CN101519341B - 一种合成含氟2,3,5(z)-三烯醇的方法 - Google Patents
一种合成含氟2,3,5(z)-三烯醇的方法 Download PDFInfo
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Abstract
本发明涉及一种高区域和立体选择性地合成含氟2,3,5(Z)-三烯醇的方法,即通过格氏试剂与5-全氟烷基-4(E)-烯-2-炔-1-醇的加成消除反应,合成含氟的2,3,5(Z)-三烯醇类化合物。本发明操作简单,原料和试剂易得,反应具有高度的区域和立体选择性,不需要贵金属参与,能同时引入多个取代基,产率高,产物易分离纯化,适用于合成各种取代的含氟2,3,5(Z)-三烯醇。
Description
技术领域
本发明涉及一种高区域和立体选择性地合成含氟2,3,5(Z)-三烯醇的方法,即通过格氏试剂与5-全氟烷基-4(E)-烯-2-炔-1-醇的加成消除反应合成含氟的2,3,5(Z)-三烯醇。
背景技术
联烯具有多官能团装载性能和丰富的反应性能,而向分子中引入氟原子可以给有机化合物带来很多独特的性质。在现代药物和农用化学中,引入氟原子来改变和提高化合物的生物活性已经成为新产品研究开发的热点。因此,含氟联烯的合成在生物技术领域,医药及农药等方面有巨大的开发利用价值。但目前合成含氟联烯的报道仍然比较有限。
因此有效方便地合成各种取代的含氟的2,3,5(Z)-三烯醇将是对以往反应的很大突破。
发明内容
本发明的目的就是提供一种通过格氏试剂与与5-全氟烷基-4(E)-烯-2-炔-1-醇的加成消除反应高区域和立体选择性合成含氟2,3,5(Z)-三烯醇。
本发明合成含一种高区域和立体选择性地的合成含氟2,3,5(Z)-三烯醇的方法,通过格氏试剂与5-全氟烷基-4(E)-烯-2-炔-1-醇的加成消除反应合成含氟2,3,5(Z)-三烯醇,反应式如下:
其中R1=烷基,烷基为CnH2n+1,式中n=4-6;R2=烷基,芳基,烷基为CnH2n+1式中n=3-5;R3=氢或甲基;X为氯,溴;Rf为CnF2n+1,式中n=4-7;其步骤是:
(1)取一反应管,抽真空下烘烤后充入氮气以除去水分,彻底干燥后,在氮气氛下冷却至室温,向反应管内加入5-全氟烷基-4(E)-烯-2-炔-1-醇和无水乙醚,然后向该反应管中滴加溶解在四氢呋喃溶液中的格氏试剂,反应2-2.5小时,加饱和氯化铵溶液淬灭,乙醚萃取有机相。
(2)萃取有机相后经饱和氯化钠溶液洗涤,无水硫酸钠干燥、过滤、浓缩、快速柱层析,获得含氟2,3,5(Z)-三烯醇。
本发明的5-全氟烷基-4(E)-烯-2-炔-1-醇与无水乙醚比为:0.138-0.211mmol/1mL,优选为0.211mmol/1mL。
本发明的5-全氟烷基-4(E)-烯-2-炔-1-醇与格氏试剂的当量比为0.222-0.250∶1,优选为0.250∶1。
本发明涉及一种含氟2,3,5(Z)-三烯醇及其合成方法,通过格氏试剂与5-全氟烷基-4(E)-烯-2-炔-1-醇在无水乙醚溶剂中在室温条件下发生加成消除反应,得到一系列的取代的含氟2,3,5(Z)-三烯醇化合物,本方法操作简单,原料和试剂易得,反应具有高度的区域和立体选择性,能同时引入多个取代基,产物易分离纯化,产率高,适用于合成各种取代的含氟2,3,5(Z)-三烯醇。
本发明克服了传统方法的弊端,具有以下优点:1)反应具有高度的区域和立体选择性;2)反应产率高;3)不需要贵金属参与;4)可以制备多取代的2,3,5(Z)-三烯醇;5)产物易分离纯化。
本发明创新点在于发展了一种含氟2,3,5(Z)-三烯醇的合成方法学。
本方法所得的相应的含氟2,3,5(Z)-三烯醇的产率为80-95%。
具体实施方式
以下实施例有助于理解本发明,但不限于本发明的内容。
实施例1
