Photochemical Aerobic Upcycling of Polystyrene Plastics via Synergistic Indirect HAT Catalysis.

Plastic pollution constitutes an evergrowing urgent environmental problem, since overaccumulation of plastic waste, arising from the immense increase of the production of disposable plastic products, overcame planet's capacity to properly handle them. Chemical upcycling of polystyrene constitutes a convenient method for the conversion of plastic waste into high-added value chemicals, suggesting an attractive perspective in dealing with the environmental crisis. We demonstrate herein a novel, easy-to-perform organocatalytic photoinduced aerobic protocol, which proceeds via synergistic indirect hydrogen atom transfer (HAT) catalysis under LED 390 nm Kessil lamps as the irradiation source. The developed method employs a BrCH2CN-thioxanthone photocatalytic system and was successfully applied to a variety of everyday-life plastic products, leading to the isolation of benzoic acid after simple base-acid work up in yields varying from 23-49%, while a large-scale experiment was successfully performed, suggesting that the photocatalytic step is susceptible to industrial application.

Expanding the Use of Benzothioxanthene Imides to Photochemistry: Eco-Friendly Aerobic Oxidation of Sulfides to Sulfoxides.

The sulfoxide moiety is one of the most commonly utilized groups in pharmaceutical and industrial chemistry. The need for sustainability and easy accessibility to sulfoxide moieties is deemed necessary, due to its ubiquity in natural products and potentially pharmaceutically active compounds. In this context, we report herein a sustainable, aerobic and environmentally friendly photochemical protocol based on the use of a benzothioxathene imide as the photocatalyst to selectively oxidise sulfides under mild irradiation (456 nm), in very low catalyst loading (0.01 mol%) and on water. In addition, to demonstrate the compatibility of our protocol with wide scope of substrates, the latter was successfully applied to the synthesis of the biologically-active Sulforaphane and Modafinil.

Computational and Spectroscopic Studies on the Formation of Halogen-Bonded Complexes Between Tertiary Amines and CBr4 and Application in the Light-Mediated Amino Acid Coupling.

In recent years, halogen-bonded complexes (XBCs), in solution, have played a pivotal role in inducing photochemical organic reactions. In this work, we explore the ability of various tertiary amines to act as XB acceptors in the presence of the XB donor CBr4 by computational and spectroscopic studies. DFT studies clearly showcase the formation of XBCs between the studied tertiary amines and CBr4. Simultaneously, computational and experimental UV-Vis studies display intense red shifts that are consistent with charge transfer observed from tertiary amines to CBr4. A detailed NMR study revealed a clear chemical shift of the carbon carrying the bromine atoms upon mixing the XB acceptor with the donor, suggesting that this spectroscopic technique is indeed an experimental tool to identify the generation of XBCs. An application of the ability of such XBCs to activate a carboxylic acid under UVA irradiation or sunlight is presented for amino acid coupling. Among the various tertiary amines studied, the pair DABCO-CBr4 was found to work well for the photochemical amide bond formation. Direct infusion-HRMS studies allowed us to propose a general mechanism for the photochemical amino acid coupling in the presence of a tertiary amine and CBr4, initiated by the photoactivation of an XBC.

Photochemical Aerobic Upcycling of Polystyrene Plastics.

Although the introduction of plastics has improved humanity's everyday life, the fast accumulation of plastic waste, including microplastics and nanoplastics, have created numerous problems with recent studies highlighting their involvement in various aspects of our lives. Upcycling of plastics, the conversion of plastic waste to high-added value chemicals, is a way to combat plastic waste that is receiving increased attention. Herein, we describe a novel aerobic photochemical process for the upcycling of real-life polystyrene-based plastics into benzoic acid. A new process employing a thioxanthone-derivative, in combination with N-bromosuccinimide, under ambient air and 390 nm irradiation is capable of upcycling real-life polystyrene-derived products in benzoic acid in yields varying from 24-54 %.

Photochemical Synthesis of Lactones, Cyclopropanes and ATRA Products: Revealing the Role of Sodium Ascorbate.

