CN111592509A - A method for copper-catalyzed synthesis of aryl (3-sulfonylbenzofuran-2-yl)methanone compounds - Google Patents

Abstract

The invention discloses a method for synthesizing an aryl (3-sulfuryl benzofuran-2-yl) ketone compound by copper catalysis, which comprises the steps of taking a 2- (1-hydroxy-3-arylpropyl-2-alkyne-1-yl) phenol compound shown in a formula (1) and p-toluenesulfonyl methyl isocyano shown in the formula (2) as raw materials and cuprous iodide as a catalyst in an organic solvent system, heating and stirring for reaction, tracking and detecting by TLC until the reaction is complete, and carrying out aftertreatment on a reaction solution to obtain the aryl (3-sulfuryl benzofuran-2-yl) ketone compound shown in the formula (3). The method has the advantages of simple operation, cheap and easily obtained raw materials, mild reaction conditions, environment-friendly reaction system and easy separation and purification of products, is suitable for synthesizing various functionalized aryl (3-sulfuryl benzofuran-2-yl) ketone compounds, is particularly suitable for large-scale industrial production, and can be used for preparing various functionalized aryl (3-sulfuryl benzofuran-2-yl) ketone compoundsThe high-purity aryl (3-sulfuryl benzofuran-2-yl) ketone compound is prepared with high efficiency and high yield, and the synthesis method of the benzofuran and sulfuryl compound is widened.

Description

A kind of copper-catalyzed synthesis of aryl (3-sulfonylbenzofuran-2-yl)methanone compounds method

technical field

The invention belongs to the field of organic synthesis, and relates to a copper-catalyzed synthesis reaction, in particular to a method for copper-catalyzed synthesis of an aryl (3-sulfonylbenzofuran-2-yl)methanone compound.

Background technique

Benzofuran is a kind of important organic small molecular framework, not only the key structural unit of many biologically active natural products, drugs and organic conductive materials, but also a multi-purpose organic synthon, so the development of synthetic methods of benzofuran has been It is one of the important research topics in organic synthetic chemistry. Among various natural and synthetic benzofuran derivatives, they have shown good anti-tumor, anti-viral, anti-fungal, antioxidant, anti-tuberculosis, immunosuppressive and other physiological activities, such as: Benzbromarone (uric acid excretion drug), Activities such as Amiodarone (antiarrhythmic), Obovaten (antitumor activity), Saprisartan (treatment of hypertension) and Anigopreissin A (antimicrobial). In recent years, some strategies to efficiently construct benzofurans have been fully developed (Nat.Chem.2019,11,797; Org.Lett.2019,21,955; Org.Lett.2019,21,8008; Adv.Synth.Catal. 2016, 358, 2984; Angew. Chem. Int. Ed. 2013, 52, 4607; J. Am. Chem. Soc. 2009, 131, 17387 etc.). However, most of these methods are extensions of the developed strategies, which cannot fundamentally solve the limitations of benzofuran synthesis and lack practical value. To date, one of the most common methods for synthesizing benzofurans utilizes base-mediated nucleophilic conjugates, followed by transition metal-catalyzed activation of alkynes with 2-halophenols Heck-type cyclization to the target compounds. This disclosed catalytic strategy also suffers from some drawbacks such as poor regioselectivity, the need to use strong oxidants and expensive ligands, and limitations of various substituents, harsh reaction conditions, and low product yields. Therefore, there is an urgent need for scientists to develop new simple and efficient methods to prepare benzofuran.

