Real-time in situ monitoring using visible spectrophotometry as a tool for probing electrochemical advanced oxidation processes for dye decolorisation.

An apparatus for real-time in situ monitoring of electrochemical processes using UV-visible spectrophotometry has been used to optimise the electrochemically-activated persulfate decolorisation of Acid Orange 7. The impacts of varying electrode composition, current density, persulfate loading, and stirring speed on the rate of decolorisation have been probed. Decolorisation through this activated persulfate approach was compared to that using anodic oxidation for nine dyes; three from each of the azo, triarylmethane, and xanthene families. The core structure and presence of functional groups have a significant impact on the rate of decolorisation. Azo and xanthene dyes decolorise faster than triarylmethane dyes, while electron-withdrawing groups and halogens are especially detrimental to the rate of decolorisation. Electrochemically-activated persulfate resulted in faster decolorization than anodic oxidation for almost every dye, an effect that was enhanced with the electron-deficient substrates. This type of systematic structural comparison study is essential for designing electrochemical degradation procedures for the remediation of real wastewater.

Scale-up of Sodium Persulfate Mediated, Nitroxide Catalyzed Oxidative Functionalization Reactions.

BACKGROUND: Oxidation is a valuable tool in preparative organic chemistry. Oxoammonium salts and nitroxides have proven valuable as reagents and catalysts in this endeavor. OBJECTIVE: The objective of this study is to scale up the oxidative amidation, ester formation, and nitrile formation using nitroxide as an organocatalyst. METHODS: Oxidative functionalization reactions were scaled from the 1 mmol to the 1-mole level. Sodium persulfate was used as the primary oxidant, and a nitroxide was employed as a catalyst. The products of the reactions were isolated in analytically pure form by extraction with no need for column chromatography. RESULTS: The oxidative amidation and esterification of aldehydes can be scaled up from 1 mmol to 1 mole effectively, with comparable product yields being obtained at each increment. This work shows that conditions developed on a small scale can be transferred to a larger scale without reoptimization. The oxidative functionalization of aldehydes to prepare nitriles is not amenable to direct scale-up due to the concomitant formation of significant quantities of the corresponding carboxylic acid, thereby compromising the product yield. CONCLUSION: Two of the three oxidative transformations studied here can be scaled up successfully from the 1 mmol to the 1-mole level.

Acetamido-TEMPO mediated electrochemical oxidation of alcohols to aldehydes and ketones.

A protocol for the oxidation of alcohols to aldehydes and ketones employing an electrochemical aminoxyl-mediated reaction is presented. The approach employs a catalytic amount of the radical and the use of a base is not required. It is performed using readily available electrodes in a commercially available electrochemistry apparatus and does not require a reference electrode. The methodology is applicable to a range of structurally and electronically diverse substrates, including the oxidation of primary alcohols to aldehydes rather than the more commonly formed carboxylic acids.

Solvent- and additive-free oxidative amidation of aldehydes using a recyclable oxoammonium salt.

A range of acyl azoles have been prepared from aromatic, heteroaromatic, and aliphatic aldehydes by means of an oxidative amidation reaction. The methodology employs a substoichiometric quantity of an oxoammonium salt as the oxidant. It avoids the need for additives such as a base, is run solvent-free, and the oxoammonium salt is recyclable.

Preparation of nitriles from aldehydes using ammonium persulfate by means of a nitroxide-catalysed oxidative functionalisation reaction.

A methodology for the preparation of nitriles from aldehydes by means of an oxidative functionalisation reaction is reported. It employs ammonium persulfate as both the primary oxidant and the nitrogen source, and a catalytic amount of a nitroxide. It is applicable to a range of structurally diverse (hetero)aromatic aldehydes furnishing the nitrile products in 30-97% isolated yield. Given the ready accessibility of aldehydes and that ammonium persulfate is cheap and less toxic than many other reagents for generating nitriles, this methodology offers a simple and easy to use approach to this valuable class of compounds.

Preparation of hexafluoroisopropyl esters by oxidative esterification of aldehydes using sodium persulfate.

A simple, metal-free route for the oxidative esterification of aldehydes to yield hexafluoroisopropyl esters is reported. The methodology employs sodium persulfate and a catalytic quantity of a nitroxide and is applicable to aromatic, heteroaromatic, and aliphatic aldehydes.

