CN107286181B - 芳基恶嗪并咪唑硫酮类化合物及制备方法 - Google Patents
芳基恶嗪并咪唑硫酮类化合物及制备方法 Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
本发明公开了一种芳基恶嗪并咪唑硫酮类化合物，具体为5H‑苯并[d]咪唑并[5,1‑b][1,3]恶嗪‑1(2H)‑硫酮类化合物；在酸性条件下，将邻氨基芳基甲醇与2,2‑二羟基‑1‑芳基乙酮、硫氰酸钾反应合成。本发明提供的制备方法具有反应条件温和，操作简单，时效快，无需金属催化剂，原料易得，能同时引入多个取代基，产物易分离等优点，且反应收率高，大部分产物的分离收率在80％以上，适用范围广。其结构式为：
Description
技术领域
本发明属化合物的合成方法，主要涉及芳基恶嗪并咪唑硫酮类化合物及制备方法，具体涉及5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物及其制备方法。
背景技术
多组分反应是近年来化学及相关领域研究和应用都非常广泛的合成技术，也是实现多样导向性合成的主要途径之一。本申请是以邻氨基芳基甲醇类化合物为起始原料，发展新的多组分反应来合成具有天然产物或药物/先导化合物分子中的杂环骨架衍生物。
目前以邻氨基芳基甲醇类化合物为起始原料构建杂环骨架的方法如下：
式一(Adv.Synth.Catal.,2017,359,1202)
式二(Org.Lett.,2017,DOI:10.1021/acs.orglett.7b01081)
式一和式二均以邻氨基芳基甲醇类化合物为起始原料，分别与腈类化合物发生关环反应得到杂环骨架类衍生物。但是这两类反应均需要有金属/配体催化(Ru3(CO)12/BINAP)，同时这两类反应的条件比较苛刻，需要高温，N2保护条件下进行，而且反应时间长，收率不高。
发明内容
本发明的目的是提供一种芳基恶嗪并咪唑硫酮类化合物，具体为5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物，本发明其结构式为：
其中：
R1为氢、甲基、甲氧基、各种卤素，其中卤素包括氟、氯、溴；
R2为氢、甲基；R3为取代的苯基、脂肪烃、萘基或者噻吩基，其中苯基上的取代基包括甲基、三氟甲基、硝基、氟、氯、甲氧基、N,N-二甲基。
本发明提供的芳基恶嗪并咪唑硫酮类化合物，选自如下任意一种：
3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例1)
3-苯基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例3)
3-(对三氟甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例4)
3-(萘-2-基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例5)
3-(对硝基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例6)
3-(对氟苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例7)
3-(对氯苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例8)
3-(间甲氧基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例9)
3-(邻氯苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例10)
3-(噻吩-2-基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例11)
3-(4-(二甲基氨基)苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例12)
3-叔丁基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例13)
9-甲基-3-苯基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例14)
5-甲基-3-对甲基苯基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例15)
6-氯-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例16)
7-溴-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例17)
7,8-二甲氧基-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例18)
8-氟-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例19)
