- Metal-free C-C bond formation: Via coupling of nitrile aimines and boronic acids
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The challenges of developing sustainable methods of carbon-carbon bond formation remains a topic of considerable importance in synthetic chemistry. Capitalizing on the highly reactive nature of the nitrile imine 1,3-dipole, we have developed a novel metal-free coupling of this species with aryl boronic acids. Photochemical generation of a nitrile imine intermediate and trapping with a palette of boronic acids enabled rapid and facile access to a broad library of more than 25 hydrazone derivatives in up to 92% yield, forming a carbon-carbon bond in a metal free fashion. This represents the first reported example of direct reaction between boronic acids and a 1,3-dipole.
- Livingstone, Keith,Bertrand, Sophie,Mowat, Jenna,Jamieson, Craig
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Read Online
- Selective Oxidation of Alkylarenes to the Aromatic Ketones or Benzaldehydes with Water
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Here a palladium-catalyzed oxidation method for converting alkylarenes into the aromatic ketones or benzaldehydes with water as the only oxygen donor is reported. This C-H bond oxidation functionalization does not require other oxidants and hydrogen accep
- Du, Jihong,Duan, Baogen,Liu, Kun,Liu, Renhua,Yu, Feifei,Yuan, Yongkun,Zhang, Chenyang,Zhang, Jin
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supporting information
(2022/02/09)
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- Phenoxy aromatic acid compound with cyclopropyl and pharmaceutically acceptable salt thereof, and preparation method and application thereof
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The invention provides a phenoxy aromatic acid compound with cyclopropyl, a preparation method of the phenoxy aromatic acid compound, pharmaceutically acceptable salt of the phenoxy aromatic acid compound and a preparation method of the pharmaceutically acceptable salt of the phenoxy aromatic acid compound, and further provides dosage forms of the phenoxy aromatic acid compound and the pharmaceutically acceptable salt of the phenoxy aromatic acid compound and application of the phenoxy aromatic acid compound and the pharmaceutically acceptable salt of the phenoxy aromatic acid compound in drugs for treating hyperlipidemia diseases. The compound provided by the invention has a relatively good blood fat reducing drug effect, so that the compound has a very good application prospect.
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Paragraph 0040-0043
(2021/07/17)
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- Phenoxy aromatic acid with cyclopropyl and pharmaceutically acceptable salt thereof as well as preparation method and application thereof
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The invention provides phenoxy aromatic acid with cyclopropyl, a preparation method of the phenoxy aromatic acid, pharmaceutically acceptable salt of the phenoxy aromatic acid with cyclopropyl and a preparation method of the pharmaceutically acceptable salt, and further provides dosage forms of the phenoxy aromatic acid with cyclopropyl and the pharmaceutically acceptable salt of the phenoxy aromatic acid with cyclopropyl. The invention also discloses application of the compound in medicines for treating hyperlipidemia diseases. The compound provided by the invention has a relatively good blood fat reducing drug effect, so that the compound has a very good application prospect.
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Paragraph 0055-0057
(2021/07/17)
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- A sodium trifluoromethanesulfinate-mediated photocatalytic strategy for aerobic oxidation of alcohols
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A sodium trifluoromethanesulfinate-mediated photocatalytic strategy for the aerobic oxidation of alcohols has been developed for the first time, and the photoredox aerobic oxidation of secondary and primary alcohols provided the corresponding ketones and carboxylic acids, respectively, in high to excellent yields.
- Zhu, Xianjin,Liu, Can,Liu, Yong,Yang, Haijun,Fu, Hua
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supporting information
p. 12443 - 12446
(2020/10/30)
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- Synthesis method of high-purity 4-chloro-4'-hydroxybenzophenone
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The invention relates to a synthesis method of high-purity 4-chloro-4'-hydroxybenzophenone. The method comprises the following steps: cooling chlorobenzene and anisole to 5 DEG C or below; adding anhydrous aluminum trichloride in three batches, controlling the temperature, dropwise adding a mixed solution of p-chlorobenzoyl chloride and chlorobenzene, and controlling the reaction temperature; maintaining the low temperature after addition is finished, raising the temperature to normal temperature, and maintaining the normal temperature for a reaction; adding anhydrous aluminum trichloride at atime, and then carrying out a two-stage heating reaction; performing cooling hydrolysis; and performing centrifuging, washing the crude product with a sodium carbonate solution and a sodium hydroxidesolution, adjusting the pH value with hydrochloric acid, and centrifugally separating out the refined product. The fine temperature control is combined with the control of the reaction time to reducebyproducts, so the purity reaches 99.9% or above.
