A lewis acid-promoted method for the non-hydrolytic deacylation of n-acyl secondary sulfonamides

Abstract

The application discloses a Lewis acid promoted N-acyl secondary sulfonamide deacylation method without hydrolysis. The method comprises the following steps: N-acyl secondary sulfonamide and Lewis acid are subjected to deacylation reaction in an organic solvent to generate primary sulfonamide. The application uses Lewis acid as a deacylation reagent without hydrolysis, and is used for substrates containing acid or base unstable functional groups. The reaction operation is simple, and the reaction efficiency is high.

Description

Technical Field

[0001] This invention belongs to the field of intermediate synthesis of pharmaceuticals and chemical raw materials, and particularly relates to a Lewis acid-promoted non-hydrolyzed deacylation method for N-acyl secondary sulfonamides. Background Technology

[0002] N-Acylsulfonamides have wide applications in organic synthesis, and the removal of their acyl groups is usually achieved through hydrolysis under acidic or basic conditions. The following are some non-hydrolysis methods for removing the acyl group of N-acylsulfonamide in the literature: (1) using Vilsmeier reagent to convert N-acylsulfonamide into N-sulfonylformamidine, and then reacting it with hydrazine hydrate to obtain primary sulfonamide (Eur.J.Org.Chem.2013,2013,5381-5386); (2) reacting N-acylsulfonamide with trimethyl orthoformate to obtain N-sulfonylacetimidate, and then alcoholystolysing it with methanol to obtain primary sulfonamide (Russ.J.Org.Chem.2006,42,1792-1799); (3) and using excess AlCl3 (4 times the amount) to directly remove the acyl group of N-acylsulfonamide by heating in acetonitrile (J.Org.Chem.2022,87,3586-3595). Hydrolysis methods are unsuitable for substrates containing functional groups that are unstable to acids or bases. Existing non-hydrolyzed acylation methods either require two steps or use excess reagents, both of which are inconvenient. Therefore, there is an urgent need to propose a simple and mild non-hydrolyzed acylation method. Summary of the Invention

[0003] To address the problem of non-hydrolyzable acyl decomposition of N-acyl secondary sulfonamides, which is difficult to solve with existing technologies, this invention provides a Lewis acid-promoted method for non-hydrolyzable acyl decomposition of N-acyl secondary sulfonamides. This method is mild, simple to operate, and highly efficient.

[0004] The objective of this invention is achieved through the following technical solution:

[0005] A Lewis acid-promoted non-hydrolyzed deacylation method for N-acyl secondary sulfonamides includes the following steps: N-acyl secondary sulfonamide (Formula I) and a Lewis acid undergo a deacylation reaction in an organic solvent to generate primary sulfonamide (Formula II), the chemical reaction formula of which is as follows:

[0006]

[0007] R and R' are independently derived from any one of alkyl, aryl, and heteroaryl groups.

[0008] Preferably, the alkyl group is one of methyl, ethyl, and isopropyl.

[0009] Preferably, the molar ratio of the acyl group in the Lewis acid and the N-acyl sec. sulfonamide is 0.01 to 4:1.

[0010] Preferably, the organic solvent is an alcohol solvent or an aqueous solution of an alcohol solvent.

[0011] Preferably, the alcohol solvent is at least one selected from methanol, ethanol, propanol, isopropanol, butanol, isobutanol, trifluoroethanol, and ethylene glycol.

[0012] Preferably, the aqueous solution of the alcohol solvent is a 95% ethanol solution, a 95% industrial ethanol solution, or a 75% ethanol solution.

[0013] Preferably, the ratio of the organic solvent to N-acyl sulfonamide is not specifically limited. Generally, if more solvent is used, the reaction will be slower, but the impact is not significant and can be compensated for by extending the reaction time.

[0014] Preferably, the deacylation reaction is carried out at a temperature ranging from room temperature to the reflux temperature of the organic solvent. Reactions at room temperature are typically slow and require extended reaction times.

[0015] Preferably, the deacylation reaction takes 0.5 to 48 hours.

[0016] Preferably, the Lewis acid is at least one selected from FeCl3, RuCl3, GaCl3, SbCl3, ScCl3, YCl3, lanthanide hydrochlorides, and lanthanide trifluoromethanesulfonates or their hydrates.

