35749-94-1Relevant articles and documents
Scalable and selective deuteration of (hetero)arenes
Bartling, Stephan,Beller, Matthias,Bourriquen, Florian,Brückner, Angelika,Junge, Kathrin,Kreyenschulte, Carsten,Lei, Aiwen,Li, Wu,Lund, Henrik,Rabeah, Jabor,Rockstroh, Nils,Surkus, Annette-Enrica,Yang, Dali
, (2022/01/19)
Isotope labelling, particularly deuteration, is an important tool for the development of new drugs, specifically for identification and quantification of metabolites. For this purpose, many efficient methodologies have been developed that allow for the small-scale synthesis of selectively deuterated compounds. Due to the development of deuterated compounds as active drug ingredients, there is a growing interest in scalable methods for deuteration. The development of methodologies for large-scale deuterium labelling in industrial settings requires technologies that are reliable, robust and scalable. Here we show that a nanostructured iron catalyst, prepared by combining cellulose with abundant iron salts, permits the selective deuteration of (hetero)arenes including anilines, phenols, indoles and other heterocycles, using inexpensive D2O under hydrogen pressure. This methodology represents an easily scalable deuteration (demonstrated by the synthesis of deuterium-containing products on the kilogram scale) and the air- and water-stable catalyst enables efficient labelling in a straightforward manner with high quality control. [Figure not available: see fulltext.].
Aromatic Hydroxylation at a Non-Heme Iron Center: Observed Intermediates and Insights into the Nature of the Active Species
Makhlynets, Olga V.,Rybak-Akimova, Elena V.
supporting information; experimental part, p. 13995 - 14006 (2011/04/12)
Mechanism of substrate oxidations with hydrogen peroxide in the presence of a highly reactive, biomimetic, iron aminopyridine complex, [Fe II(bpmen)(CH3CN)2][ClO4] 2 (1; bpmen=N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2- diamine), is elucidated. Complex 1 has been shown to be an excellent catalyst for epoxidation and functional-group-directed aromatic hydroxylation using H2O2, although its mechanism of action remains largely unknown.1, 2 Efficient intermolecular hydroxylation of unfunctionalized benzene and substituted benzenes with H2O2 in the presence of 1 is found in the present work. Detailed mechanistic studies of the formation of iron(III)-phenolate products are reported. We have identified, generated in high yield, and experimentally characterized the key FeIII(OOH) intermediate (Imax=560 nm, rhombic EPR signal with g=2.21, 2.14, 1.96) formed by 1 and H2O2. Stopped-flow kinetic studies showed that FeIII(OOH) does not directly hydroxylate the aromatic rings, but undergoes rate-limiting self-decomposition producing transient reactive oxidant. The formation of the reactive species is facilitated by acid-assisted cleavage of the O-O bond in the iron-hydroperoxide intermediate. Acid-assisted benzene hydroxylation with 1 and a mechanistic probe, 2-Methyl-1-phenyl-2-propyl hydroperoxide (MPPH), correlates with O-O bond heterolysis. Independently generated FeIV=O species, which may originate from O-O bond homolysis in FeIII(OOH), proved to be inactive toward aromatic substrates. The reactive oxidant derived from 1 exchanges its oxygen atom with water and electrophilically attacks the aromatic ring (giving rise to an inverse H/D kinetic isotope effect of 0.8). These results have revealed a detailed experimental mechanistic picture of the oxidation reactions catalyzed by 1, based on direct characterization of the intermediates and products, and kinetic analysis of the individual reaction steps. Our detailed understanding of the mechanism of this reaction revealed both similarities and differences between synthetic and enzymatic aromatic hydroxylation reactions.
Association between Polar Molecules. Part 2. Equilibrium and Thermodynamic Studies on the Dipole Association of Benzonitrile Derivatives with Hexamethylphosphoramide, Di-n-butyl Sulphone, Di-n-butyl Sulphoxide and Tetramethylurea in Non-polar Solvents
Fujiwara, Hideaki,Takagi, Tatsuya,Yamazaki, Yutaka,Sasaki, Yoshio
, p. 347 - 356 (2007/10/02)
Dipole association between p-substituted benzonitriles and polar substances such as hexamethylphosphoramide(HMPA), di-n-butyl sulphone(DBSN), di-n-butyl sulphoxide(DBSX) and tetramethylurea(TMU) is investigated in non-polar solvent by means of n.m.r. spec
