Synthesis of Indol-2-one Derivatives via Free Radical Reaction By Sulfonyl Radical
| Autor: | Yuan-HanLi, 黎瀚元 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 SUMMARY Use of radical cyclization to the unsaturated bonds is considered to be a very useful way for the synthesis of heterocyclic compounds. Alkylsulfonyl radical can undergo addition reaction with unsaturated bound or elimination reaction of intermediate. In this thesis, we use a catalytic amount of silver (I) with potassium persulfate to oxidizing p-toluenesulfinate sodium salt and oxidizing p-toluenesulfinate sodium salt by potassium persulfate in heating condition are taken as sulfonyl radical source, and then induced free radical cyclization reaction with sulfonamides or amides in our report. The results show that we can use this method to synthesize a variety of indol-2-one derivatives, and is applicable to a variety of functional groups. Moreover, this free radical cyclization reaction can react without silver(I) catalyst. INTRODUCTION Indol-2-one is an important basic skeleton of natural products, which exhibit a lot of biological activity and pharmacological activity, including relieves pain, anticancer, antitumor, and other activities. As a result, the preparation of indole-2-one derivatives compounds has attracted a great deal of interest. Reviewing the related literature, most of the methods are metal-catalyzed syntheses, including Mn(III), Pd(II), Ag(II). Recently there has been a growing interest in the application of free radical reactions in organic synthesis. Radical reactions have played an important role in organic synthesis, especially in the use of radical cyclization to the unsaturated bonds is considered as a very useful way for the synthesis of heterocyclic compounds. Alkylsulfonyl radical is a multi-function radical. It can undergo addition reaction with unsaturated bond, or elimination reaction of intermediate, or both of them. p-toluenesulfonyl radical can be generated from sodium p-toluenesulfonate in aqueous potassium persulfate and sodium p-toluenesulfonate is used as a p-toluenesulfonyl radical precursor in sulfonyl radical mediating reactions. In our laboratory previous studies, synthesis of heterocyclic compounds via silver(II) mediated oxidative radical reactions obtained good results. In the first part of this thesis, we synthesis indol-2-one compounds in two ways: one is using catalytic amount of silver (I), and the other one is metal free. In the second part of this thesis, we are using sulfonamides compounds to synthesis indol-2-one compounds by the sulfonyl radicals. In order to improve the yield of indol-2-ones, we optimized the reaction conditions, a number of different functional groups display a wide range of applicability of this reaction. In the third part of this thesis, we are trying to synthesis indol-2-ones via secondary free radical, and want to alkylation of sulfonylamide compounds. RESULTS AND DISCUSSION According to the past literature, the balance in syn form and anti form of the radical intermediate cause by steric effects. When R1 = H, radical intermediates is anti form, anti form is unfavorable to undergo cyclization reaction and will obtained reducing product. When R1 = alkyl group, radical intermediates tend to syn form, only syn form can undergo cyclization reaction. Thus, we need to change R1 into alkyl group to undergo cyclization reaction. The first part: we synthesis indole-2-one compounds with catalytic amount of silver(I) nitrate and metal free. R1 is methyl or benzyl. R2 functional group is para-substitued has good yield (74-83%). The reaction is incomplete and yield is not well when R2 functional group is ortho-substitued(38-66%). Add catalytic amount of silver(I) nitrate in this reaction can improve the yield, conversion, and reaction time. The second part: optimum reaction conditions tested, we found that reaction without silver salt has excellent yield, almost the same with using silver(I) nitrate. The solvent of reaction has to be protic solvent in two phases. When R2 functional group is electron-withdrawing group, the yield is not well (39-46%) expect ester group (83%). Add the catalytic amount silver(I) nitrate can reduce reaction time and improve conversion. When R2 functional group is electron-donating group has excellent yield (90-99%). The third part: In the first part and second part, we synthesized indol-2-one with tertiary radical, so we try to synthesized indol-2-one with secondary radical. The result shows that secondary radical need phenyl group to stabilized and yield is not well. Alkylations for sulfonylamide derivatives with weak base are failed. Alkylations for sulfonylamide derivatives need strong alkali and small alkylhalide. CONCLUSION Indol-2-one can be synthesized by the oxidative free radical reaction of acetamide derivatives and sulfonamide derivatives with catalytic amount silver(I) nitrate. Add silver (I) nitrate in reaction can improve conversion and reduce reaction time. These methods for indol-2-one with a variety of substituents have large tolerance, showing broad applicability of this reaction. We found that the cyclization reaction can also react with metal free and yield is as well as catalytic amount silver(I) nitrate. This reaction showed more efficiency and good to environmental, also responds to the green chemistry. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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