CN109652095B - 一种偕二氟双环己烷液晶材料及其中间体的合成方法 - Google Patents
一种偕二氟双环己烷液晶材料及其中间体的合成方法 Download PDFInfo
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Abstract
本发明属于有机合成技术领域,特别涉及一种偕二氟双环己烷液晶材料及其中间体的合成方法;偕二氟双环己烷液晶材料的合成方法包括以下步骤:(1)化合物1与二氟氯乙酸酯化得到化合物2,(2)由化合物2重排得到化合物3,(3)由化合物3经羰基加成消除得到化合物6,(4)由化合物6溴化得到化合物11,(5)由化合物11分子内烷基化得到化合物12,(6)由化合物12还原羰基得到化合物偕二氟双环己烷液晶材料;本发明从简单的商业化原料出发,用常见的试剂和简洁的操作完成了偕二氟双环己烷液晶材料的合成,为偕二氟双环己烷液晶材料提供了一条可能的合成路线。
Description
技术领域
本发明属于有机合成技术领域,特别涉及一种偕二氟双环己烷液晶材料及其中间体的合成方法。
背景技术
1888年奥地利植物学家F.Reinitzer首次发现液晶现象,经过科学家们接近一个世纪的探索与研究,开发出了液晶显示面板并成功应用于产业化。液晶材料是液晶显示面板的重要组成部分。
偕二氟双环己烷液晶材料(1,4-trans;4,4’-anti;4’,1’-trans)-2,2-difluoro-4,4’-dipropyl-1,1’-bi(cyclohexane),中文名称为(1,4-反式;4,4'-反式;4',1'-反式)-2,2-二氟-4,4'异丙基-1,1'-双环己烷,现有发明专利和生产工艺都是由日本OrganoScience.Lcd和Chiracol Co.Lcd所开发。
中国专利CN102822129A公开了能够混合在向列型液晶等中形成响应速度得到改良的液晶组合物的新型环己烷化合物,还提供混合了新型环己烷化合物的特定的液晶组合物。该新型环己烷化合物结构式为:
但其提供的制备方法存在一定的局限性,且原料成本较高,制备工艺较为繁琐。
发明内容
本发明解决现有技术中存在的上述技术问题,提供一种偕二氟双环己烷液晶材料的新合成方法,所述偕二氟双环己烷液晶材料为(1,4-反式;4,4'-反式;4',1'-反式)-2,2-二氟-4,4'异丙基-1,1'-双环己烷。
为解决上述问题,本发明的技术方案如下:
一种合成偕二氟双环己烷液晶材料的中间体,结构式如下:
一种偕二氟双环己烷液晶材料——(1,4-反式;4,4'-反式;4',1'-反式)-2,2-二氟-4,4'异丙基-1,1'-双环己烷及其中间体的合成方法,合成路线如下:
所述偕二氟双环己烷液晶材料的具体合成步骤为:
(1)化合物1与二氟氯乙酸酯化得到化合物2,
(2)由化合物2重排得到化合物3,
(3)由化合物3经羰基加成消除得到化合物6,
(4)由化合物6溴化得到化合物11,
(5)由化合物11分子内烷基化得到化合物12,
(6)由化合物12还原羰基得到化合物偕二氟双环己烷液晶材料。
优选地,所述步骤(1)中:化合物1和二氟氯乙酸的投加摩尔比为1:1.1-1:2.0。
优选地,所述步骤(2)的具体方法为:化合物2和Zn(锌)以及TMSCl(三甲基氯硅烷)反应发生Reformatsky-Claisen(雷福尔马茨基-克莱森)重排反应得到化合物3。
优选地,所述步骤(2)中:化合物2、锌、三甲基氯硅烷的投加摩尔比为1:2:3-1:4:5。
优选地,所述步骤(3)的具体方法为:
化合物3在DMF(N,N-二甲基甲酰胺)催化下与草酰氯反应得到化合物4,化合物4与氮甲基羟胺盐酸盐直接进行反应得到化合物5;化合物5与正丁基氯化镁或正丁基锂反应得到化合物6。
优选地,所述步骤(3)中:化合物3、草酰氯、氮甲基羟胺盐酸盐、三乙胺的投加摩尔比为1:1.3:1.3:2-1:2:2:4;化合物5和正丁基氯化镁的投加摩尔比为1:1.3-1:3。
