【作者】 刘艳红；

【导师】 陈建新；

【作者基本信息】 山西师范大学 ， 化学， 2016， 硕士

【摘要】 本文的主要内容有三部分。第一,简要概述了氨甲酰基硅烷的合成及其性质。第二,考查了一系列缺电子芳烃分别与N,N-二甲基氨甲酰基三甲基硅烷、N-甲基-N-甲氧甲基氨甲酰基三甲基硅烷、N-甲基-N-(2-苯乙基)氨甲酰基三甲基硅烷三种氨甲酰基硅烷的反应,并通过对温度、溶剂、比例的选择优化了反应条件。第三,研究了N,N-二甲基氨甲酰基三甲基硅烷与α-硝基烯酸乙酯的碳碳双键加成反应,并讨论了反应在相同温度、相同溶剂等条件下,所连官能团的空间位阻以及电子效应对反应速率、产率的影响。醇胺(酰胺)及其衍生物不仅是一种良好的离子化溶剂,而且还是一种非常重要的化工合成原料,也是各种生物活性物质、聚合物和天然产物的中间体。它的化学性质较稳定,可以与水和其他多种有机物、无机物完全混溶,是许多无机盐、高分子聚合物和天然产物的良好溶剂,因此,广泛应用于药物、染料、化妆品、石化产品等。其制备方法有很多,最常用的就是羧酸及其衍生物与氨直接反应生成酰胺,但是这种方法步骤繁琐、反应条件苛刻。随后Heck首次采用CO作底物合成酰胺,越来越多研究者们用CO作为羰基化试剂,但是这种方法的缺点也很明显,CO对人体的危害很大,而且反应往往需要在高温高压条件下进行,操作成本很高,在实际生产中受到了很大的限制。所以探索一种原料易得、操作简单、实用性强的方法非常必要。本文中我们用N，N-二甲基氨甲酰基三甲基硅烷(1)分别与3-乙酰基苯基异氰酸酯(4)、3-硝基苯甲腈(5)、1,3-二硝基苯(6)、3-硝基-4-氟-三氟甲苯(7)、3-氰基吡啶(8)、3-乙酰基吡啶(9)、2-氯-5-硝基吡啶(10)、2-氯-5-三氟甲基吡啶(11)、2-溴-5-氟吡啶(12)、2-溴-3-氯-5-三氟甲基吡啶(13)、2,4-二氯-3-硝基吡啶(14)、2-氰基-3-硝基-5-溴吡啶(15)、吡嗪(16)、2-氰基吡嗪(17)进行反应,发现,1,3-二硝基苯(6)、3-乙酰基吡啶(9)、2-氯-5-三氟甲基吡啶(11)、2-溴-5-氟吡啶(12)、吡嗪(16)与氨甲酰基硅烷1不反应,其余的生成了相应的C-H插入产物,即：2-乙酰基-6-异氰酸酯基N，N-二甲基苯甲醇胺(18)、2-氰基-6-硝基N，N-二甲基苯甲醇胺(19)、2-三氟甲基-5-氟-6硝基N，N-二甲基苯甲醇胺(21)、3-氰基N，N-二甲基吡啶-2-甲醇胺(22)、3-硝基-6-氯N，N-二甲基吡啶-2-甲酰胺(24)、3-三氟甲基-5-氯-6-溴N，N-二甲基吡啶-2-甲醇胺(27)、4,6-二氯-5-硝基N，N-二甲基吡啶-2-甲酰胺(28)、3-溴-5-硝基-6-氰基N，N-二甲基吡啶-2-甲酰胺(29)、3-氰基N，N-二甲基吡嗪-2-甲醇胺(31)。实验结果表明：芳环上取代基的吸电子能力越强,反应时间越短,产率越高。N-甲基-N-甲氧甲基氨甲酰基三甲基硅烷(2)分别与3-乙酰基苯基异氰酸酯(4)、3-硝基苯甲腈(5)、3-硝基-4-氟-三氟甲苯(7)、3-氰基吡啶(8)、2-氯-5-硝基吡啶(10)进行反应,合成仲酰胺。实验发现,这些底物都能发生反应,生成了对应的C-H插入产物,即：2-乙酰基-6-异氰酸酯基N-甲基-N-甲氧甲基苯甲醇胺(32)、2-氰基-6-硝基N-甲基-N-甲氧甲基苯甲醇胺(33)、2-三氟甲基-5-氟-6硝基N-甲基-N-甲氧甲基苯甲醇胺(34)、3-氰基N-甲基吡啶-2-甲醇胺(35)、3-硝基-6-氯N-甲基吡啶-2-甲酰胺(36)。底物8、10反应生成的产物不稳定易分解,故反应后需加盐酸水解得到仲酰胺35、仲醇胺36,叔醇胺32、33、34经水解后也可形成仲醇胺,这一方法的建立为仲酰胺(仲醇胺)的制备提供了一条新途径。N-甲基-N-(2-苯乙基)氨甲酰基三甲基硅烷(3)分别与3-乙酰基苯基异氰酸酯(4)、3-硝基苯甲腈(5)、3-硝基-4-氟-三氟甲苯(7)、3-氰基吡啶(8)、2-氯-5-硝基吡啶(10)进行反应。实验发现,这些底物均可以和氨甲酰基硅烷3反应生成相应的C-H插入产物,即：2-乙酰基-6-异氰酸酯基N-甲基-N-(2-苯乙基)苯甲醇胺(37)、2-氰基-6-硝基N-甲基-N-(2-苯乙基)苯甲酰胺(38)、2-三氟甲基-5-氟-6硝基N-甲基-N-(2-苯乙基)苯甲醇胺(39)、3-氰基N-甲基-N-(2-苯乙基)吡啶-2-甲酰胺(40)、3-硝基-6-氯N-甲基-N-(2-苯乙基)吡啶-2-甲酰胺(41)。该实验反应条件温和、无催化剂、操作简单,在不对称酰胺的合成中有着非常重要的意义。N，N-二甲基氨甲酰基三甲基硅烷(1)与α-硝基-2-己烯酸乙酯(42)、α-硝基-2-异己烯酸乙酯(43)、α-硝基-2-(对二甲氨)苯丙烯酸乙酯(44)、α-硝基-2-(对甲氧)苯丙烯酸乙酯(45)、α-硝基-2-(对甲)苯丙烯酸乙酯(46)、α-硝基-2-苯丙烯酸乙酯(47)、α-硝基-2-(对氯)苯丙烯酸乙酯(48)、α-硝基-2-(间硝α-基)苯丙烯酸乙酯(49)、α-硝基-4-苯戊烯酸乙酯(50)、α-硝基-2-呋喃丙烯酸乙酯(51)、α-硝基-2-噻吩丙烯酸乙酯(52)、α-硝基-2-吡啶丙烯酸乙酯(53)反应,生成了相应的加成产物,即：2-硝基-3-(N，N-二甲基)氨酰基己酸乙酯(54)、2-硝基-3-(N，N-二甲基)氨酰基异己酸乙酯(55)、2-硝基-3-(N，N-二甲基)氨酰基对二甲氨基苯丙酸乙酯(56)、2-硝基-3-(N，N-二甲基)氨酰基对甲氧基苯丙酸乙酯(57)、2-硝基-3-(N，N-二甲基)氨酰基对甲基苯丙酸乙酯(58)、2-硝基-3-(N,N-二甲基)氨酰基苯丙酸乙酯(59)、2-硝基-3-(N，N-二甲基)氨酰基对氯苯丙酸乙酯(60)、2-硝基-3-(N、N-二甲基)氨酰基间硝基苯丙酸乙酯(61)、2-硝基-3-(N，N-二甲基)氨酰基-4-苯戊烯酸乙酯(62)、2-硝基-3-(N，N-二甲基)氨酰基呋喃丙酸乙酯(63)、2-硝基-3-(N，N-二甲基)氨酰基噻吩丙酸乙酯(64)、2-硝基-3-(N，N-二甲基)氨酰基吡啶丙酸乙酯(65)。实验发现：取代基的电子效应、空间位阻以及共轭效应都会对反应造成不同程度的影响。当烯酸乙酯的β位上连有脂肪链时,空间位阻是影响反应的主要因素,且取代基的空间位阻越大反应时间越长,但并不影响产率；当烯酸乙酯的β位上连有芳环时,芳环上取代基的电子效应是影响反应的主要因素,取代基的吸电子能力越强,反应时间越短,产率越高,反之亦然。更多还原

