CN115572248A - Method for preparing beta-aminosulfone compound - Google Patents
Method for preparing beta-aminosulfone compound Download PDFInfo
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- CN115572248A CN115572248A CN202211389942.4A CN202211389942A CN115572248A CN 115572248 A CN115572248 A CN 115572248A CN 202211389942 A CN202211389942 A CN 202211389942A CN 115572248 A CN115572248 A CN 115572248A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 55
- 238000000034 method Methods 0.000 title claims abstract description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 120
- -1 olefin compounds Chemical class 0.000 claims abstract description 49
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 35
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000007259 addition reaction Methods 0.000 claims abstract description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 102
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 15
- 239000007810 chemical reaction solvent Substances 0.000 claims description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 150000007530 organic bases Chemical class 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 150000003141 primary amines Chemical class 0.000 claims description 6
- 150000003335 secondary amines Chemical class 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 150000003512 tertiary amines Chemical class 0.000 claims description 6
- 229940043279 diisopropylamine Drugs 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000003172 aldehyde group Chemical group 0.000 claims description 3
- 150000001345 alkine derivatives Chemical class 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 abstract description 22
- 238000003786 synthesis reaction Methods 0.000 abstract description 20
- 230000015572 biosynthetic process Effects 0.000 abstract description 17
- 150000003254 radicals Chemical class 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- 238000007342 radical addition reaction Methods 0.000 abstract description 5
- 239000000758 substrate Substances 0.000 abstract description 5
- 230000002194 synthesizing effect Effects 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000012043 crude product Substances 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 16
- 238000001228 spectrum Methods 0.000 description 16
- 238000004809 thin layer chromatography Methods 0.000 description 16
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 13
- DKENIBCTMGZSNM-UHFFFAOYSA-N benzenesulfinyl chloride Chemical compound ClS(=O)C1=CC=CC=C1 DKENIBCTMGZSNM-UHFFFAOYSA-N 0.000 description 13
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 12
- 229910052786 argon Inorganic materials 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000011521 glass Substances 0.000 description 11
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000012467 final product Substances 0.000 description 8
- 229910052739 hydrogen Inorganic materials 0.000 description 8
- 239000001257 hydrogen Substances 0.000 description 8
- 238000002390 rotary evaporation Methods 0.000 description 8
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- BOVQCIDBZXNFEJ-UHFFFAOYSA-N 1-chloro-3-ethenylbenzene Chemical compound ClC1=CC=CC(C=C)=C1 BOVQCIDBZXNFEJ-UHFFFAOYSA-N 0.000 description 1
- KTZVZZJJVJQZHV-UHFFFAOYSA-N 1-chloro-4-ethenylbenzene Chemical compound ClC1=CC=C(C=C)C=C1 KTZVZZJJVJQZHV-UHFFFAOYSA-N 0.000 description 1
- JZHGRUMIRATHIU-UHFFFAOYSA-N 1-ethenyl-3-methylbenzene Chemical compound CC1=CC=CC(C=C)=C1 JZHGRUMIRATHIU-UHFFFAOYSA-N 0.000 description 1
- CEWDRCQPGANDRS-UHFFFAOYSA-N 1-ethenyl-4-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=C(C=C)C=C1 CEWDRCQPGANDRS-UHFFFAOYSA-N 0.000 description 1
- JWVTWJNGILGLAT-UHFFFAOYSA-N 1-ethenyl-4-fluorobenzene Chemical compound FC1=CC=C(C=C)C=C1 JWVTWJNGILGLAT-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- KXYAVSFOJVUIHT-UHFFFAOYSA-N 2-vinylnaphthalene Chemical compound C1=CC=CC2=CC(C=C)=CC=C21 KXYAVSFOJVUIHT-UHFFFAOYSA-N 0.000 description 1
- NZEDMAWEJPYWCD-UHFFFAOYSA-N 3-prop-2-enylsulfonylprop-1-ene Chemical compound C=CCS(=O)(=O)CC=C NZEDMAWEJPYWCD-UHFFFAOYSA-N 0.000 description 1
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical class NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
- C07C315/06—Separation; Purification; Stabilisation; Use of additives
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- 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 chemical synthesis, and particularly relates to a method for preparing a beta-aminosulfone compound. The invention carries out addition reaction on sulfinyl chloride, hydroximes and olefin compounds in the presence of triethylamine to synthesize the beta-aminosulfone compounds. The invention realizes the synthesis of the beta-aminosulfone compound by utilizing the free radical addition reaction between the sulfinyl chloride, the hydroximes and the olefin for the first time, and fills the blank in the prior art; the method has mild process conditions, short flow, simple steps and wide substrate applicability, and meets the requirements of industrial production; the method for synthesizing the beta-aminosulfone compound has high product yield which can reach 86 percent, and the generated beta-aminosulfone compound has wide application in medicines. Therefore, the method has important application value.
