CN1166644C - Process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate - Google Patents
Process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate Download PDFInfo
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- CN1166644C CN1166644C CNB02107660XA CN02107660A CN1166644C CN 1166644 C CN1166644 C CN 1166644C CN B02107660X A CNB02107660X A CN B02107660XA CN 02107660 A CN02107660 A CN 02107660A CN 1166644 C CN1166644 C CN 1166644C
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Abstract
The present invention belongs to a process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate. The method uses 2, 6-dihydroxy-benzoic acid as an initial raw material, the 2, 6-dihydroxy-benzoic acid and sodium hydroxide are used for generating salt under the condition that an inert solvent and a catalyst exist, and then, the salt reacts with 4, 6-dimethoxypyrimidine-2-methylsulfonylpyrimidine to synthesize 2, 6-bis [(4, 6-dimethoxypyrimidine-2-yl) oxy] sodium benzoate. The sodium hydroxide is used for substituting inflammable sodium hydride which is difficult to store; the 2, 6-dihydroxy-benzoic acid is used for substituting 2, 6-dihydroxy-benylate, and the reaction steps of esterification, hydrogenation reduction, neutralization, etc. are eliminated. The method has the advantages of easy acquisition of the raw material, few reaction steps, easy operation, high reaction yield, etc., and is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of chemosynthesis 2, the novel method of two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-.Present method is applicable to 4,6-resorcylic acid, sodium hydroxide and 4, and 6-dimethoxy-2-methanesulfonyl pyrimidine is a main raw material, Synthetic 2, the occasion of two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-.
Background technology
2, two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-are a kind of low toxicity, wide spectrum, ultra-high efficiency rice field post-emergence herbicide.Can prevent and kill off annual and perennial gramineous weeds and broadleaf weeds effectively, particularly can prevent and kill off the barnyard grass grass of 1～7 leaf phase, and dosage is extremely low, application prospect is better.
United States Patent (USP) (US4906285) has disclosed 2,6-two ((4,6-dimethoxypyridin-2-yl) synthetic method of Sodium Benzoate oxygen): with sodium hydride and 2,6-resorcylic acid benzyl ester is suspended in the tetrahydrofuran (THF), stirred 15 minutes under the room temperature, add 4,6-dimethoxy-2-methanesulfonyl pyrimidine, heating reflux reaction 8 hours, after the cooling, pour in the water, use extracted with diethyl ether, organic layer washs with saturated sodium-chloride water solution, use anhydrous magnesium sulfate drying, under reduced pressure steam solvent, residue separates with silica gel column chromatography, make 6-((4,6-dimethoxypyridin-2-yl) oxygen) benzyl salicylate; Adopt similar substantially operation again, with 4,6-dimethoxy-2-methanesulfonyl pyrimidine obtains 2 with the 2-position hydroxyl etherificate of 6-((4, the 6-dimethoxypyridin-2-yl) oxygen) benzyl salicylate that makes, two ((4, the 6-dimethoxypyridin-2-yl) oxygen) peruscabins of 6-; Then, be solvent with acetate and methyl alcohol, use the 10%Pd/C catalyzer, hydrogenating reduction, hydrogenation liquid filters out catalyzer, and filtrate decompression concentrates, resistates adds ethyl acetate and water, divides water-yielding stratum, and organic layer washes with water, drying concentrates, and filters out crystal, wash with normal hexane, make 2, two ((4, the 6-dimethoxypyridin-2-yl) oxygen) phenylformic acid of 6-.Its reaction formula is as follows:
This method not only reactions steps is many, operates quite cumbersomely, use the sodium hydride of precious metals palladium catalyst, multiple organic solvent and inflammable and explosive difficult storage, and total recovery is very low.This United States Patent (USP) also provides similar compound 2; two ((4-chloro-6-methoxy pyrimidine-2-yl) oxygen) benzoic synthetic methods of 6-: sodium hydride is suspended in the tetrahydrofuran (THF); add 2; the 6-resorcylic acid; stirred 30 minutes under the room temperature; add 4-chloro-6-methoxyl group-2-methanesulfonyl pyrimidine again, reaction is after 2 days, in the reaction solution impouring water under the room temperature; use ethyl acetate extraction; organic layer washs with saturated sodium-chloride water solution, uses anhydrous sodium sulfate drying, and decompression steams solvent; resistates uses column chromatography purification; obtain 2, two ((the 4-chloro-6-methoxy pyrimidine-2-yl) oxygen) phenylformic acid of 6-, yield only has 28%.Though this method has been saved esterification and hydrogenation reduction step, yield is low, and still uses sodium hydride, is difficult to be applied to produce.
