CN114591290A - Preparation method of substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative and derivative - Google Patents

Preparation method of substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative and derivative Download PDF

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CN114591290A
CN114591290A CN202210336215.5A CN202210336215A CN114591290A CN 114591290 A CN114591290 A CN 114591290A CN 202210336215 A CN202210336215 A CN 202210336215A CN 114591290 A CN114591290 A CN 114591290A
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naphthalene
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吕钟
毕永林
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Shaanxi Vishno New Material Co ltd
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Abstract

The invention discloses a preparation method of substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivatives, which comprises the steps of reacting 2-naphthylmethyl sulfide serving as a raw material at a low temperature to obtain an intermediate S-1, carrying out a coupling reaction on the intermediate S-1 and substituted o-iodofluorobenzene to prepare an intermediate S-2, carrying out a demethylation reaction on the intermediate S-2 under the action of Lewis acid to obtain S-3, and carrying out a ring closing reaction on the S-3 under the action of alkali to obtain a product W0: substituted benzo [ B ] naphthalene-benzene [2, 3-D ] thiophene derivatives. By adopting the preparation method of the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, the obtained product has high purity, high yield and low cost, no waste solvent is generated in the whole preparation process, and the generated waste water is less, so that the foundation is laid for realizing the purpose of environmental protection.

Description

Preparation method of substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative and derivative
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a preparation method of a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative and the derivative.
Background
The substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene has various applications due to the special structure of the thiophene. Since scientists continuously research and develop organic electro-luminescent materials in recent years, introduction of various substituents into the 1, 2, 3, 4 positions of substituted benzo [ B ] naphthalene [2, 3-D ] thiophene requires higher and higher purity and yield, and with continuous breakthrough and marketization of OLED organic luminescent materials, intermediate materials thereof have higher and higher requirements, so that continuous optimization and improvement of the process for obtaining substituted benzo [ B ] naphthalene [2, 3-D ] thiophene derivatives with higher purity and high yield are one of the subjects of research and development of people at the present stage.
Disclosure of Invention
In view of the above, the present invention provides a method for preparing a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, which solves the problems of the prior art, such as large raw material pollution, high price, high toxicity of chemical additives, multiple reaction steps, complex process, low yield and complex post-treatment in the preparation method of the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative.
In order to achieve the purpose, the technical scheme of the invention is realized as follows: a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative has a chemical structural general formula as follows:
Figure BDA0003574408640000021
wherein, R is at least one of hydrogen, alkyl, halogen, nitro and cyano.
The second technical scheme of the invention is realized as follows: a preparation method of substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivatives comprises the steps of reacting 2-naphthylmethyl sulfide serving as a raw material at a low temperature to obtain an intermediate S-1, performing a coupling reaction on the intermediate S-1 and substituted o-iodofluorobenzene to obtain an intermediate S-2, performing a demethylation reaction on the intermediate S-2 under the action of Lewis acid to obtain S-3, and performing a ring closing reaction on the S-3 under the action of alkali to obtain a product W0: a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative has a chemical reaction formula:
Figure BDA0003574408640000022
wherein R is hydrogen, alkyl, halogen, nitro, cyano, etc.
Preferably, the method is realized by the following steps:
s1, dissolving 2-naphthylmethyl sulfide in a first organic solvent, cooling to-70 to-90 ℃, adding n-butyllithium and boric acid ester in sequence, reacting for 1-5h, and heating to obtain an intermediate S-1;
s2, dissolving the intermediate S-1 and substituted o-iodofluorobenzene in a second organic solvent, adding a first alkali and a catalyst for coupling reaction, and obtaining an intermediate S-2 after the reaction is finished;
s3, dissolving the intermediate S-2 in a third organic solvent, and adding Lewis acid for demethylation reaction to obtain an intermediate S-3;
s4, dissolving the intermediate S-3 in a fourth organic solvent, adding a second alkali, heating to 60-120 ℃, reacting for 1-5h, and cooling to obtain a product W0: substituted benzo [ B ] naphthalene-benzene [2, 3-D ] thiophene derivatives.
Preferably, in S2, the first base is at least one of sodium tert-butoxide, sodium carbonate, potassium phosphate, potassium acetate, sodium hydroxide, and the like.
Preferably, in the S2, the catalyst is Pd (PPh)3)4，PdCl2(dppf)，Pd(PPh3)2Cl2At least one of (1).
Preferably, in S2, the substituted o-iodofluorobenzene is at least one of 4-bromo-2-fluoroiodobenzene, 3-bromo-2-fluoroiodobenzene, 5-chloro-2-fluoroiodobenzene, 3-nitro-2-fluoroiodobenzene and 6-cyano-2-fluoroiodobenzene.
Preferably, in S3, the lewis acid is at least one of boron trichloride, iron tribromide, boron tribromide, and zinc chloride.
Preferably, in S4, the second base is at least one of sodium tert-butoxide, sodium carbonate, potassium phosphate, potassium acetate, and sodium hydroxide.
Preferably, in S2, the second organic solvent is at least one of toluene/ethanol, dioxane/water, tetrahydrofuran/water, DMF/water; in S3, the third solvent is at least one of tetrahydrofuran, dichloromethane, dioxane, and dichloroethane.
