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WO2017114121A1 - 吡啶基吡唑烷酮羧酸类化合物的制备方法 - Google Patents

吡啶基吡唑烷酮羧酸类化合物的制备方法 Download PDF

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WO2017114121A1
WO2017114121A1 PCT/CN2016/108984 CN2016108984W WO2017114121A1 WO 2017114121 A1 WO2017114121 A1 WO 2017114121A1 CN 2016108984 W CN2016108984 W CN 2016108984W WO 2017114121 A1 WO2017114121 A1 WO 2017114121A1
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sodium
pyridylpyrazolidinone
carboxylate compound
preparing
catalyst
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PCT/CN2016/108984
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English (en)
French (fr)
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于海波
王学玲
赵贵民
黄耀师
徐凤波
杨辉斌
李斌
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沈阳中化农药化工研发有限公司
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Priority to BR112018013249-7A priority Critical patent/BR112018013249B1/pt
Priority to CN201680060148.1A priority patent/CN108137535B/zh
Publication of WO2017114121A1 publication Critical patent/WO2017114121A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the invention belongs to the field of organic synthesis, and in particular relates to a method for preparing a pyridylpyrazolidinone carboxylate compound.
  • Benzoylamides are a class of highly effective and safe new insecticides.
  • 3-bromo-N-(2-methyl-4-chloro-6-(carbamoyl)phenyl)-1-(3-chloro-2-pyridyl)-1H-pyrazole-5-carboxamide (common name: chlorantraniliprole)
  • 3-bromo-N-(2-methyl-4-cyano-6-(carbamoyl)phenyl)-1-(3-chloro-2-pyridyl)-1H- Pyrazole-5-carboxamide (common name cyantraniliprole) has high insecticidal activity and DuPont has developed insecticides.
  • the bisamide compound being developed by Ishihara Sangyo Co., Ltd. 3-bromo-N-(2-chloro-4-bromo-6-((1-cyclopropylethyl) acyl)phenyl)-1-(3-chloro 2-pyridyl)-1H-pyrazole-5-carboxamide (common name: cyclaniliprole) has a broad spectrum of insecticidal activity.
  • 1-(3-Chloropyridin-2-yl)-3-pyrazolidinone-5-carboxylate is a common key intermediate for the synthesis of chlorantraniliprole, cyantraniliprole, cyclaniliprole, and 1-(3-chloropyridine) is disclosed in WO2004011453.
  • the synthesis of 2-yl)-3-pyrazolidinone-5-carboxylate is obtained by reacting mercaptopyridine with maleic acid diester at reflux temperature, and the reaction yield is only 55%.
  • reaction formula A method for preparing a pyridylpyrazolidinone carboxylate compound, the reaction formula is as follows:
  • R 1 is selected from H or Cl; and R 2 is selected from C 1 -C 6 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 6 cycloalkyl, halogen, a benzyl group which is unsubstituted or substituted with up to 6 C 1 -C 4 alkyl groups;
  • Pyridylpyridine (II) is obtained by reacting a maleic acid diester (III) with a maleic acid diester (III) under basic conditions to obtain a pyridylpyrazolidinone carboxylate compound (I).
  • the catalyst is selected from: Cu (L1) Cl, Cu (L1) Br, Cu (L1) I, Cu (L2) 2 Cl, Cu (L2) 2 Br, Cu (L2) 2 I, Ni (L1) Cl 2, Ni (L1) Br 2 , Ni (L1) I 2, Ni (L2) 2 Cl 2, Ni (L2) 2 Br 2 or Ni (L2) 2 I 2; wherein L1 is selected from:
  • L2 is selected from:
  • the catalyst is selected from the group consisting of Cu(L1)Br, Cu(L1)I, Cu(L2) 2 Br or Cu(L2) 2 I;
  • L1 is selected from:
  • L2 is selected from:
  • the catalyst is selected from Cu(L1)I or Cu(L2) 2 I, wherein
  • L1 is selected from:
  • L2 is selected from:
  • the step of preparing a pyridylpyrazolidinone carboxylate compound (I) by reacting a pyridylpyridine (II) with a maleic acid diester (III) under the action of a catalyst under basic conditions includes,
  • the molar ratio of the mercaptopyridine (II), the base, the maleic acid diester (III) and the catalyst is from 1:1 to 2:1 to 5:0.00001 to 0.01.
