CN114907335A - 2- (benzothiophene-2-yl) benzo [ d ] oxazole derivative, preparation method and application - Google Patents
2- (benzothiophene-2-yl) benzo [ d ] oxazole derivative, preparation method and application Download PDFInfo
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Abstract
The invention discloses a 2- (benzothiophene-2-yl) benzo [ d]Oxazole derivatives, process for their preparation and their use, said 2- (benzothien-2-yl) benzo [ d]The oxazole derivatives have the formula:
wherein R1 is hydrogen, alkyl, halogen or alkoxy, and R2 is hydrogen, alkyl, halogen or alkoxy. The raw materials of the invention are all conventional materials in the market, are cheap and easy to obtain, have no much danger, can obtain high-purity products after simple and convenient post-treatment, have high yield, so the cost is lower than that of other methods, no waste solvent is generated, the generated waste water is less, the atom utilization rate is high, and the invention is more environment-friendly.
Description
Technical Field
The application belongs to the technical field of organic chemical synthesis, and particularly relates to a 2- (benzothiophene-2-yl) benzo [ d ] oxazole derivative, a preparation method and application thereof.
Background
The 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives have a wide variety of applications owing to their special structure. Different active groups are introduced into the 4,5, 6,7 positions on the benzothiophene ring and the 4,5, 6,7 positions on the benzoxazole ring of the structure of the derivative, so that the derivative has different applications and more excellent performances in different fields, and due to the continuous research and development of organic electric to luminescent materials by scientists in recent years, the introduction of different active groups into the 4,5, 6,7 positions on the benzothiophene ring and the 4,5, 6,7 positions on the benzoxazole ring of the 2- (benzothiophen-2-yl) benzoxazole derivative requires higher and higher purity and yield, and the intermediate materials of the OLED derivatives have greater demands with the continuous breakthrough and marketing of the OLED organic luminescent materials, so continuous innovation and continuous optimization and improvement of the process are required.
Disclosure of Invention
In view of the above, the present invention mainly aims to provide a 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative, a preparation method and an application thereof.
In order to achieve the purpose, the technical scheme of the invention is realized as follows:
the embodiment of the invention provides a 2- (benzothien-2-yl) benzo [ d ] oxazole derivative, which is characterized in that the general formula of the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative is as follows:
wherein R1 is hydrogen, alkyl, halogen or alkoxy, and R2 is hydrogen, alkyl, halogen or alkoxy.
In the above scheme, the alkyl is C1-C40, preferably C1-C10.
In the above scheme, the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative is selected from the following specific structural formulae:
embodiments of the present invention also provide a method for preparing 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives as described in any of the above schemes comprising:
taking substituted o-fluorobenzaldehyde and methyl thioglycollate as raw materials, and firstly carrying out ring closing dehydration to obtain a first intermediate;
saponifying the first intermediate to obtain a second intermediate;
the second intermediate is reacted with substituted o-aminophenol to obtain 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivatives.
In the above scheme, the substituted o-fluorobenzaldehyde and methyl thioglycolate are used as raw materials to perform ring closing dehydration to obtain a first intermediate, specifically: adding a solvent into a reaction container under the protection of inert gas, then adding substituted o-fluorobenzaldehyde, adding alkali, finally dropwise adding methyl thioglycolate, heating to 60-120 ℃, reacting for 3-6 hours, introducing into water for quenching, extracting by ethyl acetate, and concentrating to obtain a first intermediate.
In the scheme, the substituted o-fluorobenzaldehyde adopts 3-chloro-2-fluorobenzaldehyde, 4-bromo-2-fluorobenzaldehyde, 5-iodo-2-fluorobenzaldehyde or 2, 6-difluorobenzaldehyde; the solvent adopts dimethyl sulfoxide, N-dimethylformamide, NMP, dioxane, diphenyl ether or toluene; the alkali adopts potassium carbonate, potassium phosphate, triethylamine, pyridine, sodium carbonate or sodium tert-butoxide.
