Synthesis method of high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene

Abstract

The invention discloses a method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphthyl[1,2-D]thiophene, comprising step one: mixing 2-methylthio-1-bromonaphthalene with an organic acid and a solvent, stirring and heating to 40-60°C, then adding an oxidant, stirring and keeping warm at 40-70°C until the reaction is finished, and obtaining intermediate 1 by post-treatment; step two: dissolving intermediate 1 in an organic solvent, adding a weak base aqueous solution, then adding a p-chlorobenzene coupling reagent, adding a catalyst under inert gas protection, heating to 70-80°C, reacting to the end, and obtaining intermediate 2 by post-treatment of the obtained reaction solution; step three: adding concentrated sulfuric acid to a reaction bottle, cooling to 5-5°C, adding intermediate 2 in batches, and keeping warm at 5°C for 1-3h, and obtaining the target product by post-treatment of the reaction solution. The synthesis method provided by the invention has low production cost, mild reaction conditions, simple process operation, and can obtain a high-purity target product.

Description

Technical Field

[0001] The invention relates to the field of organic optoelectronics, and in particular to a method for synthesizing a high-exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene. Background Art

[0002] As the market's requirements for display technology increase, OLED technology has been widely used in the field of small and medium-sized displays due to its unique advantages (such as high contrast, wide viewing angle, fast response, bright colors, flexible large-area preparation, etc.), and has gradually entered the fields of large-area display and lighting. In OLED technology, the development of blue light materials is relatively lagging, mainly due to the efficiency and stability issues of blue light materials. Existing blue light OLEDs mostly use fluorescent materials, and their efficiency is much lower than that of red and green light using phosphorescent technology. Therefore, the development of new and efficient blue light OLED materials, especially materials with high exciton utilization, has become an important research direction in this field. The research on high exciton OLED materials aims to improve the luminous efficiency and extend the life of the device. For example, thermally activated delayed fluorescence (TADF) materials can achieve 100% exciton utilization, but their stability problem has not been solved.

[0003] Benzo[B]naphtho[1,2-D]thiophene (9-CHLOROBENZO[B]NAPHTHO[1,2-D]THIOPHENE) and its derivatives often have good optical properties due to their unique structure and properties, and can be used in the preparation of organic light-emitting materials such as organic light-emitting diodes (OLEDs). At present, the new solution-processed blue OLED developed uses benzo[B]naphtho[1,2-D]thiophene derivatives as the main material of the luminescent material, showing excellent external quantum efficiency and exciton utilization, which indicates that benzo[B]naphtho[1,2-D]thiophene derivatives can be used as key materials for efficient solution-processed blue OLEDs. In addition, benzo[B]naphtho[1,2-D]thiophene and its derivatives also show potential applications in the pharmaceutical field, such as as fluorescent dyes for living cell imaging, or as fluorescent probes for dual recognition of protons and counter anions, thereby distinguishing different organic acids or inorganic acids.

[0004] At present, phenyl-naphthylsulfane (naphthalen-2-yl(phenyl)sulfane) can be used as the starting material to generate benzo[b]naphtho[2,3-d]thiophene in the presence of Pd(tfa)2, silver acetate, potassium carbonate, and trimethylacetic acid, with a yield of 56%. (Chem. Eur. J.2014, 20, 1-5) The raw material (naphthalen-2-yl(phenyl)sulfane) used in this method is expensive, and the amount of catalyst used is large (10% of the molar amount of the raw material), and the product yield is low, which is not conducive to industrial production. In addition, 2-methylthio-1-bromonaphthalene is used as the raw material (CN 115819430 A), and 9-chlorobenzo[B]naphtho[1,2-D]thiophene is prepared through a series of reactions. The reaction steps are long, and the reaction temperature is too high, and the yield and purity of the reaction are not clearly calibrated. Huang Jirong's team at Huazhong University of Science and Technology used a biomimetic synthesis method and Diels-Alder dimerization reaction to synthesize benzo[B]naphtho[1,2-D]thiophene (BNT) compounds with asymmetric thiophene fused rings, and studied their photophysical properties and potential application value.

[0005] Based on the above foundation, it is particularly important to develop new synthetic methods for benzo[B]naphtho[1,2-D]thiophene and its derivatives. Summary of the invention

[0006] In view of this, the purpose of the present invention is to provide a method for synthesizing a high-exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene, which uses relatively cheap raw materials, greatly reduces production costs, has mild reaction conditions, simple process operations, can obtain high-purity target products, and can be scaled up for production.

