A method for synthesizing α-cyanosulfonamide derivatives

Abstract

The invention discloses a method for synthesizing an α-cyanosulfonamide derivative. Under the protection of inert gas nitrogen, a sulfonamide represented by formula (I), a cyaniding agent, a base and a photocatalyst are added to a reaction solvent, and the mixture is fully stirred under the irradiation of a light source. After the reaction reaches the end point, the α-cyanosulfonamide derivative represented by formula (II) is separated and purified. 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 The compound is selected from hydrogen, alkyl, phenyl, hydroxyl, alkoxy, cyano, benzoate, phenoxy, chlorine or cycloalkyl. The synthesis method of the invention is green and efficient, with mild conditions and simple post-treatment.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing an alpha-cyanosulfonamide derivative. Background Art

[0002] α-Cyanamide is a class of organic synthetic intermediates with great value and multifunctionality. They contain two different reactive groups, amino and cyano, in their structures, which makes them play a key role in the synthesis of complex nitrogen-containing heterocyclic compounds, drug molecules and natural products with biological activity. The synthetic potential of α-cyanamide is reflected in its diverse reaction pathways. Through decyanation reaction, the cyano group can be converted into an iminium ion, which can then undergo addition or cyclization reactions with various carbon sources or heteroatom-containing nucleophiles to construct a variety of molecular skeletons. In addition, α-cyanamide can also generate α-amino carbon anions through α-deprotonation reaction, which can be used as equivalents of carbon anions or acyl anions, and can undergo substitution or condensation reactions with electrophilic reagents to introduce a variety of functional groups. Furthermore, α-cyanamide can convert the cyano group into a carboxyl group or an amide group through hydrolysis reaction to generate α-amino acids or α-aminoamides. These derivatives play a vital role in many biological processes.

[0003]

[0004] There are two main methods for preparing α-cyanamide: one is to use the classic Strecker reaction, that is, aldehydes or ketones react with amines and potassium cyanide to generate α-cyanamide; the other is to use safe cyanide sources, such as ferrocyanide, thiocyanate, etc., to react with imines or carbonyl compounds through metal catalysis or photochemical methods to generate α-cyanamide. Although these methods have made progress in the synthesis of α-cyanamide, they still face some challenges, including harsh reaction conditions, expensive catalysts, highly toxic cyaniding reagents, and unwanted byproducts.

[0005] Therefore, developing a new method for preparing α-cyanamide that is both efficient, environmentally friendly, and low-cost is a challenge that needs to be addressed urgently. Summary of the invention

[0006] In view of the above problems, the object of the present invention is to provide a method for synthesizing α-cyanosulfonamide derivatives.

[0007] The specific technical solutions are as follows:

[0008] Under the protection of inert gas nitrogen, the sulfonamide represented by formula (I), cyaniding agent, base and photocatalyst are added to the reaction solvent, and fully stirred at a certain temperature under the irradiation of light source. After the reaction reaches the end point, the α-cyanosulfonamide derivative represented by formula (II) is separated and purified. The reaction process is as follows:

[0009]

[0010] 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 Selected from hydrogen, alkyl, phenyl, hydroxy, alkoxy, cyano, benzoate, phenoxy, chloro or cycloalkyl.

[0011] Furthermore, the cyaniding agent is 4-cyanopyridine, 3-cyanopyridine or 2-cyanopyridine.

[0012] Further, the base is cesium carbonate, potassium carbonate or potassium phosphate.

[0013] Furthermore, the photocatalyst in the photocatalytic system is 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile, 2,4,5,6-tetrakis(carbazole-9-yl)-1,3-dicyanobenzene or tris(2-phenylpyridine)iridium.

[0014] Furthermore, the amount of the photocatalyst is 0.5% to 5% of the molar amount of the sulfonamide compound represented by formula (I).

[0015] Furthermore, the molar ratio of the sulfonamide represented by formula (I) to the cyaniding agent and the base is 1:1-2:1-3.

[0016] Furthermore, the light source is white light, blue light or purple light.

[0017] Furthermore, the reaction temperature is 0 to 50° C., and the reaction time is 6 to 48 hours.

[0018] Furthermore, the solvent is selected from one or more of acetonitrile, dichloromethane, 1,2-dichloroethane and ethyl acetate.

[0019] Furthermore, the post-treatment process of the reaction is: the reaction solution is quenched with a saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate, the organic phase is washed with saturated NaCl, separated, the organic layers are combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude product, the crude product is separated and purified by a chromatographic column to obtain the target compound α-cyanosulfonamide derivative product shown in formula (II).

[0020] The beneficial effects of the present invention are:

[0021] The invention uses readily available sulfonamide compounds as starting materials to efficiently synthesize α-cyanosulfonamide derivatives, has the advantages of simple operation, mild reaction conditions, simple post-treatment, and the like, and provides a new method for synthesizing α-cyanamide compounds. DETAILED DESCRIPTION

[0022] The present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited thereto:

[0023] Example 1

[0024] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 76%.

