One-pot preparation method of 2,5-diaryl substituted thiophenes
The one-pot synthesis of 2,5-diaryl substituted thiophenes using CuCl, TMEDA, and a solid superbase catalyst solved the problems of low yield and environmental pollution, achieving an efficient and environmentally friendly synthesis process.
Patent Information
- Application Number
- CN202311198173.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-09-18
- Publication Date
- 2025-09-19
- Estimated Expiration
- 2043-09-18
AI Technical Summary
The synthesis yield of 2,5-diaryl substituted thiophene in the existing technology is not high, and a large amount of flocculent complex by-products are produced during the reaction process, which increases the difficulty of separation and pollutes the environment.
A one-pot synthesis method was adopted, using CuCl and TMEDA as catalysts, combined with solid superbase and sulfur, to synthesize 2,5-diaryl substituted thiophenes under mild conditions. Through Glaser homocoupling reaction and cycloaddition reaction, the intermediate product separation step was reduced, and the reusable solid superbase catalyst was used to reduce environmental pollution.
The yield of 2,5-diaryl substituted thiophene was increased to 95%, the operation process was simplified, the synthesis cost and environmental pollution were reduced, and it was in line with the concept of green chemistry.
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Figure CN117486854B_ABST
Abstract
Description
Technical Field
[0001] The present invention belongs to the field of chemical engineering and relates to the technical field of organic luminescent material synthesis, and particularly relates to a one-pot preparation method of 2,5-diaryl substituted thiophene. Background Art
[0002] 2,5-Diaryl-substituted thiophenes have good optoelectronic properties and have important applications in the fields of organic semiconductors, organic field-effect transistors, organic light-emitting diodes, and solar cells. Especially in small molecule solar cell materials, 2,5-diaryl-substituted thiophenes can be used as π-electron connection units to effectively regulate the conjugation length and stacking mode of the molecule, thereby improving its energy conversion efficiency. Therefore, the synthesis of 2,5-diaryl-substituted thiophenes has received widespread attention.
[0003] Solid superbase refers to a solid alkaline substance with a base strength of ≥26.0, which has a very strong ability to donate or accept electrons at the active center and can effectively promote the formation of hydrogen anions (H - ) transfer. Solid superbases can effectively replace traditional alkaline catalysts such as NaOH, KOH, and NaNH2 for organic synthesis. They have stronger alkalinity, higher catalytic activity, and high activity. More importantly, they are reusable and environmentally friendly, making them a new type of environmentally friendly solid superbase catalyst.
[0004] Literature research shows that 2,5-diaryl-substituted thiophenes can be synthesized through Suzuki coupling reactions, Yamaoto reactions, and other methods. Guotingzhang and colleagues used 1,3-butadiyne and its derivatives with S8 under the catalysis of the strong base sodium tert-butoxide to undergo a cycloaddition reaction to form thiophene. When the terminal substituent of the 1,3-diyne is a thienyl group, 2,5-diaryl-substituted thiophene can be synthesized. However, the reaction conditions can achieve a yield of up to 92% for the synthesis of 2,5-diphenylthiophene from 1,4-diphenyl-1,3-diyne, while the yield of tertiary thiophene can only reach 63%. In addition, the reaction system cannot avoid the large amount of flocculent complex byproducts, which increases the difficulty of separation and causes serious environmental pollution during the separation process. Therefore, there is an urgent need to explore a green catalyst that can both improve the yield of 2,5-diaryl-substituted thiophenes and reduce environmental pollution. Summary of the Invention
[0005] The technical problem to be solved by the present invention is to provide a method for preparing 2,5-diaryl substituted thiophene with high yield, simple operation, mild reaction conditions and low environmental pollution.
