102-28-3Relevant articles and documents
Citric acid catalysed Beckmann rearrangement, under solvent free conditions
Thopate, Shankar Ramchandra,Kote, Santosh Rajaram,Rohokale, Sandeep Vasantrao,Thorat, Nitin Madhukar
, p. 124 - 125 (2011)
Citric acid is reported to be a highly efficient and eco-friendly catalyst for the Beckmann rearrangement under solvent free conditions.
In situ generated iron oxide nanocrystals as efficient and selective catalysts for the reduction of nitroarenes using a continuous flow method
Cantillo, David,Baghbanzadeh, Mostafa,Kappe, C. Oliver
, p. 10190 - 10193 (2012)
The best of both worlds: The benefits of homogeneous and heterogeneous nanocatalysis are combined, whereby highly reactive colloidal Fe 3O4 nanocrystals are generated in situ that remain in solution long enough to allow the efficient and selective reduction of nitroarenes to anilines in continuous-flow mode (see scheme). After completion of the reaction, the nanoparticles aggregate and can be recovered by a magnet. Copyright
Radical arylation of triphenyl phosphite catalyzed by salicylic acid: Mechanistic investigations and synthetic applications
Estruch-Blasco, Manel,Felipe-Blanco, Diego,Bosque, Irene,Gonzalez-Gomez, Jose C.
, p. 14473 - 14485 (2020)
A straightforward and scalable methodology to synthesize diphenyl arylphosphonates at 20 °C within 1-2 h is reported using inexpensive SA as the catalytic promoter of the reaction. Mechanistic investigations suggest that the reaction proceeds via radical-radical coupling, consistent with the so-called persistent radical effect. The reaction tolerated a wide range of functional groups and heteroaromatic moieties. The synthetic usefulness and the unique reactivity of the obtained phosphonates were demonstrated in different one-step transformations.
Copper nanoparticles (CuNPs) catalyzed chemoselective reduction of nitroarenes in aqueous medium
Chand, Dillip Kumar,Rai, Randhir
, (2021/08/20)
Abstract: A procedure for practical synthesis of CuNPs from CuSO4·5H2O is established, under appropriate reaction conditions, using rice (Oryza sativa) as an economic source of reducing as well as a stabilizing agent. Optical and microscopic techniques are employed for the characterization of the synthesized CuNPs and the sizes of the particles were found to be in the range of 8 ± 2 nm. The nanoparticles are used as a catalyst for chemoselective reduction of aromatic nitro compounds to corresponding amines under ambient conditions and water as a reaction medium. Graphic abstract: CuNPs are synthesized using hydrolysed rice and used as catalyst for chemoselective reduction of nitroarenes to their corresponding amines in water. [Figure not available: see fulltext.]
Preparation method of aminoacetanilide
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Paragraph 0046-0064, (2021/01/29)
The invention belongs to the technical field of dye intermediate production, and particularly relates to a preparation method of aminoacetanilide, which comprises the following steps of 1) adding an acetate compound, phenylenediamine and a catalyst triethylene diamine into a reactor, and uniformly mixing to obtain a mixed solution, 2) under the protection of nitrogen, heating the mixed solution to65-90 DEG C, dropwise adding acetic acid, and reacting for 4-9 hours after dropwise adding is finished, and 3) after the reaction is finished, cooling to 15-25 DEG C, standing for 5-8 hours, filtering, fully washing a filter cake with n-butyl alcohol, and drying in vacuum at 80 DEG C for 6 hours to obtain aminoacetanilide. Aminoacetanilide is synthesized by using an acetate method, acetic anhydride which is high in price and easy to prepare drugs is not used, the production cost is reduced, and the method is suitable for industrial production; the method has the advantages of few reaction steps, no generation of waste acid, waste water and waste salt and no pollution to the environment; the yield (based on the weight of phenylenediamine) of the aminoacetanilide product prepared by the method is up to 97% or above, and the purity is up to 98% or above.
Applicability of aluminum amalgam to the reduction of arylnitro groups
Luzzio, Frederick A.,Monsen, Paige J.
supporting information, (2020/11/02)
An array of arylnitro compounds with various functionality were treated with freshly-prepared aluminum amalgam in THF/water solution and resulted in the corresponding arylamines. The Al(Hg)-mediated reductions are relatively rapid with consumption of the amalgam and disappearance of starting material occurring over 20–30 min. The workup of the reductions involves only removal of the insoluble by-products by filtration followed by concentration. Only in some cases is chromatography required to secure the pure product. The desired arylamines are furnished in quantities of 25–100 mg, which in some cases, could be taken on to the next reaction without further purification. Reductions of 4-nitrobenzyl derivatives of carbohydrates or nucleosides were selective in affording the corresponding 4-aminobenzyl products. To show applicability in click chemistry, selected aminobenzyl products are directly azidated to yield products that were then used in click reactions to afford the corresponding 1,2,3-triazoles.