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Paragraph 0016-0030
(2020/01/25)
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- Synthesis and evaluation of fenofibric acid ester derivatives: Studies of different formulation with their bioavailability and absorption conditions
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A series of fenofibric acid ester pro-drugs (JF-1-7) were synthesized. The pharmacokinetic properties of these pro-drugs were examined after oral administration to rats at a dose of 20 mg kg-1 to evaluate the relative bioavailability in rats. The bioavailability of the ester compounds, JF-1, 2, 3, 4, 5, 6, and 7, was significantly higher than that of fenofibrate. In particular, JF-2 proved to be most promising. The oral administration (20 mg kg-1) of JF-2 showed a relative bioavailability of approximately 272.8percent compared to fenofibrate.
- Lv, Zhixiang,Wang, Zhou,Xiao, Fuyan,Jin, Guofan
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p. 280 - 287
(2020/01/03)
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- Visible Light-Mediated [2 + 2] Cycloaddition Reactions of 1,4-Quinones and Terminal Alkynes
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A single-step synthesis of 4-hydroxy-functionalized bi-aryl and aryl/alkyl ketones via oxidative coupling of terminal alkynes with benzoquinones is reported. Furthermore, with naphthoquinones, owing to the cross-resonance of carbonyl with the aromatic ring, alkene-alkyne cycloaddition is more favored to give four-membered carbocyclic adducts, thereby precluding the requirement of preactivated alkynes.
- Sultan, Shaista,Bhat, Muneer-Ul-Shafi,Rizvi, Masood Ahmad,Shah, Bhahwal Ali
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p. 8948 - 8958
(2019/08/12)
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- Preparation method of 4-chloro-4'-hydroxybenzophenone
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The invention relates to a preparation method of 4-chloro-4'-hydroxybenzophenone. The preparation method comprises the following steps: adding a proper amount of dichloroethane, phenol, 4-chlorobenzonitrile, anhydrous zinc chloride and gel type strong-acid ion exchange resin into a reaction kettle and stirring; controlling temperature to 50 DEG C to 120 DEG C and continuously introducing dry hydrogen chloride gas until the 4-chlorobenzonitrile reacts completely; cooling to room temperature and adding a proper amount of a hydrochloric acid solution; raising the temperature, reflowing and reacting for 5h to 7h; then cooling to room temperature and layering; recycling the dichloroethane into an organic layer and adding alkali into residues and dissolving; de-coloring by utilizing active carbon, carrying out acid precipitation, extracting and filtering and drying to obtain the 4-chloro-4'-hydroxybenzophenone. The preparation method of the 4-chloro-4'-hydroxybenzophenone, provided by the invention, is simple in route and high in yield.
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Paragraph 0014; 0015; 0016
(2018/03/24)
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- Synthesis method of 4-chloro-4'-hydroxybenzophenone
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The invention relates to a synthesis method of 4-chloro-4'-hydroxybenzophenone, wherein the preparation method comprises the steps: adding a proper amount of dichloroethane, phenol, p-chlorobenzonitrile, anhydrous zinc chloride and macroporous strong-acid ion exchange resin into a reaction kettle, stirring, controlling the temperature at 50 DEG C to 120 DEG C, continuously introducing dry hydrogenchloride gas until p-chlorobenzonitrile is completely subjected to reaction, cooling to room temperature, adding a proper amount of hydrochloric acid aqueous solution, heating up and carrying out a refluxing reaction for 5 h to 7 h, then cooling to room temperature, stratifying, recycling dichloroethane from an organic layer, adding an alkali to residues to dissolve, decolorizing with activated carbon, carrying out acid precipitation, carrying out suction filtration, and drying to obtain 4-chloro-4'-hydroxybenzophenone. The synthesis method of 4-chloro-4'-hydroxybenzophenone is simple in route and high in yield.
