CN112174880B - 一种1,3,4,6-四取代吡啶酮衍生物的制备方法 - Google Patents

一种1,3,4,6-四取代吡啶酮衍生物的制备方法 Download PDF

Info

Publication number
CN112174880B
CN112174880B CN202011101970.2A CN202011101970A CN112174880B CN 112174880 B CN112174880 B CN 112174880B CN 202011101970 A CN202011101970 A CN 202011101970A CN 112174880 B CN112174880 B CN 112174880B
Authority
CN
China
Prior art keywords
derivative
dimethyl
sulfinyl
oxo
imine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN202011101970.2A
Other languages
English (en)
Other versions
CN112174880A (zh
Inventor
程国林
文思
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huaqiao University
Original Assignee
Huaqiao University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huaqiao University filed Critical Huaqiao University
Priority to CN202011101970.2A priority Critical patent/CN112174880B/zh
Publication of CN112174880A publication Critical patent/CN112174880A/zh
Application granted granted Critical
Publication of CN112174880B publication Critical patent/CN112174880B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/70—Sulfur atoms

Abstract

本发明公开了一种1，3，4，6‑四取代吡啶酮衍生物的制备方法，包括如下步骤：(1)将环丙烯酮衍生物、硫叶立德和溶剂混合后，于60‑100℃反应12‑24h；(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；(3)将步骤(2)所得的有机相经干燥、过滤、浓缩和柱层析色谱或薄层色谱，获得所述1，3，4，6‑四取代吡啶酮衍生物。本发明在构建1，3，4，6‑四取代吡啶酮衍生物具有良好的区域选择性；本发明所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强，后处理简便且绿色。

