CN101747318A - 1-(3,5-dichloro-pyridyl)-1H-5-pyrazole carboxylic acid ester compound - Google Patents

1-(3,5-dichloro-pyridyl)-1H-5-pyrazole carboxylic acid ester compound Download PDF

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CN101747318A
CN101747318A CN200810182691A CN200810182691A CN101747318A CN 101747318 A CN101747318 A CN 101747318A CN 200810182691 A CN200810182691 A CN 200810182691A CN 200810182691 A CN200810182691 A CN 200810182691A CN 101747318 A CN101747318 A CN 101747318A
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杨辉斌
李斌
吴鸿飞
于海波
欧阳津
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ZHONGHUA CO Ltd CHINA
Shenyang Research Institute of Chemical Industry Co Ltd
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ZHONGHUA CO Ltd CHINA
Shenyang Research Institute of Chemical Industry Co Ltd
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Abstract

The invention provides a 1-(3,5-dichloro-pyridyl)-1H-5-pyrazole carboxylic acid ester compound which is shown as a general formula (I) and a midbody which is used for preparing the compound shown as the general formula (I) and is shown as a general formula (II), wherein the definitions of all substituent groups in the formulas are described in the specification of the invention. The compound of the invention can be used as an important midbody for organic synthesis, for example, the compound can be used for preparing O-aminobenzamide compounds which have insecticidal activity.

Description

1-(3,5-dichloropyridine base)-1H-5-pyrazole carboxylic acid ester compound
Technical field
The invention belongs to the organic synthesis field.Relate to a kind of 1-(3,5-dichloropyridine base)-1H-5-pyrazole carboxylic acid ester compound particularly.These compounds can be used as organic synthesis intermediate, for example can be used for preparing the Anthranilamide compound that some has insecticidal activity.
Background technology
1-(3,5-dichloropyridine base)-and the 1H-5-pyrazole carboxylic acid ester compound is to prepare some to have the important intermediate of the anthranilamides of insecticidal activity, (application number: part discloses this compounds to Chinese patent application 200810116198.4).
Reported the preparation and the application of following compounds (KC) among WO 03/015519A1, WO 03/015518A1 and the CN1541206:
Figure G2008101826916D00011
In the prior art, do not see openly as 1-shown in the present (3,5-dichloropyridine base)-1H-5-pyrazole carboxylic acid ester compound.
Summary of the invention
The object of the present invention is to provide a kind of 1-(3,5-dichloropyridine base)-1H-5-pyrazole carboxylic acid ester compound of novel structure, these compounds can be used for preparing some anthranilamides, and the latter has important value as sterilant.
Technical scheme of the present invention is as follows:
The invention provides a kind of 1-(3,5-dichloropyridine base)-1H-5-pyrazole carboxylic acid ester compound, shown in general formula (I):
In the formula:
R 1Be selected from OH, halogen, C 1-C 6Alkoxyl group, C 1-C 6Halogenated alkoxy, C 2-C 6Cyanogen is for alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group, C 3-C 6Halo alkynyloxy group, benzyloxy, C 1-C 3Alkylsulphonic acid base, the phenylbenzimidazole sulfonic acid base that does not replace or replace, described substituting group is selected from methyl or halogen;
R 2Be selected from C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
Among the present invention more preferably compound be, in the general formula (I):
R 1Be selected from OH, Cl, Br, C 1-C 3Alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group or benzyloxy;
R 2Be selected from C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
Further preferred compound is among the present invention, in the general formula (I):
R 1Be selected from OH, Cl or Br;
R 2Be selected from C 1-C 6Alkyl.
The present invention also comprises a kind of intermediate that can be used for preparing general formula (I) compound, shown in general formula (II):
Figure G2008101826916D00021
In the formula:
R 1Be selected from OH, halogen, C 1-C 6Alkoxyl group, C 1-C 6Halogenated alkoxy, C 2-C 6Cyanogen is for alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group, C 3-C 6Halo alkynyloxy group, benzyloxy, C 1-C 3Alkylsulphonic acid base, the phenylbenzimidazole sulfonic acid base that does not replace or replace, described substituting group is selected from methyl or halogen;
R 2Be selected from H, C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
Among the present invention more preferably compound be, in the general formula (II):
R 1Be selected from OH, Cl, Br, C 1-C 3Alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group or benzyloxy;
R 2Be selected from H, C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
Further preferred compound is among the present invention, among the general formula I I:
R 1Be selected from OH, Cl or Br;
R 2Be selected from H or C 1-C 6Alkyl.
