- Design, synthesis, molecular docking, and biological evaluation of novel selenium containing lumefantrine analogues
-
A new series of 1-(9-benzylidene-2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethanol was synthesized by a simple Knoevenagel condensation of 1-(2,7-dichloro-9H-fluoren-4-yl)-2-(methylselanyl)ethanol with different substituted aromatic aldehydes in basic media. These synthesized compounds were confirmed on the basis of their elemental analyses, infrared (IR), 1H NMR, 13C NMR, and mass spectral data and screened for the antibacterial and antifungal activity. The preliminary antibacterial and antifungal screening revealed that the compounds 8c (dichloro), 8d (fluoro), 8e (chloro), 8i (methoxy), and 8l (methyl) displayed moderate to good activity. The antibacterial results of these compounds were further supported by in silico molecular docking studies, for the inhibition of Escherichia coli MurB enzyme (PDB code: 2MBR), wherein they showed higher binding energy and good affinity towards the active pocket of the enzyme compared with that of the standard drug Ciprofloxacin. Thus, the plausible mechanism of their antibacterial activity was owed to their inhibitory action of the bacterial MurB enzyme.
- Hegde, Hemant,Nayak, Soukhyarani Gopal,Poojary, Boja,Purushotham, Nikil,Puthran, Divyaraj,Rasheed, Mohammed Shafeeulla
-
-
- Preparation method for benflumetol and matched system thereof
-
The invention belongs to the field of benflumetol, and relates to preparation and a system for the benflumetol, in particular to a preparation method for the benflumetol and a matched system thereof.The preparation method for the benflumetol is completed by sequentially through bulk drugs, a plurality of intermediates and the benflumetol. The matched system for the preparation method sequentiallycomprises an intermediate I matched system, an intermediate II matched system, an intermediate IV matched system, an intermediate V matched system and a benflumetol matched system. According to the invention, overall preparation is simple, reasonable and highly-efficient; the required time is greatly shortened; and exploration of industrial production conditions of the benflumetol is completed.
- -
-
Paragraph 0041-0053
(2020/05/02)
-
- Additive-Free Palladium-Catalyzed Decarboxylative Cross-Coupling of Aryl Chlorides
-
The cross-coupling of sodium (hetero)aryl carboxylates with (hetero)aryl chlorides proceeds with 1 mol % palladium catalyst and does not require inorganic base, silver salts, or copper salts. This coupling uses two low energy partners, and the only stoichiometric byproducts are carbon dioxide and sodium chloride. The substrate scope includes less activated aryl chlorides and carboxylates (>25 examples). The palladium loading could be reduced to 0.1 mol %, and Buchwald-style precatalysts could be used.
- Daley, Ryan A.,Liu, En-Chih,Topczewski, Joseph J.
-
supporting information
p. 4734 - 4738
(2019/06/27)
-
- Recovery processing method of 2,7-dichlorofluorene reaction mother solution
-
The invention relates to a recovery processing method of a 2,7-dichlorofluorene reaction mother solution, in particular to a method for reusing waste liquid after treatment. Reductive dechlorination is carried out on the 2,7-dichlorofluorene reaction mother solution through zinc powder to obtain a mixed liquid mainly composed of 2-chlorofluorene and fluorine, the mixed liquid is filtered to removethe zinc powder and zinc acetate, and directed chloridized or chloridized with the raw material fluorine to prepare 2,7-dichlorofluorene. The recovery processing method of the 2,7-dichlorofluorene reaction mother solution is applied to the recycling of the 2,7-dichlorofluorene reaction mother solution, and has the advantages of simple operation, cheap treatment and the like.
- -
-
Paragraph 0022-0025
(2018/10/19)
-
- Au-catalyzed biaryl coupling to generate 5- to 9-membered rings: Turnover-limiting reductive elimination versus π-complexation
-
The intramolecular gold-catalyzed arylation of arenes by aryl-trimethylsilanes has been investigated from both mechanistic and preparative aspects. The reaction generates 5- to 9-membered rings, and of the 44 examples studied, 10 include a heteroatom (N, O). Tethering of the arene to the arylsilane provides not only a tool to probe the impact of the conformational flexibility of Ar-Au-Ar intermediates, via systematic modulation of the length of aryl-aryl linkage, but also the ability to arylate neutral and electron-poor arenes-substrates that do not react at all in the intermolecular process. Rendering the arylation intramolecular also results in phenomenologically simpler reaction kinetics, and overall these features have facilitated a detailed study of linear free energy relationships, kinetic isotope effects, and the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diaryl-gold(III) species. The turnover-limiting step for the formation of a series of fluorene derivatives is sensitive to the reactivity of the arene and changes from reductive elimination to π-complexation for arenes bearing strongly electron-withdrawing substituents (σ > 0.43). Reductive elimination is accelerated by electron-donating substituents (ρ = -2.0) on one or both rings, with the individual σ-values being additive in nature. Longer and more flexible tethers between the two aryl rings result in faster reductive elimination from Ar-Au(X)-Ar and lead to the π-complexation of the arene by Ar-AuX2 becoming the turnover-limiting step.
