CN112047865B - Method for synthesizing N-alkyl sulfonamide in water - Google Patents
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- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
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- C07C303/40—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 by reactions not involving the formation of sulfonamide groups
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Abstract
The invention discloses a method for synthesizing N-alkyl sulfonamide in water, which is a method for synthesizing N-alkyl sulfonamide derivatives from sulfonamide derivatives and alcohol. Compared with the prior synthesis method, the reaction process of the invention uses a substrate with equivalent reaction amount, thus avoiding the waste of raw materials; weak base is used, and the reaction condition is mild; the reaction uses non-toxic and harmless pure water as a solvent, and the byproduct only generates water, so that the atom reaction economy is high, and the requirement of green chemistry is met.
Description
Technical Field
The invention belongs to the technical field of organic synthetic chemistry, and particularly relates to a method for synthesizing an N-alkyl sulfonamide derivative.
Background
N-alkyl sulfonamide derivatives represent an important class of nitrogen-containing compounds, exhibiting a wide range of physiological and pharmacological activities. For example, such compounds are used as secreted frizzled-related protein 1 (SFRP-1) inhibitors, potent thromboxane receptor antagonists, mycobacterium tuberculosis inhibitors, antitumor prodrugs, and the like. (a) a. Gopalsamy, m.shi, b.stauffer, r.bahat, j.billiard, h.ponce-de-Leon, l.sesqualler-Wehr, s.fukayama, a.mangine, r.moran, g.krishnamurthhy, p.bodine, j.med.chem.2008,51,7670-7672 b) c.ballator, j.h.soper, f.piscitelli, m.james, l.huang, o.atasoylu, d.m.huryn, j.q.trojanski, v.m.y.lee, k.r.brunden, a.b.smith, j.chem.54, 69-6983; c) S.r.malwal, d.sriram, p.yogeeswari, v.b.konkimalla, h.chakrapani, j.med.chem.2012, 55, 553-557; d) R.j.stevenson, w.a.denny, m.tercel, f.b.pruijn, a.ashoorzadeh, j.med.chem.2012, 55, 2780-2802)
The conventional method for synthesizing N-alkylsulfonamide derivatives is to react N-alkylamine with sulfonyl chloride, however, sulfonyl chloride is a highly toxic compound, is difficult to handle, and is not suitable for long-term storage. Processes have been developed for the direct formation of N-alkylsulfonamide derivatives by reaction with N-alkylamines using sulfonic acid esters or sulfonic acids instead of sulfonyl chlorides, which reactions produce at least equivalent amounts of toxic by-products during the reaction. March, advanced Organic Chemistry,3rd ed.; wiley: new York,1985 b) R.Cremlyn, organic fur Chemistry: an Introduction; john Wiley and Sons: new York,1996; c) R.Sridhar, B.Srinivas, V.P.Kumar, M.Nanender, K.R.Rao, adv.Synth.Catal.2007,349, 1873-1876.d) L.D.Luca, G.Giacomell, J.org.chem.2008,73, 3967-3969.)
Recently, transition metal-catalyzed activation of alcohols to replace alkyl halides as environmentally friendly alkylating agents has attracted considerable attention. Several reports have also shown that transition metals, such as ruthenium, copper, iridium, and the like, salts or complexes thereof can catalyze the reaction of sulfonamide derivatives and alcohols to form N-alkyl sulfonamide derivatives. However, these procedures are typically performed in organic solvents, such as toluene, or using multiple alcohols as solvents (a) h.s.a.hamid, c.l.allen, g.w.lamb, a.c.maxwell, h.c.maytum, a.j.a.watson, j.m.j.williams, j.am.chem.soc.2009,131,1766-1774; b) Shi, m.k.tse, s.zhou, m.m.pohl, j.radnik, s.hubner, k.j.a.bruckner, m.beller, j.am.chem.soc.2009,131,1775-1779; c) R.cano, d.j.ram, n, m.yus, j.org.chem.2011,76,5547-5557; d) M.zhu, k.fujita, r.yamaguchi, org.lett.2010,12, 1336-1339)
Compared to organic solvents, water is obviously cheap, safe and environmentally friendly. Accordingly, it would be desirable to develop a versatile and efficient process for the reaction of sulfonamide derivatives with alcohols in water using water soluble catalysts to produce N-alkyl sulfonamide derivatives.