Sulfonyl (sulfone)s are another common class of fragments that are widely found in many natural products and drug molecules with high biological activity, and are extremely useful in organic synthesis and medicinal chemistry. Due to the important position of sulfonyl compounds in medicinal chemistry, it is of great significance to research and develop the synthesis of sulfonyl compounds under mild conditions, which can open a new channel for the synthesis of sulfonyl group-containing drugs and their derivatives. Organic synthesis provides new means. At the same time, the structurally similar sulfonyl compounds obtained by the developed methodology can be directly used in the high-throughput screening of some specific biological targets. Once such a small molecule compound library has been screened by valuable biological models, the results will not only provide the possibility to obtain lead compounds with high activity and good selectivity, but also the structure-activity relationship obtained in this process will be more accurate. To reveal the life process to establish a more solid and reliable database. Therefore, it is of great significance to introduce the sulfone functional group into the benzofuran skeleton with special biological activity, and then extensively cultivate its biological properties. However, after a lot of literature research, it is found that there are only a few examples about their synthesis, and the existing methods generally have the disadvantages of pre-designed substrate molecules, low yields, harsh reaction conditions, cumbersome reaction steps, and unfriendly environment. . In recent years, copper-catalyzed organic chemical reactions have become one of the hotspots in current organic chemistry research. A variety of copper-catalyzed chemical reactions have been reported, such as carbon-carbon coupling reactions, carbon-heteroatom coupling reactions, intramolecular reactions, multicomponent reactions, etc. With the rapid deterioration of the global ecological environment, how to achieve sustainable development has become a major problem faced by human beings. Green chemistry research centered on eliminating pollution at the source and saving resources has become a powerful means to solve increasingly serious ecological and environmental problems. . The reaction of isocyanide with alkyne has the advantages of environmental friendliness and low price, and these advantages make it particularly suitable for chemical industrial production.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide a copper-catalyzed method for synthesizing aryl(3-sulfonylbenzofuran-2-yl)methanone compounds, the raw materials are cheap and easy to obtain, and the environment is friendly.

In order to achieve the above object, the technical scheme adopted in the present invention is as follows: a method for copper-catalyzed synthesis of aryl (3-sulfonylbenzofuran-2-yl)methanone compound, in an organic solvent system, with formula (1) The 2-(1-hydroxy-3-arylprop-2-yn-1-yl) phenol shown and the p-toluenesulfonyl methyl isocyanide shown in formula (2) are used as raw materials, and cuprous iodide is used as the raw material. The catalyst is heated and stirred for reaction, and is detected by TLC tracking until the reaction is complete, and the aryl (3-sulfonylbenzofuran-2-yl)methanone compound shown in formula (3) is obtained after the post-treatment of the reaction solution; wherein, 2- The molar ratio of (1-hydroxy-3-arylprop-2-yn-1-yl)phenol to p-toluenesulfonyl methyl isocyanide is 1.5:1;

In the formula, R ¹ is hydrogen, methoxy, methyl, fluorine, chlorine, Ar is phenyl, substituted phenyl, heteroaryl, condensed aryl, wherein the substituents are methyl, ethyl, methoxy, Ethoxy, fluorine or chlorine.

Preferably, the organic solvent is selected from one of acetonitrile, 1,2-dichloroethane, 1,4-dioxane, N-dimethylformamide, dimethylsulfoxide, and toluene.

More preferably, the organic solvent is selected from acetonitrile.

Preferably, the amount of cuprous iodide used is 10 mol% of the amount of 2-(1-hydroxy-3-arylprop-2-yn-1-yl)phenol represented by formula (1).

Preferably, the reaction temperature is 60-100°C.

Preferably, the post-processing method of the reaction solution is as follows: after the reaction is completed, the reaction solution is poured into saturated brine, extracted with dichloromethane, and then the organic phase is backwashed with saturated brine, dried over anhydrous calcium chloride, Suction filtration, distillation under reduced pressure and then separation by silica gel column chromatography, the obtained eluent is distilled under reduced pressure and dried to obtain aryl(3-sulfonylbenzofuran-2-yl)methane represented by formula (3). ketone compounds.

Preferably, the eluent of the silica gel column chromatography is petroleum ether:ethyl acetate=4:1, V/V.

Compared with the prior art, the present invention has the advantages of simple operation, easy availability of raw materials and reagents, mild conditions, green and environmental protection reaction system, easy separation and purification of products, and is suitable for synthesizing various highly functionalized aryl (3-sulfonyl benzoyl) compounds. Furan-2-yl)methanone compounds, especially suitable for large-scale industrial production, can produce high-purity aryl(3-sulfonylbenzofuran-2- base) ketone compounds.