Preferably, in S4, the fourth organic solvent is at least one of dioxane, N-dimethylformamide, N-dimethylacetamide and NMP.
Compared with the prior art, the preparation method of the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative has the advantages that the raw materials are easy to obtain, cheap and free of much danger; in the reaction process, the boric acid additive is adopted firstly and is carried out at low temperature, and then the conventional coupling reaction is adopted, so that the whole process is simple and easy to operate, the energy consumption is low, and the post-treatment is simpler.
In addition, by adopting the preparation method of the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, the obtained product has high purity, high yield and low cost, no waste solvent is generated in the whole preparation process, and the generated waste water is less, so that a foundation is laid for realizing the purpose of environmental protection.
Drawings
FIG. 1 is a hydrogen spectrum of 3-bromobenzo [ B ] naphthalene [2, 3-D ] thiophene obtained in example 2 of the present invention;
FIG. 2 is a hydrogen spectrum of 2-chlorobenzo [ B ] naphthalene [2, 3-D ] thiophene obtained in example 3 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The starting materials used in the following examples are either directly available commercially or prepared by the prior art.
The embodiment of the invention provides a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, which has a chemical structural general formula as follows:
Figure BDA0003574408640000041
wherein, R is at least one of hydrogen, alkyl, halogen, nitro and cyano.
Further, the substituted benzo [ B ] naphthalene [2, 3-D ] thiophene derivative is selected from the following specific structural formulas:
Figure BDA0003574408640000051
the embodiment of the invention provides a preparation method of a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, which comprises the steps of reacting 2-naphthalene dimethylsulfide serving as a raw material at a low temperature to obtain an intermediate S-1, carrying out a coupling reaction on the intermediate S-1 and substituted o-iodofluorobenzene to obtain an intermediate S-2, carrying out a demethylation reaction on the intermediate S-2 under the action of Lewis acid to obtain S-3, and carrying out a ring closing reaction on the S-3 under the action of alkali to obtain a product W0: a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative has a chemical reaction formula:
Figure BDA0003574408640000061
wherein R is hydrogen, alkyl, halogen, nitro, cyano, etc.
In a specific implementation process, the method is specifically realized by the following steps:
s1, dissolving 2-naphthylmethyl sulfide in a first organic solvent, cooling to-70 to-90 ℃, adding n-butyllithium and boric acid ester in sequence, reacting for 1-5h, and heating to obtain an intermediate S-1;
s2, dissolving the intermediate S-1 and substituted o-iodofluorobenzene in a second organic solvent, adding a first alkali and a catalyst for coupling reaction, and obtaining an intermediate S-2 after the reaction is finished;
s3, dissolving the intermediate S-2 in a third organic solvent, and adding Lewis acid for demethylation reaction to obtain an intermediate S-3;
s4, dissolving the intermediate S-3 in a fourth organic solvent, adding a second alkali, heating to 60-120 ℃, reacting for 1-5h, and cooling to obtain a product W0: substituted benzo [ B ] naphthalene-benzene [2, 3-D ] thiophene derivatives.
In the S2, the first base is at least one of sodium tert-butoxide, sodium carbonate, potassium phosphate, potassium acetate, sodium hydroxide, etc.; in the S2, the catalyst is Pd (PPh)3)4，PdCl2(dppf)，Pd(PPh3)2Cl2At least one of; in S2, the substituted o-iodofluorobenzene is at least one of 4-bromo-2-fluoroiodobenzene, 3-bromo-2-fluoroiodobenzene, 5-chloro-2-fluoroiodobenzene, 3-nitro-2-fluoroiodobenzene, and 6-cyano-2-fluoroiodobenzene; in the S3, the Lewis acid is at least one of boron trichloride, ferric tribromide, boron tribromide and zinc chloride; the second base is at least one of sodium tert-butoxide, sodium carbonate, potassium phosphate, potassium acetate and sodium hydroxide; in the S2, the second organic solvent is at least one of toluene/ethanol, dioxane/water, tetrahydrofuran/water, and DMF/water; in S3, the third solvent is at least one of tetrahydrofuran, dichloromethane, dioxane, and dichloroethane; in S4, the fourth organic solvent is at least one of dioxane, N-dimethylformamide, N-dimethylacetamide, and NMP.
The following are specific examples
Example 1
Preparation of benzo [ B ] naphthalene-2, 3-D ] thiophenes
2-naphthyl sulfide is used as a raw material to react at low temperature to obtain an intermediate S1, the intermediate S1 and o-fluoroiodobenzene are subjected to coupling reaction to obtain an intermediate S2, the intermediate S2 is subjected to demethylation reaction under the action of Lewis acid to obtain S3, and S3 is subjected to ring closure reaction under the action of alkali to obtain a product W1: benzo [ B ] naphthalene benzene [2, 3-D ] thiophene, the chemical reaction formula of which is:
Figure BDA0003574408640000071
the method is realized by the following steps:
adding 2-naphthylmethyl sulfide (50g, 0.29mol) into a 1000ML reactor containing 500ML of tetrahydrofuran, adding triisopropyl borate (70.2g, 0.37mol), replacing nitrogen, reducing the temperature to-70 to-90 ℃, dropwise adding n-butyl lithium (149.4ML,0.37mol), controlling the temperature to-70 to-90 ℃, fully reacting for 3-6 h, heating to 10-30 ℃, introducing 1000ML of acid water for quenching, concentrating under reduced pressure, performing suction filtration by using a suction filtration funnel to obtain a crude product, heating 500ML of petroleum ether to 30-50 ℃ for washing once, and filtering under reduced pressure to obtain a white solid intermediate S1: 3-methylsulfide-naphthyl-2-boronic acid, 53.3g, 99.2% HPLC, yield 85%.