优选地,所述步骤(4)的具体方法为:
化合物6与2-氯乙醇以及叔丁醇钾反应的得到化合物7;
化合物7与二苯基硅烷在三异丙基硅烷硫醇((iPr)3SiSH)、碳酸钾(K2CO3)、曙红(EY)、光照条件下反应得到化合物8;
化合物8被30%过氧化氢溶液氧化得到化合物9;
化合物9与三苯基膦以及四溴化碳反应得到化合物10;
化合物10在浓硫酸条件下脱保护得到化合物11。
优选地,所述步骤(4)中,化合物6、叔丁醇钾、2-氯乙醇的投加摩尔比为1:2:2-1:6:6;化合物7和K2CO3、EY、(iPr)3SiSH、二苯基硅烷的投加摩尔比1:0.05:0.05:0.05:2-1:0.2:0.2:0.2:2;化合物8、30%过氧化氢溶液的投加摩尔比为1:20-1:30;化合物9、四溴化碳、三苯基膦投加摩尔比为1:1.2:1.2-1:2:2;化合物10、浓硫酸的投加摩尔比为1:150-1:500。
优选地,所述步骤(5)的具体方法为:
化合物11在六甲基二硅基胺基锂(LiHMDS)作用下,发生分子内烷基化反应得到化合物12。
优选地,所述步骤(5)中,LiHMDS为HMDS与正丁基锂反应制得,化合物11和HMDS、正丁基锂的投加摩尔比为1:1.3:1.3-1:2:2。
优选地,所述步骤(6)的具体方法为:
化合物12被钠硼氢还原得到化合物13,化合物13与甲基草酰氯在DMAP(4-二甲氨基吡啶)催化下反应得到化合物14,化合物14被三丁基锡氢还原得到偕二氟双环己烷液晶材料(1,4-trans;4,4’-anti;4’,1’-trans)-2,2-difluoro-4,4’-dipropyl-1,1’-bi(cyclohe xane)。
优选地,所述步骤(6)中,化合物12、硼氢化钠、甲基草酰氯、DMAP、三正丁基锡氢的投加摩尔比为1:1:2:0.2:5-1:1:3:0.3:10。
相对于现有技术,本发明的优点如下,
本发明提供一种偕二氟双环己烷液晶材料的新合成方法;从简单的商业化原料出发,用常见的试剂和简洁的操作完成了偕二氟双环己烷液晶材料的合成,为偕二氟双环己烷液晶材料的工业化提供了一条可能的技术途径;
本发明的合成工艺成本低、工艺简单、产率高。
具体实施方式
实施例1:
取2L三口圆底烧瓶,分水器,回流冷凝管,加入磁子与二氟氯乙酸(64g,493mmol,1.3eq.)。加入正己烷(1L),室温滴入化合物1(69g,379mmol,1eq.),升温90℃回流分水。18h后反应结束,冷却至室温,加入水(500mL)使用1N NaOH(aq.)调节Ph=7。分液,EA(乙酸乙酯)萃取,依次用水、饱和食盐水洗涤有机相,无水硫酸钠干燥。旋干,得化合物2(无色液体,89g,产率80%)。1H NMR(500MHz,Chloroform-d)δ5.90-5.80(m,1H),5.55(dtd,J=15.3,6.8,1.4Hz,1H),4.76(d,J=6.7Hz,2H),1.95(dddd,J=15.1,11.2,6.8,3.5Hz,1H),1.81-1.71(m,4H),1.31(h,J=7.0Hz,2H),1.20-1.05(m,5H),0.95-0.83(m,5H).19F NMR(376MHz,Chlorof orm-d):δ–63.85(s,1F).13C NMR(101MHz,Chloroform-d)δ159.1(t,J=38.66Hz),145.1,118.9,116.9(t,J=306.67Hz),69.3,40.7,39.6,36.9,32.7,32.3,20.0,14.4.IR(KBr):vmax 2957,2921,2850,1778,1743,1450,1301,1126,969,731,628cm-1.HRMS(ESI)m/zcalculated for C14H22ClF2O2[M+H]+295.1271,found 295.1282.
