CN111943971A - Preparation method of boric acid derivative - Google Patents
Preparation method of boric acid derivative Download PDFInfo
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- CN111943971A CN111943971A CN202010977853.6A CN202010977853A CN111943971A CN 111943971 A CN111943971 A CN 111943971A CN 202010977853 A CN202010977853 A CN 202010977853A CN 111943971 A CN111943971 A CN 111943971A
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- acid
- chloride
- organic solvent
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- hydroxyphenylboronic
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- 238000002360 preparation method Methods 0.000 title claims abstract description 25
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- YDMRDHQUQIVWBE-UHFFFAOYSA-N (2-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1O YDMRDHQUQIVWBE-UHFFFAOYSA-N 0.000 claims abstract description 42
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims abstract description 28
- 239000003960 organic solvent Substances 0.000 claims abstract description 21
- 239000010410 layer Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 16
- 238000010438 heat treatment Methods 0.000 claims abstract description 14
- 239000012044 organic layer Substances 0.000 claims abstract description 14
- 150000001263 acyl chlorides Chemical class 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 239000003513 alkali Substances 0.000 claims abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 13
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 12
- 239000012346 acetyl chloride Substances 0.000 claims description 12
- -1 methoxy, ethoxy, propoxy, isopropoxy, butoxy Chemical group 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 6
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 5
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 claims description 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 7
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000011084 recovery Methods 0.000 description 5
- COIQUVGFTILYGA-UHFFFAOYSA-N (4-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=C(O)C=C1 COIQUVGFTILYGA-UHFFFAOYSA-N 0.000 description 4
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- WFWQWTPAPNEOFE-UHFFFAOYSA-N (3-hydroxyphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(O)=C1 WFWQWTPAPNEOFE-UHFFFAOYSA-N 0.000 description 3
- 239000004327 boric acid Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 229940050176 methyl chloride Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ROEQGIFOWRQYHD-UHFFFAOYSA-N (2-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC=C1B(O)O ROEQGIFOWRQYHD-UHFFFAOYSA-N 0.000 description 2
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 2
- MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 2
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- RKKOMEIYHHASIN-UHFFFAOYSA-N hydroperoxyboronic acid Chemical compound OOB(O)O RKKOMEIYHHASIN-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- DGFCTCGCMKEILT-UHFFFAOYSA-N (2-ethoxyphenyl)boronic acid Chemical compound CCOC1=CC=CC=C1B(O)O DGFCTCGCMKEILT-UHFFFAOYSA-N 0.000 description 1
- WRQNDLDUNQMTCL-UHFFFAOYSA-N (4-ethoxyphenyl)boronic acid Chemical compound CCOC1=CC=C(B(O)O)C=C1 WRQNDLDUNQMTCL-UHFFFAOYSA-N 0.000 description 1
- MUKIFYQKIZOYKT-UHFFFAOYSA-N 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CC(O)=C1 MUKIFYQKIZOYKT-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SGCLBIRCSTXTIU-UHFFFAOYSA-N boric acid;2,3-dimethylbutane-2,3-diol Chemical compound OB(O)O.CC(C)(O)C(C)(C)O.CC(C)(O)C(C)(C)O SGCLBIRCSTXTIU-UHFFFAOYSA-N 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a preparation method of o-hydroxyphenylboronic acid, which is characterized by comprising the following steps: dissolving o-alkoxyphenylboronic acid and an acyl chloride compound in a first organic solvent under the vacuum condition of-0.1 MPa and at the temperature of 0-10 ℃, then adding aluminum chloride, starting heating, heating to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 30-100 ℃, then reacting at constant temperature for 1-2 hours to obtain an intermediate compound, adding alkali to adjust the pH value of the system to 9-11, continuously adjusting the pH value of a water layer to 3-4 by using acid, extracting by using a second organic solvent, collecting an organic layer, concentrating, and recrystallizing by using a third organic solvent to obtain o-hydroxyphenylboronic acid. The method has mild reaction temperature, can obviously reduce the reaction time, reduces the dosage of the catalyst, and has higher yield and purity.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a boric acid derivative, and more particularly relates to a synthesis method of hydroxyphenylboronic acid.
