A method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride with olefins

Abstract

This invention discloses a method for photo-promoted coupling of sulfonyl chlorides with olefins to prepare vinyl sulfone compounds. Using arylsulfonyl chloride as shown in formula (I) as a raw material, iodide salt, an olefin compound as shown in formula (II), a solvent, and a base are added to a reactor. The reaction is carried out under a nitrogen atmosphere and ultraviolet light irradiation to obtain a vinyl sulfone compound as shown in formula (III). The reaction equation is as follows: In formula (I), the Ar group is phenyl, substituted phenyl, or 3,5-dimethylisoxazole, and the substituent on the substituted phenyl group is fluorine, iodine, cyano, nitro, methyl, or trifluoromethyl. In formula (II), the hydrogen on the benzene ring is substituted or unsubstituted by substituent R2, where substituent R2 is fluorine or tert-butyl, and substituent R1 is hydrogen or phenyl. This invention uses inexpensive and readily available sulfonyl chlorides to efficiently promote the preparation of vinyl sulfone compounds from arylsulfonyl chlorides and olefin compounds. It uses light irradiation instead of traditional heating reactions, does not require the addition of precious metal catalysts, and has low reaction cost and high safety.

Description

Technical Field

[0001] This invention belongs to the field of chemical organic synthesis technology, specifically relating to a method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride with olefins. Background Technology

[0002] Vinyl sulfone groups are common functional groups in organic and medicinal chemistry because of their wide range of synthetic uses and potential biological activities. They are an important component of many natural organic compounds and their applications in chemical, pharmaceutical, and food industries are becoming increasingly widespread.

[0003] The commonly reported method for synthesizing vinyl sulfone compounds is the Heck coupling reaction using olefins and sulfonyl chlorides as starting materials. Researchers have developed a series of schemes for synthesizing vinyl sulfone compounds to meet the needs of the reaction, but these methods all suffer from drawbacks such as the use of expensive transition metal catalysts, harsh reaction conditions, low atom economy, narrow substrate range, and difficulty in operation. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a method for the photo-promoted coupling of sulfonyl chlorides with olefins to prepare vinyl sulfone compounds. Using inexpensive, readily available, and highly stable arylsulfonyl chlorides as raw materials and iodide salts as catalysts, the method catalyzes the reaction of sulfonyl chlorides with olefin compounds under light to prepare vinyl sulfone compounds.

[0005] The technical solution adopted in this invention is:

[0006] A method for photo-promoted coupling of sulfonyl chloride with an olefin to prepare vinyl sulfone compounds, the principle of which includes an electron donor-acceptor (EDA) process of iodide salt under ultraviolet light irradiation, exciting the olefin to form a radical intermediate, which then adds to the sulfonyl radical. Subsequently, elimination occurs under the action of a base to eliminate a molar hydroiodic acid, yielding the desired vinyl sulfone compound. The method includes:

[0007] Using arylsulfonyl chloride with structure (I) as a raw material, iodine salt, an olefin compound with formula (II), a solvent, and a base were added to a reactor. The reaction was carried out under a nitrogen atmosphere and ultraviolet light irradiation to prepare a vinyl sulfone compound as shown in (III). The reaction equation is as follows:

[0008]

[0009] In formula (I), the Ar group is phenyl, substituted phenyl or 3,5-dimethylisoxazole, and the substituent on the substituted phenyl is fluorine, iodine, cyano, nitro, methyl or trifluoromethyl. In formula (II), the hydrogen on the benzene ring is substituted or not substituted by substituent R2. When substituted, substituent R2 is fluorine or tert-butyl, and substituent R1 is hydrogen or phenyl.

[0010] Further, the solvent is one of the following: EtOAc, THF, ACN, DCM.

[0011] Furthermore, the iodized salt is one of the following: NaI, KI.

[0012] Further, the alkali is one of the following: K3PO4, KH2PO4, KF, Na2CO3.

[0013] Furthermore, the molar ratio of the arylsulfonyl chloride to the olefin compound is 1.0 to 1.5:1.

[0014] Furthermore, the molar ratio of the arylsulfonyl chloride to the iodide salt is 0.4 to 0.5:1.

[0015] Furthermore, the molar ratio of the arylsulfonyl chloride to the base is 0.5 to 1.0:1.

