CN102659694A - Method for synthesizing quizalofop-p-ethyl intermediate 6-chlorin-2-(4-p-hydroxyl radical) quinoxaline by one pot method - Google Patents
Method for synthesizing quizalofop-p-ethyl intermediate 6-chlorin-2-(4-p-hydroxyl radical) quinoxaline by one pot method Download PDFInfo
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- CN102659694A CN102659694A CN2012101543824A CN201210154382A CN102659694A CN 102659694 A CN102659694 A CN 102659694A CN 2012101543824 A CN2012101543824 A CN 2012101543824A CN 201210154382 A CN201210154382 A CN 201210154382A CN 102659694 A CN102659694 A CN 102659694A
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Abstract
The invention relates to a method for synthesizing quizalofop-p-ethyl intermediate 6-chlorin-2-(4-p-hydroxyl radical) quinoxaline by a one pot method. The method has the main technical scheme that the method comprises the following synthetic steps that (1) p-hydroxy benzaldehyde is dissolved in solvents, then, oxidants are dripped to react with alkali liquor, and hydroquinone is prepared; and (2) distilled water and 2,6- dichloro quinoxaline are added into the prepared hydroquinone reaction solution, then, solvents are added, the 2,6- dichloro quinoxaline is dissolved, the stirring is carried out, the temperature is raised to the required temperature, the alkali liquor is dripped, and the condensation reaction is carried out, and the 6-chlorin-2-(4-p-hydroxyl radical) quinoxaline is prepared. Compared with the method for preparing the quizalofop-p-ethyl intermediate 6-chlorin-2-(4-p-hydroxyl radical) quinoxaline in the prior art, the method has the following advantages that p-hydroxy benzaldehyde is used for replacing hydroquinone, the cost for preparing the quizalofop-p-ethyl intermediate 6-chlorin-2-(4-p-hydroxyl radical) quinoxaline is reduced, and the environment protection pressure of treatment difficulty of hydroquinone sewage is relieved.
Description
Technical field
The present invention relates to the method for a kind of synthetic quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline, the method for synthetic quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline of particularly a kind of one kettle way.
Background technology
6-chloro-2-(4-hydroxyphenoxy) quinoxaline is the important intermediate of synthetic quizalofopPethyl, and in the prior art, 6-chloro-2-(4-hydroxyphenoxy) quinoxaline is mainly by Resorcinol and 2, and 6-dichloro-quinoxaline generation condensation reaction makes.But because the continuous rise of present raw materials used Resorcinol price; There is the too high shortcoming of cost in quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline that this synthesis technique is produced; And a large amount of uses of Resorcinol can produce high-content Resorcinol sewage, and the processing that contains Resorcinol sewage is relatively more difficult.
Summary of the invention
The object of the present invention is to provide the method for synthetic quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline of a kind of one kettle way; Use this compound method to reduce the production cost of quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline, and alleviated and contain the unmanageable environmental protection pressure of Resorcinol sewage.
Technical scheme of the present invention is: the method for synthetic quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline of one kettle way is characterized in that comprising following steps: (1) PARA HYDROXY BENZALDEHYDE is dissolved the back dropping oxidizing agent in solvent and alkaline reaction makes Resorcinol; (2) in the Resorcinol reaction soln for preparing, add zero(ppm) water and 2, the 6-dichloro-quinoxaline adds solvent again and makes 2; The dissolving of 6-dichloro-quinoxaline; Stirring is warming up to needed temperature, and dripping alkali liquid condensation reaction promptly takes place makes 6-chloro-2-(4-hydroxyphenoxy) quinoxaline.Used solvent is a water in the step (1), and used oxygenant is a hydrogen peroxide, and used alkali lye is sodium hydroxide solution, and the mode of dropping oxidizing agent and alkali lye is dropping simultaneously, and control reaction temperature is no more than 50 in dropping oxidizing agent and alkali lye process
oC; Used PARA HYDROXY BENZALDEHYDE is 1:1～2:1～2 with the ratio of the amount of substance of hydrogen peroxide and sodium hydroxide in the step (1); The prepared Resorcinol of step (1) need not be handled and directly be used for step (2).Used solvent is a toluene in the step (2), and used alkali lye is sodium hydroxide solution or potassium hydroxide solution; It is 80～100 that stirring described in the step (2) is warming up to needed temperature
oC needs the control reacting liquid temperature 90～95 in the dripping alkali liquid process
oBetween the C; Used sodium hydroxide and 2 in the step (2), the ratio of the amount of substance of used PARA HYDROXY BENZALDEHYDE is 1～2:1～2:1 in 6-dichloro-quinoxaline and the step (1).
The method of synthetic quizalofopPethyl midbody 6-chloro-2-of the present invention (4-hydroxyphenoxy) quinoxaline is characterized in that described compound method can represent with following reaction formula:
The method for preparing quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline in the present invention and the prior art is compared and is had the following advantages: use PARA HYDROXY BENZALDEHYDE to replace Resorcinol; Reduced the cost of preparation quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline; And this synthesis technique simply is easy to control; The yield of quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) the quinoxaline product of preparation is higher; Use PARA HYDROXY BENZALDEHYDE to replace Resorcinol to avoid the high-content Resorcinol sewage that uses Resorcinol to produce because of a large amount of simultaneously, contain the unmanageable environmental protection pressure of Resorcinol sewage thereby alleviated.
