CN116496136A - Diaryl sulfone compound and preparation method thereof - Google Patents
Diaryl sulfone compound and preparation method thereof Download PDFInfo
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- -1 Diaryl sulfone compound Chemical class 0.000 title claims abstract description 40
- 238000002360 preparation method Methods 0.000 title abstract description 20
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims abstract description 44
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims abstract description 22
- 229910000024 caesium carbonate Inorganic materials 0.000 claims abstract description 22
- 235000003270 potassium fluoride Nutrition 0.000 claims abstract description 22
- 239000011698 potassium fluoride Substances 0.000 claims abstract description 22
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001035 drying Methods 0.000 claims abstract description 17
- 239000012300 argon atmosphere Substances 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 96
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 32
- 238000013375 chromatographic separation Methods 0.000 claims description 18
- 239000003480 eluent Substances 0.000 claims description 16
- 238000000605 extraction Methods 0.000 claims description 16
- 239000003208 petroleum Substances 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 9
- 238000000034 method Methods 0.000 abstract description 8
- 229910052723 transition metal Inorganic materials 0.000 abstract description 8
- 150000003624 transition metals Chemical class 0.000 abstract description 8
- 239000003054 catalyst Substances 0.000 abstract description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 abstract description 3
- 238000006254 arylation reaction Methods 0.000 abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 abstract description 3
- 239000011737 fluorine Substances 0.000 abstract description 3
- 239000003513 alkali Substances 0.000 abstract 1
- 239000007810 chemical reaction solvent Substances 0.000 abstract 1
- 238000004587 chromatography analysis Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 230000006837 decompression Effects 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000010828 elution Methods 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- 150000003457 sulfones Chemical group 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 125000005362 aryl sulfone group Chemical group 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- ZCVSDPUSEUOUHQ-UHFFFAOYSA-N 1-(benzenesulfonyl)-2,4-dimethylbenzene Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)C1=CC=CC=C1 ZCVSDPUSEUOUHQ-UHFFFAOYSA-N 0.000 description 1
- KQSIIBOLOKJDTK-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-(trifluoromethyl)benzene Chemical compound C1=CC(C(F)(F)F)=CC=C1S(=O)(=O)C1=CC=CC=C1 KQSIIBOLOKJDTK-UHFFFAOYSA-N 0.000 description 1
- WUQDRRXKNVIWIR-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-bromobenzene Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)C1=CC=CC=C1 WUQDRRXKNVIWIR-UHFFFAOYSA-N 0.000 description 1
- OFCFYWOKHPOXKF-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-chlorobenzene Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)C1=CC=CC=C1 OFCFYWOKHPOXKF-UHFFFAOYSA-N 0.000 description 1
- YMOQFMYBDGVJKE-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-ethylbenzene Chemical compound C1=CC(CC)=CC=C1S(=O)(=O)C1=CC=CC=C1 YMOQFMYBDGVJKE-UHFFFAOYSA-N 0.000 description 1
- KXUNNMWAIMNUPH-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-methoxybenzene Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)C1=CC=CC=C1 KXUNNMWAIMNUPH-UHFFFAOYSA-N 0.000 description 1
- YBRXHRWLEFCFEG-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-methylbenzene Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C1=CC=CC=C1 YBRXHRWLEFCFEG-UHFFFAOYSA-N 0.000 description 1
- AZICHRGEWDKLBL-UHFFFAOYSA-N 1-(benzenesulfonyl)-4-tert-butylbenzene Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)C1=CC=CC=C1 AZICHRGEWDKLBL-UHFFFAOYSA-N 0.000 description 1
- RBSJYIWGJOQHJL-UHFFFAOYSA-N 1-(benzenesulfonyl)naphthalene Chemical compound C=1C=CC2=CC=CC=C2C=1S(=O)(=O)C1=CC=CC=C1 RBSJYIWGJOQHJL-UHFFFAOYSA-N 0.000 description 1
- BWDLVRMBJDJVOS-UHFFFAOYSA-N 2-(benzenesulfonyl)-1,3-dimethylbenzene Chemical compound CC1=CC=CC(C)=C1S(=O)(=O)C1=CC=CC=C1 BWDLVRMBJDJVOS-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- ORFPWVRKFLOQHK-UHFFFAOYSA-N amicarbazone Chemical compound CC(C)C1=NN(C(=O)NC(C)(C)C)C(=O)N1N ORFPWVRKFLOQHK-UHFFFAOYSA-N 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 229960000860 dapsone Drugs 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a diaryl sulfone compound and a preparation method thereof, comprising the following steps: under argon atmosphere, adding a 3- (phenylsulfinyl) propionic acid tert-butyl ester compound and a 2- (trimethylsilyl) benzotrifluoride sulfonate phenyl ester compound into a Schlenk tube, sequentially adding cesium carbonate, potassium fluoride and 18-crown ether-6, then adding a solvent DME, and reacting for 4 hours at room temperature; and after the reaction is finished, extracting, separating by chromatography and drying to obtain a target product. The method has mild reaction conditions, is simple and convenient to operate, does not need to use an expensive transition metal catalyst in the reaction, takes low-cost and easily-obtained cesium carbonate as alkali, takes potassium fluoride as a fluorine source and ethylene glycol dimethyl ether as a reaction solvent, realizes the sulfinate anion arylation reaction, and provides a new way for preparing various functionalized diaryl sulfones.
