CN110922427B - 大位阻烷基取代亚膦酸二酯的制备方法 - Google Patents
大位阻烷基取代亚膦酸二酯的制备方法 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
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Abstract
本发明公开了一种大位阻烷基取代亚膦酸二酯的制备方法，本发明使用三氟甲磺酸三甲基硅酯为催化剂，实现大位阻醇类与亚磷酸三酯的直接反应制备已知方法很难合成的大位阻烷基取代亚膦酸二酯类化合物的新方法。因此，本方法可以说是对阿尔布佐夫方法合成大位阻烷基取代亚膦酸二酯类化合物的突破，由于本方法还适用于一般的伯醇原料，因此是一种具有高普适性的改进阿尔布佐夫方法。具体地，本方法使用稳定低毒的大位阻醇类为原料，反应条件简单、易于操作、无需溶剂，催化剂不含过渡金属，产物无过渡金属残留隐患，副产物为小分子的醇类如乙醇，几乎无毒性，因此是一种大位阻烷基取代亚膦酸二酯的绿色合成方法，具有很好研究价值和合成应用前景。
Description
技术领域
本发明属于有机化学合成技术领域，具体涉及一种三氟甲磺酸三甲基硅酯催化下大位阻醇类与亚磷酸三酯直接反应制备大位阻烷基取代亚膦酸酯的绿色合成方法。
背景技术
含C-P(O)键的有机磷化合物在医药和农业领域有着广泛而重要的应用，在有机合成和催化中也有着广泛的应用。
著名的阿尔布佐夫(Arbuzov)反应，通过卤代烷烃与亚磷酸三酯在高温加热下反应生成C-P(O)化合物，是合成有机亚膦酸酯衍生物的重要的经典的方法，在实验室以及工业上被广泛应用于制造各种有机膦化合物。但是该反应的缺点也很明显，除了需高温加热、需使用毒性大的卤代烷烃为原料等缺点外，反应还不可避免地产生当量的具有毒性且沸点低易挥发的溴乙烷等副产物，该副产物还可引起亚磷酸三酯发生副反应，综合导致反应原子经济型低、产物选择性不高、反应效率较低、产物分离困难、以及污染等问题。此外，经典阿尔布佐夫反应主要适用于伯卤代烃，而仲卤代烃、叔卤代烃等由于位阻较大难作为原料用于合成具有大位阻效果的有机膦化合物。因而，经典阿尔布佐夫反应实际上适用范围有限。
为改进阿尔布佐夫方法，现有技术文献上后来陆续报道了一些以醇来代替卤代烃的新方法，例如利用ZnBr2、ZnI2、PPh3/DDQ等作为助剂促进亚磷酸三酯与醇的反应合成C-P(O)化合物。虽然使用醇代替卤代烃具有一定的优势，但这些方法还有关键缺点没有克服，例如这些方法局限于伯醇类原料，不适用于大位阻的仲醇叔醇等，而且使用当量以上的ZnBr2、ZnI2、PPh3/DDQ等试剂不仅产生大量难处理的废弃物会污染环境，实际上这些方法包含将醇现场转化为卤代烷烃的过程，与直接只用卤代烷烃的方法相比改进不大。
因此，发展可解决经典阿尔布佐夫反应和上述改良阿尔布佐夫方法存在的问题、实现一种通用的、适用于大位阻仲醇叔醇等原料的具高普适性改进阿尔布佐夫方法，用于制备之前很难合成得到的大位阻取代C-P(O)化合物的新方法，填补该领域研究的空白，在有机合成、生化和医药等领域都是非常有意义的工作。
发明内容
为解决现有技术存在的问题和不足，本发明的目的是提供一种大位阻烷基取代亚膦酸二酯的制备方法。该方法适用于大位阻仲醇叔醇等原料，具高普适性的优点，本发明使用稳定低毒的大位阻醇类为原料，反应条件简单、易于操作、无需溶剂、催化剂不含过渡金属，产物无过渡金属残留隐患，副产物为小分子的醇类如乙醇，几乎无毒性，是一种大位阻烷基取代亚膦酸二酯的绿色合成方法。
为实现上述目的，本发明的技术方案是提供大位阻烷基取代亚膦酸二酯的制备方法，包括以下步骤：以大位阻醇类化合物和亚磷酸三酯为原料，以三氟甲磺酸三甲基硅酯为催化剂，在加热条件下发生艾伯佐夫反应，直接合成大位阻烷基取代亚膦酸二酯，其反应式为
其中：R1为各种官能团取代在2-、3-、或4-位的苯基、芳基或烷基；
R2为各种官能团取代在2-、3-、或4-位的苯基、其他芳基、直链或支链取代的烷基、烯基或炔基；
R3为氢、各种官能团取代在2-、3-、或4-位的苯基、其他芳基、直链或支链取代的烷基、烯基或炔基；
R4为直链或支链的烷氧基、苯氧基、芳氧基、直链或支链的烷基、苯基或芳基；
R5为直链或支链的烷氧基、苯氧基、芳氧基、直链或支链的烷基、苯基或芳基；
R6为是直链或支链的烷基、苯基或芳基。
进一步设置是反应在有溶剂和无溶剂条件下均可进行，优选为无溶剂条件；
本发明所涉及的最优催化剂是三氟甲磺酸三甲基硅酯；
本发明的反应中，催化剂的用量为2-30mol％，优选为20mol％，基于用量少的原料计算的，一般是醇。
本发明的反应，可以在空气或惰性气体条件下进行，优选在惰性气体如N2保护下进行；
反应温度为20-120℃，优选为100℃；反应时间12-48小时，优选为24小时。
本发明所采用的催化剂三氟甲磺酸三甲基硅酯(TMSOTf)系商品化的化合物，可直接购买。与文献方法相比，本方法可使用稳定低毒的仲醇叔醇类为原料，不使用任何过渡金属催化剂和配体、不使用有机溶剂、易于操作、副产物为小分子醇类、相对绿色环保无污染。因此是一种大位阻烷基取代亚膦酸二酯的绿色合成方法，具有很好的理论研究价值和一定的合成应用前景。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚，下面将结合实施例对本发明作进一步地详细描述。
本申请提供以下实施例，尽管在以下实施例中以特定的物料比例以及催化剂的比例和温度、以及反应保护气体进行了描述，其仅用于指导实现本申请的发明目的，而实际并不限于该上述控制条件和物料参数。例如催化剂三氟甲磺酸三甲基硅酯(TMSOTf)的量在2-30mol％范围均可，如2mol％、30mol％；保护气体也可以选择氮气之外的其他惰性气体，如氩气氦气等等；其反应温度也不限于实施例的100℃和80℃，还可以为120℃或者80℃-120℃之间的任一温度。
虽然已经参考若干具体实施例描述了本发明，但是应当理解，本发明不限于所公开的具体实施例。本发明旨在涵盖所附权利要求的精神和范围内所包括的各种修改和等效布置。以下具体见实施例：
实施例1
二苯甲醇和亚磷酸三乙酯合成(二苯基)甲基亚膦酸二乙酯
管形反应器中加入二苯甲醇(0.0921g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率82％。1H NMR(500MHz,CDCl3)δ7.53(d,J＝7.0Hz,4H),7.29(t,J＝7.0Hz,4H),7.25–7.17(m,2H),4.43(d,J＝25.0Hz,1H),4.12–3.67(m,4H),1.09(t,J＝6.9Hz,6H).13C NMR(126MHz,CDCl3)δ136.90(d,J＝5.2Hz),129.47(d,J＝8.0Hz),128.56,127.11(d,J＝1.6Hz),62.62(d,J＝7.0Hz),51.35(d,J＝138.2Hz),16.22(d,J＝5.8Hz).31P NMR(202MHz,CDCl3)δ25.10。
