Preparation and application of novel Swern reagent

Abstract

The invention discloses 4-(2-(2-methyl sulfoxide)ethyl)-4-nitrobenzene)morpholine shown in the formula (I) and preparation and application thereof. A preparation method includes the steps that 2-(2-chlorine-5 nitro)phenethyl alcohol shown in the formula (II) and morpholine are mixed to prepare 2-(2-morpholine-5-nitrobenzene)ethanol shown in the formula (III); bis(trichloromethyl)carbonate ester, a sodium methyl mercaptide aqueous solution and an aqueous hydrogen peroxide solution are sequentially added dropwise to 2-(2-morpholine-5-nitrobenzene)ethanol shown in the formula (III), and finally 4-(2-methyl sulfoxide)ethyl)-4-nitrobenzene)morpholine is prepared. According to the application of 4-(2-methyl sulfoxide)ethyl)-4-nitrobenzene)morpholine, the obtained Swern reagent reacts with an alcohol compound shown in the formula (IV), and aldehyde or ketone is prepared after after-treatment. The defects of an existing Swern oxidation method are overcome, generation of a stink byproduct dimethyl sulfide and toxic carbon monoxide is avoided from the source, the reaction temperature is increased to be -30 DEG C to 0 DEG C, and an odorless byproduct novel sulfur ether can be recycled and reused. The formulas are shown in the description.

Description

(1) Technical field [0001] The invention relates to a novel methyl sulfoxide reagent based on the Swern oxidation reaction. The novel Swern reagent prepared by reacting the reagent with bis(trichloromethyl)carbonate can oxidize alcohols into corresponding aldehydes or ketones. (2) Technical background [0002] The oxidation of alcohols to carbonyl compounds is a very critical class of reactions in organic synthesis, and also plays an extremely important role in the synthesis of drugs. Swern oxidation is a method for efficiently oxidizing alcohols to carbonyl compounds, which plays an irreplaceable role in the preparation of pharmaceutical intermediates. [0003] The Swern oxidation method is a method for the efficient oxidation of alcohols to carbonyl compounds developed by Swern et al. in 1978. The reaction is carried out in anhydrous system at -60°C, and the reagents used are cheap and easy to obtain. The method has good effects on aromatic alcohols and long-chain aliphat...

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Problems solved by technology

[0007] In 2001, Crich et al. developed another odorless Swern oxidation, which replaced a methyl group in dimethyl sulfoxide with a long aliphatic chain substituted by fluorine atoms (structural formula as shown in the figure below), and also avoided The formation of dimethyl sulfide, and the reaction temperature was raised to -30 ° C, made great progress, but the separation process of the product takes a long time, uses a variety of organic solvents, and the operation is cumbersome

[0011] In 2011, methyl sulfoxide (structural formula as shown in the figure below) supported by Togo plasma replaced dimethyl sulfoxide. The reaction yield was high, and the separation and purification of the product was simple. Unfortunately, this method did not solve the problems of low reaction temperature and carbon monoxide release.

(Luca, L.D.; Giacomelli, G.; Porcheddu, A.J. Org. Chem., 2001, 66(23):7907-7909. Wang, Y.; Wang, C.; Sun, J. Synth. Commun., 2014, 44:2961-2965.Nguyen, T.V.; Hall, M.TetrahedronLet., 2014,55(50):6895-6898.) The common feature of these methods is that the reaction temperature is all improved, but the by-product di Production of methyl sulfide

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