【Abstract】 This paper consists of three part main contents. First, a brief overview of the synthesis and properties of carbamoylsilane. Second, we examined the reactions of electron-deficient aromatics respectively with N,N-dimethylcarbamoyl(trimethyl)silane 1, N-methoxymethyl-N-methylcarbamoyl(trimethyl)silane 2,N-methyl-N-(1-phenyl)ethylcarbamoyl(trimethyl)silane 3, and through the choice of temperature, solvents, proportion, reaction conditions were optimized. Third, we studied the reaction of N,N-dimethylcarbamoyl-(trimethyl)silane 1 with α-nitro-arylacrylat-es, at the same time, we have also investigated the influence of the electric effect and steric hindrance effect of the substituents to the yields and regioselectivity under the condition of same temperature, solvent.Amine and its derivatives is a good solvent for ionization, a very stable chemical properties, and is completely miscible in water and a variety of other organic compounds, inorganic, is a good solvent for many inorganic salts, polymers and natural products, is also a variety of bio-active materials, polymers and natural products and intermediates. In the past decades, organic workers have been working on aminocarbonyl reaction, developed many of the preparation of amides, the most commonly used is the acid chloride, mixed acid anhydride, an activated ester reacts with an amino amide bond, since Heck and his collaborators are using CO as a substrate to amide, more and more researchers are using CO as carbonylation agent, but the drawback of this approach is also evident, CO great harm to the human body, and the reaction often require high temperature and pressure conditions, high operating costs, actual production has been greatly restricted. So it is very necessary to explore a simple and practical method of raw material.When N,N-dimethylcarbamoyl(trimethyl)silane 1 reacts with 3-acetylphenylisocyanate 4,3-nitro-benzonitril 5,1,3-dinitrobenzen 6,3-nitro-4-fluoro-threefluorinetoluene 7,3-cyano-pyridine 8,3-acet-ylpyridine 9,2-chloro-5-nitropyridine 10,2-chloro-5-(trifluoromethy-l)pyridine 