CN114907297A - 可见光催化2-炔基芳醚与磺酰氯串联制备苯并二氢呋喃衍生物的方法 - Google Patents
可见光催化2-炔基芳醚与磺酰氯串联制备苯并二氢呋喃衍生物的方法 Download PDFInfo
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
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- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D493/10—Spiro-condensed systems
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Abstract
一种可见光催化2‑炔基芳醚与磺酰氯串联制备苯并二氢呋喃衍生物的方法,是在室温、空气氛围下,将2‑炔基芳醚类化合物和磺酰氯类化合物置于溶剂2‑甲基四氢呋喃和/或四氢呋喃中,在可见光驱动下通过磺酰基化、自由基加成、1,5‑氢迁移、环化反应合成苯并二氢呋喃衍生物。本方法具有反应底物适应范围广泛、简单高效、条件绿色温和且可持续的优点,特别适合于工业化生产。
Description
技术领域
本发明属于有机合成领域,涉及苯并二氢呋喃衍生物的制备,具体涉及一种可见光催化2-炔基芳醚与磺酰氯的串联环化反应制备苯并二氢呋喃衍生物方法。
背景技术
随着不可再生能源日益消耗,新能源尤其是太阳能的开发利用已迫在眉睫。可见光引发的光化学反应因其环境友好性、可无限利用性和安全性,备受学术界和工业界的关注。传统上,外部光催化剂(过渡金属配合物、有机染料或无机半导体)通过吸收可见光并引发后续反应,但因其价格昂贵,回收再利用困难,较难实现工业化生产。近年来,无光催化剂、氧化剂的光化学反应的出现为温和反应条件下的绿色合成带来了新的思路和可能性。然而在无光催化剂、氧化剂条件下,可见光引发的自由基反应仍然非常罕见。因此,为这一很少涉及的领域制定一些有效的战略已经变得非常紧迫。除此之外,常用有机溶剂大多来源于化石资源,不可再生,毒性大。有机合成中绿色溶剂的开发运用已经刻不容缓。近年来,生物质衍生溶剂的出现为绿色化学的发展提供了方向。新一代生物质衍生溶剂-2-甲基四氢呋喃是一种从可再生资源中利用糠醛或乙酰丙酸等基质生产的溶剂,因其具有可用性、可再生性、低毒性、可生物降解性等优点已经成为绿色溶剂。故而,开发可见光催化的无光催化剂、无氧化剂体系下使用2-甲基四氢呋喃作为绿色介质的新策略迫在眉睫。
自由基介导的分子内氢原子转移(HAT)作为一种高度区域选择性和温和的方法来实现远端C(sp3)-H键的功能化,为环状支架的组装提供了一个特殊的机会。但是传统上,这些自由基产生通常依赖于催化剂、氧化剂等的作用,以溶剂作为反应动力引擎的报道较少涉及。此类反应溶剂通常作为氢源,失氢后产生的自由基一类是被催化剂氧化,通过促进催化剂的循环来促进反应进行,另一类是溶剂自由基直接进攻反应物,促进反应物自由基的产生来完成循环。现今,由于碳碳叁键易于接近,可以通过不同自由基加成到碳碳三键键上引发串联反应来获得具有不同价值的产物。随着磺酰基在药物和有机合成的作用愈来愈大,通过磺酰氯加成到炔烃获得磺酰基取代产物也发展了一系列开创性的工作,主要通过以下三种方式:(a)光催化剂催化(b)常温氧化剂氧化(c)高温过渡金属催化。但由于过渡金属昂贵,加入氧化剂后反应条件剧烈,高温反应安全性等问题,给工业化生产带来了较大的困难。
发明内容
本发明目的在于,克服上述现有技术的不足,提供一种绿色高效的可见光催化2-炔基芳醚与磺酰氯串联制备苯并二氢呋喃衍生物的方法,本方法能在温和条件下以较高产率制备目标产物。
为达上述目的,本发明采用的技术方案是:一种可见光催化2-炔基芳醚与磺酰氯串联制备苯并二氢呋喃衍生物的方法,该方法是在室温、空气氛围下,将原料式1所示的2-炔基芳醚类化合物和式2所示的磺酰氯类化合物置于溶剂2-甲基四氢呋喃和/或四氢呋喃中,在可见光驱动下通过磺酰基化、自由基加成、1,5-氢迁移、环化反应合成式I所示的苯并二氢呋喃衍生物,反应式如下:
其中,R1选自氢、C1-C3烷基、卤素或C1-C3酯基;
R2选自氢、C1-C6烷基、C6芳基或醚基;
R3选自氢、C1-C6烷基或醚基;
R4选自取代或未取代的C6-C12芳基或噻吩基。
较佳的,所述R1选自氢、甲基、卤素或甲酸甲酯基;R2选自氢、甲基、乙基、苯基、环戊基、环己基或氧杂环己基;R3选自氢、甲基、乙基、环戊基、环己基或氧杂环己基;R4选自取代或未取代的苯基、萘基或噻吩基,进一步,R4选自苯基、甲基苯基、氰基苯基、硝基苯基、甲氧基苯基、卤素苯基、萘基或噻吩基。
所述可见光波长为465nm;反应初始时2-炔基芳醚类化合物与磺酰氯类化合物的摩尔比为1:1-2,较佳为1:2。
进一步,所述反应的后处理操作为:将反应完成后的反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去乙酸乙酯,将残余物经柱层析分离(石油醚与乙酸乙酯混合洗脱,较好的石油醚/乙酸乙酯=(6-15):1),得到式I所示的苯并二氢呋喃衍生物。