Description
Technical Field
The invention belongs to the technical field of synthesis and application of organic compounds, and particularly relates to a diaryl sulfone compound and a preparation method thereof.
Background
Sulfone motifs are widely found in a variety of bioactive compounds, natural products and some drugs that have been marketed. For example, sulfones such as dapsone and derivatives thereof are the major components of drugs for treating leprosy on the market (Wiley-VCH Verlag: weinheim, germany, 2012.); the amicarbazone commonly used as herbicide also contains an aryl sulfone backbone (j.med.chem.2011, 54,1587.). In view of the importance and wide application of sulfones, synthesis of sulfones, particularly those containing aryl structures, has been widely studied.
There are many methods for the synthesis of sulfones, the most common being the oxidation of sulfur-containing compounds using strong oxidants (j.chem. Rev.2019,1,99.) and the cross-coupling reaction of sulfinates with arylboronic acids or aryl halides using transition metal catalysis to give biaryl sulfones (acscat. 2021,11,4169.). However, these synthetic strategies suffer from serious drawbacks, such as (1) the use of strong oxidants limits the compatibility of the substrate functionalities; (2) Due to incomplete oxidation of sulfides, sulfone byproducts are typically produced; (3) The use of transition metal catalysts requires expensive transition metal catalysts and more severe reaction conditions and higher reaction temperatures during the coupling process. Therefore, although the synthesis of sulfones has been greatly advanced, it is desirable to develop a method for synthesizing aryl sulfones that is simple to operate, mild in conditions and free of excessive metal participation.
Disclosure of Invention
The invention aims to provide a synthesis and preparation method of diaryl sulfone compounds, which is simple and feasible, low in cost and easy to purify. The invention provides a method for realizing sulfinate anion arylation reaction by using low-cost and easily-obtained cesium carbonate as a base and potassium fluoride as a fluorine source under the condition of no transition metal catalyst. The method has mild reaction conditions, is simple and convenient to operate, does not need to use an expensive transition metal catalyst in the reaction, and provides a new way for preparing various functionalized diaryl sulfones.
In order to achieve the above purpose, the present invention adopts the following technical scheme:
a diaryl sulfone compound has a structural general formula:
wherein R is 1 Hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r is R 2 Is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.
The preparation method of the diaryl sulfone compound comprises the following steps: under argon atmosphere, adding a 3- (phenylsulfinyl) propionic acid tert-butyl ester compound and a 2- (trimethylsilyl) benzotrifluoride sulfonate phenyl ester compound into a 10mL Schlenk tube, sequentially adding cesium carbonate, potassium fluoride and 18-crown ether-6, then adding a solvent, and reacting for 4 hours at room temperature; extracting, chromatographic separation and drying after the reaction is finished to obtain a target product, wherein the reaction equation is as follows:
the general formula of the 3- (phenylsulfinyl) propionic acid tert-butyl ester compound is as follows:
the structural general formula of the 2- (trimethylsilyl) triflate phenyl compound is as follows:
wherein R is 1 Hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r is R 2 Is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.
