CN118439980A - Synthesis method of alpha-cyano sulfonamide derivative - Google Patents
Synthesis method of alpha-cyano sulfonamide derivative Download PDFInfo
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- -1 alpha-cyano sulfonamide derivative Chemical compound 0.000 title claims abstract description 52
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 85
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229940124530 sulfonamide Drugs 0.000 claims abstract description 8
- 239000011941 photocatalyst Substances 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 5
- 150000003456 sulfonamides Chemical class 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- 239000003513 alkali Substances 0.000 claims abstract description 3
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 3
- XJKKCLQTZOSEDY-UHFFFAOYSA-N cyano benzoate Chemical compound N#COC(=O)C1=CC=CC=C1 XJKKCLQTZOSEDY-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000004185 ester group Chemical group 0.000 claims abstract description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract description 3
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 75
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 claims description 22
- ZOMQCVKHGOMNER-UHFFFAOYSA-N 2,4,5,6-tetrakis(N-phenylanilino)benzene-1,3-dicarbonitrile Chemical group C(#N)C1=C(C(=C(C(=C1N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)N(C1=CC=CC=C1)C1=CC=CC=C1)C#N)N(C1=CC=CC=C1)C1=CC=CC=C1 ZOMQCVKHGOMNER-UHFFFAOYSA-N 0.000 claims description 20
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 20
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 20
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical group N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 230000002194 synthesizing effect Effects 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 239000002585 base Substances 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- PRWATGACIORDEL-UHFFFAOYSA-N 2,4,5,6-tetra(carbazol-9-yl)benzene-1,3-dicarbonitrile Chemical compound C12=CC=CC=C2C2=CC=CC=C2N1C1=C(C#N)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C(N2C3=CC=CC=C3C3=CC=CC=C32)C(N2C3=CC=CC=C3C3=CC=CC=C32)=C1C#N PRWATGACIORDEL-UHFFFAOYSA-N 0.000 claims description 3
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 claims description 3
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- UEEXRMUCXBPYOV-UHFFFAOYSA-N iridium;2-phenylpyridine Chemical compound [Ir].C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1.C1=CC=CC=C1C1=CC=CC=N1 UEEXRMUCXBPYOV-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000012074 organic phase Substances 0.000 claims description 2
- 230000001699 photocatalysis Effects 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 40
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 238000003760 magnetic stirring Methods 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 19
- 238000004440 column chromatography Methods 0.000 description 17
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 238000006467 substitution reaction Methods 0.000 description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 7
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- UUGLJVMIFJNVFH-UHFFFAOYSA-N Hexyl benzoate Chemical compound CCCCCCOC(=O)C1=CC=CC=C1 UUGLJVMIFJNVFH-UHFFFAOYSA-N 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- NUKZAGXMHTUAFE-UHFFFAOYSA-N methyl hexanoate Chemical compound CCCCCC(=O)OC NUKZAGXMHTUAFE-UHFFFAOYSA-N 0.000 description 2
- TYJIZFDFOVOJSE-UHFFFAOYSA-N 4-bromo-n-pentylbenzenesulfonamide Chemical compound CCCCCNS(=O)(=O)C1=CC=C(Br)C=C1 TYJIZFDFOVOJSE-UHFFFAOYSA-N 0.000 description 1
- HIIRLHVIPGFLGV-UHFFFAOYSA-N 4-fluoro-n-pentylbenzenesulfonamide Chemical compound CCCCCNS(=O)(=O)C1=CC=C(F)C=C1 HIIRLHVIPGFLGV-UHFFFAOYSA-N 0.000 description 1
- IACDZCFXBSGIKF-UHFFFAOYSA-N 4-methoxy-n-(2-methoxyethyl)benzenesulfonamide Chemical compound COCCNS(=O)(=O)C1=CC=C(OC)C=C1 IACDZCFXBSGIKF-UHFFFAOYSA-N 0.000 description 1
- VJSLUQDJVYXQFG-UHFFFAOYSA-N 4-methoxy-n-(4-phenylbutyl)benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NCCCCC1=CC=CC=C1 VJSLUQDJVYXQFG-UHFFFAOYSA-N 0.000 description 1