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Paragraph 0014-0016
(2018/03/25)
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- Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis
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An application of H-bonding interactions for directing the α-C-H oxidation of amines to amides and amino-ketones catalyzed by an organic photocatalyst is reported. The high efficiency of this method is demonstrated by the aerobic oxidation of pyrrolidines, diarylamines and benzylamines bearing urea groups with high yields and a wide substrate scope.
- Wang, Hongyu,Man, Yunquan,Wang, Kaiye,Wan, Xiuyan,Tong, Lili,Li, Na,Tang, Bo
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p. 10989 - 10992
(2018/10/08)
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- Visible Light Copper Photoredox-Catalyzed Aerobic Oxidative Coupling of Phenols and Terminal Alkynes: Regioselective Synthesis of Functionalized Ketones via C C Triple Bond Cleavage
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Direct oxidative coupling of phenols and terminal alkynes was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox process. This method allows regioselective synthesis of hydroxyl-functionalized aryl and alkyl ketones from simple phenols and phenylacetylene via C C triple bond cleavage. 47 examples were presented. From a synthetic perspective, this protocol offers an efficient synthetic route for the preparation of pharmaceutical drugs, such as pitofenone and fenofibrate.
- Sagadevan, Arunachalam,Charpe, Vaibhav Pramod,Ragupathi, Ayyakkannu,Hwang, Kuo Chu
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supporting information
p. 2896 - 2899
(2017/03/11)
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- Method for preparing fenofibrate key intermediate 4-chloro-4'-hydroxybenzophenone
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The invention relates to a method for catalytic synthesis of fenofibrate key intermediate 4-chloro-4'-hydroxybenzophenone by taking anisole and parachlorobenzoyl chloride as starting materials and taking novel magnetic nano-particle load lewis acid as a catalyst. The novel magnetic nano-particle load lewis acid is adopted as the catalyst. The method has the advantages that 1) the magnetic nano-particle load lewis acid catalyst is small in dosage and can be recycled; 2) the reaction time is greatly shortened, and reaction conversion rate and yield are improved; 3) the magnetic nano-particle load lewis acid catalyst is quickly separated and recycled easily, the process is simple, and the production cost is relatively low.
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Paragraph 0063; 0064; 0066; 0068; 0070
(2017/08/25)
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- Synthesis of a polar phosphinoferrocene amidosulfonate ligand and its application in pd-catalyzed cross-coupling reactions of aromatic boronic acids and acyl chlorides in an aqueous medium
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The reaction of [1′-(diphenylphosphino)ferrocenyl]methylamine (1), generated in situ from its hydrochloride and triethylamine, with 2-sulfobenzoic anhydride afforded an anionic phosphino-amide, which was isolated as a triethylammonium salt, Ph2PfcCH2NHCOC6H4SO3(HNEt3) (2; fc = ferrocene-1,1′-diyl). A similar reaction of 1 with phthalic anhydride only furnished the salt (Ph2PfcCH2NH3)[C6H4CO2H(CO2)]. When it was reacted with [PdCl2(MeCN)2] and [LNCPd(μ-Cl)]2 (LNC = 2-[(dimethylamino-κN)methyl]phenyl-κC1), compound 2 gave rise to the bis-phosphine complex [PdCl2(2-κP)2] and the bridge-cleavage product [LNCPdCl(2-κP)], respectively. An analogue of the latter complex containing 2′-amino-[1,1′-biphenyl]-2-yl-κ2N,C2 as the auxiliary chelating ligand, compound 8, was prepared in a similar manner from 2 and the respective Pd precursor. Finally, the reaction of 2 with [LNCPd(acac)] proceeded with the replacement of the acetylacetonate ligand (acac), affording a dipalladium complex featuring two phosphinosulfonate anions as the O,P-bridges, [LNCPd(μ(P,O)-Ph2PfcCH2NHCOC6H4SO3)]2, which was structurally characterized by single-crystal X-ray diffraction analysis. All of these Pd(II) complexes, especially compound 8, formed active catalysts for Pd-mediated cross-coupling of aromatic boronic acids with benzoyl chlorides to produce substituted benzophenones in toluene (benzene)-water biphasic mixtures. This particular coupling reaction was employed during the preparation of 4′-chloro-4-hydroxybenzophenone, which was in turn converted to fenofibrate, a generic drug widely used to reduce cholesterol levels in blood.