取一反应管,抽真空下烘烤后充入氮气以除去水分,反复三次彻底干燥后,在氮气氛下冷却至室温。向反应管内加入6,6,7,7,8,8,9,9,9-九氟-4-丁基-4(E)-壬烯-2-炔-1-醇(E-18b)(70.0mg,0.197mmol)以及0.5mL无水乙醚。室温下用注射器向反应管内滴加0.48mL苯基氯化镁的四氢呋喃溶液(1.73M),2分钟内滴加完毕,室温下继续反应2小时。之后将反应管放入冰水浴中,慢慢滴加5mL饱和NH4Cl溶液淬灭,乙醚(25mL×3)萃取,合并有机相,用饱和NaCl溶液(10mL×2)洗涤,无水Na2SO4干燥过滤,浓缩,快速柱层析,得产物75.5mg,产率为95%。产物为淡黄色液体。
1H NMR(300MHz,CDCl3)δ7.43-7.30(m,4H),7.30-7.23(m,1H),5.92(d,J=34.5Hz,1H),4.60(s,2H),2.39(t,J=7.3Hz,2H),1.76(bs,1H),1.58-1.30(m,4H),0.90(t,J=7.2Hz,3H);19F NMR(282MHz,CDCl3)δ-80.8-(-81.0)(m,3F),-118.0-(-118.3)(m,2F),-126.7-(-127.1)(m,1F),-127.2-(-127.4)(m,2F);13CNMR(75MHz,CDCl3)δ207.4(d,J=4.4Hz),1449(dt,J1=267.8Hz and J2=28.0Hz),133.4,128.8,127.7,126.4,112.1-111.7(m),108.4,103.5(d,J=3.0Hz),61.7,31.7(d,J=3.3Hz),30.4,22.2,13.8;IR(neat)v(cm-1):3342,3064,3033,2961,2933,2875,1933,1681,1599,1496,1454,1361,1230,1187,1152,1120,1056,1029;MS(EI,70eV)m/z(%):414(M+,1.85),354(100);Elemental analysis calcd for C19H18F8O:C 55.08,H 4.38;Found:C 54.79,H 4.26.
实施例2
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,9-九氟-4-丁基-4(E)-壬烯-2-炔-1-醇(318.9mg,1.25mmol)与4-甲氧基苯基溴化镁(2.0M in THF,0.40mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物83.0mg,产率为93%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.35-7.27(m,2H),6.94-6.87(m,2H),5.92(d,J=34.2Hz,1H),4.57(s,2H),3.81(s,3H),2.38(t,J=7.4Hz,2H),1.69(bs,1H),1.55-1.30(m,4H),0.90(t,J=72Hz,3H);19F NMR(282MHz,CDCl3)δ-80.8-(-80.9)(m,3F),-118.0-(-118.2)(m,2F),-127.2-(-127.6)(m,3F);13C NMR(75MHz,CDCl3)δ207.1(d,J=44Hz),159.2,144.7(dt,J1=267.8Hz and J2=27.8Hz),127.6,125.5,114.2,112.3-1120(m),108.0,103.4(d,J=3.2Hz),61.9,55.3,31.8(d,J=2.8Hz),30.4,22.2,13.8;IR(neat)v(cm-1):3390,2960,2934,2873,1930,1681,1608,1579,1512,1464,1360,1292,1230,1183,1152,1119,1033;MS(EI70eV)m/z(%):444(M+,13.49),384(100);HRMS calcd for C20H20F8O2:444.1336;Found:444.1342.
