond Cleavage of β-Hydroxy Azides
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A commercial cyclopentadienylrutenium dicarbonyl dimer ([CpRu(CO)2]2) efficiently catalyzes the formation of N-H imines and carbonyl compounds simultaneously from β-hydroxy azides via C-C bond cleavage under visible light. Density functional theory calculations for the cleavage reaction support the mechanism involving chelation of alkoxy azide species and liberation of nitrogen as the driving force. The synthetic utility of the reaction was demonstrated by a new amine synthesis promoted by chemoselective allylation of imine and synthesis of isoquinoline.
- Lee, Jeong Min,Bae, Dae Young,Park, Jin Yong,Jo, Hwi Yul,Lee, Eunsung,Rhee, Young Ho,Park, Jaiwook
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p. 4608 - 4613
(2020/06/05)
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- A Convenient Preparation Method for Benzophenone Imine Catalyzed by Tetrabutylammonium Fluoride
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Benzophenone imine is a useful ammonia equivalent in the Buchwald-Hartwig amination and an important intermediate for the synthesis of N-protected primary amines. However, the conventional synthesis of benzophenone imine requires stoichiometric amounts of metal reagents or high-pressure conditions. Herein we report a facile method for preparing benzophenone imine to enhance its potential utility. The reaction is performed by mixing commercially available benzophenone and bis(trimethylsilyl)amine in the presence of a catalytic amount of tetrabutylammonium fluoride at ambient temperature and pressure and can be readily applied to a multigram-scale synthesis even in a standard academic laboratory setup. Preliminary mechanistic studies and the application of the reaction to one-pot benzophenone imine synthesis/Buchwald-Hartwig amination are also reported.
- Kondo, Yuta,Morisaki, Kazuhiro,Hirazawa, Yoshinobu,Morimoto, Hiroyuki,Ohshima, Takashi
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p. 1718 - 1724
(2019/09/06)
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- Fe3O4@SiO2@Im[Cl]Mn(III)-complex as a highly efficient magnetically recoverable nanocatalyst for selective oxidation of alcohol to imine and oxime
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An efficient and environmentally friendly oxidation process for the one-pot preparation of oxime, imine and carbonyl compounds through alcohol oxidation in the presence of H2O2 and/or O2 have been developed by a melamine-Mn(III) Schiff base complex supported on Fe3O4@SiO2–Cl nanoparticles, named as Fe3O4@SiO2@Im[Cl]Mn(III)-complex nanocomposite, at room temperature. Direct oxidation of alcohol to carboxylic acid was performed using the catalyst in the presence of molecular O2 at room temperature in a different approach. The oxidation products were obtained with excellent yields and high TOFs. The properties of the catalyst were characterized by Fourier transform infrared spectroscopy (FTIR), elemental analysis (C, H, N), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), energy dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS), inductive coupled plasma (ICP), cyclic voltammetry (CV), nuclear magnetic resonance (1H & 13C NMR), vibration sample magnetometer (VSM), Brunauer– Emmett–Teller (BET) and differential pulse voltammetry (DPV) analyses. The mechanism of the oxidation processes was investigated for the both H2O2 and O2 oxidants. The role of the imidazolium moiety in the catalyst as a secondary functionality was investigated. Chemoselectivity behavior of the catalyst was studied by some combinations. The catalyst could be recycled from the reaction mixture by a simple external magnet and reused for several times without any considerable reactivity loss.
- Kazemnejadi, Milad,Alavi, Seyyedeh Ameneh,Rezazadeh, Zinat,Nasseri, Mohammad Ali,Allahresani, Ali,Esmaeilpour, Mohsen
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p. 230 - 249
(2019/03/28)
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- Introducing Glycerol as a Sustainable Solvent to Organolithium Chemistry: Ultrafast Chemoselective Addition of Aryllithium Reagents to Nitriles under Air and at Ambient Temperature
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Edging closer towards developing air and moisture compatible polar organometallic chemistry, the chemoselective and ultrafast addition of a range of aryllithium reagents to nitriles has been accomplished by using glycerol as a solvent, at ambient temperature in the presence of air, establishing a novel sustainable access to aromatic ketones. Addition reactions occur heterogeneously (“on glycerol conditions”), where the lack of solubility of the nitriles in glycerol and the ability of the latter to form strong intermolecular hydrogen bonds seem key to favouring nucleophilic addition over competitive hydrolysis. Remarkably, PhLi exhibits a greater resistance to hydrolysis working “on glycerol” conditions than “on water”. Introducing glycerol as a new solvent in organolithium chemistry unlocks a myriad of opportunities for developing more sustainable, air and moisture tolerant main-group-metal-mediated organic synthesis.
