A lewis acid-promoted direct transacylation of n-acylsulfonamides

Abstract

The application discloses a Lewis acid promoted direct transacylation method of N-acyl sulfonamide, which comprises the following steps: mixing N-acyl sulfonamide, an acylating agent and a Lewis acid, and carrying out direct transacylation reaction at room temperature to the refluxing temperature of the acylating agent to generate corresponding new N-acyl sulfonamide. The method has the advantages of mild conditions, simple operation and high reaction efficiency.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of intermediate synthesis of pharmaceutical and chemical raw materials, and particularly relates to a Lewis acid promoted direct transacylation method of N-acyl sulfonamide. BACKGROUND

[0002] N-acyl sulfonamide is a common and important group, which has certain stability to acid, base and nucleophile, is often used as a Kenner safety-catch linker for solid-phase organic synthesis in organic synthesis, and has a wide application in organic synthesis (Bioorg. Med. Chem. 2005, 13, 585-599). N-acyl sulfonamide has better stability to enzyme and chemical hydrolysis, and has a pH range of 3.5-4.5, which is equivalent to carboxyl, and is often used as a bioisostere of carboxyl in drug research and development (Chem. Biol. Drug Des. 2017, 90, 1094-1105), and appears in numerous drug structures (J. Org. Chem. 2019, 84, 6970-6981).

[0003] N-acyl sulfonamide and acylating agent can quickly prepare a series of different N-acyl analogues through transacylation reaction, so as to realize the structural diversification of N-acyl sulfonamide. However, due to the nucleophilicity of the amide N, the transacylation reaction of N-acyl sulfonamide is more difficult than that of ordinary amide. The transacylation of ordinary amide generally needs to be hydrolyzed and then acylated, or first converted into a perfluoroacyl amide, and then reacted with acyl chloride / tertiary amine to prepare another amide (Angew. Chem. Int. Ed. Engl. 2010, 49, 1850-1853). There are only sporadic reports on the direct transacylation reaction of ordinary amide. SUMMARY

[0004] In view of the problem of direct transacylation of N-acyl sulfonamide which cannot be solved by the prior art, the purpose of the present application is to provide a Lewis acid promoted direct transacylation method of N-acyl sulfonamide. The method has mild conditions, simple operation and high reaction efficiency.

[0005] The purpose of the present application is achieved by the following technical solutions:

[0006] A Lewis acid promoted direct transacylation method of N-acyl sulfonamide, comprising the following steps: mixing N-acyl secondary sulfonamide (formula I), acylating agent and Lewis acid to occur direct transacylation reaction, and generating corresponding new N-acyl secondary sulfonamide (formula II);

[0007] The chemical reaction formula is as follows:

[0008]

[0009] Among them, R 1 It is any one of hydrogen, alkyl, aryl, and heteroaryl;

[0010] R, R 2 and R 3 They are independently derived from any one of alkyl, aryl, and heteroaryl groups.

[0011] Preferably, the molar ratio of the acyl group in the Lewis acid and the N-acyl sec. sulfonamide is 0.1 to 4:1.

[0012] Preferably, the acylation agent is at least one of an acyl halide and an acid anhydride; more preferably, the acyl halide is an acyl chloride.

[0013] Preferably, the temperature of the direct transfer acylation reaction is from room temperature to the reflux temperature of the acylation reagent. Reactions at room temperature are typically slow and require extended reaction times.

[0014] Preferably, the direct transfer acylation reaction takes 0.5 to 48 hours.

[0015] Preferably, the Lewis acid is at least one of FeCl3, RuCl3, GaCl3, Ga(OTf)3, In(OTf)3, Fe(OTf)3, Sc(OTf)3, Cu(OTf)2, and Bi(OTf)3 and their corresponding hydrates.

[0016] It should be noted that hydrochlorides such as FeCl3 can be acylated by acyl halides and acid anhydrides, while trifluoromethanesulfonates such as Cu(OTf)2 cannot be acylated by acid anhydrides and can only be acylated by acyl halides.