Light-mediated processes have received significant attention, since they have re-surfaced unconventional reactivity platforms, complementary to conventional polar chemistry. γ-Lactones and cyclopropanes are prevalent moieties, found in numerous natural products and pharmaceuticals. Among various methods for their synthesis, light-mediated protocols are coming to the spotlight, although these are contingent upon the use of photoorgano- or metal-based catalysts. Herein, we introduce a novel photochemical activation of iodo-reagents via the use of cheap sodium ascorbate or ascorbic acid to enable their homolytic scission and addition onto double bonds. The developed protocol was applied successfully to the formal [3+2] cycloaddition for the synthesis of γ-lactones, traditional atom transfer radical addition (ATRA) reactions and the one-pot two-step conversion of alkenes to cyclopropanes. In all cases, the desired products were obtained in good to high yields, while the reaction mechanism was thoroughly investigated. Depending on the nature of the iodo-reagent, a halogen or a hydrogen-bonded complex is formed, which initiates the process.

Green and sustainable approaches for the Friedel-Crafts reaction between aldehydes and indoles.

The synthesis of indoles and their derivatives, more specifically bis(indolyl)methanes (BIMs), has been an area of great interest in organic chemistry, since these compounds exhibit a range of interesting biological and pharmacological properties. BIMs are naturally found in cruciferous vegetables and have been shown to be effective antifungal, antibacterial, anti-inflammatory, and even anticancer agents. Traditionally, the synthesis of BIMs has been achieved upon the acidic condensation of an aldehyde with indole, utilizing a variety of protic or Lewis acids. However, due to the increased environmental awareness of our society, the focus has shifted towards the development of greener synthetic technologies, like photocatalysis, organocatalysis, the use of nanocatalysts, microwave irradiation, ball milling, continuous flow, and many more. Thus, in this review, we summarize the medicinal properties of BIMs and the developed BIM synthetic protocols, utilizing the reaction between aldehydes with indoles, while focusing on the more environmentally friendly methods developed over the years.

Organocatalytic activation of hydrogen peroxide: towards green and sustainable oxidations.

The advent of organocatalysis provided an additional option in every researcher's arsenal, towards the development of elegant and sustainable protocols for various organic transformations. Oxidation reactions are considered to be key in organic synthesis since oxygenated functionalities appear in many natural products. Hydrogen peroxide is categorized as a green oxidant, since its only by-product is water, offering novel opportunities for the development of green and sustainable protocols. In this review article, we intend to present recent developments in the field of the organocatalytic activation of hydrogen peroxide, providing useful insight into the applied oxidative protocols. At the same time, we will present some interesting mechanistic studies, providing information on the oxygen transfer processes.

Photochemical Aminochlorination of Alkenes without the Use of an External Catalyst.

The niche field of photochemistry offers opportunities that are not found in "traditional" ground state chemical pathways. Aminochlorinated derivatives are an interesting family of 1,2-difunctionalised compounds that provide access to a variety of natural products and pharmaceutical active substances. A practical, catalyst-free chloroamination protocol is described herein, providing access to intermediates of great importance, utilising mild and photochemical reaction conditions (370 nm), where N-chlorosulfonamides are used as both nitrogen and chlorine sources. A wide variety of olefins, decorated with a plethora of functional groups, was tested providing excellent results (28 examples, 18-88 % yield). Mechanistic studies (UV-Vis, control experiments and quantum yield measurement) were also performed.

Photochemical [2 + 2] Cycloaddition of Alkenes with Maleimides: Highlighting the Differences between N-Alkyl vs N-Aryl Maleimides.

Throughout the last 15 years, there has been increased research interest in the use of light promoting organic transformations. [2 + 2] Cycloadditions are usually performed photochemically; however, literature precedent on the reaction between olefins and maleimides is limited to a handful of literature examples, focusing mainly on N-aliphatic maleimides or using metal catalysts for visible-light driven reactions of N-aromatic maleimides. Herein, we identify the differences in reactivity between N-alkyl and N-aryl maleimides. For our optimized protocols, in the case of N-alkyl maleimides, the reaction with alkenes proceeds under 370 nm irradiation in the absence of an external photocatalyst, leading to products in high yields. In the case of N-aryl maleimides, the reaction with olefins requires thioxanthone as the photosensitizer under 440 nm irradiation.