Description

一种1,3,4,6-四取代吡啶酮衍生物的制备方法
技术领域
本发明属于有机合成技术领域，具体涉及一种1,3,4,6-四取代吡啶酮衍生物的制备方法。
背景技术
2-吡啶酮是药物，有机材料和有机聚合物中重要且普遍存在的结构基序。在2-吡啶酮部分的不同位置处连接不同的官能团在多种生物活性天然产物中也很常见。通常，一些取代的2-吡啶酮衍生物用作含N的生物活性杂环的前体，并具有巨大的生物学活性，包括抗癌，抗病毒，抗炎，强心和抗菌活性。因此，取代的2-吡啶酮的有效合成和功能化一直是研究的热点。
发明内容
本发明的目的在于克服现有技术缺陷，提供一种1,3,4,6-四取代吡啶酮衍生物的制备方法。
本发明的反应方程式如下：
Figure GDA0003700693380000011
本发明的技术方案如下：
一种1,3,4,6-四取代吡啶酮衍生物的制备方法，包括如下步骤：
(1)将环丙烯酮衍生物、硫叶立德和溶剂混合后，于60-100℃反应12-24h；
(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相经干燥、过滤、浓缩和柱层析色谱或薄层色谱，获得所述1,3,4,6-四取代吡啶酮衍生物；
上述环丙烯酮衍生物的结构式为
Figure GDA0003700693380000012
其中的R1为氢、烷基、烷氧基、三氟甲基、芳基、卤素、杂环或氰基，X为氧或硫；
上述硫叶立德的结构式为
Figure GDA0003700693380000021
其中的R2为氢、烷基、烷氧基、三氟甲基、芳基、卤素、杂环、氰基，R3为氢、卤素或三氟甲基。
在本发明的一个优选实施方案中，所述卤素为氟、氯或溴。
进一步优选的，所述环丙烯酮衍生物为二苯基环丙烯酮或2,3-二苯基环丙-2-烯-1-硫酮。
进一步优选的，所述硫叶立德为(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(2-氟苯基)丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(间甲苯基)丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺、(Z)-1-溴-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺、(Z)-1-氯-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺或(E)-1-(二甲基(氧代)-λ6-亚磺酰基)-3,3,4,4,4-五氟-N-苯基丁烷-2-亚胺。
在本发明的一个优选实施方案中，所述溶剂为二甲基亚砜、N,N－二甲基甲酰胺、N-甲基-2-吡咯烷酮、1,2-二氯乙烷、甲苯、1,4-二氧六环、四氢呋喃、六氟异丙醇、甲基叔丁基醚、乙腈、水或无溶剂。
在本发明的一个优选实施方案中，所述环丙烯酮衍生物为二苯基环丙烯酮或2,3-二苯基环丙-2-烯-1-硫酮，所述硫叶立德为(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(2-氟苯基)丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(间甲苯基)丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺、(Z)-1-溴-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺、(Z)-1-氯-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺或(E)-1-(二甲基(氧代)-λ6-亚磺酰基)-3,3,4,4,4-五氟-N-苯基丁烷-2-亚胺，所述溶剂为无溶剂。
在本发明的一个优选实施方案中，所述环丙烯酮衍生物和硫叶立德的摩尔比为1-1.5:1-1.5。
进一步优选的，所述环丙烯酮衍生物和硫叶立德的摩尔比为1:1.2。
在本发明的一个优选实施方案中，所述步骤(1)为：将环丙烯酮衍生物、硫叶立德和溶剂混合后，于80-100℃反应24h。
进一步优选的，所述步骤(1)为：将环丙烯酮衍生物、硫叶立德和溶剂混合后，于100℃反应24h。
本发明的有益效果是：
1、本发明在构建1,3,4,6-四取代吡啶酮衍生物具有良好的化学选择性，环丙烯酮衍生物的羰基碳碳键优先发生断裂，而后环丙烯酮衍生物的烯基碳碳键发生断裂。
2、本发明所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强，后处理简便且绿色。
具体实施方式
以下通过具体实施方式对本发明的技术方案进行进一步的说明和描述。
实施例1
1,3,4-三苯基-6-(三氟甲基)吡啶-2(1H)-酮的制备
Figure GDA0003700693380000031
将二苯基环丙烯酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到37.5mg的目标产物，收率为96％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.54–7.45(m,3H),7.34(d,J＝7.4Hz,2H),7.28–7.24(m,3H),7.19(s,7H),6.90(s,1H)；13C NMR(126MHz,Chloroform-d)δ162.68,147.87,138.12,136.79,134.14,133.91,133.84(q,J＝33.2Hz),130.94,129.30,129.00(d,J＝1.9Hz),128.90,128.39,128.36,127.65(d,J＝1.8Hz),119.61(q,J＝274.1Hz),109.12(q,J＝5.7Hz)；HRMS(ESI-TOF)m/z:calcd for C24H17F3NO+:392.1257(M+H)+,found:392.1259.
实施例2
1-(2-氟苯基)-3,4-二苯基-6-(三氟甲基)吡啶-2(1H)-酮的制备
Figure GDA0003700693380000041
将二苯基环丙烯酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(2-氟苯基)丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到37.9mg的目标产物，收率为93％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.47(tdd,J＝7.7,4.9,1.7Hz,1H),7.37(t,J＝7.6Hz,1H),7.29–7.22(m,5H),7.19(s,7H),6.92(s,1H)；13C NMR(126MHz,Chloroform-d)δ161.9,158.5(d,J＝252.3Hz),148.1,137.9,133.9,133.8,133.6(q,J＝33.4Hz),131.5(d,J＝7.9Hz),130.9,130.8,128.9,128.5,128.4,127.7,127.7,124.6,124.5,124.4(d,J＝3.8Hz),119.4(q,J＝273.7Hz),116.3(d,J＝19.6Hz),109.6(q,J＝5.6Hz)；HRMS(ESI-TOF)m/z:calcd forC24H16F4NO+:410.1163(M+H)+,found:410.1160.
实施例3
3,4-二苯基-1-(间-甲苯基)-6-(三氟甲基)吡啶-2(1H)-酮的制备
Figure GDA0003700693380000042
将二苯基环丙烯酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(间甲苯基)丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到36mg的目标产物，收率为89％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.38(t,J＝7.7Hz,1H),7.29–7.24(m,4H),7.21–7.11(m,9H),6.89(s,1H),2.40(s,3H)；13C NMR(126MHz,Chloroform-d)δ162.7,147.8,139.0,138.2,136.7,134.2,133.9(q,J＝33.0Hz),133.9,131.0,130.1,129.5,128.9,128.8,128.4,128.3,127.6,125.9,119.6(q,J＝274.2Hz),109.0(q,J＝5.8Hz),21.2；HRMS(ESI-TOF)m/z:calcd forC25H19F3NO+:406.1413(M+H)+,found:406.1418.
实施例4
3,4-二苯基-6-(三氟甲基)-1-(4-(三氟甲基)苯基)吡啶-2(1H)-酮的制备
Figure GDA0003700693380000051
