Preparation method of tetrathiafulvalene
By optimizing the synthesis route of tetrathiofulvalene, intermediate 3 was prepared in a one-pot method and intermediate 5 was synthesized into tetrathiofulvalene in one step, which solved the problems of long synthesis routes and high costs in the existing technology and achieved efficient and low-cost preparation of tetrathiofulvalene.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- SUZHOU YUANQI MATERIAL TECH CO LTD
- Filing Date
- 2026-01-27
- Publication Date
- 2026-05-19
AI Technical Summary
Existing synthetic routes for tetrathione fulvalene are lengthy, and the intermediates have poor stability, resulting in excessively long production cycles and high costs, making it difficult to achieve efficient and low-cost preparation.
The synthesis route of tetrathiofulvalene was optimized by preparing intermediate 3 in a one-pot process, which shortened the reaction time, simplified the operation process, avoided the intermediate purification step, and completed the synthesis of tetrathiofulvalene from intermediate 5 in one step, simplifying the operation and improving the synthesis efficiency.
It significantly shortens the synthesis time, reduces costs, and increases yield and production efficiency. The purity of the synthesized product reaches 98.0%-98.6%, and the total yield is over 58%.
Smart Images
Figure CN122059925A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of tetrathiofulvalene synthesis technology, and specifically to a method for preparing tetrathiofulvalene. Background Technology
[0002] Tetrathiofulvalene (TTF) and its derivatives play important roles in various fields such as molecular electronics, supramolecular chemistry, macrocyclic chemistry, and optical materials due to their unique physical properties and structures. Tetrathiofulvalene chloride salts exhibit high conductivity, and the conductivity of its TCNQ salt increases abruptly below room temperature, reaching 10 at 60 K. 4 Ω -1 •cm -1 It is sufficient to be called an "organometallic". The Bechgaard salt [TMTSF]2X (where X is PF) based on tetrathiofulvalene is... 6- AsF 6- As the first molecular superconductor to be synthesized, it has generated great interest in this field.
[0003] Currently, the synthesis of tetrathione fulvalene derivatives mostly uses tetrathione as a starting material, undergoing a metallization reaction to obtain a series of derivatives. However, tetrathione fulvalene is expensive and has a low yield, necessitating the development of a low-cost, high-yield method for synthesizing TTF. The main synthetic method for tetrathione fulvalene uses carbon disulfide and piperidine as starting materials to synthesize TTF, and the reaction process is as follows:
[0004] .
[0005] However, this route has many drawbacks: it is a long route with up to 8 reaction steps, and some intermediates have poor stability; the reaction time is long, requiring 4 days to synthesize intermediate 4 and 2 days to synthesize intermediate 5, resulting in an excessively long production cycle and difficulty in ensuring process stability.
[0006] Based on the above issues, further optimization of the above reaction routes can shorten the reaction time of longer reactions to within 20 hours, which is of great significance for reducing costs and improving production efficiency. Summary of the Invention
[0007] This invention addresses the shortcomings of existing technologies by providing a method for preparing tetrathiofulvalene. The existing synthetic route for tetrathiofulvalene is optimized and improved. By changing the route and improving the reaction conditions, the synthesis efficiency and production capacity of tetrathiofulvalene are greatly improved, while reducing energy consumption and cost.
[0008] To address the aforementioned technical problems, this invention provides a method for preparing tetrathiofulvalene, comprising the following steps:
[0009] S1. In an organic solvent, piperidine, carbon disulfide and a basic sodium-containing compound are mixed and reacted to generate intermediate 1, which is then reacted with bromoacetaldehyde ethylene glycol to obtain intermediate 2.
[0010] S2. The intermediate 2 is reacted with concentrated sulfuric acid and hexafluorophosphorus to obtain intermediate 3;
[0011] S3. Intermediate 3 and sodium borohydride react in an organic solvent to obtain intermediate 4;
[0012] S4. The intermediate 4, acetic anhydride and hexafluorophosphoric acid are reacted in an organic solvent to obtain intermediate 5;
[0013] S5. The intermediate 5 and the base react in an organic solvent to obtain the tetrathiofulvalene; the reaction route is as follows:
[0014] .
[0015] In the synthetic route of this invention, the reaction conditions of the preparation process from intermediate 2 to intermediate 3 are adjusted to prepare intermediate 3 in a one-pot process, avoiding the intermediate purification step required in the preparation process of intermediate 2 to intermediate 3 in the prior art, thus shortening the synthesis time and greatly improving efficiency; the synthetic route from intermediate 5 to tetrathiofulvalene is adjusted to be completed in one step, avoiding the step of converting hexafluorophosphate into iodide, further improving the synthesis efficiency; in addition, the reaction conditions of intermediate 4 are adjusted to shorten the reaction time and improve the formation efficiency.
