- Nucleophilic aromatic substitution of unactivated fluoroarenes enabled by organic photoredox catalysis
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Nucleophilic aromatic substitution (SNAr) is a classical reaction with well-known reactivity toward electron-poor fluoroarenes. However, electron-neutral and electron-rich fluoro(hetero)arenes are considerably underrepresented. Herein, we present a method for the nucleophilic defluorination of unactivated fluoroarenes enabled by cation radical-accelerated nucleophilic aromatic substitution. The use of organic photoredox catalysis renders this method operationally simple under mild conditions and is amenable to various nucleophile classes, including azoles, amines, and carboxylic acids. Select fluorinated heterocycles can be functionalized using this method. In addition, the late-stage functionalization of pharmaceuticals is also presented. Computational studies demonstrate that the site selectivity of the reaction is dictated by arene electronics.
- Nicewicz, David A.,Pistritto, Vincent A.,Schutzbach-Horton, Megan E.
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supporting information
p. 17187 - 17194
(2020/11/02)
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- Method for preparing diaryl ester compound through efficient catalysis of pyridine palladium
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The invention discloses a method for preparing a diaryl ester compound through efficient catalysis of pyridine palladium. The method is used for high-efficiency high-yield preparation of the diaryl ester compound under mild conditions by taking a phenol compound, an iodobenzene compound and carbon monoxide as raw materials, triethylamine as alkali and pyridine palladium as a catalyst. The method provided by the invention has the advantages of less usage amount of the palladium catalyst, high catalytic activity of the palladium catalyst, stability of the palladium catalyst to air, simple operation, short reaction time and high atom economy, opens up a low-cost, green and efficient way for preparation of diaryl ester compounds, and has broad application prospects.
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Paragraph 0016-0020; 0056-0060
(2020/12/31)
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- Supramolecular Pd(II) complex of DPPF and dithiolate: An efficient catalyst for amino and phenoxycarbonylation using Co2(CO)8 as sustainable C1 source
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Highly active, efficient and robust “dppf ligated tetranuclear palladium dithiolate complex” was synthesized and applied as a catalyst for chemical fixation of carbon monoxide for the synthesis value added chemicals such as tertiary amide and aromatic esters. The synthesized catalyst was characterized using different analytical techniques such as elemental analysis, 1H and 31P NMR spectroscopy. The use of Co2(CO)8 as a cheap, less toxic and low melting solid surrogate are additional advantages over the current protocol. The catalyst showed superior activity towards the Amino (10?3 mol % catalyst) and Phenoxycarbonylation (10-2 mol % catalyst) and high TON (104 to 103) and TOF (103 to 102 h-1). The Betol and Lintrin (active drug molecules) were synthesized under an optimized reaction condition. The scalability of the current protocol has been demonstrated up-to the gram level.
- Gaikwad, Vinayak V.,Mane, Pravin A.,Dey, Sandip,Patel, Divya,Bhanage, Bhalchandra M.
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- An alternative route for boron phenoxide preparation from arylboronic acid and its application for C[sbnd]O bond formation
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An efficient synthetic route to benzyl phenyl ether preparation has been successfully developed via a one-pot synthetic protocol utilizing a combination of arylboronic acids, hydrogen peroxide (H2O2), and benzyl halides. The whole procedure consists of two consecutive reactions, formation of boron phenoxide from arylboronic acids and its nucleophilic attack. A simple operation under mild conditions such as room-temperature ionic liquid (choline hydroxide), aerobic environment, and absence of metal- and base-catalysts has been employed. Expansion to utilize benzyl surrogates was also successfully accomplished.
