- Electrochemical C?O Bond Formation: Facile Access to Aromatic Lactones
-
An efficient and robust methodology based on electrochemical techniques for the direct synthesis of aromatic lactones through dehydrogenative C?O cyclization is described. This new and useful electrochemical reaction can tolerate a variety of functional groups, and is scalable to 100 g under mild conditions. Remarkably, heterocycle-containing substrates can be employed, thus expanding the scope of radical C?O cyclization reactions.
- Tao, Xiang-Zhang,Dai, Jian-Jun,Zhou, Jie,Xu, Jun,Xu, Hua-Jian
-
-
Read Online
- Synthesis of biaryls via cross-coupling reaction of arylboronic acids with aryl chlorides catalyzed by NiCl2/Triphenylphosphine complexes
-
The cross-coupling reaction of tolylboronic acids (1.3 equiv.) with chloroarenes in toluene was carried out at 80-100°C in the presence of a NiCl2/PPh3 catalyst (3 mol%) and K3PO4·nH2O (2.6 equiv.). The reaction can be applied to various electron-deficient and -rich chloroarenes and is economical as the industrial process. (C) 2000 Elsevier Science Ltd.
- Inada, Kaoru,Miyaura, Norio
-
-
Read Online
- One-pot sequential reaction to 2-substituted-phenanthridinones from: N -methoxybenzamides
-
The sequential use of a hypervalent iodine reagent leads to the one-pot synthesis of 2-bromo/chloro-phenanthridinones via an amidation of arenes followed by a regioselective halogenation reaction. These consecutive C-H functionalization reactions can be used efficiently to construct 2-substituted-phenanthridinones at room temperature with good to high yields. Application of the current method is highlighted by the concise synthesis of the natural product PJ34.
- Liang, Dongdong,Sersen, Deanna,Yang, Chao,Deschamps, Jeffrey R.,Imler, Gregory H.,Jiang, Chao,Xue, Fengtian
-
-
Read Online
- Bis(triphenylphosphine)palladium(II)succinimide as a precatalyst for Suzuki cross-coupling - Subtle effects exerted by the succinimide ligand
-
A new palladium(II) precatalyst for Suzuki cross-coupling of aryl halides and organoboronic acids has been identified, namely bis(triphenylphosphine) palladium(II)succinimide [(Ph3P)2Pd(N-Succ)2] 2. The precatalyst is easily prepared from palladium(0) precursors, such as (Ph3P)4Pd or Pd2dba3· CHCl3/Ph3P and succinimide, is air, light and moisture stable, and may be employed with a variety of substrates to give the cross-coupled products, in good yields and in reasonable time, at relatively low catalyst loadings.
- Fairlamb, Ian J.S.,Kapdi, Anant R.,Lynam, Jason M.,Taylor, Richard J.K.,Whitwood, Adrian C.
-
-
Read Online
- Synthesis method of 4-bromomethyl-2-methyl formate biphenyl
-
The invention discloses a synthesis method of 4-bromomethyl-2-methyl formate biphenyl. The method comprises the following steps: performing bromination reaction in a mode of synchronously dropwise adding bromine and hydrogen peroxide, re-oxidizing hydrobromic acid formed after the reaction into bromine, and performing bromination reaction again, so that the bromine can fully participate in the reaction so as to reduce the use amount of bromine raw materials and improve the yield of the 4-bromomethyl-2-methyl formate biphenyl, waste difficult to treat cannot be generated, hydrogen peroxide is cheap and easy to obtain, and the production cost is remarkably saved.
- -
-
Paragraph 0025; 0029-0030; 0032; 0036-0037
(2021/07/14)
-
- N-Aroylsulfonamide-Photofragmentation (ASAP)-A Versatile Route to Biaryls
-
The photochemical fragmentation of N-aroylsulfonamides 9 (ASAP) is a powerful method for the preparation of various biaryls. Compounds 9 are easily accessible in two steps from amines by treatment with arenesulfonyl chlorides and aroyl chlorides. Many of these compounds were prepared for the first time. The irradiation takes place in a previously developed continuous-flow reactor using inexpensive UVB or UVC fluorescent lamps. Isocyanates and sulphur dioxide are formed as the only by-products. The ASAP tolerates a variety of functional groups and is even suited for the preparation of phenylnaphthalenes and terphenyls. The ASAP mechanism was elucidated by interaction of photophysical and quantum chemical (DFT) methods and revealed a spirocyclic biradical as key intermediate.
- Wessig, Pablo,Krebs, Saskia
-
supporting information
p. 6367 - 6374
(2021/09/29)
-
- Mechanochemical-Cascaded C-N Cross-Coupling and Halogenation Using N-Bromo- And N-Chlorosuccinimide as Bifunctional Reagents
-
Exploration of alternative energy sources for chemical transformations has gained significant interest from chemists, and mechanochemistry is one of those sources. Herein, we report the use of N-bromosuccinimides (NBS) and N-chlorosuccinimides (NCS) as bifunctional reagents for a cascaded C-N bond formation and subsequent halogenation reactions. Under the solvent-free mechanochemical (ball-milling) conditions, the synthesis of a wide range of phenanthridinone derivatives from N-methoxy-[1,1′-biphenyl]-2-carboxamides is accomplished. During the reactions, NBS and NCS first assisted the oxidative C-N coupling reaction and subsequently promoted a halogenation reaction. Thus, the role of NBS and NCS was established to be bifunctional. Overall, a mild, solvent-free, convenient, one-pot, and direct synthesis of various bromo- and chloro-substituted phenanthridinone derivatives was achieved.
