CN105001217A - [1,2,4]triazole[4,3-alpha]pyridine-3(2H)-ketone derivative preparation method - Google Patents
[1,2,4]triazole[4,3-alpha]pyridine-3(2H)-ketone derivative preparation method Download PDFInfo
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- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title claims abstract description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 57
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- -1 benzyl halide Chemical class 0.000 claims abstract description 7
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 230000005855 radiation Effects 0.000 claims abstract description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 7
- 239000004202 carbamide Substances 0.000 claims description 7
- 230000035484 reaction time Effects 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- GKECDORWWXXNRY-UHFFFAOYSA-N 2h-pyridin-3-one Chemical class O=C1CN=CC=C1 GKECDORWWXXNRY-UHFFFAOYSA-N 0.000 claims 12
- 150000003852 triazoles Chemical class 0.000 claims 5
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 150000003851 azoles Chemical class 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 150000005826 halohydrocarbons Chemical class 0.000 claims 1
- 229920002554 vinyl polymer Chemical group 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 230000002363 herbicidal effect Effects 0.000 abstract description 5
- 239000000575 pesticide Substances 0.000 abstract description 5
- 240000001592 Amaranthus caudatus Species 0.000 abstract description 4
- 235000009328 Amaranthus caudatus Nutrition 0.000 abstract description 4
- 244000058871 Echinochloa crus-galli Species 0.000 abstract description 3
- 244000278243 Limnocharis flava Species 0.000 abstract description 3
- 235000003403 Limnocharis flava Nutrition 0.000 abstract description 3
- 244000152045 Themeda triandra Species 0.000 abstract description 3
- 238000012827 research and development Methods 0.000 abstract description 3
- 235000013479 Amaranthus retroflexus Nutrition 0.000 abstract description 2
- 244000055702 Amaranthus viridis Species 0.000 abstract description 2
- 235000004135 Amaranthus viridis Nutrition 0.000 abstract description 2
- 244000025254 Cannabis sativa Species 0.000 abstract description 2
- 235000009344 Chenopodium album Nutrition 0.000 abstract description 2
- 235000005484 Chenopodium berlandieri Nutrition 0.000 abstract description 2
- 235000009332 Chenopodium rubrum Nutrition 0.000 abstract description 2
- 150000008282 halocarbons Chemical class 0.000 abstract description 2
- 241000219318 Amaranthus Species 0.000 abstract 1
- 244000178993 Brassica juncea Species 0.000 abstract 1
- 235000011332 Brassica juncea Nutrition 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 239000002244 precipitate Substances 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- 238000001953 recrystallisation Methods 0.000 description 14
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 9
- 238000000034 method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- XAYCTBDPZIKHCW-UHFFFAOYSA-N (3-chloropyridin-2-yl)hydrazine Chemical compound NNC1=NC=CC=C1Cl XAYCTBDPZIKHCW-UHFFFAOYSA-N 0.000 description 4
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 244000056139 Brassica cretica Species 0.000 description 2
- 235000003351 Brassica cretica Nutrition 0.000 description 2
- 235000003343 Brassica rupestris Nutrition 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 239000004178 amaranth Substances 0.000 description 2
- 235000012735 amaranth Nutrition 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 235000010460 mustard Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- MOBRMRJUKNQBMY-UHFFFAOYSA-N 1-(chloromethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CCl MOBRMRJUKNQBMY-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- BSIIGUGKOPPTPZ-UHFFFAOYSA-N 1-bromo-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Br)C=C1 BSIIGUGKOPPTPZ-UHFFFAOYSA-N 0.000 description 1
- BASMANVIUSSIIM-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)benzene Chemical compound ClCC1=CC=CC=C1Cl BASMANVIUSSIIM-UHFFFAOYSA-N 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- ZHKKNUKCXPWZOP-UHFFFAOYSA-N 1-chloroundecane Chemical compound CCCCCCCCCCCCl ZHKKNUKCXPWZOP-UHFFFAOYSA-N 0.000 description 1
