90-52-8Relevant articles and documents
Minimization of Back-Electron Transfer Enables the Elusive sp3 C?H Functionalization of Secondary Anilines
Zhao, Huaibo,Leonori, Daniele
supporting information, p. 7669 - 7674 (2021/03/08)
Anilines are some of the most used class of substrates for application in photoinduced electron transfer. N,N-Dialkyl-derivatives enable radical generation α to the N-atom by oxidation followed by deprotonation. This approach is however elusive to monosubstituted anilines owing to fast back-electron transfer (BET). Here we demonstrate that BET can be minimised by using photoredox catalysis in the presence of an exogenous alkylamine. This approach synergistically aids aniline SET oxidation and then accelerates the following deprotonation. In this way, the generation of α-anilinoalkyl radicals is now possible and these species can be used in a general sense to achieve divergent sp3 C?H functionalization.
Merging Annulation with Ring Deconstruction: Synthesis of (E)-3-(2-Acyl-1 H-benzo[ d]imidazol-4-yl)acrylaldehyde Derivatives via I2/FeCl3-Promoted Dual C(sp3)-H Amination/C-N Bond Cleavage
Xu, Cheng,Yin, Guodong,Jia, Feng-Cheng,Wu, Yan-Dong,Wu, An-Xin
supporting information, p. 2559 - 2564 (2021/04/13)
An unprecedented I2/FeCl3-promoted cascade reaction of aryl methyl ketones with 8-aminoquinolines for the convenient synthesis of (E)-3-(2-acyl-1H-benzo[d]imidazol-4-yl)acrylaldehydes was developed by merging annulation with ring deconstruction. This novel strategy unlocked the new reactivity of 8-aminoquinolines and provided an attractive platform for the ring opening of unactivated N-heteroaromatic compounds. Preliminary mechanistic investigation suggested that dual C(sp3)-H amination/C-N bond cleavage were key reaction steps. Furthermore, late-stage modification of the obtained products successfully delivered pyrazole and isoxazole derivatives, increasing the practicability and application potential of this methodology in organic synthesis.
8-amino-6-methoxyquinoline—tetrazole hybrids: Impact of linkers on antiplasmodial activity
Dolensky, Johanna,Hochegger, Patrick,Kaiser, Marcel,M?ser, Pascal,Saf, Robert,Seebacher, Werner,Weis, Robert
, (2021/09/20)
A new series of compounds was prepared from 6-methoxyquinolin-8-amine or its N-(2-aminoethyl) analogue via Ugi-azide reaction. Their linkers between the quinoline and the tert-butyltetrazole moieties differ in chain length, basicity and substitution. Compounds were tested for their antiplasmodial activity against Plasmodium falciparum NF54 as well as their cytotoxicity against L-6-cells. The activity and the cytotoxicity were strongly influenced by the linker and its substitution. The most active compounds showed good activity and promising selectivity.
High Turnover Pd/C Catalyst for Nitro Group Reductions in Water. One-Pot Sequences and Syntheses of Pharmaceutical Intermediates
Gallou, Fabrice,Li, Xiaohan,Lipshutz, Bruce H.,Takale, Balaram S.,Thakore, Ruchita R.
supporting information, p. 8114 - 8118 (2021/10/25)
Commercially available Pd/C can be used as a catalyst for nitro group reductions with only 0.4 mol % Pd loading. The reaction can be performed using either silane as a transfer hydrogenating agent or simply a hydrogen balloon (μ1 atm pressure). With this technology, a series of nitro compounds was reduced to the desired amines in high chemical yields. Both the catalyst and surfactant were recycled several times without loss of reactivity.
Synthesis and biological evaluation of benzhydryl-based antiplasmodial agents possessing Plasmodium falciparum chloroquine resistance transporter (PfCRT) inhibitory activity
Relitti, Nicola,Federico, Stefano,Pozzetti, Luca,Butini, Stefania,Lamponi, Stefania,Taramelli, Donatella,D'Alessandro, Sarah,Martin, Rowena E.,Shafik, Sarah H.,Summers, Robert L.,Babij, Simone K.,Habluetzel, Annette,Tapanelli, Sofia,Caldelari, Reto,Gemma, Sandra,Campiani, Giuseppe
supporting information, (2021/03/08)
Due to the surge in resistance to common therapies, malaria remains a significant concern to human health worldwide. In chloroquine (CQ)-resistant (CQ-R) strains of Plasmodium falciparum, CQ and related drugs are effluxed from the parasite's digestive vacuole (DV). This process is mediated by mutant isoforms of a protein called CQ resistance transporter (PfCRT). CQ-R strains can be partially re-sensitized to CQ by verapamil (VP), primaquine (PQ) and other compounds, and this has been shown to be due to the ability of these molecules to inhibit drug transport via PfCRT. We have previously developed a series of clotrimazole (CLT)-based antimalarial agents that possess inhibitory activity against PfCRT (4a,b). In our endeavor to develop novel PfCRT inhibitors, and to perform a structure-activity relationship analysis, we synthesized a new library of analogues. When the benzhydryl system was linked to a 4-aminoquinoline group (5a-f) the resulting compounds exhibited good cytotoxicity against both CQ-R and CQ-S strains of P. falciparum. The most potent inhibitory activity against the PfCRT-mediated transport of CQ was obtained with compound 5k. When compared to the reference compound, benzhydryl analogues of PQ (5i,j) showed a similar activity against blood-stage parasites, and a stronger in vitro potency against liver-stage parasites. Unfortunately, in the in vivo transmission blocking assays, 5i,j were inactive against gametocytes.