本发明在温和、空气氛围条件下使用蓝色LED,以2-甲基四氢呋喃和/或四氢呋喃作为自由基反应动力引擎,实现2-炔基芳醚的自由基加成与1,5-氢迁移串联环化反应制备系列磺酰基功能化苯并二氢呋喃衍生物。本方法具有反应底物适应范围广泛、简单高效、条件绿色温和且可持续的优点,特别适合于工业化生产。
具体实施方式
以下结合具体实施例,对本发明进行进一步详细的描述,但本发明并不局限于此。
下述实施例中所述实验方法,如无特殊说明,均为常规方法;所述试剂和原料,如无特殊说明,均可以从商业途径获得和/或根据已知的方法制备获得。
实施例1-5为反应条件优化实验。
实施例1
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-1(93%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.84-7.82(m,2H),7.75-7.73(m,2H),7.19-7.12(m,2H),6.84(t,J=7.5Hz,1H),6.72(d,J=8.0Hz,1H),3.72(t,J=6.5Hz,1H),3.47-3.43(m,1H),3.39-3.35(m,1H),1.57(s,3H),1.39(s,3H);13CNMR(126MHz,CDCl3)δ:157.9,138.5,132.9,129.5,129.4,129.2,128.0,124.9,120.6,110.0,88.8,57.5,45.3,28.1,22.8;HRMS m/z(ESI)calcd for C17H18BrO3S([M+H]+)381.0155,found 380.0151。
实施例2
四氢呋喃代替2-甲基四氢呋喃,其余条件同实施例1,得到目标产物I-1的收率为93%。
实施例3
添加2当量额外的NaOAc以考察碱是否有促进作用,其余条件同实施例1,得到目标产物I-1的收率为92%。
实施例4
对溴苯磺酰氯用量为0.24mmol,其余条件同实施例1,得到目标产物I-1的收率为81%。
实施例5
撤除蓝色18W LED(465nm)灯照射并在黑暗环境下反应,其余条件同实施例1,得到目标产物I-1的收率为0%。
由上述实施例1-5可以看出,最佳的反应条件是2-炔基芳醚类化合物与磺酰氯类化合物的摩尔比为1:2,以四氢呋喃和/或2-甲基四氢呋喃作为溶剂,在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射。在获得最佳反应条件的基础上,发明人进一步在该最佳反应条件下,选择不同取代基的2-炔基芳醚类化合物和磺酰氯类化合物为原料以发展高选择性串联环化反应方法。
实施例6
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2b所示的对甲氧基苯磺酰氯(82.7mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-2(94%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.91-7.89(m,2H),7.17-7.12(m,2H),7.07-7.05(m,2H),6.83(t,J=8.0Hz,1H),6.72(d,J=8.0Hz,1H),3.90(s,3H),3.69(t,J=6.0Hz,1H),3.47-3.43(m,1H),3.38-3.34(m,1H),1.56(s,3H),1.38(s,3H);13C NMR(126MHz,CDCl3)δ:164.0,157.9,130.9,130.2,129.1,128.3,124.9,120.5,114.7,109.9,88.9,57.8,55.8,45.6,28.1,22.8.HRMS m/z(ESI)calcd forC18H21O4S([M+H]+)333.1155,found 333.1155。
实施例7
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2c所示的对甲基苯磺酰氯(76.3mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-3(93%yield),表征数据为:1H NMR(400MHz,CDCl3)δ:7.85(d,J=8.0Hz,2H),7.40(d,J=8.0Hz,2H),7.17-7.11(m,2H),6.83(t,J=7.6Hz,1H),6.71(d,J=8.0Hz,1H),3.70(t,J=6.0Hz,1H),3.48-3.43(m,1H),3.39-3.34(m,1H),2.47(s,3H),1.56(s,3H),1.38(s,3H);13C NMR(101MHz,CDCl3)δ:157.9,145.1,136.5,130.2,129.1,128.3,128.0,124.9,120.5,109.9,88.9,57.6,45.5,28.1,22.8,21.7.HRMS m/z(ESI)calcd forC18H21O3S([M+H]+)317.1206,found 317.1206。