In the above scheme, the saponification of the first intermediate to obtain the second intermediate specifically comprises: and dissolving the first intermediate in an organic solvent, adding alkali, heating to 30-80 ℃, reacting for 1-5 hours, and cooling to obtain a second intermediate.
In the scheme, the organic solvent adopts ethanol, methanol, water or isopropanol; the alkali is sodium hydroxide, potassium hydroxide or lithium hydroxide; the condensing agent is PPA or concentrated sulfuric acid.
In the scheme, the second intermediate reacts with substituted o-aminophenol to obtain the 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative, which comprises the following specific components: dissolving the second intermediate in a condensing agent, adding phosphoric acid, and then adding substituted o-aminophenol, wherein the molar ratio of the substituted o-aminophenol to the second intermediate is 1.5-0.8: 1, heating to 100-160 ℃, reacting for 1-5 hours, and then treating to obtain the 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative.
According to the application of the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative prepared according to any one of the above schemes, the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative is applied to a synthetic drug, an organic electro-luminescence material, a polymer material or an organic flexible material.
Compared with the prior art, the raw materials of the invention are all conventional materials in the market, are cheap and easy to obtain, have no much danger, can obtain high-purity products after simple and convenient post-treatment, have high yield, so the cost is cheaper than other methods, no waste solvent is generated, the generated waste water is less, and the atom utilization rate is high, so the invention is more environment-friendly.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiment(s) of the invention and together with the description serve to explain the invention without limiting the invention. In the drawings:
FIG. 1 is a synthesis scheme showing a method for preparing 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives according to an embodiment 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 described in further detail below with reference to the accompanying drawings and 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.
It should be noted that, in this document, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other like elements in a process, article, or apparatus that comprises the element.
The embodiment of the invention provides a 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative, wherein the general formula of the 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative is as follows:
wherein R1 is hydrogen, alkyl, halogen or alkoxy, and R2 is hydrogen, alkyl, halogen or alkoxy.
The alkyl is C1-C40, preferably C1-C10.
Further, the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative is selected from the following specific structural formulae:
the embodiment of the invention also provides a preparation method of the 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative, which is shown in figure 1 and is realized by the following steps:
step 101: taking substituted o-fluorobenzaldehyde and methyl thioglycolate as raw materials to perform cyclization dehydration to obtain a first intermediate;
specifically, adding a solvent into a reaction container under the protection of inert gas, then adding substituted o-fluorobenzaldehyde, adding alkali, finally dropwise adding methyl thioglycolate, heating to 60-120 ℃ for reacting for 3-6 hours, cooling to below 50 ℃, introducing into water for quenching, extracting by ethyl acetate, and concentrating to obtain a first intermediate.
The substituted o-fluorobenzaldehyde adopts 3-chloro-2-fluorobenzaldehyde, 4-bromo-2-fluorobenzaldehyde, 5-iodo-2-fluorobenzaldehyde or 2, 6-difluorobenzaldehyde and the like;
the solvent adopts dimethyl sulfoxide, N-dimethylformamide, NMP, dioxane, diphenyl ether or toluene and the like;
the alkali adopts potassium carbonate, potassium phosphate, triethylamine, pyridine, sodium carbonate or sodium tert-butoxide and the like.
The inert gas is nitrogen or argon.
The molar ratio of the substituted o-fluorobenzaldehyde to the methyl thioglycolate is 1: 0.8 to 1.5; preferably, the molar ratio of substituted o-fluorobenzaldehyde to methyl thioglycolate used is 1: 1,
step 102: saponifying the first intermediate to obtain a second intermediate;
specifically, the first intermediate is dissolved in an organic solvent, alkali is added, the temperature is increased to 30-80 ℃, reaction is carried out for 1-5 hours, and the second intermediate is obtained after temperature reduction treatment.
The organic solvent adopts ethanol, methanol, water or isopropanol; the alkali is sodium hydroxide, potassium hydroxide or lithium hydroxide.
Step 103: the second intermediate is reacted with substituted o-aminophenol to obtain 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivatives.