Description of drawings

Fig. 1 is the nuclear magnetic resonance spectrum of 1H-NMR of aryl (3-sulfonylbenzofuran-2-yl)methanone derivative 3a;

Fig. 2 is the nuclear magnetic resonance spectrum of 13C-NMR of aryl (3-sulfonylbenzofuran-2-yl)methanone derivative 3a;

Fig. 3 is the nuclear magnetic resonance spectrum of 1H-NMR of aryl (3-sulfonylbenzofuran-2-yl)methanone derivative 3b;

Fig. 4 is the nuclear magnetic resonance spectrum of 13C-NMR of aryl(3-sulfonylbenzofuran-2-yl)methanone derivative 3b;

Fig. 5 is the nuclear magnetic resonance spectrum of 1H-NMR of aryl (3-sulfonylbenzofuran-2-yl)methanone derivative 3c;

Fig. 6 is the nuclear magnetic resonance spectrum of 13C-NMR of aryl(3-sulfonylbenzofuran-2-yl)methanone derivative 3c;

Fig. 7 is the nuclear magnetic resonance spectrum of 1H-NMR of aryl(3-sulfonylbenzofuran-2-yl)methanone derivative 3d;

Fig. 8 is the nuclear magnetic resonance spectrum of 13C-NMR of aryl(3-sulfonylbenzofuran-2-yl)methanone derivative 3d;

Fig. 9 is the nuclear magnetic resonance spectrum of 1H-NMR of aryl (3-sulfonylbenzofuran-2-yl)methanone derivative 3e;

Fig. 10 is a nuclear magnetic resonance spectrum of 13C-NMR of an aryl(3-sulfonylbenzofuran-2-yl)methanone derivative 3e.

Detailed ways

The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

Example 1: Preparation of phenyl(3-sulfonylbenzofuran-2-yl)methanone derivative 3a

To a 25 mL pressure tube with a magnetic stirring device was added CH ₃ CN (4 mL), 2-(1-hydroxy-3-arylprop-2-yn-1-yl)phenol 1a (0.224 g, 1.0 mmol) and p-toluenesulfonyl methyl isocyanide TsCH ₂ NC2a (0.293 g, 1.5 mmol), cuprous iodide (0.019 g, 0.1 mol) was added and stirred evenly, then it was placed in an 80° C. oil bath to continue stirring. TLC detected the disappearance of the substrate and the reaction ended. The reaction solution was poured into saturated aqueous sodium chloride solution (10 mL), extracted with dichloromethane (3×10 mL), the organic phases were combined, and then the organic phase was backwashed with water (3×10 mL), dried over anhydrous calcium chloride, Steps such as extraction and distillation under reduced pressure obtain a viscous solid, and finally through silica gel column chromatography (eluent is V _{petroleum ether} : V _{ethyl acetate} =4:1) to obtain a yellow solid, which is confirmed to be phenyl through NMR and MS (3-sulfonylbenzofuran-2-yl)methanone derivative 3a in 91% yield.

Spectrogram analysis data 3a:

Yellow solid, mp 115-116°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.22-8.20 (m, 1H, ArH), 8.14-8.12 (m, 2H, ArH), 7.95-7.92 (m, 2H, ArH), 7.69-7.65(m, 1H, ArH), 7.57-7.46(m, 5H, ArH), 7.34(d, J=8.0Hz, 2H, ArH), 2.41(s, 3H, CH ₃ ) (Fig. 1); ¹³ C NMR (CDCl ₃ , 100MHz): δ _C 184.7, 153.7, 152.7, 144.8, 138.1, 135.6, 134.6, 130.3, 129.8, 128.8, 128.2, 127.8, 125.54, 125.45, 123.7, 122.3, 112. (Fig. 2); HRMS (ESI-TOF, m/z): Calcd for C ₂₂ H ₁₇ O ₄ S[M+H] ⁺ : 377.0842, found 377.0839.

Example 2: Different from Example 1, the organic solvent was selected from 1,2-dichloroethane, and its yield was 83%.

Example 3: Different from Example 1, the organic solvent was selected from 1,4-dioxane, and its yield was 75%.

Example 4: Different from Example 1, the organic solvent was selected from N,N-dimethylformamide, and the yield was 87%.

Example 5: Different from Example 1, the organic solvent was selected from dimethyl sulfoxide, and its yield was 84%.

Example 6: Different from Example 1, the organic solvent was selected from toluene, and its yield was 82%.

Example 7: Different from Example 1, the reaction temperature was 60°C, and the yield was 77%.

Example 8: Different from Example 1, the reaction temperature was 100°C, and the yield was 88%.

Example 9:

Substitute 1b for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 87%.