In the definition of the general formula compound that provides above, it is as follows to compile used term General Definition:
Alkyl is meant the straight or branched form, for example groups such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, tertiary butyl, n-pentyl, isopentyl, n-hexyl.Thiazolinyl is meant the straight or branched thiazolinyl, as 1-propenyl, 2-propenyl and different butenyl, pentenyl and vinyl isomer.Thiazolinyl also comprises polyenoid, as 1, and 2-propadiene base and 2,4-hexadienyl.Alkoxyl group is meant that the alkyl end is connected with the group of Sauerstoffatom, for example methoxyl group, oxyethyl group, positive propoxy, isopropoxy, tert-butoxy etc.Halogenated alkoxy is meant that alkyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Cyanogen is meant that for alkoxyl group alkyl is replaced by one or more cyano group, and end is connected with the group of Sauerstoffatom.Alkene oxygen base is meant that the thiazolinyl end is connected with the group of Sauerstoffatom.Haloalkene oxygen base is meant that thiazolinyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Alkynyloxy group is meant that the alkynyl end is connected with the group of Sauerstoffatom.The halo alkynyloxy group is meant that alkynyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Benzyloxy is meant that the benzyl end is connected with the group of Sauerstoffatom.Alkyl sulphonyl refers to the terminal (SO of being of alkyl 2-) group, as methyl sulphonyl.The alkylsulphonic acid base refers to the terminal (SO of being of alkyl 3-) group, as the methylsulphonic acid base.(replacement) phenylbenzimidazole sulfonic acid base refers to the terminal (SO of being of phenyl 3-) group, the benzene ring hydrogen can be replaced by groups such as methyl, halogens, as the p-methyl benzenesulfonic acid base.Halogen is meant fluorine, chlorine, bromine, iodine.
Formula of the present invention (I) compound can be by following method preparation, and each group definition is the same in the reaction formula.
Figure G2008101826916D00031
General formula (II) compound in the presence of acid in The suitable solvent, temperature be 0 ℃ under the boiling point reaction oxidation in 0.5-8 hour make general formula (I) compound.Suitable oxygenant is selected from hydrogen peroxide, organo-peroxide, Potassium Persulphate, Sodium Persulfate, ammonium persulphate, Potassium peroxysulfate or potassium permanganate.The suitable solvent is selected from tetrahydrofuran (THF), dioxane, ethyl acetate, N, dinethylformamide, acetonitrile etc.Employed suitable acid is selected from sulfuric acid, phosphoric acid or acetate etc. in oxidation step.
R 1For general formula (I) compound of substituted oxy also can be used R 1For general formula (I) compound of hydroxyl and halides in the presence of suitable alkali and solvent, temperature is descended to react to boiling point and was made in 0.5-48 hour for-10 ℃.Suitable alkali is selected from organic bases such as triethylamine, N, accelerine or pyridine etc., or mineral alkali such as salt of wormwood, sodium hydroxide, potassium hydroxide, sodium methylate, sodium tert-butoxide or potassium tert.-butoxide etc.The suitable solvent is selected from methylene dichloride, chloroform, tetracol phenixin, N, dinethylformamide, tetrahydrofuran (THF), acetonitrile, dioxane or dimethyl sulfoxide (DMSO) etc.Suitable halides such as methyl iodide, allyl bromide 98, propargyl bromide, benzyl chlorine, Methanesulfonyl chloride or Tosyl chloride etc. all have commercially available.
General formula of the present invention (II) compound can be by following method preparation, and each group definition is the same in the reaction formula.
Figure G2008101826916D00032
General formula (III) compound and general formula (IV) compound (for example fumaric acid esters or maleic acid ester or their mixture) react in the presence of alkali and solvent and make general formula (II) (R 1Be OH) compound.Suitable alkali is selected from metal alkoxide such as sodium methylate, potassium methylate, sodium ethylate, potassium ethylate, potassium tert.-butoxide or sodium tert-butoxide etc.The suitable solvent is selected from alcohol as ethanol or methyl alcohol.General 1-24 of reaction times hour.Reactant adds organic acid such as acetate etc. then, or mineral acid example hydrochloric acid, sulfuric acid etc. carry out acidifying.General formula compound (IV) has commercially available as maleic acid ester etc.
Figure G2008101826916D00041
R 1For general formula (II) compound of OH in the presence of The suitable solvent with the halide reagent reaction, obtain corresponding R 1General formula (II) compound for halogen.Suitable halide reagent is selected from trihalophosporus oxide, phosphorus trihalide, phosphorus pentahalides, thionyl chloride, dihalo trialkyl phosphine, dihalo diphenylphosphine, oxalyl chloride or carbonyl chloride.Being used for halogenated suitable solvent is selected from methylene dichloride, chloroform, chloro-butane, benzene, dimethylbenzene, chlorinated benzene, tetrahydrofuran (THF), dioxane, ether, acetonitrile, N, dinethylformamide etc.Temperature of reaction is generally 20 ℃ to boiling temperature, general 1-24 of reaction times hour.Reactant mineral alkali such as sodium bicarbonate, sodium hydroxide etc., or organic bases then such as sodium acetate neutralization obtain object.