[0006] To solve the above technical problems, the present invention provides a one-pot preparation method of 2,5-diaryl substituted thiophene, comprising the following steps:
[0007] 1) Add CuCl and TMEDA (tetramethylethylenediamine) to a mixed solvent, heat and stir at 50±10°C (heat and stir for about 2 minutes) to form a complex;
[0008] Then, an aromatic terminal alkyne is added, and the temperature is maintained at 50±10° C. and stirring is continued to perform a Glaser homocoupling reaction for 3 to 10 h (preferably 4 h) to obtain a reaction solution;
[0009] Cuprous chloride is 4.0-6.0 mol% (preferably 5.0 mol%) of the aryl terminal alkyne, and TMEDA is 8-12 mol% (preferably 10 mol%) of the aryl terminal alkyne;
[0010] Description: Cuprous chloride and TMEDA act together as catalysts;
[0011] 2) Synthesis of 2,5-diaryl substituted thiophene:
[0012] Add a solid superbase (as a catalyst) and 1 / 8 S8 (sulfur) to the reaction solution obtained in step 1), and stir the reaction at room temperature under a N2 atmosphere for 0.5 to 12 hours (for example, 5 hours);
[0013] The molar ratio of the aryl terminal alkyne: 1 / 8S8 is 1:1.2 to 3 (preferably 1:1.5);
[0014] The solid superbase is 15 to 50% (preferably 20 to 50%, more preferably 20 to 30%) of the weight of the aryl terminal alkyne;
[0015] After the reaction is completed, post-treatment is performed to obtain 2,5-diaryl substituted thiophene.
[0016] As an improvement to the one-pot preparation method of 2,5-diaryl substituted thiophene of the present invention:
[0017] The aromatic terminal alkyne is any one of the following: 2-ethynylthiophene, 2-ethynylpyridine, 3-ethynylpyridine, phenylacetylene, 1-ethynyl-3-benzyl, 1-ethynyl-2-benzyl, 1-bromo-4-ethynylbenzene, 1-chloro-4-ethynylbenzene, 1-fluoro-4-ethynylbenzene, 1-alkynyl-4-(trifluoromethyl)benzene, 4-ethynylbiphenyl;
[0018] The corresponding 2,5-diaryl substituted thiophenes are: α-terthiophene, 2,5-di(pyridin-2-yl)thiophene, 2,5-di(pyridin-3-yl)thiophene, 2,5-diphenylthiophene, 2,5-di-m-phenylmethylthiophene, 2,5-di-p-phenylmethylthiophene, 2,5-bis(4-bromophenyl)thiophene, 2,5-bis(4-chlorophenyl)thiophene, 2,5-bis(4-fluorophenyl)thiophene, 2,5-bis(4-(trifluoromethyl)phenyl)thiophene, and 2,5-bis([1,1'-biphenyl]-4-yl)thiophene.
[0019] As a further improvement of the one-pot preparation method of 2,5-diaryl substituted thiophene of the present invention:
[0020] The solid superbase in step 2) is at least one (one or more) of Na-MgO, Na / γ-Al2O3, NaOH / γ-Al2O3, KOH / γ-Al2O3, Na-NaOH / γ-Al2O3, K-KaOH / γ-Al2O3, Na-KaOH / γ-Al2O3, Na-Na2CO3 / γ-Al2O3, and K-K2CO3 / γ-Al2O3;
[0021] The solid superbase comprises the following components: 2-8 parts by weight of alkali metal (Na, K), 15-25 parts by weight of MOH (NaOH, KOH, KaOH), 15-25 parts by weight of M2CO3 (Na2CO3, K2CO3), and 100 parts by weight of γ-Al2O3.
[0022] As a further improvement of the one-pot preparation method of 2,5-diaryl substituted thiophene of the present invention: post-treatment: After the reaction is completed, filtration is performed, and the filter cake is a reusable solid superbase (as a catalyst). Water is added to the obtained filtrate for extraction, and then ethyl acetate is added for back extraction. The ethyl acetate organic phase is taken and separated by column chromatography to obtain 2,5-diaryl substituted thiophene.
[0023] As a further improvement of the one-pot preparation method of 2,5-diaryl substituted thiophene of the present invention: in step 1)
[0024] The mixed solvent consists of DMSO and ethanol, with a volume ratio of DMSO:ethanol = 2:1-5:1 (preferably 3:1).
