CN105732403A - Preparation method of 2,3-dichloro-4-hydroxyaniline - Google Patents
Preparation method of 2,3-dichloro-4-hydroxyaniline Download PDFInfo
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- CN105732403A CN105732403A CN201610188877.7A CN201610188877A CN105732403A CN 105732403 A CN105732403 A CN 105732403A CN 201610188877 A CN201610188877 A CN 201610188877A CN 105732403 A CN105732403 A CN 105732403A
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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Abstract
The invention discloses a preparation method of 2,3-dichloro-4-hydroxyaniline. The preparation method comprises the steps of adding a reaction raw material 2,3-dichloro-4-phenylazo phenol and a reductant sodium borohydride into an ethanol solution, reacting at 0-25 DEG C for 2-6 hours, cooling to the room temperature after the reaction, regulating pH to 7, extracting by virtue of ethyl acetate, drying by virtue of anhydrous sodium sulfate, then carrying out rotary evaporation to remove the solvent, recrystallizing with methylbenzene, and finally drying so as to obtain 2,3-dichloro-4-hydroxyaniline. According to the preparation method of 2,3-dichloro-4-hydroxyaniline, a catalytic reduction method for utilizing hydrogen/metals at a pressurization condition is avoided, expensive and inflammable Raney nickel or other metal catalysts are not used, the operation is simple, conditions are mild, the yield can reach 90% or above, and the reaction cost is low. The preparation method is applicable to large-scale industrial production.
Description
Technical field
The invention belongs to the technical field of crop protection agent, be specifically related to a kind of intermediate 2,3-bis-chloro-4-hydroxyl
The preparation method of base aniline.
Background technology
Acid amide fungicides was successfully developed from 1966 and uses, and such crop protection agent is as antifungal
Existing nearly 50 years history.Fenhexamid be by Beyer Co., Ltd develop a kind of have interior absorption, protectiveness new
Type acid amide fungicides, in official listing in 1999.It is right that fenhexamid and derivatives class antifungal thereof have
Crop securify, favourable toxicity data, and good ecological effect, therefore become the most comprehensive pest
Administer medication.
In the middle of the 2,3-bis-chloro-4-hydroxyanilines key as fenhexamid and derivatives class crop bactericide thereof
Body, its synthetic method reported by Beyer Co., Ltd and protected, and is i.e. raw material by substituted arylazo compound,
Target compound is obtained through reduction.The method of preparation process many employings metal catalyzed hydrogenation reduction, hydrogen source is hydrogen
Gas or hydrazine hydrate, carried out in 0-150 DEG C in the presence of the metals such as Raney's nickel and adjuvant；Or use gold
Genus/hydrochloric acid reducing process, metal generally uses iron powder or zinc powder.Above method all needs by metal catalytic, and one
Aspect needs to use expensive, inflammable Raney's nickel, adds the danger of large-scale production；On the one hand again can
Produce the disagreeableness metal waste residue of a large amount of environment.
The present inventor is found that a kind of new synthetic method, this synthesis side in the research to this compounds
Method not only has mild condition, easy purification, the advantages such as production cost is low, and its operability is also greatly improved,
Effectively reduce reactivity hazard, be suitable for large-scale industrial production.
Summary of the invention
It is an object of the invention to provide the 2,3-bis-chloro-4-hydroxyanilines of a kind of low cost, reaction condition gentleness
Preparation method.
In order to reach above-mentioned technique effect, the present invention takes techniques below scheme:
A kind of 2, the preparation method of 3-bis-chloro-4-hydroxyanilines, comprise the following steps:
By reaction raw materials 2,3-bis-chloro-4-phenylazo phenol, borane reducing agent sodium hydride join in ethanol solution,
React 2～6 hours at temperature 0～25 DEG C, after reaction terminates, be cooled to room temperature, regulate pH to 7, so
After be extracted with ethyl acetate, then be dried with anhydrous sodium sulfate, then rotate and solvent and re crystallization from toluene are evaporated off,
Finally dry and obtain described 2,3-bis-chloro-4-hydroxyanilines.
Further technical scheme is, described 2,3-bis-chloro-4-phenylazo phenol and borane reducing agent sodium hydride
Mol ratio be 1:3～6.
