CN112479945A - Method for synthesizing beta-ketosulfone by one-pot method - Google Patents
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- 238000000034 method Methods 0.000 title claims description 39
- 238000005580 one pot reaction Methods 0.000 title claims description 22
- 230000002194 synthesizing effect Effects 0.000 title claims description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 47
- 239000002994 raw material Substances 0.000 claims abstract description 28
- 125000004391 aryl sulfonyl group Chemical class 0.000 claims abstract description 15
- 150000002576 ketones Chemical class 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
- 239000003153 chemical reaction reagent Substances 0.000 claims description 41
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 28
- -1 arylsulfonyl chloride Chemical compound 0.000 claims description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 239000002904 solvent Substances 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical group BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 claims description 14
- 230000035484 reaction time Effects 0.000 claims description 14
- 235000010265 sodium sulphite Nutrition 0.000 claims description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical group CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003444 phase transfer catalyst Substances 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 239000011630 iodine Substances 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical group ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 5
- OJWYYSVOSNWCCE-UHFFFAOYSA-N 2-methoxyethyl hypofluorite Chemical compound COCCOF OJWYYSVOSNWCCE-UHFFFAOYSA-N 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical group OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 238000012546 transfer Methods 0.000 claims description 4
- DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims description 3
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 claims description 2
- 229910000028 potassium bicarbonate Chemical group 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Chemical group 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical group [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 claims description 2
- 235000019252 potassium sulphite Nutrition 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 238000000746 purification Methods 0.000 abstract description 8
- 238000005516 engineering process Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- DOUHZFSGSXMPIE-UHFFFAOYSA-N hydroxidooxidosulfur(.) Chemical compound [O]SO DOUHZFSGSXMPIE-UHFFFAOYSA-N 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000007086 side reaction Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- WTLUZZXXNHRVQD-UHFFFAOYSA-N 2-(4-chlorophenyl)sulfonyl-1-phenylpropan-1-one Chemical compound C=1C=C(Cl)C=CC=1S(=O)(=O)C(C)C(=O)C1=CC=CC=C1 WTLUZZXXNHRVQD-UHFFFAOYSA-N 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- VRJYQIIUEHYEGN-UHFFFAOYSA-N 2-(4-methylphenyl)sulfonyl-1-phenylpropan-1-one Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)C(C)C(=O)C1=CC=CC=C1 VRJYQIIUEHYEGN-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- JJWKPURADFRFRB-UHFFFAOYSA-N carbonyl sulfide Chemical class O=C=S JJWKPURADFRFRB-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007809 chemical reaction catalyst Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
- DDXLVDQZPFLQMZ-UHFFFAOYSA-M dodecyl(trimethyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](C)(C)C DDXLVDQZPFLQMZ-UHFFFAOYSA-M 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical class CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- CEYYIKYYFSTQRU-UHFFFAOYSA-M trimethyl(tetradecyl)azanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCCC[N+](C)(C)C CEYYIKYYFSTQRU-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
Abstract
The invention relates to a preparation method of a beta-ketone sulfone compound, in particular to a synthesis technology using the reaction of alpha-halogenated ketone and aryl sulfonyl chloride, aiming at solving the problems of limited raw material sources, high reaction temperature, long time, low yield and high purification difficulty in the preparation of the beta-ketone sulfone compound in the prior art.
Description
Technical Field
The invention relates to a method for synthesizing beta-ketosulfone by a one-pot method, in particular to a synthesis technology using the reaction of alpha-halogenated ketone and aryl sulfonyl chloride, belonging to the technical field of the manufacture of fine chemical products.
Background
The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.