在该实施例中,化合物1和二氟氯乙酸的投加比例为(摩尔比)为1:1.1-1:2.0,均可制得化合物2,产率为80%-94%。
实施例2:
取2L三颈圆底烧瓶,回流冷凝管,加入锌粉(59g,909mmol,3eq.)与磁子。氮气保护下,加入无水乙腈(1L)与TMSCl(66g,606mmol,2eq.)。室温下滴入化合物2(89g,303mmol,1eq.),升温120℃回流。72h后反应结束,过滤除去不溶物。旋干,加入6N HCl(aq.)(600mL)搅拌1h,EA萃取;旋干,加入2N NaOH(aq.)再调节PH=14,Et2O萃取;再次使用6N HCl(aq.)调节PH=1,EA萃取。依次用水、饱和食盐水洗涤有机相,无水硫酸钠干燥。旋干,得化合物3(黑色液体,51g,产率65%)。1H NMR(400MHz,Chloroform-d)δ8.71(s,1H),5.69(dt,J=17.0,10.1Hz,1H),5.37-5.12(m,2H),2.64(dddd,J=22.1,12.2,10.0,4.2Hz,1H),1.86(dt,J=13.0,3.1Hz,1H),1.79-1.61(m,4H),1.34-1.23(m,3H),1.23-1.07(m,4H),1.04(dd,J=12.4,3.2Hz,1H),1.00-0.91(m,1H),0.86(t,J=7.3Hz,3H).19F NMR(376MHz,Chloroform-d)δ-107.62(d,J=254.7Hz,1F),-110.83(d,J=254.6Hz,1F).13C NMR(101MHz,Chloroform-d)δ168.6(t,J=38.65Hz),130.4(d,J=6.8Hz),121.9,117.2(t,J=255.99Hz),53.8(t,J=20.7Hz),39.5,36.9,36.3,33.1,32.9,31.8,28.9,20.0,14.4.IR(KBr):vmax 2956,2922,2853,1751,1450,1189.7,1048,927,774,687cm-1.HRMS(ESI)m/zcalculated for C14H21F2O2[M-H]-259.1515,found 255.1523.
在该实施例中,化合物2和锌粉、三甲基氯硅烷的投加比例为(摩尔比)为1:2:3-1:4:5,均可制得化合物3,产率为60%-80%。
实施例3:
取500mL圆底烧瓶,加入磁子与化合物3(12.9g,49.6mmol,1eq.)。氮气保护下,加入DCM(248mL)与DMF(1.1g,14.9mmol,0.3eq.),0℃下滴入草酰氯(9.4g,74.4mmol,1.5eq.),室温搅拌13h。反应结束,旋干,抽真空。
在上述体系中加入氮甲基羟胺盐酸盐(7.3g,74.4mmol,1.5eq.)与磁子。氮气保护,加入DCM(300mL),0℃下滴入三乙胺(15.0g,148.8mmol,3eq.),室温搅拌2h,反应结束。加水(150mL),淬灭反应。DCM(二氯甲烷)萃取,依次用水、饱和食盐水洗涤有机相,无水硫酸钠干燥。柱层析(PE:EA=50:1)得化合物5(淡黄色液体,13.8g,92%)。1H NMR(400MHz,Chloroform-d)δ5.71(dt,J=17.1,10.2Hz,1H),5.23(dd,J=10.2,1.9Hz,1H),5.15-5.02(m,1H),3.72(d,J=3.3Hz,3H),3.21(s,3H),2.91-2.74(m,1H),1.86(dt,J=12.8,3.1Hz,1H),1.70(ddq,J=29.9,12.6,3.2Hz,4H),1.54-1.39(m,1H),1.33-1.22(m,3H),1.20-1.06(m,4H),1.05-0.90(m,2H),0.85(t,J=7.3Hz,3H).19F NMR(376MHz,Chloroform-d)δ-104.76(d,J=254.0Hz,1F),-106.31(d,J=254.7Hz,1F).13C NMR(101MHz,Chloroform-d)δ131.9,120.7,119.0(t,J=20.9Hz),61.9,53.8(t,J=20.9Hz),39.6,37.0,36.5,33.2,33.0,32.0,29.1,20.0,14.4.IR(KBr):vmax 2921,2849,1686,1450,1185,979,924,652cm- 1.HRMS(ESI)m/z calculated for C16H27F2NO2Na[M+Na]+326.1902,found 326.1903.