An Efficient Light-Mediated Protocol for the Direct Amide Bond Formation via a Novel Carboxylic Acid Photoactivation Mode by Pyridine-CBr4.

The direct amide bond formation between a carboxylic acid and an amine still constitutes a challenging reaction for both academia and industry. We demonstrate herein that several pairs of amines (halogen bond acceptors) and organohalogen sources may be used for the photochemical amidation reaction under either UVA or sunlight irradiation. Our studies led to the identification of pyridine-CBr4 as an efficient agent to perform amide synthesis under LED 370 nm irradiation, avoiding super-stoichiometric quantities. An extended substrate scope was demonstrated, showing that the widely used amino and carboxyl protecting groups are compatible with this photochemical protocol, while a number of industrially interesting products and bioactive compounds were synthesized. Direct infusion-high resolution mass spectrometry studies suggest an unprecedented type of carboxylic acid activation mode upon irradiation, involving the generation of a symmetric anhydride, an active ester with pyridine N-oxide and a mixed anhydride with hypobromous acid.

Light-accelerated "on-water" hydroacylation of dialkyl azodicarboxylates.

The hydroacylation of dialkyl azodicarboxylates has received a lot of attention lately due to the great importance of acyl hydrazides in organic chemistry. Herein, we report an inexpensive and green photochemical approach, where light irradiation (390 nm) significantly accelerates the reaction between dialkyl azodicarboxylates and aldehydes, while water is employed as the solvent. A variety of aromatic and aliphatic aldehydes were converted into their corresponding acyl hydrazides in good to excellent yields in really short reaction times (15-210 min) and the reaction mechanism was also studied. Applications of this reaction in the syntheses of Vorinostat and Moclobemide were demonstrated.

Cyrene: a bio-based solvent for the Mizoroki-Heck reaction of aryl iodides.

The development of greener and more sustainable methods, as well as the adaptation of already existing protocols to more environmentally friendly procedures, has become crucial for organic synthesis. The introduction and utilization of greener solvents is a very promising alternative, especially when they can replace toxic organic solvents in the known and widely used organic reactions. Cyrene has appeared to be an excellent alternative solvent for a number of organic reactions. In this work, the development of a new, greener and more economical protocol for the Mizoroki-Heck reaction is described, using Cyrene as the green solvent and Pd/C as the palladium catalyst source. A wide substrate scope for the coupling of aryl iodides with acrylamides, acrylates, acrylic acid, acrylonitrile and styrene was demonstrated. The recyclability of Cyrene and the leaching of palladium in the final product were examined in order to enhance the industrial applicability of this protocol. Furthermore, the synthesis of the natural product piperlotine A is reported.

Friedel-Crafts arylation of aldehydes with indoles utilizing arylazo sulfones as the photoacid generator.

A versatile, inexpensive and sustainable protocol for the preparation of valuable bis-indolyl methanes via visible light-mediated, metal-free Friedel-Crafts arylation has been developed. The procedure, that exploits the peculiar behavior of arylazo sulfones as non-ionic photoacid generators (PAGs), was applied to the conversion of a variety of aliphatic and aromatic aldehydes into diarylmethanes in good to highly satisfactory yields, employing a low-catalyst loading (0.5 mol%) and irradiation at 456 nm.

A General Metal-Free Protocol for the Visible-Light-Driven Protection of Carbonyls.

The protection of a carbonyl is a standard procedure to mask the reactivity of this group towards nucleophiles and reductants. The present work pointed out the potentialities of arylazo sulfones as non-ionic photoacid generators (PAGs) to promote the efficient conversion of aldehydes and ketones into acetals, ketals, and 1,3-oxazolidines upon visible-light irradiation. This approach employed mild conditions and exhibited an easy scalability and a broad scope (80 examples included).

A sustainable photochemical aerobic sulfide oxidation: access to sulforaphane and modafinil.

