CN104230835B - 一种合成n‑苯乙烯基恶唑烷‑2‑酮衍生物的方法 - Google Patents
一种合成n‑苯乙烯基恶唑烷‑2‑酮衍生物的方法 Download PDFInfo
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Abstract
本发明属于精细化工产品催化合成技术领域,涉及一种合成N‑苯乙烯基恶唑烷‑2‑酮衍生物的方法,具体如下:将恶唑烷‑2‑酮、苯乙烯类化合物、催化剂、多金属氧酸盐、添加剂和碱在有机溶剂中进行脱氢偶联反应,反应完毕得到如结构1所示结构通式的N‑苯乙烯基恶唑烷‑2‑酮衍生物;所述式1结构通式中,R1、R2、R3、R4、R5均选自下述基团中的任意一种:氢、甲基、乙氧基、叔丁基和乙酰氧基。本发明的有益效果在于:催化剂Pd(OAc)2相对便宜易得,用量少,反应为脱氢偶联反应,符合绿色化学要求。
Description
技术领域
本发明属于精细化工产品催化合成技术领域,涉及一种合成N-苯乙烯基恶唑烷-2-酮衍生物的方法。
背景技术
恶唑烷-2-酮衍生物是一种重要的有机化合物,是宝贵的药物合成中间体。恶唑烷-2-酮衍生物可以用作抗菌药物,可抑制蛋白质合成的起始阶段并很少出现交叉耐药性;手性恶唑烷-2-酮衍生物在过渡金属催化有机合成中作为Evan配体用于不对称合成。因此这一类化合物已经引起众多化学家的兴趣。
N-苯乙烯基恶唑烷-2-酮衍生物是其中一种类型衍生物。目前新的合成方法是利用过渡金属钯催化恶唑烷-2-酮与苯乙烯发生脱氢偶联反应,脱氢偶联反应反应避免了底物预功能化,如预功能化合物卤代烃、卤代芳烃等的制备,因此具有更广泛的底物应用范围和更好的原子经济性。然而,过渡金属催化恶唑烷-2-酮与烯烃的脱氢偶联反应通常需要价格昂贵的催化剂如(NEt3)2PdCl2或(CH3CN)2PdCl2以及过量的终端氧化剂如氯化铜和醋酸铜等(Timokhin V.I.;Anastasi N.R.;Stahl S.S.J.Am.Chem.Soc.2003,125,12996-12997.LiuX.;Hii K.K.Eur.J.Org.Chem.2010,5181-5189);或者添加剧毒物质如hexamethylphosphoric triamide(Hosokawa,T.;Takano M.;Kuroki Y.;MurahashiS.Tetra.Lett.1992,33,6643-6646)。因此具有高效、催化剂体系廉价、实用的新型催化反应体系还需进一步研究和开发。
发明内容
本发明所要解决的技术问题是:提供一种催化剂体系廉价,环保的合成N-苯乙烯基恶唑烷-2-酮衍生物的方法。
为了解决上述技术问题,本发明采用的技术方案为:提供一种合成N-苯乙烯基恶唑烷-2-酮衍生物的方法将恶唑烷-2-酮、苯乙烯类化合物、催化剂、多金属氧酸盐、添加剂和碱在有机溶剂中进行脱氢偶联反应,反应完毕得到如结构1所示结构通式的N-苯乙烯基恶唑烷-2-酮衍生物;
所述式1结构通式中,R1、R2、R3、R4、R5均选自下述基团中的任意一种:氢、甲基、乙氧基、叔丁基和乙酰氧基;
所述催化剂为Pd(OAc)2、PdCl2和Pd(NO3)2中的一种;
所述添加剂为1,4-对苯二酚、1,4-对苯醌和乙酰丙酮中的一种。
本发明的有益效果在于:本发明的合成N-苯乙烯基恶唑烷-2-酮衍生物的方法具有如下优点:1)反应为脱氢偶联反应,反应副产物为水,原子经济性高,符合绿色化学要求;2)催化剂Pd(OAc)2相对便宜易得,用量少,反应在空气气氛中进行,操作简便;3)多金属氧酸盐用量、添加剂用量以及碱的用量少并且无毒;4)催化体系对底物的普适性强,含有各种官能团的苯乙烯衍生物都能高效的进行脱氢偶联反应。
具体实施方式
为详细说明本发明的技术内容、所实现目的及效果,以下结合实施方式予以说明。
本发明最关键的构思在于:采用了便宜易得的催化剂,并且配合使用的多金属氧酸盐,添加剂,碱的用量少无毒,反应在空气气氛中进行,具有条件温和、操作简便、底物范围广等优点。
本发明提供一种合成N-苯乙烯基恶唑烷-2-酮衍生物的方法:在空气气氛中,将恶唑烷-2-酮、苯乙烯类化合物、催化剂、多金属氧酸盐、添加剂和碱在有机溶剂中进行脱氢偶联反应,反应完毕得到结构式1所示N-苯乙烯基恶唑烷-2-酮衍生物;
所述式1结构通式中,R1、R2、R3、R4、R5均选自下述基团中的任意一种:氢、甲基、乙氧基、氰基、叔丁基和乙酰氧基。
所述恶唑烷-2-酮的结构式如结构式2,所述苯乙烯类化合物的结构式如结构式3。
上述制备方法中,所述催化剂选自Pd(OAc)2、PdCl2和Pd(NO3)2中的一种,优选Pd(OAc)2;
所述多金属氧酸盐选自(NH4)4PMo11VO40、(NH4)5H4PMo6V6O40、H4PMo11VO40和H5PMo10V2O40中的一种,优选H5PMo10V2O40;
所述添加剂为1,4-对苯二酚、1,4-对苯醌和乙酰丙酮中的一种,优选1,4-对苯二酚;
所述碱选自NaOAc、Na2CO3、Cs2CO3中的一种,优选NaOAc;
所述溶剂选自N,N-二甲基甲酰胺、乙酸、二氯甲烷、二甲亚砜和1,4二氧六环中的一种,优选N,N-二甲基甲酰胺。
