CN117247369A - Preparation method of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative - Google Patents

Preparation method of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative Download PDF

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CN117247369A
CN117247369A CN202311210074.3A CN202311210074A CN117247369A CN 117247369 A CN117247369 A CN 117247369A CN 202311210074 A CN202311210074 A CN 202311210074A CN 117247369 A CN117247369 A CN 117247369A
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thiophene
dihydrobenzo
rest
dioxide
dioxide derivative
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郭林
石伟
齐绪宽
田坚
杨川
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Harbin Institute Of Technology shenzhen Shenzhen Institute Of Science And Technology Innovation Harbin Institute Of Technology
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Harbin Institute Of Technology shenzhen Shenzhen Institute Of Science And Technology Innovation Harbin Institute Of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring

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Abstract

2, 3-dihydrobenzo [ b ]]The invention relates to a preparation method of thiophene 1, 1-dioxide derivatives, belongs to the technical field of photocatalytic synthesis, and particularly relates to a 2, 3-dihydrobenzo [ b ]]A method for synthesizing thiophene 1, 1-dioxide derivatives. The invention aims to solve the technical problems that the existing preparation method is complicated in operation steps and harsh in conditions, and the harsh conditions with strong oxidizing property or strong reducing property do not have universal substrate applicability. The method comprises the following steps: terminal alkynes, arylsulfinic acids, ir [ dF (CF) 3 )ppy] 2 (4,4’‑dCF 3 bpy)PF 6 Adding 4-methylpyridine into a quartz reaction tube containing a solvent, and irradiating with blue light at room temperature under an inert gas atmosphere; extracting and washing; rotary evaporation concentration and column chromatography separation to obtain the target product. The invention adopts a simple, green and efficient photocatalysis synthesis strategy, uses a catalytic amount of photocatalyst to synthesize the novel sulfur-containing heterocyclic compound, and has the advantages of simple operation, low-cost and easily obtained raw materials, mild reaction conditions, better functional group compatibility and the likeAdvantages are achieved. The method is applied to the field of organic synthesis.

Description

Preparation method of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative
Technical Field
The invention belongs to the technical field of photocatalytic synthesis, and particularly relates to a synthesis method of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative.
Background
2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide and its derivatives are an important class of heterocyclic compounds with a wide distribution of structural units, and have important applications in many active compounds. For example, as inhibitors of tumor necrosis factor-alpha converting enzyme (TACE), hypoglycemic agents, HIF-2 alpha inhibitors, etc. Furthermore, they are also used as important intermediates in the field of organic synthesis. Therefore, the exploration of a synthetic method of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide and its derivatives is of great importance in the fields of medicinal chemistry and organic synthesis. Traditionally, the 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide backbone is synthesized by first oxidizing benzothiophene to benzo [ b ] thiophene 1, 1-dioxide using m-chloroperoxybenzoic acid (m-CPBA), followed by palladium on carbon hydrogenation reduction; or oxidizing 2, 3-dihydrobenzothiophene with a strong oxidizing agent. These methods, while expanding the variety of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxides, have drawbacks. If the reaction raw materials are not easy to obtain, the operation steps are complicated, the conditions are harsh, and the harsh conditions with strong oxidizing property or strong reducing property do not have general substrate applicability. In addition, the synthesis of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivatives from alkynes and arylsulfinic acids has not been reported. Therefore, the novel method for synthesizing the 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative with high efficiency, simple and convenient operation and mild condition is explored to have important research value.
Disclosure of Invention
The invention provides a preparation method of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative, which aims to solve the technical problems that the existing preparation method is complicated in operation steps and harsh in conditions, and the harsh conditions with strong oxidizing property or strong reducing property do not have general substrate applicability.
The invention aims to provide a simple and mild photoinduction method for realizing 2, 3-dihydrobenzo [ b ]]Synthesis of thiophene 1, 1-dioxide derivatives by reactingWith catalytic amounts of the photocatalyst Ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 Can be used for efficiently converting alkyne and aryl sulfinic acid to synthesize 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative has the advantages of simple operation, cheap and easily available raw materials, good functional group compatibility and the like.
