CN110698369B - Method for synthesizing aryl acetylene alkyl sulfone compound based on alkyl fluoborate - Google Patents
Method for synthesizing aryl acetylene alkyl sulfone compound based on alkyl fluoborate Download PDFInfo
- Publication number
- CN110698369B CN110698369B CN201910935440.9A CN201910935440A CN110698369B CN 110698369 B CN110698369 B CN 110698369B CN 201910935440 A CN201910935440 A CN 201910935440A CN 110698369 B CN110698369 B CN 110698369B
- Authority
- CN
- China
- Prior art keywords
- alkyl
- aryl acetylene
- synthesizing
- fluoborate
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 aryl acetylene alkyl sulfone compound Chemical class 0.000 title claims abstract description 40
- 125000000217 alkyl group Chemical group 0.000 title claims abstract description 38
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 19
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000003504 photosensitizing agent Substances 0.000 claims abstract description 17
- 229910001914 chlorine tetroxide Inorganic materials 0.000 claims abstract description 10
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 claims abstract description 10
- 238000000926 separation method Methods 0.000 claims abstract description 9
- 239000011591 potassium Substances 0.000 claims abstract description 6
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 claims description 10
- 238000004440 column chromatography Methods 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 8
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 8
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 6
- 230000001681 protective effect Effects 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 claims description 4
- 229940043349 potassium metabisulfite Drugs 0.000 claims description 4
- 235000010263 potassium metabisulphite Nutrition 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 239000003960 organic solvent Substances 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 239000012973 diazabicyclooctane Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 3
- FNPNRZLYTIVLNO-UHFFFAOYSA-N Cl(=O)(=O)(=O)O.C1(=C(C(=CC(=C1)C)C)C1C2=CC=CC=C2N(C=2C=CC=CC12)C)C Chemical compound Cl(=O)(=O)(=O)O.C1(=C(C(=CC(=C1)C)C)C1C2=CC=CC=C2N(C=2C=CC=CC12)C)C FNPNRZLYTIVLNO-UHFFFAOYSA-N 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000009423 ventilation Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 4
- AZQCFLDDJHERFZ-UHFFFAOYSA-N Br.C#Cc1ccccc1 Chemical compound Br.C#Cc1ccccc1 AZQCFLDDJHERFZ-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 238000005694 sulfonylation reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000006277 sulfonation reaction Methods 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- QHZLFYTXKDWRJA-UHFFFAOYSA-N 1-ethynyl-4-(trifluoromethyl)benzene hydrobromide Chemical compound C#CC1=CC=C(C(F)(F)F)C=C1.Br QHZLFYTXKDWRJA-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- XZVOJEGKVGSHGI-UHFFFAOYSA-N C#CC(C=C1)=CC=C1F.Br Chemical compound C#CC(C=C1)=CC=C1F.Br XZVOJEGKVGSHGI-UHFFFAOYSA-N 0.000 description 1
- HNRPLDICYJKXLX-UHFFFAOYSA-N CC1=CC=CC(C#C)=C1.Br Chemical compound CC1=CC=CC(C#C)=C1.Br HNRPLDICYJKXLX-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- ZXGIHDNEIWPDFW-UHFFFAOYSA-M acid red 4 Chemical compound [Na+].COC1=CC=CC=C1N=NC1=CC(S([O-])(=O)=O)=C(C=CC=C2)C2=C1O ZXGIHDNEIWPDFW-UHFFFAOYSA-M 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000006552 photochemical reaction Methods 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- XWGJFPHUCFXLBL-UHFFFAOYSA-M rongalite Chemical compound [Na+].OCS([O-])=O XWGJFPHUCFXLBL-UHFFFAOYSA-M 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
- C07B61/02—Generation of organic free radicals; Organic free radicals per se
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/03—Free radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic chemistry, and particularly relates to a method for synthesizing aryl acetylene alkyl sulfone compounds based on alkyl fluoborate. The method for synthesizing the aryl acetylene alkyl sulfone compound provided by the invention is to use 9-mesityl-10-methylacridine perchlorate (Mes-Acr) as a photosensitizer under the condition of visible light+ClO4 ‑674783-97-2), then a photosensitizer acts on the potassium alkyl fluoborate to obtain an alkyl radical, the alkyl radical is combined with sulfur dioxide to generate an alkyl sulfonyl radical, and the alkyl sulfonyl radical and aryl acetylene bromide are added to obtain a series of aryl acetylene alkyl sulfone compounds. The preparation method of the aryl acetylene alkyl sulfone compound has the advantages of mild conditions, simplicity, high efficiency, high reaction yield, good product purity, convenience for separation and purification and good application value.
