本文關(guān)鍵詞：新型過(guò)硫化試劑的設(shè)計(jì)及其應(yīng)用研究　出處：《華東師范大學(xué)》2017年博士論文　論文類(lèi)型：學(xué)位論文

  更多相關(guān)文章： 非對(duì)稱(chēng)過(guò)硫化物 過(guò)硫化反應(yīng) 過(guò)硫試劑 歸中反應(yīng) 藥物后期修飾

【摘要】：過(guò)硫化合物是一類(lèi)非常重要的化合物,它廣泛存在于自然界中,并且在化學(xué)生物學(xué)、藥物化學(xué)、食品化學(xué)等學(xué)科具有重要應(yīng)用。因此,過(guò)硫化物的合成受到有機(jī)化學(xué)家們的廣泛關(guān)注。在對(duì)稱(chēng)過(guò)硫化物合成方法中,反應(yīng)較為簡(jiǎn)單,最主要是通過(guò)硫醇(酚)的氧化反應(yīng)構(gòu)建。而非對(duì)稱(chēng)過(guò)硫化物的合成相對(duì)而言存在一定的難度,高效構(gòu)建非對(duì)稱(chēng)過(guò)硫的方法較少,主要原因有幾點(diǎn)。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(qiáng)烈的惡臭味,并且毒性大、污染大,使用不方便。其次,反應(yīng)類(lèi)型較少并且各自存在一些不足,氧化反應(yīng)類(lèi)型制備非對(duì)稱(chēng)過(guò)硫化物的效率大部分不高,主要是因?yàn)檠趸倪x擇性不高及氧化過(guò)程生成的產(chǎn)物能被繼續(xù)氧化;對(duì)稱(chēng)過(guò)硫的交換反應(yīng)類(lèi)型中需使用貴金屬作為催化劑;親核取代反應(yīng)類(lèi)型中,需將硫醇(酚)進(jìn)行預(yù)官能團(tuán)化,步驟經(jīng)濟(jì)性降低,并且反應(yīng)過(guò)程中反應(yīng)條件較苛刻如低溫、強(qiáng)堿、無(wú)水等條件,反應(yīng)實(shí)用性降低。此外,一些反應(yīng)中需要使用當(dāng)量的預(yù)先制備的金屬硫化合物作為過(guò)硫化試劑,不利用大規(guī)模應(yīng)用。因此,發(fā)展高效綠色應(yīng)用性強(qiáng)的過(guò)硫化試劑及反應(yīng)迫在眉睫。博士論文研究期間,我主要工作集中于設(shè)計(jì)和發(fā)展過(guò)硫化試劑,并將其運(yùn)用于非對(duì)稱(chēng)過(guò)硫化物的合成。具體如下:第一部分:無(wú)機(jī)硫鹽參與的歸中反應(yīng)構(gòu)建非對(duì)稱(chēng)過(guò)硫化合物的反應(yīng)研究在無(wú)過(guò)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(jià)的硫代硫酸鈉鹽與高化合價(jià)的亞磺酸鈉鹽作為無(wú)機(jī)硫源,實(shí)現(xiàn)了歸中反應(yīng)構(gòu)建非對(duì)稱(chēng)過(guò)硫化反應(yīng)。該反應(yīng)體系官能團(tuán)兼容性良好,并且能夠高效的實(shí)現(xiàn)過(guò)硫甲基化;此外該方法可以運(yùn)用于樟腦磺酸和雌酚酮衍生物的后期過(guò)硫化。在后期的反應(yīng)機(jī)理研究中,進(jìn)一步證明了該歸中反應(yīng)過(guò)程。第二部分:親核過(guò)硫化試劑的設(shè)計(jì)及其應(yīng)用研究通過(guò)設(shè)計(jì)親核過(guò)硫化試劑和發(fā)展簡(jiǎn)單快捷實(shí)用的方法建立過(guò)硫試劑庫(kù),實(shí)現(xiàn)了高效的一步同時(shí)引入雙硫原子的非對(duì)稱(chēng)過(guò)硫化策略。該非對(duì)稱(chēng)過(guò)硫化策略是通過(guò)芳基硼酸或硅試劑與親核過(guò)硫試劑發(fā)生氧化偶聯(lián)反應(yīng)實(shí)現(xiàn)的。在反應(yīng)過(guò)程中,使用廉價(jià)的硫酸銅作為催化試劑,通過(guò)控制過(guò)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(shí)現(xiàn)溫和條件下的非對(duì)稱(chēng)過(guò)硫化反應(yīng)。該反應(yīng)體系的底物普適性?xún)?yōu)秀,并且實(shí)現(xiàn)了氨基酸、糖等生命體重要結(jié)構(gòu)單元及藥物的后期修飾。通過(guò)面具效應(yīng)和堿效應(yīng)的考察,確定了乙�；鶠閮�(yōu)秀的面具基團(tuán),并且合適的pH條件是實(shí)現(xiàn)非對(duì)稱(chēng)過(guò)硫化的關(guān)鍵,即醇解速率要與轉(zhuǎn)金屬交換速率相匹配。第三部分:親電過(guò)硫化試劑的設(shè)計(jì)及其應(yīng)用研究通過(guò)極性翻轉(zhuǎn)的策略,設(shè)計(jì)合成了一系列親電過(guò)硫試劑,并且實(shí)現(xiàn)了克級(jí)規(guī)模制備反應(yīng),在此反應(yīng)過(guò)程中催化劑的用量降至千分之一摩爾。該過(guò)硫試劑的反應(yīng)性良好,通過(guò)適當(dāng)催化體系的選擇,可以實(shí)現(xiàn)多種親核試劑的過(guò)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(shí)也可以將其運(yùn)用于多硫化物的合成。以上反應(yīng)體系條件柔和,無(wú)需使用過(guò)渡金屬催化劑和堿,高效的構(gòu)建了多種過(guò)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(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：TQ421.12
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本文編號(hào)：1365055