A preparation method of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivatives comprises the following steps:
1. the terminal alkyne, arylsulfinic acid and 4-methylpyridine are introduced into a quartz reaction tube containing a solvent, followed by Ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 ；
2. Under the condition of nitrogen atmosphere and room temperature, the reaction tube in the first step is placed under a blue light lamp for irradiation reaction;
3. after the reaction is finished, pouring the obtained reaction mixed solution into a separating funnel containing deionized water, extracting and washing for three times by adopting ethyl acetate, and merging organic phases;
4. drying the organic phase obtained in the third step by using anhydrous sodium sulfate, filtering, removing the anhydrous sodium sulfate, and concentrating the organic phase by using a rotary evaporator to obtain a crude product;
5. and (3) separating the crude product obtained in the step four by using column chromatography to obtain the target product 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative.
The reaction formula of the invention:
the preparation method of the terminal alkyne comprises the following steps: the specific synthetic route takes benzyl cyanide S1 as an example:
(1) Benzyl cyanide (S1, 10mmol,1.0 eq) was added to a 100mL two-port reaction flask equipped with a stirrer at room temperatureuiv), dissolved in N, N-dimethylformamide (DMF, 40 mL), cooled to 0 ℃, then sodium hydride (0.96 g,24.0mmol,2.40 equiv) was added and stirred at 0 ℃ for 20 minutes; after the reaction was completed, ethyl acetate (EA, 20 mL) was added to dilute the mixture, followed by extraction with EA (20 mL. Times.3) after addition of water (60 mL), and the organic phases were combined, washed with saturated brine and dried over Na 2 Drying SO4, and distilling under reduced pressure to remove most of the solvent; the crude product was purified by column chromatography, eluting with Petroleum Ether (PE)/ethyl acetate system (V) PE :V EA =20: 1) Colorless liquid S2 is obtained;
(2) The starting material S2 (6.0 mmol,1.0 equiv) obtained in the previous step was added to a dry 100mL reaction flask, dissolved in dry 40mL toluene and cooled to-78 ℃, the reaction system was deoxygenated and then filled with nitrogen, followed by slow addition of diisobutylaluminum hydride (1M in n-hexane, 7.2mL,7.2mmol,1.2 equiv); continuing stirring for 5min after the addition, and then transferring to room temperature and continuing stirring for 15-30min; after the reaction, the mixture was put into an ice-water bath, diluted hydrochloric acid (5% in H) was added 2 O) quenching the solution, distilling off most of the solvent under reduced pressure, extracting with anhydrous diethyl ether and water, combining the organic layers, and passing anhydrous Na 2 SO 4 Drying and distilling under reduced pressure to remove most of the solvent. The crude product was purified by column chromatography, eluting with Petroleum Ether (PE)/ethyl acetate system (V) PE :V EA =50: 1) Obtaining colorless liquid aryl aldehyde S3;
(3) Aryl aldehyde S3 (3.0 mmol,1.0 equiv) prepared in the previous step was added to a 100mL reaction flask and dissolved in methanol (MeOH, 20 mL), followed by cesium carbonate (2.93 g,9.0mmol,3.0 equiv) and dimethyl (1-diazo-2-oxopropyl) phosphonate (0.81 g,4.2mmol,1.4 equiv) at room temperature; after the reaction, adding EA and water for extraction, combining organic layers and anhydrous Na 2 SO 4 Drying, concentrating under reduced pressure to remove solvent, purifying the crude product by column chromatography, eluting with PE/EA system (V PE :V EA =50:1), a colorless liquid was obtained as terminal alkyne 1.
The invention has the beneficial effects that:
compared with the prior art, the invention realizes the synthesis of the 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivatives by a simple and mild photoinduction method, and mainly has the following advantages:
(1) The reaction has the step economy, avoids complex steps of oxidation, further reduction and the like of pre-synthesizing sulfur-containing heterocycle, and saves reaction steps, reaction time and complex reaction treatment.
(2) The reaction adopts a photocatalysis radical series reaction strategy, and the initial radical starting reaction generated by electron transfer between the catalyst and the substrate molecules can be realized only by the irradiation of a catalytic amount of photocatalyst under the irradiation of a 420+/-10 nm LED light source, so that the operation is simple, and the reaction condition is mild.
(3) The reaction substrates are cheap and easy to synthesize, the functional groups are good in compatibility, the obtained products are easy to separate, and the whole reaction system is economical and efficient.
The invention is used for synthesizing 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivatives.