Description
Technical Field
The invention belongs to the technical field of organic chemistry, and particularly relates to a method for synthesizing aryl acetylene alkyl sulfone compounds based on alkyl fluoborate.
Background
The sulfonyl compounds have good biological activity and are widely present in drug molecules. The traditional method for synthesizing the compounds often needs to use sulfonation reagents with high toxicity and strong corrosiveness, so that the development of a novel, efficient, economical and green sulfonylation method for constructing sulfonyl fragments is a key direction of research of chemists. In recent years, there have been increasing reports of sulfonylation reactions using sulfur dioxide substitutes, such as sodium metabisulfite, potassium metabisulfite, DABSO or sodium formaldehyde sulfoxylate as indirect sulfonation reagents. In the reaction, the reaction is green and efficient, so that the harsh conditions of strong acid or strong oxidation in the traditional synthesis are avoided, and chemists continuously explore a synthesis method for carrying out sulfonylation by using the sulfur dioxide substitute.
Among a plurality of synthetic methods, the free radical series reaction has the advantages of simple operation, economy, high efficiency, mild conditions and the like, and is widely applied to the field of organic synthesis. The photochemical reaction which has been favored for decades is a simple, efficient, clean organic synthesis strategy. In the reaction system, visible light is utilized to absorb photon excitation on the photosensitizer, so that the photosensitizer generates a specific oxidation or reduction state, and the photosensitizer and a reaction substrate can carry out single electron transfer to initiate a free radical reaction.
Based on the above, the invention aims to provide a method for synthesizing aryl acetylene alkyl sulfone compounds by catalyzing the reaction among three components, namely aryl acetylene bromide, alkyl fluoborate and a sulfur dioxide solid substitute by using a photosensitizer under the condition of visible light.
Disclosure of Invention
The invention aims to solve the defects of the prior art and provides a method for synthesizing aryl acetylene alkyl sulfone compounds based on alkyl fluoborate.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a method for synthesizing aryl acetylene alkyl sulfone compounds based on alkyl fluoborate, which comprises the following steps of in a solvent, under the condition of visible light, acting a photosensitizer on the alkyl fluoborate to generate alkyl free radicals, then combining the alkyl free radicals with sulfur dioxide to generate alkyl sulfonyl free radicals, and then adding the alkyl sulfonyl free radicals and aryl acetylene bromine to obtain the aryl acetylene alkyl sulfone compounds, wherein the method comprises the following steps:
(1) at room temperature, adding aryl acetylene bromide, a sulfur dioxide solid substitute, alkyl fluoborate, ammonium fluoride and a photosensitizer into a reaction tube according to a certain molar ratio, placing the reaction tube in a protective atmosphere to fully replace gas, adding a solvent, and reacting under the condition of visible light;
(2) and after the reaction is completed, concentrating the reaction liquid, and performing column chromatography separation on the concentrated reaction liquid to obtain the aryl acetylene alkyl sulfone compound.
Preferably, the alkyl fluoroborate described in the present invention includes potassium alkyl fluoroborate.
Preferably, the alkyl group of the alkyl fluoroborate described in the present invention includes ethyl, propyl, tert-butyl, cyclopentyl and cyclohexyl.
Preferably, the aryl group of the arylacetylene bromide in the present invention is an aryl group having an electron withdrawing group including fluorine, chlorine, bromine and trifluoromethyl or an electron donating group including alkyl, methoxy and phenyl.
Preferably, the photosensitizers described in the present invention include Mes-Acr+ClO4 -(9-mesityl-10-methylacridine perchlorate, CAS:674783-97-2) and other oxidative photosensitizers including acid Red 87 and 4 CzIPN; a more preferred photosensitizer is Mes-Acr+ClO4 -。
Preferably, the sulfur dioxide solid substitute described in the present invention comprises sodium metabisulfite (Na)2S2O5) Potassium metabisulfite (K)2S2O5) And DABCO.(SO2)2(DABSO)。
Preferably, the molar ratio of the aryl acetylene bromide, the sulfur dioxide solid substitute, the alkyl fluoborate, the ammonium fluoride and the photosensitizer in the step (1) is 1: (1.5-2.5): (1.0-2.0): (1.0-3.0): (0.05-0.25), more preferably 1: 2.0: 1.5: 2.0: 0.1.
preferably, the protective atmosphere in step (1) comprises nitrogen and argon, and more preferably, the protective atmosphere is high-purity nitrogen or argon (high purity > 99.999%).
