- Synthesis of Substituted Thiophenes through Dehydration and Heterocyclization of Alkynols
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A protocol was described for obtaining a variety of substituted thiophenes with functional potential via metal-free dehydration and sulfur cyclization of alkynols with elemental sulfur (S8) or EtOCS2K in moderate-to-good yields. The method provides the base-free generation of a trisulfur radical anion (S3?-) and its addition to alkynes as an initiator. This research broadens the applications of S3?-in the synthesis of sulfur-containing heterocycles.
- Chen, Lu,Chen, Zebin,Huang, Yubing,Ji, Xiaoliang,Li, Jiaming,Li, Jian,Li, Yibiao,Liu, Qiang,Liu, Yang
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supporting information
p. 3555 - 3566
(2022/03/14)
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- Pyrazole-Mediated C-H Functionalization of Arene and Heteroarenes for Aryl-(Hetero)aryl Cross-Coupling Reactions
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Herein we introduce a transition-metal-free protocol that involves a commercially available, inexpensive pyrazole molecule to conduct C-C cross-coupling reactions at room temperature via a radical pathway. Using this method, an aryldiazonium salt has been coupled to a wide range of arenes and heteroarenes including benzene, mesitylene, thiophene, furan, benzoxazole to result the corresponding biaryl products. The full reaction mechanism is elucidated along with the crystallographic probation of an active initiator species. A potassium-stabilized deprotonated pyrazole steers single-electron transfer to the substrate and behaves as an initiator for the reaction.
- Kundu, Abhishek,Dey, Dhananjay,Pal, Subhankar,Adhikari, Debashis
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p. 15665 - 15673
(2021/11/16)
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- Access to Substituted Thiophenes through Xanthate-Mediated Vinyl C(sp2)-Br Bond Cleavage and Heterocyclization of Bromoenynes
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An environmentally sustainable strategy for the chemoselective heterocyclization of bromoenynes through a transition-metal-free sulfuration/cyclization process is reported. Using inexpensive and safe EtOCS2K as a thiol surrogate and tetrabutylphosphonium bromide and H2O as a mixed solvent, the reaction provided a range of substituted thiophenes in moderate to good yields. In addition, 2,3,4,5-tetrasubstituted thiophenes were able to be prepared under mild reaction conditions by electrophilic heterocyclization with NH4I and EtOCS2K in good yields.
- Huang, Guoling,Li, Jian,Li, Jianrong,Li, Jiaming,Sun, Minghua,Zhou, Peng,Chen, Lu,Huang, Yubing,Jiang, Shaohua,Li, Yibiao
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p. 13037 - 13049
(2020/11/26)
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- Preparation method of intermediate
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The invention discloses a preparation method for a Canagliflozin intermediate. The preparation method comprises the steps that substituted bromobenzene as a starting material is reacted with bisdiboron to prepare a boride, and then the Canagliflozin intermediate is prepared through a Suzuki coupling reaction, a Friedel-Crafts acylation reaction and a reduction reaction. The preparation method hasthe advantages that the intermediate product CZ-2 is prepared through the Suzuki coupling reaction, the conditions are mild and easy to operate and control, and the product yield and the product purity are high; aryl methyl is introduced through the Friedel-Crafts acylation reaction, a main chain is built, by means of the route, the yield is high, technological conditions are easy to control, andthe preparation method is suitable for large-scale industrial production.
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- Transition-Metal-Free Synthesis of Heterobiaryls through 1,2-Migration of Boronate Complex
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The synthesis of a diverse range of heterobiaryls has been achieved by a transition-metal-free sp2–sp2 cross-coupling strategy using lithiated heterocycle, aryl or heteroaryl boronic ester and an electrophilic halogen source. The construction of heterobiaryls was carried out through electrophilic activation of the aryl–heteroaryl boronate complex, which triggered 1,2-migration from boron to the carbon atom. Subsequent oxidation of the intermediate boronic ester afforded heterobiaryls in good yield. A comprehensive 11B NMR study has been conducted to support the mechanism. The cross coupling between two nucleophilic cross coupling partners without transition metals reveals a reliable manifold to procure heterobiaryls in good yields. Various heterocycles like furan, thiophene, benzofuran, benzothiophene, and indole are well tolerated. Finally, we have successfully demonstrated the gram scale synthesis of the intermediates for an anticancer drug and OLED material using our methodology.
- Paul, Swagata,Das, Kanak Kanti,Manna, Samir,Panda, Santanu
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supporting information
p. 1922 - 1927
(2020/02/04)
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- Carbazole based Electron Donor Acceptor (EDA) catalysis for the synthesis of biaryl and aryl-heteroaryl compounds
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A highly regioselective, carbazole based Electron Donor Acceptor (EDA) catalyzed synthesis of biaryl and aryl-heteroaryl compounds is described. Various indole and carbazole derivatives were screened for the Homolytic Aromatic Substitution (HAS) reaction. Tetrahydrocarbazole (THC) was very efficient for the HAS transformation and proceeded via a complex formation between diazonium salt and electron rich tetrahydrocarbazole. The UV-Vis spectroscopy technique has been used to confirm the complex formation. The in situ generated EDA complex even in a catalytic amount is found to be efficient for the Single Electron Transfer (SET) process without any photoactivation. Biaryl compounds, 2-phenylfuran, 2-phenylthiophene, and 2-phenylpyrrole and bioactive compounds such as dantrolene and canagliflozin have been synthesized in moderate to excellent yields.
