CN103044471A - Method for preparing 4-amino benzene boric acid hydrochloride - Google Patents
Method for preparing 4-amino benzene boric acid hydrochloride Download PDFInfo
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- CN103044471A CN103044471A CN2012105579435A CN201210557943A CN103044471A CN 103044471 A CN103044471 A CN 103044471A CN 2012105579435 A CN2012105579435 A CN 2012105579435A CN 201210557943 A CN201210557943 A CN 201210557943A CN 103044471 A CN103044471 A CN 103044471A
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Abstract
The invention discloses a method for preparing 4-amino benzene boric acid hydrochloride. The method comprises the steps that 1), catechol and 4-nitrobromobenzene are subjected to a reaction for 2-3h in a polar solvent under the action of potassium acetate and Pd (dppf) C12, the temperature is lowered to a room temperature, filtering is performed, ethyl acetate is extracted, and a crude product is pulped and filtered through nonpolar varsol after an organic layer is concentrated, so that 4-nitrophenylboronic acid is obtained; and 2), the 4-nitrophenylboronic acid is subjected to palladium carbon catalytic hydrogenation in the ethyl acetate, hydrogenation is performed for 6-8h at the temperature ranging between 60 DEG C and 80 DEG C and under 0.8-1.0 MPa, filtering is performed at the temperature of 15-25 DEGC after the reaction, concentrated hydrochloric acid is added into the filtering liquid at the temperature of 0-10 DEG C, filtering is performed, and the crude product is obtained, then pulped with acetone, filtered and dried, so that the 4-amino benzene boric acid hydrochloride is obtained. According to the method, raw materials are low in toxicity and can be processed easily, copious cooling and low temperature are avoided simultaneously, the reaction temperature can be reached easily, the conditions are mild, the yield is high, the process is safe and reliable, and method is suitable for industrial production.
Description
Technical field
The present invention relates to the chemical synthesis technical field, be specifically related to a kind of method of the 4-of preparation amino-benzene borate hydrochlorate.
Background technology
Usually adopting the amino bromobenzene of 4-for the 4-amino-benzene borate hydrochlorate of known report is raw material, amino after protection, uses n-Butyl Lithium and boric acid ester to react under the cold condition about-78 ℃, and acidified and purifying obtains product.This method has following shortcoming: 1, raw material need to carry out amino protection and deprotection, complex operation; 2, reaction needed very low temperature-78 ℃, condition is harsh.
Summary of the invention
To the objective of the invention is in order addressing the above problem, a kind of method for preparing 4-amino-benzene borate hydrochlorate of work simplification to be provided.
The present invention for achieving the above object employed technical scheme is:
A kind of method for preparing 4-amino-benzene borate hydrochlorate is characterized in that:
1. in polar solvent, under 80 ~ 100 ℃ of temperature condition, duplex pyrocatechol and 4-nitro bromobenzene are at Potassium ethanoate and Pd (dppf) Cl
2The lower reaction 2 ~ 3h of effect is down to room temperature, filters, and ethyl acetate extraction, behind the concentrated organic layer, crude product filters through the making beating of non-polar hydrocarbon kind solvent and obtains 4-oil of mirbane boric acid;
2. 4-oil of mirbane boric acid is in ethyl acetate, palladium carbon catalytic hydrogenation, at 60 ~ 80 ℃, 0.8 hydrogenation 6 ~ 8h under the ~ 1.0MPa, 15 ~ 25 ℃ of filtrations after reaction finishes add concentrated hydrochloric acid under 0 ~ 10 ℃ in filtrate, filtration obtains crude product, crude product uses the acetone making beating, filters, the dry 4-amino-benzene borate hydrochlorate that gets.
Described polar solvent is DMF, DMSO or Isosorbide-5-Nitrae-dioxane.
Described 4-nitro bromobenzene, duplex pyrocatechol ester, Potassium ethanoate and Pd (dppf) Cl
2Mol ratio be 1:1 ~ 1.5:3 ~ 5:0.03 ~ 0.1.
Described non-polar hydrocarbon kind solvent is normal heptane or normal hexane.
Described palladium carbon content 5～10%, described palladium carbon and described 4-nitro bromobenzene
Weight ratioBe 0.005 ~ 0.01:1.
The mol ratio of described 4-oil of mirbane boric acid and concentrated hydrochloric acid is 1:1.05 ~ 1.2.
Reaction mechanism of the present invention is as follows:
Raw material hypotoxicity of the present invention is easily processed, and has avoided simultaneously deep cooling low temperature, and temperature of reaction easily reaches, mild condition, and yield is high, and process safety is reliable, is suitable for suitability for industrialized production.
