59512-17-3Relevant articles and documents
Hydration of Aliphatic Nitriles Catalyzed by an Osmium Polyhydride: Evidence for an Alternative Mechanism
Babón, Juan C.,Esteruelas, Miguel A.,López, Ana M.,O?ate, Enrique
, p. 7284 - 7296 (2021/05/29)
The hexahydride OsH6(PiPr3)2 competently catalyzes the hydration of aliphatic nitriles to amides. The main metal species under the catalytic conditions are the trihydride osmium(IV) amidate derivatives OsH3{κ2-N,O-[HNC(O)R]}(PiPr3)2, which have been isolated and fully characterized for R = iPr and tBu. The rate of hydration is proportional to the concentrations of the catalyst precursor, nitrile, and water. When these experimental findings and density functional theory calculations are combined, the mechanism of catalysis has been established. Complexes OsH3{κ2-N,O-[HNC(O)R]}(PiPr3)2 dissociate the carbonyl group of the chelate to afford κ1-N-amidate derivatives, which coordinate the nitrile. The subsequent attack of an external water molecule to both the C(sp) atom of the nitrile and the N atom of the amidate affords the amide and regenerates the κ1-N-amidate catalysts. The attack is concerted and takes place through a cyclic six-membered transition state, which involves Cnitrile···O-H···Namidate interactions. Before the attack, the free carbonyl group of the κ1-N-amidate ligand fixes the water molecule in the vicinity of the C(sp) atom of the nitrile.
One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles
Bobal, Pavel,Otevrel, Jan,Svestka, David
, p. 25029 - 25045 (2020/07/14)
We have identified a novel one-pot method for the synthesis of β-amino alcohols, which is based on C-H bond hydroxylation at the benzylic α-carbon atom with a subsequent nitrile or amide functional group reduction. This cascade process uses molecular oxygen as an oxidant and sodium bis(2-methoxyethoxy)aluminum hydride as a reductant. The substrate scope was examined on 30 entries and, although the respective products were provided in moderate yields only, the above simple protocol may serve as a direct and powerful entry to the sterically congested 1,2-amino alcohols that are difficult to prepare by other routes. The plausible mechanistic rationale for the observed results is given and the reaction was applied to a synthesis of a potentially bioactive target. This journal is
Mutual prodrugs containing bio-cleavable and drug releasable disulfide linkers
Jain, Arun K.,Gund, Machhindra G.,Desai, Dattatraya C.,Borhade, Namdev,Senthilkumar, Subrayan P.,Dhiman, Mini,Mangu, Naveen K.,Mali, Sunil V.,Dubash, Nauzer P.,Halder, Somnath,Satyam, Apparao
, p. 40 - 48 (2013/10/22)
We report herein the design and synthesis of several representative examples of novel mutual prodrugs containing nine distinct types of self-immolative drug-releasable disulfide linkers with urethane, ester, carbonate, or imide linkages between the linker and any two amine/amide/urea (primary or secondary) or carboxyl or hydroxyl (including phenolic)-containing drugs. We also report drug release profiles of a few representative mutual prodrugs in biological fluids such as simulated gastric fluid and human plasma. We also propose plausible mechanisms of drug release from these mutual prodrugs. We have also conducted a few mechanistic studies based on suggested sulfhydryl-assisted cleavage of mutual prodrugs and characterized a few important metabolites to give support to the proposed mechanism of drug release from the reported mutual prodrugs.