Adding the intermediate S1(50g,0.23mol) into a 1000ML reactor containing 360ML of toluene, 120ML of ethanol and 120ML of water, adding o-fluoroiodobenzene (53.5g, 0.24mol) and potassium carbonate (63.3g, 0.46mol) into the system, replacing three times with nitrogen, adding palladium tetratriphenylphosphine (1.2g, 0.5%), adding the system to 80-120 ℃, fully reacting for 5-20 h, monitoring the reaction with a liquid phase, stopping the reaction when the raw material is less than 1%, cooling to below 50 ℃, introducing into 1000ML of water, adding dichloromethane for extraction to obtain an organic phase, drying with anhydrous sodium sulfate, passing through a kieselguhr column to obtain a filtrate, concentrating in a reduced pressure manner, and recrystallizing with ethyl acetate to obtain an intermediate S2: 3- (2-fluorophenyl) -2-methylsulfinylnaphthalene, 43.0g, 99.1% HPLC, yield 70%;
adding an intermediate S2(30g, 0.18mol) into a 1000ML reactor containing 300ML of dichloromethane, reducing the temperature to below 10 ℃, then slowly adding boron tribromide (90.4g, 0.36mol), controlling the temperature to below 20 ℃, reacting for 1-6 h at 30 ℃ after the boron tribromide raw material is completely added, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to below 30 ℃, extracting with dichloromethane, and then concentrating under reduced pressure to obtain an intermediate S3: 3- (2-fluorophenyl) -2-naphthylthiophenol, 27.1g, 99.1% HPLC, yield 95%;
adding the intermediate S3(20g, 0.08mol) into a 500ml reactor containing 200ml of N, N-dimethylformamide, adding potassium carbonate (32.6g, 0.24mol), heating to 80-120 ℃, fully reacting for 1-6 h, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to be below 30 ℃, and then carrying out suction filtration under a reduced pressure state to obtain a white solid W1: benzo [ B ] naphthobenzo [2, 3-D ] thiophene, 17.9g, 99.3% HPLC, yield 97%.
The nuclear magnetic resonance detection of the product W1 obtained in this example 1 showed that:
1H NMR(500MHz，Chloroform-d)δ8.37(d，J＝2.2Hz，1H)，8.24–8.19(m，1H)，8.14(d，J＝2.1Hz，1H)，7.99–7.85(m，3H)，7.55–7.41(m，4H)。
example 2
Preparation of 3-bromobenzo [ B ] naphthalene [2, 3-D ] thiophene
2-naphthyl sulfide is used as a raw material to react at a low temperature to obtain an intermediate S1, the intermediate S1 and 4-bromo-2-fluoroiodobenzene are subjected to a coupling reaction to prepare an intermediate S4, the intermediate S4 is subjected to a demethylation reaction under the action of Lewis acid to obtain S5, and S5 is subjected to a ring closing reaction under the action of alkali to obtain a product W5: 3-bromobenzo [ B ] naphthalene benzene [2, 3-D ] thiophene, the chemical reaction formula of which is:
Figure BDA0003574408640000091
the method is realized by the following steps:
adding 2-naphthylmethyl sulfide (50g, 0.29mol) into a 1000ML reactor containing 500ML of tetrahydrofuran, adding trimethyl borate (38.9g, 0.37mol), replacing nitrogen, reducing the temperature to-70 to-90 ℃, dropwise adding n-butyl lithium (149.4ML,0.37mol), controlling the temperature to-70 to-90 ℃, fully reacting for 3-6 h, heating to 10-30 ℃, introducing 1000ML of acid water for quenching, concentrating under reduced pressure, performing suction filtration by using a suction filtration funnel to obtain a crude product, heating 500ML of petroleum ether to 30-50 ℃ for washing once, and filtering under reduced pressure to obtain a white solid intermediate S1: 3-methylsulfide-naphthyl-2-boronic acid, 34.5g, HPLC ═ 99.3%, yield 55%;
adding an intermediate S1(50g,0.23mol) into a 1000ML reactor containing 350ML of dioxane and 150ML of water, adding 4-bromo-2-fluoroiodobenzene (75.9g, 0.25mol) and sodium carbonate (72.9g, 0.69mol) into the system, replacing three times with nitrogen, adding tetratriphenylphosphine palladium (1.2g, 0.5%), adding the system to 80-120 ℃, fully reacting for 5-20 h, monitoring the reaction by using a liquid phase, stopping the reaction when the raw material is less than 1%, cooling to below 50 ℃, introducing into 1000ML of water, adding dichloromethane for extraction to obtain an organic phase, drying by using anhydrous sodium sulfate, passing through a kieselguhr column to obtain a filtrate, concentrating by using a reduced pressure mode, and recrystallizing by using ethyl acetate to obtain an intermediate S4: 3- (2-fluoro-4-bromophenyl) -2-methylsulfinylnaphthalene, 62.1g, 99.4% HPLC, yield 78%;
adding an intermediate S2(30g, 0.18mol) into a 1000ML reactor containing 300ML of dioxane, reducing the temperature to below 10 ℃, then slowly adding boron trichloride (42.1g, 0.36mol), controlling the temperature to below 20 ℃, reacting for 1-6 h at 30 ℃ after the boron trichloride raw material is added, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to below 30 ℃, extracting with dichloromethane, and then concentrating under reduced pressure to obtain an intermediate S5: 3- (2-fluoro-4-bromophenyl) -2-naphthylthiol, 53.9g, 99.4% HPLC, yield 90%;
adding the intermediate S5(20g, 0.08mol) into a 500ml reactor containing 200ml dioxane, adding sodium carbonate (25.4g, 0.24mol), heating to 80-120 ℃, fully reacting for 1-6 h, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature below 30 ℃, and then carrying out suction filtration under a reduced pressure state to obtain a white solid W5: 3-bromobenzo [ B ] naphthalene-2, 3-D ] thiophene, 22.1g, 99.2% HPLC, yield 88%.