Background
Suzuki reactions are used in synthetic chemistry to construct various types of sp2One of the important methods for forming a C-C single bond is that of maintaining a relatively strong market demand for an organic boronic acid, which is one of the main raw materials for the reaction. The hydroxy boric acid can be conveniently introduced into a phenol structural unit in a molecule through Suzuki coupling reaction, so that the hydroxy boric acid is widely used in daily chemical industry and drug synthesis.
The preparation methods of hydroxyphenylboronic acid reported in the prior art mainly comprise the following methods:
(1) the method takes phenylboronic acid as a raw material, and obtains the hydroxyphenylboronic acid through nitration reaction, catalytic hydrogenation reaction, diazotization reaction and hydrolysis.
(2) The method takes o-bromophenol as a raw material, has high cost, needs to add a large amount of n-butyllithium for reaction, and is not beneficial to large-scale production.
(3) The method uses sodium hydride and n-butyllithium, adopts m-bromophenol as a raw material, converts the m-bromophenol into a sodium salt by using the sodium hydride, is characterized by n-butyllithium reaction, has inconvenient operation, has the crude product yield of only 58 percent, and does not describe a purification process.
(4) The method comprises the following steps of directly reacting ortho-o, meta-o and para-substituted bromophenol isomers serving as raw materials with a diethyl ether solution containing 2 times of BuLi to obtain dilithium salt of bromophenol, reacting with boric acid ester to obtain phenyl boric acid ester, and hydrolyzing to obtain corresponding hydroxyphenylboronic acid. The method has the disadvantages that BuLi with 2 times of the amount of the substance is needed because the hydroxyl group is not protected, and the cost is higher. The dilithium salt of bromophenol, which has low solubility in hexane (the reaction product is suspended at the end of this step), hinders the next step of exchange with borate ester, and is difficult to separate and purify, and recrystallization is carried out at least three times, resulting in a great reduction in yield, and the yield of p-hydroxyphenylboronic acid is only 14%.
(5) The method is characterized in that bromophenol is used as a raw material, phenolic hydroxyl of the bromophenol is protected by a silicon ether protective group to prepare a Grignard reagent, and the Grignard reagent reacts with boric acid ester and is hydrolyzed to obtain a hydroxyphenylboronic acid product, wherein the total yield of the method is still very low and is only 30 percent, and the bromophenol is also used as the raw material, so that the production cost is high.
(6) Tetrahydropyran is used for phenolic hydroxyl protection, and metal exchange is carried out with BuLi to obtain aryl lithium, and then the aryl lithium reacts with boric acid ester, and finally hydroxyl phenylboronic acid is obtained through hydrolysis.
(7) The m-hydroxyl aryl bromide (or m-hydroxyl aryl iodide) and the bis (pinacol) borate are taken as raw materials, the m-hydroxyl phenylboronic acid pinacol ester is obtained through coupling reaction under the action of a palladium catalyst, and then the m-hydroxyl phenylboronic acid is obtained through hydrolysis.
(8) Alkoxy (or alkyl mercapto) phenylboronic acid is used as a raw material and reacts with acetyl chloride under the action of aluminum chloride to obtain an intermediate, and the intermediate is alkalized and acidified to obtain the hydroxyphenylboronic acid.
Disclosure of Invention
The invention aims to overcome a series of defects existing in the synthesis of hydroxyphenylboronic acid in the prior art, and provides a preparation method of hydroxyphenylboronic acid, which is characterized by comprising the following steps: dissolving alkoxy phenylboronic acid and acyl chloride compounds in a first organic solvent under the vacuum condition of-0.1 MPa and at the temperature of 0-10 ℃, then adding aluminum chloride, then starting heating, heating to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 30-100 ℃, then reacting at constant temperature for 1-2 hours to obtain an intermediate compound, adding alkali to adjust the pH value of the system to 9-11, continuously using acid to adjust the pH value of a water layer to 3-4, extracting with a second organic solvent, collecting an organic layer, concentrating, and recrystallizing with a third organic solvent to obtain the hydroxyphenylboronic acid.
According to the preparation method of the hydroxyphenylboronic acid, the hydroxyphenylboronic acid is preferably selected from o-hydroxyphenylboronic acid, p-hydroxyphenylboronic acid or m-hydroxyphenylboronic acid.
According to the preparation method of the hydroxyphenylboronic acid, the alkoxy in the alkoxyphenylboronic acid is selected from methoxy, ethoxy, propoxy, isopropoxy, butoxy or tert-butoxy, and preferably, the alkoxy is selected from methoxy or ethoxy.
