- Robust, efficient, and recyclable catalysts from the impregnation of preformed dendrimers containing palladium nanoparticles on a magnetic support
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The simple impregnation of ?3-Fe2O3(core)/SiO2(shell) magnetic nanoparticles with a dendrimer that contains stabilized Pd nanoparticles is presented as a new method to produce highly efficient heterogeneous catalysts. This technique provides much better stability, recyclability, and activity in C-C cross-coupling reactions and selective oxidation of benzyl alcohol to benzaldehyde in water than unsupported Pd nanoparticles.
- Deraedt, Christophe,Wang, Dong,Salmon, Lionel,Etienne, Laetitia,Labrug?¤re, Christine,Ruiz, Jaime,Astruc, Didier
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Read Online
- A Study of Heterogeneous Catalysis by Nanoparticle-Embedded Paper-Spray Ionization Mass Spectrometry
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We have developed nanoparticle-embedded paper-spray mass spectrometry for studying three types of heterogeneously catalyzed reactions: 1) Palladium-nanoparticle-catalyzed Suzuki cross-coupling reactions, 2) palladium- or silver-nanoparticle-catalyzed 4-nitrophenol reduction, and 3) gold-nanoparticle-catalyzed glucose oxidation. These reactions were almost instantaneous on the nanocatalyst-embedded paper, which subsequently transferred the transient intermediates and products to a mass spectrometer for their detection. This in situ method of capturing transient intermediates and products from heterogeneous catalysis is highly promising for investigating the mechanism of catalysis and rapidly screening catalytic activity under ambient conditions.
- Banerjee, Shibdas,Basheer, Chanbasha,Zare, Richard N.
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Read Online
- Suzuki-Miyaura cross coupling is not an informative reaction to demonstrate the performance of new solvents
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The development and study of new solvents has become important due to a proliferation of regulations preventing or limiting the use of many conventional solvents. In this work, the suitability of the Suzuki-Miyaura reaction to demonstrate the usefulness of new solvents was evaluated, including CyreneTM, dimethyl isosorbide, ethyl lactate, 2-methyltetrahydrofuran (2-MeTHF), propylene carbonate, and γ-valerolactone (GVL). It was found that the cross coupling is often unaffected by the choice of solvent, and therefore the Suzuki-Miyaura reaction provides limited information regarding the usefulness of any particular solvent for organic synthesis.
- Sherwood, James
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Read Online
- Controlling Multiple Active Sites on Pd?CeO2 for Sequential C?C Cross-coupling and Alcohol Oxidation in One Reaction System
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Ceria (CeO2)-supported metal catalysts have been widely utilized for various single-step chemical transformations. However, using such catalysts for a multistep organic reaction in one reaction system has rarely been achieved. Here, we investigate multiple active sites on Pd?CeO2 catalysts and optimize them for a multistep reaction of C?C cross-coupling and alcohol oxidation. Atomic-level imaging and spectroscopic studies reveal that metallic Pd0 and Pd?CeO2 interface are active sites on Pd?CeO2 for C?C cross-coupling and oxidation, respectively. These active sites are controlled under the structural evolution of Pd?CeO2 during reductive heat-treatments. Accordingly, we found that optimally reduced Pd?CeO2 catalysts containing ～1.5 nm-sized Pd nanoclusters with both sites in balance are ideal for multistep chemical transformations in one reaction system. Our strategy to design supported metal catalysts leads to one-pot sequential synthetic protocols for pharmaceutical building blocks.
- Antink, Wytse Hooch,Bok, Jinsol,Cho, Sung-Pyo,Choi, Hyunwoo,Hyeon, Taeghwan,Jung, Yoon,Kim, Do Heui,Kim, Jiheon,Kim, Jongchan,Kim, Ju Hee,Kim, Sumin,Kim, Young Gyu,Ko, Wonjae,Kwak, Minjoon,Lee, Byoung-Hoon,Lee, Chan Woo,Lee, Eunwon,Lee, Kug-Seung,Lee, Seong Chan,Yim, Guk Hee,Yoo, Dongwon
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- Copper-Catalyzed Ullmann-Type Coupling and Decarboxylation Cascade of Arylhalides with Malonates to Access α-Aryl Esters
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We have developed a high-efficiency and practical Cu-catalyzed cross-coupling to directly construct versatile α-aryl-esters by utilizing readily available aryl bromides (or chlorides) and malonates. These gram-scale approaches occur with turnovers of up to 1560 and are smoothly conducted by the usage of a low catalyst loading, a new available ligand, and a green solvent. A variety of functional groups are tolerated, and the application occurs with α-aryl-esters to access nonsteroidal anti-inflammatory drugs (NSAIDs) on the gram scale.
- Chen, Fen-Er,Chen, Tao,Cheng, Fei,Huang, Yin-Qiu,Li, Jia-Wei,Xiao, Xiao,Zhou, Chen
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- Visible-Light-Enabled Carboxylation of Benzyl Alcohol Derivatives with CO2 Using a Palladium/Iridium Dual Catalyst
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A highly efficient carboxylation of benzyl alcohol derivatives with CO2 using a palladium/iridium dual catalyst under visible-light irradiation was developed. A wide range of benzyl alcohol derivatives could be employed to provide benzylic carboxylic acids in moderate to high yields. Mechanistic studies indicated that the oxidative addition of benzyl alcohol derivatives was possibly the rate-determining-step. It was also found that a switchable site-selective carboxylation between benzylic C?O and aryl C?Cl moieties could be achieved simply by changing the palladium catalyst.
