本文關鍵詞：新型過硫化試劑的設計及其應用研究　出處：《華東師范大學》2017年博士論文　論文類型：學位論文

  更多相關文章： 非對稱過硫化物 過硫化反應 過硫試劑 歸中反應 藥物后期修飾

【摘要】：過硫化合物是一類非常重要的化合物,它廣泛存在于自然界中,并且在化學生物學、藥物化學、食品化學等學科具有重要應用。因此,過硫化物的合成受到有機化學家們的廣泛關注。在對稱過硫化物合成方法中,反應較為簡單,最主要是通過硫醇(酚)的氧化反應構建。而非對稱過硫化物的合成相對而言存在一定的難度,高效構建非對稱過硫的方法較少,主要原因有幾點。首先,使用的原料大部分都是硫醇(酚)或其衍生物,大部分硫醇(酚)具有強烈的惡臭味,并且毒性大、污染大,使用不方便。其次,反應類型較少并且各自存在一些不足,氧化反應類型制備非對稱過硫化物的效率大部分不高,主要是因為氧化的選擇性不高及氧化過程生成的產物能被繼續(xù)氧化;對稱過硫的交換反應類型中需使用貴金屬作為催化劑;親核取代反應類型中,需將硫醇(酚)進行預官能團化,步驟經濟性降低,并且反應過程中反應條件較苛刻如低溫、強堿、無水等條件,反應實用性降低。此外,一些反應中需要使用當量的預先制備的金屬硫化合物作為過硫化試劑,不利用大規(guī)模應用。因此,發(fā)展高效綠色應用性強的過硫化試劑及反應迫在眉睫。博士論文研究期間,我主要工作集中于設計和發(fā)展過硫化試劑,并將其運用于非對稱過硫化物的合成。具體如下:第一部分:無機硫鹽參與的歸中反應構建非對稱過硫化合物的反應研究在無過渡金屬催化和未額外添加氧化還原試劑的空氣條件下,利用低化合價的硫代硫酸鈉鹽與高化合價的亞磺酸鈉鹽作為無機硫源,實現了歸中反應構建非對稱過硫化反應。該反應體系官能團兼容性良好,并且能夠高效的實現過硫甲基化;此外該方法可以運用于樟腦磺酸和雌酚酮衍生物的后期過硫化。在后期的反應機理研究中,進一步證明了該歸中反應過程。第二部分:親核過硫化試劑的設計及其應用研究通過設計親核過硫化試劑和發(fā)展簡單快捷實用的方法建立過硫試劑庫,實現了高效的一步同時引入雙硫原子的非對稱過硫化策略。該非對稱過硫化策略是通過芳基硼酸或硅試劑與親核過硫試劑發(fā)生氧化偶聯(lián)反應實現的。在反應過程中,使用廉價的硫酸銅作為催化試劑,通過控制過硫試劑的醇解速率,完成了選擇性碳硫鍵斷裂這一難題,從而實現溫和條件下的非對稱過硫化反應。該反應體系的底物普適性優(yōu)秀,并且實現了氨基酸、糖等生命體重要結構單元及藥物的后期修飾。通過面具效應和堿效應的考察,確定了乙�；鶠閮�(yōu)秀的面具基團,并且合適的pH條件是實現非對稱過硫化的關鍵,即醇解速率要與轉金屬交換速率相匹配。第三部分:親電過硫化試劑的設計及其應用研究通過極性翻轉的策略,設計合成了一系列親電過硫試劑,并且實現了克級規(guī)模制備反應,在此反應過程中催化劑的用量降至千分之一摩爾。該過硫試劑的反應性良好,通過適當催化體系的選擇,可以實現多種親核試劑的過硫衍生化,如吲哚、富電子芳烴、雙羰基化物及氨基衍生物。同時也可以將其運用于多硫化物的合成。以上反應體系條件柔和,無需使用過渡金屬催化劑和堿,高效的構建了多種過硫及多硫化合物。
[Abstract]:Sulfur compounds are an important class of compounds, it widely exists in the nature, and medicinal chemistry in chemistry, biology, chemistry and other disciplines of food has important application. Therefore, the synthesis of persulfide attracted wide attention of organic chemists. In a symmetric sulfide synthesis method, the reaction is simple, the most important is through the construction of mercaptan (phenol) oxidation reaction. But the asymmetric synthesis of sulfide had relatively difficulty, less efficient construction method for asymmetric sulfur, mainly there are several reasons. First, the use of raw materials are mostly mercaptan (phenol) or its derivatives, most thiols (phenol) with odor strong smell, and high toxicity, high pollution, inconvenient use. Secondly, less reaction types and each has some deficiencies, the efficiency of oxidation type preparation of asymmetric persulfides most is not high, mainly Because the products of the oxidation selectivity is not high and the oxidation process can be generated to oxidation; axisymmetric use noble metals as catalyst type sulfur exchange reaction; nucleophilic substitution reaction type, the thiol (phenol) for group officer, economic steps decreased, and reaction conditions harsh such as low temperature, alkali, water and other conditions, practical reaction decreased. In addition, need to use the equivalent of pre made metal sulfur compounds were used as vulcanization reagents in the reaction, no use of large-scale applications. Therefore, the development of efficient green practical vulcanization reagents and the reaction is imminent. Doctoral dissertation of the study period, I the main work focuses on the design and development of vulcanization reagents, and applied to the asymmetric synthesis of persulfide. As follows: the first part: the reaction of inorganic sulfur salt in return to the construction of asymmetric sulfur Study on non compound reaction catalyzed by transition metal and without additional redox reagents under the condition of air, the use of low valence thiosulfate sodium and high valence sulfinic acid sodium salt as the inorganic sulfur source, can realize the construction of asymmetric reaction in the vulcanization reaction. The reaction system of functional group compatibility, and can efficiently realize sulfur methylation; late in addition the method could be used in camphorsulfonic acid and estrone derivatives overcure. In study of reaction mechanism of late, further proved that the reaction of the return process. The second part: the design and application of nucleophilic reagent vulcanization by nucleophilic vulcanization reagents and design development of simple and practical the method of establishing sulfur library, realizes asymmetric overcure efficient strategy step while introducing the double sulfur atom. The asymmetric overcure strategy is through Aryl boric acid or silicon reagents with nucleophilic sulfur reagents to achieve oxidative coupling reaction. In the reaction process, using copper sulfate as catalyst by cheap reagents, rate control of sulfur alcoholysis reagent, the selectivity of carbon sulfur bond breaking this problem, so as to realize the asymmetric vulcanization reaction under mild conditions the reaction substrate universality is excellent, and the realization of the amino acid, sugar and other life weight should be later modified structural units and drugs. Through the investigation of the mask effect and the effect of alkali, the acetyl groups to mask excellent, and the appropriate pH condition is the key to realize asymmetric vulcanization, i.e. alcoholysis rate to match to the metal exchange rate. The third part: the design and application of electrophilic reagents of sulfide by the polarity reversal strategy, a series of electrophilic sulfur reagents were designed and synthesized, and the realization of the Gram scale preparation of catalyst in this reaction, the reaction process amount to 1/1000 Moore. The reaction of sulfur reagent, through proper selection of catalyst, can achieve a variety of nucleophiles with sulfur derivatization, such as indole, electron rich aromatic hydrocarbons, double carbonylation and amino derivatives can also. Used in the synthesis of sulfide. The above reaction condition is gentle, without the use of transition metal catalyst and alkali, efficiently constructed many kinds of sulfur and polysulfide.

【學位授予單位】：華東師范大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：TQ421.12
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本文編號：1365055