1453837-89-2Relevant academic research and scientific papers
VT-NMR and cytotoxic evaluation of some new ortho-(alkylchalcogen)acetanilides
Ramos, Susana S.,Almeida, Sandra S.,Leite, Paula M.,Boto, Renato E.F.,Silvestre, Samuel,Almeida, Paulo
, p. 8930 - 8937 (2015/03/05)
Several novel atropisomeric N-alkyl-N-[(2-alkylchalcogen)phenyl)]acetamides have been synthesized and fully characterized by 1H and 13C NMR, FTIR, and HRMS (FAB). The barriers of the restricted rotation about the N-aryl bond between the two atropisomeric forms were measured by accurate lineshape simulation of variable temperature NMR (VT-NMR) spectra obtained in DMSO-d6 solution and ranged from 17.0 to 20.5 kcal/mol. The relationship between the structure of the different acetanilide moieties and both coalescence temperature and energy of rotation are herein discussed. Taking in mind the acetamide structural resemblances with nimesulide related compounds known by their anticancer activity, the in vitro cytotoxicity of 20 representative acetanilides, against human breast (MCF-7) and prostate (LNCaP) cancer cell lines as well as normal human dermal fibroblasts (NHDF) was also preliminary evaluated. Interestingly a selective antiproliferative activity was observed for cancerous cells with prominence to LNCaP within the most potent O- and/or N-benzylic and -hexyl acetanilides.
Synthesis and dynamic study of new ortho-(alkylchalcogen)acetanilide atropisomers. A second look at the hydrolysis of quaternary 2-methylbenzazol-3- ium salts
Ramos, Susana S.,Reis, Lucinda V.,Boto, Renato E.F.,Santos, Paulo F.,Almeida, Paulo
, p. 5441 - 5444 (2013/09/23)
The base-catalysed hydrolysis of N-ethyl-2-methylbenzazol-3-ium iodides was re-examined performing the reaction in boiling 96% ethanol, in the presence of triethylamine. The resulting unstable intermediates were isolated as the corresponding ether, thioether or selenoether derivatives, depending on the starting benzazole salt, by trapping via alkylation with ethyl and hexyl iodides, in moderate to good yields. Reduction of the o-(alkylchalcogen) acetanilides so obtained afforded the corresponding o-(alkylchalcogen)anilines. This methodology provides potential access to o-(alkylchalcogen)anilines bearing up to three different N-alkyl groups introduced in an unambiguous and regioselective way. The o-(alkylchalcogen)acetanilides are axially chiral molecules due to restricted rotation around the N-aryl bond. The resulting atropisomerism has been studied using dynamic variable temperature NMR spectroscopy and the corresponding rotational barriers were determined for the first time in acetanilides bearing a single ortho-substituent other than the tert-butyl and iodine groups. The estimated free energy of activation of the interconversion of the rotamers ranged from 17.1 to 20.5 kcal/mol.