- Rodríguez-álvarez, María J.,García-álvarez, Joaquín,Uzelac, Marina,Fairley, Michael,O'Hara, Charles T.,Hevia, Eva
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p. 1720 - 1725
(2018/01/27)
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- Selective Oxidative [4+2] Imine/Alkene Annulation with H2 Liberation Induced by Photo-Oxidation
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The oxidative [4+2] annulation reaction represents an elegant and versatile synthetic protocol for the construction of six-membered heterocyclic compounds. Herein, a photoinduced oxidative [4+2] annulation of NH imines and alkenes was developed by utilizing a dual photoredox/cobaloxime catalytic system. Various multisubstituted 3,4-dihydroisoquinolines can be obtained in good yields. This method is not only obviated the need of stiochiometric amounts of oxidants but also exhibited excellent atom economy by generating H2 as the only byproduct. Remarkably, high regioselectivity and trans diastereoselectivity can be achieved in this transformation even if the Z/E mixture of alkenes were employed.
- Hu, Xia,Zhang, Guoting,Bu, Faxiang,Lei, Aiwen
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supporting information
p. 1286 - 1290
(2018/01/10)
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- Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis
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An application of H-bonding interactions for directing the α-C-H oxidation of amines to amides and amino-ketones catalyzed by an organic photocatalyst is reported. The high efficiency of this method is demonstrated by the aerobic oxidation of pyrrolidines, diarylamines and benzylamines bearing urea groups with high yields and a wide substrate scope.
- Wang, Hongyu,Man, Yunquan,Wang, Kaiye,Wan, Xiuyan,Tong, Lili,Li, Na,Tang, Bo
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supporting information
p. 10989 - 10992
(2018/10/08)
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- Expansion of the Substrate Specificity of Porcine Kidney D-Amino Acid Oxidase for S-Stereoselective Oxidation of 4-Cl-Benzhydrylamine
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Discovery and development of enzymes for the synthesis of chiral amines have been a hot topic for basic and applied aspects of biocatalysts. Based on our X-ray crystallographic analyses of porcine kidney D-amino acid oxidase (pkDAO) and its variants, we rationally designed a new variant that catalyzed the oxidation of (S)-4-Cl-benzhydrylamine (CBHA) from pkDAO and obtained it by functional high-throughput screening with colorimetric assay. The variant I230A/R283G was constructed from the variant R283G which had completely lost the activity for D-amino acids, further gaining new activity toward (S)-chiral amines with the bulky substituents. The variant enzyme (I230A/R283G) was characterized to have a catalytic efficiency of 1.85 s?1 for (S)-CBHA, while that for (R)-1-phenylethylamine was diminished 10-fold as compared with the Y228L/R283G variant. The variant was efficiently used for the synthesis of (R)-CBHA in 96 % ee from racemic CBHA by the deracemization reaction in the presence of reducing agent such as NaBH4 in water. Furthermore, X-ray crystallographic analysis of the new variant complexed with (S)-CBHA, together with modelling study clearly showed the basis of understanding the structure-activity relationship of pkDAO.
- Yasukawa, Kazuyuki,Motojima, Fumihiro,Ono, Atsushi,Asano, Yasuhisa
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p. 3500 - 3505
(2018/08/06)
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- Synthesis of Benzodihydrofurans by Asymmetric C?H Insertion Reactions of Donor/Donor Rhodium Carbenes
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Metal carbenes appended with two electron-donating groups, known as “donor/donor” carbenes, undergo diastereo- and enantioselective rhodium-catalyzed C?H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2). Although this sequence often can be performed in one-pot, control experiments have elucidated why a “two-pot” process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C?H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described.
- Lamb, Kellan N.,Squitieri, Richard A.,Chintala, Srinivasa R.,Kwong, Ada J.,Balmond, Edward I.,Soldi, Cristian,Dmitrenko, Olga,Casti?eira Reis, Marta,Chung, Ryan,Addison, J. Bennett,Fettinger, James C.,Hein, Jason E.,Tantillo, Dean J.,Fox, Joseph M.,Shaw, Jared T.
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supporting information
p. 11843 - 11855
(2017/09/07)
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- Manganese-catalyzed dehydrogenative [4+2] annulation of N-H imines and alkynes by C-H/N-H activation
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Described herein is a manganese-catalyzed dehydrogenative [4+2] annulation of N-H imines and alkynes, a reaction providing highly atom-economical access to diverse isoquinolines. This transformation represents the first example of manganese-catalyzed C-H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H2 as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition-metal-catalyzed C-H activation. Mechanistic studies revealed the five-membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.
