CN106866563A - 一种制备2,4-二取代-1,3,5三嗪衍生物的方法 - Google Patents
一种制备2,4-二取代-1,3,5三嗪衍生物的方法 Download PDFInfo
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- 238000006467 substitution reaction Methods 0.000 title claims abstract description 24
- 150000003921 pyrrolotriazines Chemical class 0.000 title claims abstract description 21
- 238000000034 method Methods 0.000 title claims abstract description 15
- 150000001409 amidines Chemical class 0.000 claims abstract description 29
- RIWNFZUWWRVGEU-UHFFFAOYSA-N isocyanomethylbenzene Chemical compound [C-]#[N+]CC1=CC=CC=C1 RIWNFZUWWRVGEU-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 19
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000000741 silica gel Substances 0.000 claims description 5
- 229910002027 silica gel Inorganic materials 0.000 claims description 5
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 229910052786 argon Inorganic materials 0.000 claims description 4
- 238000006352 cycloaddition reaction Methods 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229910001544 silver hexafluoroantimonate(V) Inorganic materials 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 239000004575 stone Substances 0.000 claims description 3
- 238000005292 vacuum distillation Methods 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- QRUBYZBWAOOHSV-UHFFFAOYSA-M silver trifluoromethanesulfonate Chemical compound [Ag+].[O-]S(=O)(=O)C(F)(F)F QRUBYZBWAOOHSV-UHFFFAOYSA-M 0.000 claims description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical class BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims 1
- 239000012265 solid product Substances 0.000 claims 1
- 229930192474 thiophene Natural products 0.000 claims 1
- 238000001228 spectrum Methods 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 94
- 239000007787 solid Substances 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- -1 nitrogen-containing heterocycle compound Chemical class 0.000 description 4
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 230000005311 nuclear magnetism Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- FIDRAVVQGKNYQK-UHFFFAOYSA-N 1,2,3,4-tetrahydrotriazine Chemical compound C1NNNC=C1 FIDRAVVQGKNYQK-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- YOAKAUXEZQLOHA-UHFFFAOYSA-N 2,4-bis(4-bromophenyl)-1,3,5-triazine Chemical compound Brc1ccc(cc1)-c1ncnc(n1)-c1ccc(Br)cc1 YOAKAUXEZQLOHA-UHFFFAOYSA-N 0.000 description 1
