【摘要】：含氮雜環(huán)化合物廣泛存在于農(nóng)藥、醫(yī)學(xué)以及材料科學(xué)等研究領(lǐng)域中。例如,吡唑并吲哚酮類化合物是一類具有生物活性的分子骨架,多取代吡啶衍生物尤其是三氟甲基取代的吡啶化合物在醫(yī)藥領(lǐng)域中的用途也十分廣泛。鑒于N-雜環(huán)化合物具有重大的實(shí)際應(yīng)用價(jià)值,其合成方法學(xué)研究一直都是有機(jī)合成化學(xué)領(lǐng)域研究的熱點(diǎn)。合成氮雜環(huán)化合物的研究方法已有大量文獻(xiàn)報(bào)道,從廉價(jià)易得的原料出發(fā),高效、高選擇性構(gòu)建含氮雜環(huán)化合物一直是有機(jī)合成化學(xué)研究者追求的目標(biāo)。本論文研究旨在以肟酯為原料、過渡金屬或非金屬試劑為催化劑,發(fā)展吡唑并吲哚酮衍生物、2,4-二芳基吡啶衍生物以及三氟甲基取代吡啶衍生物等N-雜環(huán)化合物的合成方法學(xué),具體研究內(nèi)容如下:1、以2-取代吲哚和肟酯為原料,以銅鹽為催化劑,在氧氣氛圍中,通過分子間成環(huán)實(shí)現(xiàn)吲哚N1/C2/C3同時(shí)官能團(tuán)化反應(yīng),制備吡唑并吲哚酮衍生物。該方法使用的催化劑氯化銅,是一種廉價(jià)易得的過渡金屬試劑。相比以往合成氮雜環(huán)化合物的研究方法,該方法具有成本低、反應(yīng)條件溫和、產(chǎn)率高、底物適應(yīng)性廣、官能團(tuán)兼容性好、副產(chǎn)物對環(huán)境無污染、目標(biāo)產(chǎn)物易于分離提純等優(yōu)點(diǎn)。此方法的原料肟酯既作為“氮”源,又作為內(nèi)部氧化劑引發(fā)吲哚的有氧氧化成環(huán)反應(yīng),為合成吡唑并吲哚酮衍生物提供了一條新的途徑。2、以肟酯和烯醛為原料,在單質(zhì)碘和三乙胺的共同促進(jìn)下,高效、高化學(xué)選擇性制備2,4-二芳基吡啶衍生物。該方法使用的添加劑單質(zhì)碘和三乙胺廉價(jià)易得,而且該反應(yīng)條件簡單,易操作。通過初步的機(jī)理研究實(shí)驗(yàn)表明,該反應(yīng)可能是經(jīng)過一種自由基途徑進(jìn)行的。3、以肟酯和三氟甲基試劑為原料,在碘化銨促進(jìn)下,加入連二亞硫酸鈉為還原劑,合成具有重要醫(yī)用價(jià)值的三氟甲基取代的吡啶衍生物。進(jìn)一步研究發(fā)現(xiàn),使用肟酯、醛類和三氟甲基試劑為原料,在碘化銨促進(jìn)下,以三乙胺為添加劑,可以通過一鍋法合成2,3,4,6-四取代三氟甲基吡啶衍生物。該方法無需使用過渡金屬催化劑、條件簡單、產(chǎn)率高,為合成三氟甲基取代吡啶衍生物提供了一種新途徑。
[Abstract]:Nitrogen heterocyclic compounds are widely used in pesticide, medicine and material science. For example, pyrazole indole ketones are a kind of molecular skeleton with biological activity. Polysubstituted pyridine derivatives, especially trifluoromethyl substituted pyridine compounds, are also widely used in the field of medicine. Since N-heterocyclic compounds have great practical application value, their synthetic methodology has always been a hot spot in the field of organic synthesis chemistry. The research methods for the synthesis of nitrogen-heterocyclic compounds have been reported in a large number of literatures. Starting from cheap and easily available raw materials, the construction of nitrogen-containing heterocyclic compounds with high efficiency and high selectivity has always been the goal pursued by the researchers of organic synthesis chemistry. The aim of this paper is to develop pyrazole indole derivatives using oxime ester as raw material and transition metal or nonmetallic reagent as catalyst. The synthesis methods of N-heterocyclic compounds, such as 2-diarylpyridine derivatives and trifluoromethyl substituted pyridine derivatives, were studied as follows: 1. Using 2-substituted indole and oxime ester as raw materials, copper salt as catalyst, In oxygen atmosphere, pyrazolyl indole derivatives were synthesized by simultaneous functional reaction of indole N1/C2/C3 through intermolecular ring formation. The catalyst used in this method is copper chloride, which is a cheap and easily available transition metal reagent. Compared with the previous research methods for the synthesis of nitrogen heterocyclic compounds, this method has the advantages of low cost, mild reaction conditions, high yield, wide substrate adaptability, good functional compatibility, no pollution of byproducts to the environment and easy separation and purification of the target products. The oxime ester of this method is used as a "nitrogen" source as well as an internal oxidant to initiate the aerobic oxidation of indole, which provides a new way for the synthesis of pyrazolindoleone derivatives. 2Oxime ester and aldehydes are used as raw materials. Under the promotion of simple iodine and triethylamine, 2o 4-diaryl pyridine derivatives were synthesized with high efficiency and high chemical selectivity. The simple iodine and triethylamine additives used in this method are cheap and easy to obtain, and the reaction conditions are simple and easy to operate. The experimental results show that the reaction may be carried out by a free radical pathway. With oxime ester and trifluoromethyl reagent as raw materials, sodium dithioate was added as reductant with the help of ammonium iodide. Synthesis of trifluoromethyl substituted pyridine derivatives with important medical value. It was further found that the derivatives of 2o 3N 4N 6 Tetra substituted trifluoromethyl pyridine could be synthesized by one pot method using oxime ester, aldehyde and trifluoromethyl reagents as raw materials, with the promotion of ammonium iodide and triethylamine as additives. The method has the advantages of simple conditions and high yield, which provides a new way for the synthesis of trifluoromethyl substituted pyridine derivatives.
【學(xué)位授予單位】：湘潭大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O626

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