- The Phototransposition in Acetonitrile and the Photoaddition of 2,2,2-Trifluoroethanol to the Six Isomers of Dimethylbenzonitrile
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The six dimethylbenzonitriles can be divided into two independent triads in their photochemical reactivity. The first triad is comprised of the 2,3-dimethyl, 3,4-dimethyl, and 2,6-dimethyl isomers (11-2,3, 11-3,4, and 11-2,6, respectively); the second triad is comprised of the 2,4-dimethyl, 2,5-dimethyl, and 3,5-dimethyl isomers (11-2,4, 11-2,5, and 11-3,5, respectively). In acetonitrile, phototransposition converts the members of one triad to other members of the same triad, although only 11-3,4 was reactive enough to have significant conversion approaching a steady-state composition. Irradiation in 2,2,2-trifluoroethanol (TFE) resulted in the formation of addition products, 6-cyano-X,Y-dimethylbicyclo[3.1.0]hex-3-en-2-yl 2,2,2,-trifluoroethyl ethers, but in significant yield only from 11-3,4 of the first triad and 11-2,4 of the second triad. The 11-3,4 isomer gave seven major regio- and stereoisomers; the 11-2,4 isomer gave three different regio- and stereoisomers. These addition products were all explained by formation of bicyclo[3.1.0]hex-3-en-1-yl cations resulting from protonation by TFE at C6 followed by nucleophilic trapping by TFE. From these and previous results on aromatic nitriles, a consistent mechanistic picture is obtained where the critical carbon in determining the products of the phototransposition and photoaddition reactions is the cyano substituted one.
- Howell, Nisa,Pincock, James A.,Stefanova, Roumiana
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- Facile dehydration of primary amides to nitriles catalyzed by lead salts: The anionic ligand matters
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The synthesis of nitrile under mild conditions was achieved via dehydration of primary amide using lead salts as catalyst. The reaction processes were intensified by not only adding surfactant but also continuously removing the only by-product, water from the system. Both aliphatic and aromatic nitriles can be prepared in this manner with moderate to excellent yields. The reaction mechanisms were obtained with high-level quantum chemical calculations, and the crucial role the anionic ligand plays in the transformations were revealed.
- Ruan, Shixiang,Ruan, Jiancheng,Chen, Xinzhi,Zhou, Shaodong
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- Method for continuous preparation of nitriles by amides (by machine translation)
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The method comprises the following steps: preparing a lead salt supported by a molecular sieve by a lead salt and a molecular sieve through an impregnation method; and filling a molecular sieve-loaded lead catalyst into a fixed bed reactor. The amide or amide solution is sent into a fixed bed reactor from the top of the fixed bed to be subjected to catalytic dehydration, and the obtained reaction product is led out from the bottom of the fixed bed. The reaction product is separated to obtain the crude product of the nitrile corresponding to the amide. A fixed bed continuous production process is adopted, the reaction process is simple, the production efficiency is high, the product post-treatment is simple, and industrial production is easy to realize. (by machine translation)
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Paragraph 0033-0054; 0061-0065
(2020/12/15)
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- Method for continuous preparation of nitriles in a pipelined reactor (by machine translation)
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The method comprises the following steps that a tin catalyst is coated on the inner wall of the pipeline reactor; and the method comprises the following steps: coating a tin catalyst on the inner wall of the pipeline reactor. The amide solution and the catalytic auxiliary agent are mixed and then sent to a pipeline reactor, and the amide is dehydrated to generate nitrile at the reaction pressure of 0.1 - 2.0 mpa and 100 - 200 °C reaction temperature. The resulting reaction product was separated to give the crude product of the nitrile to which the amide corresponded. In the pipeline reactor, the corresponding nitrile is continuously prepared under the action of the tin catalyst, a dehydrating agent is not needed, byproducts only are water, and three wastes are reduced. (by machine translation)
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Paragraph 0036-0047; 0056-0057
(2020/12/14)
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- Dual Ligand-Enabled Nondirected C-H Cyanation of Arenes
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Aromatic nitriles are key structural units in organic chemistry and, therefore, highly attractive targets for C-H activation. Herein, the development of an arene-limited, nondirected C-H cyanation based on the use of two cooperatively acting commercially available ligands is reported. The reaction enables the cyanation of arenes by C-H activation in the absence of directing groups and is therefore complementary to established approaches.