- SBHBNFGFHVIXLD-UHFFFAOYSA-N 2,4-bis(4-chlorophenyl)-1,3,5-triazine Chemical compound C1=CC(Cl)=CC=C1C1=NC=NC(C=2C=CC(Cl)=CC=2)=N1 SBHBNFGFHVIXLD-UHFFFAOYSA-N 0.000 description 1
- RLBQITABCYNMSL-UHFFFAOYSA-N 2,4-bis(4-methoxyphenyl)-1,3,5-triazine Chemical compound COC1=CC=C(C=C1)C1=NC(=NC=N1)C1=CC=C(C=C1)OC RLBQITABCYNMSL-UHFFFAOYSA-N 0.000 description 1
- XBTOWOLCMQAGSA-UHFFFAOYSA-N 2,4-bis[4-(trifluoromethyl)phenyl]-1,3,5-triazine Chemical compound FC(F)(F)c1ccc(cc1)-c1ncnc(n1)-c1ccc(cc1)C(F)(F)F XBTOWOLCMQAGSA-UHFFFAOYSA-N 0.000 description 1
- OTJZMNIBLUCUJZ-UHFFFAOYSA-N 2,4-diphenyl-1,3,5-triazine Chemical compound C1=CC=CC=C1C1=NC=NC(C=2C=CC=CC=2)=N1 OTJZMNIBLUCUJZ-UHFFFAOYSA-N 0.000 description 1
- ZRQCFDFVXGGMEF-UHFFFAOYSA-N 2-(4-methoxyphenyl)-4-phenyl-1,3,5-triazine Chemical compound C1=CC(OC)=CC=C1C1=NC=NC(C=2C=CC=CC=2)=N1 ZRQCFDFVXGGMEF-UHFFFAOYSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- YHSXELGDJPSMIR-UHFFFAOYSA-N COc1ccc(C2N=CN=C(c3ccccc3)N2)cc1 Chemical compound COc1ccc(C2N=CN=C(c3ccccc3)N2)cc1 YHSXELGDJPSMIR-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/14—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom
- C07D251/24—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hydrogen or carbon atoms directly attached to at least one ring carbon atom to three ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明涉及一种制备对称及非对称2,4-二取代-1,3,5三嗪衍生物的方法。具体地说，是在银盐或铜盐催化下取代的脒与苄基异腈反应生成对称及非对称2,4-二取代-1,3,5三嗪衍生物。反应体系简单，反应条件温和，底物范围较广。
Description
技术领域
本发明涉及一种制备对称及非对称2,4-二取代-1,3,5三嗪衍生物的方法。具体地说，是在银盐或铜盐催化下取代的脒与苄基异腈反应生成对称及非对称2,4-二取代-1,3,5三嗪衍生物。
背景技术
三嗪是一类重要的含氮杂环化合物，具有广泛的生物活性和医药价值(文献1：(a)Saleh,M.；Abbott,S.；Perron,V.；Lauzon,C.；Penney,C.；Zacharie,B.Bioorg.Med.Chem.Lett.,2010,20,945.(b)Melato,S.；Prosperi,D.；Coghi,P.；Basilico,B.；Monti,D.ChemMedChem,2008,3,873.(c)Zhu,W.；Liu,Y.；Zhao,Y.；Wang,H.；Tan,L.；Fan,W.；Gong,P.Arch.Pharm.Chem.Life Sci.,2012,345,812.(d)Patel,R.V.；Kumari,P.；Rajani,D.P.；Chikhalia,K.H.Eur.J.Med.Chem.,2011,46,4354.)。在制备液晶材料(文献2：(a)(a)Kotha,S.；Kashinath,D.；Kumar,S.TetrahedronLett.2008,49,5419.(b)Lee,C.-H.；Yamamoto,T.Bull.Chem.Soc.Jpn.2002,75,615.)、金属有机材料(文献3：(a)Naik,S.；Kumaravel,M.；Mague,J.T.；Balakrishna,M.S.Inorg.Chem.2014,53,1370.(b)Xiao,C.-Y.；Li,Y.-M.；Lun,H.-J.；Cui,C.-Y.；Xu,Y.-Q.J.Solid State Chem.2013,208,127.)方面有重要应用。
