Synthesis method of cyclooctatetraene

Abstract

The invention provides a synthesis method of cyclooctatetraene, which comprises the following steps: taking 1, 5-cyclooctadiene as a raw material, and carrying out lithiation reaction and oxidation reaction to prepare the cyclooctatetraene. Raw materials are easy to obtain and low in cost, low-toxicity transition metal salt is adopted as an oxidizing agent, the reaction yield is high, technological conditions are easy to reach and control, the production safety and reliability are improved, the equipment and synthesis cost is reduced, green preparation is achieved, and application and popularization in industrial production are 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, mainly used to make synthetic fibers, dyes, drugs, etc., and has a large demand in industry. Currently, due to the high synthesis cost, the high sales price has greatly limited the application of cyclooctatetraene, and a safer and cheaper synthesis method is urgently needed.

[0003] In the current technology, acetylene is cyclized under high pressure to prepare cyclooctatetraene. This method needs to be carried out under high pressure, has many by-products, and is difficult to purify.

[0004] In another process, the intermediate COT is oxidized 2- To achieve the preparation. The inorganic salt cadmium chloride is used as the oxidant, dry air and iodine are used as the oxidant, and the organic substances tert-butyl peroxide and 1,2-dibromoethane are used as the oxidants. Among them, cadmium chloride as an oxidant produces a large amount of cadmium ions after use, which are highly toxic and have 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 highly dangerous, and the yield of cyclooctatetraene prepared by iodine 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 realize the reaction process, and toxic "three wastes" are easily produced, resulting in a high selling price and low output, which cannot meet the demand for cyclooctatetraene in the 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 solve the above problems, the present invention provides a method for synthesizing cyclooctatetraene. The method uses 1,5-cyclooctadiene as a raw material, which has low cost and is easy to obtain, and prepares cyclooctatetraene through lithiation reaction and oxidation reaction. The oxidant uses a low-toxic transition metal salt, the reaction yield is high, the process conditions are easy to achieve and control, the safety and reliability of production are improved, the equipment and synthesis costs are reduced, green preparation is achieved, and it is easy to promote and apply in industrial production, thereby completing the present invention.

[0008] The object of the present invention is to provide a method for synthesizing cyclooctatetraene, wherein 1,5-cyclooctadiene is used as a raw material, and a lithiation reaction and an oxidation reaction of a transition metal salt are sequentially performed to synthesize cyclooctatetraene.

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

[0010] Step 1: Add 1,5-cyclooctadiene and a lithiation reagent into a solvent, stir, and obtain a mixed solution.

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

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

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

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

[0015] (1) The method for synthesizing cyclooctatetraene provided by the present invention uses 1,5-cyclooctadiene as raw material, and the raw material can be obtained through a wide range of channels with low cost, which is conducive to expanding production.

[0016] (2) The present invention uses transition metal salts as oxidants, which are easy to obtain, have low cost, mild oxidation reaction, good safety, and relatively high yield.

[0017] (3) In the present invention, the lithiation reaction is carried out first, and then the oxidation reaction is carried out. The reaction conditions are relatively easy to achieve and control, the safety factor is high, the operation difficulty is low, the equipment requirements are low, and the process cost is controlled, which is suitable for promotion and actual large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

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

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

[0020] Description of Figure Numbers

[0021] 1- The first round bottom Dewar flask;

[0022] 2- the mouth of reaction bottle A;

[0023] 3-Syringe;

[0024] 4-Coolant inlet;

[0025] 5- Coolant outlet;

[0026] 6-Ventilation port I;

[0027] 7- transfer tube;

[0028] 8-Rubber stopper;

[0029] 9-Ventilation port II;

[0030] 10-Second round bottom Dewar flask. DETAILED DESCRIPTION

[0031] The present invention is described in detail below through specific implementation modes, and the characteristics and advantages of the present invention will become clearer and more specific with these descriptions.

[0032] The invention provides a method for synthesizing cyclooctatetraene. The method uses 1,5-cyclooctadiene as a raw material, sequentially performs a lithiation reaction and an oxidation reaction of a transition metal salt, and synthesizes cyclooctatetraene.

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

[0034] Step 1: Under a protective atmosphere, add 1,5-cyclooctadiene and a lithiation reagent into a solvent, stir, and obtain a mixed solution.

[0035] The lithiation agent 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, 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, more preferably n-hexane.

[0037] The molar ratio of the 1,5-cyclooctadiene to the lithiation agent 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 the 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 added to the solution containing 1,5-cyclooctadiene and a lithiation agent to enhance the lithiation ability of the lithiation agent. The tertiary amine is selected from one or more of tetramethylethylenediamine (TMEDA), hexamethylphosphoric triamide (HMPA) or 1,4-diazabicyclo[2.2.2]octane (DABCO), such as tetramethylethylenediamine (TMEDA).

[0040] The molar ratio of the tertiary amine to the lithiation 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 into a solution containing 1,5-cyclooctadiene and a lithiation agent at -10 to -5°C, preferably -15 to -8°C.

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

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

[0044] Step 2: adding the mixed solution into a solvent containing a transition metal salt, stirring to react, and obtaining 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 selected from one or more of the metal salts of copper, nickel, iron, cobalt, and manganese, more preferably copper salts and / or nickel salts, such as CuCl 2 、CuSO 4 , Cu 2 (OH) 2 CO 3 or NiCO 3 . Transition metal salts have the following four advantages as oxidants: 1) Compared with cadmium chloride, transition metal salts are less toxic and environmentally friendly; 2) Compared with air, transition metal salts avoid potential explosion hazards and are safer; 3) Compared with elemental iodine, transition metal salts have a higher oxidation yield; 4) Compared with tert-butyl peroxide and 1,2-dibromoethane, the oxidation reaction process of transition metal salts is milder.

[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 is 1.5-3.2, which can make the reaction proceed. When the amount is more than 2.0 times the equivalent, sufficient oxidant is ensured, and a higher conversion rate is achieved; when the amount exceeds 2.4 times the equivalent, it will be unfavorable for the later treatment of the reaction.

[0048] The solvent is selected from one or more alkane solvents, preferably one or more alkane solvents with a carbon number of C3-C8, and more preferably n-hexane. The selection of the reaction solvent mainly complies with the following two principles: 1) it cannot react with the lithium reagent; 2) it has a low boiling point, which is convenient for the later removal of the alkane reagent to ensure 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 into a solvent containing a transition metal salt at -10 to -5°C, preferably -15 to -8°C, and stirred. The temperature naturally rises to 15-30°C and the reaction is carried out for 8-16 hours, preferably 10-14 hours.

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

[0052] Preferably, an ammonium chloride solution is added, more preferably, a saturated ammonium chloride solution is added to quench the reaction.

[0053] Step 3: post-treating the reaction solution to obtain cyclooctatetraene.

[0054] The post-treatment includes washing the organic layer, drying, removing the solvent and distilling under reduced pressure.

[0055] The organic layer is washed by sequentially washing with an acetic acid solution and a saturated sodium bicarbonate solution.

[0056] The drying step is to add a solid desiccant into the washed organic layer and fully dry it.

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

[0058] The synthesis method of cyclooctatetraene provided by the present invention uses 1,5-cyclooctadiene as a raw material, undergoes lithiation and hydrogen extraction, and then uses a transition metal salt for oxidation to obtain cyclooctatetraene. The raw material is easily available, the cost is low, the synthesis method has a high yield, the reaction conditions are easy to achieve and control, the process is highly safe, the toxicity of the three wastes is reduced, industrial production can be achieved, and the demand for cyclooctatetraene is met.

[0059] Example

[0060] Example 1

[0061] Under argon protection, add 10.0 mL of n-hexane, 2.0 mL of 1,5-cyclooctadiene, and 18.7 mL of n-butyl lithium / n-hexane solution (n-butyl lithium concentration is 2.5 mol / L) to a 100 mL reaction bottle with a syringe. Add an appropriate amount of ethyl acetate to a round-bottomed Dewar flask, and add dry ice to maintain the temperature at -10°C. Under argon protection, place the reaction bottle in a round-bottomed Dewar flask and stir for 10 minutes to reduce the temperature of the reaction system to -10°C; use a syringe to extract 7.0 mL of tetramethylethylenediamine (TMEDA) and slowly inject it into the reaction bottle under stirring; the temperature of the reaction system naturally rises to room temperature, and after continuous stirring for 48 hours, a reaction "mixed solution" is obtained.

[0062] In an argon-protected glove box, weigh 4.6 g CuCl 2 In a 100 mL reaction bottle, add 10.0 mL of n-hexane; place the reaction bottle in a round-bottom Dewar flask, and maintain the temperature at -10°C with ethyl acetate and dry ice.