The nuclear magnetic resonance detection of the product W5 obtained in this example 2 showed that:
1H NMR(300MHz，Chloroform-d)δ8.37(s，1H)，8.11–7.86(m，4H)，7.73(s，1H)，7.52(p，J＝6.5，6.1Hz，3H)。
example 3
Preparation of 2-chlorobenzo [ B ] naphthalene-2, 3-D ] thiophene
2-naphthyl sulfide is used as a raw material to react at a low temperature to obtain an intermediate S1, the intermediate S1 and 5-chloro-2-fluoroiodobenzene are subjected to coupling reaction to obtain an intermediate S6, the intermediate S6 is subjected to demethylation reaction under the action of Lewis acid to obtain S7, and S7 is subjected to ring closure reaction under the action of alkali to obtain a product W10: 2-chlorobenzo [ B ] naphthalene benzene [2, 3-D ] thiophene, the chemical reaction formula is:
Figure BDA0003574408640000111
the method is realized by the following steps:
adding 2-naphthylmethyl sulfide (50g, 0.29mol) into a 1000ML reactor containing 500ML of tetrahydrofuran, adding tributyl borate (85.9g, 0.37mol), replacing nitrogen, reducing the temperature to-70-90 ℃, dropwise adding n-butyl lithium (149.4ML,0.37mol), controlling the temperature to-70-90 ℃ for full reaction for 3-6 h, heating to 10-30 ℃, introducing 1000ML of acid water for quenching, concentrating under reduced pressure, performing suction filtration by using a suction filtration funnel to obtain a crude product, heating 500ML of petroleum ether to 30-50 ℃ for washing once, and filtering under reduced pressure to obtain a white solid intermediate S1: 3-methylsulfide-naphthyl-2-boronic acid, 50.1g, HPLC ═ 99.2%, yield 80%;
intermediate S1(50g,0.23mol) was charged into a 1000ML reactor containing 350ML of tetrahydrofuran, 150ML of water, 5-chloro-2-fluoroiodobenzene (53.5g, 0.24mol), potassium phosphate (97.5g, 0.46mol) were further added to the system and replaced with nitrogen three times, PdCl was further added2(dppf) (1.1g, 0.5%) is added into the system to 80-120 ℃, fully reacted for 5-20 h, the reaction is monitored by a liquid phase, the reaction is stopped when the raw material is less than 1%, the temperature is reduced to below 50 ℃, the mixture is introduced into 1000ml of water, then dichloromethane is added for extraction to obtain an organic phase, the organic phase is dried by anhydrous sodium sulfate, the organic phase is filtered by a kieselguhr column to obtain a filtrate, the filtrate is concentrated by a decompression mode, and then ethyl acetate is used for recrystallization to obtain an intermediate S6: 3- (5-chloro-2-fluorophenyl) -2-methylsulfinylnaphthalene (46.6 g), 99.2% HPLC, yield 67％；
Adding an intermediate S6(30g, 0.10mol) into a 1000ML reactor containing 300ML of dichloroethane, reducing the temperature to below 10 ℃, then slowly adding iron tribromide (29.3g, 0.20mol), controlling the temperature to below 20 ℃, reacting for 1-6 h at 30 ℃ after the iron tribromide raw material is completely added, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to below 30 ℃, extracting with dichloromethane, and then concentrating under reduced pressure to obtain an intermediate S7: 3- (5-chloro-2-fluorophenyl) -2-naphthylthiol, 24.6g, 99.2% HPLC, yield 85%;
adding the intermediate S7(20g, 0.07mol) into a 500ml reactor containing 200ml of N, N-dimethylacetamide, adding potassium acetate (13.7g, 0.14mol), heating to 80-120 ℃, fully reacting for 1-6 h, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature below 30 ℃, and then carrying out suction filtration under a reduced pressure state to obtain a white solid W10: 2-chlorobenzo [ B ] naphthalene-2, 3-D ] thiophene (12.8 g), 99.3% HPLC, yield 68%.