Further, the mass ratio of the 3- (phenylsulfinyl) propionic acid tert-butyl ester compound to the 2- (trimethylsilyl) benzotrifluoride sulfonate compound is 3:1.
Further, the amount of cesium carbonate is 12 times the amount of the substance of the 2- (trimethylsilyl) triflate compound.
Further, the amount of potassium fluoride is 2 times the amount of the substance of the 2- (trimethylsilyl) triflate compound.
Further, the amount of the 18-crown ether-6 is 2 times the amount of the substance of the 2- (trimethylsilyl) triflate compound.
Further, the solvent was ethylene glycol dimethyl ether, and the amount of the solvent was 1mL based on the amount of 0.1mmol of the 2- (trimethylsilyl) triflate compound.
Further, the extractant adopted in the extraction is ethyl acetate.
Further, the eluent adopted by the chromatographic separation is ethyl acetate and petroleum ether with the volume ratio of 1:10.
The invention has the beneficial effects that: the invention provides a new way for preparing various functionalized diaryl sulfones. The reaction uses low-cost and easily-obtained cesium carbonate as a base and potassium fluoride as a fluorine source, and realizes the sulfinate anion arylation reaction under the condition of no transition metal catalyst. The reaction condition is mild, a high Wen Jijiang oxidant is not needed, the operation is simple and convenient, the method is efficient, the cost is low, the purification is easy, the new process of constructing the diaryl sulfone compound under the catalysis of no transition metal is enriched, and the method has important significance for further research and application of the aryl sulfone compound.
Detailed Description
The invention will be further illustrated with reference to specific examples. It is to be understood that the following examples are intended to illustrate the present invention and are not to be construed as limiting the scope of the invention, and that numerous insubstantial modifications and adaptations can be made by those skilled in the art in light of the foregoing disclosure.
Example 1
The compound (4-tolyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: 80.4mg (0.3 mmol) of tert-butyl 3- (p-tolylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether are sequentially added to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 82%; 1 H NMR(600MHz,CDCl 3 )δ7.95–7.91(m,2H),7.83(d,J＝8.3Hz,2H),7.58–7.52(m,1H),7.49(dd,J＝8.3,6.8Hz,2H),7.32–7.28(m,2H),2.39(s,3H)ppm. 13 C NMR(151MHz,CDCl 3 )δ144.2,142.0,138.7,133.0,129.9,129.2,127.7,127.5,21.6ppm.
example 2
The compound (2, 4-dimethylphenyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: 84.6mg (0.3 mmol) of tert-butyl 3- (2, 4-dimethylphenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether are added sequentially to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 73%; 1 H NMR(600MHz,CDCl 3 )δ8.10(d,J＝8.1Hz,1H),7.85(d,J＝7.0Hz,2H),7.55(t,J＝7.4Hz,1H),7.48(t,J＝7.8Hz,2H),7.19(d,J＝8.2Hz,1H),7.03(s,1H),2.39(s,3H),2.36(s,3H)ppm. 13 C NMR(151MH z,CDCl 3 )δ144.5,141.7,137.8,136.0,133.4,132.8,129.7,129.0,127.5,127.1,21.3,20.1ppm.
example 3
The compound (2, 6-dimethylphenyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: 84.6mg (0.3 mmol) of tert-butyl 3- (2, 6-dimethylphenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether are added sequentially to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and light yellow solid is obtained after drying, and the yield is 70%; 1 H NMR(600MHz,CDCl 3 )δ7.82–7.77(m,2H),7.55(t,J＝7.4Hz,1H),7.48(dd,J＝8.5,7.1Hz,2H),7.32(t,J＝7.6Hz,1H),7.13(d,J＝7.6Hz,2H),2.64(s,6H)ppm. 13 C NMR(151MHz,CDCl 3 )δ143.3,140.2,136.8,132.8,132.7,131.5,128.9,126.3,22.9ppm.