上述制备方法中苯乙烯的用量为恶唑烷-2-酮摩尔用量的100-200%,优选200%。所述催化剂的用量为恶唑烷-2-酮摩尔用量的5-15%,优选5%;所述多金属氧酸盐的用量为恶唑烷-2-酮摩尔用量的0.1-1%,优选0.1%。所述添加剂的用量为恶唑烷-2-酮摩尔用量的5-15%,优选5%。所述碱的用量为恶唑烷-2-酮摩尔用量的5%-20%,优选10%。溶剂的用量无特别限定,只需保证催化剂和恶唑烷-2-酮完全溶解即可。
该脱氢偶联反应的温度为50-80℃,优选60℃,反应时间为16-24小时,优选24小时。该反应的反应器可以选用密封的反应器,如玻璃封管等。
上述合成N-苯乙烯基恶唑烷-2-酮衍生物的方法合成反应结束后,一般还需要经过萃取、洗涤、干燥、浓缩、和柱层析等纯化过程得到产品。所述萃取是以二氯甲烷为萃取剂;洗涤一般是水洗三次;干燥是以无水硫酸镁为干燥剂;浓缩采用的是旋转蒸发方法将溶剂蒸干;柱层析以200-300目硅胶为分离树脂,洗脱剂可以选择石油醚和乙酸乙酯混合液。
上述合成N-苯乙烯基恶唑烷-2-酮衍生物的方法具有以下特点:1)反应为脱氢偶联反应,反应副产物为水,原子经济性高,符合绿色化学要求;2)催化剂Pd(OAc)2相对便宜易得,用量少,反应在空气气氛中进行,操作简便;3)多金属氧酸盐用量、添加剂用量以及碱的用量少并且无毒;4)催化体系对底物的普适性强,含有各种官能团的苯乙烯衍生物都能高效的进行脱氢偶联反应。
实施例1
3-(1-苯基乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R3=R4=R5=H)
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯(Pd(OAc)2),0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮168.9mg。分离产率89%。
3-(1-苯基乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ=7.42–7.33(m,5H),5.28(s,1H),5.23(s,1H),4.42(dd,J=8.5,7.3Hz,2H),3.76(dd,J=8.5,7.3Hz,2H).GCMS m/z(%):189(30)[M]+,144(10),130(22),117(11),103(100),91(20),77(30),51(2).
实施例2
3-(1-(2,4-二甲基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R4=H,R3=R5=甲基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(264mg)2,4-二甲基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(2,4-二甲基苯基)乙烯基)恶唑烷-2-酮184.4mg。分离产率85%。
3-(1-(2,4-二甲基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.09(d,J=7.6Hz,2H),7.03–6.93(m,2H),5.30(s,1H),4.73(s,1H),4.26(t,J=7.9,2H),3.55(t,J=7.9,2H),2.31(s,3H),2.23(s,3H);13C NMR(100MHz,CDCl3)δ154.9,142.5,138.3,135.6,133.6,130.9,129.2,126.5,103,7,61.3,45.5,21.1,19.4.
实施例3
3-(1-(4-甲基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R4=R5=H,R3=甲基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(236mg)4-甲基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(4-甲基苯基)乙烯基)恶唑烷-2-酮150.2mg。分离产率74%。
3-(1-(4-甲基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.26(d,J=8.0Hz,2H),7.15(d,J=8.0Hz,2H),5.18(s,1H),5.16(s,1H),4.35(t,J=8.0Hz,2H),3.71(t,J=8.0Hz,1H),2.34(s,3H);13C NMR(101MHz,CDCl3)δ156.0,143.1,138.7,133.1,129.2,126.6,106.0,61.8,46.5,21.2.GCMS m/z(%):203(57)[M]+,188(33),158(13),144(36),131(12),117(100),105(27),91(46),77(6),65(11),51(9).