[0007] In order to achieve the above object, the present invention adopts the following technical solution:

[0008] The present invention provides a method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene, comprising the following steps:

[0009] Step 1: Mix 2-methylthio-1-bromonaphthalene with an organic acid and a solvent, stir and heat to 40-60° C., then add an oxidant and continue stirring and keep warm at 40-70° C. until the reaction is completed, and then obtain intermediate 1 through post-treatment.

[0010] As a preferred embodiment of the present invention, the molar ratio of methylthio-1-bromonaphthalene to the oxidant is 1:(1.0-4.0), preferably 1:(1.0-3.5).

[0011] If 2-methylthio-1-bromonaphthalene does not dissolve after being mixed with an organic acid, it does not affect the addition of the solvent.

[0012] After 2-methylthio-1-bromonaphthalene is mixed with an organic acid and a solvent, the mixture is stirred evenly before heating. The even stirring means that there is no agglomeration. The stirring time is 5-10 minutes.

[0013] Before adding the oxidant, ensure that the heating temperature is stable at a certain value for 5-10 minutes. This temperature stability value can be 40°C, 45°C, 50°C, 55°C, 60°C or any other temperature between 40-60°C.

[0014] The addition of the oxidant can be divided into one-time addition, two additions, or more additions, depending on the temperature of the reaction liquid. The addition process needs to control the temperature of the entire reaction liquid between 40-70°C, not too high to avoid excessive oxidation. After the addition is completed, the reaction liquid temperature is maintained at no more than 70°C until the reaction is completed.

[0015] Step 2: Dissolve the intermediate 1 in an organic solvent, add a weak base aqueous solution, then add a p-chlorobenzene coupling reagent, add a catalyst under the protection of an inert gas, slowly heat to 70-80°C (control the temperature of the reaction liquid, not more than 80°C), keep the temperature to react until the end, and the obtained reaction liquid is post-treated to obtain the intermediate 2;

[0016] The slow heating in step 2 mainly uses programmed heating, 3-5°C / min. The temperature should not be raised too quickly, which may easily affect the reaction rate.

[0017] As a preferred embodiment of the present invention, the molar ratio of intermediate 1 to p-chlorophenylboronic acid coupling reagent is 1:(1.0-3.0); the preferred molar ratio is 1:(1.0-2.7).

[0018] As a preferred embodiment of the present invention, the molar ratio of the intermediate 1 to the weak base is 1:(1.0-5.0); the preferred molar ratio is 1:(1.0-3.0).

[0019] As a preferred embodiment of the present invention, the weight ratio of the intermediate 1 to the catalyst is 1:(0.005-0.1); the preferred molar ratio is 1:(0.005-0.06).

[0020] Adding catalyst under inert gas protection mainly refers to adding catalyst under nitrogen protection. The specific operation is to use a double-row tube to extract the gas in the reaction bottle, then flush with nitrogen, then extract the gas, and then flush with nitrogen, and repeat the above operation 3-5 times.

[0021] Step 3: Add concentrated sulfuric acid to the reaction flask, cool to -5~5°C, add intermediate 2 in batches, and keep at -5°C for 1~3h. The reaction solution is post-treated to obtain 9-chlorobenzo[B]naphtho[1,2-D]thiophene;

[0022] The molar ratio of intermediate 2 to sulfuric acid is 1:(5.0-20.0); the preferred molar ratio is 1:(10.0-20.0).

[0023] The intermediate 2 is added in batches, which can be divided into two or more additions. During the addition, it is necessary to ensure that the temperature in the reaction bottle is between -5 and 0°C.

[0024] As a preferred embodiment of the present invention, in step 1, the organic acid is at least one of benzoic acid, succinic acid and acetic acid; preferably one of succinic acid and acetic acid.

[0025] As a preferred embodiment of the present invention, the oxidant is at least one of peroxide, selenium dioxide and potassium permanganate; preferably one of peroxide and selenium dioxide.

[0026] When the peroxide is hydrogen peroxide, the mass molar concentration can be 30%, 35%, or 38%.