- Iwasawa, Nobuharu,Jin, Yushu,Toriumi, Naoyuki
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- Visible-light photoredox-catalyzed selective carboxylation of C(sp3)?F bonds with CO2
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It is highly attractive and challenging to utilize carbon dioxide (CO2), because of its inertness, as a nontoxic and sustainable C1 source in the synthesis of valuable compounds. Here, we report a novel selective carboxylation of C(sp3)?F bonds with CO2 via visible-light photoredox catalysis. A variety of mono-, di-, and trifluoroalkylarenes as well as α,α-difluorocarboxylic esters and amides undergo such reactions to give important aryl acetic acids and α-fluorocarboxylic acids, including several drugs and analogs, under mild conditions. Notably, mechanistic studies and DFT calculations demonstrate the dual role of CO2 as an electron carrier and electrophile during this transformation. The fluorinated substrates would undergo single-electron reduction by electron-rich CO2 radical anions, which are generated in situ from CO2 via sequential hydride-transfer reduction and hydrogen-atom-transfer processes. We anticipate our finding to be a starting point for more challenging CO2 utilization with inert substrates, including lignin and other biomass.
- Bo, Zhi-Yu,Chen, Lin,Gao, Tian-Yu,Jing, Ke,Lan, Yu,Liu, Shi-Han,Luo, Shu-Ping,Yan, Si-Shun,Yu, Bo,Yu, Da-Gang
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supporting information
p. 3099 - 3113
(2021/11/16)
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- Divergent Synthesis of α-Fluorinated Carbonyl and Carboxyl Derivatives by Double Electrophilic Activation of Amides
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A straightforward and divergent entry to α-fluorinated carbonyl and carboxyl derivatives is reported. Upon activation of amides with triflic anhydride and a 2-halo-pyridine and subsequent trapping of the resulting keteniminium ions with nucleophiles followed by a second electrophilic activation with NFSI and final hydrolysis, a range of amides can be transformed to α-fluorinated ketones, esters, and amides under mild conditions. Moreover, this reaction can be performed to yield enantioenriched products with a traceless chiral auxiliary.
- Dubart, Amaury,Evano, Gwilherm
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p. 8931 - 8936
(2021/11/17)
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- Cobalt-catalyzed cross-coupling reactions of aryl- And alkylaluminum derivatives with (hetero)aryl and alkyl bromides
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A simple cobalt complex, such as Co(phen)Cl2, turned out to be a highly efficient and cheap precatalyst for a host of cross-coupling reactions involving aromatic and aliphatic organoaluminum reagents with aryl, heteroaryl and alkyl bromides. New C(sp2)-C(sp2) and C(sp2)-C(sp3) bonds were formed in good to excellent yields and with high chemoselectivity, under mild reaction conditions.
- Dilauro, Giuseppe,Messa, Francesco,Bona, Fabio,Perrone, Serena,Salomone, Antonio
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supporting information
p. 10564 - 10567
(2021/10/19)
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- Desulfonylative Electrocarboxylation with Carbon Dioxide
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Electrocarboxylation of organic halides is one of the most investigated electrochemical approaches for converting thermodynamically inert carbon dioxide (CO2) into value-added carboxylic acids. By converting organic halides into their sulfone derivatives, we have developed a highly efficient electrochemical desulfonylative carboxylation protocol. Such a strategy takes advantage of CO2as the abundant C1 building block for the facile preparation of multifunctionalized carboxylic acids, including the nonsteroidal anti-inflammatory drug ibuprofen, under mild reaction conditions.
- Zhong, Jun-Song,Yang, Zi-Xin,Ding, Cheng-Lin,Huang, Ya-Feng,Zhao, Yi,Yan, Hong,Ye, Ke-Yin
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supporting information
p. 16162 - 16170
(2021/09/02)
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- Biphenyl acetic acid and preparation method thereof
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The invention discloses biphenyl acetic acid and a preparation method thereof. The preparation method comprises the following steps: dissolving bromobenzene into dimethylformamide, and performing reaction under the action of palladium powder to obtain biphenyl; dissolving biphenyl in cyclohexane, and performing chloromethylation reaction on biphenyl in a hydrochloric acid solution and a saturatedformaldehyde aqueous solution to obtain an intermediate 1; dissolving sodium cyanide in deionized water, and performing cyanidation reaction on the intermediate 1 and a sodium cyanide aqueous solutionunder the action of a catalyst n-butylammonium bromide to obtain an intermediate 2; and further hydrolyzing the intermediate 2 under the condition of an alkaline aqueous solution, and performing acidifying under the action of hydrochloric acid to obtain biphenyl acetic acid. The yield of the biphenyl acetic acid prepared by the aid of the method is higher than that of the biphenyl acetic acid prepared by the aid of traditional processes, reactants are low in price, the preparation cost of the biphenyl acetic acid can be greatly reduced, and the method is favorable for market popularization.
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- Oxidation of Alkynyl Boronates to Carboxylic Acids, Esters, and Amides
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A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.
- Li, Chenchen,Li, Ruoling,Zhang, Bing,Zhao, Pei,Zhao, Wanxiang
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supporting information
p. 10913 - 10917
(2020/05/25)
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- Method for converting benzyl borate compounds into phenylacetic acid and derivatives thereof by carbon dioxide
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The invention discloses a method for converting benzyl borate compounds into phenylacetic acid and derivatives thereof by carbon dioxide. The method comprises the steps: dissolving the benzyl borate compounds and an alkali in an organic solvent in the absence of a metal catalyst, introducing carbon dioxide into the reaction system, carrying out a reaction at the temperature of 50-150 DEG C for 3-72 hours, and acidifying to obtain phenylacetic acid or the derivatives thereof. The method is a green, simple and efficient method for synthesizing phenylacetic acid and the derivatives thereof, greenhouse gas carbon dioxide is used as a carbon source in the reaction, no transition metal catalyst is used, and the method is environmentally friendly, economical and high in efficiency.
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Paragraph 0030-0031
(2020/03/06)
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- Regioselective Arene C?H Alkylation Enabled by Organic Photoredox Catalysis
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Expanding the toolbox of C?H functionalization reactions applicable to the late-stage modification of complex molecules is of interest in medicinal chemistry, wherein the preparation of structural variants of known pharmacophores is a key strategy for drug development. One manifold for the functionalization of aromatic molecules utilizes diazo compounds and a transition-metal catalyst to generate a metallocarbene species, which is capable of direct insertion into an aromatic C?H bond. However, these high-energy intermediates can often require directing groups or a large excess of substrate to achieve efficient and selective reactivity. Herein, we report that arene cation radicals generated by organic photoredox catalysis engage in formal C?H functionalization reactions with diazoacetate derivatives, furnishing sp2–sp3 coupled products with moderate-to-good regioselectivity. In contrast to previous methods utilizing metallocarbene intermediates, this transformation does not proceed via a carbene intermediate, nor does it require the presence of a transition-metal catalyst.