常见的制备2,4-二取代-1,3,5三嗪衍生物的方法是，通过芳基脒与一种C1供体进行环加成反应得到(文献4：(a)Gold,H.Angew.Chem.1960,72,956.(b)Bredereck,H.；Effenberger,F.；Hofmann,A.Chem.Ber.1963,96,3265.(c)Huffman,K.R.；Schaefer,F.C.J.Org.Chem.1963,28,1812.(d)Wessig,P.；Schwarz,J.Monatsh.Chem.1995,126,99.(e)Xu,X.-W.；Zhang,M.；Jiang,H.-F.；Zheng,J.；L,Y.-Q.Org.Lett.2014,16,3540.(f)Huang,H.-W.；Guo,W.；Wu,W.-Q.；Li,C.-J.；Jiang,H.-F.Org.Lett.2015,17,2894)。这类方法通常具有反应条件苛刻，产率低等缺点，本文描述了一种由取代的脒与苄基异腈环加成反应合成对称及非对称2,4-二取代-1,3,5三嗪衍生物的方法。
发明内容
本发明的目的在于提供一种合成对称及非对称2,4-二取代-1,3,5三嗪衍生物的新方法。该方法以银盐或铜盐催化取代的脒与苄基异腈经环加成反应合成对称及非对称2,4-二取代-1,3,5三嗪衍生物的方法，具体为：
以取代的脒(1)与苄基异腈(2)为原料生成对称及非对称2,4-二取代-1,3,5三嗪衍生物(3)，反应方程式如下：
其中Ar1、Ar2为苯基、取代的苯基(4-甲氧基苯基、4-甲基苯基、4-氯苯基、3-溴苯基、4-溴苯基或4-三氟甲基苯基)或噻吩基中的一种或两种。
具体操作步骤如下：
氩气气氛中，加入银盐或铜盐、脒(1)和苄基异腈(2)，然后加入溶剂，加热条件下搅拌5-10小时，停止反应，冷却至室温，将反应液转移入旋蒸瓶内，减压蒸馏除掉溶剂，残留物溶于二氯甲烷上样，以300-400目硅胶为固定相，以石油醚：乙酸乙酯＝50：1(体积比)的混合溶液为洗脱剂进行硅胶柱层析，得到2,4-二取代-1,3,5三嗪衍生物(3)溶液，减压蒸馏除掉溶剂，得到白色固体。
催化剂为AgSbF6、AgOTf、AgNO3、Cu(OTf)2、CuI、Cu(Ac)2中的一种，催化剂用量为脒(1)的5mol％-50mol％；脒(1)与苄基异腈(2)的用量比为：1.5:1-1:1.5(物质的量比)；所用溶剂为DMF(N,N-二甲基甲酰胺)、THF(四氢呋喃)、甲苯、DME(乙二醇二甲醚)中的一种，用量为每毫摩尔反应物脒(1)用溶剂1–10毫升。温度为80-160℃。
本发明有以下优点：
1.反应物易于合成。
2.产物含有各类芳基，高度官能化。3.反应体系简单、条件温和。
具体实施方式
实施例1
为了更好地理解本发明，通过以下实例进行说明对称2,4-二取代-1,3,5三嗪衍生物的合成。
在反应管中进行，氩气气氛中，加入AgSbF6(0.015mmol)、脒(1)(Ar1为苯基0.4mmol)和苄基异腈(2)(0.3mmol)，然后加入溶剂甲苯(3mL)，140℃加热条件下搅拌约10小时，停止反应，冷却至室温，将反应液转移入旋蒸瓶内，减压蒸馏除掉溶剂，残留物溶于二氯甲烷上样，以300-400目硅胶为固定相，以石油醚：乙酸乙酯＝50：1(体积比)的混合溶液为洗脱剂进行硅胶柱层析，进行核磁和液相质谱检测，与2,4-二取代-1,3,5三嗪(Ar1为苯基)相符。
下表给出7个对称2,4-二取代-1,3,5三嗪衍生物的合成实施例的情况：
实施例9
为了更好地理解本发明，通过以下实例进行说明非对称2,4-二取代-1,3,5三嗪衍生物的合成。
在反应管中进行，氩气气氛中，加入AgSbF6(0.015mmol)、脒(1)(Ar1为4-氯苯基0.2mmol)、脒(1’)(Ar2为4-溴苯基0.2mmol)和苄基异腈(2)(0.3mmol)，然后加入溶剂甲苯(3mL)，140℃加热条件下搅拌约10小时，停止反应，冷却至室温，将反应液转移入旋蒸瓶内，减压蒸馏除掉溶剂，残留物溶于二氯甲烷上样，以300-400目硅胶为固定相，以石油醚：乙酸乙酯＝50：1(体积比)的混合溶液为洗脱剂进行硅胶柱层析，进行核磁和液相质谱检测，与2,4-二取代-1,3,5三嗪(Ar1为4-氯苯基，Ar2为4-溴苯基)相符，产率28％。
下表给出13个非对称2,4-二取代-1,3,5三嗪衍生物的合成实施例的情况：
各产物的表征数据如下：
实施例1
2,4-Diphenyl-1,3,5-triazine(3a)
Yield:38.5mg(82％),white solid.1H NMR(400MHz,CDCl3)δ9.24(s,1H),8.64(d,J＝7.1Hz,4H),7.60(t,J＝7.2Hz,2H),7.54(t,J＝7.3Hz,4H)；13C NMR(100MHz,CDCl3)δ171.5,166.9,135.7,132.9,129.0,128.9.实施例2
2,4-Bis(4-methoxyphenyl)-1,3,5-triazine(3b)
Yield:46.3mg(82％),white solid.1H NMR(400MHz,CDCl3)δ9.07(s,1H),8.54(d,J＝7.4Hz,4H),6.99(d,J＝7.4Hz,4H),3.86(s,6H)；13C NMR(100MHz,CDCl3)δ170.6,166.4,166.1,163.5,131.0,130.8,128.3,114.3,114.1,55.5.