[0017] Compared with the prior art, the beneficial effects of the present invention include:

[0018] (1) This invention can be used for substrates containing functional groups such as ester groups that are unstable to acids and bases. For example, Example 21 is an example containing ester groups. Conventional methods require deacylation with acid or base before acylation, which may affect the ester groups. This method can directly achieve transfer acylation, which is more convenient.

[0019] (2) The present invention uses Lewis acids such as FeCl3 and Cu(OTf)2 as catalysts for direct transfer acylation reaction, which makes the reaction operation simple and the reaction efficiency high. Detailed Implementation

[0020] 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.

[0021] Example 1

[0022] The conversion of N-(4-toluenesulfonyl)propionamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0023]

[0024] N-p-Toluenesulfonylpropionamide (0.227 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.194 g of a white solid, yield: 91%. Melting point: 136–138 °C. f =0.14 (petroleum ether / ethyl acetate = 3:1).

[0025] 1 H NMR (400MHz, CD3OD) δ7.77(d,J=8.4Hz,2H),7.29(d,J=8.0Hz,2H),2.34(s,3H),1.85(s,3H).

[0026] Example 2

[0027] The conversion of N-(4-toluenesulfonyl)propionamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0028]

[0029] N-p-Toluenesulfonyloctylamide (0.297 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.193 g of N-(4-toluenesulfonyl)propionamide, yield: 90%.

[0030] Example 3

[0031] The conversion of N-(4-toluenesulfonyl)isobutyramide to the corresponding acetamide is shown in the following chemical reaction formula:

[0032]

[0033] N-p-Toluenesulfonyl octanoamide (0.241 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.200 g of N-(4-toluenesulfonyl)acetamide, yield: 93%.

[0034] Example 4

[0035] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0036]

[0037] N-(4-Toluenesulfonyl)pentanamide (0.256 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at 65 °C for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.210 g of N-(4-toluenesulfonyl)acetamide, yield: 98%.

[0038] Example 5

[0039] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0040]

[0041] N-(4-Toluenesulfonyl)pentanamide (0.255 g, 1 mmol), FeCl3 (0.083 g, 0.5 mmol), and acetyl chloride (2.355 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.207 g of N-(4-toluenesulfonyl)acetamide, yield: 97%.

[0042] Example 6

[0043] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0044]

[0045] N-(4-Toluenesulfonyl)pentanamide (0.256 g, 1 mmol), RuCl3·xH2O (0.113 g, 0.5 mmol), and acetyl chloride (2.355 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.149 g of N-(4-toluenesulfonyl)acetamide (yield: 87%).

[0046] Example 7

[0047] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0048]

[0049] N-(4-Toluenesulfonyl)pentanamide (0.256 g, 1 mmol), Ga(OTf)3 (0.051 g, 0.1 mmol), and acetyl chloride (0.785 g, 10 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.131 g of N-(4-toluenesulfonyl)acetamide, yield: 61%.

[0050] Example 8

[0051] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0052]

[0053] N-(4-Toluenesulfonyl)pentanamide (0.255 g, 1 mmol), Ga(OTf)3 (0.076 g, 0.15 mmol), acetyl chloride (0.392 g, 5 mmol), and dichloromethane (5 mL) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.147 g of N-(4-toluenesulfonyl)acetamide, yield: 69%.

[0054] Example 9

[0055] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0056]

[0057] N-(4-Toluenesulfonyl)pentanamide (0.256 g, 1 mmol), Ga(OTf)3 (0.104 g, 0.2 mmol), and acetyl chloride (0.785 g, 10 mmol) were stirred at room temperature for 2 days. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.205 g of N-(4-toluenesulfonyl)acetamide, yield: 96%.

[0058] Example 10

[0059] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0060]

[0061] N-(4-Toluenesulfonyl)pentanamide (0.256 g, 1 mmol), Ga(OTf)3 (0.103 g, 0.2 mmol), and acetyl chloride (0.785 g, 10 mmol) were stirred at 40 °C for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.207 g of N-(4-toluenesulfonyl)acetamide, yield: 97%.

