表 1
催化剂用量对产率的影响a
Table 1.
Effect of catalyst dosage on yield
引用本文:
魏振中, 李江飞, 王泽云, 李品华, 王永秋. 腐殖酸催化合成1, 4-二氢吡啶类化合物[J]. 有机化学,
2017, 37(7): 1835-1838.
doi:
10.6023/cjoc201612055
Citation: Wei Zhenzhong, Li Jiangfei, Wang Zeyun, Li Pinhua, Wang Yongqiu. Synthesis of 1, 4-Dihydropyridine Compounds Catalyzed by Humic Acid[J]. Chinese Journal of Organic Chemistry, 2017, 37(7): 1835-1838. doi: 10.6023/cjoc201612055
Citation: Wei Zhenzhong, Li Jiangfei, Wang Zeyun, Li Pinhua, Wang Yongqiu. Synthesis of 1, 4-Dihydropyridine Compounds Catalyzed by Humic Acid[J]. Chinese Journal of Organic Chemistry, 2017, 37(7): 1835-1838. doi: 10.6023/cjoc201612055
腐殖酸催化合成1, 4-二氢吡啶类化合物
English
Synthesis of 1, 4-Dihydropyridine Compounds Catalyzed by Humic Acid
Abstract:
A novel, efficient and straightforward method to synthesize 1, 4-dihydropyridine compounds with excellent yields is reported through Hantzsch reaction of aldehydes, ammonium acetate and ethyl acetoacetate or methyl acetoacetate using humic acid as the catalyst. This method has high yield and less pollution. The catalyst is easy to recycle and environment friendly.
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Key words:
- humic acid
- / catalysis
- / 1, 4-dihydropyridine
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1, 4-二氢吡啶类化合物是一种钙离子通道阻滞剂类药物, 在K+和Na+通道调制中也发挥重要的作用[1].如正在被广泛使用的治疗高血压和心脑血管疾病的尼卡地平、尼莫地平、非洛地平等药物[2], 该类化合物还可以用来治疗阿尔茨海默氏病[3].另外作为药物或药物中间体还具有抗炎[4]、抗病毒[4]、抗细胞毒性[5]、抗惊厥[6]、抗结核病[7]、抗血栓形成[8]等作用.因此, 研究该类化合物的合成方法, 成为广大化学工作人员关注的热点.
最早合成1, 4-二氢吡啶类化合物的方法是Hantzsch法, 该方法反应时间长, 产率低, 且氨气容易对环境造成污染, 不利于工业化生产.近年来有很多文献从催化剂、合成手段、合成方法等方面研究报道1, 4-二氢吡啶类化合物的合成.催化剂方面有磁性Fe3O4纳米粒子[9]、纳米WO3负载磺酸[10]、脲酶[11]、脯氨酸[12]、氨基磺酸[13]、碘[14]、Ce(SO4)2•SiO2[15]、MCM-41-Ni复合物[16]、TBAB[17]、CuI[18]、离子液体[19]; 合成方法上有3+3环合[20]、β-环化反应[21]等; 合成手段上有超声及超声介导[18, 22]、无溶剂研磨[23, 24]等.但是一些方法存在反应条件苛刻、合成催化剂复杂、催化剂污染大、产物后处理麻烦等缺点, 因此发展一种高效、简单、催化剂可回收利用的适合于工业化生产1, 4-二氢吡啶类化合物的方法至关重要.
腐殖酸是自然界中广泛存在的大分子有机物质, 广泛应用于农、林、牧、石油、化工、建材、医药卫生、环保等各个领域; 作为催化剂或催化剂载体具有廉价易得、污染小、催化活性较高, 且易于回收利用等优点[25, 26].本文以腐殖酸催化Hantzsch反应, 以芳醛、乙酰乙酸乙酯(甲酯)和乙酸铵为原料, 一锅法合成了1, 4-二氢吡啶类化合物.方法以95%乙醇为溶剂, 反应条件温和且溶剂容易回收; 催化剂不仅无毒、无残留、廉价、易得, 且能很好的回收并连续使用, 适合放大生产; 产品后处理简便只需过滤回收催化剂、尤其是放大生产时仅需重结晶即可以95%左右的收率得到产物, 整个反应过程环境十分友好.合成路线如Eq. 1所示.
