CN115572248B - Method for preparing beta-amino sulfone compound - Google Patents
Method for preparing beta-amino sulfone compound Download PDFInfo
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- CN115572248B CN115572248B CN202211389942.4A CN202211389942A CN115572248B CN 115572248 B CN115572248 B CN 115572248B CN 202211389942 A CN202211389942 A CN 202211389942A CN 115572248 B CN115572248 B CN 115572248B
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- 238000000034 method Methods 0.000 title claims abstract description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 117
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 58
- -1 olefin compounds Chemical class 0.000 claims abstract description 44
- 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 abstract description 33
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000007259 addition reaction Methods 0.000 claims abstract description 14
- 230000008569 process Effects 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 102
- 150000001875 compounds Chemical class 0.000 claims description 17
- 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
- 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
- 150000007530 organic bases Chemical class 0.000 claims description 9
- 239000002253 acid Substances 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 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
- 238000002360 preparation method Methods 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 150000001336 alkenes Chemical class 0.000 abstract description 22
- 238000003786 synthesis reaction Methods 0.000 abstract description 19
- 230000015572 biosynthetic process Effects 0.000 abstract description 17
- 239000003814 drug Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 7
- 150000003254 radicals Chemical class 0.000 abstract description 7
- 238000007342 radical addition reaction Methods 0.000 abstract description 6
- 230000002194 synthesizing effect Effects 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 3
- 238000006243 chemical reaction Methods 0.000 description 52
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 238000001228 spectrum Methods 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
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 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
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 12
- 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
- 239000011521 glass Substances 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 125000000217 alkyl group Chemical group 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
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 230000006837 decompression Effects 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 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
- 238000012544 monitoring process Methods 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 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
- KXYAVSFOJVUIHT-UHFFFAOYSA-N 2-vinylnaphthalene Chemical compound C1=CC=CC2=CC(C=C)=CC=C21 KXYAVSFOJVUIHT-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
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 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
- 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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 beta-amino sulfone compounds. According to the invention, the addition reaction of sulfinyl chloride, hydroxamic and olefin compounds is carried out in the presence of triethylamine, and the beta-amino sulfone compounds are synthesized. The invention realizes the synthesis of the beta-amino sulfone compound by utilizing the free radical addition reaction between the sulfinyl chloride, the hydroxamic and the olefin for the first time, and fills the blank of the prior art; the method has the advantages of mild process conditions, short flow, simple steps, wide substrate applicability and meeting the industrial production requirements; the method for synthesizing the beta-amino sulfone compound has high product yield which can reach 86 percent, and the generated beta-amino sulfone compound has wide application in medicines. Therefore, the invention 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 beta-amino sulfone compounds.
Background
The beta-amino sulfone compound has various biological characteristics, is a skeleton compound with powerful functions, is commonly existing in natural products and drug molecules, and is widely applied to the fields of medicines, materials and the like. Modification of the structure of the beta-aminosulfone compound is of great significance in drug discovery and drug structural improvement.
Chiral sulfur atoms are commonly contained in commercially available drugs and most bioactive molecules containing beta-aminosulfone compounds. In recent years, although the research of catalytic asymmetric synthesis of enantiomerically enriched sulfones has been greatly advanced, the construction of chiral sulfones by enantioselective free radical reaction is still challenging, and only few studies have been reported to synthesize chiral beta-amino sulfones using asymmetric conjugated addition. For example, studies have found an enantioselective addition reaction of allylsulfones with α, β -unsaturated N-acyl pyrazoles using photoinduction and chiral Rh catalysis, in which an asymmetric addition product by sulfonyl radical addition is achieved. The formation of sulfonyl radicals using sulfinic acid has also been studied to give chiral β -sulfonyl carbonyl compounds. Although the existing researches have been advanced to a certain extent in the aspect of asymmetric conjugate addition synthesis of chiral beta-amino sulfone compounds, all the researches adopt light-induced transition metal addition reaction, and 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 and stereochemical control of the substrate, so that the light-induced transition metal addition reaction needs high-temperature conditions and the metal catalyst, and has poor functional group compatibility and low reaction efficiency.
