嚴云南，陳江韓，陳智勇，潘文龍，宋化燦

(1.中山大學化學與化學工程學院，廣東 廣州 510275；2.贛南醫(yī)學院藥學院，江西 贛州 341000；3.中國廣州分析測試中心，廣東 廣州 510070)

1 引 言

咪唑衍生物廣泛用于醫(yī)藥和農藥[1-3]、光電材料[4-12]、不對稱有機合成催化劑配體[13]、離子液體[14]、陰離子傳感器[15]等領域。本課題組多年從事具有雜環(huán)結構的發(fā)光材料的設計合成和發(fā)光性能的研究[16-18]，曾報道過一系列含有咪唑結構單元的大共軛體系的2,5-二芳基-1,3,4-噁二唑的合成[19]。但是該類化合物的溶解性能不佳，為改善其溶解性，從而改善在染料等方面的應用性能，增加烷基的長度，合成了系列含N-正癸基咪唑結構的2,5-二芳基-1,3,4-噁二唑。合成路線和目標產物的結構見圖1。

圖1 1,3,4-噁二唑衍生物的合成路線

2 實驗部分

2.1 儀器和試劑

溫度計未校準，X4 熔點儀，Bruker AVANCE-300 NMR 核磁共振儀，SHIMADZU LCMS-2010A 質譜儀，Elementar Analysensysteme GmbH Vario EL元素分析儀。其余試劑均為分析純，未經處理直接使用。

2.2 4-(2-(1-正癸基咪唑基))苯甲酸甲酯1a，1b,1c的合成

化合物1a，1b,1c參照文獻[19]合成，其結構表征如下。

4-(2-(1-正癸基苯并咪唑基))苯甲酸甲酯(1a): 淡黃色，黏稠液體，產率75%。1H NMR (DMSO-d6)δ: 0.87 (t,J= 6.6 Hz,3H,CH3),1.20～1.30 (m,14H,CH2),1.77～1.83 (m,2H,CH2),3.96 (s,3H,OCH3),4.23 (t,J= 7.5 Hz,2H,NCH2),7.27～7.35 (m,2H,ArH),7.38～7.44 (m,1H,ArH),7.78～7.83 (m,3H,ArH),8.19 (d,J= 8.7 Hz,2H,ArH)。ESI-MS (m/z): 393 [M + H]+。

4-(2-(1-正癸基-4,5-二苯基咪唑基))苯甲酸甲酯(1b): 無色固體。產率81%，熔點81～82 ℃。1H NMR (DMSO-d6,δ: 0.83 (t,J= 6.9 Hz,3H,CH3),0.86～0.94 (m,6H,CH2),0.96～1.05 (m,2H,CH2),1.07～1.16 (m,4H,CH2),1.18～1.33 (m,4H,CH2),3.89 (s,3H,OCH3),3.94 (t,J= 7.2 Hz,2H,NCH2),7.09～7.22 (m,3H,ArH),7.38～7.48 (m,4H,ArH),7.50～7.57 (m,3H,ArH),7.91 (d,J= 8.1 Hz,2H,ArH),8.10 (d,J=8.4 Hz,2H,ArH)。ESI-MS (m/z): 495 [M + H]+。

4-(2-(1-正癸基菲并[9,10-d]咪唑基))苯甲酸甲酯(1c): 淺黃色固體,產率76%，熔點72～73 ℃。1H NMR (CDCl3)δ: 0.86 (t,J= 6.9 Hz,3H,CH3),1.15～1.34 (m,14H,CH2),1.87～2.00 (m,2H,CH2),3.98 (s,3H,OCH3),4.60 (t,J= 7.2 Hz,2H,NCH2),7.58～7.71 (m,4H,ArH),7.84 (d,J= 8.1 Hz,2H,ArH),8.19-8.25 (m,3H,ArH),8.69 (d,J= 8.1 Hz,1H,ArH),8.77 (d,J= 7.8 Hz,1H,ArH),8.84 (d,J= 7.8 Hz,1H,ArH)。 ESI-MS (m/z): 493 [M + H]+。

