CN115745718B - 一种δ-羟基取代芳乙腈衍生物的制备方法 - Google Patents
一种δ-羟基取代芳乙腈衍生物的制备方法 Download PDFInfo
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Abstract
本发明公开了一种δ‑羟基取代芳乙腈衍生物的制备方法,具体包括如下步骤:在氩气气氛下,以如式(Mn‑L)所示的P‑N‑P为骨架的钳形三齿配体锰配合物Mn‑L为催化剂,在碱性物质和溶剂中促进如式(II)所示的芳乙腈与如式(III)所示的烯丙醇衍生物的δ‑羟基化反应,反应结束后经分离纯化得到如式(I)所示的δ‑羟基取代芳乙腈衍生物。本发明使用烯丙醇衍生物作为烷基化试剂,无副产物生成,符合原子经济性和环境友好的理念,同时该方法具有使用催化量的碱,反应时间短,反应效率高等优点,式中:R为氢原子、甲基或苄基;Ar为芳基或杂环芳基;R1、R2、R3独立为氢原子、C1~C3烷基、芳基或杂环芳基。
Description
技术领域
本发明属于有机及药物合成技术领域,具体涉及一种δ-羟基取代芳乙腈衍生物的制备方法。
背景技术
传统上获得δ-羟基取代芳乙腈衍生物的方法为光与金属铜协同催化醇的N-烷氧基吡啶盐的官能团化反应,但该方法需要用到昂贵的光敏剂,同时存在反应时间过长,收率不高的缺点。借氢反应是近几年兴起的一种新型偶联策略,可以将活性较低的有机化合物运用到更多的反应中去,并且该反应只产生水、氢气或氨类副产物,对环境污染小,原子利用率高,与当下绿色化学的要求相契合。在借氢领域中,将醇和腈通过形式共轭加成的交叉偶联,是一种有效的、环境友好的长碳链丁腈的合成策略,而通过廉价金属催化,一步构建δ-羟基取代芳乙腈衍生物的方法至今还未报道。因此,通过借氢策略获得δ-羟基取代芳乙腈衍生物意义重大。
发明内容
针对现有技术存在的上述技术问题,本发明的目的在于提供一种通过廉价金属锰复合物催化芳乙腈与烯丙醇衍生物的借氢反应,高效制备δ-羟基取代芳乙腈衍生物的方法。
本发明限定的一种δ-羟基取代芳乙腈衍生物的制备方法,其结构式如式(I)所示,其特征在于所述制备方法包括如下过程:在氩气氛围下,将如式(II)所示的芳乙腈与如式(III)所示的烯丙醇衍生物,Mn-L催化剂、碱性物质及溶剂依次加入到耐压封管中,于90~130℃下反应2~24小时,再减压浓缩除去溶剂,残留物经柱层析分离,得到如式(I)所示的δ-羟基取代芳乙腈衍生物;
具体反应路线如下:
式中:R为氢原子、甲基、苄基;Ar为芳基或杂环芳基;R1、R2、R3独立为氢原子、C1~C3烷基、芳基、杂环芳基。
具体地,碱性物质选自氢氧化钠、氢氧化钾、叔丁醇钾、碳酸钾、碳酸铯中的一种或两种以上混合物;所用的溶剂为甲苯、二甲苯、叔丁醇、叔戊醇中的一种或两种以上混合物。
具体地,式(II)所示的芳乙腈、式(III)所示的烯丙醇衍生物、烯丙醇衍生物、Mn-L催化剂的投料摩尔比为1:1~2:0.05~0.2:0.005~0.02。
进一步地,本发明还限定了Mn-L催化剂在制备δ-羟基取代芳乙腈衍生物中的应用,所述Mn-L催化剂的结构式如下所示:
通过采用上述技术,与现有技术相比,本发明的有益效果如下:本发明采用Mn-L催化剂促进芳乙腈与烯丙醇衍生物的借氢反应,高效制得δ-羟基取代芳乙腈衍生物,反应收率高达94%。与现有技术相比,本发明方法具有原子经济性高、绿色污染小、安全性高、易于工业化等特点,而且该方法可应用于药物阿尼帕米的合成中,大大降低了其成本,适于推广应用。
具体实施方式
以下通过具体的实施例对本发明的内容作进一步的详细说明,但本发明不局限于实施例。
实施例1:5-羟基-2,3-二苯基戊腈(Ⅰa)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、叔丁醇钾(5.6mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应24h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2,3-二苯基戊腈(Ⅰa)82mg,收率:66%。
