CN112694497A - Preparation method of 4-isopropylsulfonyl phenylboronic acid - Google Patents
Preparation method of 4-isopropylsulfonyl phenylboronic acid Download PDFInfo
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- isopropylsulfonylphenylboronic
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- IGJLXIUSOMMUIV-UHFFFAOYSA-N (4-propan-2-ylsulfonylphenyl)boronic acid Chemical compound CC(C)S(=O)(=O)C1=CC=C(B(O)O)C=C1 IGJLXIUSOMMUIV-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 18
- GXLZTSMJUOOUDW-UHFFFAOYSA-N 1-bromo-4-propan-2-ylsulfanylbenzene Chemical compound CC(C)SC1=CC=C(Br)C=C1 GXLZTSMJUOOUDW-UHFFFAOYSA-N 0.000 claims abstract description 15
- WQZTWNHNXOSAAR-UHFFFAOYSA-N 1-bromo-4-propan-2-ylsulfonylbenzene Chemical compound CC(C)S(=O)(=O)C1=CC=C(Br)C=C1 WQZTWNHNXOSAAR-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 11
- 239000007818 Grignard reagent Substances 0.000 claims abstract description 10
- 150000004795 grignard reagents Chemical class 0.000 claims abstract description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 9
- 239000004327 boric acid Substances 0.000 claims abstract description 8
- -1 boric acid ester Chemical class 0.000 claims abstract description 8
- FTBCOQFMQSTCQQ-UHFFFAOYSA-N 4-bromobenzenethiol Chemical compound SC1=CC=C(Br)C=C1 FTBCOQFMQSTCQQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical group CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 238000010791 quenching Methods 0.000 claims description 8
- 230000000171 quenching effect Effects 0.000 claims description 8
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical group [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical group [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 claims description 6
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 claims description 3
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 3
- ULYZAYCEDJDHCC-UHFFFAOYSA-N isopropyl chloride Chemical group CC(C)Cl ULYZAYCEDJDHCC-UHFFFAOYSA-N 0.000 claims description 3
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 claims description 3
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical group COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 3
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 12
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 230000003321 amplification Effects 0.000 abstract description 2
- 238000003199 nucleic acid amplification method Methods 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 230000001590 oxidative effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- SBXDENYROQKXBE-UHFFFAOYSA-N 2-phenylbenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 SBXDENYROQKXBE-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000002308 endothelin receptor antagonist Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000004537 pulping Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- MOILFCKRQFQVFS-BDNRQGISSA-N (1r,3s,4r,5r)-4,6,6-trimethylbicyclo[3.1.1]heptane-3,4-diol Chemical compound C1[C@@H]2C(C)(C)[C@H]1C[C@H](O)[C@@]2(O)C MOILFCKRQFQVFS-BDNRQGISSA-N 0.000 description 1
- MMRNCZNUMZNLBZ-UHFFFAOYSA-N 2-(4-bromophenyl)benzenethiol Chemical compound SC1=CC=CC=C1C1=CC=C(Br)C=C1 MMRNCZNUMZNLBZ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- KYOIPUDHYRWSFO-UHFFFAOYSA-N [Br].[Li] Chemical group [Br].[Li] KYOIPUDHYRWSFO-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- UNXISIRQWPTTSN-UHFFFAOYSA-N boron;2,3-dimethylbutane-2,3-diol Chemical compound [B].[B].CC(C)(O)C(C)(C)O UNXISIRQWPTTSN-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical compound CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000002351 wastewater Substances 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 System
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Abstract
The invention discloses a preparation method of 4-isopropylsulfonyl phenylboronic acid, and belongs to the technical field of organic synthesis. 4-bromophenylthiol and halogenated isopropane are used as raw materials, and 1-bromo-4-isopropylsulfanylbenzene is obtained under the action of potassium carbonate; then oxidizing by hydrogen peroxide in the presence of a catalyst to obtain 1-bromo-4-isopropylsulfonyl benzene, and finally carrying out Grignard exchange/boric acid ester reaction with a Grignard reagent to obtain 4-isopropylsulfonyl phenylboronic acid. The method has the advantages of high yield, simple process, cheap and easily-obtained raw materials, green chemistry, reusable catalyst for 6 times, and industrial amplification prospect.
Description
Technical Field
The invention relates to a preparation method of 4-isopropylsulfonyl phenylboronic acid, belonging to the technical field of organic synthesis.
Background
The organic boric acid is an important intermediate, can be subjected to coupling reaction with halogenated hydrocarbon, olefin, aldehyde, amine and phenol, and can also be used for generating chiral boric acid ester with chiral pinanediol, pinacol diboron, L-tartaric acid and the like, thereby having important effect in asymmetric synthesis.