  • the molar ratio of the mercaptopyridine (II), the base, the maleic acid diester (III) and the catalyst is 1:1.2-1.5:1.5-2:0.0001-0.001;
  • the pyridylpyridine (II) is subjected to a reaction with a maleic acid diester (III) under basic conditions to obtain a pyridylpyrazolidinone carboxylate compound (I), and the reaction temperature is controlled. 20-50 ° C.
  • the solvent is toluene, chlorobenzene, carboxylic acid esters, alkyl alcohols, ethers or polar aprotic solvents;
  • the base employed is selected from the group consisting of alkali metal hydrides, alkali metal amides or alkyl alcoholates.
  • the hydride of the alkali metal is lithium hydride, sodium hydride or potassium hydride;
  • the alkali metal amide is lithium amide, sodium amide or potassium amide;
  • the alkyl alcoholate is sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, sodium pentoxide, sodium isopropoxide, sodium isobutoxide, sec Sodium alkoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide, potassium propoxide or potassium t-butoxide;
  • the carboxylic acid esters are acetate, fumaric acid diester or maleic acid diester; alkyl alcohols are methanol, ethanol, propanol, butanol, pentanol, isopropanol, isobutanol, secondary Butanol or tert-butanol; ethers are tetrahydrofuran, 2-methyltetrahydrofuran or dioxane; polar aprotic solvents are acetonitrile, N,N-dimethylformamide, N,N-dimethyl Amide or dimethyl sulfoxide.
  • the base is selected from the group consisting of sodium methoxide, sodium ethoxide, sodium propoxide, sodium butoxide, sodium pentoxide, sodium isopropoxide, sodium isobutoxide, sodium sec-butoxide or sodium t-butoxide;
  • Suitable solvents are selected from the group consisting of methanol, ethanol, propanol, butanol, pentanol, isopropanol, isobutanol, sec-butanol or tert-butanol.
  • the base is selected from sodium ethoxide; the suitable solvent is selected from the group consisting of ethanol.
  • Alkyl means straight-chain or branched form, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, etc. Group.
  • the cycloalkyl group means a group including a cyclic chain form such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a methylcyclopropyl group, a cyclopropylcyclopropyl group or the like.
  • the alkenyl group means a linear or branched alkenyl group such as a 1-propenyl group, a 2-propenyl group and a different butenyl group.
  • Alkynyl means a straight or branched alkyne such as 1-propynyl, 2-propynyl and the different butynyl groups and the like.
  • Halogen means fluorine, chlorine, bromine or iodine.
  • the present invention has a point: the present invention employs a simple nitrogen-free phenylphosphine compound as a catalyst for catalyzing the synthesis of a pyridylpyrazolidinone carboxylate, which can greatly improve the yield of the reaction, thereby completing the present invention.
  • the reaction of the preparation method of the present invention can be carried out at 20 to 50 ° C, and the temperature is easily controlled, so that the safety of the reaction is greatly improved.
  • the catalyst of the invention has the advantages of simple synthesis and low cost, and can be prepared only by reacting a metal salt and a phenylphosphine in ethanol. Therefore, the catalyst of the present invention is easier to use in industrial production.
  • the synthesis method of the catalyst is as follows:
  • the catalyst Cu(PPh 3 ) 2 I bistriphenylphosphine cuprous iodide
  • the catalyst Cu(PPh 3 ) 2 I bistriphenylphosphine cuprous iodide
  • the present invention uses a nitrogen-free phenylphosphine compound which is simple in structure and inexpensive to obtain as a catalyst, and obtains a pyridylpyrazolidinone carboxylate compound in a relatively high yield. And got an industrial magnification application.