In summary, it is necessary to develop a new preparation method of β -aminosulfone compounds, which makes the reaction conditions milder, does not need high temperature conditions and metal catalysts, and has high efficiency and better compatibility of functional groups.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a method for preparing the beta-amino sulfone compound, which utilizes the free radical addition reaction of thionyl chloride, hydroxamic and alkene to synthesize the beta-amino sulfone compound, realizes the large-scale preparation of the beta-amino sulfone compound, has mild reaction conditions and simple process, and can be widely applied to medicines.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the invention discloses a method for preparing beta-amino sulfone compounds, which comprises the following steps: the method comprises the steps of dissolving sulfinyl chloride shown in a formula 1, hydroxamic shown in a formula 2 and olefin compounds shown in a formula 3 in a reaction solvent, and then carrying out an addition reaction in the presence of triethylamine to synthesize a beta-amino sulfone compound shown in a formula 4:
In formulas 1-4, R 1 is independently selected from benzene ring, alkoxy, alkyl, primary amine, secondary amine, tertiary amine, thio, alkyne; r 2 is independently selected from alkyl, primary amine, secondary amine, tertiary amine, sulfur; r 3-R4 is H or alkyl; r 5 is independently selected from cyano, nitro, ester, and various aromatic rings; the alkyl, benzene ring and aromatic ring are allowed to bear substituent groups, and the substituent groups are C 1～C6 alkyl, C 1～C6 alkoxy, phenyl, benzyloxy, nitro, halogen, cyano, ester, aldehyde or trifluoromethyl.
Preferably, the molar ratio of the sulfinyl chloride shown in formula 1, the hydroxamic compound shown in formula 2 and the olefin compound shown in formula 3 is 0.5-2: and the molar concentration of the olefin compound in the reaction solvent is 0.5-2mol/L, and the use amount of the triethylamine is 0.5-3mol% of the total molar amount of the olefin compound.
More preferably, the addition equivalent of the thionyl 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 ℃ for 2-24 hours. More preferably, the temperature of the addition reaction is 40℃and the time is 8-12 hours.
Further, in the reaction, the sulfinyl chloride shown in the formula 1, the hydroxamic and the triethylamine shown in the formula 2 are dissolved in a reaction solvent, and after a period of reaction, styrene is added for continuous 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 hydroxamic and the olefin compound are subjected to addition reaction in the presence of triethylamine to synthesize the beta-amino sulfone compound, so that the synthesis of the beta-amino sulfone compound by utilizing the free radical addition reaction between the sulfinyl chloride, the hydroxamic and the olefin is realized for the first time, and the blank of the prior art is filled. Compared with the traditional light-induced transition metal addition reaction, the beta-amino sulfone compound is synthesized by utilizing the addition reaction between thionyl chloride, hydroxamic and olefin, the reaction condition is milder, high-temperature conditions and metal catalysts 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 industrial production requirements; the method for synthesizing the beta-amino sulfone compound has high product yield which can reach 86 percent, and the generated beta-amino sulfone compound has wide application in medicines and important application value.
Preferably, the thionyl chloride is selected from any one of the following structural formulas:
Preferably, the hydroxamic 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 shown 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:
compared with the prior art, the invention has the beneficial effects that:
The invention discloses a method for synthesizing beta-amino sulfone compounds by utilizing the addition of thionyl chloride, hydroxamic and alkene free radicals, which enables activated alkene, thionyl chloride and hydroxamic to have difunctional reaction to obtain the beta-amino sulfone compounds. The invention realizes that the sulfonyl radical is generated by the sulfinyl chloride and the hydroxamic acid at low temperature for the first time, and then the beta-amino sulfone compound is quickly constructed by the reaction of the sulfonyl radical and the alkene, thus filling the blank of the prior art (the beta-amino sulfone compound is not obtained by utilizing the free radical addition reaction of the sulfinyl chloride and the hydroxamic acid and the alkene at present). Meanwhile, the method for synthesizing the beta-amino sulfone compound is safe and simple to operate, easy to obtain raw materials, low in price and high in reaction efficiency; the substrate has wide adaptability and is environment-friendly, thereby being beneficial to industrial production. In addition, the yield of the beta-aminocarbonyl compound synthesized by the method is high and can reach 86%; the produced beta-amino sulfone compound has wide application in medicine and organic synthesis. Therefore, the invention has important application value.