- DZTRTXFIVUJZAU-UHFFFAOYSA-N 4-methyl-n-pentylbenzenesulfonamide Chemical compound CCCCCNS(=O)(=O)C1=CC=C(C)C=C1 DZTRTXFIVUJZAU-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- 238000007059 Strecker synthesis reaction Methods 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001371 alpha-amino acids Chemical class 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007255 decyanation reaction Methods 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- YAGKRVSRTSUGEY-UHFFFAOYSA-N ferricyanide Chemical compound [Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] YAGKRVSRTSUGEY-UHFFFAOYSA-N 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- NESUQMBUIVCEGJ-UHFFFAOYSA-N n-(4-hydroxybutyl)-4-methoxybenzenesulfonamide Chemical compound COC1=CC=C(S(=O)(=O)NCCCCO)C=C1 NESUQMBUIVCEGJ-UHFFFAOYSA-N 0.000 description 1
- XIDOZGRWMHOSFW-UHFFFAOYSA-N n-pentylbenzenesulfonamide Chemical compound CCCCCNS(=O)(=O)C1=CC=CC=C1 XIDOZGRWMHOSFW-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012434 nucleophilic reagent Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- XHFLOLLMZOTPSM-UHFFFAOYSA-M sodium;hydrogen carbonate;hydrate Chemical class [OH-].[Na+].OC(O)=O XHFLOLLMZOTPSM-UHFFFAOYSA-M 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of alpha-cyano sulfonamide derivative, which comprises the steps of adding sulfonamide shown in a formula (I), cyanidation reagent, alkali and photocatalyst into a reaction solvent under the protection of inert gas nitrogen, fully stirring under the irradiation of a light source, separating and purifying after the reaction reaches the end point to obtain the alpha-cyano sulfonamide derivative shown in a formula (II), wherein the reaction process is as followsWherein n=0, 1,2 or 4, r 1 is selected from hydrogen, methyl, methoxy, trifluoromethyl or halogen; r 2 is selected from hydrogen or an ester group; r 3 is selected from hydrogen or ethyl; r 4 is selected from hydrogen, alkyl, phenyl, hydroxy, alkoxy, cyano, benzoate, phenoxy, chloro, or cycloalkyl. The synthesis method is green and efficient, mild in condition and simple in post-treatment.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of an alpha-cyano sulfonamide derivative.
Background
Alpha-cyanamide is a multifunctional and valuable organic synthesis intermediate, and the structure of the alpha-cyanamide contains two different reactive groups of amino and cyano, so that the alpha-cyanamide plays a key role in synthesizing complex nitrogen-containing heterocyclic compounds, drug molecules and natural products with biological activity. The synthesis potential of α -cyanamide is manifested in its diverse reaction pathways. Through the decyanation reaction, cyano groups can be converted into imine ions, and then the imine ions and various carbon sources or nucleophilic reagents containing hetero atoms are subjected to addition or cyclization reaction, so that various molecular frameworks are constructed. In addition, the alpha-cyanamide can generate alpha-amino carbanion through alpha-deprotonation reaction, can be used as an equivalent of carbanion or acyl anion, and can be subjected to substitution or condensation reaction with an electrophile to introduce various functional groups. Further, α -cyanamides can convert cyano groups to carboxyl or amide groups by hydrolysis to form α -amino acids or α -aminoamides, which derivatives play a vital role in a number of biological processes.
The preparation methods of alpha-cyanamide mainly comprise two methods: firstly, the classical Strecker reaction is used, namely aldehyde or ketone reacts with amine and potassium cyanide to generate alpha-cyanamide; secondly, the alpha-cyanamide is produced by reacting an imine or carbonyl compound with a safe cyanide source such as ferricyanide, thiocyanate and the like through a metal catalysis or photochemistry method and the like. Although these methods have advanced in the synthesis of α -cyanamide, they still face challenges including severe reaction conditions, high catalysts, highly toxic cyanating reagents, and unwanted byproducts.
Therefore, developing a novel method for preparing alpha-cyanamide with high efficiency, environmental protection and low cost is a challenge to be solved currently.
