Preparation and application of a swern reagent

Abstract

The invention discloses a 4-(2-(2-(methylsulfoxide)ethyl)-4-nitrophenyl)morpholine represented by formula (I), and discloses its preparation and application. Its preparation method is as follows: 2-(2-chloro-5 nitro)phenethyl alcohol and morpholine as shown in formula (II) are mixed to obtain 2-(2-morpholine-5 as shown in formula (III) -Nitrophenyl) ethanol; Then in (III), add dropwise two (trichloromethyl) carbonates successively, sodium methyl mercaptide aqueous solution, hydrogen peroxide aqueous solution, finally make 4-(2-(2-(form (sulfoxide)ethyl)-4-nitrophenyl)morpholine. Its application is to react the obtained swern reagent with the alcohol compound shown in formula (IV), and prepare the aldehyde or ketone shown in formula (V) through post-treatment. The present invention overcomes the shortcomings of the existing Swern oxidation method, avoids the generation of foul-smelling by-products dimethyl sulfide and toxic carbon monoxide from the source, increases the reaction temperature to -30°C to 0°C, and has no odor The by-product new sulfide can be recovered and reused.

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.Tetrahedron Let., 2014,55(50):6895-6898.) The common feature of these methods is that the reaction temperature is all increased, but by-products with foul smell cannot be avoided Production of dimethyl sulfide

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