  • the reaction can be carried out at a lower temperature, which reduces the production energy consumption and greatly increases the safety of the reaction, which plays an important role in reducing production cost and improving reaction safety in the production process.
  • the ethyl 3-chloropyridylpyrazolidinonecarboxylate obtained in the above examples was subjected to bromination and hydrolysis to give 3-bromo-1-pyridylpyrazole-5-carboxylic acid.
  • the pyrazole carboxylic acid obtained by hydrolysis is further acylated and oxidized to obtain pyrazole oxychloride, and then reacted with 2-amino-3-methyl-5-chlorobenzoylmethylamine to obtain a commercial chlorantraniliprole.
  • the rate was 56.7% (calculated as ethyl 3-chloropyridylpyrazolidinone).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明属于有机合成领域，具体地涉及一种吡啶基吡唑烷酮羧酸酯类化合物的制备方法。反应式如图，式中各基团定义见说明书。本发明提供了一种制备苯甲酰胺类杀虫剂关键中间体吡啶基吡唑烷酮羧酸酯类化合物的方法，采用本发明的方法提高了产物的收率，减少了能源消耗，更易于工业化生产。

Description

吡啶基吡唑烷酮羧酸类化合物的制备方法 技术领域
本发明属于有机合成领域，具体地涉及一种吡啶基吡唑烷酮羧酸酯类化合物的制备方法。
背景技术
苯甲酰胺类化合物是一类高效、安全的新型杀虫剂。其中3-溴-N-(2-甲基-4-氯-6-(甲氨酰基)苯基)-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰胺(通用名为chlorantraniliprole)、3-溴-N-(2-甲基-4-氰基-6-(甲氨酰基)苯基)-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰胺(通用名为cyantraniliprole)具有高的杀虫活性，杜邦公司已开发为杀虫剂。石原产业株式会社正在开发的双酰胺类化合物3-溴-N-(2-氯-4-溴-6-((1-环丙基乙基)酰基)苯基)-1-(3-氯-2-吡啶基)-1H-吡唑-5-甲酰胺的(通用名为cyclaniliprole)，具有广谱的杀虫活性。沈阳化工研究院发现了具有高杀虫活性的3-溴-N-(2,4-二氯-6-(甲氨酰基)苯基)-1-(3,5-二氯-2-吡啶基)-1H-吡唑-5-甲酰胺，也已经开发为杀虫剂，通用名为四氯虫酰胺。
Figure PCTCN2016108984-appb-000001
1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸酯是合成chlorantraniliprole、cyantraniliprole、cyclaniliprole的共用关键中间体，WO2004011453中公开了1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸酯的合成，由肼基吡啶与马来酸二酯在回流温度下反应制得，反应收率仅为55％。
南开大学徐凤波等报道了使用结构复杂的含蒽环的双胺配合物A做为催化剂合成1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯的方法(参考文献：农药研究与应用.14(2),14-15,2009)，收率为70％。催化剂具体结构如下：
Figure PCTCN2016108984-appb-000002