[0017] Preferably, the hydrochloride salt of the lanthanide element is LaCl3 or CeCl3.

[0018] Preferably, the lanthanide trifluoromethanesulfonate is Cu(OTf)3, Ga(OTf)3, In(OTf)3, Bi(OTf)3, Sc(OTf)3, Y(OTf)3, and La(OTf)3, Er(OTf)3 or Ce(OTf)3.

[0019] Compared with the prior art, the beneficial effects of the present invention include:

[0020] (1) The present invention can be used for substrates containing functional groups such as ester groups that are unstable to acids and bases.

[0021] (2) The present invention uses Lewis acids such as FeCl3 and Cu(OTf)2 as non-hydrolyzed acylating reagents, which makes the reaction operation simple and the reaction efficiency high. Detailed Implementation

[0022] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0023] Example 1

[0024] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0025]

[0026] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.154 g of a white solid, yield: 90%. Melting point: 136.5–137.5 °C. Rf = 0.71 (petroleum ether / ethyl acetate = 1:1).

[0027] 1H NMR (400MHz, DMSO-d6) δ7.71(d,J=8.3Hz,2H),7.36(d,J=8.0Hz,2H),7.28(s,2H),2.37(s,3H).

[0028] Example 2

[0029] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0030]

[0031] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and GaCl3 (0.087 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.156 g of p-toluenesulfonamide, 90% yield.

[0032] Example 3

[0033] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0034]

[0035] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and SbCl3 (0.114 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.168 g of p-toluenesulfonamide, yield: 98%.

[0036] Example 4

[0037] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0038]

[0039] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and ScCl3·6H2O (0.131 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.167 g of p-toluenesulfonamide, yield: 97%.

[0040] Example 5

[0041] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0042]

[0043] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and YCl3·6H2O (0.151 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.168 g of p-toluenesulfonamide, yield: 98%.

[0044] Example 6

[0045] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0046]

[0047] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and LaCl3·6H2O (0.177 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.169 g of p-toluenesulfonamide, yield: 98%.

[0048] Example 7

[0049] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0050]

[0051] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and TbCl3·6H2O (0.187 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.157 g of p-toluenesulfonamide, yield: 91%.

[0052] Example 8

[0053] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0054]

[0055] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and CeCl3·7H2O (0.186 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.168 g of p-toluenesulfonamide, yield: 98%.

[0056] Example 9

[0057] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0058]

[0059] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and In(OTf)3 (0.028 g, 0.05 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.157 g of p-toluenesulfonamide, yield: 91%.

[0060] Example 10

[0061] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0062]

[0063] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and Ce(OTf)3 (0.028 g, 0.05 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.157 g of p-toluenesulfonamide, yield: 91%.

[0064] Example 11

[0065] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0066]

[0067] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and Y(OTf)3 (0.026 g, 0.05 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.159 g of p-toluenesulfonamide, yield: 92%.

[0068] Example 12

[0069] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0070]

[0071] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and La(OTf)3 (0.026 g, 0.05 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.166 g of p-toluenesulfonamide, yield: 97%.

[0072] Example 13

[0073] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0074]

[0075] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and Ga(OTf)3 (0.025 g, 0.05 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.166 g of p-toluenesulfonamide, yield: 97%.

[0076] Example 14

[0077] N-(4-Toluenesulfonyl)trifluoroacetamide undergoes the detrifluoroacetyl group reaction, as shown in the following chemical reaction formula:

[0078]

[0079] N-(4-Toluenesulfonyl)trifluoroacetamide (0.267 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.164 g of p-toluenesulfonamide, yield: 95%.

[0080] Example 15

[0081] N-(4-Toluenesulfonyl)propionamide undergoes depropionylation, and the chemical reaction is as follows:

[0082]

[0083] N-(4-Toluenesulfonyl)propionamide (0.228 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.169 g of p-toluenesulfonamide, yield: 98%.

[0084] Example 16

[0085] N-(4-Toluenesulfonyl)octylamide undergoes deoctyl grouping, with the chemical reaction formula as follows:

[0086]

[0087] N-(4-Toluenesulfonyl)octylamide (0.119 g, 0.3 mmol) and FeCl3 (0.024 g, 0.15 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.044 g of p-toluenesulfonamide, yield: 85%.