实施例2
2-甲基二苯甲醇和亚磷酸三乙酯合成(2-甲基二苯基)甲基亚膦酸二乙酯
管形反应器中加入2-甲基二苯甲醇(0.0991g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率87％。1H NMR(500MHz,CDCl3)δ7.96(d,J＝7.5Hz,1H),7.47(d,J＝6.9Hz,2H),7.31–7.07(m,6H),4.67(d,J＝26.0Hz,1H),4.04–3.73(m,4H),2.32(s,3H),1.10(dt,J＝17.0,7.0Hz,6H).13C NMR(126MHz,CDCl3)δ136.43(s),136.37(d,J＝6.9Hz),135.34(d,J＝3.8Hz),130.61,129.80(d,J＝7.5Hz),129.50(d,J＝5.3Hz),128.43,127.12,126.97,126.20,62.57(dd,J＝15.9,7.0Hz),46.69(d,J＝139.4Hz),19.99,16.23(t,J＝5.1Hz).31P NMR(202MHz,CDCl3)δ25.95。
实施例3
4-甲基二苯甲醇和亚磷酸三乙酯合成(4-甲基二苯基)甲基亚膦酸二乙酯
管形反应器中加入4-甲基二苯甲醇(0.0991g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率85％。1H NMR(500MHz,CDCl3)δ7.51(d,J＝7.7Hz,2H),7.41(d,J＝6.8Hz,2H),7.29(t,J＝7.6Hz,2H),7.21(t,J＝7.3Hz,1H),7.11(d,J＝7.9Hz,2H),4.39(d,J＝25.1Hz,1H),4.03–3.76(m,4H),2.29(s,3H),1.11(q,J＝7.2Hz,6H).13C NMR(126MHz,CDCl3)δ137.15(d,J＝5.0Hz),136.69(d,J＝2.0Hz),133.87(d,J＝5.2Hz),129.45,129.37(d,J＝4.8Hz),129.28(d,J＝2.8Hz),128.52,127.02(d,J＝1.7Hz),62.57(dd,J＝6.9,1.7Hz),50.93(d,J＝138.2Hz),21.00,16.24(dd,J＝5.6,3.3Hz).31P NMR(202MHz,CDCl3)δ25.29。
实施例4
4-甲氧基二苯甲醇和亚磷酸三乙酯合成(4-甲氧基二苯基)甲基亚膦酸二乙酯
管形反应器中加入4-甲氧基二苯甲醇(0.1071g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率92％。1H NMR(500MHz,CDCl3)δ7.53–7.48(m,2H),7.45(dd,J＝8.7,1.7Hz,2H),7.30(t,J＝7.6Hz,2H),7.22(td,J＝7.5,1.1Hz,1H),6.85(d,J＝8.7Hz,2H),4.38(d,J＝25.2Hz,1H),4.03–3.78(m,4H),3.76(s,3H),1.12(dd,J＝14.9,7.2Hz,6H).13C NMR(126MHz,CDCl3)δ158.70(d,J＝1.9Hz),137.22(d,J＝4.8Hz),130.51(d,J＝8.0Hz),129.37(d,J＝7.9Hz),128.91(d,J＝5.4Hz),128.53,127.02(d,J＝2.0Hz),113.98,62.61(dd,J＝7.0,4.0Hz),55.19,50.39(d,J＝138.6Hz),16.25(t,J＝5.7Hz).31P NMR(202MHz,CDCl3)δ25.34。
实施例5
2-甲氧基二苯甲醇和亚磷酸三乙合成(2-甲氧基二苯基)甲基亚膦酸二乙酯
管形反应器中加入2-甲氧基二苯甲醇(0.1071g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率73％。1H NMR(500MHz,CDCl3)δ7.94(d,J＝7.7Hz,1H),7.53(d,J＝7.8Hz,2H),7.27(t,J＝7.5Hz,2H),7.20(dd,J＝16.1,8.3Hz,2H),6.96(t,J＝7.5Hz,1H),6.83(d,J＝8.3Hz,1H),5.12(d,J＝25.0Hz,1H),4.03–3.80(m,4H),3.78(s,3H),1.10(td,J＝7.0,4.9Hz,6H).13C NMR(126MHz,CDCl3)δ156.69(d,J＝10.4Hz),137.04(d,J＝5.1Hz),130.25(d,J＝5.3Hz),129.72(d,J＝7.7Hz),128.31(d,J＝1.3Hz),128.24(d,J＝1.6Hz),126.80(d,J＝2.2Hz),125.61(d,J＝3.1Hz),120.68(d,J＝1.8Hz),110.78,62.49(dd,J＝11.3,7.0Hz),55.70,41.79(d,J＝140.8Hz),16.22(d,J＝5.8Hz).31P NMR(202MHz,CDCl3)δ26.17。
实施例6
3-甲氧基二苯甲醇和亚磷酸三乙酯合成(3-甲氧基二苯基)甲基亚膦酸二乙酯
管形反应器中加入3-甲氧基二苯甲醇(0.1071g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率73％。1H NMR(500MHz,CDCl3)δ7.52(d,J＝7.6Hz,2H),7.30(t,J＝7.5Hz,2H),7.25–7.20(m,2H),7.14–7.08(m,2H),6.78(d,J＝8.2Hz,1H),4.40(d,J＝25.0Hz,1H),4.04–3.79(m,4H),3.78(s,3H),1.12(dt,J＝11.1,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ159.66,138.31(d,J＝5.0Hz),136.78(d,J＝5.3Hz),129.45(d,J＝7.9Hz),128.54(d,J＝1.0Hz),127.13(d,J＝2.1Hz),121.89(d,J＝8.0Hz),115.29(d,J＝8.2Hz),112.63(d,J＝1.9Hz),62.65(d,J＝7.0Hz),55.18,51.33(d,J＝138.3Hz),16.23(dd,J＝5.7,3.6Hz).31P NMR(202MHz,CDCl3)δ24.96。
实施例7
4,4’-二甲氧基二苯甲醇和亚磷酸三乙酯合成(4,4’-二甲氧基二苯基)甲基亚膦酸二乙酯