实施例3
2,4-Di-p-tolyl-1,3,5-triazine(3c)
Yield:46.0mg(88％).1H NMR(400MHz,CDCl3)δ9.16(s,1H),8.49(d,J＝8.1Hz,4H),7.31(d,J＝8.0Hz,4H),2.43(s,6H)；13C NMR(100MHz,CDCl3)δ171.2,166.6,143.5,133.1,129.6,129.0,21.8.
实施例4
2,4-Bis(4-chlorophenyl)-1,3,5-triazine(3d)
Yield:48.0mg(80％),white solid.1H NMR(400MHz,CDCl3)δ9.21(s,1H),8.55(d,J＝8.6Hz,4H),7.51(d,J＝8.6Hz,4H)；13C NMR(100MHz,CDCl3)δ170.6,166.9,139.5,134.0,130.4,129.2.
实施例5
2,4-Bis(3-bromophenyl)-1,3,5-triazine(3e)
Yield:55.2mg(70％),white solid,m.p.185-187℃.1H NMR(400MHz,CDCl3)δ9.27(s,1H),8.76(s,2H),8.57(d,J＝7.9Hz,2H),7.74(d,J＝8.6Hz,2H),7.44(t,J＝7.9Hz,2H)；13C NMR(100MHz,CDCl3)δ170.5,167.0,137.5,136.0,132.0,130.5,127.7,123.2.HRMS(Q-TOF,m/z)calcd for C11H10N3[M+H]+389.9236,found 389.9238.
实施例6
2,4-Bis(4-bromophenyl)-1,3,5-triazine(3f)
Yield:59.6mg(76％),white solid,m.p.143-145℃.1H NMR(400MHz,CDCl3)δ9.22(s,1H),8.47(d,J＝8.2Hz,4H),7.67(d,J＝8.2Hz,4H)；13CNMR(100MHz,CDCl3)δ170.8,167.0,134.4,132.2,130.5,128.2.HRMS(Q-TOF,m/z)calcd for C11H10N3[M+H]+389.9236,found 389.9236.
实施例7
2,4-Bis(4-(trifluoromethyl)phenyl)-1,3,5-triazine(3g)
Yield:29.3mg(49％),white solid.1H NMR(400MHz,CDCl3)δ9.33(s,1H),8.74(d,J＝8.2Hz,4H),7.81(d,J＝8.3Hz,4H)；13C NMR(100MHz,CDCl3)δ170.6,167.3,138.6,134.6(q,J＝32.6Hz),129.4,128.0,125.9(q,J＝3.8Hz),123.59(q,J＝272.6Hz)；19F NMR(375MHz,CDCl3)δ-63.04.
实施例8
2,4-Di(thiophen-2-yl)-1,3,5-triazine(3h)
Yield:46.3mg(94％),white solid,m.p.128-130℃.1H NMR(400MHz,CDCl3)δ8.99(s,1H),8.21(d,J＝3.6Hz,2H),7.62(d,J＝4.9Hz,2H),7.21–7.15(m,2H)；13C NMR(100MHz,CDCl3)δ167.5,166.5,141.0,132.9,132.1,128.7.HRMS(Q-TOF,m/z)calcd for C11H8N3S2[M+H]+246.0154,found246.0167.
实施例9
2-(4-Bromophenyl)-4-(4-chlorophenyl)-1,3,5-triazine(3i)
Yield:19.2mg(28％),white solid,m.p.184-186℃.1H NMR(400MHz,CDCl3)δ9.21(s,1H),8.54(d,J＝8.5Hz,2H),8.47(d,J＝8.5Hz,2H),7.67(d,J＝8.6Hz,2H),7.51(d,J＝8.6Hz,2H)；13C NMR(100MHz,CDCl3)δ170.8,170.6,167.0,139.5,134.4,134.0,132.2,130.5,130.4,129.2,128.2.HRMS(Q-TOF,m/z)calcd for C15H10BrClN3[M+H]+345.9741,found 345.9742.
实施例10
2-(4-Methoxyphenyl)-4-phenyl-1,3,5-triazine(3j)
Yield:20.0mg(38％),white solid,m.p.114-116℃.1H NMR(400MHz,CDCl3)δ9.18(s,1H),8.61(t,J＝7.4Hz,4H),7.60(d,J＝7.3Hz,1H),7.54(t,J＝7.2Hz,2H),7.03(d,J＝8.9Hz,2H),3.90(s,3H)；13C NMR(100MHz,CDCl3)δ171.2,171.0,166.7,163.7,135.9,132.8,131.0,129.0,128.8,128.2,114.2,55.6.HRMS(Q-TOF,m/z)calcd for C16H14N3O[M+H]+264.1131,found 264.1132.