[0088] Example 17

[0089] N-(benzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0090]

[0091] N-Benzenesulfonylacetamide (0.199 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.154 g of a white solid, yield: 98%. Melting point: 152.5–154.5 °C. Rf = 0.64 (petroleum ether / ethyl acetate = 1:1).

[0092] 1H NMR (400MHz, DMSO-d6) δ7.93-7.77(m,2H),7.67-7.51(m,3H),7.35(br s,2H).

[0093] Example 18

[0094] N-(2-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0095]

[0096] N-(2-Toluenesulfonyl)acetamide (0.107 g, 0.5 mmol) and FeCl3 (0.041 g, 0.25 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.075 g of a white solid, yield: 87%. Melting point: 154.5–156.5 °C. Rf = 0.34 (petroleum ether / ethyl acetate = 3:1).

[0097] 1H NMR (400MHz, DMSO-d6) δ7.85 (dd, J1=7.7Hz, J2=1.8Hz, 1H), 7.48 (td, J1=7.7Hz, J2=1.4Hz, 1H), 7.41-7.31 (m, 4H), 2.59 (s, 3H).

[0098] Example 19

[0099] N-(4-tert-butylbenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0100]

[0101] N-(4-tert-butylbenzenesulfonyl)acetamide (0.255 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.208 g of a white solid, yield: 97%. Melting point: 137-138 °C. Rf = 0.36 (petroleum ether / ethyl acetate = 3:1).

[0102] 1H NMR (400MHz, DMSO-d6) δ7.75(d,J=8.6Hz,2H),7.58(d,J=8.6Hz,2H),7.27(s,2H),1.30(s,9H).

[0103] Example 20

[0104] N-(4-hydroxybenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0105]

[0106] N-(4-hydroxybenzenesulfonyl)acetamide (0.108 g, 0.5 mmol) and FeCl3 (0.041 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.073 g of a white solid, yield: 84%. Melting point: 172.5–174 °C. Rf = 0.39 (petroleum ether / ethyl acetate = 1:1).

[0107] 1H NMR (400MHz, DMSO-d6) δ10.25 (s, 1H), 7.64 (d, J = 8.7Hz, 2H), 7.11 (s, 2H), 6.87 (d, J = 8.7Hz, 2H).

[0108] 13C NMR (101MHz, DMSO-d6) δ160.8, 135.0, 128.3, 115.6.

[0109] Example 21

[0110] N-(4-methoxybenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0111]

[0112] N-(4-methoxybenzenesulfonyl)acetamide (0.230 g, 1 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.170 g of a white solid, yield: 90%. Melting point: 108–109.5 °C. Rf = 0.55 (petroleum ether / ethyl acetate = 1:1).

[0113] 1H NMR (400MHz, DMSO-d6) δ7.76 (d, J = 8.8 Hz, 2H), 7.22 (s, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H).

[0114] Example 22

[0115] N-(4-benzyloxybenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0116]

[0117] N-(4-benzyloxybenzenesulfonyl)acetamide (0.153 g, 0.5 mmol) and FeCl3 (0.040 g, 0.25 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.108 g of a white solid, yield: 81%. Melting point: 168.5–170.5 °C. Rf = 0.76 (petroleum ether / ethyl acetate = 2:1).

[0118] 1H NMR (400MHz, DMSO-d6) δ7.74(d,J=8.9Hz,2H),7.49-7.31(m,5H),7.21(s,2H),7.16(d,J=8.9Hz,2H),5.20(s,2H).

[0119] 13C NMR (101MHz, DMSO-d6) δ160.5,136.3,136.3,128.4,127.9,127.6,127.5,114.7,69.4.

[0120] Example 23

[0121] N-(2-chlorobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0122]

[0123] N-(2-chlorobenzenesulfonyl)acetamide (0.234 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.183 g of a white solid, yield: 95%. Melting point: 186–188 °C. Rf = 0.74 (petroleum ether / ethyl acetate = 1:1).

[0124] 1H NMR (400MHz, DMSO-d6) δ7.99 (dd, J1=7.8Hz, J2=1.6Hz, 1H), 7.68-7.57 (m, 4H), 7.53 (ddd, J1=7.8Hz, J2=7.1Hz, J3=1.6Hz, 1H).

[0125] 13C NMR (101MHz, DMSO-d6) δ141.5,133.9,132.0,130.8,129.4,127.9.