The nuclear magnetic resonance detection of the product W10 obtained in this example 3 showed that:
1H NMR(500MHz，Chloroform-d)δ8.37(d，J＝2.3Hz，1H)，8.19(d，J＝2.2Hz，1H)，8.12–8.06(m，2H)，7.96(ddd，J＝6.0，3.3，2.3Hz，1H)，7.88(ddd，J＝5.7，3.4，2.3Hz，1H)，7.55–7.48(m，2H)，7.43(dd，J＝7.9，1.8Hz，1H)。
example 4
Preparation of 4-methylbenzo [ B ] naphthalene-2, 3-D ] thiophene
2-naphthyl sulfide is used as a raw material to react at a low temperature to obtain an intermediate S1, the intermediate S1 and 3-methyl-2-fluoroiodobenzene are subjected to coupling reaction to obtain an intermediate S8, the intermediate S8 is subjected to demethylation reaction under the action of Lewis acid to obtain S9, and S9 is subjected to ring closure reaction under the action of alkali to obtain a product W13: 4-methylbenzo [ B ] naphthalene benzene [2, 3-D ] thiophene having the chemical reaction formula: a
Figure BDA0003574408640000131
The method is specifically realized by the following steps:
adding 2-naphthylmethyl sulfide (50g, 0.29mol) into a 1000ML reactor containing 500ML of tetrahydrofuran, adding triethyl borate (42.3g, 0.37mol), replacing nitrogen, reducing the temperature to-70 to-90 ℃, dropwise adding n-butyllithium (149.4ML,0.37mol), controlling the temperature to-70 to-90 ℃, fully reacting for 3-6 h, heating to 10-30 ℃, introducing 1000ML of acid water for quenching, carrying out vacuum concentration, carrying out suction filtration by using a suction filtration funnel to obtain a crude product, washing the crude product once by using 500ML of petroleum ether, heating to 30-50 ℃, carrying out vacuum filtration to obtain a white solid intermediate S1: 3-methylsulfide-naphthyl-2-boronic acid, 46.2g, 99.2% HPLC, yield 73%;
intermediate S1(50g,0.23mol) was charged into a 1000ML reactor containing 350ML DMF, 150ML water, 3-methyl-2-fluoroiodobenzene (56.6g, 0.24mol), sodium hydroxide (18.4g, 0.46mol) were added to the system and replaced three times with nitrogen, and Pd (PPh) was added3)2Cl2(1.1g, 0.5%) adding the system to 80-120 ℃, fully reacting for 5-20 h, monitoring the reaction by using a liquid phase, stopping the reaction when the raw material is less than 1%, cooling to below 50 ℃, introducing into 1000ml of water, then adding dichloromethane for extraction to obtain an organic phase, drying the organic phase by using anhydrous sodium sulfate, passing through a kieselguhr column to obtain a filtrate, concentrating by using a reduced pressure mode, and recrystallizing by using ethyl acetate to obtain an intermediate S8: 3- (3-methyl-2-fluorophenyl) -2-methylsulfinylnaphthalene (45.3 g), 99.1% HPLC, yield 77%;
adding the intermediate S8(30g, 0.10mol) into a 1000ML reactor containing 300ML of tetrahydrofuran, reducing the temperature to below 10 ℃, then slowly adding zinc chloride (40.8g, 0.30mol), controlling the temperature to below 20 ℃, reacting at 30 ℃ for 1-6 h after the zinc chloride raw material is added, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to below 30 ℃, extracting with dichloromethane, and then concentrating under reduced pressure to obtain an intermediate S9: 3- (3-methyl-2-fluorophenyl) -2-naphthylthiol, 19.3g, 99.2% HPLC, yield 72%;
adding the intermediate S9(20g,0.07mol) into a 500ml reactor containing 200ml of N, N-dimethylformamide, adding sodium hydroxide (8.4g, 0.21mol), heating to 80-120 ℃, fully reacting for 1-6 h, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature below 30 ℃, and then carrying out suction filtration under a reduced pressure state to obtain a white solid W13: 4-methylbenzo [ B ] naphthalene-2, 3-D ] thiophene (12.3 g), 99.1% HPLC, yield 71%.