- Chen, Hao,Mondal, Arup,Wedi, Philipp,Van Gemmeren, Manuel
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p. 1979 - 1984
(2019/02/19)
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- Palladium-Catalyzed Late-Stage Direct Arene Cyanation
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Methods for direct benzonitrile synthesis are sparse, despite the versatility of cyano groups in organic synthesis and the importance of benzonitriles for the dye, agrochemical, and pharmaceutical industries. We report the first general late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance. The reaction is enabled by a dual-ligand combination of quinoxaline and an amino acid-derived ligand. The method is applicable to direct cyanation of several marketed small-molecule drugs, common pharmacophores, and organic dyes. Benzonitriles are some of the most versatile building blocks for organic synthesis, in particular in the pharmaceutical industry, but general methods to make them by direct C–H functionalization are unknown. In this issue of Chem, Ritter and coworkers describe a late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance, enabled by a palladium-dual-ligand catalyst system. The reaction may serve for the late-stage modification of drug candidates. Aryl nitriles constitute an important class of organic compounds that are widely found in natural products, pharmaceuticals, agricultural chemicals, dyes, and materials. Moreover, nitriles are versatile building blocks to access numerous other important molecular structure groups. However, no general method for direct aromatic C–H cyanation is known. All approaches to date require either an appropriate directing group or reactive electron-rich substrates, such as indoles, which limit their synthetic applications. Here we describe an undirected, palladium-catalyzed late-stage aryl C–H cyanation reaction for the synthesis of complex aryl nitriles that would otherwise be more challenging to produce. The wide substrate scope and good functional-group tolerance of this reaction provide direct and quick access to structural diversity for pharmaceutical and agrochemical development.
- Zhao, Da,Xu, Peng,Ritter, Tobias
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supporting information
p. 97 - 107
(2019/01/21)
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- Ligand-Promoted Non-Directed C?H Cyanation of Arenes
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This article reports the first example of a 2-pyridone accelerated non-directed C?H cyanation with an arene as the limiting reagent. This protocol is compatible with a broad scope of arenes, including advanced intermediates, drug molecules, and natural products. A kinetic isotope experiment (kH/kD=4.40) indicates that the C?H bond cleavage is the rate-limiting step. Also, the reaction is readily scalable, further showcasing the synthetic utility of this method.
- Liu, Luo-Yan,Yeung, Kap-Sun,Yu, Jin-Quan
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supporting information
p. 2199 - 2202
(2019/01/24)
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- Pd Catalysis in Cyanide-Free Synthesis of Nitriles from Haloarenes via Isoxazolines
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A method to obtain aryl nitriles from the corresponding halides by Pd catalysis, in the absence of any cyanide source, is reported. The reaction of an aryl halide, ethyl nitroacetate, and an olefin readily delivers an aromatic nitrile. A variety of aryl iodides/bromides have been converted into the corresponding cyanoarenes in fair to excellent yields. The reaction likely involves the following steps: (a) Pd-catalyzed α-arylation of ethyl nitroacetate; (b) nitrile oxide formation; (c) [3 + 2]-cycloaddition with an olefin to provide an isoxazoline; (d) isoxazoline cleavage to benzonitrile formation.
- Maestri, Giovanni,Ca?eque, Tatiana,Della Ca, Nicola,Derat, Etienne,Catellani, Marta,Chiusoli, Gian Paolo,Malacria, Max
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supporting information
p. 6108 - 6111
(2016/12/09)
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- Acetonitrile as a cyanating reagent: Cu-catalyzed cyanation of arenes
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A novel approach to the Cu-catalyzed cyanation of simple arenes using acetonitrile as an attractive cyano source has been documented. The C-H functionalization of arenes without directing groups involves a sequential iodination/cyanation to give the desired aromatic nitriles in good yields. A highly efficient Cu/TEMPO system for acetonitrile C-CN bond cleavage has been discovered. TEMPO is used as a cheap oxidant and enables the reaction to be catalytic in copper. Moreover, TEMPOCH2CN 6 has been identified as the active cyanating agent and shows high reactivity for forming the -CN moiety.
- Zhu, Yamin,Zhao, Mengdi,Lu, Wenkui,Li, Linyi,Shen, Zengming
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supporting information
p. 2602 - 2605
(2015/06/16)
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- Iron(II)-catalyzed direct cyanation of arenes with aryl(cyano)iodonium triflates
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A direct oxidative cyanation of arenes under FeII catalysis with 3,5-di(trifluoromethyl)phenyl(cyano)iodonium triflate (DFCT) as the cyanating agent has been developed. The reaction is applicable to wide range of aromatic substrates, including polycyclic structures and heteroaromatic compounds. Copyright
- Shu, Zhibin,Ji, Wenzhi,Wang, Xi,Zhou, Yujing,Zhang, Yan,Wang, Jianbo
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supporting information
p. 2186 - 2189
(2014/03/21)
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- One-pot conversion of aromatic bromides and aromatics into aromatic nitriles via aryllithiums and their DMF adduct
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Various aromatic bromides and iodides were smoothly converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH3. The same treatment of typical aromatics and heteroaromatics with n-butyllithium and subsequently DMF, followed by treatment with molecular iodine in aq NH3 also provided the corresponding aromatic nitriles in good yields. Moreover, the same treatment of aromatic bromides and aromatics with half amount of DIH (1,3-diiodo-5,5- dimethylhydantoin) instead of molecular iodine worked effectively to give the corresponding aromatic nitriles, respectively, in good yields. These reactions are novel and environmentally benign one-pot methods for the preparation of aromatic nitriles from aromatic bromides and aromatics, respectively, through the formation of aryllithiums and their DMF adducts.