Description of drawings
Fig. 1 is the gas phase analysis collection of illustrative plates of 6-chloro-2-(4-hydroxyphenoxy) quinoxaline among the embodiment 1; Wherein time 3.11min place is sample introduction solvent (ethanol) peak; Time 11.33min is 6-chloro-2-(4-hydroxyphenoxy) quinoxaline peak; Time 13.41min is that trace is responseless 2,6-dichloro-quinoxaline peak.
Embodiment
Below, foregoing of the present invention is explained further details, but should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment through the embodiment of embodiment form.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
The preparation of Resorcinol
The zero(ppm) water that in the three neck round-bottomed flasks of 500 ml that are furnished with TM, mechanical stirring device, adds 60 ml; The PARA HYDROXY BENZALDEHYDE that adds 20.0 g (0.16 mol) then; Behind stirring at room 10 min; Drip mass concentration simultaneously and be 30% ydrogen peroxide 50 27.2 g and mass concentration and be 23% sodium hydroxide solution 33.0 g in flask, the control rate of addition makes reacting liquid temperature be no more than 50
oC, the tracking that vapor-phase chromatography (GC) is reacted, about 40 min afterreactions finish.
The preparation of 6-chloro-2-(4-hydroxyphenoxy) quinoxaline
After the preparation feedback of treating Resorcinol finishes, in flask, add 75 ml zero(ppm) water and 41.8 g (0.21 mol) 2, the toluene of 6-dichloro-quinoxaline and 3 ml is warmed up to 90 then
oC drips mass concentration and is 14% sodium hydroxide solution 62.8 g afterwards in flask, the control reacting liquid temperature is 90～95 during dropping
oBetween the C.Be warming up to backflow after being added dropwise to complete, GC follows the tracks of reaction, and about 15 h afterreactions finish.Filtered while hot is used hot wash then, and filtration cakes torrefaction gets light gray solid 6-chloro-2-(4-hydroxyphenoxy) quinoxaline 32.2 g, and total recovery is 91%, GC content 98%.
GC measures, RT: 11.33min.ESI?MS?
m/z：273?[M+H
+]。
1H?NMR?(400?MHz?,?DMSO-
d 6)?,?
δ：9.54?(s,?1H,?4ˊ-OH),?8.86?(s,?1H,?3-H),?8.15?(d,?
J?=?2.0?Hz,?1H,?5-H),?7.78?(d,?
J?=?9.2?and?2.4?Hz,?1H,?7-H),?7.73?(d,?
J?=?8.8?Hz,?18-H),?7.13-6.85?(d,?
J?=?8.8?Hz,?4H,?2′、3′、5′、6′-H)；
13C?NMR?(100?MHz,?DMSO-d
6)?
δ：158.0?(C-2),?155.4?(C-4ˊ),?144.7?(C-1′),?141.5?(C-9),?139.6?(C-6),?138.6?(C-10),?131.9?(C-3),?131.4?(C-7),?129.3?(C-8),?127.9?(C-5),?122.9?(C-2′,?6′),?116.4?(C-3′,?5′)。
The preparation of Resorcinol
In the three neck round-bottomed flasks of 500 ml that are furnished with TM, mechanical stirring device, add 50 ml zero(ppm) water; The PARA HYDROXY BENZALDEHYDE that adds 20.0 g (0.16 mol) then; Behind stirring at room 10 min; Drip mass concentration simultaneously and be 30% ydrogen peroxide 50 18.1 g and mass concentration and be 23% sodium hydroxide solution 27.8 g in three neck round-bottomed flasks, the control rate of addition makes reacting liquid temperature be no more than 50
oC, the tracking that vapor-phase chromatography (GC) is reacted finishes to reacting.
The preparation of 6-chloro-2-(4-hydroxyphenoxy) quinoxaline
After the preparation feedback of treating Resorcinol finishes, in flask, add 70 ml zero(ppm) water and 31.8 g (0.16 mol) 2, the toluene of 6-dichloro-quinoxaline and 1 ml is warmed up to 80 then
oC drips mass concentration and is 14% sodium hydroxide solution 45.7 g afterwards in flask, the control reacting liquid temperature is 90～95 during dropping
oBetween the C.Be warming up to backflow after being added dropwise to complete, GC follows the tracks of reaction, finishes to reacting.Filtered while hot is used hot wash then, and filtration cakes torrefaction gets light gray solid 6-chloro-2-(4-hydroxyphenoxy) quinoxaline, total recovery 91.4%, GC content 98.4%.