Disclosure of Invention
In view of the above problems, an object of the present invention is to provide a method for synthesizing an α -cyano sulfonamide derivative.
The specific technical scheme is as follows:
Under the protection of inert gas nitrogen, sulfonamide shown in a formula (I), a cyanidation reagent, alkali and a photocatalyst are added into a reaction solvent, fully stirred at a certain temperature under the irradiation of a light source, and after the reaction reaches the end point, the alpha-cyano sulfonamide derivative shown in a formula (II) is obtained through separation and purification, wherein the reaction process is as follows:
In formula (i), n=0, 1,2 or 4, r 1 is selected from hydrogen, methyl, methoxy, trifluoromethyl or halogen; r 2 is selected from hydrogen or an ester group; r 3 is selected from hydrogen or ethyl; r 4 is selected from hydrogen, alkyl, phenyl, hydroxy, alkoxy, cyano, benzoate, phenoxy, chloro, or cycloalkyl.
Further, the cyanating reagent is 4-cyanopyridine, 3-cyanopyridine or 2-cyanopyridine.
Further, the base is cesium carbonate, potassium carbonate or potassium phosphate.
Further, the photocatalyst in the photocatalytic system is 2,4,5, 6-tetra (diphenylamino) isophthalonitrile, 2,4,5, 6-tetra (carbazole-9-yl) -1, 3-dicyanobenzene or tris (2-phenylpyridine) iridium.
Further, the dosage of the photocatalyst is 0.5 to 5 percent of the molar quantity of the sulfonamide compound shown in the formula (I)
Further, the molar ratio of sulfonamide to cyanating agent, base, shown in formula (I) is 1: 1-2: 1 to 3.
Further, the light source is white light, blue light or purple light.
Further, the reaction temperature is 0-50 ℃ and the reaction time is 6-48 h.
Further, the solvent is selected from one or more of acetonitrile, dichloromethane, 1, 2-dichloroethane and ethyl acetate.
Further, the post-treatment process of the reaction is as follows: the reaction solution is quenched by saturated sodium bicarbonate aqueous solution, extracted by ethyl acetate, the organic phase is washed by saturated NaCl, separated, combined, dried by anhydrous Na 2SO4 and concentrated under reduced pressure to obtain a crude product, and the crude product is separated and purified by a chromatographic column to obtain an alpha-cyano sulfonamide derivative product shown as a target compound formula (II).
The invention has the beneficial effects that:
The invention takes the easily available sulfonamide compound as the initial raw material to efficiently synthesize the alpha-cyano sulfonamide derivative, has the advantages of simple operation, mild reaction condition, simple post-treatment and the like, and provides a novel method for synthesizing the alpha-cyanamide compound.
Detailed Description
The invention is further described below with reference to examples, but the scope of the invention is not limited thereto:
Example 1
N-pentyl-4-methoxybenzenesulfonamide (257.3 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light with a power of 25 Wx 2 three times under nitrogen, stirred at 35℃for 24 hours, and after the completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a column chromatography to give the objective compound with a yield of 76%.
N- (1-cyanopentyl) -4-methoxybenzene sulfonamide
1H NMR(400MHz,Chloroform-d)δ7.84(d,J＝7.8Hz,2H),7.01(d,J＝7.8Hz,2H),5.29(d,J＝9.4Hz,1H),4.17(q,J＝7.8Hz,1H),3.87(s,3H),1.82-1.74(m,2H),1.48-1.37(m,2H),1.37-1.26(m,2H),0.89(t,J＝6.9Hz,3H).
13C NMR(101MHz,Chloroform-d)δ163.63,130.38,129.51,117.68,114.60,55.70,44.36,33.65,27.08,21.75,13.69.
Example 2
N-pentylbenzenesulfonamide (227.2 mg,1 mmol), 3-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml were added into a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light with a power of 25Wx 2 three times under nitrogen substitution, stirred at 35℃for 24 hours, and after the completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound with a yield of 78%.
N- (1-cyanopentyl) benzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.94-7.88(m,2H),7.68-7.60(m,1H),7.60-7.52(m,2H),5.68(d,J＝9.4Hz,1H),4.20(dt,J＝9.3,7.3Hz,1H),1.88-1.69(m,2H),1.46-1.35(m,2H),1.34-1.23(m,2H),0.86(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)δ139.04,133.63,129.46,127.21,117.53,44.43,33.54,27.05,21.70,13.65.