- Corrie, Tom J. A.,Ball, Liam T.,Russell, Christopher A.,Lloyd-Jones, Guy C.
-
p. 245 - 254
(2017/05/29)
-
- Au-Catalyzed Biaryl Coupling to Generate 5- To 9-Membered Rings: Turnover-Limiting Reductive Elimination versus ?-Complexation
-
The intramolecular gold-catalyzed arylation of arenes by aryl-trimethylsilanes has been investigated from both mechanistic and preparative aspects. The reaction generates 5- to 9-membered rings, and of the 44 examples studied, 10 include a heteroatom (N, O). Tethering of the arene to the arylsilane provides not only a tool to probe the impact of the conformational flexibility of Ar-Au-Ar intermediates, via systematic modulation of the length of aryl-aryl linkage, but also the ability to arylate neutral and electron-poor arenes - substrates that do not react at all in the intermolecular process. Rendering the arylation intramolecular also results in phenomenologically simpler reaction kinetics, and overall these features have facilitated a detailed study of linear free energy relationships, kinetic isotope effects, and the first quantitative experimental data on the effects of aryl electron demand and conformational freedom on the rate of reductive elimination from diaryl-gold(III) species. The turnover-limiting step for the formation of a series of fluorene derivatives is sensitive to the reactivity of the arene and changes from reductive elimination to ?-complexation for arenes bearing strongly electron-withdrawing substituents (σ > 0.43). Reductive elimination is accelerated by electron-donating substituents (ρ = -2.0) on one or both rings, with the individual σ-values being additive in nature. Longer and more flexible tethers between the two aryl rings result in faster reductive elimination from Ar-Au(X)-Ar and lead to the ?-complexation of the arene by Ar-AuX2 becoming the turnover-limiting step.
- Ball, Liam T.,Corrie, Tom J. A.,Lloyd-Jones, Guy C.,Russell, Christopher A.
-
p. 245 - 254
(2021/09/04)
-
- An improved manufacturing process for the antimalaria drug coartem. Part II
-
The manufacturing process for lumefantrine, 2, one of the two active principles in the fixed-dose combination of the anti-malarial drug Coartem, was reworked. For the conversion of 2-chloro-1-(2,7-dichloro-9H-fluoren-4-yl) ethanone, 5, to 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl)ethanol, 8, a onepot process was developed that eliminated isolation of the epoxide 2-(2,7-dichloro-9H-fluoren-4-yl)oxirane, 7. Significant increase in throughput was achieved by applying new reaction and crystallization conditions for the Knoevenagel condensation of 2-dibutylamino-1-(2,7-dichloro-9H-fluoren-4-yl) ethanol, 8, to 2-dibutylamino-1-{2,7-dichloro-9-[1-(4-chlorophenyl)meth-(Z)- ylidene]-9H-fluoren-4-yl}ethanol, 2.
- Beutler, Ulrich,Fuenfschilling, Peter C.,Steinkemper, Andreas
-
p. 341 - 345
(2012/12/31)
-
- Pinacol Formation and Reduction of Aromatic Carbonyls with Magnesium-Methanol at Ambient Temperature
-
A simple and inexpensive procedure for the pinacol formation of aromatic aldehydes and reduction of aromatic ketones to the corresponding alcohols with magnesium in dry methanol at ambient temperature is reported. The pinacol formation and reduction are proposed to be proceeding by SET from magnesium.
- Khurana, Jitender M.,Bansal, Geeti,Kukreja, Gagan,Pandey, Ravi R.