一直以来，技术人员致力于不断研究开发新的、更为先进合理的吡啶基吡唑烷酮羧酸酯类化合物制备方法，以期获得质量更优、价格更低的苯甲酰胺类杀虫剂。
发明内容
本发明的目的在于提供一种更为简便、更加高效地吡啶基吡唑烷酮羧酸酯类化合物的制备方法。
为实现上述目的，本发明采用的技术方案为：
一种吡啶基吡唑烷酮羧酸酯类化合物的制备方法，反应式如下：
Figure PCTCN2016108984-appb-000003
式中：R1选自H或Cl；R2选自C1-C6烷基、C2-C4烯基、C2-C4炔基、C3-C6环烷基、卤素、未取代或被至多6个C1-C4的烷基取代的苄基；
肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)，
其中，催化剂选自：Cu(L1)Cl、Cu(L1)Br、Cu(L1)I、Cu(L2)2Cl、Cu(L2)2Br、Cu(L2)2I、Ni(L1)Cl2、Ni(L1)Br2、Ni(L1)I2、Ni(L2)2Cl2、Ni(L2)2Br2或Ni(L2)2I2；其中L1选自：
Figure PCTCN2016108984-appb-000004
L2选自：
Figure PCTCN2016108984-appb-000005
所述催化剂选自Cu(L1)Br，Cu(L1)I，Cu(L2)2Br或Cu(L2)2I；其中
L1选自：
Figure PCTCN2016108984-appb-000006
L2选自：
Figure PCTCN2016108984-appb-000007
所述催化剂选自Cu(L1)I或Cu(L2)2I，其中
L1选自：
Figure PCTCN2016108984-appb-000008
L2选自：
Figure PCTCN2016108984-appb-000009
所述在肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)的步骤包括，
所用的肼基吡啶(II)、碱、马来酸二酯(III)和催化剂的摩尔配比为1：1-2：1-5：0.00001-0.01。
所述肼基吡啶(II)、碱、马来酸二酯(III)和催化剂的摩尔配比为1：1.2-1.5：1.5-2：0.0001-0.001；
肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)的步骤中，控制反应温度为20-50℃。
肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)的反应在以下溶剂中进行：
所述溶剂为甲苯，氯苯，羧酸酯类，烷基醇类，醚类或极性非质子性溶剂；
所采用的碱选自碱金属的氢化物、碱金属的氨化物或烷基醇化物。
所述碱金属的氢化物为氢化锂、氢化钠或氢化钾；
碱金属的氨化物为氨基锂、氨基钠或氨基钾；烷基醇化物为甲醇钠，乙醇钠，丙醇钠，丁醇钠，戊醇钠，异丙醇钠，异丁醇钠，仲丁醇钠，叔丁醇钠，甲醇钾、乙醇钾，丙醇钾或叔丁醇钾；
所述羧酸酯类为乙酸酯，富马酸二酯或马来酸二酯；烷基醇类为甲醇，乙醇，丙醇，丁醇，戊醇，异丙醇，异丁醇，仲丁醇或叔丁醇；醚类为四氢呋喃，2-甲基四氢呋喃或二氧六环；极性非质子性溶剂为乙腈，N,N-二甲基甲酰胺，N,N-二甲基乙酰胺或二甲基亚砜。
所述碱选自甲醇钠，乙醇钠，丙醇钠，丁醇钠，戊醇钠，异丙醇钠，异丁醇钠，仲丁醇钠或叔丁醇钠；
所述适宜的溶剂选自甲醇，乙醇，丙醇，丁醇，戊醇，异丙醇，异丁醇，仲丁醇或叔丁醇。
所述碱选自乙醇钠；所述适宜的溶剂选自乙醇。
上面给出的合成方法及各通式化合物中基团的定义中，汇集所用术语一般定义如下：
烷基是指直链或支链形式，例如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、特丁基、正戊基、异戊基等基团。环烷基是指包括环状链形式，例如环丙基、环丁基、环戊基、环己基、甲基环丙基、环丙基环丙基等基团。烯基是指直链或支链烯基，如1-丙烯基、2-丙烯基和不同的丁烯基等。炔基是指直链或支链炔烃，如1-丙炔基、2-丙炔基和不同的丁炔基等。卤素是指氟、氯、溴、碘。
本发明所具有有点：本发明采用结构简单的不含氮的苯基膦化合物作为催化吡啶基吡唑烷酮羧酸酯的合成的催化剂，可以大大提高反应的收率，从而完成了本发明。
可选地，本发明制备方法的反应可在20-50℃条件下进行，该温度易于控制，使反应的安全性大大提高。此外，本发明的催化剂还存在合成简单易行、价格低廉的优势，只需金属盐和苯基膦在乙醇中反应即可制得。因此，本发明的催化剂更易于在工业化生产中的应用。