- He, Ruoyu,Huang, Zhi-Tang,Zheng, Qi-Yu,Wang, Congyang
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supporting information
p. 4950 - 4953
(2014/05/20)
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- C-H activation guided by aromatic N-H ketimines: Synthesis of functionalized isoquinolines using benzyl azides and alkynes
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Aromatic N-H ketimines were in situ generated from various benzylic azides by ruthenium catalysis for the subsequent Rh-catalyzed annulation reaction with alkynes to give the corresponding isoquinolines. In contrast to conventional synthetic methods for aromatic N-H ketimines, our protocol works under mild and neutral conditions, which enabled the synthesis of isoquinolines having various functionalities such as carbonyl, ester, alkenyl, and ether groups. In addition, the imidates generated from α-azido ethers were successfully used for the synthesis of 1-alkoxyisoquinolines.
- Gupta, Sreya,Han, Junghoon,Kim, Yongjin,Lee, Soon W.,Rhee, Young Ho,Park, Jaiwook
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p. 9094 - 9103
(2014/12/11)
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- Copper nanoparticles from copper aluminum hydrotalcite: An efficient catalyst for acceptor- and oxidant-free dehydrogenation of amines and alcohols
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An efficient and simple process for the preparation of stable nanocopper(0) on alumina [Cu(0)/Al2O3] from the inorganic composite precursor copper aluminum hydrotalcite (Cu-AlHT) by a chemical reduction method is described. Cu(0)/ Al2O3 was employed as an efficient catalyst in the acceptor- and oxidant-free dehydrogenation of various amines and alcohols to their corresponding dehydrogenated products in good to excellent yields. The stability of Cu(0)/Al2O3 was assessed by studying its recoverability and reusability in the dehydrogenation of amines and alcohols for up to five cycles.
- Damodara, Dandu,Arundhathi, Racha,Likhar, Pravin R.
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supporting information
p. 189 - 198
(2014/03/21)
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- Efficient and scalable synthesis of ketones via nucleophilic Grignard addition to nitriles using continuous flow chemistry
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In the present Letter we report the development of efficient continuous flow chemistry conditions for the scalable preparation of ketones. This transformation is achieved via nucleophilic addition of Grignard reagents to the corresponding nitriles and imine hydrolysis by means of in-series plug flow reactors.
- Mateos, Carlos,Rincón, Juan A.,Villanueva, José
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supporting information
p. 2226 - 2230
(2013/05/08)
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- Synthesis of aryl ketones via decarboxylation of aromatic acids under solvothermal condition
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Aryl ketones were prepared by the condensation of aromatic carboxylic acids with alkyl/aryl nitrile via the decarboxylation of carboxylic acids under solvothermal condition. All the compounds were characterized by comparing with standard samples prepared by the known literature method.
- Rai, K.M. Lokanatha,Babu, M. Suresh,Byrappa
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experimental part
p. 1395 - 1396
(2012/08/27)
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- Intermolecular mono-and dihydroamination of activated alkenes using a recoverable gold catalyst
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A combination of gold chloride organometallic complex and a silver salt was used to catalyze intermolecular hydroamination of activated alkenes, i.e aza-Michael reactions. The gold-catalyzed reactions of activated alkenes with nitrogen substrates were investigated and found to afford various mono-and dihydroamination products, the latter being rare and original. After flash chromatography, gold NHC catalyst could be recovered as a gold hydroxide NHC complex. When combined with a silver salt, the gold complex lead again to an active hydroamination catalyst.
- Medina, Florian,Michon, Christophe,Agbossou-Niedercorn, Francine
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supporting information
p. 6218 - 6227
(2013/01/15)
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- Characterization and utility of N-unsubstituted imines synthesized from alkyl azides by ruthenium catalysis
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Shine a light: A fluorescent light-induced synthetic method for the title compounds has been developed and the chemoselective nature of the reaction is highlighted by the observation of the cis/trans isomers of various N-unsubstituted imines. The synthetic utility of this method is demonstrated by the one-pot imine formation/asymmetric allylation sequence of benzyl azide catalyzed by 1. (Ipc=isopinocampheyl). Copyright
- Lee, Jin Hee,Gupta, Sreya,Jeong, Wook,Rhee, Young Ho,Park, Jaiwook
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supporting information
p. 10851 - 10855
(2013/01/15)
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- PROCESS FOR REMOVING HYDROGEN CYANIDE FROM ETHANEDINITRILE
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Process for removing hydrogen cyanide from ethanedinitrile by contacting hydrogen cyanide-containing ethanedinitrile with an organic reagent under formation of a covalent bond.
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- PTERIDINONES AS INHIBITORS OF POLO - LIKE KINASE
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The present invention provides compounds having a structure according to Formula (I) or a salt or solvate thereof, wherein ring A, X, R1, R2, R3, R4, R5 and R6, are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.