Description
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for preparing a beta-aminosulfone compound.
Background
The beta-aminosulfone compound has various biological characteristics, is a skeleton compound with strong functions, generally exists in natural products and drug molecules, and is widely applied to the fields of medicines, materials and the like. The modification of the structure of the beta-aminosulfone compound has important significance in drug discovery and drug structure improvement.
The chiral sulfur atoms are commonly found in commercially available drugs and most biologically active molecules that contain β -aminosulfone compounds. In recent years, although the research on the catalytic asymmetric synthesis of enantiomer-rich sulfones has been greatly advanced, the construction of chiral sulfones through enantioselective free radical reaction is still challenging, and only a few studies have reported the synthesis of chiral β amino sulfones using asymmetric conjugate addition. For example, it has been found that an enantioselective addition reaction of allylsulfone with α, β -unsaturated N-acylpyrazole catalyzed by photo-induction and chiral Rh achieves an asymmetric addition product by sulfonyl radical addition in the reaction system. It has also been investigated to use sulfinic acid to generate sulfonyl radicals to obtain chiral β -sulfonylcarbonyl compounds. Although some researches have made progress in asymmetric conjugate addition synthesis of chiral beta-aminosulfone compounds, all the researches adopt photoinduced transition metal addition reaction, the metal-catalyzed free radical addition reaction is still limited by a substrate, and meanwhile, the coordination of an auxiliary group and a metal catalyst center also has important influence on the activation of the substrate and the control of stereochemistry, so that the photoinduced transition metal addition reaction needs high-temperature conditions and a metal catalyst, and has poor functional group compatibility and low reaction efficiency.
In conclusion, it is necessary to develop a new method for preparing β -aminosulfone compounds, which makes the reaction conditions milder, does not need high temperature conditions and metal catalysts, and has high reaction efficiency and better functional group compatibility.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a method for preparing beta-aminosulfone compounds, which utilizes the addition reaction of sulfinyl chloride, hydroximes and olefin free radicals to synthesize the beta-aminosulfone compounds and realizes the large-scale preparation of the beta-aminosulfone compounds.
In order to achieve the purpose, the invention adopts the technical scheme that:
the invention discloses a method for preparing a beta-aminosulfone compound, which comprises the following steps: dissolving sulfinyl chloride shown in formula 1, hydroximes shown in formula 2 and olefin compounds shown in formula 3 in a reaction solvent, and then performing addition reaction in the presence of triethylamine to synthesize a beta-aminosulfone compound shown in formula 4:
in the formulae 1 to 4, R 1 Independently selected from the group consisting of phenyl ring, alkoxy, alkyl, primary amine, secondary amine, tertiary amine, sulfur, alkyne; r 2 Independently selected from alkyl, primary amine, secondary amine, tertiary amine, sulfur; r 3 -R 4 Is H or alkyl; r 5 Independently selected from cyano, nitro, ester groups and various aromatic rings; the alkyl, benzene ring and aromatic ring are allowed to have substituents, and the substituents are C 1 ～C 6 Alkyl of (2), or C 1 ～C 6 Or phenyl, or benzyloxy, or nitro, or halogen, or cyano, or an ester group, or an aldehyde group, or trifluoromethyl.
Preferably, the molar ratio of the sulfinyl chloride shown in formula 1, the hydroximic acid shown in formula 2 and the olefin compound shown in formula 3 is 0.5-2:0.5-2, wherein the molar concentration of the olefin compound in the reaction solvent is 0.5-2mol/L, and the usage amount of the triethylamine is 0.5-3mol% of the total molar amount of the olefin compound.
More preferably, the addition equivalent of both the sulfinyl chloride represented by formula 1 and the hydroxamic acid represented by formula 2 is 1.5eq.
Preferably, the organic base comprises at least one of triethylamine, diisopropylamine, and pyridine. More preferably, the organic base is triethylamine.
Preferably, the temperature of the addition reaction is-40-40 ℃ and the time is 2-24 hours. More preferably, the temperature of the addition reaction is 40 ℃ and the time is 8-12h.
Further, during the reaction, firstly, the sulfinyl chloride shown in the formula 1, the hydroximes shown in the formula 2 and triethylamine are dissolved in a reaction solvent, and after a period of reaction, styrene is added to continue the reaction, wherein the total reaction time is 2-24 hours.
Preferably, the reaction solvent includes at least one of ethyl acetate, dimethyl sulfoxide, acetonitrile, N-dimethylformamide, and tetrahydrofuran.