[0025] N-(1-Cyanopentyl)-4-methoxybenzenesulfonamide

[0026]

[0027] 1 H 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).

[0028] 13 C 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.

[0029] Example 2

[0030] 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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 78%.

[0031] N-(1-Cyanopentyl)benzenesulfonamide

[0032]

[0033] 1 H 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).

[0034] 13 C NMR (101MHz, Chloroform-d) δ139.04,133.63,129.46,127.21,117.53,44.43,33.54,27.05,21.70,13.65.

[0035] Example 3

[0036] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 78%.

[0037] N-(1-Cyanopentyl)-4-methylbenzenesulfonamide

[0038]

[0039] 1 H 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).

[0040] 13 C 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.

[0041] Example 4

[0042] N-pentyl-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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 43%.

[0043] N-(1-Cyanopentyl)-4-(trifluoromethyl)benzenesulfonamide

[0044]

[0045] 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).

[0046] 13 C 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.

[0047] 19 F NMR(565MHz,Chloroform-d)δ-63.26.

[0048] Example 5

[0049] 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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 56%.

[0050] N-(1-Cyanopentyl)-4-fluorobenzenesulfonamide

[0051]

[0052] 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).

[0053] 13 C NMR(101MHz,Chloroform-d)δ165.61(d,J=256.4Hz),135.07(d,J=3.3Hz),130.1 1(d,J=9.6Hz),117.51,116.77(d,J=22.8Hz),44.42,33.46,27.07,21.70,13.63.

[0054] 19 F NMR(376MHz,Chloroform-d)δ-103.36.

[0055] Example 6

[0056] 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(carbazole-9-yl)-1,3-dicyanobenzene (3.9 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 72%.

[0057] 4-Chloro-N-(1-cyanopentyl)benzenesulfonamide

[0058]

[0059] 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).

[0060] 13 C NMR (151MHz, Chloroform-d) δ140.27,137.57,129.77,128.68,117.42,44.46,33.54,27.06,21.70,13.62.

[0061] Example 7

[0062] N-pentyl-3-chlorobenzenesulfonamide (261.8 mg, 1 mmol), 4-cyanopyridine (104.1 mg, 1 mmol), cesium carbonate (325.8 mg, 1 mmol), tri(2-phenylpyridine)iridium (3.3 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 81%.

[0063] 3-Chloro-N-(1-cyanopentyl)benzenesulfonamide

[0064]

[0065] 1 H 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).

[0066] 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.

[0067] Example 8

[0068] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 62%.

[0069] 2-Chloro-N-(1-cyanopentyl)benzenesulfonamide

[0070]

[0071] 1 H 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).

[0072] 13 C 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.

[0073] Example 9

[0074] 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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 57%.

[0075] 4-Bromo-N-(1-cyanopentyl)benzenesulfonamide

[0076]

[0077] 1 H 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).

[0078] 13 C NMR (151MHz, Chloroform-d) δ138.14,132.78,128.81,128.72,117.33,44.47,33.66,27.06,21.72,13.63.

[0079] Example 10

[0080] In a reaction tube equipped with a magnetic stirrer, 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) were added, and 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 76%.

[0081] N-(1-Cyano-4-phenylbutyl)-4-methoxybenzenesulfonamide

[0082]

[0083] 1 H 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).

[0084] 13 C 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.

[0085] Embodiment 11

[0086] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under white light with a power of 25 W×2, and the reaction was stirred at 35°C for 24 hours. After the reaction, the reaction solution was quenched with a saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by a chromatographic column to obtain the target compound with a yield of 74%.

[0087] N-(1-Cyano-4-hydroxybutyl)-4-methoxybenzenesulfonamide

[0088]

[0089] 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).

[0090] 13 C NMR (101MHz, Chloroform-d) δ163.53,130.52,129.46,117.69,114.58,61.55,55.70,44.11,31.13,27.64.

[0091] Example 12

[0092] 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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 purple light, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 88%.

[0093] N-(1-Cyano-2-methoxyethyl)-4-methoxybenzenesulfonamide

[0094]

[0095] 1 H 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).

[0096] 13C NMR (101MHz, Chloroform-d) δ163.65,130.34,129.54,116.21,114.59,71.87,59.50,55.71,44.44.

[0097] Example 13

[0098] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 0 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 26%.

[0099] N-(1,4-Dicyanobutyl)-4-methoxybenzenesulfonamide

[0100]

[0101] 1 H 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).

[0102] 13 C 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.

[0103] Embodiment 14

[0104] In a reaction tube equipped with magnetic stirring, 6-((4-methoxyphenyl)sulfonamido)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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added, and acetonitrile with a volume of 10 ml was added. After nitrogen replacement three times, the reaction system was placed under blue light with a power of 25 W×2, and the reaction was stirred at 50°C for 24 hours. After the reaction, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 60%.

[0105] 6-Cyano-6-((4-methoxyphenyl)sulfonamido)benzoic acid hexyl ester

[0106]

[0107] 1 H 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).