2.3 4-(2-(1-癸基咪唑基))苯甲酰肼2a,2b,2c的合成

化合物2a,2b,2c參照文獻[19]合成，其結構表征如下。

4-(2-(1-正癸基苯并咪唑基))苯甲酰肼(2a): 無色固體，產率70%，熔點95～96℃。1H NMR (CDCl3)δ: 0.86 (t,J= 6.6 Hz,3H,CH3),1.12～1.29 (m,14H,CH2),1.70～1.84 (m,2H,CH2),4.18 (t,J= 6.9 Hz,2H,NCH2),4.72 (s,2H,NH2),7.29～7.35 (m,2H,ArH),7.38～7.44 (m,1H,ArH),7.63～7.70 (m,2H,ArH),7.83～7.88 (m,3H,ArH),8.42 (s,1H,NH)。ESI-MS (m/z): 393 [M + H]+。

4-(2-(1-正癸基-4,5-二苯基咪唑))苯甲酰肼(2b): 無色固體，產率82%，熔點111～112 ℃。1H NMR (DMSO-d6)δ: 0.83 (t,J= 6.9 Hz,3H,CH3),0.88～0.96 (m,6H,CH2),0.99～1.07 (m,2H,CH2),1.09～1.17 (m,4H,CH2),1.19～1.29 (m,4H,CH2),3.92 (t,J= 7.2 Hz,2H,NCH2),4.54 (s,2H,NH2),7.09～7.21 (m,3H,ArH),7.39～7.48 (m,4H,ArH),7.50～7.57 (m,3H,ArH),7.81 (d,J= 8.4 Hz,2H,ArH),7.98 (d,J= 8.1 Hz,2H,ArH),9.89 (s,1H,CONH)。ESI-MS (m/z): 495 [M + H]+。

4-(2-(1-正癸基菲并[9,10-d]咪唑-2))苯甲酰肼(2c): 無色針狀晶體，產率78%，熔點197～198 ℃。1H NMR (CDCl3)δ: 0.87 (t,J= 6.6Hz,3H,CH3),1.11～1.32 (m,14H,CH2),1.88～1.99 (m,2H,CH2),4.20 (s,2H,NH2),4.59 (t,J= 7.5 Hz,2H,NCH2),7.61～7.74 (m,4H,ArH),7.81 (d,J= 8.4Hz,2H,ArH),7.94 (d,J= 8.4 Hz,2H,ArH),8.26 (d,J= 7.5 Hz,1H,ArH),8.72 (d,J= 7.8 Hz,1H,ArH),8.79 (dd,J1= 1.5 Hz,J2= 9.3 Hz,1H,ArH),8.86 (d,J= 7.8 Hz,1H,ArH)。 ESI-MS (m/z): 493 [M + H]+。

2.4 2,5-二芳基-1,3,4-噁二唑衍生物3a,3b,3c,3d,3e,3f,3g,3h,3i的合成

參照文獻[19]完成合成，粗產物經柱層析后得到純的目標物3a,3b,3c,3d,3e,3f,3g,3h,3i。

2-(4-(2(1-正癸基苯并咪唑基))苯基)-5-苯基-1,3,4-噁二唑(3a): 無色固體，產率45%，熔點78～80 ℃。1H NMR (CDCl3)δ: 0.85 (t,J= 6.6 Hz,3H,CH3),1.14～1.23 (m,14H,CH2),1.79～1.87 (m,2H,CH2),4.27 (t,J= 7.5 Hz,2H,NCH2),7.29～7.36 (m,2H,ArH),7.40～7.44 (m,1H,ArH),7.50～7.58 (m,3H,ArH),7.80～7.86 (m,1H,ArH),7.92 (d,J= 8.7 Hz,2H,ArH),8.14～8.17 (m,2H,ArH),8.31 (d,J= 8.7 Hz,2H,ArH)。13C NMR (CDCl3)δ: 14.0,22.5,26.6,28.9,29.1,29.3,29.3,29.7,31.7,44.8,110.0,119.9,122.4,122.9,123.4,124.6,126.7,126.9,128.8,129.7,131.6,133.6,135.5,142.8,151.8,163.6,164.5。元素分析(w/%): C31H34N4O·H2O,計算值: C,74.97; H,7.31; N,11.28；實測值: C,74.69; H,7.33; N 11.23。 ESI-MS (m/z): 479 [M + H]+。