Specifically, the second intermediate is dissolved in a condensing agent, phosphoric acid is added, and then substituted o-aminophenol is added, wherein the molar ratio of the substituted o-aminophenol to the second intermediate is 1.5-0.8: 1, heating to 100-160 ℃, reacting for 1-5 hours, and then treating to obtain the 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative.
The condensing agent is PPA or concentrated sulfuric acid.
According to the preparation method, raw materials are conventional materials on the market, the raw materials are cheap and easy to obtain, and the raw materials do not have much danger, the first step reaction is performed by replacing dehydration condensation reaction and adopting a conventional reaction kettle, the synthetic operation process is simple and convenient and easy to operate, compared with reaction steps designed by other schemes, the preparation method has the advantages that the reaction steps are fewer, only three steps of reaction are performed, the corresponding energy consumption is less, and the post-treatment is simpler.
The preparation method can obtain high-purity products after simple and convenient post-treatment, has high yield, lower cost compared with other methods, no waste solvent, less generated waste water and high atom utilization rate, and is more environment-friendly.
Example 1:
adding 2.5-difluorobenzaldehyde (30.0g and 0.21mol) into a 1000ML reactor, dissolving in 300ML of dimethyl sulfoxide, adding triethylamine (64.1g and 0.63mol), then dropwise adding methyl thioglycolate (24.6g and 0.23mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reaction for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, then carrying out suction filtration, and concentrating the obtained filtrate under reduced pressure to obtain an intermediate S1, 5-fluorobenzothiophene-2-methyl formate, 43.9g and 96.5 percent of HPLC (high performance liquid chromatography) with the yield of 99.0%.
5-fluoro benzothiophene-2-carboxylic acid methyl ester (20g,0.10mol) was charged into a 2000ML reactor, dissolved in 800ML ethanol, followed by addition of 200ML water, potassium hydroxide (16.0g,0.29mol) was added, the reaction was carried out at 20-50 ℃ for 1-8 hours, the solution became cloudy, the reaction was monitored to be complete, PE was adjusted to about 4, extraction was carried out with ethyl acetate, concentration under reduced pressure was carried out to give a white solid, recrystallization was carried out with ethyl acetate to give intermediate S2, 5-fluoro benzothiophene-2-carboxylic acid, 18.3g, HPLC ═ 98.5, yield 98.1%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 5-fluorobenzothiophene-2-formic acid (15.0g, 0.08mol) and o-aminophenol (10.0g,0.09mol), heating to 130-170 ℃, preserving heat for reaction for 1-8 hours, cooling, introducing water for quenching, performing suction filtration to obtain a crude product, then recrystallizing with toluene to obtain qualified solid W3,2- (5-fluorobenzothiophene-2-yl) benzoxazole, 17.5g, HPLC (high performance liquid chromatography) ═ 99.1, and the yield is 85%.
Example 2:
adding 4-bromo-2-fluorobenzaldehyde (30.0g and 0.15mol) into a 1000ML reactor, dissolving in 300ML of N, N-dimethylformamide, adding potassium carbonate (61.2g and 0.44mol), then dropwise adding methyl thioglycolate (15.7g and 0.15mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reacting for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, carrying out suction filtration, and concentrating the obtained filtrate under reduced pressure to obtain an intermediate S3, 6-bromobenzothiophene-2-methyl formate, 38.8g, 96.8% HPLC (HPLC), and the yield of 97.0%.
6-bromo-benzothiophene-2-carboxylic acid methyl ester (20g,0.07mol) was charged into a 2000ML reactor, dissolved in 800ML of methanol, followed by addition of 200ML of water, addition of sodium hydroxide (8.9g,0.22mol), reaction at 20-50 ℃ for 1-8 hours with the solution becoming cloudy, monitoring the end of the reaction, adjusting PE to about 4, extraction with ethyl acetate, concentration under reduced pressure to give a white solid, recrystallization from ethyl acetate to give intermediate S4, 6-bromo-benzothiophene-2-carboxylic acid, 18.1g, HPLC ═ 97.9, yield 95.5%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 6-bromobenzothiophene-2-formic acid (15.0g and 0.08mol) and o-aminophenol (13.1g and 0.12mol), heating to 130-170 ℃, preserving heat, reacting for 1-8 hours, cooling, introducing water for quenching, performing suction filtration to obtain a crude product, and then recrystallizing with toluene to obtain qualified solids W10,2- (6-bromobenzothiophene-2-yl) benzoxazole, 20.3g, HPLC (high performance liquid chromatography) ═ 99.5, and the yield is 77%.