8-氯-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮(实施例20)
本发明还同时提供了上述的5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物的制备方法，通过以下步骤实现：
(1)将邻氨基芳基甲醇化合物、2,2-二羟基-1-芳基乙酮、硫氰酸钾、三氟醋酸溶解在非质子溶剂中，于25℃或60℃反应，反应时间为0.5-2个小时，邻氨基芳基甲醇与2,2-二羟基-1-芳基乙酮、硫氰酸钾、三氟醋酸的摩尔比为1:1.2:2:5。
所述的邻氨基芳基甲醇的结构式为：
其中：R1为氢、甲基、甲氧基、卤素，所述卤素包括氟、氯、溴，R2为氢、甲基；
所述的2,2-二羟基-1-芳基乙酮类化合物的结构式为：
其中：R3为各种取代的苯基、脂肪烃、萘基或者噻吩基，其中苯基上的取代基包括甲基、三氟甲基、硝基、氟、氯、甲氧基、N,N-二甲基。
(2)将步骤(1)所得到的反应液抽滤得到固体，即为目标化合物5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物。
本发明所述温度为25℃或60℃。
本发明所述的非质子性溶剂为乙腈、二氯甲烷。
本发明提供的合成方法，是以邻氨基芳基甲醇类化合物为起始原料，通过多组分反应提供一种5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物及其制备方法，反应条件温和，反应收率高，反应时间短，后处理方便，无需金属催化剂，所用的反应原料易得，为高效合成5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物提供了一种简单易行的方法。此外，本发明的所述的5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物未见文献报道，其所述的合成方法也未见文献报道。
本发明所提供的5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮类化合物合成方法具有以下特点：(1)本发明无需借助金属催化剂；(2)反应收率高，大部分产物的分离收率在80％以上；(3)反应原料简便易得，多种底物结构均可耐受该反应条件，适用范围广。
具体实施方式
本发明将通过实施例作进一步的说明。
实施例1 3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
将邻氨基苯甲醇(0.1mmol,12.3mg),2,2-二羟基-1-对甲基苯基乙酮(0.12mmol,20mg),硫氰酸钾(0.2mmol,19.4mg),三氟醋酸(0.5mmol,37μL)加入0.5mL的无水乙腈中，加料完毕后，室温反应0.5h，点板观察。反应结束，抽滤得到白色固体，收率为95.2％。
White solid,m.p.249.6-251.8℃,1H NMR(500MHz,DMSO)δ12.68(s,1H),9.56(d,J＝8.5Hz,1H),7.63(d,J＝8.0Hz,2H),7.52-7.49(m,1H),7.43(d,J＝7.0Hz,1H),7.35-7.32(m,1H),7.23(d,J＝8.0Hz,2H),5.34(s,2H),2.30(s,3H).13C NMR(125MHz,DMSO)δ155.5,135.9,132.2,129.3,128.4,126.0,125.6,124.4,124.2,124.0,117.6,106.9,69.2,20.8.HRMS(ESI):m/z calcd for(C17H12N2OS+H)+:295.0900；found:295.0901。
实施例2实施例1的反应在不同反应条件下的收率情况比较
表1
实施例3 3-苯基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-苯基乙酮，得到白色固体，收率为89％。
White solid,m.p.237.0-237.9℃,1H NMR(500MHz,DMSO)δ12.81(s,1H),9.54(d,J＝7.8Hz,1H),7.74(d,J＝7.8Hz,2H),7.51(t,J＝7.6Hz,1H),7.43(m,3H),7.35(t,J＝7.4Hz,1H),7.25(t,J＝7.3Hz,1H),5.38(s,2H).13C NMR(125MHz,DMSO)δ156.2,137.0,132.6,130.0,129.3,128.9,127.7,127.1,126.6,126.2,124.7,124.4,118.1,107.3,69.8.HRMS(ESI):m/z calcd for(C16H12N2OS+H)+:281.0743；found:281.0746。
实施例4 3-(对三氟甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-对三氟甲基苯基乙酮，得到白色固体，收率为94.8％。