2-(4-(2-(1-正癸基苯并咪唑基))苯基)-5-(2-萘基)-1,3,4-噁二唑(3b): 無色固體，產率47%，熔點102～104 ℃。1H NMR (CDCl3)δ: 0.85 (t,J= 6.6 Hz,3H,CH3),1.14～1.32 (m,14H,CH2),1.80～1.87 (m,2H,CH2),4.28 (t,J= 7.5 Hz,2H,NCH2),7.29～7.36 (m,2H,ArH),7.54～7.61 (m,3H,ArH),7.83～7.92 (m,3H,ArH),7.95～8.00 (m,3H,ArH),8.36 (d,J= 8.1 Hz,2H,ArH),8.65 (s,1H,ArH)。13C NMR (CDCl3)δ: 13.9,22.4,26.4,28.8,29.0,29.1,29.2,29.5,31.6,44.6,109.9,119.6,120.4,122.3,122.6,122.7,124.3,126.6,126.8,127.4,127.5,128.3,128.4,128.5,129.4,132.2,133.1,134.1,135.3,142.4,151.5,163.4,164.3。元素分析(w/%): C35H36N4O·0.21H2O,計算值: C,78.95; H,6.89; N,10.52；實測值: C,78.42; H,6.28; N 9.76。ESI-MS (m/z): 529 [M + H]+。

2-(4-(2-(1-正癸基苯并咪唑基))苯基)-5-(2-噻吩基)-1,3,4-噁二唑(3c): 黃色固體，產率40%，熔點94～95 ℃。1H NMR (CDCl3)δ: 0.85 (t,J= 6.6 Hz,3H,CH3),1.15～1.24 (m,14H,CH2),1.78～1.85 (m,2H,CH2),4.26 (t,J= 7.5Hz,2H,NCH2),7.18～7.21 (m,1H,ArH),7.28～7.36 (m,2H,ArH),7.41～7.44 (m,1H,ArH),7.59 (d,J= 4.8 Hz,1H,ArH),7.81～7.87 (m,2H,ArH),7.91 (d,J= 8.1Hz,2H,ArH),8.28 (d,J= 8.1 Hz,2H,ArH)。13C NMR (CDCl3)δ: 14.0,22.6,26.7,28.9,29.2,29.3,29.4,29.8,31.8,44.9,110.0,119.9,122.4,122.9,124.4,126.9,128.1,129.7,129.8,130.2,133.7,135.6,142.9,151.9,160.9,163.2。元素分析(w/%): C29H32N4OS,計算值: C,71.87; H,6.66; N,11.56；實測值: C,71.60；H,6.50; N 11.52。 ESI-MS (m/z): 485 [M + H]+。

2-(4-(2-(1-正癸基-4,5-二苯基咪唑基))苯基)-5-苯基-1,3,4-噁二唑(3d): 無色固體，產率39%，熔點96～98 ℃。1H NMR (DMSO-d6)δ: 0.75 (t,J= 6.9 Hz,3H,CH3),0.81～1.17 (m,14H,CH2),1.22～1.36 (m,2H,CH2),3.98 (t,J= 6.9 Hz,2H,NCH2),7.10～7.23 (m,3H,ArH),7.41～7.49 (m,4H,ArH),7.51～7.58 (m,3H,ArH),7.60～7.67 (m,3H,ArH),8.02 (d,J= 8.4 Hz,2H,ArH),8.12～8.19 (m,2H,ArH),8.29 (d,J= 8.4 Hz,2H,ArH)。13C NMR (CDCl3)δ: 14.1,22.6,26.1,28.5,29.0,29.1,29.3,30.3,31.8,44.9,123.6,126.2,126.6,126.7,126.9,127.9,128.6,128.9,129.3,130.4,130.8,131.0,131.6,134.2,134.5,138.1,146.0,163.9,164.4。 ESI-MS (m/z): 581 [M + H]+。