- Annes, Sesuraj Babiola,Ramesh, Subburethinam,Saravanan, Subramanian,Saritha, Rajendhiran
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p. 2510 - 2515
(2020/04/15)
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- Preparation method of canagliflozin intermediate 2-(4-fluorophenyl) thiophene
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The invention relates to a preparation method of canagliflozin intermediate 2-(-4fluorophenyl) thiophene. The method comprises the following steps of: (1) enabling 2-bromothiophene to react with magnesium chips in a THF solvent to generate 2-thienyl magnesium bromide Grignard liquid; (2) carrying out catalytic Kumada coupling reaction on the 2-thienyl magnesium bromide Grignard liquid and p-fluorobromobenzene in the presence of a nickel or palladium complex as a catalyst, so as to obtain the 2-(-4fluorophenyl) thiophene. The method is good in product quality, high in yield, mild in reaction condition, simple to operate and easy to industrialize.
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Paragraph 0032-0066
(2021/01/04)
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- Orthogonal Nanoparticle Catalysis with Organogermanes
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Although nanoparticles are widely used as catalysts, little is known about their potential ability to trigger privileged transformations as compared to homogeneous molecular or bulk heterogeneous catalysts. We herein demonstrate (and rationalize) that nanoparticles display orthogonal reactivity to molecular catalysts in the cross-coupling of aryl halides with aryl germanes. While the aryl germanes are unreactive in LnPd0/LnPdII catalysis and allow selective functionalization of established coupling partners in their presence, they display superior reactivity under Pd nanoparticle conditions, outcompeting established coupling partners (such as ArBPin and ArBMIDA) and allowing air-tolerant, base-free, and orthogonal access to valuable and challenging biaryl motifs. As opposed to the notoriously unstable polyfluoroaryl- and 2-pyridylboronic acids, the corresponding germanes are highly stable and readily coupled. Our mechanistic and computational studies provide unambiguous support of nanoparticle catalysis and suggest that owing to the electron richness of aryl germanes, they preferentially react by electrophilic aromatic substitution, and in turn are preferentially activated by the more electrophilic nanoparticles.
- Fricke, Christoph,Sherborne, Grant J.,Funes-Ardoiz, Ignacio,Senol, Erdem,Guven, Sinem,Schoenebeck, Franziska
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supporting information
p. 17788 - 17795
(2019/11/13)
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- Gold-Catalyzed C-H Functionalization with Aryl Germanes
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The development of orthogonal Csp2-Csp2 coupling regimes to the omnipresent Pd-catalysis class would enable an additional dimension of modularity in the construction of densely functionalized biaryl motifs. In this context, the identification of potent functional groups for selective transformations is in high demand. Although organogermanium compounds are generally believed to be of low reactivity in homogenous catalysis, this report discloses the highly efficient and orthogonal reactivity of aryl germanes with arenes under gold catalysis. The method is characterized by mildness, the employment of an air- and moisture-stable gold catalyst, and robustness. Our mechanistic studies show that aryl germanes are highly reactive with Au(I) and Au(III). Our computational data suggest that the origin of this reactivity primarily lies in the relatively low bond dissociation energy and as such low distortion energy to reach the key bond activating transition state.
- Fricke, Christoph,Dahiya, Amit,Reid, William B.,Schoenebeck, Franziska
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p. 9231 - 9236
(2019/10/11)
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- Perylenequinonoid-catalyzed photoredox activation for the direct arylation of (het)arenes with sunlight
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Naturally occurring perylenequinonoid pigments (PQPs) have attracted considerable attention owing to their excellent properties of photosensitization. They have been widely investigated as an aspect of photophysics and photobiology. However, their applications in photocatalysis are yet to be explored. We report here that sunlight along with 1 mol% cercosporin, which is one of the perylenequinonoid pigments, catalyzes the direct C-H bond arylation of (het)arenes by a photoredox process with good regioselectivity and broad functional group compatibility. Furthermore, a gram-scale reaction with great conversions of substrates was achieved even by a cercosporin-containing supernatant without organic solvent extraction and purification after liquid fermentation. Thus we set up a bridge between microbial fermentation and organic photocatalysis for chemical reactions in a sustainable, environmentally friendly manner.
- Zhang, Shiwei,Tang, Zhaocheng,Bao, Wenhao,Li, Jia,Guo, Baodang,Huang, Shuping,Zhang, Yan,Rao, Yijian
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supporting information
p. 4364 - 4369
(2019/05/10)
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- METHOD FOR PRODUCING HALOGEN COMPOUND
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PROBLEM TO BE SOLVED: To provide a highly efficient and economically advantageous method for producing a halogen compound. SOLUTION: Provided is a method for converting a benzene derivative represented by the following formula (1) into a halogen compound by reacting the benzene derivative and a first halogenating agent selected from hydrogen halides and halide salts in the presence of at least one acid selected from sulfuric acid, methanesulfonic acid and trifluoromethanesulfonic acid and an oxidizing agent, or by reacting the benzene derivative and a second halogenating agent selected from N-halogen succinimide and 1,3-dihalogen-5,5-dimethylhydantoin in the presence of at least one acid selected from sulfuric acid and methanesulfonic acid. [In the formula, R1's are alkyl groups or the like; n is an integer of 1 to 4; and R2 is an aromatic ring group which may have a substituent group or a heterocyclic group which may have a substituent group.] SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
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Paragraph 0121; 0122; 0123; 0124; 0125
(2019/06/25)
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- Synthesis method of canagliflozin intermediate
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The invention relates to a synthesis method of a canagliflozin intermediate. Concretely, succinyl oxide and fluorobenzene are used as starting raw materials to be prepared into the canagliflozin crucial intermediate of 2-(4-fluorophenyl)-5-[(5-halogen-2-methyl phenyl)methyl]thiophene through the steps of Friedel-Crafts acylation ring opening, thiophene ring preparation, Friedel-Crafts acylation coupling, reduction and the like. The cheap succinyl oxide is used for preparing the thiophene ring, so that the Suzuki coupling reaction and Grignard reaction are avoided; the use of heavy metal reagents of palladium and the like is avoided; the production process is simplified; the product yield and the quality are improved; the environment pollution is reduced; the production cost is reduced.