[0016] Furthermore, in step S2, the reaction of intermediate 2 with concentrated sulfuric acid and hexafluorophosphorus specifically involves: under a protective atmosphere, concentrated sulfuric acid and intermediate 2 react at 100-120°C, then the temperature is lowered to 0-25°C, and the mixture is mixed with water and hexafluorophosphorus to obtain intermediate 3. This reaction process is completed in a one-pot manner, eliminating the extraction process of the product obtained in intermediate steps, greatly shortening the reaction time, improving the synthesis efficiency, and reducing costs; at the same time, the purification step is omitted, simplifying the operation, saving a large amount of purification solvent, reducing solvent consumption, and further reducing costs.
[0017] Furthermore, in S2, the molar ratio of intermediate 2 to concentrated sulfuric acid and hexafluorophosphorus is 1:(4-8):(1-1.2).
[0018] Furthermore, in S5, the base is selected from one or more of triethylamine, sodium carbonate, and potassium carbonate.
[0019] Furthermore, in step S5, the molar ratio of the intermediate to the base is 1:(1.1-1.3), and the reaction temperature is 0-25℃. This step adjusts the synthetic route, completing the synthesis of intermediate 5 to tetrathiofulvalene in one step, simplifying the operation and improving the synthesis efficiency.
[0020] Furthermore, in S1, the alkaline sodium-containing compound is selected from sodium hydroxide and / or sodium phosphate; the molar ratio of piperidine, carbon disulfide and alkaline sodium-containing compound is 1:(1-1.2):(1-1.5).
[0021] Furthermore, the temperatures for the two-step reactions in S1 are independently selected from 60-100℃.
[0022] Furthermore, in S3, the molar ratio of intermediate 3 to sodium borohydride is 1:(1-1.2).
[0023] Furthermore, in S4, the molar ratio of intermediate 4, acetic anhydride and hexafluorophosphate is 1:(11-14):(2.2-2.5).
[0024] Furthermore, the reaction temperature in S3 is 20-25℃ and the time is 3-6h, which optimizes the reaction conditions and greatly shortens the synthesis time; the reaction temperature in S4 is -10~0℃.
[0025] Furthermore, in S1, the organic solvent is selected from one or more of anhydrous ethanol, methanol, and isopropanol.
[0026] Furthermore, in S3, the organic solvent is selected from one or more of tetrahydrofuran, ethanol, isopropanol, and methanol.
[0027] Furthermore, in S4, the organic solvent is selected from tetrahydrofuran and / or diethyl ether.
[0028] Furthermore, in S5, the organic solvent is selected from one or more of anhydrous acetonitrile, dichloromethane, DMF (N,N-dimethylformamide) and DMSO (dimethyl sulfoxide).
[0029] The beneficial effects of this invention are:
[0030] The present invention adjusts the reaction conditions of the preparation process of intermediate 2 to intermediate 3 in the synthetic route, and prepares intermediate 3 in a one-pot method, avoiding the intermediate purification step required in the preparation process of intermediate 2 to intermediate 3 in the prior art, shortening the synthesis time and greatly improving efficiency.
[0031] This invention modifies the synthesis route of intermediate 5 to tetrathiofulvalene, completing the process in one step and avoiding the step of converting hexafluorophosphate into iodide, thus further improving the synthesis efficiency.
[0032] This invention adjusts the reaction conditions of intermediate 4, shortens the reaction time, and improves the production efficiency. Attached Figure Description
[0033] To more clearly illustrate the technical solution of the present invention, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0034] Figure 1 This is the NMR spectrum of intermediate 2 obtained in Example 1 of the present invention;
[0035] Figure 2 This is the NMR spectrum of intermediate 3 obtained in Example 1 of the present invention;
[0036] Figure 3 This is the NMR spectrum of tetrathiofulvalene obtained in Example 1 of the present invention. Detailed Implementation
[0037] The technical solution of the present invention will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0038] This embodiment relates to a method for preparing tetrathiofulvalene, comprising the following steps:
[0039] S1. In an organic solvent, piperidine, carbon disulfide and a basic sodium-containing compound are mixed and reacted to generate intermediate 1, which is then reacted with bromoacetaldehyde ethylene glycol to obtain intermediate 2.