- ?koch, Karel,Císa?ová, Ivana,?těpni?ka, Petr
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p. 3378 - 3387
(2016/10/21)
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- Synthesis and biological evaluation of novel 4-hydroxytamoxifen analogs as estrogen-related receptor gamma inverse agonists
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Estrogen-related receptor gamma (ERRγ) has recently been recognized as an attractive target for treating inflammation, cancer, and metabolic disorders. Herein, we discovered and demonstrated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that could act as highly selective inverse agonists for ERRγ. The results were comparable to those for GSK5182 (4), a leading ERRγ inverse agonist ligand. Briefly, the half-maximal inhibitory concentration (IC50) range of the synthesized compounds for ERRγ was 0.1-10 μM. Impressively, compound 24e exhibited potency comparable to 4 but was more selective for ERRγ over three other subtypes: ERRα, ERRβ, and estrogen receptor α. Furthermore, compound 24e exhibited a superior in vitro ADMET profile compared to the other compounds. Thus, the newly synthesized class of ERRγ inverse agonists could be lead candidates for developing clinical therapies for ERRγ-related disorders.
- Kim, Jina,Chin, Jungwook,Im, Chun Young,Yoo, Eun Kyung,Woo, Seoyeon,Hwang, Hee Jong,Cho, Joong-Heui,Seo, Kyung-Ah,Song, Jaeyoung,Hwang, Hayoung,Kim, Kyung-Hee,Kim, Nam Doo,Yoon, Suk Kyoon,Jeon, Jae-Han,Yoon, Seung-Yun,Jeon, Yong Hyun,Choi, Hueng-Sik,Lee, In-Kyu,Kim, Seong Heon,Cho, Sung Jin
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p. 338 - 352
(2016/07/06)
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- Synthetic method of fenofibrate drug intermediate 4-chloro-4'-hydroxybenzophenone
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The invention relates to a synthetic method of fenofibrate drug intermediate 4-chloro-4'-hydroxybenzophenone. The synthetic method comprises the following steps of adding 500ml of methylamine solution, 0.34 to 3.36mol of anisole, 0.36 to 0.37 mol of cuprous chloride into a reactor provided with a stirrer, a thermometer, a reflux condenser, and a dropping funnel, controlling the stirring speed to be 160 to 190 rpm, controlling the solution temperature to be 35 to 40 DEG C, dropwise adding 0.35mol of p-chlorobenzamide (3), rising the solution temperature to be 45 to 50 DEG C after completion of addition, keeping the stirring speed and reacting for 7 to 8h, pouring reaction liquid into a sodium bisulfite solution, keeping the solution temperature to be 3 to 5 DEG C, separating out an organic layer, extracting a water layer with the methylamine solution for 6 to 8 times, combining with the organic layer, then steaming out methylamine to obtain an intermediate (4), adding 300ml of hexane, rising the solution temperature to be 80 to 85 DEG C for dehydration, lowering the solution temperature to be 60 DEG C, adding 0.6 mol of cuprous chloride, performing a reflux reaction for 2 to 3h, steaming out the hexane, lowering the solution temperature to be 5 to 9 DEG C, adding 200ml of potassium bicarbonate solution, controlling the stirring speed to be 200 to 260 rpm, filtering, washing with a salt solution, and performing dehydration with a dehydrant, so as to obtain the 4-Chloro-4'-hydroxybenzophenone.