管形反应器中加入4,4’-二甲氧基二苯甲醇(0.1221g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率90％。1H NMR(500MHz,CDCl3)δ7.42(dd,J＝8.6,1.7Hz,4H),6.84(d,J＝8.6Hz,4H),4.33(d,J＝25.3Hz,1H),4.03–3.78(m,4H),3.77(s,6H),1.13(t,J＝7.1Hz,6H).13C NMR(126MHz,CDCl3)δ158.63(d,J＝1.9Hz),130.40(d,J＝8.0Hz),129.27(d,J＝5.0Hz),113.96(d,J＝0.6Hz),62.55(d,J＝7.1Hz),55.19,49.45(d,J＝138.9Hz),16.27(d,J＝5.7Hz).31P NMR(202MHz,CDCl3)δ25.62。
实施例8
4-氯二苯甲醇和亚磷酸三乙酯合成(4-氯二苯基)甲基亚膦酸二乙酯
管形反应器中加入4-氯二苯甲醇(0.1093g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率71％。1H NMR(500MHz,CDCl3)δ7.51–7.45(m,4H),7.34–7.22(m,5H),4.40(d,J＝25.1Hz,1H),4.04–3.76(m,4H),1.12(dt,J＝18.8,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.42(d,J＝5.3Hz),135.56(d,J＝5.2Hz),133.10(d,J＝2.6Hz),130.79(d,J＝8.0Hz),129.39(d,J＝7.9Hz),128.70(d,J＝1.2Hz),128.68,127.33(d,J＝2.0Hz),62.73(dd,J＝25.3,7.1Hz),50.61(d,J＝138.8Hz),16.23(t,J＝5.9Hz).31P NMR(202MHz,CDCl3)δ24.45。
实施例9
4-溴二苯甲醇和亚磷酸三乙酯合成(4-溴二苯基)甲基亚膦酸二乙酯
管形反应器中加入4-溴二苯甲醇(0.1316g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率60％。1H NMR(500MHz,CDCl3)δ7.49(d,J＝7.4Hz,2H),7.42(q,J＝8.7Hz,4H),7.31(t,J＝7.5Hz,2H),7.27–7.22(m,1H),4.38(d,J＝25.1Hz,1H),4.05–3.76(m,4H),1.13(dt,J＝20.2,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.33(d,J＝5.3Hz),136.08(d,J＝5.2Hz),131.67(d,J＝0.6Hz),131.14(d,J＝8.0Hz),129.39(d,J＝7.9Hz),128.69,127.34(d,J＝1.9Hz),121.24(d,J＝2.7Hz),62.76(dd,J＝26.0,7.1Hz),50.69(d,J＝138.8Hz),16.24(t,J＝6.1Hz).31PNMR(202MHz,CDCl3)δ24.30。
实施例10
4,4’-二氟二苯甲醇和亚磷酸三乙酯合成(4,4’-二氟二苯基)甲基亚膦酸二乙酯
管形反应器中加入4,4’-二氟二苯甲醇(0.1101g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率78％。1HNMR(500MHz,CDCl3)δ7.48(ddd,J＝8.6,5.3,1.7Hz,4H),7.01(t,J＝8.6Hz,4H),4.40(d,J＝25.3Hz,1H),4.04–3.80(m,4H),1.13(t,J＝7.1Hz,6H).13C NMR(126MHz,CDCl3)δ163.00(d,J＝2.3Hz),161.04(d,J＝2.2Hz),132.64–132.49(m),130.95(t,J＝8.0Hz),115.50(d,J＝21.4Hz),62.73(d,J＝7.1Hz),49.54(d,J＝139.7Hz),16.20(d,J＝5.7Hz).31PNMR(202MHz,CDCl3)δ24.48(t,J＝3.1Hz)。
实施例11
4,4’-二氯二苯甲醇和亚磷酸三乙酯合成(4,4’-二氯二苯基)甲基亚膦酸二乙酯
管形反应器中加入4,4’-二氯二苯甲醇(0.1266g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率66％。1HNMR(500MHz,CDCl3)δ7.43(d,J＝7.0Hz,4H),7.29(d,J＝8.4Hz,4H),4.37(d,J＝25.1Hz,1H),4.05–3.81(m,4H),1.14(t,J＝7.1Hz,6H).13C NMR(126MHz,CDCl3)δ135.14,133.37,130.74(d,J＝7.8Hz),128.86,62.86(d,J＝6.9Hz),49.91(d,J＝139.2Hz),16.28(d,J＝5.4Hz).31PNMR(202MHz,CDCl3)δ23.84。
实施例12
1-苯基-1-(2-萘)甲醇和亚磷酸三乙酯合成1-苯基-1-(2-萘)甲基亚膦酸二乙酯
管形反应器中加入1-苯基-1-(2-萘)甲醇(0.1171g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率63％。1HNMR(500MHz,CDCl3)δ8.03(s,1H),7.85–7.80(m,1H),7.78(d,J＝8.0Hz,2H),7.63(d,J＝8.5Hz,1H),7.59–7.56(m,2H),7.47–7.40(m,2H),7.31(t,J＝7.7Hz,2H),7.26–7.20(m,1H),4.61(d,J＝25.0Hz,1H),4.05–3.77(m,4H),1.11(dt,J＝14.5,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.86(d,J＝5.2Hz),134.44(d,J＝5.3Hz),133.45(d,J＝1.0Hz),132.48(d,J＝1.2Hz),129.60(d,J＝7.9Hz),128.62(d,J＝0.8Hz),128.31,128.23(d,J＝1.8Hz),128.02,127.66,127.58(d,J＝3.8Hz),127.20(d,J＝2.0Hz),126.12,125.94,62.74(dd,J＝6.7,5.9Hz),51.41(d,J＝138.5Hz),16.27(d,J＝5.7Hz).31P NMR(202MHz,CDCl3)δ24.95.