- Bera, Shyamal Kanti,Mal, Prasenjit
-
p. 14144 - 14159
(2021/09/13)
-
- Palladium-catalyzed intramolecular aromatic C-H acylation of 2-arylbenzoyl fluorides
-
The catalytic intramolecular cyclization of acyl fluorides using a Pd(OAc)2/PCy3 system is described. A wide range of 2-arylbenzoyl fluoride derivatives can be used as fluorenone precursors and the reaction proceeds via an intramolecular coupling between aromatic C-H bonds with acyl C-F bonds. The reaction can be applied to the synthesis of indenofluorenedione derivatives and to the construction of other molecules with fivemembered rings.
- Hayakawa, Kazuki,Ikai, Kana,Ogiwara, Yohei,Sakai, Norio,Sakurai, Yuka
-
p. 1882 - 1893
(2021/08/13)
-
- Remote and Selective C(sp2)-H Olefination for Sequential Regioselective Linkage of Phenanthrenes
-
Biphenylcarboxylic acid with two competing C(sp2)-H sites was designed for site selective C(sp2)-H functionalization by developing carboxylic acids assisted remote and selective olefination via 7-membered palladacycle. Mechanism investigation and DFT calculations reveal a kinetics-determined process, which could be utilized to explore a variety of remote site selectivity. The practicability of this method was highlighted by the precise construction of phenathrene under sequential site selectivity.
- Wei, Yi,Duan, Abing,Tang, Pan-Ting,Li, Jia-Wei,Peng, Rou-Ming,Zhou, Zheng-Xin,Luo, Xiao-Peng,Kurmoo, Mohamedally,Liu, Yue-Jin,Zeng, Ming-Hua
-
supporting information
p. 4129 - 4134
(2020/06/08)
-
- Palladium-Catalyzed Three-Component Coupling of Ynamides
-
A palladium-catalyzed regioselective three-component coupling of ynamides was developed. The reaction proceeded smoothly to furnish the desired products when carried out at 70 °C in acetonitrile/water with potassium carbonate in the presence of 2.5 mol percent Pd2(dba)3·CHCl3 without a ligand. Various iodides and boronic acids were used in this reaction, and a carbon-carbon bond was formed with satisfactory regioselectivity from the ynamides.
- Wakamatsu, Hideaki,Takahashi, Ayano,Ishii, Ayaka,Kikuchi, Youhei,Sasaki, Madoka,Saito, Yukako,Natori, Yoshihiro,Yoshimura, Yuichi
-
supporting information
p. 5299 - 5303
(2020/07/08)
-
- Visible-Light-Induced Arene C(sp 2)-H Lactonization Promoted by DDQ and tert -Butyl Nitrite
-
A visible-light photocatalytic aerobic oxidative lactonization of arene C(sp 2)-H bonds proceeds in the presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tert -butyl nitrite (TBN). Under the optimized conditions, a range of 2-arylbenzoic acids is converted into the corresponding benzocoumarin derivatives in moderate to excellent yields. This method is characterized by its atom economy, mild reaction conditions, the use of a green oxidant and metal-free catalysis.
- Chen, Bajin,Hu, Baoxiang,Hu, Xinquan,Jin, Liqun,Li, Meichao,Shen, Zhenlu,Sun, Nan,Wang, Shengpeng,Wang, Yiqing
-
supporting information
p. 261 - 266
(2020/02/18)
-
- Method for preparing high-purity 4'-methylbiphenyl-2-carboxylic acid methyl ester by using waste residues of 4'-methylbiphenyl-2-carboxylic acid methyl ester
-
The invention relates to a method for preparing high-purity 4'-methylbiphenyl-2-carboxylic acid methyl ester by using waste residues of 4'-methylbiphenyl-2-carboxylic acid methyl ester, and belongs tothe technical field of pharmaceutical synthesis. According to the method, the waste residues of 4'-methylbiphenyl-2-carboxylic acid methyl ester are taken as starting materials, after alkali hydrolysis, acidolysis and then layering are carried out after solvent extraction, after the solvent extraction, layering and re-esterification processes are carried out to synthesize the high-purity 4'-methylbiphenyl-2-carboxylic acid methyl ester. By using the method, the waste residues are recycled, the reuse of the waste residues is realized, the overall yield of the reaction is improved, and the pollution is reduced; and the method is low in cost, easy in operation and easy to realize industrial production.
- -
-
Paragraph 0022-0033
(2019/11/12)
-
- METHOD FOR THE METAL-FREE PREPARATION OF A BIARYL BY A PHOTOSPLICING REACTION AND THEIR USES
-
The present invention relates to a method for the metal-free preparation of a biaryl compound by a photosplicing reaction and its use in the preparation of chemical compounds, preferably of active ingredients e.g. in the fields of pharmaceuticals and agrochemicals. In particular, it refers to a method for the regiocontrolled preparation of a biaryl compound of formula (I): Ar-Ar' by photochemically reacting a precursor compound of formula (II): Ar-L-Ar' to form a biaryl compound of general formula: Ar-L-Ar' (II) → Ar-Ar' (I) wherein Ar and Ar', independently of each other, represent an unsubstituted or substituted C6-C20 aryl group or a heteroaryl group with 5–20 ring atoms selected from carbon, nitrogen, oxygen and sulfur, and L represents a group –X–Y–Z– as defined herein. The biaryl compounds are generally suitable as intermediates or key building blocks in a very broad spectrum of organic chemical syntheses and their respective utilities. Their use within the field of synthesis of active ingredients is an aspect of the invention, and their use in the preparation of pharmaceutically active ingredients is particularly preferred.
