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.

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.