[0027] In step 2: the p-chlorobenzene coupling reagent is at least one of p-chlorophenylboronic acid, p-chlorophenylboronic acid ester, and p-chlorobenzyltin salt; preferably one of p-chlorophenylboronic acid and p-chlorophenylboronic acid ester, and the p-chlorobenzene coupling reagent is added at one time.

[0028] As a preferred embodiment of the present invention, the weak base is at least one of sodium carbonate, potassium carbonate and sodium hydrogen phosphate; preferably one of sodium carbonate and potassium carbonate, and the weak base aqueous solution is a solution obtained by dissolving the weak base in water.

[0029] As a preferred embodiment of the present invention, the catalyst is a combination of tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide in a weight ratio of 1:(0.5-1), a combination of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium tetrabutylammonium bromide in a weight ratio of 1:(0.5-1), a combination of tetrakis(triphenyl)phosphine palladium and tributylamine in a weight ratio of 1:(0.5-1), and a combination of tetrakis(triphenyl)phosphine palladium and tetrabutylammonium hydrogen sulfate in a weight ratio of 1:(0.5-1); preferably, it is a combination of tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide in a weight ratio of 1:(0.5-1) or a combination of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium tetrabutylammonium bromide in a weight ratio of 1:(0.5-1).

[0030] As a preferred embodiment of the present invention, the concentrated sulfuric acid in step three can be 70% concentrated sulfuric acid, 73% concentrated sulfuric acid, or 77% concentrated sulfuric acid; preferably 70% concentrated sulfuric acid or 73% concentrated sulfuric acid.

[0031] As a preferred embodiment of the present invention, the solvent in step 1 is at least one of 1,2-dichloroethane, dichloromethane and dichloropropane; preferably one of 1,2-dichloroethane and dichloromethane.

[0032] As a preferred embodiment of the present invention, the organic solvent in step 2 is a mixed solution of toluene and ethanol in a volume ratio of 1: (0.2-0.5), a mixed solution of toluene and methanol in a volume ratio of 1: (0.2-0.5), or a mixed solution of dioxane and water in a volume ratio of 1: (0.2-0.5); preferably, a mixed solution of toluene and ethanol in a volume ratio of 1: (0.2-0.5), or a mixed solution of toluene and methanol in a volume ratio of 1: (0.2-0.5).

[0033] As a preferred embodiment of the present invention, the post-treatment of step 1 is: quenching the reaction with an aqueous sodium bisulfite solution, then removing the organic acid, adding an aqueous sodium hydroxide solution to adjust the pH, extracting and concentrating, and then purifying with petroleum ether or methanol to obtain intermediate 1;

[0034] The sodium bisulfite aqueous solution is obtained by dissolving sodium bisulfite in water, and the mass concentration is 20-40%.

[0035] The sodium hydroxide aqueous solution is obtained by dissolving sodium hydroxide in water, and the mass concentration is 10-20%.

[0036] The adjusted pH should be alkaline, and the pH value should be 8-10 when tested with pH test paper.

[0037] During extraction, it is necessary to extract with a saturated sodium carbonate aqueous solution at least once, and then extract with water.

[0038] The main methods for purifying petroleum ether or methanol are recrystallization or pulping. The intermediate 1 product is preferably purified by pulping at least twice.

[0039] As a preferred embodiment of the present invention, the post-treatment of step 2 is: the reaction solution is cooled to 40-60°C and allowed to stand for separation, and the organic phase is extracted and purified to obtain intermediate 2.

[0040] The purification method is recrystallization or beating.

[0041] As a preferred embodiment of the present invention, the post-treatment of step three is: the reaction solution is cooled to about -10-0°C, poured into ice water in batches, and after all dispersion is completed (meaning that the reaction solution and ice water are evenly mixed), the pH is adjusted to 8-10 with sodium hydroxide aqueous solution, and 9-chlorobenzo[B]naphtho[1,2-D]thiophene is obtained by filtration.

[0042] Among them, the time interval for adding ice water in batches is mainly determined according to the temperature change of the reaction solution, and the temperature cannot exceed 0°C.