- WAXIFMGAKWIFDQ-UHFFFAOYSA-N 1-tert-butyl-4-(chloromethyl)benzene Chemical compound CC(C)(C)C1=CC=C(CCl)C=C1 WAXIFMGAKWIFDQ-UHFFFAOYSA-N 0.000 description 1
- LOQLDQJTSMKBJU-UHFFFAOYSA-N 4-(chloromethyl)benzonitrile Chemical compound ClCC1=CC=C(C#N)C=C1 LOQLDQJTSMKBJU-UHFFFAOYSA-N 0.000 description 1
- OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 240000006162 Chenopodium quinoa Species 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- 235000005775 Setaria Nutrition 0.000 description 1
- 241000232088 Setaria <nematode> Species 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- ZEWLGAIPFJGEOQ-UHFFFAOYSA-N n-[(4-chlorophenyl)diazenyl]-n-methylacetamide Chemical compound CC(=O)N(C)N=NC1=CC=C(Cl)C=C1 ZEWLGAIPFJGEOQ-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，它将如式（Ⅱ）所示的8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮与如式（Ⅲ）所示的卤代烃或苄基卤代物在DMF，NaOH中于40~80℃进行微波辐射关环反应，充分反应后所得反应液经后处理即得产物[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物。其制备方法简单、收率高，后处理方便，该化合物在防治稗草、狗尾草、早熟禾、芥菜、苘麻、反枝苋、小藜中的应用，本发明化合物为具有除草活性的新化合物，为新农药的研发提供了基础。The present invention relates to a preparation method of [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivatives, which will be 8-chloro-[ 1,2,4]triazol[4,3-a]pyridin-3(2H)-one and halogenated hydrocarbon or benzyl halide represented by formula (Ⅲ) in DMF, NaOH at 40~80℃ Carrying out ring-closing reaction by microwave radiation, after sufficient reaction, the obtained reaction solution is post-treated to obtain the product [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative. The preparation method is simple, the yield is high, and the aftertreatment is convenient. The application of the compound in preventing and treating barnyard grass, foxtail grass, bluegrass, mustard greens, velvetleaf, amaranthus retrovertica, and pigweed is a new compound with herbicidal activity. , providing a basis for the research and development of new pesticides.
Description
技术领域 technical field
本发明涉及一种新型 [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法。 The invention relates to a preparation method of a novel [1,2,4]triazol[4,3- a ]pyridin-3( 2H )-one derivative.
背景技术 Background technique
在当下新化合物开发中杂环化合物的开发是一重要方向，其中含氮杂环占占有重要的位置。含氮杂环化合物通常具有优异的生物活性，如杀虫活性，杀菌活性，抗癌活性等。同样，此类化合物也表现出较好的除草活性。其中一些已经开发成为商品化农药，例如，唑啶草酮、氨唑草酮等。由于含氮杂环具有的多种生物活性，使得[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备，在新农药创制研究中具有重要意义。 In the current development of new compounds, the development of heterocyclic compounds is an important direction, in which nitrogen-containing heterocyclic rings occupy an important position. Nitrogen-containing heterocyclic compounds usually have excellent biological activities, such as insecticidal activity, bactericidal activity, anticancer activity, etc. Likewise, such compounds also exhibit good herbicidal activity. Some of them have been developed into commercial pesticides, for example, mefentrazone, amfentrazone and so on. Due to the various biological activities of nitrogen-containing heterocycles, the preparation of [1,2,4]triazol[4,3- a ]pyridin-3(2 H )-one derivatives is of great significance in the research of new pesticide creation. Significance.
[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物已有多种方法报道。如： [1,2,4]triazol[4,3- a ]pyridin-3(2 H )-one derivatives have been reported by various methods. like:
2004年，Venkatesan, Aranapakam M报道了合成[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的方法： In 2004, Venkatesan, Aranapakam M reported a method for the synthesis of [1,2,4]triazol[4,3- a ]pyridin-3(2 H )-one:
该反应需要在氮气做保护下进行。 The reaction needs to be carried out under the protection of nitrogen.
2006年，Sun, Chongqing报道了在DMF做溶剂下通过卤化物与胺的取代反应合成[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的方法： In 2006, Sun, Chongqing reported the synthesis of [1,2,4]triazol[4,3- a ]pyridin-3(2 H )-one derivatives through the substitution reaction of halides and amines in DMF as a solvent. method:
2007年，Shin, Ming-Hsiang报道了一种合成[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的方法： In 2007, Shin, Ming-Hsiang reported a method for synthesizing [1,2,4]triazol[4,3- a ]pyridin-3(2 H )-one derivatives:
2013年，Lindsley, Craig W报道了一种室温下搅拌合成[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的方法： In 2013, Lindsley and Craig W reported a method for synthesizing [1,2,4]triazol[4,3- a ]pyridin-3(2 H )-one derivatives with stirring at room temperature:
。 .