实施例3
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,9-九氟-4-丁基-4(E)-壬烯-2-炔-1-醇与4-氟苯基溴化镁(2.0M in THF,0.40mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物78.6mg,产率为89%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.41-7.31(m,2H),7.11-7.00(m,2H),5.91(d,J=34.2Hz,1H),4.58(s,2H),2.38(t,J=7.4Hz,2H),1.72(bs,1H),1.54-1.30(m,4H),0.90(t,J=7.2Hz,3H);19F NMR(282MHz,CDCl3)δ-80.8-(-80.9)(m,3F),-114.1-(-114.3)(m,1F),-118.0-(-118.2)(m,2F),-126.3-(-126.7)(m,1F),-127.2-(-127.4)(m,2F);13C NMR(75MHz,CDCl3)δ207.2(d,J=3.8Hz),162.3(d,J=246.5),145.0(dt,J1=266.5Hz and J2=27.8Hz),129.4(d,J=3.5Hz),128.1(d,J=7.6Hz),115.7(d,J=22.1Hz),1119-111.6(m),107.5,103.3(d,J=3.2Hz),61.9,31.8(d,J=2.9Hz),30.3,22.2,13.8;IR(neat)v(cm-1):3355,2961,2934,2876,1933,1681,1603,1510,1468,1360,1233,1188,1160,1120,1039;MS(EI,70eV)m/z(%):432(M,2.45),359(100);HRMS calcd for C19H17F9O:432.1136;Found:432.1136.
实施例4
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,9-九氟-4-丁基-4(E)-壬烯-2-炔-1-醇(71.5mg,0.201mmol)与异丙基氯化镁(2.0M in THF,0.40mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物64.2mg,产率为84%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ5.81(d,J=35.1Hz,1H),4.15(d,J=3.0Hz,2H),2.39-2.21(m,3H),1.49(bs,1H),1.46-1.29(m,4H),1.08(d,J=6.9Hz,3H),1.06(d,J=6.9Hz,3H),0.92(t,J=6.9Hz,3H);19FNMR(282MHz,CDCl3)δ-81.9-(-81.1)(m,3F),-1180-(-118.3)(m,2F),-127.4-(-127.6)(m,2F),-128.6-(-129.0)(m,1F);13C NMR(75MHz,CDCl3)δ203.0(d,J=5.8Hz),143.8(dt,J1=257.7Hz and J2=28.7Hz),114.1,113.3-112.9(m),103.0(d,J=3.3Hz),61.8,31.8(d,J=2.6Hz),30.6,28.8,22.3,21.8,21.5,13.8;IR(neat)v(cm-1):3346,2964,2934,2875,1943,1680,1467,1360,1229,1187,1151,1119,1032;MS(EI,70eV)m/z(%):380(M+,0.56),362(M+-H2O,3.03),295(100);HRMS calcd for C16H20F8O:380.1386;Found:380.1385.
实施例5
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,9-九氟-4-己基-4-壬烯-2-炔-1-醇(78.5mg,0.204mmol)与苯基氯化镁(1.73M in THF,0.46mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物84.8mg,产率为84%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.44-7.31(m,4H),7.31-7.21(m,1H),5.92(d,J=34.5Hz,1H),4.61(s,2H),2.38(t,J=7.2Hz,2H),1.68(bs,1H),158-1.42(m,2H),1.42-1.16(m,6H),0.86(t,J=6.6Hz,3H);19FNMR(282MHz,CDCl3)δ-80.8-(-81.0)(m,3F),-118.0-(-118.3)(m,2F),-126.7-(-127.1)(m,1F),-127.2-(-127.4)(m,2F);13C NMR(75MHz,CDCl3)δ207.4(d,J=5.8Hz),144.8(dt,J1=268.1Hz and J2=28.2Hz),133.4,128.7,127.7,126.4,112.1-111.7(m),108.4,1035(d,J=3.0Hz),61.7,32.0(d,J=2.7Hz),31.6,28.8,28.2,22.6,14.0;IR(neat)v(cm-1):3346,3063,2958,2931,2860,1933,1681,1599,1496,1454,1361,1262,1230,1187,1152,1120,1058,1029;MS(EI,70eV)m/z(%):442(M+,1.79),354(100);Elemental analysiscalcd for C21H22F8O:C 57.01,H 5.01;Found:C 57.52,H 5.06.