- -
-
Page/Page column 39; 45; 46
(2019/06/11)
-
- Metal-Free Aryl Cross-Coupling Directed by Traceless Linkers
-
The metal-free, highly selective synthesis of biaryls poses a major challenge in organic synthesis. The scope and mechanism of a promising new approach to (hetero)biaryls by the photochemical fusion of aryl substituents tethered to a traceless sulfonamide linker (photosplicing) are reported. Interrogating photosplicing with varying reaction conditions and comparison of diverse synthetic probes (40 examples, including a suite of heterocycles) showed that the reaction has a surprisingly broad scope and involves neither metals nor radicals. Quantum chemical calculations revealed that the C?C bond is formed by an intramolecular photochemical process that involves an excited singlet state and traversal of a five-membered transition state, and thus consistent ipso–ipso coupling results. These results demonstrate that photosplicing is a unique aryl cross-coupling method in the excited state that can be applied to synthesize a broad range of biaryls.
- Haensch, Veit G.,Neuwirth, Toni,Steinmetzer, Johannes,Kloss, Florian,Beckert, Rainer,Gr?fe, Stefanie,Kupfer, Stephan,Hertweck, Christian
-
p. 16068 - 16073
(2019/11/28)
-
- Synthesis and Biological Activity of Novel Succinate Dehydrogenase Inhibitor Derivatives as Potent Fungicide Candidates
-
In searching for novel fungicidal leads, the novel bioactive succinate dehydrogenase inhibitor (SDHI) derivatives were designed and synthesized by the inversion of carbonyl and amide groups. Bioassay indicated that compound 5i stood out with a broad spectrum of in vitro activity against five fungi. Its EC50 value (0.73 μg/mL) was comparable to that of boscalid (EC50 of 0.51 μg/mL) and fluxapyroxad (EC50 of 0.19 μg/mL) against Sclerotinia sclerotiorum. For Rhizoctonia cerealis, 5i and 5p with EC50 values of 4.61 and 6.48 μg/mL, respectively, showed significantly higher activity than fluxapyroxad with the EC50 value of 16.99 μg/mL. In vivo fungicidal activity of 5i exhibited an excellent inhibitory rate (100%) against Puccinia sorghi at 50 μg/mL, while the positive control boscalid showed only a 70% inhibitory rate. Moreover, 5i showed promising fungicidal activity with a 60% inhibitory rate against Rhizoctonia solani at 1 μg/mL, which was better than that of boscalid (30%). Compound 5i possessed better in vivo efficacy against P. sorghi and R. solani than boscalid. Molecular docking showed that even the carbonyl oxygen atom of 5i was far from the pyrazole ring. It could also form hydrogen bonds toward the hydroxyl hydrogen and amino hydrogen of TYR58 and TRP173 on SDH, respectively, which consisted of the positive control fluxapyroxad. Fluorescence quenching analysis and SDH enzymatic inhibition studies also validated its mode of action. Our studies showed that 5i was worthy of further investigation as a promising fungicide candidate.
- Yang, Dongyan,Zhao, Bin,Fan, Zhijin,Yu, Bin,Zhang, Nailou,Li, Zhengming,Zhu, Yilin,Zhou, Jinghui,Kalinina, Tatiana A.,Glukhareva, Tatiana V.
-
p. 13185 - 13194
(2019/12/02)
-
- Metal-Free Synthesis of Pharmaceutically Important Biaryls by Photosplicing
-
Many pharmaceuticals feature biaryl motifs that are crucial for their binding to the target. Yet, benchmark methods for selective cross-couplings rely on highly toxic heavy metal catalysts, which are unfavorable in the synthesis of pharmaceuticals. Metal-free coupling reactions, on the other hand, may require harsh conditions and lack selectivity. We report a novel, metal-free cross-coupling reaction that involves the tethering of two phenyl groups by a temporary, traceless sulfonamide linker that directs a photochemical aryl fusion into a single coupling product. The perfect regio- and chemoselectivity of the reaction could be rationalized by a cyclic intermediate, which fragments into the biaryl and volatile side products. Using a flow reactor, we synthesized numerous substituted biaryl building blocks for important therapeutics in high yields, such as antibiotics, antitumor, neuroprotective and cholesterol-lowering agents as well as antiarthritic non-steroidal antiinflammatory drugs (NSAIDs). The new method was successfully employed in a total synthesis of cannabinol, an important analgesic and antiemetic therapeutic. We also report a metal-free synthesis of key building blocks used for the preparation of sartans, antihypertensive agents that rank among the top blockbuster drugs worldwide. This safe and convenient protocol is a valuable alternative for the widely used metal-dependent aryl cross-coupling methods.
- Kloss, Florian,Neuwirth, Toni,Haensch, Veit G.,Hertweck, Christian
-
p. 14476 - 14481
(2018/09/06)
-
- Integrating Organic Lewis Acid and Redox Catalysis: The Phenalenyl Cation in Dual Role
-
In recent years, merging different types of catalysis in a single pot has drawn considerable attention and these catalytic processes have mainly relied upon metals. However, development of a completely metal free approach integrating organic redox and organic Lewis acidic property into a single system has been missing in the current literature. This study establishes that a redox active phenalenyl cation can activate one of the substrates by single electron transfer process while the same can activate the other substrate by a donor-acceptor type interaction using its Lewis acidity. This approach has successfully achieved light and metal-free catalytic C-H functionalization of unactivated arenes at ambient temperature (39 entries, including core moiety of a top-selling molecule boscalid), an economically attractive alternative to the rare metal-based multicatalysts process. A tandem approach involving trapping of reaction intermediates, spectroscopy along with density functional theory calculations unravels the dual role of phenalenyl cation.