- Holmberg-Douglas, Natalie,Onuska, Nicholas P. R.,Nicewicz, David A.
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supporting information
p. 7425 - 7429
(2020/03/23)
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- Synthesis of Enaminone-Pd(II) Complexes and Their Application in Catalysing Aqueous Suzuki-Miyaura Cross Coupling Reaction
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A series of Pd(II)-enaminone complexes, termed Pd(eao)2, have been synthesized and characterized. The investigation on the catalytic activities of these new Pd(II)-reagents has proved that the Pd(eao)2-1 possesses excellent catalytic activity for the Suzuki- Miyaura cross coupling reactions of aryl bromides/chlorides with aryl/vinyl boronic acids in the environmentally benign media of aqueous PEG400 at low loading (5 mol‰). The superiority of this Pd(II)-reagent to those commercial Pd(II) and Pd(0) catalysts in catalyzing the reactions has been confirmed by parallel experiments. What's more, Pd(eao)2-2 has been found as a practical catalyst for the homo-coupling reactions of aryl boronic acids.
- Fu, Leiqing,Cao, Xiaoji,Wan, Jie-Ping,Liu, Yunyun
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p. 254 - 258
(2020/01/25)
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- 4-Amino-1,2,4-triazoles-3-thiones and 1,3,4-oxadiazoles-2-thiones·palladium(II) recoverable complexes as catalysts in the sustainable Suzuki-Miyaura cross-coupling reaction
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The Suzuki-Miyaura cross-coupling reaction using 4-amino-1,2,4-triazoles and 1,3,4-oxadiazoles-2-thiones·palladium (II) is studied. The reaction is optimized and the most appropriate catalytic complex is tested with several aryl halides, boronic acids in an environmentally benign solvent system (H2O/EtOH). The recovery of the catalytic species is also surveyed because of the nature of the employed solvent. A domino process is efficiently carried out following the standard conditions. Several surface parameters of the ligands are analyzed and the resulting values are extrapolated to the insoluble palladium catalyst.
- Chehrouri, Manel,Moreno-Cabrerizo, Cristina,Othman, Adil A.,Chabour, Ihssene,Ferrándiz-Saperas, Marcos,Sempere, Inmaculada,D?nda?, H. Ali,de Gracia Retamosa,Sansano, José M.
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- DNA as a bioligand supported on magnetite for grafting palladium nanoparticles for cross-coupling reaction
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The utilization of deoxyribonucleic acid (DNA) in nanotechnology is a promising area of research wherein the distinct properties of DNA are exploited for the design and development of new materials and applications. The biodegradability and natural profusion of DNA makes it highly suitable for use in various fields. In this report, we have treated DNA as a bioligand, supported on functionalized magnetite for the grafting of palladium (Pd) nanoparticles to make Pd-DNA bio-nanocatalyst. The Pd-DNA was subjected to Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, Brunauer–Emmett–Teller, energy dispersive X-ray spectroscopy, vibrating sample magnetometry, X-ray photoelectron spectroscopy, and inductively coupled plasma optical emission spectrometry analysis. The prepared Pd-DNA was found to be highly efficient in catalyzing Suzuki–Miyaura cross-coupling reaction with excellent yields when compared with commercially available palladium-based catalysts. Also, the Pd-DNA could be easily recovered from the reaction mass using an external magnet and recycled up to six times without substantial loss of activity. Furthermore, Felbinac, a non-inflammatory drug, was synthesized in quantitative yields using the Pd-DNA bio-nanocatalyst.
- Kandathil, Vishal,Kempasiddaiah, Manjunatha,Nataraj, Sanna Kotrappanavar,Patil, Siddappa A.,Somappa, Sasidhar Balappa
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- Electrogenerated Sm(II)-Catalyzed CO2 Activation for Carboxylation of Benzyl Halides
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Sm(II)-catalyzed carboxylation of benzyl halides is reported through the electrochemical reduction of CO2. The transformation proceeds under mild reaction conditions to afford the corresponding phenylacetic acids in good to excellent yields. This user-friendly and operationally simple protocol represents an alternative to traditional strategies, which usually proceeds through the C(sp3)-halide activation pathway.
- Bazzi, Sakna,Schulz, Emmanuelle,Mellah, Mohamed
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supporting information
p. 10033 - 10037
(2019/12/24)
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- Preparation method of Sacubitril intermediate
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The invention discloses a preparation method of an intermediate compound (R)-tert-butyl (1-((1,1'-diphenyl)-4-yl)-3-hydroxypropane-2-yl) carbamate. The preparation method is represented as the formulashown in the description. According to the preparation method, the steps are simple and short, the reaction yield is increased, reaction conditions are mild, most of the intermediates obtained in thereaction process are not required to be purified and can be subjected to the next reaction directly, large-batch synthesis is facilitated, chiral amine with stereospecificity is efficiently synthesized with aminotransferase, and the preparation method is more suitable for industrial production.
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- Sustainable Ligand-Free, Palladium-Catalyzed Suzuki–Miyaura Reactions in Water: Insights into the Role of Base
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A simple and efficient system was developed for the ligand-free Pd-catalyzed Suzuki–Miyaura reaction in water under mild conditions. Quaternary ammonium hydroxides with long chains were found to be very suitable bases. This ligand-free Pd-catalyzed Suzuki–Miyaura reaction showed improved durability in water with Pd loadings decreased to ppm level. Bases were shown to stabilize active palladium species in addition to acting as a base during the catalytic process. In the catalytic system with a strong base, the soluble active PdII ion exhibited anti-reduction properties, which prevented aggregation and deactivation of Pd species. The entire catalytic system could be recycled after separating the product by simple filtration. The water-compatible and air-stable effective catalytic protocol described herein represents an attractive and green synthetic advance in Suzuki–Miyaura couplings.
