磺酰肼、N-羟基磺酰胺参与的一些硫醚化和砜基化反应研究

发布时间：2018-07-05 15:37

本文选题：磺酰肼 + 自由基串联环化　；参考：《中国科学技术大学》2017年博士论文

【摘要】：砜和硫醚化合物大量存在于天然产物和药物分子中,另外在作为合成中间体也具有广泛的应用。近年来发展的磺酰肼作为硫醚化试剂,由于其一般是固体,具有对水不敏感、操作简单、无难闻气味等优点,通过形成S-C键来得到硫醚,进而能够与各种有机化合物反应。然而与磺酰肼发生众多的反应类型相比,N-羟基磺酰胺发生的反应类型则较少,尤其是作为砜基化试剂。此外N-羟基磺酰胺作为硫醚化试剂则还未有报道。为了拓展磺酰肼作为硫醚化试剂在有机反应中的应用,以及发展N-羟基磺酰胺作为一种前所未有新型的硫醚化试剂和作为砜基化试剂在关环反应中的应用,本文进行下面四个工作的探讨。本文发展了磺酰肼作为硫醚化试剂与N-芳基丙烯酰胺在廉价碘催化下的自由基串联环化反应,选择性地给出3-硫甲基氧化吲哚和3-硫基-3,4-二氢喹啉-2(1H)-酮。初步的机理研究表明,在早期阶段磺酰肼基本上在碘催化下已经完全分解为硫代磺酸酯和二硫醚;在后一个阶段,这两个中间体进一步在碘催化下与N-芳基丙烯酰胺进行自由基串联硫醚化/环化反应。利用磺酰肼作为亲电硫试剂,本文发展了氧化吲哚与磺酰肼在碘催化下的5-位硫醚化反应,选择性合成了一系列五元和六元杂环与磺酰肼进行硫醚化反应。该反应具有高度化学区域选择性,以及反应绿色,其产生的水和氮气对环境友好。本文发展了 N-羟基磺酰胺在有机合成中的一种新应用,即它作为硫醚化试剂与芳香化合物经过S=O和S-N键的断裂得到硫醚化合物。在10 mol%的碘和30 mol%的N-羟基丁二酰亚胺的催化下,一系列N-羟基芳基磺酰胺快速地与吲哚,7-氮杂吲哚,N-甲基吡咯或2-萘酚以高度区域选择性以及中等到优秀的产率构建结构多样化的硫醚。初步的机理研究表明,N-羟基芳基磺酰胺首先分解为亚磺酸,后再与芳香化合物经过硫醚化而得到最终产物。利用N-羟基磺酰胺作为砜基化试剂,本文进一步发展了 N-羟基磺酰胺与N-芳基丙烯酰胺以及芳甲酰基甲基丙烯酰亚胺,在廉价硝酸银和过硫酸钾共同催化下的自由基串联砜基化/环化反应,得到一系列结构多样化的氧化吲哚和异喹啉-1,3(2H,4H)-二酮。
[Abstract]:Sulfone and sulfide compounds are abundant in natural products and drug molecules, and are also widely used as synthetic intermediates. Sulfonyl hydrazide, as a sulfidizing reagent developed in recent years, is generally solid, which has the advantages of being insensitive to water, simple to operate, no smell and so on. The sulfides can be obtained by forming S-C bond, which can react with various organic compounds. However, the reaction types of N-hydroxysulfonamide are less than those of sulfonyl hydrazide, especially as sulfone group reagents. In addition, N-hydroxysulfonamide as a sulfidation reagent has not been reported. In order to expand the application of sulfonyl hydrazide as a sulfidizing reagent in organic reactions, and to develop the application of N-hydroxysulfonamide as an unprecedented new sulfidizing reagent and as sulfone group reagent in the cyclization reaction, This article carries on the following four work discussion. In this paper, a series cyclization reaction of sulfonyl hydrazide with N-aryl acrylamide catalyzed by cheap iodine has been developed. The reaction of 3-thiomethyl oxoindole and 3-thio-4-dihydroquinoline-2 (1H) -one has been selectively given. Preliminary mechanism studies show that sulfonyl hydrazide has been completely decomposed into thiosulfonate and disulfide in the early stage under the catalysis of iodine, while in the latter stage, the sulfonyl hydrazine has been completely decomposed into thiosulfonate and disulfide. The two intermediates were further reacted with N-aryl acrylamide by radical series sulfation / cyclization catalyzed by iodine. Using sulfonyl hydrazine as an electrophilic sulfur reagent, the 5-position sulfidization reaction of indoles and sulfonyl hydrazides catalyzed by iodine was developed. A series of five-member and six-member heterocycles were selectively synthesized for sulfidation with sulfonyl hydrazide. The reaction is highly chemically regioselective and green, and produces water and nitrogen that are environmentally friendly. In this paper, a new application of N-hydroxysulfonamide in organic synthesis has been developed, that is, it is used as a sulfidizing reagent and the aromatic compounds are broken down by Sino and S-N bonds to form sulfides. Catalyzed by 10 mol% iodine and 30 mol% N-hydroxysuccinimide, A series of N-hydroxy-aryl sulfonamide was rapidly constructed with indole 7-azindole-N-methylpyrrole or 2-naphthol with high regioselectivity and intermediate to excellent yields. The preliminary mechanism study shows that N-hydroxy-aryl sulfonamide is first decomposed into sulfonic acid and then sulfided with aromatic compounds to obtain the final product. Using N-hydroxysulfonamide as sulfone, N-hydroxysulfonamide, N-aryl acrylamide and aryl methacrylamide were further developed. A series of oxyindole and isoquinoline -1H _ 3 (2H _ 4H) -diketone were synthesized by series sulfone / cyclization of free radical catalyzed by cheap silver nitrate and potassium persulfate.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O621.25

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