实施例13
1-苯乙醇和亚磷酸三乙酯合成1-苯乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-苯乙醇(0.0609ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率49％。1H NMR(500MHz,CDCl3)δ7.40–7.18(m,5H),4.11–3.72(m,4H),3.17(dq,J＝22.4,7.3Hz,1H),1.58(dd,J＝18.5,7.4Hz,3H),1.21(dt,J＝66.3,7.0Hz,6H).13C NMR(126MHz,CDCl3)δ138.03(d,J＝6.8Hz),128.66(d,J＝6.5Hz),128.38(d,J＝2.6Hz),127.00(d,J＝3.2Hz),62.13(dd,J＝64.0,7.1Hz),38.50(d,J＝137.9Hz),16.32(dd,J＝17.1,5.8Hz),15.57(d,J＝5.1Hz).31P NMR(202MHz,CDCl3)δ29.76。
实施例14
1-(4-甲基苯基)乙醇和亚磷酸三乙酯合成1-(4-甲基苯基)乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-(4-甲基苯基)乙醇(0.0684ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率54％。1H NMR(400MHz,CDCl3)δ7.23(dd,J＝8.1,2.2Hz,2H),7.12(d,J＝8.0Hz,2H),4.10–3.75(m,4H),3.14(dq,J＝22.3,7.4Hz,1H),2.32(d,J＝1.8Hz,3H),1.56(dd,J＝18.5,7.4Hz,3H),1.21(dt,J＝46.5,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.59(d,J＝3.4Hz),134.90(d,J＝6.9Hz),129.09(d,J＝2.6Hz),128.48(d,J＝6.5Hz),62.07(dd,J＝60.4,7.1Hz),38.03(d,J＝138.0Hz),21.02,16.35(dd,J＝14.6,5.8Hz),15.65(d,J＝4.9Hz).31P NMR(202MHz,CDCl3)δ29.94。
实施例15
1-(2-甲氧基苯基)乙醇和亚磷酸三乙酯合成1-(2-甲氧基苯基)乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-(2-甲氧基苯基)乙醇(0.0705ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率81％。1H NMR(400MHz,CDCl3)δ7.51–7.45(m,1H),7.25–7.17(m,1H),6.96(t,J＝7.5Hz,1H),6.86(d,J＝8.2Hz,1H),4.14–3.75(m,8H),1.52(dd,J＝18.4,7.4Hz,3H),1.20(dt,J＝64.8,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ156.70(d,J＝7.7Hz),128.94(d,J＝4.8Hz),127.84(d,J＝2.9Hz),126.83(d,J＝5.8Hz),120.73(d,J＝2.8Hz),110.50,61.91(dd,J＝55.5,7.1Hz),55.60,28.96(d,J＝139.5Hz),16.29(dd,J＝21.0,6.0Hz),15.60(d,J＝4.8Hz).31PNMR(202MHz,CDCl3)δ30.78。
实施例16
1-(4-甲氧基苯基)乙醇和亚磷酸三乙酯合成1-(4-甲氧基苯基)乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-(4-甲氧基苯基)乙醇(0.0705ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率91％。1H NMR(500MHz,CDCl3)δ7.27(d,J＝6.7Hz,2H),6.86(d,J＝8.2Hz,2H),4.13–3.86(m,4H),3.79(s,3H),3.21–3.04(m,1H),1.55(dd,J＝18.4,7.3Hz,3H),1.21(dt,J＝59.6,7.0Hz,6H).13CNMR(126MHz,CDCl3)δ158.59,129.86,129.55,113.77,61.98(dd,J＝63.0,6.6Hz),55.12,37.46(d,J＝138.2Hz),16.61–16.04(m),15.64.31P NMR(202MHz,CDCl3)δ29.96。
实施例17
1-(2-氯苯基)乙醇和亚磷酸三乙酯合成1-(2-氯苯基)乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-(2-氯苯基)乙醇(0.0664ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率34％。1H NMR(400MHz,CDCl3)δ7.65–7.58(m,1H),7.37(d,J＝7.9Hz,1H),7.27(dd,J＝9.3,5.2Hz,1H),7.21–7.14(m,1H),4.20–3.76(m,5H),1.55(dd,J＝18.3,7.3Hz,3H),1.22(dt,J＝76.1,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.23(d,J＝5.3Hz),134.02(d,J＝9.9Hz),129.64(d,J＝4.6Hz),129.40(d,J＝2.1Hz),128.07(d,J＝3.0Hz),127.02(d,J＝2.9Hz),62.22(dd,J＝56.6,7.1Hz),33.67(d,J＝140.1Hz),16.30(dd,J＝26.6,5.9Hz),15.80(d,J＝5.0Hz).31P NMR(202MHz,CDCl3)δ29.18。
实施例18