- Ushijima, Sousuke,Moriyama, Katsuhiko,Togo, Hideo
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experimental part
p. 958 - 964
(2011/03/19)
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- One-pot conversion of aromatic bromides and aromatics into aromatic nitriles
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Various aromatic bromides and iodides were smoothly converted into the corresponding aromatic nitriles in good to moderate yields by the treatment with butyllithium and subsequently DMF, followed by treatment with molecular iodine in aqueous ammonia. The
- Ushijima, Sousuke,Togo, Hideo
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experimental part
p. 1562 - 1566
(2010/09/05)
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- Oxidation of Aromatic Compounds. V. Oxidation of Substituted Benzonitriles and 2,4,6-Triaryl-1,3,5-Triazines in System HSO3F-PbO2
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Low-temperature oxidation of substituted benzonitriles by the system HSO3F-PbO2 proceeds with intermediate formation of cation-radicals and leads to substitution of hydrogen atoms of the methyl group or benzene ring. This reaction provides a route for preparation of chloromethylsubstituted benzonitriles, diarylmethanes, diaryls, arylfluorosulfonates and substituted benzamides with cyano groups. In the case of methyl derivatives of 2,4,6-triphenyl-1,3,5-triazine substitution of the first and then the second hydrogen atom of the same methyl group transforms it into hydroxy or chloromethyl group, or into the aldehyde function.
- Rudenko,Salfetnikova,Vasil'ev
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p. 1447 - 1470
(2007/10/03)
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- Methyl Group Effect on the Proton Affinity of Methylated Acetophenones Studied by Two Mass Spectrometric Techniques
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The proton affinities (PA) of all isomeric dimethylacetophenones were determined using the "kinetic method" with a tandem mass spectrometer and by measurements of the proton transfer equilibrium in the gas phase by Fourier transform ion cyclotron resonance mass spectrometry.For both methods acetophenone and p-methylacetophenone, with well known PA values, were used as reference bases.Both methods yielded identical PA values for all dimethylacetophenones.The PA of the dimethylacetophenones were in a narrow range between 872 and 880 kJ mol-1 except for 2,6-dimethylacetophenone, for which a PA of 856 kJ mol-1 was found.The results are discussed in terms of possible mesomeric structures stabilizing the positive charge with regard to the substitution pattern in the phenyl ring.Obviously, the significant smaller PA of 2,6-dimethylacetophenone compared with the other isomers is due to the distortion of the conjugation of the C-O double bond with the aromatic ? system.
- Kukol, A.,Strehle, F.,Thielking, G.,Gruetzmacher, H.-Fr.
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p. 1107 - 1110
(2007/10/02)
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- A new modified electrophilic cyanation of aromatics with activated aryl cyanates
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The selective cyanation of electron-rich aromatics succeeds in moderate to good yields with the activated aryl cyanates 1a-d using AlCl3/HCl. The formation of p-isomeres is preferred.
- Buttke,Reiher,Niclas
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p. 2237 - 2243
(2007/10/02)
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- ELECTROPHILIC AROMATIC SUBSTITUTION. PART 29. THE KINETICS AND PRODUCTS OF THE SOLVOLYSES IN AQUEOUS SULPHURIC ACIDS OF 2-CYANO-3,4-DIMETHYL-4-NITROCYCLOHEXA-2,5-DIENYL ACETATE: THE NON OCCURRENCE OF AN INTRAMOLECULAR 1,3-MIGRATION OF THE NITRO-GROUP IN THE SOLVOLYTIC REACTIONS OF THE ..
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The kinetics in 61.8-79.5percent H2SO4 and the products formed in 61.8-84.3percent H2SO4 for the solvolyses of the above-named diene have been determined.The reactions are interpreted as involving concurrent elimination of nitrous acid and AAL1 generation of the same ipso-intermediate as arises in the nitration of 2,3-dimethylbenzonitrile.This intermediate reacts by intermolecular rearrangement (as it is proved by the isolation from the solvolyses of 2,3-dimethylbenzonitrile and the trapping of nitronium ion by reaction with 4-fluorophenol), by nucleophilic capture by water, and by 1,2-intramolecular rearrangement to 2,3-dimethyl-4-benzonitrile.The results permit the partitioning of the overall solvolytic rate coefficient and the demonstration that the derived coefficient for the reaction competing with the elimination depends on acidity as would be expected for an AAL1 reaction.The elimination of nitrous acid is also acid-catalysed and may not be a simple E1 reaction.The solvolytic reactions of the diene do not lead to a 1,3-intramolecular rearrangement of the nitro-group and the observed 1,3-rearrangement of the diene to give 2,3-dimethyl-5-nitrobenzonitrile under non-solvolytic conditions appears to be a thermal reaction of the diene molecule.By combining the solvolysis results with those for the nitration of 2,3-dimethylbenzonitrile in 70.4-82.5percent H2SO4 it is shown that the major primary consequence of the nitration is ipso-attack and that it is possible to determine the positional reactivities in the nitrile.
- Bloomfield, Colin,Moodie, Roy B.,Schofield, Kenneth
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p. 1003 - 1010
(2007/10/02)
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