Example 3
N-pentyl-4-methylbenzenesulfonamide (241.4 mg,1 mmol), 2-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light with a power of 25 Wx 2 three times under nitrogen, stirred at 35℃for 24 hours, and after the completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a column chromatography to give the objective compound with a yield of 78%.
N- (1-cyanopentyl) -4-methylbenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.79(d,J＝8.3Hz,2H),7.35(d,J＝8.1Hz,2H),5.53(d,J＝9.4Hz,1H),4.18(dt,J＝9.4,7.2Hz,1H),2.43(s,3H),1.83-1.73(m,2H),1.45-1.36(m,2H),1.35-1.25(m,2H),0.87(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)δ144.58,136.04,130.05,127.26,117.61,44.38,33.58,27.06,21.72,21.64,13.65.
Example 4
N-amyl-4-trifluoromethylbenzenesulfonamide (295.1 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), potassium carbonate (138.2 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light with a power of 25 W.times.2 three times under nitrogen substitution, stirred at 35℃for 24 hours, and after the completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound with a yield of 43%.
N- (1-cyanopentyl) -4- (trifluoromethyl) benzenesulfonamide
1H NMR(600MHz,Chloroform-d)δ8.04(d,J＝8.2Hz,2H),7.83(d,J＝8.3Hz,2H),5.53(d,J＝9.2Hz,1H),4.26(dt,J＝9.3,7.4Hz,1H),1.87-1.76(m,2H),1.47-1.37(m,2H),1.37-1.28(m,2H),0.88(t,J＝7.3Hz,3H).
13C NMR(151MHz,Chloroform-d)δ142.71,135.27(q,J＝33.3Hz),127.76,126.62(q,J＝3.6Hz),123.07(q,J＝273.1Hz),117.31,44.54,33.54,27.05,21.66,13.56.
19F NMR(565MHz,Chloroform-d)δ-63.26.
Example 5
N-pentyl-4-fluorobenzenesulfonamide (245.3 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), potassium phosphate (212.3 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light with a power of 25 Wx 2 three times under nitrogen, stirred at 35℃for 24 hours, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a column chromatography to give the objective compound with a yield of 56%.
N- (1-cyanopentyl) -4-fluorobenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.95(dd,J＝8.9,5.0Hz,2H),7.26(t,J＝8.5Hz,2H),5.65(d,J＝9.4Hz,1H),4.22(dt,J＝9.3,7.3Hz,1H),1.87-1.75(m,2H),1.50-1.39(m,2H),1.39-1.29(m,2H),0.91(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)δ165.61(d,J＝256.4Hz),135.07(d,J＝3.3Hz),130.11(d,J＝9.6Hz),117.51,116.77(d,J＝22.8Hz),44.42,33.46,27.07,21.70,13.63.
19F NMR(376MHz,Chloroform-d)δ-103.36.
Example 6
N-pentyl-4-chlorobenzenesulfonamide (261.8 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (carbazol-9-yl) -1, 3-dicyanobenzene (3.9 mg,0.005 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light having a power of 25 Wx 2 three times with nitrogen substitution, stirred at 35℃for 24 hours, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 72%.
4-Chloro-N- (1-cyanopentyl) benzenesulfonamide
1H NMR(600MHz,Chloroform-d)δ7.84(d,J＝8.5Hz,2H),7.53(d,J＝8.5Hz,2H),5.49(d,J＝9.3Hz,1H),4.21(dt,J＝9.3,7.4Hz,1H),1.83-1.76(m,2H),1.46-1.37(m,2H),1.36-1.28(m,2H),0.89(t,J＝7.3Hz,3H).
13C NMR(151MHz,Chloroform-d)δ140.27,137.57,129.77,128.68,117.42,44.46,33.54,27.06,21.70,13.62.