R 1For general formula (II) compound of substituted oxy also can be used R 1For general formula (II) compound of hydroxyl and halides in the presence of suitable alkali and solvent, temperature is descended to react to boiling point and was made in 0.5-48 hour for-10 ℃.Suitable alkali is selected from organic bases such as triethylamine, N, accelerine or pyridine etc., or mineral alkali such as salt of wormwood, sodium hydroxide, potassium hydroxide, sodium methylate, sodium tert-butoxide or potassium tert.-butoxide etc.The suitable solvent is selected from methylene dichloride, chloroform, tetracol phenixin, N, dinethylformamide, tetrahydrofuran (THF), acetonitrile, dioxane or dimethyl sulfoxide (DMSO) etc.Suitable halides such as methyl iodide, allyl bromide 98, propargyl bromide, benzyl chlorine, Methanesulfonyl chloride or Tosyl chloride etc. all have commercially available.
The structure and the physical properties of table 1. part general formula (I) compound
Figure G2008101826916D00042
Compound R 1 R 2 Outward appearance (fusing point (℃))
1.1 OH -CH 2CH 3 Yellow solid (164-167)
1.2 OCH 3 -CH 2CH 3 Colorless oil
1.3 OCH 2CH＝CH 2 -CH 2CH 3 Yellow oil
1.4 OCH 2CH＝CCl 2 -CH 2CH 3
1.5 OCH 2CCl＝CH 2 -CH 2CH 3
1.6 OCH 2CH＝CHCl -CH 2CH 3
1.7 OCH 2C≡CH -CH 2CH 3 Yellow oil
1.8 OCH 2C≡CCl -CH 2CH 3
1.9 OCH 2C≡CH -CH 2CH＝CH 2
1.10 OCH 2C≡CH -CH 2CH 2CH 2CH 2CH 3
1.11 OCH 2C≡CH -CH 2Ph
1.12 OCH 2Ph -CH 2CH 3 Yellow oil
1.13 OCH 2CN -CH 2CH 3
1.14 OCH 2CF 3 -CH 2CH 3
1.15 OCHFCF 3 -CH 2CH 3
1.16 OSO 2CH 3 -CH 2CH 3
1.17 OSO 2Php-CH 3 -CH 2CH 3
1.18 Br -CH 2CH 3 Yellow oil
1.19 Br -CH 2CH＝CH 2
1.20 Br -CH 2CH 2CH 2CH 2CH 3
1.21 Br -CH 2Ph
1.22 Cl -CH 2CH 3 Colorless oil
1.23 Br H White solid (181-184)
1.24 Cl H White solid (176-179)
1.25 OCH 3 H White solid (225-227)
1.26 OCH 2CH＝CH 2 H White solid (123-125)
1.27 OCH 2C≡CH H White solid (153-157)
1.28 OCH 2Ph H White solid (146-148)
1.29 OCH 2CN H
1.30 OCH 2CF 3 H
1.31 OCHFCF 3 H
1.32 OSO 2CH 3 H
1.33 OSO 2Php-CH 3 H
The structure and the physical properties of table 2. part general formula (II) compound
Figure G2008101826916D00051
Compound RI R 2 Outward appearance (fusing point (℃))
2.1 OH -CH 2CH 3 Yellow solid (105-108)
2.2 Br -CH 2CH 3 Yellow oil
2.3 Cl -CH 2CH 3 Yellow oil
2.4 Br -CH 3
2.5 Br -CH 2CH＝CH 2
2.6 Br -CH 2CH 2CH 2CH 2CH 3
2.7 Br -CH 2Ph
2.8 OCH 3 -CH 2CH 3
2.9 OCH 2CH＝CH 2 -CH 2CH 3
2.10 OCH 2CH＝CCl 2 -CH 2CH 3
2.11 OCH 2CCl＝CH 2 -CH 2CH 3
2.12 OCH 2CH＝CHCl -CH 2CH 3
2.13 OCH 2C≡CH -CH 2CH 3
2.12 OCH 2CH＝CHCl -CH 2CH 3
2.14 OCH 2C≡CCl -CH 2CH 3
2.15 OCH 2C≡CH -CH 2CH＝CH 2
2.16 OCH 2C≡CH -CH 2CH 2CH 2CH 2CH 3
2.17 OCH 2C≡CH -CH 2Ph
2.18 OCH 2Ph -CH 2CH 3
2.19 OCH 2CN -CH 2CH 3
2.20 OCH 2CF 3 -CH 2CH 3
2.21 OCHFCF 3 -CH 2CH 3
2.22 OSO 2CH 3 -CH 2CH 3
2.23 OSO 2Php-CH 3 -CH 2CH 3
2.24 Br H Yellow solid (170-172)
2.25 Cl H
2.26 OCH 3 H
2.27 OCH 2CH＝CH 2 H
2.28 OCH 2C≡CH H
2.29 OCH 2Ph H
2.30 OCH 2CN H
2.31 OCH 2CF 3 H
2.32 OCHFCF 3 H
2.33 OSO 2CH 3 H
Part of compounds 1H NMR (300MHz, CDCl 3) data are as follows:
Compound 1.1:10.600 (br s, 1H), 8.445 (d, 1H), 7.912 (d, 1H), 6.373 (s, 1H), 4.214 (q, 2H), 1.241 (t, 3H).