2-(4-(2-(1-正癸基-4,5-二苯基咪唑基))苯基)-5-(2-萘基)-1,3,4-噁二唑(3e): 無色固體，產率43%，熔點133～134 ℃。1H NMR (DMSO-d6)δ: 0.73 (t,J= 6.6 Hz,3H,CH3),0.83～1.20 (m,14H,CH2),1.24～1.36 (m,2H,CH2),3.98 (t,J= 7.2 Hz,2H,NCH2),7.10～7.23 (m,3H,ArH),7.42～7.50 (m,4H,ArH),7.52～7.59 (m,3H,ArH),7.62～7.70 (m,2H,ArH),8.04 (d,J= 8.4 Hz,3H,ArH),8.14～8.23 (m,3H,ArH),8.34 (d,J= 8.4 Hz,2H,ArH),8.80 (s,1H,ArH)。13C NMR (CDCl3)δ: 14.2,22.7,26.2,28.7,29.2,29.3,29.4,30.5,31.9,45.0,120.9,123.1,123.8,126.3,126.7,127.1,127.2,127.9,128.0,128.7,128.9,129.4,130.4,130.9,131.1,132.7,134.2,134.6,138.2,146.1,164.1,164.8。 ESI-MS (m/z): 631 [M + H]+。

2-(4-(2-(1-正癸基-4,5-二苯基咪唑基))苯基)-5-(2-噻吩基)-1,3,4-噁二唑(3f): 無色固體，產率40%，熔點106～108 ℃。1H NMR (DMSO-d6)δ: 0.76 (t,J= 6.6 Hz,3H,CH3),0.83～1.22 (m,10H,CH2),1.22～1.36 (m,2H,CH2),3.97 (t,J= 7.2 Hz,2H,NCH2),7.09～7.23 (m,3H,ArH),7.32～7.35 (m,1H,ArH),7.40～7.50 (m,4H,ArH),7.51～7.59 (m,3H,ArH),7.96～8.01 (m,4H,ArH),8.24 (d,J= 8.4 Hz,2H,ArH)。13C NMR (CDCl3)δ: 14.1,22.6,26.1,28.6,29.1,29.2,29.3,30.4,31.8,44.9,123.4,124.9,126.2,126.6,126.9,127.9,128.0,128.6,128.9,129.3,129.7,130.1,130.4,130.8,131.0,134.2,134.6,138.2,146.0,160.8,163.4。 ESI-MS (m/z): 587 [M + H]+。

2-(4-(2-(1-正癸基菲并[9,10-d]咪唑基))苯基)-5-苯基-1,3,4-噁二唑(3g): 淺黃色固體，產率36%，熔點160～162 ℃。1H NMR (CDCl3)δ: 0.82 (t,J= 6.6 Hz,3H,CH3),1.07～1.30 (m,14H,CH2),1.86～2.03 (m,2H,CH2),4.69 (t,J= 6.9 Hz,2H,NCH2),7.49～7.74 (m,7H,ArH),8.00 (d,J= 7.5 Hz,2H,ArH),8.10～8.20 (m,2H,ArH),8.27 (d,J= 7.5 Hz,1H,ArH),8.32 (d,J= 7.5 Hz,2H,ArH),8.67 (d,J= 7.8 Hz,1H,ArH),8.81 (t,J= 7.2 Hz,2H,ArH)。13C NMR (CDCl3)δ: 14.1,22.6,26.2,28.8,29.2,29.3,29.4,30.1,31.8,47.3,120.8,122.7,122.8,123.6,124.3,124.7,125.1,125.8,126.2,126.8,126.9,127.3,128.1,128.9,129.2,130.6,131.7,150.4,163.8,164.6。ESI-MS(m/z): 579 [M + H]+。

