A method for synthesizing a cyclooctatetraene

Abstract

The application provides a synthesis method of cyclooctatetraene. The cyclooctatetraene is prepared from 1,5-cyclooctadiene through a lithiation reaction and an oxidation reaction. The raw material is easy to obtain and low in cost. The low-toxicity transition metal salt is used as an oxidant, the reaction yield is high, the process condition is easy to achieve and control, the safety and reliability of production are improved, the equipment and synthesis cost are reduced, the green preparation is realized, and the application in industrial production is facilitated.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing cyclooctatetraene. Background Art

[0002] Cyclooctatetraene is a typical unsaturated hydrocarbon, primarily used in the manufacture of synthetic fibers, dyes, and pharmaceuticals, and is in high industrial demand. However, the high cost of synthesis, and thus the high selling price, significantly limits its application. A safer and more cost-effective synthesis method is urgently needed.

[0003] In current technology, acetylene is cyclized under high pressure to prepare cyclooctatetraene. This method requires high pressure, produces many by-products, and is difficult to purify.

[0004] In another process, the intermediate COT is oxidized 2- Preparation is achieved. Inorganic salt cadmium chloride is used as an oxidant, dry air and iodine element are used as oxidants, and organic substances tert-butyl peroxide and 1,2-dibromoethane are used as oxidants. Among them, cadmium chloride as an oxidant produces a large amount of cadmium ions after use, which is highly toxic and poses great harm to the environment and human body, so it is difficult to use in large quantities. The preparation of cyclooctatetraene by air oxidation is a highly dangerous operation process, and the yield of cyclooctatetraene prepared by iodine element oxidation is low. The oxidation process of tert-butyl peroxide and 1,2-dibromoethane is violent and highly dangerous.

[0005] It can be seen that the current raw material cost for synthesizing cyclooctatetraene is too high, the preparation conditions are harsh, the process is highly dangerous, special equipment is required to carry out the reaction process, and toxic "three wastes" are easily produced, resulting in high selling price and low output, which cannot meet the demand for cyclooctatetraene in industry.

[0006] Therefore, it is necessary to continue to develop the synthesis method of cyclooctatetraene, utilize easily available raw materials, reduce process difficulty and conditions, improve yield, reduce the toxicity of three wastes, and achieve safe and large-scale production. Summary of the Invention

[0007] To address the above-mentioned issues, the present invention provides a method for synthesizing cyclooctatetraene. This method uses 1,5-cyclooctadiene as a low-cost, readily available raw material. Cyclooctatetraene is prepared through lithiation and oxidation reactions. A low-toxic transition metal salt is used as the oxidant, resulting in a high reaction yield. The process conditions are easily achieved and controlled, improving production safety and reliability while reducing equipment and synthesis costs. This method achieves environmentally friendly production and facilitates widespread application in industrial production, thus completing the present invention.

[0008] The present application aims to provide a synthesis method of cyclooctatetraene, which synthesizes cyclooctatetraene by sequentially performing a lithiation reaction and an oxidation reaction of a transition metal salt, taking 1,5-cyclooctadiene as a raw material.

[0009] Preferably, the method specifically comprises the following steps:

[0010] Step 1, adding 1,5-cyclooctadiene and a lithiating reagent into a solvent, stirring to obtain a mixed solution.

[0011] Step 2, adding the mixed solution into a transition metal salt solution, stirring to react, to obtain a reaction solution.

[0012] Step 3, post-treating the reaction solution to obtain cyclooctatetraene.

[0013] The present application also aims to provide cyclooctatetraene obtained by the method.

[0014] The synthesis method of cyclooctatetraene provided by the present application has the following beneficial effects:

[0015] (1) The synthesis method of cyclooctatetraene provided by the present application takes 1,5-cyclooctadiene as a raw material, which has a wide access to raw materials and low cost, and is conducive to expanding production.

[0016] (2) The present application uses a transition metal salt as an oxidizing agent, which is easy to obtain, has low oxidizing agent cost, mild oxidation reaction, good safety, and relatively high yield.