[0043] Compared with the prior art, the present invention has the following beneficial effects:

[0044] The present invention provides a method for synthesizing a high-exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene. The method uses a relatively cheap raw material 2-methylthio-1-bromonaphthalene and greatly reduces the production cost. The reaction conditions are mild, the process operation is simple, a high-purity target product can be obtained, and the process can be scaled up for production. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of the intermediate 1 of the present invention;

[0046] Figure 2 is the hydrogen nuclear magnetic resonance spectrum of the intermediate 2 of the present invention;

[0047] Figure 3 is a chromatogram of 9-chlorobenzo[B]naphtho[1,2-D]thiophene of the present invention;

[0048] Figure 4 The hydrogen nuclear magnetic resonance spectrum of 9-chlorobenzo[B]naphtho[1,2-D]thiophene of the present invention is shown in FIG. DETAILED DESCRIPTION

[0049] The technical scheme of the present invention is further described below in conjunction with specific embodiments, but the present invention is not limited to these embodiments, and in order to better illustrate the content of the present application, numerous specific details are given in the specific embodiments below. It should be understood by those skilled in the art that without certain specific details, the present application can be implemented equally. In the embodiments, some methods, means, instruments, equipment, etc. well known to those skilled in the art are not described in detail, so as to highlight the purpose of the present application under the premise of not conflicting, the technical features disclosed in the embodiments of the present application can be arbitrarily combined, and the obtained technical scheme belongs to the content disclosed in the embodiments of the present application.

[0050] The synthetic route of the present invention is as follows:

[0051]

[0052] Example 1

[0053] Synthesis of intermediate 1: Add 2-methylthio-1-bromonaphthalene (300g, 1.185mol) and acetic acid (1500ml) to a four-necked bottle, stir and disperse evenly. At this time, the solution is not completely dissolved. Continue to add DCM (150ml), stir for 10min and heat to 40℃, start to drop 30% hydrogen peroxide (137g, 1.02mol) and control the temperature in the reaction bottle at about 45℃. When the hydrogen peroxide drips off, the system becomes clear and keeps at 45℃ for 2h. After the above reaction solution returns to room temperature, add sodium bisulfite aqueous solution (prepared by dissolving 97g sodium bisulfite in 500g water) to the reaction solution to quench the reaction, take the liquid in the reaction bottle and drop it on starch potassium iodide test paper. Until the test paper does not change color. The reaction system was distilled at 70°C under normal pressure to evaporate most of the acetic acid, and then DCM (1000 mL) and water (500 ml) were added for extraction and separation, and the organic phase was taken and the pH value was adjusted to alkaline (pH 8-10) with 10% sodium hydroxide. The organic phase was separated and washed once with saturated brine. The concentrated crude oil was dried, and petroleum ether (1200 ml) was added to the oil for slurrying, and a white solid precipitated. The temperature was lowered to 20°C and filtered to obtain a wet crude product, and methanol (350 ml) was added for slurrying. The intermediate 1 (287 g, yield 89.9%) was obtained after filtration and drying.

[0054] Synthesis of intermediate 2: Add intermediate 1 (200 g, 0.743 mol), a mixed solution of toluene (600 ml) and ethanol (200 ml) into a four-necked flask, and continuously drop a sodium carbonate aqueous solution (118 g, 1.1145 mol, dissolved in 1 kg of water). After the dropwise addition is complete, add p-chlorophenylboric acid (139.6 g, 0.892 mol), replace with nitrogen 6 times, add tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide 3 g (tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide are 2 g and 1 g, respectively), slowly heat to 78 ° C for reaction, pay attention to observe the state of the reaction liquid in the reaction bottle during the heating process, and do not allow the material to rush, and maintain this temperature until the end of the reaction. After the reaction was completed, the reaction solution was cooled to about 60°C for separation, and the organic phase was removed and washed once with water. After separation, the organic phase was purified by column chromatography on silica gel, and the collected eluent was directly concentrated to dryness and added with petroleum ether (1.5 L) and slurried for 30 minutes. Subsequently, a solid appeared, which was filtered and dried to obtain intermediate 2 (202.8 g, yield 91%).

[0055] Synthesis of 9-chlorobenzo[B]naphtho[1,2-D]thiophene: Add concentrated sulfuric acid (1500g, concentration 70%) to a four-necked bottle, cool to -5~5℃ in an ice-water bath, add intermediate 2 (280g, 0.933mol) in four portions, and ensure that the temperature of the reaction solution is -5~0℃ during the addition process. After the addition is completed, keep the temperature at -5℃ for 1.5h until the reaction is completed. Cool the reaction solution to about -10℃, and then pour it into ice water (3kg) in batches, and control the temperature below 10℃. After all the dispersion is completed, a large amount of white solid will appear. Use sodium hydroxide aqueous solution (1300g dissolved in 3L water) to adjust the pH to alkaline (pH 8-10), and filter to obtain a white solid. The white solid was dissolved in icy DCM (4 L), and a colorless clear eluent was obtained by column chromatography. The eluent was concentrated to obtain a white solid. Methanol (200 ml) was then added to the white solid for slurrying. The filtered wet product was dried to obtain 9-chlorobenzo[B]naphtho[1,2-D]thiophene (235.7 g, yield 94%).