实施例11
2-(4-Bromophenyl)-4-(4-methoxyphenyl)-1,3,5-triazine(3k)
Yield:25.8mg(38％),white solid,m.p.149-151℃.1H NMR(400MHz,CDCl3)δ9.16(s,1H),8.57(d,J＝9.0Hz,2H),8.47(d,J＝8.7Hz,2H),7.66(d,J＝8.7Hz,2H),7.03(d,J＝9.0Hz,2H),3.91(s,3H)；13C NMR(100MHz,CDCl3)δ171.1,170.4,166.7,163.8,134.8,132.1,131.0,130.4,128.0,127.8,114.3,55.6.HRMS(Q-TOF,m/z)calcd for C16H13BrN3O[M+H]+342.0237,found 342.0242.
实施例12
2-(3-Bromophenyl)-4-(4-methoxyphenyl)-1,3,5-triazine(3l)
Yield:20.6mg(30％),white solid,m.p.135-137℃.1H NMR(400MHz,CDCl3)δ9.16(s,1H),8.74(s,1H),8.57(d,J＝9.0Hz,2H),8.53(d,J＝7.9Hz,1H),7.70(d,J＝9.9Hz,1H),7.40(t,J＝7.9Hz,1H),7.03(d,J＝9.0Hz,2H),3.90(s,3H)；13C NMR(100MHz,CDCl3)δ171.1,169.9,166.7,163.9,138.0,135.6,131.9,131.1,130.3,127.9,127.5,123.1,114.3.HRMS(Q-TOF,m/z)calcd for C16H13BrN3O[M+H]+342.0237,found 342.0242.
实施例13
2-(4-Chlorophenyl)-4-(4-methoxyphenyl)-1,3,5-triazine(3m)
Yield:23.0mg(39％),white solid,m.p.143-145℃.1H NMR(400MHz,CDCl3)δ9.15(s,1H),8.55(t,J＝9.1Hz,4H),7.49(d,J＝8.6Hz,2H),7.02(d,J＝8.9Hz,2H),3.90(s,3H)；13C NMR(100MHz,CDCl3)δ171.1,170.3,166.7,163.8,139.1,134.4,131.0,130.3,129.1,128.0,114.3,55.6.HRMS(Q-TOF,m/z)calcd for C16H13ClN3O[M+H]+298.0742,found 298.0747.
实施例14
2-(4-Methoxyphenyl)-4-(p-tolyl)-1,3,5-triazine(3n)
Yield:17.0mg(33％),white solid,m.p.134-136℃.1H NMR(400MHz,CDCl3)δ9.14(s,1H),8.59(d,J＝8.8Hz,2H),8.50(d,J＝8.1Hz,2H),7.33(d,J＝8.0Hz,2H),7.03(d,J＝8.8Hz,2H),3.90(s,3H),2.45(s,3H)；13C NMR(100MHz,CDCl3)δ171.2,170.9,166.6,163.6,143.4,133.2,130.9,129.6,129.0,128.3,114.2,55.6,21.8.HRMS(Q-TOF,m/z)calcd for C11H8N3S2[M+H]+278.1288,found 278.1296.
实施例15
2-(4-Methoxyphenyl)-4-(4-(trifluoromethyl)phenyl)-1,3,5-triazine(3o)Yield:17.0mg(26％),white solid,m.p.104-106℃.1H NMR(400MHz,CDCl3)δ9.22(s,1H),8.73(d,J＝8.1Hz,2H),8.60(d,J＝9.0Hz,2H),7.80(d,J＝8.2Hz,2H),7.05(d,J＝9.0Hz,2H),3.92(s,3H)；13C NMR(100MHz,CDCl3)δ171.2,169.9,166.8,163.9,139.2,134.1(q,J＝32.5Hz),131.1,129.2,128.1,127.8,125.72(q,J＝3.8Hz),124.04(q,J＝272.5Hz),114.3,55.6.19F NMR(375MHz,CDCl3)δ-62.93.HRMS(Q-TOF,m/z)calcdfor C17H13F3N3O[M+H]+332.1005,found 332.1012.