将二苯基环丙烯酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到43.7mg的目标产物，收率为95％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.78(d,J＝8.1Hz,2H),7.49(d,J＝8.1Hz,2H),7.27(dd,J＝5.1,1.8Hz,3H),7.19(s,7H),6.94(s,1H)；13C NMR(126MHz,Chloroform-d)δ162.4,148.2,140.0,137.8,134.1,133.8,133.3(q,J＝33.3Hz),131.6(q,J＝32.9Hz),130.8,129.8,128.9,128.6,128.4,127.9,127.8,126.3(q,J＝3.7Hz),123.6(q,J＝272.5Hz),119.5(q,J＝273.9Hz),109.6(q,J＝5.6Hz)；HRMS(ESI-TOF)m/z:calcdfor C25H16F6NO+:460.1131(M+H)+,found:460.1130.
实施例5
1-苯乙基-3,4-二苯基-6-(三氟甲基)吡啶-2(1H)-酮的制备
Figure GDA0003700693380000052
将二苯基环丙烯酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到40.5mg的目标产物，收率为97％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.35(d,J＝7.0Hz,2H),7.33(t,J＝7.4Hz,2H),7.28–7.21(m,7H),7.21–7.16(m,2H),7.14–7.08(m,2H),6.85(s,1H),4.33–4.25(m,2H),3.10(dd,J＝10.5,6.3Hz,2H)；13C NMR(126MHz,Chloroform-d)δ162.1,147.4,138.0,138.0,134.6,133.6,133.2(q,J＝33.1Hz),130.7,129.0,128.8,128.6,128.3,127.9,127.7,126.7,120.3(q,J＝273.7Hz),109.5(q,J＝6.1Hz),48.6(d,J＝3.2Hz),34.6；HRMS(ESI-TOF)m/z:calcd for C26H21F3NO+:420.1570(M+H)+,found:420.1571.
实施例6
6-(二氟甲基)-1,3,4-三苯基吡啶-2(1H)-酮的制备
Figure GDA0003700693380000061
将二苯基环丙烯酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于100℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到33.1mg的目标产物，收率为89％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.54(t,J＝7.4Hz,2H),7.49(t,J＝7.3Hz,1H),7.36(d,J＝7.5Hz,2H),7.28–7.22(m,3H),7.18(tt,J＝6.4,2.8Hz,7H),6.81(s,1H),6.14(t,J＝53.6Hz,1H).；13C NMR(126MHz,Chloroform-d)δ162.4,148.8,138.6,138.3(t,J＝25.0Hz),136.2,134.5,132.4(t,J＝1.9Hz),131.0,129.7,129.5,129.0,128.7,128.2,128.2,127.6,127.4,109.0(t,J＝240.9Hz),107.4(t,J＝7.5Hz)；HRMS(ESI-TOF)m/z:calcd for C24H18F2NO+:374.1351(M+H)+,found:374.1354.
实施例7
6-(溴二氟甲基)-1,3,4-三苯基吡啶-2(1H)-酮的制备
Figure GDA0003700693380000062
将二苯基环丙烯酮0.1mmol、(Z)-1-溴-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到38.7mg的目标产物，收率为86％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.54–7.44(m,3H),7.40(d,J＝7.3Hz,2H),7.26(dd,J＝4.9,2.0Hz,3H),7.18(dq,J＝7.3,2.9,2.5Hz,7H),6.85(s,1H)；13CNMR(126MHz,Chloroform-d)δ162.9,147.9,139.5(t,J＝24.9Hz),138.2,136.4,134.2,133.3,131.0,130.0,129.3,128.9,128.7,128.4,128.3,127.6(d,J＝1.7Hz),111.7(t,J＝304.9Hz),107.6(t,J＝8.0Hz)；HRMS(ESI-TOF)m/z:calcd for C24H17BrF2NO+:452.0456(M+H)+,found:452.0453.
实施例8
6-(氯二氟甲基)-1,3,4-三苯基吡啶-2(1H)-酮的制备
Figure GDA0003700693380000071
将二苯基环丙烯酮0.1mmol、(Z)-1-氯-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥，过滤，浓缩,柱层析色谱纯化得到37.4mg的目标产物，收率为92％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.53–7.42(m,3H),7.37(d,J＝7.2Hz,2H),7.28–7.22(m,3H),7.18(tt,J＝7.6,3.2Hz,7H),6.89(s,1H)；13C NMR(126MHz,Chloroform-d)δ162.9,147.9,138.2,138.2(t,J＝27.7Hz),136.6,134.2,133.4,131.0,129.8,129.2,128.9,128.8,128.4,128.3,127.6,121.1(t,J＝290.9Hz),108.0(t,J＝7.6Hz)；HRMS(ESI-TOF)m/z:calcd for C24H17ClF2NO+:408.0961(M+H)+,found:408.0964.
实施例9
6-(全氟乙基)-1,3,4-三苯基吡啶-2(1H)-酮的制备
Figure GDA0003700693380000072
将二苯基环丙烯酮0.1mmol、(E)-1-(二甲基(氧代)-λ6-亚磺酰基)-3,3,4,4,4-五氟-N-苯基丁烷-2-亚胺0.12mmol加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化得到42.6mg的目标产物，收率为97％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.52–7.41(m,3H),7.30(d,J＝7.6Hz,2H),7.29–7.23(m,3H),7.22–7.14(m,7H),6.81(s,1H)；13C NMR(126MHz,Chloroform-d)δ163.0,147.6,138.0,137.3,134.0,134.0,132.4(t,J＝23.5Hz),130.9,129.1,129.0,128.9,128.8,128.5,128.4,127.7,127.6,111.7(t,J＝6.4Hz)；HRMS(ESI-TOF)m/z:calcd for C25H17F5NO+:442.1225(M+H)+,found:442.1222.
实施例10
1,3,4-三苯基-6-(三氟甲基)吡啶-2(1H)-硫酮的制备
Figure GDA0003700693380000081
将2,3-二苯基环丙-2-烯-1-硫酮0.1mmol、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺0.12mmol加入到15mL的反应管中，置于80℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相依次经无水Na2SO4干燥、过滤、浓缩和柱层析色谱纯化23.1mg的目标产物，收率为57％。本实施例制得的目标产物的核磁和高分辨质谱表征如下：1H NMR(500MHz,Chloroform-d)δ7.58–7.47(m,3H),7.30(d,J＝7.6Hz,2H),7.25–7.18(m,7H),7.12(ddd,J＝7.6,5.1,2.2Hz,4H)；13C NMR(126MHz,Chloroform-d)δ187.3,146.8,143.8,140.9,138.3,137.9,137.0(q,J＝33.5Hz),130.3,129.5,129.3,129.0,128.6,128.4,128.2,127.9,127.5,119.3(q,J＝274.4Hz),114.9(q,J＝5.5Hz)；HRMS(ESI-TOF)m/z:calcd for C24H17F3NS+:408.1028(M+H)+,found:408.1027.
以上所述，仅为本发明的较佳实施例而已，故不能依此限定本发明实施的范围，即依本发明专利范围及说明书内容所作的等效变化与修饰，皆应仍属本发明涵盖的范围内。