在该实施例中,化合物3和草酰氯、氮甲基羟胺盐酸盐、三乙胺的投加比例为(摩尔比)为1:1.3:1.3:2-1:2:2:4,均可制得化合物5,产率为80%-94%。
实施例4:
取500mL的圆底烧瓶,加入磁子与化合物5(13.8g,45.5mmol,1eq.)。氮气保护下,加入THF(228mL)。0℃下将正丁基氯化镁(45.5mL,91mmol,2eq.)滴入其中。室温搅拌,2h后反应结束,滴入饱和氯化铵溶液淬灭反应。用EA萃取,依次用水、饱和食盐水洗涤有机相,无水硫酸钠干燥。旋干,柱层析(PE(石油醚))得化合物6(淡黄色油状液体,12.9g,94%)。1HNMR(400MHz,Chloroform-d)δ5.64(ddt,J=17.0,12.8,10.1Hz,1H),5.23(dt,J=10.2,1.5Hz,1H),5.10(ddd,J=17.2,5.7,1.7Hz,1H),2.69-2.53(m,3H),1.90-1.81(m,1H),1.77-1.69(m,2H),1.65(dq,J=11.8,3.7Hz,1H),1.60-1.52(m,4H),1.49-1.39(m,1H),1.36-1.23(m,5H),1.16-1.09(m,3H),1.01(td,J=12.5,3.2Hz,1H),0.95-0.82(m,6H).19FNMR(376MHz,Chloroform-d)δ-107.93(d,J=261.8Hz,1F),-112.09(d,J=262.1Hz,1F).13CNMR(101MHz,Chloroform-d)δ201.9,130.9(d,J=6.5Hz),121.5,119.0(t,J=233.94Hz),52.6(d,J=20.8Hz),39.6,37.2,36.9,36.2,33.1,33.0,31.9,28.9,24.6,22.0,20.0,14.3,13.8.IR(KBr):vmax 2957,2923,2852,2024,1742,1451,1188,1039,998,927,736cm- 1.HRMS(ESI)m/z calculated for C18H30F2O2Na[M+Na]+323.2157,found 323.2158
在该实施例中,化合物5和正丁基氯化镁的投加比例为(摩尔比)为1:1.3-1:3,均可制得化合物6,产率为80%-95%。
实施例5:
取250mL的圆底烧瓶,加入磁子与化合物6(6.16g,20.7mmol,1eq.)。氮气保护,加入2-氯乙醇(3.33g,41.4mmol,2eq.)与DMF(160mL),置于-60℃下。将t-BuOK(叔丁醇钾)(4.61g,41.4mmol,2eq.)用DMF(20mL)溶解后滴入到反应体系中,缓慢升温至80℃搅拌2d,然后冷却至-60℃下,补加2-氯乙醇(1.67g,20.7mmol,1eq.)与t-BuOK(2.31g,20.7mmol,1eq.)缓慢升温至80℃搅拌1d。继续反复重复3次。将反应用H2O(50mL)淬灭后,将DMF旋干,加入H2O(500mL),EA萃取,先后使用水、饱和食盐水洗涤,无水硫酸钠干燥。旋干,柱层析(PE:DCM=100:1)得化合物7(淡黄色液体,6.85g,97%)。1H NMR(400MHz,Chloroform-d)δ5.78(dt,J=17.2,10.2Hz,1H),5.18(tt,J=10.1,1.8Hz,1H),5.05-4.89(m,1H),4.16-3.91(m,4H),2.43(dtd,J=25.2,9.8,2.4Hz,1H),1.89(dtd,J=17.6,14.4,13.2,2.9Hz,2H),1.80-1.65(m,4H),1.43(dp,J=12.7,3.2Hz,1H),1.39-1.18(m,7H),1.16-1.05(m,3H),1.01(dd,J=12.6,3.1Hz,1H),0.94-0.81(m,7H).19F NMR(376MHz,Chloroform-d)δ-111.50(d,J=256.8Hz,1F),-113.69(d,J=256.7Hz,1F).13C NMR(101MHz,Chloroform-d)δ133.1,123.8(t,J=257.2Hz),118.0,109.6(d,J=26.3Hz),66.9,66.6,52.4(t,J=21.6Hz),39.7,37.0,36.7(d,J=4.8Hz),33.3,33.2,33.1,31.8,28.2,23.9,22.8,20.0,14.4,14.1.HRMS(ESI)m/z calculated for C20H34F2O2Na[M+Na]+367.2419,found367.2413.IR(KBr):vmax 2957,2921,2849,1591,1449,1212,1164,1046,988,731cm-1.
