CN111138323B - Preparation method of sulfonamide compound - Google Patents
Preparation method of sulfonamide compound Download PDFInfo
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- CN111138323B CN111138323B CN201911314746.9A CN201911314746A CN111138323B CN 111138323 B CN111138323 B CN 111138323B CN 201911314746 A CN201911314746 A CN 201911314746A CN 111138323 B CN111138323 B CN 111138323B
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- -1 sulfonamide compound Chemical class 0.000 title claims abstract description 70
- 229940124530 sulfonamide Drugs 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000012954 diazonium Substances 0.000 claims abstract description 25
- 239000007787 solid Substances 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 238000000926 separation method Methods 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 238000004440 column chromatography Methods 0.000 claims description 8
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 239000012973 diazabicyclooctane Substances 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical group C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 239000012295 chemical reaction liquid Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000002950 deficient Effects 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 1
- 238000005160 1H NMR spectroscopy Methods 0.000 abstract description 6
- 238000010438 heat treatment Methods 0.000 abstract description 6
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 abstract description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 abstract description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 abstract description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 abstract 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract 1
- 150000001989 diazonium salts Chemical class 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- 235000010269 sulphur dioxide Nutrition 0.000 description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 5
- 238000012512 characterization method Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000009423 ventilation Methods 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 238000006713 insertion reaction Methods 0.000 description 2
- NLRKCXQQSUWLCH-UHFFFAOYSA-N nitrosobenzene Chemical compound O=NC1=CC=CC=C1 NLRKCXQQSUWLCH-UHFFFAOYSA-N 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- IEYSGPZUULPJPQ-UHFFFAOYSA-N 1-chloro-4-nitrosobenzene Chemical compound ClC1=CC=C(N=O)C=C1 IEYSGPZUULPJPQ-UHFFFAOYSA-N 0.000 description 1
- LDOCMFAHAVONEI-UHFFFAOYSA-N 4-fluoro-n-phenylbenzenesulfonamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)NC1=CC=CC=C1 LDOCMFAHAVONEI-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- CAFWWZWJFFJXTF-UHFFFAOYSA-N methyl 4-nitrosobenzoate Chemical compound COC(=O)C1=CC=C(N=O)C=C1 CAFWWZWJFFJXTF-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- DOPAQNXFOIXWPI-UHFFFAOYSA-N n-(4-chlorophenyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(Cl)C=C1 DOPAQNXFOIXWPI-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000027756 respiratory electron transport chain Effects 0.000 description 1
- 150000003456 sulfonamides Chemical group 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 239000004291 sulphur dioxide Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B45/00—Formation or introduction of functional groups containing sulfur
- C07B45/04—Formation or introduction of functional groups containing sulfur of sulfonyl or sulfinyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of a sulfonamide compound. The structure of the sulfonamide compound synthesized by the method is shown in the specification1H NMR、13C NMR was characterized and confirmed. In an organic solvent, aryl diazonium salt, a sulfur dioxide solid complex and an aryl nitroso compound react under the heating condition in the presence of a reducing agent, the diazonium salt and the sulfur dioxide solid complex react to generate aryl sulfonyl free radicals, then the aryl nitroso compound is attacked, and the generated hydroxylamine is reduced to obtain the sulfonamide compound. The preparation method of the compound has the advantages of mild conditions, simplicity, high efficiency, no need of catalysts, no need of pre-synthesizing sulfonyl chloride or sodium sulfonate reagents, wide application range of substrates, strong functional group compatibility, convenience for separation and purification, and excellent industrial and pharmaceutical chemical application values.
Description
Technical Field
The invention belongs to the technical field of organic chemistry, and particularly relates to a preparation method of a sulfonamide compound.