产物Ⅰa的结构表征:Colorless oil;66%yield,1H NMR(400MHz,CDCl3,ppm):δ7.24–7.30(m,6H),7.09–7.18(m,4H),4.08(m,1H),3.49–3.59(m,1H),3.25–3.43(m,2H),2.03–2.28(m,3H).13C NMR(100MHz,CDCl3,ppm):δ139.3,138.6,134.3,134.3,128.7,128.5,128.5,128.3,128.2,128.1,128.1,127.7,127.6,120.0,119.8,60.1,60.1,47.3,47.1,44.8,44.3,35.7,34.4.HRMS(ESI)m/z calcd for C17H18NO[M+H]+:252.1388,found:252.1384.
实施例2:5-羟基-2,3-二苯基戊腈(Ⅰa)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、肉桂醇(Ⅲa)(67mg,0.5mmol)、催化剂Mn-L(3.2mg,0.005mmol)、叔丁醇钾(5.6mg,0.05mmol)和二甲苯(1mL),在氩气气氛下130℃下反应8h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2,3-二苯基戊腈(Ⅰa)79mg,收率:63%。
实施例3:5-羟基-2,3-二苯基戊腈(Ⅰa)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(6.4mg,0.01mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应2h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2,3-二苯基戊腈(Ⅰa)106mg,收率:85%。
实施例4:5-羟基-2,3-二苯基戊腈(Ⅰa)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(1.6mg,0.0025mmol)、碳酸钾(3.5mg,0.025mmol)和甲苯(1mL),在氩气气氛下110℃下反应12h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2,3-二苯基戊腈(Ⅰa)103mg,收率:82%。
实施例5:5-羟基-2-(4-甲氧基苯基)-3-苯基戊腈(Ⅰb)的制备
在氩气气氛下,往10mL的耐压封管中依次加入4-甲氧基苯乙腈(Ⅱb)(73.5mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸铯(8.2mg,0.025mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2-(4-甲氧基苯基)-3-苯基戊腈(Ⅰb)126mg,收率:90%。
产物Ⅰb的结构表征:Colorless oil;90%yield,1H NMR(400MHz,CDCl3,ppm)δ7.23–7.33(m,3H),7.15(d,J=6.4Hz,2H),7.09(d,J=8.4Hz,2H),6.81(d,J=8.8Hz,2H),3.98(d,J=7.2Hz,1H),3.79(s,3H),3.56–3.61(m,1H),3.35–3.41(m,1H),3.23–3.28(m,1H),2.21–2.31(m,1H),2.06–2.18(m,1H),1.51(s,1H).13C NMR(100MHz,CDCl3,ppm)δ159.3,139.3,129.2,128.7,128.2,127.6,126.3,120.2,114.1,60.2,60.2,55.3,47.4,44.0,34.5.HRMS(ESI)m/z calcd for C18H20NO2[M+H]+:282.1494,found:282.1497.