According to the invention, the sulfinyl chloride, the hydroximes and the olefin compounds are subjected to addition reaction in the presence of triethylamine to synthesize the beta-aminosulfone compounds, so that the beta-aminosulfone compounds are synthesized by utilizing the free radical addition reaction among the sulfinyl chloride, the hydroximes and the olefin for the first time, and the blank in the prior art is filled. Compared with the traditional photoinduced transition metal addition reaction, the beta-aminosulfone compound is synthesized by utilizing the addition reaction among the sulfinyl chloride, the hydroximes and the olefin, the reaction condition is milder, a high-temperature condition and a metal catalyst are not needed, the reaction is efficient, and the functional group compatibility is better. Meanwhile, the method has the advantages of mild process conditions, short flow, simple steps and wide substrate applicability, and meets the requirements of industrial production; the method for synthesizing the beta-aminosulfone compound has the advantages that the product yield is high and can reach 86%, and the generated beta-aminosulfone compound is widely applied to medicines and has important application value.
Preferably, the sulfinyl chloride is selected from any one of the following structural formulas:
preferably, the hydroxamic acid is selected from any one of the following structural formulas:
preferably, the olefinic compound is selected from any one of the following structural formulas:
preferably, the beta-aminocarbonyl compound is selected from any one of the following structural formulas:
more preferably, the structural formulas of the sulfinyl chloride and the hydroxamic acid are respectively as follows:
the olefin compound is selected from any one of the following structural formulas:
the beta-amino carbonyl compound is selected from any one of the following structural formulas:
compared with the prior art, the invention has the beneficial effects that:
the invention discloses a method for synthesizing beta-aminosulfone compounds by adding sulfenyl chloride, hydroximes and olefin free radicals, which leads activated olefin, sulfenyl chloride and hydroximes to carry out bifunctional reaction to obtain the beta-aminosulfone compounds. The invention firstly realizes the generation of sulfonyl free radicals by sulfinyl chloride and hydroximes at low temperature, and then the beta-aminosulfone compound is quickly constructed by the reaction of the sulfonyl free radicals and olefin, thereby filling the gap of the prior art (the beta-aminosulfone compound is not obtained by the free radical addition reaction of sulfinyl chloride, hydroximes and olefin at present). Meanwhile, the method for synthesizing the beta-aminosulfone compound is safe and simple to operate, easily available in raw materials, low in price and high in reaction efficiency; the substrate has wide adaptability and is environment-friendly and beneficial to industrial production. In addition, the yield of the beta-aminocarbonyl compound synthesized by the method is high and can reach 86 percent; the generated beta-aminosulfone compound has wide application in medicine and organic synthesis. Therefore, the method has important application value.
Drawings
FIG. 1 is a scheme of 1-phenyl-2- (phenylsulfonyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 2 is a scheme showing 1-phenyl-2- (phenylsulfonyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 3 is a scheme showing 2- (benzenesulfonyl) -1- (p-tolyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 4 is a scheme showing 2- (benzenesulfonyl) -1- (p-tolyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 5 is a schematic representation of 1- (4-fluorophenyl) -2- (phenylsulfonyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 6 is a schematic representation of 1- (4-fluorophenyl) -2- (phenylsulfonyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 7 is a schematic representation of 1- (4-fluorophenyl) -2- (phenylsulfonyl) ethan-1-amine 19 FNMR spectrogram;
FIG. 8 is a scheme showing that 1- (4-chlorophenyl) -2- (benzenesulfonyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 9 is a drawing of 1- (4-chlorophenyl) -2- (benzenesulfonyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 10 is a schematic representation of 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 11 is a scheme showing the preparation of 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 12 is a scheme showing the preparation of 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine 19 FNMR spectrogram;
FIG. 13 is a scheme showing that 1- (naphthalen-2-yl) -2- (benzenesulfonyl) eth-1-amine 1 HNMR spectrogram;
FIG. 14 is a schematic representation of 1- (naphthalen-2-yl) -2- (benzenesulfonyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 15 is a scheme showing the preparation of 2- (phenylsulfonyl) -1- (m-tolyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 16 is a scheme showing the preparation of 2- (phenylsulfonyl) -1- (m-tolyl) ethan-1-amine 13 CNMR spectrogram;
FIG. 17 is a schematic representation of 1- (3-chlorophenyl) -2- (phenylsulfonyl) ethan-1-amine 1 HNMR spectrogram;
FIG. 18 is 1- (3-chlorophenyl) -2- (phenylsulfonyl) ethan-1-amine 13 CNMR spectrogram.
Detailed Description
The following further describes embodiments of the present invention. It should be noted that the description of the embodiments is provided to help understanding of the present invention, and is not intended to limit the present invention. In addition, the technical features involved in the respective embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.
