CN102001955A - Method for synthesizing 4-benzyloxy aniline hydrochloride - Google Patents
Method for synthesizing 4-benzyloxy aniline hydrochloride Download PDFInfo
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- CN102001955A CN102001955A CN2010105021839A CN201010502183A CN102001955A CN 102001955 A CN102001955 A CN 102001955A CN 2010105021839 A CN2010105021839 A CN 2010105021839A CN 201010502183 A CN201010502183 A CN 201010502183A CN 102001955 A CN102001955 A CN 102001955A
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Abstract
The invention relates to a method for synthesizing 4-benzyloxy aniline hydrochloride. The method is characterized by comprising the following steps of: performing a benzyloxy reaction on 4-nitrophenol serving as a raw material to generate 4-benzyloxy nitrobenzene; performing a reduction reaction to generate 4-benzyloxy aniline; and performing a salification reaction to generate the 4-benzyloxy aniline hydrochloride. The synthesizing process is simple, and has mild conditions and over 68 percent of total molar yield.
Description
Technical field
The invention belongs to technical field of organic synthesis, relate to a kind of synthetic method of 4-benzyloxy-aniline hydrochloride
Background technology
4-benzyloxy-aniline hydrochloride is a kind of important medicine intermediate and organic synthesis raw material, and it is the important source material of synthetic 4-benzyloxy hydrazinobenzene hydrochloride salt.
4-benzyloxy-aniline hydrochloride is a kind of novel cpd, and synthetic method is not appeared in the newspapers.
Summary of the invention
The object of the invention is to provide a kind of synthetic method of 4-benzyloxy-aniline hydrochloride, it is characterized in that with the 4-nitrophenols be raw material, through the benzyloxy glycosylation reaction, generates 4-benzyloxy oil of mirbane; Through reduction reaction, generate the 4-benzyloxy-aniline; Generate 4-benzyloxy-aniline hydrochloride through salt-forming reaction.
The present invention realizes by following method:
The first step: the 4-nitrophenols of 1.0 parts of molal quantities and the cylite of 1.0～1.05 parts of molal quantities, the ethanol of 4～10 parts of molal quantities and the water of 5～15 parts of molal quantities, the salt of wormwood of 1.5～2.5 parts of molal quantities and the catalyzer Tetrabutyl amonium bromide of 0.005～0.01 part of molal quantity are added in the there-necked flask, load onto return line, thermometer, be heated to 80～90 ℃, reacted 3～5 hours, refluxed again 5～6 hours, be cooled to 30～40 ℃, filter, extremely neutral with massive laundering.
Second step: the 4-benzyloxy-aniline of the ethanol of 2～5 parts of molal quantities and the water of 5～15 parts of molal quantities, 1.0～1.1 parts of molal quantities and the catalyzer ammonium chloride of .005～0.2 part molal quantity and the hydrochloric acid of 0.2～0.6 part of molal quantity are added in the there-necked flask, load onto return line, thermometer, reflux adds the tin protochloride of 1.3～2.3 parts of molal quantities in batches.Reflux 5～6 hours, filtered while hot remove to be considered mud, the filtrate crystallisation by cooling, filter 4-benzyloxy-aniline crude product.
The 3rd step: the 4-benzyloxy-aniline adds 1: 1 dilute hydrochloric acid at 20 ℃～30 ℃, gets hydrochloride, the centrifugal material that gets rid of.
Embodiment
Below in conjunction with specific embodiment, the invention will be further elaborated, but the invention is not restricted to these specific embodiments.
Example one:
1.4-the preparation of benzyloxy oil of mirbane is in the 1000ml reaction flask, add 400g water and 150g ethanol earlier, add 2g Tetrabutyl amonium bromide, 85g salt of wormwood, 70g 4-nitrophenols and 93g cylite then successively, stir and to be warming up to 85 ℃, in 85 ℃～90 ℃ reactions temperature rising reflux after 5 hours.T=106 ℃～108 ℃ insulation reaction 4 hours, insulation reaction finished below the postcooling to 30 ℃, the centrifugal material that gets rid of, with massive laundering to neutral, solid 105.6g (yield 91.58%).