Background
The strategy of synthesizing sulfones and sulfones compounds through the direct insertion of sulfur dioxide has received a great deal of attention from chemists. Sulfonyl functional groups such as sulfone, sulfonamide and the like widely exist in the skeleton of a natural product, and part of the compounds have good biological activity and excellent medicinal value. The sulfur dioxide insertion reaction is a simple, efficient and environment-friendly organic synthesis strategy (P.Bisseret, N.Blanchard, org.Biomol.Chem.2013,11,5393; G.Liu, C.Fan, J.Wu, Org.Biomol.Chem.2015,13,1592; J.Zhu, W.C.Yang, X.D.Wang, L.Wu, adv.Synth.Cat.2018, 360, 386), and has the advantages of avoiding the use and preparation of strong acid sulfonic acid or sulfonyl chloride in the traditional sulfonyl compound synthesis process and directly completing the construction of a sulfonyl functional group in one step through a series reaction. In such reaction systems, the synthesis of some biologically active compounds by radical-initiated sulfur dioxide insertion is particularly rapid.
The existing synthesis method of the sulfonamide compound still has certain limitations and still depends on sulfonate and sulfonyl chloride compounds to a great extent. In recent years, a reaction method for synthesizing sulfonamide compounds by sulfur dioxide insertion reaction has been studied (b.nguyen, e.j.emmett, m.c.willis, j.am.chem.soc.2010,132, 16372; d.zheng, y.an, z.li, j.wu, angelw.chem.int.ed.2014, 53,2451; y.chen, p.r.d.murray, a.t.davies, m.c.willis, j.am.chem.soc.2018,140, 8781.).
Disclosure of Invention
The invention aims to solve the defects of the prior art and provide a simple, convenient and efficient preparation method of sulfonamide compounds. The preparation method of the sulfonamide compound is to utilize aryl nitroso compound, sulfur dioxide complex, aryl diazonium salt and reducing agent to carry out free radical reaction in solvent and under the heating condition so as to efficiently construct the sulfonamide compound.
In order to achieve the above object, the present invention provides the following technical solutions:
a preparation method of sulfonamide compounds comprises the following steps:
(1) adding an aryl nitroso compound, a sulfur dioxide solid complex and an aryl diazonium salt into a reaction tube at room temperature, adding an organic solvent and a reducing agent under the protection of inert gas, and reacting for a certain time at a certain temperature;
(2) and after the TLC monitoring reaction is completed, carrying out post-treatment on the reaction liquid to obtain the sulfonamide compound.
Preferably, the aryl group in the arylnitroso compound in the step (1) is a phenyl or heterocyclic substituent containing an electron withdrawing group or an electron donating group; more preferably, the electron-withdrawing group is a fluorine, chlorine, bromine, trifluoromethyl, acyl or ester group substituent group, the electron-donating group is an alkyl or alkoxy group, and the heterocycle is an electron-deficient or electron-rich heterocycle.
Preferably, the aryl group in the aryl diazonium salt in the step (1) is a phenyl or heterocyclic substituent containing an electron-withdrawing group or an electron-donating group; more preferably, the electron-withdrawing group is a fluorine, chlorine, bromine or trifluoromethyl substituent group, the electron-donating group is an alkyl group or an alkoxy group, and the heterocycle is an electron-deficient or electron-rich heterocycle.
Preferably, the aryl diazonium salt in the step (1) is aryl diazonium tetrafluoroborate or aryl diazonium hexafluorophosphate, and is more preferably aryl diazonium tetrafluoroborate.
Preferably, the molar ratio of the aryl nitroso compound, the sulfur dioxide solid complex, the aryl diazonium salt and the reducing agent in the step (1) is 1: (1-2): (1.5-2.5): (1-3); more preferably, the molar ratio of aryl nitroso compound, sulphur dioxide solid complex, aryl diazonium salt and reducing agent is 1:1.5:2: 2.
Preferably, the sulfur dioxide solid complex in the step (1) is triethylene diamine sulfur dioxide complex DABCO (SO)2)2。
Preferably, the reducing agent in the step (1) is 1, 4-cyclohexadiene.
Preferably, the organic solvent in step (1) is acetonitrile (MeCN), Dimethylformamide (DMF), 1, 2-Dichloroethane (DCE) or Dichloromethane (DCM), more preferably the solvent is acetonitrile (MeCN); the amount of the organic solvent is 0.05 to 0.2mol/L based on the aryl nitroso compound, and more preferably, the amount of the organic solvent is 0.1mol/L based on the aryl nitroso compound.
