C-H键活化构建芳基C-N键和C-C键的方法研究
发布时间：2019-02-18 22:16
【摘要】：C-H键广泛存在于自然界中，通过C-H键活化构建C-X（X=C, N, P, S）键。由于不需要通过对C-H键进行官能团化，缩短了有机合成路线，具有步骤经济性和原子经济性。而C-N键和C-C键是最常见的两种化学键，通过C-H活化构建芳基C-N键和芳杂环C-C键具有重要的研究意义。 含有C-N键的有机化合物广泛存在于自然界，是一类构成生命基础的重要化合物。芳胺作为一种重要的含氮化合物，广泛存在与具有生物活性的天然产物和药物分子中，并且是很多化工产品的重要原料和组成部分，对我们的生活有着重要的意义。因此，高效、经济、环保的构建芳基C-N键始终有机化学的一个研究热点。 构建芳基C-N键的方法有很多，例如铜催化的Ullmann偶联反应，钯催化的Buchwald-Hartwig偶联反应和芳基硼酸参与的Chan-Lam偶联反应。这些都是构建芳基C-N键的有效方法，被广泛的应用于实验合成中。但这些反应常常需要先将Ar-H键进行官能团化再和胺发生偶联，无疑增加了合成的工作量，不具步骤经济性。因此，直接利用芳基C-H键和N-H键脱氢偶联构建芳基C-N键成为了许多有机化学家追求的目标。 近年来，氧化脱氢偶联反应构建C-N键的研究取得了一定的进展。已经实现了用机过氧化物或者无机盐作氧化剂的条件下使芳香sp2C-H键与N-H键直接脱氢偶联，这种直接脱氢偶联合成苯胺化合物的方法具有突出的步骤经济性。但同时大量的过氧化物和高价金属盐等氧化剂在反应中的使用，也带来一些无法避免的问题，，例如大量副产物产生，导致原子经济性下降；体系残留大量氧化剂残体，造成分离困难；普遍价格较高，造成环境污染等。而O2替代有机过氧化物和高价金属盐等作氧化剂，不仅可以有效避免上述问题，而且O2廉价、易得、绿色环保，是一种既具有步骤经济性，又具有原子经济性的芳香sp2C-H键和胺基N-H键偶合构建芳基C-N键的方法。因此，本文以此为基础用亚铜催化，O2气氧化2-苯基吡啶衍生物与乙酰苯胺衍生物脱氢偶联建芳基C-N键，合成了一些列芳胺化合物。 本文内容如下： 1.以2-苯基吡啶及其衍生物与乙酰苯胺及其衍生物作为底物，CuBr作为催化剂，O2氧化脱氢直接构建芳基C-N键。合成一系列含有吡啶基的芳胺化合物。同时对反应溶剂及溶剂量、催化剂及其用量、温度和时间等因素进行了筛选，并推测了反应机理。共合成了19个芳胺化合物，其结构均经过了NMR的鉴定。 2.以喹啉衍生物和苯氧乙酸衍生物为底物，AgNO3为催化剂，K2S2O8为氧化剂，水和二氯甲烷为溶剂（体积比为1：1），在三氟乙酸的存在下合成了一系列2-（苯氧甲基）喹啉化合物，并对反应条件进行了优化，分别讨论了催化剂、溶剂、氧化剂、温度、时间对反应的影响。共合成了11个目标化合物，其结构均经过NMR鉴定。
[Abstract]:C-H bond exists widely in nature. C-X (XC, N, P, S) bond is formed by activation of C-H bond. Because the C-H bond does not need to be functionalized, the organic synthesis route is shortened and the step economy and atomic economy are obtained. C-N bond and C-C bond are the two most common chemical bonds. The aryl C-N bond and heterocyclic C-C bond can be synthesized by C-H activation. Organic compounds containing C-N bonds are widely found in nature and are important compounds that form the basis of life. As an important nitrogen-containing compound, aromatic amines are widely found in natural products and drug molecules with biological activity, and are important raw materials and components of many chemical products, which are of great significance to our life. Therefore, efficient, economical and environmentally friendly construction of aryl C-N bond has always been a hot spot in organic chemistry. There are many methods to construct aryl C-N bond, such as copper catalyzed Ullmann coupling reaction, palladium catalyzed Buchwald-Hartwig coupling reaction and aryl boric acid Chan-Lam coupling reaction. These are effective methods for the construction of aryl C-N bonds and are widely used in experimental synthesis. However, these reactions often require the Ar-H bond to be functionalized and then coupled with amine, which no doubt increases the workload of synthesis and is not economical in step. Therefore, the direct dehydrogenation coupling of aryl C-H bond and N-H bond to form aryl C-N bond has become the goal of many organic chemists. In recent years, some progress has been made in the synthesis of C-N bond by oxidative dehydrogenation coupling reaction. Direct dehydrogenation coupling of aromatic sp2C-H bond and N-H bond with mechanical peroxide or inorganic salt as oxidant has been realized. This method of direct dehydrogenation coupling to aniline compound has remarkable step economy. However, at the same time, the use of a large number of oxidants such as peroxide and high-valence metal salts also brings some unavoidable problems, such as the production of a large number of by-products, resulting in the reduction of atomic economy. A large number of oxidant residues in the system make it difficult to separate, and the general price is high, resulting in environmental pollution. The substitution of O2 for organic peroxides and high value metal salts as oxidants can not only effectively avoid the above problems, but also be cheap, easy to obtain, green and environmentally friendly. It is a step economy. The aryl C-N bond was constructed by coupling the aromatic sp2C-H bond and the amino N-H bond with atomic economy. Therefore, some aromatic amines were synthesized on the basis of Cu _ 2O _ 2 gas oxidation of 2-phenylpyridine derivatives with acetaniline derivatives by dehydrogenation of aryl C-N bonds. The content of this paper is as follows: 1. The aryl C-N bond was directly synthesized by oxidative dehydrogenation of O2 with 2-phenylpyridine and its derivatives and acetanilide and CuBr as catalyst. A series of aromatic amines containing pyridyl were synthesized. At the same time, the reaction solvent and solvent amount, catalyst and its dosage, temperature and time were screened, and the reaction mechanism was deduced. Nineteen aromatic amines were synthesized and their structures were all identified by NMR. 2. Using quinoline derivative and phenoxyacetic acid derivative as substrate, AgNO3 as catalyst, K2S2O8 as oxidant, water and dichloromethane as solvent (1:1 by volume), A series of 2- (phenoxymethyl) quinoline compounds were synthesized in the presence of trifluoroacetic acid, and the reaction conditions were optimized. The effects of catalyst, solvent, oxidant, temperature and time on the reaction were discussed. Eleven target compounds were synthesized and their structures were all identified by NMR.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914