Example 3:
adding 4-chloro-2-fluorobenzaldehyde (30.0g and 0.19mol) into a 1000ML reactor, dissolving in 300ML of NMP, adding potassium phosphate (120g and 0.57mol), dropwise adding methyl thioglycolate (15.7g and 0.15mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reacting for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, carrying out suction filtration, and concentrating the obtained filtrate under reduced pressure to obtain an intermediate S5, 6-chlorobenzothiophene-2-methyl formate, 39.6g and 94.9 percent of HPLC (high performance liquid chromatography), wherein the yield is 92.8 percent.
6-chlorobenzothiophene-2-carboxylic acid methyl ester (20g,0.09mol) was charged into a 2000ML reactor, dissolved in 800ML of t-butanol, and 200ML of water was added, potassium hydroxide (14.8g,0.26mol) was added, and the reaction was carried out at 20 to 50 ℃ for 1 to 8 hours, whereupon the solution became cloudy, the reaction was monitored for completion, PE was adjusted to about 4, extraction was carried out with ethyl acetate, and concentration under reduced pressure was carried out to obtain a white solid, which was recrystallized from ethyl acetate to obtain intermediate S6, 6-chlorobenzothiophene-2-carboxylic acid, 18.1g, HPLC ═ 96.8, and the yield was 96.2%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 6-chlorobenzothiophene-2-formic acid (15.0g, 0.07mol) and 5-chloro-2-aminophenol (10.1g,0.07mol), heating to 130-170 ℃, keeping the temperature for reaction for 1-8 hours, cooling, introducing water for quenching, carrying out suction filtration to obtain a crude product, and then recrystallizing with toluene to obtain qualified solid W22, 6-chloro-2- (6 '-bromobenzothiophene-2' -yl) benzoxazole, 15.5g, 98.9 percent HPLC (high performance liquid chromatography) and 69 percent yield.
Example 4:
adding 3-bromo-2-fluorobenzaldehyde (30.0g and 0.15mol) into a 1000ML reactor, dissolving in 300ML of N, N-dimethylformamide, adding sodium carbonate (47.7g and 0.45mol), then dropwise adding methyl thioglycolate (23.3g and 0.22mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reacting for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, then carrying out suction filtration, and concentrating the obtained filtrate under reduced pressure to obtain an intermediate S7, 7-bromobenzothiophene-2-methyl formate, 38.4g, 97.2 HPLC (high performance liquid chromatography) and 94.5% yield.
To a 2000ML reactor was added 7-bromobenzothiophene-2-carboxylic acid methyl ester (20g,0.07mol), dissolved in 800ML ethanol, followed by addition of 200ML water, potassium hydroxide (11.8g,0.21mol) at 20-50 ℃ for 1-8 hours, the solution became cloudy, the reaction was monitored for completion, PE was adjusted to about 4, extraction was performed with ethyl acetate, and concentration under reduced pressure gave a white solid which was recrystallized from ethyl acetate to give intermediate S8, 7-bromobenzothiophene-2-carboxylic acid, 17.6g, HPLC ═ 96.5, yield 98.1%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 7-bromobenzothiophene-2-formic acid (15.0g and 0.08mol) and 6-fluoro-2-aminophenol (12.2g and 0.10mol), heating to 130-170 ℃, keeping the temperature for reaction for 1-8 hours, cooling, introducing water for quenching, carrying out suction filtration to obtain a crude product, and then recrystallizing with toluene to obtain qualified solid W33, 7-fluoro-2- (7 '-bromobenzothiophene-2' -yl) benzoxazole, 22.0g, 99.0% of HPLC (high performance liquid chromatography) and 79% of yield.