Preferably, the reaction temperature in the step (1) is 30 ℃ to 90 ℃, more preferably the reaction temperature is the boiling point of the solvent, and more preferably the reaction temperature is 60 ℃.
Preferably, the reaction time in the step (1) is 12 h.
Preferably, the inert gas in step (1) is high-purity nitrogen or argon.
Preferably, the post-treatment in step (2) is to concentrate the reaction solution under reduced pressure, and perform column chromatography separation on the concentrated reaction solution to obtain a sulfonamide compound; more preferably, the mobile phase adopted by the column chromatography separation is a mixed system of petroleum ether and ethyl acetate, and the proportion of the mixed system is that the petroleum ether and the ethyl acetate are (2-8): 1.
the preferred reaction formula of the process of the present invention is as follows:
DABSO sulfur dioxide solid Complex DABCO (SO)2)2。
The structure of the compound synthesized by the method of the invention is shown in the specification1H NMR、13The reaction yield was 80% or more, which was confirmed by characterization such as C NMR.
Compared with the prior art, the invention has the following beneficial effects: the invention provides a preparation method of sulfonamide compounds, which is characterized in that aryl diazonium salt and sulfur dioxide solid complex are subjected to single electron transfer to generate aryl sulfonyl free radicals under the conditions of being very mild and simple and needing no metal catalyst, then the aryl sulfonyl free radicals are attacked by aryl nitroso compounds, and the sulfonamide compounds are obtained by reduction after addition. The method constructs a series of sulfonamide compounds, avoids the use of strong acid sulfonyl chloride in the traditional sulfonamide compound synthesis, is easy to synthesize various substituted aryl diazonium salts and various substituted aryl nitroso compounds, and avoids the synthesis of sulfonyl chloride and sulfonate compounds which are difficult to synthesize in the traditional method, so that the sulfonamide compounds are synthesized in a green and high-efficiency manner, can be used for industrial preparation, and have good guiding significance and application prospect in the fields of scientific research, industry and pharmaceutical chemistry.
Detailed Description
The technical solution of the present invention will be further specifically described below by way of specific examples.
Example 1:
to a dry tube at room temperature were added 0.2mmol of nitrosobenzene, 0.3mmol of the sulfur dioxide solid complex DABCO (SO)2)20.4mmol of p-fluorophenyl tetrafluoroborate diazonium salt, plugging the reaction tube by a plug, placing the reaction tube in high-purity argon for ventilation, and enabling the system to be positioned inAfter anhydrous and anaerobic conditions, 2.0mL of dry acetonitrile and 0.4mmol of 1, 4-cyclohexadiene are added, and the mixture is placed in a heating device at 60 ℃ to be stirred and reacted for 12 hours. After TLC monitoring complete reaction, the reaction solution is decompressed and concentrated, and column chromatography separation is carried out by using a mixed solution of 8:1 petroleum ether and ethyl acetate as a mobile phase, so as to obtain the corresponding N-phenyl-4-fluorobenzenesulfonamide 4-Fluoro-N-phenylbenezenesulfonamide example 1.
Structural characterization of compound example 1:1H NMR(400MHz,Chloroform-d)δ7.81–7.73(m,2H),7.30–7.21(m,2H),7.17–7.03(m,5H),6.72(s,1H).13C NMR(101MHz,Chloroform-d)δ166.67,136.20,130.18,130.09,129.60,125.99,122.18,116.56,116.34.
example 2:
to a dry tube at room temperature were added 0.2mmol of nitrosobenzene, 0.2mmol of the sulfur dioxide solid complex DABCO (SO)2)2And 0.3mmol of p-methoxyphenyl tetrafluoroborate diazonium salt, plugging the reaction tube by a plug, placing the reaction tube in high-purity argon for ventilation, adding 4.0mL of dichloromethane and 0.2mmol of 1, 4-cyclohexadiene after the system is in an anhydrous and anaerobic condition, and placing the mixture in a heating device at 40 ℃ for stirring and reacting for 12 hours. After TLC monitoring complete reaction, the reaction liquid is decompressed and concentrated, and column chromatography separation is carried out by adopting a mixed liquid of 4:1 petroleum ether and ethyl acetate as a mobile phase, thus obtaining the corresponding N-phenyl-4-methoxybenzenesulfonamide 4-Methoxy-N-phenylbenzylbenzylsulfonaphthamide example 2.