实施例8
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2d所示的苯磺酰氯(70.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-4(91%yield),表征数据为:1H NMR(400MHz,CDCl3)δ:7.99-7.97(m,2H),7.72-7.68(m,1H),7.63-7.59(m,2H),7.17-7.11(m,2H),6.83(t,J=7.6Hz,1H),6.71(d,J=8.0Hz,1H),3.73(t,J=6.0Hz,1H),3.50-3.45(m,1H),3.41-3.36(m,1H),1.56(s,3H),1.39(s,3H);13C NMR(101MHz,CDCl3)δ:157.9,139.4,134.1,129.6,129.1,128.2,128.0,124.9,120.5,109.9,88.8,57.5,45.4,28.0,22.8.HRMS m/z(ESI)calcd for C17H19O3S([M+H]+)303.1049,found 303.1049。
实施例9
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2e所示的对氟苯磺酰氯(77.8mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-5(82%yield),表征数据为:1HNMR(400MHz,CDCl3)δ:8.02-7.98(m,2H),7.28(t,J=8.8Hz,2H),7.19-7.12(m,2H),6.84(t,J=7.6Hz,1H),6.72(d,J=8.0Hz,1H),3.73(t,J=6.0Hz,1H),3.49-3.44(m,1H),3.40-3.35(m,1H),1.57(s,3H),1.39(s,3H);13C NMR(101MHz,CDCl3)δ:166.0(d,JC-F=258.1Hz),157.9,135.5(d,JC-F=3.1Hz),130.9(d,JC-F=9.6Hz),129.2,128.1,124.9,120.6,116.9(d,JC-F=22.8Hz),110.0,88.8,57.7,45.4,28.0,22.8;19F NMR(471MHz,CDCl3)δ:-102.7.HRMS m/z(ESI)calcd forC17H18FO3S([M+H]+)321.0955,found 321.0955。
实施例10
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2f所示的对氯苯磺酰氯(84.4mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-6(84%yield,),表征数据为:1H NMR(500MHz,CDCl3)δ:7.92-7.90(m,2H),7.59-7.57(m,2H),7.19-7.12(m,2H),6.84(t,J=7.5Hz,1H),6.72(d,J=8.0Hz,1H),3.73(t,J=6.0Hz,1H),3.47-3.43(m,1H),3.39-3.35(m,1H),1.57(s,3H),1.39(s,3H);13C NMR(126MHz,CDCl3)δ:157.9,140.9,138.0,129.9,129.5,129.2,128.0,124.9,120.6,110.0,88.8,57.6,45.4,28.1,22.8.HRMS m/z(ESI)calcd for C17H18ClO3S([M+H]+)337.0660,found 337.0660。
实施例11
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2g所示的对氰基苯磺酰氯(80.6mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-7(81%yield),表征数据为:1HNMR(500MHz,CDCl3)δ:8.12-8.10(m,2H),7.92-7.91(m,2H),7.19-7.14(m,2H),6.85(t,J=8.0Hz,1H),6.73(d,J=8.0Hz,1H),3.76(t,J=6.5Hz,1H),3.49-3.45(m,1H),3.40-3.36(m,1H),1.58(s,3H),1.41(s,3H);13CNMR(125MHz,CDCl3)δ:158.0,143.7,133.3,129.4,128.7,127.6,124.9,120.6,117.9,116.9,110.1,88.6,57.4,45.2,28.0,22.8.HRMS m/z(ESI)calcd for C18H18NO3S([M+H]+)328.1002,found 328.1002。
实施例12