Drawings
FIG. 1 is a 1 HNMR spectrum of 1-phenyl-2- (benzenesulfonyl) ethan-1-amine;
FIG. 2 is a 13 CNMR spectra of 1-phenyl-2- (benzenesulfonyl) ethan-1-amine;
FIG. 3 is a 1 HNMR spectrum of 2- (benzenesulfonyl) -1- (p-tolyl) ethan-1-amine;
FIG. 4 is a 13 CNMR spectra of 2- (benzenesulfonyl) -1- (p-tolyl) ethan-1-amine;
FIG. 5 is a 1 HNMR spectrum of 1- (4-fluorophenyl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 6 is a 13 CNMR spectra of 1- (4-fluorophenyl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 7 is a 19 F NMR spectrum of 1- (4-fluorophenyl) -2- (benzenesulfonyl) ethyl-1-amine;
FIG. 8 is a 1 HNMR spectrum of 1- (4-chlorophenyl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 9 is a 13 CNMR spectrum of 1- (4-chlorophenyl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 10 is a 1 HNMR spectrum of 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine;
FIG. 11 is a 13 CNMR spectra of 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine;
FIG. 12 is a 19 FNMR spectrum of 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine;
FIG. 13 is a 1 HNMR spectrum of 1- (naphthalen-2-yl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 14 is a 13 CNMR spectra of 1- (naphthalen-2-yl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 15 is a 1 HNMR spectra of 2- (benzenesulfonyl) -1- (m-tolyl) ethan-1-amine;
FIG. 16 is a 13 CNMR spectra of 2- (benzenesulfonyl) -1- (m-tolyl) ethan-1-amine;
FIG. 17 is a 1 HNMR spectrum of 1- (3-chlorophenyl) -2- (benzenesulfonyl) ethan-1-amine;
FIG. 18 is a CNMR spectrum of 1- (3-chlorophenyl) -2- (benzenesulfonyl) ethyl-1-amine 13.
Detailed Description
The following describes the invention in more detail. The description of these embodiments is provided to assist understanding of the present invention, but is not intended to limit the present invention. In addition, the technical features of the embodiments of the present invention described below may be combined with each other as long as they do not collide with each other.
The experimental methods in the following examples, unless otherwise specified, are conventional, and the experimental materials used in the following examples, unless otherwise specified, are commercially available.
The invention provides a method for preparing beta-amino sulfone compounds, which utilizes sulfinyl chloride, hydroxamic and olefin to synthesize the beta-amino sulfone compounds through addition reaction:
the sulfinyl chloride shown in the formula 1, the hydroxamic compound shown in the formula 2 and the olefin compound shown in the formula 3 are dissolved in a reaction solvent to carry out an addition reaction in the presence of an organic base to obtain a beta-amino sulfone compound shown in the formula 4:
In formulas 1-4, R 1 is independently selected from benzene ring, alkoxy, alkyl, primary amine, secondary amine, tertiary amine, thio, alkyne; r 2 is independently selected from alkyl, primary amine, secondary amine, tertiary amine, sulfur; r 3-R4 is H or alkyl; r 5 is independently selected from cyano, nitro, ester, and various aromatic rings.
The substituent allowed on the alkyl, benzene ring and aromatic ring is C 1～C6 alkyl, or C 1～C6 alkoxy, or phenyl, or benzyloxy, or nitro, or halogen, or cyano, or ester, or aldehyde, or trifluoromethyl.
Preferably, the molar ratio of the sulfinyl chloride shown in formula 1, the hydroxamic compound shown in formula 2 and the olefin compound shown in formula 3 is 0.5-2: and the molar concentration of the olefin compound in the reaction solvent is 0.5-2mol/L, and the use 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 time is 2-24 hours.
