N-hydroxy ester preparation method

Abstract

The invention discloses an N-hydroxy ester preparation method. According to the method, an aldehyde derivative and a hydroxylamine derivative are adopted as reaction substrates, iodide is adopted as an accelerant, tertbutyl alcohol hydrogen peroxide is adopted as an oxidant, and then N-hydroxy ester is prepared through diradical cross coupling reaction. The chemical structural formula of the aldehyde derivative is shown in the description, and in the formula, R1 is naphthyl, alkyl or monosubstituted aryl; and the iodide is sodium iodide NaI, potassium iodide KI, cuprous iodide CuI, lithium iodide LiI, iodine I2, tetrabutyl ammonium iodide, or tetraheptylammonium iodide. As the iodide is adopted as the accelerant, the N-hydroxy ester is prepared by using a diradical cross coupling method, and the traditional expensive high-toxicity metal accelerant and a traditional cumbersome experiment method are not used, the reaction is simpler, more convenient, more feasible, safer, more environment-friendly and more economical, the reaction conditions are quite mild, and the aftertreatment is simpler.

Description

technical field [0001] The present invention relates to a process for the preparation of N-hydroxyesters. Background technique [0002] N-hydroxy esters are a very important structural unit, which widely exist in natural products and drug molecules with physiological activity, and are often seen in synthetic intermediates. [0003] At present, the method for preparing N-hydroxy esters has the disadvantages of large amount of catalyst, high price, high toxicity, harsh reaction conditions, low selectivity, and narrow use range of substrates. E.g: [0004] (1) Somu, Ravindranadh V. et al. reported the use of carboxylic acid and its derivatives with hydroxylamine coupling reaction to prepare N-hydroxyl esters, (see: Somu, Ravindranadh V.; Boshoff, Helena; Qiao, Chunhua; Bennett, Eric M.; Barry, Clifton E.; Aldrich, Courtney C., Journal of Medicinal Chemistry, 2006, 49, 31-34); the limitation of this method is that only carboxylic acids can be used as reaction substrates. [0...

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Problems solved by technology

[0004] (1) Somu, Ravindranadh V. et al. reported the use of carboxylic acid and its derivatives with hydroxylamine coupling reaction to prepare N-hydroxyl esters, (see: Somu, Ravindranadh V.; Boshoff, Helena; Qiao, Chunhua; Bennett, Eric M.; Barry, Clifton E.; Aldrich, Courtney C., Journal of Medicinal Chemistry, 2006, 49, 31-34); the limitation of this method is that only carboxylic acids can be used as reaction substrates

[0005] (2) Lou, Rongliang et al reported the synthesis of a class of N-hydroxyl esters through the multicomponent reaction of halogenated aromatics with hydroxylamine and carbon monoxide, (see: Lou, Rongliang; VanAlstine, Melissa; Sun, Xufeng; Wentland, Mark P ., Tetrahedron Letters, 2003, 44, 2477-2480) and the halogenated aromatic hydrocarbons used in this method have greater toxicity

[0006] (3) Malmstroem, Eva et al. reported that the coupling reaction of acid chloride and hydroxylamine directly produced the reaction of N-hydroxyl ester, (seeing: Malmstroem, Eva; Miller, Robert D.; Hawker, Craig J., Tetrahedron, 1997, 53, 15225-15236), while acid chlorides are easily hydrolyzed and relatively dangerous to handle

[0007] (4) Colton, Ian J. et al reported the efficient preparation of N-hydroxyl esters using carboxylate as an acylating agent, (see: Colton, Ian J.; Anderson, Janelle R.; Gao, Jinming; Chapman, Robert G.; Isaacs, Lyle; Whitesides, George M., Journal of the American Chemical Society, 1997, 119, 12701-12709); the limitation of this method is that only carboxylic acids can be used as reaction substrates

[0008] (5) Bailen, Miguel A. et al reported the efficient preparation of N-hydroxyl esters using carboxylic acid and hydroxyl-protected hydroxylamine, (see: Bailen, Miguel A.; Chinchilla, Rafael; Dodsworth, David J.; Najera , Carmen, Tetrahedron Letters, 2002, 43, 1661-1664), and the method of hydroxyl protection is obviously cumbersome

[0009] Although there are many methods for synthesizing N-hydroxyl esters, some catalysts used in these methods are more expensive (such as Ru, Rh, Pd, Ni, Cu), some catalytic systems are more loaded down with trivial details, and some reactants are troublesome to prepare, and the price is more expensive. The use range of the substrate is narrow and has great limitations, which limits its large-scale application

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