Disclosure of Invention
The invention aims to provide a method for synthesizing N-alkyl sulfonamide derivatives.
The invention is realized by the following technical scheme: method for synthesizing N-alkyl sulfonamides (formula I)
Which comprises reacting a sulfonamide derivative (formula II)
With a compound alcohol (formula III)
The reaction is carried out under the catalysis of a water-soluble iridium complex, and the reaction general formula is
Wherein R is 1 Is selected from C 1 -C 3 Alkyl, benzyl, aryl, mono-or polysubstituted aryl, such as methylphenyl, nitrophenyl, methoxyphenyl, trifluoromethylphenyl, trifluoromethoxyphenyl, halophenyl, naphthyl;
R 2 is selected from C 4 -C 7 Alkyl, aryl, mono-or polysubstituted aryl, such as methylphenyl, isopropylphenyl, methoxyphenyl, nitrophenyl, trifluoromethylphenyl, trifluoromethoxyphenyl, halophenyl, thienyl, naphthyl. The method is realized by the following steps:
adding a sulfonamide derivative II, a water-soluble iridium complex catalyst, alkali, a compound alcohol III and solvent water into a reaction container, reacting the reaction mixture at 130 +/-10 ℃ for several hours, cooling to room temperature, removing the solvent by rotary evaporation, and separating by a column to obtain the target compound.
Among them, a water-soluble iridium complex (Cp × = pentamethyycyclopentadienyl) has the following structure:
the base is selected from sodium carbonate, potassium carbonate, cesium carbonate or potassium hydroxide; the molar ratio of the water-soluble iridium complex to the sulfonamide derivative is 1.0mol%; the base to sulfonamide derivative molar ratio was 0.1 equiv; the molar ratio of the compound alcohol to the sulfonamide derivative was 1.2.
Compared with the prior art, the N-alkyl sulfonamide derivative is obtained by reacting the sulfonamide derivative with alcohol. The invention uses water-soluble iridium complex as catalyst, and uses safe and environment-friendly water as reagent instead of organic solvent; the reaction time is only 2 hours, so the reaction meets the requirement of green chemistry and has wide development prospect.
Detailed Description
The following examples are shown to illustrate certain embodiments of the present invention and should not be construed as limiting the scope of the invention. Many modifications, variations and changes in the materials, methods and reaction conditions may be made to the present disclosure at the same time. All such modifications, variations and changes are believed to fall within the spirit and scope of the present invention.
Example 1 n-benzyl-4-methylbenzenesulfonamide
N-benzyl-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube reaction flask. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 91 percent.
1 H NMR(500MHz,CDCl 3 )δ7.74(d，J＝8.4Hz,2H,ArH),7.29-7.23(m,5H,ArH),7.19-7.17(m,2H,ArH),4.99(br s,1H,NH),4.09(d,J＝6.0Hz,2H,CH 2 NH)； 13 C NMR(125MHz,CDCl 3 )δ143.4,136.8,136.3,129.7,128.6,127.81,127.78,127.1,47.2,21.4.。
Example 2
N-(2-methylbenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube reaction flask. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 83 percent.
1H NMR(500MHz,CDCl3)δ7.74(d,J＝8.2Hz,2H),7.28(d,J＝8.1Hz,2H),7.15(t,J＝7.0Hz,1H),7.11-7.06(m,3H),4.06(s,2H),2.43(s,3H),2.23(s,3H)；13C NMR(125MHz,CDCl3)δ143.4,136.6,133.9,130.5,129.7,128.8,128.1,127.1,126.1,45.3,21.4,18.7.。
Example 3
N-(4-Methylbenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol,1.0 mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 4-methylbenzyl alcohol (146.6 mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 82 percent.
1H NMR(500MHz,CDCl3)δ7.74(d,J＝7.7Hz,2H),7.29(d,J＝7.8Hz,2H),7.06(s,4H),4.85(br s,1H),4.05(s,2H),2.43(s,3H),2.30(s,3H)；13C NMR(125MHz,CDCl3)δ143.8,143.2,139.5,136.6,129.8,128.5,127.5,127.0,46.4,44.4,21.5.。
Example 4
N-(3-Methoxybenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 3-methoxybenzyl alcohol (166mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 82 percent.