[0062] Example 11

[0063] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0064]

[0065] N-(4-Toluenesulfonyl)pentanamide (0.255 g, 1 mmol), Fe(OTf)3 (0.100 g, 0.2 mmol), and acetyl chloride (0.785 g, 10 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.209 g of N-(4-toluenesulfonyl)acetamide, yield: 98%.

[0066] Example 12

[0067] The N-(4-toluenesulfonyl)pentylamide is converted to the corresponding acetamide by the following chemical reaction:

[0068]

[0069] N-(4-Toluenesulfonyl)pentanamide (0.255 g, 1 mmol), In(OTf)3 (0.110 g, 0.2 mmol), and acetyl chloride (0.785 g, 10 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.198 g of N-(4-toluenesulfonyl)acetamide, yield: 92%.

[0070] Example 13

[0071] The chemical reaction formula for the conversion of N-(4-toluenesulfonyl)phenylacetamide to the corresponding acetamide is as follows:

[0072]

[0073] N-(4-Toluenesulfonyl)phenylacetamide (0.290 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.187 g of N-(4-toluenesulfonyl)acetamide, yield: 87%.

[0074] Example 14

[0075] The conversion of N-(4-toluenesulfonyl)cyclohexylformamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0076]

[0077] N-(4-Toluenesulfonyl)cyclohexylformamide (0.282 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.213 g of N-(4-toluenesulfonyl)acetamide, yield: 99%.

[0078] Example 15

[0079] The conversion of N-(4-toluenesulfonyl)-1-naphthylcarboxamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0080]

[0081] N-(4-Toluenesulfonyl)-1-naphthylcarboxamide (0.326 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 N-(4-toluenesulfonyl)acetamide, yield: 97%.

[0082] Example 16

[0083] The (E)-N-(4-toluenesulfonyl)-2-butenamide is converted to the corresponding acetamide, and the chemical reaction formula is as follows:

[0084]

[0085] (E)-N-(4-toluenesulfonyl)-2-butenamide (0.153 g, 0.64 mmol), FeCl3 (0.052 g, 0.32 mmol), and acetic anhydride (1.960 g, 19.2 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.134 g of N-(4-toluenesulfonyl)acetamide, yield: 98%.

[0086] Example 17

[0087] The N-(benzenesulfonyl)butyramide is converted to the corresponding acetamide, and the chemical reaction formula is as follows:

[0088]

[0089] N-(benzenesulfonyl)butyramide (0.227 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.192 g of a white solid, yield: 96%. Melting point: 124–125.5 °C. f =0.64 (petroleum ether / ethyl acetate = 1:1).

[0090] 1 H NMR (400MHz, DMSO-d6) δ12.09(br s,1H),7.98-7.86(m,2H),7.76-7.68(m,1H),7.68-7.59(m,2H),1.92(s,3H).

[0091] Example 18

[0092] The conversion of N-(4-fluorobenzenesulfonyl)octylamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0093]

[0094] N-(4-fluorobenzenesulfonyl)octylamide (0.301 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.187 g of a white solid, yield: 86%. Melting point: 125.5–127 °C. f =0.57 (petroleum ether / ethyl acetate = 1:1).

[0095] 1 H NMR (400MHz, DMSO-d6) δ12.15 (br s, 1H), 7.98 (dd, J1 = 9.0Hz, J2 = 5.2Hz, 2H), 7.47 (t, J = 8.8Hz, 2H), 1.93 (s, 3H).

[0096] Example 19

[0097] The N-(4-trifluorotoluenesulfonyl)pentanamide is converted to the corresponding acetamide, and the chemical reaction formula is as follows:

[0098]

[0099] N-(4-trifluorotoluenesulfonyl)pentanamide (0.322 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.242 g of a white solid, yield: 90%. Melting point: 213–214 °C. f =0.57 (petroleum ether / ethyl acetate = 2:1).

