104-81-4Relevant academic research and scientific papers
Copper-Catalyzed Synthesis of Trifluoroethylarenes from Benzylic Bromodifluoroacetates
Ambler, Brett R.,Zhu, Lingui,Altman, Ryan A.
, p. 8449 - 8457 (2015)
Trifluoroethylarenes are found in a variety of biologically active molecules, and strategies for accessing this substructure are important for developing therapeutic candidates and biological probes. Trifluoroethylarenes can be directly accessed via nucleophilic trifluoromethylation of benzylic electrophiles; however, current catalytic methods do not effectively transform electron-deficient substrates and heterocycles. To address this gap, we report a Cu-catalyzed decarboxylative trifluoromethylation of benzylic bromodifluoroacetates. To account for the tolerance of sensitive functional groups, we propose an inner-sphere mechanism of decarboxylation.
Photobromination of Side-Chain Methyl Groups on Arenes with N-Bromosuccinimide - Convenient and Selective Syntheses of Bis(bromomethyl)- and (Bromomethyl)methylarenes -
Futamura, Shigeru,Zong, Zhi-Min
, p. 345 - 348 (1992)
Photobromination of side-chain methyl groups on arenes with N-bromosuccinimide (NBS) was investigated.Visible light irradiation in benzene solvent was extremely effective in increasing the selectivity of the reaction and the efficiency for product purification.The photobromination of 1,4-, 1,8, 2,3-, and 2,6-dimethylnaphthalenes, 4,4'-dimethylbiphenyl, and p-xylene with 2.2 mol equivalents of NBS quantitatively afforded the corresponding bis(bromomethyl)arenes, respectively.The (bromomethyl)methylarenes were also obtained in good yields in the photobromination reactions of the above dimethylarenes with 1.1 mol equivalents of NBS.
Kinetics and activation energy of the oxidation of para-tolyl radical by cobalt(III) in acetic acid: Competition kinetics
Espenson, James H.,Yiu, Douglas Tak-Yeung
, p. 599 - 604 (2005)
The title reaction gives rise to a benzylic cation that is rapidly transformed to its bromide in competition with the reaction of the radical with carbon tetrachloride. Experiments were carried out over 17-69°C in acetic acid containing cobalt(II) acetate, para-xylene, hydrobromic acid, carbon tetrachloride, and meta-chloroperoxybenzoic acid. The product ratio, ArCH 2Cl/ArCH2Br, in combination with other pertinent rate constants, was used to determine the rate constant for the step of interest: log script k sign (L mol-1 s-1) = 19.9 - (75 ± 11 kJ mol-1/2.303 RT). The large pre-exponential factor, which gives ΔS? = 128 J K-1 mol-1, signals an unusual transition state, because a negative value of ΔS? would be expected for a simple bimolecular reaction. The production of the ion pair ArCH 2+||OAc- in HOAc, which has the same dielectric constant as benzene, may be responsible, at least in part. Furthermore, inner sphere reorganization of cobalt may also contribute.
[1,3]-Claisen rearrangement via removable functional group mediated radical stabilization
Alam, Md Nirshad,Dash, Soumya Ranjan,Mukherjee, Anirban,Pandole, Satish,Marelli, Udaya Kiran,Vanka, Kumar,Maity, Pradip
supporting information, p. 890 - 895 (2021/02/01)
A thermal O-to-C [1,3]-rearrangement of α-hydroxy acid derived enol ethers was achieved under mild conditions. The 2-aminothiophenol protection of carboxylic acids facilitates formation of the [1,3] precursor and its thermal rearrangement via stabilization of a radical intermediate. Experimental and theoretical evidence for dissociative radical pair formation, its captodative stability via aminothiophenol, and a unique solvent effect are presented. The aminothiophenol was deprotected from rearrangement products as well as after derivatization to useful synthons.
Synthesis, Docking, and Biological activities of novel Metacetamol embedded [1,2,3]-triazole derivatives
Battu, Satyanarayana,Joolakanti, Hima Bindhu,Kamepalli, Ramanjaneyulu,Miryala, Jeevanreddy
, (2021/06/18)
ERα controls the breast tissue development and progression of breast cancer. In our search for novel compounds to target Estrogen Receptor Alpha Ligand-Binding Domain, we identified “N-(3-((1H-1,2,3-triazol-4-yl)methoxy)phenyl)acetamide” derivatives as lead compounds. The Docking studies indicated good docking score for Metacetamol derivatives when docked into the 1XP6. A series of metacetamol derivatives have been synthesized, characterized and evaluated for cytotoxicity, anti bacterial and anti oxidant activities. Among the tested twelve hybrid compounds, “7a, 7g, 7h and 7i” derivatives showed promising cytotoxicity with IC50 value of 50 value of 30 μM, whereas Compounds “7a, 7b, 7c, 7d, 7g, 7j, 7k and 7l” showed moderate anti bacterial activity with the MIC value of 300 μM.