在该实施例中,化合物6和叔丁醇钾、2-氯乙醇的投加比例为(摩尔比)为1:2:2-1:6:6,均可制得化合物7,产率为50%-97%。
实施例6:
取三个50mL的反应管,分别加入磁子、化合物7(1.03g,3mmol,1eq.)、K2CO3(碳酸钾)(21mg,0.15mmol,0.05eq.)与EY(曙红)(21mg,0.15mmol,0.05eq.)。氮气保护下,加入1,4-二氧六环(30mL)与H2O(0.3mL)。于室温下加入催化剂(iPr)3SiSH(三异丙基硅硫氢)(29mg,0.15mmol,0.05eq.)与二苯基硅烷(1.10g,6mmol,2eq.),50W white LED(50瓦白色LED灯)光照3d。点板检测反应不发生变化,停止反应。旋干反应液,加入(100mL)水,EA萃取,饱和食盐水洗涤,无水硫酸钠干燥,旋干,得粗产物化合物8(淡黄色液体,4.8g)。1H NMR(400MHz,Chloroform-d)δ7.56(ddt,J=6.0,4.1,1.8Hz,5H),7.46-7.31(m,5H),4.09-3.84(m,4H),1.83(dtt,J=10.5,8.0,5.2Hz,3H),1.76-1.57(m,5H),1.51(ddt,J=12.6,8.4,2.2Hz,2H),1.44-1.17(m,10H),1.17-1.03(m,4H),0.88(dt,J=17.1,7.2Hz,8H).19F NMR(376MHz,Chloroform-d)δ-108.47(d,J=258.7Hz,1F),-113.63(d,J=258.8Hz,1F).13CNMR(101MHz,Chloroform-d)δ135.2,134.3(d,J=21.2Hz),129.5,128.0,109.7(d,J=26.0Hz),66.9,66.6,49.9(t,J=20.1Hz),39.7,37.8,37.2,33.8,33.3,33.2,31.2,28.3,24.0,22.8,20.00,19.5,14.4,14.1,13.4.HRMS(ESI)m/z calculated for C32H46F2O2SiNa[M+Na]+551.3127,found551.3124.IR(KBr):vmax 2956,2922,2117,1428,1167,1109,1052,988,804,730,697cm-1.
取100mL的反应管,加入磁子、粗产物化合物8(4.8g,2mmol,1.0eq.)、KHCO3(4.5g,45mmol,5eq.)以及MeOH-THF(100mL)。将30%H2O2(aq.)(22.5mL,180mmol,20eq.),于0℃下滴入到体系中,室温搅拌48h,反应结束。使用饱和硫代硫酸钠溶液淬灭反应,EA萃取,饱和氯化钠溶液洗涤,无水硫酸钠干燥。旋干,抽真空。柱层析(PE:EA=150:1~25:1)得化合物9(无色液体,2.01g,61%over two steps from Compound 7)。1H NMR(500MHz,Chloroform-d)δ4.20-3.94(m,4H),3.66(t,J=6.7Hz,2H),2.02-1.95(m,1H),1.93-1.84(m,2H),1.80-1.72(m,4H),1.72-1.60(m,3H),1.48(dp,J=12.7,3.3Hz,1H),1.40-1.23(m,7H),1.12(dq,J=6.1,3.4Hz,4H),0.88(dt,J=22.3,7.2Hz,8H).19F NMR(471MHz,Chloroform-d)δ-107.47(d,J=257.8Hz,1F),-114.61(d,J=258.0Hz,1F).13C NMR(126MHz,Chloroform-d)δ125.0(dd,J=259.2,254.7Hz),109.9(t,J=25.7Hz),67.0,66.6,62.8(d,J=3.4Hz),42.8(t,J=20.9Hz),39.6,37.4(t,J=3.7Hz),37.2,33.6,33.1,33.0,31.3,27.7(d,J=3.3Hz),27.5(t,J=4.1Hz),24.0,22.8,20.0,14.4,14.1.HRMS(ESI)m/z calculated forC20H36F2O3Na[M+Na]+385.2525,found 385.2526.IR(KBr):vmax 2956,2925,2871,1741,1450,1240,1170,1047,987,897,701cm-1.
