N-hydroxyphthalimide Research Articles

Decarboxylative Selective Phosphorylation of Aliphatic Acids: A Transition‐Metal‐ and Photocatalyst‐Free Avenue to Dialkyl and Trialkyl Phosphine Oxides from White Phosphorus

Developing practical and mild strategies for the direct functionalization of white phosphorus (P4 ) without chlorination is an appealing but formidable challenge. To this end, we report a breakthrough in the preparation of structurally diverse dialkylphosphines and trialkylphosphines that rely on the successive generation of carbon-centered radicals from N-hydroxyphthalimide (NHPI) esters and the controllable alkylation of the P4 molecule under transition-metal- and photocatalyst-free conditions. To facilitate separation and prevent product losses during purification, the corresponding oxidation products dialkylphosphine oxides (DAPOs) and trialkylphosphine oxides (TAPOs) were isolated. This photoinduced phosphorylation reaction features one-pot operation, high product selectivity, and tolerates a broad range of alkyl NHPI esters, including derivatives of complex natural products and pharmaceuticals. Further diversified transformation of DAPOs to construct P-F, P-C, P-N, and P-O bonds was also demonstrated.

Decarboxylative Selective Phosphorylation of Aliphatic Acids: A Transition‐Metal‐ and Photocatalyst‐Free Avenue to Dialkyl and Trialkyl Phosphine Oxides from White Phosphorus

AbstractDeveloping practical and mild strategies for the direct functionalization of white phosphorus (P4) without chlorination is an appealing but formidable challenge. To this end, we report a breakthrough in the preparation of structurally diverse dialkylphosphines and trialkylphosphines that rely on the successive generation of carbon‐centered radicals from N‐hydroxyphthalimide (NHPI) esters and the controllable alkylation of the P4 molecule under transition‐metal‐ and photocatalyst‐free conditions. To facilitate separation and prevent product losses during purification, the corresponding oxidation products dialkylphosphine oxides (DAPOs) and trialkylphosphine oxides (TAPOs) were isolated. This photoinduced phosphorylation reaction features one‐pot operation, high product selectivity, and tolerates a broad range of alkyl NHPI esters, including derivatives of complex natural products and pharmaceuticals. Further diversified transformation of DAPOs to construct P−F, P−C, P−N, and P−O bonds was also demonstrated.

A Horseradish Peroxidase-Mediator System for Benzylic C-H Activation.

Enzyme-mediator systems generate radical intermediates that abstract hydrogen atoms under mild conditions. These systems have been employed extensively for alcohol oxidation, primarily in biomass degradation, but they are underexplored for direct activation of C(sp3)-H bonds in alkyl groups. Here, we combine horseradish peroxidase (HRP), H2O2, and redox mediator N-hydroxyphthalimide (NHPI) for C(sp3)-H functionalization of alkylbenzene-type substrates. The HRP-NHPI system is >10-fold more active than existing enzyme-mediator systems in converting alkylbenzenes to ketones and aldehydes under air, and it operates from 0-50 °C and in numerous aqueous-organic solvent mixtures. The benzylic substrate radical can be trapped through a reaction with NHPI, demonstrating the formation of benzylic products beyond ketones. Furthermore, we demonstrate a one-pot, two-step enzymatic cascade for converting alkylbenzenes to benzylic amines. Overall, the HRP-NHPI system enables the selective benzylic C-H functionalization of diverse substrates under mild conditions using a straightforward procedure.

Boosting the visible-light-induced toluene oxidation via synergistic effect between nanoparticulate Pd/BiVO4 photocatalyst and a cyclic nitroxyl redox mediator

Selective organic conversion using semiconductor photocatalysts has been focused on the viewpoint of sustainable synthesis processes. Especially, C-H activation is one of the most attractive reactions. We recently reported photo-oxidation of toluene to benzaldehyde over visible-light responsible Pd-loaded BiVO4 (Pd/BiVO4) photocatalyst. However, it remains challenging due to its low efficiency. Herein, we introduce a novel strategy to apply a cyclic nitroxide compound as an efficient redox mediator along with Pd/BiVO4 for toluene oxidation. Including N-hydroxyphthalimide (NHPI) could significantly expedite the activity of benzaldehyde production up to ca. 28 times compared to without NHPI under blue-to-green light irradiation. The sustainable conditions realized a conversion in high efficiency (apparent quantum yield = 10.8 and 5.4 %@420 and 520 nm, respectively) and with excellent selectivity (>99 %). The excellent efficiency was realized by the synergistic effect between the presence of NHPI and the use of nanoparticulate Pd/BiVO4 with a relatively large surface area.