实施例4
3-(1-(3-甲基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R3=R5=H,R4=甲基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(236mg)3-甲基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(4-甲基苯基)乙烯基)恶唑烷-2-酮144.1mg。分离产率71%。
3-(1-(4-甲基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.28–7.12(m,4H),5.21(s,1H),5.19(s,1H),4.37(d,J=8.0Hz,2H),3.72(d,J=8.0Hz,2H),2.35(s,3H);13C NMR(100MHz,CDCl3)δ156.0,143.2,138.1,135.9,129.6,128.4,127.4,123.9,106.6,61.8,46.5,21.5.
实施例5
3-(1-(4-甲氧基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R4=R5=H,R3=甲氧基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(268mg)4-甲氧基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(4-甲氧基苯基)乙烯基)恶唑烷-2-酮170.8mg。分离产率78%。
3-(1-(4-甲氧基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.32–7.26(m,2H),6.89–6.84(m,2H),5.16(s,1H),5.15(s,1H),4.42–4.35(m,2H),4.04(q,J=7.0Hz,2H),3.78–3.71(m,2H),1.41(t,J=7.0Hz,3H);13C NMR(101MHz,CDCl3)δ159.6,156.2,142.8,128.2,128.1,114.5,105.7,63.7,61.9,46.7,14.9.
实施例6
3-(1-(2,4,6-三甲氧基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R2=R4=H,R1=R3=R5=甲基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(292mg)2,4,6-三甲基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(2,4,6-三甲氧基苯基)乙烯基)恶唑烷-2-酮76.2mg。分离产率33%。
3-(1-(2,4,6-三甲氧基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ=6.86(s,2H),5.45(s,1H),4.59(s,1H),4.27(t,J=8.0,2H),3.52(t,J=8.0,2H),2.27(s,3H),2.23(s,6H);13C NMR(100MHz,CDCl3)δ154.8,140.1,137.9,136.2,133.3,128.3,102.0,61.2,45.1,21.2,20.0.
实施例7
3-(1-(4-叔丁基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R4=R5=H,R3=叔丁基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(320mg)4-叔丁基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(4-叔丁基苯基)乙烯基)恶唑烷-2-酮196.0mg。分离产率80%。
3-(1-(4-叔丁基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.39–7.34(m,2H),7.33–7.27(m,2H),5.21(s,1H),5.20(s,1H),4.38–4.30(m,2H),3.74–3.67(m,2H),1.31(s,9H);13C NMR(101MHz,CDCl3)δ156.0,151.8,142.9,132.9,126.3,125.3,106.3,61.8,46.5,34.6,31.3.GCMS m/z(%):245(44)[M]+,230(100),188(15),159(7),145(30),128(41),117(54).103(22),91(31),51(9).
实施例8
3-(1-(4-溴苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R4=R5=H,R3=氰基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(364mg)4-溴苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(3:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-(4-溴苯基)乙烯基)恶唑烷-2-酮61.4mg。分离产率23%。
3-(1-(4-溴苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.49(d,J=8.5Hz,2H),7.25(d,J=8.5Hz,2H),5.19(s,1H),5.17(s,1H),4.42(t,J=7.8,2H),3.77(t,J=7.8,2H);13C NMR(100MHz,CDCl3)δ155.8,142.61,135.1,131.8,128.6,123.1,106.7,61.9,46.6.
实施例9
3-(1-(4-乙酰氧基苯基)乙烯基)恶唑烷-2-酮的合成(结构式I中R1=R2=R4=R5=H,R3=乙酰氧基):
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(324mg)4-乙酰氧基苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(3:1)柱分离(200-300目硅胶),得到纯度大于99%的9、3-(1-(4-乙酰氧基苯基)乙烯基)恶唑烷-2-酮158.1mg。分离产率64%。
9、3-(1-(4-乙酰氧基苯基)乙烯基)恶唑烷-2-酮的核磁共振数据:1H NMR(400MHz,CDCl3)δ7.38(d,J=8.4Hz,2H),7.08(d,J=8.4Hz,2H),5.22(s,1H),5.19(s,1H),4.38(t,J=7.8,2H),3.74(t,J=7.8,2H),2.29(s,3H);13C NMR(100MHz,CDCl3)δ169.4,156.0,151.1,142.4,133.6,127.9,121.7,107.0,61.9,46.5,21.2.