[0056] Example 2

[0057] Synthesis of intermediate 1: Add 2-methylthio-1-bromonaphthalene (100 g, 0.395 mol) and succinic acid (350 ml) to a four-necked flask, stir and disperse evenly, continue to add DCM (150 ml), stir for 10 min and heat to 56 ° C, start to add sodium peroxide (92.4 g, 1.185 mol) three times and control the temperature in the reaction flask at about 56 ° C. When the sodium peroxide is added, the system is semi-clear, and the temperature is kept at 56 ° C for about 2.2 hours to end the reaction. After the above reaction solution is restored to room temperature, the reaction system is distilled under reduced pressure at 70 ° C to evaporate succinic acid, and then ethyl acetate (1000 mL) and water (500 ml) are added for extraction and stratification. The organic phase is washed once with saturated brine, and the concentrated crude product is dried. The obtained crude product is recrystallized using petroleum ether, cooled and filtered to obtain a white solid, and dried to obtain intermediate 1 (85.70 g, yield 80%).

[0058] Synthesis of intermediate 2: Add intermediate 1 (100g, 0.372mol), toluene (200ml) and methanol (50ml) mixed solution to a four-necked flask, continuously drop sodium carbonate aqueous solution (78.86g, 0.744mol, dissolved in 500ml water), add p-chlorophenyl borate (177.45g, 0.744mol) after the dropwise addition is complete, replace with nitrogen 6 times, add tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide 6g (tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide are 3g each), slowly heat to 90℃ for reaction, pay attention to observe the state of the reaction liquid in the reaction flask during the heating process, and do not allow the material to rush. Maintain this temperature until the reaction is completed. After the reaction was completed, the reaction solution was cooled to about 60°C for separation, and the organic phase was removed and washed once with water. After separation, the organic phase was purified by column chromatography on silica gel, and the collected eluent was directly concentrated to dryness and added with petroleum ether (600 ml) for slurrying for 30 minutes. Subsequently, a solid appeared, which was filtered and dried to obtain intermediate 2 (85.98 g, yield 86%).

[0059] Synthesis of 9-chlorobenzo[B]naphtho[1,2-D]thiophene: Add concentrated sulfuric acid (429.6 g, concentration 73%) to a four-necked flask, cool to -5~5°C in an ice-water bath, add intermediate 2 (85.98 g, 0.32 mol) twice, and ensure that the temperature of the reaction solution is -5~0°C during the addition process. After the addition is completed, keep the temperature at -5°C for 1.5 hours until the reaction is completed. Cool the reaction solution to about -10°C, and then pour it into ice water (1 kg) in batches, and control the temperature below 10°C. After all the dispersion is completed, a large amount of white solid will appear. Use sodium hydroxide aqueous solution (160 g dissolved in 1L water) to adjust the pH to alkaline (pH 8-10) and filter to obtain a white solid. The white solid was dissolved in ice DCM (2.5 L), and a colorless clear eluent was obtained after column chromatography. The eluent was concentrated to obtain a white solid. Methanol (150 ml) was then added to the white solid for slurrying. The filtered wet product was dried to obtain 9-chlorobenzo[B]naphtho[1,2-D]thiophene (85.96 g, yield 96%).

[0060] Example 3

[0061] Synthesis of intermediate 1: Add 2-methylthio-1-bromonaphthalene (100 g, 0.395 mol) and acetic acid (400 ml) to a four-necked flask, stir and disperse evenly. At this time, the solution is not completely dissolved. Continue to add DCM (100 ml), stir for 10 min and heat to 50 ° C. Start to add selenium dioxide (87.69 g, 0.79 mol) twice and control the temperature in the reaction flask at about 50 ° C. When the addition of selenium dioxide is complete, the system is semi-clear. Continue to heat to 60 ° C and keep the reaction for 3 hours. After the above reaction solution is restored to room temperature, the reaction system is distilled at 70 ° C under normal pressure to evaporate acetic acid, then DCM (1000 mL) and water (500 ml) are added for extraction and stratification. The organic phase is washed once with saturated brine, and the concentrated crude product is dried. The obtained crude product is recrystallized using petroleum ether, cooled and filtered to obtain a white solid, and dried to obtain intermediate 1 (90.45 g, yield 85%).