Pullulan Oxidation in the Presence of Hydrogen Peroxide and N-Hydroxyphthalimide.

The C-6 in the maltotriose unit of pullulan was oxidized in an alkaline medium (pH = 10), utilizing a green method that included hydrogen peroxide (H2O2) as an oxidant and N-hydroxyphthalimide (NHPI) as a catalyst for various reaction times. The structure of the resulting oxidized pullulans (PO) was carefully characterized by titration, intrinsic viscosity, FTIR, 13C-NMR, and zeta potential. The content of carboxyl groups in PO was dependent on reaction time and varied accordingly. Furthermore, a fast reaction rate was found in the first 2–3 h of the reaction, followed by a decreased rate in the subsequent hours. FTIR and 13C-NMR proved that the selective oxidation of the primary alcohol groups of pullulan was achieved. The oxidation also caused the glycoside linkages in the pullulan chain to break, and the viscosity of the pullulan itself went down.

Research on dissolution behavior of N-hydroxyphthalimide in three binary solvents: Measurement, modeling, molecular simulation and thermodynamics

Solubility data, relevant thermodynamic parameters as well as molecular interactions of N-hydroxyphthalimide (NHPI) in three binary solvents of (2-methoxyethanol (EGME), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone(NMP)) + water were focus of this research work. Experimental solubility values of NHPI in selected solvents ranged from 278.15 K to 323.15 K were obtained by laser monitoring method at 0.1 MPa. Corresponding results suggested that NHPI solubility increased with ascending temperature and increasing mass fraction of positive solvents (EGME, DMF, NMP) of binary solvents. The maximum solubility data of NHPI was found in neat DMF at 323.15 K while the minimum solubility data was obtained in pure water at 278.15 K. For investigation of solubility behavior, molecular electrostatic potential surface (MEPS), solvation free energy as well as radial distribution function (RDF) were performed by Multiwfn program and Material Studio (MS) 2017 software. Results indicated that solute–solvent interaction and solvent–solvent interaction played an important role in solubility behavior. Moreover, solubility modeling was realized by Wilson model, λh equation and modified Apelblat equation, three models acquired acceptable results with average relative deviation (ARD) less than 6.601 % and root mean square deviation (RMSD) no more than 1.461 ‰. Furthermore, thermodynamic parameters of dissolution process including enthalpy, entropy and Gibbs free energy were also discussed in this research work. The dissolution process was always endothermic and entropically driven.

Intermetallic Copper-Based Electride Catalyst with High Activity for C-H Oxidation and Cycloaddition of CO2 into Epoxides.

Inorganic electrides have been proved to be efficient hosts for incorporating transition metals, which can effectively act as active sites giving an outstanding catalytic performance. Here, it is demonstrated that a reusable and recyclable (for more than 7 times) copper-based intermetallic electride catalyst (LaCu0.67 Si1.33 ), in which the Cu sites activated by anionic electrons with low-work function are uniformly dispersed in the lattice framework, shows vast potential for the selective C-H oxidation of industrially important hydrocarbons and cycloaddition of CO2 with epoxide. This leads to the production of value-added cyclic carbonates under mild reaction conditions. Importantly, the LaCu0.67 Si1.33 catalyst enables much higher turnover frequencies for the C-H oxidation (up to 25 276 h-1 ) and cycloaddition of CO2 into epoxide (up to 800 000 h-1 ), thus exceeding most nonnoble as well as noble metal catalysts. Density functional theory investigations have revealed that the LaCu0.67 Si1.33 catalyst is involved in the conversion of N-hydroxyphthalimide (NHPI) into the phthalimido-N-oxyl (PINO), which then triggers selective abstraction of an H atom from ethylbenzene for the generation of a radical susceptible to further oxygenation in the presence of O2 .

Oxyfunctionalization of Benzylic C-H Bonds of Toluene Mediated by Covalently Anchored Co-Schiff Bases.

Oxyfunctionalization of toluene to value-added benzaldehyde, benzyl alcohol and benzoic acid is of great significance. In this work, Co-Schiff bases were immobilized on commercial silica gel by covalent anchoring, and resulting catalysts were used to catalyze the oxidation of toluene in the presence of the cocatalyst N-hydroxyphthalimide (NHPI). The catalysts exhibited excellent textural and structural properties, reliable bonding and a predomination of the cobaltous ions. The catalyst synthesized by diethylamino salicylaldehyde (EASA) possessed a grafting density of 0.14 mmol/g and exhibited a toluene conversion of 37.5%, with predominant selectivities to benzaldehyde, benzyl alcohol and benzoic acid under solvent-free conditions. It is concluded that the effect of ligands on their catalytic performance might be related to their electron-donating or -withdrawing properties.