[0126] Example 24

[0127] N-(3-bromobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0128]

[0129] N-(3-bromobenzenesulfonyl)acetamide (0.278 g, 1 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.217 g of a white solid, yield: 91%. Melting point: 154.5–156.5 °C. Rf = 0.75 (petroleum ether / ethyl acetate = 1:1).

[0130] 1H NMR (400MHz, DMSO-d6) δ7.98(t,J=1.8Hz,1H),7.85-7.82(m,1H),7.82-7.81(m,1H),7.55(t,J=7.9Hz,1H),7.52(br s,2H).

[0131] Example 25

[0132] N-(4-fluorobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0133]

[0134] N-(4-fluorobenzenesulfonyl)acetamide (0.217 g, 1 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.158 g of a white solid, yield: 90%. Melting point: 124.5–126 °C. Rf = 0.71 (petroleum ether / ethyl acetate = 1:1).

[0135] 1H NMR (400MHz, DMSO-d6) δ7.92-7.85(m,2H),7.46-7.37(m,4H).

[0136] Example 26

[0137] N-(4-cyanobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0138]

[0139] N-(4-cyanobenzenesulfonyl)acetamide (0.224 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.173 g of a white solid, yield: 95%. Melting point: 169–170 °C. Rf = 0.62 (petroleum ether / ethyl acetate = 1:1).

[0140] 1H NMR (400MHz, DMSO-d6) δ8.08(d,J=8.8Hz,2H),7.98(d,J=8.8Hz,2H),7.66(br s,2H).

[0141] Example 27

[0142] N-(4-acetylbenzenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0143]

[0144] N-(4-acetylbenzenesulfonyl)acetamide (0.250 g, 1.04 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.195 g of an off-white solid, yield: 95%. Melting point: 177.5–179 °C. Rf = 0.59 (petroleum ether / ethyl acetate = 1:1).

[0145] 1H NMR (400MHz, DMSO-d6) δ8.13(d,J=8.1Hz,2H),7.96(d,J=8.1Hz,2H),7.56(s,2H),2.64(s,3H).

[0146] Example 28

[0147] N-(4-trifluoromethylbenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0148]

[0149] N-(4-trifluoromethylbenzenesulfonyl)acetamide (0.267 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.209 g of a white solid, yield: 92%. Melting point: 176–180 °C. Rf = 0.78 (petroleum ether / ethyl acetate = 1:1).

[0150] 1H NMR (400MHz, DMSO-d6) δ8.04(d,J=8.3Hz,2H),7.98(d,J=8.2Hz,2H),7.62(br s,2H).

[0151] Example 29

[0152] N-(3-nitrobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0153]

[0154] N-(3-nitrobenzenesulfonyl)acetamide (0.245 g, 1 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.184 g of a white solid, yield: 90%. Melting point: 166–168 °C. Rf = 0.61 (petroleum ether / ethyl acetate = 1:1).

[0155] 1H NMR (400MHz, DMSO-d6) δ8.60 (t, J = 2.1Hz, 1H), 8.46 (dd, J1 = 8.3Hz, J2 = 2.4Hz, 1H), 8.30-8.18 (m, 1H), 7.90 (t, J = 8.0Hz, 1H), 7.73 (s, 2H).

[0156] Example 30

[0157] N-(3-nitrobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0158]

[0159] N-(3-nitrobenzenesulfonyl)acetamide (0.244 g, 1 mmol) and Sc(OTf)3 (0.024 g, 0.05 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.188 g of a white solid, yield: 93%.

[0160] Example 31

[0161] N-(4-nitrobenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0162]

[0163] N-(4-nitrobenzenesulfonyl)acetamide (0.244 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.197 g of a white solid, yield: 97%. Melting point: 178–180 °C. Rf = 0.73 (petroleum ether / ethyl acetate = 1:1).

[0164] 1H NMR (400MHz, DMSO-d6) δ8.42(d,J=8.9Hz,2H),8.07(d,J=8.9Hz,2H),7.73(br s,2H).

[0165] Example 32

[0166] N-(2-methoxycarbonylbenzenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0167]

[0168] N-(2-methoxycarbonylbenzenesulfonyl)acetamide (0.256 g, 1 mmol) and FeCl3 (0.085 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.196 g of a white solid, yield: 91%. Melting point: 123–125 °C. Rf = 0.68 (petroleum ether / ethyl acetate = 1:1).