[0100] 1 H NMR (400MHz, DMSO-d6) δ12.37(br s,1H),8.13(d,J=8.2Hz,2H),8.03(d,J=8.3Hz,2H),1.95(s,3H).

[0101] Example 20

[0102] The conversion of N-(4-nitrobenzenesulfonyl)butyramide to the corresponding acetamide is shown in the following chemical reaction formula:

[0103]

[0104] N-(4-nitrobenzenesulfonyl)butyramide (0.272 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.237 g of a white solid, yield: 97%. Melting point: 193.5–194 °C. f =0.22 (petroleum ether / ethyl acetate = 1:1).

[0105] 1 H NMR (400MHz, DMSO-d6) δ12.46(br s,1H),8.44(d,J=8.9Hz,2H),8.17(d,J=8.9Hz,2H),1.96(s,3H).

[0106] Example 21

[0107] The conversion of N-(2-methoxycarbonylbenzenesulfonyl)butyramide to the corresponding acetamide is shown in the following chemical reaction formula:

[0108]

[0109] N-(2-methoxycarbonylbenzenesulfonyl)butyramide (0.285 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.234 g of a white solid, yield: 90%. Melting point: 153–154.5 °C. f =0.46 (petroleum ether / ethyl acetate = 1:1).

[0110] 1 H NMR (400MHz, DMSO-d6) δ12.12(br s,1H),8.12-8.06(m,1H),7.82-7.72(m 2H),7.69(dd,J1=7.2Hz,J2=1.8Hz,1H),3.88(s,3H),1.97(s,3H).

[0111] Example 22

[0112] The conversion of N-[4-[5-(4-tolyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]methanesulfonyl]butyramide to the corresponding acetamide is shown in the following chemical reaction formula:

[0113]

[0114] N-[4-[5-(4-tolyl)-3-(trifluoromethyl)-1H-pyrazole-1-yl]methanesulfonyl]butyramide (0.226 g, 0.5 mmol), FeCl3 (0.040 g, 0.25 mmol), and acetic anhydride (1.531 g, 15 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.210 g of a white solid, yield: 99%. Melting point: 90–92 °C. f =0.51 (petroleum ether / ethyl acetate = 1:1).

[0115] 1 H NMR (400MHz, CDCl3) δ8.04(d,J=8.8Hz,2H),7.51(d,J=8.8Hz,2H),7.19(d,J=7.7Hz,2H),7.12(d,J=8.3Hz,2H),6.75(s,1H),2.39(s,3H),2.06(s,3H).

[0116] 13 C NMR (101MHz, CDCl3) δ167.9,145.4,144.3(q, 2 J C-F =38.8Hz),143.6,140.0,137.7,129.8,129.5,128.7,125.6,125.2,121.0(q, 1 J C-F =270.3Hz), 106.6, 23.6, 21.4.

[0117] Example 23

[0118] The N-(benzylsulfonyl)butyramide is converted to the corresponding acetamide, and the chemical reaction formula is as follows:

[0119]

[0120] N-(benzylsulfonyl)butyramide (0.241 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.201 g of a white solid, yield: 94%. Melting point: 131–132 °C. f =0.30 (petroleum ether / ethyl acetate = 2:1).

[0121] 1 H NMR (400MHz, DMSO-d6) δ11.54(br s,1H),7.45-7.35(m,3H),7.34-7.28(m,2H),4.68(s,2H),1.98(s,3H).

[0122] Example 24

[0123] The conversion of N-(4-toluenesulfonyl)acetamide to the corresponding trifluoroacetamide is shown in the following chemical reaction formula:

[0124]

[0125] N-(4-Toluenesulfonyl)butyramide (0.213 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in trifluoroacetic anhydride (6.300 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.162 g of a white solid, yield: 60%. Melting point: 147–149 °C. f =0.60 (petroleum ether / ethyl acetate = 1:1).

[0126] 1 H NMR (400MHz, DMSO-d6) δ7.71(d,J=8.3Hz,2H),7.29(d,J=8.0Hz,2H),2.35(s,3H).