发明内容 Contents of the invention
针对现有技术中存在的上述问题，本发明目的是提供一种[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物及其制备与应用，具体为一种具有除草活性的8-氯代-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物及其制备方法与应用。 In view of the above-mentioned problems existing in the prior art, the object of the present invention is to provide a kind of [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative and its preparation and application, specifically It is an 8-chloro-[1,2,4]triazol[4,3- a ]pyridin-3( 2H )-one derivative with herbicidal activity, its preparation method and application.
所述的一种[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，[1,2,4]如唑[4,3-a]吡啶-3(2H)-酮衍生物其结构式如式（I）所示，其特征在于其制备方法包括下述步骤：将3-氯-2-肼基吡啶与尿素反应合成制得如式（Ⅱ）所示的8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮与如式（Ⅲ）所示的卤代烃或苄基卤代物在DMF，NaOH中于40~80℃进行微波辐射关环反应，充分反应后所得反应液经后处理即得产物[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物； The preparation method of a kind of [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative, [1,2,4] such as azole[4,3-a ] Pyridin-3 (2H)-ketone derivatives whose structural formula is shown in formula (I), is characterized in that its preparation method comprises the following steps: 3-chloro-2-hydrazinopyridine and urea are reacted and synthesized to obtain the following formula: (Ⅱ) 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, 8-Chloro-[1,2,4]triazol[4 ,3-a]pyridin-3(2H)-one and halogenated hydrocarbon or benzyl halide represented by formula (Ⅲ) are subjected to microwave radiation ring closure reaction at 40~80°C in DMF and NaOH, after full reaction The resulting reaction solution is post-treated to obtain the product [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative;
式（I）或式（III）中，R代表C1~C11的烷基、乙烯基、氰基、取代苯基。 In formula (I) or formula (III), R represents a C1-C11 alkyl group, vinyl group, cyano group, or substituted phenyl group.
所述的[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，其特征在于所述取代苄基的取代基各自独立选自下列之一：叔丁基、甲氧基、氰基、氯原子、溴原子、氟原子。 The preparation method of the [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative is characterized in that the substituents of the substituted benzyl groups are independently selected from the following One: tert-butyl group, methoxy group, cyano group, chlorine atom, bromine atom, fluorine atom.
所述的[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，其特征在于：所述的3-氯-2-肼基吡啶和尿素的投料摩尔比为1:2.0～4.0，投料摩尔比优选为1:3.0。 The preparation method of the [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative is characterized in that: the 3-chloro-2-hydrazinopyridine and The feeding molar ratio of urea is 1:2.0-4.0, and the feeding molar ratio is preferably 1:3.0.
所述的[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，其特征在于：8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮, RCH2Cl和 NaOH 的投料摩尔比为1:1.0~1.5:1.0~2.0.，投料摩尔比优选为1:1.1:1.2。 The preparation method of the [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative is characterized in that: 8-chloro-[1,2,4]triazole The molar ratio of [4,3-a]pyridin-3(2H)-one, RCH2Cl and NaOH is 1:1.0~1.5:1.0~2.0. The molar ratio of feeding is preferably 1:1.1:1.2.
所述的[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，其特征在于：3-氯-2-肼基吡啶和尿素的反应温度为120-180℃，优选为160℃，反应时间为20-40 min，优选为30min。 The preparation method of the described [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative is characterized in that: the reaction of 3-chloro-2-hydrazinopyridine and urea The temperature is 120-180°C, preferably 160°C, and the reaction time is 20-40 min, preferably 30 min.
所述的[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物的制备方法，其特征在于：8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮和RCH2Cl的关环反应温度为80-100℃，反应时间为10-20 min.，反应温度优选为90℃，反应时间优选为15 min。 The preparation method of the [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative is characterized in that: 8-chloro-[1,2,4]triazole The ring closure reaction temperature of [4,3-a]pyridin-3(2H)-one and RCH2Cl is 80-100°C, and the reaction time is 10-20 min. The reaction temperature is preferably 90°C, and the reaction time is preferably 15 min. .
与现有技术相比，本发明的有益效果主要体现在：本发明提供了一种[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮衍生物及中间体的其制备方法及应用，其制备方法简单、操作方便，对设备要求低，反应收率高，产品后处理方便，纯度高，且该化合物为具有除草活性的新化合物，特别对于防治稗草、狗尾草、早熟禾、芥菜、苘麻、反枝苋或小藜上有很好的效果，为新农药的研发提供了基础。 Compared with the prior art, the beneficial effects of the present invention are mainly reflected in: the present invention provides a [1,2,4]triazol[4,3-a]pyridin-3(2H)-one derivative and intermediate Its preparation method and application of the compound, its preparation method is simple, easy to operate, low in equipment requirements, high in reaction yield, convenient in post-processing of the product, high in purity, and the compound is a new compound with herbicidal activity, especially for the control of barnyardgrass , Setaria, bluegrass, mustard, velvetleaf, amaranth or quinoa, which provide a basis for the research and development of new pesticides.