Preferably, the reaction solvent includes ethyl acetate, dimethyl sulfoxide, acetonitrile, N-dimethylformamide and tetrahydrofuran.
Examples 1-8 are provided for further illustration in order to better demonstrate the synthesis of β -aminosulfones using the addition of thionyl chloride, hydroxamic and olefins (the thionyl chloride of formula 1, the hydroxamic of formula 2, the olefinic compound of formula 3 and the β -aminosulfone compound of formula 4 are shown in Table 1):
Example 1A method for synthesizing beta-aminosulfones by addition of thionyl chloride, hydroxamic and olefins
The beta-aminosulfone compound synthesized in the embodiment is 1-phenyl-2- (benzenesulfonyl) ethyl-1-amine:
in a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula see Table 1;0.3mmol,1.5 eq.) acetone oxime (structural formula see Table 1;0.3mmol,1.5 eq.), dry ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were added, and the reaction was stirred at-20℃for 3h, followed by styrene (structural formula see Table 1;0.2mmol,1.0 eq.) and 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 after decompression rotary evaporation, 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), and the 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 are (fig. 1 and 2):
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 2 Synthesis of beta-aminosulfones Using thionyl chloride, hydroxamic and olefins addition
The beta-aminosulfone compound synthesized in the embodiment is 2- (benzenesulfonyl) -1- (p-tolyl) ethyl-1-amine:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (structural formula see Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20℃with stirring for 3h, followed by p-toluylene (structural formula see Table 1;0.2mmol,1.0 eq.) and 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 after decompression rotary evaporation, 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), and the final product 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 are (fig. 3 and 4);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 Synthesis of beta-aminosulfones Using thionyl chloride, hydroxamic and olefins addition
The beta-aminosulfone compound synthesized in the embodiment is 1- (4-fluorophenyl) -2- (benzenesulfonyl) ethyl-1-amine:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (structural formula see Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20℃with stirring for 3h, followed by 4-fluorostyrene (structural formula see Table 1;0.2mmol,1.0 eq.) and 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 after decompression rotary evaporation, 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), and the 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 are (fig. 5, 6 and 7);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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).19F NMR(377MHz,CDCl3)δ-114.12(s).
example 4 Synthesis of beta-aminosulfones Using thionyl chloride, hydroxamic and olefins addition
The beta-aminosulfone compound synthesized in the embodiment is 1- (4-chlorophenyl) -2- (phenylsulfonyl) ethyl-1-amine:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (structural formula see Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20℃with stirring for 3h, followed by 4-chlorostyrene (structural formula see Table 1;0.2mmol,1.0 eq.) and 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 after decompression rotary evaporation, 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), and the final product 1- (4-chlorophenyl) -2- (benzenesulfonyl) ethyl-1-amine is obtained, wherein the yield is 65%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product are (fig. 8 and 9);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 5 Synthesis of beta-aminosulfones Using thionyl chloride, hydroxamic and olefins addition
The beta-aminosulfone compound synthesized in the embodiment is 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethan-1-amine:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (formula see Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20℃with stirring for 3h, followed by 4-trifluoromethylstyrene (formula see Table 1;0.2mmol,1.0 eq.) and 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 after decompression rotary evaporation, 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), and the final product 2- (benzenesulfonyl) -1- (4- (trifluoromethyl) phenyl) ethyl-1-amine is obtained, wherein the yield is 52%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product are (fig. 10, 11 and 12);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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).19F NMR(377MHz,CDCl3)δ-62.33–-63.02(m).