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Paragraph 0015; 0016
(2016/11/17)
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- Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel
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We synthesized and evaluated a series of compounds for their allosteric modulation at the Kv11.1 (hERG) channel. Most compounds were negative allosteric modulators of [3H]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly increasing the dissociation rate of dofetilide in the radioligand kinetic binding assay, while remarkably reducing the affinities of dofetilide and astemizole in a competitive displacement assay. Additionally, both 7f and 7p displayed peculiar displacement characteristics with Hill coefficients significantly distinct from unity as shown by e.g., dofetilide, further indicative of their allosteric effects on dofetilide binding. Our findings in this investigation yielded several promising negative allosteric modulators for future functional and clinical research with respect to their antiarrhythmic propensities, either alone or in combination with known Kv11.1 blockers.
- Yu, Zhiyi,Van Veldhoven, Jacobus P.D.,'T Hart, Ingrid M.E.,Kopf, Adrian H.,Heitman, Laura H.,Ijzerman, Adriaan P.
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- Acid and base stable diphenylmethanol derivatives and methods of use
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The invention provides compounds that are useful as linkers for solid phase synthesis and as protecting groups, and methods for producing and using the same.
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Page/Page column 8-9
(2008/12/08)
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- Improved process for the production of poly (ether ketone) - PEK- and its monomer
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4-Chloro-4'-hydroxybenzophenone - preferably prepared by reaction of 4-chlorobenzoyl chloride and phenol using AlCl3 catalyst in orthodichlorobenzene solvent - is purified by distillation under vacuum, more conveniently in combination with a solvent such as diphenyl sulfone, to give a high purity monomer which can be polymerized, using, e.g.,K2CO3 at 330°C, to yield poly(ether ketone) - PEK - with excellent properties.
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Page/Page column 4
(2010/11/30)
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- Discovery of 1,4-didydroxy-2-naphthoate prenyltransferase inhibitors: New drug leads for multidrug-resistant gram-positive pathogens
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Since utilization of menaquinone in the electron transport system is a characteristic of Gram-positive organisms, the 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) inhibitors 1a and 2a act as selective antibacterial agents against organisms such as methicillin-resistant Stapylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), and Mycobacterium spp. Growth of drug-resistant Gram-positive organisms was sensitive to the MenA inhibitors, indicating that menaquinone synthesis is a valid new drug target in Gram-positive organisms.
- Kurosu, Michio,Narayanasamy, Prabagaran,Biswas, Kallolmay,Dhiman, Rakesh,Crick, Dean C.
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p. 3973 - 3975
(2008/02/11)
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- A laser flash photolysis study on fenofibric acid
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Fenofibric acid (FA) is a photosensitizing drug used in the treatment of hyperlipidemia. This compound follows two different photodegradation pathways: the free acid exhibits the typical benzophenone photoreactivity, while its sodium salt undergoes photodecarboxylation via a triplet biradical, that undergoes intramolecular electron transfer to form a carbanion, or cyclization to give an intramolecular light-absorbing transient (LAT). The obtained photoproducts are explained as the result of protonation of the carbanion, ring opening of the LAT with rearrangement or oxygen trapping of any of the triplet intermediates. The above mechanism is supported by direct detection of the triplet state of FA and two long-lived intermediates in laser flash photolysis experiments. The triplet lifetime of the carboxylate form in methanol is 0.06 μs; by contrast, in the case of the free acid, it is 10 times longer. The benzophenone moiety is clearly the key chromophore involved in the photobehavior of FA.
- Bosca, Francisco,Miranda, Miguel A.
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p. 853 - 857
(2007/10/03)
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- Equilibrium and Dynamic Dielectric Properties of Acrylate Polymers with (Phenyl)(4-chlorophenyl)methanone Groups in Their Structure
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The curves describing the relaxation behavior of poly(4-(acryloxy)phenyl)(4-chlorophenyl)methanone at several frequencies present in the dielectric loss-temperature plane a β relaxation centered at -76 deg C at 10 Hz, whose activation energy shows a slight tendency to increase as the temperature goes up.The relaxation spectra exhibit an ostensible glass-rubber relaxation or α process centered at 106 deg C at 10 Hz, in which free charge conductivity and blocking electrode phenomena become dominant at frequencies below 10 Hz.An electric model is used to separate the dipolar response from conductivity contributions in the glass-rubber relaxation, and the dipole time correlation function for this process is obtained at several temperatures.The intramolecular correlation coefficient gintra, determined from dielectric measurements in solution, is somewhat larger than the coefficient g involving both intra- and intermolecular interactions, obtained from dielectric measurements in the bulk.A rotational state scheme is developed which gives a good account of the intramolecular dipolar correlation coefficient.Finally whereas the relaxation mechanisms involved in the glass-rubber relaxation seem to be governed by the volume, the conductive processes exhibit Arrhenius behavior.