实施例6
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,9-九氟-4-己基-4-壬烯-2-炔-1-醇(76.3mg,0.199mmol)与4-甲氧基苯基化镁(2.0M in THF,0.40mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物76.5mg,产率为82%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.36-7.27(m,2H),6.94-6.86(m,2H),5.92(d,J=33.9Hz,1H),4.57(s,2H),3.81(s,3H),2.37(t,J=7.2Hz,2H),1.70(bs,1H),1.58-1.41(m,2H),1.41-1.18(m,6H),0.86(t,J=6.9Hz,3H);19F NMR(282MHz,CDCl3)δ-80.8-(-81.0)(m,3F),-117.9-(-118.2)(m,2F),-127.2-(-1276)(m,3F);13C NMR(75MHz,CDCl3)δ207.1(d,J=4.7Hz),159.2,144.7(dt,J1=267.1Hz and J2=27.9Hz),127.6,125.5,114.2,112.3-112.0(m),108.0,103.4(d,J=2.8Hz),61.9,55.3,32.1(d,J=2.7Hz),31.6,28.8,28.2,22.6,14.0;IR(neat)v(cm-1):3410,2958,2932,2859,1931,1680,1608,1579,1512,1465,1359,1292,1231,1182,1153,1119,1034;MS(EI,70eV)m/z(%)472(M+,5.78),384(100);HRMS calcd for C22H24F8O2:472.1649,Found:472.1652.
实施例7
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,9-九氟-4-己基-4-烯-2-炔-1-醇(76.2mg,0.198mmol)与4-甲氧基苯基化镁(2.0M in THF,0.40mL,0.80mmol)室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物85.3mg,产率为93%。产物黄色液体。
1H NMR(300MHz,CDCl3)δ7.42-7.30(m,2H),7.11-6.99(m,2H),5.91(d,J=34.2Hz,1H),4.58(s,2H),2.37(t,J=7.2Hz,2H),1.80(bs,1H),1.58-1.41(m,2H),1.41-1.18(m,6H),0.86(t,J=6.9Hz,3H);19FNMR(282MHz,CDCl3)δ-80.8-(-81.0)(m,3F),-114.2-(-114.3)(m,1F),-118.0-(-118.3)(m,2F),-126.3-(-126.7)(m,1F),-127.3(m,2F);13C NMR(75MHz,CDCl3)δ207.3(d,J=4.0Hz),162.3(d,J=245.6Hz),145.0(dt,J1=267.4Hz and J2=28.3Hz),129.4(d,J=3.3Hz),128.1(d,J=7.6Hz),115.6(d,J=18.9Hz),111.8(m),107.5,103.3(d,J=2.4Hz),61.9,32.1(d,J=2.8Hz),31.6,28.8,28.2,22.6,13.9;IR(neat)v(cm-1):3355,2959,2932,2860,1933,1682,1603,1510,1468,1361,1233,1187,1160,1120,1078,1042;MS(EI,70eV)m/z(%):460(M+,1.63),359(100);Elemental analysis calcd for C21H21F9O:C 54.79,H 4.60;Found:C 54.97,H 4.75
实施例8
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,10,10,11,11,11-十三氟-4-丁基-4(E)-十一烯-2-炔-1-醇(91.1mg,0.200mmol)与苯基氯化镁(1.73M in THF,0.46mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物93.6mg,产率为91%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.44-7.31(m,4H),7.31-722(m,1H),5.93(d,J=34.5Hz,1H),4.60(s,2H),2.39(t,J=7.5Hz,2H),1.77(bs,1H),1.57-1.29(m,4H),0.90(t,J=7.2Hz,3H);19F NMR(282MHz,CDCl3)δ-81.8-(-81.0)(m,3F),-117.0-(-117.3)(m,2F),-122.9-(-123.2)(m,4F),-126.2-(-1265)(m,2F),-126.5-(-126.9)(m,1F);13C