具体实施方式 Detailed ways
下面结合具体实施例对本发明进行进一步描述，但本发明的保护范围并不仅限于此： The present invention is further described below in conjunction with specific embodiment, but protection scope of the present invention is not limited thereto:
（四）具体实施方式 (4) Specific implementation methods
下面结合实施例对本发明的技术方案作进一步说明，但本发明的保护范围并不限于此。 The technical solutions of the present invention will be further described below in conjunction with the examples, but the protection scope of the present invention is not limited thereto.
实施例1 8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮 Example 1 8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
将3-氯-2-肼基吡啶(143 mg, 1mmol)与尿素 (3 mmol)加入到CEM Discovery单模微波合成仪的微波反应瓶中，在160 °C下反应30min。 然后将混合物加入到40ml水中形成沉淀后过滤、重结晶得到中间体8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，收率为95%。 3-Chloro-2-hydrazinopyridine (143 mg, 1 mmol) and urea (3 mmol) were added to the microwave reaction flask of CEM Discovery single-mode microwave synthesizer, and reacted at 160 °C for 30 min. Then the mixture was added to 40ml of water to form a precipitate, filtered and recrystallized to obtain the intermediate 8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one with a yield of 95 %.
实施例2 Example 2
4-((8-氯-3-氧代-[1,2,4]三唑[4,3-a]吡啶-2(3H)-基)甲基)苄腈的合成 Synthesis of 4-((8-chloro-3-oxo-[1,2,4]triazol[4,3-a]pyridin-2(3H)-yl)methyl)benzonitrile
8-氯-[1,2,4]三唑4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 4-氯甲基苯腈 (1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即4-((8-氯-3-氧代-[1,2,4]三唑[4,3-a]吡啶-2(3H)-基)甲基)苄腈，产率 95%, m.p.216-218℃; 1H NMR (CDCl3, 400 MHz), δ: 5.25 (s, 2H, NCH2), 6.52(t, J=6.8Hz, 1H, Py-H), 7.20(d, J=7.2Hz, 1H, Py-H), 7.52(d, J=8.4Hz, 2H, Ar-H), 7.64(d, J=8.0Hz, 2H, Ar-H), 7.75(d, J=6.8Hz, 1H, Py-H). HR-ESI-MS for C14H9ClN4NaO: calcd. 307.0357[M+Na]+; found: 307.0360[M+Na]+. 8-Chloro-[1,2,4]triazole 4,3-a]pyridin-3(2H)-one (1 mmol), DMF (5 mL), 4-chloromethylbenzonitrile (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) was irradiated with microwaves at 90°C for 15 min in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. Namely 4-((8-chloro-3-oxo-[1,2,4]triazol[4,3-a]pyridin-2(3H)-yl)methyl)benzonitrile, yield 95%, m.p.216-218℃; 1H NMR (CDCl3, 400 MHz), δ: 5.25 (s, 2H, NCH2), 6.52(t, J=6.8Hz, 1H, Py-H), 7.20(d, J=7.2Hz , 1H, Py-H), 7.52(d, J=8.4Hz, 2H, Ar-H), 7.64(d, J=8.0Hz, 2H, Ar-H), 7.75(d, J=6.8Hz, 1H , Py-H). HR-ESI-MS for C14H9ClN4NaO: calcd. 307.0357[M+Na]+; found: 307.0360[M+Na]+.
实施例3 8-氯-2-(4-氯苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 3 Synthesis of 8-chloro-2-(4-chlorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-氯-4-氯甲基苯 (1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-(4-氯苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率 94%, m.p.166-168℃; 1H NMR (CDCl3, 400 MHz), δ: 5.17 (s, 2H, NCH2), 6.48(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.30(d, J=8.4Hz, 2H, Ar-H), 7.48(d, J=8.4Hz, 2H, Ar-H), 7.73(d, J=6.8Hz, 1H, Py-H). HR-ESI-MS for C13H10Cl2N3O: calcd. 294.0195[M+H]+; found: 294.0190[M+H]+. 8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-chloro-4-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. 8-Chloro-2-(4-chlorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 94%, m.p.166-168 ℃; 1H NMR (CDCl3, 400 MHz), δ: 5.17 (s, 2H, NCH2), 6.48(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py -H), 7.30(d, J=8.4Hz, 2H, Ar-H), 7.48(d, J=8.4Hz, 2H, Ar-H), 7.73(d, J=6.8Hz, 1H, Py-H ). HR-ESI-MS for C13H10Cl2N3O: calcd. 294.0195[M+H]+; found: 294.0190[M+H]+.