本文编号：2426268
[Abstract]:C-H bond exists widely in nature. C-X (XC, N, P, S) bond is formed by activation of C-H bond. Because the C-H bond does not need to be functionalized, the organic synthesis route is shortened and the step economy and atomic economy are obtained. C-N bond and C-C bond are the two most common chemical bonds. The aryl C-N bond and heterocyclic C-C bond can be synthesized by C-H activation. Organic compounds containing C-N bonds are widely found in nature and are important compounds that form the basis of life. As an important nitrogen-containing compound, aromatic amines are widely found in natural products and drug molecules with biological activity, and are important raw materials and components of many chemical products, which are of great significance to our life. Therefore, efficient, economical and environmentally friendly construction of aryl C-N bond has always been a hot spot in organic chemistry. There are many methods to construct aryl C-N bond, such as copper catalyzed Ullmann coupling reaction, palladium catalyzed Buchwald-Hartwig coupling reaction and aryl boric acid Chan-Lam coupling reaction. These are effective methods for the construction of aryl C-N bonds and are widely used in experimental synthesis. However, these reactions often require the Ar-H bond to be functionalized and then coupled with amine, which no doubt increases the workload of synthesis and is not economical in step. Therefore, the direct dehydrogenation coupling of aryl C-H bond and N-H bond to form aryl C-N bond has become the goal of many organic chemists. In recent years, some progress has been made in the synthesis of C-N bond by oxidative dehydrogenation coupling reaction. Direct dehydrogenation coupling of aromatic sp2C-H bond and N-H bond with mechanical peroxide or inorganic salt as oxidant has been realized. This method of direct dehydrogenation coupling to aniline compound has remarkable step economy. However, at the same time, the use of a large number of oxidants such as peroxide and high-valence metal salts also brings some unavoidable problems, such as the production of a large number of by-products, resulting in the reduction of atomic economy. A large number of oxidant residues in the system make it difficult to separate, and the general price is high, resulting in environmental pollution. The substitution of O2 for organic peroxides and high value metal salts as oxidants can not only effectively avoid the above problems, but also be cheap, easy to obtain, green and environmentally friendly. It is a step economy. The aryl C-N bond was constructed by coupling the aromatic sp2C-H bond and the amino N-H bond with atomic economy. Therefore, some aromatic amines were synthesized on the basis of Cu _ 2O _ 2 gas oxidation of 2-phenylpyridine derivatives with acetaniline derivatives by dehydrogenation of aryl C-N bonds. The content of this paper is as follows: 1. The aryl C-N bond was directly synthesized by oxidative dehydrogenation of O2 with 2-phenylpyridine and its derivatives and acetanilide and CuBr as catalyst. A series of aromatic amines containing pyridyl were synthesized. At the same time, the reaction solvent and solvent amount, catalyst and its dosage, temperature and time were screened, and the reaction mechanism was deduced. Nineteen aromatic amines were synthesized and their structures were all identified by NMR. 2. Using quinoline derivative and phenoxyacetic acid derivative as substrate, AgNO3 as catalyst, K2S2O8 as oxidant, water and dichloromethane as solvent (1:1 by volume), A series of 2- (phenoxymethyl) quinoline compounds were synthesized in the presence of trifluoroacetic acid, and the reaction conditions were optimized. The effects of catalyst, solvent, oxidant, temperature and time on the reaction were discussed. Eleven target compounds were synthesized and their structures were all identified by NMR.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914
【参考文献】
相关期刊论文 前1条
1 丁著明,郭振宇,王强,田呈祥,闫贺华,张金国,索士满;苯并三唑类光稳定剂的合成及应用[J];天津化工;2000年01期
本文编号：2426268
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