White solid,m.p.248.3-248.6℃,1H NMR(500MHz,DMSO)δ12.99(s,1H),9.54(d,J＝8.5Hz,1H),7.92(d,J＝8.0Hz,2H),7.78(d,J＝8.0Hz,2H),7.54-7.51(m,1H),7.46(d,J＝7.4Hz,1H),7.38-7.35(m,1H),5.43(s,2H).13C NMR(125MHz,CDCl3)δ156.4,138.2,132.0,131.2,128.5,126.3,126.1,125.8(q,J＝3.75Hz),125.7,124.3,124.2(d,J＝270Hz),123.8,117.6,105.7,69.4.HRMS(ESI):m/z calcd for(C17H11F3N2OS+H)+:349.0617；found:349.0616。
实施例5 3-(萘-2-基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(萘-2-基)乙酮，得到白色固体，收率为91％。
White solid,m.p.244.8-245.3℃,1H NMR(500MHz,DMSO)δ12.83(s,1H),9.63(d,J＝8.2Hz,1H),8.01–7.96(m,3H),7.62–7.57(m,4H),7.54-7.52(m,1H),7.42(d,J＝6.7Hz,1H),7.37-7.34(m,1H),5.32(s,2H).13C NMR(125MHz,DMSO)δ155.7,136.4,133.4,132.6,130.4,128.8,128.5,128.4,128.0,126.6,126.3,126.1,125.7,125.6,125.5,124.3,124.2,117.7,105.4,69.0.HRMS(ESI):m/z calcd for(C20H14N2OS+H)+:331.0900；found:331.0903。
实施例6 3-(对硝基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(对硝基苯基)乙酮，得到黄色固体，收率为86.2％。
White solid,m.p.>250℃,1H NMR(500MHz,DMSO)δ13.07(s,1H),9.53(d,J＝8.0Hz,1H),8.27(d,J＝8.0Hz,2H),7.94(d,J＝8.5Hz,2H),7.53(t,J＝7.5Hz,1H),7.46(d,J＝7.0Hz,1H),7.38(t,J＝7.0Hz,1H),5.47(s,2H).13C NMR(125MHz,DMSO)δ157.0,144.6,139.5,133.6,131.8,128.6,126.5,125.8,124.4,124.2,123.6,117.6,105.6,69.5.HRMS(ESI):m/z calcd for(C16H11N3O3S+H)+:326.0594；found:326.0593。
实施例7 3-(对氟苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(对氟苯基)乙酮，得到浅黄色固体，收率为61％。
Light yellow solid,m.p.241.6-242.0℃,1H NMR(500MHz,DMSO)δ12.84(s,1H),9.54(d,J＝8.5Hz,1H),7.76(dd,J＝8.5,5.5Hz,2H),7.53-7.50(m,1H),7.44(d,J＝7.0Hz,1H),7.36-7.33(m,1H),7.28(t,J＝9Hz,2H),5.37(s,2H).13C NMR(125MHz,DMSO)δ160.7(d,J＝242.5Hz),155.7,136.3,132.2,128.5,126.3(d,J＝7.5Hz),126.2,125.7,124.0,123.8(d,J＝2.5Hz),117.7,115.9(d,J＝21.3Hz),106.1,69.4.HRMS(ESI):m/z calcd for(C16H11FN2OS+H)+:299.0649；found:299.0648。
实施例8 3-(对氯苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(对氯苯基)乙酮，得到白色固体，收率为63.7％。
White solid,m.p.>250℃,1H NMR(500MHz,DMSO)δ12.87(s,1H),9.53(d,J＝8.5Hz,1H),7.74(d,J＝8.5Hz,2H),7.52(d,J＝8.0Hz,1H),7.49(d,J＝8.5Hz,2H),7.44(d,J＝7.5Hz,1H),7.35(t,J＝7.5Hz,1H),5.39(s,2H).13C NMR(125MHz,DMSO)δ155.9,136.9,132.1,130.8,128.9,128.5,126.2,126.2,125.8,125.7,123.9,117.7,105.9,69.4.HRMS(ESI):m/z calcd for(C16H11ClN2OS+H)+:315.0354；found:315.0352。