Compound 1.2:8.451 (d, 1H), 7.898 (d, 1H), 6.447 (s, 1H), 4.238 (q, 2H), 3.953 (s, 3H), 1.246 (t, 3H).
Compound 1.3:8.446 (d, 1H), 7.896 (d, 1H), 6.463 (s, 1H), 6.082 (m, 1H), 5.446 (m, 2H), 4.764 (m, 2H), 4.237 (q, 2H), 1.258 (t, 3H).
Compound 1.7:8.445 (d, 1H), 7.902 (d, 1H), 6.498 (s, 1H), 4.896 (d, 2H), 4.240 (q, 2H), 2.547 (t, 1H), 1.260 (t, 3H).
Compound 1.12:8.428 (d, 1H), 7.855 (d, 1H), 7.443 (m, 5H), 6.473 (s, 1H), 5.273 (s, 2H), 4.204 (q, 2H), 1.229 (t, 3H).
Compound 1.18:8.461 (d, 1H), 7.933 (d, 1H), 7.035 (s, 1H), 4.263 (q, 2H), 1.262 (t, 3H).
Compound 1.22:8.456 (d, 1H), 7.931 (d, 1H), 6.943 (s, 1H), 4.260 (q, 2H), 1.257 (t, 3H).
Compound 1.23:(DMSO-d 6) 8.641 (d, 1H), 8.529 (d, 1H), 7.186 (s, 1H).
Compound 1.24:8.446 (d, 1H), 7.936 (d, 1H), 6.995 (s, 1H).
Compound 1.25:(DMSO-d 6) 8.485 (d, 1H), 8.228 (d, 1H), 6.365 (s, 1H), 3.870 (s, 3H).
Compound 1.26:(DMSO-d 6) 8.549 (d, 1H), 7.388 (d, 1H), 6.468 (s, 1H), 6.027 (m, 1H), 5.423-5.234 (m, 2H), 4.676 (m, 2H).
Compound 1.27:8.429 (d, 1H), 7.900 (d, 1H), 6.563 (s, 1H), 4.882 (s, 2H), 2.550 (s, 1H).
Compound 1.28:11.244 (br s, 1H), 8.432 (d, 1H), 7.876 (d, 1H), 7.452-7.247 (m, 5H), 6.527 (s, 1H), 5.264 (s, 2H).
Compound 2.1:8.146 (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).
Compound 2.2:8.027 (d, 1H), 7.673 (d, 1H), 5.201 (dd, 1H), 4.202 (q, 2H), 3.464 (dd, 1H), 3.248 (dd, 1H), 1.223 (t, 3H).
Compound 2.3:8.025 (d, 1H), 7.669 (d, 1H), 5.248 (dd, 1H), 4.180 (q, 2H), 3.386 (dd, 1H), 3.187 (dd, 1H), 1.247 (t, 3H).
Compound 2.24:(DMSO-d 6) 8.126 (d, 1H), 7.873 (d, 1H), 5.106 (dd, 1H), 3.566 (dd, 1H), 3.239 (dd, 1H).
Should be clear and definite be in claim of the present invention institute restricted portion, can carry out various conversion and change.
General formula provided by the present invention (I), (II) compound are the important organic synthesis intermediates of a class, for example can be used for preparing the logical formula V compound with insecticidal activity:
Figure G2008101826916D00071
In the formula V:
R 1Be selected from OH, halogen, C 1-C 6Alkoxyl group, C 1-C 6Halogenated alkoxy, C 2-C 6Cyanogen is for alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group, C 3-C 6Halo alkynyloxy group, benzyloxy, C 1-C 3Alkylsulphonic acid base, the phenylbenzimidazole sulfonic acid base that does not replace or replace, described substituting group is selected from methyl or halogen;
R 3Be selected from H or C 1-C 6Alkyl;
R 4Be selected from H, amino, C 1-C 6Alkyl, C 3-C 6Thiazolinyl, C 3-C 6Alkynyl or C 3-C 6Cycloalkyl, a hydrogen or a plurality of hydrogen optional on the described alkyl can be replaced by following substituting group: halogen, CN, hydroxyl or C 1-C 4Alkyl sulphonyl;
Perhaps R 3And R 4Form together with the nitrogen that is connected: Or
R 5Be selected from Cl, Br or CN;
R 6Be selected from Cl, Br or methyl.