The experimental procedures in the following examples were carried out by conventional methods unless otherwise specified, and the test materials used in the following examples were commercially available by conventional methods unless otherwise specified.
The invention provides a method for preparing a beta-aminosulfone compound, which utilizes sulfinyl chloride, hydroximes and olefin to synthesize the beta-aminosulfone compound through an addition reaction:
dissolving sulfinyl chloride shown in formula 1, hydroximes shown in formula 2 and olefin compounds shown in formula 3 in a reaction solvent, and carrying out addition reaction in the presence of an organic base to obtain a beta-aminosulfone compound shown in formula 4:
in the formulae 1 to 4, R 1 Independently selected from the group consisting of benzene ring, alkoxy, alkyl, primary amine, secondary amine, tertiary amine, sulfur, alkyne; r is 2 Independently selected from alkyl, primary amine, secondary amine, tertiary amine, sulfur; r is 3 -R 4 Is H or alkyl; r 5 Independently selected from cyano, nitro, ester groups and various aromatic rings.
The alkyl, benzene ring and aromatic ring may have a substituentIs C 1 ～C 6 Alkyl of (2), or C 1 ～C 6 Or phenyl, or benzyloxy, or nitro, or halogen, or cyano, or an ester group, or an aldehyde group, or trifluoromethyl.
Preferably, the molar ratio of the sulfinyl chloride shown in formula 1, the hydroximic acid shown in formula 2 and the olefin compound shown in formula 3 is 0.5-2:0.5-2, wherein the molar concentration of the olefin compound in the reaction solvent is 0.5-2mol/L, and the usage amount of the triethylamine is 0.5-3mol% of the total molar amount of the olefin compound.
Preferably, the organic base comprises at least one of triethylamine, diisopropylamine, and pyridine.
Preferably, the reaction temperature is-40-40 ℃ and the reaction time is 2-24 hours.
Preferably, the reaction solvent includes ethyl acetate, dimethyl sulfoxide, acetonitrile, N-dimethylformamide, and tetrahydrofuran.
To better illustrate the synthesis of β -aminosulfones from the addition of sulfinyl chloride, hydroximes and olefins, examples 1-8 are provided for further illustration (sulfinyl chloride, hydroximes, 3 and 4 of formula 1 are shown in table 1):
EXAMPLE 1 Synthesis of beta-aminosulfones by addition of sulfenyl chloride, hydroximes and alkenes
The beta-aminosulfone compound synthesized in the embodiment is 1-phenyl-2- (benzenesulfonyl) ethyl-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.), acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added to a 20mL dry transparent glass reaction flask, stirred at-20 ℃ for reaction for 3h, followed by addition of styrene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 h). The reaction progress is monitored by Thin Layer Chromatography (TLC), after the reaction is finished, a crude product is obtained by reduced pressure rotary evaporation, and the crude product is separated and purified by a silica gel chromatographic column (an eluent system used by the silica gel chromatography is petroleum ether/ethyl acetate =10/1,2% triethylamine, petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine), so that a final product 1-phenyl-2- (benzenesulfonyl) ethyl-1-amine is obtained, wherein the yield is 58%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (figure 1 and figure 2):
1 H NMR(400MHz,CDCl 3 )δ8.01–7.83(m,2H),7.66(t,J＝7.4Hz,1H),7.57(t,J＝7.7Hz,2H),7.37–7.21(m,5H),4.69(dd,J＝9.9,2.6Hz,1H),3.55(dd,J＝14.0,9.7Hz,1H),3.35(dd,J＝14.1,2.6Hz,1H),2.78(s,2H). 13 C NMR(101MHz,CDCl 3 )δ142.11(s),139.58(s),133.89(s),129.41(s),128.91(s),128.17(s),127.90(s),126.47(s),64.00(s),50.96(s)。
example 2A method for the synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and olefins
The β -aminosulfone compound synthesized in this example is 2- (benzenesulfonyl) -1- (p-tolyl) ethan-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.), acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added to a 20mL dry transparent glass reaction flask, stirred at-20 ℃ for 3h, followed by addition of p-toluylene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 h). The reaction progress is monitored by Thin Layer Chromatography (TLC), after the reaction is finished, a crude product is obtained by reduced pressure rotary evaporation, and the crude product is separated and purified by a silica gel chromatographic column (an eluent system used by the silica gel chromatography is petroleum ether/ethyl acetate =10/1,2% triethylamine, petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine), so that a final product, namely 2- (benzenesulfonyl) -1- (p-tolyl) ethyl-1-amine is obtained, wherein the yield is 84%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 3 and 4);