Claims (5)

1.一种1,3,4,6-四取代吡啶酮衍生物/硫酮衍生物的制备方法，其特征在于：包括如下步骤：
(1)将环丙烯酮衍生物、硫叶立德和溶剂混合后，于60-100℃反应12-24h，该溶剂为无溶剂；
(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相经干燥、过滤、浓缩和柱层析色谱或薄层色谱，获得所述1,3,4,6-四取代吡啶酮衍生物/硫酮衍生物，其结构式为
Figure FDA0003654021960000011
Figure FDA0003654021960000012
上述环丙烯酮衍生物的结构式为
Figure FDA0003654021960000013
其为二苯基环丙烯酮或2,3-二苯基环丙-2-烯-1-硫酮；
上述硫叶立德的结构式为
Figure FDA0003654021960000014
其为(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-苯基丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(2-氟苯基)丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1,1-三氟-N-(间甲苯基)丙烷-2-亚胺、(E)-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺、(Z)-1-溴-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺、(Z)-1-氯-3-(二甲基(氧代)-λ6-亚磺酰基)-1,1-二氟-N-苯基丙烷-2-亚胺或(E)-1-(二甲基(氧代)-λ6-亚磺酰基)-3,3,4,4,4-五氟-N-苯基丁烷-2-亚胺。
2.如权利要求1所述的制备方法，其特征在于：所述环丙烯酮衍生物和硫叶立德的摩尔比为1-1.5:1-1.5。
3.如权利要求2所述的制备方法，其特征在于：所述环丙烯酮衍生物和硫叶立德的摩尔比为1:1.2。
4.如权利要求1至3中任一权利要求所述的制备方法，其特征在于：所述步骤(1)为：将环丙烯酮衍生物、硫叶立德和溶剂混合后，于80-100℃反应24h。
5.如权利要求4所述的制备方法，其特征在于：所述步骤(1)为：将环丙烯酮衍生物、硫叶立德和溶剂混合后，于100℃反应24h。
CN202011101970.2A 2020-10-15 2020-10-15 一种1,3,4,6-四取代吡啶酮衍生物的制备方法 Active CN112174880B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202011101970.2A CN112174880B (zh) 2020-10-15 2020-10-15 一种1,3,4,6-四取代吡啶酮衍生物的制备方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202011101970.2A CN112174880B (zh) 2020-10-15 2020-10-15 一种1,3,4,6-四取代吡啶酮衍生物的制备方法

