Spinning Reactors for Process Intensification of Flow Photochemistry.

The design of new and more sustainable synthetic protocols to access new materials or valuable compounds will have a high impact on the broader chemistry community. In this sense, continuous-flow photochemistry has emerged as a powerful technique which has been employed successfully in various areas such as biopharma, organic chemistry, as well as materials science. However, it is important to note that chemical processes must not only advance towards new or improved chemical transformations, but also implement new technologies that enable new process opportunities. For this reason, the design of novel photoreactors is key to advancing photochemical strategies. In this sense, the use of equipment and techniques embracing processes intensification is important in developing more sustainable protocols. Among the most recent applications, spinning continuous flow reactors, such as rotor reactors or vortex reactors, have shown promising performance as new synthetic tools. Nevertheless, there is currently no review in the literature that effectively summarizes and showcases the most recent applications of such type of photoreactors. Herein, we highlight fundamental aspects and applications of two categories of spinning reactors, the Spinning Disc Reactors (SDRs) and Thin Film Vortex reactors, critiquing the scope and limitations of these advanced processing technologies. Further, we take a view on the future of spinning reactors in flow as a synthetic toolbox to explore new photochemical transformations.

Expanding Diterpene Complexity and Diversity via Photoinduced Ring Distortions.

Natural products and their semi-synthetic derivatives undoubtedly constitute an important source of therapeutic agents. Their importance lies in their own origin and evolution, since they have great chemical diversity, biochemical specificity, and pharmacological properties. Currently, there is a renewed interest in the development of methodologies capable of efficiently modifying the chemical structure of these bioactive platforms. In this work, the photoderivatization of the diterpene solidagenone was performed using a complexity-to-diversity-oriented approach. By exploring [2+2]-photocycloaddition, photoinduced-hydrogen abstraction, and photoxygenation reactions, a set of solidagenone derivatives was obtained, showing different ring fusions, side chain rearrangements, and modifications of the original furan ring's substitution pattern. The derivatives obtained were characterised by NMR methodologies. To evaluate the structural diversity of the labdane-derived compounds, their physicochemical properties, structural similarity, and chemical space were analysed. These results suggest that photochemical reactions are a useful tool for performing ring distortion transformations, generating derivatives of natural compounds with wide diversity, structural complexity, and with potential biological properties.

Photochemical Csp2-H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches.

Herein, we report an eco-friendly photochemical oxidative Csp2-H thiocyanation and selenocyanation of activated arenes. The reaction proceeds under Violet LED irradiation in the presence of K2S2O8, which quickly oxidizes KSCN and KSeCN, finally producing arylthio/selenocyanates. Using this benign, atom-economic protocol, the desired chalcogenide products were obtained regioselectively, with isolated yields that range from very good to excellent. Although, mechanistic study indicates that it is difficult to distinguish between a radical to a SEAr reaction mechanism between the photo-induced formed •SCN, for the former, or NCSSCN, for the latter, to the aromatic heterocycles. The inhibition experiment together with the observed reactivity and regioselectivity, would be in agreement with the latter. The synthetic methodology designed could be successfully adapted to continuous-flow systems in a segmented-flow regime, employing the organic phase as the product reservoir. Using this setup, the advantage of the latter can be demonstrated by reducing the reaction time and improving the product yields. Similarly, the scaling up of the reaction to gram scale resulted in favorable outcomes by the flow setup, which installs the photo-flow chemistry as a powerful tool to be included into routine reaction procedures, which have great relevance for the pharmaceutical industry.

Azide-alkyne cycloadditions in a vortex fluidic device: enhanced "on water" effects and catalysis in flow.

The Vortex Fluidic Device is a flow reactor that processes reactions in thin films. Running the metal-free azide-alkyne cycloaddition in this reactor revealed a dramatic enhancement of the "on water" effect. For the copper-catalyzed azide-alkyne cycloaddition, stainless steel or copper jet feeds were effective reservoirs of active copper catalyst.

Regioselective Photocycloaddition of Saccharin Anion to π-Systems: Continuous-Flow Synthesis of Benzosultams.

Saccharin is a versatile scaffold to build up different heterocycles with relevance in asymmetric catalysis, agricultural chemistry, medicinal chemistry, and so forth. Here, we report a photochemical strategy to obtain seven-membered ring benzosultams in one step, using saccharin anion as starting material. The reaction can be improved in a photoflow reactor and its scope was evaluated. Furthermore, computational study at the CASPT2//CASSCF level of theory was also performed to rationalize the involved mechanism.

More than Just Size: Challenges and Opportunities of Hybrid Dendritic Nanocarriers.