1 结果与讨论
以4-甲氧基苯甲醛、乙酰乙酸乙酯和醋酸铵为例, 探究了催化剂用量和溶剂对反应的影响.结果如表 1和表 2.
表 1
催化剂用量对产率的影响a
Table 1.
Effect of catalyst dosage on yield
序号 用量/g 产率/% 1 0.02 85 2 0.06 90 3 0.08 93 4 0.10 95 5 0.12 94.5 6 0.15 95 a1.0 mmol 4-甲氧基苯甲醛, 2.1 mmol乙酰乙酸乙酯, 2.0 mmol醋酸铵, 10 mL95%乙醇, 回流4.0 h.
表 2
溶剂对反应的影响a
Table 2.
Effect of solvent on reaction
序号 溶剂 Time/h 产率/% 1 CH3CN 4.0 88 2 CH2Cl2 8.0 20 3 CHCl3 8.0 35 4 THF 4.0 93 5 CH3OH 5.0 84 6 C2H5OH 4.0 90 7 95% C2H5OH 4.0 95 8 V(C2H5OH):V(H2O)＝1:1 4.5 93 9 V(C2H5OH):V(H2O)＝4:1 4.0 95 10 H2O 8.0 40 a 1.0 mmol 4-甲氧基苯甲醛, 2.1 mmol乙酰乙酸乙酯, 2.0 mmol醋酸铵, 0.1 g腐殖酸, 回流. 由表 1可以看出, 催化剂的量增加到0.10 g以上后对产率影响不大, 因此选用催化剂的用量为0.10 g.由表 2可以看出, 在醇、醇水、四氢呋喃为溶剂时可以有较好的收率.在优化条件下, 我们对催化剂回收套用情况进行实验, 具体实验结果如表 3.通过5次的回收套用实验表明, 腐殖酸催化剂活性并未有明显下降, 说明腐殖酸催化剂回收使用效果较好.
表 3
催化剂回收套用情况a
Table 3.
Results of catalyst recycle applied
循环次数 0 1 2 3 4 5 产率/% 95 95.5 95.5 94.5 95 94.5 a1.0 mmol 4-甲氧基苯甲醛, 2.1 mmol乙酰乙酸乙酯, 0.1 g腐殖酸, 2.0 mmol醋酸铵, 10 mL 95%乙醇, 回流4 h. 我们进一步将腐殖酸原样和回收的腐殖酸进行X射线粉末衍射(PXRD)和透射电子显微镜(TEM)检测分析, 如图 2和图 3.通过对比可知, 两者粉末衍射位置和强度几乎是完全一致的, 这说明催化剂在反应前后的结构并没有变化; 透射电镜数据反映两者反应前后尺寸大小基本一致, 这说明在催化反应过程中, 即使不断搅拌催化剂的颗粒大小也没有发生变化.更好的说明催化剂可以重复利用.
图 2
腐殖酸的粉末衍射图
Figure 2.
PXRD patterns of humic caid
图 3
腐殖酸的投射电镜图
Figure 3.
Tem patterns of humic caid(a) After the catalytic reaction; (b) As-prepared
此外我们对部分化合物进行放大10倍实验(表 4).放大实验反应完全后, 我们将腐殖酸趁热过滤, 洗涤, 烘干回收, 滤液旋干回收乙醇, 用[V(乙醇):V(水)＝3:1]重结晶得到目标化合物.
表 4
腐殖酸催化合成1, 4-二氢吡啶类化合物a
Table 4.
