CN105001217A - 一种[1,2,4]三唑[4,3-α]吡啶-3(2H)-酮衍生物的制备方法 - Google Patents
一种[1,2,4]三唑[4,3-α]吡啶-3(2H)-酮衍生物的制备方法 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
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- 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
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Classifications
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- 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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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。
Description
技术领域
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。
背景技术
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。
[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：
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：
该反应需要在氮气做保护下进行。
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：
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：
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：
。
发明内容
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。
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；
式（I）或式（III）中，R代表C1~C11的烷基、乙烯基、氰基、取代苯基。
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。
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。
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。
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。
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。
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。
具体实施方式
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：
（四）具体实施方式
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。
实施例1 8-氯-[1,2,4]三唑[4,3-a]吡啶-3(2H)-酮
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%。
实施例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
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]+.
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
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]+.
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
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]+.
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
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]+.
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
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.
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
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]+.
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
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]+.
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
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]+.
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
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]+.
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
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.
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
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.、
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
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.
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
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.
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
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]+.
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。
Claims (6)
1.一种[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；
式（I）或式（III）中，R代表C1~C11的烷基、乙烯基、氰基、取代苯基。
2.如权利要求1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。
3.如权利要求1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。
4.如权利要求1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。
5.如权利要求1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。
6.如权利要求1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。
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Application publication date: 20151028 |