- Ahmed, Jasimuddin,Chakraborty, Soumi,Jose, Anex,Sreejyothi,Mandal, Swadhin K.
-
supporting information
p. 8330 - 8339
(2018/06/19)
-
- Iodobenzene-Catalyzed Synthesis of Phenanthridinones via Oxidative C-H Amidation
-
We report a novel synthesis of phenanthridinones from N-methoxybenzamides using an oxidative C-H amidation reaction at room temperature in open air with modest to excellent yields. This method demonstrated unprecedented substrate scope. In particular, it solved the long-standing challenge in the synthesis of phenanthridinones with sterically demanding substitutions.
- Liang, Dongdong,Yu, Wenbo,Nguyen, Nam,Deschamps, Jeffrey R.,Imler, Gregory H.,Li, Yue,MacKerell, Alexander D.,Jiang, Chao,Xue, Fengtian
-
p. 3589 - 3596
(2017/04/11)
-
- Synthetic method of 4'-bromomethylbiphenyl-2-carboxylate
-
The invention discloses a synthetic method of 4'-bromomethylbiphenyl-2-carboxylate. The synthetic method comprises the following steps: 1, hydrolyzing 4'-methyl-2-cyanobiphenyl to obtain 4'-methyl-2-biphenyl formic acid; 2, esterifying 4'-methyl-2-biphenyl formic acid to obtain 4'-methyl-2-biphenyl formate; and 3, reacting 4'-methyl-2-biphenyl formate under the illumination of 15000-20000lx at 20-30DEG C for 4-6h to obtain 4'-bromomethylbiphenyl-2-carboxylate. The synthetic method of 4'-bromomethylbiphenyl-2-carboxylate allows 4'-bromomethylbiphenyl-2-carboxylate to be obtained after hydrolysis, esterification and bromination of 4'-methyl-2-cyanobiphenyl used as an initial material. The route of the method is short, so the problem of raw material waste caused by bromine removal and bromo group introduction is avoided; and a bromination reaction is an illumination reaction, so 4'-bromomethylbiphenyl-2-carboxylate can be directly used in telmisartan synthesis without purifying, thereby the cost is reduced.
- -
-
Paragraph 0056; 0057
(2017/02/02)
-
- New telmisartan-derived PPARγ agonists: Impact of the 3D-binding mode on the pharmacological profile
-
In previous studies, the 4′-((2-propyl-1H-benzo[d]imidazol-1-yl)methyl)-[1,1′-biphenyl]-2-carboxylic acid was identified as pharmacophoric core for PPARγ activation. In this structure-activity relationship study the C2-alkyl chain was elongated and the 2-COOH group was changed to a carbamide/carbonitrile or shifted to the 3- or 4-position. Furthermore, the benzo[d]imidazole was exchanged by 2,3-dihydrobenzo[d]thiazole or 1H-indole. C2-propyl derivatives showed the profile of partial agonists, while elongation of the C2-chain to that of an n-heptyl group or a 4-COOH shift changed the pharmacological profile to that of a potent full agonist. This finding can be explained by binding to the LBD in different ligand conformations. Two anchoring points (Tyr473 and Arg288) exist in the LBD, which have to be contacted to achieve receptor activation. In a crystal violet chemosensitivity assay using COS-7?cells and LNCaP cells expressing PPARγ only the carbamide derivatives influenced the cell growth, independently on the presence of the PPARγ. Therefore, receptor mediated cytotoxicity can be excluded.
- Obermoser, Victoria,Urban, Margarethe E.,Murgueitio, Manuela S.,Wolber, Gerhard,Kintscher, Ulrich,Gust, Ronald
-
supporting information
p. 138 - 152
(2016/08/30)
-
- An Indefinitely Air-Stable σ-NiII Precatalyst for Quantitative Cross-Coupling of Unreactive Aryl Halides and Mesylates with Aryl Neopentylglycolboronates
-
Three classes of Ni precatalysts based on π-NiII, π-Ni0 and σ-NiII complexes have been elaborated and employed in different laboratories for the functionalization and cross-coupling of otherwise inert aryl C-O, C-Cl, and C-F electrophiles. Various Ni precatalysts, ligands, boron sources, and reaction conditions that were developed in various research groups, necessitated the selection of the most suitable conditions for desired cross-coupling partners. Here a universal, bench-stable, easily prepared NiIICl(1-naphthyl)(PCy3)2/PCy3 σ-complex, for efficient and quantitative cross-coupling of aryl chlorides, bromides, iodides, mesylates, and fluorides with aryl neopentylglycolboronates is reported. This precatalyst will most probably help to advance the applications of Ni catalysis in organic, supramolecular, and macromolecular synthesis and will provide an easier access to the selection of reaction conditions for various transformations.