The sulfone compounds have wide application in organic synthesis, and synthetic chemists particularly pay attention to the sulfone compounds containing functional groups in sulfone derivatives. Wherein the beta-ketosulfone compounds are general synthetic intermediates for preparing different kinds of organic compounds. The beta-ketosulfone can be conveniently converted into heterocyclic compounds such as beta-hydroxy sulfone, vinyl sulfone, alpha-halogenated methyl sulfone, substituted quinoline compounds and the like. However, the inventors found that the synthesis method disclosed at present has the problems of difficult raw material availability, long reaction time, large catalyst dosage, low yield and the like:
1. reacting alpha-haloketone with sodium sulfinate;
however, the sulfinate used as a raw material in the reaction is not easy to obtain and has few varieties, the sulfinate is mainly prepared from sulfonyl chloride, and the yield of the synthesized beta-ketosulfone compound is not high.
2. Oxidation of carbonyl thioethers
However, the raw material beta-carbonyl sulfide for the reaction has the odor of rotten eggs, has certain toxicity and is not easy to obtain.
3. Reaction of aryl alkynes with sulfinic acids
However, the method has long reaction time and low yield, and is not suitable for batch production.
4. Reaction of aryl alkene with sulfinic acid
However, the method uses a large amount of organic solvent, and the iodine simple substance has high toxicity.
5. Reaction of aryl alkynes with sulfonyl chlorides
However, this reaction requires the use of an excess of catalyst and results in low yields.
6. Reaction of alpha-halo ketones with sulfonyl chlorides
However, the reaction catalyst is a noble metal, the cost is high, the whole reaction process is carried out in an organic solvent, the boiling point of the organic solvent is high, the metal reduction coupling is added, the side reactions are more, after the reaction is finished, organic reagent extraction, concentration and silica gel column chromatography purification are needed, the post-treatment operation is complicated, and the purification is difficult.
Disclosure of Invention
The problems of difficult obtainment of raw materials or low reaction yield in the synthesis of various beta-ketosulfone compounds in the prior art are solved, so the invention provides the method for synthesizing the beta-ketosulfone by the one-pot method.
Specifically, the invention is realized by the following technical scheme:
in a first aspect of the invention, the invention provides a one-pot synthesis method of beta-ketosulfone, comprising:
taking aryl sulfonyl chloride and alpha-halogenated ketone as raw materials, firstly adding a reagent A and a reagent B for reaction, then adding the alpha-halogenated ketone, and synthesizing the beta-ketosulfone compound by a one-pot method, wherein the synthetic route is as follows:
wherein, the reagent A is a reducing agent, and the reagent B is bicarbonate;
the R is1Selected from the group consisting of hydrogen, linear or branched alkyl, linear or branched alkoxy and halogen, R2Selected from hydrogen, linear or branched alkyl, linear or branched alkoxy, and X is halogen.
In a second aspect of the invention, the invention provides an application of a method for synthesizing beta-ketosulfone by a one-pot method in preparing beta-ketosulfone.
Has the advantages that:
1) the raw materials used by the method are wide in source, and the commercial reagents of the sulfonyl chloride are more and more easily obtained.
2) Compared with the prior art, the preparation method has the advantages of mild reaction conditions, short time, less catalyst consumption, 81-95% yield, no need of purification and concentration of the product and low purification difficulty.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any methods and materials similar or equivalent to those described herein can be used in the methods of the present invention. The preferred embodiments and materials described herein are intended to be exemplary only.
In order to solve the problems of limited raw material sources, high reaction temperature, long time, low yield and high purification difficulty in the preparation of the beta-ketone sulfone compound in the prior art, the invention provides a method for synthesizing the beta-ketone sulfone compound by using aryl sulfonyl chloride and alpha-halogenated ketone as raw materials through a one-pot method. Specifically, the method comprises the following steps:
in a first aspect of the present invention, the present invention provides a method for synthesizing β -ketosulfone by a one-pot method, comprising:
taking aryl sulfonyl chloride and alpha-halogenated ketone as raw materials, firstly adding a reagent A and a reagent B for reaction, then adding the alpha-halogenated ketone, and synthesizing the beta-ketosulfone compound by a one-pot method, wherein the synthetic route is as follows:
wherein, the reagent A is a reducing agent, and the reagent B is bicarbonate;
the R is1Selected from the group consisting of hydrogen, linear or branched alkyl, linear or branched alkoxy and halogen, R2Selected from hydrogen, linear or branched alkyl, linear or branched alkoxy, and X is halogen.