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2h所示的对硝基苯磺酰氯(88.6mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=12:1),得到目标产物I-8(80%yield),表征数据为:1HNMR(500MHz,CDCl3)δ:8.46-8.45(m,2H),8.20-8.18(m,2H),7.21-7.14(m,2H),6.85(t,J=7.5Hz,1H),6.74(d,J=8.0Hz,1H),3.78(d,J=6.0Hz,1H),3.52-3.47(m,1H),3.43-3.39(m,1H),1.59(s,3H),1.42(s,3H);13CNMR(126MHz,CDCl3)δ:158.0,151.0,145.2,129.5,129.4,127.6,124.9,124.8,120.6,110.2,88.6,57.5,45.1,28.1,22.8;HRMS m/z(ESI)calcd for C17H18NO5S([M+H]+)348.0900,found 348.0908。
实施例13
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2i所示的间氯苯磺酰氯(84.4mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-9(80%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.97(t,J=2.0Hz,1H),7.87-7.85(m,1H),7.68-7.66(m,1H),7.56(t,J=8.0Hz,1H),7.20(d,J=7.5Hz,1H),7.15(t,J=8.0Hz,1H),6.85(t,J=7.5Hz,1H),6.73(d,J=8.0Hz,1H),3.76(t,J=6.5Hz,1H),3.48-3.44(m,1H),3.40-3.36(m,1H),1.58(s,3H),1.40(s,3H);13C NMR(126MHz,CDCl3)δ:157.9,141.3,135.9,134.2,130.9,129.3,128.1,127.9,126.1,124.9,120.6,110.0,88.7,57.6,45.3,28.0,22.8;HRMS m/z(ESI)calcd for C17H18ClO3S([M+H]+)337.0660,found 337.0666。
实施例14
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2j所示的邻氯苯磺酰氯(84.4mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=15:1),得到目标产物I-10(78%yield,),表征数据为:1HNMR(500MHz,CDCl3)δ:8.19(d,J=9.0Hz,1H),7.63-7.59(m,2H),7.53-7.49(m,1H),7.26-7.24(m,1H),7.14(t,J=7.5Hz,1H),6.85(t,J=7.5Hz,1H),6.72(d,J=8.0Hz,1H),3.84-3.79(m,1H),3.75-3.71(m,2H),1.56(s,3H),1.44(s,3H);13C NMR(126MHz,CDCl3)δ:157.9,136.9,135.1,132.6,132.1,131.7,129.2,128.1,127.7,124.9,120.6,110.0,88.9,55.4,45.4,28.1,23.0.HRMS m/z(ESI)calcd for C17H18ClO3S([M+H]+)337.0660,found 337.0660。
实施例15
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol),式2k所示的萘磺酰氯(90.7mg,0.4mmol),2-甲基四氢呋喃(1.0mL),然后将反应器在室温,空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时),反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1)得到目标产物I-11(78%yield);1H NMR(500MHz,CDCl3)δ:8.56(s,1H),8.06-8.01(m,2H),7.96-7.92(m,2H),7.72-7.64(m,2H),7.21(d,J=7.5Hz,1H),7.12(t,J=8.0Hz,1H),6.82(t,J=8.0Hz,1H),6.72(d,J=8.0Hz,1H),3.79(t,J=6.0Hz,1H),3.56-3.52(m,1H),3.48-3.44(m,1H),1.57(s,3H),1.41(s,3H);13C NMR(126MHz,CDCl3)δ:157.9,136.2,135.4,132.2,130.0,129.9,129.6,129.5,129.1,128.2,128.1,128.0,125.0,122.4,120.5,109.9,88.9,57.5,45.5,28.1,22.9.HRMS m/z(ESI)calcd for C21H21O3S([M+H]+)353.1206,found353.1206。