1-(4-氯苯基)乙醇和亚磷酸三乙合成合成1-(4-氯苯基)乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-(4-氯苯基)乙醇(0.0669ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率32％。1H NMR(500MHz,CDCl3)δ7.28(d,J＝7.4Hz,4H),4.11–3.79(m,4H),3.15(dq,J＝22.5,7.4Hz,1H),1.55(dd,J＝18.3,7.4Hz,3H),1.22(dt,J＝53.3,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.64(d,J＝7.0Hz),132.88(d,J＝3.9Hz),129.96(d,J＝6.6Hz),128.53(d,J＝2.6Hz),62.23(dd,J＝52.6,7.1Hz),37.91(d,J＝138.6Hz),16.34(dd,J＝12.6,5.8Hz),15.50(d,J＝5.1Hz).31P NMR(202MHz,CDCl3)δ28.94。
实施例19
1-(4-溴苯基)乙醇和亚磷酸三乙酯合成1-(4-溴苯基)乙基亚膦酸二乙酯
管形反应器抽换氮气三次，于氮气保护下加入1-(4-溴苯基)乙醇(0.0689ml,0.5mmol)，亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率38％。1H NMR(400MHz,CDCl3)δ7.44(d,J＝7.9Hz,2H),7.22(dd,J＝8.5,2.3Hz,2H),4.12–3.77(m,4H),3.13(dq,J＝22.5,7.4Hz,1H),1.55(dd,J＝18.3,7.4Hz,3H),1.23(dt,J＝41.7,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ137.19(d,J＝7.0Hz),131.50(d,J＝2.6Hz),130.33(d,J＝6.5Hz),120.96(d,J＝4.2Hz),62.24(dd,J＝51.9,7.1Hz),37.99(d,J＝138.6Hz),16.35(dd,J＝12.3,5.8Hz),15.45(d,J＝5.1Hz).31P NMR(202MHz,CDCl3)δ28.76。
实施例20
(E)-1,3-二苯基-3-丙烯醇和亚磷酸三乙酯合成(E)-1,3-二苯基-3-丙烯基亚膦酸二乙酯
管形反应器中加入(E)-1,3-二苯基-3-丙烯醇(0.1051g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率72％。1H NMR(500MHz,CDCl3)δ7.45(d,J＝7.6Hz,2H),7.35(dd,J＝17.5,7.7Hz,4H),7.31–7.17(m,4H),6.61–6.48(m,2H),4.14–3.90(m,4H),3.87–3.75(m,1H),1.18(dt,J＝68.3,7.1Hz,6H).13C NMR(126MHz,CDCl3)δ136.82(d,J＝2.7Hz),136.05(d,J＝7.3Hz),133.70(d,J＝13.8Hz),129.09(d,J＝7.0Hz),128.68(d,J＝2.1Hz),128.53,127.67,127.27(d,J＝2.9Hz),126.44(d,J＝1.6Hz),124.71(d,J＝9.6Hz),62.70(dd,J＝15.9,7.2Hz),49.45(d,J＝137.3Hz),16.35(dd,J＝23.5,5.8Hz).31P NMR(202MHz,CDCl3)δ24.79。
实施例21
(E)-1-苯基-3-(4-氯苯基)-3-丙烯醇和亚磷酸三乙酯合成(E)-1-苯基-3-(4-氯苯基)-3-丙烯基亚膦酸二乙酯和(E)-1-(4-氯苯基)-3-苯基-3-丙烯基亚膦酸二乙酯
管形反应器中加入(E)-1-苯基-3-(4-氯苯基)-3-丙烯醇(0.1220g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离总收率82％。1H NMR(500MHz,CDCl3)δ7.54–7.16(m,18H),6.51(pd,J＝15.9,6.1Hz,4H),4.16–3.92(m,8H),3.91–3.74(m,2H),1.30–1.07(m,12H).13C NMR(126MHz,CDCl3)δ136.58(d,J＝2.6Hz),135.75(d,J＝7.3Hz),135.30(d,J＝2.6Hz),134.63(d,J＝7.4Hz),134.07(d,J＝13.7Hz),133.32,133.20(d,J＝3.5Hz),132.42(d,J＝13.8Hz),130.40(d,J＝7.0Hz),129.06(d,J＝7.0Hz),128.82(d,J＝2.1Hz),128.72(d,J＝2.1Hz),128.68,128.57,127.83,127.63(d,J＝1.6Hz),127.36(d,J＝2.8Hz),126.43(d,J＝1.4Hz),125.47(d,J＝9.5Hz),124.05(d,J＝9.5Hz),62.94–62.56(m),49.38(d,J＝137.7Hz),48.69(d,J＝138.2Hz),16.16-16.50(m).31P NMR(202MHz,CDCl3)δ24.54(s),24.21。
实施例22
(E)-1-(4-氟苯基)-3-苯基-3-丙烯醇和亚磷酸三乙酯合成(E)-1-(4-氟苯基)-3-苯基-3-丙烯基亚膦酸二乙酯和(E)-1-苯基-3-(4-氟苯基)-3-丙烯基亚膦酸二乙酯
管形反应器中加入(E)-1-(4-氟苯基)-3-苯基-3-丙烯醇(0.1140g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离总收率81％。1H NMR(500MHz,CDCl3)δ7.49–7.18(m,14H),7.01(dt,J＝33.2,8.5Hz,4H),6.62–6.36(m,4H),4.17–3.91(m,8H),3.90–3.74(m,2H),1.26(t,J＝7.0Hz,6H),1.13(dt,J＝14.3,7.0Hz,6H).13CNMR(126MHz,CDCl3)δ163.36,163.05(d,J＝3.2Hz),161.39,161.09(d,J＝3.0Hz),136.65(d,J＝2.5Hz),135.92(d,J＝7.3Hz),133.88(d,J＝13.7Hz),132.98(t,J＝2.9Hz),132.46(d,J＝13.9Hz),131.81(dd,J＝7.2,3.3Hz),130.61(t,J＝7.5Hz),129.05(d,J＝7.0Hz),128.70(d,J＝2.1Hz),128.56,128.05–127.86(m),127.78,127.31(d,J＝2.7Hz),126.42(d,J＝1.4Hz),124.66–124.25(m),115.63(d,J＝2.1Hz),115.50,115.46(d,J＝2.0Hz),115.33,62.90–62.52(m),49.35(d,J＝137.7Hz),48.50(d,J＝138.5Hz),16.48–16.18(m).31P NMR(202MHz,CDCl3)δ24.73,24.55(d,J＝4.5Hz)。
