Norrish Type Research Articles

Visible Light Photocatalyzed Norrish Type II Reaction of Acrylamides for the Synthesis of β‐Lactams

AbstractHere, we present a strategy for the visible‐light‐catalyzed synthesis of β‐lactams based on the Norrish type II reaction. This protocol uses acetonitrile as solvent and commercially available photocatalyst to drive the reaction. Notably, various challenging substrate types reported in previous studies undergo conversion. DFT calculations further elucidate the reaction mechanism, while discussing the competitiveness between [2+2] cycloaddition and the Norrish II reaction.

In Situ Generation of 1‐Acetylpyrene as a Visible‐Light Photocatalyst for the Thia‐Paternò‐Büchi Reaction

AbstractThe thia‐Paternò‐Büchi reaction represents a straightforward approach to build thietane cores. Unfortunately, the significant instability of thiocarbonyls, particularly thioketones and thioaldehydes, has hitherto rendered this photochemical [2+2]‐cycloaddition underexploited. To address this limitation, we report herein a visible‐light photochemical domino reaction including: the in situ generation of thiocarbonyls though a Norrish type II fragmentation of pyrenacyl sulfides, and the aforementioned thia‐Paternò‐Büchi reaction with various non‐volatile electron‐rich alkenes. The highly efficient synthesis of a wide range of unprecedented thietanes from intrinsically highly unstable thiocarbonyls, such as thioaldehydes and aliphatic thioketones, was made possible by the multitasking capability of pyrenacyl sulfides as a source of thiocarbonyl substrates and as precursors of 1‐acetylpyrene, which acts as the photocatalyst for the thia‐Paternò‐Büchi reaction. The photosensitizer properties of the latter have been experimentally established and a triplet‐triplet Dexter energy transfer based mechanism is proposed.

Phenacyl bromide as Norrish type I photoinitiator for the facile synthesis of chain-end functional PMMA and polystyrene

Phenacyl bromide has been explored as a new Norrish Type I photoinitiator for radically polymerizing methyl methacrylate and styrene monomers. A straightforward radical photopolymerization method using UVA light for the synthesis of chain-end functional poly(methyl methacrylate) and polystyrene has been developed. The process has been refined for both bulk and solution photopolymerizations. Chain-end functionalization was demonstrated by the formation of block-copolymers of the bromine-ended homopolymers, utilized as macroinitiators, resulting in an increase in the molecular weight of the corresponding precursor, observed by gel permeation chromatography (GPC). Block copolymerization was initiated by radicals generated at the chain-ends by a halogen-atom transfer reagent, namely, dimanganese decacarbonyl (Mn2(CO)10). This simple light-induced method is promising for the additive manufacturing field such as vat photopolymerization, stereolithography, digital light processing as it yields chain-end functional materials that can be further processed.

Anti-inflammatory bicyclic polyprenylated acylphloroglucinols with diverse architectures including an unprecedented 6/6/6 tricyclic core from Garcinia yunnanensis

Garciyunnanol A (1), an unprecedented 1,2-seco-bicyclic polyprenylated acylphloroglucinol (BPAP) possessing a unique 6/6/6 tricyclic core, was characterized from Garcinia yunnanensis together with 16 BPAPs, including eight new compounds (garciyunnanols B–I, 2–9). Biogenetically, the bicyclo[3.3.1]nonane-2,4,9-trione moiety of 12 reconstructed the bicyclic δ-lactone core of 2 through Norrish type Ⅰ cleavage and cyclization, followed by a cyclization of two side chains to form an intriguing 6/6/6 tricyclic core of 1. Their structures were elucidated through analysis of spectroscopic data, calculation and comparison of ECD spectra. Bioactivity evaluation manifested that compounds 1, 2, 5, 6 and 14 demonstrated superior inhibition of NO production compared to the positive control dexamethasone. Notably, compound 5 exhibited a dose-dependent inhibitory effect on NO production, with an IC50 value of 0.25 ± 0.87 µM. Furthermore, experiments involving ELISA, Western blotting, and immunofluorescence staining revealed that 5 effectively reduced the secretion of interleukin-1β in LPS plus nigericin-stimulated THP-1 macrophages by inhibiting the activation of the NLRP3 inflammasome.