[0108] 13 C NMR(101MHz,Chloroform-d)δ166.85,163.55,133.06,130.46,130.20,129.58,1 29.49,128.45,117.71,114.58,64.69,55.69,44.26,33.71,28.36,25.16,24.76.

[0109] Embodiment 15

[0110] In a reaction tube equipped with a magnetic stirrer, 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-tetrakis(diphenylamino)isophthalonitrile (4.0 mg, 0.005 mmol) were added, and 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 6 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 56%.

[0111] N-(1-Cyano-6-phenoxyhexyl)-4-methoxybenzenesulfonamide

[0112]

[0113] 1 H 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).

[0114] 13 C NMR(101MHz,Chloroform-d)δ163.65,158.92,130.37,129.53,129.49,120.6 8,117.66,114.64,114.51,67.36,55.71,44.31,33.82,28.89,25.25,24.86.

[0115] Example 16

[0116] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of acetonitrile was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 48 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 49%.

[0117] N-(6-Chloro-1-cyanohexyl)-4-methoxybenzenesulfonamide

[0118]

[0119] 1 H 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).

[0120] 13 C 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.

[0121] Embodiment 17

[0122] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of dichloromethane was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 43%.

[0123] N-(1-cyano-2-ethylhexyl)-4-methoxybenzenesulfonamide

[0124]

[0125] 1 H 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).

[0126] 13 C 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.

[0127] Embodiment 18

[0128] 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) were added to a reaction tube equipped with a magnetic stirrer, and then 10 ml of 1,2-dichloroethane was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 43%.

[0129] N-(Cyclohexyl)methyl)-4-methoxybenzenesulfonamide

[0130]

[0131] 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).

[0132] 13 C 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.

[0133] Embodiment 19

[0134] In a reaction tube equipped with magnetic stirring, methyl 2-((4-methoxyphenyl)sulfonamido)hexanoate (315.4 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) were added, and 10 ml of ethyl acetate was added. After nitrogen replacement three times, the reaction system was placed under 25 W × 2 blue light irradiation, stirred at 35 ° C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 23%.

[0135] 2-Cyano-2-((4-methoxyphenyl)sulfonamido)hexanoic acid methyl ester

[0136]

[0137] 1 H 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).

[0138] 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.

[0139] Embodiment 20

[0140] 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) were added to a reaction tube equipped with a magnetic stirrer, and a mixed solvent of acetonitrile and dichloromethane in a ratio of 1:1 with a total volume of 10 ml was added. After nitrogen replacement three times, the reaction system was placed under 25 W×2 blue light irradiation, stirred at 35°C for 24 hours, and after the reaction was completed, the reaction solution was quenched with saturated sodium bicarbonate aqueous solution, extracted with ethyl acetate, dried, filtered, and concentrated under reduced pressure. Finally, it was separated and purified by chromatographic column to obtain the target compound with a yield of 59%.

[0141] N-(1-cyano-2,2-dimethylhexyl)-4-methoxybenzenesulfonamide

[0142]

[0143] 1 H 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=1 0.5Hz,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).

[0144] 13 C 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.

[0145] The above implementation is only used to illustrate the technical solution of the present invention rather than to limit the present invention. Although the present invention is described in detail with reference to the preferred embodiments, a person skilled in the art should understand that the technical solution of the invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present invention, which should be included in the scope of the claims of the present invention.

Claims

1. A method for synthesizing an α-cyanosulfonamide derivative, characterized in that: Under the protection of inert gas nitrogen, the sulfonamide represented by formula (I), cyaniding agent, base and photocatalyst are added to the reaction solvent, and fully stirred under the irradiation of light source. After the reaction reaches the end point, the α-cyanosulfonamide derivative represented by formula (II) is separated and purified. The reaction process is as follows: ， Where 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 cyaniding agent is 4-cyanopyridine, 3-cyanopyridine or 2-cyanopyridine; The photocatalyst in the photocatalytic system is 2,4,5,6-tetrakis(diphenylamino)isophthalonitrile, 2,4,5,6-tetrakis(carbazole-9-yl)-1,3-dicyanobenzene or tris(2-phenylpyridine)iridium.

2. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The base is cesium carbonate, potassium carbonate or potassium phosphate.

3. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The amount of the photocatalyst used is 0.5% to 5% of the molar amount of the sulfonamide compound represented by formula (I).

4. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The molar ratio of the sulfonamide represented by formula (I) to the cyaniding agent and the base is 1:1-2:1-3.

5. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The light source is white light, blue light or purple light.

6. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The reaction temperature is 0~50℃ and the reaction time is 6~48h.

7. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The solvent is selected from one or more of acetonitrile, dichloromethane, 1,2-dichloroethane and ethyl acetate.

8. The method for synthesizing an α-cyanosulfonamide derivative according to claim 1, characterized in that: The post-treatment process of the reaction is: the reaction solution is quenched with a saturated sodium bicarbonate aqueous solution, then extracted with ethyl acetate, the organic phase is washed with saturated NaCl, separated, the organic layers are combined, dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain a crude product, the crude product is separated and purified by a chromatographic column to obtain the target compound α-cyanosulfonamide derivative product represented by formula (II).

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