[0016] Furthermore, the reaction time is 12–16 hours.

[0017] Furthermore, the wavelength of the ultraviolet lamp is 415nm, 425nm, 455nm or 465nm.

[0018] The beneficial effects of this invention are mainly reflected in:

[0019] 1) Using inexpensive and readily available sulfonyl chlorides, the preparation of vinyl sulfone compounds from aryl sulfonyl chlorides and olefins is efficiently promoted.

[0020] 2) The reaction uses light instead of traditional heating, does not require the addition of precious metal catalysts, has low reaction cost and high safety.

[0021] 3) The substrates are widely applicable and can yield the corresponding vinyl sulfone compounds in good yield.

[0022] 4) The operation process is simple and efficient. Detailed Implementation

[0023] The present invention will be further described below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto:

[0024] Example 1: Preparation of 1-(tert-butyl)-4-(2-((4-fluorophenyl)sulfonyl)vinyl)benzene

[0025]

[0026] In a 100 mL three-necked flask, 0.388 g (2.0 mmol) of 4-fluorobenzenesulfonyl chloride (Formula I, R = 4-F), 0.320 g (2.0 mmol) of 4-tert-butylstyrene, 0.664 g (4.0 mmol) of potassium iodide, 0.849 g (4.0 mmol) of tripotassium phosphate, and 40 mL of ethyl acetate were added sequentially. The mixture was stirred for 12 h under a nitrogen atmosphere and irradiated with a 425 nm UV lamp. After the reaction was complete, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.509 g of 1-(tert-butyl)-4-(2-((4-fluorophenyl)sulfonyl)vinyl)benzene, with a purity of 98% and a yield of 80% (based on olefins). 1H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ8.00-7.95(m,2H),7.69(d,J=15.4Hz,1H),7.45(s,4H),7.26-7.21(m,2H),6.82(d,J=15.4Hz,1H),1.33(s,9H).

[0027] Example 2: Preparation of 1-(tert-butyl)-4-(2-((4-iodophenyl)sulfonyl)vinyl)benzene

[0028]

[0029] In a 100 mL single-necked flask, 0.664 g (2.2 mmol) of 4-iodobenzenesulfonyl chloride (Formula I, R = 4-I), 0.320 g (2.0 mmol) of 4-tert-butylstyrene, 0.659 g (4.4 mmol) of sodium iodide, 0.499 g (3.7 mmol) of potassium dihydrogen phosphate, and 40 mL of acetonitrile were added sequentially. The mixture was stirred for 13 h under a nitrogen atmosphere and irradiated with a 415 nm UV lamp. After the reaction was completed, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.741 g of 1-(tert-butyl)-4-(2-((4-iodophenyl)sulfonyl)vinyl)benzene with a purity of 99% and a yield of 87% (based on olefins).

[0030] 1H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ7.93-7.90(m,2H),7.71-7.65(m,3H),7.44(s,4H),6.80(d,J=15.4Hz,1H),1.33(s,9H).

[0031] Example 3: Preparation of 1-(tert-butyl)-4-(2-((4-(trifluoromethyl)phenyl)sulfonyl)vinyl)benzene

[0032]

[0033] In a 100 mL single-necked flask, 0.510 g (2.4 mmol) of 4-trifluoromethylbenzenesulfonyl chloride (Formula I, R = 4-CF3), 0.320 g (2.0 mmol) of 4-tert-butylstyrene, 0.996 g (6.0 mmol) of potassium iodide, 0.199 g (3.4 mmol) of potassium fluoride, and 40 mL of tetrahydrofuran were added sequentially. The mixture was stirred for 14 h under a nitrogen atmosphere and irradiated with a 455 nm UV lamp. After the reaction was completed, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.663 g of 1-(tert-butyl)-4-(2-((4-(trifluoromethyl)phenyl)sulfonyl)vinyl)benzene with a purity of 99% and a yield of 90% (based on olefins).

[0034] 1H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ8.10(d,J=8.3Hz,2H),7.83(d,J=8.5Hz,2H),7.75(d,J=15.4Hz,1H),7.46(s,4H),6.82(d,J=15.4Hz,1H),1.34(s,9H).