[0017] (3) In the present application, the lithiation reaction is performed first, and then the oxidation reaction is performed. The reaction conditions are relatively easy to achieve and control, have high safety factor, low operation difficulty, low equipment requirement, controlled process cost, and are suitable for popularization and actual large-scale production. BRIEF DESCRIPTION OF DRAWINGS

[0018] Figure 1 The nuclear magnetic resonance spectrum of cyclooctatetraene prepared in Example 1 of the present application is shown;

[0019] Figure 2 The schematic diagram of the test device that can be used in Example 1 of the present application is shown.

[0020] REFERENCE SIGNS

[0021] 1 - first round-bottomed Dewar flask;

[0022] 2 - mouth of reaction flask A;

[0023] 3 - syringe;

[0024] 4 - cooling liquid inlet;

[0025] 5 - cooling liquid outlet;

[0026] 6-vent I;

[0027] 7-transfer tube;

[0028] 8-rubber stopper;

[0029] 9-vent II;

[0030] 10-second round-bottomed dewar. DETAILED DESCRIPTION

[0031] The present application will be described in detail below with specific embodiments, and the features and advantages of the present application will become more apparent with these descriptions.

[0032] The present application provides a synthesis method of cyclooctatetraene, which synthesizes cyclooctatetraene by sequentially performing a lithiation reaction and an oxidation reaction of a transition metal salt, using 1,5-cyclooctadiene as a raw material.

[0033] Preferably, the method specifically comprises the following steps:

[0034] Step 1, under a protective atmosphere, 1,5-cyclooctadiene and a lithiating reagent are added to a solvent, and stirred to obtain a mixed solution.

[0035] The lithiating reagent is selected from one or more of alkyl lithium and phenyl lithium, preferably one or more of butyl lithium, ethyl lithium, phenyl lithium and methyl lithium, and more preferably n-butyl lithium.

[0036] The solvent is selected from one or more of ether solvents and alkane solvents, preferably one or more of pentane, n-hexane, diethyl ether and tetrahydrofuran, and more preferably n-hexane.

[0037] The molar ratio of 1,5-cyclooctadiene to the lithiating reagent is (0.6-1.4):3, preferably (0.8-1.2):3, and more preferably (0.9-1.1):3.

[0038] The molar volume ratio of 1,5-cyclooctadiene to the solvent is (6-28) mmol:10 mL, preferably (9-24) mmol:10 mL, and more preferably (12-18) mmol:10 mL.

[0039] Preferably, a tertiary amine is also added to the solution containing 1,5-cyclooctadiene and the lithiating reagent to enhance the lithiating ability of the lithiating reagent. The tertiary amine is selected from one or more of tetramethyl ethylenediamine (TMEDA), hexamethyl phosphoric triamide (HMPA) or 1,4-diazabicyclo[2.2.2]octane (DABCO), such as tetramethyl ethylenediamine (TMEDA).

[0040] The molar ratio of the tertiary amine to the lithiating agent is (0.5-1.5):1, preferably (0.7-1.3):1, and more preferably (0.9-1.1):1.

[0041] The tertiary amine is added to the solution containing 1,5-cyclooctadiene and the lithiating agent at a temperature of -10 to -5°C, preferably -15 to -8°C.

[0042] After the addition of the tertiary amine, the temperature of the reaction solution is naturally increased to 15-30°C, and the reaction is stirred for 35-60 h, preferably 40-55 h, to obtain a mixed solution.

[0043] The protective atmosphere is preferably nitrogen and / or argon, such as argon.

[0044] Step 2: The mixed solution is added to a solvent containing a transition metal salt, and the reaction is stirred to obtain a reaction solution.

[0045] Step 2 is carried out under a protective atmosphere.