1H NMR(500MHz,CDCl3)δ7.74(s,2H),7.28-7.16(m，3H)，6.76-6.71(m,3H),4.99(br s,1H),4.07(s，2H),3.72(s,3H),2.42(s,3H)；13C NMR(125MHz，CDCl3)δ159.7，143.4,137.8，136.8,129.7,129.6,127.1,120.0,113.6,113.0,55.1,47.1,21.4.。
Example 5N- (4-methoxybenzyl) -4-methylbenzenesulfonamide
N-(4-methoxybenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 4-methoxybenzyl alcohol (166mg, 1.2mmol), and water (1 ml) were added to a microwave tube in this order. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 84 percent.
1H NMR(500MHz,CDCl3)δ7.73(d,J＝7.7Hz,2H),7.29(d,J＝7.7Hz,2H),7.09(d,J＝8.0Hz,2H),6.77(d,J＝8.0Hz,2H),4.85(br s,1H),4.03(d,J＝5.9Hz,2H),3.76(s,3H),2.43(s,3H)；13C NMR(125MHz,CDCl3)δ159.2,143.3,136.8,129.6,129.2,127.7,127.1,113.9，55.2,46.7,21.5.。
Example 6
N-(4-Fluorobenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 4-fluorobenzyl alcohol (151mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 86 percent.
1H NMR(500MHz,CDCl3)δ7.72(d,J＝7.8Hz,2H),7.28(d,J＝7.7Hz,2H),7.15(dd,J＝8.2Hz and 5.6Hz,2H),6.92(t,J＝8.4Hz,2H),4.91(br s,1H),4.07(s,2H),2.42(s,3H)；13C NMR(125MHz,CDCl3)δ162.3(d,JC-F＝246.7Hz),143.5,136.8,132.2,129.7，129.6(d,JC-F＝8.2Hz),127.1,115.4(d,JC-F＝21.6Hz),46.4,21.5.。
Example 7N- (2-chlorobenzyl) -4-methylbenzenesulfonamide
N-(4-fluorobenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 2-chlorobenzyl alcohol (171mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 81 percent.
1H NMR(500MHz,CDCl3)δ7.70(d,J＝8.4Hz,2H),7.24-7.31(m,4H),7.14-7.21(m,2H),5.00(s,2H),4.23(d,J＝6.1Hz,2H),2.41(s,3H)；13C NMR(125MHz,CDCl3)δ143.4,136.9,133.9,133.3,130.3,129.6,129.4,129.2,127.1,45.1,21.5.。
Example 8
N-(2-chlorobenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol,1.0 mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 2-chlorobenzyl alcohol (171mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 90 percent.
1H NMR(500MHz,CDCl3)δ7.72(d,J＝7.6Hz,2H),7.29(d,J＝7.3Hz,2H),7.22(d,J＝7.5Hz,2H),7.13(d,J＝7.2Hz,2H),5.20(br s,1H),4.07(s,2H),2.44(s,3H)；13C NMR(125MHz,CDCl3)δ143.7,136.8,134.8,133.8,129.8,129.2,128.8,127.1,46.6,21.5.。
Example 9
N-(4-Bromobenzyl)-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 4-bromobenzylalcohol (224.4mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 91 percent.
1H NMR(500MHz,CDCl3)δ7.70(d,J＝7.4Hz,2H)，7.35(d,J＝7.8Hz,2H),7.27(d,J＝7.4Hz,2H),7.05(d,J＝7.7Hz,2H),5.24(br s,1H),4.05(s,2H),2.43(s,3H)；13C NMR(125MHz，CDCl3)δ143.5，136.7,135.4,131.5，129.6，129.5,127.0,121.6,46.4,21.4。
Example 10
N-[4-(Trifluoromethyl)benzyl]-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol,1.0 mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 4-trifluoromethylbenzyl alcohol (211.4mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 80 percent.
1H NMR(500MHz,DMSO-d6)δ8.22(br s,1H),7.66(d,J＝8.2Hz,2H),7.62(d,J＝8.1Hz,2H),7.45(d,J＝7.9Hz,2H),7.35(d,J＝7.9Hz,2H),4.07(s,2H),2.37(s,3H)；13C NMR(125MHz,DMSO-d6)δ143.6,138.8,130.5,129.2,128.7(q,JC-F＝31.9Hz),127.5,127.2,126.3,126.0,125.2(q,JC-F＝272.2Hz),46.5,21.8.。
Example 11N- (4- (trifluoromethoxy) benzyl) -4-methylbenzenesulfonamide
N-[4-(Trifluoromethoxy)benzyl]-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1.0mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 4-trifluoromethoxy-benzyl alcohol (230mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 88 percent.