实施例6:2-(4-氯苯基)-5-羟基-3-苯基戊腈(Ⅰc)的制备
在氩气气氛下,往10mL的耐压封管中依次加入4-氯苯乙腈(Ⅱc)(75.8mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得2-(4-氯苯基)-5-羟基-3-苯基戊腈(Ⅰc)111mg,收率:78%。
产物Ⅰc的结构表征:Colorless oil;78%yield,1H NMR(400MHz,CDCl3,ppm)δ7.25–7.31(m,5H),7.01–7.13(m,4H),4.08(m,1H),3.58–3.70(m,1H),3.35–3.51(m,1H),3.25–3.30(m,1H),2.08–2.17(m,2H),1.66(s,1H).13C NMR(100MHz,CDCl3,ppm)δ138.8,138.1,134.1,132.8,132.8,129.5,129.5,128.9,128.9,128.8,128.6,128.5,128.2,127.8,127.8,119.6,119.3,60.0,60.0,47.3,47.0,44.1,43.6,35.6,34.6.HRMS(ESI)m/zcalcd for C17H17ClNO[M+H]+:286.0998,found:286.0994.
实施例7:2-(4-(叔丁基)苯基)-5-羟基-3-苯基戊腈(Ⅰd)的制备
在氩气气氛下,往10mL的耐压封管中依次加入4-叔丁基苯乙腈(Ⅱd)(86.7mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得2-(4-(叔丁基)苯基)-5-羟基-3-苯基戊腈(Ⅰd)130mg,收率:85%。
产物Ⅰd的结构表征:Colorless oil;85%yield,1H NMR(400MHz,CDCl3,ppm)δ7.28–7.34(m,5H),7.14–7.17(m,2H),7.06–7.09(m,2H),4.05(d,J=7.6Hz,1H),3.58–3.63(m,1H),3.40–3.47(m,1H),3.24–3.30(m,1H),2.01–2.07(m,2H),1.51(s,1H),1.32(s,9H).13CNMR(100MHz,CDCl3,ppm)δ151.3,139.0,131.2,128.6,128.4,127.9,127.7,125.7,119.9,60.3,47.2,44.0,35.6,34.6,31.3.HRMS(ESI)m/zcalcd for C21H26NO[M+H]+:308.2014,found:308.2018.
实施例8:5-羟基-3-苯基-2-(噻吩-2-基)戊腈(Ⅰe)的制备
在氩气气氛下,往10mL的耐压封管中依次加入2-噻吩乙腈(Ⅱe)(61.6mg,0.5mmol)、肉桂醇(Ⅲa)(134mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-3-苯基-2-(噻吩-2-基)戊腈(Ⅰe)105mg,收率:82%。
产物Ⅰe的结构表征:Colorless oil;82%yield,1H NMR(400MHz,CDCl3,ppm)δ7.28–7.32(m,4H),7.13–7.21(m,2H),7.00–7.11(m,1H),6.86–6.90(m,1H),4.20(m,1H),3.58–3.69(m,1H),3.29–3.51(m,2H),2.09–2.27(m,2H),1.60(s,1H).13C NMR(100MHz,CDCl3,ppm)δ139.4,138.7,134.3,134.2,128.8,128.6,128.4,128.1,127.7,126.8,126.8,126.6,126.6,123.6,123.6,119.8,119.5,60.1,60.1,46.5,46.4,40.1,39.5,35.6,34.5.HRMS(ESI)m/z calcd for C15H16NOS[M+H]+:258.0952,found:258.0948.
实施例9:5-羟基-2-苯基-3-(邻甲苯基)戊腈(Ⅰf)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、2-甲基肉桂醇(Ⅲf)(146mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2-苯基-3-(邻甲苯基)戊腈(Ⅰf)100mg,收率:76%。
产物Ⅰf的结构表征:Colorless oil;76%yield,1H NMR(400MHz,CDCl3,ppm)δ7.41–7.44(d,J=7.6Hz,1H),7.29–7.31(m,3H),7.25–7.28(m,1H),7.08–7.20(m,4H),4.03(m,1H),3.67–3.72(m,1H),3.58–3.63(m,1H),3.35–3.41(m,1H),2.01–2.19(m,5H),1.62(s,1H).13C NMR(100MHz,CDCl3,ppm)δ137.6,137.2,134.4,130.5,128.7,128.3,128.2,127.3,126.4,120.0,60.1,44.3,40.9,36.1,19.5.HRMS(ESI)m/z calcd for C18H20NO[M+H]+:266.1545,found:266.1542.
