CN111205184A - 一种合成(9z,12e)-十四碳-9,12-二烯-1-醇乙酸酯的方法 - Google Patents
一种合成(9z,12e)-十四碳-9,12-二烯-1-醇乙酸酯的方法 Download PDFInfo
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- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
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Abstract
本发明属于绿色农药合成技术领域,公开了一种新的合成(9Z,12E)‑十四碳‑9,12‑二烯‑1‑醇乙酸酯的方法。该方法以丙二酸和9‑溴‑1‑壬醇为两种起始原料。丙二酸与丙醛在哌啶乙酸盐存在下发生Knoevenagel缩合反应,生成(E)‑3‑戊烯酸,然后经氢化铝锂还原得到(E)‑3‑戊烯‑1‑醇,再经过溴代反应,与三苯基膦在乙腈中回流制得(E)‑3‑戊烯基三苯基溴化膦。9‑溴‑1‑壬醇经过PCC氧化反应得到9‑溴壬醛,然后和乙酸钾反应得到9‑乙酰氧基壬醛。最后(E)‑3‑戊烯基三苯基溴化膦与9‑乙酰氧基壬醛发生过Wittig反应制得(9Z,12E)‑十四碳‑9,12‑二烯‑1‑醇乙酸酯。本发明利用丙二酸与丙醛的Knoevenagel缩合反应构建E‑型双键,具有反应条件温和,对环境友好、合成路线简捷等优点。
Description
技术领域
本发明属于绿色农药合成技术领域,具体涉及一种合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的方法。
背景技术
(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯(式1)是植物害虫印度谷螟(Plodiainterpunctella Hübner)性信息素的主要成分,可用于该类害虫的综合防治(Brady,U.E.;Tumlinson,J.H.,III;Brownlee,R.G.;Silverstein,R.M.Science 1971,171,802-804.Kuwahara,Y.;Kitamura,C.;Takahashi,S.;Hara,H.;Ishii,S.;Fukami,H.Science1971,171,801-802.)。(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯也是烟草粉螟(Ephestiaelutella Hübner)性信息素的次要成分(Brady,U.E.;Nordlund,D.A.Life Sci.1971,10,797-801.Brady,U.E.Life Sci.1973,13,227-235.)。另外,(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯还是草地贪夜蛾(Spodoptera frugiperda Smith)性信息素的活性成分,具有吸引雄虫的生理活性(Jacobson,M.;Redfern,R.E.;Jones,W.A.;Aldrige,M.H.Science1970,170,542-544.)。
(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯虽然具有显著的生理活性,但在植物害虫雌虫体内含量很少,极难提取,阻碍了其在植物病虫害生物防治领域的应用研究。因此,研究(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的合成具有重要的意义。目前合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的方法主要包括“sila-Cope”消除法、环丙基乙醇开环法、反式烯酸酯法与烯烃复分解反应法。
(1)“sila-Cope”消除法是以2-乙基吡啶为原料,先与叔丁基二甲基氯硅烷、碘甲烷反应,然后经硼氢化钠还原、与碘甲烷反应,得到四氢吡啶盐,接着用CsF处理发生“sila-Cope”消除,得到(2Z,5E)-1-二甲氨基-2,5-庚二烯,最后经格氏偶联、脱保护与乙酰化等多步反应制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯(Bac,N.V.;Langlois,Y.J.Am.Chem.Soc.1982,104,7666-7667.)。
(2)环丙基乙醇开环法是以1-环丙基乙醇为原料,先与溴化氢反应构建E型双键,得到(E)-5-溴-2-戊烯,然后与三苯膦反应得到季鏻盐,最后与羰基酯发生Wittig反应构建Z型双键,制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯(Bestmann,H.J.;Koschatzky,K.H.;Plenchette,A.;Suess,J.;Vostrowsky,O.Liebigs Ann.Chem.1982,536-544.)。
(3)反式烯酸酯法是以(E)-3-戊烯酸甲酯为原料,先经还原、溴代,然后与三苯膦反应生成季鏻盐,再与羰基酯发生Wittig反应构建Z型双键,制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯(Hornyanszky,G.;Rohaly,J.;Novak,L.Synth.Commun.2008,38,1533-1540.)。