NMR(75MHz,CDCl3)δ207.4(d,J=4.8Hz),145.1(dt,J1=267.2Hz and J2=27.7Hz),133.4,128.8,127.7,126.4,112.2-111.8(m),108.5,103.5(d,J=2.8Hz),61.7,31.8(d,J=2.7Hz),30.4,22.2,13.7;IR(neat)v(cm-1):3373,3064,3033,2961,2934,2876,1932,1680,1599,1496,1453,1362,1238,1203,1143,1110,1054,1027;MS(EI,70eV)m/z(%):514(M+,2.01),454(100);Elemental analysis calcd forC21H18F12O:C 49.04,H 3.53;Found:C 49.28,H 3.57
实施例9
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,10,10,11,11,11-十三氟-4-己基-4(E)-十一烯-2-炔-1-醇(93.9mg,0.194mmol)与苯基氯化镁(1.73M in THF,0.46mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物96.5mg,产率为92%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.43-730(m,4H),7.30-722(m,1H),5.93(d,J=34.5Hz,1H),4.60(s,2H),2.39(t,J=7.2Hz,2H),1.77(bs,1H),1.58-1.42(m,2H),1.42-1.17(m,6H),0.86(t,J=6.9Hz,3H);19FNMR(282MHz,CDCl3)δ-80.9(-81.1)(m,3F),-117.0-(-117.3)(m,2F),-122.9-(-123.3)(m,4F),-126.2-(-126.5)(m,2F),-126.5-(-126.9)(m,1F);13C NMR(75MHz,CDCl3)δ207.5(d,J=4.9Hz),145.1(dt,J1=267.8Hz and J2=28.1Hz),133.4,128.7,127.7,126.4,112.2-111.8(m),108.4,103.5(d,J=3.0Hz),61.7,32.1(d,J=3.3Hz),31.6,28.8,28.2,22.6,13.9;IR(neat)v(cm-1):3356,3064,3033,2931,2860,1933,1680,1599,1496,1454,1363,1241,1203,1143,1110,1055,1028;MS(EI,70eV)m/z(%):542(M+,1.78),454(100);Elemental analysis calcd for C23H22F12O:C 50.93,H 4.09;Found:C 51.42,H 4.15.
实施例10
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,13-十七氟-4-丁基-4(E)-十三烯-2-炔-1-醇(111.5mg,0.201mmol)与苯基氯化镁(1.73M in THF,0.46mL,0.80mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物116.8mg,产率为95%。产物为黄色液体。
1H NMR(300MHz,CDCl3)δ7.45-7.31(m,4H),7.31-7.22(m,1H),5.93(d,J=34.5Hz,1H),4.61(s,2H),2.39(t,J=7.4Hz,2H),1.72(bs,1H),1.58-1.30(m,4H),0.90(t,J=7.2Hz,3H);19F NMR(282MHz,CDCl3)δ-81.0(t,J=10.2Hz,3F),-117.0-(-117.3)(m,2F),-121.9-(-122.4)(m,4F),-122.7-(-123.1)(m,4F),-126.2-(-126.5)(m,2F),-126.5-(-126.9)(m,1F);13C NMR(75MHz,CDCl3)δ207.4(d,J=5.2Hz),145.1(dt,J1=267.0Hz and J2=27.8Hz),133.5,128.8,127.7,126.5,112.2-111.8(m),108.5,103.5(d,J=3.0Hz),61.8,31.8(d,J=3.2Hz),30.4,22.2,13.7;IR(neat)v(cm-1):3384,3064,2961,2932,2864,1932,1680,1599,1496,1454,1347,1318,1241,1151,1106,1055,1027,1000;MS(EI,70eV)m/z(%):614(M+,0.97),91(100);Elemental analysis calcd for C23H18F16O:C 44.96,H 2.95;Found:C 45.33,H 3.01.