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Paragraph 0041; 0042; 0043; 0044; 0045
(2018/03/26)
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- Decarbonylation of Aromatic Aldehydes and Dehalogenation of Aryl Halides Using Maghemite-Supported Palladium Catalyst
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A facile decarbonylation reaction of a variety of aromatic and heteroaromatic aldehydes using maghemite-supported palladium catalyst has been developed. The magnetic properties of catalyst facilitated an easy and efficient recovery of the catalyst from the reaction mixture using an external magnet. It was found that the catalyst could be reused up to four consecutive catalytic runs without a significant change in activity. In addition, the catalyst was also very effective in the dehalogenation of aryl halides. This is the first report on efficient utilization of directly immobilized Pd on maghemite in decarbonylation and dehalogenation reactions.
- Ajda?i?, Vladimir,Nikoli?, Andrea,Simi?, Stefan,Manojlovi?, Dragan,Stojanovi?, Zoran,Nikodinovic-Runic, Jasmina,Opsenica, Igor M.
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p. 119 - 126
(2017/12/27)
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- Continuous Visible-Light Photoflow Approach for a Manganese-Catalyzed (Het)Arene C?H Arylation
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Manganese photocatalysts enabled versatile room-temperature C?H arylation reactions by means of continuous visible-light photoflow, thus allowing for efficient C?H arylations in 30 minutes with ample scope. The robustness of the manganese-catalyzed photoflow strategy was shown by visible light-induced gram-scale synthesis, clearly outperforming the batch performance.
- Liang, Yu-Feng,Steinbock, Ralf,Yang, Long,Ackermann, Lutz
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supporting information
p. 10625 - 10629
(2018/08/01)
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- Sterically hindered N-aryl/benzyl substituted piperidoimidazolin-2-ylidene palladium complexes and their catalytic activities
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A series of N-aryl (2a,b) or benzyl (2c,d) substituted piperidoimidazolinium salts and their palladium complexes (3a-d) were prepared and characterized by 1H, 13C NMR, IR spectroscopy and elemental analysis. The crystal structures of 3a and 3c have been determined by X-ray crystallography. Thermogravimetric analysis (TGA) was applied to complexes (3a–d). The palladium complexes have been employed as catalyst for Suzuki-Miyaura cross coupling. The N-aryl substituted complex 3b was a highly efficient precatalyst and successfully employed in Suzuki-Miyaura cross coupling reactions of (hetero)aryl chlorides with arylboronic acids in air. In addition, the oxidative addition step of the reaction mechanism involving chlorobenzene and the catalysts 3a, 3b, 3c and 3d were computationally investigated by the DFT-ω-B97X-D method and complete agreement were obtained with the catalytic results. To measure σ-donating and π-acceptor properties of the new ligands, the rhodium carbonyl complexes were also prepared.
- Gacal, Elif,Denizalt?, Serpil,K?nal, Arma?an,G?k?e, Ayta? Gürhan,Türkmen, Hayati
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p. 6829 - 6838
(2018/10/20)
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- Preparation method of high-purity 2-(4-fluorophenyl)thiophene
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The invention relates to a preparation method of high-purity 2-(4-fluorophenyl)thiophene. The method comprises the following steps: performing a kumada coupling reaction between a Grignard reagent 4-fluorophenyl magnesium bromide and 2-bromo-thiophene under the action of a catalyst 1,2-bis(diphenylphosphine)ethane nickel chloride, to obtain high-purity 2-(4-fluorophenyl)thiophene. The preparationmethod provided by the invention has the following advantages: the particle size and appearance of the catalyst DPPE.NICl2 are adjusted, then the DPPE.NICl2 in a specific particle size range has a better catalysis effect, and the dosage of the catalyst is greatly reduced; moreover, the reaction efficiency is appropriately increased, and the nickel residue in the product is perfectly controlled; meanwhile, the impurity 2,2'-bithiophene in the system is inhibited quite well. The product quality is remarkably improved while the cost is lowered. The preparation method is more suitable for industrial production.
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Page/Page column 4-9
(2018/11/03)
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- Iodine-Catalyzed Synthesis of Chalcogenophenes by the Reaction of 1,3-Dienyl Bromides and Potassium Selenocyanate/Potassium Sulfide (KSeCN/K2S)
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The methods available for the synthesis of chalcogenophenes, in general, are associated with drawbacks of harsh conditions, use of costly metals, broad applicability, tedious purification process and low yield. To avoid these drawbacks a transition metal-free iodine-catalyzed reaction of aryl-susbstituted 1,3-dienyl bromides with potassium selenocyanate/potassium sulfide (KSeCN/K2S) leading to the corresponding selenophenes and thiophenes has been developed. Iodine is relatively benign, less expensive and readily available. Several diversely substituted selenophenes and thiophenes have been obtained by this procedure in high yields. Using this procedure 2-(4-chlorophenyl)thiophene, a key intermediate for the synthesis of a melanin concentrating hormone receptor ligand involved in the treatment of eating disorders, weight gain, obesity, depression and anxiety has been synthesized. Although the reaction is one-pot essentially it proceeds in two steps involving a selenocyanate/thiolate intermediate leading to the selenophene/thiophene. The simple operation, use of inexpensive reagents and a metal-free process make this procedure more attractive for an easy access to substituted selenophenes and thiophenes. (Figure presented.).