- Joo, Seong-Ryu,Kim, Seung-Hoi,Lim, In-Kyun
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- Oxime palladacycle in PEG as a highly efficient and recyclable catalytic system for phenoxycarbonylation of aryl iodides with phenols
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In this report, we have developed a sustainable protocol for the synthesis of aromatic esters by a carbonylative method using di-μ-chlorobis [5-hydroxy-2-[1-(hydroxyimino-?N) ethyl] phenyl-?C] palladium (II) dimer (1) catalyst in PEG-400 as a greener and recyclable solvent. The reaction is carried out at room temperature using CO in a balloon. Good to excellent yield of various esters can be synthesize using this protocol. Direct insertion of CO moiety leads to the high atom and step economy. Compared to previous protocol this phosphine free approach for the synthesis of aromatic esters provides high Turnover Number (TON) and Turnover Frequency (TOF). Developed approach has an alternative route for use of conventional palladium precursor with high conversion and selectivity. The catalyst system and product can easily be separated using diethyl ether as a solvent. The Pd/PEG-400 system could be reused up to a fifth consecutive cycle without any loss of its activity and selectivity.
- Gaikwad, Vinayak V.,Bhanage, Bhalchandra M.
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- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE 4 POLYPEPTIDES
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The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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Paragraph 1504-1505
(2019/06/07)
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- Nickel-Catalyzed Cross-Coupling of Aryl Redoxactive Esters with Aryl Zinc Reagents
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A nickel-catalyzed aryl-aroyloxyl C(sp2)-O radical cross-coupling reaction conducted using a redox active ester with aryl zinc reagent was developed. This method demonstrates a new disconnection approach for formation of aryl aryl esters. In the one-pot sequential process, the readily available aryl carboxylic acids can be converted into functionalized aryl aryl esters and heteroaryl esters. This protocol is amenable to the gram-scale synthesis. The present method has a wide substrate scope and high functional group tolerance.
- Shih, Bo-Hao,Basha, R. Sidick,Lee, Chin Fa
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p. 8862 - 8866
(2019/09/30)
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- Electrodimerization of N-Alkoxyamides for Zinc(II) Catalyzed Phenolic Ester Synthesis under Mild Reaction Conditions
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An electrochemical On-Off method for phenolic ester synthesis from N-alkoxyamides has been reported. This one-pot protocol begins with rapid and selective electrodimerization of the amide using n-Bu4NI (TBAI) as an electrocatalyst. The reaction proceeds further in the absence of current via Zn catalyzed C?N bond activation of the amide dimer followed by its coupling with phenol to form the ester. The present methodology is ligand-free and takes place under mild reaction conditions. This transformation incorporates a wide variety of phenols and amide substrates leading to the formation of functionalized esters highlighting its versatility. (Figure presented.).
- Subramanian, Kripa,Yedage, Subhash L.,Bhanage, Bhalchandra M.
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p. 2511 - 2521
(2018/05/14)
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- Pd/C catalyzed phenoxycarbonylation using: N -formylsaccharin as a CO surrogate in propylene carbonate, a sustainable solvent
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This work reports the first Pd/C catalyzed phenoxycarbonylation of aryl iodides using N-formylsaccharin as a CO surrogate. Advantageously, the reaction could be carried out in propylene carbonate, an environmentally benign and sustainable polar aprotic solvent under CO surrogacy. Using N-formylsaccharin as a CO surrogate allows the usage of cheaper and readily available phenols as the coupling partner. A range of phenyl esters could be synthesized under mild, co-catalyst free, ligand free and additive free conditions, including multi-substituted novel phenyl esters. The Pd/C catalyst could be recycled up to four times with only a slight loss in activity. The reaction could be scaled up to gram scale synthesis.
- Gautam, Prashant,Kathe, Prasad,Bhanage, Bhalchandra M.
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supporting information
p. 823 - 830
(2017/08/15)
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- Ph3P-I2 mediated aryl esterification with a mechanistic insight
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In order to better understand the reaction mechanism and to obtain optimal conditions, the Ph3P-I2/Et3N mediated aryl esterification reaction was thoroughly investigated. Using a specific reagent addition sequence, the reaction proceeds remarkably well especially with acidic substrates. 31P NMR studies revealed that the formation of an aryloxyphosphonium salt is crucial in governing the reaction path toward the formation of phenolic esters.