Photochemical phosphorus-enabled scaffold remodeling of carboxylic acids.

The excitation of carbonyl compounds by light to generate radical intermediates has historically been restricted to ketones and aldehydes; carboxylic acids have been overlooked because of high energy requirements and low quantum efficiency. A successful activation strategy would necessitate a bathochromic shift in the absorbance profile, an increase in triplet diradical lifetime, and ease of further functionalization. We present a single-flask transformation of carboxylic acids to acyl phosphonates that can access synthetically useful triplet diradicals under visible light or near-ultraviolet irradiation. The use of phosphorus circumvents unproductive Norrish type I processes, promoting selectivity that enables hydrogen-atom transfer reactivity. Use of this strategy promotes the efficient scaffold remodeling of carboxylic acids through various annulation, contraction, and expansion manifolds.

In Situ Generation of 1-Acetylpyrene as a Visible-Light Photocatalyst for the Thia-Paternò-Büchi Reaction.

The thia-Paternò-Büchi reaction represents one of the straightforward approaches to build thietane cores. Unfortunately, the significant instability of thiocarbonyls, particularly thioketones and thioaldehydes, has hitherto rendered this photochemical [2+2]-cycloaddition underexploited. To address this limitation, we report here a visible-light photochemical domino reaction including: the in situ generation of thiocarbonyls, though a Norrish type II fragmentation of pyrenacyl sulfides, and the aforementioned thia-Paternò-Büchi reaction with various non-volatile electron-rich alkenes. The highly efficient synthesis of a wide range of unprecedented thietanes from intrinsically highly unstable thiocabonyls, such as thioaldehydes and aliphatic thioketones, was made possible by the multitasking capability of pyrenacyl sulfides, as a source of thiocarbonyl substrates and as precursors of 1-acetylpyrene, which acts as the photocatalyst for the thia-Paternò-Büchi reaction. The photosensitizer properties of the latter have been experimentally established and a triplet-triplet Dexter energy transfer-based mechanism is proposed.

Tuning the Mechanical Properties of 3D-Printed Objects by Mixing Chain Transfer Agents in Norrish Type I Photoinitiated RAFT Polymerization.

Photoinduced 3D printing via photocontrolled reversible-deactivation radical polymerization (photoRDRP) techniques has emerged as a robust technique for creating polymeric materials. However, methods for precisely adjusting the mechanical properties of these materials remain limited. In this study, we present a facile approach for adjusting the mechanical properties of 3D-printed objects by adjusting the polymer dispersity within a Norrish type I photoinitiated reversible addition-fragmentation chain transfer (NTI-RAFT) polymerization-based 3D printing process. We investigated the effects of varying the concentrations and molar ratios of trithiocarbonate (BTPA) and xanthate (EXEP) on the mechanical properties of the printed materials. Our findings demonstrate that increased concentrations of RAFT agents or higher proportions of the more active BTPA lead to a decrease in Young's modulus and glass transition temperatures, along with an increase in elongation at break, which can be attributed to the enhanced homogeneity of the polymer network. Using a commercial LCD printer, the NTI-RAFT-based 3D printing system effectively produced materials with tailored mechanical properties, highlighting its potential for practical applications.

Visible-Light-Mediated Activation of Remote C(sp3)-H Bonds by Carbon-Centered Biradical via Intramolecular 1,5- or 1,6-Hydrogen Atom Transfer.

In this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish-Yang reaction. This process is facilitated by excited triplet-state carbon-centered biradicals, enabling the 1,5-HAT reaction by suppressing the critical 1,4-biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6-HAT reactions initiated by excited triplet-state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large-scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern-Volmer experiments, and density functional theory (DFT) calculations.