实施例10:5-羟基-3-(2-甲氧基苯基)-2-苯基戊腈(Ⅰg)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、2-甲氧基肉桂醇(Ⅲg)(162mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-3-(2-甲氧基苯基)-2-苯基戊腈(Ⅰg)112mg,收率:80%。
产物Ⅰg的结构表征:Colorless oil;80%yield,1H NMR(400MHz,CDCl3,ppm)δ7.19–7.32(m,7H),6.84–7.01(m,2H),4.19(m,1H),3.67–3.84(m,4H),3.49–3.58(m,1H),3.32–3.39(m,1H),1.93–2.30(m,2H),1.69(s,1H).13C NMR(100MHz,CDCl3,ppm)δ157.5,157.2,135.1,134.5,128.7,128.7,128.6,128.6,138.5,128.4,128.2,128.0,127.9,127.8,127.3,127.2,121.1,120.9,120.4,120.0,111.0,110.8,60.4,55.5,55.5,43.0,42.9,34.5,32.6.HRMS(ESI)m/z calcd for C18H20NO2[M+H]+:282.1494,found:282.1490.
实施例11:5-羟基-3-(4-苯氧基苯基)-2-苯基戊腈(Ⅰh)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、4-苯氧基肉桂醇(Ⅲh)(226mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-3-(4-苯氧基苯基)-2-苯基戊腈(Ⅰh)145mg,收率:85%。
产物Ⅰh的结构表征:Colorless oil;85%yield,1H NMR(400MHz,CDCl3,ppm)δ7.24–7.36(m,6H),7.09–7.18(m,3H),6.87–7.00(m,4H),6.70–6.75(m,1H),4.06(m,1H),3.59–3.68(m,1H),3.37–3.50(m,1H),3.24–3.31(m,1H),2.04–2.34(m,2H),1.53(s,1H).13CNMR(100MHz,CDCl3,ppm)δ157.1,157.0,141.3,140.7,134.2,134.2,130.1,130.0,129.8,129.7,128.8,128.8,128.2,128.1,128.1,123.3,123.2,123.1,122.9,119.6,119.3,119.0,118.7,118.6,118.3,118.2,60.0,47.3,47.0,44.6,44.1,35.7,34.8.HRMS(ESI)m/zcalcd for C23H22NO2[M+H]+:344.1651,found:344.1657.
实施例12:3-(4-氟苯基)-5-羟基-2-苯基戊腈(Ⅰi)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、4-氟肉桂醇(Ⅲi)(152mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得3-(4-氟苯基)-5-羟基-2-苯基戊腈(Ⅰi)104mg,收率:78%。
产物Ⅰi的结构表征:Colorless oil;78%yield,1H NMR(400MHz,CDCl3,ppm)δ7.29–7.31(m,3H),7.04–7.17(m,4H),6.94–7.00(m,2H),4.07(m,1H),3.64–3.76(m,1H),3.43–3.62(m,1H),3.28–3.39(m,1H),2.05–2.31(m,2H),1.65(s,1H).13C NMR(100MHz,CDCl3,ppm)δ163.5,161.0,134.1,134.0,130.1,130.0,129.8,129.7,128.8,128.8,128.2,128.2,128.1,128.1,119.5,115.5,115.3,59.9,59.9,46.5,46.4,44.8,44.3,35.8,34.5.HRMS(ESI)m/z calcd for C17H17FNO[M+H]+:270.1294,found:270.1297.