(4)烯烃复分解反应法是在钌催化剂下,(Z)-9-十八碳烯-1-醇与反式1,4-己二烯发生烯烃复分解反应,直接得到(9Z,12E)-十四碳-9,12-二烯-1-醇,然后乙酰化制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯(Herbert,M.B.;Marx,V.M.;Pederson,R.L.;Grubbs,R.H.Angew.Chem.,Int.Ed.2013,52,310-314.)。
(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的合成研究虽然已取得较大进展,但仍然存在许多问题,例如:反应条件苛刻、反应路线冗长、试剂毒性较大等。因此,研究路线简捷、反应条件温和、对环境友好的合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的新方法,具有重要的理论意义与应用价值。
发明内容
本发明旨在提供一种合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的新方法。该方法以丙二酸和9-溴-1-壬醇为两种起始原料。丙二酸与丙醛在哌啶乙酸盐存在下发生Knoevenagel缩合反应,生成反式戊烯酸2,然后经氢化铝锂还原得到戊烯醇3,再经过溴代反应,与三苯基膦在乙腈中回流制得季鏻盐4。9-溴-1-壬醇经过PCC氧化反应得到溴代醛6,然后和乙酸钾反应得到羰基酯7。最后季鏻盐4和羰基酯7发生过Wittig反应制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯。本发明合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的合成路线参见式2。
本发明合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的方法包括如下步骤。
(1)(E)-3-戊烯酸2的合成
氩气保护下,在丙二酸、哌啶、冰醋酸与DMSO的混合液中,滴加丙醛,升温至40℃,反应2h后,升温至100℃,反应8h。反应结束后,用冷水淬灭反应。水相用乙醚萃取,合并有机相,经水洗和饱和氯化钠水溶液洗涤。干燥后减压浓缩,最后经硅胶柱色谱纯化,制得(E)-3-戊烯酸2。
(2)(E)-3-戊烯-1-醇3的合成
氩气保护下,在氢化铝锂与四氢呋喃的混合物中,滴加(E)-3-戊烯酸2的四氢呋喃溶液。升温至室温,反应8h。反应结束后,用氢氧化钠水溶液淬灭反应。反应混合物经硅藻土抽滤,并用乙醚洗涤滤饼。滤液经水洗和饱和氯化钠水溶液洗涤,干燥后减压浓缩,最后利用常压蒸馏纯化,制得(E)-3-戊烯-1-醇3。
(3)(E)-3-戊烯基三苯基溴化膦4的合成。
氩气保护下,在(E)-3-戊烯-1-醇3、四溴化碳与二氯甲烷的混合液中,滴加三苯基膦的二氯甲烷溶液。升温至室温反应5h,反应结束后,减压脱溶。残余物经硅藻土抽滤,无水乙醚洗涤滤饼。滤液减压浓缩,制得(E)-5-溴-2-戊烯粗产物。
氩气保护下,将三苯基膦、乙腈和(E)-5-溴-2-戊烯粗产物的混合液,回流反应48h。反应结束后,减压浓缩,最后经硅胶柱色谱纯化,制得(E)-3-戊烯基三苯基溴化膦4。
(4)9-溴壬醛6的合成
氩气保护下,在PCC氧化剂和硅胶的混合物中加入二氯甲烷,搅拌均匀,滴加9-溴-1-壬醇的二氯甲烷溶液,升温至室温,反应4h。反应结束后,减压脱溶,残余物经硅藻土抽滤,无水乙醚洗涤滤饼。滤液减压浓缩,最后经硅胶柱色谱纯化,制得9-溴壬醛6。
(5)9-乙酰氧基壬醛7的合成
在9-溴壬醛6与乙酸钾的混合物中加入DMF,升温至120℃,反应2h。反应结束后,加水淬灭反应。分液,水相用乙醚萃取,合并有机相。经水洗和饱和氯化钠水溶液洗涤,干燥后减压浓缩。最后经硅胶柱色谱纯化,制得9-乙酰氧基壬醛7。
(6)(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的合成
氩气保护下,将(E)-3-戊烯基三苯基溴化膦4的四氢呋喃溶液降温至-78℃,滴加双(三甲基硅基)氨基钠,反应1h。再滴加9-乙酰氧基壬醛7的四氢呋喃溶液,升温至室温,反应24h。反应结束后,用饱和氯化铵水溶液淬灭反应。分液,水相乙醚萃取,合并有机相。经水洗和饱和氯化钠溶液洗涤,干燥后减压浓缩。最后经硅胶柱色谱纯化,制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯。
具体实施方式
实施例1
(E)-3-戊烯酸2的合成
氩气保护下,向装有回流冷凝管的100mL三口瓶中依次加入丙二酸(10.40g,100mmol)、哌啶(0.086g,1mmol)、冰醋酸(0.060g,1mmol)与DMSO(40mL),室温下搅拌溶解,缓慢滴加丙醛(2.90g,50mmol)。滴完后,升温至40℃,搅拌反应2h,然后升温至100℃,继续反应8h。反应结束后,将反应混合液降至室温。加冷水(30mL)淬灭反应,分液。水相用乙醚(3×30mL)萃取,合并有机相。有机相依次用水(3×100mL)与饱和氯化钠水溶液(100mL)洗涤。无水硫酸钠干燥后减压浓缩,得到粗产物。粗产物经硅胶柱色谱(石油醚/乙酸乙酯2:1)纯化,制得淡黄色液体化合物(E)-3-戊烯酸2(7.01g,产率70%)。1H NMR(300MHz,CDCl3)δ10.61(s,1H),5.68–5.47(m,2H),3.07(ddd,J=4.5,2.3,1.3Hz,2H),1.72–1.69(m,3H).13CNMR(75MHz,CDCl3)δ178.75,130.01,121.94,37.74,17.82.