Example 5:
adding 3-bromo-2-fluorobenzaldehyde (30.0g, 0.15mol) into a 1000ML reactor, dissolving in 300ML of dimethyl sulfoxide, adding pyridine (33.3g,0.45mol), then dropwise adding methyl thioglycolate (15.9g,0.15mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reaction for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, then carrying out suction filtration, and concentrating the obtained filtrate under reduced pressure to obtain an intermediate S9, 5-bromobenzothiophene-2-methyl formate, 39.7g, 96.2 HPLC (high performance liquid chromatography) ═ 96.2, and the yield is 97.7%.
5-bromo-benzothiophene-2-carboxylic acid methyl ester (20g,0.07mol) was charged into a 2000ML reactor, dissolved in 800ML of ethanol, followed by addition of 200ML of water, addition of sodium hydroxide (8.4g,0.21mol), reaction at 20-50 ℃ for 1-8 hours, turbidity of the solution, monitoring the end of the reaction, adjusting PE to about 4, extraction with ethyl acetate, concentration under reduced pressure to give a white solid, recrystallization from ethyl acetate to give intermediate S10, 5-bromo-benzothiophene-2-carboxylic acid, 16.9g, HPLC ═ 96.5, yield 94.2%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 5-bromobenzothiophene-2-formic acid (15.0g and 0.08mol) and 4-methoxy-2-aminophenol (10.0g and 0.08mol), heating to 130-170 ℃, keeping the temperature for reaction for 1-8 hours, cooling, introducing water for quenching, carrying out suction filtration to obtain a crude product, and then recrystallizing with toluene to obtain qualified solid W33, 5-methoxy-2- (5 '-bromobenzothiophene-2' -yl) benzoxazole, 19.9g, 98.5 percent of HPLC (high performance liquid chromatography), wherein the yield is 72 percent.
Example 6:
adding 3-chloro-2-fluorobenzaldehyde (30.0g and 0.19mol) dissolved in 300ML of N, N-dimethyl sulfoxide into a 1000ML reactor, adding triethylamine (57.6g and 0.57mol), then dropwise adding methyl thioglycolate (26.2g and 0.25mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reacting for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, then carrying out suction filtration, and carrying out reduced pressure concentration on the obtained filtrate to obtain an intermediate S11, 7-chlorobenzothiophene-2-methyl formate, 41.3g, 95.3 percent of HPLC (high performance liquid chromatography), wherein the yield is 95.8 percent.
To a 2000ML reactor was added 7-chlorobenzothiophene-2-carboxylic acid methyl ester (20g,0.09mol), dissolved in 800ML of methanol, followed by addition of 200ML of water, addition of sodium hydroxide (10.8g,0.27mol), reaction at 20-50 ℃ for 1-8 hours, clouding of the solution, monitoring of the end of the reaction, adjusting PE to about 4, extraction with ethyl acetate, concentration under reduced pressure to give a white solid, recrystallization with ethyl acetate to give intermediate S12, 7-chlorobenzothiophene-2-carboxylic acid, 33.2g, HPLC ═ 97.2, yield 95.9%.
120ML of polyphosphoric acid and 80ML of phosphoric acid are added into a 1000ML reactor, the temperature is raised to 100-130 ℃, stirring is started, then 7-chlorobenzothiophene-2-formic acid (15.0g, 0.07mol) and 6-methyl-2-aminophenol (11.2g,0.09mol) are added, the temperature is raised to 130-170 ℃, the reaction is kept for 1-8 hours, the mixture is cooled, introduced into water for quenching and filtered to obtain a crude product, and then the crude product is recrystallized by toluene to obtain qualified solid W53, 7-methyl-2- (7 '-chlorobenzothiophene-2' -yl) benzoxazole, 14.9g, HPLC (high performance liquid chromatography) 98.3, and the yield is 71 percent.