在该实施例中,化合物7和K2CO3、EY、(iPr)3SiSH、二苯基硅烷的投加比例为(摩尔比)为1:0.05:0.05:0.05:2-1:0.2:0.2:0.2:2,均可制得化合物8;
在该实施例中,化合物8和碳酸氢钾、30%过氧化氢溶液的投加比例为(摩尔比)为1:5:20-1:10:30,均可制得化合物9,两部总产率为40%-61%。
实施例7:
取100mL的圆底烧瓶,加入磁子、PPh3(641mg,2.44mmol,2eq.)与化合物9(443mg,1.22mmol,1eq.)。氮气保护,加入DCM(20mL)与Et3N(617mg,6.10mmol,5eq.)。将CBr4(812mg,2.44mmol,2eq.)用DCM(5mL)溶解后于0℃下滴入到体系中,室温搅拌10h,反应结束。加入水(10mL)淬灭反应,DCM萃取,饱和食盐水洗涤,无水硫酸钠干燥。旋干,柱层析(PE:DCM=50:1),得化合物10(无色液体,417mg,81%)。1H NMR(400MHz,Chloroform-d)δ4.21-3.96(m,4H),3.66-3.50(m,1H),3.44(dt,J=9.7,7.6Hz,1H),2.25(dtd,J=14.8,7.4,5.5Hz,1H),2.06-1.85(m,3H),1.82-1.64(m,5H),1.56-1.46(m,1H),1.45-1.24(m,7H),1.14(qd,J=4.9,2.1Hz,3H),1.05(td,J=12.2,3.2Hz,1H),0.89(dt,J=19.9,7.2Hz,8H).19F NMR(376MHz,Chloroform-d)δ-106.13(d,J=259.2Hz,1F),-115.12(d,J=259.4Hz,1F).13CNMR(101MHz,Chloroform-d)δ124.9(dd,J=260.2,254.5Hz),109.8(d,J=25.6Hz),67.0,66.7,45.4(t,J=20.7Hz),39.6,37.2,37.1(d,J=4.3Hz),34.13(d,J=5.6Hz),34.10,33.5,33.0,31.6,28.2,27.7,24.0,22.8,20.0,14.4,14.1.HRMS(ESI)m/z calculated forC20H35F2O2BrNa[M+Na]+447.1681,found 447.1675.IR(KBr):vmax 2956,2927,2870,1450,1219,1172,1129,1052,988,954,915,897,766cm-1.
在该实施例中,化合物9和四溴化碳、三苯基膦、三乙胺的投加比例为(摩尔比)为1:1.2:1.2:2-1:2:2:5,均可制得化合物10,产率为70%-91%。
实施例8:
取50mL的圆底烧瓶,加入磁子与化合物10(121mg,0.29mmol,1eq.)。氮气保护,加入THF(10mL),于0℃下将浓硫酸(5mL)滴入到体系中。室温搅拌24h,反应结束,将反应液倒入冰水浴(100mL)并调节PH=7,EA萃取,饱和食盐水洗涤,无水硫酸钠干燥。旋干,柱层析(PE:DCM=50:1)得,化合物11(无色液体,103mg,95%)。1H NMR(500MHz,Chloroform-d)δ3.58-3.47(m,1H),3.42(dt,J=10.0,7.7Hz,1H),2.65(t,J=7.4Hz,2H),2.29(dddd,J=23.1,15.6,7.1,3.7Hz,1H),2.14(dtd,J=15.0,7.7,5.8Hz,1H),1.96(dtd,J=15.3,7.9,4.3Hz,1H),1.80-1.68(m,3H),1.61(p,J=7.3Hz,2H),1.54(dt,J=6.1,3.1Hz,1H),1.41-1.33(m,3H),1.32-1.20(m,4H),1.15-1.02(m,4H),0.89(dt,J=35.7,7.3Hz,8H).19F NMR(471MHz,Chloroform-d)δ-102.56(dd,J=271.9,3.6Hz,1F),-113.07(dd,J=272.2,6.4Hz,1F).13C NMR(101MHz,Chloroform-d)δ201.6,120.1(dd,J=259.8,253.6Hz),44.8(t,J=19.5Hz),39.5,37.3(d,J=4.8Hz),37.0,36.7,33.3,33.0,32.6(d,J=3.8Hz),31.7,28.2,28.1,24.7,22.1,19.9,14.3,13.8.HRMS(ESI)m/z calculated forC18H30F2O2BrNa[M-H]-379.1454,found 379.1462.IR(KBr):vmax 2957,2925,2871,1741,1451,1403,1379,1226,1134,1021,953,757,632cm-1.