Spectrogram analysis data 3b:

Yellow solid, mp 112-113°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H .8.12 (d, J=8.0 Hz, 2H, ArH), 7.98-7.93 (m, 3H, ArH), 7.70-7.66 ( m,1H,ArH),7.55-7.51(m,2H,ArH),7.43-7.38(m,1H,ArH),7.35(d,J=8.0Hz,2H,ArH),7.26-7.21(m,1H , ArH), 2.40 (s, 3H, CH ₃ ) (Fig. 3); ¹³ CNMR (CDCl ₃ , 100 MHz): δ _C 184.2, 153.5, 147.9 (d, J _FC =251.9 Hz), 145.1, 141.1 (d, _JFC = 12.5Hz), 137.6, 135.2, 134.8, 130.3, 129.8, 128.8, 128.2, 126.8(d, _JFC = 2.2Hz), 126.3(d, _JFC = 5.7Hz), 125.1(d, _JFC = 2.2 Hz), 117.7 (d, J _FC = 4.6 Hz), 113.8 (d, J _FC = 15.5 Hz), 21.6 (Fig. 4); HRMS (ESI-TOF, m/z): Calcd for C ₂₂ H ₁₆ FO ₄ S[M+H] ⁺ :395.0748, found 395.0752.

Example 10:

Substitute 1c for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 79%.

Spectrogram analysis data 3c:

Yellow solid, mp 102-103°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.11 (d, J=8.0 Hz, 2H, ArH), 8.00 (d, J=8.0 Hz, 1H, ArH), 7.96- 7.04(m, 2H, ArH), 7.69-7.64(m, 1H, ArH), 7.54-7.50(m, 2H, ArH), 7.38-7.28(m, 4H, ArH), 2.47(s, 3H, CH _{3 The} ^_ _{_ _} 128.1, 125.6, 125.3, 123.1, 122.7, 119.4, 21.6, 14.8 (Fig. 6); HRMS (ESI-TOF, m/z): Calcd for C ₂₃ H ₁₉ O ₄ S[M+H] ⁺ :391.0999, found 391.0986.

Example 11:

Substitute 1d for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 81%.

Spectrogram analysis data 3d:

White solid, mp 121-122°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.11 (d, J=8.4 Hz, 2H, ArH), 7.96-7.04 (m, 2H, ArH), 7.74 (dd, J =8.0Hz and 0.8Hz,1H,ArH),7.68-7.63(m,1H,ArH),7.53-7.49(m,2H,ArH),7.40-7.32(m,3H,ArH),6.97(dd,J = 8.0 Hz and 0.8 Hz, 1H, ArH), 3.96 (s, 3H, OCH ₃ ), 2.40 (s, 3H, CH ₃ ) (Fig. 7); ¹³ C NMR (CDCl ₃ , 100 MHz): δ _C 184.6, HRMS (ESI-TOF, m/z) :Calcd for C ₂₃ H ₁₉ O ₅ S[M+H] ⁺ :407.0948,found 407.0952.

Example 12:

Substitute 1e for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 74%.

Spectrogram analysis data 3e:

White solid, mp 132-133°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.15 (d, J=8.8 Hz, 1 H, ArH), 8.12-8.09 (m, 2H, ArH), 7.93-7.91 (m ,2H,ArH),7.70-7.66(m,1H,ArH),7.58(d,J=2.0Hz,1H,ArH),7.55-7.51(m,2H,ArH),7.47(dd,J=8.4Hz and 2.0 Hz, 1H, ArH), 7.35 (d, J=8.4 Hz, 2H, ArH), 2.41 (s, 3H, CH ₃ ) (Fig. 9); ¹³ C NMR (CDCl ₃ , 100 MHz): δ _C 184.1 ,153.5,153.0,145.1,137.8,135.3,134.7,134.0,130.2,129.8,128.8,128.2,126.5,125.6,122.9,122.4,112.8,21.7(Figure 10); HRMS(ESI-TOF,m/z): Calcd for C ₂₂ H ₁₆ ClO ₄ S[M+H] ⁺ : 411.0452, found 411.0461.

Example 13:

Substitute 1f for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 75%.