[0035] Example 4: Preparation of 4-((4-(tert-butyl)styryl)sulfonyl)benzonitrile

[0036]

[0037] In a 100 mL single-necked flask, 0.522 g (2.6 mmol) of 4-cyanobenzenesulfonyl chloride (Formula I, R = 4-CN), 0.320 g (2.0 mmol) of 4-tert-butylstyrene, 0.896 g (5.9 mmol) of sodium iodide, 0.496 g (4.7 mmol) of sodium carbonate and 40 mL of dichloromethane were added sequentially. The mixture was stirred for 16 h under a nitrogen atmosphere and irradiated with a 465 nm UV lamp. After the reaction was completed, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.624 g of 4-((4-(tert-butyl)styrene)sulfonyl)benzonitrile with a purity of 98% and a yield of 96% (based on olefins).

[0038] 1H NMR spectrum: 1H NMR (400MHz, CDCl3) δ7.98(d,J=8.2Hz,2H),7.76(d,J=8.1Hz,2H),7.65(d,J=15.3Hz,1H),7.36(s,4H),6.72(d,J=15.4Hz,1H),1.24(s,9H).

[0039] Example 5: Preparation of 1-(tert-butyl)-4-(2-p-toluenesulfonylvinyl)benzene

[0040]

[0041] In a 100 mL single-necked flask, 0.532 g (2.8 mmol) of p-toluenesulfonyl chloride (Formula I, R = CH3), 0.320 g (2.0 mmol) of 4-tert-butylstyrene, 0.664 g (4.0 mmol) of potassium iodide, 0.849 g (4.0 mmol) of tripotassium phosphate, and 40 mL of ethyl acetate were added sequentially. The mixture was stirred for 15 h under a nitrogen atmosphere and irradiated with a 425 nm UV lamp. After the reaction was completed, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.578 g of 1-(tert-butyl)-4-(2-p-toluenesulfonylvinyl)benzene with a purity of 98% and a yield of 92% (based on olefins).

[0042] 1H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ7.86–7.82(m,2H),7.67(d,J=15.4Hz,1H),7.43(d,J=0.6H z,4H),7.35(d,J=7.9Hz,2H),6.82(d,J=15.4Hz,1H),2.45(s,3H),1.33(s,9H).

[0043] Example 6: Preparation of 1-(tert-butyl)-4-(2-((4-nitrophenyl)sulfonyl)vinyl)benzene

[0044]

[0045] In a 100 mL single-necked flask, 0.566 g (3.0 mmol) of 4-nitrobenzenesulfonyl chloride (Formula I, R = NO2), 0.320 g (2.0 mmol) of 4-tert-butylstyrene, 0.896 g (5.8 mmol) of sodium iodide, 0.199 g (3.4 mmol) of potassium fluoride, and 40 mL of tetrahydrofuran were added sequentially. The mixture was stirred for 14 h under a nitrogen atmosphere and irradiated with a 415 nm UV lamp. After the reaction was complete, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.414 g of 1-(tert-butyl)-4-(2-((4-nitrophenyl)sulfonyl)vinyl)benzene, with a purity of 98% and a yield of 60% (based on olefins). 1H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ8.33-8.28(m,2H),8.09-8.03(m,2H),7.68(d,J=15.4Hz,1H),7.37(d,J=1.1Hz,4H),6.74(d,J=15.4Hz,1H),1.24(s,9H).

[0046] Example 7: Preparation of 1-(tert-butyl)-4-(2-(benzenesulfonyl)vinyl)benzene

[0047]

[0048] In a 100 mL single-necked flask, benzenesulfonyl chloride, (Formula I, R=H) 0.422 g (2.4 mmol), 0.320 g (2.0 mmol) 4-tert-butylstyrene, 0.896 g (5.9 mmol) sodium iodide, 0.499 g (3.7 mmol) potassium dihydrogen phosphate, and 40 mL ethyl acetate were added sequentially. The mixture was stirred for 13 h under a nitrogen atmosphere and irradiated with a 455 nm UV lamp. After the reaction was completed, 50 mL ethyl acetate was added to dilute the mixture, followed by washing three times with 50 mL water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.546 g of 1-(tert-butyl)-4-(2-(benzenesulfonyl)vinyl)benzene with a purity of 99% and a yield of 91% (based on olefins).

[0049] 1H NMR spectrum: 1 H NMR (400MHz, CDCl3) δ7.99–7.95(m,2H),7.70(d,J=15.4Hz,1H),7.65–7.60(m,1H ),7.58–7.54(m,2H),7.44(d,J=2.0Hz,4H),6.84(d,J=15.4Hz,1H),1.33(s,9H).