- Phakhodee, Wong,Duangkamol, Chuthamat,Pattarawarapan, Mookda
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supporting information
p. 2087 - 2089
(2016/04/26)
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- Erbium trifluoromethanesulfonate catalyzed Friedel-Crafts acylation using aromatic carboxylic acids as acylating agents under monomode-microwave irradiation
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Erbium trifluoromethanesulfonate is found to be a good catalyst for the Friedel-Crafts acylation of arenes containing electron-donating substituents using aromatic carboxylic acids as the acylating agents under microwave irradiation. An effective, rapid and waste-free method allows the preparation of a wide range of aryl ketones in good yields and in short reaction times with minimum amounts of waste.
- Tran, Phuong Hoang,Hansen, Poul Erik,Nguyen, Hai Truong,Le, Thach Ngoc
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p. 612 - 618
(2015/02/19)
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- A metal-free, carbon-based catalytic system for the oxidation of lignin model compounds and lignin
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Nitrogen-containing graphene material (LCN) has been identified as an effective catalyst for the oxidation of β-O-4 and α-O-4 types of lignin model compounds in the presence of tert-butyl hydroperoxide, to provide aromatic aldehydes, acids and other organic chemicals in high yield. The transformations of five lignin model compounds over LCN were investigated systematically. Instrumentation analysis, kinetic study and radical trapping experiments highlight the mechanistic features of the reaction, including: 1) the reaction pathway starts by benzylic C-H or C-OH bond activation, followed by Cα-Cβ or Cα-O bond cleavage, and finally further oxidation of intermediate aromatics; and 2) the reaction follows a free-radical mechanism with all the key steps involving radical species. In addition, the LCN proved to be a highly stable catalyst; no significant activity decrease was observed for four consecutive runs, and X-ray photoelectron spectroscopy analysis indicates negligible decrease in the content of the active nitrogen species in the catalyst. Notably, this new catalytic system can be extended to the oxidative depolymerisation of real lignin, to produce a significant portion of liquefied, low-molecular-mass products. Low mass, high conversion: Nitrogen-containing graphene-based carbon material has been used to establish a metal-free catalytic system for the oxidation of α-O-4 and β-O-4 types of lignin model compounds in the presence of tert-butyl hydroperoxide (see figure). In the oxidative depolymerization of organosolv lignin, a significant portion of liquefied, low-molecular-mass product is produced. Copyright
- Gao, Yongjun,Zhang, Jiaguang,Chen, Xi,Ma, Ding,Yan, Ning
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p. 825 - 834
(2014/07/08)
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- Visible-light-triggered direct benzoyloxylation of electron-rich arenes at room temperature without chelation assistance
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A RuII photocatalytic method was developed for the direct mono-benzoyloxylation of electron-rich aromatic and heteroaromatic systems even with an excess amount of benzoyl peroxide. The reaction was conducted at room temperature under visible light. The direct ArC-H benzoyloxylations occur without the assistance of any directing groups and can also tolerate various functional groups that have already shown diverse reactivities in transition-metal catalysis.
- Rao, Honghua,Wang, Ping,Li, Chao-Jun
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supporting information
p. 6503 - 6507
(2013/01/15)
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- Palladium-catalyzed aerobic oxidative coupling of acyl chlorides with arylboronic acids
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The first example of a palladium-catalyzed aerobic oxidative coupling of acyl chlorides with arylboronic acids has been developed, leading to a wide range of aryl benzoates in good to excellent yields. This catalytic system shows broad functional group tolerance. Preliminary mechanistic experiments using deuterium labeling showed that the oxygen atom was derived from dioxygen. Copyright
- Chen, Jiuxi,Peng, Yong,Liu, Miaochang,Ding, Jinchang,Su, Weike,Wu, Huayue
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supporting information
p. 2117 - 2122
(2012/11/07)
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- Palladium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols
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A palladium/NHC-catalyzed tandem benzylic oxidation/oxidative esterification of benzylic alcohols with phenols to access aryl benzoate derivatives is described. The procedure tolerates a series of functional groups, such as methoxy, nitro, cyano, chloro, fluoro and bromo groups. Thus, it represents a practically alternative method to access aryl benzoate derivatives.