Spectrogram analysis data 3f:

White solid, mp 113-114°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.22-8.20 (m, 1H, ArH), 8.12 (d, J=8.4 Hz, 2H, ArH), 8.01-7.96 (m , 2H, ArH), 7.58-7.46 (m, 3HV), 7.34 (d, J=8.0Hz, 2H, ArH), 7.22-7.17 (m, 2H, ArH), 2.40 (s, 3H, CH ₃ ); ¹³ C NMR (CDCl ₃ , 100 MHz): δ _C 183.0, 166.6 (d, J _FC = 256.6 Hz), 153.7, 152.3, 144.9, 138.0, 133.0 (d, J _FC = 9.6 Hz), 132.0 (d, J _FC = 9.6 Hz) = 2.7Hz), 129.7, 128.1, 127.9, 125.6, 123.6, 122.3 (d, J _FC = 22.3 Hz), 116.1, 112.3, 21.6; HRMS (ESI-TOF, m/z): Calcd for C ₂₂ H ₁₆ FO ₄ S[M+H] ⁺ :395.0748, found 395.0738.

Example 14:

Substitute 1g for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 79%.

Spectrogram analysis data 3g:

White solid, mp 137-138°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.22 (dd, J=6.8 Hz and 1.6 Hz, 1H, ArH), 8.13-8.11 (m, 2H, ArH), 7.91- 7.87 (m, 2H, ArH), 7.58-7.46 (m, 5H, ArH), 7.34 (d, J=8.0Hz, 2H, ArH), 2.40 (s, 3H, CH ₃ ); ¹³ C NMR (CDCl ₃ ) , 100MHz): δ _C 183.3, 153.7, 152.0, 144.9, 141.1, 137.9, 133.9, 131.5, 129.7, 129.1, 128.1, 128.0, 125.8, 125.6, 123.6, 122.3, 112.3, 21.6; HRMS (ESI-TOF z): Calcd for C ₂₂ H ₁₆ ClO ₄ S[M+H] ⁺ : 411.0452, found 411.0451.

Example 15:

Substitute 1h for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 82%.

Spectrogram analysis data 3h:

White solid, mp 141-142°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.19 (dd, J=6.4 Hz and 2.0 Hz, 1H, ArH), 8.12 (d, J=8.4 Hz, 2H, ArH) , 7.84(d, J=8.4Hz, 2H, ArH), 7.56-7.44(m, 3H, ArH), 7.34-7.31(m, 4H, ArH), 2.46(m, 3H, CH ₃ ), 2.40(s , 3H, CH ₃ ); ¹³ C NMR (CDCl ₃ , 100 MHz): δ _C 184.3, 153.6, 153.1, 145.9, 144.7, 138.1, 133.1, 130.4, 129.7, 129.5, 128.1, 127.6, 125.4, 125.0, 123.6, 122.1 , 112.3, 21.9, 21.6; HRMS(ESI-TOF, m/z): Calcd for C ₂₃ H ₁₉ O ₄ S[M+H] ⁺ : 391.0999, found 391.0982.

Example 16:

Substitute 1i for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 81%.

Spectrogram analysis data 3i:

White solid, mp 151-152°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.17 (dd, J=6.8 Hz and 2.8 Hz, 1H, ArH), 8.12 (d, J=8.0 Hz, 2H, ArH) ,7.93(d,J＝8.8Hz,2H,ArH),7.55-7.43(m,3H,ArH),7.33(d,J＝8.0Hz,2H,ArH),6.98(d,J＝8.8Hz,2H , ArH), 3.90 (m, 3H, OCH ₃ ), 2.39 (s, 3H, CH ₃ ); ¹³ C NMR (CDCl ₃ , 100MHz): δ _C 183.1, 164.8, 153.6, 153.4, 144.7, 138.1, 132.8, 129.7, 128.6, 128.1, 127.5, 125.4, 124.5, 123.6, 122.0, 114.1, 112.2, 55.6, 21.6; HRMS(ESI-TOF, m/z): Calcd for C ₂₃ H ₁₉ O ₅ S[M+H] ⁺ :407.0948,found 407.0953.

Example 17:

Substitute 1j for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 87%.