1H NMR(500MHz,DMSO)δ8.15(br s,1H),7.64(d,J＝8.2Hz,2H),7.34(d,J＝8.2Hz,4H),7.25(d,J＝8.7Hz,2H),3.99(ds,2H),2.36(s,3 H)；13C NMR(125MHz,DMSO)δ147.7,143.6,138.8,138.2,130.5,130.4,127.5,121.8,121.2(q,JC-F＝255.3Hz),46.4,21.8.。
Example 12-methyl-N- (1-naphthylmethyl) benzenesulfonamide
4-methyl-N-(naphthalen-1-ylmethyl)benzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol,1.0 mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), 1-naphthalenemethanol (190mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 84 percent.
1H NMR(500MHz,CDCl3)δ7.88-7.75(m,5H),7.47(s,sH),7.32-7.27(m,4H),4.52(s,2H),2.43(s,3H)；13C NMR(125MHz,CDCl3)δ143.5,136.5,133.7,131.3,131.1,129.7,129.0,128.7.127.2,126.9,126.7,126.0,125.2,123.2,45.4,21.5.。
Example 13N-hexyl-4-methylbenzenesulfonamide
N-hexyl-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (66mg, 0.2mmol, 0.2equiv.), n-hexanol (204mg, 2mmol) and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 84 percent.
1H NMR(500MHz,CDCl3)δ7.75(d,J＝7.7Hz,2H),7.31(d,J＝7.9Hz,2H),4.54(br s,1H),2.92(q,J＝6.8Hz，2H)，2.43(s,3H)，1.47-1.41(m,2H),1.26-1.19(m,6H),0.84(t,J＝6.9Hz,3H)；13C NMR(125MHz,CDCl3)δ143.3,137.0，129.6，127.1,43.2,31.2，29.5,26.1,22.4，21.5,13.9.。
Example 14 n-isoamyl-4-methylbenzenesulfonamide
N-isopentyl-4-methylbenzenesulfonamide
4-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (66mg, 0.2mmol, 0.2equiv.), isoamyl alcohol (176mg, 2mmol) and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 74 percent.
1H NMR(500MHz,CDCl3)δ7.75(d,J＝8.1Hz,2H),7.30(d,J＝7.9Hz,2H),4.91(br s,1H),2.73(d,J＝5.9Hz,2H),2.42(s,3H),1.67-1.60(m,5H),1.40-1.38(m,1H),1.17-1.07(m,3H),0.88-0.80(m,2H)；13C NMR(125MHz,CDCl3)δ143.1,137.0,129.6,127.0,49.3,37.6,30.5,26.2,25.6,21.4.。
Example 15 n-benzyl-2-methylbenzenesulfonamide
N-benzyl-2-methylbenzenesulfonamide
2-methylbenzenesulfonamide (171mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 80 percent.
1H NMR(500MHz,CDCl3)δ7.99(d,J＝7.6Hz,1H),7.46(t,J＝7.3Hz,1H),7.34-7.24(m,5H),7.16-7.15(m,2H),4.79(br s,1H),4.11(d,J＝5.9Hz,2H),2.61(s,3H)；13C NMR(125MHz,CDCl3)δ137.7,137.0,136.2,132.8,132.5,129.6,128.7,127.9,126.2,47.1,20.3.。
Example 16N-benzyl-4-methoxybenzenesulphonamide
N-benzyl-4-methoxybenzenesulfonamide
4-methoxybenzenesulfonamide (187mg, 1mmol), a catalyst (7.7 mg,0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 87 percent.
1H NMR(500MHz,CDCl3)δ7.79(d,J＝8.8Hz,2H),7.28-7.24(m,3H),7.18(d,J＝7.8Hz,2H),6.96(d,J＝8.9Hz,2H),4.49(br s,1H),4.10(d,J＝5.1Hz,2H),3.87(s,3H)；13C NMR(125MHz,CDCl3)δ162.9,136.3,131.4,129.3,128.6,127.8,114.2，55.6,47.2.。
Example 17 n-benzyl-4-fluorobenzenesulfonamide
N-benzyl-4-fluorobenzenesulfonamide
4-fluorobenzenesulfonamide (175mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 82 percent.