Example 7
N-amyl-3-chlorobenzenesulfonamide (261.8 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), tris (2-phenylpyridine) iridium (3.3 mg,0.005 mmol) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with 25 Wx 2 blue light at 35℃for 24 hours after the nitrogen substitution, the reaction mixture was quenched with saturated aqueous sodium hydrogen carbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 81%.
3-Chloro-N- (1-cyanopentyl) benzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.89(t,J＝1.8Hz,1H),7.80(d,J＝7.9Hz,1H),7.63-7.58(m,1H),7.51(t,J＝7.9Hz,1H),5.61(d,J＝9.4Hz,1H),4.21(dt,J＝9.3,7.3Hz,1H),1.85-1.75(m,2H),1.48-1.37(m,2H),1.37-1.25(m,2H),0.88(t,J＝7.2Hz,3H).
13C NMR(101MHz,Chloroform-d)δ140.72,135.61,133.76,130.82,127.30,125.33,117.33,44.49,33.52,27.07,21.71,13.65.
Example 8
N-pentyl-2-chlorobenzenesulfonamide (261.8 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (39.8 mg,0.05 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light having a power of 25 Wx 2 three times with nitrogen substitution, stirred at 35℃for 24 hours, and after completion of the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally purified by column chromatography to give the objective compound in a yield of 62%.
2-Chloro-N- (1-cyanopentyl) benzenesulfonamide
1H NMR(600MHz,Chloroform-d)δ8.13(d,J＝7.6Hz,1H),7.63-7.57(m,2H),7.52-7.46(m,1H),5.55(d,J＝9.8Hz,1H),4.23(dt,J＝9.6,7.3Hz,1H),1.90-1.83(m,2H),1.53-1.44(m,2H),1.40-1.32(m,2H),0.92(t,J＝7.3Hz,2H).
13C NMR(151MHz,Chloroform-d)δ136.37,134.66,131.90,131.74,131.19,127.50,116.69,44.58,33.50,27.03,21.71,13.63.
Example 9
N-pentyl-4-bromobenzenesulfonamide (306.2 mg,1 mmol), 4-cyanopyridine (208.2 mg,2 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light with a power of 25 Wx 2 three times under nitrogen, stirred at 35℃for 24 hours, the reaction solution was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a column chromatography to give the objective compound with a yield of 57%.
4-Bromo-N- (1-cyanopentyl) benzenesulfonamide
1H NMR(600MHz,Chloroform-d)δ7.76(d,J＝8.5Hz,2H),7.71(d,J＝8.5Hz,2H),5.21(d,J＝9.3Hz,1H),4.23(dt,J＝9.2,7.3Hz,1H),1.85-1.77(m,2H),1.49-1.40(m,2H),1.38-1.30(m,2H),0.90(t,J＝7.3Hz,3H).
13C NMR(151MHz,Chloroform-d)δ138.14,132.78,128.81,128.72,117.33,44.47,33.66,27.06,21.72,13.63.
Example 10
4-Methoxy-N- (4-phenylbutyl) benzenesulfonamide (319.4 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (977.5 mg,3 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, and after three times of nitrogen substitution, the reaction system was irradiated with blue light having a power of 25 Wx 2, stirred at 35℃for 24 hours, and after the completion of the reaction, the reaction solution was quenched with saturated aqueous sodium hydrogencarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 76%.
N- (1-cyano-4-phenylbutyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.82(d,J＝8.9Hz,2H),7.28(t,J＝7.3Hz,2H),7.20(t,J＝7.3Hz,1H),7.12(d,J＝7.1Hz,2H),7.00(d,J＝9.0Hz,2H),5.42(d,J＝9.5Hz,1H),4.23-4.13(m,1H),3.86(s,3H),2.61(t,J＝6.8Hz,2H),1.86-1.70(m,4H).
13C NMR(101MHz,Chloroform-d)δ163.63,140.70,130.31,129.50,128.56,128.38,126.24,117.59,114.64,55.71,44.23,34.62,33.24,26.64.
Example 11
N- (4-hydroxybutyl) -4-methoxybenzenesulfonamide (259.3 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile having a volume of 10ml were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with white light having a power of 25 Wx 2 three times with nitrogen, stirred at 35℃for 24 hours, and after completion of the reaction, the reaction solution was quenched with saturated aqueous sodium hydrogencarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 74%.