[0025] As a further improvement to the one-pot preparation method of 2,5-diaryl substituted thiophene of the present invention: 8 to 12 mL of ethanol is used for every 10 mmol of aryl terminal alkyne.
[0026] In the present invention:
[0027] The conversion rate of the terminal aromatic alkyne in step (1) is 93-99%, the conversion rate of 1,4-(diaryl-yl)but-1,3-diyne in step (2) is 92%-99%, and the isolated yield is 90%-95%.
[0028] The one-pot preparation method of 2,5-diaryl substituted thiophene provided by the present invention has good applicability and can be used to synthesize 2,5-di(pyridin-2-yl)thiophene from 2-ethynylpyridine, synthesize 2,5-di(pyridin-3-yl)thiophene from 3-ethynylpyridine, synthesize 2,5-diphenylthiophene from phenylacetylene, synthesize 2,5-di-m-benzylthiophene from 1-ethynyl-3-benzyl, and synthesize 2,5-di-p-phenylthiophene from 1-ethynyl-2-benzyl. methylthiophene, the synthesis of 2,5-bis(4-bromophenyl)thiophene from 1-bromo-4-ethynylbenzene, the synthesis of 2,5-bis(4-chlorophenyl)thiophene from 1-chloro-4-ethynylbenzene, the synthesis of 2,5-bis(4-fluorophenyl)thiophene from 1-fluoro-4-ethynylbenzene, the synthesis of 2,5-bis(4-(trifluoromethyl)phenyl)thiophene from 1-alkynyl-4-(trifluoromethyl)benzene, and the synthesis of 2,5-bis([1,1'-biphenyl]-4-yl)thiophene from 4-ethynylbiphenyl.
[0029] Compared with the prior art, the technical solution of the present invention has the following beneficial technical effects:
[0030] The present invention provides a method for preparing 2,5-diaryl substituted thiophenes using a one-pot process, using an aryl-terminal alkyne as the starting material, thereby reducing synthesis costs. The separation step of the intermediate Glaser homo-coupling product is eliminated; namely, the reaction solution obtained in step 1) is directly used in step 2). This simplifies the operation, reduces environmental pollution, and further reduces production costs.
[0031] 2. The present invention provides a method for preparing 2,5-diaryl substituted thiophene, which uses a solid superbase as a catalyst. The yield of 2,5-diaryl substituted thiophene can be as high as 95% under mild conditions. While showing good catalytic activity, the catalyst can be reused, separation is simpler, and the salt content in the wastewater during the extraction process can be reduced, thereby reducing environmental pollution and complying with the concept of green chemistry.
[0032] Specifically: In the prior art, sodium tert-butoxide, KOH, etc. are used as strong base catalysts, which are homogeneous catalysts; while the present invention uses a solid superbase as a catalyst, which has stronger alkalinity and catalytic activity, and is a heterogeneous catalysis with a different catalytic mechanism; the present invention uses a solid superbase as a catalyst, which is different from homogeneous catalysts such as sodium tert-butoxide and KOH that are soluble in solvents, can be recycled, and is more environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS
[0033] The specific embodiments of the present invention are further described in detail below with reference to the accompanying drawings.
[0034] Figure 1 This is a flow chart of the one-pot preparation method of 2,5-diaryl substituted thiophene in Example 1. DETAILED DESCRIPTION
[0035] Below in conjunction with accompanying drawing and embodiment, the present invention is described in further detail, and these embodiment are only used for illustrating the present invention and do not limit the scope of the present invention.In addition, it should be understood that after reading the content of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope limited by the appended claims of the application.
[0036] In the present invention:
[0037] TMEDA: tetramethylethylenediamine;
[0038] DMSO: dimethyl sulfoxide;
[0039] EtOH: ethanol;
[0040] 1 / 8S8: Sulfur.
[0041] t BuOH: tert-butyl alcohol;
[0042] t BuONa: sodium tert-butoxide.
[0043] The solid superbase catalysts of the present invention are all known substances and can be prepared, for example, by referring to "Study on Self-Aldol Condensation Reaction of Cyclopentanone Catalyzed by Solid Superbase" and the like.