实施例16
向Schlenk瓶中加入式1a所示的1-乙炔基-2-异丙氧基苯(32.0mg,0.2mmol)、式2l所示的噻吩磺酰氯(73.0mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-12(90%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.77-7.76(m,2H),7.20(t,J=4.5Hz,1H),7.16-7.12(m,2H),6.84(t,J=7.5Hz,1H),6.72(d,J=7.5Hz,1H),3.73(t,J=6.0Hz,1H),3.63-3.59(m,1H),3.54-3.50(m,1H),1.57(s,3H),1.40(s,3H);13C NMR(126MHz,CDCl3)δ:157.9,140.3,134.5,134.4,129.2,128.2,128.1,124.8,120.6,110.0,88.8,59.1,45.9,28.1,22.8.HRMS m/z(ESI)calcd for C15H17O3S2([M+H]+)309.0614,found 309.0614。
实施例17
向Schlenk瓶中加入式1b所示的4-甲基-2-乙炔基-1-异丙氧基苯(34.8mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-13(92%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.85-7.83(m,2H),7.76-7.75(m,2H),6.93-6.89(m,2H),6.61(d,J=8.0Hz,1H),3.68(t,J=6.0Hz,1H),3.46-3.42(m,1H),3.38-3.34(m,1H),2.24(s,3H),1.55(s,3H),1.38(s,3H);13C NMR(126MHz,CDCl3)δ:155.8,138.5,132.9,131.7,129.9,129.6,129.4,127.9,125.3,109.6,88.7,57.6,45.5,28.0,22.8,20.8;HRMS m/z(ESI)calcd for C18H20BrO3S([M+H]+)395.0311,found 395.0317。
实施例18
向Schlenk瓶中加入式1c所示的4-氟-2-乙炔基-1-异丙氧基苯(35.6mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-14(82%yield),表征数据为:1HNMR(500MHz,CDCl3)δ:7.84-7.82(m,2H),7.76-7.74(m,2H),7.02-7.00(m,1H),6.84-6.80(m,1H),6.64-6.61(m,1H),3.72(t,J=6.0Hz,1H),3.43-3.39(m,1H),3.34-3.30(m,1H),1.54(s,3H),1.35(s,3H);13C NMR(126MHz,CDCl3)δ157.2(d,JC-F=237.8Hz),154.0,138.4,132.9,129.6,129.5,129.3(d,JC-F=8.6Hz),115.3(d,JC-F=24.1Hz),112.4(d,JC-F=25.5Hz),110.1(d,JC-F=8.3Hz),89.5,57.2,45.5,27.8,22.6.19F NMR(471MHz,CDCl3)δ:-123.3;HRMS m/z(ESI)calcd for C17H17BrFO3S([M+H]+)399.0060found 399.0066。
实施例19
向Schlenk瓶中加入式1d所示的4-氯-2-乙炔基-1-异丙氧基苯(38.9mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-15(86%yield),表征数据为:1HNMR(500MHz,CDCl3)δ:7.84-7.83(m,2H),7.77-7.75(m,2H),7.15(s,1H),7.10-7.08(m,1H),6.64(d,J=8.5Hz,1H),3.73(t,J=6.0Hz,1H),3.43-3.39(m,1H),3.34-3.30(m,1H),1.56(s,3H),1.37(s,3H);13C NMR(126MHz,CDCl3)δ:156.7,138.3,133.0,129.9,129.6,129.5,129.1,125.2(2),111.0,89.8,57.2,45.3,27.8,22.7;HRMS m/z(ESI)calcd for C17H17BrClO3S([M+H]+)414.9765,found 414.9761。
实施例20