example 6 Synthesis of beta-aminosulfones Using thionyl chloride, hydroxamic and olefins addition
The beta-aminosulfone compound synthesized in the embodiment is 1- (naphthalene-2-yl) -2- (benzenesulfonyl) ethyl-1-amine:
In a20 mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (structural formula see Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20deg.C with stirring for 3h, followed by 2-vinylnaphthalene (structural formula see Table 1;0.2mmol,1.0 eq.) and at 40℃overnight (8-12 h). Monitoring the reaction process through Thin Layer Chromatography (TLC), after the reaction is finished, performing reduced pressure rotary evaporation to obtain a crude product, and separating and purifying the crude product through a silica gel chromatographic column (an eluent system used in the 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 a final product: 1- (naphthalen-2-yl) -2- (phenylsulfonyl) ethan-1-amine was produced in 87% yield.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product are (fig. 13 and 14);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 7 Synthesis of beta-aminosulfones by addition of thionyl chloride, hydroxamic and olefins
The beta-aminosulfone compound synthesized in the embodiment is 2- (benzenesulfonyl) -1- (m-tolyl) ethyl-1-amine:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (structural formula see Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20℃with stirring for 3h, followed by 3-methylstyrene (structural formula see Table 1;0.2mmol,1.0 eq.) and 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 after decompression rotary evaporation, 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), and the final product 2- (benzenesulfonyl) -1- (m-tolyl) ethyl-1-amine is obtained, wherein the yield is 70%.
The nuclear magnetic hydrogen spectrum and carbon spectrum information of the product are (fig. 15 and 16);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 8 Synthesis of beta-aminosulfones by addition of thionyl chloride, hydroxamic and olefins
The beta-aminosulfone compound synthesized in the embodiment is 1- (3-chlorophenyl) -2- (phenylsulfonyl) ethyl-1-amine:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (formula see Table 1;0.3mmol,1.5 eq.) was added, acetoxime (formula see Table 1;0.3mmol,1.5 eq.) was added, dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were added, the reaction was stirred at-20℃for 3h, followed by 3-chlorostyrene (formula see Table 1;0.2mmol,1.0 eq.) and reacted at 40℃overnight (8-12 h). Monitoring the reaction process through Thin Layer Chromatography (TLC), after the reaction is finished, performing reduced pressure rotary evaporation to obtain a crude product, and separating and purifying the crude product through a silica gel chromatographic column (an eluent system used in the 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 a final product: 1- (3-chlorophenyl) -2- (benzenesulfonyl) ethyl-1-amine was 75% in yield.
The nuclear magnetic hydrogen and carbon spectrum information of the product is (fig. 17 and 18);
1H NMR(400MHz,CDCl3)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).13C NMR(101MHz,CDCl3)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 sulfenate chlorides, hydroxamates, activated olefins and products of examples 1-8
EXAMPLE 9 exploration of influencing factors for the Synthesis of beta-amino sulfones Using thionyl chloride, hydroxamic and olefins addition
Taking example 1 as an example, the influence factors of synthesizing the beta-amino sulfone compound by utilizing thionyl chloride, hydroxamic and olefin addition are explored, and the influence factors are specifically as follows:
(1) Effect of the addition equivalent of thionyl chloride and hydroxamic acid on 1-phenyl-2- (benzenesulfonyl) ethan-1-amine Synthesis
The difference compared to example 1 is mainly that the addition equivalent (molar ratio of the thionyl chloride compound to the activated olefin) of the thionyl chloride of formula 1 and the hydroxamic acid of formula 2 are different, i.e., the addition equivalent of the phenylthionyl chloride to the acetoxime (structural formula see table 1) is 1eq,1.5eq,2.0eq, respectively.
The specific operation is as follows:
In a 20mL dry clear glass reaction flask, after three replacements with argon, 1eq,1.5eq,2.0eq of phenylsulfinyl chloride and acetoxime, respectively, were added, dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20℃with stirring for 3h, followed by styrene (structural formula see Table 1;0.2mmol,1.0 eq.) and at 40℃overnight (8-12 h) in yields of 50%,58%,49%, respectively. The experimental results show that the yields of the compounds of formula 1 and formula 2 added at 1.5eq are optimal.
(2) Effect of reaction temperature on 1-phenyl-2- (benzenesulfonyl) ethan-1-amine Synthesis
The difference compared to example 1 is mainly that the reaction temperature was changed, i.e., the reaction was carried out at 0℃and 10℃and 40℃respectively overnight.