- Nunes, R.C.,Diaz-Calleja, R.,Pinto, M.,Saiz, E.,Riande, E.
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p. 12962 - 12970
(2007/10/02)
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- Amino terminated poly(aryl ether ketones)
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Described herein are novel amino-terminated poly(aryl ether ketone) oligomers and methods for their production. These amino-terminated poly(aryl ether ketone) oligomers are used as building blocks for a variety of polymers and copolymers.
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- Polymerisation and Related Reactions involving Nucleophilic Aromatic Substitution. Part 1. The Rates of Reaction of Substituted 4-Halogenobenzophenones with the Potassium Salts of Substituted 4-Hydroxybenzophenones
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The rate of displacement of fluorine from 4'-X,4-fluorobenzophenones by the potassium salts of 4'-X,4-hydroxybenzophenones (X = CF3, Cl, F, H, OPh, and OMe) has been studied at 175-225 deg C in diphenyl sulphone as solvent.Comparison with the corresponding rate of displacement of chlorine indicates that the reaction is a bimolecular nucleophilic aromatic substitution.The reaction obeys the Hammett equation using normal ? values for substitution in both the substrate (ρ 1.19) and the phenolate (ρ -0.53).There is also a marked salt effect on the reaction rate and this has been included with the substituent constants in a general equation for the calculation of rate coefficients.The effect of an O- substituent is more marked than would have been expected from the previous range of ? values ascribed to this substituent.
- Ridd, John H.,Yousaf, Taher I.,Rose, John B.
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p. 1729 - 1734
(2007/10/02)
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- Production of hydroxy arylophenones
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Production of a hydroxy arylophenone by reacting an aromatic carboxylic acid Ar(--CO2 H)p where Ar is an aromatic radical, (--CO2 H) is an aromatic carboxylic acid group, and p is 1 or 2 with an aromatic compound H--Ar'--OH where Ar' is an aromatic radical and --H and --OH are aromatically bound para to each other in a benzenoid ring, in the presence of an alkyl sulphonic acid, particularly methane sulphonic acid, to produce a hydroxy arylophenone of formula Ar(--CO--Ar'--OH)p where the carbonyl and hydroxyl groups are para to each other in the hydroxyl-containing benzenoid ring of Ar'. The production of the hydroxy arylophenone proceeds through the intermediate ester (H--Ar'--O--CO--)p Ar and the production of the hydroxy arylophenone starting from the ester is also claimed.
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- Pesticidal compounds, compositions and methods
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Novel compounds are described which are substituted benzophenone hydrazones. They have pesticidal activity, especially against insects and acarids, and pesticidal compositions and methods are described. Methods of making the compounds, and novel intermediates, are also described.
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- Pesticide compounds
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Novel compounds are described which are substituted benzophenone hydrazones. They have pesticidal activity, especially against insects and acarids, and pesticidal compositions and methods are described. Methods of making the compounds, and novel intermediates, are also described.
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- Phenylmethylphenoxy propionic acid esters
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Compounds of the formula STR1 in which A is lower alkyl, or a substituted or unsubstituted phenyl, thienyl, furyl, indolyl or thiaindolyl radical, R, X4 and X5 are hydrogen or lower alkyl, Y is hydrogen, hydroxy, etherified hydroxy, substituted amino, or N-attached heterocyclyl, X0 is O or OCH2 CH2 O, R' represents hydrogen, lower alkyl or acetyl; and acid-addition salts thereof, are novel and useful in pharmacy as hypolipaemiant, hypocholesterolaemiant and cholagogic agents or in the preparation of such agents.
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