BACKGROUND: Dendrimers and hyperbranched polymers are emerging polymer architectures that attract increasing attention due to their unique topological structure and interesting physicochemical properties. Their enormous potential makes them particularly attractive to form new and fascinating nanometric drug delivery systems, solving several typical shortcomings encountered in nanomedicine. OBJECTIVE: In this context, the recent developments of dendritic and hyperbranched based systems, together with their application as nanocarriers, have been comprehensively reviewed. CONCLUSION: This review highlights how the structural complexity can be taken as an evolution parameter of these nanosystems, starting with hyperbranched polymers and evolving to more complex structures such as hybrid dendritic- inorganic nanoparticles and dendronized nano-objects hierarchically designed. Finally, future directions and perspectives in this promising field are briefly discussed.

Exploring the Photophysical and Photochemical Properties of N-(Thioalkyl)-saccharins as an Alternative Route to the Synthesis of Tricyclic Sultams.

Photocyclization of N-(thioalkyl)-saccharin was carried out to obtain different polycyclic sultams in good yields. These photoreactions were efficient under inert atmosphere and acetone triplet-sensitized conditions indicating that the triplet excited state is directly involved in the formation of annulated products. The presence of molecular oxygen changes product distribution, and only photo-oxygenation products (sulfoxides and sulfones) were found. This result is especially valuable since, by simple changing from nitrogen- to oxygen-saturated solvent conditions, the reaction outcome can be tuned from cyclized to sulfur oxidation products. Additionally, steady-state photolysis, electrochemistry, and laser time-resolved spectroscopic studies confirmed that these reactions mainly proceeded by intramolecular electron transfer (ET) between the triplet excited saccharin moiety and sulfur atom.

Photoremoval of protecting groups: mechanistic aspects of 1,3-dithiane conversion to a carbonyl group.

Photodeprotection of 1,3-dithianes in the presence of thiapyrylium was performed to return to the parent carbonyl compound, and the mechanism was studied by steady state photolysis, laser flash photolysis, and theoretical calculations. Electron transfer from dithianes to triplet sensitizers is extremely fast, and the decay of dithiane radical cations was not affected by the presence of water or oxygen as the consequence of a favorable unimolecular fragmentation pathway. Similar behaviors were observed for dithianes bearing electron-releasing or electron-withdrawing substituents on the aryl moiety, evidenced by C-S bond cleavage to form a distonic radical cation species. The lack of reaction under nitrogen atmosphere, requirement of oxygen for good conversion yields, inhibition of the photodeprotection process by the presence of p-benzoquinone, and absence of a labeled carbonyl final product when the reaction is performed in the presence of H2(18)O all suggest that the superoxide anion drives the deprotection reaction. Density functional theory computational studies on the reactions with water, molecular oxygen, and the superoxide radical anion support the experimental findings.

Photochemistry of N-(selenoalkyl)-phthalimides. Formation of N, Se-heterocyclic systems.

A variety of N-(selenomethyl)alkyl-phthalimides (alkyl = -(CH2)n-; n = 2-5, 1a, b, d, e) and N-(selenobenzyl)propyl phthalimide (1c) were synthesized and their photochemistry was studied at λ = 300 nm. Steady-state photolysis and laser time-resolved spectroscopy studies confirmed that these reactions proceeded by direct or acetone-sensitized excitation followed by intramolecular electron transfer (ET) between Se atom and the phthalimide moiety. Two main pathways are possible after ET: proton transfer to the ketyl radical anion from the CH3Se(+)˙ or the -CH2Se(+)˙- moieties, yielding the corresponding biradicals. Collapse of these biradicals yields cyclization products with the respective endo or exo selenium-containing heterocycles. Competition between both proton transfer processes depends on the chain length of the alkyl spacer between the phthalimide and Se groups as well as the size of the cycle being formed.

Stereoselective one-pot synthesis of ß-alkylsulfide enol esters. Base-triggered rearrangement under mild conditions.

A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a base-triggered rearrangement. This transition metal-free multicomponent approach can be performed under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and generally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration.

Photochemical and thermal stability of some dihydroxyacetophenones used as UV-MALDI-MS matrices.

2,4-, 2,5-, 2,6- and 3,5-dihydroxyacetophenone (DHA) used as matrices in matrix-assisted ultraviolet laser desorption/ionization mass spectrometry (UV-MALDI-MS) were studied by steady-state and transient absorption spectroscopy, together with DFT calculations at the B3LYP level of theory. All compounds have low fluorescence quantum yields, possibly due to an efficient excited-state intramolecular proton transfer (ESIPT). Laser flash photolysis (LFP) results showed that, only for 2,4-DHA, a phototautomer could be detected at λ = 400 nm. Their photochemical stability in solution at different wavelengths and conditions was analyzed by UV-Vis and (1)H nuclear magnetic resonance spectroscopy ((1)H-NMR), together with thin layer chromatography and ultraviolet laser desorption/ionization mass spectrometry (UV-LDI-MS). Only 3,5-DHA showed decomposition when irradiated, probably because phototautomerization is not possible. Thermal stability studies of these compounds in solid state were also conducted.