Drawings
FIG. 1 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3a obtained in example 1;
FIG. 2 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3a obtained in example 1;
FIG. 3 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3b obtained in example 2;
FIG. 4 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3b obtained in example 2;
FIG. 5 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3c obtained in example 3;
FIG. 6 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3c obtained in example 3;
FIG. 7 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3d obtained in example 4;
FIG. 8 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3d obtained in example 4;
FIG. 9 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3e obtained in example 5;
FIG. 10 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3e obtained in example 5;
FIG. 11 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3f obtained in example 6;
FIG. 12 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3f obtained in example 6;
FIG. 13 is a hydrogen spectrum of 3g of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative obtained in example 7;
FIG. 14 is a graph showing the carbon spectrum of 3g of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative obtained in example 7;
FIG. 15 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3h obtained in example 8;
FIG. 16 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3h obtained in example 8;
FIG. 17 is a hydrogen spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3i obtained in example 9;
FIG. 18 is a carbon spectrum of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative 3i obtained in example 9.
Detailed Description
The first embodiment is as follows: the preparation method of the 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative comprises the following steps:
1. the terminal alkyne, arylsulfinic acid and 4-methylpyridine are introduced into a quartz reaction tube containing a solvent, followed by Ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 ；
2. Under the condition of nitrogen atmosphere and room temperature, the reaction tube in the first step is placed under a blue light lamp for irradiation reaction;
3. after the reaction is finished, pouring the obtained reaction mixed solution into a separating funnel containing deionized water, extracting and washing for three times by adopting ethyl acetate, and merging organic phases;
4. drying the organic phase obtained in the third step by using anhydrous sodium sulfate, filtering, removing the anhydrous sodium sulfate, and concentrating the organic phase by using a rotary evaporator to obtain a crude product;
5. and (3) separating the crude product obtained in the step four by using column chromatography to obtain the target product 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative.
The second embodiment is as follows: the first difference between this embodiment and the specific embodiment is that: the structural formula of the terminal alkyne compound in the first step is as follows:
wherein R is 1 、R 2 、R 3 、R 4 And R is 5 All are H; or R is 3 Is CH 3 The rest are all H; or R is 3 F, and the rest are all H; or R is 3 Cl and the rest are all H; or R is 3 Br, the remainder all being H. The other is the same as in the first embodiment.
And a third specific embodiment: this embodiment differs from the first or second embodiment in that: in the step one, the aryl sulfinic acid is p-toluene sulfinic acid, benzene sulfinic acid, p-fluorobenzene sulfinic acid, p-chlorobenzene sulfinic acid or p-methoxy benzene sulfinic acid. The other is the same as the first or second embodiment.
The specific embodiment IV is as follows: this embodiment differs from one of the first to third embodiments in that: step one the Ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 Is photocatalyst of bis [2- (2, 4-difluorophenyl) -5-trifluoromethyl pyridine][2-2' -Bis (4-trifluoromethylpyridine)]Iridium bis (hexafluorophosphate) salt with the structural formula:
the others are the same as in one to one fourth embodiments.
Fifth embodiment: this embodiment differs from one of the first to third embodiments in that: step one the solvent is 1, 2-dichloroethane. The others are the same as in one to one fourth embodiments.
Specific embodiment six: this embodiment differs from one of the first to fifth embodiments in that: step one, the ratio of the terminal alkyne compound to the solvent is 0.1mmol:1mL; the ratio of arylsulfinic acid to solvent was 0.35mmol:1mL; ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 The ratio to solvent was 2.3mg:1mL; the ratio of 4-methylpyridine to solvent was 0.2mmol:1mL. The others are the same as in one of the first to fifth embodiments.
Seventh embodiment: this embodiment differs from one of the first to sixth embodiments in that: and step two, the wavelength of the blue light lamp is 410-430 nm, and the power is 10W. The others are the same as in one of the first to sixth embodiments.
Eighth embodiment: this embodiment differs from one of the first to seventh embodiments in that: and the irradiation time in the second step is 12h. The other is the same as in one of the first to seventh embodiments.
Detailed description nine: this embodiment differs from one to eight of the embodiments in that: and fifthly, separating products by column chromatography by adopting silica gel and a mobile phase, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate according to a volume ratio of 2:1. The others are the same as in one to eight embodiments.
