4165-62-2Relevant academic research and scientific papers
A density functional, infrared linear dichroism, and normal coordinate study of phenol and its deuterated derivatives: Revised interpretation of the vibrational spectra
Keresztury, Gabor,Billes, Ferenc,Kubinyi, Miklos,Sundius, Tom
, p. 1371 - 1380 (1998)
The assignment of the vibrational spectra of phenol has been reexamined on the basis of Raman and new IR measurements and theoretical analysis of the normal modes of vibrations in the electronic ground state. The infrared spectra of C6H5OH, C6D5OD, and C6D5OH have been studied in solution and vapor phases, as well as has the Raman spectra in solutions. New experimental data were obtained from infrared linear dichroism (IR-LD) studies of phenol aligned in uniaxially oriented nematic liquid crystal solution. The measured dichroic ratios and orientation factors indicate an effective Cs symmetry of the molecule with coplanar orientation of OH bond with the benzene ring and supply unique information on the extent of symmetry lowering of benzene normal modes. The fundamental vibrational frequencies, force constants, and dipole derivatives have been calculated by ab initio quantum chemical methods applying the B3P86 density functional approximation with 6-311G** basis set. The force field optimized by means of a least-squares scaling procedure for phenol-d0 (using six scale factors) was used to calculate the frequencies (with a mean deviation from the observed values less than 1%), normal modes, potential energy distributions, transition moment vectors, and IR intensities for phenol-d0, -d1, -d5, and -d6 isotopomers. Compared to the deviations between the calculated and observed absorption intensities, a more satisfactory correlation was found between the calculated and experimentally determined vibrational transition moment directions. The results indicate unanimously that the perturbation of the normal modes of benzene by the asymmetric hydroxyl substituent is so great that the previous practice of assigning the normal vibrations of phenol to those of benzene or even to C2v symmetry species is not justified.
Acid p Ka Dependence in O-O Bond Heterolysis of a Nonheme FeIII-OOH Intermediate to Form a Potent FeVa? O Oxidant with Heme Compound I-Like Reactivity
Xu, Shuangning,Draksharapu, Apparao,Rasheed, Waqas,Que, Lawrence
, p. 16093 - 16107 (2019)
Protons play essential roles in natural systems in controlling O-O bond cleavage of peroxoiron(III) species to give rise to the high-valent iron oxidants that carry out the desired transformations. Herein, we report kinetic and mechanistic evidence that acids can control the mode of O-O bond cleavage for a nonheme S = 1/2 FeIII-OOH species [(BnTPEN)FeIII(OOH)]2+ (2, BnTPEN = N-benzyl-N,N′,N′-tris(2-pyridylmethyl)-1,2-diaminoethane). Addition of acids having pKa values of >8.5 in CH3CN results in O-O bond homolysis, leading to the formation of hydroxyl radicals that give rise to alcohol/ketone (A/K) ratios of around 1 in the oxidation of cyclohexane. However, the introduction of acids with pKa values of III-OOH intermediate at -40 °C. These results implicate the generation of a highly reactive FeV? O species via proton-assisted O-O bond heterolysis of the FeIII-OOH intermediate, which is unprecedented for nonheme iron complexes supported by neutral pentadentate ligands and serves as a nonheme analogue for heme enzyme compounds I.
Aerobic C?C Bond Cleavage Catalyzed by Whole-Cell Cultures of the White-Rot Fungus Dichomitus albidofuscus
Zhuk, Tatyana S.,Babkina, Valeriia V.,Zorn, Holger
, (2021/12/30)
Whole-cell cultures of the basidiomycetous white-rot fungus Dichomitus albidofuscus exhibit varying catalytic activity towards aromatic compounds depending on the growth stage. This study reveals the catalytic behavior of mature whole-cell cultures that effectively catalyze a C?C bond cleavage oxidizing toluene, benzaldehyde and acetophenone to phenol. The reaction products were analyzed by GC-MS and NMR techniques. To exclude the de novo formation of phenol by the fungus, its origin has been proven by bioconversion of benzaldehyde-d5. The key step involves an aerobic Baeyer-Villiger type rearrangement where the incorporation of oxygen into the product was confirmed based on isotope labelling experiments with 18O2. Intermediate esters were not found in reaction mixture presumably due to the detected esterase activity in the mycelium as well as in supernatant of the whole-cell cultures. As a result, the sequence of biocatalytic reactions catalyzed by D. albidofuscus for the degradation of toluene via C?C bond cleavage has been disclosed.
Efficient continuous-flow HD exchange reaction of aromatic nuclei in D2O/2-PrOH mixed solvent in a catalyst cartridge packed with platinum on carbon beads
Park, Kwihwan,Ito, Naoya,Yamada, Tsuyoshi,Sajiki, Hironao
supporting information, p. 600 - 605 (2021/03/29)
Herein, a continuous-flow deuteration methodology for various aromatic compounds is developed based on heterogeneous platinum-catalyzed hydrogen-deuterium exchange. The reaction entails the transfer of a substrate dissolved in a mixed solvent of 2-propanol and deuterium oxide into a catalyst cartridge packed with platinum on carbon beads (Pt/CB). Pt/ CB could be continuously used without significant deterioration of catalyst activity for at least 24 h. Deuteration proceeded within 60 s of the substrate solutions being passed through the Pt/CB layer in the Pt/CB-packed cartridge.
Entry to 1,2,3,4-Tetrasubstituted Arenes through Addressing the " Meta Constraint" in the Palladium/Norbornene Catalysis
Dong, Guangbin,Liu, Peng,Wang, Jianchun,Xu, Xiaolong,Zhou, Yun
, p. 3050 - 3059 (2020/03/10)
Arenes with four different contiguous substituents, i.e. 1,2,3,4-tetrasubstituted arenes, are commonly found in bioactive compounds, but they are nontrivial to access via conventional methods. Through addressing the "meta constraint" in the palladium/norbornene (Pd/NBE) cooperative catalysis, which is the difficulty of tolerating a sizable meta substituent in aryl halide substrates, here a modular and regioselective approach is realized for preparing 1,2,3,4-tetrasubstituted arenes. One key is the use of a C2-amide-substituted NBE, and a combined experimental and computational study reveals its role in promoting the NBE insertion and the ortho C-H metalation steps. The scope is broad: A variety of electrophiles and nucleophiles could be introduced to the ortho and ipso positions, respectively, with 1,4-disubstituted aryl halides, leading to diverse unsymmetrical contiguous tetrasubstituted arenes. Application of this approach has been demonstrated in streamlined syntheses of several bioactive compounds.
Single-step benzene hydroxylation by cobalt(ii) catalysts: Via a cobalt(iii)-hydroperoxo intermediate
Anandababu, Karunanithi,Mayilmurugan, Ramasamy,Muthuramalingam, Sethuraman,Velusamy, Marappan
, p. 2540 - 2548 (2020/05/14)
The cobalt(ii) complexes of 4N tetradentate ligands have been synthesized and characterized as the catalysts for phenol synthesis in a single step. The molecular structure of the complexes showed a geometry in between square pyramidal and trigonal bipyramidal (τ, 0.49-0.88) with Co-Namine and Co-NPy bond distances of 2.104-2.254 ? and 2.043-2.099 ?, respectively. The complexes exhibited a Co2+/Co3+ redox potential around 0.489-0.500 V vs. Ag/Ag+ in acetonitrile. The complexes catalyzed hydroxylation of benzene using H2O2 (30%) and afforded phenol selectively as the major product. A maximum yield of phenol up to 29% and turnover number (TON) of 286 at 60 °C, and a yield of 19% and TON of 191 at 25 °C are achieved. This is the highest catalytic performance reported using cobalt(ii) complexes as catalysts to date. This aromatic hydroxylation presumably proceeded via a cobalt(iii)-hydroperoxo species, which was characterized by ESI-MS, and vibrational and electronic spectral methods. The formation of key intermediate [(L)CoIII(OOH)]2+ was accompanied by the appearance of the characteristic O → Co(iii) ligand to metal charge transfer (LMCT) transition around 488-686 nm and vibration modes at 832 cm-1 (O-OH) and 564 cm-1 (Co-O). The geometry of one of the catalytically active intermediates was optimized by DFT and its spectral properties were calculated by TD-DFT calculations. These data are comparable to the experimental observations. The kinetic isotope effect (KIE) values (0.98-1.07) support the involvement of cobalt-bound oxygen species as a key intermediate. Isotope-labeling experiments using H218O2 showed an 89% incorporation of 18O, revealing that H2O2 is the main oxygen supplier for phenol formation from benzene. The catalytic efficiencies of cobalt complexes are tuned by ligand architectures via their geometrical configurations and steric properties.
Cu(i) complexes obtained: Via spontaneous reduction of Cu(ii) complexes supported by designed bidentate ligands: Bioinspired Cu(i) based catalysts for aromatic hydroxylation
Kumari, Sheela,Muthuramalingam, Sethuraman,Dhara, Ashish Kumar,Singh,Mayilmurugan, Ramasamy,Ghosh, Kaushik
supporting information, p. 13829 - 13839 (2020/10/26)
Copper(i) complexes [Cu(L1-7)2](ClO4) (1-7) of bidentate ligands (L1-L7) have been synthesized via spontaneous reduction and characterized as catalysts for aromatic C-H activation using H2O2 as the oxidant. The single crystal X-ray structure of 1 exhibited a distorted tetrahedral geometry. All the copper(i) complexes catalyzed direct hydroxylation of benzene to form phenol with good selectivity up to 98%. The determined kinetic isotope effect (KIE) values, 1.69-1.71, support the involvement of a radical type mechanism. The isotope-labeling experiments using H218O2 showed 92% incorporation of 18O into phenol and confirm that H2O2 is the key oxygen supplier. Overall, the catalytic efficiencies of the complexes are strongly influenced by the electronic and steric factor of the ligand, which is fine-tuned by the ligand architecture. The benzene hydroxylation reaction possibly proceeded via a radical mechanism, which was confirmed by the addition of radical scavengers (TEMPO) to the catalytic reaction that showed a reduction in phenol formation. This journal is
Synthesis and biological evaluation of deuterated sofosbuvir analogs as HCV NS5B inhibitors with enhanced pharmacokinetic properties
Ao, Wangwei,Ma, Xueqin,Lin, Youping,Wang, Xiaojing,Song, Wei,Wang, Qinglin,Zhang, Xiquan,Xu, Hongjiang,Zhang, Yinsheng
, p. 215 - 229 (2019/05/07)
A series of deuterated sofosbuvir analogs were designed and prepared with the aim of improving their pharmacokinetic properties. The devised synthetic routes allow for site-selective deuterium incorporation with high levels of isotopic purity. As expected, the deuterated analogs (37-44) are as efficacious as sofosbuvir when tested in vitro inhibition of viral replication (replicon) assays. Compared with sofosbuvir, deuterated analog 40 displays improved in vivo pharmacokinetics profiles in rats and dogs in terms of the metabolite and the prodrug. The Cmax and area under the curve (AUC) of 40 in dogs were increased by 3.4- and 2.7-fold, respectively. Due to the enhanced pharmacokinetic properties and the great synthetic advantage of an inexpensive deuterium source (D2O) for 40, it was chosen for further investigation.
H-D Exchange Deuteration of Arenes at Room Temperature
Sawama, Yoshinari,Nakano, Akihiro,Matsuda, Takumi,Kawajiri, Takahiro,Yamada, Tsuyoshi,Sajiki, Hironao
supporting information, p. 648 - 653 (2019/02/14)
Arene nuclei efficiently underwent the hydrogen (H)-deuterium (D) exchange reaction catalyzed by platinum group metals on carbon in a mixed solvent of 2-propanol and D2O at room temperature to produce deuterium-labeled arenes. Platinum on carbon (Pt/C) and iridium on carbon (Ir/C) were applicable catalysts, and the various arenes bearing a carbonyl group, fluorine, phenolic hydroxy group, amino group, or phosphonic acid on the aromatic nucleus were effectively deuterated. Nonheating conditions are valuable for the scalable industrial preparation.
Deuterated nucleoside derivative
-
Paragraph 0077; 0078-0082, (2016/10/07)
The present invention relates to deuterated nucleoside derivative, particularly to a compound having a structure represented by a formula I or a pharmaceutically acceptable salt thereof. According to the present invention, the compound represented by the formula I has excellent pharmacokinetic properties and is expected to reduce the clinical dose so as to reduce the treatment and benefit more patients. The formula I is defined in the specification.