- Malineni, Jagadeesh,Jezorek, Ryan L.,Zhang, Na,Percec, Virgil
-
supporting information
p. 2795 - 2807
(2016/08/31)
-
- Pincer-Nickel-Catalyzed Cross-Coupling of Aryl Sulfamates with Arylzinc Chlorides
-
The nickel N,N,N-pincer complex 2 was demonstrated to effectively catalyze the cross-coupling of aryl sulfamates with arylzinc chlorides under mild conditions. The reaction is suitable for a wide range of substrates, and tolerates various functional groups. A nickel N,N,N-pincer complex effectively catalyzes the cross-coupling of aryl sulfamates with arylzinc chlorides under mild conditions. The reaction is suitable for a wide range of substrates, and tolerates various functional groups.
- Tao, Jian-Long,Wang, Zhong-Xia
-
p. 6534 - 6540
(2015/10/19)
-
- Electronic effects on the substitution reactions of benzhydrols and fluorenyl alcohols. Determination of mechanism and effects of antiaromaticity
-
A range of substituted benzhydrols and fluorenols were prepared and subjected to acid catalysed methanolysis. Analysis of the rates of each of these processes showed correlation with Hammett σ+ parameters as is consistent with the significant build-up of positive charge adjacent to the ring. In combination with the similarity of the electronic susceptibility of the processes, these data suggest that both reactions proceed through a unimolecular rate-determining step. This shows that the effect of fusion of the phenyl systems (and hence potentially introducing an antiaromatic carbocation intermediate) is only to slow the rate of reaction rather than change the mechanism of the process.
- George, Stephen R. D.,Elton, Timothy E.,Harper, Jason B.
-
supporting information
p. 10745 - 10750
(2015/11/17)
-
- Very efficient and broad-in-scope palladium-catalyzed Hiyama cross-coupling. the role of water and copper(I) salts
-
A very high-yielding Pd-catalyzed cross-coupling between aryl halides and aryl(trialkoxy)silanes is achieved in the presence of Cu(i) and a measured amount of water. This novel methodology is useful for the generation of a wide range of biaryls, particularly non-para substituted derivatives, which are usually less reported.
- Traficante, Carla I.,Mata, Ernesto G.,Delpiccolo, Carina M. L.
-
p. 26796 - 26800
(2015/03/30)
-
- Silver-Catalyzed C(sp2)-H Functionalization/C-O Cyclization Reaction at Room Temperature
-
Silver-catalyzed C(sp2)-H functionalization/C-O cyclization has been developed. The scalable reaction proceeds at room temperature in an open flask. The present method exhibits good functional-group compatibility because of the mild reaction conditions. Using a AgNO3 catalyst and a (NH4)2S2O8 oxidant in CH2Cl2/H2O solvent, various lactones are obtained in good to excellent yields. A kinetic isotope effect (KIE) study indicates that the reaction may occur via a radical process.
- Dai, Jian-Jun,Xu, Wen-Tao,Wu, Ya-Dong,Zhang, Wen-Man,Gong, Ying,He, Xia-Ping,Zhang, Xin-Qing,Xu, Hua-Jian
-
p. 911 - 919
(2015/01/30)
-
- Photocatalytic Dehydrogenative Lactonization of 2-Arylbenzoic Acids
-
A metal-free dehydrogenative lactonization of 2-arylbenzoic acids at room temperature was developed. This work illustrates the first application of visible-light photoredox catalysis in the preparation of benzo-3,4-coumarins, an important structural motif in bioactive molecules. The combination of photocatalyst [Acr+-Mes] with (NH4)2S2O8 as a terminal oxidant provides an economical and environmentally benign entry to different substituted benzocoumarins. Preliminary mechanistic studies suggest that this reaction most likely occurs through a homolytic aromatic substitution pathway.
- Ramirez, Nieves P.,Bosque, Irene,Gonzalez-Gomez, Jose C.
-
supporting information
p. 4550 - 4553
(2015/09/28)
-
- Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies
-
New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards β-tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of β-tubulin.
- Shashikumar, Nellisara D,Krishnamurthy, Ganganaika,BhojyaNaik, Halehatti S,Lokesh, Mayasandra R,Jithendrakumara, Kaginalli S
-
p. 205 - 212
(2016/03/01)
-
- Nickel-catalyzed cross-coupling of aryl fluorides and organozinc reagents
-
Ni(PCy3)2Cl2 was demonstrated to effectively catalyze cross-coupling of aryl fluorides and organozinc reagents. Both electron-poor and -rich aryl fluorides can react effectively with nucleophiles including aryl-, methyl-, and benzylzinc chlorides. A wide range of substituents and functional groups are tolerated. In the presence of a directing group, PhC(O), the reaction is selective for cleavage of the C-F bond ortho to the carbonyl substituent in a difluoroarene.
- Zhu, Feng,Wang, Zhong-Xia
-
p. 4285 - 4292
(2014/06/09)
-
- Synthesis and evaluation of quinazoline derivatives as phosphodiesterase 7 inhibitors
-
The latest scientific findings concerning PDE7 and PDE4 inhibition suggest that selective small-molecule inhibitors of both enzymes could provide a novel approach to treat a variety of immunological diseases. In this context, we describe a new series of quinazoline derivatives from quinazolin-4-thiones which include a substituted biphenyl fragment. Some of these compounds show inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7.