- Maity, Pintu,Ranu, Brindaban C.
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p. 4369 - 4378
(2017/12/26)
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- A g-C3N4/rGO nanocomposite as a highly efficient metal-free photocatalyst for direct C-H arylation under visible light irradiation
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Visible light mediated photoredox arylations can proceed under very mild conditions and have therefore become attractive. Nowadays, various metal nanomaterials and metal complexes have been developed as photocatalysts for direct arylation of heteroaromatics. These photocatalysts, however, still suffer from corrosion, high cost, aggregation or poor stability. We report the design and fabrication of a g-C3N4/rGO nanocomposite and demonstrate its excellent activity, high apparent quantum efficiency, and recyclability to catalyze the metal free direct arylation of heteroaromatics under visible light at room temperature. Moreover, the g-C3N4/rGO catalyst can be reused more than five times without significant loss of activity, confirming this catalyst's excellent stability. The present strategy to fabricate a metal-free g-C3N4/rGO nanocomposite for direct C-H arylation open a new avenue towards replacing metal-based catalysts in fine organic synthesis.
- Cai, Xiaohui,Liu, Hanwen,Zhi, Lihua,Wen, Huang,Yu, Ailing,Li, Lianhua,Chen, Fengjuan,Wang, Baodui
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p. 46132 - 46138
(2017/10/10)
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- Method for cleaving alpha carbon-carbon single bonds in ketone under condition of metal-free catalysis
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The invention discloses a method for selectively activating and cleaving alpha carbon-carbon single bonds in ketone under the condition of metal-free catalysis. The method is characterized in that the alpha carbon-carbon single bonds in the ketone are activated and cleaved by solvent induction and driving of intermediate structure factors formed by the ketone and hydrazine without metal catalysts. Transition metal for catalysis is omitted, the method is environmentally friendly, reaction cost is reduced to a certain degree, methodology of selective cleavage of the carbon-carbon single bonds is enriched, and a new idea is provided for activation of inertial chemical bonds under mild conditions.
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Paragraph 0017; 0032
(2017/10/07)
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- Manganese-Catalyzed Aerobic Heterocoupling of Aryl Grignard Reagents
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An improved protocol has been developed for the MnCl2-catalyzed cross-coupling reaction of two arylmagnesium bromides under dioxygen. The reaction was achieved by using the Grignard reagents in a 2:1 ratio and 20 % of MnCl2. Very good yields of the heterocoupling product were obtained when the limiting Grignard reagent underwent little homocoupling under the reaction conditions. Arylmagnesium bromides that contain p-methoxy, p-(dimethylamino), p-fluoro, and p-chloro substituents were shown to afford high product yields in the cross-coupling reactions with a variety of substituted aryl Grignard reagents. Heterocyclic Grignard reagents, on the other hand, were less effective substrates for this transformation because of the rapid homocoupling of these reagents under the reaction conditions.
- Ghaleshahi, Hajar Golshahi,Antonacci, Giuseppe,Madsen, Robert
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p. 1331 - 1336
(2017/03/23)
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- Selective Reductive Removal of Ester and Amide Groups from Arenes and Heteroarenes through Nickel-Catalyzed C?O and C?N Bond Activation
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An inexpensive nickel(II) catalyst and a hydrosilane were used for the efficient reductive defunctionalization of aryl and heteroaryl esters through a decarbonylative pathway. This versatile method could be used for the removal of ester and amide functional groups from various organic molecules. Moreover, a scale-up experiment and a synthetic application based on the use of a removable carboxylic acid directing group highlight the usefulness of this reaction.
- Yue, Huifeng,Guo, Lin,Lee, Shao-Chi,Liu, Xiangqian,Rueping, Magnus
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supporting information
p. 3972 - 3976
(2017/03/27)
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- Nickel-catalyzed reductive defunctionalization of esters and amides to aromatic hydrocarbons
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The removal of ester and amide groups is of fundamental significance in organic syntheses. Under non-catalytic conditions, hydride sources are chiefly used for their reduction. Recently developed Ni-catalyzed one-pot reductive activation of esters and ami
- Mondal, Manoj,Bharali, Pankaj
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p. 13211 - 13214
(2017/11/27)
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- End-Capping Groups for Small-Molecule Organic Semiconducting Materials: Synthetic Investigation and Photovoltaic Applications through Direct C–H (Hetero)arylation
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A Pd-catalyzed C–H (hetero)arylation methodology has been optimized for the efficient synthesis of various useful end-capping groups that are widely applied in small-molecule optoelectronic materials. We report herein the synthesis of a broad scope of target molecules ranging from donor-type through acceptor-type to hybrid-type end-capping groups. To demonstrate their application in dye-sensitized solar cells, we have designed two new D–A–π–A′-type organic sensitizers (CYL-3 and CYL-4), which were synthesized in a step-economic manner by sequential C–H arylations using the facilely obtained end-capping groups. The devices based on CYL-3 and CYL-4 give Vocvalues of 0.67–0.71 V, Jscvalues of 10.07–11.63 mA cm–2, and FF values of 70.6–72.9 %, which correspond to overall power conversion efficiencies of 4.76–6.02 %. This work is expected to become a practical synthetic alternative allowing materials scientists to access small-molecule organic materials in fewer synthetic transformations.