The nuclear magnetic resonance detection of the product W13 obtained in this example 4 showed that:
1H NMR(500MHz，Chloroform-d)δ8.32(d，J＝2.2Hz，1H)，8.18–8.16(m，1H)，7.98–7.85(m，3H)，7.54–7.49(m，2H)，7.37–7.32(m，1H)，7.16(dt，J＝7.5，0.9Hz，1H)，2.53(d，J＝0.7Hz，3H)。
example 5
Preparation of 2-cyanobenzo [ B ] naphthalene [2, 3-D ] thiophene
2-naphthyl sulfide is used as a raw material to react at a low temperature to obtain an intermediate S1, the intermediate S1 and 5-cyano-2-fluoroiodobenzene are subjected to coupling reaction to obtain an intermediate S10, the intermediate S10 is subjected to demethylation reaction under the action of Lewis acid to obtain S11, and S11 is subjected to ring closure reaction under the action of alkali to obtain a product W23: 2-cyanobenzo [ B ] naphthalene benzene [2, 3-D ] thiophene, the chemical reaction formula of which is:
Figure BDA0003574408640000151
the method is realized by the following steps:
adding 2-naphthylmethyl sulfide (50g, 0.29mol) into a 1000ML reactor containing 500ML of tetrahydrofuran, adding triisopropyl borate (70.2g, 0.37mol), replacing nitrogen, reducing the temperature to-70 to-90 ℃, dropwise adding n-butyl lithium (149.4ML,0.37mol), controlling the temperature to-70 to-90 ℃, fully reacting for 3-6 h, heating to 10-30 ℃, introducing 1000ML of acid water for quenching, concentrating under reduced pressure, performing suction filtration by using a suction filtration funnel to obtain a crude product, heating 500ML of petroleum ether to 30-50 ℃ for washing once, and filtering under reduced pressure to obtain a white solid intermediate S1: 3-methylsulfide-naphthyl-2-boronic acid, 53.3g, HPLC ═ 99.2%, yield 85%;
intermediate S1(50g,0.23mol) was charged into a 1000ML reactor containing 350ML DMF, 150ML water, and 5-cyano-2-fluoroiodobenzene (59.3g, 0.24mol), sodium tert-butoxide (102.1g, 0.46mol) were added to the system and replaced with nitrogen three times, and Pd (PPh) was added3)4(1.2g, 0.5%) adding the system to 80-120 ℃, fully reacting for 5-20 h, monitoring the reaction by using a liquid phase, stopping the reaction when the raw material is less than 1%, cooling to below 50 ℃, introducing into 1000ml of water, then adding dichloromethane for extraction, drying the obtained organic phase by using anhydrous sodium sulfate, passing through a kieselguhr column to obtain a filtrate, concentrating by using a reduced pressure mode, and recrystallizing by using ethyl acetate to obtain an intermediate S10: 3- (5-cyano-2-fluorophenyl) -2-methylsulfinylnaphthalene, 53.9g, 99.3% HPLC, yield 80%;
adding an intermediate S10(30g, 0.10mol) into a 1000ML reactor containing 300ML of dichloromethane, reducing the temperature to below 10 ℃, then slowly adding boron tribromide (40.8g, 0.30mol), controlling the temperature to below 20 ℃, reacting for 1-6 h at 30 ℃ after the boron tribromide raw material is completely added, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to below 30 ℃, extracting with dichloromethane, and then concentrating under reduced pressure to obtain an intermediate S11: 3- (5-cyano-2-fluorophenyl) -2-naphthylthiol, 26.3g, 99.2% HPLC, yield 92%;
adding the intermediate S11(20g, 0.07mol) into a 500ml reactor containing 200ml of NMP, adding sodium tert-butoxide (31.1g, 0.14mol), heating to 80-120 ℃, fully reacting for 1-6 h, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature below 30 ℃, and then carrying out suction filtration under a reduced pressure state to obtain a white solid W23: 2-cyanobenzo [ B ] naphthalene-benzo [2, 3-D ] thiophene, 16.0g, 99.2% HPLC, yield 88%.
The nuclear magnetic resonance detection of the product W23 obtained in this example 5 showed that:
1H NMR(500MHz，Chloroform-d)δ8.39(d，J＝2.1Hz，1H)，8.33(d，J＝1.8Hz，1H)，8.25(d，J＝6.3Hz，1H)，8.20(d，J＝2.1Hz，1H)，7.96(ddd，J＝6.0，3.4，2.3Hz，1H)，7.88(ddd，J＝5.7，3.4，2.3Hz，1H)，7.75(dd，J＝6.4，2.0Hz，1H)，7.55–7.48(m，2H)。
example 6
Preparation of 1-fluorobenzo [ B ] naphthalene-2, 3-D ] thiophene
2-naphthyl sulfide is used as a raw material to react at low temperature to obtain an intermediate S1, the intermediate S1 and 2, 6-difluoroiodobenzene are subjected to coupling reaction to obtain an intermediate S12, the intermediate S12 is subjected to demethylation reaction under the action of Lewis acid to obtain S13, and S13 is subjected to ring closure reaction under the action of alkali to obtain a product W30: 3-bromobenzo [ b ] naphthalene benzene [2, 3-D ] thiophene, the chemical reaction formula of which is:
Figure BDA0003574408640000171
the method is realized by the following steps:
adding 2-naphthylmethyl sulfide (50g, 0.29mol) into a 1000ML reactor containing 500ML of tetrahydrofuran, adding triisopropyl borate (70.2g, 0.37mol), replacing nitrogen, reducing the temperature to-70-90 ℃, dropwise adding n-butyllithium (149.4ML,0.37mol), controlling the temperature to-70-90 ℃ for full reaction for 3-6 h, heating to 10-30 ℃, introducing 1000ML of acid water for quenching, carrying out vacuum concentration, carrying out suction filtration by using a suction filtration funnel to obtain a crude product, heating 500ML of petroleum ether to 30-50 ℃ for washing once, and carrying out vacuum filtration to obtain a white solid intermediate S1: 3-methylsulfide-naphthyl-2-boronic acid, 53.3g, HPLC ═ 99.2%, yield 85%;