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Page/Page column 90; 91
(2011/07/09)
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- METHOD OF PRODUCING BENZOPHENONEIMINES
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A process for the preparation of benzophenonimine (BPI) of the general formula I where R1 and R2 are C1- to C4-alkoxy, C1- to C2-alkylamine and C2- to C4-dialkylamine and m and n are integers from 0 to 5 and R1 and R2, independently of one another, may be identical or different, by reacting benzophenone (BP) of the general formula II where R1, R2, m and n have the abovementioned meanings, in ammonia and in the presence of titanium dioxide, the titanium dioxide being present substantially in the anatase modification.
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Page/Page column 4
(2009/04/24)
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- Diastereo- And enantioselective synthesis of β-Hydroxy-α-amino acids: Application to the synthesis of a key intermediate for lactacystin
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The development of a highly efficient and stereoselective methodology for the preparation of β-hydroxy-α- amino acids is described. Nucleophilic addition of enolates of tricyclic iminolactones 1a and 1b to aldehydes in the presence of 6 equiv of lithium chloride in THF at -78 °C leads to aldol adducts in good yield (63-86%) and high diastereoselectivity (up to >25:1 dr). Subsequently, hydrolysis of the aldol adducts under acidic conditions leads to the corresponding β-hydroxy-a-amino acids in good yields (up to 83%) and excellent enantiomeric excesses (99% ee) with good recovery yields of the chiral auxiliaries 6 and 7. This methodology was applied to the facile synthesis of the key intermediate for lactacystin along with several isomers.
- Li, Qiong,Yang, Shao-Bo,Zhang, Zhihui,Li, Lei,Xu, Peng-Fei
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supporting information; experimental part
p. 1627 - 1631
(2009/09/24)
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- Aminoimidazoles as potent and selective human β-secretase (BACE1) inhibitors
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The identification of small molecule aminoimidazoles as potent and selective human β-secretase inhibitors is reported. These analogues demonstrate low nannomolar potency for BACE1 in a FRET assay, exhibit comparable activity in a cell-based (ELISA) assay, and show>100x selectivity for the other structurally related aspartyl proteases BACE2, cathepsin D, renin, and pepsin. Our design strategy was supported by molecular modeling studies based on the cocrystal structure of the HTS-hit 3 in the BACE1 active site. These strategies enabled us to integrate pyridine and pyrimidine groups on 3 extending deep into the S3 region of the BACE1 binding pocket and enhancing the ligand's potency. Compound (R)-37 displayed an IC50 value for BACE1 of 20 nM, cellular activity of 90 nM, and > 100-fold selectivity over related aspartyl proteases. Acute oral administration of (R)-37 at 30 mg/kg resulted in a significant 71% reduction of plasma Aβ40 measured at the 6 h time point in a Tg2576 mouse model (p 0.001). 2009 American Chemical Society.
- Malamas, Michael S.,Erdei, Jim,Gunawan, Iwan,Barnes, Keith,Johnson, Matthew,Yu, Hui,Turner, Jim,Yun, Hu,Wagner, Erik,Fan, Kristi,Olland, Andrea,Bard, Jonathan,Robichaud, Albert J.
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experimental part
p. 6314 - 6323
(2010/03/31)
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- Configurationally stable propeller-like triarylphosphine and triarylphosphine oxide
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Configurationally stable, propeller-like triarylphosphine and triarylphosphine oxide can be synthesized; a chiral scaffold based on Lissoclinum-cyclopeptides linked via three peptide bonds with a triphenylphosphine and triphenylphosphine oxide moiety, respectively, prevents effectively epimerization at the chiral phosphorus atom. The Royal Society of Chemistry.
- Pinter, Aron,Haberhauer, Gebhard,Hyla-Kryspin, Isabella,Grimme, Stefan
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p. 3711 - 3713
(2008/03/14)
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- Synthesis of homo- and heterobiarylmethylamines
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A variety of homo- and heterobiarylmethylamines were prepared in modest to high yields via a convenient one-pot process. Georg Thieme Verlag Stuttgart.
- Terrasson, Vincent,Marque, Sylvain,Scarpacci, Annabelle,Prim, Damien
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p. 1858 - 1862
(2008/01/27)
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- Rhodium-catalyzed arylation using arylboron compounds: Efficient coupling with aryl halides and unexpected multiple arylation of benzonitrile
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(Chemical Equation Presented) The Suzuki-Miyaura-type cross-coupling of arylboron compounds with aryl halides proceeds efficiently in the presence of a rhodium-based catalyst system to produce the corresponding biaryls. Furthermore, it has unexpectedly been observed that the treatment with benzonitrile under similar conditions brings about its multiple arylation, in which nucleophilic arylation on the cyano group and subsequent ortho arylation via C-H bond cleavage are involved.