According to the preparation method of the hydroxyphenylboronic acid, the acyl chloride compound is selected from acetyl chloride, propionyl chloride, butyryl chloride, isobutyryl chloride or oxalyl chloride, and preferably, the acyl chloride compound is acetyl chloride.
According to the preparation method of the hydroxyphenylboronic acid, the first organic solvent is selected from toluene, xylene or diphenyl ether.
According to the preparation method of the hydroxyphenylboronic acid, the second organic solvent is selected from ethyl acetate, dichloromethane or chloroform.
According to the preparation method of the hydroxyphenylboronic acid, the third organic solvent is selected from hydrocarbon solvents, preferably heptane or n-hexane.
According to the preparation method of the hydroxyphenylboronic acid, the alkali is selected from sodium carbonate or potassium carbonate.
According to the preparation method of the hydroxyphenylboronic acid, the acid is selected from hydrochloric acid or sulfuric acid.
According to the preparation method of the hydroxyphenylboronic acid, the molar ratio of the p-alkoxyphenylboronic acid to the acyl chloride compound to the aluminum chloride is 1: 1-2: 0.1-0.2.
The main contributions of the present invention with respect to the prior art are the following:
(1) the system reacts under the vacuum condition, and chloralkane gas generated in the reaction process is rapidly removed in vacuum, so that the influence of chloralkane on the reaction can be reduced to the greatest extent, the reaction speed is effectively increased, and the yield and the purity of the product are improved.
(2) The gradient temperature rise is adopted, so that the stability of the reaction can be improved, the reaction can be more sufficient, the generation of byproducts in the reaction process is reduced, the yield and the purity of the product are improved, and the post-treatment pressure of the product can be reduced.
(3) By adopting the method, the reaction temperature is mild, the reaction time can be obviously reduced, the dosage of the catalyst is reduced, the yield and the purity are high, and the unexpected technical effect is achieved.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present disclosure more apparent, the technical solutions of the embodiments of the present disclosure are clearly and completely described. It is to be understood that the described embodiments are only a few embodiments of the present disclosure, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the described embodiments of the disclosure without any inventive step, are within the scope of protection of the disclosure.
Unless otherwise defined, technical or scientific terms used herein shall have the ordinary meaning as understood by one of ordinary skill in the art to which this disclosure belongs. The use of "first," "second," and similar terms in this disclosure is not intended to indicate any order, quantity, or importance, but rather is used to distinguish one element from another.
The invention provides a preparation method of hydroxyphenylboronic acid, which is characterized by comprising the following steps: dissolving alkoxy phenylboronic acid and acyl chloride compounds in a first organic solvent under the vacuum condition of-0.1 MPa and at the temperature of 0-10 ℃, then adding aluminum chloride, then starting heating, heating to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 30-100 ℃, then reacting at constant temperature for 1-2 hours to obtain an intermediate compound, adding alkali to adjust the pH value of the system to 9-11, continuously using acid to adjust the pH value of a water layer to 3-4, extracting with a second organic solvent, collecting an organic layer, concentrating, and recrystallizing with a third organic solvent to obtain the hydroxyphenylboronic acid.
According to the preparation method of the hydroxyphenylboronic acid, the hydroxyphenylboronic acid is preferably selected from o-hydroxyphenylboronic acid, p-hydroxyphenylboronic acid or m-hydroxyphenylboronic acid.
According to the preparation method of the hydroxyphenylboronic acid, the alkoxy in the alkoxyphenylboronic acid is selected from methoxy, ethoxy, propoxy, isopropoxy, butoxy or tert-butoxy, and preferably, the alkoxy is selected from methoxy or ethoxy.
According to the preparation method of the hydroxyphenylboronic acid, the acyl chloride compound is selected from acetyl chloride, propionyl chloride, butyryl chloride, isobutyryl chloride or oxalyl chloride, and preferably, the acyl chloride compound is acetyl chloride.
According to the preparation method of the hydroxyphenylboronic acid, the first organic solvent is selected from toluene, xylene or diphenyl ether.
According to the preparation method of the hydroxyphenylboronic acid, the second organic solvent is selected from ethyl acetate, dichloromethane or chloroform.