Using experimental and computational approaches to probe an unusual carbon-carbon bond cleavage observed in the synthesis of benzimidazole N-oxides.

Experimental and computational studies have been performed in order to investigate an unusual carbon-carbon bond cleavage that occurs in the preparation of certain benzimidazole N-oxides from anilines. The key factor determining the outcome of the reaction was found to be the substituents on the amine functionality of the aniline.

Oxidative Amidation of Amines in Tandem with Transamidation: A Route to Amides Using Visible-Light Energy.

A methodology is reported for preparing amides using amines as an acyl source. The protocol involves the visible-light-promoted oxidative amidation of amines with pyrazole to synthesize N-acyl pyrazoles followed by transamidation. By combining photoredox catalysis with oxoammonium cations in the presence of sodium persulfate as a terminal oxidant, the N-acyl pyrazoles could be prepared efficiently and effectively using blue LEDs. The transamidation step was performed without the need to purify the N-acyl pyrazole intermediate, and a range of amides were generated in good to excellent yields.

One-Pot Two-Step Synthesis of 2-Aryl benzimidazole N-oxides Using Microwave Heating as a Tool.

A methodology is reported for the preparation of 2-aryl-benzimidazole-3-oxide derivatives. By means of a one-pot two-step protocol, a library of 42 new compounds has been prepared. Reactions were performed in a total time of 40 min using microwave heating as a tool. A streamlined work-up process was also developed, allowing for facile isolation of the products. The methodology offers a more sustainable approach than previous routes, with only water and ethanol being used as solvents, and the products being isolated by means of a simple filtration without the need for any further purification.

Visible-light-driven catalytic oxidation of aldehydes and alcohols to nitriles by 4-acetamido-TEMPO using ammonium carbamate as a nitrogen source.

A mild and efficient route to prepare nitriles from aldehydes by combining photoredox catalysis with oxoammonium cations is reported. The reaction is performed using ammonium carbamate as the nitrogen source. The practicality of the method is increased by the extension of the dual catalytic system to one-pot two-step conversion of alcohols to nitriles.

Oxidation of α-trifluoromethyl and non-fluorinated alcohols via the merger of oxoammonium cations and photoredox catalysis.

We present an alcohol oxidation strategy to access α-trifluoromethyl ketones (TFMKs) merging catalytic oxoammonium cation oxidation with visible-light photoredox catalysis. This work uses 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl as an organic oxidant capable of generating TFMKs in good yields. The methodology serves as an improvement over previous reports of an analogous oxidation strategy requiring superstoichiometric quantities of oxidant. Both primary and secondary non-fluorinated alcohols can also be oxidised in good yields.

Oxidative functionalisation of alcohols and aldehydes via the merger of oxoammonium cations and photoredox catalysis.

We present a new paradigm for nitroxyl-mediated processes via the merger of oxoammonium cation-mediated oxidation with visible-light photoredox catalysis. The integration of these two forms of catalysis has been realised for the oxidative amidation of aldehydes, furnishing N-acylated heterocycles. Extension of this process to the oxidative amidation of alcohols via the intermediacy of an aldehyde was successfully pursued, thus proffering a general oxidation platform. The activated amides synthesised here are excellent synthetic handles for acylation.

Accessing N-Acyl Azoles via Oxoammonium Salt-Mediated Oxidative Amidation.

An operationally simple, robust, metal-free approach to the synthesis of N-acyl azoles from both alcohols and aldehydes is described. Oxidative amidation is facilitated by a commercially available organic oxidant (4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and proceeds under very mild conditions for an array of structurally diverse substrates. Tandem reactions of these activated amides, such as transamidation and esterification, enable further elaboration. Also, the spent oxidant can be recovered and used to regenerate the oxoammonium salt.

Oxidation of terminal diols using an oxoammonium salt: a systematic study.

A systematic study of the oxidation of a range of terminal diols is reported, employing the oxoammonium salt 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (4-NHAc-TEMPO+ BF4-) as the oxidant. For substrates bearing a hydrocarbon chain of seven carbon atoms or more, the sole product is the dialdehyde. A series of post-oxidation reactions have been performed showing that the product mixture resulting from the oxidation step can be taken on directly to a subsequent transformation. For diols containing four to six carbon atoms, the lactone product is the major product upon oxidation. In the case of 1,2-ethanediol and 1,3-propanediol, when using a 1 : 0.5 stoichiometric ratio of substrate to oxidant, the corresponding monoaldehyde is formed which reacts rapidly with further diol to yield the acetal product. This is of particular synthetic value given both the difficulty of their preparation using other approaches and also their potential application in further reaction chemistry.