对比例1
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H4PMo10VO40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮126.6mg。分离产率67%。
对比例2
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.9mg)(NH4)4PMo11VO40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮9.4mg。分离产率5%。
对比例3
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.6mg)(NH4)5H4PMo6V6O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮68.0mg。分离产率36%。
对比例4
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(8.8mg)氯化钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮41.6mg。分离产率22%。
对比例5
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.5mg)硝酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮7.5mg。分离产率4%。
对比例6
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(10.6mg)Na2CO3,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮90.7mg。分离产率48%。
对比例7
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(32.5mg)Cs2CO3,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮143.6mg。分离产率76%。
对比例8
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(13.8mg)K2CO3,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮105.8mg。分离产率56%。
对比例9
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.4mg)1,4-对苯醌,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮77.5mg。分离产率41%。
对比例10
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.0mg)乙酰丙酮,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮34.0mg。分离产率18%。
对比例11
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL二甲亚砜溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮73.7mg。分离产率39%。
对比例12
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL1,4-二氧六环溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮0mg。分离产率0%。
对比例13
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL二氯甲烷溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮77.5mg。分离产率41%。
对比例14
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL乙酸溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在60℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮86.9mg。分离产率46%。
对比例15
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在50℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮151.2mg。分离产率80%。
对比例16
向25ml的Schlenk反应管中加入1.0mmol(87.1mg)恶唑烷-2-酮,0.05mmol(11.2mg)醋酸钯,0.001mmol(1.7mg)H5PMo10V2O40,0.05mmol(5.6mg)1,4-对苯二酚,0.1mmol(8.2mg)NaOAc,再加入1mL N,N-二甲基甲酰胺溶剂,然后用移液枪量取2.0mmol(208mg)苯乙烯,在70℃的油浴中反应24小时,反应结束后,所得产物先采用简易柱层析装置,用二氯甲烷洗脱产物,再用蒸馏水洗涤三次,加入无水硫酸镁干燥,过滤,滤液旋转蒸发浓缩得到粗产物。粗产物用石油醚和乙酸乙酯做洗脱剂(5:1)柱分离(200-300目硅胶),得到纯度大于99%的3-(1-苯基乙烯基)恶唑烷-2-酮141.7mg。分离产率75%。
以上所述仅为本发明的实施例,并非因此限制本发明的专利范围,凡是利用本发明说明书内容所作的等同变换,或直接或间接运用在相关的技术领域,均同理包括在本发明的专利保护范围内。
Claims (4)
1.一种合成式1所示N-苯乙烯基恶唑烷-2-酮衍生物的方法,其特征在于,将恶唑烷-2-酮、式3所示苯乙烯类化合物、催化剂、多金属氧酸盐、添加剂和碱在有机溶剂中进行脱氢偶联反应,反应完毕得到式1所示N-苯乙烯基恶唑烷-2-酮衍生物;
所述式1、式3结构中R1、R2、R3、R4、R5中任一个为甲基、乙氧基、叔丁基、其余均为氢;或R1、R3为甲基,R2、R4、R5为氢;
所述催化剂为Pd(OAc);
所述添加剂为1,4-对苯二酚;
所述多金属氧酸盐为H5PMo10V2O40;
所述碱选为NaOAc;
所述有机溶剂选自N,N-二甲基甲酰胺;
所述制备方法中苯乙烯类化合物的用量为恶唑烷-2-酮摩尔用量的100-200%,所述催化剂的用量为恶唑烷-2-酮摩尔用量的5-15%;所述多金属氧酸盐的用量为恶唑烷-2-酮摩尔用量的0.1-1%;所述添加剂的用量为恶唑烷-2-酮摩尔用量的5-15%;所述碱的用量为恶唑烷-2-酮摩尔用量的5%-20%,溶剂的用量无特别限定,只需保证催化剂和恶唑烷-2-酮完全溶解即可。
2.根据权利要求1所述的合成式1所示N-苯乙烯基恶唑烷-2-酮衍生物的方法,其特征在于,所述脱氢偶联反应的温度为50-80℃,反应时间为16-24小时。
3.根据权利要求1所述的合成式1所示N-苯乙烯基恶唑烷-2-酮衍生物的方法,其特征在于,所述脱氢偶联反应结束后,依次进行萃取、洗涤、干燥、浓缩和柱层析纯化。
4.根据权利要求3所述的合成式1所示N-苯乙烯基恶唑烷-2-酮衍生物的方法,其特征在于,所述萃取是以二氯甲烷为萃取剂;所述洗涤是水洗三次;所述干燥是以无水硫酸镁为干燥剂;所述浓缩采用的是旋转蒸发方法将溶剂蒸干;所述柱层析以200-300目硅胶为分离树脂,所述柱层析的洗脱剂为石油醚和乙酸乙酯混合液。
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