[0040] S2. The intermediate 2 is reacted with concentrated sulfuric acid and hexafluorophosphorus to obtain intermediate 3;
[0041] S3. Intermediate 3 and sodium borohydride react in an organic solvent to obtain intermediate 4;
[0042] S4. The intermediate 4, acetic anhydride and hexafluorophosphoric acid are reacted in an organic solvent to obtain intermediate 5;
[0043] S5. The intermediate 5 and the base react in an organic solvent to obtain the tetrathiofulvalene; the reaction route is as follows:
[0044] .
[0045] In this embodiment, the reaction conditions for the preparation of intermediates 2 to 3 are adjusted to prepare intermediate 3 in a one-pot process, avoiding the intermediate purification step required in the preparation of intermediates 2 to 3 in the prior art, thus shortening the synthesis time and greatly improving efficiency. The synthesis route for intermediate 5 to tetrathiofulvalene is adjusted to be completed in one step, avoiding the step of converting hexafluorophosphate into iodide, further improving the synthesis efficiency. In addition, the reaction conditions for intermediate 4 are adjusted to shorten the reaction time and improve the generation efficiency.
[0046] In a preferred embodiment, in step S2, the reaction of intermediate 2 with concentrated sulfuric acid and hexafluorophosphorus specifically involves: under a protective atmosphere, concentrated sulfuric acid and intermediate 2 react at 100-120°C, then the temperature is lowered to 0-25°C, and the mixture is mixed with water and hexafluorophosphorus to obtain intermediate 3. This reaction process is completed in a one-pot manner, eliminating the extraction process of the product obtained in intermediate steps, greatly shortening the reaction time, improving the synthesis efficiency, and reducing costs; at the same time, the purification step is omitted, simplifying the operation, saving a large amount of purification solvent, reducing solvent consumption, and further reducing costs. Preferably, the molar ratio of intermediate 2 to concentrated sulfuric acid and hexafluorophosphorus is 1:(4-8):(1-1.2).
[0047] In a preferred embodiment, in step S5, the base is selected from one or more of triethylamine, sodium carbonate, and potassium carbonate. Preferably, the molar ratio of the intermediate to the base is 1:(1.1-1.3), and the reaction temperature is 0-25°C. This step adjusts the synthetic route, completing the synthesis of intermediate 5 to tetrathiofulvalene in one step, simplifying the operation and improving the synthesis efficiency.
[0048] In a preferred embodiment, in S1, the alkaline sodium-containing compound is selected from sodium hydroxide and / or sodium phosphate; the molar ratio of piperidine, carbon disulfide, and the alkaline sodium-containing compound is 1:(1-1.2):(1-1.5). Preferably, the temperatures of the two reactions in S1 are independently selected from 60-100°C.
[0049] In a preferred embodiment, in step S3, the molar ratio of intermediate 3 to sodium borohydride is 1:(1-1.2). Preferably, the reaction temperature is 20-25°C and the reaction time is 3-6 hours, thus optimizing the reaction conditions and significantly shortening the synthesis time.
[0050] In a preferred embodiment, in step S4, the molar ratio of intermediate 4, acetic anhydride, and hexafluorophosphoric acid is 1:(11-14):(2.2-2.5). Preferably, the reaction temperature is -10 to 0°C.
[0051] In a preferred embodiment, in S1, the organic solvent is selected from one or more of anhydrous ethanol, methanol, and isopropanol. In S3, the organic solvent is selected from one or more of tetrahydrofuran (THF), ethanol, isopropanol, and methanol. In S4, the organic solvent is selected from tetrahydrofuran and / or diethyl ether. In S5, the organic solvent is selected from one or more of anhydrous acetonitrile, dichloromethane, DMF (N,N-dimethylformamide), and DMSO (dimethyl sulfoxide).