Preferably, the sufficient replacement gas described in step (1) is such that the reaction system is in an oxygen-free environment.
Preferably, the solvent in step (1) is an organic solvent comprising acetonitrile and 1, 2-dichloroethane, more preferably acetonitrile; the amount of the solvent is a usual amount for allowing the reaction to proceed uniformly, and in the present invention, it is preferably 2.0 mL.
Preferably, the visible light in step (1) is a 35W fluorescent lamp, and the reaction is preferably carried out under stirring conditions.
Preferably, the monitoring method for the completion of the reaction in the step (2) is TLC monitoring, and the reaction time is preferably 48 h.
Preferably, the reaction solution is concentrated under reduced pressure in the step (2).
Preferably, the solvent used for column chromatography separation in step (2) is a common separation solvent system, and comprises a mixed solution of petroleum ether and ethyl acetate.
The preferred reaction formula of the present invention is as follows:
compared with the prior art, the invention has the following beneficial effects: the invention provides a method for synthesizing aryl acetylene alkyl sulfone compounds based on alkyl fluoborate, which comprises the steps of utilizing a photosensitizer to act on the alkyl fluoborate under the irradiation of visible light to obtain alkyl free radicals under very mild and simple conditions, then combining the alkyl free radicals with sulfur dioxide to generate alkyl sulfonyl free radicals, carrying out addition reaction on the alkyl sulfonyl free radicals and aryl acetylene bromide, and leaving bromide anions to obtain a target product. The method has the advantages of simple raw material preparation and mild reaction conditions, and provides a simple, convenient and efficient synthetic method for constructing a series of aryl acetylene alkyl sulfone compounds. The method avoids harsh conditions in the synthesis of the traditional sulfonyl compounds, can be used for large-scale industrial preparation, and has good guiding significance and application prospect in the fields of scientific research and industry.
Detailed Description
The method for synthesizing aryl acetylene alkyl sulfones based on alkyl fluoroborate provided by the invention is described in detail with reference to the following specific examples, and it is obvious that the described examples are only a part of the examples of the invention, but not all the examples. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1:
0.2mmol of phenylacetylene bromide, 0.4mmol of sodium metabisulfite, 0.3mmol of cyclopentyl potassium fluoroborate, 0.4mmol of ammonium fluoride and 2.0 mmol% of Mes-Acr are sequentially added into a reaction tube+ClO4 -The reaction tube is plugged with a rubber plug and placed in high-purity nitrogen for ventilation, 2.0mL of acetonitrile is added after the system is in an anaerobic condition, and the mixture is stirred and reacts under the irradiation of a 35W fluorescent lamp. After 48 hours of reaction, the reaction solution is directly concentrated under reduced pressure, column chromatography separation is carried out, and a mixed solution of petroleum ether and ethyl acetate is used as a mobile phase, so that the compound example 1 can be obtained. The yield was 74%.
Structural characterization of compound example 1:
1H NMR(400MHz,CDCl3)：δ7.58(d,J＝7.2Hz,2H),7.52(m,1H),7.42(m,2H),3.87–3.59(m,1H),2.44–2.07(m,4H),1.79(m,4H).13C NMR(101MHz,CDCl3)：δ32.7,131.5,128.7,117.7,92.6,82.5,66.1,27.3,26.0.HRMS(ESI)calcd for C13H14O2S+:235.0787(M+H+),found:235.0781.
example 2:
0.2mmol of phenylacetylene bromide, 0.3mmol of potassium metabisulfite, 0.2mmol of potassium ethylfluoroborate, 0.2mmol of ammonium fluoride and 1.0 mmol% of Mes-Acr are sequentially added into a reaction tube+ClO4 -The reaction tube is plugged with a rubber plug and placed in high-purity nitrogen for ventilation, 2.0mL of 1, 2-dichloroethane is added after the system is in an anaerobic condition, and the reaction is stirred under the irradiation of a 35W fluorescent lamp. After 48 hours of reaction, the reaction liquid is directly decompressed and concentrated, and is separated by column chromatography, and stone is adoptedThe compound example 2 was obtained using a mixed solution of oleyl ether and ethyl acetate as a mobile phase. The yield was 50%.