In the definition of the general formula compound that provides above, it is as follows to compile used term General Definition:
Alkyl is meant the straight or branched form, for example groups such as methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, isobutyl-, sec-butyl, tertiary butyl, n-pentyl, isopentyl, n-hexyl.Cycloalkyl is meant and comprises the closed chain form, for example groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.Thiazolinyl is meant the straight or branched thiazolinyl, as 1-propenyl, 2-propenyl and different butenyl, pentenyl and vinyl isomer.Thiazolinyl also comprises polyenoid, as 1, and 2-propadiene base and 2,4-hexadienyl.Alkynyl is meant the straight or branched alkynyl, as 1-proyl, 2-propynyl and different butynyl, pentynyl and hexin base isomer.Alkynyl also comprises and contains a plurality of triple-linked groups, as 2, and 5-hexadiyne base.Alkoxyl group is meant that the alkyl end is connected with the group of Sauerstoffatom, for example methoxyl group, oxyethyl group, positive propoxy, isopropoxy, tert-butoxy etc.Halogenated alkoxy is meant that alkyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Cyanogen is meant that for alkoxyl group alkyl is replaced by one or more cyano group, and end is connected with the group of Sauerstoffatom.Alkene oxygen base is meant that the thiazolinyl end is connected with the group of Sauerstoffatom.Haloalkene oxygen base is meant that thiazolinyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Alkynyloxy group is meant that the alkynyl end is connected with the group of Sauerstoffatom.The halo alkynyloxy group is meant that alkynyl is replaced by one or more halogen atoms, and end is connected with the group of Sauerstoffatom.Benzyloxy is meant that the benzyl end is connected with the group of Sauerstoffatom.Alkyl sulphonyl refers to the terminal (SO of being of alkyl 2-) group, as methyl sulphonyl.The alkylsulphonic acid base refers to the terminal (SO of being of alkyl 3-) group, as the methylsulphonic acid base.(replacement) phenylbenzimidazole sulfonic acid base refers to the terminal (SO of being of phenyl 3-) group, the benzene ring hydrogen can be replaced by groups such as methyl, halogens, as the p-methyl benzenesulfonic acid base.Halogen is meant fluorine, chlorine, bromine, iodine.
Embodiment
Can be used to further specify the present invention with the following example, but do not mean that restriction the present invention.
General formula (I), (II) compound example
Synthesizing of embodiment 1,1-(3,5-dichloropyridine-2-yl)-3-pyrazolidone-5-carboxylic acid, ethyl ester (compound 2.1)
(1), 3,5-two chloro-2-hydrazino pyridines synthetic
Figure G2008101826916D00081
In reaction flask, add 2,3 successively, 5-trichloropyridine (20 grams, 0.11 mole), 80% hydrazine hydrate (34 grams, 0.55 mole) and 200 milliliters of dioxane, reflux temperature stirred 20 hours down.The reaction solution cool overnight, the adularescent crystal is separated out, and filters, and gets solid 14 grams after the drying, yield: 72%, fusing point: 187～189 ℃.Nuclear magnetic data is as follows:
1H?NMR(300MHz，DMSO-d 6)：8.123(d，1H)，7.849(d，1H)。
(2), 1-(3,5-dichloropyridine-2-yl)-3-pyrazolidone-5-carboxylic acid, ethyl ester (compound 2.1) is synthetic
Figure G2008101826916D00082
In reaction flask, add 300 milliliters of dehydrated alcohols and sodium ethylate (4.1 grams, 61 mmoles), 3,5-two chloro-2-hydrazino pyridines (10 grams, 56 mmoles), mixture heating up refluxed 5 minutes, dripped ethyl maleate (10 grams, 61 mmoles).Continued reflux 10 minutes.To be cooled after 65 ℃ with reaction mixture with glacial acetic acid (13 grams, 224 mmoles) neutralization.Mixture dilutes with 300 ml waters, is chilled to room temperature, has solid to separate out.Solid collected by filtration, the aqueous ethanolic solution with 40% (3 * 50 milliliters) washing.Obtain orange solids 8 grams after the drying, yield 47%, fusing point: 105～108 ℃.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：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)。
Synthesizing of embodiment 2,1-(3,5-dichloropyridine-2-yl)-3-bromo-2-pyrazoline-5-carboxylic acid, ethyl ester (compound 2.2)
Figure G2008101826916D00091
In reaction flask, add 65 milliliters of acetonitriles, 1-(3,5-dichloropyridine-2-yl)-3-pyrazolidone-5-carboxylic acid, ethyl ester (compound 2.1, embodiment 1 preparation, 3.0 grams, 9.8 mmoles) and tribromo oxygen phosphorus (2.8 grams, 9.8 mmoles).Reflux 2 hours, 30 milliliters of solvents are removed in distillation.Above-mentioned concentration response thing is added in water (40 milliliters) solution of sodium bicarbonate (10 grams, 120 mmoles), stirs 20 minutes to no longer including gas evolution.Mixture dilutes with 100 milliliters of methylene dichloride, stirs then 50 minutes.Use methylene dichloride (3 * 100 milliliters) extraction again.Concentrating under reduced pressure gets the dark amber oily thing of 2.4 grams, yield: 67% after organic phase washing, the dried over mgso.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：8.027(d，1H)，7.673(d，1H)，5.201(dd，1H)，4.202(q，2H)，3.464(dd，1H)，3.248(dd，1H)，1.223(t，3H)。