具体实施方式
下面通过列举实施例来对本发明进行更详细的说明吡啶基吡唑烷酮羧酸酯类化合物制备方法，但并不意味着限制本发明。
实施例1
1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯的合成
Figure PCTCN2016108984-appb-000010
在2000毫升反应瓶内加入1000毫升无水乙醇和乙醇钠(65.7克，0.966摩尔)， 3-氯-2-肼基吡啶(101.04克，98％，0.69摩尔)，再加入催化剂Cu(PPh3)2I(0.15克，0.00021摩尔)(双三苯基膦碘化亚铜，合成方法参加：Chemistry-A European Journal,16(39),11822-11826,2010)混合物加热至40℃，滴加马来酸二乙酯(145.7克，0.83摩尔)。保持此温度4h，而后将反应混合物用冰乙酸(60克)中和。混合物用1000毫升水稀释，冷至室温，有固体析出。过滤收集固体，用3×150毫升40％的乙醇水溶液洗涤。干燥后得1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-甲酸乙酯橙色固体149.91克，外标法定量分析其含量为98％，收率79％。1H NMR(300MHz,DMSO)：8.289-8.269(q,1H),7.956-7.190(q,1H),7.231-7.190(q,1H),4.862-4.816(q,1H),4.236-4.165(q,2H),2.967-2.879(q,1H),2.396-2.336(q,1H),1.250-1.202(t,3H)。
催化剂的合成方法如下：
在2000毫升反应瓶内依次加入1000毫升无水乙醇、三苯基膦(500克,1,9mol)、CuI(181克,0.95mol)，升温至80℃反应1h后，自然降温至室温，过滤，干燥，得产品644.9克，收率95％。
下述其它催化剂选择适宜的原料可按照此方式制备获得。
实施例2
1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯的合成
Figure PCTCN2016108984-appb-000011
在1000毫升反应瓶内加入300毫升无水乙醇和乙醇钠(16.97克，0.249摩尔)，3-氯-2-肼基吡啶(30.75克，98％，0.21摩尔)，再加入催化剂Cu(binap)I(0.017克，0.000021摩尔)(2,2'-双-(二苯膦基)-1,1'-联萘简称binap，合成方法参加：Chemistry-A European Journal,16(39),11822-11826,2010)混合物加热至30℃，滴
加马来酸二乙酯(44.23克，0.252摩尔)。保持此温度4h，而后将反应混合物用冰乙酸(15克，)中和。混合物用300毫升水稀释，冷至室温，有固体析出。过滤收集固体，用3×50毫升40％的乙醇水溶液洗涤。干燥后得1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-甲酸乙酯橙色固体47.06克，外标法定量分析其含量为95％，收率79％。
实施例3
1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯的合成
Figure PCTCN2016108984-appb-000012
在1000毫升反应瓶内加入300毫升无水乙醇和乙醇钠(16.97克，0.249摩尔)，3-氯-2-肼基吡啶(30.75克，98％，0.21摩尔)，再加入催化剂Cu(PPh3)2Br(0.042克，0.000063摩尔)(双三苯基膦溴化亚铜，合成方法参加：Chemistry-A European Journal,16(39),11822-11826,2010)，混合物加热至35℃，滴加马来酸二乙酯(44.23克，0.252摩尔)。保持此温度4h，而后将反应混合物用冰乙酸(15克)中和。混合物用300毫升水稀释，冷至室温，有固体析出。过滤收集固体，用3×50毫升40％的乙醇水溶液洗涤。干燥后得1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-甲酸乙酯橙色 固体45.98克，外标法定量分析其含量为96％，收率78％。
实施例4
1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯的合成