11,2-bromine-5-fluoridepyridine 12,2-bromine-3-chloro-5-(trifluoromethyl)pyridine 13,2,4-dichloro-3-nitropyridine 14,2-cyan-o-3-nitro-5-bromidepyrid-ine 15, pyrazine 16,2-cyanopyrazine 17. Among these reaction 1,3-dinitrobenzene 6,3-acetylpyridine 9, 2-chloro-5-(trifluoromethyl)pyridine 11,2-bromine-5-fluoridepyridin-e 12, pyrazine 16 not action, other products are 2-(3-acetylphenyl)-isocyanate(N,N-dimethyl)carbinolamine 18,2-(3-nitro)benzonitril-(N,N-dimethyl)carbinolamine 19,2-(3-nitro-4-fluoro)threefluorinetol-uene(N,N-Mdimethyl)carbinolamine 21,2-(3-cyano)pyridine(N,N-dime-thyl)carbinolamine 22,2-(2-chloro-5-nitro)pyridine(N,N-dimethyl)-formamide 24,2-(2-bromine-3-chloro-5-trifluoromethyl)pyridine-(N,N-dimethyl)carbinolamine 27,2-(2,4-dichloro-3-nitro)pyridine-(N,N-dimethyl)f or ma mide 28,2-(2-cyano-3-nitro-5bromide)pyridine (N,N-dimethyl)formamide 29,2-(2-cyano)pyrazine(N,N-dimethyl) carbinolamine 31. The experimental results show that the substituents on the electron-deficient aromatics ability stronger, shorter reaction time, higher yield.When N-methoxymethyl-N-methylcarbamoyl(trimethyl)silane 2 react with 3-acetylphenylisocyanate 4,3-nitro-benzonitril 5,3-nitro-4-fluoro-threefluorinetoluene 7,3-cyanopyridine 8,2-chloro-5-nitro pyridine 10, we could afford the products 2-(3-acetylphenyl)isocya-nate(N-methoxymethyl-N-methyl)carbinolamin 32,2-(3-nitro)benzo-nitril(N-methoxymethyl-N-methyl)carbinolamine 33,2-(3-nitro-4-fluoro)threefluorinetoluene(N-methoxymethyl-N-methyl)carbinolam ine 34,2-(3-cyano)pyridine(N-methyl)carbinolamine 35,2-(2-chloro-5-nitro)pyridine(N-methyl)formamide 36. In the experiment, we found that the substrate 8,10, a product of the reaction is not stable and easy to decompose, directly after the reaction of hydrochloric acid hydrolysis of the processed by secondary amide 35,36 secondary alcohol amine, so the substrate 4,5,7 and carbamoylsilane resulting from the reaction of tertiary alcohol amine,32,33 and 34 after hydrolysis can form secondary alcohol amine, the establishment of this method for the preparation of secondary amide (secondary alcohol amine) provides a new way of thinking.When N-methyl-N-(1-phenyl)ethylcarbamoyl(trimethyl)silane 3 react with 3-acetylphenylisocyanate 4,3-nitro-benzonitril 5,3-nitro-4-fluoro-threefluorinetoluene 7,3-cyanopyridine 8,2-chloro-5-nitro-pyridine 10, we could afford the products 2-(3-acetylphenyl)isocya-nate(N-methyl-N-(1-phenyl)ethyl)carbinolamine 