2.4-the preparation of benzyloxy-aniline is in the 1000ml reaction flask, add in hydrochloric acid, 400g water and the 160g ethanol of 5g 36%, stir and add protochloride glass putty 95g down in batches, slow heat adds (about ten crowdes) 60g to benzyloxy oil of mirbane to 70 ℃～90 ℃ in batches, reflux is 5～6 hours then, lower the temperature slightly about 70 ℃ and add protochloride glass putty 7g, hydrochloric acid 1g continues to reflux 1 hour.Filtered while hot is removed solid impurity, and the filtrate crystallisation by cooling gets solid 43.37g (yield 83.08%).
3.4-the preparation of benzyloxy-aniline hydrochloride in the 1000ml reaction flask, adds 1: 1 dilute hydrochloric acid of 500ml, adds 150g 4-benzyloxy-aniline at 20 ℃～30 ℃, stirs 20～30 minutes, gets hydrochloride, the centrifugal material that gets rid of gets solid 161.7g (yield 91.11%).
Example two:
1.4-the preparation of benzyloxy oil of mirbane is in the 1000ml reaction flask, add 350g water and 130g ethanol earlier, add 1.5g Tetrabutyl amonium bromide, 100g salt of wormwood, 70g 4-nitrophenols and 105g cylite then successively, stir and to be warming up to 85 ℃, in 80 ℃～95 ℃ reactions temperature rising reflux after 6 hours.T=105 ℃～110 ℃ insulation reaction 4 hours, insulation reaction finished below the postcooling to 30 ℃, the centrifugal material that gets rid of, with massive laundering to neutral, solid 107.7g (yield 93.40%).
2.4-the preparation of benzyloxy-aniline is in the 1000ml reaction flask, add in hydrochloric acid, 400g water and the 150g ethanol of 5g 36%, stir and add protochloride glass putty 90g down in batches, slow heat adds (about ten crowdes) 50g to benzyloxy oil of mirbane to 70 ℃～90 ℃ in batches, reflux is 5～6 hours then, lower the temperature slightly about 70 ℃ and add protochloride glass putty 8g, hydrochloric acid 2g continues to reflux 1 hour.Filtered while hot is removed solid impurity, and the filtrate crystallisation by cooling gets solid 36.57g (yield 84.11%).
3.4-the preparation of benzyloxy-aniline hydrochloride in the 1000ml reaction flask, adds 1: 1 dilute hydrochloric acid of 500ml, adds 150g 4-benzyloxy-aniline at 20 ℃～30 ℃, stirs 20～30 minutes, gets hydrochloride, the centrifugal material that gets rid of gets solid 163.6g (yield 92.19%).
Claims (5)
1. the present invention relates to a kind of synthetic method of 4-benzyloxy-aniline hydrochloride, it is characterized in that with the 4-nitrophenols be raw material,, generate 4-benzyloxy oil of mirbane through the benzyloxy glycosylation reaction; Through reduction reaction, generate the 4-benzyloxy-aniline; Generate 4-benzyloxy-aniline hydrochloride through salt-forming reaction.
2. according to claim 1., it is characterized in that the benzyloxy glycosylation reaction is 4-nitrophenols and cylite, under catalyzer Tetrabutyl amonium bromide, the effect of promotor salt of wormwood and carry out in the etoh solvent water, generate 4-benzyloxy oil of mirbane.
3. according to claim 1., it is characterized in that reduction reaction is 4-benzyloxy oil of mirbane and tin protochloride, under the effect of catalyzer ammonium chloride, in etoh solvent and water, carry out, generate the 4-benzyloxy-aniline.
4. according to claim 1., it is characterized in that into the salinization reaction is 4-benzyloxy-aniline and dilute hydrochloric acid reaction, generates 4-benzyloxy-aniline hydrochloride.