Synthesizing of embodiment 3,1-(3,5-dichloropyridine-2-yl)-3-hydroxyl-1H-pyrazoles-5-ethyl formate (compound 1.1)
Figure G2008101826916D00092
The sulfuric acid (2.6 grams, 26 mmoles) that in reaction flask, adds 50 milliliters of 1-(3,5-dichloropyridine-2-yl)-3-pyrazolidone-5-carboxylic acid, ethyl esters (compound 2.1, embodiment 1 preparation, 4.0 grams, 13 mmoles), acetonitrile and 98%.Stir after 10 minutes, add Potassium Persulphate (5.7 grams, 21 mmoles), reflux 5 hours.Reacting liquor while hot (50-65 ℃) is filtered, and filter cake washs with 10 milliliters of acetonitriles.Filtrate is concentrated into about 10 milliliters on Rotary Evaporators, add 50 ml waters, the solid collected by filtration product.Product washs with 3 * 15 milliliter 25% acetonitrile solution, obtains orange solids 3.0 grams after the drying, yield 76%, fusing point: 164～167 ℃.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：8.445(d，1H)，7.912(d，1H)，6.546(s，1H)，4.262(q，2H)，1.236(t，3H)。
Synthesizing of embodiment 4,1-(3,5-dichloropyridine-2-yl)-3-(2-alkynes propoxy-)-1H-pyrazoles-5-ethyl formate (1.7)
Figure G2008101826916D00101
In reaction flask, add 1-(3 successively, 5-dichloropyridine-2-yl)-3-hydroxyl-1H-pyrazoles-5-ethyl formate (compound 1.1, embodiment 1 preparation, 0.7 gram, 2.3 mmole), 10 milliliters of acetonitriles, salt of wormwood (0.27 gram, 2.3 mmoles) and propargyl bromides (0.31 gram, 2.3 mmoles), be heated to 60 ℃, reacted 2 hours.After reacting completely, in reaction solution impouring 100 ml waters, with 2 * 100 milliliters of ethyl acetate extractions, organic layer washs with saturated sodium carbonate solution, saturated aqueous common salt (3 * 50 milliliters), concentrate behind the anhydrous magnesium sulfate drying, the resistates silica gel column chromatography is purified, and gets 0.3 gram yellow oil, yield 38%.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：8.445(d，1H)，7.902(d，1H)，6.498(s，1H)，4.896(d，2H)，4.240(q，2H)，2.547(t，1H)，1.260(t，3H)。
Synthesizing of embodiment 5,1-(3,5-dichloropyridine-2-yl)-3-bromo-1H-pyrazoles-5-carboxylic acid, ethyl ester (compound 1.18)
Figure G2008101826916D00102
The sulfuric acid (1.1 grams, 10.9 mmoles) that in reaction flask, adds 1-(3,5-chloropyridine-2-yl)-3-bromo-2-pyrazoline-5-carboxylic acid, ethyl ester (compound 2.1, embodiment 1 preparation, 2.0 grams, 5.4 mmoles), 10 milliliters of acetonitriles and 98%.Stir after 30 minutes, add Potassium Persulphate (2.4 grams, 8.7 mmoles), reflux 5 hours.Reacting liquor while hot (50-65 ℃) is filtered, and filter cake washs with 10 milliliters of acetonitriles.Filtrate is concentrated into about 10 milliliters on Rotary Evaporators, add 50 ml waters, the solid collected by filtration product.Product washs with 3 * 15 milliliter 25% acetonitrile solution, obtains orange solids 1.6 grams after the drying, yield: 80%.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：8.461(d，1H)，7.933(d，1H)，7.035(s，1H)，4.263(q，2H)，1.262(t，3H)。
Synthesizing of embodiment 6,1-(3,5-dichloropyridine-2-yl)-3-(2-alkynes propoxy-)-1H-pyrazoles-5-formic acid (compound 1.27)
In reaction flask, add 1-(3,5-dichloropyridine-2-yl)-3-(2-alkynes propoxy-)-1H-pyrazoles-5-ethyl formate (compound 1.7, embodiment 4 preparations, 0.3 gram, 0.88 mmole), methyl alcohol, each 10 milliliters in water and sodium hydroxide (0.04 gram, 0.88 mmole).Stirring at room 1 hour reacts completely.On Rotary Evaporators, concentrate the dark brown orange solution that forms and arrive about 10 milliliters, add 40 milliliters in water then.The aqueous solution is with 50 milliliters of extracted with diethyl ether, be acidified to pH=4 with concentrated hydrochloric acid, add ethyl acetate (150 milliliters) extraction, organic layer washs with saturated nacl aqueous solution (3 * 50 milliliters), anhydrous magnesium sulfate drying, decompression steam solvent to the greatest extent, get little yellow solid 0.2 gram of target compound, yield 73%, fusing point: 153～157 ℃.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：8.429(d，1H)，7.900(d，1H)，6.563(s，1H)，4.882(s，2H)，2.550(s，1H)。
General formula (I) application of compound example
Compound 3-bromo-N-(4-chloro-2-methyl-6-(methylformamide) phenyl)-1-(3,5-two chloro-2-pyridyl)-1H-pyrazoles-5-methane amide that embodiment 7, preparation have insecticidal activity
