利用縮合反應合成去甲基類白葉藤鹼的前驅物

Sythesis of the Precursors of Norneocryptolepine through the Condensation Reaction

謝昌燏(Chang-Yu Hsieh)

指導教授 ： 謝仁傑

淡江大學/理學院/化學學系碩士班/碩士(2019年)

https://doi.org/10.6846/TKU.2019.00518

摘要

本論文重點在發展一新的合成去甲基類白葉藤鹼前驅物的方法。由於實驗室同仁在合成去甲基類白葉藤鹼的合環反應有初步的結果，因此我們提供去甲基類白葉藤鹼的前驅物使合環反應完成。先以2-硝基苯乙腈及2-溴基苯甲醛兩種化合物為主要起始物，進行最佳化克腦文蓋爾縮合反應得產物c1，使用有機鹼吡咯烷再加少量無機鹼氫氧化鉀就能得到最佳的產率，再以含2-硝基苯乙腈及2-溴基苯甲醛的衍生物做反應的官能基耐受度測試做出多樣的衍生物，在含2-硝基苯乙腈的衍生物中有幾個官能基的衍生物需要從溴化再氰化得到，有使用NBS或PBr3的兩種溴化反應，氰化反應以氰化鉀為主但在4號碳位接上氟基會有副反應性太強，經由改良多加了18-crown-6幫助反應。將產物c1加入一些過渡金屬做還原反應的最佳化得去甲基類白葉藤鹼的前驅物r1，得出用錫金屬十當量左右可以有最佳產率，然後以此去做官能基耐受性的測試，所有縮合反應的產物都能做還原反應，產率也相當不錯。

關鍵字

縮合反應 ； 還原反應 ； 去甲基類白葉藤鹼

並列摘要

This thesis focuses on the development of a new method for the synthesis of the precursors of Neocryptolepine. Since the synthesis of the Neocryptolepine has preliminary results, we provide a precursor of the Neocryptolepine to complete the ring reaction. First, we used the two kinds of compounds that 2-nitrophenylacetonitrile and 2-bromobenzaldehyde as the main starting materials to optimize the Knoevenagel condensation reaction to get product c1, and we found that pyrrolidine with a small amount of Potassium hydroxide can get the best yield. Further, The substrate scope of 2-nitrophenylacetonitrile and 2-bromobenzaldehyde has been fully examined, and the yield was also quite good. Some of derivatives containing 2-nitrophenylacetonitrile needed to be obtained from bromination and then cyanidation. There are two kinds of bromination reactions using NBS or PBr3. The cyanidation reaction is mainly carried out by potassium cyanide. However, one of the derivatives that the number 4 carbon attached by the fluorine group has strong side reaction, and the addition of 18-crown-6 can help the reaction. The product c1 was added to some transition metal for optimization of the reduction reaction to get product r1. We found ten equivalents of tin metal is the best condition. The substrate scope has been fully examined, and the products of all the condensation reactions were all subjected to the reduction reaction, and the yield was also quite good.

並列關鍵字

Condensation ； reduction ； Norneocryptolepine

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