DABCO催化的“一鍋法”水相合成苯并色烯衍生物*

孫宏偉, 王浩宇, 連春霞, 張曉梅, 袁偉成

(1. 中國科學院 成都有機化學研究所 不對稱合成與手性技術四川省重點實驗室，四川 成都 610041;2. 中國科學院 研究生院,北京 100049)

苯并色烯衍生物具有廣泛的藥理活性和生理活性，如抗發育不全[1]、抗過敏[2]和抗癌活性[3]等。苯并色烯環上連有氰基和氨基等取代基的衍生物是合成某些具有特殊結構的天然產物的重要中間體[4,5]。文獻[6～8]方法合成苯并色烯大多是通過Knoevenagel縮合和Michael加成兩步反應分步完成的。

本文在前期[9]綠色合成工作的基礎上，以1,4-二氮雜二環[2.2.2]辛烷(DABCO)為催化劑，水為溶劑，采用“一鍋法”合成了苯并色烯衍生物(2a～2q, Scheme 1),收率26%～95%，其結構經1H NMR，13C NMR和MS確認。

該方法是一種簡潔、有效的綠色合成方法。避免了使用有機溶劑造成的環境污染；“一鍋法”合成目標產物可減少分步反應的產率損失。

1 實驗部分

1．1 儀器與試劑

Büchi B-545型熔點測定儀;Bruker-300 MHz型核磁共振儀(DMSO-d6為溶劑，TMS為內標);Bruker BIO TOF ⅢQ型高分辨質譜儀。

Scheme1

薄層層析硅膠，青島海洋化工廠；其余所用試劑均為分析純。

1.2 合成(以2a為例)

在反應管中加入苯甲醛(1a) 64 mg(0.6 mmol),丙二腈46 mg(0.7 mmol)和DABCO 11 mg(0.1 mmol)的水溶液5 mL,攪拌下于室溫反應30 min;加入2-羥基-1,4-萘醌 87 mg(0.5 mmol),于100 ℃反應至終點(TLC跟蹤)。旋干水后經硅膠柱層析[洗脫劑:V(二氯甲烷) ∶V(乙酸乙酯)=20 ∶1]分離得紅褐色固體2a130 mg。

用類似方法合成紅褐色固體2b～2q，其熔點與文獻[10～12]值一致。

2a:1H NMRδ: 4.59(s, 1H), 7.20～7.31(m, 7H), 7.80～7.87(m, 3H), 8.02～8.04(m, 1H);13C NMRδ: 36.6, 57.6, 119.4, 122.1, 125.9, 126.1, 127.2, 127.8, 128.7, 130.6, 131.1, 134.2, 134.6, 143.6, 149.0, 158.4, 176.9, 182.6。

2c:1H NMRδ: 3.78(s, 3H), 4.93(s, 1H), 6.86(t,J=7.2 Hz, 1H), 6.99(d,J=8.1 Hz, 1H), 7.17～7.23(m, 4H), 7.82～7.87(m, 3H), 8.04～8.07(m, 1H);13C NMRδ: 31.2, 55.8, 56.5, 111.7, 119.4, 120.7, 121.9, 125.8, 126.0, 128.4, 129.1, 130.5, 131.0, 131.3, 134.1, 134.6, 149.5, 156.8, 158.9, 177.0, 182.5; HR-ESI-MS: Calcd for C21H14N2O4Na{[M+Na]+} 381.084 6, found 381.084 1。

2d:1H NMRδ: 5.15(s, 1H), 7.23～7.26(m, 2H), 7.34～7.44(m, 4H), 7.84～7.87(m, 3H), 8.05～8.07(m, 1H);13C NMRδ: 33.5, 56.3, 118.8, 121.3, 125.8, 126.1, 127.8, 128.7, 129.4, 130.5, 130.6, 130.9, 132.0, 134.2, 134.6, 140.9, 149.5, 158.4, 176.8, 182.4; HR-ESI-MS: Calcd for C20H11N2O3ClNa{[M+Na]+} 385.035 0, found 385.034 3。

2h:1H NMRδ: 5.15(s, 1H), 7.15～7.60(m, 6H), 7.82～7.84(m, 3H), 8.03～8.05(m, 1H);13C NMRδ: 35.9, 56.5, 118.7, 121.4, 122.7, 125.8, 126.1, 128.4, 128.9, 130.6, 130.9, 132.6, 124.2, 134.6, 142.8, 149.5, 158.3, 176.8, 182.4; HR-ESI-MS: Calcd for C20H11N2O3BrNa{[M+Na]+} 428.984 5, found 428.984 8。

2k:1H NMRδ: 5.39(s, 1H), 7.45～7.48(m, 3H), 7.58～7.67(m, 2H), 7.82～7.84(m, 3H), 7.91～7.93(m, 1H), 8.03～8.05(m, 1H);13C NMRδ: 31.1, 55.9, 118.6, 121.2, 124.0, 125.8, 126.1, 128.4, 130.6, 130.7, 131.3, 133.8, 134.2, 134.6, 137.8, 148.5, 149.0, 158.9, 176.7, 182.6; HR-ESI-MS: Calcd for C20H11N3O5Na{[M+Na]+} 396.059 1, found 396.059 9。

2m:1H NMRδ: 4.65(s, 1H), 7.02～7.07(m, 1H), 7.16～7.19(m, 2H), 7.32～7.37(m, 3H), 7.81～7.89(m, 3H), 8.03～8.06(m, 1H);13C NMRδ: 36.3, 57.1, 113.8, 114.1, 114.4, 114.7, 119.2, 121.1, 123.9, 125.8, 126.1, 130.4, 130.5, 130.8, 131.1, 134.2, 134.5, 146.5, 146.6, 149.3, 158.4, 160.7, 164.0, 176.8, 182.6; HR-ESI-MS: Calcd for C20H11N2O3FNa{[M+Na]+} 369.064 6, found 369.065 2。

2 結果與討論

2.1 芳醛底物擴展

反應條件同1.2，擴展芳醛底物(2b～2q),實驗結果見表1。由表1可見，芳環上有給電子取代基時，收率較高。芳環上有吸電子取代基時，收率相對較低。底物的空間位阻對反應的影響也很大，位阻越大，收率越低。

表 1 芳醛底物的擴展*

*反應條件同1.2

Scheme 2

2.2 DABCO的作用及反應機理

DABCO做為堿，催化Knoevenagel縮合和Michael加成反應，經環化異構化得到產物2。DABCO在反應過程中起到重要作用，推測其反應機理如Scheme 2所示。

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