- Ueura, Kenji,Satoh, Tetsuya,Miura, Masahiro
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p. 2229 - 2231
(2007/10/03)
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- Thermolyses of O-Phenyl Oxime Ethers. A New Source of Iminyl Radicals and a New Source of Aryloxyl Radicals
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Six O-phenyl ketoxime ethers, RR′C=NOPh 1-6, with RR′= diaryl, dialkyl, and arylalkyl, together with N-phenoxybenzimidic acid phenyl ether, PhO(Ph)C=NOPh, 7, have been shown to thermolyze at moderate temperatures with "clean" N-O bond homolyses to yield iminyl and phenoxyl radicals, RR′C=N. and PhO.. Since 1-6 can be synthesized at room temperature, these compounds provide a new and potentially useful source of iminyls for syntheses. The iminyl from 7 undergoes a competition between β-scission, to PhCN and PhO., and cyclization to an oxazole. Rate constants, 106 k/s-1, at 90 °C for 1-6 range from 4.2 (RR′ = 9-fluorenyl) to 180 (RR′ = 9-bicyclononanyl), and that for 7 is 0.61. The estimated activation enthalpies for N-O bond scission are in satisfactory agreement with the results of DFT calculations of N-O bond dissociation enthalpies, BDEs, and represent the first thermochemical data for any reaction yielding iminyl radicals. The small range in k (N-O homolyses) is consistent with the known σ structure of these radicals, and the variations in k and N-O BDEs with changes in RR′ are rationalized in terms of iminyl radical stabilization by hyperconjugation: RR′C=N . ? R.R′C≡N. Calculated N-H BDEs in the corresponding RR′C= NH are also presented.
- Blake, Jessie A.,Pratt, Derek A.,Lin, Shuqiong,Walton, John C.,Mulder, Peter,Ingold
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p. 3112 - 3120
(2007/10/03)
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- Thermal decomposition of O-benzyl ketoximes; role of reverse radical disproportionation
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Thermolyses of seven dialkyl, two alkyl-aryl and two diaryl O-benzyl ketoxime ethers, R1R2C=NOCH2Ph, have been examined in three hydrogen donor solvents: tetralin, 9,10-dihydrophenanthrene, and 9,10-dihydroanthracene. All the oxime ethers gave the products expected from homolytic scission of both the O-C bond (viz., R1R2C=NOH and PhCH3) and N-O bond (viz., R1R2C=NH and PhCH2OH). The yields of these products depended on which solvent was used and the rates of decomposition of the O-benzyl oxime ethers were greater in 9,10-dihydrophenanthrene and 9,10-dihydroanthracene than in tetralin. These results indicated that a reverse radical disproportionation reaction in which a hydrogen atom was transferred from the solvent to the oxime ether, followed by β-scission of the resultant aminoalkyl radical, must be important in the latter two solvents. Benzaldehyde was found to be an additional product from thermolyses conducted in tetralin. This, and other evidence, indicated that another induced decomposition mode involving abstraction of a benzylic hydrogen atom, followed by β-scission of the resulting benzyl radical, became important for some substrates. Participation by minor amounts of enamine tautomers of the oxime ethers was shown to be negligible by comparison of thermolysis data for the O-benzyloxime of bicyclo[3.3.1]nonan-9-one, which cannot give an enamine tautomer, with that of the O-benzyloxime of cyclohexanone.
- Blake, Jessie A.,Ingold, Keith U.,Lin, Shuqiong,Mulder, Peter,Pratt, Derek A.,Sheeller, Brad,Walton, John C.
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p. 415 - 420
(2007/10/03)
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- Nitrile ylide dimerization: Investigation of the carbene reactivity of nitrile ylides
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A series of novel hexaaryl diazatrienes 5 ("nitrile ylide dimers") were synthesized directly from the corresponding diaryl ketimines 12 and dichlorotoluenes 13 in a facile one-pot synthesis. The carbene character of the nitrile ylides was investigated by varying the substituents on the aromatic ring adjacent to the carbene center. The isolation of the corresponding carbene dimers as stable crystalline materials with absorption maxima (λmax) from 363 to 422 nm was shown to be promoted by the absence of strongly electron-withdrawing substituents. The crystal structures indicate that the E-isomers were isolated when phenyl, 3-methylphenyl, and 3-chlorophenyl substituents are present at the carbene carbon; the Z-isomer was isolated when the more sterically hindered 2,4,6-trimethylphenyl substituent (Mes) is present. The 1H NMR spectra of the E-isomers demonstrate the nonequivalence of the aromatic rings, in which two of the aromatic rings of the imine moiety are pseudoaxial and the remaining aromatic rings are pseudoequatorial. The reactions proceed via the intermediate nitrile ylides 1 generated by the base-promoted 1,1-elimination of HCl from the intermediate chloroimine 14. The nitrile ylide was also generated by 1,3-elimination of HCl from the imidoyl chloride 18, confirming common pathways via the nitrile ylide as the dimer products obtained from these different routes were identical. The strongly electron-withdrawing 4-nitrophenyl substituent promotes the linear carbanion character of the 1,3-dipole and no dimer is formed.