In one or more embodiments of the invention, R is1Selected from hydrogen, C1-C6 linear or branched alkyl, C1-C6 linear or branched alkoxy and halogen,
preferably, said R is1Selected from hydrogen, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy and halogen,
preferably, said R is1Selected from hydrogen, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine and iodine.
Preferably, said R is1Is positioned at the ortho, meta, or para positions of the sulfonyl chloride functional group, preferably at the para position.
Further, said R2Selected from hydrogen, C1-C6 linear or branched alkyl, C1-C6 linear or branched alkoxy,
preferably, said R is2Selected from hydrogen, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy,
preferably, said R is2Selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, methoxy and ethoxy.
Further, X is selected from fluorine, chlorine, bromine and iodine.
In one or more embodiments of the invention, R is1Selected from hydrogen, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine and iodine, wherein R is2Selected from hydrogen, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy, and X is selected from fluorine, chlorine, bromine and iodine.
Preferably, the aryl sulfonyl chloride is selected from p-toluene sulfonyl chloride, benzene sulfonyl chloride, p-chlorobenzene sulfonyl chloride and p-methoxybenzene sulfonyl chloride, and the alpha-halogenated ketone is selected from 2-bromoacetophenone and 2-chloroacetophenone.
In one or more embodiments of the invention, raw materials of arylsulfonyl chloride, a reagent A and a reagent B are reacted in a solvent C, and alpha-haloketone and a phase transfer catalyst are added for reaction and extraction, so as to obtain the compound.
If all the raw materials are added simultaneously in one step, the reaction yield is low, the number of byproducts is large, and the synthesis value is not high.
Specifically, raw materials of arylsulfonyl chloride, a reagent A and a reagent B are carried out in solvent water, the reaction temperature is 20-100 ℃, and the reaction time is 3-10 hours. The reaction is monitored by TLC, after the arylsulfonyl chloride basically reacts, acetonitrile or ethanol solution of halogenated ketone and a small amount of phase transfer catalyst are added, and the reaction is continued for 2 to 10 hours.
In one or more embodiments of the invention, the agent a is a sulfite, preferably sodium sulfite or potassium sulfite.
Further, the reagent B is sodium bicarbonate or potassium bicarbonate.
In addition to the advantage of low cost of the reaction, the use of sulfite and bicarbonate actually uses the reduction of sulfite to reduce arylsulfonyl chloride to sodium sulfinate for the next substitution reaction. Compared with the coupling reaction with metal, the method reduces the free radical reaction and is beneficial to improving the yield.
In the research process, the invention discovers that the use of metal reduction coupling has more side reactions, complex post-treatment operation and difficult purification. Therefore, the sulfite is selected as the reducing agent, so that the cost is lower than that of metal catalysts such as indium, nickel and the like, and the yield of the prepared product is high.
Further, the molar ratio of the alpha-halo ketone to the arylsulfonyl chloride is 1: 1.0 to 1.5, preferably 1: 1.0-1.2, preferably 1: 1.2.
in one or more embodiments of the present invention, the amount of the substance of the reagent A is 1 to 4 times, preferably 1 to 2 times, and more preferably 2 times that of the reaction raw material arylsulfonyl chloride. When the amount of the reagent A substance is 2 times of that of the aryl sulfonyl chloride serving as a reaction raw material, the product yield is higher.
In one or more embodiments of the present invention, the amount of the reagent B substance is 1 to 4 times, preferably 1 to 2 times, and more preferably 2 times that of the reaction raw material arylsulfonyl chloride. When the amount of the reagent B substance is 2 times of that of the aryl sulfonyl chloride serving as a reaction raw material, the product yield is higher.
In one or more embodiments of the invention, solvent C is an aqueous solution, and the molar ratio to arylsulfonyl chloride is 1 ml: 0.1-0.5mmol, preferably 1 ml: 0.3 mmol.