实施例23
(E)-1-(4-甲氧基苯基)-3-苯基-3-丙烯醇和亚磷酸三乙酯合成(E)-1-(4-甲氧基苯基)-3-苯基-3-丙烯基亚膦酸二乙酯和(E)-1-苯基-3-(4-甲氧基苯基)-3-丙烯基亚膦酸二乙酯
管形反应器中加入(E)-1-(4-甲氧基苯基)-3-苯基-3-丙烯醇(0.1201g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离总收率78％。1H NMR(400MHz,CDCl3)δ7.51–7.14(m,1H),6.85(dd,J＝25.9,8.6Hz,1H),6.62–6.30(m,1H),4.14–3.89(m,1H),3.88–3.73(m,1H),1.30–1.08(m,1H).13CNMR(126MHz,CDCl3)δ159.33,158.85(d,J＝2.6Hz),136.88(d,J＝2.6Hz),136.27(d,J＝7.2Hz),133.44(d,J＝13.8Hz),133.13(d,J＝13.9Hz),130.11(d,J＝7.0Hz),129.65(d,J＝2.6Hz),129.05(d,J＝7.0Hz),128.62(d,J＝2.1Hz),128.50,127.88(d,J＝7.5Hz),127.60,127.17(d,J＝2.8Hz),126.41(d,J＝1.4Hz),124.96(d,J＝9.0Hz),122.35(d,J＝9.6Hz),114.14(d,J＝1.9Hz),113.97,62.80–62.52(m),55.24,49.41(d,J＝137.6Hz),48.42(d,J＝138.6Hz),16.52-16.18(m).31P NMR(202MHz,CDCl3)δ25.14,25.07。
实施例24
(E)-1,3-二(4-甲基苯基)-3-丙烯醇和亚磷酸三乙酯合成(E)-1,3-二(4-甲基苯基)-3-丙烯基亚膦酸二乙酯
管形反应器中加入(E)-1,3-二(4-甲基苯基)-3-丙烯醇(0.1191g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率83％。1H NMR(500MHz,CDCl3)δ7.33(d,J＝6.8Hz,2H),7.26(d,J＝7.9Hz,2H),7.14(d,J＝7.7Hz,2H),7.09(d,J＝7.8Hz,2H),6.57–6.40(m,2H),4.13–3.89(m,4H),3.87–3.77(m,1H),2.31(d,J＝7.2Hz,6H),1.19(dt,J＝57.1,7.0Hz,6H).13C NMR(126MHz,CDCl3)δ137.41,136.81(d,J＝3.0Hz),134.14(d,J＝2.5Hz),133.39(d,J＝13.9Hz),133.03(d,J＝7.4Hz),129.34(d,J＝2.0Hz),129.19,128.92(d,J＝7.0Hz),126.33(d,J＝1.1Hz),123.79(d,J＝9.4Hz),62.64(t,J＝7.8Hz),48.99(d,J＝137.4Hz),21.09(d,J＝12.4Hz),16.36(dd,J＝20.6,5.8Hz).31P NMR(202MHz,CDCl3)δ25.15。
实施例25
2-苯基-2-丙醇和亚磷酸三乙酯合成2-苯基-2-丙基亚合成酸二乙酯
管形反应器中加入2-苯基-2-丙醇(0.0681ml,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.2572ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率40％。1H NMR(500MHz,CDCl3)δ7.58–7.52(m,2H),7.33(t,J＝7.7Hz,2H),7.24(td,J＝7.3,1.8Hz,1H),3.98–3.78(m,4H),1.62(d,J＝16.6Hz,6H),1.18(t,J＝7.1Hz,6H).13C NMR(126MHz,CDCl3)δ141.57(d,J＝4.8Hz),127.94(d,J＝2.7Hz),127.71(d,J＝5.3Hz),126.65(d,J＝3.1Hz),62.32(d,J＝7.4Hz),39.13(d,J＝136.6Hz),23.97(d,J＝4.1Hz),16.34(d,J＝5.7Hz).31PNMR(202MHz,CDCl3)δ32.11。
实施例26
1-金刚烷醇和亚磷酸三乙酯合成1-金刚烷基亚膦酸二乙酯
管形反应器中加入1-金刚烷醇(0.0761g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率71％。1H NMR(500MHz,CDCl3)δ4.23–3.98(m,4H),1.98(s,3H),1.90(dd,J＝5.3,3.0Hz,6H),1.80–1.68(m,6H),1.31(t,J＝7.1Hz,6H).13C NMR(126MHz,CDCl3)δ61.57(d,J＝7.3Hz),36.54(d,J＝1.4Hz),35.41(d,J＝4.2Hz),34.81,33.64,27.12(d,J＝12.2Hz),16.52(d,J＝5.6Hz).31PNMR(202MHz,CDCl3)δ32.58。
实施例27
1,3-二苯基-1-丁炔-3-醇和亚磷酸三乙酯合成1,3-二苯基-1-丁炔-3-亚膦酸二乙酯