- Lu, Te-Jui,Lin, Po-Han,Lee, Kun-Mu,Liu, Ching-Yuan
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p. 111 - 123
(2017/01/14)
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- Gram-scale synthesis of aligned C3N4-polypyrrole heterojunction aerogels with tunable band structures as efficient visible and near infrared light-driven metal-free photocatalysts
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The assembly of aligned porous materials from simple building blocks is of widespread interest for engineering materials with enhanced and synergistic properties. To date, however, how to develop 3D heterojunction aerogels with aligned porosity based on 2D semiconductor materials and 1D conducting polymers for solar energy conversion in the visible and near-infrared (NIR) light region remains a significant challenge. Here a new class of gram-scale 3D aligned heterojunction aerogels of polypyrrole (PPy)/C3N4 nanosheets (NSs) were designed and synthesized by directional freezing of polypyrrole (PPy)/polyvinyl alcohol (PVA) and C3N4 NS aqueous suspension. The synthesis of aligned C3N4-PPy heterojunction aerogels can be achieved on a large scale. The formed aerogel expresses stable and uniform dispersion of the two building blocks, long-range channel aligned structures along the whole monolithic sample, and additional special complementary optical properties between PPy and C3N4 NSs. Based on the above unique structure and optical properties, this novel metal-free heterojunction aerogel exhibits excellent photocatalytic activity and long-term stability for direct arylation of heteroaromatics under visible and near infrared (NIR) light irradiation at room temperature, far exceeding those of the single- and two-component systems. Our work therefore not only provides a new approach to obtain aligned heterojunction aerogels based on metal free semiconductors but also paves a way to develop gram-scale aerogels as a new type of highly efficient visible and NIR light induced heterogeneous photocatalyst.
- Liu, Jian,Wang, Hao,Bai, Jinwei,Li, Tianrong,Yang, Yanmei,Peng, Yong,Wang, Baodui
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p. 24920 - 24928
(2017/12/15)
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- A antidiabetic drug synthesis of intermediates method
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The invention discloses a synthetic method of an antidiabetic drug intermediate (I). According to the method, in the presence of a particular reducing agent, a compound shown in the formula II is converted into a compound shown in the formula I.
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Paragraph 0012-0016
(2017/10/06)
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- N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicine for treating diabetes
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The invention discloses an N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicines for treating diabetes. The structural formula of the derivative is as shown in the specification, and in the formula, R1 is halogen or C1-C4 alkyl; R2 is substituted aryl; R3 is H or acyl with 1-4 atoms. The compound disclosed by the invention has functions of remarkably reducing blood sugar and promoting discharge of glucose from urea, and can be used for preparing medicines for treating diabetes.
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Paragraph 0098; 0099; 0100
(2017/07/18)
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- Synthetic method of 2-(4-fluorophenyl) thiophene
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The invention discloses a synthetic method of 2-(4-fluorophenyl) thiophene. The synthetic method comprises the following steps: 1), performing Vilsmeier-Haack reaction on 4-fluoroacetophenone under the action of solid triphosgene and N,N-dimethylfomamide to obtain 2-chloro-2-(4-fluorophenyl) acetaldehyde; 2), performing ring-closing reaction between 2-chloro-2-(4-fluorophenyl) acetaldehyde and ethyl thioglycolate under the action of alkali to obtain 5-(4-fluorophenyl) thiophene-2-carboxylic acid ethyl ester; 3), performing esterolysis on 5-(4-fluorophenyl) thiophene-2-carboxylic acid ethyl ester under the action of alkali to obtain 5-(4-fluorophenyl) thiophene-2-formic acid; and 4), preparing 2-(4-fluorophenyl) thiophene from 5-(4-fluorophenyl) thiophene-2-formic acid under the catalysis of copper powder. The invention provides a synthetic method with low-price and easily-available raw materials and mild reaction conditions for synthesis of 2-(4-fluorophenyl) thiophene, the entire reaction has no special requirements on equipment and reaction conditions, and the yield of a product is relatively high; and the synthetic method is simple and convenient to operate, can ensure the safety of operators, and has a good market prospect.
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Paragraph 0053
(2017/02/24)
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- 2-Aryl-indenylphosphine ligands: Design, synthesis and application in Pd-catalyzed Suzuki-Miyaura coupling reactions
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A focused library of phosphine ligands was constructed for structural optimization. The catalyst can be used to perform the Suzuki-Miyaura cross-coupling reaction of aryl and heteroaryl chlorides.
- Lian, Ze-Yu,Yuan, Jia,Yan, Meng-Qi,Liu, Yan,Luo, Xue,Wu, Qing-Guo,Liu, Sheng-Hua,Chen, Jian,Zhu, Xiao-Lei,Yu, Guang-Ao
-
supporting information
p. 10090 - 10094
(2016/11/06)
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- Radical C-H arylations of (hetero)arenes catalysed by gallic acid
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Gallic acid efficiently catalyses radical arylations in water-acetone at room temperature. This methodology proved to be versatile and scalable. Therefore, it constitutes a greener alternative to arylation. Moreover, considering that gallic acid is an abundant vegetable tannin, this work also unleashes an alternative method for the reutilisation of bio-wastes.