Further, the alpha-halogenated ketone is dissolved in a solvent D and then reacts with the reacted aryl sulfonyl chloride, wherein the solvent D is ethanol or acetonitrile, and the volume molar ratio of the solvent D to the aryl sulfonyl chloride is 1 ml: 0.1-0.5mmol, preferably 1 ml: 0.3 mmol.
The ethanol or acetonitrile used as a solvent has large polarity and good dissolving and dispersing effects.
Further, the phase transfer catalyst is tetrabutylammonium bromide or other commonly used quaternary ammonium salt type phase transfer catalysts, such as: benzyltriethylammonium chloride (TEBA), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, and the like, and also cyclic crown ethers. When tetrabutylammonium bromide is adopted, the purity and yield of the product are high.
The ratio of phase transfer reagent to arylsulfonyl chloride was 1 mg: 0.1-0.15mmol, preferably 1 mg: 0.12mmol, 1 mg: the purity and the yield of the product are higher under the condition of the proportion of 0.12 mmol. The phase transfer agent is too high in content, aggregation and coating phenomena occur, and the function of the phase transfer agent cannot be exerted.
In one or more embodiments of the invention, the reaction temperature of raw materials of arylsulfonyl chloride, reagent A and reagent B in a solvent C is 20-100 ℃, the reaction time is 3-10h, a solution of alpha-haloketone and a phase transfer catalyst are added, the reaction time is 2-10h, the reaction time is too short, the reaction cannot be completely carried out, the reaction time is too long, and side reactions are easy to occur;
preferably, the reaction temperature of the raw materials of the arylsulfonyl chloride, the reagent A and the reagent B in the solvent C is 50-80 ℃, preferably 70 ℃, and the reaction time is 4-6h, preferably 5 h;
preferably, the solution of the alpha-haloketone and the phase transfer catalyst are added for a reaction time of 4 to 6 hours, preferably 5 hours.
The cost of the sodium sulfite and the sodium bicarbonate used by the invention is far lower than that of the metal catalysts such as indium, nickel and the like in the prior art.
The invention reduces the dosage of the catalyst and shortens the reaction time by designing proper raw material compositions and chemical reagents under specific reagent types and proportions. In the operation steps, the aryl sulfonyl chloride, sodium sulfite and sodium bicarbonate are firstly reacted in aqueous solution, and then acetonitrile or ethanol solvent of halogenated ketone is added for reaction. In the research, the metal reduction coupling is found, so that the side reaction is more, the post-treatment operation is complicated, and the purification is difficult. In addition, the existing reaction needs to use elemental iodine with high toxicity and a solvent DMA (N, N-dimethylacetamide with a boiling point of 164-. The invention uses cheap and low boiling point ethanol and acetonitrile (the boiling point is 81.6 ℃), and the difficulty of purifying the product is low.
In a second aspect of the invention, the invention provides an application of a method for synthesizing beta-ketosulfone by a one-pot method in preparing beta-ketosulfone.
Example 1
Synthesis of 2-p-methyl benzenesulfonyl propiophenone
0.24mmol of p-toluenesulfonyl chloride, 0.48mmol of sodium sulfite, 0.48mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.2mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, after 5 hours of reaction, the organic layer was extracted with dichloromethane and separated by column chromatography to obtain 48.7mg of a white solid with a yield of 89% and mp: 105-and 106 ℃.
1H NMR(400MHz,CDCl3)δ7.97(d,J＝7.8Hz,2H),7.65(d,J＝8.1Hz,2H),7.59(t,J＝7.4Hz,1H),7.46(t,J＝7.8Hz,2H),7.29(d,J＝8.1Hz,2H),5.18(q,J＝6.9Hz,1H),2.41(s,3H),1.55(d,J＝6.9Hz,3H)；13C NMR(100MHz,CDCl3)δ192.5,145.2,136.1,133.8,132.9,129.6,129.4,129.0,128.6,64.7,21.5,13.0.
Example 2:
synthesis of 2-p-methoxybenzenesulfonylpropiophenone
0.24mmol of p-methoxybenzenesulfonyl chloride, 0.48mmol of sodium sulfite, 0.48mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.2mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, and after 7 hours of reaction, the organic layer was extracted with dichloromethane and separated by column chromatography to obtain 49.3mg of a white solid with a yield of 85% and mp:98-100 ℃.