[0062] Synthesis of intermediate 2: Add intermediate 1 (90.45 g, 0.336 mol), a mixed solution of toluene (200 ml) and methanol (50 ml) into a four-necked flask, and continuously drop a sodium carbonate aqueous solution (71.23 g, 0.672 mol, dissolved in 360 ml of water). After the dropwise addition is complete, add p-chlorophenylboric acid (131.35 g, 0.84 mol), replace with nitrogen four times, add dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium and tetrabutylammonium bromide 4.5 g (wherein dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium and tetrabutylammonium bromide are 2.5 g and 2 g, respectively), and slowly heat to 90°C for reaction. During the heating process, pay attention to the state of the reaction liquid in the reaction flask. Do not allow the material to rush, and maintain this temperature until the reaction is completed. After the reaction was completed, the reaction solution was cooled to about 60°C for separation, and the organic phase was removed and washed once with water. After separation, the organic phase was purified by column chromatography on silica gel, and the collected eluent was directly concentrated to dryness and added with petroleum ether (500 ml) for slurrying for 30 minutes. Subsequently, a solid appeared, which was filtered and dried to obtain intermediate 2 (83.98 g, yield 84%).

[0063] Synthesis of 9-chlorobenzo[B]naphtho[1,2-D]thiophene: Add concentrated sulfuric acid (390.6 g, concentration 70%) to a four-necked flask, cool to -5~5°C in an ice-water bath, add intermediate 2 (83.98 g, 0.279 mol) twice, and ensure that the temperature of the reaction solution is -5~0°C during the addition process. After the addition is completed, keep the temperature at -5°C for 1.5 hours until the reaction is completed. Cool the reaction solution to about -10°C, and then pour it into ice water (1 kg) in batches, and control the temperature to less than 10°C. After all the dispersion is completed, a large amount of white solid will appear. Use sodium hydroxide aqueous solution (160 g dissolved in 1L water) to adjust the pH to alkaline (pH 8-10), and filter to obtain a white solid. The white solid was dissolved in ice DCM (2 L), and a colorless clear eluent was obtained after column chromatography. The eluent was concentrated to obtain a white solid. Methanol (150 ml) was then added to the white solid for slurrying. The filtered wet product was dried to obtain 9-chlorobenzo[B]naphtho[1,2-D]thiophene (86.9 g, yield 97.1%).

[0064] Comparative Example 1

[0065] Synthesis of Intermediate 1: Add 2-methylthio-1-bromonaphthalene (100 g, 0.395 mol) and succinic acid (350 ml) to a four-necked flask, stir and disperse evenly, continue to add DCM (150 ml), stir for 10 min, and start to add sodium peroxide (92.4 g, 1.185 mol) three times and control the temperature in the reaction flask at about 56 ° C. When the sodium peroxide is added, the system is semi-clear. Continue to keep the temperature at 56 ° C for about 2.2 h to complete the reaction. After the above reaction solution is restored to room temperature, the reaction system is distilled under reduced pressure at 70 ° C to evaporate succinic acid, and then ethyl acetate (1000 mL) and water (500 ml) are added for extraction and stratification. The organic phase is washed once with saturated brine, and the concentrated crude product is dried. The obtained crude product is recrystallized using petroleum ether, cooled and filtered to obtain a white solid, and dried to obtain Intermediate 1 (46.06 g, yield 43%).

[0066] Synthesis of intermediate 2: Add intermediate 1 (46.06 g, 0.171 mol), a mixed solution of toluene (92 ml) and methanol (23 ml) to a four-necked flask, and continuously drop sodium carbonate aqueous solution (36.28 g, 0.34 mol, dissolved in 230 ml water). After the dropwise addition is complete, add p-chlorophenyl borate (81.62 g, 0.34 mol), replace with nitrogen 6 times, add tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide 3 g (tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide are 1.8 g and 1.2 g, respectively), and slowly heat to 90°C for reaction. During the heating process, pay attention to the state of the reaction liquid in the reaction flask, and do not allow the material to rush. Maintain this temperature until the reaction is completed. After the reaction was completed, the reaction solution was cooled to about 60°C for separation, and the organic phase was removed and washed once with water. After separation, the organic phase was purified by column chromatography on silica gel, and the collected eluent was directly concentrated to dryness and added with petroleum ether (280 ml) and slurried for 30 minutes. Subsequently, a solid appeared, which was filtered and dried to obtain intermediate 2 (81.6 g, yield 82%).