实施例11
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,10,10,11,11,11-十三氟-4-苯基-4(E)-十一烯-2-炔-1-醇(95.8mg,0.20mmol)与苯基溴化镁(2.0M in THF,0.30mL,0.60mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物85.9mg,产率为80%。产物为白色固体,熔点72-74℃(正己烷中重结晶)。
1H NMR(300MHz,CDCl3)δ7.50-7.42(m,2H),7.42-7.32(m,6H),7.32-7.24(m,2H),6.36(d,J=30.6Hz,1H),4.72(s,2H),1.87(bs,1H);19F NMR(282MHz,CDCl3)δ-80.8-(-81.0)(m,3F),-117.3-(-117.5)(m,2F),-122.3-(-122.7)(m,1F),-122.8-(-123.2)(m,4F),-126.2-(-126.5)(m,2F);13C NMR(75MHz,CDCl3)δ208.3(d,J=5.4Hz),147.1(dt,J1=269.9Hz and J2=28.0Hz),134.2,132.6,128.93,128.88,128.2,128.1,126.6,126.2,111.2,110.2-109.8(m),102.9,61.6;IR(KBr)v(cm-1):3417,2930,2873,1927,1682,1599,1493,1448,1364,1244,1202,1141,1110,1050,1030;MS(EI,70eV)m/z(%):534(M+,25.04),503(100);HRMScalcd for C23H14F12O:534.0853;Found:534.0859.
实施例12
按实施例1所述的方法,不同的是所用底物和试剂为:6,6,7,7,8,8,9,9,10,10,11,11,12,12,13,13,13-十七氟-4-苯基-4(E)-十三烯-2-炔-1-醇(128.7mg,0.22mmol)与苯基溴化镁(2.0M in THF,0.32mL,0.64mmol)在室温下,在0.5mL无水乙醚作为溶剂下,反应2小时得产物116.4mg,产率为83%。产物为白色固体,熔点74-76℃(正己烷中重结晶)。
1H NMR(400MHz,CDCl3)δ7.50-7.43(m,2H),7.42-7.34(m,6H),7.34-7.27(m,2H),6.36(d,J=30.8Hz,1H),4.75(d,J=4.8Hz,2H),1.75(t,J=5.6Hz,1H);19F NMR(282MHz,CDCl3)δ-80.9-(-81.0)(m,3F),-117.2-(-117.5)(m,2F),-121.8-(-122.3)(m,4F),-122.3-(-122.7)(m,1F),-122.7-(-123.1)(m,4F),-126.2-(-126.5)(m,2F);13C NMR(75MHz,CDCl3)δ208.3(d,J=5.5Hz),147.1(dt,J1=269.5Hz and J2=27.7Hz),134.2,132.6,128.94,128.89,128.2,128.1,126.6,126.2,111.2,110.2-109.9(m),102.9,61.6;IR(KBr)v(cm-1):3387,3062,2928,1928,1682,1598,1493,1446,1431,1371,1309,1279,1212,1142,1105,1089,1053,1008;MS(EI,70eV)m/z(%):634(M+,12.30),233(100);Elemental analysis cdlcd for C25H14F16O:C 47.33,H2.22;Found:C 47.31,H 2.32.
实施例13
按实施例1所述的方法,不同的是所用底物和试剂为:7,7,8,8,9,9,10,10,10-九氟-5-丁基-5(E)-癸烯-3-炔-2-醇(148.2mg,0.40mmol)和苯基氯化镁(1.8M in THF,0.90mL,1.62mmol)在室温下,在1.0mL无水乙醚作为溶剂下,反应2小时得到两种非对映异构体的产物,分别为小极性产物128.5mg,产率为75%;大极性产物24.7mg,产率14%。产物均为黄色液体。
小极性产物:1H NMR(300MHz,CDCl3)δ744-7.31(m,4H),7.31-7.23(m,1H),5.93(d,J=34.5Hz,1H),4.89(q,J=6.3Hz,1H),2.37(t,J=6.9Hz,2H),1.91(bs,1H),1.55-1.30(m,7H),0.90(t,J=6.9Hz,3H);19F NMR(282MHz,CDCl3)δ-80.8-(-81.0)(m,3F),-118.0-(-118.2)(m,2F),-126.6-(-127.0)(m,1F),-127.2-(-127.4)(m,2F);13C NMR(75MHz,CDCl3)δ206.7(d,J=5.3Hz),144.8(dt,J1=266.5Hz and J2=29.3Hz),134.1,128.7,127.6,127.0,113.3,112.2-111.9(m),104.0(d,J=3.3Hz),66.4,31.8(d,J=2.9Hz),30.4,22.5,223,13.8;IR(neat)v(cm-1):3421,3064,3032,2963,2933,2875,1935,1682,1598,1495,1452,1360,1229,1187,1152,1119,1078,1031;MS(EI,70eV)m/z(%):428(M+,13.54),342(100);HRMS calcd forC20H20F8O:428.1386;Found:428.1384.