Humic acid catalyzed synthesis of 1, 4-dihydropyridines
Entry R1 R2 Time/h Yield/% m.p./℃ Actual Reference 3a OC2H5 4-CH3OC6H4 4.0 95 158~159 157~159[11] 3b OC2H5 4-O2NC6H4 5.5 94 128~129 129~130[10] 3c OC2H5 4-CH3C6H4 4.5 95 137~139 138~141[10] 3d OC2H5 4-BrC6H4 4.0 97 160~161 158~160[10] 3e OC2H5 2, 4-(Cl)2C6H3 5.0 95 147~149 148~150[10] 3f OC2H5 (CH3)2NC6H4 4.5 94 195~196 198~199[10] 3g OC2H5 4-HO-3-CH3C6H3 4.5 93 144~146 145~148[10] 3h OCH3 4-CH3OC6H4 3.5 96 183~185 185~188[10] 3i OCH3 4-O2NC6H4 5.0 95 168~169 174~177[10] 3j OCH3 4-CH3C6H4 4.5 96 176~177 177~180[10] 3k OCH3 4-BrC6H4 3.5 98 200~201 201~202[9] 3l OCH3 2, 4-(Cl)2C6H3 4.5 96 188~190 189~192[11] aAmplification experiment: 3a, time 5.5 h, yield 96.5%; 3d, time: 5.5 h, yield 98.5%; 3k, time: 5.0 h, yield 98.5%; 3l, time: 5.5 h, yield 97%. 2 结论
本文将腐殖酸用于催化有机合成反应.报道了腐殖酸催化醛、1, 3-二羰基化合物和乙酸铵合成1, 4-二氢吡啶类化合物.方法操作方法简单、后处理方便、催化剂廉价易得且能回收套用.为1, 4-二氢吡啶类化合物的合成寻找到了一种简捷绿色的方法.
3 实验部分
3.1 仪器与试剂
WRS-1型数字熔点仪(温度计未校正); ZF-II型四用紫外线分析仪(TLC); BRUKER D8 ADVANCE型X射线衍射仪(扫描电压电流分别为40 kV、40 mA, λ＝0.15418 nm, 扫描范围2θ＝10°~80°); 300 kV高分辨透射电子显微镜(Tecnai, 荷兰FEI公司); Bruker核磁共振仪(TMS为内标, 400 MHz); 所用试剂均为分析纯级, 腐殖酸购于阿拉丁, 其中黄腐酸≥90%.
3.2 实验方法
3.2.1 1, 4-二氢吡啶(3a)合成步骤
将4-甲氧基苯甲醛(0.136 g, 1 mmol)、乙酰乙酸乙酯(0.275 g, 2.1 mmol)、醋酸铵(0.154 g, 2 mmol)、腐殖酸催化剂(0.1 g)和10 mL 95%的乙醇加入25 mL圆底烧瓶中, 加热回流, 薄层色谱(TCL)跟踪反应进程, 4 h后反应结束, 将腐殖酸趁热过滤, 催化剂用乙醇洗涤, 烘干回收利用.滤液合并旋干后, 分批加入15 mL乙酸乙酯溶解, 分出乙酸乙酯, 无水硫酸钠干燥、抽滤、脱溶, 残余物经柱层析[V(石油醚):V(乙酸乙酯)＝10:1]分离得到目标化合物3a.
2, 6-二甲基-4-(4-甲氧基苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3a): 1H NMR (400 MHz, CDCl3) δ: 7.20~6.75 (m, 4H, C6H4), 5.79 (s, 1H, NH), 4.94 (s, 1H, CH), 4.10 (q, J＝7.1 Hz, 4H, 2×CH2), 3.76 (s, 3H, CH3), 2.32 (s, 6H, 2×CH3), 1.23 (t, J＝7.1 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.60, 143.50, 140.23, 128.82, 113.07, 104.22, 59.56, 55.01, 38.63, 19.39, 14.15.