Further technical scheme is that described reaction temperature is 0～10 DEG C.
Present invention also offers another embodiment, described ethanol solution adds sodium hydroxide.
Further technical scheme is, described 2,3-bis-chloro-4-phenylazo phenol and borane reducing agent sodium hydride
Mol ratio be 1:3～5.
Further technical scheme is that described reaction temperature is 0～15 DEG C.
The present invention is further illustrated below.
In the present invention 2,3-bis-chloro-4-hydroxyanilines is pesticide fenhexamid and derivant key intermediates thereof,
Its structural formula is as follows:
In the present invention, the preparation method of 2,3-bis-chloro-4-hydroxyanilines is all with the chloro-4-of arylazo compound 2,3-bis-
Phenylazo phenol is prepared by raw material, and the structural formula of 2,3-bis-chloro-4-phenylazo phenol is as follows:
A kind of 2, the preparation method of 3-bis-chloro-4-hydroxyanilines, comprise the following steps:
By reaction raw materials 2,3-bis-chloro-4-phenylazo phenol, borane reducing agent sodium hydride join in ethanol solution,
React 2～6 hours at 0～25 DEG C, after reaction terminates, be cooled to room temperature, regulate pH to 7, then use
Ethyl acetate extracts, then is dried with anhydrous sodium sulfate, then rotates and solvent and re crystallization from toluene is evaporated off, finally
Dry and obtain described 2,3-bis-chloro-4-hydroxyanilines.
The principle of the preparation method of the present invention is hydride ion reduction mechanism.
A specific embodiment according to the present invention, by reaction raw materials 2,3-bis-chloro-4-phenylazo phenol, boron
Sodium hydride joins in ethanol solution, reacts 2～6 hours at 0～10 DEG C, after reaction terminates, is cooled to
Room temperature, regulates pH to 7, is then extracted with ethyl acetate, then is dried with anhydrous sodium sulfate, then rotate steaming
Except solvent and re crystallization from toluene, finally dry and obtain described 2,3-bis-chloro-4-hydroxy benzenes.
In the above-described embodiment, the mol ratio of 2,3-bis-chloro-4-phenylazo phenol and sodium borohydride be 1:3～
6, if the mol ratio of 2,3-bis-chloro-4-phenylazo phenol and sodium borohydride is less than 1:3, then reduction reaction can not
Thoroughly carry out；If 2,3-bis-chloro-4-phenylazo phenol are more than 1:6 with the mol ratio of sodium borohydride, then can produce
A large amount of by-products, are unfavorable for the carrying out of reduction reaction, therefore, and 2,3-bis-chloro-4-phenylazo phenol and hydroborations
The mol ratio of sodium be 1:3～6 be suitable.According to a preferred embodiment of the invention, described 2, the chloro-4-of 3-bis-
Phenylazo phenol is 1:4～6 with the mol ratio of sodium borohydride.
In the above-described embodiment, reaction temperature is 0～10 DEG C, if reaction temperature is less than 0 DEG C, then reduction is anti-
Can not occur；If reaction temperature is more than 10 DEG C, then can produce a large amount of by-product, be unfavorable for reduction reaction
Carrying out, therefore reaction temperature is 0～10 DEG C is suitable.According to a preferred embodiment of the invention, described reaction
Temperature is 0～10 DEG C.
According to another embodiment of the invention, by reaction raw materials 2,3-bis-chloro-4-phenylazo phenol, boron hydrogen
Change in the ethanol solution that sodium joins sodium hydroxide, react 2～6 hours at 0～15 DEG C, after reaction terminates,
It is cooled to room temperature, regulates pH to 7, be then extracted with ethyl acetate, then be dried with anhydrous sodium sulfate, then
Rotation is evaporated off solvent and re crystallization from toluene, finally dries and obtains described 2,3-bis-chloro-4-hydroxy benzenes.