1 H NMR(400MHz,CDCl 3 )δ7.98–7.85(m,2H),7.68–7.63(m,1H),7.58–7.53(m,1H),7.16(d,J＝19.7Hz,2H),7.09(d,J＝17.6Hz,1H),4.60(dd,J＝9.9,2.4Hz,1H),3.42(dd,J＝14.0,9.9Hz,1H),3.28(dd,J＝14.0,2.4Hz,1H),2.30(s,3H),1.95(s,2H). 13 C NMR(101MHz,CDCl 3 )δ139.96(s),139.75(s),137.77(s),133.82(s),129.44(d,J＝12.0Hz),127.87(s),126.19(s),64.66(s),50.69(s),21.05(s)。
example 3 a method for the synthesis of beta-aminosulfones by the addition of sulfenyl chloride, hydroximes and olefins
The beta-aminosulfone compound synthesized in the embodiment is 1- (4-fluorophenyl) -2- (benzenesulfonyl) ethyl-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.), acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added to a 20mL dry transparent glass reaction flask, stirred at-20 ℃ for 3h, followed by addition of 4-fluorostyrene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 h). The reaction progress is monitored by Thin Layer Chromatography (TLC), after the reaction is finished, a crude product is obtained by reduced pressure rotary evaporation, and the crude product is separated and purified by a silica gel chromatographic column (an eluent system used by the silica gel chromatography is petroleum ether/ethyl acetate =10/1,2% triethylamine, petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine), so that a final product 1- (4-fluorophenyl) -2- (benzenesulfonyl) ethyl-1-amine is obtained, wherein the yield is 86%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 5, 6 and 7);
1 H NMR(400MHz,CDCl 3 )δ7.96–7.88(m,2H),7.66(t,J＝7.4Hz,1H),7.57(t,J＝7.7Hz,2H),7.28(dd,J＝8.7,5.3Hz,2H),6.97(t,J＝8.7Hz,2H),4.65(dd,J＝9.8,2.5Hz,1H),3.42(dd,J＝14.0,9.7Hz,1H),3.27(dd,J＝14.0,2.5Hz,1H),2.15(d,J＝6.8Hz,2H). 13 C NMR(101MHz,CDCl 3 )δ163.50(s),161.05(s),139.57(s),138.62(s),133.94(s),129.44(s),128.19–127.64(m),115.77(s),115.56(s),64.45(s),50.35(s). 19 F NMR(377MHz,CDCl 3 )δ-114.12(s)。
example 4A method for the synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and olefins
The beta-aminosulfone compound synthesized in the embodiment is 1- (4-chlorphenyl) -2- (benzenesulfonyl) ethyl-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.), acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added to a 20mL dry transparent glass reaction flask, and the mixture was stirred at-20 ℃ for 3 hours, followed by addition of 4-chlorostyrene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 hours). The progress of the reaction was monitored by Thin Layer Chromatography (TLC), after the reaction was completed, crude product was obtained by reduced pressure rotary evaporation, and the crude product was separated and purified by silica gel column chromatography (eluent system used in silica gel chromatography was petroleum ether/ethyl acetate =10/1,2% triethylamine; petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine) to obtain the final product 1- (4-chlorophenyl) -2- (phenylsulfonyl) ethan-1-amine with a yield of 65%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 8 and 9);
1 H NMR(400MHz,CDCl 3 )δ7.90(d,J＝7.1Hz,2H),7.66(t,J＝7.5Hz,1H),7.55(t,J＝7.7Hz,2H),7.24(s,4H),4.63(dd,J＝9.7,2.7Hz,1H),3.43(dd,J＝14.0,9.6Hz,1H),3.27(dd,J＝14.0,2.7Hz,1H),2.39(s,2H). 13 C NMR(101MHz,CDCl 3 )δ141.15(s),139.48(s),133.83(d,J＝28.2Hz),129.46(s),128.96(s),127.85(d,J＝2.0Hz),64.14(s),50.44(s)。
example 5A Synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and alkenes
The β -aminosulfone compound synthesized in this example is 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.), acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added to a 20mL dry transparent glass reaction flask, and the mixture was stirred at-20 ℃ for 3 hours, followed by addition of 4-trifluoromethylstyrene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 hours). The progress of the reaction was monitored by Thin Layer Chromatography (TLC), after the reaction was completed, crude product was obtained by reduced pressure rotary evaporation, and the crude product was separated and purified by silica gel column chromatography (eluent system used in silica gel chromatography was petroleum ether/ethyl acetate =10/1,2% triethylamine; petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine) to obtain the final product 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine with a yield of 52%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 10, fig. 11 and fig. 12);
