CN111138325B - 一种(Z)-β-磺酰基烯胺类化合物的制备方法 - Google Patents
一种(Z)-β-磺酰基烯胺类化合物的制备方法 Download PDFInfo
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- 239000012973 diazabicyclooctane Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 12
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims abstract description 10
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- 229940045803 cuprous chloride Drugs 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims description 2
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- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- WOEYXRRXUBAVOU-UHFFFAOYSA-N (cyclobutylideneamino) 4-(trifluoromethyl)benzoate Chemical compound FC(C1=CC=C(C(=O)ON=C2CCC2)C=C1)(F)F WOEYXRRXUBAVOU-UHFFFAOYSA-N 0.000 description 5
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- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
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- 229940127528 Transpeptidase Inhibitors Drugs 0.000 description 1
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- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
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- 238000003379 elimination reaction Methods 0.000 description 1
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000004291 sulphur dioxide Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属有机化学技术领域,具体涉及一种(Z)‑β‑磺酰基烯胺类化合物的制备方法。该类化合物的结构经1H NMR、13C NMR、HRMS、单晶X衍射等方法表征并得以确认。本发明方法是在溶剂中,在铜和配体的存在下,氮杂环丙烯,O‑酰基环酮肟与DABCO·(SO2)2在室温下发生自由基开环和随后的自由基交叉偶联反应,一步快速生成(Z)‑β‑磺酰基烯胺化合物。本发明方法反应简单高效,立体构型单一,副反应少,便于分离提纯,条件温和,底物的适用范围广,原料合成方便,成本较低,可适用于较大规模的制备,具有非常好的应用前景。
Description
技术领域
本发明属于有机化学技术领域,具体涉及一种(Z)-β-磺酰基烯胺类化合物的制备方法。
背景技术
磺酰基片段是一个非常重要的基团,广泛存在于药物分子、农药分子及材料分子当中(M.Bartholow,Top 200Drug of 2011.Pharmacy Times.http://www.pharmacytimes.com/publications/issue/2012/July2012/Top-200-Dru gs-of-2011,accessed on Jan 9,2013;P.S.Santos,M.T.S.Mello,J.Mol.Struc.1988,178,121;El-Hibri,M.J.Weinberg,S.A.In Encyclopedia of Polymer Science and Technology,Ed.Mark,H.F.Wiley:New York,2014,179)。近几年来化学家们不断努力去开发高效绿色的新方法来合成这类化合物。