A combined computational and experimental investigation of the oxidative ring-opening of cyclic ethers by oxoammonium cations.

The propensity of oxoammonium cations to facilitate the oxidative ring-opening of cyclic ethers to their corresponding distal hydroxy ketones is investigated. The reaction has been evaluated using experimental and computational methods to gain deeper insight into trends in reactivity.

Rules of Macrocycle Topology: A [13]-Macrodilactone Case Study.

Shape is an inherent trait of a molecule that dictates how it interacts with other molecules, either in binding events or intermolecular reactions. Large-ring macrocyclic compounds in particular leverage their shape when they are selectively bound by biomolecules and also when they exhibit macrocyclic diastereoselectivity. Nonetheless, rules that link structural parameters to the conformation of a macrocycle are still rudimentary. Here we use a structural investigation of a family of [13]-macrodilactones as a case study to develop rules that can be applied generally to macrocycles of different sizes and with a variety of functionality. A characteristic "ribbon" shape is adopted by the [13]-macrodilactones in the absence of stereogenic centres, which exhibits planar chirality. When one stereogenic centre at key positions on the backbone is incorporated into the structure, the planar chirality is dictated by the configuration of the centre. In cases where two stereogenic centres are present, their relationships can either reinforce the characteristic ribbon shape or induce alternative shapes to be adopted. The rules established in the case study are then applied to the analysis of a structure of the natural product migrastatin. They lay the groundwork for the development of models to understand macrocycle-biomolecule interactions and for the preparation of macrocycles with designed properties and activities.

Real-time Monitoring of Reactions Performed Using Continuous-flow Processing: The Preparation of 3-Acetylcoumarin as an Example.

By using inline monitoring, it is possible to optimize reactions performed using continuous-flow processing in a simple and rapid way. It is also possible to ensure consistent product quality over time using this technique. We here show how to interface a commercially available flow unit with a Raman spectrometer. The Raman flow cell is placed after the back-pressure regulator, meaning that it can be operated at atmospheric pressure. In addition, the fact that the product stream passes through a length of tubing before entering the flow cell means that the material is at RT. It is important that the spectra are acquired under isothermal conditions since Raman signal intensity is temperature dependent. Having assembled the apparatus, we then show how to monitor a chemical reaction, the piperidine-catalyzed synthesis of 3-acetylcoumarin from salicylaldehyde and ethyl acetoacetate being used as an example. The reaction can be performed over a range of flow rates and temperatures, the in-situ monitoring tool being used to optimize conditions simply and easily.

Toward a Unified Mechanism for Oxoammonium Salt-Mediated Oxidation Reactions: A Theoretical and Experimental Study Using a Hydride Transfer Model.

A range of oxoammonium salt-based oxidation reactions have been explored computationally using density functional theory (DFT), and the results have been correlated with experimentally derived trends in reactivity. Mechanistically, most reactions involve a formal hydride transfer from an activated C-H bond to the oxygen atom of the oxoammonium cation. Several new potential modes of reactivity have been uncovered and validated experimentally.

Oxidative cleavage of allyl ethers by an oxoammonium salt.

A method to oxidatively cleave allyl ethers to their corresponding aldehydes mediated by an oxoammonium salt is described. Using a biphasic solvent system and mild heating, cleavage proceeds readily, furnishing a variety of α,ß-unsaturated aldehydes and ketones.

Access to nitriles from aldehydes mediated by an oxoammonium salt.

A scalable, high yielding, rapid route to access an array of nitriles from aldehydes mediated by an oxoammonium salt (4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate) and hexamethyldisilazane (HMDS) as an ammonia surrogate has been developed. The reaction likely involves two distinct chemical transformations: reversible silyl-imine formation between HMDS and an aldehyde, followed by oxidation mediated by the oxoammonium salt and desilylation to furnish a nitrile. The spent oxidant can be easily recovered and used to regenerate the oxoammonium salt oxidant.