[0169] 1H NMR (400MHz, CDCl3) δ8.16 (d, J = 9.2Hz, 1H), 7.87 (d, J = 9.0Hz, 1H), 7.70-7.60 (m, 2H), 5.76 (br s, 2H), 4.00 (s, 3H).

[0170] 13C NMR (101MHz, CDCl3) δ168.0,141.5,132.4,132.1,130.8,129.8,128.4,53.5.

[0171] Example 33

[0172] N-(2-naphthalenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0173]

[0174] N-(2-naphthalenesulfonyl)acetamide (0.124 g, 0.5 mmol) and FeCl3 (0.040 g, 0.25 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.102 g of a white solid, yield: 98%. Melting point: 214.5–216.5 °C. Rf = 0.68 (petroleum ether / ethyl acetate = 1:1).

[0175] 1H NMR (400MHz, DMSO-d6) δ8.46-8.40(m,1H),8.18-8.08(m,2H),8.06-8.00(m,1H),7.89(dd,J1=8.6Hz ,J2=1.9Hz,1H),7.69(dt,J1=6.8Hz,J2=1.6Hz,1H),7.66(dt,J1=6.8Hz,J2=1.6Hz,1H),7.46(s,2H).

[0176] Example 34

[0177] N-(2-thiophenesulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0178]

[0179] N-(2-thiophenesulfonyl)acetamide (0.206 g, 1 mmol) and FeCl3 (0.083 g, 0.5 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.142 g of a white solid, yield: 86%. Melting point: 144.5–146 °C. Rf = 0.70 (petroleum ether / ethyl acetate = 1:1).

[0180] 1H NMR (400MHz, DMSO-d6) δ7.84 (d, J = 4.9Hz, 1H), 7.66 (s, 2H), 7.56 (t, J = 3.2Hz, 1H), 7.23-7.05 (m, 1H).

[0181] Example 35

[0182] N-(benzylsulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0183]

[0184] N-(benzylbenzenesulfonyl)acetamide (0.213 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.168 g of a white solid, yield: 98%. Melting point: 101.5–103.5 °C. Rf = 0.30 (petroleum ether / ethyl acetate = 2:1).

[0185] 1H NMR (400MHz, DMSO-d6) δ7.46-7.28(m,5H),6.84(s,2H),4.26(s,2H).

[0186] Example 36

[0187] N-(tert-butylsulfonyl)acetamide undergoes deacetylation, with the chemical reaction formula as follows:

[0188]

[0189] N-(tert-butylsulfonyl)acetamide (0.179 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, the solvent was removed by rotary evaporation. The residue was purified by recrystallization from n-hexane and ethyl acetate to give 0.132 g of a white solid, yield: 96%. Melting point: 167.5–169 °C.

[0190] 1H NMR (400MHz, CDCl3) δ4.47 (br s, 2H), 1.45 (s, 9H).

[0191] Example 37

[0192] The chemical reaction formula for the deacetylation of N-((3-benzisoxazole)methanesulfonyl)acetamide is as follows:

[0193]

[0194] N-((3-benzisoxazole)methanesulfonyl)acetamide (0.254 g, 1 mmol) and FeCl3 (0.082 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 95% industrial ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.181 g of a white solid, yield: 85%. Melting point: 161.5–163.5 °C. Rf = 0.28 (petroleum ether / ethyl acetate = 3:1).

[0195] 1H NMR (400MHz, DMSO-d6) δ7.98(d,J=7.9Hz,1H),7.78(d,J=8.5Hz,1H),7.68(ddd,J1=8.4Hz,J2=7 .0Hz, J3=1.2Hz, 1H), 7.44 (ddd, J1=7.9Hz, J2=7.0Hz, J2=0.9Hz, 1H), 7.27 (s, 2H), 4.86 (s, 2H).

[0196] Example 38

[0197] Celecoxib impurity 25 undergoes deacetylation, and the chemical reaction formula is as follows:

[0198]

[0199] Celecoxib impurity 25 (0.212 g, 0.5 mmol) and FeCl3 (0.040 g, 0.25 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.176 g of a white solid, yield: 92%. Melting point: 163–163.5 °C. Rf = 0.83 (petroleum ether / ethyl acetate = 1:1).