实施实例2
(E)-3-戊烯-1-醇3的合成
氩气保护下,在200mL Schlenk反应瓶中加入四氢铝锂(1.39g,36.62mmol),然后加入四氢呋喃(60mL),搅拌均匀。冰浴冷却下缓慢滴加(E)-3-戊烯酸2(2.82g,28.17mmol)的四氢呋喃溶液(20mL)。滴完后,将反应混合液逐渐升温至室温,搅拌反应8h。反应结束后,冰浴冷却下缓慢滴加20%氢氧化钠水溶液(3mL)淬灭反应。反应混合物用硅藻土抽滤,用乙醚(500mL)洗涤滤饼,滤液依次用水(50mL)和饱和氯化钠水溶液(100mL)洗涤。无水硫酸钠干燥后,减压浓缩得到粗产物。粗产物经常压蒸馏纯化,收集沸点135~150℃馏分,得到无色液体化合物(E)-3-戊烯-1-醇3(2.06g,产率85%)。1H NMR(300MHz,CDCl3)δ5.60–5.38(m,2H),3.61(t,J=6.4Hz,2H),2.28–2.21(m,2H),2.17(br s,1H),1.68(ddt,J=6.3,2.5,1.2Hz,3H).13C NMR(75MHz,CDCl3)δ128.09,127.10,61.93,35.84,17.85.
实施实例3
(E)-3-戊烯基三苯基溴化膦4的合成。
氩气保护下,在200mL Schlenk反应瓶中依次加入(E)-3-戊烯-1-醇3(2.00g,23.22mmol)、四溴化碳(11.55g,34.83mmol)和二氯甲烷(60mL),室温下搅拌溶解。冰浴冷却下缓慢滴加三苯基膦(18.27g,69.66mmol)的二氯甲烷溶液(50mL)。滴完后,将反应混合液自然升温至室温,继续搅拌反应5h。反应结束后,将反应液浓缩得到粗产物。粗产物经硅藻土抽滤,用乙醚(500mL)洗涤滤饼,滤液减压浓缩,制得浅黄色液体化合物(E)-5-溴-2-戊烯粗产物(2.98g,粗产率86%)。
氩气保护下,向装有回流冷凝管的100mL三口瓶中依次加入三苯基膦(2.64g,10.07mmol)、无水乙腈(60mL)和(E)-5-溴-2-戊烯粗产物(1.00g,6.71mmol),搅拌溶解。将反应液温度升温至85℃,继续回流反应48h。反应结束后,将反应液温度降至室温,减压浓缩得到粗产物。粗产物经硅胶柱色谱(二氯甲烷/甲醇10:1)纯化,制得黏稠化合物(E)-3-戊烯基三苯基溴化膦4(1.77g,产率64%)。1H NMR(300MHz,CDCl3)δ7.87–7.70(m,15H),5.58–5.41(m,2H),3.82–3.73(m,2H),2.47–2.36(m,2H),1.54(d,J=6.0Hz,3H).13C NMR(75MHz,CDCl3)δ134.94,133.53,130.42,130.25,128.16,127.39,118.53,117.39,25.41,23.11,17.43.
实施实例4
9-溴壬醛6的合成
氩气保护下,在200mL Schlenk反应瓶中加入PCC氧化剂(8.69g,40.32mmol)和硅胶(8.69g),然后加入二氯甲烷(70mL),搅拌均匀。冰浴冷却下缓慢滴加9-溴-1-壬醇(3.00g,13.44mmol)的二氯甲烷溶液(20mL)。滴完后,将反应液自然升温至室温,搅拌反应4h。反应结束后,减压浓缩,经硅藻土抽滤,用无水乙醚(500mL)洗涤滤饼。滤液减压浓缩得到粗产物,粗产物经硅胶柱色谱(石油醚/乙酸乙酯40:1)纯化,制得淡黄色液体化合物9-溴壬醛6(2.47g,产率83%)。1H NMR(300MHz,CDCl3)δ9.77(s,1H),3.41(t,J=6.8Hz,2H),2.43(t,J=7.3Hz,2H),1.87–1.83(m,2H),1.65–1.61(m,2H),1.50–1.32(m,8H).13C NMR(75MHz,CDCl3)δ202.72,43.73,33.79,32.65,29.03,28.91,28.42,27.95,21.89.