Figure PCTCN2016108984-appb-000013
在1000毫升反应瓶内加入300毫升无水乙醇和乙醇钠(16.97克，0.249摩尔)，3-氯-2-肼基吡啶(30.75克，98％，0.21摩尔)，再加入催化剂Ni(PPh3)2Br2(0.047克，0.000063摩尔)(双三苯基膦二溴化镍合成方法参加：Appl.Organometal.Chem.,23,455-459,2009)，混合物加热至45℃，滴加马来酸二乙酯(44.23克，0.252摩尔)。保持此温度4h，而后将反应混合物用冰乙酸(15克)中和。混合物用300毫升水稀释，冷至室温，有固体析出。过滤收集固体，用3×50毫升40％的乙醇水溶液洗涤。干燥后得1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-甲酸乙酯橙色固体45.98克，外标法定量分析其含量为96％，收率78％。
按照实施例1中的方法，使用催化剂Cu(PPh3)2I(双三苯基膦碘化亚铜)可以高收率的制得1-(3,5-二氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯。1H NMR(300MHz,CDCl3)：8.146(q,1H),7.658(q,1H),5.073(dd,1H),4.241(q,2H),3.029(dd,1H),2.721(dd,1H),1.258(t,3H)。
实施例5
1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯的合成
Figure PCTCN2016108984-appb-000014
在1000升反应釜内加入600升无无水乙醇和乙醇钠(34.6公斤，500摩尔)，3-氯-2-肼基吡啶(61.5公斤，98％，420千摩尔)，再加入催化剂Cu(PPh3)2I(90克)，混合物加热至35℃，滴加马来酸二乙酯(88.4公斤，500摩尔)。保持此温度4h，而后将反应混合物用冰乙酸(20公斤)中和。混合物用300升水稀释，冷至室温，有固体析出。过滤收集固体，用100升40％的乙醇水溶液打浆。经离心过滤、干燥后，得1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-甲酸乙酯橙色固体92公斤，外标法定量分析其含量为96％，收率78％。
对照实施例
按照南开大学公开方法(参考文献：农药研究与应用.14(2),14-15,2009)合成了1-(3-氯吡啶-2-基)-3-吡唑烷酮-5-羧酸乙酯。
Figure PCTCN2016108984-appb-000015
在1000毫升反应瓶内加入300毫升无水乙醇和钠(5.22克，0.227摩尔)，搅拌至无气泡产生，加入3-氯-2-肼基吡啶(30.00克，0.205摩尔)，混合物加热至 回流5min，再加入催化剂A 0.003克，滴加马来酸二乙酯(36.00克，0.209摩尔)。保持回流30min，而后将反应混合物冷却至65℃用冰乙酸(25.2克)中和。混合物用300毫升水稀释，冷至室温，有固体析出。过滤收集固体，用3×50毫升40％的乙醇水溶液洗涤。干燥后得1-(3-氯-2-吡啶基)-3-吡唑烷酮-5-甲酸乙酯，橙色固体45.2克，归一含量96％，外标法定量分析其含量为85.4％，收率70％。
从上述各实施例以及对比例可见，本发明采用结构简单、廉价易得的的不含氮的苯基膦化合物作为催化剂，以较高收率制得了吡啶基吡唑烷酮羧酸酯类化合物，并得到了工业放大应用。使用本发明的催化剂后，该反应可在较低温度下进行，降低了生产能源消耗，同时使反应的安全性大大提高，这对生产过程中降低生产成本、提高反应安全性起到了重要作用。
应用实例
Figure PCTCN2016108984-appb-000016
按照上述反应式，将上述实施例制备所得3-氯吡啶基吡唑烷酮羧酸乙酯经溴化、水解得到3-溴代-1-吡啶基吡唑-5-羧酸。水解所得吡唑羧酸再经过酰化、氧化，制得吡唑酰氯，再与2-氨基-3-甲基-5-氯苯甲酰甲胺反应制得商品化品种chlorantraniliprole，反应的总收率为56.7％(以3-氯吡啶基吡唑烷酮羧酸乙酯计)。

Claims (10)

  1. 一种吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：
    反应式如下：
    Figure PCTCN2016108984-appb-100001