[0200] 1H NMR (400MHz, CDCl3) δ7.90(d,J=8.7Hz,2H),7.47(d,J=8.7Hz,2H),7.18(d,J=7.8Hz,2H),7.11(d,J=8.2Hz,2H),6.74(s,1H),4.98(s,2H),2.38(s,3H).

[0201] Example 39

[0202] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0203]

[0204] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and FeCl3 (0.649 g, 4 mmol) were reacted in anhydrous ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.164 g of p-toluenesulfonamide, with a yield of 95%.

[0205] Example 40

[0206] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0207]

[0208] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and FeCl3 (0.650 g, 4 mmol) were reacted in anhydrous ethanol (5 mL) in an oil bath at 50 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.105 g of p-toluenesulfonamide, yield 61%.

[0209] Example 41

[0210] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0211]

[0212] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and FeCl3 (0.096 g, 0.35 mmol) were reacted in an oil bath at 75 °C for 48 hours in 5 mL of 95% ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.156 g of p-toluenesulfonamide, with a yield of 91%.

[0213] Example 42

[0214] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0215]

[0216] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were reacted in an oil bath at 75 °C for 18 hours in 5 mL of 75% ethanol. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 to 1:1) to give 0.107 g of p-toluenesulfonamide, in 62% yield.

[0217] Example 43

[0218] N-(4-Toluenesulfonyl)acetamide undergoes deacetylation, and the chemical reaction is as follows:

[0219]

[0220] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and Sc(OTf)3 (0.005 g, 0.01 mmol) were reacted in 95% industrial ethanol (5 mL) in an oil bath at 75 °C for 18 hours. After cooling to room temperature, 100-mesh silica gel was added, and the solvent was removed by rotary evaporation. The residue was purified by rapid column chromatography (eluent: petroleum ether / ethyl acetate = 3:1–1:1) to give 0.152 g of p-toluenesulfonamide, in 88% yield.

[0221] The specific embodiments of the present invention described above do not constitute a limitation on the scope of protection of the present invention. Any other corresponding changes and modifications made in accordance with the technical concept of the present invention should be included within the scope of protection of the claims of the present invention.

Claims

1. A Lewis acid-promoted N -A non-hydrolyzed acyl-secondary sulfonamide deacetylation method, characterized in that... Includes the following steps: N - Acyl secondary sulfonamides and Lewis acids undergo a deacylation reaction in organic solvents to form primary sulfonamides, as shown in the following chemical reaction formula: Wherein, R and R' are independently derived from any one of alkyl, aryl, and heteroaryl groups; The organic solvent is an alcohol solvent or an aqueous solution of an alcohol solvent; The alcohol solvent is at least one selected from methanol, ethanol, propanol, isopropanol, butanol, isobutanol, trifluoroethanol, and ethylene glycol. The Lewis acid is at least one of FeCl3, GaCl3, SbCl3, ScCl3, YCl3, LaCl3, CeCl3, Ga(OTf)3, In(OTf)3, Sc(OTf)3, Y(OTf)3, La(OTf)3, Ce(OTf)3, and TbCl3, and all of them include their hydrates.

2. The Lewis acid-promoted method according to claim 1 N -A non-hydrolyzed acyl-secondary sulfonamide deacetylation method, characterized in that... The molar ratio of acyl groups in the Lewis acid and N-acyl sec. sulfonamide is 0.01 to 4:

1.

3. The Lewis acid-promoted method according to claim 1 N -A non-hydrolyzed acyl-secondary sulfonamide deacetylation method, characterized in that... The deacylation reaction is performed at temperatures ranging from room temperature to the reflux temperature of the organic solvent.

4. The Lewis acid-promoted method according to any one of claims 1 to 3 N -A non-hydrolyzed acyl-secondary sulfonamide deacetylation method, characterized in that... The deacylation reaction takes 0.5 to 48 hours.

5. The Lewis acid-promoted [product / treatment] according to any one of claims 1 to 3 N -A non-hydrolyzed acyl-secondary sulfonamide deacetylation method, characterized in that... The aqueous solution of the alcohol solvent is a 95% ethanol solution, a 95% industrial ethanol solution, or a 75% ethanol solution.

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