Structural characterization of compound example 2:
1H NMR(400MHz,CDCl3)：δ7.60(d,J＝7.4Hz,2H),7.52(m,1H),7.43(m,2H),3.31(d,J＝7.3Hz,2H),1.54(t,J＝7.3Hz,3H).13C NMR(101MHz,CDCl3)：δ132.8,131.6,128.7,117.5,92.4,82.6,52.7,7.6.HRMS(ESI)calcd for C10H10O2S+:195.0474(M+H+),found:195.0475.
example 3:
0.2mmol of phenylacetylene bromide, 0.5mmol of sodium metabisulfite, 0.4mmol of potassium tert-butylfluoroborate, 0.6mmol of ammonium fluoride and 5.0 mmol% of Mes-Acr were sequentially added to a reaction tube+ClO4 -The reaction tube is plugged with a rubber plug and placed in high-purity nitrogen for ventilation, 2.0mL of acetonitrile is added after the system is in an anaerobic condition, and the mixture is stirred and reacts under the irradiation of a 35W fluorescent lamp. After 48 hours of reaction, the reaction solution is directly concentrated under reduced pressure, column chromatography separation is carried out, and a mixed solution of petroleum ether and ethyl acetate is used as a mobile phase, so that the compound example 3 can be obtained. The yield was 75%.
Structural characterization of compound example 3:
1H NMR(400MHz,CDCl3)：δ7.60(d,J＝7.4Hz,2H),7.51(m,1H),7.42(m,2H),1.53(s,9H).13C NMR(101MHz,CDCl3)：δ132.7,131.5,128.7,117.8,93.8,80.4,60.9,22.9.HRMS(ESI)calcd for C12H14O2S+:223.0787(M+H+),found:223.0780.
example 4:
to the reaction tube were added 0.2mmol of 4-fluorophenylacetylene bromide, 0.4mmol of sodium metabisulfite, 0.3mmol of potassium cyclopentylfluoroborate, 0.4mmol of ammonium fluoride and 2.0 mmol% of Mes-Acr in this order+ClO4 -The reaction tube is plugged with a rubber plug and placed in high-purity nitrogen for ventilation, 2.0mL of acetonitrile is added after the system is in an anaerobic condition, and the mixture is stirred and reacts under the irradiation of a 35W fluorescent lamp. After 48 hours of reaction, the reaction solution is directly concentrated under reduced pressure, column chromatography separation is carried out, and a mixed solution of petroleum ether and ethyl acetate is used as a mobile phase, so that the compound example 4 can be obtained. The yield was 54%.
Structural characterization of compound example 4:
1H NMR(400MHz,CDCl3)：δ7.61(d,J＝6.0Hz,2H),7.14(m,2H),3.78–3.60(m,1H),2.40–2.05(m,2H),1.99–1.69(m,2H).13C NMR(101MHz,CDCl3)：δ165.6,135.1(d,J＝9.0Hz),116.4(d,J＝22.4Hz),91.5,82.6,66.1,27.3,26.0.HRMS(ESI)calcd for C13H13FO2S+:253.0693(M+H+),found:253.0695.
example 5:
to the reaction tube were added 0.2mmol of 4-trifluoromethylphenylacetylene bromide, 0.4mmol of sodium metabisulfite, 0.3mmol of cyclopentylpotassium fluoroborate, 0.4mmol of ammonium fluoride and 2.0 mmol% of Mes-Acr in this order+ClO4 -The reaction tube is plugged with a rubber plug and placed in high-purity nitrogen for ventilation, 2.0mL of acetonitrile is added after the system is in an anaerobic condition, and the mixture is stirred and reacts under the irradiation of a 35W fluorescent lamp. After the TCL monitoring reaction is completed, directly carrying out reduced pressure concentration on the reaction liquid, carrying out column chromatography separation, and using a mixed liquid of petroleum ether and ethyl acetate as a mobile phase to obtain a compound example 5. The yield was 58%.