New 3-(1H-benzo[d]imidazol-2-yl)quinolin-2(1H)-one-based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis-inducing agents
Gaikwad, Nikhil B.,Bansode, Sapana,Biradar, Shankar,Ban, Mayuri,Srinivas, Nanduri,Godugu, Chandraiah,Yaddanapudi, Venkata M.
, (2021/08/07)
A series of 1,2,3-triazole derivatives based on the quinoline–benzimidazole hybrid scaffold was designed, synthesized, and screened against a panel of NCI-60 humanoid cancer cell lines for in vitro cytotoxicity evaluation, which revealed that compound Q6 was the most potent cytotoxic agent with excellent GI50, TGI, and LC50 values on multiple cancer cell lines. Q6 was tested further on the BT-474 breast cancer line to evaluate the mechanism of action. Preliminary screening studies based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that compound Q6 had an excellent antiproliferative effect against human breast cancer cells, BT-474, with IC50 values of 0.59 ± 0.01 μM. The detailed study based on the acridine orange/ethidium bromide staining (AO/EB) and the 4′,6-diamidino-2-phenylindole (DAPI) assay suggested that the antiproliferative activity shown was due to the induction of apoptosis on exposure to Q6. Further, DCFDA staining showed the generation of reactive oxygen species, altering the mitochondrial potential and leading to the initiation of apoptosis. This was further supported by JC-1 staining, indicating that this scaffold can contribute to the development of more potent derivatives.
Triptycenyl Sulfide: A Practical and Active Catalyst for Electrophilic Aromatic Halogenation Using N-Halosuccinimides
Nishii, Yuji,Ikeda, Mitsuhiro,Hayashi, Yoshihiro,Kawauchi, Susumu,Miura, Masahiro
, p. 1621 - 1629 (2020/02/04)
A Lewis base catalyst Trip-SMe (Trip = triptycenyl) for electrophilic aromatic halogenation using N-halosuccinimides (NXS) is introduced. In the presence of an appropriate activator (as a noncoordinating-anion source), a series of unactivated aromatic compounds were halogenated at ambient temperature using NXS. This catalytic system was applicable to transformations that are currently unachievable except for the use of Br2 or Cl2: e.g., multihalogenation of naphthalene, regioselective bromination of BINOL, etc. Controlled experiments revealed that the triptycenyl substituent exerts a crucial role for the catalytic activity, and kinetic experiments implied the occurrence of a sulfonium salt [Trip-S(Me)Br][SbF6] as an active species. Compared to simple dialkyl sulfides, Trip-SMe exhibited a significant charge-separated ion pair character within the halonium complex whose structural information was obtained by the single-crystal X-ray analysis. A preliminary computational study disclosed that the πsystem of the triptycenyl functionality is a key motif to consolidate the enhancement of electrophilicity.
Photochemical benzylic bromination in continuous flow using BrCCl3 and its application to telescoped p-methoxybenzyl protection
Otake, Yuma,Williams, Jason D.,Rincón, Juan A.,De Frutos, Oscar,Mateos, Carlos,Kappe, C. Oliver
supporting information, p. 1384 - 1388 (2019/02/14)
BrCCl3 represents a rarely used benzylic brominating reagent with complementary reactivity to other reagents. Its reactivity has been revisited in continuous flow, revealing compatibility with electron-rich aromatic substrates. This has brought about the development of a p-methoxybenzyl bromide generator for PMB protection, which was successfully demonstrated on a pharmaceutically relevant intermediate on 11 g scale, giving 91% yield and a PMB-Br space-time-yield of 1.27 kg L?1 h?1
Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein aggregation
Liu, Hao,Chen, Li,Zhou, Fei,Zhang, Yun-Xiao,Xu, Ji,Xu, Meng,Bai, Su-Ping
supporting information, p. 3089 - 3096 (2019/06/14)
Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09 μM. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.
COMBINATION TREATMENTS COMPRISING ADMINISTRATION OF 1H-PYRAZOLO[4,3-B]PYRIDINES
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Page/Page column 109, (2019/07/19)
The present invention provides 1H-pyrazolo[4,3-b]pyridin-7-amines of formula (I) as PDE1 inhibitors together with a second compound useful in the treatment of a neurodegenerative disorder and their combined use as a medicament, in particular for the treatment of neurodegenerative and/or cognitive disorders.