2-(4-(2-(1-正癸基菲并[9,10-d]咪唑基))苯基)-5-(2-萘基)-1,3,4-噁二唑(3h): 黃色固體，產率30%，熔點151～153 ℃。1H NMR (CDCl3)δ: 0.83 (t,J= 6.6 Hz,3H,CH3),1.17～1.30 (m,14H,CH2),1.87～2.06 (m,2H,CH2),4.73 (t,J= 7.2 Hz,2H,NCH2),7.56～7.74 (m,6H,ArH),7.87～7.94 (m,1H,ArH),7.98～8.05 (m,4H,ArH),8.23 (d,J=7.8,1H,ArH),8.30 (d,J= 7.5 Hz,1H,ArH),8.39 (d,J= 8.4 Hz,2H,ArH),8.61～8.71 (m,2H,ArH),8.83 (d,J= 8.1 Hz,1H,ArH),8.87 (d,J= 8.4 Hz,1H,ArH)。13C NMR (CDCl3)δ: 14.1,22.6,26.2,28.8,29.2,29.3,29.4,30.1,31.8,47.4,120.7,120.8,122.7,122.8,122.9,124.2,124.7,125.2,125.9,126.1,126.8,126.9,127.2,127.3,127.7,127.8,128.1,128.6,128.8,129.2,130.7,132.6,134.5,150.2,163.6,164.7。 ESI-MS (m/z): 629 [M + H]+。

2-(4-(2-(1-正癸基菲并[9,10-d]咪唑基)苯基)-5-(2-噻吩基)-1,3,4-噁二唑(3i): 黃色固體，產率32%，熔點118～119 ℃。1H NMR (CDCl3)δ: 0.79 (t,J= 6.6 Hz,3H,CH3),1.02～1.07 (m,14H,CH2),1.83 (m,2H,CH2),4.95 (t,J= 7.2 Hz,2H,NCH2),7.20 (t,J= 7.8 Hz,1H,ArH),7.39 (m,1H,ArH),7.47 (t,J= 7.8 Hz,1H,ArH),7.59～7.75 (m,4H,ArH),8.10 (d,J= 7.8 Hz,2H,ArH),8.23 (d,J= 8.1 Hz,1H,ArH),8.31 (t,J= 8.4 Hz,3H,ArH),8.50 (d,J= 7.8 Hz,1H,ArH),8.91 (d,J=8.1 Hz,1H,ArH)。13C NMR (CDCl3)δ: 13.9,22.4,25.8,28.4,29.0,29.1,29.2,29.3,31.6,48.5,120.7,120.8,121.6,122.4,124.1,124.3,124.7,124.9,126.6,126.8,127.4,127.5,128.0,128.1,128.3,129.4,130.2,130.8,131.6,147.0,160.8,162.0。 ESI-MS (m/z): 585 [M + H]+。

3 結果與討論

眾所周知，咪唑衍生物的溶解性往往較差，尤其是具有大共軛體系的咪唑化合物，如本文中的4-(2-咪唑基)苯甲酸甲酯衍生物，其溶解性更差，往往不溶于一般的有機溶劑，使其在合成應用方面受到極大的限制。因此，本合成研究的首要工作是實現(xiàn)4-(2-咪唑基)苯甲酸甲酯衍生物的癸基化，也是本合成工作的關鍵所在。為得到目標物，采用了前期報道的w=50% K2CO3-丁酮-TBAB體系[19]。該體系對4-(2-咪唑基)苯甲酸甲酯衍生物的長鏈烷基化具有顯著的優(yōu)勢，產率為75%以上，溶劑可循環(huán)使用，產物的提純較為簡便，適合批量生產。

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