(1), 1-(3,5-dichloropyridine-2-yl)-3-bromo-1H-pyrazoles-5-carboxylic acid is synthetic
Figure G2008101826916D00111
In reaction flask, add 1-(3,5-dichloropyridine-2-yl)-3-bromo-1H-pyrazoles-5-carboxylic acid, ethyl ester (compound 1.18, embodiment 5 preparations, 2.0 grams, 5.5 mmoles), 10 milliliters of methyl alcohol, 10 milliliters in water and sodium hydroxide (0.3 gram, 5.5 mmoles).Stirring at room 1 hour reacts completely.On Rotary Evaporators, concentrate the dark brown orange solution that forms and arrive about 10 milliliters, add 40 milliliters in water then.The aqueous solution is acidified to pH=4 with 50 milliliters of extracted with diethyl ether with concentrated hydrochloric acid.Filter and collect the solid product that generates,, obtain white solid 0.97 gram after the drying, yield: 48% with the washing of 2 * 50 ml waters.Nuclear magnetic data is as follows:
1H?NMR(300MHz，DMSO-d 6)：8.641(d，1H)，8.529(d，1H)，7.186(s，1H)。
(2), 1-(3,5-dichloropyridine-2-yl)-3-bromo-1H-pyrazoles-5-formyl chloride is synthetic
Figure G2008101826916D00112
In reaction flask, add 1-(3,5-dichloropyridine-2-yl)-3-bromo-1H-pyrazoles-5-carboxylic acid (0.4 gram, 1.2 mmoles), 10 milliliters of methylene dichloride and oxalyl chloride (0.31 gram, 2.4 mmoles), splash into 5 dimethyl formamides again, have a large amount of gases to generate.The stirring at room reaction after 8 hours is evaporated to reaction solution dried, adds 100 milliliters of toluene again, gets 0.42 gram green solid behind the concentrating under reduced pressure, yield: 100%.
(3), compound 3-bromo-N-(4-chloro-2-methyl-6-(methylformamide) phenyl)-1-(3,5-two chloro-2-pyridyl)-1H-pyrazoles-5-methane amide is synthetic
Figure G2008101826916D00121
In reaction flask, add N-methyl-5-chloro-3-methyl-2-aminobenzamide (0.34 gram, 1.7 mmole), 20 milliliters of methylene dichloride, 1-(3,5-dichloropyridine-2-yl)-3-bromo-1H-pyrazoles-5-formyl chloride (0.60 gram, 1.7 mmole) and triethylamine (0.17 the gram, 1.7 mmole), stirring at room is 3 hours.In reaction solution impouring 100 ml waters, with 2 * 100 milliliters of ethyl acetate extractions, organic layer saturated sodium carbonate solution, saturated common salt water washing, concentrate behind the anhydrous magnesium sulfate drying, the purification of resistates silica gel column chromatography (leacheate is an ethyl acetate: sherwood oil=1:2), get 0.21 gram white solid, yield: 24%, fusing point: 135～138 ℃.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：10.208(br?s，1H)，8.383(d，1H)，7.853(d，1H)，7.252(s，1H)，7.106-7.084(m，2H)，6.411(br?s，1H)，2.903(d，3H)，2.085(s，3H)。
This compound has excellent insecticidal activity, and (application number: it is better to disclose the prevention effect of this compound (compound number 1.24) to beet armyworm when concentration is 1ppm 200810116198.4), and mortality ratio is more than 90% for Chinese patent application.
Compound 3-bromo-N-(2,4-two chloro-6-(methylformamide) phenyl)-1-(3,5-two chloro-2-pyridyl)-1H-pyrazoles-5-methane amide that embodiment 8, preparation have insecticidal activity
(1), 2-(3-bromo-1-(3,5-dichloropyridine-2-yl)-1H-5-pyrazolyl)-6, the preparation of 8-two chloro-4H-benzo [d] [1,3] oxazine-4-ketone
Figure G2008101826916D00122
In reaction flask, add Methanesulfonyl chloride (1.1 grams, 9.8 mmole), acetonitrile (20 milliliters), drip 1-(3 under the room temperature, 5-dichloropyridine-2-yl)-(embodiment 7 steps 1 preparation of 3-bromo-1H-pyrazoles-5-carboxylic acid, 3.0 gram, 8.9 mmole) and triethylamine (0.89 the gram, 8.9 acetonitrile solution mmole) (30 milliliters), dripped off in 10 minutes, reacted 1 hour, in reaction system, add 3,5-two chloro-2-benzaminic acid (1.6 grams, 8.9 mmole), solution is brown, stirred 30 minutes, drip triethylamine (1.8 grams, 17 mmoles) acetonitrile solution (10 milliliters), there is yellow solid to generate, stirred 1 hour, add Methanesulfonyl chloride (1.1 grams again, 9.8 acetonitrile solution mmole) (10 milliliters), it is yellow that solution is, and has a large amount of solids to generate, and reacted 1 hour, drip triethylamine (0.89 gram again, 8.9 acetonitrile solution mmole) (4 milliliters), room temperature reaction spends the night then, in reaction solution impouring 100 ml waters, with 2 * 100 milliliters of ethyl acetate extractions, the organic layer saturated sodium carbonate solution, the saturated common salt water washing concentrates behind the anhydrous magnesium sulfate drying, and the purification of resistates silica gel column chromatography (leacheate is an ethyl acetate: sherwood oil=1:2), get yellow solid 2 grams, yield: 45%.