向Schlenk瓶中加入式1d所示的3-乙炔基-4-异丙氧基苯甲酸甲酯(43.7mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=6:1),得到目标产物I-16(81%yield),表征数据为:1H NMR(400MHz,CDCl3)δ:7.90-7.84(m,3H),7.78-7.75(m,3H),6.74(d,J=8.4Hz,1H),3.86(s,3H),3.79(t,J=6.0Hz,1H),3.47-3.45(m,2H),1.66(s,3H),1.44(s,3H);13C NMR(101MHz,CDCl3)δ:166.6,162.0,138.3,133.0,132.2,129.6,129.5,128.3,126.5,122.7,109.8,90.9,57.0,52.0,44.9,28.1,22.8;HRMS m/z(ESI)calcd for C19H20BrO5S([M+H]+)439.0209,found439.0205。
实施例21
向Schlenk瓶中加入式1f所示的4-乙炔基-3-异丙氧基苯甲酸甲酯(43.7mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=6:1),得到目标产物I-17(80%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.85-7.83(m,2H),7.77-7.76(m,2H),7.58-7.56(m,1H),7.36(s,1H),7.30(d,J=8.0Hz,1H),3.89(s,3H),3.78(t,J=6.0Hz,1H),3.45-3.41(m,1H),3.38-3.34(m,1H),1.58(s,3H),1.39(s,3H);13C NMR(126MHz,CDCl3)δ:166.7,158.1,138.4,133.5,133.0,131.5,129.6,129.5,124.9,122.5,110.9,89.6,57.1,52.2,45.3,27.9,22.7;HRMS m/z(ESI)calcd for C19H20BrO5S([M+H]+)439.0209,found 439.0213。
实施例22
向Schlenk瓶中加入式1g所示的1-乙炔基-2-异戊氧基苯(37.7mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-18(85%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.84-7.82(m,2H),7.75-7.74(m,2H),7.30(d,J=7.5Hz,1H),7.13(t,J=8.0Hz,1H),6.83(t,J=7.5Hz,1H),6.72(d,J=8.0Hz,1H),3.89(t,J=7.5Hz,1H),3.50-3.46(m,1H),3.36-3.32(m,1H),1.85-1.76(m,2H),1.69-1.61(m,2H),0.94-0.88(m,6H);13C NMR(126MHz,CDCl3)δ:158.3,138.6,132.9,129.6,129.4,129.1,128.8,125.2,120.5,109.6,92.7,57.6,41.9,29.1,26.4,8.0,7.8;HRMS m/z(ESI)calcd for C19H22BrO3S([M+H]+)409.0468,found409.0462。
实施例23
向Schlenk瓶中加入式1h所示的1-乙炔基-2-异丁氧基苯(38.4mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-19(87%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.84-7.82(m,2H),7.74-7.72(m,2H),7.25-7.19(m,1H),7.12(t,J=8.0Hz,1H),6.83(t,J=8.5Hz,1H),6.72(d,J=8.0Hz,1H),3.80-3.74(m,1H),3.50-3.44(m,1H),3.38-3.34(m,1H),1.85-1.81(m,1H),1.72-1.60(m,1H),1.49(s,1.2H),1.33(s,1.8H),1.00-0.95(m,3H);13C NMR(126MHz,CDCl3)δ:158.1(2),138.5,132.9(2),129.6(2),129.4,129.2,129.1,128.5,128.1125.1,124.8,120.5(2),109.9,109.8,91.0,90.6,57.8,56.9,45.9,42.9,33.2,27.9,24.4,20.7,8.1(2);HRMS m/z(ESI)calcd for C18H20BrO3S([M+H]+)395.0311,found395.0315。
实施例24