2, 6-二甲基-4-(4-硝基苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3b): 1H NMR (400 MHz, CDCl3) δ: 8.17~7.39 (m, 4H, C6H4), 5.69 (s, 1H, NH), 5.10 (s, 1H, CH), 4.10 (q, J＝7.1 Hz, 4H, 2×CH2), 2.37 (s, 6H, 2×CH3), 1.23 (t, J＝7.1 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 166.99, 144.47, 128.87, 123.26, 103.28, 59.97, 40.14, 19.66, 14.24.
2, 6-二甲基-4-(4-甲基苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3c): 1H NMR (400 MHz, CDCl3) δ: 7.18~7.02 (m, 4H, C6H4), 5.63 (s, 1H, NH), 4.97 (s, 1H, CH), 4.10 (q, J＝7.0, 4H, 2×CH2), 2.33 (s, 6H, 2×CH3), 2.28 (s, 3H, CH3), 1.24 (t, J＝7.0 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.96, 144.41, 144.01, 135.50, 128.63, 127.34, 103.86, 50.82, 38.69, 20.90, 19.40.
2, 6-二甲基-4-(4-溴苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3d): 1H NMR (400 MHz, CDCl3) δ: 7.42~7.07 (m, 4H, C6H4), 5.61 (s, 1H, NH), 4.96 (s, 1H, CH), 4.10 (q, J＝7.1, 3.9 Hz, 4H, 2×CH2), 2.34 (s, 6H, 2×CH3), 1.23 (t, J＝7.1 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.33, 146.78, 143.86, 130.87, 129.81, 103.88, 59.80, 39.34, 19.60, 14.24.
2, 6-二甲基-4-(2, 4-二氯苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3e): 1H NMR (400 MHz, CDCl3) δ: 7.37~7.10 (m, 3H, C6H3), 5.85 (s, 1H, NH), 5.35 (s, 1H, CH), 4.08 (q, J＝6.4 Hz, 4H, 2×CH2), 2.29 (s, 6H, 2×CH3), 1.21 (t, J＝6.4 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.32, 144.16, 144.02, 133.07, 132.39, 131.97, 128.76, 126.87, 103.34, 59.72, 37.26, 19.40, 14.20.
2, 6-二甲基-4-(4-N, N-二甲基胺基苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3f):1H NMR (400 MHz, CDCl3) δ: 7.25~6.54 (m, 4H, C6H4), 5.54 (s, 1H, NH), 4.90 (s, 1H, CH), 4.10 (q, J＝7.2 Hz, 4H, 2×CH2), 2.90 (s, 6H, 2×CH3), 2.33 (s, 6H, 2×CH3), 1.25 (t, J＝7.2 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.61, 146.58, 143.19, 131.12, 128.55, 124.33, 100.06, 59.49, 38.16, 18.87, 14.15.
2, 6-二甲基-4-(3-甲基-4-羟基苯基)-3, 5-二乙氧羰基-1, 4-二氢吡啶(3g): 1H NMR (400 MHz, CDCl3) δ: 6.86~6.75 (m, 3H, C6H3), 5.66 (s, 1H, NH), 5.48 (s, 1H, CH), 4.94 (s, 1H), 4.12 (q, J＝7.1 Hz, 4H, 2×CH2), 3.84 (s, 3H, CH3), 2.33 (s, 6H, 2×CH3), 1.25 (t, J＝7.1 Hz, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.56, 145.71, 143.81, 143.33, 120.38, 113.74, 110.84, 104.26, 59.55, 55.66, 39.05, 19.45, 14.20.