实施例16
2-(4-Methoxyphenyl)-4-(thiophen-2-yl)-1,3,5-triazine(3p)
Yield:30.0mg(56％),white solid,m.p.106-108℃.1H NMR(400MHz,CDCl3)δ9.05(s,1H),8.53(d,J＝9.0Hz,2H),8.23(dd,J＝3.7,1.2Hz,1H),7.61(dd,J＝5.0,1.1Hz,1H),7.20(dd,J＝4.9,3.8Hz,1H),7.01(d,J＝8.9Hz,2H),3.89(s,3H)；13C NMR(101MHz,CDCl3)δ170.8,167.5,166.5,163.7,141.6,132.5,131.7,131.0,128.7,127.8,114.2,55.6.HRMS(Q-TOF,m/z)calcd for C14H12N3OS[M+H]+270.0696,found 270.0699.
实施例17
2-(4-Chlorophenyl)-4-(thiophen-2-yl)-1,3,5-triazine(3q)
Yield:24.3mg(44％),white solid,m.p.153-155℃.1H NMR(400MHz,CDCl3)δ9.10(s,1H),8.50(d,J＝8.6Hz,2H),8.25(dd,J＝3.7,1.1Hz,1H),7.64(dd,J＝5.0,1.1Hz,1H),7.49(d,J＝8.6Hz,2H),7.21(dd,J＝4.9,3.9Hz,1H)；13C NMR(100MHz,CDCl3)δ170.4,167.9,166.8,141.2,139.4,133.9,133.1,132.2,130.3,129.2,128.9.HRMS(Q-TOF,m/z)calcdfor C13H9ClN3S[M+H]+274.0200,found 274.0204.
实施例18
2-(4-Bromophenyl)-4-(thiophen-2-yl)-1,3,5-triazine(3r)
Yield:21.4mg(34％),white solid,m.p.153-155℃.1H NMR(400MHz,CDCl3)δ9.11(s,1H),8.44(d,J＝8.6Hz,2H),8.26(d,J＝4.6Hz,1H),7.67(s,1H),7.65(d,J＝2.7Hz,2H),7.24–7.19(m,1H)；13C NMR(100MHz,CDCl3)δ170.6,167.9,166.8,141.2,134.3,133.1,132.2,132.2,130.5,128.9,128.1.HRMS(Q-TOF,m/z)calcd for C13H9BrN3S[M+H]+317.9696,found317.96977.
实施例19
2-(3-Bromophenyl)-4-(thiophen-2-yl)-1,3,5-triazine(3s)
Yield:27.5mg(43％),white solid,m.p.107-109℃.1H NMR(400MHz,CDCl3)δ9.11(s,1H),8.69(s,1H),8.49(d,J＝7.9Hz,1H),8.26(d,J＝4.9Hz,1H),7.70(d,J＝8.9Hz,1H),7.65(d,J＝6.1Hz,1H),7.39(t,J＝7.9Hz,1H),7.24–7.19(m,1H)；13C NMR(100MHz,CDCl3)δ170.1,167.9,166.8,141.1,137.4,135.8,133.2,132.3,131.9,130.3,128.9,127.5,123.1.HRMS(Q-TOF,m/z)calcd for C13H9N3S[M+H]+317.9696,found 317.9700.
实施例20
2-(Thiophen-2-yl)-4-(p-tolyl)-1,3,5-triazine(3t)
Yield:18.0mg(36％),white solid,m.p.93-95℃.1H NMR(400MHz,CDCl3)δ9.09(s,1H),8.46(d,J＝8.2Hz,2H),8.25(dd,J＝3.7,1.2Hz,1H),7.62(dd,J＝5.0,1.1Hz,1H),7.32(d,J＝8.1Hz,2H),7.20(dd,J＝4.9,3.8Hz,1H),2.44(s,3H)；13C NMR(100MHz,CDCl3)δ171.3,167.7,166.6,143.7,141.5,132.7,131.9,129.6,129.0,128.7,21.9.HRMS(Q-TOF,m/z)calcd for C14H12N3S[M+H]+254.0746,found 254.0748.