- Fergus, Suzanne,Eustace, Stephen J.,Hegarty, Anthony F.
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p. 4663 - 4669
(2007/10/03)
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- A one-pot access to 6-substituted phenanthridines from fluoroarenes and nitriles via 1,2-arynes
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A one-pot f-BuLi-induced synthesis of 6-substituted phenanthridines from fluoroarenes and nitriles via 1,2-arynes is reported. Aryl-and hetaryl nitriles, cyanamides, and trimethylacetonitrile gave phenanthridine products. The method was extended to provide bisphenanthridine 10 by a one-pot bis-cyclization, using 1,3-dicyanobenzene and PhF in 1:5 ratio. Reaction of 1-fluoronaphthalene and 4-chlorofluorobenzene with benzonitrile afforded the regioisomerically pure products 11 and 12, respectively.
- Pawlas, Jan,Begtrup, Mikael
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p. 2687 - 2690
(2007/10/03)
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- Synthesis of substituted benzhydrylamines
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The synthesis of para di- and monosubstituted benzhydrylamines by addition of Grignard reagents to benzonitriles and subsequent reduction, is evaluated and discussed. The reduction step with sodium borohydride allows simple handling and mild conditions. An optimized synthesis of 4,4'-dimethoxybenzhydrylamine by this method is disclosed.
- Dejaegher,Mangelinckx,De Kimpe
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p. 113 - 115
(2007/10/03)
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- Synthesis and characterization of new ca-disubstituted (diarylaminomethyl)phosphonates
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A convenient and efficient three-step procedure for the preparation of W-protected or unprotected C-disubstituted (di-arylaminomethyOphosphonates 1 is reported. This method allows diversification of the substituents on the carbon in the a-position to the phosphorus, as well as the protective group on the amine and the phosphonate ester group.
- Cristau, Henri-Jean,Lambert, Jean-Marc,Pirat, Jean-Luc
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p. 1167 - 1170
(2007/10/03)
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- Synthesis of 1,2:5,6-di-O-isopropylidene-D-glucofuranos-3-yl and 1,2:3,4-di-O-isopropylidene-D-galactopyranos-6-yl-(N-diphenylmethylene )glycinates
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1,2:3,4-di-O-isopropylidene-D-galactopyranos-6-yl-(N-diphenylmethylene )-glycinate 3, was prepared via a trans-esterification process from ethyl (N-diphenylmethylene)-glycinate and 1,2:5,6-di-O-isopropylidene-D-glucofuranos-3-yl-(N-diphenylmethylene) glycinate 9, via a trans-imination reaction from 1,2:5,6-di-O-isopropylidene-D-glucofuranos-3-yl glycinate 6 and diphenyl-ketiminium chloride.
- Solladie, Guy,Saint Clair, Jean-Francois,Philippe, Michel,Semeria, Didier,Maignan, Jean
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p. 2359 - 2364
(2007/10/03)
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- Osmium Complexes of the Half-Sandwich Type with Oximes, Imines, and Azavinylidenes as Ligand
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Azavinylideneosmium complexes of the general composition X (L = PMe3, PMetBu2, PiPr3) have been prepared by two methods.The first one uses the hydrido compound (2) and oximes HON=CRR' as starting materials and proceeds via the oxime complexes (PMetBu2)>PF6 (10, 11) as intermediates.They react with Al2O3 with elimination of water to give the final products 6-9.The second method starts with the dichloro- or diiodoosmium(II) compounds (14, 16, 19, 21; arene = C6H6, 1,3,5-Me3C6H3; R = Me, iPr) which upon treatment with HN=CPh2 or imine derivatives XN=C(R)Ph (X = Li, SiMe3) afford the azavinylidene complexes 13b, 18, 23, 33.In the reactions with HN=CPh2, the corresponding imine complexes X (15, 17, 20, 22) are formed as the primary products.Whereas nucleophilic addition of H- and CH3- to the N=C carbon atom of + (6) gives the imidoosmium(II) compounds (24, 25), the reaction of PF6 (13b) with LiAlH(OtBu)3 yields the hydrido(imino) derivative PF6 (26).The bis(azido) complex (27), which is prepared either from 13b or (14) and NaN3, undergoes a cycloaddition reaction with C2(CO2Me)2.Two isomeric (triazole)osmium compounds 28, 29 have been isolated.Treatment of PF6 with HX (X = O2CCF3) leads to addition of the acid to the Os=N bond and, for a five-membered metallaheterocycle 31.The X-ray structural analysis of PF6 (6) reveals an allenelike arrangement of the ligands and substituents around the Os=N=C unit. - Key Words: Azavinylidene osmium complexes, preparation from oximes or imines/ Hydrido(oxime) osmium complexes/ Chloro-, hydrido- and iodo(imine) osmium complexes/ Imido osmium complexes, formation by nucleophilic addition/ Triazole osmium complexes, preparation from a bis(azido) osmium(II) compound and alkyne
- Daniel, Thomas,Knaup, Wolfgang,Dziallas, Michael,Werner, Helmut
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p. 1981 - 1994
(2007/10/02)
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- Vinyl Glycine derivatives for memory and learning enhancement or treatment of a cognitive disorder
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A class of vinyl glycine derivatives is described for use in memory and learning enhancement or for treatment of a cognitive disorder. The vinyl glycine derivatives of particular interest are compounds of Formula I wherein the double bond is in trans configuration, R 1 is lower alkyl, R 2 is hydrido, R 3 is amino and X is hydroxymethyl. STR1
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- A Novel Addition-Rearrangement of O-(1-Benzotriazolylaklyl)oximes with Organolithium Reagents. Convenient Non-oxidative Conversions of Aldehydes into Amides
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Condensation of an aldehyde, an oxime and benzotriazole gives an O-(1-benzotriazolylalkyl)oxime which undergoes an addition-rearrangement on treatment with an organolithium reagent.This reaction provides a novel non-oxidative method for the transformation of aldehydes into amides which has afforded several new N-monosubstituted amides with crowded structures.Grignard reactions of the O-(1-benzotriazolylalkyl)oximes give alcohols as the major products.
- Katritzky, Alan R.,Jiang, Jinlong,Greenhill, John V.,Steel, Peter J.
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p. 3055 - 3060
(2007/10/02)
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- AN EXPLORATIVE INVESTIGATION INTO THE REACTION OF AMMONIA WITH KETONES. MEDIATED BY LOW-VALENT TITANIUM
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Mediated by low-valent titanium, generated from TiCl3/LiAl4, ammonia is incorporated into benzophenone to give N-(diphenylmethylene)-N-(diphenylmethyl) amine in a synthetically useful reaction.A good yield (65 percent) requires that the temperatures of the reaction stages are well controled and that ammonia and ketone are simultaneously introduced keeping their molar ration 1:1.The possible sequence of reactions is discussed.
- Volckaerts, E.,Geise, H. J.,Daelmans, F.
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p. 503 - 508
(2007/10/02)
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- Nickel-catalyzed dehydrogenation of amines to nitriles
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Aliphatic primary amines having α-methylene underwent oxidative dehydrogenation on treatment with NiSO4 as a catalyst and K2S2O8 as an oxidant to give the corresponding nitriles in good yields. Benzhydrylamine was converted to benzhydrylideneamine quantitatively under the same reaction conditions.
- Yamazaki,Yamazaki
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p. 301 - 303
(2007/10/02)
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- Ruthenium Complex Catalyzed Selective Deoxygenation of Ketoximes to Ketimines
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Ru3(CO)12 showed high catalytic activity for the deoxygenation of various ketoximes to the corresponding ketimines under carbon monoxide pressure (20 kg/cm2).For the deoxygenation of propiophenone oxime, ethyl phenyl ketimine was obtained in 100 percent yield.On the other hand, heptanal oxime which was aldoxime was dehydrated under the same conditions to the corresponding nitrile in 32 percent yield.