(2), the preparation of compound 3-bromo-N-(2,4-two chloro-6-(methylformamide) phenyl)-1-(3,5-two chloro-2-pyridyl)-1H-pyrazoles-5-methane amide
Figure G2008101826916D00131
In reaction flask, add 2-(3-bromo-1-(3 successively, 5-dichloropyridine-2-yl)-and the 1H-5-pyrazolyl)-6,8-two chloro-4H-benzos [d] [1,3] oxazine-4-ketone (0.3 gram, 0.6 mmole), tetrahydrofuran (THF) (4 milliliters) drips methylamine (0.09 gram under the stirring and dissolving, room temperature, 0.9 mmole, 30%), reacted 30 minutes, react completely, add ethyl acetate, the extraction of moisture liquid, organic layer is used the saturated common salt solution washing successively, anhydrous magnesium sulfate drying, decompression steam solvent to the greatest extent, the resistates silica gel column chromatography purify 0.14 gram white solid, yield: 43%, fusing point: 175～178 ℃.Nuclear magnetic data is as follows:
1H?NMR(300MHz，CDCl 3)：10.000(br?s，1H)，8.395(d，1H)，7.856(d，1H)，7.311(s，1H)，7.223-7.142(m，2H)，6.434(br?s，1H)，2.885(d，3H)。
This compound has excellent insecticidal activity, and (application number: it is better to disclose the prevention effect of this compound (compound number 1.25) to beet armyworm when concentration is 1ppm 200810116198.4), and mortality ratio is more than 90% for Chinese patent application.

Claims (6)

1. a 1-(3,5-dichloropyridine base)-1H-5-pyrazole carboxylic acid ester compound, shown in general formula (I):
Figure F2008101826916C00011
In the formula:
R 1Be selected from OH, halogen, C 1-C 6Alkoxyl group, C 1-C 6Halogenated alkoxy, C 2-C 6Cyanogen is for alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group, C 3-C 6Halo alkynyloxy group, benzyloxy, C 1-C 3Alkylsulphonic acid base, the phenylbenzimidazole sulfonic acid base that does not replace or replace, described substituting group is selected from methyl or halogen;
R 2Be selected from C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
2. according to the described compound of claim 1, it is characterized in that: in the general formula (I)
R 1Be selected from OH, Cl, Br, C 1-C 3Alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group or benzyloxy;
R 2Be selected from C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
3. according to the described compound of claim 2, it is characterized in that: in the general formula (I)
R 1Be selected from OH, Cl or Br;
R 2Be selected from C 1-C 6Alkyl.
4. intermediate that is used to prepare general formula (I) compound, shown in general formula (II):
Figure F2008101826916C00012
In the formula:
R 1Be selected from OH, halogen, C 1-C 6Alkoxyl group, C 1-C 6Halogenated alkoxy, C 2-C 6Cyanogen is for alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group, C 3-C 6Halo alkynyloxy group, benzyloxy, C 1-C 3Alkylsulphonic acid base, the phenylbenzimidazole sulfonic acid base that does not replace or replace, described substituting group is selected from methyl or halogen;
R 2Be selected from H, C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
5. according to the described compound of claim 4, it is characterized in that: in the general formula (II)
R 1Be selected from OH, Cl, Br, C 1-C 3Alkoxyl group, C 3-C 6Alkene oxygen base, C 3-C 6Haloalkene oxygen base, C 3-C 6Alkynyloxy group or benzyloxy;
R 2Be selected from H, C 1-C 6Alkyl, C 3-C 6Thiazolinyl or benzyl.
6. according to the described compound of claim 5, it is characterized in that: in the general formula (II)
R 1Be selected from OH, Cl or Br;
R 2Be selected from H or C 1-C 6Alkyl.
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CN103155929B (en) * 2011-12-09 2014-07-23 沈阳科创化学品有限公司 Binary pesticide composition and application thereof
CN103238603A (en) * 2012-02-01 2013-08-14 中国中化股份有限公司 Insecticidal preparation and its application
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