A new sustainable
green protocol for obtaining polyethylene glycol
(PEG) conjugates, with a prototype molecule, which in this work was
coumarin, by means of click chemistry is presented. The organic solvents
commonly used for this type of reaction were replaced by supercritical
carbon dioxide (scCO2). The synthesis and characterization
of PEG-coumarin were successfully reported using FTIR, 1H NMR, and MALDI TOF. Subsequently, a preliminary study was carried
out using the response surface methodology to examine the variables
that most affect the use of scCO2 as a reaction medium.
The main effects caused by these variables, individually and their
binary interaction, have been estimated. The response surface methodology
has been used in this work to screen variables using a factorial design
23. The p-values of temperature and pressure
were 0.006 and 0.0117, being therefore the most significant variables
of the response surface methodology study. Subsequently, a more intensive
study has been carried out on the variables that have shown the greatest
significant effect on reaction performance where an 82.32% synthesis
success was achieved, which broadens the scope of the use of scCO2 as a reaction medium. The conjugated coumarin with mPEG-alkyne
and coumarin were evaluated for their in vitro antioxidant activities
by the DPPH radical scavenging assay and were found to exhibit substantial
activities. The click product showed comparable or even better efficacy
than the initial coumarin.
Background: Chemical industry has increased the investment into and innovation capacity to supply chemicals from safe and sustainable sources, which will be essential to offering new solutions and supporting the green transition of the global economy and society. In this sense, the use of green solvents and reusable heterogeneous catalysts has emerged as a promising sustainable process strategy for engineering, chemistry and the environment. In this work, different homogeneous (copper bromide, CuBr and copper(II) acetate, Cu (CH3COO)2·H2O) and heterogeneous (Cu Wire, Cu Plate, Cu/β-SiC, pre-treated Cu Wire and pre-treated Cu Plate) copper catalysts were tested for the copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. In addition, the influence of different reaction media was analyzed, comparing the use of an organic solvent such as toluene and a green solvent such as supercritical CO2 (scCO2). Methods: Characterization of the catalysts includes by X-ray diffraction (XRD), Scan Electron Microscopy (SEM), Atomic absorption spectrophotometry (AA) and Temperature Programmed Reduction (TPR). Parameters such as catalyst loading, reaction time, reusability and leaching of the catalysts were studied to obtain more information on the CuAAC reaction in scCO2. Results: The pre-treated copper plate achieved a 57% increase in reaction yield compared to the non pre-treated copper plate. However, the recovery and reuse of the pre-treated copper plate showed a severe deterioration and a considerable change in its surface. Cu Wire (without pre-treatment) achieved yields of up to 94.2% after reusing it for five cycles. Conclusions: These results suggest the possibility to exploit the combination of heterogeneous catalysts and scCO2 and justify further research to highlight green solvents and simultaneously address the challenges of reaction, purification and recycling.
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