[0127] 13 C NMR (101MHz, DMSO-d6) δ159.0 (q, J = 34.1Hz), 142.0, 140.5, 129.1, 127.6, 117.2 (q, J = 292.3Hz), 21.4.

[0128] Example 25

[0129] The chemical reaction formula for the conversion of N-(4-toluenesulfonyl)acetamide to the corresponding propionamide is as follows:

[0130]

[0131] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in propionic anhydride (3.904 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.200 g of a white solid, yield: 87%. Melting point: 110–111.5 °C. f =0.66 (petroleum ether / ethyl acetate = 1:1).

[0132] 1 H NMR (400MHz, DMSO-d6) δ11.97(br s,1H),7.80(d,J=8.4Hz,2H),7.42(d,J=7.7Hz,2H),2.40(s,3H),2.21(q,J=7.5Hz,2H),0.88(t,J=7.5Hz,3H).

[0133] Example 26

[0134] The conversion of N-(4-toluenesulfonyl)pentylamide to the corresponding propionamide is shown in the following chemical reaction formula:

[0135]

[0136] N-(4-Toluenesulfonyl)propionamide (0.256 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in propionic anhydride (3.904 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.214 g of N-(4-toluenesulfonyl)propionamide, yield: 93%.

[0137] Example 27

[0138] The conversion of N-(4-toluenesulfonyl)acetamide to the corresponding isobutyramide is shown in the following chemical reaction formula:

[0139]

[0140] N-(4-Toluenesulfonyl)acetamide (0.213 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in isobutyric anhydride (4.746 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.238 g of a white solid, yield: 98%. Melting point: 114–116 °C. f =0.49 (petroleum ether / ethyl acetate = 2:1).

[0141] 1 H NMR (400MHz, DMSO-d6) δ11.96(br s,1H),7.79(d,J=8.4Hz,2H),7.42(d,J=7.9Hz,2H),2.44(septet,J=6.9Hz,1H),2.40(s,3H),0.93(d,J=6.8Hz,6H).

[0142] Example 28

[0143] The conversion of N-(4-toluenesulfonyl)acetamide to the corresponding isobutyramide is shown in the following chemical reaction formula:

[0144]

[0145] N-(4-Toluenesulfonyl)-Pivalamide (0.256 g, 1 mmol) and GaCl3 (0.088 g, 0.5 mmol) were stirred in isobutyric anhydride (4.746 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.228 g of N-(4-Toluenesulfonyl)-isobutyric acid, yield: 94%.

[0146] Example 29

[0147] The chemical reaction formula for the conversion of N-(4-toluenesulfonyl)acetamide to the corresponding pivalamide is as follows:

[0148]

[0149] N-(4-Toluenesulfonyl)acetamide (0.214 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in pentanoic anhydride (5.588 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.193 g of a white solid, yield: 75%. Melting point: 167.5–168 °C. f =0.46 (petroleum ether / ethyl acetate = 3:1).

[0150] 1 H NMR (400MHz, DMSO-d6) δ11.64(br s,1H),7.77(d,J=8.3Hz,2H),7.42(d,J=7.7Hz,2H),2.40(s,3H),1.05(s,9H).

[0151] Example 30

[0152] The conversion of N-(4-toluenesulfonyl)isobutyramide to the corresponding pivalamide is shown in the following chemical reaction formula:

[0153]

[0154] N-(4-Toluenesulfonyl)isobutyramide (0.241 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in pentanoic anhydride (5.588 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.239 g of product, yield: 93%.

[0155] Example 31

[0156] The conversion of N-(4-toluenesulfonyl)butyramide to the corresponding pivalamide is shown in the following chemical reaction formula:

[0157]

[0158] N-(4-Toluenesulfonyl)butyramide (0.241 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in pivalic anhydride (5.588 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.251 g of N-(4-toluenesulfonyl)pivalamide, yield: 98%.

[0159] Example 32

[0160] The conversion of N-methyl-N-(4-toluenesulfonyl)pentylamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0161]

[0162] N-Methyl-N-(4-toluenesulfonyl)pentanamide (0.269 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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: 91%. Melting point: 49.5–51.5 °C. f =0.10 (petroleum ether / ethyl acetate = 5:1).