Detailed description ten: this embodiment differs from one of the embodiments one to nine in that: and step five, the structural formula of the target product 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative is as follows:
wherein R is 8 And R is 11 Is CH 3 The rest are all H; or R is 3 、R 8 And R is 11 Is CH 3 The rest are all H; or R is 3 Is F, R 8 And R is 11 Is CH 3 The rest are all H; or R is 3 Is Cl, R 8 And R is 11 Is CH 3 The rest are all H; or R is 3 Is Br, R 8 And R is 11 Is CH 3 The rest are all H; or R is 1-13 All are H; or R is 8 And R is 11 F, and the rest are all H; or R is 8 And R is 11 Cl and the rest are all H; or R is 8 And R is 11 OMe, the rest are all H. The others are the same as in one of the embodiments one to nine.
The present invention is not limited to the above embodiments, and the object of the invention can be achieved by one or a combination of several embodiments.
Example 1:
this example 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative was prepared according to the following procedure:
(1) Taking 0.1mmol of terminal alkyne compound 1a(R 1 、R 2 、R 3 、R 4 And R is 5 H), 0.35mmol of p-toluene sulfinic acid and 0.2mmol of 4-methylpyridine were introduced into a quartz reaction tube containing 1mL of 1, 2-dichloroethane, and then 2.3mg of the photocatalyst Ir [ dF (CF) was introduced into the reaction tube 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 ；
(2) Under the condition of nitrogen atmosphere and room temperature, the reaction tube in the step (1) is put under an LED lamp with power of 10W and wavelength of 420nm, and the irradiation reaction is carried out for 12 hours;
(3) After the reaction of the step (2), pouring the obtained reaction mixture into a separating funnel containing 15.0mL of deionized water, extracting and washing three times by adopting ethyl acetate, 10.0mL each time, and combining organic phases;
(4) Drying the organic phase obtained in the step (3) by using anhydrous sodium sulfate, carrying out suction filtration, removing the anhydrous sodium sulfate, and concentrating the organic phase by using a rotary evaporator to obtain a crude product;
(5) Separating the crude product obtained in the step (4) by column chromatography (silica gel, mobile phase: petroleum ether: ethyl acetate volume ratio=2:1) to obtain the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3a(R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 8 And R is 11 Is CH 3 ) The yield was 59% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]The thiophene 1, 1-dioxide derivative 3a is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.39(s,1H),7.71(d,J＝8.1Hz,2H),7.38-7.33(m,4H),7.29(d,J＝8.0Hz,3H),6.23(s,1H),4.02(dd,J＝8.9,4.1Hz,1H),3.52(dd,J＝14.2,9.0Hz,1H),3.39(dd,J＝14.2,4.2Hz,1H),2.40(s,3H),2.25(s,3H),1.35(s,3H),1.28(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:147.0,144.9,143.5,142.4,141.2,138.7,136.6,131.9,129.9,128.9,128.2,127.1,126.2,122.6,53.3,49.1,41.8,27.8,23.4,21.6,20.7.HRMS(ESI):([M+H] + )Calcd for C 25 H 27 O 4 S 2 + :455.1351,Found:455.1358.
example 2:
this embodiment differs from embodiment 1 in that: in step (1), terminal alkyne compound 1b is adopted(R 1 、R 2 、R 4 And R is 5 Is H, R 3 Is CH 3 ). Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivatives 3b(R 1 、R 2 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 3 、R 8 And R is 11 Is CH 3 ) The yield was 67% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]Thiophene 1, 1-dioxide derivative 3b is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.43(s,1H),7.74(d,J＝7.9Hz,2H),7.31(d,J＝8.1Hz,2H),7.24(d,J＝8.0Hz,2H),7.18(d,J＝8.1Hz,2H),6.35(s,1H),4.03(dd,J＝8.9,4.2Hz,1H),3.53(dd,J＝14.2,9.0Hz,1H),3.40(dd,J＝14.2,4.2Hz,1H),2.42(s,3H),2.36(s,3H),2.29(s,3H),1.34(s,3H),1.29(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:144.8,144.0,143.7,142.4,141.1,138.7,136.7,132.0,129.9,129.5,128.1,126.0,122.5,53.4,49.1,41.4,27.6,23.7,21.6,20.8,20.7.HRMS(ESI):([M+H] + )Calcd for C 26 H 29 O 4 S 2 + :469.1507,Found:469.1504.
example 3:
this embodiment differs from embodiment 1 in that: in the step (1), the terminal alkyne compound 1c is adopted(R 1 、R 2 、R 4 And R is 5 Is H, R 3 F). Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3c(R 1 、R 2 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 3 Is F, R 8 And R is 11 Is CH 3 ) The yield was 54% as white solid.