1 H NMR(400MHz,CDCl 3 )δ7.97–7.84(m,2H),7.70–7.63(m,1H),7.56(t,J＝8.5Hz,4H),7.44(d,J＝8.2Hz,2H),4.74(d,J＝9.7Hz,1H),3.41(dd,J＝13.9,9.7Hz,1H),3.27(dd,J＝14.0,2.6Hz,1H),1.93(s,2H). 13 C NMR(101MHz,CDCl 3 )δ146.77(s),139.48(s),134.02(s),130.12(s),129.47(s),127.84(s),126.85(s),126.28–125.56(m),122.54(s),77.35(s),77.03(s),76.71(s),64.25(s),50.71(s). 19 F NMR(377MHz,CDCl3)δ-62.33–-63.02(m)。
example 6A Synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and alkenes
The beta-aminosulfone compound synthesized in the embodiment is 1- (naphthalene-2-yl) -2- (benzenesulfonyl) ethyl-1-amine:
after replacement with argon three times in a 20mL dry clear glass reaction flask, benzene sulfinyl chloride (formula: 0.3mmol, 1.5eq.), acetone oxime (formula: 0.3mmol, 1.5eq.), dry ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added, reacted at-20 ℃ for 3h with stirring, followed by addition of 2-vinylnaphthalene (formula: 0.2mmol, 1.0eq.), and reacted at 40 ℃ overnight (8-12 h). The reaction progress is monitored by Thin Layer Chromatography (TLC), after the reaction is finished, crude product is obtained by reduced pressure rotary evaporation, and the crude product is separated and purified by silica gel chromatographic column (eluent system used by silica gel chromatography is petroleum ether/ethyl acetate =10/1,2% triethylamine; petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine), so as to obtain the final product: 1- (naphthalen-2-yl) -2- (benzenesulfonyl) ethan-1-amine in 87% yield.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 13 and 14);
1 H NMR(400MHz,CDCl 3 )δ7.98–7.90(m,2H),7.77(t,J＝7.5Hz,3H),7.65–7.60(m,1H),7.56–7.50(m,1H),7.49–7.43(m,2H),7.40–7.35(m,1H),4.81(dd,J＝9.8,2.5Hz,1H),3.51(dd,J＝14.0,9.7Hz,1H),3.39(dd,J＝14.0,2.5Hz,1H),2.16(s,2H). 13 C NMR(101MHz,CDCl 3 )δ140.13(s),139.67(s),133.88(s),133.32(s),133.04(s),129.40(s),128.78(s),127.90(d,J＝2.0Hz),127.67(s),126.42(s),126.19(s),125.18(s),124.24(s),64.47(s),51.12(s)。
example 7A Synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and alkenes
The β -aminosulfone compound synthesized in this example is 2- (benzenesulfonyl) -1- (m-tolyl) ethan-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.), acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added to a 20mL dry transparent glass reaction flask, and the mixture was stirred at-20 ℃ for reaction for 3 hours, followed by addition of 3-methylstyrene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 hours). The reaction progress is monitored by Thin Layer Chromatography (TLC), after the reaction is finished, a crude product is obtained by reduced pressure rotary evaporation, and the crude product is separated and purified by a silica gel chromatographic column (an eluent system used by the silica gel chromatography is petroleum ether/ethyl acetate =10/1,2% triethylamine, petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine), so that a final product, namely the 2- (benzenesulfonyl) -1- (m-tolyl) ethyl-1-amine is obtained, and the yield is 70%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 15 and 16);
1 H NMR(400MHz,CDCl 3 )δ7.93(dd,J＝8.4,1.3Hz,2H),7.66(t,J＝7.4Hz,1H),7.56(t,J＝7.7Hz,2H),7.18(t,J＝7.5Hz,1H),7.14–7.03(m,3H),4.61(dd,J＝9.9,2.5Hz,1H),3.47(dd,J＝14.0,9.8Hz,1H),3.32(dd,J＝14.0,2.5Hz,1H),2.30(s,5H). 13 C NMR(101MHz,CDCl 3 )δ142.66(s),139.68(s),138.60(s),133.86(s),129.40(d,J＝2.5Hz),128.77(s),127.87(s),127.02(s),123.39(s),64.42(s),50.94(s),21.37(s)。
example 8A method for the Synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and olefins
The beta-aminosulfone compound synthesized in the embodiment is 1- (3-chlorphenyl) -2- (benzenesulfonyl) ethyl-1-amine:
after replacement with argon three times, benzene sulfinyl chloride (structural formula shown in table 1, 0.3mmol, 1.5eq.) and acetone oxime (structural formula shown in table 1, 0.3mmol, 1.5eq.) were added, dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added, the reaction was stirred at-20 ℃ for 3 hours, followed by addition of 3-chlorostyrene (structural formula shown in table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 hours). The reaction progress is monitored by Thin Layer Chromatography (TLC), after the reaction is finished, crude product is obtained by reduced pressure rotary evaporation, and the crude product is separated and purified by silica gel chromatographic column (eluent system used by silica gel chromatography is petroleum ether/ethyl acetate =10/1,2% triethylamine; petroleum ether/dichloromethane/ethyl acetate =5/5/1,2% triethylamine), so as to obtain the final product: 1- (3-chlorophenyl) -2- (benzenesulfonyl) ethan-1-amine in 75% yield.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product is (fig. 17 and 18);