-
p. 1365 - 1371
(2007/10/03)
-
- Energy transfer in bichromophoric molecules: The effect of symmetry and donor/acceptor energy gap
-
The dependence of the rate of singlet excitation transfer on the donor-acceptor energy gap was investigated in bichromophoric spiranes with symmetry-forbidden zero-order electronic coupling. The fluorescence measurements were performed in a supersonic jet in order to avoid collisional and inhomogeneous line broadening. Fluorescence excitation spectra and single-vibronic-level emission spectra of the model chromophores cyclopentaphenanthrene and 1,8-dimethylnaphthalene and the bichromophores spirofluorenephenanthrene and spirofluorenenaphthalene are presented and analyzed. Although the transition moments of the linked chromophores are rigorously perpendicular and the exchange coupling between the v′ = 0 states is computationally shown to be zero, all spiranes with energy gaps larger than ~1000 cm-1 exhibited complete electronic energy transfer from all vibrational states of the electronically excited donor, including the undistorted v′ = 0 state. This behavior is explained in terms of vibronic coupling between the sparse states of the donor and the dense manifold (pseudocontinuum) of the acceptor states. The electronic energy transfer was sufficiently fast to result in measurable lifetime broadening of the donor absorption lines, from which the kEET was estimated. The results demonstrate that the zero-order picture overestimates the degree of the molecular orbital symmetry control over electronic energy transfer and charge-transfer rates and that at sufficiently high driving forces the vibronically mediated "symmetry-forbidden" electronic energy transfer can be very rapid (~1 × 1012 s-1).
- Yip,Levy, Donald H.,Kobetic, Renata,Piotrowiak, Piotr
-
-
- Studies on the alkylation and chlorination of fluorenes: Preparation of 9-(2-hydroxyethyl)fluorene and 2,7-dichloro-9-(2-hydroxyethyl)fluorene
-
Efficient large-scale syntheses of 9-(2-hydroxyethyl)fluorene (1) and its 2,7-dichloro derivative 2 are described. Major differences exist in the reactivity of fluorene and its 2,7-dichloro derivative toward 9-alkylation. These differences are attributed to the difference in acidity of the protons in the 9-position of these compounds. Also 2,7-dichlorination of fluorene and its derivatives was satisfactorily achieved by treatment with NCS and conc. HCl in acetonitrile under carefully controlled conditions. Specifically, a highly concentrated solution of substrates and elevated temperatures were required for facile 2,7-dichlorination.
- Perumattam,Shao,Confer
-
p. 1181 - 1184
(2007/10/02)
-
- Investigation of the 2,7-Dihalofluorenylidenes: Search for Heavy Atom Effects in the Reactions of Triplet Carbenes
-
The properties of the 2,7-dihalofluorenylidenes (Cl, Br, I) were examined by laser and EPR spectroscopy and by conventional chemical analyses.Their reactions with alcohols and olefins were studied.No evidence was found for the operation of a heavy atom effect in their reaction with methyl alcohol.Analysis of the kinetic and product results indicates an energy gap between the triplet (ground state) and the singlet for the three dihalofluorenylidenes of 4.2 +/- 0.5 kcal/mol, ca. twice the value of fluorenylidene itself.
- Rak, Stanton F.,Lapin, Stephen C.,Falvey, Daniel E.,Schuster, Gary B.
-
p. 5003 - 5008
(2007/10/02)
-
- Selective Preparation of Fluorene Derivatives Using the t-Butyl Function as a Positional Protective Group
-
Several 4-substituted 2,7-di-t-butylfluorene derivatives (3) were prepared by electrophilic substitutions of 2,7-di-t-butylfluorene (1). 4-Substituted fluorene (4), such as 4-bromo- (4a), 4-methyl (4e), and 4-aacetylaminofluorene (4j), were obtained by the trans-t-butylations of 3.Although we attempted to synthesize 1,8-disubstituted fluorene from 3,6-di-t-butylfluorene (2) which was derived from 2,2'-diiodo-4,4'-di-t-butyldiphenylmethane (5), by the same methods, we obtained only 2,7-disubstituted fluorene derivatives (8); it turned out electrophilic substitutions of 2 gave 2,7-disubstituted 3,6-di-t-butylfluorene derivatives.
- Kajigaeshi, Shoji,Kadowaki, Toshiya,Nishida, Akiko,Fujisaki, Shizuo
-
-
- Process and reactant for halogenating organic compounds
-
A process and solvent and/or reactant for halogenating organic compounds. The organic compounds are contacted with a solution of trialkyl phosphate and a halogen. The solution of trialkyl phosphate may additionally include phosphorous pentoxide.
- -
-
-