实施例21
2-Phenyl-4-(thiophen-2-yl)-1,3,5-triazine(3u)
Yield:24.1mg(50％),white solid,m.p.100-102℃.1H NMR(400MHz,CDCl3)δ9.13(s,1H),8.62–8.55(m,2H),8.27(d,J＝3.7Hz,1H),7.64(d,J＝4.9Hz,1H),7.59(d,J＝7.1Hz,1H),7.53(t,J＝7.4Hz,2H),7.24–7.19(m,1H)；13C NMR(100MHz,CDCl3)δ171.4,167.8,166.7,141.4,135.4,133.0,132.9,132.0,129.0,128.9,128.8.HRMS(Q-TOF,m/z)calcdfor C13H10N3S[M+H]+240.0590,found 240.0590.
实施例22
2-(Thiophen-2-yl)-4-(4-(trifluoromethyl)phenyl)-1,3,5-triazine(3v)
Yield:20.1mg(33％),white solid,m.p.131-133℃.1H NMR(400MHz,CDCl3)δ9.16(s,1H),8.68(d,J＝8.2Hz,2H),8.28(dd,J＝3.7,1.1Hz,1H),7.79(d,J＝8.3Hz,2H),7.67(dd,J＝4.9,1.1Hz,1H),7.23(dd,J＝4.9,3.9Hz,1H)；13C NMR(100MHz,CDCl3)δ170.0,167.9,166.9,140.9,138.6,134.3(q,J＝32.6Hz),133.3,132.4,129.2,128.9125.7(q,J＝272.5Hz),124.0(q,J＝3.7Hz)；19F NMR(375MHz,CDCl3)δ-62.98.HRMS(Q-TOF,m/z)calcd for C11H8N3S2[M+H]+308.0464,found 308.0467。
Claims (4)
1.一种制备2,4-二取代-1,3,5三嗪衍生物的方法，其特征在于：是银盐或铜盐催化取代的脒与苄基异腈经环加成反应合成对称及非对称2,4-二取代-1,3,5三嗪衍生物的方法，具体为：
以取代的脒(1和1’)与苄基异腈(2)为原料生成对称及非对称2,4-二取代-1,3,5三嗪衍生物(3)，反应方程式如下：
其中Ar1、Ar2分别为苯基、4-甲氧基苯基、4-甲基苯基、4-氯苯基、3-溴苯基、4-溴苯基、4-三氟甲基苯基或噻吩中的一种或两种；
具体操作步骤如下：
氩气气氛中，加入银盐或铜盐、脒(1)和苄基异腈(2)，然后加入溶剂，加热条件下搅拌5-10小时，停止反应，冷却至室温，将反应液转移入旋蒸瓶内，减压蒸馏除掉溶剂，残留物溶于二氯甲烷上样，以300-400目硅胶为固定相，以石油醚：乙酸乙酯＝100:1-50：1(体积比)的混合溶液为洗脱剂进行硅胶柱层析，得到2,4-二取代-1,3,5三嗪衍生物(3)溶液，减压蒸馏除掉溶剂，得到白色固体产物。
2.按照权利要求1所述的方法，其特征在于：
催化剂为AgSbF6、AgOTf、AgNO3、Cu(OTf)2、CuI、Cu(Ac)2中的一种或两种以上，催化剂用量为脒(1)的5mol％-50mol％；脒(1)与苄基异腈(2)的用量比为：1.5:1-1:1.5(物质的量比)。
3.按照权利要求1所述的方法，其特征在于：
所用溶剂为DMF(N,N-二甲基甲酰胺)、THF(四氢呋喃)、甲苯、DME(乙二醇二甲醚)中的一种或二种以上，用量为每毫摩尔反应物脒(1)用溶剂1–10毫升。
4.按照权利要求1所述的方法，其特征在于：反应温度为80-160℃。
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| CN109810069A (zh) * | 2019-03-27 | 2019-05-28 | 郑州轻工业学院 | 一种多取代1,3,5-三嗪的制备方法 |
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| CN113173889A (zh) * | 2021-05-08 | 2021-07-27 | 新乡市润宇新材料科技有限公司 | 一种合成1,3,5-三嗪衍生物的方法 |
| CN113173889B (zh) * | 2021-05-08 | 2023-11-10 | 新乡市润宇新材料科技有限公司 | 一种合成1,3,5-三嗪衍生物的方法 |
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