RESUMO
Besides the racemate, the S-enantiomer of ibuprofen (Ibu) is used for the treatment of inflammation and pain. Since the configurational stability of S-Ibu in solid state is of interest, it was studied by means of ball milling experiments. For the evaluation of the enantiomeric composition, a chiral CE method was developed and validated according to the ICH guideline Q2(R1). The addition of Mg2+ , Ca2+ , or Zn2+ ions to the background electrolyte (BGE) was found to improve Ibu enantioresolution. Chiral separation of Ibu enantiomers was achieved on a 60.2 cm (50.0 cm effective length) x 75 µm fused-silica capillary using a background electrolyte (BGE) composed of 50 mM sodium acetate, 10 mM magnesium acetate tetrahydrate, and 35 mM heptakis-(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD) as chiral selector. The quantification of R-Ibu in the mixture was performed using the normalization procedure. Linearity was evaluated in the range of 0.68-5.49% R-Ibu (R2 = 0.999), recovery was found to range between 97 and 103%, the RSD of intra- and interday precision below 2.5%, and the limit of quantification for R- in S-Ibu was calculated to be 0.21% (extrapolated) and 0.15% (dilution of racemic ibuprofen), respectively. Isomerization of S-Ibu was observed under basic conditions by applying long milling times and high milling frequencies.
Assuntos
Eletroforese Capilar , Eletrólitos , Concentração de Íons de Hidrogênio , Ibuprofeno/análogos & derivados , Isomerismo , EstereoisomerismoRESUMO
The enantioselective synthesis of chiral [7]-helical dispirodihydro[2,1-c]indenofluorenes (DSF-IFs) was achieved for the first time in good yields with high er values (er up to 99 : 1). The crucial step of the whole reaction sequence was the enantioselective intramolecular [2+2+2] cycloaddition of tethered triynediols to indenofluorenediols, which was catalyzed by a Rh/SEGPHOS® complex. Further transformations led to the corresponding DSF-IFs. The prepared helically chiral DSF-IFs combine circularly polarized luminescence (CPL) activity (glum =â¼10-3 ) with exceptionally high fluorescence quantum yields (up to Φlum =0.97).
Assuntos
Ródio , Catálise , Fluorenos , Luminescência , EstereoisomerismoRESUMO
This work presents a general approach for synthesis of substituted [5]-helical dispiroindeno[2,1-c]fluorenes based on Rh-catalyzed intramolecular cyclotrimerization of triynes. This approach was further extended for the first synthesis of configurationally stable [7]-helical dispiroindeno[2,1-c]fluorenes. A series of variously substituted derivatives was prepared and their photophysical and electrochemical properties were evaluated. Their fluorescence emission maxima were in the region of 351-428â nm and quantum yields up to 88 % are the highest measured among the full-carbon helical compounds.
RESUMO
Synthesis of selectively 4-substituted 9,9'-spirobifluorenes was accomplished by using catalytic [2 + 2 + 2]-cyclotrimerization of specifically substituted diynols with alkynes to the corresponding fluorenols. Further synthetic transformations provided the target molecules. The measurement of the photophysical properties of the prepared 4-substituted 9,9'-spirobifluorenes revealed that their emission maxima depended on the electronic properties of the substituents present in the para position: the presence of an electron accepting group strongly favored the maxima red shift toward the blue VIS region (CF3λmax = 361 nm vs. MeO λmax = 330 nm). Adding further substituents (aryl or arylethynyl moieties) on the phenyl ring in position 4 did not lead to a dramatic improvement in the emission maxima (CF3C6H4, λmax = 369 nm, CF3C6H4C[triple bond, length as m-dash]C, λmax = 370 nm), but increased their quantum yields considerably. In addition, a series of 9,9'-spirobifluorenes possessing various extended π-systems (pyrene, anthracene, etc.) were synthesized. In general, the emission maxima pattern reflected that of the parent π-systems, but they were red shifted by 10-30 nm. Finally, also a 1-[4-(9,9'-spirobifluorene-4-yl)phenyl]-2-aryl-ortho-carborane was prepared. These data thus may provide guidelines for further design of 9,9'-spirobifluorenes with tailored properties.
RESUMO
Synthesis of selectively substituted fluorenes and fluorenols was achieved by using catalytic [2+2+2]cyclotrimerization. Various starting diynes were reacted with different alkynes in the presence of a catalytic amount of Wilkinson's catalyst (RhCl(PPh3)3) providing the compounds possessing the fluorene scaffold in good isolated yields. A set of four regioselectively substituted fluorenols was converted to the corresponding 9,9'-spirobifluorenes and their spectral characteristics were measured.
RESUMO
A method for forced oxidative mechanochemical degradation of active pharmaceutical ingredients (APIs) using clopidogrel hydrogensulfate as a model compound is presented. Considerable and selective formation of degradants occurs already after very short reaction times of less than 15 minutes and the nature of the products is strongly dependent on the used oxidant.