    式中：R1选自H或Cl；R2选自C1-C6烷基、C2-C4烯基、C2-C4炔基、C3-C6环烷基、卤素、未取代或被至多6个C1-C4的烷基取代的苄基；
    肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)，
    其中，催化剂选自：Cu(L1)Cl、Cu(L1)Br、Cu(L1)I、Cu(L2)2Cl、Cu(L2)2Br、Cu(L2)2I、Ni(L1)Cl2、Ni(L1)Br2、Ni(L1)I2、Ni(L2)2Cl2、Ni(L2)2Br2或Ni(L2)2I2；
    其中L1选自：
    Figure PCTCN2016108984-appb-100002
    L2选自：
    Figure PCTCN2016108984-appb-100003
  2. 按权利要求1所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：
    所述催化剂选自Cu(L1)Br，Cu(L1)I，Cu(L2)2Br或Cu(L2)2I；其中
    L1选自：
    Figure PCTCN2016108984-appb-100004
    L2选自：
    Figure PCTCN2016108984-appb-100005
  3. 按权利要求2所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：所述催化剂选自Cu(L1)I或Cu(L2)2I，其中
    L1选自：
    Figure PCTCN2016108984-appb-100006
    L2选自：
    Figure PCTCN2016108984-appb-100007
  4. 按权利要求1所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：在肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)的步骤包括，
    所用的肼基吡啶(II)、碱、马来酸二酯(III)和催化剂的摩尔配比为1：1-2：1-5：0.00001-0.01。
  5. 按权利要求4所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：所述肼基吡啶(II)、碱、马来酸二酯(III)和催化剂的摩尔配比为1：1.2-1.5：1.5-2：0.0001-0.001。
  6. 按权利要求1所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)的步骤中，控制反应温度为20-50℃。
  7. 按权利要求1所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：肼基吡啶(II)在碱性条件下，通过催化剂的作用与马来酸二酯(III)反应制得吡啶基吡唑烷酮羧酸酯类化合物(I)的反应在以下溶剂中进行：
    所述溶剂为甲苯，氯苯，羧酸酯类，烷基醇类，醚类或极性非质子性溶剂；
    所采用的碱选自碱金属的氢化物、碱金属的氨化物或烷基醇化物。
  8. 按权利要求7所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：所述碱金属的氢化物为氢化锂、氢化钠或氢化钾；
    碱金属的氨化物为氨基锂、氨基钠或氨基钾；烷基醇化物为甲醇钠，乙醇钠，丙醇钠，丁醇钠，戊醇钠，异丙醇钠，异丁醇钠，仲丁醇钠，叔丁醇钠，甲醇钾、乙醇钾，丙醇钾或叔丁醇钾；
    所述羧酸酯类为乙酸酯，富马酸二酯或马来酸二酯；烷基醇类为甲醇，乙醇，丙醇，丁醇，戊醇，异丙醇，异丁醇，仲丁醇或叔丁醇；醚类为四氢呋喃，2-甲基四氢呋喃或二氧六环；极性非质子性溶剂为乙腈，N,N-二甲基甲酰胺，N,N-二甲基乙酰胺或二甲基亚砜。
  9. 按权利要求8所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：所述碱选自甲醇钠，乙醇钠，丙醇钠，丁醇钠，戊醇钠，异丙醇钠，异丁醇钠，仲丁醇钠或叔丁醇钠；
    所述溶剂选自甲醇，乙醇，丙醇，丁醇，戊醇，异丙醇，异丁醇，仲丁醇或叔丁醇。
  10. 按权利要求9所述的吡啶基吡唑烷酮羧酸酯类化合物的制备方法，其特征在于：所述碱选自乙醇钠；所述溶剂选自乙醇。
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