Example 7:
5-chloro-2-fluorobenzaldehyde (30.0g, 0.19mol) is added into a 1000ML reactor and dissolved in 300ML of NMP, potassium phosphate (120g,0.57mol) is added, methyl thioglycolate (20.1g,0.19mol) is added dropwise, under the protection of nitrogen, the temperature is raised to 60-120 ℃, the reaction is heated for 1-5 hours, the reaction is finished and cooled to room temperature, ethyl acetate and water are used for extraction, an organic phase is dried and then is filtered, the obtained filtrate is concentrated under reduced pressure, and then the intermediate S13, 5-chlorobenzothiophene-2-methyl formate, 40.2g, HPLC (high performance liquid chromatography) ═ 94.9 and the yield is 93.3 percent are obtained.
5-chlorobenzothiophene-2-carboxylic acid methyl ester (20g,0.09mol) was charged into a 2000ML reactor, dissolved in 800ML of ethanol, and then 200ML of water was added, potassium hydroxide (14.8g,0.26mol) was added, and the reaction was carried out at 20 to 50 ℃ for 1 to 8 hours, whereupon the solution became cloudy, after monitoring the completion of the reaction, PE was adjusted to about 4, and the mixture was extracted with ethyl acetate, and concentrated under reduced pressure to give a white solid, which was recrystallized from ethyl acetate to give intermediate S14, 5-chlorobenzothiophene-2-carboxylic acid, 33.6g, HPLC ═ 97.5, and the yield was 96.9%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 5-chlorobenzothiophene-2-formic acid (15.0g and 0.07mol) and 4-bromo-2-aminophenol (14.5g and 0.08mol), heating to 130-170 ℃, keeping the temperature for reaction for 1-8 hours, cooling, introducing water for quenching, performing suction filtration to obtain a crude product, and then recrystallizing with toluene to obtain qualified solid W63, 5-bromo-2- (5 '-bromobenzothiophene-2' -yl) benzoxazole, 18.4g, 98.8 percent of HPLC (high performance liquid chromatography) and 72 percent of yield.
Example 8:
adding 3-bromo-2-fluorobenzaldehyde (30.0g, 0.15mol) into a 1000ML reactor, dissolving in 300ML of NMP, adding potassium carbonate (62.1g,0.45mol), then dropwise adding methyl thioglycolate (22.3g,0.21mol), heating to 60-120 ℃ under the protection of nitrogen, heating for reaction for 1-5 hours, cooling to room temperature after the reaction is finished, extracting by using ethyl acetate and water, drying an organic phase, then carrying out suction filtration, and concentrating the obtained filtrate under reduced pressure to obtain an intermediate S15, 7-bromobenzothiophene-2-methyl formate, 39.0g, 96.0% HPLC (HPLC), and the yield is 96.0%.
To a 2000ML reactor was added 7-bromobenzothiophene-2-carboxylic acid methyl ester (20g,0.07mol), dissolved in 800ML ethanol, followed by addition of 200ML water, potassium hydroxide (11.8g,0.21mol) at 20-50 ℃ for 1-8 hours, the solution became cloudy, the reaction was monitored for completion, PE was adjusted to about 4, extraction was performed with ethyl acetate, and concentration under reduced pressure gave a white solid which was recrystallized from ethyl acetate to give intermediate S16, 7-bromobenzothiophene-2-carboxylic acid, 16.8g, HPLC ═ 96.1, yield 94.0%.
Adding 120ML of polyphosphoric acid and 80ML of phosphoric acid into a 1000ML reactor, heating to 100-130 ℃, starting stirring, then adding 7-bromobenzothiophene-2-formic acid (15.0g and 0.08mol) and 4-bromo-2-aminophenol (16.5g and 0.09mol), heating to 130-170 ℃, keeping the temperature for reaction for 1-8 hours, cooling, introducing water for quenching, carrying out suction filtration to obtain a crude product, and then recrystallizing with toluene to obtain qualified solid W65, 5-bromo-2- (7 '-bromobenzothiophene-2' -yl) benzoxazole, 24.9g, HPLC (high performance liquid chromatography) 99.0 and the yield of 76%.