intermediate S1(50g,0.23mol) was charged into a 1000ML reactor containing 350ML of DMF, and 2, 6-difluoroiodobenzene (57.6g, 0.24mol), potassium carbonate (63.5g, 0.46mol) were further added to the system and replaced with nitrogen three times, and Pd (PPh) was further added3)4(1.2g, 0.5%) adding the system to 80-120 ℃, fully reacting for 5-20 h, monitoring the reaction by using a liquid phase, stopping the reaction when the raw material is less than 1%, cooling to below 50 ℃, introducing1000ml of water, followed by extraction with dichloromethane gave an organic phase, which was dried over anhydrous sodium sulfate and then passed through a celite column to give a filtrate, which was concentrated under reduced pressure and recrystallized from ethyl acetate to give S12: 3- (2.6-difluorophenyl) -2-methylsulfinylnaphthalene, 54.0g, 99.3% HPLC, yield 82%;
adding an intermediate S12(30g, 0.11mol) into a 1000ML reactor containing 300ML of dichloroethane, reducing the temperature to below 10 ℃, then slowly adding boron tribromide (55.2g, 0.22mol), controlling the temperature to below 20 ℃, reacting for 1-6 h at 30 ℃ after the boron tribromide raw material is completely added, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to below 30 ℃, extracting with dichloromethane, and then concentrating under reduced pressure to obtain an intermediate S13: 3- (2.6-difluorophenyl) -2-naphthylthiol, 28.1g, 99.2% HPLC, yield 94%;
adding the intermediate S13(20g, 0.07mol) into a 500ml reactor containing 200ml of N, N-dimethylacetamide, adding potassium carbonate (19.3g, 0.14mol), heating to 80-120 ℃, fully reacting for 1-6 h, monitoring with a liquid phase, slowly adding water for quenching when the raw material is less than 1%, controlling the quenching temperature to be below 30 ℃, and then carrying out suction filtration under a reduced pressure state to obtain a white solid W30: 1-fluorobenzo [ B ] naphthalene-2, 3-D ] thiophene (6.6 g), 99.1% HPLC, yield 94%.
The nuclear magnetic resonance detection of the product W30 obtained in this example 6 showed that:
1H NMR(500MHz，Chloroform-d)δ8.33(d，J＝2.2Hz，1H)，8.09(d，J＝2.2Hz，1H)，7.96(ddd，J＝6.0，3.4，2.3Hz，1H)，7.88(ddd，J＝5.7，3.5，2.3Hz，1H)，7.70(dd，J＝6.4，1.3Hz，1H)，7.54–7.45(m，3H)，7.19(ddd，J＝8.3，7.1，1.1Hz，1H)。
in conclusion, by adopting the preparation method of the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, the purity of the obtained product is as high as 99.1-99.4%, the yield is as high as 97%, the cost is low, no waste solvent is generated in the whole preparation process, and meanwhile, less waste water is generated, so that a foundation is laid for achieving the purpose of environmental protection.
In addition, the embodiment of the invention also provides an application of the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, which specifically comprises the following steps: the substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative is applied to the synthesis of drugs, the organic luminescent material, the high polymer material and the organic flexible material.
The following will explain the technical effects in more detail by using examples
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims (10)

1. A preparation method of substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivatives is characterized in that 2-naphthalene methyl sulfide is used as a raw material to react at a low temperature to obtain an intermediate S-1, the intermediate S-1 and substituted o-iodofluorobenzene are subjected to a coupling reaction to prepare an intermediate S-2, the intermediate S-2 is subjected to a demethylation reaction under the action of Lewis acid to obtain S-3, and the S-3 is subjected to a ring closure reaction under the action of alkali to obtain a product W0: a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative has a chemical reaction formula as follows:
Figure FDA0003574408630000011
wherein R is hydrogen, alkyl, halogen, nitro, cyano, etc.
2. The method for preparing substituted benzo [ B ] naphthalene [2, 3-D ] thiophene derivative according to claim 1, which is specifically realized by the following steps:
s1, dissolving 2-naphthylmethyl sulfide in a first organic solvent, cooling to-70 to-90 ℃, adding n-butyllithium and boric acid ester in sequence, reacting for 1-5h, and heating to obtain an intermediate S-1;
s2, dissolving the intermediate S-1 and substituted o-iodofluorobenzene in a second organic solvent, adding a first alkali and a catalyst for coupling reaction, and obtaining an intermediate S-2 after the reaction is finished;
s3, dissolving the intermediate S-2 in a third organic solvent, and adding Lewis acid for demethylation reaction to obtain an intermediate S-3;
s4, dissolving the intermediate S-3 in a fourth organic solvent, adding a second alkali, heating to 60-120 ℃, reacting for 1-5h, and cooling to obtain a product W0: substituted benzo [ B ] naphthalene-benzene [2, 3-D ] thiophene derivatives.
3. A substituted benzo [ B ] according to claim 2]Naphthalene benzene [2, 3-D]A thiophene derivative preparation method, wherein in S2, the first base is at least one of sodium tert-butoxide, sodium carbonate, potassium phosphate, potassium acetate, sodium hydroxide and the like; the catalyst is Pd (PPh)3)4，PdCl2(dppf)，Pd(PPh3)2Cl2At least one of (1).