1 H NMR(400MHz,CDCl 3 )δ7.98–7.87(m,2H),7.67(t,J＝7.4Hz,1H),7.58(t,J＝7.6Hz,2H),7.33(s,1H),7.26–7.17(m,3H),4.64(dd,J＝9.7,2.5Hz,1H),3.40(dd,J＝14.0,9.7Hz,1H),3.28(dd,J＝14.0,2.5Hz,1H),2.14–1.93(m,2H). 13 C NMR(101MHz,CDCl 3 )δ144.93(s),139.51(s),134.68(s),134.01(s),130.15(s),129.46(s),128.17(s),127.86(s),126.63(s),124.61(s),64.29(s),50.63(s)。
TABLE 1 structural formulas and yields of the sulfinyl chlorides, hydroxamates, activated olefins, and products of examples 1-8
EXAMPLE 9 discovery of the influencing factors for the Synthesis of beta-aminosulfones by addition of sulfinyl chloride, hydroximes and alkenes
Taking example 1 as an example, the influence factors of synthesizing the β -aminosulfone compound by the addition of sulfinyl chloride, hydroximes and olefins are explored, and the influence factors are specifically as follows:
(1) Influence of the addition equivalents of sulfinyl chloride and hydroximes on the Synthesis of 1-phenyl-2- (phenylsulfonyl) ethan-1-amine
Compared with example 1, the difference is mainly that the added equivalent of the sulfinyl chloride of formula 1 and the hydroxyoxime of formula 2 (molar ratio of sulfinyl chloride compound to activated olefin) is different, i.e. the added equivalent of benzene sulfinyl chloride and acetone oxime (formula shown in table 1) is 1eq,1.5eq and 2.0eq, respectively.
The specific operation is as follows:
in a 20mL dry transparent glass reaction bottle, after being replaced by argon for three times, 1eq,1.5eq,2.0eq of benzene sulfinyl chloride and acetone oxime, dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.) were added, respectively, and the mixture was stirred at-20 ℃ for reaction for 3 hours, followed by addition of styrene (structural formula shown in Table 1, 0.2mmol, 1.0eq.) and reaction at 40 ℃ overnight (8-12 hours), with yields of 50%,58% and 49%, respectively. The experimental results show that the yield of the compounds of formula 1 and 2 is optimal with the addition of 1.5eq.
(2) Effect of reaction temperature on Synthesis of 1-phenyl-2- (phenylsulfonyl) ethan-1-amine
The difference compared to example 1 is mainly that the reaction temperature was changed, i.e. the reaction was carried out overnight at 0 deg.C, 10 deg.C and 40 deg.C, respectively.
The specific operation is as follows:
after replacement with argon three times in a 20mL dry clear glass reaction flask, benzene sulfinyl chloride (formula: 0.3mmol, 1.5eq.), acetone oxime (formula: 0.3mmol, 1.5eq.), dried ethyl acetate (5 mL) and triethylamine (0.3mmol, 1.5eq.)) were added, the reaction was stirred at-20 ℃ for 3h, followed by addition of styrene (formula: 0.2mmol, 1.0eq.)) and reaction at 0 ℃, 10 ℃,40 ℃ overnight (8-12 h) with yields of 44%, 48%, and 58%, respectively. The experimental results show that the yield is optimal for the reaction at 40 ℃ overnight.
(3) Influence of the type of base added in the reaction on the synthesis of 1-phenyl-2- (phenylsulfonyl) ethan-1-amine
The difference compared to example 1 is mainly that the kind of the organic base used is changed, i.e. the reaction is carried out under triethylamine, diisopropylamine, pyridine respectively.
The specific operation is as follows:
in a 20mL dry transparent glass reaction bottle, after being replaced by argon gas for three times, benzene sulfinyl chloride (the structural formula is shown in Table 1, 0.3mmol, 1.5eq.), acetone oxime (the structural formula is shown in Table 1, 0.3mmol, 1.5eq.), dry ethyl acetate (5 mL) and triethylamine, diisopropylamine and pyridine (0.3mmol, 1.5eq.) are respectively added, the mixture is stirred and reacted for 3h at-20 ℃, then styrene (the structural formula is shown in Table 1, 0.2mmol, 1.0eq.) is added, and the mixture is reacted overnight (8-12 h) at 40 ℃, and the yield is 58%,49% and 44% respectively. The experimental results show that the yield is lower than in example 1 even though the product can be prepared by using other organic bases.