In the above-described embodiment, the mol ratio of 2,3-bis-chloro-4-phenylazo phenol and sodium borohydride be 1:3～
5, if the mol ratio of 2,3-bis-chloro-4-phenylazo phenol and sodium borohydride is less than 1:3, then reduction reaction can not
Carry out；If 2,3-bis-chloro-4-phenylazo phenol are more than 1:5 with the mol ratio of sodium borohydride, then can produce a large amount of
By-product, is unfavorable for the carrying out of reduction reaction, therefore, and 2,3-bis-chloro-4-phenylazo phenol and sodium borohydride
Mol ratio be 1:3～5 be suitable.According to a preferred embodiment of the invention, described 2,3-bis-chloro-4-benzene is even
Nitrilo phenol is 1:4～5 with the mol ratio of sodium borohydride.
In the above-described embodiment, reaction is 0～15 DEG C, if reaction temperature is less than 0 DEG C, then reaction can not be entered
OK；If reaction temperature is more than 15 DEG C, then can produce a large amount of by-product, be unfavorable for the carrying out of reduction reaction, because of
It is suitable that this reaction temperature is 0～15 DEG C.According to a preferred embodiment of the invention, described reaction temperature be 0～
10℃。
In the above-described embodiment, the effect of sodium hydroxide is the alkalescence of intensified response system, increases boron hydrogen
Change the stability of sodium, improve reaction rate.
The present invention compared with prior art, has a following beneficial effect:
The preparation method of 2,3-bis-provided by the present invention chloro-4-hydroxyanilines avoids use hydrogen under pressurized conditions
The catalytic reduction method of gas/metal, it is not necessary to use expensive and inflammable Raney's nickel or other metallic catalysts,
Simple to operate, mild condition, productivity is up to more than 90%, and reaction cost is low, is suitable for large-scale industry metaplasia
Produce.
Accompanying drawing explanation
Fig. 1 is the synthetic route chart of compound 2,3-bis-chloro-4-hydroxyanilines；
Fig. 2 is compound 2,3-bis-chloro-4-hydroxyanilines1H NMR characterizes collection of illustrative plates；
Fig. 3 is compound 2,3-bis-chloro-4-hydroxyanilines13C NMR characterizes collection of illustrative plates；
Fig. 4 is that the HPLC-MS of compound 2,3-bis-chloro-4-hydroxyanilines characterizes collection of illustrative plates.
Detailed description of the invention
Below in conjunction with embodiments of the invention, the invention will be further elaborated.
Embodiment 1:
Sodium borohydride/ethanol system reduction preparation 2,3-bis-chloro-4-hydroxyanilines
Equipped with in 100 milliliters of two mouthfuls of flasks of stirrer and reflux condensing tube, add 8.0 grams (0.03 moles)
Raw material 2,3-bis-chloro-4-phenylazo phenol, it is dissolved in 40 milliliters of ethanol solution, in ice-water bath the most in batches
Add sodium borohydride 4.5 grams (0.12 mole).After dropping, under agitation remove ice bath, be warmed to room temperature
Continue reaction 4 hours.After reaction terminates, dilute hydrochloric acid solution is neutralized to pH=7, and ethyl acetate extracts three times,
Merging organic facies anhydrous sodium sulfate to be dried, Rotary Evaporators is evaporated off solvent, 20 milliliters of re crystallization from toluene, mistake
It is 4.95 grams of lightpink crystal that filter post-drying obtains product, productivity 92%.
Fig. 2～4 shows 2,3-bis-chloro-4-hydroxyanilines1H NMR sign collection of illustrative plates,13C NMR phenogram
Spectrum and HPLC-MS characterize collection of illustrative plates, can obtain obtaining in the present embodiment 2,3-bis-chloro-4-hydroxy benzenes from Fig. 4
The purity of amine is 100%.
Embodiment 2:
Sodium borohydride, sodium hydroxide/ethyl alcohol reduction system prepare 2,3-bis-chloro-4-hydroxyanilines
Equipped with in 100 milliliters of two mouthfuls of flasks of stirrer and reflux condensing tube, add 8.0 grams (0.03 moles)
Raw material 2,3-bis-chloro-4-phenylazo phenol, 1 gram of sodium hydroxide is dissolved in 40 milliliters of ethanol solution, frozen water
Bath is dividedly in some parts sodium borohydride 4.5 grams (0.12 mole) on a small quantity.After dropping, under agitation remove ice
Bath, is warmed to room temperature continuation reaction 4 hours.After reaction terminates, dilute hydrochloric acid solution is neutralized to pH=7, acetic acid second
Ester extracts three times, merges organic facies anhydrous sodium sulfate and is dried, and Rotary Evaporators is evaporated off solvent, 20 milliliters of first
Benzene recrystallization, filter post-drying obtaining product is 5.08 grams of lightpink crystal, and productivity 95%, purity is 100%.