- Sánchez, Ana I.,Martínez-Barrasa, Valentín,Burgos, Carolina,Vaquero, Juan J.,Alvarez-Builla, Julio,Terricabras, Emma,Segarra, Víctor
-
p. 2370 - 2378
(2013/05/09)
-
- General and practical carboxyl-group-directed remote C-H oxygenation reactions of arenes
-
Two methods for remote aromatic C-H oxygenation reactions, have been developed. Method1, the Cu-catalyzed oxygenation reaction, is highly efficient for cyclization of electron-neutral and electron-rich biaryl carboxylic acids into 3,4-benzocoumarins. Method2, the K2S2O 8-mediated oxygenation reaction, is more general and practical for cyclization of substrates with electron-donating and -withdrawing groups (see scheme). Copyright
- Wang, Yang,Gulevich, Anton V.,Gevorgyan, Vladimir
-
supporting information
p. 15836 - 15840
(2014/04/03)
-
- Nickel-catalyzed Suzuki-Miyaura reaction of aryl fluorides
-
Two protocols for the nickel-catalyzed cross-coupling of aryl fluorides with aryl boronic esters have been developed. The first employs metal fluoride cocatalysts, such as ZrF4 and TiF4, which enable Suzuki-Miyaura reactions of aryl fluorides bearing electron-withdrawing (ketones, esters, and CF3), aryl and alkenyl groups as well as those comprising fused aromatic rings, such as fluoronaphthalenes and fluoroquinolines. The second protocol employs aryl fluorides bearing ortho-directing groups, which facilitate the difficult C-F bond activation process via cyclometalation. N-heterocycles, such as pyridines, quinolines, pyrazoles, and oxazolines, can successfully promote cross-coupling with an array of organoboronic esters. A study into the substituent effects with respect to both coupling components has provided fundamental insights into the mechanism of the nickel-catalyzed cross-coupling of aryl fluorides.
- Tobisu, Mamoru,Xu, Tian,Shimasaki, Toshiaki,Chatani, Naoto
-
supporting information; experimental part
p. 19505 - 19511
(2012/01/31)
-
- 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl} -pyrrolidine-2-carboxamide: Investigation of structural variations
-
We recently reported a series of 1-acyl-N-(biphenyl-4-ylmethyl)pyrrolidine- 2-carboxamides as AT1 receptor ligands. The most potent compound of the series, 1-pentanoyl-N-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}- pyrrolidine-2-carboxamide, showed an interesting affinity for the receptor. To investigate the influence of structure variations on affinity, the synthesis of additional compounds belonging to this series has been performed. Biological tests run on the newly synthesized compounds on CHO-hAT1 cells stably expressing the human AT1 receptor confirm our previous hypothesis, i.e. that, within this series, the length of the acyl chain, the substitution of the amidic group and the nature of the acidic one are crucial for the receptor interaction, being a valeric chain, a secondary amidic function and the tetrazole moiety, respectively, the optimal ones. New 1-acyl-N-(biphenyl-4- ylmethyl)pyrrolidine-2-carboxamides have been designed by enlarging our previously reported series in order to clarify the requirements for AT 1 receptor interaction. Copyright
- Catalano, Alessia,Carocci, Alessia,Di Mola, Antonia,Bruno, Claudio,Vanderheyden, Patrick M. L.,Franchini, Carlo
-
p. 617 - 626
(2012/06/29)
-
- A Simple, efficient, green, cost effective and chemoselective process for the esterification of carboxylic acids
-
Carboxylic acids have been esterified under mild and solvent-free conditions in high yield and purity using the green reagents, dimethyl carbonate and diethyl carbonate, under acid catalysis. The present methodology is free of the disadvantages of base catalysis described earlier, such as high temperatures, use of autoclaves, use of the expensive DBU as base in stoichiometric amounts and the carbonate as solvent. High chemoselectivity is observed in the case of hydroxybenzoic acids.
- Rekha,Ramani, Modukuri V.,Ratnamala,Rupakalpana, Vempati,Subbaraju, Gottumukkala V.,Satyanarayana, Chava,Rao, C. Someswara
-
experimental part
p. 769 - 773
(2010/04/22)
-
- Versatile Suzuki-Miyaura coupling reaction using diphenylvinylphosphine ligands
-
The scope of the utility of diphenylvinylphosphine ligands has been extended to include the Suzuki-Miyaura coupling reaction. A catalyst composed of phosphines and palladium efficiently mediates the reactions of a variety of aryl halides with aryl-boronic acids to afford the corresponding biphenyls in good to excellent yields. Georg Thieme Verlag Stuttgart.
- Suzuki, Ken,Fontaine, Arnaud,Hori, Yoji,Kobayashi, Tohru
-
p. 3206 - 3208
(2008/09/20)
-
- An aryl to imidoyl palladium migration process involving intramolecular C-H activation
-
Biologically interesting fluoren-9-one and xanthen-9-one derivatives have been prepared by a novel aryl to imidoyl palladium migration, followed by intramolecular arylation. The fluoren-9-one synthesis appears to involve both a palladium migration mechanism and a C-H activation process proceeding through an unprecedented organopalladium(IV) hydride intermediate. The results from deuterium labeling experiments are consistent with the proposed dual mechanism.
- Zhao, Jian,Yue, Dawei,Campo, Marino A.,Larock, Richard C.
-
p. 5288 - 5295
(2008/02/02)
-
- Microwave-assisted Suzuki coupling reactions with an encapsulated palladium catalyst for batch and continuous-flow transformations
-
This article describes the design, optimisation and development of a Suzuki cross-coupling protocol mediated by an efficient palladium-en-capsulated catalyst (Pd EnCat) under microwave irradiation. The methodology has been used in both batch mode for classical library preparation and in continuous-flow applications furnishing multigram quantities of material. Described is a method that uses direct focused microwave heating whilst applying an external cooling source. This enables a lower than normal bulk temperature to be maintained throughout the reaction period leading to significant improvements in the overall yield and purity of the reaction products. Additional aspects of this novel heating protocol are discussed in relation to the prolonged lifetime and enhanced reactivity of the immobilised catalyst system.