4. The method for preparing a substituted benzo [ B ] naphthalene [2, 3-D ] thiophene derivative according to claim 3, wherein in S2, said substituted iodofluorobenzene is at least one of 4-bromo-2-fluoroiodobenzene, 3-bromo-2-fluoroiodobenzene, 5-chloro-2-fluoroiodobenzene, 3-nitro-2-fluoroiodobenzene, and 6-cyano-2-fluoroiodobenzene.
5. The method of claim 4, wherein the Lewis acid of S3 is at least one of boron trichloride, iron tribromide, boron tribromide and zinc chloride.
6. The method for preparing a substituted benzo [ B ] naphthalene [2, 3-D ] thiophene derivative according to claim 5, wherein in S4, said second base is at least one of sodium tert-butoxide, sodium carbonate, potassium phosphate, potassium acetate, and sodium hydroxide.
7. The method of claim 6, wherein in S2, the second organic solvent is at least one of toluene/ethanol, dioxane/water, tetrahydrofuran/water, and DMF/water; in S3, the third solvent is at least one of tetrahydrofuran, dichloromethane, dioxane, and dichloroethane.
8. The method for preparing a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative according to claim 7, wherein in S4, said fourth organic solvent is at least one of dioxane, N, N-dimethylformamide, N, N-dimethylacetamide, and NMP.
9. A substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative, characterized by being prepared by the method for preparing a substituted benzo [ B ] naphthalene benzene [2, 3-D ] thiophene derivative according to any one of claims 1 to 8, and having a chemical structural formula as follows:
Figure FDA0003574408630000031
wherein, R is at least one of hydrogen, alkyl, halogen, nitro and cyano.
10. The substituted benzo [ B ] napthalene [2, 3-D ] thiophene derivative of claim 9, wherein said substituted benzo [ B ] napthalene [2, 3-D ] thiophene derivative is selected from the following specific structural formulas:
Figure FDA0003574408630000032
Figure FDA0003574408630000041
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Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104672126A (en) * 2014-12-31 2015-06-03 北京鼎材科技有限公司 Benzo-naphtho five-membered heterocycle derivative and application thereof
CN106938992A (en) * 2016-01-05 2017-07-11 三星显示有限公司 Fused ring compound and the organic light emitting apparatus for including the fused ring compound
CN106967045A (en) * 2015-10-21 2017-07-21 三星电子株式会社 The intermediate of miscellaneous acene compound, the synthetic method using its miscellaneous acene compound and include the electronic device of miscellaneous acene compound
CN108299383A (en) * 2018-01-23 2018-07-20 南京邮电大学 The method of palladium chtalyst one pot process oil-source rock correlation
CN108658932A (en) * 2018-05-18 2018-10-16 长春海谱润斯科技有限公司 One kind containing the aromatic amine compound and its organic electroluminescence device of 9,9 '-spiral shell, two fluorenes and dibenzothiophenes
CN110483533A (en) * 2019-07-08 2019-11-22 宁波卢米蓝新材料有限公司 A kind of compound and its preparation method and application
CN111225905A (en) * 2018-02-13 2020-06-02 株式会社Lg化学 Heterocyclic compound and organic light emitting device including the same
CN111511734A (en) * 2017-12-21 2020-08-07 德山新勒克斯有限公司 Compound for organic electric element, organic electric element using same, and electronic device using same
WO2022039520A1 (en) * 2020-08-19 2022-02-24 주식회사 엘지화학 Novel compound and organic light-emitting device comprising same

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104672126A (en) * 2014-12-31 2015-06-03 北京鼎材科技有限公司 Benzo-naphtho five-membered heterocycle derivative and application thereof
CN106967045A (en) * 2015-10-21 2017-07-21 三星电子株式会社 The intermediate of miscellaneous acene compound, the synthetic method using its miscellaneous acene compound and include the electronic device of miscellaneous acene compound
CN106938992A (en) * 2016-01-05 2017-07-11 三星显示有限公司 Fused ring compound and the organic light emitting apparatus for including the fused ring compound
CN111511734A (en) * 2017-12-21 2020-08-07 德山新勒克斯有限公司 Compound for organic electric element, organic electric element using same, and electronic device using same
CN108299383A (en) * 2018-01-23 2018-07-20 南京邮电大学 The method of palladium chtalyst one pot process oil-source rock correlation
CN111225905A (en) * 2018-02-13 2020-06-02 株式会社Lg化学 Heterocyclic compound and organic light emitting device including the same
CN108658932A (en) * 2018-05-18 2018-10-16 长春海谱润斯科技有限公司 One kind containing the aromatic amine compound and its organic electroluminescence device of 9,9 '-spiral shell, two fluorenes and dibenzothiophenes
CN110483533A (en) * 2019-07-08 2019-11-22 宁波卢米蓝新材料有限公司 A kind of compound and its preparation method and application
WO2022039520A1 (en) * 2020-08-19 2022-02-24 주식회사 엘지화학 Novel compound and organic light-emitting device comprising same

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JUAN SONG等: "A Pd-catalyzed optional approach for the synthesis of dibenzothiophenes", 《ORG. BIOMOL. CHEM.》, pages 2083 - 2087 *
PRATAP, RAM等: "The synthesis of the monomethyl derivatives of benzo[b]naphtho[2, 3-d]thiophene", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》, pages 865 - 869 *

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