5. according to the synthetic method of claim 1 or 2～4 described a kind of 4-benzyloxy-aniline hydrochlorides, it is characterized in that concrete synthesis step is:
The first step: the 4-nitrophenols of 1.0 parts of molal quantities and the cylite of 1.0～1.05 parts of molal quantities, the ethanol of 4～10 parts of molal quantities and the water of 5～15 parts of molal quantities, the salt of wormwood of 1.5～2.5 parts of molal quantities and the catalyzer Tetrabutyl amonium bromide of 0.005～0.01 part of molal quantity are added in the there-necked flask, load onto return line, thermometer, be heated to 80～90 ℃, reacted 3～5 hours, refluxed again 5～6 hours, be cooled to 30～40 ℃, filter, extremely neutral with massive laundering.
Second step: the ethanol of 2～5 parts of molal quantities and the water of 5～15 parts of molal quantities, the 4-benzyloxy-aniline of 1.0～1.1 parts of molal quantities, the catalyzer ammonium chloride of 0.05～0.2 part of molal quantity and the hydrochloric acid of 0.2～0.6 part of molal quantity are added in the there-necked flask, load onto return line, thermometer, reflux adds the tin protochloride of 1.3～2.3 parts of molal quantities in batches.Reflux 5～6 hours, filtered while hot remove to be considered mud, the filtrate crystallisation by cooling, filter 4-benzyloxy-aniline crude product.
The 3rd step: the 4-benzyloxy-aniline adds in 1: 1 dilute hydrochloric acid at 20 ℃～30 ℃, hydrochloride, the centrifugal material that gets rid of.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010105021839A CN102001955A (en) | 2010-10-11 | 2010-10-11 | Method for synthesizing 4-benzyloxy aniline hydrochloride |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010105021839A CN102001955A (en) | 2010-10-11 | 2010-10-11 | Method for synthesizing 4-benzyloxy aniline hydrochloride |
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| CN2010105021839A Pending CN102001955A (en) | 2010-10-11 | 2010-10-11 | Method for synthesizing 4-benzyloxy aniline hydrochloride |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1472191A (en) * | 2003-06-26 | 2004-02-04 | 上海交通大学 | 1,3,5-tri(3-hydroxy-4-aminophenoxy)benzene and its hydrochlorides and preparation thereof |
| CN1733703A (en) * | 2005-08-04 | 2006-02-15 | 浙江大学 | 3-benzyloxy-4-butylaniline hydrochloride preparation method |
| WO2006023843A2 (en) * | 2004-08-20 | 2006-03-02 | Bayer Pharmaceuticals Corporation | Novel heterocycles |
| US20080113967A1 (en) * | 2004-12-23 | 2008-05-15 | Deciphera Pharmaceuticals, Llc | Enzyme modulators and treatments |
| CN101367794A (en) * | 2007-07-20 | 2009-02-18 | 上海恒瑞医药有限公司 | Preparation method for quinazoline derivants and medical uses thereof |
-
2010
- 2010-10-11 CN CN2010105021839A patent/CN102001955A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1472191A (en) * | 2003-06-26 | 2004-02-04 | 上海交通大学 | 1,3,5-tri(3-hydroxy-4-aminophenoxy)benzene and its hydrochlorides and preparation thereof |
| WO2006023843A2 (en) * | 2004-08-20 | 2006-03-02 | Bayer Pharmaceuticals Corporation | Novel heterocycles |
| US20080113967A1 (en) * | 2004-12-23 | 2008-05-15 | Deciphera Pharmaceuticals, Llc | Enzyme modulators and treatments |
| CN1733703A (en) * | 2005-08-04 | 2006-02-15 | 浙江大学 | 3-benzyloxy-4-butylaniline hydrochloride preparation method |
| CN101367794A (en) * | 2007-07-20 | 2009-02-18 | 上海恒瑞医药有限公司 | Preparation method for quinazoline derivants and medical uses thereof |
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Application publication date: 20110406 |