2, 6-二甲基-4-(4-甲氧基苯基)-3, 5-二甲氧羰基-1, 4-二氢吡啶(3h): 1H NMR (400 MHz, CDCl3) δ: 7.24~6.70 (m, 4H, C6H4), 5.84 (s, 1H, NH), 4.95 (s, 1H, CH), 3.76 (s, 3H, CH3), 3.65 (s, 6H, 2×CH3), 2.32 (s, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 168.00, 157.84, 143.86, 139.84, 128.46, 113.28, 103.96, 55.01, 50.83, 38.32, 19.38.
2, 6-二甲基-4-(4-硝基苯基)-3, 5-二甲氧羰基-1, 4-二氢吡啶(3i): 1H NMR (400 MHz, CDCl3) δ: 8.17~7.37 (m, 4H, C6H4), 5.86 (s, 1H, NH), 5.11 (s, 1H, CH), 3.65 (s, 6H, 2×CH3), 2.36 (s, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.43, 154.73, 146.41, 144.88, 128.57, 123.43, 102.99, 51.12, 39.86, 19.60.
2, 6-二甲基-4-(4-甲基苯基)-3, 5-二甲氧羰基-1, 4-二氢吡啶(3j): 1H NMR (400 MHz, CDCl3) δ: 7.16~7.03 (m, 4H, C6H4), 5.81 (s, 1H, NH), 4.98 (s, 1H, CH), 3.66 (s, 6H, 2×CH3), 2.33 (s, 6H, 2×CH3), 2.29 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ: 167.96, 144.41, 143.99, 135.50, 128.64, 127.35, 103.88, 50.81, 38.70, 20.89, 19.40.
2, 6-二甲基-4-(4-溴苯基)-3, 5-二甲氧羰基-1, 4-二氢吡啶(3k): 1H NMR (400 MHz, CDCl3) δ: 7.39~7.15 (m, 4H, C6H4), 5.72 (s, 1H, NH), 4.97 (s, 1H, CH), 3.65 (s, 6H, 2×CH3), 2.34 (s, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.77, 146.46, 144.25, 131.06, 129.47, 119.97, 103.60, 51.01, 39.04, 19.57.
2, 6-二甲基-4-(2, 4-二氯苯基)-3, 5-二甲氧羰基-1, 4-二氢吡啶(3l): 1H NMR (400 MHz, CDCl3) δ: 7.36~7.11 (m, 3H, C6H4), 5.79 (s, 1H, NH), 5.36 (s, 1H, CH), 3.61 (s, 6H, 2×CH3), 2.31 (s, 6H, 2×CH3); 13C NMR (100 MHz, CDCl3) δ: 167.63, 144.45, 144.14, 133.03, 131.99, 131.97, 128.78, 127.09, 103.44, 50.72, 36.96, 19.27.
辅助材料(Supporting Information)化合物的1H NMR和13C NMR谱图.这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.
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-
[1]
Goldmann, S.; Stoltefuss, J. Angew. Chem., Int. Ed. 1991, 30, 1559. doi: 10.1002/(ISSN)1521-3773
-
[2]
鲁玲玲, 许辉, 周攀, 余富朝, 有机化学, 2016, 36, 2858. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract345667.shtmlLu, L.-L.; Xu, H.; Zhou, P.; Yu, F.-C. Chin. J. Org. Chem. 2016, 36, 2858(in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract345667.shtml
-
[3]
Soo-Jeong, C.; Joong-Heui, C.; Isak, I. Eur. J. Med. Chem. 2010, 45, 2578. doi: 10.1016/j.ejmech.2010.02.046
-
[4]
Hilgroth, A.; Lilie, H. Eur. J. Med. Chem. 2003, 38, 495. doi: 10.1016/S0223-5234(03)00060-6
-
[5]
Prashantha, K. B. R.; Pankaj, M.; Karthikeyan, E.; Ankur, B.; Suja, P. V. Med. Chem. Res. 2010, 19, 344. doi: 10.1007/s00044-009-9195-7
-
[6]
Samzadeh, K. A.; Shafaroodi, H.; Miri, R.; Mirkhani, H. Med. Chem. Res. 2009, 18, 112. doi: 10.1007/s00044-008-9112-5