- Wang, Yanyan,Liu, Yuanyuan,Zhang, Wei-qiang,Sun, Huaming,Zhang, Kan,Jian, Yajun,Gu, Quan,Zhang, Guofang,Li, Jiyang,Gao, Ziwei
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p. 5265 - 5273
(2019/11/29)
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- Green synthesis of biphenyl carboxylic acids via Suzuki–Miyaura cross-coupling catalyzed by a water-soluble fullerene-supported PdCl2 nanocatalyst
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A green synthesis of variously substituted biphenyl carboxylic acids was achieved through Suzuki–Miyaura cross-coupling of a bromobenzoic acid with an aryl boronic acid using a water-soluble fullerene-supported PdCl2 nanocatalyst (C60-TEGs/ PdCl2). Yields of more than 90% were obtained at room temperature in 4 h using 0.05 mol% catalyst and 2 equiv. K2CO3.
- Liu, Wanyun,Zhou, Xiuming,Huo, Ping,Li, Jingbo,Mei, Guangquan
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- From agriculture residue to catalyst support; A green and sustainable cellulose-based dip catalyst for C–C coupling and direct arylation
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The core characteristics of a perfect catalyst include good activity, simple design, excellent stability, easy recovery from reaction mixture, recyclability, and have the provision for easy scale up. The ease in synthesis, recyclability and scale up makes the dip catalyst a major contender in this regard which possess most of the aforementioned characteristics. In this work, we report a dip catalyst made of cellulose, isolated from agriculture residue (sugarcane bagasse), in which biogenically synthesized palladium nanoparticles were dispersed. The prepared dip catalyst was characterized by FESEM, EDS, XRD, ATR-IR, TGA, TEM, XPS and ICP-OES analysis. Also, the activity of the dip catalyst was studied in the Suzuki-Miyaura cross-coupling reaction and was found to give excellent conversion with 15 recycles. Further, the activity of dip catalyst in C5-arylation of 2-substituted thiophenes was evaluated for which promising yields were obtained.
- Kandathil, Vishal,Kempasiddaiah, Manjunatha,B. S., Sasidhar,Patil, Siddappa A.
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- Visible-Light-Driven External-Reductant-Free Cross-Electrophile Couplings of Tetraalkyl Ammonium Salts
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Cross-electrophile couplings between two electrophiles are powerful and economic methods to generate C-C bonds in the presence of stoichiometric external reductants. Herein, we report a novel strategy to realize the first external-reductant-free cross-electrophile coupling via visible-light photoredox catalysis. A variety of tetraalkyl ammonium salts, bearing primary, secondary, and tertiary C-N bonds, undergo selective couplings with aldehydes/ketone and CO2. Notably, the in situ generated byproduct, trimethylamine, is efficiently utilized as the electron donor. Moreover, this protocol exhibits mild reaction conditions, low catalyst loading, broad substrate scope, good functional group tolerance, and facile scalability. Mechanistic studies indicate that benzyl radicals and anions might be generated as the key intermediates via photocatalysis, providing a new direction for cross-electrophile couplings.
- Liao, Li-Li,Cao, Guang-Mei,Ye, Jian-Heng,Sun, Guo-Quan,Zhou, Wen-Jun,Gui, Yong-Yuan,Yan, Si-Shun,Shen, Guo,Yu, Da-Gang
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p. 17338 - 17342
(2019/01/04)
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- A General, Activator-Free Palladium-Catalyzed Synthesis of Arylacetic and Benzoic Acids from Formic Acid
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A new catalyst for the carboxylative synthesis of arylacetic and benzoic acids using formic acid (HCOOH) as the CO surrogate was developed. In an improvement over previous work, CO is generated in situ without the need for any additional activators. Key to success was the use of a specific system consisting of palladium acetate and 1,2-bis((tert-butyl(2-pyridinyl)phosphinyl)methyl)benzene. The generality of this method is demonstrated by the synthesis of more than 30 carboxylic acids, including non-steroidal anti-inflammatory drugs (NSAIDs), under mild conditions in good yields.
- Wang, Lin,Neumann, Helfried,Beller, Matthias
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supporting information
p. 6910 - 6914
(2018/06/04)
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- Ruthenium-catalyzed umpolung carboxylation of hydrazones with CO2
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The first ruthenium-catalyzed umpolung carboxylation of hydrazones with CO2 to generate important aryl acetic acids is reported. Besides aldehyde hydrazones, a variety of ketone hydrazones, which have not been successfully applied in previous umpolung reactions with other reactive electrophiles, also show high reactivity and selectivity under mild conditions. Moreover, this operationally simple protocol features good functional group tolerance, is readily scalable, and offers easy derivation of important structures, including bioactive felbinac and adiphenine. Computational studies reveal that this umpolung reaction proceeds through the generation of a Ru-nitrenoid followed by concerted [4 + 2] cycloaddition with CO2.
- Yan, Si-Shun,Zhu, Lei,Ye, Jian-Heng,Zhang, Zhen,Huang, He,Zeng, Huiying,Li, Chao-Jun,Lan, Yu,Yu, Da-Gang
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p. 4873 - 4878
(2018/06/07)
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- Ligand-Free Bioinspired Suzuki–Miyaura Coupling Reactions using Aryltrifluoroborates as Effective Partners in Deep Eutectic Solvents
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Pd-catalyzed Suzuki–Miyaura cross-coupling between (hetero)aryl halides (Cl, Br, I) and versatile, moisture-stable mono- and bifunctional potassium aryltrifluoroborates proceeded efficiently and chemoselectively in air and under generally mild conditions; a catalyst loading as low as 1 mol % combined with Na2CO3 as a base in choline chloride/glycerol (1:2) deep eutectic solvent (DES) was used as a sustainable and environmentally responsible medium. The catalyst, base, and DES were easily and successfully recycled up to six times with an E-factor as low as 8.74. Valuable biaryls and terphenyl derivatives were furnished in yields of up to 98 %; over 50 reactions were compared and discussed. The methodology was applied for the synthesis of the nonsteroidal anti-inflammatory drugs Felbinac and Diflunisal.