Structural characterization of compound example 5:
1H NMR(400MHz,CDCl3)：δ7.70(d,J＝2.1Hz,2H),7.26(m,2H),3.77–3.59(m,1H),2.21(m,4H),1.95–1.63(m,4H).13C NMR(101MHz,CDCl3)：δ133.0,125.6,121.6,90.1,84.5,66.1,27.2,25.9.HRMS(ESI)calcd for C14H13F3O2SNa+:325.0481(M+Na+),found:325.0497.
example 6:
to the reaction tube were added 0.2mmol of 3-methylphenylacetylenebromide, 0.4mmol of sodium metabisulfite, 0.3mmol of cyclopentylpotassium fluoroborate, 0.4mmol of ammonium fluoride and 2.0 mmol% of Mes-Acr in this order+ClO4 -The reaction tube is plugged with a rubber plug and placed in high-purity nitrogen for ventilation, 2.0mL of acetonitrile is added after the system is in an anaerobic condition, and the mixture is stirred and reacts under the irradiation of a 35W fluorescent lamp. After 48 hours of reaction, the reaction solution was directly concentrated under reduced pressure, column chromatography was performed, and a mixed solution of petroleum ether and ethyl acetate was used as a mobile phase, whereby compound example 6 was obtained. The yield was 62%.
Structural characterization of compound example 6:
1H NMR(400MHz,CDCl3)：δ7.39(m,2H),7.30(d,J＝7.5Hz,2H),3.67(m,1H),2.37(s,3H),2.20(m,4H),1.90–1.68(m,4H).13C NMR(101MHz,CDCl3)：δ138.6,133.1,132.4,129.8,128.6,117.6,92.9,82.2,66.2,27.3,26.0 21.1.HRMS(ESI)calcd for C14H16O2S+:249.0944(M+H+),found:249.0945.
it will be appreciated by persons skilled in the art that the above examples are illustrative only and not intended to be limiting of the invention, and that modifications to the above-described embodiments will fall within the scope of the appended claims provided they fall within the true spirit of the invention.
Claims (8)
1. A method for synthesizing aryl acetylene alkyl sulfone compounds based on alkyl fluoborate is characterized in that under the condition of visible light, a photosensitizer acts on the alkyl fluoborate to generate alkyl free radicals, the alkyl free radicals and sulfur dioxide provided by a sulfur dioxide solid substitute are combined to generate alkyl sulfonyl free radicals, and the alkyl sulfonyl free radicals and aryl acetylene bromine react to obtain the aryl acetylene alkyl sulfone compounds, and comprises the following steps:
(1) at room temperature, adding aryl acetylene bromide, a sulfur dioxide solid substitute, alkyl fluoborate, ammonium fluoride and a photosensitizer into a reaction tube according to a certain molar ratio, placing the reaction tube in a protective atmosphere to fully replace gas, adding a solvent, and reacting under the condition of visible light;
(2) after the reaction is completed, concentrating the reaction liquid, and carrying out column chromatography separation on the concentrated reaction liquid to obtain an aryl acetylene alkyl sulfone compound;
wherein the sulfur dioxide solid substitute is sodium metabisulfite, potassium metabisulfite or DABCO.(SO2)2At least one of;
the aryl of the aryl acetylene bromide is an aryl with or without an electron-withdrawing group or an electron-donating group, the electron-withdrawing group is at least one of fluorine, chlorine, bromine or trifluoromethyl, and the electron-donating group is at least one of alkyl, methoxy or phenyl;
the photosensitizer is Mes-Acr+ClO4 -。
2. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoroborate as claimed in claim 1, wherein the alkyl fluoroborate is potassium alkyl fluoroborate.
3. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoroborate as claimed in claim 1 or 2, wherein the alkyl group of the alkyl fluoroborate is at least one of ethyl, propyl, tert-butyl, cyclopentyl or cyclohexyl.
4. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoborate as claimed in claim 1, wherein the molar ratio of the aryl acetylene bromide, the sulfur dioxide solid substitute, the alkyl fluoborate, the ammonium fluoride and the photosensitizer in the step (1) is 1: (1.5-2.5): (1.0-2.0): (1.0-3.0): (0.05-0.25).
5. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoroborate as claimed in claim 1, wherein the protective atmosphere in the step (1) is at least one of nitrogen or argon.
6. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoborate as claimed in claim 1, wherein the solvent in the step (1) is an organic solvent, and the amount of the solvent is 10mL/mmol based on the amount of the aryl acetylene bromide.
7. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoroborate as claimed in claim 6, wherein the organic solvent is at least one of acetonitrile or 1, 2-dichloroethane.