Visible‐Light‐Mediated Activation of Remote C(sp3)−H Bonds by Carbon‐Centered Biradical via Intramolecular 1,5‐ or 1,6‐Hydrogen Atom Transfer

AbstractIn this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish‐Yang reaction. This process is facilitated by excited triplet‐state carbon‐centered biradicals, enabling the 1,5‐HAT reaction by suppressing the critical 1,4‐biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6‐HAT reactions initiated by excited triplet‐state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large‐scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern–Volmer experiments, and density functional theory (DFT) calculations.

The Effect of β-Hydrogens on the Tropospheric Photochemistry of Aldehydes: Norrish Type 1, Triple Fragmentation, and Methylketene Formation from Propanal.

Wavelength and pressure dependent quantum yields (ϕ, QYs) of propanal photolysis have been measured for photolysis wavelengths, λ = 300-330 nm, and buffer gases of 3-10 Torr propanal and 0-757 Torr N2. Following laser photolysis, three photochemical pathways were established, using Fourier transform infrared spectroscopy of the stable end-products. Photolysis is dominated by the Norrish Type 1 reaction, which has been reported previously, but with inconsistent quantum yields. The propanal α-hydrogen leads to a 4-center elimination of H2, as observed in CH3CHO, here leading to methylketene. The presence of hydrogen attached to the β-carbon allows a new photochemical pathway: concerted triple fragmentation into CO + H2 + C2H4 via a 5-center transition state. Neither of these channels has been reported previously. No evidence for the previously reported C2H6 + CO, C2H4 + H2CO or CH3 + CH2CHO channels, nor for phototautomerization to 1-propenol (CH3CH═CHOH) was found. Modeling of the wavelength, pressure and collision partner dependence of the QYs allows us to reconcile the previous NT1a results and make recommendations for the quantum yields of all three channels under tropospheric conditions. The general impact of β-hydrogen atoms in the photochemistry of aldehydes is to open up new pathways from cyclic transition states and to reduce the importance of other photolysis or isomerization channels.

Combination of NIR and UV‐LEDs enables physical and chemical drying of aqueous coating dispersions as new green technology

AbstractHeptamethine based cyanines, namely 1,3,‐trimethyl‐2‐(2‐2[2‐phenylsulfanyl‐3‐[2‐(1,3,3‐trimethyl‐1,3,3‐trithyl‐1,3‐dihydro‐indol‐2‐ylidene)‐ethylidene]cyclohex‐1‐enyl]vinyl)‐3H‐indolium chloride (S1) and 2‐[2‐(2‐chloro‐[2‐[1,1‐dimethyl‐7‐sulfo‐3‐(4‐sulfobutyl)‐1,3‐dihydro‐benzo[e]indol‐2‐ylidene]‐ethylidene]cyclopent‐1‐enyl]vinyl]‐1,1‐dimethyl‐7‐sulfo‐3‐(4‐sulfobutyl)‐1Hbenzo[e]indolium hydroxide, inner salt, triethylammonium salt (S2), efficiently result in physical drying of an aqueous dispersion comprising a polyurethane binder. S2 possesses a water solubility of 40 g/L. A high‐intensity near‐infrared‐LED emitting at 820 nm with an intensity of 1 W/cm2 served as light source. The cyanine converted the light absorbed into heat by internal conversion needing less drying time compared to conventional drying. Water content after film formation showed less then 1%. In the second step, ultraviolet (UV) exposure with a LED emitting at 395 nm resulted in formation of semi‐interpenetrating polymer networks by crosslinking of the multifunctional (meth)acrylate operating as reactive diluent. Ethyl phenyl(2,4,6‐trimethylbenzoyl)phosphinate‐L served as effective UV‐photoinitiator. Furthermore, the UV‐exposure together with Norrish Type I and Type II photoinitator systems results in a very efficient bleaching of the green physical dried film. This contribution shows for the first time a new photonic hybrid technique describing successful replacement of an oven‐based process by a photonic based step that generates heat needed for drying.

α-Cleavage of 2,2-Diazido-2,3-dihydroinden-1-one in Solution and Cryogenic Matrices.

The Norrish type I (α-cleavage) reaction is an excellent photochemical method for radical-pair formation in solution. However, in cryogenic matrices, the starting material typically re-forms before the radical pair diffuses apart. This study focused on N2 extrusion from an azido alkyl radical to prevent radical-pair recombination. Irradiation of 2,2-diazido-2,3-dihydroinden-1-one (1) in methanol mainly yielded methyl 2-cyanomethylbenzoate (2) and 2-cyanomethylbenzoic acid (3) via α-cleavage. Laser flash photolysis of 1 in argon-saturated acetonitrile resulted in α-cleavage to form triplet biradical 31Br1 (λmax ∼ 410 nm, τ ∼ 400 ns). In contrast, upon irradiation in glassy 2-methyltetrahydrofuran matrices, triplet alkylnitrene 31N was directly detected using electron spin resonance (D/hc = 1.5646 cm-1, E/hc = 0.00161 cm-1) and absorption spectroscopy (λmax = 276 and 341 nm). Irradiation of 1 in argon matrices generated 31N, benzoyl azide 4, singlet benzoylnitrene 14N, and isocyanide 5, as revealed by IR spectroscopy. The experimental results supported by density functional theory calculations [B3PW91/6-311++G(d,p)] suggest that irradiation of 1 in matrices results in α-cleavage to form biradical 31Br1, which extrudes N2 to yield 31Br2. Rearrangement of 31Br2 into 31N competes with cleavage of a N3 radical to form radical 1Ra3. The N3/1Ra3 radical pair combines to form 4, which upon irradiation yields 14N and 5.

Visible light radical photoinitiators of polymerization based on photochromic molecules

A series of photochromic compounds linked to a benzophenone nucleus were synthetized and evaluated regarding their ability to act as Norrish type II radical photoinitiators, promoting the polymerization of a polyacrylate monomer after the consecutive absorption of LED UV and Vis light.

3D printing of a photo-curable hydrogel to engineer mechanically robust porous structure for ion capture or sustained potassium ferrate(VI) release for water treatment

Contaminated water and scarcity of clean water are becoming progressively serious environmental concerns. Removal of hazardous pollutants from wastewater is vital and urgently needed attention for the protection of pure water resources. To tackle the aforementioned challenges, macroporous structures have great potential to be used in the treatment of heavy metal ions to improve the adsorption efficiency and sustainability of wastewater treatment methodologies. In this context, additive manufacturing technologies have gained considerable attention because of their ability to construct intricate macroporous shapes with multifunctionalities using diverse materials. Here, we used a photocrosslinking graft copolymerization of polyvinyl alcohol/acrylic acid-based ink using UV irradiation in the presence of Norrish type II photosensitizer through a hot-melt extrusion-type 3D printer to improve the printing quality of crosslinked ink. The photocured inks offered strong shear-thinning behavior that allowed layer-by-layer deposition to generate well-defined 3D structures, while having sufficiently high viscoelasticity to retain the shape after printing process. With an adequate viscosity at the higher extrusion shearing forces, the 3D printed structures could create multifaceted self-supporting scaffolds with an internal lattice structure that possesses high level of porosity. The hierarchically porous structure of 3D objects showed a recoverable structure yet robust matrix, offering more specific surface area, capable of effectively removing heavy metal ions from water with fast-responsiveness and a high capacity. The ferrate(VI)-contained 3D capsule-like object was also detected to be efficient regarding chemical oxygen demand reduction and decolorization of real wastewater. Such 3D-printed hierarchical macroporous objects can offer great prospects in the treatment of water and wastewater purification applications.

Continuous Flow Synthesis of Benzotriazin-4(3H)-ones via Visible Light Mediated Nitrogen-Centered Norrish Reaction.

We report a new protocol for the synthesis of substituted benzotriazin-4(3H)-ones which are underrepresented heterocyclic scaffolds with important pharmacological properties. Our method exploits acyclic aryl triazine precursors that undergo a photocyclization reaction upon exposure to violet light (420 nm). Continuous flow reactor technology is exploited to afford excellent yields in only 10 min residence time with no additives or photocatalysts needed. The underlying reaction mechanism appears to be based on an unprecedented variation of the classical Norrish type II reaction with concomitant fragmentation and formation of N-N bonds. Scalability, process robustness, and green credentials of this intriguing transformation are highlighted.