example 4
The compound (4-ethylphenyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: 84.6mg (0.3 mmol) of tert-butyl 3- (4-ethylphenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, ethylene glycol dimethyl ether 1mL were sequentially added to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 76%; 1 H NMR(600MHz,CDCl 3 )δ7.94(d,J＝7.1Hz,2H),7.85(d,J＝8.4Hz,2H),7.54(t,J＝7.4Hz,1H),7.49(t,J＝7.6Hz,2H),7.32(d,J＝8.3Hz,2H),2.68(q,J＝7.6Hz,2H),1.22(t,J＝7.6Hz,3H)ppm. 13 C NMR(151MHz,CDCl 3 )δ150.3,142.0,138.9,133.0,129.2,128.8,127.8,127.5,28.8,15.0ppm.
example 5
The compound (4-tert-butylphenyl) phenylsulfone of the present example has the structural formula:
the preparation method comprises the following steps: to a 10mL Schlemen tube under argon, 93.1mg (0.3 mmol) of tert-butyl 3- (4-tert-butylphenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown ether-6, 1mL of ethylene glycol dimethyl ether were added in this order and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation is carried out after decompression concentration200-300 meshes of silica gel, and eluent: gradient leaching with ethyl acetate/petroleum ether at a ratio of 1:10), and drying to obtain white solid with a yield of 82%; 1 H NMR(600MHz,CDCl 3 )δ7.95(d,J＝7.7Hz,2H),7.86(d,J＝8.5Hz,2H),7.52(dd,J＝24.6,7.7Hz,5H),1.31(s,9H)ppm. 13 C NMR(151MHz,CDCl 3 )δ157.1,142.0,138.6,133.0,129.2,127.6,127.5,126.3,35.2,31.0ppm.
example 6
The compound (4-methoxyphenyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: to a 10mL Schlemen tube under argon, 85.2mg (0.3 mmol) of tert-butyl 3- (4-methoxyphenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether were sequentially added and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 65%; 1 H NMR(600MHz,CDCl 3 )δ7.92(d,J＝7.2Hz,2H),7.88(d,J＝8.9Hz,2H),7.54(t,J＝7.4Hz,1H),7.48(t,J＝7.4Hz,2H),6.96(d,J＝8.9Hz,2H),3.84(s,3H)ppm. 13 C NMR(151MHz,CDCl 3 )δ163.4,142.4,133.2,132.8,129.9,129.2,127.3,114.5,55.6ppm.
example 7
The compound (4-chlorophenyl) phenylsulfone of this example has the formula:
the preparation method comprises the following steps: 86.4mg (0.3 mmol) of the tert-butyl 3- (4-chlorophenyl sulfinyl) propionate compound were successively added to 10mL of Schlenk's tube under argon atmosphere29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether, and the reaction time is 4 hours at room temperature; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 67%; 1 H NMR(600MHz,CDCl 3 )δ7.96–7.90(m,2H),7.88(d,J＝8.7Hz,2H),7.58(t,J＝7.4Hz,1H),7.52(t,J＝7.7Hz,2H),7.49–7.46(m,2H)ppm. 13 C NMR(151MHz,CDCl 3 )δ141.3,140.2,139.9,133.4,129.6,129.4,129.1,127.7ppm.
example 8
The compound (4-bromophenyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: to a 10mL Schlemk tube under argon atmosphere were successively added 99.6mg (0.3 mmol) of tert-butyl 3- (4-bromophenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether, and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 57%; 1 H NMR(600MHz,CDCl 3 )δ7.95–7.91(m,2H),7.82–7.78(m,2H),7.64(d,J＝8.6Hz,2H),7.58(t,J＝7.4Hz,1H),7.54–7.49(m,2H)ppm. 13 C NMR(151MHz,CDCl 3 )δ141.2,140.7,133.5,132.6,129.4,129.2,128.5,127.7ppm.
example 9
The compound (4-trifluoromethylphenyl) phenylsulfone of this example has the structural formula:
the preparation method comprises the following steps: 99.6mg (0.3 mmol) of tert-butyl 3- (4-trifluoromethylphenylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, ethylene glycol dimethyl ether 1mL are sequentially added to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 67%; 1 H NMR(600MHz,CDCl 3 )δ8.08(d,J＝8.2Hz,2H),7.97(d,J＝7.1Hz,2H),7.77(d,J＝8.2Hz,2H),7.61(t,J＝7.4Hz,1H),7.54(t,J＝7.8Hz,2H)ppm. 13 C NMR(151MHz,CDCl 3 )δ145.3,140.6,134.9(q, 2 J C-F ＝33.2Hz),133.8,129.5,128.2,127.9,126.4,(q, 3 J C-F ＝3.6Hz)123.1(q, 1 J C-F ＝273.3Hz)ppm.