4-isopropylsulfonylphenylboronic acid, CAS: 850567-98-5, as important functional group skeleton, is used in synthesizing key intermediate of biphenyl sulfonamide endothelin antagonist, and through introducing 4-hydrophobic isopropyl group, the bioactivity and binding affinity of biphenyl sulfonamide endothelin antagonist are raised. It has unique chemical structure and important pharmacological activity, and has attracted the attention of chemical and medicinal chemical researchers in recent years. However, the synthesis of 4-isopropylsulfonylphenylboronic acid has not been reported.
Therefore, it is necessary to develop a proper synthesis method, which improves the utilization rate of reaction atoms, is green and environment-friendly, provides a better reaction route with easily available raw materials, mild reaction temperature, safety and stability, and is suitable for industrial scale-up production.
Disclosure of Invention
In order to meet the industrial requirement and advocate green chemistry, the invention discloses a preparation method of 4-isopropylsulfonyl phenylboronic acid, which takes 4-bromophenylthiol and halogenated isopropane as raw materials to obtain 1-bromo-4-isopropylsulfanylbenzene under the action of potassium carbonate; then adding hydrogen peroxide to oxidize in the presence of a catalyst to obtain 1-bromo-4-isopropylsulfonyl benzene, and finally carrying out Grignard exchange/boric acid ester reaction with a Grignard reagent to obtain 4-isopropylsulfonyl phenylboronic acid.
The invention relates to a preparation method of 4-isopropylsulfonyl phenylboronic acid, which comprises the following steps:
the first step is as follows: adding 4-bromophenylthiol and halogenated isopropane into an organic solvent, and carrying out substitution reaction in the presence of potassium carbonate to obtain 1-bromo-4-isopropylsulfanylbenzene;
the second step is that: adding 1-bromo-4-isopropylsulfanylbenzene into an organic solvent, and reacting under the conditions of a catalyst and hydrogen peroxide to obtain 1-bromo-4-isopropylsulfonylbenzene;
the third step: adding 1-bromo-4-isopropylsulfonyl benzene into an organic solvent, cooling, adding a Grignard reagent for Grignard exchange, adding a borate ester, and quenching to obtain 4-isopropylsulfonyl phenylboronic acid.
Further, in the above technical scheme, in the first step, the halogenated isopropane is selected from 2-chloropropane or 2-bromopropane, the organic solvent is selected from acetonitrile or acetone, and the reaction temperature is 40-82 ℃.
Further, in the above technical solution, in the first step, the molar ratio of the 4-bromophenylthiophenol, the halogenated isopropane and the potassium carbonate is 1: 1.0-1.05: 2.5-3.5.
Further, in the technical scheme, in the second step, the organic solvent is selected from tert-butyl alcohol or acetone, the catalyst is selected from sodium periodate, and the concentration of hydrogen peroxide is 25-28%. The reaction temperature is 20-30 ℃.
Further, in the above technical scheme, in the second step, the molar ratio of the 1-bromo-4-isopropylsulfanylbenzene, the catalyst and hydrogen peroxide is 1: 0.05-0.1: 2.2-2.5. The reaction temperature is-15 to 0 ℃.
Further, in the above technical solution, in the third step, the organic solvent is selected from tetrahydrofuran or 2-methyltetrahydrofuran, the grignard reagent is selected from isopropyl magnesium chloride or isopropyl magnesium bromide, and the borate is selected from trimethyl borate or triisopropyl borate.
Further, in the above technical scheme, in the third step, the molar ratio of 1-bromo-4-isopropylsulfonylbenzene, grignard reagent and borate is 1: 1.10-1.15: 1.20-1.25.
Furthermore, in the above technical solution, in the third step, when n-butyllithium is used for bromine-lithium exchange, the isopropyl sulfonamide is also oriented at the ortho position, and a part of byproducts is generated. After optimization, the exchange is carried out in an optimal mode by adopting an isopropyl Grignard reagent.
In the course of the experiments, it was found that the oxidation of boric acid to hydroxyl groups also occurred during the oxidation to sulfone, by means of oxidation of 1-bromo-4-isopropylsulfanylbenzene to sulfoxide, followed by grignard exchange/boronation to boric acid, followed by oxidation of sulfoxide to sulfone to 4-isopropylsulfonylphenylboronic acid.
Advantageous effects of the invention
The method takes 4-bromophenylthiol and halogenated isopropane as raw materials to obtain 1-bromo-4- (isopropylthio) benzene under the action of potassium carbonate; then under the catalysis of a catalyst, hydrogen peroxide is added for oxidation to obtain 1-bromine-4- (isopropylsulfonyl) benzene, and finally the benzene and a Grignard reagent are subjected to Grignard exchange/boric acid ester reaction to obtain 4-isopropylsulfonyl phenylboronic acid. The method has the advantages of high yield, simple process, mild and accessible raw materials, green chemistry, applicability of the catalyst for 6 times, small amount of wastewater, high product content of more than 99%, and industrial amplification prospect.
DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION
The invention is further illustrated by the following specific examples.
These examples are to be construed as merely illustrative and not limitative of the remainder of the disclosure in any way whatsoever. After reading the description of the invention, one skilled in the art can make various changes and modifications to the invention, and such equivalent changes and modifications also fall into the scope of the invention defined by the claims.
Synthesis of 1-bromo-4- (isopropylthio) benzene
Example 1
Adding 4-bromobenzothiophenol (100g,0.529mol), 2-chloropropane (45.7g,0.528mol) and acetonitrile 800mL into a reaction bottle, adding ground potassium carbonate powder (182.8g,1.323mol) under stirring, controlling the temperature at 80-82 ℃, stirring and reacting for 6-8 hours, sampling and detecting 1% of the raw material by HPLC, cooling to 10-15 ℃, adding water for quenching, extracting by using ethyl acetate, concentrating an organic phase until no liquid flows out, adding ethyl acetate clear solution, filtering inorganic salt, concentrating a filtrate, adding n-heptane for pulping, filtering, and drying to obtain 114.4g of 1-bromo-4- (isopropylthio) benzene, wherein the yield is as follows: 93.6%, HPLC: 98.9 percent.1HNMR(400MHz,CDCl3):7.50-7.41(d,2H),7.31-7.25(d,2H),3.34-3.27(m,1H),1.31-1.26(d,6H).
Example 2
Adding (100g,0.529mol) 4-bromophenylthiol, 2-bromopropane (64.9g,0.528mol) and 1000mL of acetone into a reaction bottle, adding ground potassium carbonate (255.9g,1.852mol) under stirring, controlling the temperature at 40-46 ℃ for reflux reaction for 12 hours, sampling and detecting 1.5% of the raw material by HPLC, cooling to 10-15 ℃, adding water for quenching, adding ethyl acetate for extraction, concentrating an organic phase until no liquid flows out, adding ethyl acetate for clearing, filtering inorganic salt, concentrating a filtrate, adding n-heptane for pulping, filtering, and drying to obtain 112.1g of 1-bromo-4- (isopropylthio) benzene, wherein the yield is as follows: 91.7%, HPLC: 98.3 percent.
Synthesis of 1-bromo-4- (isopropylsulfonyl) benzene
Example 3
Under the protection of nitrogen, 1-bromo-4- (isopropylthio) benzene (100g,0.433mol), sodium periodate (9.2g,0.043mol,0.1eq) and 400mL of tert-butyl alcohol are added into a reaction bottle, 28% hydrogen peroxide (126.2g,1.039mol,2.4eq) is slowly dripped at 10-25 ℃, the temperature is raised to 35 ℃ after the dripping is finished, the reaction is carried out for 3 hours, the reaction of raw materials is detected by sampling HPLC, the tert-butyl alcohol is removed by concentration at 40 ℃, the water phase is extracted by dichloromethane, and the water phase is reserved and can be repeatedly applied for 6 times. The organic phase was concentrated, n-heptane was added and slurried to give 105.1g of 1-bromo-4- (isopropylsulfonyl) benzene, yield: 92.3%, GC: 99.1 percent.1HNMR(400MHz,CDCl3):7.91-7.82(d,2H),7.71-7.63(d,2H),3.37-3.29(m,1H),1.39-1.30(d,6H).
Example 4
Under the protection of nitrogen, 1-bromo-4- (isopropylthio) benzene (100g,0.433mol), sodium periodate (4.6g,0.022mol,0.05eq) and 400mL of acetone are added into a reaction bottle, 28% hydrogen peroxide (120.8g,0.995mol,2.3eq) is slowly dripped at 10-25 ℃, the temperature is increased to 35 ℃ after the dripping is finished, the reaction is carried out for 3 hours, the reaction of raw materials is detected by sampling HPLC, the acetone is concentrated and removed at 40 ℃, a water phase is extracted by dichloromethane, an organic phase is concentrated, n-heptane is added, and the mixture is pulped to obtain 106.3g of 1-bromo-4- (isopropylsulfonyl) benzene, wherein the yield is as follows: 93.4%, GC: 98.7 percent.