[0044] Example 1: Preparation of α-terthiophene using a one-pot method:
[0045] (1) Synthesis of 1,4-(thiophen-2-yl)butane-1,3-diyne
[0046] 0.0500 g (0.5 mmol) of CuCl, 0.15 mL (1 mmol) of TMEDA, 30 mL of DMSO, and 10 mL of ethanol were weighed separately and added to a 50 mL round-bottom flask. The mixture was heated to 50° C. in air and stirred for 2 min to form a complex. 1.0826 g (10.00 mmol) of 2-ethynylthiophene was then added, and the temperature was maintained and stirred, i.e., the reaction was carried out at 50° C. for 4 h to obtain a reaction solution containing 1,4-(thiophen-2-yl)butane-1,3-diyne (about 9.8 mmol).
[0047] 2-Ethynylthiophene, that is, 2-ethynylthiophene.
[0048] (2) Synthesis of terthiophene
[0049] To the reaction solution containing 1,4-di(thiophen-2-yl)butane-1,3-diyne, 0.4826 g (15 mmol) of 1 / 8 S8 and 20% (20 wt%) of NaOH / γ-Al2O3 were added. The mixture was stirred at 25°C under N2 atmosphere and reacted for 5 h.
[0050] NaOH / γ-Al2O3 is a solid superbase catalyst composed of NaOH and γ-Al2O3. Its preparation method can be referred to "Study on the Self-Aldol Condensation Reaction of Cyclopentanone Catalyzed by Solid Superbase", where the mass ratio of NaOH to γ-Al2O3 is 20:100.
[0051] After the reaction is completed, post-processing is carried out as follows:
[0052] Filtration (thereby separating the solid superbase catalyst), the filter cake obtained is a reusable solid superbase catalyst, 20 mL of water is first added to the obtained filtrate for extraction, and then 10 mL of ethyl acetate is directly added for back extraction 3 times, the ethyl acetate organic phase is taken, 4 g of 200-300 mesh silica gel is added, spin-dried, dry-loaded, and separated by column chromatography. The column chromatography separation is specifically as follows:
[0053] The silica gel phase loaded with the product was loaded onto a chromatographic column filled with 200-300 mesh silica gel and eluted with sufficient pure petroleum ether (PE) (until the product was no longer detected in the eluate), and then rotary evaporated and dried to constant weight to obtain 2.03 g of solid α-terthiophene, with a yield of 82%.
[0054] The yield is calculated as follows: actual mass of α-terthiophene obtained / theoretical mass of α-terthiophene obtained.
[0055] Example 2: Preparation of α-terthiophene using a one-pot method:
[0056] The "NaOH / γ-Al2O3" in step 2) of Example 1 was changed to "Na-NaOH / γ-Al2O3", and the weight ratio to 2-ethynylthiophene remained unchanged at 20%; the rest was the same as Example 1.
[0057] The mass ratio of Na, NaOH and γ-Al2O3 in the Na-NaOH / γ-Al2O3 is 6:20:100.
[0058] 2.36 g of solid α-terthiophene were obtained, so the yield was 95%.
[0059] Example 3: Preparation of α-terthiophene using a one-pot method:
[0060] The "NaOH / γ-Al2O3" in step 2) of Example 1 was changed to "Na-Na2CO3 / γ-Al2O3", and the weight ratio to 2-ethynylthiophene remained unchanged at 20%; the rest was the same as Example 1.
[0061] The mass ratio of Na, Na2CO3 and γ-Al2O3 in Na-Na2CO3 / γ-Al2O3 is 6:20:100.
[0062] 2.33 g of solid α-terthiophene was obtained, so the yield was 94%.
[0063] Example 4: Preparation of α-terthiophene using a one-pot method:
[0064] The "Na-NaOH / γ-Al2O3" in step 2) of Example 2 was replaced with the solid superbases described in Table 1 below; the weight ratio to 2-ethynylthiophene remained unchanged at 20%; and the rest was the same as in Example 2.