example 10
The structural formula of the compound phenylnaphthyl sulfone of this example is:
the preparation method comprises the following steps: 91.2mg (0.3 mmol) of tert-butyl 3- (naphthylsulfinyl) propionate, 29.8mg (0.1 mmol) of phenyl 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether are sequentially added to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 68%; 1 H NMR(600MHz,CDCl 3 )δ8.58(d,J＝1.9Hz,1H),8.03–7.96(m,3H),7.93(d,J＝8.7Hz,1H),7.89–7.84(m,2H),7.66–7.58(m,2H),7.55(t,J＝7.4Hz,1H),7.50(t,J＝7.5Hz,2H)ppm. 13 C NMR(151MHz,CDCl 3 )δ141.7,138.5,135.0,133.2,132.3,129.7,129.4,129.3,129.2,129.1,127.9,127.7,127.6,122.7ppm.
example 11
The structural formula of the compound (3-methoxyphenyl) tolylsulfone of this example is:
the preparation method comprises the following steps: 80.4mg (0.3 mmol) of tert-butyl 3- (p-tolylsulfinyl) propionate, 32.8mg (0.1 mmol) of phenyl 6-methoxy-2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, ethylene glycol dimethyl ether 1mL are added to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 67%; 1 H NMR(600MHz,CDCl 3 )δ7.82(d,J＝8.3Hz,2H),7.49(d,J＝8.5Hz,1H),7.44(dd,J＝2.6,1.6Hz,1H),7.38(t,J＝8.0Hz,1H),7.29(d,J＝8.0Hz,2H),7.06(dd,J＝8.3,1.6Hz,1H),3.83(s,3H),2.40(s,3H)ppm. 13 C NMR(151MHz,CDCl 3 )δ160.0,144.2,143.2,138.7,130.3,129.9,127.7,119.8,119.4,112.1,55.7,21.5ppm.
example 12
The structural formula of the compound (3, 4-dimethylphenyl) tolylsulfone of this example is:
the preparation method comprises the following steps: 80.4mg (0.3 mmol) of tert-butyl 3- (p-tolylsulfinyl) propionate compound, 32.6mg (0.1 mmol) of benzene 4, 5-dimethyl-2- (trimethylsilyl) triflate are added successively to a 10mL Schlenk under argon atmosphere391mg (1.2 mmol) cesium carbonate, 11.6mg (0.2 mmol) potassium fluoride, 53mg (0.2 mmol) 18-crown-6, ethylene glycol dimethyl ether 1mL, for 4 hours at room temperature; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 70%; 1 H NMR(600MHz,CDCl 3 )δ7.81(d,J＝8.3Hz,2H),7.67(s,1H),7.65(d,J＝7.9Hz,1H),7.28(d,J＝8.0Hz,2H),7.23(d,J＝7.9Hz,1H),2.38(s,3H),2.29(d,J＝3.5Hz,6H)ppm. 13 C NMR(151MHz,CDC l 3 )δ143.8,142.6,139.3,139.2,138.0,130.4,129.8,128.3,127.6,125.1,21.5,19.9,19.8ppm.
example 13
The structural formula of the compound tolylnaphthalene sulfone of this example is:
the preparation method comprises the following steps: 80.4mg (0.3 mmol) of tert-butyl 3- (p-tolylsulfinyl) propionate, 34.8mg (0.1 mmol) of naphthalene 2- (trimethylsilyl) triflate, 391mg (1.2 mmol) of cesium carbonate, 11.6mg (0.2 mmol) of potassium fluoride, 53mg (0.2 mmol) of 18-crown-6, 1mL of ethylene glycol dimethyl ether are sequentially added to a 10mL Schlenk under argon atmosphere and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation is carried out after decompression concentration (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, the proportion is 1:10), white solid is obtained after drying, and the yield is 48%; 1 H NMR(600MHz,CDCl 3 )δ8.58–8.53(m,1H),7.97(d,J＝7.5Hz,1H),7.94–7.82(m,5H),7.65-7.65(m,2H),7.29(d,J＝8.1Hz,2H),2.38(s,3H)ppm. 13 C NMR(151MHz,CDCl 3 )δ144.2,138.9,138.8,135.0,132.3,129.9,129.6,129.4,129.0,128.9,127.9,127.8,127.6,122.7,21.6ppm.