The embodiment of the invention also provides application of the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative in the preparation of synthetic drugs, organic electro-luminescent materials, high molecular materials or organic flexible materials.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the scope of the present invention.
Claims (10)
1. A2- (benzothien-2-yl) benzo [ d ] oxazole derivative characterized in that the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative has the general formula:
wherein R1 is hydrogen, alkyl, halogen or alkoxy, and R2 is hydrogen, alkyl, halogen or alkoxy.
2. 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives as claimed in claim 1, characterized in that the alkyl radicals are from C1 to C40, preferably from C1 to C10.
3. The 2- (benzothien-2-yl) benzo [ d ] oxazole derivative according to claim 2 wherein the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative is selected from the following specific structural formulae:
4. a process for preparing 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives as claimed in any one of claims 1 to 3, which comprises:
taking substituted o-fluorobenzaldehyde and methyl thioglycollate as raw materials, and firstly carrying out ring closing dehydration to obtain a first intermediate;
saponifying the first intermediate to obtain a second intermediate;
the second intermediate reacts with substituted o-aminophenol to obtain the 2- (benzothiophene-2-yl) benzo [ d ] oxazole derivative.
5. The process for preparing 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives according to claim 4, wherein the substituted o-fluorobenzaldehyde and methyl thioglycolate are used as raw materials and subjected to ring closing dehydration to obtain a first intermediate, which comprises: adding a solvent into a reaction container under the protection of inert gas, then adding substituted o-fluorobenzaldehyde, adding alkali, finally dropwise adding methyl thioglycolate, heating to 60-120 ℃, reacting for 3-6 hours, introducing into water for quenching, extracting by ethyl acetate, and concentrating to obtain a first intermediate.
6. The process for producing 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives according to claim 5, characterized in that the substituted o-fluorobenzaldehyde is 3-chloro-2-fluorobenzaldehyde, 4-bromo-2-fluorobenzaldehyde, 5-iodo-2-fluorobenzaldehyde or 2, 6-difluorobenzaldehyde; the solvent adopts dimethyl sulfoxide, N-dimethylformamide, NMP, dioxane, diphenyl ether or toluene; the alkali adopts potassium carbonate, potassium phosphate, triethylamine, pyridine, sodium carbonate or sodium tert-butoxide.
7. The process for producing 2- (benzothien-2-yl) benzo [ d ] oxazole derivative according to any one of claims 4 to 6, characterized in that the first intermediate is saponified to give a second intermediate, specifically: and dissolving the first intermediate in an organic solvent, adding alkali, heating to 30-80 ℃, reacting for 1-5 hours, and cooling to obtain a second intermediate.
8. The process for producing 2- (benzothien-2-yl) benzo [ d ] oxazole derivatives according to claim 6, characterized in that the organic solvent is ethanol, methanol, water or isopropyl alcohol; the alkali is sodium hydroxide, potassium hydroxide or lithium hydroxide; the condensing agent is PPA or concentrated sulfuric acid.
9. The process for producing 2- (benzothien-2-yl) benzo [ d ] oxazole derivative according to claim 6, characterized in that the second intermediate is reacted with a substituted o-aminophenol to obtain a 2- (benzothien-2-yl) benzo [ d ] oxazole derivative, which is characterized in that: dissolving the second intermediate in a condensing agent, adding phosphoric acid, and then adding substituted o-aminophenol, wherein the molar ratio of the substituted o-aminophenol to the second intermediate is 1.5-0.8: 1, heating to 100-160 ℃, reacting for 1-5 hours, and then treating to obtain the 2- (benzothiophen-2-yl) benzo [ d ] oxazole derivative.
10. Use of the 2- (benzothien-2-yl) benzo [ d ] oxazole derivative prepared according to any one of claims 4 to 9 for a synthetic drug, an organic electro-to-luminescent material, a polymer material or an organic flexible material.
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