- Baxendale, Ian R.,Griffiths-Jones, Charlotte M.,Ley, Steven V.,Tranmer, Geoffrey K.
-
p. 4407 - 4416
(2008/02/07)
-
- Synthesis and biological evaluation of benzimidazole derivatives as potent AMP-activated protein kinase activators
-
Design, synthesis and structure-activity relationships of benzimidazole derivatives as activators of the AMP-activated protein kinase (AMPK) are presented in this paper. AMPK is the central component of a protein kinase cascade that plays a key role in the regulation of energy balance. Once activated, AMPK initiates a series of responses that are aimed at restoring the energy balance of the cell and recent studies have indicated that AMPK plays an important role in regulation of the whole-body energy metabolism. The following study based on the lead compound S27847 involved modification of three regions of this compound. Preliminary structure-activity relationships are being described.
- Charton, Julie,Girault-Mizzi, Sophie,Debreu-Fontaine, Marie-Ange,Foufelle, Fabienne,Hainault, Isabelle,Bizot-Espiard, Jean-Guy,Caignard, Daniel-Henri,Sergheraert, Christian
-
p. 4490 - 4518
(2007/10/03)
-
- A new precatalyst for the Suzuki reaction - A pyridyl-bridged dinuclear palladium complex as a source of mono-ligated palladiuin(0)
-
A dinuclear pyridyl-bridged palladium complex, trans-(P,N)-[PdBr(μ- C5H4N-C2,N)(PPh3)]2 1, was obtained from material isolated from the Suzuki cross-coupling reaction of 2-bromopyridine with 2,4-difluorophenylboronic acid in the presence of catalytic (PPh3)4Pd. Complex 1 is an effective precatalyst for the Suzuki cross-coupling reactions of a variety organoboronic acids and aryl bromides, and represents a useful source of mono-ligated palladium(0), "(Ph3P)Pd(0)".
- Beeby, Andrew,Bettington, Sylvia,Fairlamb, Ian J. S.,Goeta, Andres E.,Kapdi, Anant R.,Niemelae, Elina H.,Thompson, Amber L.
-
p. 600 - 605
(2007/10/03)
-
- 2-(biarylalkyl)amino-3-(alkanoylamino)pyridine derivatives
-
Compounds disclosed herein are bradykinin B1 antagonist compounds useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
- -
-
Page/Page column 14
(2010/02/05)
-
- 2-(Biarylalkyl)amino-3-(cyanoalkanoylamino)pyridine derivatives
-
Compounds disclosed herein are bradykinin B1 antagonist compounds useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.
- -
-
Page/Page column 14
(2010/02/05)
-
- Palladium-catalyzed biaryl-coupling reaction of arylboronic acids in water using hydrophilic phosphine ligands
-
Hydrophilic phosphine ligands possessing a carbohydrate side-chain, such as N-(4-diphenylphosphinophenyl)methyl gluconamide (9), N-[4-(2′-dicyclohexylphosphinobiphenyl)phenylmethyl] gluconamide (10), and N-[4-(2′-di-t-butylphosphinobiphenyl)]phenylmethyl gluconamide (11), were newly synthesized to carry out palladium-catalyzed biaryl coupling of arylboronic acids in a single aqueous medium. The catalyst prepared in situ from Pd(OAc)2 and 10 exhibited a higher efficiency than that of 9, 11, Ph2P(m-C6H4SO3Na) (TPPMS) or P(m-C6H4SO3Na)3 (TPPTS) for representative aryl bromides, chlorides, or triflates. The catalyst prepared in situ from Pd(OAc)2 (0.001mol%) and 10 (0.002mol%) achieved 96,000 TON in the reaction of p-tolylboronic acid with 4-bromoacetophenone in water.
- Nishimura, Masato,Ueda, Masato,Miyaura, Norio
-
p. 5779 - 5787
(2007/10/03)
-
- Process for the preparation of 2-(4-methylphenyl)-benzoic acid derivatives
-
A process for the preparation of 2-(4-methylphenyl)benzoic acid C1-6alkyl esters by reaction of a sulfonic derivative of formula wherein R is C1-6alkyl and R1is optionally perfluorinated C1-6alkyl or optionally substituted C1-6aryl, with a 4-methylphenylzinc halide.
- -
-
-
- Correlation of anti-HIV activity with anion spacing in a series of cosalane analogues with extended polycarboxylate pharmacophores
-
Cosalane and its synthetic derivatives inhibit the binding of gp120 to CD4 as well as the fusion of the viral envelope with the cell membrane. The binding of the cosalanes to CD4 is proposed to involve ionic interactions of the negatively charged carboxylates of the ligands with positively charged arginine and lysine amino acid side chains of the protein. To investigate the effect of anion spacing on anti-HIV activity in the cosalane system, a series of cosalane tetracarboxylates was synthesized in which the two proximal and two distal carboxylates are separated by 6-12 atoms. Maximum activity was observed when the proximal and distal carboxylates are separated by 8 atoms. In a series of cosalane amino acid derivatives containing glutamic acid, glycine, aspartic acid, β-alanine, leucine, and phenylalanine residues, maximum activity was displayed by the di(glutamic acid) analogue. A hypothetical model has been devised for the binding of the cosalane di(glutamic acid) conjugate to CD4. In general, the compounds in this series are more potent against HIV-1RF in CEM-SS cells than they are vs HIV-1IIIB in MT-4 cells, and they are least potent vs HIV-2ROD in MT-4 cells.