Reactive Oxygen Species Formation and Peroxide and Carbonyl Decomposition in Aqueous Photolysis of Secondary Organic Aerosols.

The mechanism and kinetics of reactive oxygen species (ROS) formation when atmospheric secondary organic aerosol (SOA) is exposed to solar radiation are poorly understood. In this study, we combined an in situ UV-vis irradiation system with electron paramagnetic resonance (EPR) spectroscopy to characterize the photolytic formation of ROS in aqueous extracts of SOA formed by the oxidation of isoprene, α-pinene, α-terpineol, and toluene. We observed substantial formation of free radicals, including •OH, superoxide (HO2•), and organic radicals (R•/RO•) upon irradiation. Compared to dark conditions, the radical yield was enhanced by a factor of ∼30 for •OH and by a factor of 2-10 for superoxide radicals, and we observed the emergence of organic radicals. Total peroxide measurements showed substantial decreases of peroxide contents after photoirradiation, indicating that organic peroxides can be an important source of the observed radicals. A liquid chromatography interfaced with high-resolution mass spectrometry was used to detect a number of organic radicals in the form of adducts with a spin trap, BMPO. The types of detected radicals and aqueous photolysis of model compounds indicated that photolysis of carbonyls by Norrish type I mechanisms plays an important role in the organic radical formation. The photolytic ROS formation serves as the driving force for cloud and fog processing of SOA.

Highly effective photocatalytic degradation of plastic film (LDPE) using Ruthenium-incorporated g-C3N4 via the Norrish mechanism

Microplastics (MPs) are pollutants generated by plastic debris of diameters ≤ 5 mm and are a global concern that can pose severe threats to human and environmental health in both aquatic and terrestrial areas. In this study, low-density polyethylene (LDPE, MW = ∼35000) blended with Ru-incorporated g-C3N4 (Ru-gCN) was fabricated to examine its degradation efficiency. Plastic film (Ru-gCN@PE) degradation was performed by adding an aqueous medium with pH values ranging from 1 to 6 and at different temperatures (0, 35, 50, and 70 °C). The Ru-gCN@PE showed a significant weight loss of approximately 66.04, 74.51, and 69.64 wt% in pH 3 at 0, 50, and 70 °C, respectively, upon light irradiation for 24 h. The high activity of Ru-gCN can result from the formation of a heterojunction of Ru and g-C3N4 (Ru-gCN), which facilitates the transfer of the photoinduced π electrons of g-C3N4. Moreover, H+ is produced at an appropriate pH and temperature to further convert into hydroperoxides and accelerate the formation of macroradicals (∙ROO, ∙RO, and ∙OH) for plastic degradation, which follows the Norrish Type I and II mechanisms. Our study demonstrated the outstanding efficacy of the photocatalytic degradation of LDPE.

Methoxyacetone revisited

Conformational space of methoxyacetone (MA) was studied at the MP2/6–311++G(d,p) and DFT(B3LYP)/6–311++G(d,p) levels of theory. Computations predict MA to adopt four conformations, resulting from internal rotations around the O=C−C−O (Trans, Cis) and C−C−O−C (trans, gauche) dihedral angles. The Tt (Trans-trans) conformer is the most stable. The computed energies of two gauche (Tg and Cg) conformers fall in the 3–8 kJ mol−1 range above Tt and should account for 1/3 of the room-temperature gas-phase equilibrium. The energy of Ct form is 11 kJ mol−1 above Tt, and its expected population is negligible (below 1 %). In our earlier work, MA monomers were isolated in cryogenic argon matrices and characterized by infrared spectroscopy. In the experiment, only the most stable Tt conformer was detected in the sample. Signatures of the other conformers were not detected, either in freshly deposited samples, or in samples subjected to different UV irradiations. We rationalize those observations in terms of computed barriers for intramolecular torsions, indicating occurrence of conformational cooling during deposition. The experimental infrared spectrum of the Tt form is now assigned with the aid of anharmonic DFT computations. Exposure of MA to UV irradiation in the 300–260 nm range led to photolysis, according to the Norrish type II mechanism, resulting in dimer between enol acetone and formaldehyde observed as a cage-confined intermediate photoproduct. The subsequent photolysis resulted in the formation of carbon monoxide as the dominating photoproduct, formed in the Norrish type I photoreaction. Mechanistic interpretation of this photo decarbonylation reaction is presented.