实施例4 8-氯-2-(4-甲氧苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 4 Synthesis of 8-chloro-2-(4-methoxybenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-氯甲基-4-甲氧基苯 (1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-(4-甲氧苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率 98%, m.p.116-118℃; 1H NMR (CDCl3, 400 MHz), δ: 3.78(S, 3H, OCH3), 5.17 (s, 2H, NCH2), 6.44(t, J=7.2Hz, 1H, Py-H), 6.86(d, J=8.0Hz, 2H, Ar-H), 7.14(d, J=6.8Hz, 1H, Py-H), 7.40(d, J=8.4Hz, 2H, Ar-H), 7.72(d, J=7.2Hz, 1H, Py-H). HR-ESI-MS for C17H19ClN3O: calcd. 316.1211[M+H]+; found: 316.1212[M+H]+. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-chloromethyl-4-methoxybenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 8-chloro-2-(4-methoxybenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 98%, m.p.116- 118℃; 1H NMR (CDCl3, 400 MHz), δ: 3.78(S, 3H, OCH3), 5.17 (s, 2H, NCH2), 6.44(t, J=7.2Hz, 1H, Py-H), 6.86( d, J=8.0Hz, 2H, Ar-H), 7.14(d, J=6.8Hz, 1H, Py-H), 7.40(d, J=8.4Hz, 2H, Ar-H), 7.72(d, J=7.2Hz, 1H, Py-H). HR-ESI-MS for C17H19ClN3O: calcd. 316.1211[M+H]+; found: 316.1212[M+H]+.
实施例5 8-氯-2-(3-氯苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 5 Synthesis of 8-chloro-2-(3-chlorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-氯-4-氯甲基苯 (1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-(3-氯苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率95%, m.p.155-156℃; 1H NMR (CDCl3, 400 MHz), δ: 5.18 (s, 2H, NCH2), 6.48(t, J=7.2Hz, 1H, Py-H), 7.18(d, J=7.2Hz, 1H, Py-H), 7.28-7.31(m, 3H, Ar-H), 7.41(s, 1H, Ar-H), 7.75(d, J=7.2Hz, 1H, Py-H). HR-ESI-MS for C13H9Cl2N3NaO: calcd. 316.0015[M+Na]+; found: 316.0021[M+Na]+. 8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-chloro-4-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 8-chloro-2-(3-chlorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 95%, m.p.155-156 ℃; 1H NMR (CDCl3, 400 MHz), δ: 5.18 (s, 2H, NCH2), 6.48(t, J=7.2Hz, 1H, Py-H), 7.18(d, J=7.2Hz, 1H, Py -H), 7.28-7.31(m, 3H, Ar-H), 7.41(s, 1H, Ar-H), 7.75(d, J=7.2Hz, 1H, Py-H). HR-ESI-MS for C13H9Cl2N3NaO: calcd. 316.0015[M+Na]+; found: 316.0021[M+Na]+.
实施例6 2-苯甲基-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 6 Synthesis of 2-benzyl-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL),氯甲基苯 (1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即2-苯甲基-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率 97%, m.p.115-117℃; 1H NMR (CDCl3, 400 MHz), δ: 5.21 (s, 2H, NCH2), 6.45(t, J=6.8Hz, 1H, Py-H), 7.15(d, J=7.2Hz, 1H, Py-H), 7.31-7.34(m, 3H, Ar-H), 7.43-7.45(m, 2H, Ar-H), 7.75(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C13H10ClN3O: found C 59.99, H 3.76, N 16.01; calcd. C, 60.12; H, 3.88; N, 16.18. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1 mmol), DMF (5 mL), chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2mmol) was reacted under microwave irradiation for 15min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. Namely 2-benzyl-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 97%, m.p.115-117℃; 1H NMR ( CDCl3, 400 MHz), δ: 5.21 (s, 2H, NCH2), 6.45(t, J=6.8Hz, 1H, Py-H), 7.15(d, J=7.2Hz, 1H, Py-H), 7.31 -7.34(m, 3H, Ar-H), 7.43-7.45(m, 2H, Ar-H), 7.75(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C13H10ClN3O: found C 59.99, H 3.76, N 16.01; calcd. C, 60.12; H, 3.88; N, 16.18.
