CN1376145A - A meta-nitro phenol derivative and a process for producing it - Google Patents
A meta-nitro phenol derivative and a process for producing it Download PDFInfo
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- CN1376145A CN1376145A CN 99815841 CN99815841A CN1376145A CN 1376145 A CN1376145 A CN 1376145A CN 99815841 CN99815841 CN 99815841 CN 99815841 A CN99815841 A CN 99815841A CN 1376145 A CN1376145 A CN 1376145A
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
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- C07D213/643—2-Phenoxypyridines; Derivatives thereof
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- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D239/34—One oxygen atom
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- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/18—Oxygen or sulfur atoms
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- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
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- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
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Abstract
The present invention relates to a meta-nitro phenol derivative of formula (I) wherein X is halogen, cyano, nitro, C1-6haloalkyl or C1-6haloalkoxy; Y is hydrogen, halogen, cyano, nitro, C1-6haloalkyl or C1-6haloalkoxy; Z is oxygen, sulfur or NR; R is hydrogen or C1-6alkyl; Ar is pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, s-triazinyl or s-tetrazinyl in which Ar may be substituted with at least one substituent selected from the group consisting of halogen, cyano, C1-6alkyl, C1-6haloalkyl, C1-6alkoxy, C1-6haloalkoxy, C1-6alkylsulfonyl and C1-6haloalkylsulfonyl.
Description
The present invention relates to a kind of agrochemicals intermediate and production method thereof.
Background of invention
Some herbicidal compound and preparation method thereof are disclosed in international Invention Announce WO98/41093.But the m-nitro amphyl among the present invention is not described.
Make the m-nitro amphyl from corresponding phenolic has some difficulties, because phenols-there is ortho position-contraposition orienting effect in the OH base in nitrifying process.Therefore, the nitration reaction of phenols must just can be carried out after protection-OH bases such as suitable blocking group such as alkoxycarbonyl are arranged.Though the m-nitro amphyl can make in this way, its shortcoming is operational path length and is not suitable for suitability for industrialized production.
The inventor studies to overcome the shortcoming in the described method.The result be obtain relevant when phenols-OH carried out when being replaced by specific substituting group between the nitrated in position knowledge of reacting.
The present invention's summary
One aspect of the present invention is the m-nitro amphyl with formula (I),
X is halogen, cyano group, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula; Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl.
Another aspect of the present invention be with the compound with formula (II) and nitric acid reaction production formula (I) m-nitro amphyl method, the definition of formula (II) middle X, Y, Z and Ar is the same.
The present invention describes in detail
In above-mentioned definition, term halogen is represented F, Cl, Br or I.The part that term C1-6 haloalkyl or C1-6 halogenated alkoxy are represented C1-6 alkyl or C1-6 moieties or all replaced by identical or different halogen atom.Term C1-6 alkyl represent contains the straight or branched alkane of 1-6 carbon atom.
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar representative can replace with at least a substituting group that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl.If two or more substituting groups are arranged on the Ar, they can be identical or different.
M-nitro amphyl of the present invention is preferably as follows:
(1) compound of formula (I), wherein X is a halogen, and Y is hydrogen, halogen or cyano group, and Z is an oxygen.
(2) compound of formula (I), wherein X is a fluorine, and Y is hydrogen or chlorine, and Z is an oxygen.
(3) compound of formula (I), wherein Ar is 2-pyridyl or 2-pyrimidyl, wherein this pyridyl and pyrimidyl can replace with above-mentioned substituting group.
More preferably formula (I) compound, wherein X is a fluorine, and Y is hydrogen or chlorine, and Z is that oxygen and Ar are 2-pyridyl or 2-pyrimidyl, and wherein this pyridyl and pyrimidyl can replace with above-mentioned substituting group.
Production have formula (I) the m-nitro amphyl in the method, nitration reaction both can be finished with the nitric acid in the presence of nitrosonitric acid or the also available sulfuric acid of the nitrosonitric acid in acetic acid separately.The compound of every mole of formula (II) uses the nitric acid of 1 to 4 mole (preferred 1 to 2 mole) usually in this method.