在该实施例中,化合物10和四氢呋喃、浓硫酸的投加比例为(摩尔比)为1:100:150-1:400:500,均可制得化合物11,产率为80%-95%。
实施例9:
取100mL的圆底烧瓶,加入磁子,氮气保护下加入THF(50mL)与HMDS(六甲基二硅氮烷)(875mg,5.42mmol,1.5eq.)。将其置于-40℃下,将n-BuLi(2.17mL,5.42mmol,1.5eq.)缓慢滴入到体系中,并搅拌30min。然后,缓慢升至0℃下并搅拌30min。
将化合物11(1.03g,2.71mmol,1eq.)用THF(4mL)稀释后缓慢(2h)滴入到体系中,并保持该温度搅拌过夜,然后缓慢升温至80℃。搅拌2d反应结束,冷却至室温,加入饱和氯化铵溶液(30mL)淬灭反应。EA萃取,饱和食盐水洗涤,无水硫酸钠干燥,旋干,柱层析(PE:DCM=100:1)得化合物12(白色固体,488mg,60%)。1H NMR(400MHz,Chloroform-d)δ2.67(dp,J=12.6,6.3Hz,1H),2.15(ddt,J=13.0,6.1,3.3Hz,1H),1.93-1.86(m,1H),1.85-1.70(m,6H),1.69-1.57(m,2H),1.29(dddd,J=18.8,11.1,8.5,5.7Hz,6H),1.21(d,J=3.3Hz,1H),1.15(tdd,J=11.6,4.9,2.9Hz,4H),0.89(dt,J=16.8,7.2Hz,8H).19F NMR(376MHz,Chloroform-d)δ-114.74(d,J=243.9Hz,1F),-119.72(d,J=244.1Hz,1F).13CNMR(101MHz,Chloroform-d)δ200.8(dd,J=21.7,28.6Hz),118.8(dd,J=261.1,249.4Hz),51.4(dd,J=22.2,18.6Hz),47.6,39.6,37.1,36.1,33.4,33.2,32.4,31.9,30.4,29.6(d,J=3.0Hz),23.0(d,J=7.6Hz),20.07,19.97,14.4,14.1.HRMS(ESI)m/z calculated forC18H30F2NaO[M+Na]+323.2162,found 323.2154.IR(KBr):vmax 2956,2922,2850,1449,1260,1191,1093,1019,798cm-1.