Spectrogram analysis data 3j:

White solid, mp 144-145°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.19 (dd, J=6.4 Hz and 2.0 Hz, 1H, ArH), 8.13 (d, J=8.4 Hz, 2H, ArH) , 7.87-7.85 (m, 2H, ArH), 7.55-7.44 (m, 3H, ArH), 7.35-7.32 (m, 4H, ArH), 2.75 (q, J=7.6Hz, 2H, CH ₂ ), 2.40 (s, 3H, CH ₃ ), 1.28 (t, J=7.6 Hz, 3H, CH ₃ ); ¹³ C NMR (CDCl ₃ , 100 MHz): δ _C 184.4, 153.7, 153.2, 152.0, 144.8, 138.2, 133.4, 130.6, 129.8, 128.4, 128.2, 127.7, 125.5, 125.0, 123.7, 122.2, 112.3, 29.2, 21.7, 15.1; HRMS(ESI-TOF, m/z): Calcd for C ₂₄ H ₂₁ O ₄ S[M+H ] ⁺ :405.1155,found 405.1161.

Example 18:

Substitute 1k for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 81%.

Spectrogram analysis data 3k:

White solid, mp 145-147°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.16 (dd, J=6.0 Hz and 1.6 Hz, 1H, ArH), 8.12 (d, J=8.4 Hz, 2H, ArH) ,7.93-7.89(m,2H,ArH),7.55-7.52(m,1H,ArH),7.50-7.43(m,2H,ArH),7.32(d,J=8.4Hz,2H,ArH),6.98- 6.94 (m, 2H, ArH), 4.13 (q, J=6.8 Hz, 2H, CH ₂ ), 2.39 (s, 3H, CH ₃ ), 1.45 (t, J=7.2 Hz, 3H, CH ₃ ); ¹³ C NMR (CDCl ₃ , 100MHz): δ _C 183.2, 164.4, 153.7, 153.6, 144.8, 138.3, 132.9, 129.8, 128.5, 128.2, 127.6, 125.5, 124.5, 123.7, 122.1, 114.6, 112.4, 64.1, 212.4, 64.1 ;HRMS(ESI-TOF,m/z):Calcd forC ₂₄ H ₂₁ O ₅ S[M+H] ⁺ : 421.1104, found 421.1121.

Example 19:

Substitute 11 for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 75%.

Spectrogram analysis data 3l:

White solid, mp 123-124°C; ¹ H NMR (CDCl ₃ , 400 MHz): δ _H 8.25-8.22 (m, 1H, ArH), 8.14-8.12 (m, 2H, ArH), 7.73-7.71 (m, 1H, ArH), 7.68-7.65 (m, 1H, ArH), 7.58-7.47 (m, 4H, ArH), 7.39-7.34 (m, 3H, ArH), 2.41 (s, 3H, CH ₃ ); ¹³ C NMR ( CDCl ₃ , 100MHz): δ _C 183.2 (d, J _FC = 2.6 Hz), 162.6 (d, J _FC = 247.2 Hz), 153.7, 151.8, 144.9, 137.9, 137.4 (d, J _FC = 6.8 Hz), 130.5 (d, _JFC = 7.6Hz), 129.8, 128.2, 128.1, 126.2 (d, _JFC = 3.1Hz), 126.1, 125.7, 123.6, 122.3, 121.6 (d, _JFC = 21.4Hz), 116.6(d, J _FC = 22.8Hz), 112.4, 21.7; HRMS (ESI-TOF, m/z): Calcd for C ₂₂ H ₁₆ FO ₄ S[M+H] ⁺ : 395.0748, found 395.0752.

Example 20:

Substitute 1m for 1a in Example 1, other conditions are the same as in Example 1, and the yield is 85%.

Spectrogram analysis data 3m:

White solid, mp 152-153°C; ¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.32 (s, 1H), 8.24-8.22 (m, 1H), 8.10 (d, J=8.0 Hz 2H), 8.06 (dd ,J=8.4Hz and 2.0Hz,1H),7.95(d,J=8.8Hz,1H),7.91-7.87(m,2H),7.66-7.62(m,1H),7.59-7.47(m,4H) , 7.30(d, J=8.4Hz, 2H), 2.38(s, 3H); ¹³ C-NMR (CDCl ₃ , 100MHz) δ 184.7, 153.8, 153.0, 144.8, 138.1, 136.2, 133.5, 133.0, 132.2, 129.9, 129.7,129.4,128.8,128.1,127.9,127.7,127.0,125.5,125.2,124.4,123.7,122.1,112.4,21.6.; HRMS(ESI-TOF)m/z calculated for C ₂₆ H ₁₉ O ₄ S[M+ H] ⁺ :427.0999found:427.0992.