1H NMR(500MHz,CDCl3)δ7.84(dd,J＝8.7Hz and 5.1Hz,2H),7.25-7.24(m,3H),7.17-7.12(m,4H),4.80(br s,1H),4.13(s,2H)；13C NMR(125MHz,CDCl3)δ165.0(d,JC-F＝254.2Hz),136.0,129.7(d,JC-F＝9.3Hz),128.6,127.9,127.8,116.2(d,JC-F＝22.6Hz),47.2.。
Example 18N-benzyl-4-chlorobenzenesulfonamide
N-benzyl-4-chlorobenzenesulfonamide
4-chlorobenzenesulfonamide (192mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 85 percent.
1H NMR(500MHz,CDCl3)δ7.78(d,J＝7.8Hz,1H),7.46(d,J＝7.8Hz,2H),7.32-7.25(m,5H),7.28-7.26(m,3H),7.19-7.17(m,2H),4.82(br s,1H),4.15(s,2H)；13C NMR(125MHz,CDCl3)δ139.2,138.5,135.9,129.4,128.8,128.6,128.1,127.9,47.3。
Example 19N-benzyl-4-bromobenzenesulfonamide
N-Benzyl-4-bromobenzenesulfonamide
4-bromobenzenesulfonamide (236mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol) and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 85 percent.
1H NMR(500MHz,CDCl3)δ7.69(d,J＝8.0Hz,2H),7.60(d,J＝8.0Hz,2H),7.25(s,3H),7.17(s,2H),5.03(br s,1H),4.13(s,2H)；13C NMR(125MHz,CDCl3)δ139.0,135.9,132.3,128.7,128.6,128.0,127.8,127.6,47.2.。
Example 20N-benzyl-4- (trifluoromethyl) benzenesulfonamide
N-benzyl-4-(trifluoromethyl)benzenesulfonamide
4-trifluoromethylbenzenesulfonamide (225mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 90 percent.
1H NMR(500MHz，CDCl3)δ7.95(d,J＝7.7Hz,2H),7.73(d,J＝8.6Hz,2H),7.26-7.25(m，3H)，7.17-7.17(m,2H),4.19(s,2H)；13C NMR(125MHz，DMSO)δ145.8，138.2，133.0(q,JC-F＝31.9Hz),129.2,128.6,128.4,128.1,127.3,124.5(q,JC-F＝272.2Hz),47.1.。
Example 21N-benzyl-4- (trifluoromethoxy) benzenesulfonamide
N-benzyl-4-(trifluoromethoxy)benzenesulfonamide
4-trifluoromethoxybenzenesulfonamide (241mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 88 percent.
1H NMR(500MHz,CDCl3)δ7.85(d,J＝8.8Hz,2H),7.27-7.23(m,5H),7.16-7.15(m,2H),4.47(br s,1H),4.15(s,2H)；13C NMR(125MHz,CDCl3)δ151.9,138.7,136.0,129.2,128.6,127.9,127.9,120.9,120.2(q,JC-F＝259.7Hz),47.3.。
Example 22
N-benzylbenzenesulfonamide
Benzenesulfonamide (157mg, 1mmol), a catalyst (7.7 mg,0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol) and water (1 ml) were added to a microwave tube in this order. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 85 percent.
1H NMR(500MHz,CDCl3)δ7.86(d,J＝7.5Hz,2H),7.57(t,J＝7.1Hz,1H),7.49(t,J＝7.9Hz,2H),7.24(d,J＝6.8Hz,3H),7.18-7.17(m,2H),4.85(brs,1H),4.12(s,2H)；13C NMR(125MHz,CDCl3)δ139.8,136.2,132.6,129.1,128.6,127.8,127.0,47.1.。
Example 23N-benzyl-2-naphthalenesulfonamide
N-benzylnaphthalene-2-sulfonamide
Naphthalene-2-sulfonamide (207mg, 1mmol), catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: 85 percent.