Synthesis of 4-isopropylsulfonylphenylboronic acid
Example 5
Under the protection of nitrogen, adding 1-bromo-4- (isopropylsulfonyl) benzene (50g,0.19mol) and 400mL tetrahydrofuran into a reaction bottle, cooling to-10 ℃, dropwise adding 84mL (0.209mol,1.1eq) of 2.5mol/L isopropyl magnesium chloride/tetrahydrofuran solution, after the dropwise adding is finished, heating to 0 ℃ for reacting for 1.5 hours, sampling, quenching and detecting that the raw material exchange is complete, cooling to-15 ℃, dropwise adding trimethyl borate (23.7g,0.228mol,1.2eq), reacting for 2 hours, slowly heating to 5 ℃, reacting for 2 hours, adding saturated ammonium chloride aqueous solution for quenching, demixing, extracting with ethyl acetate, combining organic phases, concentrating under reduced pressure to remove a solvent, adding a mixed solvent of ethanol and water, and recrystallizing to obtain 33.2g of 4-isopropylsulfonyl phenylboronic acid, wherein the yield is as follows: 76.6%, GC: 99.6 percent.1HNMR(400MHz,DMSO-d6):7.99-7.90(d,2H),7.65-7.56(d,2H),6.12(s,2H),3.38-3.27(m,1H),1.36-1.28(m,6H).
Example 6
Under the protection of nitrogen, adding 400mL of 1-bromo-4- (isopropylsulfonyl) benzene (50g,0.19mol) and 2-methyltetrahydrofuran into a reaction bottle, cooling to-10 ℃, dropwise adding 107mL (0.213mol,1.12eq) of 2.0mol/L isopropylmagnesium bromide/2-methyltetrahydrofuran solution, after dropwise adding, heating to 0 ℃ for reaction for 1.5 hours, sampling and quenching to detect that the exchange of raw materials is finished, cooling to-15 ℃, dropwise adding 42.9g of triisopropyl borate (0.228mol,1.2eq), reacting for 2 hours, slowly heating to 5 ℃, reacting for 2 hours, adding a saturated ammonium chloride aqueous solution for quenching, demixing, extracting an aqueous phase with ethyl acetate, combining organic phases, concentrating under reduced pressure to remove a solvent, adding a mixed solvent of ethanol and water, and recrystallizing to obtain 36.5g of 4-isopropylsulfonyl phenylboronic acid, wherein the yield is as follows: 84.2%, GC: 99.2 percent.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to cover the technical solutions and the inventive concepts of the present invention within the technical scope of the present invention.
Claims (7)
1. The preparation method of the 4-isopropylsulfonyl phenylboronic acid is characterized by comprising the following steps:
the first step is as follows: adding 4-bromophenylthiol and halogenated isopropane into an organic solvent, and carrying out substitution reaction in the presence of potassium carbonate to obtain 1-bromo-4-isopropylsulfanylbenzene;
the second step is that: adding 1-bromo-4-isopropylsulfanylbenzene into an organic solvent, and reacting under the conditions of a catalyst and hydrogen peroxide to obtain 1-bromo-4-isopropylsulfonylbenzene;
the third step: adding 1-bromo-4-isopropylsulfonyl benzene into an organic solvent, cooling, adding a Grignard reagent for Grignard exchange, adding a borate ester, and quenching to obtain 4-isopropylsulfonyl phenylboronic acid.
2. The method for producing 4-isopropylsulfonylphenylboronic acid according to claim 1, wherein: in the first step, the halogenated isopropane is selected from 2-chloropropane or 2-bromopropane, the organic solvent is selected from acetonitrile or acetone, and the reaction temperature is 40-82 ℃.
3. The method for producing 4-isopropylsulfonylphenylboronic acid according to claim 1, wherein: in the first step, the molar ratio of the 4-bromophenylthiol, the halogenated isopropane to the potassium carbonate is 1: 1.0-1.05: 2.5-3.5.
4. The method for producing 4-isopropylsulfonylphenylboronic acid according to claim 1, wherein: in the second step, the organic solvent is selected from tert-butyl alcohol or acetone, the catalyst is selected from sodium periodate, and the reaction temperature is 20-30 ℃.
5. The method for producing 4-isopropylsulfonylphenylboronic acid according to claim 1, wherein: in the second step, the molar ratio of the 1-bromo-4-isopropylsulfanylbenzene to the catalyst to hydrogen peroxide is 1: 0.05-0.1: 2.2-2.5.
6. The method for producing 4-isopropylsulfonylphenylboronic acid according to claim 1, wherein: in the third step, the organic solvent is selected from tetrahydrofuran or 2-methyltetrahydrofuran, the Grignard reagent is selected from isopropyl magnesium chloride or isopropyl magnesium bromide, and the borate is selected from trimethyl borate or triisopropyl borate.
7. The method for producing 4-isopropylsulfonylphenylboronic acid according to claim 1, wherein: in the third step, the mol ratio of the 1-bromo-4-isopropylsulfonyl benzene, the Grignard reagent and the boric acid ester is 1: 1.10-1.15: 1.20-1.25.
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