1H NMR(400MHz,CDCl3)δ8.01–7.95(m,2H),7.73–7.67(m,2H),7.61(t,J＝7.4Hz,1H),7.48(t,J＝7.7Hz,2H),6.97(t,J＝5.9Hz,2H),5.16(q,J＝6.9Hz,1H),3.86(s,3H),1.55(d,J＝6.9Hz,3H).
13C NMR(100MHz,CDCl3)δ192.7,164.1,136.2,134.0,131.9,129.1,128.7,127.2,114.0,64.9,55.6,13.2.
Example 3: synthesis of 2-p-chlorobenzenesulfonyl propiophenone
0.24mmol of p-chlorobenzenesulfonyl chloride, 0.48mmol of sodium sulfite, 0.48mmol of sodium bicarbonate and 0.8mL of water are added into a test tube and reacted at 70 ℃ for 5 hours, then 0.2mmol of 2-bromoacetophenone, 0.8mL of acetonitrile solution and 2mg of tetrabutylammonium bromide are added, after 5 hours of reaction, an organic layer is extracted by dichloromethane and separated by column chromatography to obtain 56mg of white solid with the yield of 95 percent and 118 percent and 119 ℃ respectively.
1H NMR(400MHz,CDCl3)δ7.94(d,J＝7.9Hz,2H),7.83(d,J＝8.4Hz,2H),7.64(t,J＝7.3Hz,1H),7.53–7.46(m,4H),4.74(s,2H).
13C NMR(100MHz,CDCl3)δ187.9,141.2,137.1,135.7,134.6,130.2,129.5,129.3,129.0,63.3.
Example 4: synthesis of 2-p-chlorobenzenesulfonyl propiophenone
0.24mmol of p-chlorobenzenesulfonyl chloride, 0.24mmol of sodium sulfite, 0.24mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.2mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, and after 5 hours of reaction, the organic layer was extracted with dichloromethane and separated by column chromatography, 43mg of a white solid, yield 74%, 118 and 119 ℃.
Example 5: synthesis of 2-p-chlorobenzenesulfonyl propiophenone
0.2mmol of p-chlorobenzenesulfonyl chloride, 0.4mmol of sodium sulfite, 0.4mmol of sodium bicarbonate and 0.8mL of water are added into a test tube and reacted at 70 ℃ for 5 hours, then 0.2mmol of 2-bromoacetophenone, 0.8mL of acetonitrile solution and 2mg of tetrabutylammonium bromide are added, after 5 hours of reaction, an organic layer is extracted by dichloromethane and separated by column chromatography to obtain 48mg of white solid with the yield of 82 percent and 118 percent.
In addition, the following experiment was also performed in accordance with the raw material ratio of example 1, and the product yield was measured.
TABLE 1 yield of various sulfonyl chlorides and alpha-haloketones
Comparative example 1
To a test tube were added 0.24mmol of p-toluenesulfonyl chloride, 0.48mmol of sodium sulfite, 0.48mmol of sodium bicarbonate, 0.8mL of water, 0.2mmol of 2-bromoacetophenone in 0.8mL of acetonitrile, and 2mg of tetrabutylammonium bromide, and reacted at 70 ℃ for 10 hours, followed by extraction of the organic layer with dichloromethane and column chromatography to give 3mg of a white solid in 5% yield.
Comparative example 2
To a test tube were added 0.24mmol of p-toluenesulfonyl chloride, 0.6mmol of Mn, and 0.02mmol of I20.8mL of N-dimethylacetamide was reacted at 70 ℃ for 5 hours, and then 0.2mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, and after 5 hours of reaction, the organic layer was extracted with dichloromethane and subjected to column chromatography to obtain 7mg of a white solid with a yield of 13%.