2010年,Willis小组首先使用固体DABCO·(SO2)2作为二氧化硫的来源实现苯磺酰肼的制备,该方法简单高效,避免了气体二氧化硫的使用,满足绿色化学的发展要求(J.Am.Chem.Soc.2010,132,16372)。随后,化学家们对此种通过直接插入二氧化硫合成磺酰类化合物的策略进一步研究,并发表了很多相关文献(for reviews:Org.Chem.Front.2018,5,691;Org.Biomol.Chem.2015,13,1592;electronicEncyclopedia of Reagents for Organic Synthesis,2018;Book:“Sulfur DioxideInsertion Reactions for Organic Synthesis”,Nature Springer:Berlin,2017;Chem.Eur.J.2018,24,1;Chem.Commun.2019,55,1013;Chem.Commun.2018,54,10405;Chem.Commun.2018,54,12561)。
另一方面,烯基砜是一种有用的有机合成中间体。由于其特殊的碳碳不饱和键及碳硫极性键的存在,使得其具有多样的反应性能,从而能够参与众多的化学反应;同时,烯基砜类化合物还具有潜在的生物活性及优良的药物功能。在一些抗癌药物或者具有抗癌活性的药物分子中,烯基砜及其衍生物都是其重要的活性结构部分;在医药、生物领域中酶催化过程的很多抑制剂都具有取代烯基砜结构,例如,半胱氨酸蛋白酶抑制剂、转肽酶抑制剂等。所以,发展合成结构多样性的烯基砜类化合物具有重大意义。目前,合成的烯基砜类化合物大多为三取代结构,而四取代的多官能团烯基砜类化合物的合成还存在很大的挑战。
基于此,本发明选用固体DABCO·(SO2)2作为二氧化硫的来源,同时作为还原剂,利用铜催化氮杂环丙烯和O-酰基环酮肟双开环反应,一步完成四取代的(Z)-β-磺酰基烯胺类化合物的构建,成功在烯基砜的骨架上引入氨基官能团,丰富了烯基砜类化合物的多样性。
发明内容
本发明的目的在于解决现有技术问题的不足,提供一种(Z)-β-磺酰基烯胺类化合物的制备方法。
为了实现上述发明目的,本发明提供以下技术方案:
一种(Z)-β-磺酰基烯胺类化合物的制备方法,所述方法是在溶剂中,铜催化下,氮杂环丙烯、O-酰基环酮肟和DABCO·(SO2)2三组分发生分子间的自由基开环和自由基交叉偶联反应,得到(Z)-β-磺酰基烯胺类化合物,包括如下步骤:
(1)在反应管中加入O-酰基环酮肟、氮杂环丙烯、DABCO·(SO2)2、铜盐和配体,惰性气体保护下,加入溶剂,在一定温度下反应一定时间;
(2)反应结束后,对反应液进行反应后处理,得到(Z)-β-磺酰基烯胺类化合物;
反应式如下所示:
优选的,X为碳原子或氧原子。
优选的,R1为苯基、酰胺基、烷基、酯基或含有供电子基团或吸电子基团的芳香取代基;更优选的,所述含有供电子基团的芳香取代基是对甲基苯基、对甲氧基苯基、对叔丁基苯基、邻甲基苯基、邻甲氧基苯基、间甲基苯基或间甲氧基苯基,所述含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、邻氯苯基、邻氟苯基、邻溴苯基、间氯苯基、间氟苯基或间溴苯基。
优选的,Ar1为苯基、噻吩、呋喃、萘环或含有供电子基团或吸电子基团的芳香取代基;更优选的,所述含有供电子基团的芳香取代基是对甲基苯基、对甲氧基苯基、对叔丁基苯基、邻甲基苯基、邻甲氧基苯基、间甲基苯基或间甲氧基苯基,所述含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、邻氯苯基、邻氟苯基、邻溴苯基、间氯苯基、间氟苯基或间溴苯基。
优选的,Ar2为苯基或者含有供电子基团或吸电子基团的芳香取代基;更优选的,所述含有供电子基团的芳香取代基是对甲基苯基、对叔丁基苯基、邻甲基苯基或间甲基苯基,所述含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、邻氯苯基、邻氟苯基、邻溴苯基、间氯苯基、间氟苯基或间溴苯基。
优选的,所述步骤(1)中O-酰基环酮肟、DABCO·(SO2)2、氮杂环丙烯、铜盐和配体的摩尔比为1:(1-3):(1-3):(0.1-0.5):(0.1-0.5);更优选的,O-酰基环酮肟、DABCO·(SO2)2、氮杂环丙烯、铜盐和配体的摩尔比为1:1.5:1.5:0.2:0.2。
优选的,所述步骤(1)中溶剂为有机溶剂,包括乙腈、N,N-二甲基甲酰胺、二氯甲烷、1,4-二氧六环、1,2-二氯乙烷和2,2'-联吡啶,更优选溶剂为乙腈;所述溶剂用量以O-酰基环酮肟计为0.05-0.2mol/L,更优选的溶剂用量以O-酰基环酮肟计为0.1mol/L。
优选的,所述步骤(1)中铜盐为醋酸亚铜、噻吩-2-甲酸亚铜、碘化亚铜、氧化亚铜、三氟甲磺酸亚铜、三氟醋酸亚铜、溴化亚铜或氯化亚铜,更优选铜盐为醋酸亚铜。