[0065] The yield of solid α-terthiophene is shown in Table 1 below.
[0066] Table 1
[0067]
[0068] Example 5: Preparation of α-terthiophene using a one-pot method:
[0069] The amount of "Na-NaOH / γ-Al2O3" added in step 2) of Example 2 was changed from 20 wt% (i.e., 20% by weight of 2-ethynylthiophene) to that described in Table 2 below; the rest was the same as in Example 2.
[0070] The yield of solid α-terthiophene is shown in Table 2 below.
[0071] Table 2
[0072]
[0073] Example 6: Reuse of catalyst
[0074] The filter cake obtained by filtration in step 2) of Example 2 was directly used as a solid superbase catalyst;
[0075] That is, the "20 wt% Na-NaOH / γ-Al2O3" in step 2) of Example 2 was replaced with "the filter cake obtained by filtration in step 2) of Example 2". The rest was the same as in Example 2. This was the first reuse of the solid superbase catalyst.
[0076] And so on, until the solid superbase catalyst is reused for the third time.
[0077] The comparison of the obtained results with Example 2 is as follows:
[0078] Table 3
[0079]
[0080] Example 7: Synthesis of other 2,5-diaryl substituted thiophenes:
[0081] The "2-ethynylthiophene" in step 2) of Example 2 was changed to that described in Table 4 below, and the molar amount was the same as that of Example 2; the developing solvent used in the post-treatment was changed accordingly, and the rest was the same as that of Example 2.
[0082] The yields of 2,5-diaryl substituted thiophenes are shown in Table 2 below.
[0083] Table 2
[0084]
[0085]
[0086] Description: The product obtained by the present invention has been conventional 1 H NMR and 13 C NMR spectrum verification, thus proving the correctness of the product.
[0087] Comparative Example 1
[0088] In step 1) of Example 1, “10 mL of ethanol” was replaced with “ t BuOH 10 mL", the rest is the same as step 1 of Example 1);
[0089] (2) Synthesis of α-terthiophene
[0090] 1 / 8 S8 0.4826 g (15 mmol) was added to the reaction solution containing 1,4-di(thiophen-2-yl)butane-1,3-diyne, t BuONa 2.8833 g (30 mmol) was added and stirred at 25° C. under N 2 atmosphere for 5.0 h.
[0091] After the reaction is completed, dilute with hydrochloric acid (6 mL, 2.0 M), add 20 mL of water for extraction, and then directly add 10 mL of ethyl acetate for back extraction 3 times. Take the ethyl acetate organic phase, add 4 g of 200-300 mesh silica gel, spin dry, dry-load, and separate by column chromatography. The column chromatography separation is specifically as follows:
[0092] The silica gel phase loaded with the product was placed on a chromatographic column filled with 200-300 mesh silica gel, eluted with sufficient pure petroleum ether, and then rotary evaporated and dried to constant weight to obtain 1.39 g of solid α-terthiophene, so the yield was 56%.
[0093] Comparative Example 2
[0094] Step 1) is the same as step 1) of Example 1;
[0095] (2) Synthesis of terthiophene
[0096] 0.4826 g (15 mmol) of 1 / 8 S8 and 1.6834 g (30 mmol) of KOH were added to the reaction solution containing 1,4-di(thiophen-2-yl)butane-1,3-diyne, and the mixture was stirred at 25° C. under N 2 atmosphere and reacted for 5.0 h.
[0097] After the reaction is completed, dilute with hydrochloric acid (6 mL, 2.0 M), add 20 mL of water for extraction, and then directly add 10 mL of ethyl acetate for back extraction 3 times. Take the ethyl acetate organic phase, add 4 g of 200-300 mesh silica gel, spin dry, dry-load, and separate by column chromatography. The column chromatography separation is specifically as follows:
[0098] The silica gel phase loaded with the product was placed on a chromatographic column filled with 200-300 mesh silica gel, eluted with pure petroleum ether, and then rotary evaporated and dried to constant weight to obtain 0.819 g of solid α-terthiophene, so the yield was 33%.
