- Green Oxidation Process in the Synthesis of LLM-105 with H2O2/Peroxotungstate System and its Theoretical Study
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A new catalytic system was developed and applied to the oxidation reactions involved in the synthesis of LLM-105, in which protonated peroxotungstate combining chitosan was used as catalyst. With H2O2as oxidant, good to excellent yields could be achieved in the synthesis of pyrazine-1-oxide, 2,6-dimethoxypyrazine-1-oxide, 2,6-dichloropyrazine-1-oxide, and 2-chloro-6-methoxypyrazine-1-oxide without any addition of trifluoracetic acid, which provided a significant exploration toward novel and environmentally benign synthetic route for LLM-105. Theoretical studies were also carried out with Gaussian 03 to evaluate the oxidation process. All of the calculated data matched well with our experimental results.
- Zhu, Jie,Zhao, Xue-Jing,Wang, Peng-Cheng,Lu, Ming
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- C2-Selective, Functional-Group-Divergent Amination of Pyrimidines by Enthalpy-Controlled Nucleophilic Functionalization
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Synthesis of heteroaryl amines has been an important topic in organic chemistry because of their importance in small-molecule discovery. In particular, 2-Aminopyrimidines represent a highly privileged structural motif that is prevalent in bioactive molecules, but a general strategy to introduce the pyrimidine C2-N bonds via direct functionalization is elusive. Here we describe a synthetic platform for site-selective C-H functionalization that affords pyrimidinyl iminium salt intermediates, which then can be transformed into various amine products in situ. Mechanism-based reagent design allowed for the C2-selective amination of pyrimidines, opening the new scope of site-selective heteroaryl C-H functionalization. Our method is compatible with a broad range of pyrimidines with sensitive functional groups and can access complex aminopyrimidines with high selectivity.
- Ham, Won Seok,Choi, Hoonchul,Zhang, Jianbo,Kim, Dongwook,Chang, Sukbok
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supporting information
p. 2885 - 2892
(2022/02/23)
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- A Biocatalytic Synthesis of Heteroaromatic N-Oxides by Whole Cells of Escherichia coli Expressing the Multicomponent, Soluble Di-Iron Monooxygenase (SDIMO) PmlABCDEF
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Aromatic N-oxides (ArN?OX) are desirable biologically active compounds with a potential for application in pharmacy and agriculture industries. As biocatalysis is making a great impact in organic synthesis, there is still a lack of efficient and convenient enzyme-based techniques for the production of aromatic N-oxides. In this study, a recombinant soluble di-iron monooxygenase (SDIMO) PmlABCDEF overexpressed in Escherichia coli was showed to produce various aromatic N-oxides. Out of 98 tested N-heterocycles, seventy were converted to the corresponding N-oxides without any side oxidation products. This whole-cell biocatalyst showed a high activity towards pyridines, pyrazines, and pyrimidines. It was also capable of oxidizing bulky N-heterocycles with two or even three aromatic rings. Being entirely biocatalytic, our approach provides an environmentally friendly and mild method for the production of aromatic N-oxides avoiding the use of strong oxidants, organometallic catalysts, undesirable solvents, or other environment unfriendly reagents. (Figure presented.).
- Petkevi?ius, Vytautas,Vaitekūnas, Justas,Taurait?, Daiva,Stankevi?iūt?, Jonita,?arlauskas, Jonas,??nas, Narimantas,Me?kys, Rolandas
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supporting information
p. 2456 - 2465
(2019/01/25)
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- Strategic Approach on N-Oxides in Gold Catalysis – A Case Study
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An extensive kinetic study of selected key reactions of (oxidative) gold catalysis concentrates on the decrease of the catalytic activity due to inhibition of the gold(I) catalyst caused by pyridine derivatives that are obtained as by-products if N-oxides are applied as oxygen donors. The choice of the examined pyridine derivatives and their corresponding N-oxides has been made regardless of their commercial availability; particular attention has been paid to the practical benefit which up to now has been neglected in most of the reaction screenings. The test reactions were monitored by GC and 1H NMR spectroscopy. The received reaction constants provide information concerning a correlation between the electronic structure of the heterocycle and the catalytic activity. Based on the collected kinetic data, it was possible to develop a basic set of three N-oxides which have to be taken into account in further oxidative gold(I)-catalyzed reactions. (Figure presented.).
- Schie?l, Jasmin,Stein, Philipp M.,Stirn, Judith,Emler, Kirsten,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
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supporting information
p. 725 - 738
(2018/10/20)
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- Pd-Catalyzed Direct C-H Alkenylation and Allylation of Azine N -Oxides
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A Pd-catalyzed direct C2-alkenylation of azine N-oxides with allyl acetate is disclosed. The products are formed through an allylation/isomerization cascade process. The use of a tri-tert-butylphosphonium salt as the ligand precursor and KF is mandatory for optimal yields. When cinnamyl acetate is used, the same catalytic system promotes C2-cinnamylation of the azine N-oxide without subsequent isomerization. A mechanism is proposed on the basis of experimental studies and DFT calculations.
- Roudesly, Fares,Veiros, Luis F.,Oble, Julie,Poli, Giovanni
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supporting information
p. 2346 - 2350
(2018/04/30)
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- Synthesis of N,N-Dioxopyridazines
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Despite many efforts, one of the smallest heterocycles containing two nitrogen atoms, pyridazine, could not be converted to its N,N-dioxide (see, however, Nakadate et al. Chem. Pharm. Bull. 1970, 18, 1211-1218). HOF·CH3CN, made easily from diluted fluorine, was able to accomplish this task in a fast reaction with good yields.
- Rozen, Shlomo,Shaffer, Avshalom
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supporting information
p. 4707 - 4709
(2017/09/23)
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- Visible-Light-Induced C2 Alkylation of Pyridine N-Oxides
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A photoredox catalytic method has been developed for the direct C2 alkylation of pyridine N-oxides. This reaction is compatible with a range of synthetically relevant functional groups for providing efficient synthesis of a variety of C2-alkylated pyridine N-oxides under mild conditions. Mechanistic studies are consistent with the generation of a radical intermediate along the reaction pathway.
- Zhang, Wen-Man,Dai, Jian-Jun,Xu, Jun,Xu, Hua-Jian
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p. 2059 - 2066
(2017/02/26)
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- Stabilizing volatile liquid chemicals using co-crystallization
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A convenient, effective, and scalable protocol for stabilizing volatile liquid chemicals is reported. Through the use of halogen-bond driven co-crystal synthesis, several examples of liquid iodoperfluoroalkanes are transformed into crystalline materials with low-vapor pressure, considerable thermal stability, and moisture resistance. The target compounds can subsequently be re-generated through simple solvent-extractions.
- Aaker?y, Christer B.,Wijethunga, Tharanga K.,Benton, Joshua,Desper, John
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supporting information
p. 2425 - 2428
(2015/02/05)
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- Ranking relative hydrogen-bond strengths in hydroxybenzoic acids for crystal-engineering purposes
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Systematic co-crystallizations resulting in a total of six new crystal structures involving either 3-hydroxy- or 4-hydroxybenzoic acid, complemented by calculated molecular electrostatic potential surfaces and existing structural data, have shown that in a competitive molecular recognition situation, the -OH moiety is a more effective hydrogen-bond donor than the -COOH moiety which, in turn, highlights that electrostatic charge can offer more useful guidance than acidity for predicting competitive hydrogen-bond preferences.