2, 3-Di prepared in this exampleHydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3c is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.45(s,1H),7.74(d,J＝8.3Hz,2H),7.36-7.31(m,4H),7.08(t,J＝8.6Hz,2H),6.37(s,1H),4.02(dd,J＝9.0,4.0Hz,1H),3.54(dd,J＝14.3,9.1Hz,1H),3.39(dd,J＝14.3,4.0Hz,1H),2.43(s,3H),2.31(s,3H),1.36(s,3H),1.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:161.5(d,J＝248.5Hz),144.9,143.3,142.8(d,J＝3.2Hz),142.5,141.2,138.8,136.5,131.8,129.9,128.1,127.8(d,J＝7.7Hz),122.6,115.6(d,J＝21.2Hz),53.3,49.1,41.4,27.6,24.0,21.6,20.7. 19 F NMR(376MHz,CDCl 3 )δ:-115.4.HRMS(ESI):([M+H] + )Calcd for C 25 H 26 FO 4 S 2 + :473.1257,Found:473.1260.
example 4:
this embodiment differs from embodiment 1 in that: in step (1), terminal alkyne compound 1d is adopted(R 1 、R 2 、R 4 And R is 5 Is H, R 3 Cl). Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivatives 3d(R 1 、R 2 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 3 Is Cl, R 8 And R is 11 Is CH 3 ) The yield was 62% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]The thiophene 1, 1-dioxide derivative 3d is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.44(s,1H),7.74(d,J＝8.0Hz,2H),7.37-7.30(m,6H),6.42(s,1H),4.01(dd,J＝8.8,3.6Hz,1H),3.53(dd,J＝14.1,9.2Hz,1H),3.37(dd,J＝14.3,3.7Hz,1H),2.43(s,3H),2.33(s,3H),1.33(d,J＝12.1Hz,6H). 13 C NMR(101MHz,CDCl 3 )δ:145.7,144.9,143.2,142.6,141.4,138.8,136.6,132.9,131.8,129.9,128.9,128.2,127.6,122.7,53.3,48.9,41.6,27.4,24.0,21.6,20.8.HRMS(ESI):([M+H] + )Calcd for C 25 H 26 ClO 4 S 2 + :489.0961,Found:489.0956.
example 5:
this embodiment differs from embodiment 1 in that: in the step (1), the terminal alkyne compound 1e is adopted(R 1 、R 2 、R 4 And R is 5 Is H, R 3 Br). Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3e(R 1 、R 2 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 3 Is Br, R 8 And R is 11 Is CH 3 ) The yield was 53% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]Thiophene 1, 1-dioxide derivative 3e is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.44(s,1H),7.74(d,J＝8.2Hz,2H),7.51(d,J＝8.5Hz,2H),7.32(d,J＝8.1Hz,2H),7.25(d,J＝8.6Hz,2H),6.41(s,1H),4.00(dd,J＝9.0,4.0Hz,1H),3.53(dd,J＝14.3,9.1Hz,1H),3.36(dd,J＝14.3,4.0Hz,1H),2.43(s,3H),2.33(s,3H),1.34(s,3H),1.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:146.2,145.0,143.1,142.6,141.4,138.8,136.5,131.9,131.8,129.9,128.2,128.0,122.7,121.0,53.3,48.9,41.7,27.3,23.9,21.6,20.8.HRMS(ESI):([M+H] + )Calcd for C 25 H 26 BrO 4 S 2 + :533.0456,Found:533.0462.
example 6:
this embodiment differs from embodiment 1 in that: in the step (1), benzene sulfinic acid is adopted as the aryl sulfinic acid. Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3f(R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 ，R 9 、R 10 、R 11 ，R 12 And R is 13 H), yield was 46% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]The thiophene 1, 1-dioxide derivative 3f is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.23(d,J＝1.7Hz,1H),7.92(d,J＝7.3Hz,2H),7.83(dd,J＝8.4,1.8Hz,1H),7.60(t,J＝7.4Hz,1H),7.52(t,J＝7.6Hz,2H),7.42-7.36(m,4H),7.34-7.29(m,1H),6.64(d,J＝8.4Hz,1H),4.14(dd,J＝8.9,4.6Hz,1H),3.57(dd,J＝14.2,8.9Hz,1H),3.43(dd,J＝14.2,4.6Hz,1H),1.35(s,3H),1.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:146.9,143.7,143.1,141.5,140.2,133.9,131.2,129.6,129.0,128.9,127.9,127.1,126.0,121.2,53.3,49.0,41.7,28.1,23.3.HRMS(ESI):([M+H] + )Calcd for C 25 H 23 O 4 S 2 + :427.1038,Found:427.1036.