Publications (2)

Publication Number Publication Date
CN112174880A CN112174880A (zh) 2021-01-05
CN112174880B true CN112174880B (zh) 2022-07-29

Family

ID=73950357

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202011101970.2A Active CN112174880B (zh) 2020-10-15 2020-10-15 一种1,3,4,6-四取代吡啶酮衍生物的制备方法

Country Status (1)

Country Link
CN (1) CN112174880B (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114644578B (zh) * 2022-04-12 2023-05-30 贵州大学 一种氮杂环卡宾催化的含环丙烷骨架烯酮化合物的制备方法及用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109867643A (zh) * 2017-12-01 2019-06-11 中国科学院大连化学物理研究所 一种多取代呋喃衍生物及其合成

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109867643A (zh) * 2017-12-01 2019-06-11 中国科学院大连化学物理研究所 一种多取代呋喃衍生物及其合成

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
基于烯胺酮底物构建杂环化合物的研究;葛百潞;《华侨大学硕士学位论文》;20200610;全文 *
新药TW9186合成工艺的优化研究;李贝贝;《华侨大学硕士学位论文》;20180627;全文 *

Also Published As

Publication number Publication date
CN112174880A (zh) 2021-01-05

Similar Documents

Publication Publication Date Title
CN111675662A (zh) 一种2-三氟甲基取代的喹唑啉酮化合物的制备方法
CN112645958B (zh) 一种手性螺环吡唑啉酮化合物及制备方法
CN107973779A (zh) 一种n-（2-吡啶/嘧啶基）吲哚衍生物的制备方法
CN112174880B (zh) 一种1,3,4,6-四取代吡啶酮衍生物的制备方法
CN112209876B (zh) 一种3-三氟甲基异喹啉酮衍生物的制备方法
CN108586519A (zh) 一种有机硅烷或有机锗烷衍生物的制备方法
CN109535086B (zh) 一种喹喔啉-2(1h)-酮c-3位羧酸酯化合物的合成方法
Duan et al. Convenient one-pot three-component synthesis of trifluoromethylated tetrahydrobenzo [g] chromene derivatives
Bouet et al. Preparation of new axially chiral bridged 2, 2′-bipyridines and pyridyl monooxazolines (pymox). Evaluation in copper (i)-catalyzed enantioselective cyclopropanation
CN110105355B (zh) 一种1,2,3-三唑-[1,5-a]并喹啉类化合物的制备方法
CN109867632B (zh) 一种1,2,3-三唑衍生物及其合成和应用
CN112047879B (zh) 一种铜催化选择性合成卤代芳胺的方法
CN112851691B (zh) 一种手性噁二嗪杂环类化合物及制备方法
EP3613730A1 (en) Method for producing pyridine compound
CN106957254B (zh) 一种3-烷氧基烷基吲哚衍生物及其制备方法和应用
CN111018800B (zh) 一种n2-芳基取代-1,2,4-三嗪衍生物及其合成和应用
CN113429409A (zh) 一种含硫的多取代吲嗪类化合物及其制备方法
CN102718694B (zh) 3-氰基取代吲哚化合物及其合成方法
CN113234015A (zh) 一种3-酰基二氢喹啉衍生物及其制备方法和应用
CN112920129B (zh) 一种1,2,3-三唑-2-氧化物及其制备方法
CN105745210B (zh) 用于制备8‑(4‑氨基苯氧基)‑4h‑吡啶并[2,3‑b]吡嗪‑3‑酮衍生物的方法
Sandaroos et al. Synthesis of 10-aryl-7, 9-dihydro-3 H-furo [3, 4-b] pyrazolo [4, 3-f] quinolin-9-one using supported ionic liquid
CN114315708B (zh) 一种2-磺酰胺基吡啶衍生物的制备方法
CN109879832B (zh) 一种4-烷氧基-2-芳基巯基吗啉-3,5-二酮类化合物及制备方法
CN111138346B (zh) 2-乙基-4,6-二取代吡啶类化合物及其制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant