A method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol

Abstract

A method for synthesizing 2-(benzothiazole-2-yl)-5-(hex-1-yne-1-yl)phenol, wherein p-iodosalicylic acid, o-aminothiophenol and triphenyl phosphite are used as raw materials, reacted under the catalysis of a catalyst, and 2-(benzothiazole-2-yl)-5-iodophenol is generated. 2-(benzothiazole-2-yl)-5-iodophenol and 1-hexyne are subjected to a Sonogashira coupling reaction under the action of a solvent, a catalyst and a base to obtain 2-(benzothiazole-2-yl)-5-(hex-1-yne-1-yl)phenol. The technical scheme provided by the present invention has higher safety of raw materials and synthesis process than the existing synthesis method, higher product yield and less impurities.

Description

Technical Field

[0001] The invention relates to the technical field of compound synthesis, in particular to a method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol. Background Art

[0002] Since Weller first reported the excited-state intramolecular proton transfer (ESIPT) phenomenon, the ESIPT of organic molecules has attracted widespread attention. Fluorophores based on the ESIPT property have significant advantages such as ultrafast reaction rate and ultra-large fluorescence shift, so they have great potential application value in optical devices.

[0003] Some rod-shaped small molecule liquid crystals with ESIPT properties are transparent in the visible light region and miscible with traditional small molecule mixed liquid crystals. These advantages allow them to omit a layer of polarizer when making liquid crystal display components, making them more energy-efficient. 2-(Benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol (abbreviated as C4-CH≡C-HBT) is one of them.

[0004] At present, C4-CH≡C-HBT is mainly synthesized by the following method: in the first step, iodosalicylic acid, o-aminothiophenol and phosphorus trichloride are used as raw materials for reflux reaction in toluene, and 2-(benzothiazol-2-yl)-5-iodophenol is obtained after post-treatment, and the yield is only 40%; in the second step, 2-(benzothiazol-2-yl)-5-iodophenol and 1-hexyne are subjected to Sonogashira coupling to obtain C4-CH≡C-HBT.

[0005] The phosphorus trichloride in the first step of the above method is relatively dangerous, the feed and reaction process must be strictly anhydrous, and the post-treatment hydrolysis reaction is violent, a large amount of HCl gas is generated, the process yield is low, and there are many impurities. Summary of the invention

[0006] The present invention aims to solve the shortcomings existing in the background technology and provide a method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol with safe raw materials, safe synthesis process and higher yield.

[0007] To achieve the above object, the present invention provides the following technical solutions:

[0008] The present invention provides a method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol, which specifically comprises the following steps:

[0009] Step 1: using p-iodosalicylic acid, o-aminothiophenol and triphenyl phosphite as raw materials, reacting under the catalysis of a catalyst to generate 2-(benzothiazol-2-yl)-5-iodophenol (abbreviated as I-HBT);

[0010] Step 2: 2-(Benzothiazol-2-yl)-5-iodophenol and 1-hexyne undergo Sonogashira coupling reaction in the presence of a solvent, a catalyst and a base to obtain 2-(Benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol (referred to as C4-C≡C-HBT);

[0011] The chemical synthesis reaction formula of the above synthesis step is:

[0012]

[0013] Furthermore, the catalyst in step 1 is any one of tetrabutylammonium bromide, tetrabutylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, or a combination of two or more thereof.

[0014] Preferably, the catalyst is tetrabutylammonium bromide.

[0015] Furthermore, in step 1, the reaction temperature is 60-150°C.

[0016] Preferably, the reaction temperature in step 1 is 110-130°C.

[0017] Beneficial effects of the present invention:

[0018] In the present application, triphenyl phosphite (P(OPh)3) is used instead of traditional phosphorus trichloride as a reaction raw material, thereby improving the safety of the raw materials and the synthesis process, and by adding a catalyst, the yield of the intermediate product 2-(benzothiazol-2-yl)-5-iodophenol is increased, and ultimately the yield of 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol is increased. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:

[0020] Figure 1 The H-NMR spectrum of (2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol prepared by the present invention. DETAILED DESCRIPTION

[0021] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work are within the scope of protection of the present invention.

[0022] The disclosure below provides many different embodiments or examples for realizing the technical scheme of the present invention. In order to simplify the disclosure of the present invention, different catalysts and different temperatures are used to describe specific examples below. Of course, they are merely examples, and the purpose is not to limit the present invention. In addition, the present invention can repeat reference numbers and / or reference letters in different examples. This repetition is for the purpose of simplification and clarity, and does not indicate the relationship between the various embodiments and / or settings discussed in itself. In addition, the present invention provides various specific examples of processes and materials, but those of ordinary skill in the art can be aware of the application of other processes and / or the use of other materials.

[0023] Example 1: Using tetrabutylammonium bromide as catalyst

[0024] Add 79.2g of p-iodosalicylic acid, 90.3g of triphenyl phosphite, 41.3g of o-aminothiophenol, and 150g of tetrabutylammonium bromide into a 500mL single-mouth bottle. After adding, heat to 120 degrees and stir to react for 1 hour. TLC is followed until the raw materials react. After cooling, slowly add 100mL of methanol, filter the reaction solution, rinse the solid with methanol, and dry to obtain 103.0g of light yellow solid 2-(benzothiazol-2-yl)-5-iodophenol, with a yield of 97.2%.

[0025] Under nitrogen protection, 53g of 2-(benzothiazole-2-yl)-5-iodophenol, 1g of cuprous iodide, 0.5g of tetrakis(triphenyl)phosphine palladium, 250mL of toluene, and 100mL of triethylamine were added to a 500mL three-necked flask. 12.3g of 1-hexyne was added dropwise at 35-40 degrees under stirring. After the addition was completed, the temperature was kept at 40-50 degrees for about 6 hours. TLC was followed until the reaction was completed. After cooling to room temperature, the reaction solution was slowly poured into 200ml of water under stirring, allowed to stand for separation, and then extracted twice with 100mL of toluene. The organic phases were combined, washed twice with 200mL of water, dried over anhydrous sodium sulfate, filtered off the desiccant, concentrated to dry solvent, and recrystallized to obtain a red solid with a yield of 85%.

[0026] Example 2: Using Tetrabutylammonium Chloride as Catalyst

[0027] Add 79.2g of p-iodosalicylic acid, 90.3g of triphenyl phosphite, 41.3g of o-aminothiophenol, and 150g of tetrabutylammonium chloride to a 500mL single-mouth bottle. After adding, heat to 120 degrees and stir to react for 1 hour. TLC is followed until the raw materials react. After cooling, slowly add 100mL of methanol, filter the reaction solution, rinse the solid with methanol, and dry to obtain 95.8g of light yellow solid 2-(benzothiazol-2-yl)-5-iodophenol with a yield of 90.5%.

[0028] Under nitrogen protection, 53g of 2-(benzothiazole-2-yl)-5-iodophenol, 1g of cuprous iodide, 0.5g of tetrakis(triphenyl)phosphine palladium, 250mL of toluene, and 100mL of triethylamine were added to a 500mL three-necked flask. 12.3g of 1-hexyne was added dropwise at 35-40 degrees under stirring. After the addition was completed, the temperature was kept at 40-50 degrees for about 6 hours. TLC was followed until the reaction was completed. After cooling to room temperature, the reaction solution was slowly poured into 200ml of water under stirring, and the solution was allowed to stand for separation. The solution was then extracted twice with 100mL of toluene, the organic phases were combined, washed twice with 200mL of water, dried over anhydrous sodium sulfate, the desiccant was filtered out, the dry solvent was concentrated, and a red solid was obtained by recrystallization with a yield of 83.4%.

[0029] Example 3: Effect of Temperature

[0030] Add 79.2g of p-iodosalicylic acid, 90.3g of triphenyl phosphite, 41.3g of o-aminothiophenol, and 150g of tetrabutylammonium bromide into a 500mL single-mouth bottle. After adding, heat to 150 degrees and stir to react for 1 hour. TLC is followed until the raw materials react. After cooling, slowly add 100mL of methanol, filter the reaction solution, rinse the solid with methanol, and dry to obtain 75.8g of yellow-brown solid 2-(benzothiazol-2-yl)-5-iodophenol, with a yield of 75.6%.

[0031] Under nitrogen protection, add 53g of the above-mentioned yellow-brown 2-(benzothiazole-2-yl)-5-iodophenol, 1g of cuprous iodide, 0.5g of tetrakis(triphenyl)phosphine palladium, 250mL of toluene, and 100mL of triethylamine in a 500mL three-necked flask. Add 12.3g of 1-hexyne dropwise at 35-40 degrees under stirring, keep at 40-50 degrees for about 6 hours after the addition is complete, track the reaction by TLC until the reaction is complete, cool to room temperature, slowly pour the reaction solution into 200ml of water under stirring, stand for separation, extract twice with 100mL of toluene, combine the organic phases, wash twice with 200mL of water, dry with anhydrous sodium sulfate, filter out the desiccant, concentrate the dry solvent, and recrystallize to obtain a red solid with a yield of 69.1%.

[0032] Comparative Example 1: Literature 1 (Zhang, W.; Sakurai, T.; Aotani, M.; Watanabe, G.; Yoshida, H.; Padalkar, VS; Tsutsui, Y.; Sakamaki, D.; Ozaki, M.; Seki, S., Adv. Opt. Mater. 2019, 7, 1801349.).

[0033] In this document, the following steps are used to synthesize 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol, and the specific synthesis steps are as follows:

[0034] The first step: using p-iodosalicylic acid, o-aminothiophenol and phosphorus trichloride as raw materials for reflux reaction in toluene, and post-processing to obtain 2-(benzothiazol-2-yl)-5-iodophenol, the yield is only 40%.

[0035] Step 2: 2-(Benzothiazol-2-yl-5-iodophenol and 1-hexyne are coupled by Sonogashira to obtain the product.

[0036] Compared with the comparative example, the yield of 2-(benzothiazol-2-yl)-5-iodophenol prepared in Examples 1 to 3 is much higher than that in the comparative example.

[0037] Compared with Example 2, when tetrabutylammonium bromide is used as the catalyst, the yield of 2-(benzothiazol-2-yl)-5-iodophenol is higher than that when tetrabutylammonium chloride is used as the catalyst.

[0038] Compared with Example 3, when the reaction temperature is 120°C, the yield of 2-(benzothiazol-2-yl)-5-iodophenol is higher than that when the reaction temperature is 150°C.

[0039] As can be seen from the above, the synthesis method provided in this scheme has a higher yield of 2-(benzothiazol-2-yl)-5-iodophenol than the existing synthesis method.

[0040] The above is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as above in the preferred embodiment, it is not used to limit the present invention. Any technician familiar with this profession can make equivalent embodiments with slight changes or modifications using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol, characterized in that: The specific steps include: Step 1: using p-iodosalicylic acid, o-aminothiophenol and triphenyl phosphite as raw materials, reacting under the catalysis of a catalyst to generate 2-(benzothiazol-2-yl)-5-iodophenol (abbreviated as I-HBT); Step 2: 2-(Benzothiazol-2-yl)-5-iodophenol and 1-hexyne undergo Sonogashira coupling reaction in the presence of a solvent, a catalyst and a base to obtain 2-(Benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol (abbreviated as C4-C≡C-HBT); The chemical synthesis reaction formula of the above synthesis step is: 。 2. A method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol, characterized in that: The catalyst in step 1 is any one of tetrabutylammonium bromide, tetrabutylammonium chloride, benzyltriethylammonium chloride, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, tetradecyltrimethylammonium chloride, or a combination of two or more thereof.

3. The method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol according to claim 2, characterized in that: The catalyst is tetrabutylammonium bromide.

4. The method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol according to claim 1, characterized in that: The reaction temperature in step 1 is 60-150°C.

5. The method for synthesizing 2-(benzothiazol-2-yl)-5-(hex-1-yn-1-yl)phenol according to claim 4, characterized in that: The reaction temperature in step 1 is 110-130°C.

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