[0052] Example 1
[0053] This embodiment relates to a method for preparing tetrathiofulvalene, comprising the following steps:
[0054] (1) Under a nitrogen atmosphere, piperidine (2.56 kg, 30.06 mol) and ethanol (10.0 L) were added to a 50 L reactor. The temperature was lowered to 0 °C, and sodium hydroxide (1.2 kg, 30.06 mol) was added in batches. After the addition was complete, the temperature was lowered to -5 °C, and carbon disulfide (2.29 kg, 30.06 mol) was slowly added dropwise. After the addition was complete, the temperature was maintained for 1 h, and then the temperature was raised to 80 °C and refluxed for 2 h to obtain intermediate 1. Under reflux conditions, ethylene glycol bromoacetaldehyde (5.93 kg, 30.06 mol) was slowly added dropwise, and after the addition was complete, the reaction was refluxed for 6 h. The reaction endpoint was monitored by TLC, and the temperature was lowered to room temperature. 15 L of water was added to precipitate the solid, which was filtered, washed with water, and the crude intermediate 2 was obtained. Add 18 L of n-hexane and crude intermediate 2 to a 50 L reactor. Heat to 45 ± 5 °C and stir to dissolve crude intermediate 2. Separate the lower aqueous phase and cool to 5 °C to induce crystallization. Filter, wash with n-hexane, and dry the filter cake to obtain 7.8 kg of solid intermediate 2, yield 93%. NMR spectrum is shown below. Figure 1 .
[0055] (2) Under a nitrogen atmosphere, concentrated sulfuric acid (13.79 kg, 140.57 mol) was added to a 20 L reactor. The temperature was lowered to 0 °C, and intermediate 2 (7.80 kg, 28.11 mol) was added in batches. After the addition was complete, the temperature was raised to 105 °C and reacted for 24 h to obtain reaction solution A. The reaction endpoint was monitored by TLC, and the temperature was lowered to room temperature. 25 L of water was added to a 50 L reactor, the temperature was lowered to 5 °C, and a 60% aqueous solution of HPF6 (6.50 kg, 28.11 mol) was added dropwise. The temperature was controlled at 10 °C and reaction solution A was added dropwise. Solid precipitated out, and the mixture was stirred at room temperature for 2 h. The mixture was filtered, and the filter cake was washed with water to obtain crude intermediate 3. Crude intermediate 3 was added to a 50 L reactor and dissolved in 25 L of dichloromethane and stirred for 2 h. The mixture was filtered, and the filter cake was dried to obtain 8.3 kg of solid intermediate 3, with a yield of 89%. The NMR spectrum is shown in [reference needed]. Figure 2 .
[0056] (3) Under a nitrogen atmosphere, intermediate 3 (4.00 kg, 12.07 mol), 16 L of isopropanol, and 16 L of anhydrous THF were added to a 50 L reactor. The temperature was lowered to 0 °C, and sodium borohydride (502.48 g, 13.28 mol) was added in batches, and the system gradually became clear. After the addition was complete, the reaction was brought back to room temperature (25 °C) for 3 h, and the reaction endpoint was monitored by TLC. The reaction was quenched with dilute hydrochloric acid, and the pH of the reaction solution was adjusted to neutral. The reaction solution was concentrated to 9 L, and 25 L of water and 8 L of methyl tert-butyl ether were added and stirred for 0.5 h. The mixture was separated, and the aqueous phase was extracted a second time with 8 L of methyl tert-butyl ether. The mixture was separated, and the crude intermediate 4 was obtained. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain 2 kg of liquid, with a yield of 90%.
[0057] (4) Under a nitrogen atmosphere, acetic anhydride (12.75 kg, 124.92 mol) was added to a 50 L reactor. The temperature was lowered to -5 °C, and a 60% aqueous solution of HPF6 (5.61 kg, 23.06 mol) was slowly added dropwise. After the addition was complete, the current temperature was maintained for 1 h. Then, intermediate 4 (1.80 kg) was dissolved in 10 L of a mixture of tetrahydrofuran and slowly added dropwise to the reaction system, and a solid gradually precipitated out. After the addition was complete, 20 L of tetrahydrofuran was added, the mixture was restored to room temperature, and the reaction was stirred for 3 h. The mixture was filtered, washed with tetrahydrofuran, and the filter cake was dried to obtain 2.17 kg of off-white solid, with a yield of 91%.
[0058] (5) Under a nitrogen atmosphere, intermediate 5 (1.85 kg, 7.46 mol) and 11 L of anhydrous acetonitrile were added to a 50 L reactor. The temperature was lowered to -5 °C, and an aqueous solution of triethylamine (905.33 kg, 8.95 mol) was slowly added dropwise. After the addition was complete, the reaction was allowed to return to room temperature for 1 h. The reaction endpoint was monitored by TLC, and 27 L of water was added and stirred for 1 h. The mixture was filtered, and the filter cake was washed with water. The filter cake was dissolved in 25 L of dichloromethane in a 50 L reactor, and the organic phase was washed with water and saturated brine, respectively. The mixture was dried with anhydrous sodium sulfate and concentrated to dryness. 13 L of cyclohexane was added, and the mixture was heated to reflux to dissolve the material. The mixture was hot filtered, washed with n-hexane, and slowly cooled to room temperature with stirring to crystallize for 4 h. The mixture was filtered, washed with n-hexane, and dried to obtain 1.32 kg of orange solid tetrathiofulvalene, with a yield of 86%. The NMR spectrum is shown in [reference needed]. Figure 3 .