[0067] Synthesis of 9-chlorobenzo[B]naphtho[1,2-D]thiophene: Add concentrated sulfuric acid (400g, concentration 73%) to a four-necked bottle, cool to -5~5℃ in an ice-water bath, add intermediate 2 (81.6g, 0.30mol) twice, and ensure that the temperature of the reaction solution is -5~0℃ during the addition process. After the addition is completed, keep the temperature at -5℃ for 1.5h until the reaction is completed. Cool the reaction solution to about -10℃, and then pour it into ice water (1kg) in batches, and control the temperature below 10℃. After all the dispersion is completed, a large amount of white solid will appear. Use sodium hydroxide aqueous solution (150g dissolved in 1L water) to adjust the pH to alkaline (pH 8-10), and filter to obtain a white solid. The white solid was dissolved in icy DCM (2.5 L), and a colorless clear eluent was obtained after column chromatography. The eluent was concentrated to obtain a white solid. Methanol (150 ml) was then added to the white solid for slurrying. The filtered wet product was dried to obtain 9-chlorobenzo[B]naphtho[1,2-D]thiophene (81.5 g, yield 91%).

[0068] Among them, compared with Example 2, in the preparation process of intermediate 1, the step of "mixing 2-methylthio-1-bromonaphthalene with an organic acid and a solvent, stirring for 10 minutes and heating to 56° C." is changed to "mixing 2-methylthio-1-bromonaphthalene with an organic acid and a solvent", and the other steps remain unchanged, that is, compared with Example 2, the reaction conditions are changed in the preparation of intermediate 1 in Comparative Example 1, heating is no longer performed, and sodium peroxide is directly added.

[0069] Comparative Example 2

[0070] Compared with Example 1, the synthesis of intermediate 2: "Use nitrogen to replace 6 times, add tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide 3g (wherein tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide are 1.8g and 1.2g respectively), slowly heat up to 78°C for reaction, pay attention to observe the state of the reaction liquid in the reaction bottle during the heating process, and do not allow the material to rush." ​​is changed to "Use nitrogen to replace 6 times, add tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide 3g (wherein tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide are 1.8g and 1.2g respectively), quickly heat up to 100°C for reaction, pay attention to observe the state of the reaction liquid in the reaction bottle during the heating process, and do not allow the material to rush", and the rapid heating refers to the change from "3-5°C / min" to "10-15°C / min", to prepare intermediate 2.

[0071] Synthesis of specific intermediate 2: Add intermediate 1 (200 g, 0.743 mol), a mixed solution of toluene (600 ml) and ethanol (200 ml) into a four-necked flask, and continuously drop an aqueous sodium carbonate solution (118 g, 1.1145 mol, dissolved in 1 kg of water). After the dropwise addition is completed, add p-chlorophenylboric acid (139.6 g, 0.892 mol), replace with nitrogen 6 times, add tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide 3 g (tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide are 2 g and 1 g, respectively), and heat to 100°C at 10-15°C / min for reaction. During the heating process, pay attention to observe the state of the reaction liquid in the reaction flask. No material rushing should occur, and maintain the temperature until the reaction is completed. After the reaction was completed, the reaction solution was cooled to about 60°C for separation, and the organic phase was removed and washed once with water. After separation, the organic phase was purified by column chromatography on silica gel, and the collected eluent was directly concentrated to dryness and added with petroleum ether (1.5 L) and slurried for 30 minutes. Subsequently, a solid appeared, which was filtered and dried to obtain intermediate 2 (49.76 g, yield 50%).

[0072] In summary, the present invention provides a method for synthesizing a high-exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene. The method uses a relatively cheap raw material 2-methylthio-1-bromonaphthalene and greatly reduces the production cost. The reaction conditions are mild, the process operation is simple, and a high-purity target product can be obtained, which can be scaled up for production.