Although reference be made herein to invention has been described for the explanatory embodiment of the present invention, and above-described embodiment is only
For the present invention preferably embodiment, embodiments of the present invention are also not restricted to the described embodiments, it should
Understanding, those skilled in the art can be designed that a lot of other amendments and embodiment, and these are revised and real
The mode of executing will fall within spirit disclosed in the present application and spirit.
Claims (6)
1. one kind 2, the preparation method of 3-bis-chloro-4-hydroxyanilines, it is characterised in that comprise the following steps:
By reaction raw materials 2,3-bis-chloro-4-phenylazo phenol, borane reducing agent sodium hydride join in ethanol solution,
React 2～6 hours at temperature 0～25 DEG C, after reaction terminates, be cooled to room temperature, regulate pH to 7,
Then it is extracted with ethyl acetate, then is dried with anhydrous sodium sulfate, then rotate and solvent and toluene weight are evaporated off
Crystallization, finally dries and obtains described 2,3-bis-chloro-4-hydroxyanilines.
The preparation method of the most according to claim 12,3-bis-chloro-4-hydroxyanilines, it is characterised in that described
Ethanol solution in add sodium hydroxide.
The preparation method of the most according to claim 12,3-bis-chloro-4-hydroxyanilines, it is characterised in that described
The mol ratio of 2,3-bis-chloro-4-phenylazo phenol and borane reducing agent sodium hydride be 1:3～6.
The preparation method of the most according to claim 22,3-bis-chloro-4-hydroxyanilines, it is characterised in that described
The mol ratio of 2,3-bis-chloro-4-phenylazo phenol and borane reducing agent sodium hydride be 1:3～5.
The preparation method of the most according to claim 12,3-bis-chloro-4-hydroxyanilines, it is characterised in that described
Reaction temperature be 0～10 DEG C.
The preparation method of the most according to claim 22,3-bis-chloro-4-hydroxyanilines, it is characterised in that described
Reaction temperature be 0～15 DEG C.
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| CN201610188877.7A CN105732403A (en) | 2016-03-29 | 2016-03-29 | Preparation method of 2,3-dichloro-4-hydroxyaniline |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475475A (en) * | 2002-08-15 | 2004-02-18 | 李宽义 | Method of producing hydroquinone by palladium carbon low pressure catalytic hydrogenation |
| CN105418441A (en) * | 2015-12-22 | 2016-03-23 | 中国工程物理研究院化工材料研究所 | Preparation method for 2,3-dichloro-4-hydroxyaniline |
-
2016
- 2016-03-29 CN CN201610188877.7A patent/CN105732403A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1475475A (en) * | 2002-08-15 | 2004-02-18 | 李宽义 | Method of producing hydroquinone by palladium carbon low pressure catalytic hydrogenation |
| CN105418441A (en) * | 2015-12-22 | 2016-03-23 | 中国工程物理研究院化工材料研究所 | Preparation method for 2,3-dichloro-4-hydroxyaniline |
Non-Patent Citations (5)
| Title |
|---|
| AKIRA NAKAMURA等: "Molybenum-sulfur chelates as catalyts in the reductive cleavage of azobenzene by electron donors in protic media", 《JOURNAL OF MOLECULAR CATALYSIS》 * |
| 宋航主编: "《药物与精细有机品合成》", 31 January 2009, 高等教育出版社 * |
| 浙江大学等主编: "《化学工艺学》", 31 July 2001, 高等教育出版社 * |
| 金国新等: "钼硫、钨硫原子簇化合物催化偶氮苯还原的反应", 《分子催化》 * |
| 黄伟等: "环酰菌胺合成工艺", 《农药》 * |
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Application publication date: 20160706 |