example 7:
this embodiment differs from embodiment 1 in that: in the step (1), p-fluorobenzenesulfinic acid is adopted as the aryl sulfinic acid. Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3g(R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 8 And R is 11 F) yield was 47% as brown oily liquid.
2, 3-Dihydrobenzo [ b ] prepared in this example]3g of thiophene 1, 1-dioxide derivatives are characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.41(d,J＝6.4Hz,1H),8.00(dd,J＝7.7,5.1Hz,2H),7.42-7.36(m,4H),7.35-7.31(m,1H),7.21(t,J＝8.5Hz,2H),6.12(d,J＝10.6Hz,1H),4.12(dd,J＝8.9,4.7Hz,1H),3.62(dd,J＝14.2,8.9Hz,1H),3.48(dd,J＝14.2,4.8Hz,1H),1.39(s,3H),1.31(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:166.1(d,J＝259.6Hz),160.7,(d,J＝264.6Hz),147.5(d,J＝9.7Hz),146.3,137.0(d,J＝2.5Hz),135.4(d,J＝2.8Hz),131.5(d,J＝9.7Hz),131.1(d,J＝17.0Hz),129.1,127.4,125.9,123.6,116.7(d,J＝22.8Hz),53.2,48.9,41.6,28.4,22.7. 19 F NMR(376MHz,CDCl 3 )δ:-99.9,-101.9.HRMS(ESI):([M+Na] + )Calcd for C 23 H 20 F 2 O 4 S 2 Na + :485.0669,Found:485.0665.
example 8:
this embodiment differs from embodiment 1 in that: in the step (1), p-chlorobenzene sulfinic acid is adopted as the aryl sulfinic acid. Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivatives 3h(R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 8 And R is 11 Cl), yield was 52% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]The thiophene 1, 1-dioxide derivative 3h is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.61(s,1H),7.86(d,J＝8.6Hz,2H),7.47(d,J＝8.6Hz,2H),7.41-7.29(m,5H),6.39(s,1H),4.05(dd,J＝9.0,4.4Hz,1H),3.58(dd,J＝14.3,9.0Hz,1H),3.46(dd,J＝14.3,4.4Hz,1H),1.38(s,3H),1.30(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:146.3,145.3,141.0,139.8,139.7,137.3,136.8,131.5,130.4,129.4,129.1,127.4,126.0,124.5,53.2,49.1,41.8,28.1,23.1.HRMS(ESI):([M+H] + )Calcd for C 23 H 21 Cl 2 O 4 S 2 + :495.0258,Found:495.0258.
example 9:
this embodiment differs from embodiment 1 in that: in the step (1), p-methoxybenzene sulfinic acid is adopted as the aryl sulfinic acid. Otherwise, the same as in example 1 was used.
This example gives the target product 2, 3-dihydrobenzo [ b ]]Thiophene 1, 1-dioxide derivative 3i(R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 、R 12 And R is 13 Is H, R 8 And R is 11 OMe) yield was 49% as white solid.
2, 3-Dihydrobenzo [ b ] prepared in this example]The thiophene 1, 1-dioxide derivative 3i is characterized as follows: 1 H NMR(400MHz,CDCl 3 )δ:8.41(s,1H),7.84(d,J＝9.0Hz,2H),7.42-7.37(m,4H),7.32-7.28(m,1H),6.92(d,J＝9.0Hz,2H),5.69(s,1H),4.09(dd,J＝8.9,4.6Hz,1H),3.84(s,3H),3.64(dd,J＝14.1,9.0Hz,1H),3.52(dd,J＝14.1,4.6Hz,1H),3.33(s,3H),1.42(s,3H),1.26(s,3H). 13 C NMR(101MHz,CDCl 3 )δ:163.6,159.3,147.2,146.3,132.1,131.34,131.3,131.0,129.0,127.0,126.4,123.3,113.8,110.7,55.7,55.6,53.1,48.9,41.6,29.6,21.4.HRMS(ESI):([M+H] + )Calcd for C 25 H 27 O 6 S 2 + :487.1249,Found:487.1243.