Visible-Light-Photocatalyzed Reductions of N-Heterocyclic Nitroaryls to Anilines Utilizing Ascorbic Acid Reductant
Todorov, Aleksandar R.,Aikonen, Santeri,Muuronen, Mikko,Helaja, Juho
supporting information, p. 3764 - 3768 (2019/05/24)
A photoreductive protocol utilizing [Ru(bpy)3]2+ photocatalyst, blue light LEDs, and ascorbic acid (AscH2) has been developed to reduce nitro N-heteroaryls to the corresponding anilines. Based on experimental and computational results and previous studies, we propose that the reaction proceeds via proton-coupled electron transfer between AscH2, photocatalyst, and the nitro N-heteroaryl. The method offers a green catalytic procedure to reduce, e.g., 4-/8-nitroquinolines to the corresponding aminoquinolines, substructures present in important antimalarial drugs.
Visible Light-Promoted Photocatalytic C-5 Carboxylation of 8-Aminoquinoline Amides and Sulfonamides via a Single Electron Transfer Pathway
Sen, Chiranjit,Sahoo, Tapan,Singh, Harshvardhan,Suresh, Eringathodi,Ghosh, Subhash Chandra
, p. 9869 - 9896 (2019/08/20)
An efficient photocatalytic method was developed for the remote C5-H bond carboxylation of 8-aminoquinoline amide and sulfonamide derivatives. This methodology uses in situ generated ?CBr3 radical as a carboxylation agent with alcohol and is further extended to a variety of arenes and heteroarenes to synthesize the desired carboxylated product in moderate-to-good yields. The reaction proceeding through a single electron transfer pathway was established by a control experiment, and a butylated hydroxytoluene-trapped aryl radical cation intermediate in high-resolution mass spectrometry was identified.
Uncatalyzed, on water oxygenative cleavage of inert C-N bond with concomitant 8,7-amino shift in 8-aminoquinoline derivatives
Botla, Vinayak,Pilli, Navyasree,Malapaka, Chandrasekharam
supporting information, p. 1735 - 1742 (2019/04/08)
Oxygenative cleavage of an inert CAr-NH2 bond with concomitant 1,2 amine migration in 8-aminoquinoline derivatives is reported in water at room temperature. The reaction is highly atom- and step-economical as both C- and N-containing fragments of the C-N bond cleavage are incorporated into the target molecule and is effected without the need for N-oxide. The reaction is scalable to gram level, and the products are useful as electrophilic partners for coupling reactions, ligands in catalysis and bioactive compounds.
Systematic ligand variation to modulate the electrochemical properties of iron and manganese complexes
Rohner, Stefan S.,Kinzel, Niklas W.,Werlé, Christophe,Leitner, Walter
supporting information, p. 13205 - 13211 (2019/09/18)
A series of iron(+iii) and manganese(+ii) complexes based on the dpaqR-ligand system (dpaq = 2-[bis(pyridine-2-ylmethyl)]amino-N-quinolin-8-yl-acetamide) were investigated using cyclic voltammetry (CV) to elucidate how the electronic properties of the ligands influence the overpotential and catalytic current in the context of water oxidation catalysis. For the Fe-complexes an electron withdrawing NO2 or CF3 group attached to the 5-position of the quinoline unit increased the catalytic current, but only with a simultaneous increase of the overpotential. However, when a pyrene moiety was attached to the dipicolylamine unit of the ligand, the overpotential decreased with concomitant increase of the catalytic current. Although the manganese complexes showed no reversible formation of a molecular catalytically active species for water oxidation, the variations of the ligand scaffold affected largely the same trends in their electrochemical behavior.
Influence of Functionalized Substituents on the Electron-Transfer Abilities of Copper Guanidinoquinoline Complexes
Stanek, Julia,Konrad, Marc,Mannsperger, Johannes,Hoffmann, Alexander,Herres-Pawlis, Sonja
, p. 4997 - 5006 (2018/12/11)
The influence of functionalized ligands on the electron-transfer abilities of copper guanidinoquinoline complexes as entatic state models has been examined. An electron donating group (OCH3) or electron withdrawing group (Br) was introduced in 6-position of the quinoline unit of the ligands TMGqu and DMEGqu. The electron self-exchange rates k11 of the copper complexes with these ligands were determined using the Marcus cross relation. The k11 values of the functionalized complexes are smaller or equal to the values of their unsubstituted forms. These results were complemented by the examination of the reorganization energies of the electron-transfer via Eyring theory and DFT calculations. The higher reorganization energies of the [Cu(DMEG6Xqu)2]+/2+ (X = H, Br, OCH3) systems correspond with their decelerated electron-transfer velocities. Additionally, the calculated molecular electrostatic potentials show the influence of the functional groups on the electron-transfer. With the addition of the substituent a further charge distribution over the CH3O-/Br-group leads to a larger reorganization required during the oxidation reaction. The impact of the functionalization of the ligand on the electron-transfer of the [Cu(GUA6Xqu)2]+/2+ cations reveals a closer insight in the electronic structure of the complexes and its influence on their electron-transfer abilities.