- Perretti, Marcelle D.,Monzón, Diego M.,Crisóstomo, Fernando P.,Martín, Víctor S.,Carrillo, Romen
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supporting information
p. 9036 - 9039
(2016/07/21)
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- Method for preparing Canagliflozin intermediate 2-(4-fluoro-phenyl) thiophene
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The invention relates to a method for preparing Canagliflozin intermediate 2-(4-fluoro-phenyl) thiophene. The method comprises a step (1) of causing 2-bromothiophene to react with magnesium chips in a THF solvent to generate 2-thienyl magnesium bromide ringer solution; a step (2) of causing 2-thienyl magnesium bromide ringer solution and p-fluoro bromo benzene to undergo catalytic Kumada coupling reaction under the conditions of taking a nickel or palladium complex as a catalyst, and obtaining 2-(4-fluoro-phenyl) thiophene. According to the method, the product is good in quality and high in yield, reaction conditions are mild, and the method is simple to operate and easy to industrialize.
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Paragraph 0016; 0030-0065
(2017/03/25)
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- PROCESS FOR THE PURIFICATION OF CANAGLIFLOZIN
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The present invention provides a process for the preparation of (1S)-2,3,4,6-tetra- O-acetyl-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-thienyl]methyl]-4-methylphenyl]-D- glucitol of Formula III. The invention also provides a process for the purification of canagliflozin using (1S)-2,3,4,6-tetra-O-acetyl-1,5-anhydro-1-[3-[[5-(4-fluorophenyl)-2-5 thienyl]methyl]-4-methylphenyl]-D-glucitol of Formula III.
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Page/Page column 6
(2016/03/12)
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- POPd/TBAB co-catalyzed Suzuki cross-coupling reaction of heteroaryl chlorides/bromides with 4-fluorophenylboronic acid in water
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An organic solvent free and efficient heterogeneous synthesis for bridging heteroaryl halides and 4-fluorophenylboronic acid was studied in aqueous media according to the Suzuki cross-coupling protocol. High yields of heteroaryl-aryl fluorides were successfully obtained with: chloro-/bromo-substituted pyridine, thiophene, indole, and inzole in neat water using palladium phosphinous acid complexes (POPd)/tetrabutylammonium bromide (TBAB) as co-catalysts. A possible mechanism for the heterogeneous coupling reaction is proposed and discussed according to the function of the TBAB interphases. The notable properties of the reported method are highly co-catalytic activity, hetero-atom tolerance, simple separating procedure and little environmental disposal impact.
- Li, Ben,Zhang, Zhiqiang
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p. 637 - 644
(2016/02/19)
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- Method for synthesizing 2-(4-fluorophenyl) thiophene
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The invention discloses a method for synthesizing 2-(4-fluorophenyl) thiophene. The method comprises the following steps: 1) preparing 4-fluorophenylboronic acid: separately preserving heat for a 4-fluorophenylmagnesium bromide solution which is taken as a material 1 and a boric acid ester solution which is taken as a material 2 to the reaction temperature, carrying out mixing reaction, and carrying quenching and post-treatment to obtain 4-fluorophenylboronic acid; and 2) preparing 2-(4-fluorophenyl) thiophene): adding the 4-fluorophenylboronic acid, 2-bromo thiophene and a Pd catalyst into an organic solvent to dissolve to obtain a material 3, separately preserving the heat for the material 3 and an inorganic alkali aqueous solution which is taken as a material 4 to the reaction temperature, carrying out mixing reaction, and carrying out post-treatment to obtain 2-(4-fluorophenyl) thiophene. The method is simple in operation process, is short in production period, is gentle in condition, is fewer in side reactions and is high in yield; and the obtained product is high in purity.
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Paragraph 0046; 0047; 0048
(2016/12/16)
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- Light-Induced C-H Arylation of (Hetero)arenes by in Situ Generated Diazo Anhydrides
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Diazo anhydrides (Ar-N=N-O-N=N-Ar) have been known since 1896 but have rarely been used in synthesis. This communication describes the development of a photochemical catalyst-free C-H arylation methodology for the preparation of bi(hetero)aryls by the one-pot reaction of anilines with tert-butyl nitrite and (hetero)arenes under neutral conditions. The key step in this procedure is the in situ formation and subsequent photochemical (>300 nm) homolytic cleavage of a transient diazo anhydride intermediate. The generated aryl radical then efficiently reacts with a (hetero)arene to form the desired bi(hetero)aryls producing only nitrogen, water, and tert-butanol as byproducts. The scope of the reaction for several substituted anilines and (hetero)arenes was investigated. A continuous-flow protocol increasing selectivity and safety has been developed enabling the experimentally straightforward preparation of a variety of substituted bi(hetero)aryls within 45 min of reaction time.
- Cantillo, David,Mateos, Carlos,Rincon, Juan A.,De Frutos, Oscar,Kappe, C. Oliver
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supporting information
p. 12894 - 12898
(2015/09/07)
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- Kinetic Studies on the Palladium(II)-Catalyzed Oxidative Cross-Coupling of Thiophenes with Arylboron Compounds and Their Mechanistic Implications
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Reaction orders for the key components in the palladium(II)-catalyzed oxidative cross-coupling between phenylboronic acid and ethyl thiophen-3-yl acetate were obtained by the method of initial rates. It turned out that the reaction rate not only depended on the concentration of palladium trifluoroacetate (reaction order: 0.97) and phenylboronic acid (reaction order: 1.26), but also on the concentration of the thiophene (reaction order: 0.55) and silver oxide (reaction order: -1.27). NMR spectroscopy titration studies established the existence of 1:1 complexes between the silver salt and both phenylboronic acid and ethyl thiophen-3-yl acetate. A low inverse kinetic isotope effect (kH/kD=0.93) was determined upon employing the 4-deuterated isotopomer of ethyl thiophen-3-yl acetate and monitoring its reaction to the 4-phenyl-substituted product. A Hammett analysis performed with para-substituted 2-phenylthiophenes gave a negative ρ value for oxidative cross-coupling with phenylboronic acid. Based on the kinetic data and additional evidence, a mechanism is suggested that invokes transfer of the phenyl group from phenylboronic acid to a 1:1 complex of palladium trifluoroacetate and thiophene as the rate-determining step. Proposals for the structure of relevant intermediates are made and discussed.