the reactants, products and yields of the above examples are summarized in Table 1, where 1 represents the terminal alkyne compound, 2 represents the aryl sulfinic acid, and 3 represents the product:
TABLE 1
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Claims (10)

1. A process for the preparation of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative, characterized in that the process is carried out according to the following steps:
1. the terminal alkyne, arylsulfinic acid and 4-methylpyridine are introduced into a quartz reaction tube containing a solvent, followed by Ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 ；
2. Under the condition of nitrogen atmosphere and room temperature, the reaction tube in the first step is placed under a blue light lamp for irradiation reaction;
3. after the reaction is finished, pouring the obtained reaction mixed solution into a separating funnel containing deionized water, extracting and washing for three times by adopting ethyl acetate, and merging organic phases;
4. drying the organic phase obtained in the third step by using anhydrous sodium sulfate, filtering, removing the anhydrous sodium sulfate, and concentrating the organic phase by using a rotary evaporator to obtain a crude product;
5. and (3) separating the crude product obtained in the step four by using column chromatography to obtain the target product 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative.
2. The process for preparing a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative according to claim 1, wherein the terminal alkyne compound in step one has the structural formula:
wherein R is 1 、R 2 、R 3 、R 4 And R is 5 All are H; or R is 3 Is CH 3 The rest are all H; or R is 3 F, and the rest are all H; or R is 3 Cl and the rest are all H; or R is 3 Br, the remainder all being H.
3. The process for the preparation of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative according to claim 1, wherein step one the aryl sulfinic acid is p-toluene sulfinic acid, benzene sulfinic acid, p-fluorobenzene sulfinic acid, p-chlorobenzene sulfinic acid or p-methoxy benzene sulfinic acid.
4. A 2, 3-dihydrobenzo [ b ] according to claim 1]Process for the preparation of thiophene 1, 1-dioxide derivatives, characterized in that step one the Ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 Is photocatalyst of bis [2- (2, 4-difluorophenyl) -5-trifluoromethyl pyridine][2-2' -Bis (4-trifluoromethylpyridine)]Iridium bis (hexafluorophosphate) salt with the structural formula:
5. process for the preparation of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative according to claim 1, characterized in that step one the solvent is 1, 2-dichloroethane.
6. A 2, 3-dihydrobenzo [ b ] according to claim 1]A process for the preparation of thiophene 1, 1-dioxide derivatives, characterized in that in step one the ratio of terminal alkyne compound to solvent is 0.1mmol:1mL; the ratio of arylsulfinic acid to solvent was 0.35mmol:1mL; ir [ dF (CF) 3 )ppy] 2 (4,4’-dCF 3 bpy)PF 6 The ratio to solvent was 2.3mg:1mL; the ratio of 4-methylpyridine to solvent was 0.2mmol:1mL.
7. The process for preparing a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative according to claim 1, wherein the blue light lamp in step two has a wavelength of 410-430 nm and a power of 10W.
8. The process for the preparation of a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative according to claim 1, wherein the irradiation time in step two is 12h.
9. The process for preparing a 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative according to claim 1, wherein in step five, the column chromatography separation is performed by using silica gel and a mobile phase separation product, wherein the mobile phase is a mixture of petroleum ether and ethyl acetate in a volume ratio of 2:1.
10. The process for preparing 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivatives according to claim 1, wherein the structural formula of the target 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivatives in step five is as follows:
wherein R is 8 And R is 11 Is CH 3 The rest are all H; or R is 3 、R 8 And R is 11 Is CH 3 The rest are all H; or R is 3 Is F, R 8 And R is 11 Is CH 3 The rest are all H; or R is 3 Is Cl, R 8 And R is 11 Is CH 3 The rest are all H; or R is 3 Is Br, R 8 And R is 11 Is CH 3 The rest are all H; or R is 1-13 All are H; or R is 8 And R is 11 F, and the rest are all H; or R is 8 And R is 11 Cl and the rest are all H; or R is 8 And R is 11 OMe, the rest are all H.
CN202311210074.3A 2023-09-19 2023-09-19 Preparation method of 2, 3-dihydrobenzo [ b ] thiophene 1, 1-dioxide derivative Pending CN117247369A (en)

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