[0099] Finally, it should be noted that the above examples are merely specific embodiments of the present invention. Obviously, the present invention is not limited to the above examples and is subject to numerous variations. All variations that can be directly derived or conceived by a person of ordinary skill in the art from the disclosure of the present invention are considered to be within the scope of protection of the present invention.
Claims
1. A one-pot preparation method for 2,5-diaryl substituted thiophene, characterized in that The following steps are involved: 1) Add CuCl and TMEDA to a mixed solvent, heat and stir at 50±10°C to form a complex; Then, an aromatic terminal alkyne is added, and the temperature is maintained at 50±10°C and stirring is continued to perform a Glaser homocoupling reaction for 3 to 10 hours to obtain a reaction solution; Cuprous chloride is 4.0-6.0 mol% of the aryl terminal alkyne, and TMEDA is 8-12 mol% of the aryl terminal alkyne; The mixed solvent consists of DMSO and ethanol, with a volume ratio of DMSO:ethanol = 2:1 to 5:1; 2) Synthesis of 2,5-diaryl substituted thiophene: Add solid superbase and 1 / 8 S8 to the reaction solution obtained in step 1), and stir the reaction under N2 atmosphere at room temperature for 0.5 to 12 hours; The molar ratio of the aryl terminal alkyne: 1 / 8S8 is 1:1.2-3; The solid superbase is 20 to 50% by weight of the aryl terminal alkyne; After the reaction is completed, post-treatment is performed to obtain 2,5-diaryl substituted thiophene; The solid superbase is at least one of Na / γ-Al2O3, NaOH / γ-Al2O3, KOH / γ-Al2O3, Na-NaOH / γ-Al2O3, K-KaOH / γ-Al2O3, Na-KaOH / γ-Al2O3, Na-Na2CO3 / γ-Al2O3, and K-K2CO3 / γ-Al2O3; The solid superbase comprises 2-8 parts by weight of alkali metal, 15-25 parts by weight of MOH, 15-25 parts by weight of M2CO3, and 100 parts by weight of γ-Al2O3; Alkali metal is Na or K; MOH is NaOH, KOH or KaOH, and M2CO3 is Na2CO3 or K2CO3.
2. The one-pot preparation method of 2,5-diaryl substituted thiophene according to claim 1, characterized in that: The aromatic terminal alkyne is any one of the following: 2-ethynylthiophene, 2-ethynylpyridine, 3-ethynylpyridine, phenylacetylene, 1-ethynyl-3-benzyl, 1-ethynyl-2-benzyl, 1-bromo-4-ethynylbenzene, 1-chloro-4-ethynylbenzene, 1-fluoro-4-ethynylbenzene, 1-alkynyl-4-(trifluoromethyl)benzene, 4-ethynylbiphenyl; The corresponding 2,5-diaryl substituted thiophenes are: α-terthiophene, 2,5-di(pyridin-2-yl)thiophene, 2,5-di(pyridin-3-yl)thiophene, 2,5-diphenylthiophene, 2,5-di-m-phenylmethylthiophene, 2,5-di-p-phenylmethylthiophene, 2,5-bis(4-bromophenyl)thiophene, 2,5-bis(4-chlorophenyl)thiophene, 2,5-bis(4-fluorophenyl)thiophene, 2,5-bis(4-(trifluoromethyl)phenyl)thiophene, and 2,5-bis([1,1'-biphenyl]-4-yl)thiophene.
3. The one-pot preparation method of 2,5-diaryl substituted thiophene according to claim 1 or 2, characterized in that The post-treatment is as follows: after the reaction is completed, filtering is performed, and the filter cake obtained is a reusable solid superbase. Water is added to the obtained filtrate for extraction, and then ethyl acetate is added for back extraction. The ethyl acetate organic phase is taken and separated by column chromatography to obtain 2,5-diaryl substituted thiophene.
4. The one-pot preparation method of 2,5-diaryl substituted thiophene according to claim 3, characterized in that: For every 10 mmol of aryl terminal alkyne, 8-12 mL of ethanol was used.