- Luo, Fang,Pan, Changduo,Cheng, Jiang,Chen, Fan
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supporting information; experimental part
p. 5878 - 5882
(2011/09/12)
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- Palladium/NHC-catalyzed oxidative esterification of aldehydes with phenols
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A palladium-catalyzed oxidative esterification of aldehydes with phenols is described, using air as the clean oxidant. This reaction tolerates many functional groups, providing esters with yields ranging from moderate to excellent.
- Zhang, Manli,Zhang, Shouhui,Zhang, Guoying,Chen, Fan,Cheng, Jiang
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experimental part
p. 2480 - 2483
(2011/05/16)
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- METHOD FOR PRODUCING OPTICALLY ACTIVE ESTER AND METHOD FOR PRODUCING OPTICALLY ACTIVE CARBOXYLIC ACID
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Disclosed is a method for producing an optically active ester by highly selectively esterifying one enantiomer of a racemic carboxylic acid, while producing an optically active carboxylic acid which is the other enantiomer. An optically active ester is produced while producing an optically active carboxylic acid at the same time by reacting a racemic carboxylic acid with a specific alcohol or phenol derivative in the presence of benzoic anhydride or a derivative thereof and a catalyst such as tetramisole or benzotetramisole, thereby selectively esterifying one enantiomer of the racemic carboxylic acid.
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Page/Page column 6
(2010/09/18)
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- 5,5′-Dimethyl-3,3′-azoisoxazole as a new heterogeneous azo reagent for esterification of phenols and selective esterification of benzylic alcohols under Mitsunobu conditions
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5,5′-Dimethyl-3,3′-azoisoxazole is used as a new efficient heterogeneous azo reagent for the highly selective esterification of primary and secondary benzylic alcohols and phenols with aliphatic and aromatic carboxylic acids via Mitsunobu protocols. The reaction is highly selective for primary benzylic alcohols versus secondary ones, aliphatic alcohols and also phenols. The isoxazole hydrazine byproduct can be simply isolated by filtration and recycled to its azoisoxazole by oxidation.
- Iranpoor, Nasser,Firouzabadi, Habib,Khalili, Dariush
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supporting information; experimental part
p. 4436 - 4443
(2010/11/05)
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- Easily prepared azopyridines as potent and recyclable reagents for facile esterification reactions. An efficient modified mitsunobu reaction
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(Chemical Equation Presented) The 2,2′-, 3,3′-, and 4,4′-azopyridines (azpy) and their alkyl pyridinium ionic liquids were studied as a new class of electron-deficient reagents for Mitsunobu esterification reactions. Among these compounds, 4,4′-azopyridine was found to be the most suitable one for esterification and thioesterification reactions. This new reagent promises to provide general and complementary solutions for separation problems in Mitsunobu reactions without restricting the reaction scope and facilitates the isolation of its hydrazine byproduct. The pyridine hydrazine byproduct can be simply recycled to its azopyridine by an oxidation reaction.
- Iranpoor, Nasser,Firouzabadi, Habib,Khalili, Dariush,Motevalli, Somayeh
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p. 4882 - 4887
(2008/09/21)
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- Total Synthesis and Absolute Configuration of Otteliones A and B, Novel and Potent Antitumor Agents from a Freshwater Plant
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(Matrix presented) The first enantioselective total synthesis of otteliones A and B, biologically important and structurally novel natural products, has been successfully achieved. This total synthesis fully confirms the absolute configuration of these natural products.
- Araki, Hiroshi,Inoue, Munenori,Katoh, Tadashi
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p. 3903 - 3906
(2007/10/03)
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- Free radical reactions for heterocycle synthesis. Part 4: A double ipso substitution reaction for azacoumarins
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A highly efficient route to azacoumarins with an unusual mechanism of double ipso substitutions is described.
- Zhang, Wei,Pugh, Georgia
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p. 5613 - 5615
(2007/10/03)
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- A stereoselective synthesis of (R)-(-)-rolipram from L-glutamic acid
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A stereoselective synthesis of (R)-(-)-rolipram from L-glutamic acid is described. The key step is a stereoselective Michael addition of an arylcuprate to a modified pyroglutamic derivative which acts as the template to induce the stereoselectivity. Facile manipulation of the enantiomerically pure Michael product afforded the expected therapeutic agent.