向Schlenk瓶中加入式1i所示的1-乙炔基-2-苄氧基苯(41.7mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-20(81%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.68-7.62(m,3H),7.39-7.29(m,6H),7.24-7.18(m,1H),7.17-7.11(m,1H),6.98-6.90(m,2H),5.84(s,1H),3.89(t,J=13.5Hz,1H),3.52-3.47(m,1H),3.44-3.36(m,1H);13C NMR(126MHz,CDCl3)δ:159.3,140.3,138.0,132.8,131.8,129.7,129.5,129.2,128.7,128.4,125.9,124.8,121.5,110.0,87.7,60.5,45.3;HRMS m/z(ESI)calcd for C21H18BrO3S([M+H]+)429.0155,found429.0159。
实施例25
向Schlenk瓶中加入式1j所示的1-乙炔基-2-环戊氧基苯(37.3mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=15:1),得到目标产物I-21(90%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.82-7.80(m,2H),7.74-7.72(m,2H),7.20(d,J=7.5Hz,1H),7.12(t,J=8.0Hz,1H),6.83(t,J=7.5Hz,1H),6.71(d,J=8.0Hz,1H),3.85(t,J=6.0Hz,1H),3.49-3.45(m,1H),3.34-3.29(m,1H),2.04(t,J=8.5Hz,1H),1.89-1.76(m,7H);13C NMR(126MHz,CDCl3)δ:157.9,138.7,132.9,129.5,129.3,129.1,129.0,125.0,120.6,110.1,99.8,58.9,42.2,39.0,33.4,23.6,23.0;HRMS m/z(ESI)calcd for C19H20BrO3S([M+H]+)407.0311,found 407.0317。
实施例26
向Schlenk瓶中加入式1k所示的1-乙炔基-2-环己氧基苯(39.9mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-22(88%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.86-7.82(m,2H),7.78-7.74(m,2H),7.26-7.14(m,2H),6.86(t,J=7.0Hz,1H),6.75(d,J=7.5Hz,1H),4.27(t,J=11.0Hz,1H),3.47-3.43(m,1H),3.33-3.28(m,1H),2.27(t,J=12.0Hz,2H),1.93-1.85(m,3H),1.79-1.74(m,2H),1.68-1.57(m,2H),1.29-1.25(m,1H);13C NMR(126MHz,CDCl3)δ:157.5,138.5,133.0,129.6,129.5,129.4,127.2,125.0,120.9,110.2,90.4,56.9,56.5,45.4,41.8,36.0,35.1,21.9;HRMS m/z(ESI)calcd for C20H22BrO3S([M+H]+)421.0468,found 421.0462。
实施例27
向Schlenk瓶中加入式1l所示的3-(2-乙炔基苯氧基)四氢-2H-吡喃(40.5mg,0.2mmol)、式2a所示的对溴苯磺酰氯(102.2mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=15:1),得到目标产物I-23(72%yield),表征数据为:1H NMR(500MHz,CDCl3)δ:7.84-7.80(m,2H),7.75(t,J=9.5Hz,2H),7.35(d,J=7.5Hz,1H),7.17(t,J=7.5Hz,1H),6.92-6.88(m,1H),6.77(d,J=8.0Hz,1H),3.97-3.90(m,2H),3.79-3.74(m,2H),3.59-3.55(m,2H),3.26(d,J=6.5Hz,0.6H),3.24(d,J=6.5Hz,0.4H),2.03-1.95(m,2H),1.79-1.73(m,2H);13C NMR(126MHz,CDCl3)δ:157.3,156.5,138.7,138.4,133.0,132.9,129.7,129.6,129.5,129.4(3),127.4,126.8,125.9,125.6,121.9,121.1,110.6,110.3,93.3,91.5,88.2,88.0,61.2,57.1,56.8,55.7,45.5,44.6,38.2,35.5,35.4,35.3;HRMS m/z(ESI)calcd for C19H20BrO4S([M+H]+)423.0260,found 423.0266。