[0046] The transition metal salt is selected from one or more of the fourth period transition metal salts, preferably one or more of the metal salts of copper, nickel, iron, cobalt, and manganese, and more preferably a copper salt and / or a nickel salt, such as CuCl2, CuSO4, Cu2(OH)2CO3, or NiCO3. The transition metal salt as an oxidizing agent has the following four advantages: 1) compared with cadmium chloride, the transition metal salt is less toxic and more environmentally friendly; 2) compared with air, the transition metal salt avoids potential hidden dangers of combustion and explosion, and is safer; 3) compared with iodine, the transition metal salt has a higher oxidation yield; and 4) compared with tert-butyl hydroperoxide and 1,2-dibromoethane, the transition metal salt has a more mild oxidation reaction process.

[0047] The molar ratio of the transition metal salt to 1,5-cyclooctadiene is (1.5-3.2):1, preferably (1.8-2.8):1, and more preferably (2.0-2.4):1. The molar ratio of the transition metal salt to 1,5-cyclooctadiene in the range of 1.5-3.2 allows the reaction to proceed, and when the amount is more than 2.0 equivalents, there is enough oxidizing agent to ensure a higher conversion rate; when the amount exceeds 2.4 equivalents, it will be unfavorable for the later processing of the reaction.

[0048] The solvent is selected from one or more of the alkane solvents, preferably one or more of the alkane solvents containing C3-C8, and more preferably n-hexane. The selection of the reaction solvent mainly follows the following two principles: 1) it cannot react with the lithiating agent; and 2) it has a low boiling point, which facilitates the removal of the alkane reagent in the later stage, and ensures a high yield and purity of cyclooctatetraene.

[0049] The molar volume ratio of the transition metal salt to the solvent is (30-36) mmol:(4-18) mL, preferably (30-36) mmol:(6-15) mL, and more preferably (30-36) mmol:(8-12) mL.

[0050] The mixed solution is added to the solvent containing the transition metal salt at -10 to -5 ℃, preferably -15 to -8 ℃, and stirred, and the temperature is naturally increased to 15-30 ℃, and the reaction is carried out for 8-16 h, preferably 10-14 h.

[0051] After the reaction is completed, the reaction is quenched to obtain a reaction solution.

[0052] The reaction is quenched by adding an ammonium chloride solution, and more preferably, a saturated ammonium chloride solution.

[0053] Step 3, the reaction solution is treated to obtain cyclooctatetraene.

[0054] The treatment includes washing the organic layer, drying, removing the solvent, and vacuum distillation.

[0055] The washing of the organic layer is carried out by using acetic acid solution and saturated sodium bicarbonate solution in sequence.

[0056] The drying is carried out by adding a solid drying agent to the washed organic layer and fully drying.

[0057] The removal of the solvent is carried out by rotary evaporation to concentrate the organic layer, and the rotary evaporation temperature is not higher than 30 ℃, and the vacuum degree is not lower than 100 mbar.

[0058] The synthesis method of cyclooctatetraene provided by the application uses 1,5-cyclooctadiene as a raw material, carries out lithiumation and hydrogen abstraction, and then uses a transition metal salt for oxidation to obtain cyclooctatetraene. The raw material is easy to obtain, the cost is low, the synthesis method has high yield, the reaction conditions are easy to achieve and control, the process is safe, the toxicity of three wastes is reduced, industrial production can be realized, and the demand for cyclooctatetraene can be met.

[0059] Examples

[0060] Example 1

[0061] Under argon protection, 10.0 mL of n-hexane, 2.0 mL of 1,5-cyclooctadiene, and 18.7 mL of n-butyllithium / n-hexane solution (n-butyllithium concentration of 2.5 mol / L) were sequentially added into a 100 mL reaction bottle by using a syringe. An appropriate amount of ethyl acetate was added into a round-bottomed Dewar flask, and dry ice was added to maintain the temperature at -10°C. The reaction bottle was placed in the round-bottomed Dewar flask under argon protection, and stirred for 10 minutes to reduce the temperature of the reaction system to -10°C; 7.0 mL of tetramethylethylenediamine (TMEDA) was extracted by a syringe and slowly injected into the reaction bottle under stirring; the temperature of the reaction system was naturally increased to room temperature, and the reaction was continuously stirred for 48 hours to obtain a “mixed solution”.

