CN111333523A - Synthetic method of 3-nitro-4-hydroxyethylaminophenol - Google Patents
Synthetic method of 3-nitro-4-hydroxyethylaminophenol Download PDFInfo
- Publication number
- CN111333523A CN111333523A CN202010286246.5A CN202010286246A CN111333523A CN 111333523 A CN111333523 A CN 111333523A CN 202010286246 A CN202010286246 A CN 202010286246A CN 111333523 A CN111333523 A CN 111333523A
- Authority
- CN
- China
- Prior art keywords
- nitro
- hydroxyethylaminophenol
- compound
- synthesizing
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- 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
-
- C—CHEMISTRY; METALLURGY
- 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
- C07C213/08—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 not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- 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
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
Abstract
The invention relates to a synthesis method of 3-nitro-4-hydroxyethylaminophenol, which comprises the following steps of reacting a compound shown in the following formula I with ethanolamine under the heating condition to obtain a compound shown in the following formula II; heating the compound II obtained in the step (1) and hydrobromic acid to perform demethylation reaction under the reflux condition to obtain a compound 3-nitro-4-hydroxyethylaminophenol hydrobromide, and reacting the compound 3-nitro-4-hydroxyethylaminophenol hydrobromide with concentrated ammonia water to obtain a compound shown in the following formula III, namely the target product. The invention provides a brand new reaction route, cheap and easily-obtained 4-dimethoxy-2-nitrobenzene and ethanolamine are used as main raw materials, the whole preparation process is simple and easy to operate, high in toxicity and risk and high in yield of the obtained product, and industrial production is easy to realize; the raw materials ethanolamine and hydrobromic acid in the reaction process can be recycled, so that the three wastes are reduced, and the cost is saved.
Description
Technical Field
The invention relates to the technical field of compound synthesis, in particular to a synthesis method of 3-nitro-4-hydroxyethylaminophenol.
Background
Hair dye is a cosmetic with special effect and capable of changing hair color. Hair dyes have been developed for a long time, and a series of hair dyes have been formed, for example, phenol hair dyes are hair dyes which are widely used. 3-nitro-4-hydroxyethylaminophenol (RED54) is used as an intermediate of the phenolic high-end hair dye, and shows higher application value.
Japanese patent JP2010248122 reports that 3-nitro-4-hydroxyethylaminophenol is obtained by reacting 3-nitro-4-aminophenol with chloroethyl chloroformate under alkaline conditions. The 3-nitro-4-aminophenol used as the raw material in the method has higher market price, the chloroethyl chloroformate belongs to a high-class substance and has strong irritation, and a large amount of wastewater is generated in the reaction process, so that the industrial production cost of the synthetic route is higher.
Disclosure of Invention
The invention aims to solve the technical problem of the prior art and provides a synthetic method of 3-nitro-4-hydroxyethylaminophenol, which has the advantages of cheap and easily obtained raw materials, simple operation, high safety, high yield and easy realization of industrialization.
The technical scheme adopted by the invention for solving the technical problems is as follows: a synthetic method of 3-nitro-4-hydroxyethylaminophenol is characterized by comprising the following steps:
(1) under the heating condition, reacting a compound shown in the following formula I with ethanolamine to obtain a compound shown in the following formula II;
(2) heating the compound II obtained in the step (1) and hydrobromic acid to perform demethylation reaction under the reflux condition to obtain a compound 3-nitro-4-hydroxyethylaminophenol hydrobromide, reacting the compound 3-nitro-4-hydroxyethylaminophenol hydrobromide with concentrated ammonia water to obtain a compound shown in the following formula III, namely the target product 3-nitro-4-hydroxyethylaminophenol,
in the scheme, in the step (1), after the reaction of the compound shown in the formula I and ethanolamine is finished, the temperature is reduced to room temperature, then concentrated hydrochloric acid with the mass fraction of 36.5% is dripped into the reaction system until solid matters are separated out, and the solid matters are filtered to obtain the compound shown in the formula II.
Preferably, concentrated hydrochloric acid is added dropwise to the reaction system to a pH of 10 ± 0.5, followed by filtration.
Preferably, after the solid is precipitated and filtered, the resulting filtrate is distilled under reduced pressure to recover the ethanolamine, and the solid is recrystallized from alcohol to obtain a purified compound of formula II. The alcohol used for alcohol recrystallization is selected from one of methanol, ethanol and isopropanol. According to the invention, the ethanolamine is recycled and can be reused, so that the use cost is reduced.
In the step (1), the reaction temperature is 80-120 ℃, and the mass ratio of the compound of the formula I and the ethanolamine is 1 (4-8). In the step (2), the mass fraction of the hydrobromic acid is 40-48%, and the dosage of the hydrobromic acid is 8-12 times of that of the compound shown in the formula II.