- Dilauro, Giuseppe,García, Sergio Mata,Tagarelli, Donato,Vitale, Paola,Perna, Filippo M.,Capriati, Vito
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p. 3495 - 3501
(2018/09/21)
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- Method for synthesizing biphenylcarboxylic acid compound by using Suzuki coupling reaction
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The invention provides a method for synthesizing a biphenylcarboxylic acid compound by using the Suzuki coupling reaction. According to the method, brominated aromatic hydrocarbon and arylboronic acidare used as raw materials, and water-soluble fullerene nanopalladium is used as a catalyst; and the equation of the Suzuki coupling reaction is as described in the specification. In the equation, R1and R2 represent substituents at different positions, may be acceptor or donor substituents, and may be monosubstitutents or polysubstitutent; and R1 and R2 may be identical or different groups. The water-soluble fullerene nanopalladium catalyst is cheap, easily available and environmentally friendly, and has high catalytic activity and stable properties. When the catalyst is used for catalysis ofthe Suzuki coupling reaction, conditions are mild, anhydrous anaerobic treatment and high-temperature treatment are not needed, and cost is low. The method can be applied to the industrial synthesisof non-steroidal anti-inflammatory drugs such as diphenylacetic acid and diflunisal.
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Paragraph 0027
(2018/09/21)
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- Method for preparing 4-biphenyl acetic acid
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The invention discloses a method for preparing high-purity 4-biphenyl acetic acid and belongs to the technical field of drug synthesis. The synthetic route specifically comprises the following two steps: (a) enabling a compound 2-chlorophenylacetophenone to act with 1,2-ethanediol so as to produce a ketal intermediate; and (b) directly producing the 4-biphenyl acetic acid from the intermediate in the presence of zinc acetate and cuprous iodide. The preparation method disclosed by the invention is low in price and readily available, the reaction route is high in yield, the reaction conditions are mild, the operation is simple, the production cost is low, and the method is suitable for industrial production. The total yield is 80% or higher, the prepared 4-biphenyl acetic acid does not need to be refined, and the purity reaches 99.5% or higher.
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Paragraph 0024; 0040-0042
(2017/11/29)
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- Simple preparation method of felbinac
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The invention provides a simple preparation method of felbinac. The method comprises the following steps: taking biphenyl and ethyl oxalyl monochloride as initial raw materials; carrying out Friedel-Crafts reaction under the action of aluminum trichloride to generate biphenylethyl glyoxylate under the condition of low temperature; then carrying out alkaline hydrolysis to obtain felbinac salt; carrying out Huang-Minlon reaction reduction and acidification to obtain the felbinac. The method has the advantages of no need of intermediate separation, simplicity and convenience in operation, environment friendliness, high yield and industrial production value.
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Paragraph 0032; 0036; 0037; 0043; 0044; 0052-0054
(2017/08/29)
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- Synthesis of zwitterionic palladium complexes and their application as catalysts in cross-coupling reactions of aryl, heteroaryl and benzyl bromides with organoboron reagents in neat water
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N-(3-Chloro-2-quinoxalinyl)-N′-arylimidazolium salts (aryl = 2,6-diisopropylphenyl [HL1Cl]Cl, aryl = mesityl [HL2Cl]Cl) have been synthesized by treating 2,3-dichloroquinoxaline with the corresponding N′-arylimidazole in neat water. Facile reactions of these imidazolium salts with Pd(PPh3)4 and Pd2(dba)3/PPh3 (dba = dibenzyledene acetone) at 50 °C have afforded zwitterionic palladium(ii) complexes [Pd(HL1)(PPh3)Cl2] (I) and [Pd(HL2)(PPh3)Cl2] (II) in excellent yields. I and II have been tested for their ability to catalyze Suzuki-Miyaura cross coupling (SMC) reactions in neat water/K2CO3 and are found to be highly active for carrying out these reactions between aryl bromides and organoboron reagents. Furthermore, the scope of the catalyst I was also examined by employing (hetero)aryl bromides, hydrophilic aryl bromides, benzyl bromides and various organoboron reagents. More than 80 aryl/benzyl bromide-arylboronic acid combinations were screened in neat water/K2CO3 and it was found that I was a versatile catalyst, which produced biaryls/diarylmethanes in excellent yields. A TON of 82 000 was achieved by using I. Studies on the mechanism have also been carried out to investigate the involvement of carbene complexes in the catalytic path. Poison tests and a two-phase test were also conducted and the results are reported.
- Ramakrishna,Dastagiri Reddy
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supporting information
p. 8598 - 8610
(2017/07/12)
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- Ligand-Free C–C Coupling Reactions Promoted by Hexagonal Boron Nitride-Supported Palladium(II) Catalyst in Water
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A micron-scale palladium(II) material has been successfully prepared using Schiff base-modified hexagonal boron nitride as a support and used for the first time as an efficient and recyclable catalyst in organic synthesis. The morphology, composition, metal loading and thermal stability of the catalyst were studied using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), infrared spectroscopy (FT-IR), inductively coupled plasma (ICP) and thermogravimetric (TG) analyses. Then, the micron material was tested in various C–C cross-coupling reactions and exhibited excellent catalytic activities in the Suzuki and Heck reactions. Moreover, the catalyst could be easily recovered by simple filtration and reused at least ten times without significant loss of its catalytic activity. In general, this work demonstrates the possibility of using Schiff-base@hexagonal boron nitride as an efficient support for heterogeneous catalysts. (Figure presented.).