[0062] In an argon-protected glove box, 4.6 g of CuCl2 was weighed into a 100 mL reaction bottle, and 10.0 mL of n-hexane was added; the reaction bottle was placed in a round-bottomed Dewar flask, and the temperature was maintained at -10°C by using ethyl acetate and dry ice.

[0063] Under argon protection, the “mixed solution” was slowly transferred to the reaction bottle containing CuCl2 by using a plastic tube through the siphon principle; the temperature of the reaction system was naturally increased to room temperature, and the reaction was continuously stirred for 12 hours; then 5 mL of saturated ammonium chloride solution was added to quench the reaction, and the stirring was continued for 10 minutes.

[0064] Firstly, the upper organic phase was washed with 5 wt% aqueous acetic acid, 20 mL each time, for 3 times; secondly, saturated aqueous sodium bicarbonate solution was used for washing, 20 mL each time, for 3 times. The organic layer was collected, an appropriate amount of anhydrous magnesium sulfate was added, and stirred for drying for 60 minutes; the magnesium sulfate was removed by suction filtration, and the organic phase was concentrated by using a rotary evaporator, with a water bath temperature not higher than 30°C and a vacuum degree not lower than 100 mbar; the target product was separated by vacuum distillation, and a golden yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance hydrogen spectrum, and the nuclear magnetic resonance hydrogen spectrum results are shown in Figure 1 As shown in the figure, the yield of cyclooctatetraene was calculated to be 0.79 g, and the molar yield was 48.97%.

[0065] The test device can be carried out as shown in Figure 2 .

[0066] Among them, the first round-bottomed Dewar flask 1 and the second round-bottomed Dewar flask 10 are filled with ethyl acetate and dry ice mixture with liquid level higher than the reaction liquid, used to maintain low temperature; the three-necked reaction bottle A containing n-hexane, 1,5-cyclooctadiene and n-butyllithium / n-hexane solution is placed in the first round-bottomed Dewar flask 1, and the reaction bottle B containing CuCl2 and n-hexane is placed in the second round-bottomed Dewar flask 10.

[0067] When the raw materials are put in, the bottle mouth 2 of the three-mouth reaction bottle A is plugged with a rubber plug with a needle for keeping the sealing during the feeding of the raw materials. A syringe 3 is used for drawing and feeding the reaction raw materials. The reaction bottle A is connected to a condenser with a cooling liquid inlet 4 and a cooling liquid outlet 5. The reaction bottle A is also connected to a vent 6 for drawing vacuum or filling argon. When the argon is filled, it is filled from the vent 6 and discharged from the upper outlet of the condenser.

[0068] The reaction bottle B is connected to a vent 9 for drawing vacuum or filling argon.

[0069] According to the siphon principle, the reaction liquid in the reaction bottle A is transferred to the reaction bottle B by using a plastic tube 7. When the reaction liquid is transferred, the plastic tube passes through the rubber plug 8 into the B bottle. The rubber plug is used to keep the sealing during the transfer of the reaction liquid. The plastic tube 7 is connected to the bottle mouth 2 of the reaction bottle A.

[0070] Example 2

[0071] Under the protection of argon, 200.0 mL of n-hexane, 43.0 mL of 1,5-cyclooctadiene, and 400.0 mL of n-butyllithium / n-hexane solution (the concentration of n-butyllithium is 2.5 mol / L) are sequentially added into a 1000 mL reaction bottle by using a syringe. A proper amount of ethyl acetate is added into a round-bottomed Dewar flask, and dry ice is added to maintain the temperature at -10°C. The reaction bottle is placed in the round-bottomed Dewar flask under the protection of argon, and stirred for 10 minutes to reduce the temperature of the reaction system to -10°C. 150.0 mL of tetramethylethylenediamine is drawn by using a syringe and slowly injected into the reaction bottle under stirring. The temperature of the reaction system is naturally increased to room temperature, and the reaction is continuously stirred for 48 hours to obtain a reaction "mixture".