37,2-(3-nitro)benzo-nitril(N-methyl-N-(1-phenyl)ethyl)formamide 38,2-(3-nitro-4-fluoro) threefluorinetoluene(N-methyl-N-(1-phenyl)ethyl)carbinolamine 39, 2-(3-cyano)pyridine(N-methyl-N-(1-phenyl)ethyl)formamide 40,2-(2-chloro-5-nitro)pyridine(N-methyl-N-(1-phenyl)ethyl)formamide 41. The experiment mild reaction conditions, no catalysts, the operation is simple in the synthesis of asymmetric amide has very important significance.N,N-dimethylcarbamoyl(trimethyl)silane 1 was used to react of α-nitro-2-hexene acid ethyl ester 42, α-nitro-2-isopropylacrylic acid ethyl ester 43,α-nitro-2-(4-dimethylamino)phenylacrylate 44, α-nitro-2-(4-methoxyl)phenylacrylate 45,α-nitro-2-(4-methyl)phenyl-acrylate 46, α-nitro-2-phenylacrylate 47,α-nitro-2-(4-chloro)phenyl-acrylate 48, α-nitro-2-(3-nitro)phenylacrylate 49, α-nitro-4-benzene-pentenyl acid ethyl ester 50, α-nitro-2-furylacrylate 51, α-nitro-2-thienylacrylate 52,α-nitro-2-pyridylacrylate 53 to afford 2-nitro-3-(N,N-dimethyl) ammonia acyl ethyl caproate 54, 2-nitro-3-(N,N-dimethyl) ammonia acyl alien acid ethyl ester 55, 2-nitro-3-(N,N-dimethyl)ammonia acyl of dimethyl aminobenzoic acid ethyl 56,2-nitro-3-(N,N-dimethyl)ammonia acyl of methoxy benzoic acid ethyl 57,2-nitro-3-(N,N-dimethyl)ammonia acyl methyl benzoic acid ethyl ester 58,2-nitro-3-(N,N-dimethyl)ammonia acyl benzoic acid ethyl ester 59,2-nitro-3-(N,N-dimethyl)ammonia acyl of chlorobenzoic acid ethyl ester 60,2-nitro-3-(N,N-dimethyl)between ammonia acyl nitrobenzene acid ethyl ester 61,2-nitro-3-(N,N-dimet-hyl)ammoniacyl-4-benzene pentene acid ethyl ester 62,2-nitro-3-(N,N-dimethyl)ammonia acyl furan acid ethyl ester 63, 2-nitro-3-(N,N-dimethyl)ammonia acyl thiophene acid ethyl ester 64, 2-nitro-3-(N,N-dimethyl)ammonia acyl pyridine acid ethyl ester 65.The experiment found that the electronic effect of substituent, space steric hindrance and conjugation effect will be different degrees of effects on the reaction. When the β of ethyl acrylate on even a fat chain, space steric hindrance is the main factors influencing the reaction, and the greater the space steric hindrance of substituent reaction time longer, but does not affect the production rate; When the β of ethyl acrylate with aromatic ring, electronic effect are the main factors influencing the reaction, strong electron-withdrawing ability of the substituents, shorter reaction time, higher yield, and vice versa.更多还原