实施例9 3-(间甲氧基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(间甲氧基苯基)乙酮，得到白色固体，收率为96.8％。
Pink solid,m.p.222.0-223.0℃,1H NMR(500MHz,DMSO)δ12.83(s,1H),9.54(d,J＝8.5Hz,1H),7.53-7.50(m,1H),7.44(d,J＝7.4Hz,1H),7.40-7.32(m,4H),6.83-6.80(m,1H),5.38(s,2H),3.79(s,3H).13C NMR(125MHz,DMSO)δ159.6,155.7,136.8,132.2,130.0,128.5,128.4,126.2,125.7,124.0,117.7,116.7,112.5,109.3,106.8,69.3,55.2.HRMS(ESI):m/z calcd for(C17H14N2O2S+H)+:311.0849；found:311.0849。
实施例10 3-(邻氯苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(邻氯苯基)乙酮，得到白色固体，收率为67.7％。
White solid,m.p.209.7-210.6℃,1H NMR(500MHz,DMSO)δ12.71(s,1H),9.55(d,J＝8.0Hz,1H),7.60-7.57(m,1H),7.54-7.50(m,2H),7.45-7.42(m,3H),7.37-7.33(m,1H),5.30(s,2H).13C NMR(125MHz,DMSO)δ155.5,136.5,132.4,132.3,131.8,130.3,129.9,128.5,127.3,126.2,125.8,125.8,124.0,117.6,104.4,68.9.HRMS(ESI):m/z calcd for(C16H11ClN2OS+H)+:315.0354；found:315.0351。
实施例11 3-(噻吩-2-基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲基苯基乙酮换成2,2-二羟基-1-(噻吩-2-基)乙酮，得到紫色固体，收率为66.1％。
Purple solid,m.p.235.3-235.7℃,1H NMR(500MHz,DMSO)δ12.95(s,1H),9.52(d,J＝8.0Hz,1H),7.53-7.49(m,2H),7.46-7.41(m,2H),7.35(td,J＝7.4,0.9Hz,1H),7.09(dd,J＝5.0,3.7Hz,1H),5.39(s,2H).13C NMR(125MHz,DMSO)δ155.5,135.2,132.2,128.5,128.2,127.4,126.2,125.8,125,123.8,122.7,117.5,103.4,69.5.HRMS(ESI):m/z calcdfor(C14H10N2OS2+H)+:287.0308；found:287.0306。
实施例12 3-(4-(二甲基氨基)苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲苯基乙酮换成2,2-二羟基-1-(4-(二甲基氨基)苯基)乙酮，得到灰白色固体，收率为93.8％。
Gray solid,m.p.220.2-220.7℃,1H NMR(500MHz,DMSO)δ12.82(s,1H),9.53(d,J＝8.5Hz,1H),7.77(d,J＝8.5Hz,2H),7.53-7.50(m,1H),7.45(d,J＝6.8Hz,1H),7.43–7.37(m,2H),7.36-7.34(m,1H),5.37(s,2H),3.11(s,6H).13C NMR(125MHz,DMSO)δ156.1,132.6,130.3,128.9,126.6,126.2,125.8,124.4,118.1,106.7,69.8,44.2.HRMS(ESI):m/z calcdfor(C18H17N3OS+H)+:324.1165；found:324.1161。
实施例13 3-叔丁基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲苯基乙酮换成2,2-二羟基-1-叔丁基乙酮，得到白色固体，收率为71.2％。
White solid,m.p.>250℃,1H NMR(500MHz,DMSO)δ12.12(s,1H),9.46(d,J＝8.0Hz,1H),7.47-7.44(m,1H),7.37(d,J＝7.0Hz,1H),7.30-7.26(m,1H),5.14(s,2H),1.27(s,9H).13C NMR(125MHz,DMSO)δ154.3,134.1,132.6,128.2,125.6,125.5,124.5,117.8,114.8,69.1,30.3,29.1.HRMS(ESI):m/z calcd for(C14H16N2OS+H)+:261.1056；found:261.1066。