- Cheng, Xu,Li, Weijian,Nie, Ruifang,Ma, Xiaojun,Sang, Rui,Guo, Li,Wu, Yong
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supporting information
p. 454 - 466
(2017/02/10)
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- Novel cyclodextrin-modified h-BN@Pd(II) nanomaterial: An efficient and recoverable catalyst for ligand-free C-C cross-coupling reactions in water
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An environmentally friendly palladium(II) catalyst supported on cyclodextrin-modified h-BN was successfully prepared. The catalyst was characterized by FT-IR, SEM, TG, XRD and XPS, and the loading level of Pd in h-BN@β-CD@Pd(II) was measured to be 0.088?mmol g?1 by ICP. It exhibits excellent catalytic activity for the Suzuki and Heck reactions in water, and can be easily separated and consecutively reused for at least nine times. In addition, a series of pharmacologically interesting products were successfully synthesized using this catalyst to demonstrate its potential applications in pharmaceutical industries. Above all, this work opens up an interesting and attractive avenue for the use of cyclodextrin-functionalized h-BN as an efficient support for hydrophilic heterogeneous catalysts.
- Ma, Xiaojun,Lv, Guanghui,Cheng, Xu,Li, Weijian,Sang, Rui,Zhang, Yong,Wang, Qiantao,Hai, Li,Wu, Yong
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- Aqueous-Phase Chemistry of η3-Allylpalladium(II) Complexes with Sulfonated N-Heterocyclic Carbene Ligands: Solvent Effects in the Protolysis of Pd-C Bonds and Suzuki-Miyaura Reactions
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The synthesis of water-soluble η3-allyl Pd(II) complexes containing sulfonated N-heterocyclic carbene (NHC) ligands of general formula [Pd(NHC)n(η3-allyl)Cl2-n] is reported (n = 1 (1) or 2 (8)). Monocarbene complexes were obtained with the most sterically hindered NHC ligands, and biscarbenes with the less sterically hindered NHCs. The behavior of the isolated complexes in water under acidic, neutral, or alkaline conditions has been studied. The complexes are rather stable in water under neutral or alkaline conditions, although displacement of the chlorido ligand by water or hydroxide occurs under these conditions. In acidic media, Pd-NHC bonds are protolysed, and it is especially noteworthy that this protolysis occurs preferentially to that of the Pd-allyl bonds in the case of the complexes with the less-sterically hindered NHC ligands. This behavior contrasts with that observed in dimethyl sulfoxide (dmso), where the Pd-allyl bonds are selectively broken upon treatment with Br?nsted acids. In addition, Pd-NHC bond breaking was promoted by the addition of a strong σ-donor ligand such as cyanide. Complex 1a is an active catalyst for the Suzuki-Miyaura cross-coupling of water-soluble aryl chlorides in neat water under moderate conditions (typically, 0.5 mol % Pd and 60 °C).
- Asensio, Juan M.,Andrés, Román,Gómez-Sal, Pilar,De Jesús, Ernesto
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supporting information
p. 4191 - 4201
(2017/11/21)
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- Preparation and purification methods of 4-biphenylacetic acid
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The invention relates to the field of production preparation of compounds, in particular to preparation and purification methods of 4-biphenylacetic acid. The preparation and purification methods comprise steps as follows: 1) biphenyl is subjected to a chloromethylation reaction to produce 4-phenyl benzyl chloride; 2) 4-phenyl benzyl chloride reacts with sodium cyanide to produce 4-biphenyl acetonitrile; 3) 4-biphenyl acetonitrile is hydrolyzed and a crude 4-bphenylacetic acid product is obtained; 4) the crude 4-bphenylacetic acid product and methanol are subjected to an esterification reaction to produce 4-biphenyl methyl acetate, 4-biphenyl methyl acetate is purified and hydrolyzed into 4-biohenylacetic acid, 4-bihenylacetic acid is refined, and a finished product is prepared.
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Paragraph 0063; 0069; 0070; 0076; 0077; 0083; 0084
(2017/04/03)
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- Preparation method of high purity acetyl biphenyl
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The invention relates to a preparation method of a high purity biphenyl acetic acid intermediate namely acetyl biphenyl (I). The preparation method is characterized in that 4-dimethylaminopyridine is taken as the catalyst, and biphenyl and acetic anhydride carry out Friedel-Crafts acylation reactions to generate acetyl biphenyl (I). The method has the advantages that 4-dimethylaminopyridine is taken as the catalyst, the obtained product purity is high, the byproducts are few, the purity can reach 99%, the refinement is not needed, and the yield is increased. The impurities are eliminated, so the impurities will not participate in the subsequent reactions and the final product will not contain the impurities. Acetyl biphenyl and morpholine carry out condensation reactions. Finally, the reaction product is saponified and acidified to obtain a crude product. The crude product is refined for once, and the purity can reach 100%. The multiple refinements are eliminated. The product better satisfies the pharmaceutical requirements. The quality of biphenyl acetic acid is improved. The cost is reduced. The total yield is increased from 63-65% to 75-80%.
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Paragraph 0034; 0035
(2018/03/24)
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- NEW PROCESS AND INTERMEDIATES
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The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis route.
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Page/Page column 70
(2017/07/06)
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- Palladium(II)-Schiff base complex immobilized covalently on h-BN: An efficient and recyclable catalyst for aqueous organic transformations
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A moisture- and air-stable palladium(II)-Schiff base complex supported on h-BN was simply prepared by using commercially available reagents. This nanomaterial was applied as an excellent and recyclable heterogeneous catalyst for the Suzuki and Heck cross-coupling reactions. And it has been characterized by FT-IR, XRD, SEM, XPS, TG and ICP-AES techniques. High yields, ligand-free, low reaction time, water as solvent, non-toxicity and recyclability of the catalyst are the main merits of these protocols. In addition, a series of pharmacologically relevant products were successfully synthesized using this catalyst. Above all, this work opens up an interesting and attractive avenue for the use of h-BN as an efficient support for heterogeneous catalysts.
- Li, Weijian,Lv, Guanghui,Cheng, Xu,Sang, Rui,Ma, Xiaojun,Zhang, Yong,Nie, Ruifang,Li, Jie,Guan, Mei,Wu, Yong
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supporting information
p. 8557 - 8564
(2016/12/07)
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- Electrochemical direct carboxylation of benzyl alcohols having an electron-withdrawing group on the phenyl ring: One-step formation of phenylacetic acids from benzyl alcohols under mild conditions
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Electrochemical direct carboxylation of benzyl alcohols having an electron-withdrawing group on the phenyl ring was successfully carried out by constant current electrolysis using an undivided cell equipped with a platinum plate cathode and a magnesium rod anode in DMF in the presence of carbon dioxide. Reductive cleavage of the C-O bond followed by fixation of carbon dioxide efficiently took place at the benzylic position without any additive to give the corresponding phenylacetic acids in good yields in one step under neutral and mild conditions.
- Senboku, Hisanori,Yoneda, Kenji,Hara, Shoji
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p. 6772 - 6776
(2016/01/30)
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- Efficient and magnetically recoverable "click" PEGylated γ-Fe2O3-Pd nanoparticle catalysts for Suzuki-Miyaura, Sonogashira, and Heck reactions with positive dendritic effects
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The engineering of novel catalytic nanomaterials that are highly active for crucial carbon-carbon bond formations, easily recoverable many times, and biocompatible is highly desirable in terms of sustainable and green chemistry. To this end, catalysts comprising dendritic "click" ligands that are immobilized on a magnetic nanoparticle (MNP) core, terminated by triethylene glycol (TEG) groups, and incorporate Pd nanoparticles (PdNPs) have been prepared. These nanomaterials are characterized by transmission electron microscopy (TEM), high-resolution TEM, inductively coupled plasma analysis, Fourier transform infrared spectroscopy, X-ray photoelectron spectra and energy-dispersive X-ray spectroscopy. They are shown to be highly active, dispersible, and magnetically recoverable many times in Suzuki, Sonogashira, and Heck reactions. In addition, a series of pharmacologically relevant or natural products were successfully synthesized using these magnetic PdNPs as catalyst. For comparison, related PdNP catalysts deposited on MNPs bearing linear "click" PEGylated ligands are also prepared. Strong positive dendritic effects concerning ligand loading, catalyst loading, catalytic activity, and recyclability are observed, that is, the dendritic catalysts are much more efficient than nondendritic analogues.
- Wang, Dong,Deraedt, Christophe,Salmon, Lionel,Labrugre, Christine,Etienne, Laetitia,Ruiz, Jaime,Astruc, Didier
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supporting information
p. 1508 - 1519
(2015/01/30)
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- Safe palladium-catalyzed cross-couplings with microwave heating using continuous-flow silicon carbide reactors
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Herein we present a 200 mm × 3 mm i silicon carbide (SiC) tube reactor for use in a commercially available microwave heated continuous-flow system. The SiC flow reactor enables palladium(0)-catalyzed reactions that, due to precipitation and subsequent hot spot formation, often followed by reactor failure, are unsuitable to conduct in standard microwave-transparent borosilicate glass reactors. We report continuous-flow protocols for the Mizoroki-Heck reaction (10 examples, 81-86% yield) as well as the Suzuki-Miyaura cross-coupling (14 examples, 70-87% yield), showing the utility of the SiC reactor. Furthermore, we performed a scale-out of the NSAID biphenylacetic acid, achieving outputs of 14 mmol/h of the Suzuki-Miyaura reaction, and a 72% overall yield over three steps. The SiC reactor enabled fast and efficient temperature control, high robustness, and easy maintenance.
- Konda, Vivek,Rydfjord, Jonas,S?vmarker, Jonas,Larhed, Mats
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p. 1413 - 1418
(2015/02/19)
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- Sequential one-pot access to molecular diversity through aniline aqueous borylation
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On the basis of our recently reported aniline aqueous borylation, molecular diversity was achieved in a one-pot process by combining other reactions such as esterification, Suzuki-Miyaura coupling, hydrogenolysis, or Petasis borono-Mannich.
- Erb, William,Albini, Mathieu,Rouden, Jacques,Blanchet, Jrme
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p. 10568 - 10580
(2015/01/08)
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- The ketene-surrogate coupling: Catalytic conversion of aryl iodides into aryl ketenes through ynol ethers
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tert-Butoxyacetylene is shown to undergo Sonogashira coupling with aryl iodides to yield aryl-substituted tert-butyl ynol ethers. These intermediates participate in a [1,5]-hydride shift, which results in the extrusion of isobutylene and the generation of aryl ketenes. The ketenes are trapped in situ with multiple nucleophiles or undergo electrocyclic ring closure to yield hydroxynaphthalenes and quinolines.
- Zhang, Wenhan,Ready, Joseph M.
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supporting information
p. 8980 - 8984
(2014/11/07)
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- Ni-catalyzed carboxylation of C(sp2)- and C(sp3)-O bonds with CO2
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In recent years a significant progress has been made for the carboxylation of aryl and benzyl halides with CO2, becoming convenient alternatives to the use of stoichiometric amounts of well-defined metal species. Still, however, most of these processes require the use of pyrophoric and air-sensitive reagents and the current methods are mostly restricted to organic halides. Therefore, the discovery of a mild, operationally simple alternate carboxylation that occurs with a wide substrate scope employing readily available coupling partners will be highly desirable. Herein, we report a new protocol that deals with the development of a synergistic activation of CO2 and a rather challenging activation of inert C(sp2)-O and C(sp3)-O bonds derived from simple and cheap alcohols, a previously unrecognized opportunity in this field. This unprecedented carboxylation event is characterized by its simplicity, mild reaction conditions, remarkable selectivity pattern and an excellent chemoselectivity profile using air-, moisture-insensitive and easy-to-handle nickel precatalysts. Our results render our method a powerful alternative, practicality and novelty aside, to commonly used organic halides as counterparts in carboxylation protocols. Furthermore, this study shows, for the first time, that traceless directing groups allow for the reductive coupling of substrates without extended π-systems, a typical requisite in many C-O bond-cleavage reactions. Taking into consideration the limited knowledge in catalytic carboxylative reductive events, and the prospective impact of providing a new tool for accessing valuable carboxylic acids, we believe this work opens up new vistas and allows new tactics in reductive coupling events.