The specific operation is as follows:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula shown in Table 1;0.3mmol,1.5 eq.) was added, acetoxime (structural formula shown in Table 1;0.3mmol,1.5 eq.), dried ethyl acetate (5 mL) and triethylamine (0.3 mmol,1.5 eq.) were reacted at-20deg.C with stirring for 3h, followed by styrene (structural formula shown in Table 1;0.2mmol,1.0 eq.) and at 0deg.C at 10deg.C overnight (8-12 h) with yields of 44%, 48% and 58%, respectively. Experimental results show that the overnight reaction yield at 40 ℃ is optimal.
(3) Influence of the kind of base added in the reaction on the Synthesis of 1-phenyl-2- (benzenesulfonyl) ethan-1-amine
The difference compared to example 1 is mainly that the kind of 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 clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (formula: table 1;0.3mmol,1.5 eq.) acetone oxime (formula: table 1;0.3mmol,1.5 eq.) dry ethyl acetate (5 mL) was added, and triethylamine, diisopropylamine, pyridine (0.3 mmol,1.5 eq.) were added, respectively, and the reaction was stirred at-20℃for 3h, followed by styrene (formula: table 1;0.2mmol,1.0 eq.) and reacted overnight (8-12 h) at 40℃in 58%, 49%, 44% yields, respectively. Experimental results show that the use of other organic bases, although also capable of producing the product, yields are lower than in example 1.
(4) Effect of the reaction solvent on the Synthesis of 1-phenyl-2- (benzenesulfonyl) ethan-1-amine
The difference compared to example 1 is mainly that the reaction solvent is changed, i.e. dry 5mL of ethyl acetate, benzotrifluoride, N-dimethylformamide, 1, 2-dichloroethane and dimethyl sulfoxide are added respectively.
The specific operation is as follows:
In a 20mL dry clear glass reaction flask, after three replacements with argon, phenylsulfinyl chloride (structural formula shown in Table 1;0.3mmol,1.5 eq.), acetoxime (structural formula shown in Table 1;0.3mmol,1.5 eq.), triethylamine (0.3 mmol,1.5 eq.) and dried ethyl acetate, benzotrifluoride, N-dimethylformamide, 1, 2-dichloroethane and dimethyl sulfoxide (5 mL) were added respectively as reaction solvents, and the reaction was stirred at-20℃for 3 hours, followed by addition of styrene (structural formula shown in Table 1;0.2mmol,1.0 eq.) and reaction was carried out overnight at 40℃for 8-12 hours. The yields were 58%, 52%, 40%, 39% and 47%, respectively. Experimental results show that ethyl acetate, benzotrifluoride, N-dimethylformamide, 1, 2-dichloroethane and dimethyl sulfoxide are all suitable for the reaction, wherein ethyl acetate is 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 to these embodiments without departing from the principles and spirit of the invention, and yet fall within the scope of the invention.
Claims (5)
1. A method for preparing beta-amino sulfone compounds is characterized in that sulfinyl chloride, hydroxamic and olefin compounds are dissolved in a reaction solvent, and then an addition reaction is carried out in the presence of organic base, so that the beta-amino sulfone compounds are synthesized:
The structural formulas of the sulfinyl chloride and the hydroxamic acid are respectively shown 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:
2. A process for the preparation of β -aminosulfones according to claim 1, characterized in that the molar ratio of sulfinyl chloride, hydroxamic and olefinic compounds is from 0.5 to 2: and the molar concentration of the olefin compound in the reaction solvent is 0.5-2mol/L, and the use amount of the organic base is 0.5-3mol% of the total molar amount of the olefin compound.
3. A method for preparing β -aminosulfones according to claim 1, characterized in that said organic base comprises at least one of triethylamine, diisopropylamine, pyridine.
4. The method for preparing the beta-amino sulfone according to claim 1, wherein the temperature of the addition reaction is-40-40 ℃ for 2-24 hours.
5. The method for preparing β -aminosulfone according to claim 1, wherein the reaction solvent comprises at least one of ethyl acetate, dimethyl sulfoxide, acetonitrile, N-dimethylformamide and tetrahydrofuran.
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| CN106536479A (en) * | 2014-05-28 | 2017-03-22 | 斯洛文尼亚莱柯制药股份有限公司 | Processes for the preparation of beta-aminosulfone compounds |
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