8. The method for synthesizing the aryl acetylene alkyl sulfone compound based on the alkyl fluoroborate as claimed in claim 1, wherein the visible light in the step (1) is a 35W fluorescent lamp.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910935440.9A CN110698369B (en) | 2019-09-29 | 2019-09-29 | Method for synthesizing aryl acetylene alkyl sulfone compound based on alkyl fluoborate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910935440.9A CN110698369B (en) | 2019-09-29 | 2019-09-29 | Method for synthesizing aryl acetylene alkyl sulfone compound based on alkyl fluoborate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110698369A CN110698369A (en) | 2020-01-17 |
| CN110698369B true CN110698369B (en) | 2021-08-24 |
Family
ID=69196415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910935440.9A Expired - Fee Related CN110698369B (en) | 2019-09-29 | 2019-09-29 | Method for synthesizing aryl acetylene alkyl sulfone compound based on alkyl fluoborate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110698369B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112574077B (en) * | 2020-12-12 | 2022-02-22 | 河南大学 | Method for synthesizing sulfone compound under photocatalysis condition |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106045955A (en) * | 2016-07-11 | 2016-10-26 | 复旦大学 | Method for preparing 3-sulfonyl coumarin compound |
| CN109336860A (en) * | 2018-10-12 | 2019-02-15 | 嘉兴学院 | A kind of 3- mesyl -2- replaces the preparation method of benzothienyl compounds |
-
2019
- 2019-09-29 CN CN201910935440.9A patent/CN110698369B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106045955A (en) * | 2016-07-11 | 2016-10-26 | 复旦大学 | Method for preparing 3-sulfonyl coumarin compound |
| CN109336860A (en) * | 2018-10-12 | 2019-02-15 | 嘉兴学院 | A kind of 3- mesyl -2- replaces the preparation method of benzothienyl compounds |
Non-Patent Citations (3)
| Title |
|---|
| Visible-Light-Induced Chemoselective Deboronative Alkynylation under Biomolecule-Compatible Conditions;Hanchu Huang 等;《Journal of the American Chemical Society》;20140203;第136卷;第2280-2283页 * |
| 利用多样性导向合成策略构建几类小分子化合物骨架;叶盛青;《复旦大学博士学位论文》;20150331;第1-295页 * |
| 氧杂蒽类有机染料在可见光诱导有机合成中的应用;徐雯秀 等;《有机化学》;20180716;第38卷;第2807-2832页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110698369A (en) | 2020-01-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109336860B (en) | Preparation method of 3-methylsulfonyl-2-substituted benzothiophene compound | |
| CN110698369B (en) | Method for synthesizing aryl acetylene alkyl sulfone compound based on alkyl fluoborate | |
| CN109134326A (en) | A kind of synthetic method of S- arylthio sulfone compound | |
| CN105198683A (en) | Preparation method of sulfuryl fluoride compound | |
| CN110683971B (en) | Method for synthesizing aryl acetylene alkyl sulfone compounds based on Hantzsch esters | |
| CN113880800B (en) | Synthetic method of methylsulfonyl substituted thioflavonoid compound | |
| CN114573512B (en) | Method for synthesizing C2-difluoro alkyl benzimidazole derivative | |
| CN111269153B (en) | Synthetic method of alpha, alpha-difluoro-beta-carbonyl sulfone compound | |
| CN111072531B (en) | Synthesis method of beta-ketosulfone compound | |
| CN116496316A (en) | Method for synthesizing fluorine alkenyl phosphorus | |
| CN112939891B (en) | Method for preparing biphenyl benzothiazole compound | |
| CN115010635B (en) | Synthesis method of (E) -beta-selenenyl sulfone compound | |
| CN112979580A (en) | Method for preparing alkyl benzothiazole derivative under visible light | |
| CN111892553A (en) | Method for synthesizing ammonium acetate mediated benzothiazole compound | |
| CN113816884B (en) | Synthetic method of arylthio naphthol, naphthylamine compound and thiophenyl indole compound | |
| CN115490621B (en) | Preparation method of iodo-bicyclo [1.1.1] pentane derivative | |
| CN115286547B (en) | Method for synthesizing aryl benzyl thioether compound | |
| CN111138323B (en) | Preparation method of sulfonamide compound | |
| CN111217766A (en) | method for synthesizing visible light-promoted beta-amino selenide | |
| CN117986097B (en) | Novel method for Suzuki coupling based on photocatalysis | |
| CN103980201A (en) | Preparation method of sulfonyl-containing completely substituted parazole | |
| Gillani et al. | A Facile Synthesis of Derivatives of Tetraphenylcyclopentadienone and a Linear Polymer | |
| CN114411267B (en) | Method for constructing beta-aliphatic substituted ketone compound by On-DNA reaction | |
| CN113527154B (en) | Method for preparing N-sulfimide | |
| CN114773245B (en) | Preparation method of trifluoromethyl selenoether |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210824 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |