19836-78-3Relevant academic research and scientific papers
Design, synthesis and antimalarial evaluation of novel thiazole derivatives
Bueno, José María,Carda, Miguel,Crespo, Benigno,Cu?at, Ana Carmen,de Cozar, Cristina,León, María Luisa,Marco, J. Alberto,Roda, Nuria,Sanz-Cervera, Juan F.
, p. 3938 - 3944 (2016)
As part of our medicinal chemistry program's ongoing search for compounds with antimalarial activity, we prepared a series of thiazole analogs and conducted a SAR study analyzing their in vitro activities against the chloroquine-sensitive Plasmodium falciparum 3D7 strain. The results indicate that modifications of the N-aryl amide group linked to the thiazole ring are the most significant in terms of in vitro antimalarial activity, leading to compounds with high antimalarial potency and low cytotoxicity in HepG2 cell lines. Furthermore, the observed SAR implies that non-bulky, electron-withdrawing groups are preferred at ortho position on the phenyl ring, whereas small atoms such as H or F are preferred at para position. Finally, replacement of the phenyl ring by a pyridine affords a compound with similar potency, but with potentially better physicochemical properties which could constitute a new line of research for further studies.
Novelty of immobilized enzymatic synthesis of 3-ethyl-1,3-oxazolidin-2-one using 2-aminoalcohol and dimethyl carbonate: Mechanism and kinetic modeling of consecutive reactions
Yadav, Ganapati D.,Pawar, Sandip V.
, p. 62 - 69 (2014)
Oxazolidinones are multifunctional compounds possessing diverse biological and pharmacological activity. Enzymatic synthesis of oxazolidin-2-one was studied using 2-aminoalochol and dimethyl carbonate and synthesis of 3-ethyl-1,3-oxazolidin-2-one was chosen as the model reaction using a variety of immobilized lipases; among which Candida antarctica lipase B (Novozyme 435) was the best catalyst. The reaction leads to the final product oxazolidin-2-one via methyl ethyl (2-hydroxyethyl) carbamate as the intermediate. The parameters affecting rate of reaction and the conversion of both steps were studied systematically and covered effects of agitation speed, solvent, catalyst loading and reaction temperature. A reaction mechanism was proposed wherein the coproduct methanol is generated in the first step leading to the formation of methyl ethyl (2-hydroxyethyl) carbamate as the intermediate which rearranges itself leading to the final products 3-ethyl-1,3-oxazolidin-2-one and methanol. The kinetic constant and activation energy were determined for each step of the reaction. The study was further extended to other 2-aminoalochols under optimized reaction conditions to prepare different oxazolidinones. This is a first report of its kind describing kinetics and mechanism of bimolecular consecutive enzyme catalyzed reactions.
Self-immolative polymers containing rapidly cyclizing spacers: Toward rapid depolymerization rates
Chen, Eric K. Y.,McBride, Ryan A.,Gillies, Elizabeth R.
, p. 7364 - 7374 (2012)
Self-immolative polymers containing 4-hydroxybenzyl alcohol alternating with either N-methylaminoethanol or 2-mercaptoethanol spacers were synthesized and demonstrated to controllably depolymerize in response to the cleavage of a stabilizing end-cap from
Facile formation of N-alkyl-oxazolidin-2-ones from N-alkyl- nitroxyethylamines and carbonate anion in biphasic media
Sitzmann, Michael E.,Kenar, James A.,Trivedi, Nirupam J.
, p. 8211 - 8212 (1998)
Nitration of N-alkyl ethanolamines (1) followed by treatment of their corresponding N-alkyl-N-(2-nitroxyethyl)amine salts (2) in a biphasic CH2Cl2/aqueous Na2CO3 or NaHCO3 mixture at 25°C gives N-alkyl- oxazolidin-2-ones (3). This represents a new method that allows the preparation of oxazolidinones at ambient temperature with the use of aqueous carbonate.
Damage and Repair in Informational Poly(N-substituted urethane)s
Charles, Laurence,Lutz, Jean-Fran?ois,Mondal, Tathagata
supporting information, p. 20390 - 20393 (2020/09/21)
The degradation and repair of uniform sequence-defined poly(N-substituted urethane)s was studied. Polymers containing an ω-OH end-group and only ethyl carbamate main-chain repeat units rapidly degrade in NaOH solution through an ω→α depolymerization mechanism with no apparent sign of random chain cleavage. The degradation mechanism is not notably affected by the nature of the side-chain N-substituents and took place for all studied sequences. On the other hand, depolymerization is significantly influenced by the molecular structure of the main-chain repeat units. For instance, hexyl carbamate main-chain motifs block unzipping and can therefore be used to control the degradation of specific sequence sections. Interestingly, the partially degraded polymers can also be repaired; for example by using a combination of N,N′-disuccinimidyl carbonate with a secondary amine building-block. Overall, these findings open up interesting new avenues for chain-healing and sequence editing.
Visible-Light-Mediated Liberation and In Situ Conversion of Fluorophosgene
Petzold, Daniel,Nitschke, Philipp,Brandl, Fabian,Scheidler, Veronica,Dick, Bernhard,Gschwind, Ruth M.,K?nig, Burkhard
supporting information, p. 361 - 366 (2018/11/23)
The first example for the photocatalytic generation of a highly electrophilic intermediate that is not based on radical reactivity is reported. The single-electron reduction of bench-stable and commercially available 4-(trifluoromethoxy)benzonitrile by an organic photosensitizer leads to its fragmentation into fluorophosgene and benzonitrile. The in situ generated fluorophosgene was used for the preparation of carbonates, carbamates, and urea derivatives in moderate to excellent yields via an intramolecular cyclization reaction. Transient spectroscopic investigations suggest the formation of a catalyst charge-transfer complex-dimer as the catalytic active species. Fluorophosgene as a highly reactive intermediate, was indirectly detected via its next downstream carbonyl fluoride intermediate by NMR. Furthermore, detailed NMR analyses provided a comprehensive reaction mechanism including a water dependent off-cycle equilibrium.
Synthesis and kinetics of disassembly for silyl-containing ethoxycarbonyls using fluoride ions
Camerino, Eugene,Daniels, Grant C.,Wynne, James H.,Iezzi, Erick B.
, p. 1884 - 1888 (2018/02/06)
In this study, a series of silyl-containing ethoxycarbonates and ethoxycarbamates on electron poor anilines and phenols were synthesized and their kinetics of disassembly determined in real-time upon exposure to fluoride ion sources at room temperature. The results provide a greater understanding of stability and kinetics for silyl-containing protecting groups that eliminate volatile molecules upon removal, which will allow for simplification of orthogonal protection in complex organic molecules.
Copper(II)-catalysed oxidative carbonylation of aminols and amines in water: A direct access to oxazolidinones, ureas and carbamates
Casiello, Michele,Iannone, Francesco,Cotugno, Pietro,Monopoli, Antonio,Cioffi, Nicola,Ciminale, Francesco,Trzeciak, Anna M.,Nacci, Angelo
, p. 8 - 14 (2015/07/01)
Copper(II) chloride catalyses the oxidative carbonylation of aminols, amine and alcohols to give 2-oxazolidinones, ureas and carbamates. Reaction proceeds smoothly in water under homogeneous conditions (Ptot = 4 MPa; PO2 = 0.6 MPa, PCO), at 100°C in relatively short reaction times (4 h) and without using bases or any other additives. This methodology represents an economic and environmentally benign non-phosgene alternative for the preparation of these three important N-containing carbonyl compounds.
Combining Low-Pressure CO2 Capture and Hydrogenation to Form Methanol
Khusnutdinova, Julia R.,Garg, Jai Anand,Milstein, David
, p. 2416 - 2422 (2015/04/14)
This paper describes a novel approach to CO2 hydrogenation, in which CO2 capture with aminoethanols at low pressure is coupled with hydrogenation of the captured product, oxazolidinone, directly to MeOH. In particular, (2-methylamino)ethanol or valinol captures CO2 at 1-3 bar in the presence of catalytic Cs2CO3 to give the corresponding oxazolidinones in up to 65-70 and 90-95% yields, respectively. Efficient hydrogenation of oxazolidinones was achieved using PNN pincer Ru catalysts to give the corresponding aminoethanol (up to 95-100% yield) and MeOH (up to 78-92% yield). We also have shown that both CO2 capture and oxazolidinone hydrogenation can be performed in the same reaction mixture using a simple protocol that avoids intermediate isolation or purification steps. For example, CO2 can be captured by valinol at 1 bar with Cs2CO3 catalyst followed by 4-isopropyl-2-oxazolidinone hydrogenation in the presence of a bipy-based pincer Ru catalyst to produce MeOH in 50% yield after two steps.
Novelty of immobilized enzymatic synthesis of 3-ethyl-1,3-oxazolidin-2-one using 2-aminoalcohol and dimethyl carbonate: Mechanism and kinetic modeling of consecutive reactions
Yadav, Ganapati D.,Pawar, Sandip V.
, p. 62 - 69 (2014/12/10)
Oxazolidinones are multifunctional compounds possessing diverse biological and pharmacological activity. Enzymatic synthesis of oxazolidin-2-one was studied using 2-aminoalochol and dimethyl carbonate and synthesis of 3-ethyl-1,3-oxazolidin-2-one was chosen as the model reaction using a variety of immobilized lipases; among which Candida antarctica lipase B (Novozyme 435) was the best catalyst. The reaction leads to the final product oxazolidin-2-one via methyl ethyl (2-hydroxyethyl) carbamate as the intermediate. The parameters affecting rate of reaction and the conversion of both steps were studied systematically and covered effects of agitation speed, solvent, catalyst loading and reaction temperature. A reaction mechanism was proposed wherein the coproduct methanol is generated in the first step leading to the formation of methyl ethyl (2-hydroxyethyl) carbamate as the intermediate which rearranges itself leading to the final products 3-ethyl-1,3-oxazolidin-2-one and methanol. The kinetic constant and activation energy were determined for each step of the reaction. The study was further extended to other 2-aminoalochols under optimized reaction conditions to prepare different oxazolidinones. This is a first report of its kind describing kinetics and mechanism of bimolecular consecutive enzyme catalyzed reactions.