[0050] Example 8: Preparation of 4-((4-fluorostyryl)sulfonyl)-3,5-dimethylisoxazole

[0051]

[0052] In a 100 mL single-necked flask, 0.429 g (2.2 mmol) of 3,5-dimethylisoxazole-4-sulfonyl chloride, 0.244 g (2.0 mmol) of 4-fluorostyrene, 0.664 g (4.0 mmol) of potassium iodide, 0.849 g (4.0 mmol) of tripotassium phosphate, and 40 mL of acetonitrile were added sequentially. The mixture was stirred for 14 h under a nitrogen atmosphere and irradiated with a 425 nm UV lamp. After the reaction was completed, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.489 g of 4-((4-fluorostyrene)sulfonyl)-3,5-dimethylisoxazole with a purity of 98% and a yield of 87% (based on olefins).

[0053] 1H NMR spectrum: 1 H NMR (400MHz, CDCl3)7.63(d,J=15.4Hz,1H),7.51(td,J=5.8,2.8Hz,2H),7.15–7.10(m,2H),6.77(d,J=15.4Hz,1H),2.69(s,3H),2.40(s,3H).

[0054] Example 9: Preparation of 4-((2,2-stilbeneyl))sulfonyl)-3,5-dimethylisoxazole

[0055]

[0056] In a 100 mL single-necked flask, 0.507 g (2.6 mmol) of 3,5-dimethylisoxazole-4-sulfonyl chloride, 0.396 g (2.2 mmol) of 1,1-stilbene, 0.896 g (5.8 mmol) of sodium iodide, 0.496 g (4.7 mmol) of sodium carbonate, and 40 mL of tetrahydrofuran were added sequentially. The mixture was stirred for 12 h under a nitrogen atmosphere and irradiated with a 465 nm UV lamp. After the reaction was complete, 50 mL of ethyl acetate was added for dilution, followed by washing three times with 50 mL of water. The mixture was then washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated to obtain 0.536 g of 4-((2,2-stilbeneyl))sulfonyl)-3,5-dimethylisoxazole, with a purity of 98% and a yield of 79% (based on olefins). 1H NMR spectrum: 1H NMR(400MHz,CDCl3)δ7.36–7.26(m,7H),7.21–7.11(m,3H),7.06–7.02(m,2H),6.97(s,1H),2.24(s,3H),2.12(s,3H)。

Claims

1. A method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride with olefins, characterized in that, The method includes: Using arylsulfonyl chloride with structure (I) as a raw material, iodine salt, an olefin compound with formula (II), a solvent, and a base were added to a reactor. The reaction was carried out under a nitrogen atmosphere and ultraviolet light irradiation to prepare a vinyl sulfone compound as shown in (III). The reaction equation is as follows: ， In formula (I), the Ar group is phenyl, substituted phenyl or 3,5-dimethylisoxazole, and the substituent on the substituted phenyl is fluorine, iodine or methyl. In formula (II), the hydrogen on the benzene ring is substituted or not substituted by substituent R2. When substituted, substituent R2 is fluorine or tert-butyl, and substituent R1 is hydrogen or phenyl. The solvent is one of the following: EtOAc, THF, ACN, DCM; The iodized salt is one of the following: NaI, KI; The alkali is one of the following: K3PO4, KH2PO4, KF, or Na2CO3.

2. The method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride and olefins as described in claim 1, characterized in that, The molar ratio of the arylsulfonyl chloride to the olefin compound is 1.0~1.5 :

1.

3. The method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride and olefins as described in claim 1, characterized in that, The molar ratio of the arylsulfonyl chloride to the iodide salt is 0.4~0.7:

1.

4. The method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride and olefins as described in claim 1, characterized in that, The molar ratio of the arylsulfonyl chloride to the base is 0.5~1.0 :

1.

5. The method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride and olefins as described in claim 1, characterized in that, The reaction time is 12-16 hours.

6. The method for preparing vinyl sulfone compounds by photo-promoted coupling of sulfonyl chloride and olefins as described in claim 1, characterized in that, The wavelength of the ultraviolet lamp is 415nm, 425nm, 455nm or 465nm.

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