实施例14 9-甲基-3-苯基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将2,2-二羟基-1-对甲苯基乙酮换成2,2-二羟基-1-苯基乙酮，将邻氨基苯甲醇换成2-氨基-3-甲基-苯甲醇，得到白色固体，收率为98.6％。
White solid,m.p.181.9-182.3℃,1NMR(500MHz,DMSO)δ12.78(s,1H),7.75(d,J＝7.5Hz,2H),7.43(t,J＝8.0Hz,2H),7.39(d,J＝6.5Hz,1H),7.36-7.33(m,2H),7.26(t,J＝7.0Hz,1H),5.38(s,1H),5.11(s,1H),2.61(s,3H).13C NMR(125MHz,DMSO)δ157.0,138.6,132.6,131.2,129.8,129.6,128.9,127.3,126.7,126.6,124.4,123.3,108.3,72.4,22.6.HRMS(ESI):m/z calcd for(C17H14N2OS+H)+:295.0900；found:295.0904。
实施例15 5-甲基-3-对甲基苯基-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将邻氨基苯甲醇换成2-(1’-羟基乙基)-苯胺，得到白色固体，收率为66.7％。
White solid,m.p.231.2-232.4℃,1H NMR(500MHz,DMSO)δ12.76(s,1H),9.57(d,J＝8.5Hz,1H),7.65(d,J＝8.0Hz,2H),7.51(t,J＝7.5Hz,1H),7.44(d,J＝7.5Hz,1H),7.36(t,J＝7.5Hz,1H),7.23(d,J＝8.0Hz,2H),5.56(q,J＝6.5Hz,1H),2.30(s,3H),1.65(d,J＝6.5Hz,3H).13C NMR(125MHz,DMSO)δ155.4,136.0,134.7,131.5,129.4,128.3,128.1,126.2,124.9,124.5,124.1,117.8,107.7,75.6,20.8,19.2.HRMS(ESI):m/z calcd for(C18H16N2OS+H)+:309.1056；found:309.1059。
实施例16 6-氯-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将邻氨基苯甲醇换成2-氨基-6-氯-苯甲醇，得到白色固体，收率为92.3％。
White solid,m.p.239.7-234.3℃,1H NMR(500MHz,DMSO)δ12.85(s,1H),9.59(d,J＝8.0Hz,1H),7.62(d,J＝8.0Hz,2H),7.55(t,J＝8.0Hz,1H),7.47-7.45(m,1H),7.24(d,J＝8.0Hz,2H),5.45(s,2H),2.30(s,3H).13C NMR(125MHz,DMSO)δ155.9,136.2,135.4,133.6,129.7,129.5,129.4,126.6,124.3,124.2,122.1,116.7,107.1,66.8,20.8.HRMS(ESI):m/z calcd for(C17H13ClN2OS+H)+:329.0510；found:329.0512。
实施例17 7-溴-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将邻氨基苯甲醇换成2-氨基-5-溴-苯甲醇，得到淡黄色固体，收率为60.8％。
Light yellow solid,m.p.245.8-246.0℃,1H NMR(500MHz,DMSO)δ12.81(s,1H),9.52(d,J＝9.0Hz,1H),7.72(d,J＝8.5Hz,1H),7.69(s,1H),7.61(d,J＝8.5Hz,2H),7.22(d,J＝8.0Hz,2H),5.35(s,2H),2.29(s,3H).13C NMR(125MHz,DMSO)δ155.6,136.1,135.6,131.5,131.2,129.4,128.4,126.5,124.3,119.6,118.1,107.2,68.6,20.8.HRMS(ESI):m/zcalcd for(C17H13BrN2OS+H)+:373.0005；found:373.0003。
实施例18 7,8-二甲氧基-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将邻氨基苯甲醇换成2-氨基-4,5-二甲氧基-苯甲醇，得到黄色固体，收率为84.7％。
Yellow solid,m.p.234.2-234.5℃,1H NMR(500MHz,DMSO)δ12.68(s,1H),9.40(s,1H),7.62(d,J＝8.0Hz,2H),7.22(d,J＝8.0Hz,2H),7.07(s,1H),5.28(s,2H),3.80(s,3H),3.80(s,3H),2.30(s,3H).13C NMR(125MHz,DMSO)δ154.5,147.8,146.4,135.9,135.8,129.3,125.4,124.5,124.1,115.8,108.9,106.8,102.7,69.0,55.8,20.8.HRMS(ESI):m/zcalcd for(C19H18N2O3S+H)+:355.1111；found:355.1112。