管形反应器中加入1,3-二苯基-1-丁炔-3-醇(0.1111g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率48％。1H NMR(400MHz,CDCl3)δ7.83–7.73(m,2H),7.50(dd,J＝6.2,2.9Hz,2H),7.42–7.22(m,6H),4.27–3.82(m,4H),1.99(d,J＝16.1Hz,3H),1.24(dt,J＝46.5,7.0Hz,6H).13C NMR(126MHz,CDCl3)δ138.05(d,J＝6.8Hz),131.74(d,J＝3.0Hz),128.29,128.25,128.11,128.09,128.05,127.42(d,J＝3.0Hz),123.16(d,J＝3.6Hz),89.14(d,J＝13.4Hz),85.40(d,J＝8.9Hz),63.84(dd,J＝40.8,7.6Hz),41.77(d,J＝139.3Hz),24.22(d,J＝5.8Hz),16.39(dd,J＝13.3,5.6Hz).31P NMR(202MHz,CDCl3)δ23.21。
实施例28
1-环丙基-1-苯基乙醇和亚磷酸三乙酯合成1-环丙基-1-苯基乙基亚膦酸二乙酯
管形反应器中加入1-环丙基-1-苯基乙醇(0.0811g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三乙酯(0.1715ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率56％。1HNMR(400MHz,CDCl3)δ7.69(d,J＝7.7Hz,1H),7.33(t,J＝7.6Hz,1H),7.24(t,J＝6.9Hz,1H),4.09–3.72(m,2H),1.75–1.59(m,1H),1.29(d,J＝17.1Hz,2H),1.18(dt,J＝24.1,7.0Hz,3H),0.71–0.20(m,2H).13C NMR(126MHz,CDCl3)δ140.68(d,J＝4.0Hz),127.65(d,J＝5.6Hz),127.21(d,J＝2.3Hz),126.06(d,J＝2.8Hz),61.70(dd,J＝13.8,7.4Hz),41.43(d,J＝136.6Hz),15.75(dd,J＝12.3,5.6Hz),15.56(d,J＝2.9Hz),15.28(d,J＝4.4Hz),2.34(d,J＝1.6Hz),-0.04(d,J＝9.9Hz).31P NMR(202MHz,CDCl3)δ31.26。
实施例29
二苯甲醇和亚磷酸三甲酯合成二苯甲基亚膦酸二甲酯
管形反应器中加入二苯甲醇(0.0921g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三甲酯(0.1179ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在80℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率65％。1H NMR(500MHz,CDCl3)δ7.52(d,J＝7.8Hz,4H),7.32(t,J＝7.6Hz,4H),7.27–7.22(m,2H),4.46(d,J＝25.1Hz,1H),3.55(d,J＝10.7Hz,6H).13C NMR(126MHz,CDCl3)δ136.56(d,J＝5.3Hz),129.40(d,J＝8.0Hz),128.67(d,J＝1.1Hz),127.25(d,J＝2.1Hz),53.36(d,J＝7.0Hz),50.90(d,J＝138.3Hz).31P NMR(202MHz,CDCl3)δ27.37。
实施例30
1-(4-甲氧基苯基)乙醇和亚磷酸三异丙酯合成1-(4-甲氧基苯基)乙基亚膦酸二异丙酯
管形反应器中加入1-(4-甲氧基苯基)乙醇(0.0705ml,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三异丙酯(0.3701ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率27％。1H NMR(500MHz,CDCl3)δ7.38–7.15(m,2H),6.85(d,J＝8.4Hz,2H),4.79–4.33(m,2H),3.79(s,3H),3.04(dq,J＝22.3,7.4Hz,1H),1.52(dd,J＝18.4,7.4Hz,3H),1.31–0.93(m,12H).13C NMR(126MHz,CDCl3)δ158.58(d,J＝3.0Hz),130.40(d,J＝6.8Hz),129.75(d,J＝6.7Hz),113.72(d,J＝2.4Hz),70.69(d,J＝7.3Hz),70.04(d,J＝7.5Hz),55.23,38.16(d,J＝140.5Hz),24.21(d,J＝3.2Hz),24.03(d,J＝3.5Hz),23.94(d,J＝5.2Hz),23.45(d,J＝5.5Hz),15.98(d,J＝4.6Hz).31P NMR(202MHz,CDCl3)δ28.26。
实施例31
二苯甲醇和亚磷酸三正丁酯合成二苯甲基亚膦酸二正丁酯
管形反应器中加入二苯甲醇(0.0921g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三正丁酯(0.2706ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率58％。1H NMR(500MHz,CDCl3)δ7.53(d,J＝7.8Hz,4H),7.30(t,J＝7.6Hz,4H),7.22(t,J＝7.2Hz,2H),4.43(d,J＝25.1Hz,1H),3.96–3.70(m,4H),1.48–1.37(m,4H),1.25–1.15(m,4H),0.80(t,J＝7.4Hz,6H).13C NMR(126MHz,CDCl3)δ136.96(d,J＝5.3Hz),129.47(d,J＝8.0Hz),128.52(d,J＝0.8Hz),127.06(d,J＝2.0Hz),66.28(d,J＝7.3Hz),51.34(d,J＝138.3Hz),32.41(d,J＝5.9Hz),18.54,13.48.31P NMR(202MHz,CDCl3)δ24.91。
实施例32
二苯甲醇和甲基二乙氧基膦合成二苯甲基甲基亚膦酸乙酯