N- (1-cyano-4-hydroxybutyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.85(d,J＝8.9Hz,2H),7.03(d,J＝8.9Hz,2H),6.41(s,1H),4.32(q,J＝7.4Hz,1H),3.89(s,3H),3.81-3.62(m,2H),2.37(s,1H),2.06-1.89(m,2H),1.86-1.70(m,2H).
13C NMR(101MHz,Chloroform-d)δ163.53,130.52,129.46,117.69,114.58,61.55,55.70,44.11,31.13,27.64.
Example 12
4-Methoxy-N- (2-methoxyethyl) benzenesulfonamide (245.3 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with 25 W.times.2 violet light under nitrogen substitution three times, stirred at 35℃for 24 hours, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in 88% yield.
N- (1-cyano-2-methoxyethyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.84(d,J＝9.0Hz,2H),7.01(d,J＝9.0Hz,2H),5.51(d,J＝9.5Hz,1H),4.39(dt,J＝9.5,3.9Hz,1H),3.87(s,3H),3.69-3.56(m,2H),3.40(s,3H).
13C NMR(101MHz,Chloroform-d)δ163.65,130.34,129.54,116.21,114.59,71.87,59.50,55.71,44.44.
Example 13
N- (4-cyanobutyl) -4-methoxybenzenesulfonamide (268.3 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light having a power of 25 Wx 2 three times with nitrogen, stirred at 0℃for 24 hours, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 26%.
N- (1, 4-dicyanobutyl) -4-methoxybenzene sulfonamide
1H NMR(400MHz,Chloroform-d)δ8.57(d,J＝9.1Hz,1H),7.73(d,J＝8.9Hz,2H),7.09(d,J＝8.9Hz,2H),4.38(dt,J＝8.8,7.2Hz,1H),3.80(s,3H),2.47(t,J＝6.3Hz,2H),1.80-1.64(m,2H),1.64-1.44(m,2H).
13C NMR(101MHz,Chloroform-d)δ167.87,136.60,134.18,125.39,123.61,119.71,60.92,48.22,37.22,26.06,20.60.
Example 14
6- ((4-Methoxyphenyl) sulfamido) hexyl benzoate (291.5 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile with a volume of 10ml are added into a reaction tube with magnetic stirring, after three times of nitrogen replacement, the reaction system is irradiated with blue light with a power of 25W×2, stirred at 50 ℃ for 24 hours, after the reaction, the reaction solution is quenched by saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a chromatographic column to obtain the target compound with a yield of 60%.
6-Cyano-6- ((4-methoxyphenyl) sulfamido) benzoic acid hexyl ester
1H NMR(400MHz,Chloroform-d)δ8.06-7.99(m,2H),7.82(d,J＝8.9Hz,2H),7.59-7.51(m,1H),7.47-7.39(m,2H),6.98(d,J＝9.0Hz,2H),5.83(d,J＝9.5Hz,1H),4.27(t,J＝6.5Hz,2H),4.18(dt,J＝9.4,7.2Hz,1H),3.83(s,3H),1.81(q,J＝7.3Hz,2H),1.72(q,J＝6.9Hz,2H),1.58-1.36(m,4H).
13C NMR(101MHz,Chloroform-d)δ166.85,163.55,133.06,130.46,130.20,129.58,129.49,128.45,117.71,114.58,64.69,55.69,44.26,33.71,28.36,25.16,24.76.
Example 15
4-Methoxy-N- (6-phenoxyhexyl) benzenesulfonamide (368.5 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light having a power of 25 W.times.2 three times with nitrogen substitution, stirred at 35℃for 6 hours, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 56%.
N- (1-cyano-6-phenoxyhexyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.84(d,J＝8.8Hz,2H),7.31-7.25(m,2H),7.01(d,J＝8.8Hz,2H),6.94(t,J＝7.3Hz,1H),6.88(d,J＝7.8Hz,2H),5.47-5.37(m,1H),4.19(dt,J＝9.3,7.2Hz,1H),3.93(t,J＝6.3Hz,2H),3.86(s,3H),1.87-1.70(m,4H),1.58-1.42(m,4H).