2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase
Bayliss, Richard,Boxall, Kathy,Carbain, Benoit,Coxon, Christopher R.,Fry, Andrew M.,Golding, Bernard T.,Griffin, Roger J.,Hardcastle, Ian R.,Harnor, Suzannah J.,Mas-Droux, Corine,Matheson, Christopher J.,Newell, David R.,Richards, Mark W.,Sivaprakasam, Mangaleswaran,Turner, David,Cano, Céline
supporting information, p. 707 - 731 (2020/08/24)
Renewed interest in covalent inhibitors of enzymes implicated in disease states has afforded several agents targeted at protein kinases of relevance to cancers. We now report the design, synthesis and biological evaluation of 6-ethynylpurines that act as covalent inhibitors of Nek2 by capturing a cysteine residue (Cys22) close to the catalytic domain of this protein kinase. Examination of the crystal structure of the non-covalent inhibitor 3-((6-cyclohexylmethoxy-7H-purin-2-yl)amino)benzamide in complex with Nek2 indicated that replacing the alkoxy with an ethynyl group places the terminus of the alkyne close to Cys22 and in a position compatible with the stereoelectronic requirements of a Michael addition. A series of 6-ethynylpurines was prepared and a structure activity relationship (SAR) established for inhibition of Nek2. 6-Ethynyl-N-phenyl-7H-purin-2-amine [IC50 0.15 μM (Nek2)] and 4-((6-ethynyl-7H-purin-2-yl)amino)benzenesulfonamide (IC50 0.14 μM) were selected for determination of the mode of inhibition of Nek2, which was shown to be time-dependent, not reversed by addition of ATP and negated by site directed mutagenesis of Cys22 to alanine. Replacement of the ethynyl group by ethyl or cyano abrogated activity. Variation of substituents on the N-phenyl moiety for 6-ethynylpurines gave further SAR data for Nek2 inhibition. The data showed little correlation of activity with the nature of the substituent, indicating that after sufficient initial competitive binding to Nek2 subsequent covalent modification of Cys22 occurs in all cases. A typical activity profile was that for 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide [IC50 0.06 μM (Nek2); GI50 (SKBR3) 2.2 μM] which exhibited >5-10-fold selectivity for Nek2 over other kinases; it also showed > 50% growth inhibition at 10 μM concentration against selected breast and leukaemia cell lines. X-ray crystallographic analysis confirmed that binding of the compound to the Nek2 ATP-binding site resulted in covalent modification of Cys22. Further studies confirmed that 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide has the attributes of a drug-like compound with good aqueous solubility, no inhibition of hERG at 25 μM and a good stability profile in human liver microsomes. It is concluded that 6-ethynylpurines are promising agents for cancer treatment by virtue of their selective inhibition of Nek2. This journal is
Probing 2H-Indazoles as Templates for SGK1, Tie2, and SRC Kinase Inhibitors
Schoene, Jens,Gazzi, Thais,Lindemann, Peter,Christmann, Mathias,Volkamer, Andrea,Nazaré, Marc
, p. 1514 - 1527 (2019/08/07)
The broader and systematic application of a novel scaffold is often hampered by the unavailability of a short and reliable synthetic access. We investigated a new strategy for the design and synthesis of an array of N2-substituted aza-2H-indazole derivatives as potential kinase inhibitors. Guided by a rational ligand alignment approach to qualify the so-far underrepresented aza-2H-indazole scaffold, indazoles were connected at the N2 position with a phenyl spacer and an arylsulfonamide or amide linkage. Initial profiling against a panel of 30 kinases confirmed the in silico predicted selectivity bias. A synthesized focused library of 52 different aza-2H-indazole derivatives showed good initial selective inhibition against SGK1, Tie2, and SRC kinases, with the best representatives having IC50 values in the range of 500 nm. In a comparative computational study, these data were analyzed and rationalized in light of docking studies.
Synergistic effects in Fe nanoparticles doped with ppm levels of (Pd + Ni). A new catalyst for sustainable nitro group reductions
Pang, Haobo,Gallou, Fabrice,Sohn, Hyuntae,Camacho-Bunquin, Jeffrey,Delferro, Massimiliano,Lipshutz, Bruce H.
supporting information, p. 130 - 135 (2018/01/12)
A remarkable synergistic effect has been uncovered between ppm levels of Pd and Ni embedded within iron nanoparticles that leads to mild and selective catalytic reductions of nitro-containing aromatics and heteroaromatics in water at room temperature. NaBH4 serves as the source of inexpensive hydride. Broad substrate scope is documented, along with several other features including: low catalyst loading, low residual metal in the products, and recycling of the catalyst and reaction medium, highlight the green nature of this new technology.
Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase
Tahara, Yu-Ki,Auld, Douglas,Ji, Debin,Beharry, Andrew A.,Kietrys, Anna M.,Wilson, David L.,Jimenez, Marta,King, Daniel,Nguyen, Zachary,Kool, Eric T.
supporting information, p. 2105 - 2114 (2018/02/19)
The activity of DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1), which excises oxidized base 8-oxoguanine (8-OG) from DNA, is closely linked to mutagenesis, genotoxicity, cancer, and inflammation. To test the roles of OGG1-mediated repair in these pathways, we have undertaken the development of noncovalent small-molecule inhibitors of the enzyme. Screening of a PubChem-annotated library using a recently developed fluorogenic 8-OG excision assay resulted in multiple validated hit structures, including selected lead hit tetrahydroquinoline 1 (IC50 = 1.7 μM). Optimization of the tetrahydroquinoline scaffold over five regions of the structure ultimately yielded amidobiphenyl compound 41 (SU0268; IC50 = 0.059 μM). SU0268 was confirmed by surface plasmon resonance studies to bind the enzyme both in the absence and in the presence of DNA. The compound SU0268 was shown to be selective for inhibiting OGG1 over multiple repair enzymes, including other base excision repair enzymes, and displayed no toxicity in two human cell lines at 10 μM. Finally, experiments confirm the ability of SU0268 to inhibit OGG1 in HeLa cells, resulting in an increase in accumulation of 8-OG in DNA. The results suggest the compound SU0268 as a potentially useful tool in studies of the role of OGG1 in multiple disease-related pathways.