管形反应器中加入二苯甲醇(0.0921g,0.5mmol)，抽换氮气三次，于氮气保护下加入甲基二乙氧基膦(0.1513ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率65％。1H NMR(500MHz,CDCl3)δ7.56(dd,J＝22.4,7.1Hz,4H),7.36–7.20(m,6H),4.28(d,J＝16.8Hz,1H),3.97–3.57(m,2H),1.36(d,J＝13.6Hz,3H),1.10(t,J＝7.0Hz,3H).13C NMR(126MHz,CDCl3)δ136.98(d,J＝2.3Hz),136.80(d,J＝6.6Hz),129.57(d,J＝6.5Hz),129.36(d,J＝7.3Hz),128.83(d,J＝0.7Hz),128.63(d,J＝1.1Hz),127.27(d,J＝1.8Hz),127.18(d,J＝1.9Hz),61.19(d,J＝6.9Hz),55.12(d,J＝87.3Hz),16.47(d,J＝5.6Hz),14.53(d,J＝94.6Hz).31P NMR(202MHz,CDCl3)δ50.27。
实施例33
二苯甲醇和二苯基乙氧基膦合成二苯甲基二苯基氧化膦
管形反应器中加入二苯甲醇(0.0921g,0.5mmol)，抽换氮气三次，于氮气保护下加入1,4-二氧六环1ml，二苯基乙氧基膦(0.2160ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在80℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率68％。1H NMR(500MHz,CDCl3)δ7.66–7.57(m,4H),7.49(d,J＝8.0Hz,4H),7.40(td,J＝7.5,1.2Hz,2H),7.32(td,J＝7.5,2.9Hz,4H),7.15(ddd,J＝14.5,11.2,4.0Hz,6H),4.73(d,J＝8.9Hz,1H).13C NMR(126MHz,CDCl3)δ137.19(d,J＝4.7Hz),132.55(d,J＝98.6Hz),131.38(d,J＝4.2Hz),131.33(d,J＝8.7Hz),129.82(d,J＝6.7Hz),128.21(d,J＝11.6Hz),126.93(d,J＝1.5Hz),53.59(d,J＝65.9Hz).31P NMR(202MHz,CDCl3)δ31.10。
实施例34
二苯甲醇和亚磷酸三苯酯合成二苯甲基亚膦酸二苯酯
管形反应器中加入二苯甲醇(0.0921g,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三苯酯(0.2621ml，2.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率78％。1H NMR(500MHz,CDCl3)δ7.61(d,J＝7.7Hz,4H),7.33(t,J＝7.5Hz,4H),7.29–7.24(m,2H),7.18(t,J＝7.8Hz,4H),7.07(t,J＝7.4Hz,2H),6.83(d,J＝8.3Hz,4H),4.81(d,J＝25.5Hz,1H).13C NMR(126MHz,CDCl3)δ150.55(d,J＝9.9Hz),135.81(d,J＝5.2Hz),129.71(d,J＝8.5Hz),129.51,128.84,127.58(d,J＝2.2Hz),124.99,120.59(d,J＝4.3Hz),51.45(d,J＝139.4Hz).31PNMR(202MHz,CDCl3)δ17.86。
实施例35
1-(4-甲氧基苯基)乙醇和亚磷酸三苯酯合成1-(4-甲氧基苯基)乙基亚膦酸二苯酯
管形反应器中加入1-(4-甲氧基苯基)乙醇(0.0705ml,0.5mmol)，抽换氮气三次，于氮气保护下加入亚磷酸三苯酯(0.3931ml，3.0equiv.)，TMSOTf(0.0181ml，20mol％)，然后在100℃,搅拌下反应24h。TLC监测反应完全后，产物用柱色谱分离提纯，分离收率81％。1H NMR(500MHz,CDCl3)δ7.34(dd,J＝8.7,2.2Hz,2H),7.28–7.21(m,2H),7.17(t,J＝7.8Hz,2H),7.07(tt,J＝14.9,7.4Hz,4H),6.87(dd,J＝8.6,2.8Hz,4H),3.75(s,3H),3.51(dq,J＝22.3,7.4Hz,1H),1.75(dd,J＝19.8,7.4Hz,3H).13C NMR(126MHz,CDCl3)δ159.10(d,J＝3.2Hz),150.73(d,J＝9.9Hz),129.99(d,J＝7.0Hz),129.61(d,J＝17.5Hz),128.67(d,J＝7.4Hz),124.92(d,J＝14.5Hz),120.52(dd,J＝14.3,4.3Hz),114.18(d,J＝2.5Hz),55.30,38.01(d,J＝138.7Hz),15.80(d,J＝4.6Hz).31P NMR(202MHz,CDCl3)δ23.24。
以上所揭露的仅为本发明较佳实施例而已，当然不能以此来限定本发明之权利范围，因此依本发明权利要求所作的等同变化，仍属本发明所涵盖的范围。
Claims (8)
1.大位阻烷基取代亚膦酸二酯的制备方法，其特征在于包括以下步骤：以大位阻醇类化合物和亚磷酸三酯为原料，以三氟甲磺酸三甲基硅酯为催化剂，在加热条件下发生阿尔布佐夫反应，直接合成大位阻烷基取代亚膦酸二酯，其反应式为：
其中：R1为各种官能团取代在2-、3-、或4-位的苯基或烷基；
R2为各种官能团取代在2-、3-、或4-位的苯基、其他芳基、直链或支链取代的烷基、烯基或炔基；
R3为氢、各种官能团取代在2-、3-、或4-位的苯基、其他芳基、直链或支链取代的烷基、烯基或炔基；
R4为直链或支链的烷氧基、苯氧基、直链或支链的烷基、苯基；
R5为直链或支链的烷氧基、苯氧基、直链或支链的烷基、苯基；
R6为是直链或支链的烷基、苯基；
所述催化剂的用量为20 mol %。
2.根据权利要求1所述的制备方法，其特征在于：所述反应在有溶剂或无溶剂条件下均可进行。
3.根据权利要求1所述的制备方法，其特征在于：所述反应在空气或惰性气体条件下进行。
4.根据权利要求3所述的制备方法，其特征在于：惰性气体为N2。
5.根据权利要求1所述的制备方法，其特征在于：反应温度为80-120℃。
6.根据权利要求5所述的制备方法，其特征在于：反应温度为100 ℃。
7.根据权利要求1所述的制备方法，其特征在于：反应时间为12-48 小时。
8. 根据权利要求7所述的制备方法，其特征在于：反应时间为24 小时。
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