Application of molecular dynamic simulations in modeling the excited state behavior of confined molecules.

Relative to isotropic organic solvent medium, the structure and conformation of a reactant molecule in an organized and confining medium are often different. In addition, because of the rigidity of the immediate environment, the reacting molecule have a little freedom to undergo large changes even upon gaining energy or modifications in the electronic structure. These alterations give rise to differences in the photochemistry of a molecular and supramolecular species. In this study, one such example is presented. α-Alkyl dibenzylketones upon excitation in isotropic solvents give products via Norrish type I and type II reactions that are independent of the chain length of the alkyl substituent. On the other hand, when these molecules are enclosed within an organic capsule of volume ~ 550Å3, they give products that are strikingly dependent on the length of the α-alkyl substitution. These previously reported experimental observations are rationalized based on the structures generated by molecular modeling (docking and molecular dynamics (MD) simulations). It is shown that MD simulations that are utilized extensively in biologically important macromolecules can also be useful to understand the excited state behavior of reactive molecules that are part of supramolecular assemblies. These simulations can provide structural information of the reactant molecule and the surroundings complementing that with the one obtained from 1 and 2D NMR experiments. MD simulated structures of seven α-alkyl dibenzylketones encapsulated within the octa acid capsule provide a clear understanding of their unique behavior in this restricted medium. Because of the rigidity of the medium, these structures although generated in the ground state can rationalize the photochemical behavior of the molecules in the excited state.

Synthesis and Characterization of Thiol-Protected Silver Nanoclusters for Photodynamic Therapy Applications

Aqueous metal nanoclusters have emerged as versatile tools in biomedical applications, particularly in the scope of imaging and cancer therapeutics. This research paper investigates a thiol-protected silver nanocluster (AgNC), focusing on establishing a reproducible synthesis method to obtain a pure cluster species for use in biological stability studies. Conventionally, nanocluster synthesis employs reducing agents, like NaBH4, which often poses challenges in reaction control and product purity. This study adopts an alternative approach, utilizing a Norrish Type I reaction to enhance synthesis. This light-activated reaction leverages the regulated concentration of alpha-hydroxy radicals from a photoinitiator (Omnirad 2959) achieved through UVA-induced homolytic bond cleavage. Monitoring AgNC formation through ultraviolet-visible (UV-Vis) and fluorescence emission-excitation matrix (EEM) spectroscopy and confirming product purity via parallel factor analysis (PARAFAC), this work offers insight into the influence of parameters such as light intensity, reactant concentration, irradiation wavelength, and oxygen presence on consistency and reproducibility of the AgNC syntheses. Methods like Polyacrylamide Gel Electrophoresis (PAGE) and centrifugation are also employed to facilitate separation and purification, preparing the AgNC for subsequent evaluation within biologically significant contexts (tumor microenvironments and phosphate buffer solutions). Although diverse reaction conditions yielded an array of nanocluster species, characterization of the AgNCs reveals challenges in reproducing a pure cluster species consistently. EEM and PARAFAC analyses underscore similarities across synthesized clusters, yet significant variations in reaction conditions persist. The primary application envisioned for these AgNCs is in Photodynamic Therapy (PDT), a form of radiative therapy that exploits the optical properties of metal nanoclusters to induce reactive oxygen species, thus eliciting cancer cell death. It is evident that further investigation is necessary to deepen the comprehension of AgNCs and validate their potential use in PDT. Future research should focus on refining reaction conditions, and effective separation, of AgNC, allowing for advancement in therapeutic interventions such as PDT.