13C NMR(101MHz,Chloroform-d)δ163.65,158.92,130.37,129.53,129.49,120.68,117.66,114.64,114.51,67.36,55.71,44.31,33.82,28.89,25.25,24.86.
Example 16
N- (6-chlorohexyl) -4-methoxybenzenesulfonamide (305.8 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile (10 ml) were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light having a power of 25 Wx 2 three times with nitrogen, stirred at 35℃for 48 hours, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution after the completion of the reaction, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in a yield of 49%.
N- (6-chloro-1-cyanohexyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.83(d,J＝8.9Hz,2H),7.01(d,J＝8.9Hz,2H),5.56(d,J＝9.5Hz,1H),4.16(dt,J＝9.3,7.2Hz,1H),3.87(s,3H),3.49(t,J＝6.5Hz,2H),1.85-1.67(m,4H),1.51-1.38(m,4H).
13C NMR(101MHz,Chloroform-d)δ163.67,130.29,129.51,117.61,114.65,55.73,44.64,44.23,33.69,32.05,25.86,24.37.
Example 17
N- (2-ethylhexyl) -4-methoxybenzenesulfonamide (299.4 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and 10ml of methylene chloride were added to a reaction tube equipped with magnetic stirring, the reaction system was irradiated with blue light having a power of 25 Wx 2 three times with nitrogen, stirred at 35℃for 24 hours, the reaction mixture was quenched with saturated aqueous sodium hydrogencarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in 43% yield.
N- (1-cyano-2-ethylhexyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.84(d,J＝8.9Hz,2H),7.01(d,J＝8.9Hz,2H),5.49-5.42(m,1H),4.21(dt,J＝10.0,5.6Hz,1H),3.87(s,3H),1.65-1.56(m,1H),1.53-1.31(m,4H),1.30-1.18(m,4H),0.94-0.83(m,6H).
13C NMR(101MHz,Chloroform-d)δ163.58,130.43,129.49,117.28,114.59,55.69,47.23,47.21,43.57,43.51,29.08,28.79,28.71,22.71,22.65,22.56,22.31,13.91,13.89,11.05,10.98.
Example 18
N- (cyclohexylmethyl) -4-methoxybenzenesulfonamide (383.4 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and 10ml of 1, 2-dichloroethane were added to the reaction tube with magnetic stirring, the reaction system was irradiated with 25 Wx 2 blue light after three times of nitrogen substitution, stirred at 35℃for 24 hours, the reaction mixture was quenched with saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by column chromatography to give the objective compound in 43% yield.
N- (cyano (cyclohexyl) methyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,DMSO-d6)δ8.51(d,J＝9.2Hz,1H),7.83-7.75(m,2H),7.16-7.09(m,2H),4.13(dd,J＝9.1,7.1Hz,1H),3.84(s,3H),1.79-1.62(m,4H),1.62-1.49(m,2H),1.24-0.98(m,4H),0.97-0.83(m,1H).
13C NMR(101MHz,DMSO-d6)δ162.99,132.17,129.44,118.24,114.82,56.14,49.37,40.84,28.70,28.54,25.88,25.39,25.38.
Example 19
Methyl 2- ((4-methoxyphenyl) sulfamido) hexanoate (315.4 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetra (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and ethyl acetate with a volume of 10ml were added into a reaction tube equipped with magnetic stirring, after three times of nitrogen replacement, the reaction system was irradiated with blue light with a power of 25W×2, stirred at 35 ℃ for 24 hours, after the reaction, the reaction solution was quenched with saturated aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a chromatographic column to obtain the target compound with a yield of 23%.
2-Cyano-2- ((4-methoxyphenyl) sulfamido) hexanoic acid methyl ester
1H NMR(600MHz,Chloroform-d)δ7.90(d,J＝8.8Hz,2H),6.99(d,J＝8.8Hz,2H),5.58(s,1H),3.88(s,3H),3.87(s,3H),2.17-2.09(m,1H),2.04-1.97(m,1H),1.44-1.28(m,4H),0.88(t,J＝7.1Hz,3H).
13C NMR(151MHz,Chloroform-d)δ167.28,163.59,131.28,129.90,114.98,114.24,59.23,55.66,54.46,38.23,25.71,21.93,13.56.
