4764-13-0Relevant academic research and scientific papers
Br?nsted acid catalysed chemo- andortho-selective aminomethylation of phenol
Li, Dongdong,Liu, Lu,Peng, Dan,Tang, Zhiqiong,Yue, Yidi
supporting information, p. 5777 - 5781 (2021/07/12)
We have developed a Br?nsted acid catalysed highlyortho-selective functionalization of free phenols with readily availableN,O-acetals under mild conditions, furnishing various corresponding aminomethylated phenol products in moderate to excellent yields. The salient features of this transformation include mild conditions, good substrate scope, excellentortho-selectivity, high efficiency, and ease of further transformation.
Ruthenium-Catalyzed Aminomethylation and Methylation of Phenol Derivatives Utilizing Methanol as the C1 Source
Kim, Seoksun,Hong, Soon Hyeok
, p. 798 - 810 (2017/03/11)
A reaction involving ortho-aminomethylation of phenol was developed via ruthenium-catalyzed dehydrogenation of methanol, an environmentally benign C1 building block, without the use of reactive reagents. The reaction was successfully applied to a range of substrates. When naphthol was employed instead of phenol, only methylation was observed. On the basis of various mechanistic studies, we propose that formamide barely participates in the reaction, which mainly occurs through an iminium cation intermediate. The difference in the reactivities of phenol and naphthol is attributable to stronger basicity of naphtholate as a conjugate base owing to its lower aromaticity. Plausible reaction pathways were proposed for both reactions. (Figure presented.).
Novel bis-arylalkylamines as myeloperoxidase inhibitors: Design, synthesis, and structure-activity relationship study
Aldib, Iyas,Gelbcke, Michel,Soubhye, Jalal,Prévost, Martine,Furtmüller, Paul G.,Obinger, Christian,Elfving, Betina,Alard, Ibaa Chikh,Roos, Goedele,Delporte, Cédric,Berger, Gilles,Dufour, Damien,Zouaoui Boudjeltia, Karim,Nève, Jean,Dufrasne, Francois,Van Antwerpen, Pierre
supporting information, p. 746 - 762 (2016/08/18)
Human myeloperoxidase (MPO) plays an important role in innate immunity but also aggravates tissue damage by oxidation of biomolecules at sites of inflammation. As a result from a recent high-throughput virtual screening approach for MPO inhibitors, bis-2,2′-[(dihydro-1,3(2H,4H) pyrimidinediyl)bis(methylene)]phenol was detected as a promising lead compound for inhibition of the MPO-typical two-electron oxidation of chloride to hypochlorous acid (IC50= 0.5 μM). In the present pharmacomodulation study, 37 derivatives of this lead compound were designed and synthesized driven by comprehensive docking studies and the impact on the chlorination activity of MPO. We describe the structural requirements for optimum (i) binding to the heme periphery and (ii) inhibition capacity. Finally, the best three inhibitors (bis-arylalkylamine derivatives) were probed for interaction with the MPO redox intermediates Compound I and Compound II. Determined apparent bimolecular rate constants together with determination of reduction potential and nucleophilicity of the selected compounds allowed us to propose a mechanism of inhibition. The best inhibitor was found to promote the accumulation of inactive form of MPO-Compound II and has IC50= 54 nM, demonstrating the successful approach of the drug design. Due to the similarity of ligand interactions between MPO and serotonine transporter, the selectivity of this inhibitor was also tested on the serotonin transporter providing a selectivity index of 14 (KiSERT/IC50MPO).
Syntheses and in Vitro Antiplasmodial Activity of Aminoalkylated Chalcones and Analogues
Wilhelm, Anke,Kendrekar, Pravin,Noreljaleel, Anwar E. M.,Abay, Efrem T.,Bonnet, Susan L.,Wiesner, Lubbe,De Kock, Carmen,Swart, Kenneth J.,Van Der Westhuizen, Jan Hendrik
supporting information, p. 1848 - 1858 (2015/09/08)
(Chemical Equqation Presented). A series of readily synthesized and inexpensive aminoalkylated chalcones and diarylpropane analogues (1-55) were synthesized and tested against chloroquinone-sensitive (D10 and NF54) and -resistant (Dd2 and K1) strains of Plasmodium falciparum. Hydrogenation of the enone to a diarylpropane moiety increased antiplasmodial bioactivity significantly. The influence of the structure of the amine moiety, A-ring substituents, propyl vs ethyl linker, and chloride salt formation on further enhancing antiplasmodial activity was investigated. Several compounds have IC50 values similar to or better than chloroquine (CQ). The most active compound (26) had an IC50 value of 0.01 μM. No signs of resistance were detected, as can be expected from compounds with structures unrelated to CQ and other currently used antimalarial drugs. Toxicity tests (in vitro CHO cell assay) gave high SI indices.