- Correa, Arkaitz,Leon, Thierry,Martin, Ruben
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p. 1062 - 1069
(2014/02/14)
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- Melamine and melamine-formaldehyde polymers as ligands for palladium and application to Suzuki-Miyaura cross-coupling reactions in sustainable solvents
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The Suzuki-Miyaura cross-coupling reaction is a foundation stone of modern organic synthesis, as evidenced by its widespread use in the preparation of pharmaceuticals, agrochemicals, polymers, and other functional materials. With the prevalence of this venerable reaction in industrial synthesis, it is prudent to ensure its application adheres to the tenets of green chemistry. The introduction of cross-coupling catalysts that are active in sustainable solvents is therefore an important endeavor. In this report, a melamine-palladium complex is introduced as a versatile catalyst for the Suzuki-Miyaura cross-coupling reaction. This catalyst is soluble and active in both water and the renewable organic solvent ethyl lactate. The melamine-palladium catalyst can also be cross-linked by reaction with formaldehyde to generate an insoluble polymeric catalyst that can be recovered after the cross-coupling. The melamine-palladium system is inexpensive, easy to handle, bench-stable, and effective in catalysis in the presence of a variety of impurities (high cross-coupling yields were obtained in reactions run in unfiltered river water to illustrate this final point). Additionally, investigations reported herein revealed an intriguing relationship between catalytic efficiency and the base employed in the cross-coupling reaction. Implications for the mechanism of transmetalation in aqueous Suzuki-Miyaura cross-coupling reaction are discussed.
- Edwards, Grant A.,Trafford, Mitchell A.,Hamilton, Alaina E.,Buxton, Audrey M.,Bardeaux, Matthew C.,Chalker, Justin M.
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p. 2094 - 2104
(2014/04/03)
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- An efficiently cobalt-catalyzed carbonylative approach to phenylacetic acid derivatives
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A highly efficient cobalt-catalyzed carbonylative approach to phenylacetic acid derivatives under one atmosphere pressure is reported. This methodology represents a useful extension of benzimidazole used as ligand in metal catalysis, and the catalytic mechanism has been proved by computer simulation. Notably, this new cobalt precatalyst, which promotes the carbonylation reaction dramatically and has already been used for scale-up experiment of phenylacetic acid derivatives.
- She, Meng-Yao,Xiao, Da-Wei,Yin, Bing,Yang, Zheng,Liu, Ping,Li, Jian-Li,Shi, Zhen
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p. 7264 - 7268
(2013/08/23)
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- NHC-ligand effectiveness in the fluorine-free hiyama reaction of aryl halides
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1-Benzyl-3-(2-hydroxy-2-phenylethyl)imidazolium chloride (5), which is a precursor of an N-heterocyclic carbene ligand, in combination with palladium acetate, has been employed as an effective catalyst for the fluorine-free Hiyama reaction. A systematic study of the catalytic mixture, by a 32 factorial design, has revealed that both the amount of palladium and the Pd/NHC precursor ratio are important factors for obtaining good yields of the coupling products, indicating an interaction between them. The best catalytic system involves mixing 0.1 mol-% palladium acetate in a 1:5 ratio (Pd/salt 5), which allows the effective coupling of a range of aryl bromides and chlorides with trimethoxy(phenyl)silane. The Hiyama reactions are carried out in NaOH solution (50 % H2O w/w), at 120 °C under microwave irradiation during 60 min. The optimal catalytic system for the fluorine-free Hiyama reaction involving palladium and an NHC-ligand precursor has been determined by adjusting the amount of palladium and the corresponding imidazolium salt. Various aryl bromides and chlorides have successfully been coupled by means of this methodology under microwave irradiation. Copyright
- Penafiel, Itziar,Pastor, Isidro M.,Yus, Miguel
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supporting information
p. 1479 - 1484
(2013/04/23)
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- Pyrene-tagged dendritic catalysts noncovalently grafted onto magnetic Co/C nanoparticles: An efficient and recyclable system for drug synthesis
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Hold on to your palladium! Phosphines have been grafted on magnetic Co/C nanoparticles through π-π interactions. The resulting Pd complexes showed high activity for Suzuki couplings and the system involving a dendritic ligand was recyclable, allowing the preparation of the drug Felbinac over 12 consecutive runs with minimal Pd leaching. After extraction with CH 2Cl2, Felbinac met the requirements of the pharmaceutical industry (5 ppm Pd). Copyright
- Keller, Michel,Collière, Vincent,Reiser, Oliver,Caminade, Anne-Marie,Majoral, Jean-Pierre,Ouali, Armelle
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supporting information
p. 3626 - 3629
(2013/05/09)
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- (NHC)palladium complexes from hydroxy-functionalized imidazolium salts as catalyst for the microwave-accelerated fluorine-free Hiyama reaction
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Palladium acetate reacts with 1-benzyl-3-(2-hydroxy-2-phenylethyl)-1H- imidazolium chloride to give the corresponding bis(carbene)palladium(II) complex 5 [(NHC)2PdCl2] by direct metalation. The X-ray diffraction structure of the complex is reported. In the presence of NaOH solution (50 % H2O, w/w) in air and under microwave irradiation, the bis(NHC)pallalium(II) complex 5 is an active precatalyst for the Hiyama coupling of aryl halides with trialkoxy(aryl)silanes, providing biaryls and heterobiaryls. For some deactivated aryl bromides and for aryl chlorides, the corresponding cross-coupling reactions require tetrabutylammonium bromide (TBAB) as additive. The fluoride-free Hiyama reactions are performed with low (NHC)palladium loadings (0.1 mol-%). The active catalyst can also be prepared in situ from Pd(OAc)2 and the corresponding imidazolium salt 4.
- Penafiel, Itziar,Pastor, Isidro M.,Yus, Miguel,Esteruelas, Miguel A.,Olivan, Montserrat,Onate, Enrique
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experimental part
p. 7174 - 7181
(2012/01/06)
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