In the invention, in the step (2), after the demethylation reaction is finished, the reaction liquid is firstly decompressed and distilled to remove most hydrobromic acid in the reaction liquid, and the obtained solution is cooled to 0-10 ℃ for crystallization under heat preservation to obtain the 3-nitro-4-hydroxyethylaminophenol hydrobromide. The hydrobromic acid of the invention is used as a reactant, a solvent and a catalyst in a reaction system, and most (70-80%) of the hydrobromic acid is removed after the reaction is finished, thereby being beneficial to improving the crystallization effect and improving the yield.
Preferably, the reduced pressure distillation condition is-0.95 to-0.1 MPa and 80 to 100 ℃.
In the invention, the 3-nitro-4-hydroxyethylaminophenol hydrobromide is dissolved in water, 25-28 mass percent of concentrated ammonia water is dripped into the system to adjust the pH value to be neutral or alkalescent, and then the target product, namely the compound shown in the formula III, is obtained by extraction and drying with an organic solvent.
Preferably, the pH value of the system is adjusted to 7-8 by the concentrated ammonia water; the organic solvent for extraction is selected from ethyl acetate, dichloromethane, toluene, and 1, 2-dichloroethane.
Compared with the prior art, the invention has the advantages that: the invention provides a brand new reaction route, cheap and easily-obtained 4-dimethoxy-2-nitrobenzene and ethanolamine are used as main raw materials, the whole preparation process is simple and easy to operate, high in toxicity and risk and high in yield of the obtained product, and industrial production is easy to realize; the raw materials ethanolamine and hydrobromic acid in the reaction process can be recycled, so that the three wastes are reduced, and the cost is saved.
Drawings
FIG. 1 is an HPLC chromatogram of a target product obtained in example 1 of the present invention;
FIG. 2 is the HNMR spectrum of the target product obtained in example 1 of the present invention.
Detailed Description
The invention is described in further detail below with reference to the accompanying examples.
Example 1:
the synthesis method of 3-nitro-4-hydroxyethylaminophenol of this example comprises the following steps:
(1) weighing 18.3g of 2, 5-dimethoxy nitrobenzene (compound shown in formula I) and 90g of ethanolamine in a round-bottom flask, starting heating and stirring for reaction, controlling the temperature to be 100-105 ℃, cooling to room temperature after 4h of reaction, adjusting the pH to 10 by using concentrated hydrochloric acid, slowly beginning to precipitate solids, and continuing stirring until the product is completely precipitated; filtering to obtain 19.5g of a crude product of the 2-nitro-N-hydroxyethyl-P-anisidine, and performing reduced pressure distillation on ethanolamine in the filtrate for recycling; recrystallizing the crude product of 2-nitro-N-hydroxyethyl-P-anisidine with methanol to obtain 18.2g of 2-nitro-N-hydroxyethyl-P-anisidine (compound of formula II), with yield of 86% and purity of 99.4%;
(2) weighing 10.6g of 2-nitro-N-hydroxyethyl-P-anisidine (a compound shown in a formula II) into a round-bottom flask, adding 100g of hydrobromic acid, heating and refluxing, after the reaction is finished for 5 hours, carrying out reduced pressure distillation and desolventizing at-0.95 to-0.1 MPa at 80-100 ℃, removing most of solvent for recycling, cooling the obtained solution to 5-10 ℃, carrying out heat preservation and crystallization, and filtering to obtain 3-nitro-4-hydroxyethylaminophenol hydrobromide; dissolving 3-nitro-4-hydroxyethylaminophenol hydrobromide in water, adjusting pH to 7.5 with concentrated ammonia water, extracting with ethyl acetate, drying with anhydrous sodium sulfate, and desolventizing under reduced pressure to obtain 9.1g of 3-nitro-4-hydroxyethylaminophenol (compound shown in formula III) with a yield of 92%; purity 99.47% (see HPLC profile of fig. 1).
From the HNMR spectrum of fig. 2, the obtained product was the target product.