(4) Effect of reaction solvent on Synthesis of 1-phenyl-2- (phenylsulfonyl) ethan-1-amine
The difference compared to example 1 is mainly that the reaction solvent was changed by adding 5mL of dry ethyl acetate, trifluorotoluene, N-dimethylformamide, 1, 2-dichloroethane and dimethylsulfoxide, respectively.
The specific operation is as follows:
after replacement with argon three times in a 20mL dry clear glass reaction flask, benzene sulfinyl chloride (formula: 0.3mmol, 1.5eq.), acetone oxime (formula: 0.3mmol,1.5eq., table 1), triethylamine (0.3mmol, 1.5eq.), and dried ethyl acetate, trifluorotoluene, N-dimethylformamide, 1, 2-dichloroethane, and dimethyl sulfoxide (5 mL) were added as reaction solvents, respectively, and stirred at-20 ℃ for 3h, followed by addition of styrene (formula: 0.2mmol, 1.eq., table 1) and allowed to react overnight (8-12 h) at 40 ℃. The yields were 58%, 52%, 40%, 39% and 47%, respectively. The experimental results show that ethyl acetate, trifluorotoluene, N-dimethylformamide, 1, 2-dichloroethane and dimethyl sulfoxide are all suitable for the reaction, with ethyl acetate being the most preferred.
The embodiments of the present invention have been described in detail above, but the present invention is not limited to the described embodiments. It will be apparent to those skilled in the art that various changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, and the scope of protection is still within the scope of the invention.
Claims (10)
1. A method for preparing beta-aminosulfone compounds is characterized in that sulfinyl chloride shown in a formula 1, hydroximes shown in a formula 2 and olefin compounds shown in a formula 3 are dissolved in a reaction solvent, and then an addition reaction is carried out in the presence of organic alkali to synthesize the beta-aminosulfone compounds shown in a formula 4:
in the formulae 1 to 4, R 1 Independently selected from the group consisting of phenyl ring, alkoxy, alkyl, primary amine, secondary amine, tertiary amine, sulfur, alkyne; r 2 Independently selected from alkyl, primary amine, secondary amine, tertiary amine, sulfur; r 3 -R 4 Is H or alkyl; r 5 Independently selected from cyano, nitro, ester groups and various aromatic rings; the alkyl, benzene ring and aromatic ring are allowed to have substituents, and the substituents are C 1 ～C 6 Alkyl of (2), or C 1 ～C 6 Or phenyl, or benzyloxy, or nitro, or halogen, or cyano, or ester group, or aldehyde group, or trifluoromethyl.
2. The method for preparing a β -aminosulfone compound according to claim 1, wherein the molar ratio of the sulfinyl chloride represented by formula 1, the hydroximic acid represented by formula 2 and the olefin compound represented by formula 3 is 0.5-2:0.5-2, wherein the molar concentration of the olefin compound in the reaction solvent is 0.5-2mol/L, and the usage amount of the triethylamine is 0.5-3mol% of the total molar amount of the olefin compound.
3. The method for preparing a beta-aminosulfone compound according to claim 1, wherein the organic base comprises at least one of triethylamine, diisopropylamine and pyridine.
4. The method for preparing a beta-aminosulfone compound according to claim 1, wherein the temperature of the addition reaction is-40 to 40 ℃ and the time is 2 to 24 hours.
5. The method as claimed in claim 1, wherein the reaction solvent comprises at least one of ethyl acetate, dimethyl sulfoxide, acetonitrile, N-dimethylformamide and tetrahydrofuran.
6. The method for preparing a β -aminosulfone compound according to claim 1, wherein the sulfinyl chloride is selected from any one of the following structural formulas:
7. the method for preparing beta-aminosulfone compound according to claim 1, wherein the hydroxamic acid is selected from any one of the following structural formulas:
8. the method for preparing beta-aminosulfone compound according to claim 1, wherein the alkene compound is selected from any one of the following structural formulas:
9. the method for preparing a β -aminosulfone compound as claimed in claim 1, wherein the β -aminocarbonyl compound is selected from any one of the following structural formulas:
10. the method for preparing a β -aminosulfone compound according to any one of claims 1 to 9, wherein the structural formulas of the sulfinyl chloride and the hydroximes are respectively as follows:
the olefin compound is selected from any one of the following structural formulas:
the beta-aminocarbonyl compound is selected from any one of the following structural formulas:
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| CN113929605A (en) * | 2021-11-12 | 2022-01-14 | 山东大学 | Ortho-sulfonylated arylamine compound and synthesis method thereof |
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