Sulfoxide-containing molecules are an important class of compounds in the pharmaceutical industry and many efforts have been made to develop new and green protocols, targeting the chemoselective transformation of sulfides into sulfoxides. Photochemistry is a rapidly expanding research field employing light as the energy source. Photochemical aerobic processes possess additional advantages to photochemistry and may find applications in the chemical industries. Herein, a 370 nm catalyst-free aerobic protocol was developed, using 2-Me-THF as the green solvent. At the same time, two low-catalyst-loading anthraquinone-based processes (under a CFL lamp or 427 nm irradiation) in 2-Me-THF were developed. Furthermore, a broad range of substrates was tested. We also implemented our protocols towards the synthesis of the pharmaceutical active ingredients (APIs) sulforaphane and modafinil.

A Unified Mechanism for the PhCOCOOH-mediated Photochemical Reactions: Revisiting its Action and Comparison to Known Photoinitiators.

Since 2014, we have introduced in literature the use of phenylglyoxylic acid (PhCOCOOH), a small and commercially available organic molecule, as a potent promoter in a variety of photochemical processes. Although PhCOCOOH has a broad scope of photochemical reactions that can promote, the understanding of its mode of action in our early contributions was moderate. Herein, we are restudying and revisiting the mechanism of action of PhCOCOOH in most of these early contributions, providing a unified mechanism of action. Furthermore, the understanding of its action as a photoinitiator opened a new comparison study with known and commercially available photoinitiators.

Hexafluoroisopropanol-Promoted or Brønsted Acid-Mediated Photochemical [2+2] Cycloadditions of Alkynes with Maleimides.

Although the use of light stimulating organic transformations has been known for more than a century, there is an increasing research interest on expanding the established knowledge. While [2+2] cycloadditions are promoted photochemically, literature precedent on the reaction between alkynes and maleimides is limited and only a handful of examples exist, focusing mainly on N-aliphatic maleimides. Herein, the differences in reactivity between N-alkyl and N-aryl maleimides were identified, and the use of hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA) as viable solutions was proposed in order to achieve high yields. In the case of N-alkyl maleimides, both HFIP-mediated or TFA-promoted reactions were established using LED 370 nm irradiation, without the use of an external photocatalyst. In the case of N-aryl maleimides, thioxanthone (THX) was employed as the energy transfer photocatalyst along with LED 427 nm irradiation and HFIP. Mechanistic studies were performed, supporting the pivotal role of HFIP or TFA, in acquiring good to high yields in both classes of maleimides.

Photochemical C-H acetalization of O-heterocycles utilizing phenylglyoxylic acid as the photoinitiator.

A novel, mild, metal-free and easy-to-execute procedure for the C-H acetalization of O-heterocycles via visible light activation is presented, utilizing phenylglyoxylic acid as the photoinitiator. Biomass-derived O-heterocycles, like THF, can be employed, while primary, secondary alcohols and alcohols bearing a variety of functionalities were succesfully employed, affording the desired acetals in high yields. Facile acidic deprotection was also performed.

Aldehyde-catalyzed epoxidation of unactivated alkenes with aqueous hydrogen peroxide.

The organocatalytic epoxidation of unactivated alkenes using aqueous hydrogen peroxide provides various indispensable products and intermediates in a sustainable manner. While formyl functionalities typically undergo irreversible oxidations when activating an oxidant, an atropisomeric two-axis aldehyde capable of catalytic turnover was identified for high-yielding epoxidations of cyclic and acyclic alkenes. The relative configuration of the stereogenic axes of the catalyst and the resulting proximity of the aldehyde and backbone residues resulted in high catalytic efficiencies. Mechanistic studies support a non-radical alkene oxidation by an aldehyde-derived dioxirane intermediate generated from hydrogen peroxide through the Payne and Criegee intermediates.

Thioxanthone: a powerful photocatalyst for organic reactions.

Photoorganocatalysis has been recognised by the organic chemistry community as an important part of photochemistry and catalysis. In general, aromatic ketones constitute key players in this type of catalysis as they are involved in a plethora of examples in the literature. Among the various aromatic ketones, thioxanthone (TX) seems to play a unique role in photochemistry. In comparison with other aromatic ketones, TX has a high triplet energy and a relatively long triplet lifetime, while it has the ability to participate successfully in merger reactions with metal complexes. In this review, we will discuss the photophysical properties of this small organic molecule, as well as the numerous examples of photochemical reactions, where it is employed as a mediator and more specifically in polymerisation reactions, and organic transformations.