Summary of the invention
The objective of the invention is to overcome the shortcoming of existing synthetic method, provide a kind of raw material to be easy to get, reactions steps is few, easy and simple to handle and yield is higher 2, the chemical synthesis process of two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-.
Of the present invention 2, the chemical synthesis process of two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-, it is characterized in that: in the presence of organic solvent and phase-transfer catalyst, 2,6-resorcylic acid and sodium hydroxide are under reflux temperature, behind the salify 3～4 hours, add 4,6-dihydroxyl-2-methanesulfonyl pyrimidine, back flow reaction 6～8 hours, cooling is filtered, dry, make 2, two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-; Wherein, the mol ratio of used reaction raw materials is 2,6-resorcylic acid: sodium hydroxide: 4, and 6-dimethoxy-2-methanesulfonyl pyrimidine=1: 3.0～4.0: 2.2～2.5.
Chemical equation of the present invention is as follows:
Described organic solvent is an inert under this synthetic reaction conditions, and comprising benzene,toluene,xylene, chlorobenzene, methyl alcohol, ethanol, Virahol and tetrahydrofuran (THF), consumption is 4～6 liters/every mole 2, the 6-resorcylic acid.
Described phase-transfer catalyst is quaternary ammonium salt, polyoxyethylene glycol, crown ether, and add-on is 2,1～3% of 6-resorcylic acid weight;
Described quaternary ammonium salt is trimethyl benzyl ammonium halide, triethyl benzyl ammonium halide, tributyl benzyl ammonium halide, trimethyldodecane base ammonium halide, trimethylammonium hexadecyl ammonium halide, triethyl dodecyl ammonium halide, triethyl hexadecyl ammonium halide, tetramethyl-ammonium halide, tetraethyl-ammonium halide, tetrabutyl ammonium halide, described polyoxyethylene glycol is Macrogol 200, poly(oxyethylene glycol) 400, Polyethylene Glycol-600, polyoxyethylene glycol 800, cetomacrogol 1000, and described crown ether is 15 crown ethers-five, 18 crown ether-six.
Described ammonium halide is ammonium chloride, brometo de amonio, ammonium iodide.
Of the present invention 2,6-two ((4,6-dimethoxypyridin-2-yl) chemical synthesis process of Sodium Benzoate oxygen), its key problem in technology is: in the presence of organic solvent and phase-transfer catalyst, replace sodium hydride with sodium hydroxide, directly use 2, the 6-resorcylic acid, need not to prepare in advance 2, salify and etherificate again behind the 6-resorcylic acid benzyl ester.Method of the present invention not only raw material is easy to get, and has avoided reactions steps such as esterification, hydrogenating reduction and neutralization, and is easy and simple to handle, the yield height, and help safety operation, be easy to industrialization.
Embodiment
Embodiment 1
In the reaction flask of 1000ml, add 800ml benzene, 24.7g (0.16mol) 2,6-resorcylic acid, 23g (0.576mol) sodium hydroxide and 0.74g triethyl benzyl ammonia chloride; be warming up to reflux temperature gradually, salify 3～4 hours adds 76.8g (0.352mol) 4; 6-dimethoxy-2-methanesulfonyl pyrimidine, back flow reaction 6～8 hours, cooling; filter; drying makes 2, and 6-two ((4; 6-dimethoxypyridin-2-yl) Sodium Benzoate oxygen), total recovery 70.4%.
Embodiment 2
In the reaction flask of 1000ml, add 800ml tetrahydrofuran (THF), 24.7g (0.16mol) 2,6-resorcylic acid, 23g (0.576mol) sodium hydroxide and 0.25g 18 crown ether one or six; be warming up to reflux temperature gradually, salify 3～4 hours adds 76.8g (0.352mol) 4; 6-dimethoxy-2-methanesulfonyl pyrimidine, back flow reaction 6～8 hours, cooling; filter; drying makes 2, and 6-two ((4; 6-dimethoxypyridin-2-yl) Sodium Benzoate oxygen), total recovery 71.2%.