example 14
The compound 5- (p-tolylsulfinyl) benzo [ d ] [1,3] dioxan of this example has the structural formula:
the preparation method comprises the following steps: 80.4mg (0.3 mmol) of 3- (trimethylsilyl) naphthalen-2-yl trifluoromethane sulfonate compound, 34.2mg (0.1 mmol) of 6- (trimethylsilyl) benzo [1,3] are added successively to a 10mL Schlenk under argon atmosphere]Dioxolan-5-yl trifluoromethane sulfonate, 391mg (1.2 mmol) cesium carbonate, 11.6mg (0.2 mmol) potassium fluoride, 53mg (0.2 mmol) 18-crown-6, ethylene glycol dimethyl ether 1mL, and reacted at room temperature for 4 hours; after the reaction is finished, ethyl acetate is used for extraction, and chromatographic separation (silica gel 200-300 meshes, eluent: ethyl acetate/petroleum ether gradient elution, proportion 1:10) is carried out after decompression concentration, and white solid is obtained after drying, and the yield is 68%; 1 H NMR(600MHz,CDCl 3 )δ7.79(d,J＝8.3Hz,2H),7.52(dd,J＝8.2,1.8Hz,1H),7.32–7.25(m,3H),6.86(d,J＝8.2Hz,1H),6.03(s,2H),2.39(s,3H)ppm. 13 C NMR(151MHz,CDCl 3 )δ151.7,148.3,143.9,139.1,135.4,129.9,127.5,123.4,108.5,107.8,102.3,21.5ppm.
the foregoing has shown and described the basic principles and main features of the present invention and the advantages of the present invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that the above embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the spirit and scope of the invention, which is defined in the appended claims. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (10)
1. A diaryl sulfone compound has a structural general formula:
wherein R is 1 Hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r is R 2 Is hydrogen, alkyl,Alkoxy, halogen or trifluoromethyl.
2. The method for producing a diaryl sulfone compound according to claim 1, characterized by comprising the steps of: under argon atmosphere, adding a 3- (phenylsulfinyl) propionic acid tert-butyl ester compound and a 2- (trimethylsilyl) benzotrifluoride sulfonate phenyl ester compound into a Schlenk tube, sequentially adding cesium carbonate, potassium fluoride and 18-crown ether-6, then adding a solvent, and reacting at room temperature; extracting, chromatographic separation and drying after the reaction is finished to obtain a target product, wherein the reaction equation is as follows:
the general formula of the 3- (phenylsulfinyl) propionic acid tert-butyl ester compound is as follows:
the structural general formula of the 2- (trimethylsilyl) triflate phenyl compound is as follows:
wherein R is 1 Hydrogen, alkyl, alkoxy, halogen or trifluoromethyl; r is R 2 Is hydrogen, alkyl, alkoxy, halogen or trifluoromethyl.
3. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the mass ratio of the 3- (phenylsulfinyl) propionic acid tert-butyl ester compound to the 2- (trimethylsilyl) triflate phenyl ester compound is 3:1.
4. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the ratio of the amount of cesium carbonate to the amount of the substance of the 2- (trimethylsilyl) triflate phenyl compound is 12:1.
5. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the ratio of the amount of the potassium fluoride to the amount of the substance of the 2- (trimethylsilyl) triflate compound is 2:1.
6. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the mass ratio of the 18-crown ether-6 to the 2- (trimethylsilyl) triflate phenyl ester compound is 2:1.
7. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the solvent is ethylene glycol dimethyl ether, and based on 0.1mmol of 2- (trimethylsilyl) triflate phenyl compounds, the dosage of the solvent is 1mL.
8. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the reaction temperature was room temperature and the reaction time was 4 hours.
9. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the extractant adopted in the extraction is ethyl acetate.
10. The method for producing a diaryl sulfone compound according to claim 2, characterized in that: the eluent adopted by the chromatographic separation is ethyl acetate and petroleum ether with the volume ratio of 1:10.
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