Example 2:
the synthesis method of 3-nitro-4-hydroxyethylaminophenol of this example comprises the following steps:
(1) weighing 36.6g of 2, 5-dimethoxy-2-nitrobenzene and 148g of ethanolamine recovered in example 1 into a round-bottom flask, starting heating and stirring for reaction, controlling the temperature at 105 ℃ under 100 ℃, cooling to room temperature after the reaction is finished, adjusting the pH to 10 by using concentrated hydrochloric acid, slowly extracting solid from the beginning, continuously stirring until the product is completely separated out, filtering to obtain 39.5g of a crude product of 2-nitro-N-hydroxyethyl-P-anisidine, performing reduced pressure distillation and recycling of the ethanolamine in the filtrate, and recrystallizing by using ethanol to obtain 35.7g of 2-nitro-N-hydroxyethyl-P-anisidine with the yield of 85% and the purity of 99.3%;
(2) weighing 30g of 2-nitro-N-hydroxyethyl-P-anisidine into a round bottom flask, adding 240g of hydrobromic acid recovered in the example 1, heating and refluxing, distilling under reduced pressure to desolventize and remove most of solvent after the reaction is finished, recycling and reusing, cooling to 5-10 ℃, keeping the temperature and crystallizing, filtering to obtain 3-nitro-4-hydroxyethylaminophenol hydrobromide, dissolving the 3-nitro-4-hydroxyethylaminophenol hydrobromide in a proper amount of water, adjusting the pH to 7.1 by using concentrated ammonia water, extracting by using dichloromethane, drying by using anhydrous sodium sulfate, and desolventizing under reduced pressure to obtain 25.4g of 3-nitro-4-hydroxyethylaminophenol, wherein the yield is 91%, and the purity is 99.2%.
Example 3:
the synthesis method of 3-nitro-4-hydroxyethylaminophenol of this example comprises the following steps:
(1) weighing 27.5g of 2, 5-dimethoxy-2-nitrobenzene and 220g of ethanolamine in a round-bottom flask, starting heating and stirring for reaction, controlling the temperature at 100 ℃ and 105 ℃, cooling to room temperature after the reaction is finished, adjusting the pH to 10 by using concentrated hydrochloric acid, slowly beginning to extract solids, continuing to stir until the product is completely separated out, filtering to obtain 31.1g of a crude product of 2-nitro-N-hydroxyethyl-P-anisidine, performing reduced pressure distillation and recycling of the ethanolamine in the filtrate, and recrystallizing by using isopropanol to obtain 27.6g of 2-nitro-N-hydroxyethyl-P-anisidine with the yield of 87% and the purity of 99.3%;
(2) weighing 21.2g of 2-nitro-N-hydroxyethyl-P-anisidine into a round-bottom flask, adding 240g of hydrobromic acid, heating and refluxing, distilling under reduced pressure to remove most of solvent after the reaction is finished, recycling, cooling to 5-10 ℃, preserving heat, crystallizing, filtering to obtain 3-nitro-4-hydroxyethylaminophenol hydrobromide, dissolving in proper amount of water, adjusting pH to 8 with concentrated ammonia water, extracting with 1, 2-dichloroethane, drying with anhydrous sodium sulfate, and precipitating under reduced pressure to obtain 18.4g of 3-nitro-4-hydroxyethylaminophenol, wherein the yield is 93%, and the purity is 99.1%.
Claims (10)
1. A synthetic method of 3-nitro-4-hydroxyethylaminophenol is characterized by comprising the following steps:
(1) under the heating condition, reacting a compound shown in the following formula I with ethanolamine to obtain a compound shown in the following formula II;
(2) heating the compound II obtained in the step (1) and hydrobromic acid to perform demethylation reaction under the reflux condition to obtain a compound 3-nitro-4-hydroxyethylaminophenol hydrobromide, reacting the compound 3-nitro-4-hydroxyethylaminophenol hydrobromide with concentrated ammonia water to obtain a compound shown in the following formula III, namely the target product 3-nitro-4-hydroxyethylaminophenol,
2. the method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 1, characterized in that: in the step (1), after the reaction of the compound of the formula I and ethanolamine is finished, the temperature is firstly reduced to room temperature, then concentrated hydrochloric acid is dripped into the reaction system until solid matters are separated out, and the solid matters are filtered to obtain the compound of the formula II.
3. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 2, characterized in that: concentrated hydrochloric acid was added dropwise to the reaction system to a PH of 10 ± 0.5, followed by filtration.
4. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 2, characterized in that: and after the solid is separated out and filtered, recovering the ethanolamine from the obtained filtrate through reduced pressure distillation, and recrystallizing the solid through alcohol to obtain the purified compound shown in the formula II.
5. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 1, characterized in that: in the step (1), the reaction temperature is 80-120 ℃, and the mass ratio of the compound of the formula I and the ethanolamine is 1 (4-8).
6. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to any one of claims 1 to 5, wherein: in the step (2), the mass fraction of the hydrobromic acid is 40-48%, and the dosage of the hydrobromic acid is 8-12 times of that of the compound shown in the formula II.
7. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to any one of claims 1 to 5, wherein: in the step (2), after the demethylation reaction is finished, the reaction liquid is subjected to reduced pressure distillation to remove most hydrobromic acid in the reaction liquid, and the obtained solution is cooled to 0-10 ℃ for heat preservation and crystallization to obtain the 3-nitro-4-hydroxyethylaminophenol hydrobromide.
8. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 7, wherein: the reduced pressure distillation condition is-0.95 to-0.1 MPa and 80 to 100 ℃.
9. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 7, wherein: dissolving the 3-nitro-4-hydroxyethylaminophenol hydrobromide in water, dropwise adding concentrated ammonia water into the system to adjust the pH value to be neutral or alkalescent, extracting by using an organic solvent, and drying to obtain a target product, namely the compound shown in the formula III.
10. The method for synthesizing 3-nitro-4-hydroxyethylaminophenol according to claim 9, characterized in that: the pH value of the system is adjusted to 7-8 by the strong ammonia water; the organic solvent for extraction is selected from ethyl acetate, dichloromethane, toluene, and 1, 2-dichloroethane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010286246.5A CN111333523A (en) | 2020-04-13 | 2020-04-13 | Synthetic method of 3-nitro-4-hydroxyethylaminophenol |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010286246.5A CN111333523A (en) | 2020-04-13 | 2020-04-13 | Synthetic method of 3-nitro-4-hydroxyethylaminophenol |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111333523A true CN111333523A (en) | 2020-06-26 |
Family
ID=71180858
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010286246.5A Pending CN111333523A (en) | 2020-04-13 | 2020-04-13 | Synthetic method of 3-nitro-4-hydroxyethylaminophenol |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111333523A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5508467A (en) * | 1993-09-03 | 1996-04-16 | Cassella Aktiengesellschaft | Process for the preparation of hydroxyalkylaminonitrobenzene derivatives |
-
2020
- 2020-04-13 CN CN202010286246.5A patent/CN111333523A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5508467A (en) * | 1993-09-03 | 1996-04-16 | Cassella Aktiengesellschaft | Process for the preparation of hydroxyalkylaminonitrobenzene derivatives |
Non-Patent Citations (2)
| Title |
|---|
| HUNG HOANG，ET AL.: ""Synthesis and Biological Evaluation of Imidazoquinoxalinones, Imidazole Analogues of Pyrroloiminoquinone Marine Natural Products"", 《J. MED. CHEM.》 * |
| VICTOR BLANCO，ET AL.: ""A Switchable [2]Rotaxane Asymmetric Organocatalyst That Utilizes an Acyclic Chiral Secondary Amine"", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60013021T2 (en) | Preparation of S, S and R, S amino acid isosteres | |
| CN112020498B (en) | Buvalracetam intermediate, preparation method thereof and preparation method of Buvalracetam | |
| CN112125805A (en) | Water-soluble magnolol derivative, preparation method of honokiol derivative and intermediate thereof, and related monohydroxy protected intermediate | |
| KR20030059206A (en) | Crystalline venlafaxine base and novel polymorphs of venlafaxine hydrochloride, processes for preparing thereof | |
| CN109503513B (en) | One-pot synthesis method of febuxostat intermediate | |
| EP3215484B1 (en) | Telescoping synthesis of 2-methoxymethyl-p-phenylenediamine | |
| CN111333523A (en) | Synthetic method of 3-nitro-4-hydroxyethylaminophenol | |
| CN108164423B (en) | Preparation method of naftifine hydrochloride | |
| CN114315755B (en) | Synthesis method of key intermediate of Tubulysin and analogues thereof | |
| CN107814757B (en) | Method for synthesizing polysubstituted pyrrole derivative | |
| CN109293587B (en) | Preparation method of clofazimine and intermediate thereof | |
| US5082969A (en) | Industrial process for obtaining an aryloxypropanolamine | |
| CN115286504B (en) | Method for synthesizing (R) -2- (2- (tert-butoxy) -2-oxyethyl) pentanoic acid | |
| WO2010001379A1 (en) | A process for preparing atovaquone and associate intermediates | |
| CN112341413A (en) | Intermediate for synthesizing brivaracetam and preparation method thereof | |
| CN112521298B (en) | Synthesis method of lidocaine | |
| CN106866494A (en) | A kind of preparation method of gliclazide intermediate octahydro pentamethylene simultaneously [c] pyrroles | |
| CN110563687B (en) | Preparation method of 4- (aminomethyl) chroman-3-ol | |
| CN111349012B (en) | Preparation method of halogenated aromatic compound and intermediate thereof | |
| CN109053382B (en) | Preparation method of phloroglucinol | |
| EP2240442B1 (en) | Preparation process useful in synthesis of atorvastatin | |
| EP0285109B1 (en) | Process for the preparation of 2-amino-4-acylamino-phenyl ether | |
| CN108069846B (en) | Method for resolving cis-1-hydroxy- [1,1' -bis (cyclohexyl) ] -2-formic acid and intermediate | |
| CN111100083A (en) | Method for reducing solid waste in antioxidant 3114 production | |
| EP0548897A2 (en) | Cyclohexanone-oxime derivatives, method for their preparation as well as method for their further processing into cyclohexanone- and cyclohexylamine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200626 |
|
| WD01 | Invention patent application deemed withdrawn after publication |