以芳香醛、乙酰乙酸乙酯(乙酰丙酮)及碳酸氢铵为原料,研究超声条件下蒙脱土固载路易斯酸催化合成1,4-二氢吡啶衍生物.单因素筛选法考察催化剂、溶剂、温度、超声时间、氮源对产率的影响.反应在水溶液中顺利进行,在反应温度80 ℃,超声时间15 min,芳香醛、乙酰乙酸乙酯及碳酸氢铵的物质的量比为1.2∶2.0∶1.0,催化剂为蒙脱土固载氯化铝,催化剂(醛的物质的量分数为10%)的最优条件下,合成的1,4-二氢吡啶衍生物产率最高可达93.7%.催化剂循环使用3次后产率仍可达85.9%.产物通过红外、核磁、熔点进行表征.该方法与现有合成方法相比,具有操作简便、收率高、用时短等优点,有潜在的应用前景.
Using the aromatic aldehydes,ethyl acetoacetate(acetylacetonate)and ammonium bicarbonate as raw materials,under ultrasonic condition,montmorillonite/Lewis acid catalysis the synthesis of 1,4-dihydropyridine derivatives was performed.The effects of the reaction temperature,reaction time,solvent,catalyst and nitrogen source were investigated by single factor screening.Reaction was found to proceed smoothly in aqueous solution at a reaction temperature of 80 ℃,and ultrasonic time 15min.The molar ratio of aromatic aldehyde,ethyl acetoacetate and bicarbonate ammonium molar ratio of 1.2∶2.0∶1.0.Catalyst is immobilized aluminum chloride catalyst in an amount of 10%(molar ratio of aldehyde).Under optimal conditions,the synthesis of 1,4-dihydropyridine derivatives yield up to 93.7%.With the catalyst recycled three times,the production yield was still up to 85.9%.The product was characterized by IR,NMR,melting point.Compared with the conventional synthesis method,ultrasonic method is simple,high yield,rapid,showing potential applications.
[1] STOUD D M,MEYERS A I.Recent advances in the chemistry of dihydropyridines[J].Chemical Reviews,1982,82(2):223-243.DOI:10.1021/cr00048a004.
[2] WANG D H,LIU Q,CHEN B,et al.Photooxidation of Hantzsch 1,4-dihydropyridines by molecular oxygen[J].Chinese Science Bulletin,2010,55(25):2855-2858.DOI:10.1007/s11434-010-3143-2.
[3] 赵兴华,牟书勇,赵莉.无溶剂超声辐射下硝酸镱高效催化合成1,4-二氢吡啶衍生物[J].高等学校化学学报,2012,33(5):954-957.DOI:10.3969/j.issn.0251-0790.2012.05.016. ZHAO X H,MU S Y,ZHAO L.Solvent-free synthesis of 1,4-dihydropyridine derivatives under ultrasonic irradiation with ytterbium nitrate as catalyst[J].Chemical HEMICAL Journal of Chinese Universities,2012,33(5):954-957.DOI:10.3969/j.issn.0251-0790.2012.05.016.
[4] 史达清,牟杰,庄启亚,等.水溶液中4-芳基-1,4-二氢吡啶衍生物的一步合成法[J].有机化学,2004,24(9):1042-1044.DOI:10.3321/j.issn:0253-2786.2004.09.07. SHI D Q,MU J,ZHUANG Q Y,et al.One-pot synthesis of 4-aryl-1,4-dihydropyridines in water[J].Chinese Journal of Organic Chemistry,2004,24(9):1042-1044.DOI:10.3321/j.issn:0253-2786.2004.09.07.
[5] 陈翠,谭丽泉,邱会华.乙酰乙酰芳胺类化合物导向的五取代1,4-二氢吡啶衍生物的合成[J].有机化学,2014,34(8):1673-1676.DOI:10.6023/cjoc201403016. CHEN C,TAN L Q,QIU H H.Synthesis of multi-substituted 1,4-dihydropyridine derivatives from acetoacetanilides [J].Chinese Journal of Organic Chemistry,2014,34(8):1673-1676.DOI:10.6023/cjoc201403016.
[6] 王道林,吴健莹,董哲,等.3,3'-芳基(烷基)二(4-氨基香豆素)和1,4-二氢吡啶并[3,2-c] [5,6-c] 双香豆素类衍生物的有效合成[J].有机化学,2015,35(1):200-206.DOI:10.6023/cjoc201408031. WANG D L,WU J Y,DONG Z,et al.Efficient synthesis of 3,3'-aryl(alkyl)-bis(4-aminocoumarine)and 1,4-dihydropyridino[3,2-c] [5,6-c] dicoumarines[J].Chinese Journal of Organic Chemistry,2015,35(1):200-206.DOI:10.6023/cjoc201408031.
[7] JAVAD S,SAYED H B,SHIVA D K.Cobalt nanoparticles promoted highly efficient one pot four-component synthesis of 1,4-dihydropyridines under solvent-free conditions [J].Chinese Journal of Catalysis,2011,32(12):1850-1855.DOI:10.1016/S1872-2067(10)60295-1.
[8] DODD S P,SAUNDERS G A,CANKURTARAN M,et al.Ultrasonic study of the temperature and hydrostatic-pressure dependences of the elastic properties of polycrystalline cementite(Fe3C)[J].Physica Status Solidi(a),2003,198(2):272-281.DOI:10.1002/pssa.200306613.
[9] BASAVEGOWDA N,MISHRA K,YONG R L,et al.Ultrasonic-assisted green synthesis of palladium nanoparticles and their nanocatalytic application in multicomponent reaction[J].New Journal of Chemistry,2015,39(145):972-977.DOI:10.1039/C4NJ01543F.
[10] 沈咏梅,谢晓娜,荀二娜,等.超声辅助酶促己酸乙酯的合成[J].合成化学,2012,20(5):612-615.DOI:10.3969/j.issn.1005-1511. SHEN Y M,XIE X N,XUN E N,et al.Ultrasound-promoted synthesis of ethyl hexanoate catalyzed by lipase[J].Chinese Journal of Synthetic Chemistry,2012,20(5):612-138.DOI:10.3969/j.issn.1005-1511.
[11] 李记太,蔺志平.蒙脱土K10-ZnCl2催化下研磨法合成二吲哚甲烷衍生物[J].有机化学,2008,28(7):1238-1242. LI J T,LIN Z P.Synthesis of Bis(indol-3-yl)methanes catalyzed by montmorillonite K10-ZnCl2 by grinding[J].Chinese Journal of Organic Chemistry,2008,28(7):1238-1242.
[12] 蔡小华,张国林.无溶剂一锅法合成1,4-二氢吡啶[J].有机化学,2005,25(8):930-933.DOI:10.3321/j.issn:0253-2786. CAI X H,ZHANG G L.One-pot synthesis of dihydropyridines under solvent-free condition[J].Chinese Journal of Organic Chemistry,2005,25(8):930-933.DOI:10.3321/j.issn:0253-2786.2005.08.007.
[13] 白路军,白银娟,杨秉勤,等.1,4-二氢吡啶衍生物合成方法的改进和芳构化研究[J].有机化学,2000,20(4):514-517.DOI:10.3321/j.issn:0253-2786.2000.04.011. BAI L J,BAI Y J,YANG B Q,et al.Improved synthesis and aromatization of 1,4-dihydropyridines[J].Chinese Journal of Organic Chemistry,2000,20(4):514-517.DOI:10.3321/j.issn:0253-2786.2000.04.011.