Structural characterization of compound example 2:1H NMR(400MHz,Chloroform-d)δ7.74(d,J＝8.1Hz,2H),7.23(t,J＝7.4Hz,2H),7.16(s,1H),7.09(d,J＝7.6Hz,3H),6.88(d,J＝8.2Hz,2H),3.82(s,3H).13C NMR(101MHz,Chloroform-d)δ163.21,136.78,130.63,129.55,129.40,125.31,121.58,114.30,55.68.
example 3:
to a dry tube at room temperature were added 0.2mmol of p-chloronitrosobenzene, 0.4mmol of the sulfur dioxide solid complex DABCO (SO)2)2And 0.5mmol of p-tolyl tetrafluoroborate diazonium salt, plugging the reaction tube by a plug, placing the reaction tube in high-purity argon for ventilation, adding 2.0mL of dry acetonitrile and 0.6mmol of 1, 4-cyclohexadiene after the system is in an anhydrous and anaerobic condition, and placing the mixture in a heating device at 30 ℃ for stirring and reacting for 12 hours. After TLC monitoring complete reaction, the reaction liquid is decompressed and concentrated, and column chromatography separation is carried out by adopting a mixed liquid of 6:1 petroleum ether and ethyl acetate as a mobile phase, thus obtaining the corresponding N- (4-chlorphenyl) -p-toluenesulfonamide N- (4-chlorophenylyl) -4-methyllbenzenesufonamide example 3.
Structural characterization of compound example 3:1H NMR(400MHz,Chloroform-d)δ7.68(d,J＝7.5Hz,2H),7.39(s,1H),7.24(d,J＝7.7Hz,2H),7.18(d,J＝7.6Hz,2H),7.04(d,J＝7.8Hz,2H),2.38(s,3H).13C NMR(101MHz,Chloroform-d)δ144.31,135.72,135.30,130.88,129.91,129.50,127.38,122.90,21.68.
example 4:
to a dry tube at room temperature were added 0.2mmol of methyl p-nitrosobenzoate and 0.3mmol of the sulfur dioxide solid complex DABCO (SO)2)2And 0.4mmol of p-tolyl tetrafluoroborate diazonium salt, plugging the reaction tube by a plug, placing the reaction tube in high-purity argon for ventilation, adding 2.0mL of dry acetonitrile and 0.4mmol of 1, 4-cyclohexadiene after the system is in an anhydrous and anaerobic condition, and placing the mixture in a heating device at 90 ℃ for stirring and reacting for 12 hours. After TLC monitoring complete reaction, the reaction liquid is decompressed and concentrated, and column chromatography separation is carried out by adopting a mixed liquid of 2:1 petroleum ether and ethyl acetate as a mobile phase, so as to obtain the corresponding Methyl 4-p-toluenesulfonamide benzoate Methyl4- ((4-methylphenenyl) sulfonamido) benzoate example 4.
Structural characterization of compound example 4:1H NMR(400MHz,Acetone-d6)δ9.41(s,1H),7.89(d,J＝7.8Hz,2H),7.76(d,J＝7.6Hz,2H),7.34(d,J＝7.7Hz,4H),3.82(s,3H),2.35(s,3H).13C NMR(101MHz,Acetone-d6)δ166.67,144.96,143.43,137.83,131.62,130.64,128.08,126.37,119.50,52.24,21.43.
the above-described embodiments are merely preferred embodiments of the present invention, which is not intended to be limiting in any way, and other variations and modifications are possible without departing from the scope of the invention as set forth in the appended claims.