- Diaz, Adolfo,Siro, Jorge G.,García-Navío, José L.,Vaquero, Juan J.,Alvarez-Builla, Julio
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p. 559 - 562
(2007/10/03)
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- 1-Alkoxy-2-(alkoxy- or cycloalkoxy-)-4-(cyclothioalkyl- or cyclothioalkenyl-) benzenes as inhibitors of cyclic AMP phosphodiesterase and tumor necrosis factor
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This invention is directed to 1-alkoxy-2-(alkoxy- or cycloalkyloxy-)-4-(cyclothioalkyl- or cyclothioalkenyl-)benzene compounds that inhibit cyclic AMP phosphodiesterase or tumor necrosis factor (TNF) and are useful in treating patients suffering from disease state capable of being modulated by inhibiting production of cyclic AMP phosphodiesterase or TNF by administering the compound to the patient. The invention is also directed to the preparation of these compounds, pharmaceutical compositions containing these compounds and methods for their pharmaceutical use.
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- Aryloxenium Ions. Generation from N-(Aryloxy)pyridinium Tetrafluoroborates and Reaction with Anisole and Benzonitrile
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N-(Aryloxy)pyridinium tetrafluoroborates (4) decompose thermally at 180-200 deg C in anisole and benzonitrile to form products of intermolecular C-O-C and C-C bond formation.With anisole, diphenyl ethers (5) and hydroxybiphenyls (6) are formed; with benzonitrile, the main product is benzoxazole (14).A homolytic process was ruled out by showing that none of these products were formed when perbenzoyl p-nitrophenyl carbonate (18) was decomposed in these solvents.The main products in this case were those of homolytic phenylation (and benzoyloxylation with anisole).A concerted SN2-type heterolytic process was ruled out by showing that the nature of the substituent in the pyridine ring had no effect on the isomer ratios of 5 and 6 in the thermolysis of 4 (X = p-NO2) in anisole.The results are explained in terms of a unimolecular heterolysis of 4 to give the pyridine and aryloxenium ion 2 which now attacks solvent molecules.When an electron-withdrawing substituent is present in 2, more C-O-C than C-C products are formed in anisole.When it is absent only products of C-C bond formation are found.PhO+ is apparently electrophilic enough to attack anisole and give the four possible hydroxymethoxybiphenyls (10-13).
- Abramovitch, Rudolph A.,Alvernhe, Gerard,Bartnik, Romuald,Dassanayake, Nissanke L.,Inbasekaran, Mutiah N.,Kato, Shiego
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p. 4558 - 4565
(2007/10/02)
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- Aroyl Peroxides. Part 7. The Effects of Additives on the Thermolysis of Aroyl Peroxides in Arenes and the Elimination of Possible Complications in the Measurement of Partial Rate Factors for Phenylation
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Competitive homolytic arylation of arenes has been carried out under conditions in which biaryl formation is maximised.Improved yields of biaryl were obtained with o-chloroanil, nitro- and nitroso-compounds, and transition metal salts; nitrosobenzene, pentafluoronitrosobenzene, copper(II)benzoate, and iron(III)benzoate caused nearly theoretical yields of biaryl and aroic acid.Partial rate factors, measured under such conditions, are free from uncertainties arising from the selective removal of ?-complexes by side-processes such as dimerisation.The possibility that arenes form complexes with aryl radicals or their precursors as a necessary part of the selection process between substrate molecules was not confirmed in studies of the application of the additivity principle and of the multiplication rule, and of variation in the relative concentration of the two competing arenes.The absence of any discrepancies indicates that the measured partial rate factors are not influenced by such putative complex formation.The mechanism of action of these catalysts has been investigated.
- Bolton, Roger,Dailly, Bryce N.,Hirakubo, Kazuko,Lee, Kong Hung,Williams, Gareth H.
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p. 1109 - 1120
(2007/10/02)
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