实施例13:3-(3,5-二甲氧基苯基)-5-羟基-2-苯基戊腈(Ⅰj)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、3,5-二甲氧基肉桂醇(Ⅲj)(194mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得3-(3,5-二甲氧基苯基)-5-羟基-2-苯基戊腈(Ⅰj)133mg,收率:86%。
产物Ⅰj的结构表征:Colorless oil;86%yield,1H NMR(400MHz,CDCl3,ppm)δ7.28–7.32(m,3H),7.14–7.22(m,2H),6.34–6.37(m,1H),6.26–6.31(m,2H)4.05(m,1H),3.72–3.74(d,J=6.8Hz,6H),3.59–3.65(m,1H),3.43–3.50(m,1H),3.18–3.24(m,1H),1.99–2.06(m,2H),1.65(s,1H).13C NMR(100MHz,CDCl3,ppm)δ161.0,160.8,141.8,141.0,134.4,134.3,128.7,128.2,128.1,128.1,128.1,120.0,119.8,106.6,106.3,99.7,99.4,60.1,55.3,55.3,55.3,47.6,47.4,44.6,44.2,35.6,34.3.HRMS(ESI)m/z calcd forC19H22NO3[M+H]+:312.1599,found:312.1595.
实施例14:5-羟基-2,3-二苯基己腈(Ⅰk)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、4-苯基丁烯-3-烯-2-醇(Ⅲk)(148mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、氢氧化钾(4.2mg,0.1mmol)和叔丁醇(1mL),在氩气气氛下110℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2,3-二苯基己腈(Ⅰk)112mg,收率:85%。
产物Ⅰk的结构表征:Colorless oil;85%yield,1H NMR(400MHz,CDCl3,ppm)δ7.28(s,5H),7.10–7.15(d,J=20.0Hz,4H),4.11(m,1H),3.63–3.85(m,1H),3.13–3.23(m,1H),1.98–2.30(m,2H),1.61(s,1H),1.11–1.20(dd,J1=6.8Hz,J2=6.4Hz,3H).13C NMR(100MHz,CDCl3,ppm)δ139.4,138.9,134.2,134.1,128.8,128.7,128.7,128.6,128.5,128.4,128.2,128.1,128.1,128.1,127.7,120.0,119.6,66.3,65.7,48.4,47.4,44.9,43.7,42.1,41.2,23.5,22.9.HRMS(ESI)m/z calcd for C18H20NO[M+H]+:266.1537,found:266.1532.
实施例15:5-羟基-3-甲基-2-苯基戊腈(Ⅰl)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)巴豆醇(58.5mg,0.5mmol)、(Ⅲl)(72mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-3-甲基-2-苯基戊腈(Ⅰl)80mg,收率:85%。
产物Ⅰl的结构表征:Colorless oil;85%yield,1H NMR(400MHz,CDCl3,ppm)δ7.32–7.41(m,5H),3.82–4.01(m,1H),3.60–3.79(m,2H),2.18–2.28(m,1H),1.98(s,1H),1.77–1.86(m,1H),1.45–1.67(m,2H),1.04(dd,J1=6.8Hz,J2=6.4Hz,1H).13C NMR(100MHz,CDCl3,ppm)δ134.8,134.3,128.9,128.9,128.1,128.1,128.0,127.8,127.8,120.1,119.5,60.1,60.1,44.2,43.4,37.5,35.4,35.3,35.1,17.5,15.6.HRMS(ESI)m/zcalcd for C12H16NO[M+H]+:190.1232,found:190.1230.
实施例16:3-(2-羟乙基)-2-苯基己腈(Ⅰm)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、己-2-烯-1-醇(Ⅲm)(72mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得3-(2-羟乙基)-2-苯基己腈(Ⅰm)95mg,收率:94%。
产物Ⅰm的结构表征:Colorless oil;94%yield,1H NMR(400MHz,CDCl3,ppm)δ7.29–7.46(m,5H),7.47(t,J=5.8Hz,2H),7.04(t,J=7.6Hz,2H),7.32(d,J=7.2Hz,1H),3.47–3.80(m,2H),2.13–2.20(m,1H),1.95–2.02(m,1H),1.72(d,J=9.6Hz,3H),1.20–1.61(m,2H),1.02(m,3H).13C NMR(100MHz,CDCl3,ppm)δ140.3,140.2,128.9,128.8,128.8,127.7,127.7,126.0,125.9,122.6,122.4,60.3,60.3,47.6,47.4,39.4,39.2,35.5,34.6,25.2,24.6,15.4,14.7.HRMS(ESI)m/z calcd for C13H18NO[M+H]+:204.1388,found:204.1385.