Example 20
N- (2, 2-dimethylhexyl) -4-methoxybenzenesulfonamide (299.4 mg,1 mmol), 4-cyanopyridine (104.1 mg,1 mmol), cesium carbonate (325.8 mg,1 mmol), 2,4,5, 6-tetrakis (diphenylamino) isophthalonitrile (4.0 mg,0.005 mmol) and acetonitrile in a total volume of 10ml in a methylene chloride ratio of 1 were added to a reaction tube equipped with magnetic stirring: 1, and after nitrogen replacement for three times, the reaction system is irradiated under blue light with the power of 25W multiplied by 2, stirred at 35 ℃ for reaction for 24 hours, after the reaction is finished, the reaction liquid is quenched by saturated sodium bicarbonate water solution, extracted by ethyl acetate, dried, filtered, concentrated under reduced pressure, and finally separated and purified by a chromatographic column to obtain the target compound with the yield of 59 percent.
N- (1-cyano-2, 2-dimethylhexyl) -4-methoxybenzenesulfonamide
1H NMR(400MHz,Chloroform-d)δ7.84(d,J＝8.8Hz,2H),7.01(d,J＝8.8Hz,2H),5.54(d,J＝10.5Hz,1H),3.92(d,J＝10.5Hz,1H),3.87(s,3H),1.39-1.31(m,2H),1.29-1.17(m,4H),1.00(s,3H),0.99(s,3H),0.88(t,J＝7.1Hz,3H).
13C NMR(101MHz,Chloroform-d)δ163.56,130.45,129.48,116.90,114.59,55.67,53.71,37.97,37.73,25.62,23.28,23.18,22.87,13.96.
The above embodiments are only for illustrating the technical solution of the present invention and not for limiting the present invention, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the claims of the present invention.
Claims (10)
1. The synthesis process of alpha-cyano sulfonamide derivative includes adding sulfonamide shown in the formula (I), cyanidation reagent, alkali and photocatalyst into reaction solvent under the protection of inert gas nitrogen, stirring thoroughly under the irradiation of light source, separating and purifying to obtain alpha-cyano sulfonamide derivative shown in the formula (II), and the reaction process is as follows:
Wherein n=0, 1, 2 or 4, r 1 is selected from hydrogen, methyl, methoxy, trifluoromethyl or halogen; r 2 is selected from hydrogen or an ester group; r 3 is selected from hydrogen or ethyl; r 4 is selected from hydrogen, alkyl, phenyl, hydroxy, alkoxy, cyano, benzoate, phenoxy, chloro, or cycloalkyl.
2. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the cyanating agent is 4-cyanopyridine, 3-cyanopyridine or 2-cyanopyridine.
3. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the base is cesium carbonate, potassium carbonate or potassium phosphate.
4. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the photocatalyst in the photocatalytic system is 2,4,5, 6-tetra (diphenylamino) isophthalonitrile, 2,4,5, 6-tetra (carbazol-9-yl) -1, 3-dicyanobenzene, or tris (2-phenylpyridine) iridium.
5. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the amount of the photocatalyst is 0.5% to 5% of the molar amount of the sulfonamide compound represented by formula (I).
6. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the molar ratio of sulfonamide represented by formula (i) to cyanating agent, base is 1: 1-2: 1 to 3.
7. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the light source is white light, blue light or violet light.
8. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the reaction temperature is 0 to 50 ℃ and the reaction time is 6 to 48 hours.
9. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the solvent is selected from one or more of acetonitrile, dichloromethane, 1, 2-dichloroethane, and ethyl acetate.
10. The method for synthesizing an α -cyano sulfonamide derivative according to claim 1, wherein the post-treatment of the reaction is: the reaction solution is quenched by saturated sodium bicarbonate aqueous solution, extracted by ethyl acetate, the organic phase is washed by saturated NaCl, separated, combined, dried by anhydrous Na 2SO4 and concentrated under reduced pressure to obtain a crude product, and the crude product is separated and purified by a chromatographic column to obtain an alpha-cyano sulfonamide derivative product shown as a target compound formula (II).
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