实施例7 8-氯-2-(2-氯苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 7 Synthesis of 8-chloro-2-(2-chlorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-氯-2-氯甲基苯(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-(2-氯苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率98%, m.p.184-186℃; 1H NMR (CDCl3, 400 MHz), δ: 5.35 (s, 2H, NCH2), 6.48(t, J=7.2Hz, 1H, Py-H), 7.17-7.24(m, 4H, Py-H and Ar-H), 7.38(s, 1H, Ar-H), 7.77(d, J=5.2Hz, 1H, Py-H). HR-ESI-MS for C13H10Cl2N3O: calcd. 294.0195[M+H]+; found: 294.0195[M+H]+. 8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-chloro-2-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 8-chloro-2-(2-chlorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 98%, m.p.184-186 ℃; 1H NMR (CDCl3, 400 MHz), δ: 5.35 (s, 2H, NCH2), 6.48(t, J=7.2Hz, 1H, Py-H), 7.17-7.24(m, 4H, Py-H and Ar-H), 7.38(s, 1H, Ar-H), 7.77(d, J=5.2Hz, 1H, Py-H). HR-ESI-MS for C13H10Cl2N3O: calcd. 294.0195[M+H]+; found: 294.0195[M+H]+.
实施例8 8-氯-2-(2-氟苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 8 Synthesis of 8-chloro-2-(2-fluorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-氟-2-氯甲基苯(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-(2-氟苯甲基)-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率95%, m.p.170-172℃; 1H NMR (CDCl3, 400 MHz), δ: 5.30 (s, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.07-7.11(m, 2H, Ar-H), 7.16(d, J=6.4Hz, 1H, Py-H), 7.27-7.32(m, 2H, Ar-H), 7.75(d, J=6.8Hz, 1H, Py-H). HR-ESI-MS for C10H11ClF2N3O2: calcd. 278.0502[M+H]+; found: 278.0499[M+H]+. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-fluoro-2-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 8-chloro-2-(2-fluorobenzyl)-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 95%, m.p.170-172 ℃; 1H NMR (CDCl3, 400 MHz), δ: 5.30 (s, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.07-7.11(m, 2H, Ar-H) , 7.16(d, J=6.4Hz, 1H, Py-H), 7.27-7.32(m, 2H, Ar-H), 7.75(d, J=6.8Hz, 1H, Py-H). HR-ESI- MS for C10H11ClF2N3O2: calcd. 278.0502[M+H]+; found: 278.0499[M+H]+.
实施例9 2-(4-溴苯甲基)-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 9 Synthesis of 2-(4-bromobenzyl)-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-溴-4-氯甲基苯(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即2-(4-溴苯甲基)-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率98%, m.p.224-226℃; 1H NMR (CDCl3, 400 MHz), δ: 5.16 (s, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.31(d, J=8.4Hz, 2H, Ar-H), 7.46(d, J=8.4Hz, 2H, Ar-H), 7.73(d, J=6.8Hz, 1H, Py-H). HR-ESI-MS for C13H9BrClN3NaO: calcd. 359.9510[M+Na]+; found: 359.9515[M+Na]+. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-bromo-4-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. Namely 2-(4-bromobenzyl)-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 98%, m.p.224-226 ℃; 1H NMR (CDCl3, 400 MHz), δ: 5.16 (s, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py -H), 7.31(d, J=8.4Hz, 2H, Ar-H), 7.46(d, J=8.4Hz, 2H, Ar-H), 7.73(d, J=6.8Hz, 1H, Py-H ). HR-ESI-MS for C13H9BrClN3NaO: calcd. 359.9510[M+Na]+; found: 359.9515[M+Na]+.
实施例10 2-(4-叔丁基苯甲基)-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 10 Synthesis of 2-(4-tert-butylbenzyl)-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5 mL), 1-叔丁基-4-氯甲基苯(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即2-(4-叔丁基苯甲基)-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率95%, m.p.160-162℃; 1H NMR (CDCl3, 400 MHz), δ: 1.29 (s, 9H, t-Bu), 5.18 (s, 2H, NCH2), 6.42(t, J=7.2Hz, 1H, Py-H), 7.12(d, J=7.2Hz, 1H, Py-H), 7.34-7.40(m, 4H, Ar-H), 7.72(d, J=7.2Hz, 1H, Py-H). HR-ESI-MS for C10H13ClN3O5: calcd. 290.0538[M+H]+; found: 290.0543[M+H]+. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5 mL), 1-tert-butyl-4-chloromethylbenzene (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) were reacted under microwave irradiation for 15 min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. Namely 2-(4-tert-butylbenzyl)-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 95%, m.p.160 -162℃; 1H NMR (CDCl3, 400 MHz), δ: 1.29 (s, 9H, t-Bu), 5.18 (s, 2H, NCH2), 6.42(t, J=7.2Hz, 1H, Py-H) , 7.12(d, J=7.2Hz, 1H, Py-H), 7.34-7.40(m, 4H, Ar-H), 7.72(d, J=7.2Hz, 1H, Py-H). HR-ESI- MS for C10H13ClN3O5: calcd. 290.0538[M+H]+; found: 290.0543[M+H]+.