[0073] The above examples are only some specific embodiments of the present invention. Obviously, the present invention is not limited to the above embodiments, and there are many variations. All variations that can be directly derived or associated with the content disclosed by a person skilled in the art should be considered as the protection scope of the present invention.

[0074] Although the present invention has been described and illustrated with specific embodiments, it will be apparent to those skilled in the art that many other changes and modifications may be made without departing from the spirit and scope of the present invention. Therefore, all such changes and modifications within the scope of the present invention are consciously included in the appended claims.

Claims

1. A method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene, characterized in that: The following steps are involved: Step 1: Mix 2-methylthio-1-bromonaphthalene with an organic acid and a solvent, stir and heat to 40-60°C, then add an oxidant, continue stirring and keep warm at 40-70°C until the reaction is complete, and obtain intermediate 1 after post-treatment; Step 2: Dissolve the intermediate 1 in an organic solvent, add a weak base aqueous solution, then add a p-chlorobenzene coupling reagent, add a catalyst under the protection of an inert gas, raise the temperature to 70-80°C, keep the temperature to react until the end, and post-treat the resulting reaction solution to obtain the intermediate 2; Step 3: Add concentrated sulfuric acid to the reaction flask, cool to -5~5°C, add intermediate 2 in batches, and keep at -5°C for 1~3h. The reaction solution is post-treated to obtain 9-chlorobenzo[B]naphtho[1,2-D]thiophene; Wherein, in step 1, the organic acid is at least one of benzoic acid, succinic acid, and acetic acid; the oxidant is at least one of peroxide, selenium dioxide, and potassium permanganate; the solvent is at least one of 1,2-dichloroethane, dichloromethane, and dichloropropane; In step 2, the p-chlorobenzene coupling reagent is at least one of p-chlorophenylboronic acid, p-chlorophenylboronic acid ester, and p-chlorobenzyltin salt; the catalyst is a combination of tetrakis(triphenyl)phosphine palladium and tetrabutylammonium bromide in a weight ratio of 1:(0.5-1) or a combination of dichloro[1,1'-bis(diphenylphosphino)ferrocene]palladium and tetrabutylammonium bromide in a weight ratio of 1:(0.5-1) or a combination of tetrakis(triphenyl)phosphine palladium and tributylamine in a weight ratio of 1:(0.5-1) or a combination of tetrakis(triphenyl)phosphine palladium and tetrabutylammonium hydrogen sulfate in a weight ratio of 1:(0.5-1); The organic solvent is a mixed solution of toluene and ethanol in a volume ratio of 1:(0.2-0.5) or a mixed solution of toluene and methanol in a volume ratio of 1:(0.2-0.5) or a mixed solution of dioxane and water in a volume ratio of 1:(0.2-0.5).

2. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The molar ratio of 2-methylthio-1-bromonaphthalene to the oxidant is 1:(1.0-4.0).

3. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The molar ratio of intermediate 1 to p-chlorophenylboronic acid coupling reagent is 1:(1.0-3.0).

4. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The molar ratio of intermediate 1 to weak base is 1:(1.0-5.0).

5. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The weight ratio of intermediate 1 to catalyst is 1:(0.005-0.10).

6. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The molar ratio of intermediate 2 to concentrated sulfuric acid is 1:(5.0-20.0).

7. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: In step 3, the concentrated sulfuric acid is 70% concentrated sulfuric acid, 73% concentrated sulfuric acid or 77% concentrated sulfuric acid.

8. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The post-treatment of step 1 is: quenching the reaction with an aqueous sodium bisulfite solution, then removing the organic acid, adding an aqueous sodium hydroxide solution to adjust the pH, extracting and concentrating, and then purifying with petroleum ether or methanol to obtain intermediate 1.

9. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The post-treatment of step 2 is as follows: the reaction solution is cooled to 40-60° C. and allowed to stand for separation, and the organic phase is extracted and purified to obtain intermediate 2.

10. The method for synthesizing a high exciton key intermediate 9-chlorobenzo[B]naphtho[1,2-D]thiophene according to claim 1, characterized in that: The post-treatment of step three is as follows: the reaction solution is cooled to -10-0°C, poured into ice water in batches, and after all the solution is dispersed, the pH is adjusted to 8-10 with an aqueous sodium hydroxide solution, and 9-chlorobenzo[B]naphtho[1,2-D]thiophene is obtained by filtration.

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