5281-20-9Relevant articles and documents
Kinetics of a Criegee intermediate that would survive high humidity and may oxidize atmospheric SO2
Huang, Hao-Li,Chao, Wen,Lin, Jim Jr-Min
, p. 10857 - 10862 (2015)
Criegee intermediates are thought to play a role in atmospheric chemistry, in particular, the oxidation of SO2, which produces SO3 and subsequently H2SO04, an important constituent of aerosols and acid rain. However, the impact of such oxidation reactions is affected by the reactions of Criegee intermediates with water vapor, because of high water concentrations in the troposphere. In this work, the kinetics of the reactions of dimethyl substituted Criegee intermediate (CH3)2 COO with water vapor and with SO2 were directly measured via UV absorption of (CH3)2COO under near-atmospheric conditions. The results indicate that (i) the water reaction with (CH3)2 COO is not fast enough (kH2O -16 cm3s-1) to consume atmospheric (CH3)2COO significantly and (ii) (CH3)2COO reacts with SO2 at a near-gas-kinetic-limit rate (kSO2 = 1.3 × 10-10 cm3s-1). These observations imply a significant fraction of atmospheric (CH3)2 COO may survive under humid conditions and react with SO2, very different from the case of the simplest Criegee intermediate CH2OO, in which the reaction with water dimer predominates in the CH2OO decay under typical tropospheric conditions. In addition, a significant pressure dependence was observed for the reaction of (CH3)2COO with SO2, suggesting the use of low pressure rate may underestimate the impact of this reaction. This work demonstrates that the reactivity of a Criegee intermediate toward water vapor strongly depends on its structure, which will influence the main decay pathways and steady-state concentrations for various Criegee intermediates in the atmosphere.
Discovery of pyrazole derivatives as cellular active inhibitors of histone lysine specific demethylase 5B (KDM5B/JARID1B)
Liang, Qianqian,Liu, Hong-Min,Ma, Li-Ying,Ren, Hongmei,Wu, Yang,Zhang, Kun,Zhang, Xinhui,Zhao, Bing,Zheng, Yi-Chao
, (2020/03/10)
KDM5B (also known as PLU-1 and JARID1B) is 2-oxoglutarate and Fe2+ dependent oxygenase that acts as a histone H3K4 demethylase, which is a key participant in inhibiting the expression of tumor suppressors as a drug target. Here, we present the discovery of pyrazole derivatives compound 5 by structure-based virtual screening and biochemical screening with IC50 of 9.320 μM against KDM5B, and its subsequent optimization to give 1-(4-methoxyphenyl)-N-(2-methyl-2-morpholinopropyl)-3-phenyl-1H-pyrazole-4-carboxamide (27 ab), a potent KDM5B inhibitor with IC50 of 0.0244 μM. In MKN45 cells, compound 27 ab can bind and stabilize KDM5B and induce the accumulation of H3K4me2/3, bona fide substrates of KDM5B, while keep the amount of H3K4me1, H3K9me2/3 and H3K27me2 without change. Further biological study also indicated that compound 27 ab is a potent cellular active KDM5B inhibitor that can inhibit MKN45 cell proliferation, wound healing and migration. In sum, our finding gives a novel structure for the discovery of KDM5B inhibitor and targeting KDM5B may be a new therapeutic strategy for gastric cancer treatment.
Hydrogenative metathesis of enynes via piano-stool ruthenium carbene complexes formed by alkyne gem-hydrogenation
Peil, Sebastian,Bistoni, Giovanni,Goddard, Richard,Fürstner, Alois
supporting information, p. 18541 - 18553 (2020/11/17)
The only recently discovered gem-hydrogenation of internal alkynes is a fundamentally new transformation, in which both H atoms of dihydrogen are transferred to the same C atom of a triple bond while the other position transforms into a discrete metal carbene complex. [Cp?RuCl]4 is presently the catalyst of choice: the resulting piano-stool ruthenium carbenes can engage a tethered alkene into either cyclopropanation or metathesis, and a prototypical example of such a reactive intermediate with an olefin ligated to the ruthenium center has been isolated and characterized by X-ray diffraction. It is the substitution pattern of the olefin that determines whether metathesis or cyclopropanation takes place: a systematic survey using alkenes of largely different character in combination with a computational study of the mechanism at the local coupled cluster level of theory allowed the preparative results to be sorted and an intuitive model with predictive power to be proposed. This model links the course of the reaction to the polarization of the double bond as well as to the stability of the secondary carbene complex formed, if metathesis were to take place. The first application of "hydrogenative metathesis"to the total synthesis of sinularones E and F concurred with this interpretation and allowed the proposed structure of these marine natural products to be confirmed. During this synthesis, it was found that gem-hydrogenation also provides opportunities for C-H functionalization. Moreover, silylated alkynes are shown to participate well in hydrogenative metathesis, which opens a new entry into valuable allylsilane building blocks. Crystallographic evidence suggests that the polarized [Ru-Cl] bond of the catalyst interacts with the neighboring R3Si group. Since attractive interligand Cl/R3Si contacts had already previously been invoked to explain the outcome of various ruthenium-catalyzed reactions, including trans-hydrosilylation, the experimental confirmation provided herein has implications beyond the present case.