实施例17:2-苄基-5-羟基-3-甲基-2-苯基戊腈(Ⅰn)的制备
在氩气气氛下,往10mL的耐压封管中依次加入2,3-二苯基丙腈(Ⅱn)(103mg,0.5mmol)、巴豆醇(Ⅲl)(72mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得2-苄基-5-羟基-3-甲基-2-苯基戊腈(Ⅰn)125mg,收率:90%。
产物Ⅰn的结构表征:Colorless oil;90%yield,1H NMR(400MHz,CDCl3,ppm)δ7.25–7.29(m,5H),7.07–7.13(m,3H),6.82–6.87(m,2H),3.75–3.95(m,2H),3.03–3.54(m,2H),2.34–2.51(m,2H),1.68–1.74(m,1H),1.15(m,3H).13C NMR(100MHz,CDCl3,ppm)δ137.4,137.3,135.4,135.3,135.3,130.2,128.6,128.5,128.5,127.8,127.8,127.7,127.6,127.1,127.0,127.0,126.9,120.8,120.7,60.4,60.4,55.4,55.2,44.6,44.1,38.2,37.8,35.6,35.5,15.7,15.4.HRMS(ESI)m/z calcd for C19H22NO[M+H]+:280.1701,found:280.1708.
实施例18:5-羟基-4-甲基-2-苯基戊腈(Ⅰo)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、甲基烯丙醇(Ⅲo)(72mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、氢氧化钠(4.0mg,0.1mmol)和叔戊醇(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-4-甲基-2-苯基戊腈(Ⅰo)83mg,收率:88%。
产物Ⅰo的结构表征:Colorless oil;88%yield,1H NMR(400MHz,CDCl3,ppm)δ7.31–7.42(m,5H),3.92–4.04(m,1H),3.48–3.66(m,2H),1.88–2.22(m,2H),1.61–1.84(m,2H),1.02(m,3H).13C NMR(100MHz,CDCl3,ppm)δ136.2,129.2,128.1,127.3,127.3,121.4,120.8,67.6,67.2,40.1,39.8,35.5,35.3,33.8,33.5,16.9,16.0.HRMS(ESI)m/zcalcd forC12H16NO[M+H]+:190.1232,found:190.1230.
实施例19:5-羟基-2,4-二苯基戊腈(Ⅰp)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、2-苯基丙-2-烯-1-醇(Ⅲp)(134mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2,4-二苯基戊腈(Ⅰp)106mg,收率:85%。
产物Ⅰp的结构表征:Colorless oil;85%yield,1H NMR(400MHz,CDCl3,ppm)δ7.32–7.45(m,7H),7.18–7.27(m,3H),3.70–3.87(m,2H),3.49–3.68(m,1H),2.77–3.25(m,1H),2.09–2.46(m,2H),1.85(s,1H).13C NMR(100MHz,CDCl3,ppm)δ140.2,140.2,140.0,140.0,136.1,135.4,129.2,129.2,129.1,129.0,128.3,128.1,128.0,127.8,127.6,127.5,127.1,121.3,120.4,67.0,66.9,46.9,45.3,38.8,37.8,35.5,34.8.HRMS(ESI)m/zcalcd for C17H18NO[M+H]+:252.1388,found:252.1386.
实施例20:5-(4-氯苯基)-5-羟基-2-苯基戊腈(Ⅰq)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、2-苯基丙-2-烯-1-醇(Ⅲq)(168mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-(4-氯苯基)-5-羟基-2-苯基戊腈(Ⅰq)114mg,收率:80%。
产物Ⅰq的结构表征:Colorless oil;80%yield,1H NMR(400MHz,CDCl3,ppm)δ7.31–7.42(m,9H),4.72–4.77(m,1H),3.83–3.89(m,1H),1.86–2.03(m,4H),1.64(s,1H).13CNMR(100MHz,CDCl3,ppm)δ143.9,135.7,129.1,128.7,128.7,128.1,127.9,127.9,127.3,127.3,125.7,120.7,74.0,73.7,37.3,37.0,36.1,35.8,32.3,31.9.HRMS(ESI)m/z calcdfor C17H17ClNO[M+H]+:286.0998,found:286.0994.