在该实施例中,化合物11和HMDS、正丁基锂的投加比例为(摩尔比)为1:1.3:1.3-1:2:2,均可制得化合物12,产率为30%-60%。
实施例10:
1)取25mL的圆底烧瓶,加入磁子、化合物12(120mg,0.4mmol,1eq.)以及MeOH-THF(5:1,8mL)。置于0℃下,并在该温度下加入NaBH4(15mg,0.4mmol,1eq.)。搅拌1h,反应结束,将反应溶剂旋干。加入水(20mL),EA萃取,饱和食盐水洗涤,无水硫酸钠干燥,旋干,抽真空得粗产物120mg。
2)取25mL的圆底烧瓶,加入磁子、粗产物(120mg,0.4mmol,1eq.)与DMAP(10mg,0.08mmol,0.2eq.)。氮气保护下,加入DCE(8mL)以及Et3N(202mg,2mmol,5eq.)。置于0℃下,并在该温度下加入甲基草酰氯(Methyloxalychlotide)(98mg,0.8mmol,2eq.)。缓慢升至室温搅拌9h,反应结束,加入饱和氯化铵溶液(10mL)淬灭反应。DCM萃取,饱和食盐水洗涤,无水硫酸钠干燥,旋干,抽真空得粗产物150mg。
3)取25mL的三口圆底烧瓶,加入磁子、粗产物(150mg,0.39mmol,1eq.)以及AIBN(偶氮二异丁腈)(13mg,0.08mmol,0.2eq.)。氮气保护下加入除氧的甲苯(toluene)(9.5mL)以及Bu3SnH(三丁基锡氢)(567mg,1.95mmol,5eq.),升温回流6.5h反应结束。冷却至室温加入饱和氟化钾溶液(10mL)淬灭反应搅拌过夜。EA萃取,饱和食盐水洗涤,无水硫酸钠干燥,旋干,抽真空,柱层析(正己烷)得偕二氟双环己烷液晶材料(1,4-trans;4,4’-anti;4’,1’-trans)-2,2-difluoro-4,4’-dipropyl-1,1’-bi(cyclohexane)(无色液体,30mg,35%overthree steps)。1H NMR(400MHz,Chloroform-d)δ2.09(ddd,J=9.6,4.0,2.1Hz,1H),1.86-1.70(m,5H),1.62(dt,J=13.0,3.1Hz,1H),1.56(t,J=7.3Hz,1H),1.49(dq,J=13.1,3.2Hz,1H),1.45-1.38(m,1H),1.38-1.34(m,1H),1.34-1.25(m,5H),1.25-1.09(m,6H),1.08-0.81(m,10H).19F NMR(376MHz,Chloroform-d)δ-93.91(d,J=244.59Hz,1F),-110.01(d,J=235.0Hz,1F).13C NMR(101MHz,Chloroform-d)δ126.9(d,J=244.9Hz),48.8(dd,J=22.5,19.3Hz),41.8(dd,J=25.6,21.6Hz),39.7,38.6,37.3,35.6,34.5(d,J=9.5Hz),33.7,33.4,32.6,29.9(d,J=21.4Hz),29.3(d,J=3.5Hz),24.4(d,J=8.2Hz),20.0,19.8,14.4,14.2.MS(ESI)m/z[M-H]-185.
在该实施例中,化合物12和硼氢化钠、甲基草酰氯、DMAP、三乙胺、AIBN、三正丁基锡氢的投加比例为(摩尔比)为1:1:2:0.2:5:0.2:5-1:1:3:0.3:5:0.5:10,均可制得产物,三步连投产率为35%-45%。
需要说明的是上述实施例仅仅是本发明的较佳实施例,并没有用来限定本发明的保护范围,在上述基础上做出的等同替换或者替代均属于本发明的保护范围。
Claims (9)
3.如权利要求2所述的偕二氟双环己烷液晶材料的合成方法,其特征在于,包括以下步骤:
(1)化合物1与二氟氯乙酸酯化得到化合物2,
(2)由化合物2重排得到化合物3,
(3)由化合物3经羰基加成消除得到化合物6,
(4)由化合物6溴化得到化合物11,
(5)由化合物11分子内烷基化得到化合物12,
(6)由化合物12还原羰基得到化合物偕二氟双环己烷液晶材料。
4.如权利要求3所述的偕二氟双环己烷液晶材料的合成方法,其特征在于,所述步骤(1)中:化合物1和二氟氯乙酸的投加摩尔比为1:1.1-1:2.0。
5.如权利要求3所述的偕二氟双环己烷液晶材料的合成方法,其特征在于,所述步骤(2)的具体方法为:化合物2和Zn以及TMSCl反应发生Reformatsky-Claisen重排反应得到化合物3。
8.如权利要求3所述的偕二氟双环己烷液晶材料的合成方法,其特征在于,所述步骤(5)的具体方法为:
化合物11在LiHMDS作用下,发生分子内烷基化反应得到化合物12。
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