Degradation of three typical hydroxamic acids collectors via UVA-B activated H2O2 and persulfate: Kinetics, transformation pathway, DFT calculation and toxicity evaluation

This work systematically studied the kinetics and mechanism of degradation of salicylhydroxamic acid (SHA), benzhydroxamic acid (BHA) and N-hydroxyphthalimide (NOP) by UVA-B/H2O2 and UVA-B/peroxodisulfate (PDS). UVA-B irradiation could induce a direct photolysis of SHA and dominated SHA destruction in both systems. BHA and NOP were effectively degraded via HO•- and SO4•−-mediated oxidation. UVA-B/PDS displayed a better degradation performance for HAAs investigated than UVA-B/H2O2. An acidic pH was more suitable for three HAAs removal in the UVA-B/H2O2 system. However, basic pH was more efficient for HAAs degradation in the UVA-B/PDS system. The degradation of BHA and NOP was predominantly driven by SO4•− at all pH levels used (5.0–9.0). The second-order rate constants for SHA, BHA and NOP reactions with HO• and SO4•− were calculated to be (4.16–5.22) × 109 M−1·s−1 and (1.19–7.22) × 109 M−1·s−1, respectively. Presence of various water constituents had different influence on HAA removal, with a enhancement in the presence of HCO3–, Fe2+ and Cu2+. When real waters were used as a background, dissolved organic carbon and Cl− were the main factors that consumed radicals and affected the degradation performance of HAAs. Analysis of the transformation products and density functional theory revealed that all of the investigated HAAs first generated amidated products but the formation mechanisms might have been different. HAAs degradation pathways mainly included hydrolysis, hydroxylation, decarboxylation and ring opening processes. Toxicity evaluation showed that the UV/AOP degradation of HAAs generated some transformation products with higher acute toxicity than the parent compounds.

Experimental and computational thermochemical study of three hydroxy-substituted phthalimides

We report experimental determinations of enthalpies and fusion temperatures, heat capacities (provided as polynomial functions of temperature), enthalpies of sublimation, and standard enthalpies of formation in the crystalline and gas phases at 298.15 K, for three phthalimide derivatives. These derivatives are N-hydroxy phthalimide, N-(hydroxymethyl) phthalimide, and N-(2-hydroxyethyl) phthalimide. The thermodynamic properties were experimentally obtained through thermal analysis techniques and combustion calorimetry. The enthalpies of formation in the gas phase at 298.15 K were calculated as well, using the G4 composite method in conjunction with atomization reactions and a Boltzmann weighted average that considers all stable conformers of each compound. The weights were estimated with the conformers' Gibbs energies. We found hydrogen bonds to be present in N-(hydroxymethyl) phthalimide and N-(2-hydroxyethyl) phthalimide, which were confirmed by means of theoretical analyses of the electron density. We also located weak non-covalent interactions in each stable conformer, which adds to the confirmation of hydrogen bonding. The experimental and theoretical thermochemical properties are in good agreement (less than 4 kJ difference per compound).

N‐Alkoxyphtalimides as Versatile Alkoxy Radical Precursors in Modern Organic Synthesis

AbstractO‐substituted derivatives of N‐hydroxyphthalimide (NHPI) have attracted much attention recently as synthetically available, stable, and convenient reagents for the generation of free radicals under mild conditions. The single‐electron reduction by a photoredox catalyst or another reagent results in the N−O bond cleavage of an NHPI derivative with the release of free radicals that undergo selective synthetic transformations. Whereas N‐acyloxyphtalimides (NHPI esters) are well known as a convenient C‐radical source due to the facile one‐electron reduction followed by the decarboxylation, N‐alkoxyphtalimides are much less studied as radical precursors. The present review shows that N‐alkoxyphtalimides are effective reagents for free‐radical transformations starting from the generation of alkoxy free radicals. Visible light induced reactions are discussed first, these processes are classified according to the way how intermediate alkoxy radicals transformed to C‐centered radicals: via hydrogen atom transfer to oxygen atom (HAT, including 1,5‐HAT, 1,2‐HAT, and intermolecular HAT) or via β‐scission. Other photochemical radical reactions of alkoxyphthalimides and non‐photochemical tin‐mediated processes are discussed separately.