Comparative example 3
0.24mmol of p-chlorobenzenesulfonyl chloride, 0.48mmol of sodium sulfite, 0.48mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.1mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, and after 5 hours of reaction, the organic layer was extracted with dichloromethane and separated by column chromatography to obtain 28mg of a white solid with a yield of 48%.
Comparative example 4
0.24mmol of p-chlorobenzenesulfonyl chloride, 0.48mmol of sodium sulfite, 0.48mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.4mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, and after 5 hours of reaction, the organic layer was extracted with dichloromethane and separated by column chromatography to obtain 52mg of a white solid with a yield of 88%.
When the dosage of the 2-bromoacetophenone is too high, the yield can not be increased any more, but the cost is too high and the practical significance is lacked.
Comparative example 5
0.24mmol of p-chlorobenzenesulfonyl chloride, 0.1mmol of sodium sulfite, 0.1mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.4mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto and reacted for 5 hours, and then the organic layer was extracted with dichloromethane and separated by column chromatography to obtain 17mg of a white solid with a yield of 29%.
Comparative example 6
0.24mmol of p-chlorobenzenesulfonyl chloride, 1.0mmol of sodium sulfite, 1.0mmol of sodium bicarbonate and 0.8mL of water were added to a test tube and reacted at 70 ℃ for 5 hours, then 0.4mmol of 2-bromoacetophenone in 0.8mL of acetonitrile and 2mg of tetrabutylammonium bromide were added thereto, and after 5 hours of reaction, the organic layer was extracted with dichloromethane and separated by column chromatography to obtain 22mg of a white solid with a yield of 37%.
It can be seen from the data obtained in the examples and comparative examples that the product yield is directly influenced by any change in the kind, ratio and operation sequence of the raw materials of the present invention.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method for synthesizing beta-ketosulfone by a one-pot method is characterized by comprising the following steps:
taking aryl sulfonyl chloride and alpha-halogenated ketone as raw materials, firstly adding a reagent A and a reagent B for reaction, then adding the alpha-halogenated ketone, and synthesizing the beta-ketosulfone compound by a one-pot method, wherein the synthetic route is as follows:
wherein, the reagent A is a reducing agent, and the reagent B is bicarbonate;
the R is1Selected from the group consisting of hydrogen, linear or branched alkyl, linear or branched alkoxy and halogen, R2Selected from hydrogen, linear or branched alkyl, linear or branched alkoxy, and X is halogen.
2. The one-pot method for synthesizing beta-ketosulfone of claim 1, wherein,
the R is1Selected from hydrogen, C1-C6 linear or branched alkyl, C1-C6 linear or branched alkoxy and halogen,
preferably, said R is1Selected from hydrogen, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy and halogen,
preferably, said R is1Selected from hydrogen, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine, iodine;
preferably, said R is1Is positioned at the ortho position, the meta position and the para position of the sulfonyl chloride functional group, and is preferably the para position;
further, said R2Selected from hydrogen, C1-C6 linear or branched alkyl, C1-C6 linear or branched alkoxy,
preferably, said R is2Selected from hydrogen, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy,
preferably, said R is2Selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, methoxy and ethoxy;
further, X is selected from fluorine, chlorine, bromine, iodine;
preferably, the aryl sulfonyl chloride is selected from p-toluene sulfonyl chloride, benzene sulfonyl chloride, p-chlorobenzene sulfonyl chloride and p-methoxybenzene sulfonyl chloride, and the alpha-halogenated ketone is selected from 2-bromoacetophenone and 2-chloroacetophenone.
3. The one-pot method for synthesizing beta-ketosulfone of claim 1, wherein,
the R is1Selected from hydrogen, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, fluorine, chlorine, bromine and iodine, wherein R is2Selected from hydrogen, C1-C3 linear or branched alkyl, C1-C3 linear or branched alkoxy, and X is selected from fluorine, chlorine, bromine and iodine.
4. The one-pot method for synthesizing β -ketosulfone of claim 1, comprising:
reacting raw materials of arylsulfonyl chloride, a reagent A and a reagent B in a solvent C, adding alpha-haloketone and a phase transfer catalyst, and carrying out reaction and extraction to obtain the compound.