[0072] In a glove box under the protection of argon, 98.50 g of CuCl2 is weighed into a 1000 mL reaction bottle, and 100.0 mL of n-hexane is added. The reaction bottle is placed in a round-bottomed Dewar flask, and the temperature is maintained at -30°C by using ethyl acetate and dry ice.

[0073] Under the protection of argon, the "mixture" is slowly transferred to the reaction bottle containing CuCl2 by using a plastic tube according to the siphon principle. The temperature of the reaction system is naturally increased to room temperature, and the reaction is continuously stirred for 12 hours. Then, 20 mL of saturated ammonium chloride solution is added to quench the reaction, and the stirring is continuously performed for 30 minutes.

[0074] First, the upper organic phase was washed with 10 wt% acetic acid aqueous solution, 100 mL each time, for 5 times; second, the upper organic phase was washed with saturated sodium bicarbonate aqueous solution, 100 mL each time, for 3 times. The organic layer was collected, and an appropriate amount of anhydrous magnesium sulfate was added, and stirred for 60 minutes. The magnesium sulfate was removed by suction filtration, and the organic phase was concentrated by a rotary evaporator, with a water bath temperature of no more than 30°C, and a vacuum degree of no less than 100 mbar. The target product was separated by reduced pressure distillation, and a golden yellow liquid was obtained. The target product was confirmed by nuclear magnetic resonance hydrogen spectrum results; the yield of cyclooctatetraene was calculated to be 16.00 g, with a molar yield of 46%.

[0075] The raw material input amount of this example was 21 times the test amount in Example 1, which was a large-scale test. The results showed that there was no great difference in yield between the large-scale test and the small-scale test (Example 1), indicating that the present application has potential for industrial production.

[0076] Example 3

[0077] Cyclooctatetraene was synthesized according to the method of Example 1, with the difference being that 5.46 g of CuSO4 was added instead of 4.60 g of CuCl2 in a 100 mL reaction bottle. 0.63 g of cyclooctatetraene was prepared, with a molar yield of 39%.

[0078] Example 4

[0079] Cyclooctatetraene was synthesized according to the method of Example 1, with the difference being that 4.06 g of NiCO3 was added instead of 4.60 g of CuCl2 in a 100 mL reaction bottle. 1.00 g of cyclooctatetraene was prepared, with a molar yield of 62%.

[0080] Example 5

[0081] Cyclooctatetraene was synthesized according to the method of Example 1, with the difference being that 3.78 g of Cu2(OH)2CO3 was added instead of 4.60 g of CuCl2 in a 100 mL reaction bottle. 0.57 g of cyclooctatetraene was prepared, with a molar yield of 35%.

[0082] Example 6

[0083] Cyclooctatetraene was synthesized according to the method of Example 1, with the difference being that 2.2 times the amount of FeCl3 was added instead of 4.60 g of CuCl2 in a 100 mL reaction bottle. 0.11 g of cyclooctatetraene was prepared, with a molar yield of 6.85%.

[0084] Example 7

[0085] The synthesis of cyclooctatetraene was carried out according to the method of Example 1, with the exception that 2.2 equivalents of Co(N03)2was added instead of 4.60 g of CuCl2in a 100 mL reaction flask. 0.033 g of cyclooctatetraene was produced, with a molar yield of 2.04%.

[0086] Example 8

[0087] The synthesis of cyclooctatetraene was carried out according to the method of Example 1, with the exception that 2.2 equivalents of MnCl2was added instead of 4.60 g of CuCl2in a 100 mL reaction flask. 0.015 g of cyclooctatetraene was produced, with a molar yield of 0.93%.

[0088] The present application uses 1,5-cyclooctadiene as a starting material, and successively adds n-butyllithium and tetramethylethylenediamine, and synthesizes cyclooctatetraene under the oxidation of a transition metal salt. The present application has the advantages of high safety, low cost, and less toxicity.

[0089] The present application is described in detail in connection with the specific embodiments and / or exemplary examples and the accompanying drawings, but these descriptions cannot be understood as limiting the present application. Those skilled in the art understand that the technical solutions and embodiments of the present application can be variously replaced, modified or improved without departing from the spirit and scope of the present application, and these all fall within the scope of the present application. The scope of protection of the present application is subject to the appended claims.

Claims

1. A method for synthesizing cyclooctatetraene, the method comprising the following steps: Step 1, adding 1, 5-cyclooctadiene and a lithiating reagent into a solvent and stirring to obtain a mixture; Step 2, adding the mixture into a solution of a transition metal salt and stirring to obtain a reaction solution; and Step 3, post-treating the reaction solution to obtain cyclooctatetraene. The transition metal salt is selected from CuCl 2 or NiCO 3.

2. The method of claim 1, wherein, The method specifically comprises the following steps: Step 1, adding 1, 5-cyclooctadiene and a lithiating reagent into a solvent and stirring to obtain a mixture; Step 2, adding the mixture into a solution of a transition metal salt and stirring to obtain a reaction solution; Step 3, post-treating the reaction solution to obtain cyclooctatetraene.

3. The method of claim 2, wherein, In Step 1, The lithiating reagent is selected from one or more of alkyl lithium and phenyl lithium, The molar ratio of 1, 5-cyclooctadiene to the lithiating reagent is (0.6-1.4) :

3. 4.The method of claim 3, wherein The lithiating reagent is selected from one or more of butyl lithium, ethyl lithium, phenyl lithium and methyl lithium. 5.The method of claim 4, wherein The lithiating reagent is n-butyl lithium. 6.The method of claim 3, wherein The molar ratio of 1, 5-cyclooctadiene to the lithiating reagent is (0.8-1.2) :

3. 7.The method of claim 6, wherein The molar ratio of 1, 5-cyclooctadiene to the lithiating reagent is (0.9-1.1) :

3.

8. The method of claim 2, wherein, In Step 1, The solvent is selected from one or more of alkanes and ether solvents, The molar volume ratio of 1, 5-cyclooctadiene to the solvent is (6-28) mmol: 10 mL. 9.The method of claim 8, wherein The solvent is one or more of pentane, n-hexane, diethyl ether and tetrahydrofuran. 10.The method of claim 8, wherein The molar volume ratio of 1, 5-cyclooctadiene to the solvent is (9-24) mmol: 10 mL. 11.The method of claim 10, wherein The molar volume ratio of 1, 5-cyclooctadiene to the solvent is (12-18) mmol: 10 mL.

12. The method of claim 2, wherein, In Step 1, a tertiary amine is further added to the solution containing 1, 5-cyclooctadiene and the lithiating reagent, The tertiary amine is added to the solution containing 1, 5-cyclooctadiene and the lithiating reagent at a temperature of -10 to -5 ℃, After the tertiary amine is added, the temperature of the reaction solution is naturally increased to 15-30 ℃, and the reaction is stirred for 35-60 h to obtain the mixture.

13. The method of claim 2, wherein, In Step 2, The solvent is selected from one or more of alkanes, The molar volume ratio of the transition metal salt to the solvent is (30-36) mmol: (4-18) mL. 14.The method of claim 13, wherein The solvent is one or more of alkanes with a carbon number of C 3-C 8. 15.The method of claim 14, wherein The solvent is n-hexane. 16.The method of claim 13, wherein The molar volume ratio of the transition metal salt to the solvent is (30-36) mmol: (6-15) mL. 17.The method of claim 16, wherein The molar volume ratio of the transition metal salt to solvent is (30-36) mmol: (8-12) mL.

18. The method of claim 2, wherein, In Step 2, the molar ratio of the transition metal salt to 1,5-cyclooctadiene is (1.5-3.2):

1.

19. The method of claim 18, wherein, The molar ratio of the transition metal salt to 1,5-cyclooctadiene is (1.8-2.8):

1.

20. The method of claim 19, wherein, The molar ratio of the transition metal salt to 1,5-cyclooctadiene is (2.0-2.4):

1.

21. The method of claim 2, wherein, In Step 3, the work-up includes washing the organic layer, drying, removing the solvent, and distillation under reduced pressure.

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