The role of trace N-Oxyl compounds as redox mediator in enhancing antiviral ribavirin elimination in UV/Chlorine process

Ribavirin (RBV) is an antiviral drug used for treating COVID-19 infection. Its release into natural waters would threaten the health of aquatic ecosystem. This study reports an effective approach to degrade RBV by the trace N-oxyl compounds (2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) and N-Hydroxyphthalimide (NHPI)) enhanced UV activated free chlorine (UV/Chlorine) process. The results indicated that TEMPO and NHPI at low concentrations (0.1 μM and 1 μM, respectively) could strongly enhance RBV degradation in both deionized water with different pHs and practical surface water. The enhancement was verified to be attributed to the transformation of TEMPO and NHPI into their reactive forms (i.e., TEMPO+ and PINO), which generations deeply relied on radicals. The two N-oxyl compounds inhibit ClO• yield by hindering the reaction of free chlorine vs. HO• and Cl•. The analyses on acute toxicities of RBV degradation products indicate that UV/Chlorine/N-oxyl compounds process can detoxify RBV more efficiently than UV/Chlorine process.

Control of Redox‐Active Ester Reactivity Enables a General Cross‐Electrophile Approach to Access Arylated Strained Rings**

AbstractStrained rings are increasingly important for the design of pharmaceutical candidates, but cross‐coupling of strained rings remains challenging. An attractive, but underdeveloped, approach to diverse functionalized carbocyclic and heterocyclic frameworks containing all‐carbon quaternary centers is the coupling of abundant strained‐ring carboxylic acids with abundant aryl halides. Herein we disclose the development of a nickel‐catalyzed cross‐electrophile approach that couples a variety of strained ringN‐hydroxyphthalimide (NHP) esters, derived from the carboxylic acid in one step, with various aryl and heteroaryl halides under reductive conditions. The chemistry is enabled by the discovery of methods to control NHP ester reactivity, by tuning the solvent or using modified NHP esters, and the discovery thatt‐BuBpyCamCN, an L2X ligand, avoids problematic side reactions. This method can be run in flow and in 96‐well plates.

Control of Redox-Active Ester Reactivity Enables a General Cross-Electrophile Approach to Access Arylated Strained Rings.

Strained rings are increasingly important for the design of pharmaceutical candidates, but cross‐coupling of strained rings remains challenging. An attractive, but underdeveloped, approach to diverse functionalized carbocyclic and heterocyclic frameworks containing all‐carbon quaternary centers is the coupling of abundant strained‐ring carboxylic acids with abundant aryl halides. Herein we disclose the development of a nickel‐catalyzed cross‐electrophile approach that couples a variety of strained ring N‐hydroxyphthalimide (NHP) esters, derived from the carboxylic acid in one step, with various aryl and heteroaryl halides under reductive conditions. The chemistry is enabled by the discovery of methods to control NHP ester reactivity, by tuning the solvent or using modified NHP esters, and the discovery that t‐BuBpyCamCN, an L2X ligand, avoids problematic side reactions. This method can be run in flow and in 96‐well plates.

Utilization of photocatalysts in decarboxylative coupling of carboxylic N-hydroxyphthalimide (NHPI) esters

Recently, the visible-light photoredox decarboxylative couplings of N-(acyloxy)phthalimides (NHPI esters) and its derivatives have become an efficient chemical transformation. Under visible light, the NHPI esters undergo a single-electron transfer (SET) process to afford the corresponding carbon or nitrogen radicals that participate in many chemical transformations. The photoredox decarboxylative couplings have been applied to achieve construction of an array of carbon–carbon and carbon–heteroatom bonds as well as the synthesis of carbocycles and heterocycles. This review categorises photocatalysts, discusses the application and catalysis mechanisms of NHPI esters, and details recent progress in this field.

Highly efficient and low pollution catalytic oxidation of ramie degumming by NHPI

A new ramie degumming method, N-Hydroxyphthalimide (NHPI) catalytic oxidation degumming method (NCODM), was proposed to solve the environmental pollution problems as well as the energy consumption problems of the traditional alkaline degumming method (TADM) and the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidation degumming method (TODM). In this paper, the effect of parameters on the properties of ramie fibers degummed by NCODM was investigated. Then, the degumming process was optimized by comparing with the different degumming methods using central composite design method. The results showed that the H2O2 concentration and reaction time were significant factors that determined the properties of ramie fibers. The optimum H2O2 concentration was 16.70 g/L and the optimum reaction time was 19.38 min. The time required for NCODM was only 79.38 min, which was 26.46% and 62.19% of that of TADM (300 min) and TODM (127.64 min), respectively. Moreover, the chemical oxygen demand (COD) value of the wastewater from NCODM was 31% and 3% lower than that of TADM and TODM, respectively. Therefore, NCODM has great potential to replace the TADM and TODM for ramie degumming.