Highly efficient and eco-friendly synthesis of tertiary amines by reductive alkylation of aldehydes with secondary amines over a Pt nanowires catalyst
Wu, Junjie,Lu, Shuanglong,Ge, Danhua,Gu, Hongwei
, p. 81395 - 81398 (2015/10/06)
Plentiful tertiary amine derivates are synthesized by direct formation of tertiary amines by the interaction of aldehydes with secondary amines over Pt nanowires under mild conditions. This method offers a green and rapid approach to transform secondary amines into various tertiary amines.
Copper(I)-catalyzed coupling reaction of aryl boronic acids with N,O-acetals and N,N-aminals under atmosphere leading to α-aryl glycine derivatives and diarylmethylamine derivatives
Sakai, Norio,Hori, Hiroaki,Yoshida, Yoshihiro,Konakahara, Takeo,Ogiwara, Yohei
, p. 4722 - 4729 (2015/07/27)
We demonstrated a copper(I)-catalyzed coupling reaction of aryl boronic acids with N,O-acetals and N,N-aminals leading to the synthesis of α-aryl glycines and diarylmethylamines. Under an ambient atmosphere, this catalytic system could be applied to the activation of a C(sp3)-O bond of N,O-acetals with an ester and an aryl group, or without a coordinating substituent, as well as to a C(sp3)-N bond of N,N-aminals.
Structural and medium effects on the reactions of the cumyloxyl radical with intramolecular hydrogen bonded phenols. the interplay between hydrogen-bonding and acid-base interactions on the hydrogen atom transfer reactivity and selectivity
Salamone, Michela,Amorati, Riccardo,Menichetti, Stefano,Viglianisi, Caterina,Bietti, Massimo
, p. 6196 - 6205 (2014/07/21)
A time-resolved kinetic study on the reactions of the cumyloxyl radical (CumO?) with intramolecularly hydrogen bonded 2-(1-piperidinylmethyl)phenol (1) and 4-methoxy-2-(1-piperidinylmethyl)phenol (2) and with 4-methoxy-3-(1-piperidinylmethyl)phenol (3) has been carried out. In acetonitrile, intramolecular hydrogen bonding protects the phenolic O-H of 1 and 2 from attack by CumO? and hydrogen atom transfer (HAT) exclusively occurs from the C-H bonds that are α to the piperidine nitrogen (α-C-H bonds). With 3 HAT from both the phenolic O-H and the α-C-H bonds is observed. In the presence of TFA or Mg(ClO 4)2, protonation or Mg2+ complexation of the piperidine nitrogen removes the intramolecular hydrogen bond in 1 and 2 and strongly deactivates the α-C-H bonds of the three substrates. Under these conditions, HAT to CumO? exclusively occurs from the phenolic O-H group of 1-3. These results clearly show that in these systems the interplay between intramolecular hydrogen bonding and Br?nsted and Lewis acid-base interactions can drastically influence both the HAT reactivity and selectivity. The possible implications of these findings are discussed in the framework of the important role played by tyrosyl radicals in biological systems.
Divergent reaction: Metal & oxidant free direct C-H aryloxylation and hydride free formal reductive N-benzylation of N-heterocycles
Mahato, Sujit,Haque, Md Ashraful,Dwari, Soumita,Jana, Chandan K.
, p. 46214 - 46217 (2015/02/19)
Metal, oxidant and other additive-free novel methods for direct C-H aryloxylation of aliphatic amines are developed. In the presence of excess amine, the course of the reaction was diverted, producing various arylmethylamines via hydride-free formal reductive amination. Involvement of a quinone methide intermediate was revealed from mechanistic studies. This journal is
Aerobic oxidative heck/dehydrogenation reactions of cyclohexenones: Efficient access to meta-substituted phenols
Izawa, Yusuke,Zheng, Changwu,Stahl, Shannon S.
supporting information, p. 3672 - 3675 (2013/04/23)
Jockeying for the (meta)position: A new dicationic palladium(II) catalyst, employing a 6,6′-dimethyl-2,2′-bipyridine ligand, promotes both the aerobic oxidative Heck coupling and dehydrogenation reactions of cyclohexenones. These reactions may be combined in a one-pot sequence to enable the straightforward synthesis of meta-substituted phenols (see scheme). Copyright
Anionic ortho-fries rearrangement, a facile route to arenol-based mannich bases
Assimomytis, Nikos,Sariyannis, Yiannis,Stavropoulos, Georgios,Tsoungas, Petros G.,Varvounis, George,Cordopatis, Paul
experimental part, p. 2777 - 2782 (2010/03/03)
Phenol and 1-naphthol-based carbamates undergo the anionic ortho-Fries rearrangement to their corresponding amides. Bulky substitution at position 8 of 1-naphthol-based carbamates makes the rearrangement an exclusive reaction, even at -90 C, under a variety of conditions. The amides can be efficiently reduced to the corresponding Mannich bases. A novel route to 7-[(dialkylamino)methyl]-8- hydroxy-1-naphthaldehydes is presented.