- Akazome, Motohiro,Tsuji, Yasushi,Watanabe, Yoshihisa
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p. 635 - 638
(2007/10/02)
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- Electron Paramagnetic Resonance Study of Imine Radical Cations in Low-temperature Solid Matrices
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A series of imine radical cations has been studied by EPR spectroscopy, generated in low-temperature halogenocarbon matrices by γ-radiolysis.Radicals of the type ArCH=NR.+ tend to be formed in the 2A'state, corresponding to ionisation of the in-plane (mainly the nitrogen lone-pair) a' orbital (I).These are isostructural with the corresponding vinyl radicals and show angular geometries at the radical centres and large couplings (ca. 85 G) to the proton trans to the nominally nitrogen-localised SOMO (I).When R = But, a 12 G long-range coupling is observed to a single proton from the But group, arising via the W-configuration (II).This coupling was found to persist in the CFCl3 matrix up to its melting point (ca. 160 K), but was lost reversibly in the higher melting CCl4 matrix at ca. 200 K. When R = phenyl, the radical centre is rendered linear, because of the partial ?-bonding between the aromatic ring and the nitrogen atom due to delocalisation of the unpaired electron, as shown by a fall in the parallel (14N) coupling with a concomitant increase in the nitrogen 2p/2s ratio, and by the observation of couplings to the ortho and para phenyl protons. For imines derived from benzophenone (Ph2C=NR) the tendency is for ionisation to occur from the ?-orbital (III) which has large spin densities on the para carbon atoms. Benzophenone imine (Ph2C=NH), in addition to forming the ?-state (III), was found to deprotonate, giving rise to the Ph2C=N. radical.Similar behaviour was shown by benzophenone oxime, which gave only the corresponding iminoxyl radical (Ph2C=N-O.), and we propose that this is due to the dissolution of the latter two materials in the form of hydrogen-bonded molecular clusters in the non-polar freon solvent, thus facilitating deprotonation of the primary cations.
- Rhodes, Christopher J.,Agirbas, Hikmet
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p. 3303 - 3308
(2007/10/02)
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- Action of Alkylmagnesium and Alkyllithium Reagents on Some Quaternary Hydrazonium Salts
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Benzophenone N-methyl-N,N-pentane-1,5-diylhydrazonium iodide (1a) and its p,p'-dichloro and p,p'-dimethoxy analogues undergo loss of CH3I in boiling ethyl ether or THF, but the fluoroborates are stable.The complexes formed from 1 and Grignard reagents do not undergo incorporation of deuterium when they are hydrolyzed with D2O.When 1 and analogues are treated with propyl- and decylmagnesium bromide, the corresponding alkane, alkene, and bialkyl are produced, facts imply formation of alkyl radicals by a single-electron-transfer process.With all alkyl Grignard reagents studied, the overwhelming reaction is reductive cleavage of the N,N bond to form imines unsubstituted on nitrogen; no N-alkyl imines were detected.Small amounts of 1,1-diarylalkylamines, formed about 2percent of benzhydrylamine in reaction with 1a.Sodium cyanide reacted with the tetrafluoroborate analogue of 1a to form acetonitrile by demethylation; neither addition nor reduction was detected.Sodium azide behaved analogously.
- Smith, Peter A.S.,Messing, Calvin R.
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p. 2959 - 2965
(2007/10/02)
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- KETIMINES FROM KETONES AND AMMONIA
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The direct synthesis of ketimines from ammonia and ketones catalyzed by ammonium chloride is described.
- Verardo, Giancarlo,Giumanini, Angelo G.,Strazzolini, Paolo,Poiana, Marco
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p. 1501 - 1512
(2007/10/02)
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- Reactivity of the Labile Silaethene Me2Si=C(SiMe3)2, Stored as Ph2C=NSiMe3 Adducts
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Silaethene Me2Si=C(SiMe3)2 (1), stored as Ph2C=NSiMe3 adducts and regenerated from the adducts at about 100 deg C as a reaction intermediate, combines with reactants a-b (e.g.HO-H, RO-H, RCOO-H, RS-H, RHN-H, Ph2CN-H, RO-SiR3, R2N-SiR3, Ph2CN-SiR3, Cl-GeR3, Cl-SnR3) with insertion into the a-b bond, with a=b (e.g.O=CPh2, Me3SiN=CPh2, CH2=CHOMe, cis-piperylene), a=b=c (e.g.RN=N=N, O=N=N), a=b-c=d (e.g. butadiene, isoprene, trans-piperylene, 2,3-dimethylbutadiene, cyclopentadiene, anthracene, benzophenone, N-trimethylsilylbenzophenoneimine) under -, - as well as -c ycloaddition and with a=b-c-H (e.g. propene, butenes, isoprene, 2,3-dimethylbutadiene, acetone) under ene reaction.According to relative reaction rates, insertion and -cycloadditions seem to proceed in two reaction steps, whereas -cycloadditions and ene reactions with organic dienes and enes obviously are one step reactions.For reactivities cf.Table I. - Key words: Silaethene Me2Si=C(SiMe3)2, Insertions, Cycloadditions, Relative Reactivities
- Wiberg, N.,Preiner, G.,Wagner, G.,Koepf, H.
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p. 1062 - 1074
(2007/10/02)
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- N-Acyl- and N-Aryl-N'-alkylidenureas as Precursors of Isocyanates or Acylisocyanates
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Derivatives of isocyanates or acylisocyanates were prepared by reactions with ketimines.Fragmentation reactions of the product were examined.
- Schweim, Harald G.,Juergens, Sabine
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p. 844 - 850
(2007/10/02)
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