背景:氧化是制备有机化学中的有价值的工具。在这一努力中,已经证明氧铵盐和氮氧化物作为试剂和催化剂是有价值的。
目的:本研究的目的是扩大氧化酰胺化,酯的形成,和使用氮氧化物作为有机催化剂形成腈。
方法:将氧化官能化反应从1mmol缩放到1-摩尔水平。过硫酸钠用作主要氧化剂,和硝基氧用作催化剂。通过萃取分离分析纯形式的反应产物,无需柱色谱。
结果:醛的氧化酰胺化和酯化可以有效地从1mmol增加到1mol,在每次增量时获得可比的产品产量。这项工作表明,小规模开发的条件可以转移到更大规模,而无需重新优化。醛的氧化官能化以制备腈不适合直接放大,因为伴随着大量相应的羧酸的形成。从而损害产品产量。
结论:本文研究的三种氧化转化中的两种可以成功地从1mmol放大到1-mol水平。
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.
CONCLUSIONS: Two of the three oxidative transformations studied here can be scaled up successfully from the 1 mmol to the 1 mole level.