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| 研究生： |
曾家凱 Tseng, Chia-Kai |
|---|---|
| 論文名稱： |
探討銅(I)催化碳-氮偶合反應之中間產物 Intermediates in the copper-catalyzed C-N cross-coupling reaction |
| 指導教授： |
韓建中
Han,Chien-Chung 徐新光 Shyu, Shin-Guang |
| 口試委員: |
洪上程
Hung, Shang-Cheng 蔡易州 Tsai,Yi-Chou 林俊成 Lin,Chun-Cheng |
| 學位類別： |
博士 Doctor |
| 系所名稱： |
理學院 - 化學系 Department of Chemistry |
| 論文出版年： | 2012 |
| 畢業學年度： | 100 |
| 語文別： | 中文 |
| 論文頁數： | 180 |
| 中文關鍵詞： | 電灑式游離化質譜 、碳-氮耦合 、叔丁醇鈉 、1,10-二氮雜菲 、銅(I) |
| 相關次數： | 點閱：2 下載：0 |
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本篇論文主要研究銅(I)催化碳-氮耦合反應機制，以4-碘甲苯和二苯胺為銅(I)催化碳-氮耦合反應之起始物，1,10-二氮雜菲為銅(I)之配位基、以叔丁醇鈉為鹼，甲苯為溶劑的反應條件下，在室溫下產生錯合物[Na(phen)3][Cu(NPh2)2] (2)。1,10-二氮雜菲配位基與鈉陽離子結合形成[Na(phen)3]+，二苯胺脫氫攻擊銅(I)產生[Cu(NPh2)2]-，從銅(I)催化碳-氮耦合反應中分離出錯合物2，並以化學計量的反應條件和4-碘甲苯在120 oC反應四十小時後可獲得70.3%的碳-氮耦合產物。此結果顯示錯合物2為銅(I)催化的碳-氮耦合反應中之中間產物。利用電灑式游離化質譜儀觀察銅(I)催化碳-氮耦合反應過程之中間產物，根據同位素理論分布圖推測在催化過程中有[Cu(NPh2)2]-、[Cu(NPh2)I]-和Na[Cu(NPh2)2(p-tolyl)]+的分子離子訊號，根據Na[Cu(NPh2)2(p-tolyl)]+結構，推斷銅(I)催化的碳-氮耦合反應機制中，4-碘甲苯會與[Cu(NPh2)2]-進行氧化加成反應，產生中間產物[Cu(NPh2)2(p-tolyl)I]-。
當使用不同的鹼參與反應時，銅(I)催化碳-氮耦合反應機制會有所改變，如以叔丁醇鈉/碳酸鉀取代單純叔丁醇鈉為鹼反應時，產率從38%提升到93%，以電灑式游離化質譜儀在120 oC之催化反應條件下觀察，發現除了[Cu(NPh2)2]-、[Cu(NPh2)I]-的分子離子訊號外，還有K[(phen)Cu(NPh2)(p-tolyl)]+的分子離子訊號。我們推測K[(phen)Cu(NPh2)(p-tolyl)]+分子離子訊號是由甲苯自由基加成至錯合物[(phen)Cu(NPh2)]而得的。經由加入自由基抑制劑(TEMPO)可發現產率由原本的93%降到64%。反之，在叔丁醇鈉為鹼的反應條件下，產率則無明顯改變(38%降到35%)。此等結果顯示叔丁醇鈉/碳酸鉀為鹼的條件下，銅(I)催化碳-氮耦合反應機制除了進行2e的氧化加成，還原脫除反應路徑外，也會有自由基加成反應之路徑出現，導致產率的提升。
在4-碘甲苯和二苯胺為起始物，1,10-二氮雜菲為配位基，甲苯為溶劑的反應條件下，以叔丁醇鉀取代叔丁醇鈉為鹼時，室溫時產生錯合物[K3(phen)8][Cu(NPh2)2]3 (4)。此錯合物在120 oC以化學計量的反應條件和4-碘甲苯反應六小時可得50%的碳-氮耦合產物。加入自由基抑制劑(TEMPO)發現產率下降至12%，相較於錯合物2在120 oC以化學計量的反應條件和4-碘甲苯反應六小時獲得到61%的產物，並且在加入TEMPO時其產率微降至50%，顯示錯合物2與錯合物4的反應性並不相同，因此我們推測陽離子的不同會導致在碳-氮耦合反應機制下，錯合物4大部分是經由自由基加成反應路徑，反之錯合物2則是大部分經由2e氧化加成反應路徑。
My research is about copper-catalyzed C-N cross coupling reaction. Initially, a mixture of diphenylamine, 4-iodotoluene, NaOtBu, CuI and 1,10-phenanthroline was allowed to stir in toluene at room temperature. A yellow precipitate was obtained and identified as complex [Na(phen)3][Cu(NPh2)2] (2). This complex was allowed to react with two equivalents of 4-iodotoluene in the absence of NaOtBu and obtained 70.3% (GC yield). These observation suggest that complex 2 is an intermediate in the CuI/phen/NaOtBu catalytic system. ESI-MS analysis of the reaction solution was undertaken and the [Cu(NPh2)2]-, [Cu(NPh2)I]- and Na[Cu(NPh)2(p-tolyl)]+ were observed, which are confirmed to their isotopic distribution. Base on these results, we proposed that the complex 2 first react with 4-iodotoluene then through an reductive elimination to produce the product.
In addition, a mixed base (K2CO3/NaOtBu) copper(I)-catalyzed C-N cross coupling reaction was found to have a higher than double catalytic reactivity than that of using only NaOtBu as the base. In situ ESI-MS analysis for the catalytic system under the catalytic reaction condition reveals the presence of [Cu(NPh2)2]-, [Cu(NPh2)I]- and K[(phen)Cu(NPh2)(p-tolyl)]+ suggesting that they are intermediates in the reaction. The formation of the Cu(II) complex, K[(phen)Cu(NPh2)(p-tolyl)]+, implies that a free radical [CH3C6H4]• reacts with the [(phen)Cu(NPh2)] by a radical path. In order to confirm the existence of the free radical path, the 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) was added and the yield of the reaction reduced from 93% to 64%. While the addition of TEMPO to the catalytic system with NaOtBu as the base, the yield only slightly reduced by 7% (38% to 35%). Based on these observations, a reaction mechanism composed of a free radical path and a 2e oxidative addition path is proposed.
Furthermore, complexes [K3(phen)8][Cu(NPh2)2]3 (4) and 2 have been isolated from the catalytic C-N cross coupling reaction with the CuI-phen- MOtBu (for M= K, Na) respectively. The stoichiometric reaction of complex 2 with 4-iodotoluene undergoes more efficiently than that of complex 4 under the similar conditions. The yield of the stoichiometric reaction of complex 4 with 4-iodotoluene decreased dramatically from 50% to 12% by the addition of TEMPO, indicating that the reaction was major going through a radical pathway. When TEMPO was added to the stoichiometric reaction of complex 2 with 4-iodotoluene, the yield of the reaction decreased only slightly from 61% to 50% indicating that the reaction was major going through a 2e oxidative addition pathway.
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