21898-84-0Relevant articles and documents
Photoinduced Reactivity in a Dispiro-1,2,4-trioxolane: Adamantane Ring Expansion and First Direct Observation of the Long-Lived Triplet Diradical Intermediates
Brás, Elisa M.,Cabral, Lília I. L.,Amado, Patrícia S. M.,Abe, Manabu,Cristiano, Maria L. S.,Fausto, Rui
, p. 4202 - 4210 (2020)
Dispiro-1,2,4-trioxolane, 1, an ozonide with efficient and broad antiparasitic activity, was synthesized and investigated using matrix isolation FTIR and EPR spectroscopies together with both B3LYP/6-311++G(3df,3dp) and M06-2X/6-311++G(3df,3dp) theoretical methods. Irradiations (λ ≥ 290 nm) of the matrix isolated 1 (Ar or N2) afforded exclusively 4-oxahomoadamantan-5-one, 4, and 1,4-cyclohexanedione, 5. These results suggested that the reaction proceeded via a dioxygen-centered diradical intermediate, formed upon homolytic cleavage of the labile peroxide bond, which regioselectively isomerized to form the more stable (secondary carbon-centered)/oxygen-centered diradical. In situ EPR measurements during the photolysis of 1 deposited in a MeTHF-matrix led to the detection of signals corresponding to two triplet species, one of which was short-lived while the other proved to be persistent at 10 K. These observations strongly support the proposed mechanism for the photogeneration of 4 and 5, which involves intramolecular rearrangement of the intermediate diradical species 2 to afford the triplet diradical 3.
Selective Aerobic Oxidation of Secondary C (sp3)-H Bonds with NHPI/CAN Catalytic System
Wang, Lingyao,Zhang, Yuanbin,Yuan, Haoran,Du, Renfeng,Yao, Jia,Li, Haoran
, p. 1663 - 1669 (2020/10/21)
Abstract: The direct aerobic oxidation of secondarty C(sp3)-H bonds was achieved in the presence of N-hydroxyphthalimide (NHPI) and cerium ammonium nitrate (CAN) under mild conditions. Various benzylic methylenes could be oxidized to carbonyl compounds in satisfied selectivity while saturated cyclic alkanes could be further oxidized to the corresponding lactones with the catalytic system. Remarkably, 25% of isochroman was converted to corresponding ketone with a selectivity of 96%. The reaction was initiated by hydrogen atom abstraction from NHPI by cerium and nitrates under oxygen atmosphere to form PINO radicals. 2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) addition experiments showed that the oxidation proceeded via a complex radical chain mechanism and an ion pathway. Graphic Abstract: [Figure not available: see fulltext.]
ε-Caprolactone manufacture via efficient coupling Baeyer-Villiger oxidation with aerobic oxidation of alcohols
Du, Renfeng,Li, Haoran,Wang, Yongtao,Yao, Jia,Yuan, Haoran,Zhao, Chenxuan
, (2020/04/27)
To avoid the use of peracids oxidant or highly concentrated hydrogen peroxide which is potentially hazardous and explosive, herein, a new route to ε-caprolactone was developed in which molecule oxygen was employed as the terminal oxidant. The commercial available N-hydroxyphthalimide and ammonium cerium nitrate were used as the key catalysts for the increased yield of ε-caprolactone. For instance, the selectivity of ε-caprolactone was obtained 92 % with 85 % conversion of cyclohexanone which was comparable to the strategies using highly concentrated hydrogen peroxide. The sacrificed alcohols were transformed into corresponding ketones which were also valuable chemicals. Furthermore, the efficiency of the alcohols was achieved to unprecedented 52 %. The Baeyer-Villiger oxidation of various other cycloalkanones was also examined. The substituent group effect on the efficiency of sacrificed alcohols was investigated in which weak electron-donating substituent induced nearly quantitative yield of ε-caprolactone. The reaction mechanism was studied with the help of electron paramagnetic resonance which indicated the existence of a radical pathway.
New perspectives on polyoxometalate catalysts: Alcohol oxidation with Zn/Sb-polyoxotungstates
Ni, Lubin,Patscheider, Joerg,Baldridge, Kim K.,Patzke, Greta R.
supporting information, p. 13293 - 13298 (2013/01/15)
Catalytic belts are the crucial feature of Zn/Sb-polyoxometalates as efficient and selective catalysts for alcohol oxidation. Comprehensive theoretical, analytical, and catalytic studies identify the active role of the Sb atom in the polyoxometalate metal belt. This sheds new light on low-cost catalyst tuning strategies for crucial oxidative transformations.
Comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine
Bousejra-El Garah, Fatima,Wong, Michael He-Long,Amewu, Richard K.,Muangnoicharoen, Sant,Maggs, James L.,Stigliani, Jean-Luc,Park, B. Kevin,Chadwick, James,Ward, Stephen A.,O'Neill, Paul M.
supporting information; scheme or table, p. 6443 - 6455 (2011/12/04)
Dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. We investigated the reactivity of a series of potent amide functionalized tetraoxanes with Fe(II)gluconate, FeSO4, FeSO4/TEMPO, FeSO 4/phosphatidylcholine, and heme to gain knowledge of their potential mechanism of bioactivation and to compare the results with the corresponding 1,2,4-trioxolanes. Spin-trapping experiments demonstrate that Fe(II)-mediated peroxide activation of tetraoxanes produces primary and secondary C-radical intermediates. Reaction of tetraoxanes and trioxolanes with phosphatidylcholine, a predominant unsaturated lipid present in the parasite digestive vacuole membrane, under Fenton reaction conditions showed that both endoperoxides share a common reactivity in terms of phospholipid oxidation that differs with that of artemisinin. Significantly, when tetraoxanes undergo bioactivation in the presence of heme, only the secondary C-centered radical is observed, which smoothly produces regioisomeric drug derived-heme adducts. The ability of these tetraoxanes to alkylate the porphyrin ring was also confirmed with Fe IITPP and MnIITPP, and docking studies were performed to rationalize the regioselectivity observed in the alkylation process. The efficient process of heme alkylation and extensive lipid peroxidation observed here may play a role in the mechanism of action of these two important classes of synthetic endoperoxide antimalarial.
Endoperoxide carbonyl falcipain 2/3 inhibitor hybrids: Toward combination chemotherapy of malaria through a single chemical entity
Gibbons, Peter,Verissimo, Edite,Araujo, Nuna C.,Barton, Victoria,Nixon, Gemma L.,Amewu, Richard K.,Chadwick, James,Stocks, Paul A.,Biagini, Giancarlo A.,Srivastava, Abhishek,Rosenthal, Philip J.,Gut, Jiri,Guedes, Rita C.,Moreira, Rui,Sharma, Raman,Berry, Neil,Cristiano, M. Lurdes S.,Shone, Alison E.,Ward, Stephen A.,O'Neill, Paul M.
supporting information; experimental part, p. 8202 - 8206 (2011/02/26)
We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially cytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.
Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: Mechanistic comparators for artemisinin in the context of reaction pathways with iron(II)
Tang, Yuanqing,Dong, Yuxiang,Wang, Xiaofang,Sriraghavan, Kamaraj,Wood, James K.,Vennerstrom, Jonathan L.
, p. 5103 - 5110 (2007/10/03)
Single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1) forms primary and secondary carbon-centered radicals. The complex structure of 1 does not lend itself to a satisfactory dissection of the electronic and steric effects that influence the formation and subsequent reaction of these carbon-centered free radicals. To help demarcate these effects, we characterized the reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7 with ferrous bromide and 4-oxo-TEMPO. Our results suggest a small preference for attack of Fe(II) on the nonketal peroxide oxygen atom of 1. For 4, but not for 5 and 6, there was a strong preference for attack of Fe(II) on the less hindered peroxide bond oxygen atom. The steric hindrance afforded by a spiroadamantane in a five-membered trioxolane is evidently much greater than that for a corresponding six-membered trioxane. Unlike 1, 5-7 fragment by entropically favored β-scission pathways forming relatively stable α-oxa carbon-centered radicals. These data suggest that formation of either primary or secondary carbon-centered radicals is a necessary but insufficient criterion for antimalarial activity of 1 and synthetic peroxides.
A new one-step method for oxaadamantane synthesis
Krasutsky, Pavel A.,Kolomitsin, Igor V.,Carlson, Robert M.,Jones Jr., Maitland
, p. 5673 - 5674 (2007/10/03)
Oxidation of 2-methyl-2-hydroxyadamantane by trifluoroperacetic acid in trifluoroacetic acid gives oxaadamantane and exo-2-oxaadamantane-4-ol in a good yield. Other 2-hydroxyadamantane derivatives do not undergo this transformation. An oxidative cleavage and subsequent cyclization mechanism is proposed.
OXIDATIVE FRAGMENTATION OF SATURATED HYDROCARBONS. I. A NEW OXIDATIVE FRAGMENTATION IN THE ADAMANTANE SERIES - A PATH TO THE SYNTHESIS OF 1,3,5-ALL-CIS-DERIVATIVES OF CYCLOHEXANE
Krasutskii, P. A.,Baula, O. P.,Yurchenko, A. G.
, p. 396 - 400 (2007/10/02)
The oxidation of adamantane and 1-hydroxyadamantane in solutions of perfluorobutyric and perfluoroacetic acids by the corresponding perfluoroperoxy acids leads to a high degree of fragmentation of the tricyclic framework structure to the monocyclic cyclohexane structure and the preferential formation of the esters of the corresponsing perfluorinated acids and all-cis-1,3-dihydroxymethylcyclohexan-5-acetic acid. A small amount of 2-oxahomoadamantan-3-one is formed as side product. The mechanisms of the described transformations are discussed.
SINGLET OXYGEN AND TRIAZOLINEDIONE ADDITION TO AZINES
Sato, Rikiya,Sonobe, Hideki,Akasaka, Takeshi,Ando, Wataru
, p. 5273 - 5280 (2007/10/02)
Photooxygenation of azines, i.e., adamantanone azine (1) and benzonorborn-7-one azine (4), afforded in addition to the corresponding ketones, lactones derived from a carbonyl oxide intermediate via an electron transfer pathway.On the other hand, 4-substitued-1,2,4-triazoline-3,5-diones (TAD) react with azine 1 to give a 1,3-dipole, an azomethinimine intermediate as nitrogen analogue of a carbonyl oxide, which afforded the -cycloadducts in treatment with dipolarophiles.The mechanistic implications are discussed.