5. The one-pot method for synthesizing beta-ketosulfone according to claim 4, wherein,
the reagent A is sulfite, preferably sodium sulfite or potassium sulfite;
further, the reagent B is sodium bicarbonate or potassium bicarbonate;
further, the molar ratio of the alpha-halo ketone to the arylsulfonyl chloride is 1: 1.0 to 1.5, preferably 1: 1.0-1.2, preferably 1: 1.2.
6. the one-pot method for synthesizing beta-ketosulfone according to claim 4, wherein,
the amount of the reagent A substance is 1 to 4 times, preferably 1 to 2 times, and more preferably 2 times that of the reaction raw material arylsulfonyl chloride.
7. The one-pot method for synthesizing beta-ketosulfone according to claim 4, wherein,
the amount of the reagent B substance is 1 to 4 times, preferably 1 to 2 times, and more preferably 2 times that of the reaction raw material arylsulfonyl chloride.
8. The one-pot method for synthesizing beta-ketosulfone according to claim 4, wherein,
the solvent C is an aqueous solution, and the volume molar ratio of the solvent C to the arylsulfonyl chloride is 1 ml: 0.1-0.5mmol, preferably 1 ml: 0.3 mmol;
further, the alpha-halogenated ketone is dissolved in a solvent D and then reacts with the reacted aryl sulfonyl chloride, wherein the solvent D is ethanol or acetonitrile, and the volume molar ratio of the solvent D to the aryl sulfonyl chloride is 1 ml: 0.1-0.5mmol, preferably 1 ml: 0.3 mmol;
further, the ratio of phase transfer reagent to arylsulfonyl chloride was 1 mg: 0.1-0.15mmol, preferably 1 mg: 0.12 mol.
9. The one-pot method for synthesizing beta-ketosulfone according to claim 4, wherein the reaction temperature of raw materials of arylsulfonyl chloride, reagent A and reagent B in the solvent C is 20-100 ℃, the reaction time is 3-10h, the solution of alpha-haloketone and the phase transfer catalyst are added, and the reaction time is 2-10 h;
preferably, the reaction temperature of the raw materials of the arylsulfonyl chloride, the reagent A and the reagent B in the solvent C is 50-80 ℃, preferably 70 ℃, and the reaction time is 4-6h, preferably 5 h;
preferably, the solution of the alpha-haloketone and the phase transfer catalyst are added for a reaction time of 4 to 6 hours, preferably 5 hours.
10. Use of the one-pot synthesis method of β -ketosulfone according to any of claims 1 to 9 for the preparation of β -ketosulfone.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6162841A (en) * | 1995-09-11 | 2000-12-19 | Lamberti S.P.A. | Betaketosulphones derivatives suitable to the use as polymerization photoinitiators and photopolymerizable systems containing the same |
| CN107286062A (en) * | 2017-06-16 | 2017-10-24 | 江南大学 | A kind of synthetic method of β ketone sulphones |
-
2020
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6162841A (en) * | 1995-09-11 | 2000-12-19 | Lamberti S.P.A. | Betaketosulphones derivatives suitable to the use as polymerization photoinitiators and photopolymerizable systems containing the same |
| CN107286062A (en) * | 2017-06-16 | 2017-10-24 | 江南大学 | A kind of synthetic method of β ketone sulphones |
Non-Patent Citations (4)
| Title |
|---|
| C. CURTI等: ""Rapid synthesis of sulfone derivatives as potential anti-infectious agents"", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| DMITRY DAR’IN等: ""Facile One-Pot Access to α-Diazo-β-ketosulfones from Sulfonyl Chlorides and α-Haloketones"", 《SYNTHESIS》 * |
| LUCIE PALOQUE等: ""Synthesis and evaluation of monoamidoxime derivatives: Toward new antileishmanial compounds"", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| SAROSH IQBAL等: ""Synthesis of β-Ketosulfone Derivatives As New Non-Cytotoxic Urease Inhibitors In Vitro"", 《MEDICINAL CHEMISRTY》 * |
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