The preparation of Resorcinol
In the three neck round-bottomed flasks of 500 ml that are furnished with TM, mechanical stirring device, add 70 ml zero(ppm) water; The PARA HYDROXY BENZALDEHYDE that adds 20.0 g (0.16 mol) then; Behind stirring at room 10 min; Drip mass concentration simultaneously and be 30% ydrogen peroxide 50 36.2 g and mass concentration and be 23% sodium hydroxide solution 55.6 g in three neck round-bottomed flasks, the control rate of addition makes reacting liquid temperature be no more than 50
oC, the tracking that vapor-phase chromatography (GC) is reacted finishes to reacting.
The preparation of 6-chloro-2-(4-hydroxyphenoxy) quinoxaline
After the preparation feedback of treating Resorcinol finishes, in flask, add 80 ml zero(ppm) water and 63.7 g (0.32 mol) 2, the toluene of 6-dichloro-quinoxaline and 5 ml is warmed up to 100 then
oC drips mass concentration and is 14% sodium hydroxide solution 91.4 g afterwards in flask, the control reacting liquid temperature is 90～95 during dropping
oBetween the C.Be warming up to backflow after being added dropwise to complete, GC follows the tracks of reaction, finishes to reacting.Filtered while hot is used hot wash then, and filtration cakes torrefaction gets light gray solid 6-chloro-2-(4-hydroxyphenoxy) quinoxaline, total recovery 91.2%, GC content 98.8%.
Claims (8)
1. one kettle way synthesizes the method for quizalofopPethyl midbody 6-chloro-2-(4-hydroxyphenoxy) quinoxaline, it is characterized in that comprising following steps: (1) PARA HYDROXY BENZALDEHYDE is dissolved the back dropping oxidizing agent in solvent and alkaline reaction makes Resorcinol; (2) in the Resorcinol reaction soln for preparing, add zero(ppm) water and 2, the 6-dichloro-quinoxaline adds solvent again and makes 2; The dissolving of 6-dichloro-quinoxaline; Stirring is warming up to needed temperature, and dripping alkali liquid condensation reaction promptly takes place makes 6-chloro-2-(4-hydroxyphenoxy) quinoxaline.
2. the method for synthetic quizalofopPethyl midbody 6-chloro-2-according to claim 1 (4-hydroxyphenoxy) quinoxaline; It is characterized in that solvent used in the step (1) is a water; Used oxygenant is a hydrogen peroxide; Used alkali lye is sodium hydroxide solution, and the mode of dropping oxidizing agent and alkali lye is dropping simultaneously, and control reaction temperature is no more than 50 in dropping oxidizing agent and alkali lye process
oC.
3. the method for synthetic quizalofopPethyl midbody 6-chloro-2-according to claim 1 (4-hydroxyphenoxy) quinoxaline is characterized in that the used PARA HYDROXY BENZALDEHYDE of step (1) and the ratio of the amount of substance of hydrogen peroxide and sodium hydroxide are 1:1～2:1～2.
4. the method for synthetic quizalofopPethyl midbody 6-chloro-2-according to claim 1 (4-hydroxyphenoxy) quinoxaline is characterized in that the prepared Resorcinol of step (1) need not be handled and directly is used for step (2).
5. the method for synthetic quizalofopPethyl midbody 6-chloro-2-according to claim 1 (4-hydroxyphenoxy) quinoxaline is characterized in that solvent used in the step (2) is a toluene, and used alkali lye is sodium hydroxide solution or potassium hydroxide solution.
6. the method for synthetic quizalofopPethyl midbody 6-chloro-2-according to claim 1 (4-hydroxyphenoxy) quinoxaline is characterized in that it is 80～100 that the stirring described in the step (2) is warming up to needed temperature
oC needs the control reacting liquid temperature 90～95 in the dripping alkali liquid process
oBetween the C.
7. the method for synthetic quizalofopPethyl midbody 6-chloro-2-according to claim 1 (4-hydroxyphenoxy) quinoxaline; It is characterized in that sodium hydroxide and 2 used in the step (2), the ratio of the amount of substance of used PARA HYDROXY BENZALDEHYDE is 1～2:1～2:1 in 6-dichloro-quinoxaline and the step (1).
8. according to the method for the described synthetic quizalofopPethyl midbody 6-chloro-2-of claim 1 ~ 7 (4-hydroxyphenoxy) quinoxaline, it is characterized in that described compound method can represent with following reaction formula:
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115536518A (en) * | 2022-11-30 | 2022-12-30 | 苏州开元民生科技股份有限公司 | Preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid |
-
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- 2012-05-18 CN CN2012101543824A patent/CN102659694A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| 《农药》 20080430 胡美华等 "4-(6-氯喹喔啉-2-氧基)苯酚的合成" 248-249、260 1-8 第47卷, 第4期 * |
| 杨善中等: "《有机结构理论》", 31 January 2003, 合肥工业大学出版社 * |
| 胡美华等: ""4-(6-氯喹喔啉-2-氧基)苯酚的合成"", 《农药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115536518A (en) * | 2022-11-30 | 2022-12-30 | 苏州开元民生科技股份有限公司 | Preparation method of R- (+) -2- (4-hydroxyphenoxy) propionic acid |
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Application publication date: 20120912 |