Laser‐Mediated Photo‐High‐p,T Intensification of Vitamin D₃ Synthesis in Continuous Flow

Abstract

A new reactor design for photosynthesis in microflow is presented based on spatial overlap of a laser beam through a capillary tube. A conical Archimedean spiral facilitates exposure of the entire volume of the reaction solution to the irradiation beam. In this fashion, photo‐high‐p,T intensification of the photolysis of 7‐dehydrocholesterol is achieved using either a pulsed ultraviolet (UV) laser excitation (in the order of femtoseconds) alone or in tandem with a conventional UV lamp. The goal is to control the kinetics of the side photoreactions under pulsed photolysis, as well as to reduce the reaction time and enhance the vitamin D3 yield. Three kinds of effects are targeted: a) Utilizing a very large and spatially homogeneous photon flux inside the flowing solution; b) the novel process window of combining photo‐ with thermal intensification to promote the final, irreversible thermal step to vitamin D3; and c) the use of sub‐ps laser pulses to supply excitation energy on a timescale shorter than the formation of side photoproducts. Finally, photo‐processing with the laser alone is compared to the tandem irradiation by the laser‐UV lamp.

Circular Economy Metrics for the Photo-High-p,T Continuous Multistep Synthesis of Vitamin D3

“…Escribà-Gelonch et al implemented a laser operation and even combined the irradiation of a UV-lamp and a laser. Only 27% yield was obtained when operating with the laser, with only 19% side photocompounds, which amounts to half of the losses of the combined action of the laser and the UV-lamp . Since these results resulted in a higher side compounds control, these data were taken for the recycling design.…”

“…One enabler for this industrial transformation can be the conversion of batch processes to continuous end-to-end manufacturing of active pharmaceutical ingredients (APIs), as encouraged by Food and Drug Administration (FDA) . This shift implies the development of new process designs, which can foster circularity and contribute to 14 of the 17 UN sustainable targets. , In this context, we previously developed an end-to-end continuous process for the synthesis of vitamin D 3 (VD3) from 7-dehydrocholesterol (7DHC) , and evaluated its environmental impact through LCA . This paper revisits our sustainability direction by applying circular metrics as a measure of a recycling process, i.e ., to explore how to reach circularity with the aid of advanced process development enabled by flow chemistry.…”

Life cycle assessment of vitamin D3 synthesis: from batch to photo-high p,T

“…The first approach to continuous processing was proposed by Fuse et al (2010), where a two-stage continuous microreactor was employed. Recently, an intensification of the process was achieved using either a UV lamp or a laser (Escribà-Gelonch et al 2018a). With the aid of microreactors, operation at harsh Fig.…”

Automated High-Pressure Atline Analysis of Photo-High-P,T Vitamin D3 Microfluidic Synthesis

“…Yet, the specific wavelength demanded in the reactions, such as VD3 synthesis, requires the use of monochromatic laser light sources, asking for a specific design for tubing irradiation. In this context, we have previously reported a method to transfer light to 0.55 mm internal diameter capillary placed in a continuous microreactor using a conical curled-fashioned coil, which enabled deep light penetration along the walls, irradiating equally throughout the tube within the beam section (Escribà-Gelonch et al, 2018b). This effect combined with faster mass and heat transfer allowed by the microreactor made it possible to achieve photo-high-p,T intensification using also high pressure (p) and temperature (T) (Escribà-Gelonch et al, 2018b).…”

“…The study presented herewith describes the effects of the fully automated sampling operation using a photo-high-p,T microreactor for the synthesis of VD3. The operating conditions are always taken according to previous process optimization described in the literature (Escribà-Gelonch et al, 2018b). In the case presented herewith, the sampling was performed by pressure drop, since the slow increase of the volume promoted by the extraction system contributed to a controlled depressurization.…”