实施实例5
9-乙酰氧基壬醛7的合成
在50mL反应瓶中依次加入9-溴壬醛6(2.34g,10.58mmol)、乙酸钾(1.14g,1.16mmol)和DMF(20mL),搅拌溶解,将反应液升温至120℃,继续搅拌反应2h。反应结束后,将反应混合液温度降至室温,加水(30mL)淬灭反应。分液,水相用乙醚(3×40mL)萃取,合并有机相。有机相依次用水(3×40mL)和饱和氯化钠水溶液(50mL)洗涤,无水硫酸钠干燥,减压浓缩得到粗产物。粗产物经硅胶柱色谱(石油醚/乙酸乙酯20:1)纯化,制得淡黄色液体化合物9-乙酰氧基壬醛7(1.53g,产率72%)。1H NMR(300MHz,CDCl3)δ9.77(t,J=1.8Hz,1H),4.05(t,J=6.7Hz,2H),2.43(td,J=7.3,1.8Hz,2H),2.05(s,3H),1.66–1.59(m,4H),1.40–1.33(m 8H).13C NMR(75MHz,CDCl3)δ202.80,171.25,64.54,43.78,28.94,28.87,28.49,25.76,24.57,21.95,20.91.
实施实例6
(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的合成
氩气保护下,在100mL Schlenk反应瓶中加入(E)-3-戊烯基三苯基溴化膦4(1.70g,4.13mmol)和无水四氢呋喃(40mL),搅拌溶解。将混合液温度降温至-78℃,缓慢滴加双(三甲基硅基)氨基钠(2.1mL,2M THF溶液,4.2mmol),滴完后,搅拌1h。然后滴加9-乙酰氧基壬醛7(0.83g,4.13mmol)的四氢呋喃溶液(5mL)。滴完后,将反应液缓慢升温至室温,继续搅拌反应24h。反应结束后,冰浴下滴加饱和氯化铵水溶液(20mL)淬灭反应。分液,水相用乙醚(3×30mL)萃取,合并有机相。有机相依次用水(50mL)和饱和氯化钠水溶液(50mL)洗涤,无水硫酸钠干燥。减压浓缩得到粗产物,粗产物经硅胶柱色谱(石油醚/乙酸乙酯80:1)纯化,制得淡黄色液体化合物(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯(0.58g,产率56%)。1H NMR(300MHz,CDCl3)δ5.46–5.30(m,4H),4.05(t,J=6.8Hz,2H),2.73–2.70(m,2H),2.04(s,3H),2.02–1.99(m,2H),1.65–1.64(m,5H),1.36–1.30(m,10H).13C NMR(75MHz,CDCl3)δ171.07,130.28,129.56,127.64,124.98,64.54,30.37,29.55,29.31,29.16,29.10,28.56,27.01,25.84,20.89,17.79.
Claims (5)
1.一种合成(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的方法,其特征在于包括如下步骤:以丙二酸和9-溴-1-壬醇为两种起始原料;丙二酸与丙醛在哌啶乙酸盐存在下发生Knoevenagel缩合反应,生成(E)-3-戊烯酸,然后经氢化铝锂还原得到(E)-3-戊烯-1-醇,再经过溴代反应,与三苯基膦在乙腈中回流制得(E)-3-戊烯基三苯基溴化膦;9-溴-1-壬醇经过PCC氧化反应得到9-溴壬醛,然后和乙酸钾反应得到9-乙酰氧基壬醛;最后(E)-3-戊烯基三苯基溴化膦与9-乙酰氧基壬醛发生过Wittig反应制得(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯。
2.根据权利要求1所述的(9Z,12E)-十四碳-9,12-二烯-1-醇乙酸酯的合成方法,其特征在于合成(E)-3-戊烯酸的方法为:氩气保护下,在丙二酸、哌啶、冰醋酸与DMSO的混合液中,滴加丙醛,升温至40℃,反应2h后,升温至100℃,反应8h;反应结束后,用冷水淬灭反应;水相用乙醚萃取,合并有机相,经水洗和饱和氯化钠水溶液洗涤;干燥后减压浓缩,最后经硅胶柱色谱纯化,制得(E)-3-戊烯酸。
3.根据权利要求2所述的合成方法,其特征在于合成(E)-3-戊烯酸所用的反应溶剂为N,N-二甲基甲酰胺、甲苯、二甲基亚砜,优选二甲基亚砜。
4.根据权利要求2所述的合成方法,其特征在于合成(E)-3-戊烯酸的反应温度范围为25-120℃,优选100℃。
5.根据权利要求2所述的合成方法,其特征在于合成(E)-3-戊烯酸所使用的催化剂为氢氧化钠、碳酸钠、磷酸氢二铵、哌啶,优选哌啶。
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Cited By (1)
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CN113620913A (zh) * | 2021-07-26 | 2021-11-09 | 安徽华业香料股份有限公司 | 一种γ-壬烯内酯的合成方法 |
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