-
[7]
Kharkar, P. S.; Desai, B.; Gaveria, H. J. Med. Chem. 2002, 45, 4858. doi: 10.1021/jm020217z
-
[8]
Cooper, K.; Fray, M. J.; Parry, M. J. J. Med. Chem. 1992, 35, 3115. doi: 10.1021/jm00095a005
-
[9]
Nasr, M.; Hoseini, S.; Montazerozohori, M.; Mehrabi, R.; Nasrabadi, H. J. Mol. Catal. A:Chem. 2014, 382, 99. doi: 10.1016/j.molcata.2013.11.010
-
[10]
Bitaraf, M.; Ali, A.; Otokesh, S. J. Chin. Chem. Soc. 2016, 63, 336. doi: 10.1002/jccs.v63.4
-
[11]
Tamaddon, F.; Ghazi, S. Catal. Commun. 2015, 72, 63. doi: 10.1016/j.catcom.2015.09.006
-
[12]
郭圣荣, 袁艳琴, 张春牛, 吴香梅, 孙晨, 有机化学, 2010, 28, 811.Guo, S.-R.; Yuan, Y.-Q.; Zhang, C.-N.; Wu, X.-M.; Sun, C. Chin. J. Org. Chem. 2010, 28, 811(in Chinese).
-
[13]
李建平, 仇记宽, 李会娟, 张贵生, 有机化学, 2011, 29, 511.Li, J.-P.; Chou, J.-K.; Li, H.-J.; Zhang, G.-S. Chin. J. Org. Chem. 2011, 29, 511(in Chinese).
-
[14]
王道林, 董哲, 刘忠, 赵伟, 杨菲菲, 有机化学, 2014, 34, 783. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract343694.shtmlWang, D.-L.; Dong, Z.; Liu Z.; Zhao W.; Yang, F.-F. Chin. J. Org. Chem. 2014, 34, 783(in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract343694.shtml
-
[15]
Pei, W.; Wang, Q.; Li, X.-N.; Sun, C. Chin. J. Chem. 2010, 28, 483. doi: 10.1002/cjoc.v28:3
-
[16]
Nikoorazm, M.; Ghorbani, C. A.; Khanmoradi, M. RSC Adv. 2016, 6, 56549. doi: 10.1039/C6RA09371J
-
[17]
Ananda, K. T.; Mohan, C. V. S.; Satyanarayana, K. Synth. Commun. 2014, 44, 574. doi: 10.1080/00397911.2013.825807
-
[18]
Tabassum, S.; Govindaraju, S.; Khan, R.; Pasha, M. A. RSC Adv. 2016, 6, 29802. doi: 10.1039/C6RA05441B
-
[19]
Khaskel, A.; Barman, P. Heteroat. Chem. 2016, 27, 114. doi: 10.1002/hc.21308
-
[20]
Zhang, Z.; Zeng, X.; Xie, D.; Chen, D.; Ding, L, ; Wang, A.; Yang, L.; Zhong, G. Org. Lett. 2015, 17, 5052. doi: 10.1021/acs.orglett.5b02527
-
[21]
Jiang, Y.-H.; Yan, C.-G. Chin. J. Chem. 2016, 34, 1255. doi: 10.1002/cjoc.v34.12
-
[22]
林伟, 郑永祥, 黄志斌, 史达清, 有机化学, 2017, 37, 508. http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract345793.shtmlLin, W.; Zheng, Y.-X.; Huang, Z.-B.; Shi, D.-Q. Chin. J. Org. Chem. 2017, 37, 508(in Chinese). http://sioc-journal.cn/Jwk_yjhx/CN/abstract/abstract345793.shtml
-
[23]
Shabalala, N.; Maddila, S.; Jonnalagadda, S. B. New J. Chem. 2016, 40, 5107. doi: 10.1039/C5NJ03574K
-
[24]
Kumar, A.; Sharma, S. Green Chem. 2011, 13, 2017. doi: 10.1039/c1gc15223h
-
[25]
Wang, R.; Liu, X.; Wu, R.; Yu, B.; Li, H. RSC Adv. 2016, 6, 11.