优选的,所述步骤(1)中配体为1,10-菲罗啉、4,7-二甲氧基-1,10-菲咯啉、4,7-二甲基-1,10-菲咯啉、3,4,7,8-四甲基-1,10-菲罗啉、4,4'-二甲基-2,2'-联吡啶、4,4'-二叔丁基-2,2'-联吡啶、2,2'-联吡啶、四甲基乙二胺、N,N'-二甲基乙二胺、4-二甲氨基吡啶或2,6-二叔丁基吡啶,更优选配体为1,10-菲罗啉。
优选的,所述步骤(1)中反应温度为20-80℃,更优选的反应温度为20-50℃,更优选的反应温度为25℃。
优选的,所述步骤(1)中反应时间为2-20h,更优选的反应时间为12h。
优选的,所述步骤(1)中惰性气体为氮气或氩气。
优选的,所述步骤(2)中的反应后处理操作为:反应液用乙酸乙酯稀释,再用饱和碳酸钠水溶液萃取洗涤,有机层用无水硫酸钠干燥,浓缩,柱层析分离得到产物;更优选的,所述柱层析分离采用的流动相为石油醚和乙酸乙酯,石油醚和乙酸乙酯体积比为(3-1):1。
上述反应收率达30-70%。
该类化合物的结构经1H NMR、13C NMR、HRMS、单晶X衍射等方法表征并得以确认。
本发明与现有技术相比,其有益效果主要体现在:本发明提供的(Z)-β-磺酰基烯胺类化合物的制备方法,是利用O-酰基环酮肟在一价铜的还原作用下发生N-O键消除得到亚胺氮自由基,继而四元环开环得到烷基自由基,再与二氧化硫分子结合产生磺酰基自由基,同时,氮杂环丙烯被一价铜单电子还原产生苄基自由基,与体系产生的磺酰基自由基交叉偶合,再经异构化生成(Z)-β-磺酰基烯胺类化合物,反应过程中的二价铜可以被DABCO·(SO2)2还原成一价铜完成催化循环。本发明所述方法具有反应温和高效、立体选择性好、副反应少、便于分离提纯、原料合成方便和成本较低等优点,可适用于较大规模的制备,具有非常好的应用前景。
具体实施方式
下面通过具体实施例对本发明的技术方案作进一步的具体说明。
实施例1:
以O-酰基环酮肟为1当量计,在反应管中依次加入2-(4-氟苯基)-3-苯基-2H-氮杂环丙烯(1.5当量),DABCO·(SO2)2(1.5当量),环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.2mmol),醋酸亚铜(0.2当量)和1,10-菲罗啉(0.2当量),把试管中的空气置换成高纯度氮气后加入2mL乙腈为溶剂,于25℃搅拌12小时,至TLC检测完全反应。反应完后,反应液用EA稀释,用饱和碳酸钠溶液洗涤,随后有机层干燥,浓缩并用石油醚和乙酸乙酯体积比3:1的流动相柱层析分离,以64%收率得到相应四取代的(Z)-β-磺酰基烯胺化合物3a。
1H NMR(400MHz,DMSO):δ(ppm)7.21-7.10(m,9H),6.90(t,J=8.5Hz,2H),3.07-3.00(m,2H),2.66(t,J=7.1Hz,2H),2.10-1.98(m,2H);19F NMR(376MHz,DMSO):δ(ppm)-115.33--115.41(m);13C NMR(101MHz,DMSO):δ(ppm)161.4(1JCF=247.8Hz),158.5,137.7,136.1(1JCF=8.3Hz),131.3,129.2,129.0,128.3,120.4,114.9(1JCF=21.2Hz),99.3,52.3,19.2,15.7;HRMS calcd for C18H18FN2O2S+:345.1068(M+H+),found:345.1075.
实施例2:
以O-酰基环酮肟为1当量计,在反应管中依次加入2-(4-甲氧基苯基)-3-苯基-2H-氮杂环丙烯(3当量),DABCO·(SO2)2(3当量),环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.2mmol),醋酸亚铜(0.5当量)和1,10-菲罗啉(0.5当量),把试管中的空气置换成高纯度氮气后加入5mL乙腈为溶剂,于25℃搅拌20小时,至TLC检测完全反应。反应完后,反应液用EA稀释,用饱和碳酸钠溶液洗涤,随后有机层干燥,浓缩并用石油醚和乙酸乙酯体积比2:1的流动相柱层析分离,以63%收率得到相应四取代的(Z)-β-磺酰基烯胺化合物3b。
1H NMR(400MHz,DMSO):δ(ppm)7.12-7.07(m,9H),6.72(d,J=8.2Hz,2H),3.65(s,3H),3.12–2.96(m,2H),2.65(t,J=7.1Hz,2H),2.14–1.95(m,2H);13C NMR(101MHz,DMSO):δ(ppm)159.8,157.9,135.2,134.0,130.6,129.9,128.1,127.0,120.4,113.5,100.2,55.5,52.4,19.3,15.6;HRMS calcd for C19H21N2O3S+:357.1267(M+H+),found:357.1274.