1H NMR(500MHz,CDCl3)δ8.43(s,1H),7.95-7.90(m,3H),7.63(dd,J＝8.7Hz and 1.8Hz,1H),7.67-7.60(m,2H),7.25-7.17(m,5H),4.16(s,2H)；13C NMR(125MHz,CDCl3)δ136.6,136.1,134.8,132.1,129.5,129.2,128.8，128.7，128.6,127.9,127.9，127.6，122.3,47.4.。
Example 24
N-benzylmethanesulfonamide
Methanesulfonamide (95mg, 1mmol), catalyst (7.7 mg,0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol) and water (1 ml) were added to a microwave tube in this order. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then purified by column chromatography (developing solvent: petroleum ether/ethyl acetate) to give the pure title compound in the following yields: and 76 percent.
1H NMR(500MHz,CDCl3)δ7.37-7.30(m,5H),4.30(s,2H),2.84(s,3H)；13C NMR(125MHz,CDCl3)δ136.7,128.8,128.0,127.9,47.1，40.0.。
Example 25 [ sic ]
N-benzylcyclopropanesulfonamide
Methanesulfonamide (121mg, 1mmol), a catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol), and water (1 ml) were sequentially added to a microwave tube. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 83 percent.
1H NMR(500MHz,CDCl3)δ7.36-7.30(m,5H),4.87(br s,1H),4.32(d,J＝5.1Hz,2H),2.34-2.32(m,1H),1.14-1.23(m,2H),0.91(d,J＝7.7Hz,2H)；13C NMR(125MHz,CDCl3)δ137.1,128.7,127.9,127.8,47.2,30.5,5.4.。
Example 26
N-benzyl(phenyl)methanesulfonamide
Benzylsulfonamide (171mg, 1mmol), catalyst (7.7mg, 0.01mmol, 1mol%), cesium carbonate (33mg, 0.1mmol, 0.1equiv.), benzyl alcohol (130mg, 1.2mmol) and water (1 ml) were added to a microwave tube in this order. After the reaction mixture was reacted at 130 ℃ for 2 hours, it was cooled to room temperature. The solvent was removed by rotary evaporation and then column chromatography (developing solvent: petroleum ether/ethyl acetate) gave the pure title compound in yields: 78 percent.
1H NMR(500MHz,CDCl3)δ7.38-7.26(m,10H),4.19(s,2H),4.13(s,2H)；13C NMR(125MHz,CDCl3)δ136.8,130.6,129.1,128.8,128.0,59.3,47.6.。
Claims (7)
1. A process for the synthesis of N-alkylsulfonamides I in water which comprises
Sulfonamide derivatives II
With the compound alcohol III
A step of reacting in an aqueous solvent in the presence of a base under catalysis of a water-soluble Cp-Ir complex,
wherein R is 1 Is selected from C 1 -C 4 Alkyl, substituted benzyl, aryl, methylphenyl, methoxyphenyl, trifluoromethoxyphenyl, halophenyl;
R 2 represents a substituent selected from C 1 -C 7 Alkyl, aryl, methylphenyl, methoxyphenyl, trifluoromethyl, trifluoromethoxyphenyl, halophenyl;
the structure of the water-soluble Cp × Ir complex is as follows:
2. the method of claim 1, wherein the base is selected from the group consisting of sodium carbonate, potassium carbonate, cesium carbonate, and potassium hydroxide.
3. The process according to claim 1 or 2, wherein the molar amount of base relative to sulfonamide derivative ii is 0.1equiv.
4. The method according to claim 1, wherein the molar amount of water-soluble Cp x Ir complex relative to sulfonamide derivative ii is 1.0mol%.
5. The process according to claim 1, wherein the molar ratio of the compound alcohol III relative to the sulfonamide derivative II is 1.2.
6. The process of claim 1, wherein the reaction temperature is 130 ± 10 ℃.
7. The method of claim 1, wherein the reaction time is 2 hours.
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| CN106146358A (en) * | 2015-04-15 | 2016-11-23 | 南京理工大学 | A kind of method of synthesizing amino-(N-alkyl) benzsulfamide |
| CN110857278A (en) * | 2018-08-23 | 2020-03-03 | 南京理工大学 | Method for synthesizing N-methylsulfonamide in water |
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| CN106146358A (en) * | 2015-04-15 | 2016-11-23 | 南京理工大学 | A kind of method of synthesizing amino-(N-alkyl) benzsulfamide |
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