Embodiment
Below by specific examples the present invention is further detailed, but is not limited to the content of specific embodiment.
Embodiment 1
A kind of method for preparing 4-amino-benzene borate hydrochlorate with duplex pyrocatechol boric acid ester:
The first step, in the 1L four-hole bottle of magnetic agitation, the protection of nitrogen gas is lower, adds 500.0gDMF; 101.0g4-nitro bromobenzene (0.50mol, 1eq), 130.8g duplex pyrocatechol boric acid ester (0.55mol, 1.2eq); 147.2g Potassium ethanoate (1.5mol, 3eq), 18.3gPd (dppf) Cl
2(0.025mol, 0.05eq), 80 ℃ of lower reaction 3h.Be cooled to 20 ~ 25 ℃, filter, filtrate is added drop-wise in the 500.0g water, stirs 1h, is warming up to 20 ~ 25 ℃.Use ethyl acetate extraction 2 times (200mL * 2), merge organic layer concentrated, use ℃ making beating of 50.0g normal heptane-5 ~ 0 to filter, filtration cakes torrefaction obtains white solid 63.7g, GC:97.6%, yield: 76.3%.
Second step, with 63.7g4-oil of mirbane boric acid (0.38mol, 1eq) be dissolved in the 255g ethyl acetate, and adding 2.0g palladium carbon (10%, 0.005eq), 0.8 ~ 1.0MPa, 70 ~ 80 ℃ of hydrogenation reaction 6h, reaction finishes, and uses diatomite filtration, filtrate is cooled to 0 ℃, drip 51.0g concentrated hydrochloric acid (30%, 0.38mol, 1.1eq), 0 ~ 10 ℃ is stirred 0.5h, filter, filter cake uses the making beating of 80g acetone to obtain 52.4g off-white color solid 4-amino-benzene borate hydrochlorate, HPLC:98.2%, second step yield 79.2%, total recovery 60.4%.
Embodiment 2
A kind of method for preparing 4-amino-benzene borate hydrochlorate with duplex pyrocatechol boric acid ester:
The first step in the 1L four-hole bottle of magnetic agitation, under the argon shield, adds 500.0gDMSO; 101.0g4-nitro bromobenzene (0.50mol, 1eq), 130.8g duplex pyrocatechol boric acid ester (0.55mol, 1.2eq); 147.2g Potassium ethanoate (1.5mol, 3eq), 18.3gPd (dppf) Cl
2(0.025mol, 0.05eq), 90 ℃ of lower reaction 2.5h.Be cooled to 20 ~ 25 ℃, filter, filtrate is added drop-wise in the 500.0g water, stirs 1h, is warming up to 20 ~ 25 ℃.Use ethyl acetate extraction 2 times (200mL * 2).Merge organic layer concentrated, use ℃ making beating of 50.0g normal heptane-5 ~ 0 to filter, filtration cakes torrefaction obtains white solid 65.6g, GC:97.1%, yield: 78.6%.
Second step, with 65.6g4-oil of mirbane boric acid (0.39mol, 1eq) be dissolved in the 262g ethyl acetate, adding 2.1g palladium carbon (10%, 0.005eq), 0.8 ~ 1.0MPa, 70 ~ 80 ℃ of hydrogenation reaction 6h, reaction finishes, and uses diatomite filtration, and filtrate is cooled to 0 ℃, drip 52.5g concentrated hydrochloric acid (30%, 0.39mol 1.1eq), 0 ~ 10 ℃ is stirred 0.5h and filters, filter cake uses the making beating of 80g acetone to obtain 54.5g off-white color solid 4-amino-benzene borate hydrochlorate, HPLC:98.0%, second step yield 80.0%, total recovery 62.8%.
Embodiment 3
A kind of method for preparing 4-amino-benzene borate hydrochlorate with duplex pyrocatechol boric acid ester:
The first step; in the 1L four-hole bottle of magnetic agitation, under the argon shield, add 500.0g1; the 4-dioxane; 101.0g4-nitro bromobenzene (0.50mol, 1eq), 130.8g duplex pyrocatechol boric acid ester (0.55mol; 1.2eq); 147.2g Potassium ethanoate (1.5mol, 3eq), 18.3gPd (dppf) Cl
2(0.025mol, 0.05eq), 100 ℃ of lower reaction 2h.Be cooled to 20 ~ 25 ℃, filter, filtrate is added drop-wise in the 500.0g water, stirs 1h, is warming up to 20 ~ 25 ℃.Use ethyl acetate extraction 2 times (200mL * 2), merge organic layer concentrated, use ℃ making beating of 50.0g normal heptane-5 ~ 0 to filter, filtration cakes torrefaction obtains white solid 60.4g, GC:98.3%, yield: 72.4%.