实施例28
向Schlenk瓶中加入式1m所示的1-乙炔基-2-环戊氧基苯(37.3mg,0.2mmol)、式2a所示的对甲氧基苯磺酰氯(82.6mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时)。反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-24(90%yield),表征数据为:1HNMR(500MHz,CDCl3)δ:7.88-7.87(m,2H),7.18(d,J=7.0Hz,1H),7.11(t,J=8.0Hz,1H),7.05-7.03(m,2H),6.82(t,J=7.5Hz,1H),6.71(d,J=8.0Hz,1H),3.89(s,3H),3.83-3.81(m,1H),3.49-3.45(m,1H),3.33-3.29(m,1H),2.05-2.02(m,1H),1.89-1.76(m,7H);13C NMR(126MHz,CDCl3)δ:163.9,157.9,130.2,129.3,128.9,124.9,120.5,114.7,109.9,99.9,59.2,55.8,42.4,39.0,33.4,23.6,23.0;HRMS m/z(ESI)calcd for C20H23O4S([M+H]+)359.1312,found 359.1318。
实施例29
向Schlenk瓶中加入式1m所示的1-乙炔基-2-环戊氧基苯(37.3mg,0.2mmol)、式2a所示的对甲氧基苯磺酰氯(73.0mg,0.4mmol)和2-甲基四氢呋喃(1.0mL),然后将反应器在室温、空气氛围条件下使用蓝色18W LED(465nm)灯照射搅拌反应,经TLC监测反应进程至原料消失(反应时间为12小时),反应完成后,将反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去溶剂,将残余物经柱层析分离(洗脱溶剂为:石油醚/乙酸乙酯=10:1),得到目标产物I-25(90%yield),表征数据为:1HNMR(500MHz,CDCl3)δ:7.76-7.75(m,2H),7.20-7.16(m,2H),7.13(t,J=8.0Hz,1H),6.83(t,J=8.0Hz,1H),6.72(d,J=8.0Hz,1H),3.85(t,J=6.0Hz,1H),3.65-3.61(m,1H),3.48-3.44(m,1H),2.06-2.03(m,1H),1.89-1.76(m,7H);13C NMR(126MHz,CDCl3)δ:157.9,140.5,134.4,129.1,129.0,128.2,124.9,120.6,110.0,99.8,60.5,42.8,39.0,33.4,23.6,23.0;HRMS m/z(ESI)calcd forC17H19O3S2([M+H]+)335.0770,found 335.0778。
实施例30控制实验研究反应机理
向实施例30的反应(a)中加入2.0当量的四甲基哌啶氮氧化物(TEMPO)或2,6-二叔丁基对甲酚(BHT)作为自由基清除剂,只检测到痕量的目标产物I-3。用2.0当量的(1-环丙基乙烯基)苯作为探针进行自由基钟实验,得到的II-1的收率为78%,并检测到了痕量的目标产物I-3。这些控制实验表明该反应确实经过自由基反应过程。
由此可知,本发明的可能的反应机理可以推导如下式所示:
以上所述实施例仅为本发明的优选实施例,而并非本发明可行实施的穷举。对于本领域技术人员而言,在不背离本发明原理和精神的前提下,对其所作出的任何显而易见的改动,都应当被认为包含在本发明的权利要求保护范围之内。
Claims (10)
2.根据权利要求1所述的方法,其特征在于,所述R1选自氢、甲基、卤素或甲酸甲酯基。
3.根据权利要求1所述的方法,其特征在于,所述R2选自氢、甲基、乙基、苯基、环戊基、环己基或氧杂环己基。
4.根据权利要求1所述的方法,其特征在于,所述R3选自氢、甲基、乙基、环戊基、环己基或氧杂环己基。
5.根据权利要求1所述的方法,其特征在于,所述R4选自取代或未取代的苯基、萘基或噻吩基。
6.根据权利要求5所述的方法,其特征在于,所述R4选自苯基、甲基苯基、氰基苯基、硝基苯基、甲氧基苯基、卤素苯基、萘基或噻吩基。
7.根据权利要求1所述的方法,其特征在于,所述可见光波长为465nm。
8.根据权利要求1所述的方法,其特征在于,所述反应初始时2-炔基芳醚类化合物与磺酰氯类化合物的摩尔比为1:1-2。
9.根据权利要求1-8中任一项所述的方法,其特征在于,所述反应的后处理操作为:将反应完成后的反应液用乙酸乙酯萃取,有机相用无水硫酸钠干燥,过滤并减压浓缩除去乙酸乙酯,将残余物经柱层析分离,得到式I所示的苯并二氢呋喃衍生物。
10.根据权利要求9所述的方法,其特征在于,所述柱层析分离采用乙酸乙酯和石油醚的混合液洗脱。
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