Claims (6)
1. A preparation method of sulfonamide compounds is characterized by comprising the following steps:
(1) adding an aryl nitroso compound, a sulfur dioxide solid complex and an aryl diazonium salt into a reaction tube at room temperature, adding an organic solvent and a reducing agent under the protection of inert gas, and reacting for a certain time at a certain temperature;
(2) after TLC monitoring reaction is completed, carrying out post-treatment on the reaction liquid to obtain a sulfonamide compound, wherein the structural formula of the sulfonamide compound is as follows:
wherein,
the aryl in the aryl nitroso compound in the step (1) is (Het) Ar2A phenyl or heterocyclic substituent containing an electron withdrawing group or an electron donating group; the electron-withdrawing group is a fluorine, chlorine, bromine, trifluoromethyl, acyl or ester group substituent group, the electron-donating group is an alkyl group or an alkoxy group, and the heterocycle is an electron-deficient or electron-rich heterocycle;
in the step (1), the aryl diazonium salt is aryl tetrafluoroborate diazonium salt or aryl hexafluorophosphate diazonium salt; the aryl group in the aryl diazonium salt is (Het) Ar1A phenyl or heterocyclic substituent containing an electron withdrawing group or an electron donating group; the electron-withdrawing group is a fluorine, chlorine, bromine or trifluoromethyl substituted group, and the electron-donating groupThe group is alkyl and alkoxy group, and the heterocycle is electron-deficient or electron-rich heterocycle;
the sulfur dioxide solid complex in the step (1) is triethylene diamine sulfur dioxide complex DABCO.(SO2)2The reducing agent is 1, 4-cyclohexadiene.
2. The process for producing a sulfonamide compound according to claim 1, wherein the molar ratio of the arylnitroso compound, the sulfur dioxide solid complex, the aryldiazonium salt and the reducing agent in step (1) is 1: (1-2): (1.5-2.5): (1-3).
3. The process for producing a sulfonamide compound according to claim 1, wherein the organic solvent in the step (1) is acetonitrile, dimethylformamide, 1, 2-dichloroethane or dichloromethane; the dosage of the organic solvent is 0.05-0.2mol/L calculated by aryl nitroso compound.
4. The process for producing a sulfonamide compound according to claim 1, wherein the reaction temperature in the step (1) is 20 to 90 ℃ and the reaction time is 12 hours.
5. The process for producing a sulfonamide compound according to any one of claims 1 to 4, wherein the molar ratio of the aryl nitroso compound, the sulfur dioxide solid complex, the aryl diazonium salt and the reducing agent in step (1) is 1:1.5:2:2, the aryl diazonium salt is aryl tetrafluoroborate diazonium salt, the organic solvent is acetonitrile, the amount of the organic solvent is 0.1mol/L based on the aryl nitroso compound, and the reaction temperature is 60 ℃.
6. The method for preparing sulfonamide compounds according to claim 1, wherein the post-treatment in step (2) comprises concentrating the reaction solution under reduced pressure, and subjecting the concentrated reaction solution to column chromatography to obtain sulfonamide compounds; the mobile phase adopted by the column chromatography separation is a mixed system of petroleum ether and ethyl acetate, and the ratio is 2:1 to 8: 1.
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| CN109134326A (en) * | 2018-10-12 | 2019-01-04 | 嘉兴学院 | A kind of synthetic method of S- arylthio sulfone compound |
| CN109438296A (en) * | 2018-11-11 | 2019-03-08 | 华东师范大学 | Sulfamide compound and its synthetic method and application |
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| CN109134326A (en) * | 2018-10-12 | 2019-01-04 | 嘉兴学院 | A kind of synthetic method of S- arylthio sulfone compound |
| CN109438296A (en) * | 2018-11-11 | 2019-03-08 | 华东师范大学 | Sulfamide compound and its synthetic method and application |
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| "Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides";Chen Yiding等;《J. Am. Chem. Soc.》;20180702;第140卷;第8781-8787页 * |
| "Synthesis of Aromatic Sulfonamides through a Copper-Catalyzed Coupling of Aryldiazonium Tetrafluoroborates, DABCO•(SO2)2, and N Chloroamines";Zhang Feng等;《Org. Lett.》;20180126;第20卷;第1167-1170页 * |
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