Kinetic analysis of the partial synthesis of artemisinin: Photooxygenation to the intermediate hydroperoxide

Abstract

The price of the currently best available antimalarial treatment is driven in large part by the limited availability of its base drug compound artemisinin. One approach to reduce the artemisinin cost is to efficiently integrate the partial synthesis of artemisinin starting from its biological precursor dihydroartemisinic acid (DHAA) into the production process. The optimal design of such an integrated process is a complex task that is easier to solve through simulations studies and process modelling. In this article, we present a quantitative kinetic model for the photooxygenation of DHAA to an hydroperoxide, the essential initial step of the partial synthesis to artemisinin. The photooxygenation reactions were studied in a two-phase photo-flow reactor utilizing Taylor flow for enhanced mixing and fast gas-liquid mass transfer. A good agreement of the model and the experimental data was achieved for all combinations of photosensitizer concentration, photon flux, fluid velocity and both liquid and gas phase compositions. Deviations between simulated predictions and measurements for the amount of hydroperoxide formed are 7.1 % on average. Consequently, the identified and parameterized kinetic model is exploited to investigate different behaviors of the reactor under study. In a final step, the kinetic model is utilized to suggest attractive operating windows for future applications of the photooxygenation of DHAA exploiting reaction rates that are not affected by mass transfer limitations.

Modelling approaches to predict light absorption in gas-liquid flow photosensitized oxidations

“…Figure 8 shows that lavg is only constant for the case of a square channel with collimated light, which leads to the conclusion that lavg is extremely sensitive to the path of the rays. On the other hand, as discussed by Triemer et al [28] and shown in Section 3.3, the dependence of the absorbed photon flux on the values of optical pathlength becomes weak at strong light attenuation.…”

“…[18] Triemer et al developed a model to observe the behavior of a gas-liquid Taylor flow photoreactor during photooxygenation of dihydroartemisinic acid and to identify the mass transfer limiting regimes. [28] The model was based on 5 unknown parameters which were fitted with experimental data: mass transfer coefficient, three kinetic constants and optical pathlength.…”

“…Due to the complex optical phenomena occurring in multi-phase photoreactors, the optical pathlength was previously considered either equal to the reactor channel height [29] or was fitted with experimental data [28,30,31]. The path of light scattered by gas bubbles can be simulated using geometrical optics (ray tracing) when the size of the gas bubble is much larger than the radiation wavelength.…”

Trendbericht: Technische Chemie 2024

“…Diese sind in den letzten Jahren weit fortgeschritten. [6][7][8] Jedoch erzeugt die Erweiterung der Technologiepalette auch Lärm, da Abb. 1.…”

Dynamically triggering photoreactions for high performance and efficiency

“…This can be gained by photonic characterization of photochemistry equipment and includes chemical actinometry, radiometry and numerical simulations like ray tracing or modelling of the radiative transfer equation. [44,45] Even thought that various techniques are at hand to measure photons or calculate their spatial and temporal distribution, photonic characterization is seldom reported in the literature. Chemical actinometry measures the photon flux incident inside the reactor in an integral manner.…”