实施例11 2-(8-氯-3-氧代-[1,2,4]三唑[4,3-a]吡啶-2(3H)-基)乙腈的合成 Example 11 Synthesis of 2-(8-chloro-3-oxo-[1,2,4]triazol[4,3-a]pyridin-2(3H)-yl)acetonitrile
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5mL), 2-氯乙腈(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即2-(8-氯-3-氧代-[1,2,4]三唑[4,3-a]吡啶-2(3H)-基)乙腈，产率95%, m.p.180-182℃; 1H NMR (CDCl3, 400 MHz), δ: 4.97 (s, 2H, NCH2), 6.56(t, J=7.2Hz, 1H, Py-H), 7.26(d, J=7.2Hz, 1H, Py-H), 7.73(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C8H5ClN4O: found C 45.89, H 2.65, N 26.78; calcd. C, 46.06; H, 2.42; N, 26.86. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1 mmol), DMF (5 mL), 2-chloroacetonitrile (1.1 mmol) and NaOH (0.05 g , 1.2mmol) in a CEM Discovery single-mode microwave synthesizer at 90°C for 15min under microwave irradiation. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. Namely 2-(8-chloro-3-oxo-[1,2,4]triazol[4,3-a]pyridin-2(3H)-yl)acetonitrile, yield 95%, m.p.180-182℃ ; 1H NMR (CDCl3, 400 MHz), δ: 4.97 (s, 2H, NCH2), 6.56(t, J=7.2Hz, 1H, Py-H), 7.26(d, J=7.2Hz, 1H, Py- H), 7.73(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C8H5ClN4O: found C 45.89, H 2.65, N 26.78; calcd. C, 46.06; H, 2.42; N, 26.86.
实施例12 8-氯-2-丙基- [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 12 Synthesis of 8-chloro-2-propyl-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5mL), 1-氯丙烷(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-丙基-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率94%, m.p.120-122℃; 1H NMR (CDCl3, 400 MHz), δ: 0.98(t, J=7.6Hz, CH3), 1.90(q, J=7.2Hz, 2H, CH2), 4.01 (t, J=7.6Hz, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.75(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C9H10ClN3O: found C 50.89, H 4.97, N 19.99; calcd. C, 51.07; H, 4.76; N, 19.85.、 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1 mmol), DMF (5 mL), 1-chloropropane (1.1 mmol) and NaOH (0.05 g , 1.2mmol) in a CEM Discovery single-mode microwave synthesizer at 90°C for 15min under microwave irradiation. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 8-chloro-2-propyl-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 94%, m.p.120-122℃; 1H NMR (CDCl3 , 400 MHz), δ: 0.98(t, J=7.6Hz, CH3), 1.90(q, J=7.2Hz, 2H, CH2), 4.01 (t, J=7.6Hz, 2H, NCH2), 6.47(t , J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.75(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C9H10ClN3O: found C 50.89, H 4.97, N 19.99; calcd. C, 51.07; H, 4.76; N, 19.85.,
实施例13 8-氯-2-十一烷基- [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 13 Synthesis of 8-chloro-2-undecyl-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5mL), 1-氯-十一烷烃(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即8-氯-2-十一烷基- [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率94%, m.p.131-132℃; 1H NMR (CDCl3, 400 MHz), δ: 0.87(t, J=7.2Hz, CH3), 1.25-1.33(m, 16H, CH2), 1.85-1.88(m, 2H, CH2), 4.03 (t, J=7.2Hz, 2H, NCH2), 6.46(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.74(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C17H26ClN3O: found C 62.99, H 8.03, N 13.01; calcd. C, 63.05; H, 8.09; N, 12.97. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1 mmol), DMF (5 mL), 1-chloro-undecane (1.1 mmol) and NaOH (0.05 g, 1.2 mmol) was irradiated with microwaves at 90°C for 15 min in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. Namely 8-chloro-2-undecyl-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 94%, m.p.131-132℃; 1H NMR (CDCl3, 400 MHz), δ: 0.87(t, J=7.2Hz, CH3), 1.25-1.33(m, 16H, CH2), 1.85-1.88(m, 2H, CH2), 4.03 (t, J=7.2 Hz, 2H, NCH2), 6.46(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.74(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C17H26ClN3O: found C 62.99, H 8.03, N 13.01; calcd. C, 63.05; H, 8.09; N, 12.97.