According to the preparation method of the hydroxyphenylboronic acid, the third organic solvent is selected from hydrocarbon solvents, preferably heptane or n-hexane.
According to the preparation method of the hydroxyphenylboronic acid, the alkali is selected from sodium carbonate or potassium carbonate.
According to the preparation method of the hydroxyphenylboronic acid, the acid is selected from hydrochloric acid or sulfuric acid.
According to the preparation method of the hydroxyphenylboronic acid, the molar ratio of the p-alkoxyphenylboronic acid to the acyl chloride compound to the aluminum chloride is 1: 1-2: 0.1-0.2.
Example 1
Vacuumizing a reaction kettle to-0.1 Mpa by using a vacuum pump, reducing the temperature of the reaction kettle to 0 ℃, adding 1.52kg (10mol) of p-methoxyphenylboronic acid, 1kg (12.7mol) of acetyl chloride and 12L of toluene into the reaction kettle, mixing and stirring the mixture uniformly, then adding 1mol of aluminum chloride, heating the mixture to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 50 ℃, then carrying out constant-temperature reaction for 1 hour (methyl chloride gas generated in the reaction process is removed to a recovery system in vacuum), obtaining an intermediate compound, adding a sodium carbonate solution to adjust the pH value of the system to be 9, obtaining a water layer, continuously adjusting the pH value of the water layer to be 3 by using hydrochloric acid, extracting the water layer by using ethyl acetate, collecting an organic layer, concentrating, recrystallizing the organic layer by using heptane, obtaining 1.25kg of p-hydroxybenzoic acid, wherein the yield is 90.6% and the purity is 98.
Example 2
Vacuumizing a reaction kettle to-0.1 Mpa by using a vacuum pump, reducing the temperature of the reaction kettle to 10 ℃, adding 1.66kg (10mol) of p-ethoxyphenylboronic acid, 1.57kg (20mol) of acetyl chloride and 15L of toluene into the reaction kettle, mixing and stirring uniformly, then adding 2mol of aluminum chloride, heating to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 80 ℃, then carrying out constant-temperature reaction for 2 hours (monochloroethane gas generated in the reaction process is removed to a recovery system in vacuum), obtaining an intermediate compound, adding a potassium carbonate solution to adjust the pH value of the system to be 9, obtaining a water layer, continuously adjusting the pH value of the water layer to be 3 by using sulfuric acid, extracting by using ethyl acetate, collecting an organic layer, concentrating, recrystallizing by using heptane, obtaining 1.29kg of p-hydroxybenzoic acid, wherein the yield is 93.5% and the purity is 99.1%.
Example 3
Vacuumizing a reaction kettle to-0.1 Mpa by using a vacuum pump, reducing the temperature of the reaction kettle to 10 ℃, adding 1.52kg (10mol) of o-methoxyphenylboronic acid, 1.57kg (20mol) of acetyl chloride and 12L of toluene into the reaction kettle, mixing and stirring the materials uniformly, adding 2mol of aluminum chloride, heating the materials to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 100 ℃, then carrying out constant-temperature reaction for 1.5h (methyl chloride gas generated in the reaction process is removed to a recovery system in vacuum), obtaining an intermediate compound, adding a sodium carbonate solution to adjust the pH value of the system to 10, obtaining a water layer, continuously adjusting the pH value of the water layer to 4 by using hydrochloric acid, extracting the water layer by using ethyl acetate, collecting an organic layer, concentrating, recrystallizing the organic layer by using n-hexane to obtain 1.27kg of o-hydroxyphenylboronic acid, wherein the yield is 92% and the purity is 99..
Example 4
Vacuumizing a reaction kettle to-0.1 Mpa by using a vacuum pump, reducing the temperature of the reaction kettle to 10 ℃, adding 1.66kg (10mol) of o-ethoxyphenylboronic acid, 785g (10mol) of acetyl chloride and 12L of dimethylbenzene into the reaction kettle, mixing and stirring uniformly, then adding 1.5mol of aluminum chloride, heating to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 100 ℃, then carrying out constant-temperature reaction for 2 hours (monochloroethane gas generated in the reaction process is removed to a recovery system in vacuum), obtaining an intermediate compound, adding a sodium carbonate solution to adjust the pH value of the system to 10, obtaining a water layer, continuously adjusting the pH value of the water layer to 4 by using hydrochloric acid, extracting by using ethyl acetate, collecting an organic layer, concentrating, recrystallizing by using heptane, obtaining 1.31kg of o-hydroxyphenylboronic acid, wherein the yield is 94.9% and 99.2%.
Comparative example 1
Reducing the temperature of a reaction kettle to 0 ℃ under normal pressure, adding 1.52kg (10mol) of p-methoxyphenylboronic acid, 1kg (12.7mol) of acetyl chloride and 12L of toluene into the reaction kettle, mixing and stirring the mixture uniformly, then adding 1mol of aluminum chloride, heating the mixture to 10 ℃ at intervals of 15 minutes in the reaction process until the temperature is raised to 50 ℃, then carrying out constant-temperature reaction for 1 hour (methyl chloride gas generated in the reaction process is removed to a recovery system through vacuum) to obtain an intermediate compound, adding a sodium carbonate solution to adjust the pH value of the system to 9 to obtain a water layer, continuously adjusting the pH value of the water layer to 3 by using hydrochloric acid, extracting the water layer by using ethyl acetate, collecting an organic layer, concentrating the organic layer, and recrystallizing the organic layer by using heptane to obtain 1.01kg of p-hydroxyphenylboronic acid, wherein the yield is 73.2%.
Comparative example 2
Vacuumizing a reaction kettle to-0.1 Mpa by using a vacuum pump, reducing the temperature of the reaction kettle to 10 ℃, adding 1.52kg (10mol) of o-methoxyphenylboronic acid, 1.57kg (20mol) of acetyl chloride and 12L of toluene into the reaction kettle, mixing and stirring uniformly, then adding 2mol of aluminum chloride, heating to 100 ℃, reacting at constant temperature for 1.5h to obtain an intermediate compound, adding a sodium carbonate solution to adjust the pH value of the system to 10 to obtain a water layer, continuously adjusting the pH value of the water layer to 4 by using hydrochloric acid, extracting by using ethyl acetate, collecting an organic layer, concentrating, recrystallizing by using n-hexane to obtain 1.07kg of o-hydroxyphenylboronic acid, wherein the yield is 77.5% and the purity is 81.2%.
Finally, it should be noted that: it should be understood that the above examples are only for clearly illustrating the present invention and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications of the invention may be made without departing from the scope of the invention.
Claims (9)
1. The preparation method of the o-hydroxyphenylboronic acid is characterized by comprising the following steps: dissolving o-alkoxyphenylboronic acid and an acyl chloride compound in a first organic solvent under the vacuum condition of-0.1 MPa and at the temperature of 0-10 ℃, then adding aluminum chloride, starting heating, heating to 10 ℃ every 15 minutes in the reaction process until the temperature is raised to 30-100 ℃, then reacting at constant temperature for 1-2 hours to obtain an intermediate compound, adding alkali to adjust the pH value of the system to 9-11, continuously adjusting the pH value of a water layer to 3-4 by using acid, extracting by using a second organic solvent, collecting an organic layer, concentrating, and recrystallizing by using a third organic solvent to obtain o-hydroxyphenylboronic acid.
2. The method according to claim 1, wherein the alkoxy group of the o-alkoxyphenylboronic acid is selected from the group consisting of methoxy, ethoxy, propoxy, isopropoxy, butoxy, and tert-butoxy, preferably methoxy and ethoxy.
3. The method according to claim 1, wherein the acyl chloride compound is acetyl chloride, propionyl chloride, butyryl chloride, isobutyryl chloride or oxalyl chloride.
4. The method of claim 1, wherein the first organic solvent is selected from toluene, xylene, or diphenyl ether.
5. The method according to claim 1, wherein the second organic solvent is selected from ethyl acetate, dichloromethane or chloroform.
6. The method for preparing orthohydroxyphenylboronic acid according to claim 1, wherein the third organic solvent is selected from hydrocarbon solvents, preferably heptane or n-hexane.
7. The method of claim 1, wherein the base is selected from sodium carbonate and potassium carbonate.
8. The method of claim 1, wherein the acid is selected from hydrochloric acid and sulfuric acid.
9. The method for preparing o-hydroxyphenylboronic acid according to claim 1, wherein the molar ratio of the o-alkoxyphenylboronic acid to the acid chloride compound to the aluminum chloride is 1:1 to 2:0.1 to 0.2.
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