Example 21:

1a in Example 1 was replaced by 1n, and other conditions were the same as in Example 1, and the yield was 74%.

Spectrogram analysis data 3n:

White solid, mp 125-126°C; ¹ H-NMR (400MHz, CDCl ₃ ) δ 8.34 (d, J=7.6 Hz, 1H), 8.18 (d, J=8.0 Hz, 2H), 7.97 (d, J= 4.0Hz,1H),7.83(d,J=4.4Hz,1H),7.61-7.48(m,3H),7.34(d,J=8.0Hz,2H),7.23-7.20(m,1H),2.40( s, 3H); ¹³ C-NMR (CDCl ₃ , 100MHz) δ 174.9, 153.4, 151.2, 144.8, 142.1, 138.2, 136.4, 136.2, 129.6, 128.6, 128.3, 128.3, 126.2, 125.6, 124.1, 122.9, 112.3. ;HRMS(ESI-TOF)m/z calculated for C ₂₀ H ₁₅ O ₄ S ₂ [M+H] ⁺ :383.0406 found:383.0411.

Claims (7)

1. a method for synthesizing an aryl (3-sulfuryl benzofuran-2-yl) ketone compound by copper catalysis is characterized in that 2- (1-hydroxy-3-arylpropyl-2-alkyne-1-yl) phenol shown in a formula (1) and p-toluenesulfonyl methyl isocyano shown in the formula (2) are used as raw materials in an organic solvent system, cuprous iodide is used as a catalyst, heating and stirring are carried out for reaction, TLC tracking detection is carried out until the reaction is complete, and the aryl (3-sulfuryl benzofuran-2-yl) ketone compound shown in the formula (3) is obtained after the reaction liquid is subjected to post-treatment; wherein the feeding molar ratio of the 2- (1-hydroxy-3-arylprop-2-yne-1-yl) phenol to the p-toluenesulfonylmethylisocyan is 1.5: 1;

in the formula, R¹Is hydrogen, methoxy, methyl, fluorine or chlorine, Ar is phenyl, substituted phenyl,Heteroaryl, fused aryl, wherein the substituents are methyl, ethyl, methoxy, ethoxy, fluoro or chloro.

2. The method for copper-catalyzed synthesis of aryl (3-sulfuryl benzofuran-2-yl) ketone compound according to claim 1, wherein the organic solvent is one selected from acetonitrile, 1, 2-dichloroethane, 1, 4-dioxane, N-dimethylformamide, dimethyl sulfoxide and toluene.

3. The method for copper-catalyzed synthesis of aryl (3-sulfuryl benzofuran-2-yl) ketone compound according to claim 2, wherein the organic solvent is selected from acetonitrile.

4. The method for copper-catalyzed synthesis of aryl (3-sulfuryl benzofuran-2-yl) ketone compound according to claim 1, wherein the amount of cuprous iodide is 10 mol% of the substance of 2- (1-hydroxy-3-arylprop-2-yn-1-yl) phenol represented by formula (1).

5. The method for copper-catalyzed synthesis of aryl (3-sulfuryl benzofuran-2-yl) ketone compound according to claim 1, wherein the reaction temperature is 60-100 ℃.

6. The method for synthesizing aryl (3-sulfuryl benzofuran-2-yl) ketone compound by copper catalysis according to claim 1, wherein the method for post-treating the reaction liquid comprises the following steps: after the reaction is finished, pouring the reaction liquid into saturated saline solution, extracting with dichloromethane, then backwashing an organic phase with the saturated saline solution, drying by anhydrous calcium chloride, filtering, distilling under reduced pressure, then separating by silica gel column chromatography, distilling the obtained eluent under reduced pressure, and drying to obtain the aryl (3-sulfonyl benzofuran-2-yl) ketone compound shown in the formula (3).

7. The method for copper-catalyzed synthesis of aryl (3-sulfuryl benzofuran-2-yl) ketone compound according to claim 6, wherein the eluent of the silica gel column chromatography is petroleum ether: ethyl acetate 4:1, V/V.

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