Hydrogenative Cyclopropanation and Hydrogenative Metathesis
Peil, Sebastian,Guthertz, Alexandre,Biberger, Tobias,Fürstner, Alois
supporting information, p. 8851 - 8856 (2019/05/28)
The unusual geminal hydrogenation of a propargyl alcohol derivative with [CpXRuCl] as the catalyst entails formation of pianostool ruthenium carbenes in the first place; these reactive intermediates can be intercepted with tethered alkenes to give either cyclopropanes or cyclic olefins as the result of a formal metathesis event. The course of the reaction is critically dependent on the substitution pattern of the alkene trap.
Safe and Facile Access to Nonstabilized Diazoalkanes Using Continuous Flow Technology
Rullière, Pauline,Benoit, Guillaume,Allouche, Emmanuelle M. D.,Charette, André B.
supporting information, p. 5777 - 5782 (2018/05/14)
Despite the high synthetic potential of nonstabilized diazo compounds, their utilization has always been hampered by stability, toxicity, and safety issues. The present method opens up access to the most reactive nonstabilized diazoalkanes. Among diazo compounds, nonstabilized alkyl diazo compounds are the least represented because of their propensity to degrade during preparation. The continuous flow oxidation process of hydrazones on a silver oxide column afforded an output stream of base- and metal-free pure diazo solution in dichloromethane. Starting from innocuous ketones and aldehydes, this methodology allows the production of a broad range of unprecedented diazoalkanes compounds in excellent yields, while highlighting their synthetic potential and the possibility of safe large-scale diazo production.
En route to stable all-carbon-substituted silylenes: Synthesis and reactivity of a bis(α-spirocyclopropyl)silylene
Redies, Kai M.,Fallon, Thomas,Oestreich, Martin
supporting information, p. 3235 - 3238 (2014/08/05)
The synthesis of a bis(α-spirocyclopropyl)silylene is reported and its reactivity revealed. Liberation of the silylene was accomplished by UV-light-mediated photolysis of a trisilane precursor. Insertion and addition reactions prove the existence and versatility of this new family of bis(α-spirocyclopropyl)-substituted silylenes. Substitution on the flanking cyclopropyls for improved steric shielding of the reactive center remains challenging.
A regioselective synthesis of some new pyrazol-1′-ylpyrazolo[1,5-a] pyrimidines in aqueous medium and their evaluation as antimicrobial agents
Aggarwal, Ranjana,Sumran, Garima,Garg, Neelam,Aggarwal, Ashok
scheme or table, p. 3038 - 3046 (2011/07/08)
An efficient and environmental benign regioselective synthesis of some new pyrazol-1′-ylpyrazolo[1,5-a]pyrimidines (7b-h) has been accomplished via treatment of 3(5)-amino-5(3)-hydrazinopyrazole dihydrochloride (5) with several unsymmetrical 1,3-diketones (6b-h) using water as a solvent without any catalysts or additives. The structure of 7b-h was established on the basis of rigorous analysis of 1H, 13C NMR, IR spectral data and MS. Eight compounds (7a-h) were screened for their antibacterial activity against two gram-positive and two gram-negative bacteria and compounds (7a, b, d and e) for antifungal activity against four phytopathogenic fungi. Compounds 7c and 7e manifest rather broad antibacterial activity than standard antibiotics. One lead compound, 7a (10 mg/ml and 200 mg/ml) exhibited equipotent or more potent antifungal activity against all tested microorganisms than standard drug.
Gold-catalyzed hydroamination of alkynes and allenes with parent hydrazine
Kinjo, Rei,Donnadieu, Bruno,Bertrand, Guy
scheme or table, p. 5560 - 5563 (2011/07/30)
A diverse array of nitrogen-containing compounds were formed by the addition of hydrazine to alkynes, diynes, enynes, and allenes in the presence of cationic gold(I) complexes with a cyclic (alkyl)(amino)carbene ligand (see scheme; the X-ray crystal structure of the gold-hydrazine complex is shown). This hydroamination is an ideal initial step for the preparation of acyclic and heterocyclic bulk chemicals. Dipp=2,6-diisopropylphenyl. Copyright
Oxadiazoline ligands for modulating the expression of exogenous genes via an ecdysone receptor complex
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Page/Page column 27, (2008/06/13)
The present invention relates to non-steroidal ligands for use in nuclear receptor-based inducible gene expression system, and a method to modulate exogenous gene expression in which an ecdysone receptor complex comprising: a DNA binding domain; a ligand binding domain; a transactivation domain; and a ligand is contacted with a DNA construct comprising: the exogenous gene and a response element; wherein the exogenous gene is under the control of the response element and binding of the DNA binding domain to the response element in the presence of the ligand results in activation or suppression of the gene.
Kinetics and mechanism of oxidation of thiosemicarbazones by acid bromate
Pardhasaradhi, V,Gowda, B Thimme
, p. 175 - 181 (2007/10/02)
The kinetics of oxidation of benzaldehyde, propanaldehyde, acetone and acetophenone thiosemicarbazones by acid bromate have been studied in aqueous acetic acid medium (1:1, v/v).The rates show first order dependence on in all the cases, but show varying orders in +> depending upon +>.In the +> range 0.001-0.02 mol dm-3 the reaction order is fractional in +> and it is above 1 in the +> range above 0.02 mol dm-3.The reactions show fractional order in , in both the ranges of .Addition of KBr has little effect on the rates of oxidations.Suitable mechanisms consistent with the observed results have been suggested and the related rate laws deduced.Coefficients of the rate limiting steps have been calculated at different temperatures and the activation parameters are computed.The validity of rate laws is also tested by recalculating the rate constants from the deduced rate laws as and +> are varied.Reasonably good agreement between the recalculated values and the experimental constants provides support to the proposed mechanisms.