实施例21:5-羟基-2-苯基戊腈(Ⅰr)的制备
在氩气气氛下,往10mL的耐压封管中依次加入苯乙腈(Ⅱa)(58.5mg,0.5mmol)、烯丙醇(Ⅲr)(58mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2-苯基戊腈(Ⅰr)74mg,收率:85%。
产物Ⅰr的结构表征:Colorless oil;85%yield,1H NMR(400MHz,CDCl3,ppm):δ7.34–7.42(m,5H),3.88(t,J=7.4Hz,1H),3.68–3.71(m,2H),2.00–2.06(m,2H),1.86(s,1H),1.70–1.77(m,2H).13C NMR(100.MHz,CDCl3,ppm):δ135.8,129.1,128.1,127.3,120.8,61.8,37.2,32.4,29.8.HRMS(ESI)m/z calcd for C11H14NO[M+H]+:176.1075,found:176.1073.
实施例22:5-羟基-2-甲基-2-苯基戊腈(Ⅰs)的制备
在氩气气氛下,往10mL的耐压封管中依次加入2-苯基丙腈(Ⅱs)(65.6mg,0.5mmol)、烯丙醇(Ⅲr)(58mg,1mmol)、催化剂Mn-L(3.2mg,0.005mmol)、碳酸钾(6.9mg,0.05mmol)和甲苯(1mL),在氩气气氛下90℃下反应4h,反应结束后,减压浓缩回收溶剂,残留物经柱层析分离(正己烷:乙酸乙酯=1:5),制得5-羟基-2-甲基-2-苯基戊腈(Ⅰs)87mg,收率:92%。
Ⅰs的结构表征:Colorless oil;92%yield,1H NMR(400MHz,CDCl3,ppm)δ7.44–7.46(m,2H),7.39(t,J=7.6Hz,2H),7.32(d,J=7.2Hz,1H),3.59(t,J=6.2Hz,2H),2.01–2.07(m,3H),1.73(s,3H),1.67–1.73(m,1H),1.42–1.51(m 1H).13C NMR(100MHz,CDCl3,ppm)δ140.0,129.0,127.8,125.4,123.4,61.9,61.9,42.3,38.5,28.7,27.8.HRMS(ESI)m/zcalcd for C12H16NO[M+H]+:190.1232,found:190.1230.
实施例23:阿尼帕米的制备
1)在氮气保护下,向耐压封管(150mL,配备搅拌棒)中依次加入Mn-L(0.1mmol)、K2CO3(1mmol)、3-甲氧基苯基乙腈(10mmol)、十二烷醇(20mmol)和甲苯(30mL)。混合物在氮气保护下搅拌,回流(油浴温度135℃)反应8小时。反应完全后,蒸发溶剂,使用乙酸乙酯/环己烷(2:98)作为洗脱剂,通过硅胶(100-200目)柱色谱纯化,得到2.67g产物B,收率80%;
2)在氮气保护下,向耐压封管(38mL,配备搅拌棒)中依次加入Mn-L(0.05mmol)、K2CO3(0.5mmol),2-(3-甲氧基苯基)十四碳腈(5mmol)、烯丙醇(7.5mmol)和甲苯(10mL)。混合物在氮气保护下搅拌,回流反应4小时。反应完全后,蒸发溶剂,使用乙酸乙酯/环己烷(20:80)作为洗脱剂,通过硅胶(100-200目)柱色谱纯化得到1.84g产物C,收率67%。
3)在氮气保护下,向圆底烧瓶(配备搅拌棒)中加入2-(3-羟丙基)-2-(3-甲氧基苯基)十四碳腈(0.5mmol,1当量)和甲苯(1mL)。冷却至-5℃后,向该溶液中缓慢滴加PBr3(0.6mmol,1.1当量)并搅拌30分钟。随后将反应混合物加热至室温,在油浴100℃下加热反应2小时。反应完全后,将反应混合物冷却至室温,倒入冰中。使用乙醚(2×10mL)提取所得水溶液,用饱和食盐水洗涤合并的有机层,并用无水Na2SO4干燥。旋蒸除去溶剂,粗产品直接用于下一步。