[0163] 1 H NMR (400MHz, CDCl3) δ7.77 (d, J = 8.4Hz, 2H), 7.36 (d, J = 8.6Hz, 2H), 3.28 (s, 3H), 2.45 (s, 3H), 2.39 (d, J = 0.7Hz, 3H).

[0164] Example 33

[0165] The chemical reaction formula for the conversion of N-methanesulfonyl-N-phenylpentanamide to the corresponding acetamide is as follows:

[0166]

[0167] N-Methanesulfonyl-N-phenylpentanamide (0.255 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.200 g of a white solid, yield: 93%. Melting point: 120–121 °C. f =0.17 (petroleum ether / ethyl acetate = 3:1).

[0168] 1 H NMR (400MHz, CDCl3) δ7.56-7.44(m,3H),7.36-7.27(m,2H),3.47(s,3H),1.97(s,3H).

[0169] Example 34

[0170] The conversion of N-(4-toluenesulfonyl)-N-phenylpentylamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0171]

[0172] N-Methanesulfonyl-N-phenylpentanamide (0.331 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.248 g of a white solid, yield: 85%. Melting point: 150.5–152.5 °C. f =0.20 (petroleum ether / ethyl acetate = 5:1).

[0173] 1 H NMR (400MHz, CDCl3) δ7.93 (d, J = 8.4Hz, 2H), 7.53-7.44 (m, 3H), 7.36 (s, 2H), 7.30-7.25 (m, 2H), 2.46 (s, 3H), 1.87 (s, 3H).

[0174] Example 35

[0175] The conversion of N-benzyl-N-(4-toluenesulfonyl)cyclopropylformamide to the corresponding acetamide is shown in the following chemical reaction formula:

[0176]

[0177] N-Benzyl-N-(4-Toluenesulfonyl)cyclopropylformamide (0.329 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and acetic anhydride (3.063 g, 30 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.296 g of a white solid, yield: 97%. Melting point: 95–96.5 °C. f =0.85 (petroleum ether / ethyl acetate = 3:1).

[0178] 1 H NMR (400MHz, DMSO-d6) δ7.81 (d, J = 8.4Hz, 2H), 7.46-7.36 (m, 4H), 7.34-7.28 (m, 3H), 5.07 (s, 2H), 2.41 (s, 3H), 2.18 (s, 3H).

[0179] Example 36

[0180] The conversion of N-(tert-butylsulfonyl)acetamide to the corresponding benzamide is shown in the following chemical reaction formula:

[0181]

[0182] N-(tert-butylsulfonyl)acetamide (0.179 g, 1 mmol), FeCl3 (0.081 g, 0.5 mmol), and benzoyl chloride (4.218 g, 30 mmol) were stirred in dichloromethane (5 mL) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 a white solid, yield: 64%. Melting point: 148–150 °C. f =0.75 (petroleum ether / ethyl acetate = 2:1).

[0183] 1 H NMR (400MHz, CDCl3) δ8.45 (br s, 1H), 7.88 (d, J = 7.1Hz, 2H), 7.61 (t, J = 7.4Hz, 1H), 7.49 (t, J = 7.8Hz, 2H), 1.55 (s, 9H).

[0184] Example 37

[0185] The conversion of N-benzyl-N-(4-toluenesulfonyl)acetamide to the corresponding isobutyramide is shown in the following chemical reaction formula:

[0186]

[0187] N-Benzyl-N-(4-Toluenesulfonyl)acetamide (0.303 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in isobutyric anhydride (4.746 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The combined organic phases were dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.190 g of a white solid, yield: 57%. Melting point: 117–119 °C. f =0.67 (petroleum ether / ethyl acetate = 3:1).