实施例19 8-氟-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将邻氨基苯甲醇换成2-氨基-4-氟-苯甲醇，得到白色固体，收率为73.5％。
White solid,m.p.249.4-250.0℃,1H NMR(500MHz,DMSO)δ12.86(s,1H),9.51(dd,J＝11.5,2.5Hz,1H),7.62(d,J＝8.5Hz,2H),7.50(dd,J＝8.2,6.0Hz,1H),7.23(d,J＝8.0Hz,2H),7.22-7.20(m,1H),5.35(s,2H),2.30(s,3H).13C NMR(125MHz,DMSO)δ161.0(d,J＝241Hz),155.8,136.1,135.5,133.2(d,J＝12.5Hz),129.3,127.5(d,J＝8.8Hz),124.3,124.2,120.1(d,J＝2.5Hz),112.7(d,J＝21.2Hz),107.0,105.1(d,J＝30Hz),68.7,20.8.HRMS(ESI):m/z calcd for(C17H13FN2OS+H)+:313.0806；found:313.0806。
实施例20 8-氯-3-(对甲基苯基)-5H-苯并[d]咪唑并[5,1-b][1,3]恶嗪-1(2H)-硫酮
合成步骤同实施例1，只是将邻氨基苯甲醇换成2-氨基-4-氯-苯甲醇，得到白色固体，收率为66.7％。
White solid,m.p.246.7-247.1℃,1H NMR(500MHz,DMSO)δ12.86(s,1H),9.73(d,J＝2.0Hz,1H),7.61(d,J＝8.0Hz,2H),7.48(d,J＝8.0Hz,1H),7.44-7.41(m,1H),7.23(d,J＝8.0Hz,2H),5.36(s,2H),2.29(s,3H).13C NMR(125MHz,DMSO)δ155.7,136.2,135.6,133.2,132.4,129.4,127.4,125.9,124.3,124.2,122.9,117.3,107.1,68.8,20.8.HRMS(ESI):m/z calcd for(C17H13ClN2OS+H)+:329.0510；found:329.0511。
Claims (3)
1.一种芳基恶嗪并咪唑硫酮类化合物的制备方法，其特征在于，通过以下步骤实现：
（1）将邻氨基芳基甲醇类化合物、2,2-二羟基-1-芳基乙酮、硫氰酸钾、三氟醋酸溶解在非质子溶剂中，于25℃或60℃反应，反应时间为0.5-2个小时，邻氨基芳基甲醇类化合物与2,2-二羟基-1-芳基乙酮、硫氰酸钾、三氟醋酸的摩尔比为1:1.2:2:5；
所述的邻氨基芳基甲醇类化合物的结构式为：
其中R1为氢、甲基、甲氧基、卤素；R2为氢、甲基；
所述的2,2-二羟基-1-芳基乙酮的结构式为：
其中R3为取代的苯基、萘基，其中苯基上的取代基选用甲基、三氟甲基、硝基、氟、氯、甲氧基、N,N-二甲基；
（2）将步骤（1）所得到的反应液抽滤得到固体，即得目标化合物；
结构式为：
其中：
R1为氢、甲基、甲氧基、卤素；
R2为氢、甲基；
R3为取代的苯基、萘基，其中苯基上的取代基选用甲基、三氟甲基、硝基、氟、氯、甲氧基、N,N-二甲基。
2.根据权利要求1所述的一种芳基恶嗪并咪唑硫酮类化合物的制备方法，其特征在于，步骤（1）-（2）所述卤素选用氟、氯、溴。
3.根据权利要求1所述的一种芳基恶嗪并咪唑硫酮类化合物的制备方法，其特征在于，步骤（1）所述的非质子性溶剂为乙腈、二氯甲烷。
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Non-Patent Citations (2)
| Title |
|---|
| Fluorinated Unsymmetrical N,N’-Diaryl Imidazolium Salts—New Functionalized NHC-Ligand Precursors;Maxim A. Topchiy,et al.,;《Chem. Eur. J.》;20170421;第23卷;第6663-6674页 |
| Mild ArI-Catalyzed C(sp2)-H or C(sp3)-H Functionalization/C-O Formation: An Intriguing Catalyst-Controlled Selectivity Switch;Xueqiang Wang，et al.;《Angew. Chem. Int. Ed.》;20140825;第53卷;第11084 –11087页 |
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