- Aakeroey, Christer B.,Epa, Kanishka,Forbes, Safiyyah,Schultheiss, Nathan,Desper, John
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p. 14998 - 15003
(2013/11/06)
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- Experimental and theoretical molecular and electronic structures of the N-oxides of pyridazine, pyrimidine and pyrazine
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The structures of pyridazine N-oxide, pyrimidine N-oxide and pyrazine N-oxide have been determined by X-ray diffraction for the first time. Comparison with theoretical predictions of the equilibrium structures using the B3LYP method together with a cc-pVTZ basis set, show close agreement with the structural parameters observed, and experimental dipole moments, which suggests that the charge distribution is realistic. An 'atoms in molecules' (AIM) analysis of the computed wave-functions shows total electron densities rather different from the classical picture of a dative bond, whereas the same wave-functions subjected to Mulliken analysis show a more conventional view of the electron distribution. This latter procedure allows a bond dipole analysis of the N-oxide charge distribution.
- Aitken, R. Alan,Fodi, Bernd,Palmer, Michael H.,Slawin, Alexandra M.Z.,Yang, Jing
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experimental part
p. 5845 - 5851
(2012/09/08)
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- Use of N-oxide compounds in coupling reactions
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Metal-catalyzed coupling process comprising reacting a compound of general formula 1 with a compound A-X, to obtain a compound of general formula 2, which may further be converted to a compound of general formula 3
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Page/Page column 17-18
(2008/12/05)
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- Palladium-catalyzed cross-coupling reactions of diazine N-oxides with aryl chlorides, bromides, and iodides
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New aspects of N-oxides: Pyrazine, pyridazine, and pyrimidine N-oxides are regioselectively arylated with aryl iodides, bromides, and chlorides in the presence of a palladium catalyst (see scheme). The resulting products can be deoxygenated in high yield
- Leclerc, Jean-Philippe,Fagnou, Keith
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p. 7781 - 7786
(2007/10/03)
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- Oxidation methods for aromatic diazines: Substituted pyrazine-N-oxides, pyrazine-N,N′-dioxides, and 2,2′:6′,2″-terpyridine-1,1″-dioxide
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In the course of investigations into the intermolecular interactions of azaaromatic N-oxides it was necessary to perform oxidations of the pyridine and pyrazine moieties. Generally, it was found that direct oxidation with OXONE gave efficient preparation of pyrazine dioxides. Oxidation with dimethyldioxirane was used to preclude problems associated with the isolation of particularly hydrophilic pyrazine and pyrazine-N-oxides.
- McKay, Scott E.,Sooter, Joseph A.,Bodige, Satish G.,Blackstock, Silas C.
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p. 307 - 312
(2007/10/03)
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- The Mechanism of Thermal Eliminations. Part 20. The Relative Rates of Pyrolysis of the 2-Ethoxy, 2-Isopropoxy, and 2-t-Butoxy Derivatives of Pyrazine and Pyrimidine to Pyrazine-2-one, pyrimidin-2-one, respectively: Polarity of the Transition States and the Importance of Nucleophilic ...
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We have measured rates of thermal elimination of the title compounds to give the corresponding cyclic amides, between 587.0 and 698.5 K.The relative rates (primary:secondary:tertiary) at 600 K are 1:27.0:3720 for the pyrazines, and 1:26.4:4150 for the pyrimidines.These ratios are somewhat larger than for the corresponding 2-alkoxypyridines and suggest that C-O bond breaking is kinetically more significant in the pyrazines and pyrimidines, leading to a transition state with greater carbocationic character.This is consistent with electron withdrawal provided by the aza 'substituent' facilitating C-O bond cleavage.It does not however lead to a general increase in reactivity (as would be the case for pyrolysis of comparable esters) because this electron withdrawal reduces the nucleophilicity of the nitrogen involved in the elimination.This latter is particularly important for the primary and secondary compounds (which have more Ei-like transition states) than for the tertiary compounds, which therfore show a normal reactivity vs. rate spread pattern.The importance of the nucleophilicity of the nitrogen in the alkoxy-heterocycles, and its ability to be modified, may stem in part from the dual pathway available for transmission of substituent effects in the aromatic ring.
- Al-Awardi, Nouria,Taylor, Roger
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p. 1585 - 1588
(2007/10/02)
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