[0059] Example 2
[0060] The difference between this embodiment and Example 1 is that the equivalent ratio of intermediate 2 and concentrated sulfuric acid is adjusted, while other steps and parameters remain unchanged. The yield of intermediate 3 is calculated, and the specific parameters are shown in Table 1.
[0061] Table 1
[0062]
[0063] As shown in Table 1, the yield is better when the equivalent ratio of intermediate 2 to concentrated sulfuric acid is 1:(4-8).
[0064] Example 3
[0065] The difference between this embodiment and Example 1 is that the reaction temperature and reaction time are adjusted, while other steps and parameters remain unchanged. The yield of intermediate 3 is calculated, and the specific parameters are shown in Table 2.
[0066] Table 2
[0067]
[0068] As shown in Table 2, when the equivalence ratio of intermediate 2 to concentrated sulfuric acid is 1:5, the optimal yield of 91% is achieved at 110℃ and after 22 hours of reaction.
[0069] The synthesized product of the present invention was determined by mass spectrometry, which showed that the final product synthesized by the present invention was tetrathiofulvalene with an HPLC purity of 98.0%-98.6% and a total yield of over 58%.
[0070] In summary, the synthetic route of this invention adjusts the reaction conditions of the preparation process from intermediate 2 to intermediate 3, and prepares intermediate 3 in a one-pot process, avoiding the intermediate purification step required in the preparation process of intermediate 2 to intermediate 3 in the prior art, thus shortening the synthesis time and greatly improving efficiency; the synthetic route from intermediate 5 to tetrathiofulvalene is adjusted to be completed in one step, avoiding the step of converting hexafluorophosphate into iodide, further improving the synthesis efficiency; the reaction conditions of intermediate 4 are adjusted to shorten the reaction time and improve the formation efficiency.
[0071] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.
Claims
1. A method for preparing tetrathiofulvalene, characterized in that, Includes the following steps: S1. In an organic solvent, piperidine, carbon disulfide and a basic sodium-containing compound are mixed and reacted to generate intermediate 1, which is then reacted with bromoacetaldehyde ethylene glycol to obtain intermediate 2. S2. The intermediate 2 is reacted with concentrated sulfuric acid and hexafluorophosphorus to obtain intermediate 3; S3. Intermediate 3 and sodium borohydride react in an organic solvent to obtain intermediate 4; S4. Intermediate 4, acetic anhydride and hexafluorophosphoric acid react in an organic solvent to obtain intermediate 5; S5. The intermediate 5 and the base react in an organic solvent to obtain the tetrathiofulvalene; the reaction route is as follows: 。 2. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S2, the reaction of intermediate 2 with concentrated sulfuric acid and hexafluorophosphorus is specifically as follows: under a protective atmosphere, concentrated sulfuric acid and intermediate 2 react at 100-120°C, then the temperature is lowered to 0-25°C, and the mixture is mixed with water and hexafluorophosphorus to obtain intermediate 3.
3. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S2, the molar ratio of intermediate 2 to concentrated sulfuric acid and hexafluorophosphorus is 1:(4-8):(1-1.2).
4. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S5, the base is selected from one or more of triethylamine, sodium carbonate, and potassium carbonate.
5. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S5, the molar ratio of the intermediate to the base is 1:(1.1-1.3), and the reaction temperature is 0-25℃.
6. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S1, the alkaline sodium-containing compound is selected from sodium hydroxide and / or sodium phosphate; the molar ratio of piperidine, carbon disulfide and alkaline sodium-containing compound is 1:(1-1.2):(1-1.5).
7. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, The temperatures for the two-step reactions in S1 are independently selected from 60-100℃.
8. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S3, the molar ratio of intermediate 3 and sodium borohydride is 1:(1-1.2).
9. The method for preparing tetrathiofulvalene as described in claim 1, characterized in that, In S4, the molar ratio of intermediate 4, acetic anhydride and hexafluorophosphate is 1:(11-14):(2.2-2.5).
10. The method for preparing tetrathiofulvalene according to claim 1, characterized in that, The reaction temperature in S3 is 20-25℃, and the reaction time is 3-6 hours; the reaction temperature in S4 is -10 to 0℃.