4)将粗产品(上述)、[2-(3-甲氧基苯基)乙基]甲胺(0.3mmol,1当量)和乙腈(1mL)装入圆底烧瓶中。加入新研磨的无水Na2CO3(0.9mmol),并将反应混合物在油浴80℃下加热反应6小时。反应完全后,旋蒸去除溶剂,将所得粗产品溶解在水(2mL)中,使用乙酸乙酯(3×10mL)提取水溶液,用饱和食盐水洗涤合并的有机层,并用无水Na2SO4干燥。除去溶剂后用DCM/MeOH(95:5)作为洗脱剂,通过硅胶(100-200目)柱色谱纯化得到1.56g阿尼帕米粗,收率58%。
本说明书所述的内容仅仅是对发明构思实现形式的列举,本发明的保护范围不应当被视为仅限于实施例所陈述的具体形式。
Claims (4)
1.一种δ-羟基取代芳乙腈衍生物的制备方法,其特征在于所述制备方法为:在氩气氛围下,以如式(II)所示的芳乙腈与如式(III)所示的烯丙醇衍生物为原料,在Mn-L催化剂、碱性物质存在下,与溶剂一起加入耐压封管中,于90~130 ℃下进行反应2~24小时,反应结束后减压浓缩除去溶剂,残留物经柱层析分离得到如式(I)所示的δ-羟基取代芳乙腈衍生物,溶剂为甲苯、二甲苯、叔丁醇、叔戊醇中的一种或两种以上混合物;
其反应路线如下:
,
式中:R为氢原子、甲基或苄基;Ar为芳基或杂环芳基;R1、R2、R3独立为氢原子、C1~C3烷基、芳基或杂环芳基。
2.根据权利要求1所述的δ-羟基取代芳乙腈衍生物的制备方法,其特征在于碱性物质选自氢氧化钠、氢氧化钾、叔丁醇钾、碳酸钾、碳酸铯中的一种或两种以上混合物。
3. 根据权利要求1所述的δ-羟基取代芳乙腈衍生物的制备方法,其特征在于式(II)所示的芳乙腈、式(III)所示的烯丙醇、碱性物质、Mn-L催化剂的投料摩尔比为1 : 1~2 :0.05~0.2 : 0.005~0.02。
4.一种Mn-L催化剂在制备δ-羟基取代芳乙腈衍生物中的应用,所述Mn-L催化剂的结构式如下所示:
。
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CN104744410A (zh) * | 2015-02-28 | 2015-07-01 | 华东师范大学 | 多取代四氢呋喃衍生物及其合成方法和应用 |
CN110026244A (zh) * | 2019-04-22 | 2019-07-19 | 郑州大学 | 腈的α烷基化反应催化剂及其应用 |
CN111777477A (zh) * | 2019-10-25 | 2020-10-16 | 四川大学 | 一种丁二酸衍生物或3-芳基丙酸的合成方法 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104744410A (zh) * | 2015-02-28 | 2015-07-01 | 华东师范大学 | 多取代四氢呋喃衍生物及其合成方法和应用 |
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CN111777477A (zh) * | 2019-10-25 | 2020-10-16 | 四川大学 | 一种丁二酸衍生物或3-芳基丙酸的合成方法 |
Non-Patent Citations (1)
Title |
---|
Catalytic Formal Conjugate Addition: Direct Synthesis of δ-Hydroxynitriles from Nitriles and Allylic Alcohols;Thiyagarajan等;American Chemical Society;第12卷(第4期);2191-2202 * |
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