- Schnapperelle, Ingo,Breitenlechner, Stefan,Bach, Thorsten
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supporting information
p. 18407 - 18416
(2015/12/24)
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- Novel glycosyl pyridyl-triazole@palladium nanoparticles: Efficient and recoverable catalysts for C-C cross-coupling reactions
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We report the development of a series of glycosyl pyridyl-triazole@palladium nanoparticles (GPT-Pd) which were synthesized by the reaction of azidoglycosides with 2-ethynylpyridine via click chemistry. These palladium nanoparticles were obtained in high yields and were fully characterized by 1H and 13C NMR, elemental analysis, transmission electron microscopy, and thermogravimetric analysis. The single crystal structure of GPT-Pd catalyst 5c was determined to show that the glycosyl pyridyl-triazole coordinated with palladium in a bidentate (N,N) coordination mode. Their use in palladium-catalyzed C-C coupling reactions such as Suzuki-Miyaura coupling, Heck reaction and Sonogashira reaction achieved quantitative production under mild conditions. Furthermore, the catalysts can be easily separated from the reaction mixture and the catalytic activity remained unchanged even after 8 successive catalytic cycles. This journal is
- Shen, Hongyun,Shen, Chao,Chen, Chao,Wang, Anming,Zhang, Pengfei
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p. 2065 - 2071
(2015/04/14)
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- Heterogeneously catalyzed direct C-H thiolation of heteroarenes
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The first general methodology for the direct thiolation of electron-rich heteroarenes was developed by employing Pd/Al2O3, a recoverable and commercially available heterogeneous catalyst, and CuCl2. This method represents an operationally simple approach for the synthesis of these valuable compounds. Preliminary mechanistic studies indicate a heterogeneous catalytic system, in which both metals play a complementary role in the formation of the thiolated products. (Hetero)genius: A general method for the direct thiolation of electron-rich heteroarenes was developed by employing Pd/Al2O3, a recoverable and commercially available heterogeneous catalyst, and CuCl2. Preliminary mechanistic studies indicate a heterogeneous active catalytic species, with the two metals playing complementary roles in the formation of the thiolated products.
- Vsquez-Cspedes, Suhelen,Ferry, Anglique,Candish, Lisa,Glorius, Frank
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supporting information
p. 5772 - 5776
(2015/06/17)
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- GLUCOSYLCERAMIDE SYNTHASE INHIBITORS FOR THE TREATMENT OF DISEASES
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Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
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Paragraph 000763
(2015/04/15)
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- Flexible routes to thiophenes
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Three convergent routes to thiophenes are described, hinging on the radical addition of α-xanthyl ketones to ethyl vinyl sulfide or to vinyl pivalate. The latter route ultimately proved to be the most versatile and efficient (61-94%).
- Jullien, Helene,Quiclet-Sire, Beatrice,Tetart, Thomas,Zard, Samir Z.
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supporting information
p. 302 - 305
(2014/01/23)
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- Pd/C as a catalyst for completely regioselective c=h functionalization of thiophenes under mild conditions
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The completely C3-selective arylation of thiophenes and benzo[b]thiophenes was achieved by using Pd/C as a heterogeneous catalyst without ligands or additives under mild reaction conditions. The practicability of this transformation is demonstrated by notable functional group tolerance and the insensitivity of the reaction to H2O and air. This method is also applicable to nitrogen- and oxygen-containing heterocycles, yielding the corresponding C2-arylated products. Three-phase tests along with Hg-poisoning and hot-filtration tests suggest that the catalytically active species is heterogeneous in nature. I+ can do better! Pd/C can be used without ligands or additives to catalyze the completely C3-selective arylation of diversely substituted thiophenes and benzo[b]thiophenes under mild reaction conditions. The physical nature of the catalytic species was investigated and the mechanism was studied. Relative rate data generated in a "robustness screen" were used to design a complex substrate that undergoes highly chemoselective sequential functionalization. Copyright
- Tang, Dan-Tam D.,Collins, Karl D.,Ernst, Johannes B.,Glorius, Frank
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supporting information
p. 1809 - 1813
(2014/03/21)
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- C-ARYL GLUCOSIDE DERIVATIVES, PREPARATION PROCESS AND PHARMACEUTICAL USE THEREOF
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C-aryl glucoside derivatives, preparation processes and pharmaceutical uses thereof are disclosed. In particular, C-aryl glucoside derivatives represented by formula (I), with each substituent defined in the application, pharmaceutically acceptable salts or stereoisomers thereof, their preparation methods, and pharmaceutical compositions containing the derivatives as well as their uses as therapeutic agents, particularly as sodium-dependent glucose cotransporter (SGLT)-1 inhibitors, are disclosed.