Second step is dissolved into 60.4g4-oil of mirbane boric acid (0.36mol, 1eq) in the 241g ethyl acetate, adding 2.0g palladium carbon (10%, 0.005eq), 0.8 ~ 1.0MPa, 70 ~ 80 ℃ of hydrogenation reaction 6h, reaction finishes, and uses diatomite filtration, filtrate is cooled to 0 ℃, drips 48.4g concentrated hydrochloric acid (30%, 0.36mol, 1.1eq), 0 ~ 10 ℃ is stirred the 0.5h filtration, and filter cake uses the making beating of 80g acetone to obtain 50.4g off-white color solid, HPLC:98.2%, second step yield 80.3%, total recovery 58.1%.
Embodiment 4
A kind of method for preparing 4-amino-benzene borate hydrochlorate with duplex pyrocatechol boric acid ester:
The first step; in the 1L four-hole bottle of magnetic agitation, under the argon shield, add 300.0g 1; the 4-dioxane; 60.6g4-nitro bromobenzene (0.30mol, 1eq), 78.5g duplex pyrocatechol boric acid ester (0.33 mol; 1.2eq); 88.3g Potassium ethanoate (0.9mol, 3eq), 11.0gPd (dppf) Cl
2(0.015mol, 0.05eq), 90 ℃ of lower reaction 2.5h.Be cooled to 20 ~ 25 ℃, filter, filtrate is added drop-wise to 150.0g, in the water, stirs 1h, is warming up to 20 ~ 25 ℃.Use ethyl acetate extraction 2 times (120mL * 2), merge organic layer, concentrated, use ℃ making beating of 30.0g normal hexane-5 ~ 0 to filter, filtration cakes torrefaction obtains white solid 39.8g, GC:98.0%, yield: 79.7%.
Second step is dissolved into 39.8g4-oil of mirbane boric acid (0.24mol, 1eq) in the 160g ethyl acetate, adding 2.5g palladium carbon (5%, 0.005eq), 0.8 ~ 1.0MPa, 70 ~ 80 ℃ of hydrogenation reaction 6h, reaction finishes, and uses diatomite filtration, filtrate is cooled to 0 ℃, drips 31.5g concentrated hydrochloric acid (30%, 0.39mol, 1.1eq), 0 ~ 10 ℃ is stirred the 0.5h filtration, and filter cake uses the making beating of 50g acetone to obtain 33.1g off-white color solid, HPLC:98.3%, second step yield 79.9%, total recovery 63.5%.
The above; only be the better embodiment of the present invention; but protection scope of the present invention is not limited to this; anyly be familiar with those skilled in the art in the technical scope that the present invention discloses; be equal to replacement or change according to technical scheme of the present invention and inventive concept thereof, all should be encompassed within protection scope of the present invention.
Claims (6)
1. method for preparing 4-amino-benzene borate hydrochlorate is characterized in that:
1. in polar solvent, under 80 ~ 100 ℃ of temperature condition, duplex pyrocatechol and 4-nitro bromobenzene are at Potassium ethanoate and Pd (dppf) Cl
2The lower reaction 2 ~ 3h of effect is down to room temperature, filters, and ethyl acetate extraction, behind the concentrated organic layer, crude product filters through the making beating of non-polar hydrocarbon kind solvent and obtains 4-oil of mirbane boric acid;
2. 4-oil of mirbane boric acid is in ethyl acetate, palladium carbon catalytic hydrogenation, at 60 ~ 80 ℃, 0.8 hydrogenation 6 ~ 8h under the ~ 1.0MPa, 15 ~ 25 ℃ of filtrations after reaction finishes add concentrated hydrochloric acid under 0 ~ 10 ℃ in filtrate, filtration obtains crude product, crude product uses the acetone making beating, filters, the dry 4-amino-benzene borate hydrochlorate that gets.
2. the described method for preparing 4-amino-benzene borate hydrochlorate according to claim 1, it is characterized in that: described polar solvent is DMF, DMSO or Isosorbide-5-Nitrae-dioxane.
3. the described method for preparing 4-amino-benzene borate hydrochlorate according to claim 1 is characterized in that: described 4-nitro bromobenzene, duplex pyrocatechol ester, Potassium ethanoate and Pd (dppf) Cl
2Mol ratio be 1:1 ~ 1.5:3 ~ 5:0.03 ~ 0.1.
4. the described method for preparing 4-amino-benzene borate hydrochlorate according to claim 1, it is characterized in that: described non-polar hydrocarbon kind solvent is normal heptane or normal hexane.