- Santhosh,Paul,De Clercq,Pannecouque,Witvrouw,Loftus,Turpin,Buckheit, Jr.,Cushman
-
p. 703 - 714
(2007/10/03)
-
- A process for the preparation of 2-(4-methylphenyl) benzoic acid derivatives
-
A process for the preparation of 2-(4-methylphenyl)benzoic acid C1-6alkyl esters by reaction of a sulfonic derivative of formula ???wherein R is C1-6alkyl and R1 is optionally perfluorinated C1-6alkyl or optionally substituted C1-6aryl, with a 4-methylphenylzinc halide.
- -
-
-
- Exploiting poly(ethylene glycol) as a matrix for liquid-phase organic synthesis
-
Soluble polymer-supported chemistry is a technology that allows the blending of the benefits of polymer-supported synthesis and solution-phase chemistry. Herein, we describe our recent efforts in this area targeted at exploring the scope of poly(ethylene glycol) (PEG) as the matrix. Specifically we describe the use of PEG as a support for triphenyl phosphine and for the Stille reaction.
- Sieber, Frank,Wentworth Jr., Paul,Janda, Kim D.
-
p. 1018 - 1032
(2007/10/03)
-
- Identification of optimal anion spacing for anti-HIV activity in a series of cosalane tetracarboxylates
-
The binding of the anti-HIV agent cosalane to CD4 is thought to involve ionic interactions of negatively charged carboxylates of the ligand with positively charged residues on the surface of the protein. An investigation of the optimal anion distances for anti-HIV activity in a series of cosalane tetracarboxylate analogues has been completed, and maximal activity results when the two proximal and the two distal carboxylates are separated by eight atoms. (C) 2000 Elsevier Science Ltd.
- Paul, Gitendra C.,De Clercq, Erik,Pannecouque, Christophe,Witvrouw, Myriam,Loftus, Tracy L.,Turpin, Jim A.,Buckheit Jr., Robert W.,Cushman, Mark
-
p. 2149 - 2152
(2007/10/03)
-
- Synthesis of biaryls via nickel-catalyzed cross-coupling reaction of arylboronic acids and aryl mesylates
-
The cross-coupling reaction of arylboronic acids (1.3 equivs) with aryl methanesulfonates was carried out in the presence of a nickel(0) catalyst (3 mol%) and K3PO4·nH2O (3 equivs). The use of toluene as the solvent and the nickel(0)-dppf catalyst prepared from NiCl2(dppf) plus dppf with BuLi were recognized to be the most efficient to achieve both high yields and high selectivity. The reaction can be applied to various electron-deficient and - rich aryl methanesulfonates to give high yields.
- Ueda, Masato,Saitoh, Atsushi,Oh-tani, Saori,Miyaura, Norio
-
p. 13079 - 13086
(2007/10/03)
-
- Nonpeptide angiotensin II receptor antagonists: Synthesis and biological activity of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives
-
A series of 1H-Imidazo and 1H-[1,2,3]-Triazolo fused derivatives have been obtained and tested as non peptide AII receptor antagonists. Modification of the classical biphenyl moiety to a 4-arylthienyl fragment afforded interesting activities.
- Delgado,Pastor,Garcia-Navio,Vaquero,Alvarez-Builla,Sunkel,De Casa-Juana,Priego,Santos,Statkow,Straumann
-
p. 147 - 155
(2007/10/03)
-
- Nonpeptide arginine vasopressin antagonists for both V(1A) and V2 receptors: Synthesis and pharmacological properties of 2-Phenyl-4'- [(2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanilide derivatives
-
A series of compounds structurally related to 4'-[(2,3,4,5-tetrahydro- 1H-1-benzazepin-1-yl)carbonyl]benzanilide was synthesized and demonstrated to have arginine vasopressin (AVP) antagonist activity for both V(1A) and V2 receptors. The introduction of a phenyl or a 4-substituted phenyl group into the ortho position of the benzoyl moiety resulted in an increase in both binding affinity and antagonistic activity. The 2-(4-methylphenyl) derivative (1g) exhibited high antagonistic activities for both V(1A) (8.6- fold) and V2 (38-fold) receptors and high oral activity (8.6-fold) compared with the 2-methyl lead compound (1a). Detail of the synthesis and the pharmacological properties of this series are presented.
- Matsuhisa, Akira,Tanaka, Akihiro,Kikuchi, Kazumi,Shimada, Yoshiaki,Yatsu, Takeyuki,Yanagisawa, Isao
-
p. 1870 - 1874
(2007/10/03)
-
- Practical synthesis of 4'-methylbiphenyl-2-carboxylic acid
-
Treatment of 2,6-di-tert-butyl-4-methylphenyl 2-methoxybenzoate (5) with 4-methylphenylmagnesium bromide (6) in diethyl ether-benzene affords the 4'-methylbiphenyl-2-carboxylate (7) in excellent yield via an ester-assisted nucleophilic aromatic substitution (S(N)Ar) reaction. Carboxylate 7 is in turn readily and quantitatively saponified to 4'-methylbiphenyl-2-carboxylic acid (2a) via transesterification by treatment with sodium methoxide in toluene-1-methyl-2-pyrrolidone followed by aqueous hydrolysis.
- Hattori,Hayashizaka,Miyano
-
-