实施例14 2-丁基-8-氯- [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 14 Synthesis of 2-butyl-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5mL), 1-氯丁烷(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即2-丁基-8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，产率93%, m.p.113-115℃; 1H NMR (CDCl3, 400 MHz), δ: 0.97(t, J=1.8Hz, CH3), 1.37-1.43(m, 2H, CH2), 1.84-1.88(m, 2H, CH2), 4.05 (t, J=7.2Hz, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.74(d, J=7.2Hz, 1H, Py-H). Elemental analysis for C10H12ClN3O: found C 53.41, H 5.44, N 18.76; calcd. C, 53.22; H, 5.36; N, 18.62. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1mmol), DMF (5mL), 1-chlorobutane (1.1mmol) and NaOH (0.05 g, 1.2mmol) was reacted under microwave irradiation for 15min at 90°C in a CEM Discovery single-mode microwave synthesizer. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 2-butyl-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 93%, m.p.113-115℃; 1H NMR (CDCl3 , 400 MHz), δ: 0.97(t, J=1.8Hz, CH3), 1.37-1.43(m, 2H, CH2), 1.84-1.88(m, 2H, CH2), 4.05 (t, J=7.2Hz, 2H, NCH2), 6.47(t, J=7.2Hz, 1H, Py-H), 7.17(d, J=7.2Hz, 1H, Py-H), 7.74(d, J=7.2Hz, 1H, Py- H). Elemental analysis for C10H12ClN3O: found C 53.41, H 5.44, N 18.76; calcd. C, 53.22; H, 5.36; N, 18.62.
实施例15 2-烯丙基-8-氯- [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮的合成 Example 15 Synthesis of 2-allyl-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one
8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮(1mmol), DMF (5mL), 烯丙基氯(1.1 mmol)和 NaOH (0.05 g, 1.2mmol)在CEM Discovery单模微波合成仪中90°C下微波辐射反应15min。反应结束后，将混合物倒入碎冰中形成沉淀过滤后重结晶收集。即2-烯丙基-8-氯- [1,2,4]三唑[4,3-a]吡啶-3(2H)-酮，收率95%, m.p.99-100℃; 1H NMR (CDCl3, 400 MHz), δ: 4.66 (d, J=5.6Hz, 2H, NCH2), 5.31 (d, J=9.2Hz, 2H, =CH2), 5.95-6.06(m, 1H, =CH), 6.48(t, J=7.2Hz, 1H, Py-H), 7.18(d, J=7.2Hz, 1H, Py-H), 7.75(d, J=7.2Hz, 1H, Py-H). HR-ESI-MS for C8H6ClN4O: calcd. 209.0225[M+H]+; found: 209.0226[M+H]+. 8-Chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one (1 mmol), DMF (5 mL), allyl chloride (1.1 mmol) and NaOH (0.05 g , 1.2mmol) in a CEM Discovery single-mode microwave synthesizer at 90°C for 15min under microwave irradiation. After the reaction, the mixture was poured into crushed ice to form a precipitate, which was filtered and collected by recrystallization. That is, 2-allyl-8-chloro-[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, yield 95%, m.p.99-100℃; 1H NMR ( CDCl3, 400 MHz), δ: 4.66 (d, J=5.6Hz, 2H, NCH2), 5.31 (d, J=9.2Hz, 2H, =CH2), 5.95-6.06(m, 1H, =CH), 6.48 (t, J=7.2Hz, 1H, Py-H), 7.18(d, J=7.2Hz, 1H, Py-H), 7.75(d, J=7.2Hz, 1H, Py-H). HR-ESI -MS for C8H6ClN4O: calcd. 209.0225[M+H]+; found: 209.0226[M+H]+.
本发明实施例制得的化合物为具有除草活性的新化合物，特别对于防治稗草、狗尾草、早熟禾、芥菜、苘麻、反枝苋或小藜上有很好的效果，为新农药的研发提供了基础。 The compounds prepared in the examples of the present invention are new compounds with herbicidal activity, especially for the prevention and control of barnyard grass, foxtail grass, bluegrass, mustard, velvetleaf, amaranth or pigweed, and are very good for the research and development of new pesticides. provides the basis.
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