Synthesis of Polycyclic Quinazolinones through C(sp3)−H Functionalization of Inert Alkanes or Visible‐Light‐Promoted Oxidation Decarboxylation of N‐Hydroxyphthalimide Esters

AbstractTwo novel C(sp3)−H functionalization of inert alkanes and visible‐light promoted oxidation decarboxylation of N‐hydroxyphthalimide (NHP) esters to access polycyclic quinazolinones have been described. These methods do not involve metal catalysts and are carried out in water or water/DMSO media. The wide substrate scope, even including the seven‐membered ring under mild reaction conditions, demonstrate the practicability of these strategies.

Development of lucigenin-N-hydroxyphthalimide chemiluminescence system and its application to sensitive detection of Co2+

N-hydroxyphthalimide (NHPI) is an efficient organic catalyst and an important chemical raw material which can be used as an intermediate in organic synthesis of drugs and pesticides. In this study, NHPI has been used as a coreactant of lucigenin chemiluminescence (CL) for the first time. The CL of the developed system is significantly enhanced in the presence of Co2+. Therefore, we developed a novel lucigenin-NHPI CL method coupled with flow injection analysis for the sensitive, precise, and selective determination of Co2+. The linear range of this method is 1–1000 nM, and the detection limit is 67 pM (S/N = 3). In addition, this method has a good selectivity for Co2+. It has been applied to the detection of Co2+ in lake water, and the standard recovery rate is 95.9–103.2%, indicating that the method is feasible.

A facile electrosynthesis of N-acyl benzotriazoles from aldehydes and benzotriazole

An electrochemical synthesis of N-acylbenzotriazoles has been developed under mild conditions with good to excellent yields using aldehydes and benzotriazole as starting materials. In addition, a one-pot reaction of aldehyde, benzotriazole and phenol has been achieved affording phenolic esters in moderate yields under the combination of electricity-on/off conditions, where N-acyl benzotriazole acted as the benign acylating reagent. It is noteworthy the research provided environmental friendly syntheses in that no superstoichiometric hazardous chemical oxidants were required, corrosive/toxic reagents have been avoided and waste production has significantly been reduced. The key of the electrochemical synthesis involves the oxidation of benzotriazole-aldehyde adduct by phthalimido-N-oxy (PINO), which was generated by N-hydroxyphthalimide (NHPI) as a redox mediator.

Enhanced photoelectrochemical aptasensing for sensitive detection of diazinon pesticide used N-hydroxyphthalimide as an effective hole mediator

Signal amplification strategies are of great interest in photoelectrochemical (PEC) sensing research. Herein, we explored a novel approach whereby hole transfer was accelerated from the photosensitive material Blue-TiO2 (B-TiO2) to the hole mediator N-hydroxyphthalimide (NHPI). Simultaneously, the introduction of the organic molecule NHPI can promote the efficiency of visible light absorption and expand the absorption range of B-TiO2. Under visible light irradiation, the photocurrent value of NHPI/B-TiO2 is 2.7-fold larger than that of B-TiO2, which can be ascribed to the acceleration of hole transfer by NHPI. More specifically, NHPI acts as a hole mediator, which effectively transfers photo-generated holes from the valence band (VB) of B-TiO2 to NHPI. NHPI can be oxidized to phthalimide-N-oxyl radical (PINO*), thereby causing inhibition of photo-generated carrier recombination and enhancement of the photocurrent. Furthermore, a PEC aptasensor for the sensitive detection of diazinon (DIA) was constructed by combining specific aptamers on an NHPI/B-TiO2 nanocomposite surface. The oxidation product of NHPI, PINO*, oxidizes the DIA captured by the aptamer. Under optimized experimental conditions, the linear range for DIA detection was 0.1–1000 nM, and the detection limit of the NHPI/B-TiO2 nanocomposite aptamer sensing was 0.03 nM (S/N = 3). Therefore, this proposed method involving the hole mediator can be used as a new strategy to improve the performance of PEC.