-
[26]
Xu, Q.-J.; Zhou, D.-P.; Cui, Y.-C. Chin. J. Org. Chem. 2007, 27, 1520(in Chinese).
-
[1]
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图 3 腐殖酸的投射电镜图
Figure 3 Tem patterns of humic caid(a) After the catalytic reaction; (b) As-prepared
表 1 催化剂用量对产率的影响a
Table 1. Effect of catalyst dosage on yield
序号 用量/g 产率/% 1 0.02 85 2 0.06 90 3 0.08 93 4 0.10 95 5 0.12 94.5 6 0.15 95 a1.0 mmol 4-甲氧基苯甲醛, 2.1 mmol乙酰乙酸乙酯, 2.0 mmol醋酸铵, 10 mL95%乙醇, 回流4.0 h. 
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表 2 溶剂对反应的影响a
Table 2. Effect of solvent on reaction
序号 溶剂 Time/h 产率/% 1 CH3CN 4.0 88 2 CH2Cl2 8.0 20 3 CHCl3 8.0 35 4 THF 4.0 93 5 CH3OH 5.0 84 6 C2H5OH 4.0 90 7 95% C2H5OH 4.0 95 8 V(C2H5OH):V(H2O)＝1:1 4.5 93 9 V(C2H5OH):V(H2O)＝4:1 4.0 95 10 H2O 8.0 40 a 1.0 mmol 4-甲氧基苯甲醛, 2.1 mmol乙酰乙酸乙酯, 2.0 mmol醋酸铵, 0.1 g腐殖酸, 回流.
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表 3 催化剂回收套用情况a
Table 3. Results of catalyst recycle applied
循环次数 0 1 2 3 4 5 产率/% 95 95.5 95.5 94.5 95 94.5 a1.0 mmol 4-甲氧基苯甲醛, 2.1 mmol乙酰乙酸乙酯, 0.1 g腐殖酸, 2.0 mmol醋酸铵, 10 mL 95%乙醇, 回流4 h.
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表 4 腐殖酸催化合成1, 4-二氢吡啶类化合物a
Table 4. Humic acid catalyzed synthesis of 1, 4-dihydropyridines
Entry R1 R2 Time/h Yield/% m.p./℃ Actual Reference 3a OC2H5 4-CH3OC6H4 4.0 95 158~159 157~159[11] 3b OC2H5 4-O2NC6H4 5.5 94 128~129 129~130[10] 3c OC2H5 4-CH3C6H4 4.5 95 137~139 138~141[10] 3d OC2H5 4-BrC6H4 4.0 97 160~161 158~160[10] 3e OC2H5 2, 4-(Cl)2C6H3 5.0 95 147~149 148~150[10] 3f OC2H5 (CH3)2NC6H4 4.5 94 195~196 198~199[10] 3g OC2H5 4-HO-3-CH3C6H3 4.5 93 144~146 145~148[10] 3h OCH3 4-CH3OC6H4 3.5 96 183~185 185~188[10] 3i OCH3 4-O2NC6H4 5.0 95 168~169 174~177[10] 3j OCH3 4-CH3C6H4 4.5 96 176~177 177~180[10] 3k OCH3 4-BrC6H4 3.5 98 200~201 201~202[9] 3l OCH3 2, 4-(Cl)2C6H3 4.5 96 188~190 189~192[11] aAmplification experiment: 3a, time 5.5 h, yield 96.5%; 3d, time: 5.5 h, yield 98.5%; 3k, time: 5.0 h, yield 98.5%; 3l, time: 5.5 h, yield 97%.
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