大极性产物:1H NMR(300MHz,CDCl3)δ7.44-7.32(m,4H),7.32-7.23(m,1H),5.87(d,J=34.5Hz,1H),4.96-4.84(m,1H),2.38(t,J=75Hz,2H),1.72(bs,1H),1.56-1.31(m,7H),0.91(t,J=6.9Hz,3H);19FNMR(282MHz,CDCl3)δ-80.8-(-80.9)(m,3F),-118.0-(-118.3)(m,2F),-126.2-(-126.6)(m,1F),-127.3-(-1274)(m,2F);13C NMR(75MHz,CDCl3)δ206.6(d,J=5.3Hz),144.8(dt,J1=266.1Hz and J2=28.5Hz),134.2,128.7,127.7,127.0,113.5,112.1-111.7(m),103.9(d,J=2.9Hz),66.6,32.0(d,J=3.3Hz),30.5,22.5,22.3,13.8;IR(neat)v(cm-1):3415,3063,3031,2961,2931,2863,1934,1681,1598,1495,1452,1360,1228,1187,1152,1120,1081,1032;MS(EI,70eV)m/z(%):428(M+,426),342(100);HRMS calcd forC20H20F8O:428.1386;Found:428.1383.
Claims (5)
1.一种合成含氟2,3,5(Z)-三烯醇的方法,其特征是通过格氏试剂与5-全氟烷基-4(E)-烯-2-炔-1-醇的加成消除反应合成含氟2,3,5(Z)-三烯醇,反应式如下:
其中R1=烷基,烷基为CnH2n+1,式中n=4-6;R2=烷基或芳基,其中烷基为CnH2n+1式中n=3-5;R3=氢或甲基;X为氯,溴;Rf为CnF2n+1,式中n=4-7;其步骤是:
(1)取一反应管,抽真空下烘烤后充入氮气以除去水分,彻底干燥后,在氮气氛下冷却至室温,向反应管内加入5-全氟烷基-4(E)-烯-2-炔-1-醇和无水乙醚,然后向该反应管中滴加溶解在四氢呋喃溶液中的格氏试剂,反应2-2.5小时,将反应管放入冰水浴中,滴加饱和氯化铵溶液淬灭,乙醚萃取有机相;
(2)萃取有机相后经饱和氯化钠溶液洗涤后用无水硫酸钠干燥、过滤、浓缩、快速柱层析,获得含氟2,3,5(Z)-三烯醇。
2.根据权利要求1所述的合成含氟2,3,5(Z)-三烯醇的方法,其特征是5-全氟烷基-4(E)-烯-2-炔-1-醇与无水乙醚用量比为:0.138-0.211mmol/1mL。
3.根据权利要求2所述的合成含氟2,3,5(Z)-三烯醇的方法,其特征是5-全氟烷基-4(E)-烯-2-炔-1-醇与无水乙醚用量比为0.211mmol/1mL。
4.根据权利要求1所述的合成含氟2,3,5(Z)-三烯醇的方法,其特征是5-全氟烷基-4(E)-烯-2-炔-1-醇与格氏试剂的当量比为0.222-0.250∶1。
5.根据权利要求4所述的合成含氟2,3,5(Z)-三烯醇的方法,其特征是5-全氟烷基-4(E)-烯-2-炔-1-醇与格氏试剂的当量比为0.250∶1。
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Masayuki Mae et al..Highly Regioselective Synthesis of gem-Difluoroallenes through Magnesium Organocuprate SN2 Substitution.《Organic Letters》.2006,第8卷(第3期),479-482. * |
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