經由 Proline 及 Pyrrole 進行脫羧基耦合反應製備 2-(Pyrrol-2-yl)pyrrolidine
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2012
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本篇論文主要分為兩個部份。第一部份主旨為 GFP 吸光基團類似物的合成研究。利用 N-acylglycine 為起始物，在醋酸鈉 / 醋酸酐的條件下與各種取代基的苯甲醛進行 Erlenmeyer azlactone synthesis 反應形成 4-arylidene-5-oxazolinone 衍生物。接下來再使用一級胺在室溫下對 oxazolinone 進行開環反應，可以得到含有直鏈結構的 N-alkyl-2-acylamido-3-arylacrylamide。接下來有兩個方法可以進行合環反應，一個是使用 pyridine 作為反應試劑和反應溶劑，進行脫水合環反應形成 4-arylidene-5-imidazolinone 衍生物，適用於不同官能基上；另外一個是使用改良後的 Mitsunobu 反應，一樣可以進行合環反應，雖然有些例子產率不高，但這是一個較為溫和的反應。
第二部份是合成 α-(pyrrol-2-yl)pyrrolidine 衍生物。使用氮上有 Bn 保護的 proline 當作起始物，與 thionyl chloride 反應得到醯氯的中間物，隨後使用鹼和 pyrrole 反應，得到α-(pyrrol-2-yl)pyrrolidine 衍生物。在本論文中，我們研究了本反應的適用性，並用來製備一系列α-(pyrrol-2-yl)pyrrolidine 衍生物。
This thesis is divided into two parts. The main focus of the first part is to study the synthesis of Green Fluorescent Protein (GFP) chromophore analogs. N-acylglycine as the starting material was heated with sodium acetate and various benzaldehydes in acetic anhydride to undergo the Erlenmeyer azlactone synthesis reaction to afford a series of 4-arylidene-5-oxazolinones. The oxazolinones were treated with primary amines to give the ring-opened adducts which contain the N-alkyl-2-acylamido-3-arylacrylamide moiety. We first demonstrated that, using pyridine as the reagent and solvent, the ring-opened adducts were heated in pyridine to undergo the dehydrative cyclization reaction to afford the ring-closed 4-arylidene-5-imidazolinone derivatives as the GFP chromophore analogs. Alternatively, our investigation also showed that a modified Mitsunobu reaction condition could also accomplish the same reaction to give the 4-arylidene-5-imidazolinone derivatives. The second part reported a novel reaction for the synthesis of α-(pyrrol-2-yl)pyrrolidine derivatives. N-benzylproline as starting material was treated with thionyl chloride to afford the acyl chloride intermediate. Subsequently, pyrrole was added in the presence of a base to result a decarbonylated product which was identified as an α-(pyrrol-2-yl)pyrrolidine derivative. The scope and generality were examined and the reaction is applicable to a series of pyrrole derivatives.
This thesis is divided into two parts. The main focus of the first part is to study the synthesis of Green Fluorescent Protein (GFP) chromophore analogs. N-acylglycine as the starting material was heated with sodium acetate and various benzaldehydes in acetic anhydride to undergo the Erlenmeyer azlactone synthesis reaction to afford a series of 4-arylidene-5-oxazolinones. The oxazolinones were treated with primary amines to give the ring-opened adducts which contain the N-alkyl-2-acylamido-3-arylacrylamide moiety. We first demonstrated that, using pyridine as the reagent and solvent, the ring-opened adducts were heated in pyridine to undergo the dehydrative cyclization reaction to afford the ring-closed 4-arylidene-5-imidazolinone derivatives as the GFP chromophore analogs. Alternatively, our investigation also showed that a modified Mitsunobu reaction condition could also accomplish the same reaction to give the 4-arylidene-5-imidazolinone derivatives. The second part reported a novel reaction for the synthesis of α-(pyrrol-2-yl)pyrrolidine derivatives. N-benzylproline as starting material was treated with thionyl chloride to afford the acyl chloride intermediate. Subsequently, pyrrole was added in the presence of a base to result a decarbonylated product which was identified as an α-(pyrrol-2-yl)pyrrolidine derivative. The scope and generality were examined and the reaction is applicable to a series of pyrrole derivatives.
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Proline, Pyrrole, 脫羧基耦合, proline, pyrrole, decarboxylative coupling