【摘要】：鈀催化硫葉立德反應(yīng)是一種構(gòu)建碳-碳、碳-雜鍵的重要手段,在藥物、生物活性中間體、天然產(chǎn)物、功能有機(jī)材料的合成和制備方面有重要應(yīng)用,是當(dāng)前合成化學(xué)研究前沿�；谒鼈儶毺氐幕瘜W(xué)反應(yīng)性,研究了硫葉立德與不同的烯酮和鄰苯二胺的反應(yīng)、丙炔醇化合物與對甲苯磺酰異氰酸酯的反應(yīng),擴(kuò)展反應(yīng)的底物范圍,得到了芳基羧酸酯類、喹喔啉類和惡唑烷酮烷酮類等合成藥物的前體化合物。采用核磁共振譜和質(zhì)譜對所合成的系列化合物進(jìn)行了結(jié)構(gòu)表征,個別難以確定的化合物采用X-單晶衍射驗證其結(jié)構(gòu)。通過實驗結(jié)果,結(jié)合文獻(xiàn)數(shù)據(jù)分析,提出了相關(guān)反應(yīng)的催化機(jī)理。(1)鈀催化硫葉立德與烯酮反應(yīng)合成芳基羧酸酯類化合物。以硫葉立德與烯酮為反應(yīng)底物,于60℃下,采用Pd(PPh3)4作催化劑,THF作反應(yīng)溶劑,反應(yīng)24 h,得到9個芳基羧酸酯化合物,柱層析分離產(chǎn)率為64%-85%,并確定其結(jié)構(gòu)。實驗結(jié)果表明:當(dāng)葉立德的苯環(huán)上帶有吸電子基團(tuán),烯酮連有吸電子基產(chǎn)率較高,反應(yīng)更容易發(fā)生。提出了鈀催化合成芳基羧酸酯的反應(yīng)機(jī)理,鈀催化劑是誘導(dǎo)烯酮生成中間體烯醇式的關(guān)鍵因素,有利于產(chǎn)物的生成。(2)鈀催化溴代硫鹽和鄰苯二胺環(huán)化合成喹喔啉類化合物。以溴代硫鹽和鄰苯二胺為底物,Pd(PPh3)4作催化劑,PPh3作配體,K2CO3作堿,THF作溶劑,反應(yīng)18 h,得到12個喹喔啉類化合物,柱層析分離產(chǎn)率為55%-90%,并確定其結(jié)構(gòu)。實驗結(jié)果顯示:當(dāng)硫鹽的苯環(huán)上帶有吸電子基團(tuán)時,產(chǎn)率較高,有利于反應(yīng)的進(jìn)行。提出了鈀催化環(huán)化的反應(yīng)機(jī)理,鈀催化劑促進(jìn)了中間體烯醇式與鄰苯二胺氨基的結(jié)合,堿起輔助作用,有利于親核反應(yīng)的發(fā)生,環(huán)化生成目標(biāo)產(chǎn)物。(3)堿催化丙炔醇與對甲苯磺酰異氰酸酯環(huán)化生成N-取代基-4-亞甲基-惡唑烷酮類化合物。以NEt3為堿催化劑,采用toluene作溶劑,反應(yīng)溫度為125℃,反應(yīng)8 h,得到12個惡唑烷酮類化合物,柱層析分離產(chǎn)率為42%-99%,并確定其結(jié)構(gòu)。實驗結(jié)果表明:芳基丙炔醇和烷基丙炔醇都能順利反應(yīng),芳環(huán)上所帶的取代基團(tuán)對反應(yīng)影響不大,產(chǎn)物惡唑烷酮類化合物的產(chǎn)率較好。提出堿催化偶聯(lián)環(huán)化機(jī)理,堿催化引發(fā)的環(huán)化關(guān)鍵因素是堿能夠容易的獲取質(zhì)子,從而發(fā)生親核加成-消除反應(yīng)生成目標(biāo)產(chǎn)物。許多天然產(chǎn)物和活性物質(zhì)中存在芳基羧酸酯結(jié)構(gòu)單元,所合成芳基羧酸酯類化合物可以用于合成含有芳基羧酸酯結(jié)構(gòu)單元的染料、皮革劑、香料和殺蟲劑;喹喔啉類化合物是一類重要的含氮生物堿,所合成喹喔啉類化合物可以用于合成抗菌、抗病毒、消炎和抗癌藥物的中間體,例如合成吡嗪酰胺類抗結(jié)核藥物;N-取代-4-亞甲基-惡唑烷酮類化合物含有氧氮的雜環(huán),在精細(xì)化工品,復(fù)合材料,農(nóng)藥,纖維,防銹劑,活性染料,潤滑劑和醫(yī)藥等領(lǐng)域應(yīng)用廣泛。本文的研究結(jié)果為這些重要化合物的合成提供了一種更加簡單和高效的合成方法。
[Abstract]:Palladium-catalyzed ylide reaction is an important method to construct carbon-carbon, carbon-heterogeneity bonds, and has important applications in the synthesis and preparation of drugs, bioactive intermediates, natural products and functional organic materials. Based on their unique chemical properties, the reactions of thiolides with different enones and o-phenylenediamine, propargyl alcohols and p-toluenesulfonyl isocyanate were studied, and the base range of the reaction was expanded to obtain aryl carboxylic esters. A precursor compound of synthetic drugs such as quinoxaline and oxazolidinone. The structures of the synthesized compounds were characterized by NMR and MS, and the structures of some compounds which were difficult to be determined were confirmed by X-ray single crystal diffraction. Based on the experimental results and the analysis of literature data, the catalytic mechanism of the related reactions was proposed. (1) Palladium catalyzed reaction of ylide and ketene to synthesize aryl carboxylic acid esters. Nine aryl carboxylate compounds were obtained by using Pd (PPh3) 4 as catalyst and THF as solvent at 60 鈩，

本文編號：2393201