实施例3:
以O-酰基环酮肟为1当量计,在反应管中依次加入2,3-二苯基-2H-氮杂环丙烯(1当量),DABCO·(SO2)2(1当量),2-(((4-(三氟甲基)苯甲酰基)氧基)亚氨基)-7-氮杂螺[3.5]壬烷-7-羧酸叔丁酯(0.2mmol),醋酸亚铜(0.1当量)和1,10-菲罗啉(0.1当量),把试管中的空气置换成高纯度氮气后加入1mL乙腈为溶剂,于80℃搅拌2小时,至TLC检测完全反应。反应完后,反应液用EA稀释,用饱和碳酸钠溶液洗涤,随后有机层干燥,浓缩并用石油醚和乙酸乙酯体积比1:1的流动相柱层析分离,以62%收率得到相应四取代的(Z)-β-磺酰基烯胺化合物3c。
1H NMR(400MHz,DMSO):δ(ppm)7.26–6.97(m,12H),3.5-3.2(m,6H),2.99(s,2H),1.93-1.73(m,2H),1.59-1.42(m,2H),1.39(s,9H);13C NMR(101MHz,DMSO):δ(ppm)157.3,154.3,137.7,134.9,134.0,129.2,129.1,128.2,127.9,127.0,118.6,104.0,79.2,57.0,35.5,34.0,28.5,25.9;HRMS calcd for C27H34FN3O4S+:518.2084(M+Na+),found:518.2097.
实施例4:
以O-酰基环酮肟为1当量计,在反应管中依次加入2,3-二苯基-2H-氮杂环丙烯(1.2当量),DABCO·(SO2)2(1.0当量),环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.2mmol),碘化亚铜(0.2当量)和1,10-菲罗啉(0.2当量),把试管中的空气置换成高纯度氮气后加入2mL1,4-二氧六环为溶剂,于25℃搅拌12小时,至TLC检测完全反应。反应完后,反应液用EA稀释,用饱和碳酸钠溶液洗涤,随后有机层干燥,浓缩并用石油醚和乙酸乙酯体积比1:1的流动相柱层析分离,以47%收率得到相应四取代的(Z)-β-磺酰基烯胺化合物3d。
1H NMR(400MHz,DMSO):δ(ppm)7.28–6.98(m,12H),3.06–3.00(m,2H),2.66(t,J=7.1Hz,2H),2.06(dd,J=14.7,7.2Hz,2H).13C NMR(101MHz,DMSO):δ(ppm)158.1,137.7,134.8,134.0,129.0,128.9,128.1,127.9,127.1,120.3,100.4,52.3,19.2,15.6.HRMS(ESI)calcd for C18H19N2O2S+:327.1162(M+H+),found:327.1168.
实施例5:
以O-酰基环酮肟为1当量计,在反应管中依次加入2,3-二苯基-2H-氮杂环丙烯(1.5当量),DABCO·(SO2)2(1.5当量),环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.2mmol),氧化亚铜(0.2当量)和2,2'-联吡啶(0.2当量),把试管中的空气置换成高纯度氮气后加入2mL乙腈为溶剂,于20℃搅拌12小时,至TLC检测完全反应。反应完后,反应液用EA稀释,用饱和碳酸钠溶液洗涤,随后有机层干燥,浓缩并用石油醚和乙酸乙酯体积比1:1的流动相柱层析分离,以60%收率得到相应四取代的(Z)-β-磺酰基烯胺化合物3d。
实施例6:
以O-酰基环酮肟为1当量计,在反应管中依次加入2,3-二苯基-2H-氮杂环丙烯(1.5当量),DABCO·(SO2)2(1.5当量),环丁酮O-(4-(三氟甲基)苯甲酰基)肟(0.2mmol),醋酸亚铜(0.2当量)和1,10-菲罗琳(0.2当量),把试管中的空气置换成高纯度氮气后加入2mL乙腈为溶剂,于50℃搅拌8小时,至TLC检测完全反应。反应完后,反应液用EA稀释,用饱和碳酸钠溶液洗涤,随后有机层干燥,浓缩并用石油醚和乙酸乙酯体积比1:1的流动相柱层析分离,以69%收率得到相应四取代的(Z)-β-磺酰基烯胺化合物3d。
以上所述的实施例只是本发明较佳的方案,并非对本发明作任何形式上的限制,在不超出权利要求所记载的技术方案的前提下还有其它的变体及改型。
Claims (9)
1.一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,包括如下步骤:
(1)在反应管中加入O-酰基环酮肟、氮杂环丙烯、DABCO·(SO2)2、铜盐和配体,惰性气体保护下,加入溶剂,在一定温度下发生分子间自由基开环和自由基交叉偶联反应;
(2)反应结束后,对反应液进行反应后处理,得到(Z)-β-磺酰基烯胺类化合物;
反应式如下所示:
其中:
X为碳原子或氧原子;
R1为苯基、酰胺基、烷基、酯基或含有供电子基团或吸电子基团的芳香取代基;
Ar1为苯基、噻吩、呋喃、萘环或含有供电子基团或吸电子基团的芳香取代基;
Ar2为苯基或者含有供电子基团或吸电子基团的芳香取代基;
所述步骤(1)中铜盐为醋酸亚铜、噻吩-2-甲酸亚铜、碘化亚铜、氧化亚铜、三氟甲磺酸亚铜、三氟醋酸亚铜、溴化亚铜或氯化亚铜;
所述步骤(1)中配体为1,10-菲罗啉、4,7-二甲氧基-1,10-菲咯啉、4,7-二甲基-1,10-菲咯啉、3,4,7,8-四甲基-1,10-菲罗啉、4,4'-二甲基-2,2'-联吡啶、4,4'-二叔丁基-2,2'-联吡啶或2,2'-联吡啶。
2.根据权利要求1所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述R1和Ar1中含有供电子基团的芳香取代基是对甲基苯基、对甲氧基苯基、对叔丁基苯基、邻甲基苯基、邻甲氧基苯基、间甲基苯基或间甲氧基苯基,含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、邻氯苯基、邻氟苯基、邻溴苯基、间氯苯基、间氟苯基或间溴苯基;所述Ar2中含有供电子基团的芳香取代基是对甲基苯基、对叔丁基苯基、邻甲基苯基或间甲基苯基,含有吸电子基团的芳香取代基是对氯苯基、对氟苯基、对溴苯基、邻氯苯基、邻氟苯基、邻溴苯基、间氯苯基、间氟苯基或间溴苯基。
3.根据权利要求1所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述步骤(1)中O-酰基环酮肟、DABCO·(SO2)2、氮杂环丙烯、铜盐和配体的摩尔比为1:(1-3):(1-3):(0.1-0.5):(0.1-0.5)。
4.根据权利要求1所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述步骤(1)中溶剂为有机溶剂;所述溶剂用量以O-酰基环酮肟计为0.05-0.2mol/L。
5.根据权利要求4所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述有机溶剂为乙腈、N,N-二甲基甲酰胺、二氯甲烷、1,4-二氧六环、1,2-二氯乙烷和2,2'-联吡啶。
6.根据权利要求1所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述步骤(1)中反应温度为20-80℃,反应时间为2-20h。
7.根据权利要求1-6所述任意一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述步骤(1)中惰性气体为氮气或氩气;所述O-酰基环酮肟、DABCO·(SO2)2、氮杂环丙烯、铜盐和配体的摩尔比为1:1.5:1.5:0.2:0.2;所述铜盐为醋酸亚铜;所述配体为1,10-菲罗啉;所述溶剂为乙腈;所述溶剂用量以O-酰基环酮肟计为0.1mol/L;所述反应温度为25℃,反应时间为12h。
8.根据权利要求1所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述步骤(2)中的反应后处理操作为:反应液用乙酸乙酯稀释,再用饱和碳酸钠水溶液萃取洗涤,有机层用无水硫酸钠干燥,浓缩,柱层析分离得到产物。
9.根据权利要求8所述一种(Z)-β-磺酰基烯胺类化合物的制备方法,其特征在于,所述柱层析分离采用的流动相为石油醚和乙酸乙酯,石油醚和乙酸乙酯体积比为(3-1):1。
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CN106045955B (zh) * | 2016-07-11 | 2019-10-15 | 复旦大学 | 一种3-磺酰基香豆素类化合物的制备方法 |
CN108689901B (zh) * | 2018-05-05 | 2020-04-28 | 西北大学 | 一种氮杂环丙烯类化合物的合成方法 |
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