[0188] 1 H NMR (400MHz, CDCl3) δ7.61 (d, J = 8.4Hz, 2H), 7.36-7.24 (m, 7H), 5.11 (s, 2H), 3.13 (hept, J = 6.6Hz, 1H), 2.42 (s, 3H), 0.97 (d, J = 6.7Hz, 6H).

[0189] Example 38

[0190] The conversion of N-benzyl-N-(4-toluenesulfonyl)pentylamide to the corresponding isobutyramide is shown in the following chemical reaction formula:

[0191]

[0192] N-Benzyl-N-(4-Toluenesulfonyl)pentylamide (0.345 g, 1 mmol) and FeCl3 (0.081 g, 0.5 mmol) were stirred in isobutyric anhydride (4.746 g, 30 mmol) at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.300 g of N-Benzyl-N-(4-Toluenesulfonyl)isobutyric acid amide, yield: 90%.

[0193] Example 39

[0194] Parecoxib is converted into the corresponding acetamide, which is then converted into the corresponding N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl]acetamide, as shown in the following chemical reaction formula:

[0195]

[0196] Parecoxib (0.185 g, 0.5 mmol), FeCl3 (0.040 g, 0.25 mmol), and acetic anhydride (1.53 g, 15 mmol) were stirred at room temperature for 18 h. Water (20 mL) was then added, and the mixture was extracted with ethyl acetate (50 mL × 3). The organic phases were combined and dried over anhydrous magnesium sulfate. The mixture was filtered, 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 0.150 g of a pale yellow solid, yield: 89%. Melting point: 160.5–162.5 °C. f =0.19 (petroleum ether / ethyl acetate = 3:1).

[0197] 1 H NMR (400MHz, CDCl3) δ8.03 (d, J = 8.5Hz, 2H), 7.44-7.30 (m, 7H), 2.51 (s, 3H), 2.09 (s, 3H).

[0198] 13 C NMR (101MHz, CDCl3) δ168.3,167.5,161.2,137.6,136.6,130.1,129.8,128.8,128.7,128.5,128.3,114.4,23.6,11.9.

[0199] 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 direct transfer acylation method for -acylsulfonamides, characterized in that... Includes the following steps: N A mixture of acyl-secondary sulfonamide, acylating agent, and Lewis acid undergoes a transfer acylation reaction to generate the corresponding new... N - Acyl secondary sulfonamide; Its chemical reaction formula is as follows: Among them, R 1 It is any one of hydrogen, alkyl, aryl, and heteroaryl; R, R 2 and R 3 Each can be independently derived from any one of alkyl, aryl, and heteroaryl groups; The acylation reagent is at least one of an acyl halide and an acid anhydride; The acyl halide is at least one selected from acyl fluoride, acyl iodide, and acyl chloride; the acyl halide is an acyl chloride; The Lewis acid is at least one of FeCl3, RuCl3, GaCl3, Ga(OTf)3, In(OTf)3, Fe(OTf)3, Sc(OTf)3, Cu(OTf)2, and Bi(OTf)3 and their corresponding hydrates.

2. The Lewis acid-promoted method according to claim 1 N A direct transfer acylation method for -acylsulfonamides, characterized in that... The Lewis acid and N The molar ratio of acyl groups in acyl-secondary sulfonamides is 0.1 to 4:

1.

3. The Lewis acid-promoted method according to claim 2 N A direct transfer acylation method for -acylsulfonamides, characterized in that... The Lewis acid and N The molar ratio of acyl groups in acyl-secondary sulfonamides is 0.1~0.5:

1.

4. The Lewis acid-promoted method according to any one of claims 1 to 3 N A direct transfer acylation method for -acylsulfonamides, characterized in that... The temperature of the transfer acylation reaction is from room temperature to the reflux temperature of the acylation reagent.

5. The Lewis acid-promoted [treatment] according to claim 1 N A direct transfer acylation method for -acylsulfonamides, characterized in that... The transfer acylation reaction takes 0.5 to 48 hours.

6. The Lewis acid-promoted method according to claim 5 N A direct transfer acylation method for -acylsulfonamides, characterized in that... The transfer acylation reaction takes 18–48 h.

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