5. the described method for preparing 4-amino-benzene borate hydrochlorate according to claim 1 is characterized in that: described palladium carbon content 5～10%, described palladium carbon and described 4-nitro bromobenzene
Weight ratioBe 0.005 ~ 0.01:1.
6. the described method for preparing 4-amino-benzene borate hydrochlorate according to claim 1, it is characterized in that: the mol ratio of described 4-oil of mirbane boric acid and concentrated hydrochloric acid is 1:1.05 ~ 1.2.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103626791A (en) * | 2013-11-26 | 2014-03-12 | 大连联化化学有限公司 | Method for synthesizing 3-amino-4-fluorophenylboronic acid |
| CN104530107A (en) * | 2014-12-31 | 2015-04-22 | 大连联化化学有限公司 | Synthetic method for 3-amino-4-fluorophenylboronic acid |
| CN105246901A (en) * | 2013-05-06 | 2016-01-13 | 意优特克股份公司 | Acyclic nucleoside phosphonate diesters |
| CN109467569A (en) * | 2018-12-23 | 2019-03-15 | 沧州普瑞东方科技有限公司 | The synthetic method of 3- amino phenyl boric acid |
| CN114262340A (en) * | 2021-11-29 | 2022-04-01 | 蚌埠中实化学技术有限公司 | Preparation method of aminophenylboronic acid |
| CN115784895A (en) * | 2022-11-14 | 2023-03-14 | 汕头大学 | Method for preparing arylamine compound by nonmetallic reduction of aryl nitro compound |
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| US4462819A (en) * | 1983-04-07 | 1984-07-31 | Allied Corporation | Urease inhibited urea based fertilizer compositions containing organo boron acid compounds |
| CN1255123A (en) * | 1997-04-09 | 2000-05-31 | 联邦科学和工业研究组织 | Process for covalently coupling organic compounds utilizing diboron derivatives |
| CN101362710A (en) * | 2008-09-27 | 2009-02-11 | 丽源（内蒙古）科技有限公司 | Method for preparing aminobenzenesulfonic acid by catalytic hydrogenation |
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Patent Citations (3)
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| US4462819A (en) * | 1983-04-07 | 1984-07-31 | Allied Corporation | Urease inhibited urea based fertilizer compositions containing organo boron acid compounds |
| CN1255123A (en) * | 1997-04-09 | 2000-05-31 | 联邦科学和工业研究组织 | Process for covalently coupling organic compounds utilizing diboron derivatives |
| CN101362710A (en) * | 2008-09-27 | 2009-02-11 | 丽源（内蒙古）科技有限公司 | Method for preparing aminobenzenesulfonic acid by catalytic hydrogenation |
Non-Patent Citations (1)
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| H.C.BEACHELL ET AL.: "Nuclear Magnetic Resonance Spectra of Phenylboronic Acids", 《INORGANIC CHEMISTRY》, vol. 3, no. 7, 31 July 1964 (1964-07-31), pages 1028 - 1032 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105246901A (en) * | 2013-05-06 | 2016-01-13 | 意优特克股份公司 | Acyclic nucleoside phosphonate diesters |
| CN105246901B (en) * | 2013-05-06 | 2018-04-10 | 意优特克股份公司 | For preparing aminoaryl boric acid and the method for aminoheteroaryl boric acid and ester |
| CN103626791A (en) * | 2013-11-26 | 2014-03-12 | 大连联化化学有限公司 | Method for synthesizing 3-amino-4-fluorophenylboronic acid |
| CN103626791B (en) * | 2013-11-26 | 2016-04-06 | 大连联化化学有限公司 | A kind of method of synthesizing 3-amino-4-fluorobenzoic boric acid |
| CN104530107A (en) * | 2014-12-31 | 2015-04-22 | 大连联化化学有限公司 | Synthetic method for 3-amino-4-fluorophenylboronic acid |
| CN109467569A (en) * | 2018-12-23 | 2019-03-15 | 沧州普瑞东方科技有限公司 | The synthetic method of 3- amino phenyl boric acid |
| CN114262340A (en) * | 2021-11-29 | 2022-04-01 | 蚌埠中实化学技术有限公司 | Preparation method of aminophenylboronic acid |
| CN114262340B (en) * | 2021-11-29 | 2023-09-26 | 蚌埠中实化学技术有限公司 | Preparation method of aminophenylboric acid |
| CN115784895A (en) * | 2022-11-14 | 2023-03-14 | 汕头大学 | Method for preparing arylamine compound by nonmetallic reduction of aryl nitro compound |
| CN115784895B (en) * | 2022-11-14 | 2024-03-26 | 汕头大学 | Method for preparing arylamine compound by nonmetal reduction of aryl nitro compound |
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Application publication date: 20130417 |