Embodiment 3
In the reaction flask of 1000ml, add 800ml ethanol, 24.7g (0.16mol) 2,6-resorcylic acid, 23g (0.576mol) sodium hydroxide and 0.74g Polyethylene Glycol-600; be warming up to reflux temperature gradually, salify 4 hours adds 76.8g (0.352mol) 4; 6-dihydroxyl-2-methanesulfonyl pyrimidine, back flow reaction 8 hours, cooling; filter; drying makes 2, and 6-two ((4; 6-dimethoxypyridin-2-yl) Sodium Benzoate oxygen), total recovery 69.3%.
Claims (5)
1. one kind 2, the chemical synthesis process of two ((4, the 6-dimethoxypyridin-2-yl) oxygen) Sodium Benzoates of 6-, it is characterized in that: in the presence of organic solvent and phase-transfer catalyst, 2,6-resorcylic acid and sodium hydroxide are under reflux temperature, behind the salify 3～4 hours, add 4,6-dihydroxyl-2-methanesulfonyl pyrimidine, back flow reaction 6～8 hours, cooling is filtered, drying makes 2, and 6-two ((4,6-dimethoxypyridin-2-yl) Sodium Benzoate oxygen), total recovery 70%; Wherein, the mol ratio of used reaction raw materials is 2,6-resorcylic acid: sodium hydroxide: 4, and 6-dimethoxy-2-methanesulfonyl pyrimidine=1: 3.0～4.0: 2.2～2.5.
2. chemical synthesis process according to claim 1, it is characterized in that described organic solvent is one of following: benzene,toluene,xylene, chlorobenzene, methyl alcohol, ethanol, Virahol, tetrahydrofuran (THF), consumption are 4～6 liters/every mole 2, the 6-resorcylic acid.
3. chemical synthesis process according to claim 1, it is characterized in that described phase-transfer catalyst is one of following: quaternary ammonium salt, polyoxyethylene glycol, crown ether, add-on are 2,1～3% of 6-resorcylic acid weight.
4. chemical synthesis process according to claim 3 is characterized in that described quaternary ammonium salt is one of following: trimethyl benzyl ammonium halide, triethyl benzyl ammonium halide, tributyl benzyl ammonium halide, trimethyldodecane base ammonium halide, trimethylammonium hexadecyl ammonium halide, triethyl dodecyl ammonium halide, triethyl hexadecyl ammonium halide, tetramethyl-ammonium halide, tetraethyl-ammonium halide, tetrabutyl ammonium halide; Described polyoxyethylene glycol is one of following: Macrogol 200, poly(oxyethylene glycol) 400, Polyethylene Glycol-600, polyoxyethylene glycol 800, cetomacrogol 1000; Described crown ether is one of following: 15 crown ethers-five, 18 crown ether-six.
5. chemical synthesis process according to claim 4 is characterized in that described ammonium halide is one of following: ammonium chloride, brometo de amonio, ammonium iodide.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB02107660XA CN1166644C (en) | 2002-03-22 | 2002-03-22 | Process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate |
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| CNB02107660XA CN1166644C (en) | 2002-03-22 | 2002-03-22 | Process for chemically synthesizing 2,6-bis [(4,6-dimethoxypyrimidine-2-yl) oxy] sodium bezoate |
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| CN1166644C true CN1166644C (en) | 2004-09-15 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101265235B (en) * | 2008-05-08 | 2012-04-25 | 上海交通大学 | Method for preparing herbicide bispyribac-sodium |
| CN102010326B (en) * | 2010-10-28 | 2013-07-24 | 华南理工大学 | Industrial method for synthesizing 2-(4-methoxyphenoxy)-propionic acid through phase transfer |
| BR112015019795B1 (en) * | 2013-02-18 | 2020-06-16 | Gharda Chemicals Ltd | PROCESS FOR THE PREPARATION OF SODIUM BISPIRIBAC AND INTERMEDIARIES OF THE SAME |
| CN106083738A (en) * | 2016-07-06 | 2016-11-09 | 淄博新农基农药化工有限公司 | A kind of method utilizing phase transfer catalyst to prepare herbicide bispyribac-sodium |
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