Be reflected under 0-30 ℃ and carry out, the reaction times is generally 0.5 to 2 hour.
Formula (II) compound can make by the following method.
In above-mentioned reaction formula, the definition of X, Y, Z and Ar is the same, and Hal is a halogen, and R is alkyl, phenyl or a benzyl unsubstituted or that replace with halogen and alkyl etc.
Originally be reflected under the existence of solvent and alkali and carry out.For example, solvent can be as non-proton type polar solvent such as acetonitrile, methyl ethyl ketone, dimethyl sulfoxide (DMSO) or N, dinethylformamide.Alkali can be for as alkalimetal hydride such as sodium hydride or potassium hydride KH; Alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; Alkali metal alkoxide such as sodium methylate or sodium ethylate; Alkaline carbonate such as yellow soda ash or salt of wormwood; Or tertiary amine such as triethylamine; Or pyridine.Temperature of reaction is generally from 0 ℃ to 250 ℃, is preferably from 20 ℃ to 150 ℃.Reaction times is generally from 1 to 12 hour.
In formula (II) compound, 2-(2-chloro-4-fluorophenoxy) pyrimidine or 2-(4-fluorophenoxy) pyrimidine are novel cpds.
Formula (I) compound is used as the particularly intermediate of herbicidal compound of agrochemicals.Can prepare herbicidal compound from formula (I) compound or its corresponding aminoderivative by the method described in the WO98/41093.Formula (I) compound can change into aminoderivative.
In above-mentioned reaction formula, the definition of X, Y, Z and Ar is the same.
Originally be reflected under the typical reaction conditions and carry out, in acetic acid or alcoholic hydrochloric acid, handle, perhaps come nickel, rhodium or ruthenium to carry out hydrogenation as catalyzer with palladium charcoal, platinum dioxide, Ruan as using iron, tin, tin protochloride (divalence) or zinc.
In aminoderivative, wherein Y is that the derivative of hydrogen atom can be converted into wherein that Y is the amido derivative of halogen.
In above-mentioned reaction formula, the definition of X, Z and Ar is the same.
Halogenating reaction can be implemented being with or without under the condition that dehydrohalogenating agent exists under 10-150 ℃ temperature reaction as the N-chlorosuccinimide, SULPHURYL CHLORIDE or the chlorine that are dissolved in the solvent by using halogenating agent in 1-24 hour.The amount of halogenating agent and dehydrohalogenating agent can be respectively the 1-4 equivalent and the 0.001-1 equivalent of initial compounds.The example of the solvent that is used to react has aliphatic hydrocarbon such as hexane, pentane; Halohydrocarbon such as methylene dichloride, chloroform, 1,2-ethylene dichloride, chlorobenzene; Ethers such as Anaesthetie Ether, diox, tetrahydrofuran (THF); Ester class such as ethyl acetate, butylacetate; Nitro-compound such as oil of mirbane; Amides such as N, dinethylformamide; Sulphur compound such as dimethyl sulfoxide (DMSO); Amine such as pyridine, triethylamine etc.Can use single solvent or mixed solvent of planting.Dehydrohalogenating agent can be with organic bases or mineral alkali.This class example has pyridine, triethylamine, sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood etc.Reaction finishes, product with conventional post-treating method as adding entry and fetching separation with organic solvent extracting.Can in all sorts of ways as recrystallization or chromatographic purification if necessary.
Formula (I) compound can make by the following method.
In above-mentioned reaction formula, the definition of X, Y, Z and Ar is the same, and G is a halogen; Can be by the alkyl sulphonyl of halogen or alkyl replacement; Can be by the phenyl sulfonyl of halogen or alkyl replacement; Can be by the benzyl alkylsulfonyl of halogen or alkyl replacement.
Originally be reflected under the existence of alkali and carry out.Alkali can be for as alkalimetal hydride such as sodium hydride or potassium hydride KH; Alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; Alkaline carbonate such as yellow soda ash or salt of wormwood; Or pyridine.
If desired, originally be reflected under the existence of solvent and carry out.For example, solvent can be polar solvent such as dimethyl sulfoxide (DMSO), N, dinethylformamide or 1,3-dimethyl-2-imidazolidinone; Aromatic solvent such as toluene, dimethylbenzene or pyridine; Ethers such as tetrahydrofuran (THF) Huo diox.
This reaction is preferably in to be carried out under the existence of catalyzer to improve yield.The example of catalyzer can be alkali metal halide such as potassiumiodide, Potassium Bromide or Repone K; Cuprous halide such as cuprous iodide, cuprous bromide or cuprous chloride; Copper halide such as cupric iodide, cupric bromide or cupric chloride; Metallic copper.
If necessary, be reflected under the azeotropic distillation and carry out.
Temperature of reaction is generally 0 ℃ to 350 ℃, is preferably 100 ℃ to 200 ℃.Reaction times is generally 1 to 12 hour.
Formula (III) compound can make by following reaction equation.
In above-mentioned reaction formula, the definition of X, Y, Z and Ar is the same.Solvent can be aprotic polar solvent such as Anaesthetie Ether, nitrile, methyl ethyl ketone or dimethyl sulfoxide (DMSO), protonic solvent such as water, ethanol or acetic acid.Use the mixed solvent of above-mentioned solvent can obtain better result sometimes.
Diazotization agent can use various nitrite (ester) compound such as Sodium Nitrite, ethyl nitrite or nitrite tert-butyl.
Temperature of reaction is generally-10 ℃ to 10 ℃, is preferably-5 ℃ to 5 ℃.Reaction times is generally 0.5 to 12 hour.
Formula (III) compound is a useful as intermediates, and by providing herbicidal compound (IV) with some (mixing) aromatics acid reaction, compound (IV) has the C-C key between benzyl rings and (mixing) aromatic ring according to following reaction formula for it.
Embodiment
The present invention will be further described in the following example, but the present invention is not limited thereto.Synthesizing of embodiment 1. 2-(2-chloro-4-fluorophenoxy) pyrimidine
The 2-chloro-4-fluorophenol of 6.0g, the 2-chloropyrimide of 5.3g and the salt of wormwood of 0.61g are mixed in the DMSO of 150ml methyl ethyl ketone and 50ml, and under reflux temperature, heated 4 hours.Reaction mixture distributes in water and ethyl acetate, uses dried over sodium sulfate, evaporation and obtain target compound (solid, 8.54g, yield 93%).[
1H?NMR，CDCl
3，δ7.08(2H，m)，7.25(2H，m)，8.57(2H，d，J＝4.8Hz)ppm]。Synthesizing of embodiment 2. 2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine
2-(the 2-chloro-4-fluorophenoxy) pyrimidine of 7.0g is dissolved in the 70ml sulfuric acid, at room temperature is added dropwise to 4ml nitric acid and stirred 2 hours.Reaction mixture is poured in the trash ice and is stirred 1 hour (last volume is 700ml).Filter collecting precipitation, wash with water, obtain 6.17g 2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine at air drying.Filtrate neutralizes with sodium hydroxide, with ethyl acetate 100ml extraction, it is obtained a kind of oily matter (0.39g) with 50ml water washing evaporation.Total recovery is 78%.[
1H?NMR，CDCl
3，δ7.20(1H，t，J＝4.8Hz)，7.50(1H，d，J＝10.0Hz)，8.07(1H，d，J＝6.9Hz)，8.61(2H，d，J＝4.8Hz)ppm]。
With the synthetic following compounds of similar method.
4-chloro-2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine [
1H NMR, DMSO-d
6, δ 6.21 (1H, d, J=7.0Hz), 7.81 (1H, d, J=10.5Hz), 7.87 (1H, d, J=6.9Hz), 8.12 (1H, d, J=7.0Hz) ppm].
6-chloro-3-(2-chloro-4-fluoro-5-nitro-phenoxy) pyridazine [
1H NMR, acetone-d
6, δ 7.54 (1H, d, J=9.1Hz), 7.63 (1H, d, J=10.1Hz), 7.78 (1H, d, J=9.1Hz), 8.16 (1H, d, J=6.9Hz) ppm].
3-chloro-2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrazine [
1H NMR, DMSO-d
6, δ 8.04 (1H, d, J=10.6Hz), 8.16 (1H, d, J=2.6Hz), 8.29 (1H, d, J=2.6Hz), 8.40 (1H, d, J=7.1Hz) ppm].
6-chloro-2-(2-chloro-4-fluoro-5-nitro phenolic group) pyrazine [
1H NMR, DMSO-d
6, δ 8.1 (1H, d, J=10.6Hz), 8.42 (1H, d, J=6.9Hz), 8.56 (1H, s), 8.69 (1H, s) ppm].Synthesizing of embodiment 3. 2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine
2-(the 2-chloro-4-fluorophenoxy) pyrimidine of 0.5g is under agitation slowly added in the 2ml nitrosonitric acid.Solution at room temperature stirred 2 hours and added frozen water.Product distributes with ethyl acetate and separates, and organic layer washes with water, dry (anhydrous sodium sulphate) and evaporate and obtain 0.47g title compound (78%).Synthesizing of embodiment 4. 2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine
In the 2ml acetic acid that contains 1.0g 2-(2-chloro-4-fluorophenoxy) pyrimidine, add the 20ml nitrosonitric acid.Solution at room temperature stirs and spends the night.Reaction mixture is poured in the trash ice.The sedimentation and filtration that produces is collected, and washes dry air and obtain the subalbous solid of 0.75g (yield 62%) with water.Synthesizing of embodiment 5. 2-(5-amino-2-chloro-4-fluorophenoxy) pyrimidine
Add the iron powder of 6.79g in the 70ml acetum that contains 6.56g 2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine, the mixture of generation at room temperature stirs 3 hours (TLC monitoring).Reaction mixture is used the 100ml water washing with the dilution of 200ml ethyl acetate, uses 50ml saturated nacl aqueous solution washed twice then.Water 100ml ethyl acetate extraction.Acetic acid ethyl acetate extract 20ml saturated sodium-chloride washed twice.The combined ethyl acetate phase is used dried over sodium sulfate, is concentrated into 20ml.Filter and collect crystal,, obtain 2-(5-amido-2-chloro-4-fluorine phenolic group) pyrimidine (5.36g, productive rate 92% at air drying with hexane-ethyl acetate (4: 1) washing.[
1H?NMR，CDCl
3，δ6.69(1H，d，J＝8.3Hz)，7.06(1H，t，J＝4.8Hz)，7.10(1H，d，J＝10.5Hz)，8.56(2H，d，J＝4.8Hz)ppm]。Synthesizing of embodiment 6. 2-(5-amido-2-chloro-4-fluorophenoxy) pyrimidine
Adding 0.02g content is 5% palladium charcoal (4%, weight) in the 5ml ethanolic soln that contains 0.5g 2-(2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine.Mixture stirred 18 hours in the atmosphere of hydrogen of room temperature.Reaction finishes, and filtration catalizer, evaporating solvent obtain 2-(5-amino-2-chloro-4-fluorophenoxy) pyrimidine 0.43g.Synthesizing of embodiment 7. 2-(5-amino-2-chloro-4-fluorophenoxy) pyrimidine
In the 40ml ethanolic soln that contains the 2-of 2.00g (2-chloro-4-fluoro-5-nitro-phenoxy) pyrimidine, add 0.06g hydration platinum dioxide (3%, weight).Mixture stirred 6 hours in the atmosphere of hydrogen of room temperature.Reaction finishes, filtration catalizer, and the filtrate evaporation obtains crude product 1.83g.Crude product is obtained pure 2-(5-amino-2-chloro-4-fluorophenoxy) pyrimidine 1.61g by silica gel column chromatography (methylene dichloride is an elutriant) purifying.Embodiment 8. 4-chloro-2-fluoro-5-(2-pyrimidyl oxygen) benzene diazonium fluorides are boratory synthetic
4-chloro-2-fluoro-5-(the 2-pyrimidyl oxygen) aniline of 1.2g (5mmol) is mixed (thermopositive reaction) with 1.8ml fluoroboric acid (55%) and 0.75ml water, and be cooled to-5 ℃, be dissolved in the solution-treated that 2ml water forms with 420mg Sodium Nitrite (6mmol).Xanchromatic 4-chloro-2-fluoro-5-(2-pyrimidyl oxygen) benzene diazonium fluoride borate crystallizes out.Stirring 1 hour after-filtration, water and diethyl ether washing, vacuum-drying.Output 0.6g, decomposition temperature 188-90 ℃.Synthesizing of embodiment 9. 2-(4-fluorophenoxy) pyrimidine
12.5g 4-fluorophenol, 14.05g 2-chloropyrimide and 18.47g salt of wormwood are mixed in the DMSO of 125ml, and solution stirred 2 hours down at 110 ℃.After the cooling, solution is added in the water, the filtering separation precipitation obtains title compound 17.17g (yield 81%).[
1H?NMR，CDCl
3，7.0-7.21(5H，m)8.57(2H，d，J＝4.8Hz)ppm]。Synthesizing of embodiment 10. 2-(4-fluoro-3-nitro-phenoxy) pyrimidine
2-(4-fluorophenoxy) pyrimidine of 9.3g is dissolved in the 33.8ml vitriol oil, and solution stirs under the cooling of ice.Stirring down, dropping 3.4ml concentrated nitric acid also at room temperature stirred 2 hours.Solution is poured in the frozen water into the product ethyl acetate extraction.Obtain 8.05g product (yield 70%) with the ether grinding powder.[
1H?NMR，CDCl
3，7.15(1H，t，J＝4.8Hz)，7.37(1H，dd，J＝9.3Hz)，7.52(1H，m)，7.99(1H，dd，J＝2.9，6.2Hz)8.60(2H，d，J＝4.8Hz)ppm]。Synthesizing of embodiment 11. 2-(3-amino-4-fluorophenoxy) pyrimidine
2.85g 2-(4-fluoro-3-nitro-phenoxy) pyrimidine is dissolved in the Glacial acetic acid of 121ml, under agitation slowly adds the 3.39g iron powder in batches.Solution at room temperature stirred 12 hours in the nitrogen atmosphere.Add entry, product ethyl acetate extraction, organic layer water and salt water washing.Evaporation obtains 1.86g title compound (yield 75%).[
1H?NMR，CDCl
3，5.30(2H，br?s)，6.28(1H，m)，6.52(1H，dd，J＝2.7，7.7Hz)，7.00(1H，dd，J＝8.8，11.1Hz)，7.24(1H，t，J＝4.7Hz)，8.63(2H，d，J＝4.7Hz)ppm]。Synthesizing of embodiment 12. 2-(5-amino-2-chloro-4-fluorophenoxy) pyrimidine
2-(3-amino-4-fluorophenoxy) pyrimidine of 0.5g is dissolved in the anhydrous N of 10ml, in the dinethylformamide, and the N-chlorosuccinimide of adding 0.33g.Solution stirred 2 hours down at 80 ℃, and added entry.The product ethyl acetate extraction, organic layer water and salt water washing, evaporation then.Residuum crystallization in ether obtains 0.44g title compound (yield 75%).Synthesizing of embodiment 13. 2-(5-amino-2-bromo-4-fluorophenoxy) pyrimidine
2-(3-amino-4-fluorophenoxy) pyrimidine of 0.45g is dissolved in the anhydrous N of 10ml, in the dinethylformamide, adds the N-bromosuccinimide of 0.39g.Solution stirred 2 hours down at 80 ℃, added entry.The product ethyl acetate extraction.Organic layer water and salt water washing, evaporation then.Product obtains 0.41g title compound (yield 66%) with silica gel column chromatography (with hexane: ethyl acetate (6: 4) is made eluent) purifying.[
1H NMR, acetone-d
6, 5.07 (2H, br s), 6.80 (1H, d, J=8.3Hz), 7.21 (1H, t, J=4.7Hz), 7.29 (1H, d, J=10.6Hz), 8.59 (2H, d, J=4.7Hz) ppm].Synthesizing of embodiment 14. 2-chloro-4-fluoro-5-nitro-phenoxy 2-pyrimidyl ethers
The 2-chloro-4-fluoro-5-nitrophenols of 1.98g is dissolved in the anhydrous tetrahydro furan of 10ml, adds the 42mg sodium hydride.Under reduced pressure remove solvent, add the 2-chloropyrimide of 166mg potassium iodide catalyst and 1.27g then.Mixture heated 3 hours down at 120 ℃, heated 1.5 hours about 130 ℃ again.Add ethyl acetate after the cooling, solution adopts suction filtration by the Sai Lite diatomite filtration, and filtrate is washed with the potassium hydroxide solution of salt solution and 3%.Organic layer is being used anhydrous sodium sulfate drying, under reduced pressure removes and desolvates, and obtains brown oil.This oily matter obtains 1.69g title compound (yield 63%) by silica gel column chromatography (making eluent with methylene dichloride) purifying.
Table I is classified the structural formula of representative compounds more of the present invention as.
Table I
| Sequence number | ????X | ???Y | ????Z | ????Ar |
| ????1 | ????F | ???Cl | ????O | The 2-pyrimidyl |
| ????2 | ????Cl | ???Cl | ????O | The 2-pyrimidyl |
| ????3 | ????F | ???Br | ????O | The 2-pyrimidyl |
| ????4 | ????F | ???CN | ????O | The 2-pyrimidyl |
| ????5 | ????F | ???CF 3 | ????O | The 2-pyrimidyl |
| ????6 | ????F | ???NO 2 | ????O | The 2-pyrimidyl |
| ????7 | ????F | ???OCHF 2 | ????O | The 2-pyrimidyl |
| ????8 | ????F | ???Cl | ????O | 4-chloro-2-pyrimidyl |
| ????9 | ????F | ???Cl | ????O | ????3-CF 3-2-pyridyl |
| ???10 | ????F | ???Cl | ????O | ????5-CF 3-2-pyridyl |
| ???11 | ????F | ???Cl | ????O | The 3-pyridazinyl |
| ???12 | ????F | ???Cl | ????O | 6-chloro-3-pyridazinyl |
| ???13 | ????F | ???Cl | ????O | The 2-pyrazinyl |
| ???14 | ????F | ???Cl | ????O | 3-chloro-2-pyrazinyl |
| ???15 | ????F | ???Cl | ????O | 6-chloro-2-pyrazinyl |
| ???16 | ????F | ???Cl | ????O | 4,6-dimethoxy-2-triazinyl |
| ???17 | ????F | ???Cl | ????O | 4,6-dimethyl-2-triazinyl |
| ???18 | ????F | ???Cl | ????O | 3-s-tetrazine base |
| ???19 | ????F | ???Cl | ????S | The 2-pyrimidyl |
| ???20 | ????F | ???Cl | ????NH | The 2-pyrimidyl |
| ???20 | ????F | ???Cl | ????NCH 3 | The 2-pyrimidyl |
| ???21 | ????F | ???H | ????O | The 2-pyrimidyl |
Claims (12)
1. compound with formula (I),
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl.
2. according to the compound of claim 1, wherein X is a halogen, and Y is hydrogen, halogen or cyano group, and Z is an oxygen.
3. according to the compound of claim 1, wherein X is a fluorine, and Y is hydrogen or chlorine, and Z is an oxygen.
4. according to the compound of claim 1, wherein Ar can use 2-pyridyl or the 2-pyrimidyl that defined substituting group replaces in the claim 1 on pyridyl and pyrimidyl.
5. according to the compound of claim 1, wherein X is a fluorine, and Y is hydrogen or chlorine, and Z is an oxygen, and Ar can use 2-pyridyl or the 2-pyrimidyl that defined substituting group replaces in the claim 1 on pyridyl and pyrimidyl.
One kind prepare have formula (I) the m-nitro amphyl method,
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl;
This preparation method comprises with having formula (II)
Compound, the definition of X, Y, Z and Ar in the formula (II) is the same, with nitric acid reaction.
(7.2-2-chloro-4-fluorophenoxy) pyrimidine or 2-(4-fluorophenoxy) pyrimidine.
8. method for preparing compound with following formula,
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Hal is a halogen;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl;
This preparation method comprises the compound of following formula
Wherein the definition of X, Z and Ar is the same, with the reaction of halogenating agent.
9. compound with formula (III),
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl.
10. one kind prepares the have formula method of compound of (III),
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl;
This preparation method comprises the compound with following formula,
Wherein the definition of X, Y, Z and Ar is the same, with the reaction of fluoroboric acid and diazotization agent.
11. a method for preparing aminoderivative, it comprises:
(1) a kind of compound with following formula,
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
With formula be Ar-Hal or Ar-SO
2The compound of R ' carries out condensation reaction, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl in the following formula; Hal is a halogen; R ' is for being selected from alkyl, phenyl or the benzyl of the group replacement of halogen and alkyl by at least one;
Thereby production (II) compound,
The definition of X, Y, Z and Ar is the same in the formula;
(2) nitration reaction preparation formula (I) compound of formula (II) compound and nitric acid,
The definition of X, Y, Z and Ar is the same in the formula; With
(3) reduction of formula (I) compound is made the compound with following formula,
The definition of X, Y, Z and Ar is the same in the formula.
12. one kind prepare have formula (I) the m-nitro amphyl method,
X is halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy in the formula;
Y is hydrogen, halogen, cyano group, nitro, C1-6 haloalkyl or C1-6 halogenated alkoxy;
Z is oxygen, sulphur or NR; R is hydrogen or C1-6 alkyl;
Pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, symmetrical triazinyl or the s-tetrazine base of Ar for replacing with at least a substituted radical that is selected from halogen, cyano group, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxyl group, C1-6 halogenated alkoxy, C1-6 alkyl sulphonyl and C1-6 halogenated alkyl sulfonyl;
This preparation method comprises the compound that has following formula with a kind of,
The definition of X, Y and Z is the same in the formula; with the reaction of the compound of a kind of formula Ar-G, in the following formula the same and G of the definition of Ar be halogen, the alkyl sulphonyl that can be replaced by halogen or alkyl, the phenyl sulfonyl that can be replaced by halogen or alkyl, the benzyl alkylsulfonyl that can be replaced by halogen or alkyl.
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US20318098A | 1998-11-30 | 1998-11-30 | |
| US09/203180 | 1998-11-30 | ||
| US28106799A | 1999-03-09 | 1999-03-09 | |
| US09/281067 | 1999-03-09 | ||
| US42600099A | 1999-10-25 | 1999-10-25 | |
| US09/426000 | 1999-10-25 |
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| Publication Number | Publication Date |
|---|---|
| CN1376145A true CN1376145A (en) | 2002-10-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 99815841 Pending CN1376145A (en) | 1998-11-30 | 1999-11-22 | A meta-nitro phenol derivative and a process for producing it |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1144380A4 (en) |
| JP (1) | JP2003506312A (en) |
| CN (1) | CN1376145A (en) |
| AU (1) | AU2145500A (en) |
| WO (1) | WO2000032573A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103288763A (en) * | 2013-06-20 | 2013-09-11 | 郑州福源动物药业有限公司 | Industrial production method of 2,6-dichloropyrazine |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| IL167957A (en) | 2000-02-04 | 2009-07-20 | Sumitomo Chemical Co | Hydroxypyridine compound |
| US6613718B2 (en) | 2001-10-01 | 2003-09-02 | Ishihara Sangyo Kaisha, Ltd. | Aryl ether derivatives and processes for their preparation and herbicidal and desiccant compositions containing them |
| CN103265820B (en) * | 2013-05-23 | 2014-07-30 | 大连理工大学 | Method for preparing azo dye with alkalescent arylamine serving as diazotization ingredient |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ188244A (en) * | 1977-09-13 | 1981-04-24 | Ici Australia Ltd | 2-substituted pyrimidines compositions growth regulating processes |
| US4326880A (en) * | 1979-08-14 | 1982-04-27 | Ciba-Geigy Corporation | Derivatives of 5-(pyridyl-2-oxy)-2-nitrobenzoic acid, and herbicidal compositions containing them, and herbicidal methods for using same |
| JPS5686162A (en) * | 1979-12-17 | 1981-07-13 | Mitsui Toatsu Chem Inc | Pyridyl-2-oxy-benzene derivative |
| NO810064L (en) * | 1980-01-10 | 1981-07-13 | Nyegaard & Co As | PROCEDURE FOR THE PREPARATION OF PHYSIOLOGICALLY ACTIVE PYRIMIDINE-2-SULPHIDES AND S-OXIDES THEREOF |
| CA1167445A (en) * | 1981-05-18 | 1984-05-15 | Clive A. Henrick | Compositions |
| US4451284A (en) * | 1981-07-28 | 1984-05-29 | Ciba-Geigy Corporation | Derivatives of 2-nitro-4- or -5-pyridyloxyphenylphosphonic acid, the preparation thereof, the use thereof as herbicides and/or plant growth regulators |
| US4371537A (en) * | 1981-08-13 | 1983-02-01 | The Dow Chemical Company | Sulfur-substituted phenoxypyridines having antiviral activity |
| US4484941A (en) * | 1981-09-01 | 1984-11-27 | Sumitomo Chemical Company, Limited | Tetrahydrophthalimides, and their production and use as herbicides |
| US4526608A (en) * | 1982-07-14 | 1985-07-02 | Zoecon Corporation | Certain 2-pyridyloxyphenyl-oximino-ether-carboxylates, herbicidal compositions containing same and their herbicidal method of use |
| US4605434A (en) * | 1983-07-20 | 1986-08-12 | Ciba-Geigy Corporation | Herbicidal and plant-growth-regulating (2-nitro-5-aryloxy-phenylamino)-alkylphosphine oxide derivatives and compositions |
| DE3614060A1 (en) * | 1986-04-23 | 1987-10-29 | Schering Ag | PYRIMIDINE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS FUNGICIDES |
| US4966622A (en) * | 1988-04-12 | 1990-10-30 | Ciba-Geigy Corporation | N-phenyl-N-pyrimidin-2-ylureas |
| BR9808334A (en) * | 1997-03-14 | 2000-05-16 | Isk Americas Inc | diaryl ethers, processes for their preparation and herbicidal and desiccant compositions containing the same |
-
1999
- 1999-11-22 EP EP99965757A patent/EP1144380A4/en not_active Withdrawn
- 1999-11-22 JP JP2000585215A patent/JP2003506312A/en active Pending
- 1999-11-22 WO PCT/US1999/026016 patent/WO2000032573A1/en not_active Application Discontinuation
- 1999-11-22 CN CN 99815841 patent/CN1376145A/en active Pending
- 1999-11-22 AU AU21455/00A patent/AU2145500A/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103288763A (en) * | 2013-06-20 | 2013-09-11 | 郑州福源动物药业有限公司 | Industrial production method of 2,6-dichloropyrazine |
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| Publication number | Publication date |
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| EP1144380A1 (en) | 2001-10-17 |
| WO2000032573A8 (en) | 2001-09-13 |
| EP1144380A4 (en) | 2003-11-26 |
| JP2003506312A (en) | 2003-02-18 |
| AU2145500A (en) | 2000-06-19 |
| WO2000032573A1 (en) | 2000-06-08 |
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