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Paragraph 0189
(2013/06/04)
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- FAMILY OF ARYL, HETEROARYL, O-ARYL AND O-HETEROARYL CARBASUGARS
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The present invention relates to a compound of the following formula (I): as well as its process of preparation, pharmaceutical and cosmetics composition comprising it and use thereof, notably as an inhibitor of the sodium-dependent glucose co-transporter, such as SGLTl, SGLT2 and SGLT3, in particular in the treatment or prevention of diabetes, and more particularly type-II diabetes, diabetes-related complications, such as arthritis of the lower extremities, cardiac infarction, renal insufficiency, neuropathy or blindness, hyperglycemia, hyperinsulinemia, obesity, hypertriglyceridemia, X syndrome and arteriosclerosis, as well as for its use as an anticancer, anti-infective, anti-viral, anti-thrombotic or anti- inflammatory drug, or for lightening, bleaching, depigmenting the skin, removing blemishes from the skin, particularly age spots and freckles, or preventing pigmentation of the skin.
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Page/Page column 71
(2012/12/13)
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- Pd-catalyzed β-selective direct C-H bond arylation of thiophenes with aryltrimethylsilanes
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Direct arylation of thiophenes and benzothiophenes with aryltrimethylsilanes was effectively catalyzed by PdCl2(MeCN) 2 in the presence of CuCl2 as an oxidant. The reaction preferentially occurred at the β-position of both
- Funaki, Kenji,Sato, Tetsuo,Oi, Shuichi
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supporting information
p. 6186 - 6189
(2013/02/23)
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- Selective rhodium(III)-catalyzed cross-dehydrogenative coupling of furan and thiophene derivatives
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A hot couple: An unprecedented rhodium(III)-catalyzed cross-dehydrogenative coupling (CDC) of various furan and thiophene derivatives leads to valuable 2,2'-bi(heteroaryl) products in good yields and selectivities (see scheme). In addition, pyrroles and indoles can also be used as coupling partners, giving C3-arylated products. Copyright
- Kuhl, Nadine,Hopkinson, Matthew N.,Glorius, Frank
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supporting information; experimental part
p. 8230 - 8234
(2012/09/08)
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- Asymmetric hydrogenation of thiophenes and benzothiophenes
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An efficient and highly asymmetric ruthenium-N-heterocyclic carbene-catalyzed hydrogenation of substituted thiophenes and benzothiophenes is described, providing a new strategy for the formation of valuable enantiomerically pure tetrahydrothiophenes and 2,3-dihydrobenzothiophenes.
- Urban, Slawomir,Beiring, Bernhard,Ortega, Nuria,Paul, Daniel,Glorius, Frank
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supporting information
p. 15241 - 15244
(2012/11/07)
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- Synthesis of functionalized 2-arylthiophenes with triarylbismuths as atom-efficient multicoupling organometallic nucleophiles under palladium catalysis
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Atom-efficient cross-coupling reactions of functionalized 2-bromo- and 2-iodothiophenes have been demonstrated using triarylbismuths as atom-efficient multicoupling organometallic nucleophiles under palladium-catalyzed conditions. These couplings with various functionalized triarylbismuths proceeded smoothly to afford the corresponding functionalized 2-arylthiophenes in high yields. Georg Thieme Verlag Stuttgart · New York.
- Rao, Maddali L. N.,Banerjee, Debasis,Dhanorkar, Ritesh J.
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supporting information; experimental part
p. 1324 - 1330
(2011/07/07)
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- PROCESS FOR THE PREPARATION OF COMPOUNDS USEFUL AS INHIBITORS OF SGLT
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The present invention is directed to a novel process for the preparation of compounds having inhibitory activity against sodium-dependent glucose transporter (SGLT) being present in the intestine or kidney.
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Page/Page column 43-44
(2010/05/13)
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- Synthesis of 2-aryl- and 2,5-diarylfurans and thiophenes by Suzuki-Miyaura reactions using potassium trifluoroborate salts and heteroaryltellurides
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The Suzuki-Miyaura cross-coupling reaction of 2-(butyltellanyl) or 2,5-bis-(butyltellanyl)furans and thiophenes with potassium aryltrifluoroborate salts catalyzed by palladium afforded 2-aryl- or 2,5-diaryl-furans and thiophenes in moderate to good yields.
- Botteselle, Giancarlo V.,Hough, Thomas L. S.,Venturoso, Raphael C.,Cella, Rodrigo,Vieira, Adriano S.,Stefani, Helio A.
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experimental part
p. 870 - 873
(2009/04/11)
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- The synthesis and applications of a micro-pine-structured nanocatalyst
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Dendritic nanoferrites with a micro-pine morphology have been synthesized for the first time under microwave irradiation conditions without using any reducing or capping reagent; the nanoferrites were then functionalized and coated with Pd metal, which catalyzes various organic transformations. The Royal Society of Chemistry 2008.
- Polshettiwar, Vivek,Nadagouda, Mallikarjuna N.,Varma, Rajender S.
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supporting information; experimental part
p. 6318 - 6320
(2009/04/13)
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- Pd-N-heterocyclic carbene (NHC) organic silica: synthesis and application in carbon-carbon coupling reactions
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The first Pd-N-heterocyclic carbene (NHC) complex in the form of organic silica was prepared using sol-gel method and its application in Heck and Suzuki reactions was demonstrated. These C-C coupling reactions proceeded efficiently under the influence of microwave irradiation, with excellent yield, without any change in catalytic activity for at least five reaction cycles, with negligible Pd concentration in the end product.
- Polshettiwar, Vivek,Varma, Rajender S.
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p. 4637 - 4643
(2008/09/20)
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