[0063] Under the protection of argon, the "mixed liquid" was slowly transferred to the CuCl 2 The temperature of the reaction system was naturally raised to room temperature in the reaction bottle, and the reaction was stirred continuously for 12 hours, then 5 mL of saturated ammonium chloride solution was added to quench the reaction, and stirring was continued for 10 minutes.

[0064] First, wash the upper organic phase with 5wt% acetic acid aqueous solution, 20mL each time, wash 3 times; then wash with saturated sodium bicarbonate aqueous solution, 20mL each time, wash 3 times. Collect the organic layer, add an appropriate amount of anhydrous magnesium sulfate, stir and dry for 60 minutes; remove the magnesium sulfate by suction filtration, and concentrate the organic phase using a rotary evaporator, the water bath temperature is not higher than 30°C, and the vacuum degree is not lower than 100 mbar; separate the target product by reduced pressure distillation to obtain a golden liquid. The target product is confirmed by the results of nuclear magnetic resonance hydrogen spectrum, and the results of nuclear magnetic resonance hydrogen spectrum are shown in Figure 1 As shown, the calculated yield of cyclooctatetraene is 0.79 g, and the molar yield is 48.97%.

[0065] You can use Figure 2 The test apparatus shown is carried out.

[0066] The first round-bottom Dewar flask 1 and the second round-bottom Dewar flask 10 are filled with a mixture of ethyl acetate and dry ice whose liquid level is higher than the reaction liquid, so as to maintain low temperature; a three-necked reaction flask A containing n-hexane, 1,5-cyclooctadiene and n-butyl lithium / n-hexane solution is placed in the first round-bottom Dewar flask 1, and a three-necked reaction flask A containing CuCl 2 The reaction flask B containing n-hexane is equipped with a second round-bottom Dewar flask 10.

[0067] When adding raw materials, the mouth 2 of the three-mouth reaction bottle A is plugged with a rubber stopper with a needle to maintain the sealing when adding materials, and a syringe 3 is used to extract and add reaction raw materials. The reaction bottle A is connected to a condenser with a coolant inlet 4 and a coolant outlet 5; the reaction bottle A is also connected to a vent Ⅰ6 for vacuuming or filling with argon. When introducing argon, it is introduced from the vent Ⅰ6 and discharged from the outlet at the upper end of the condenser.

[0068] The reaction bottle B is connected to the vent port II9 for vacuuming or filling with argon.

[0069] According to the siphon principle, the reaction liquid in the reaction bottle A is transferred to the reaction bottle B by using the plastic tube 7. When transferring the reaction liquid, the plastic tube is used to pass through the rubber stopper 8 to enter the B bottle. The rubber stopper is used to maintain the sealing when transferring the reaction liquid. The plastic tube 7 is connected from the bottle mouth 2 of the reaction bottle A.

[0070] Example 2

[0071] Under argon protection, add 200.0mL of n-hexane, 43.0mL of 1,5-cyclooctadiene, and 400.0mL of n-butyl lithium / n-hexane solution (n-butyl lithium concentration is 2.5mol / L) to a 1000mL reaction bottle with a syringe. Add an appropriate amount of ethyl acetate to a round-bottomed Dewar flask, and add dry ice to maintain the temperature at -10°C. Under argon protection, place the reaction bottle in a round-bottomed Dewar flask and stir for 10 minutes to reduce the temperature of the reaction system to -10°C; use a syringe to extract 150.0mL of tetramethylethylenediamine and slowly inject it into the reaction bottle under stirring; the temperature of the reaction system naturally rises to room temperature, and after continuous stirring and reaction for 48 hours, a reaction "mixed solution" is obtained.

[0072] In an argon-protected glove box, weigh 98.50 g CuCl 2 In a 1000 mL reaction bottle, add 100.0 mL of n-hexane; place the reaction bottle in a round-bottom Dewar flask, and maintain the temperature at -30°C with ethyl acetate and dry ice.

[0073] Under the protection of argon, the "mixed liquid" was slowly transferred to the CuCl 2 the temperature of the reaction system naturally rose to room temperature, and after continuous stirring for 12 hours, 20 mL of saturated ammonium chloride solution was added to quench the reaction, and stirring was continued for 30 minutes.

[0074] First, the upper organic phase is washed with 10wt% acetic acid aqueous solution, 100mL each time, and washed 5 times; secondly, it is washed with saturated sodium bicarbonate aqueous solution, 100mL each time, and washed 3 times. Collect the organic layer, add an appropriate amount of anhydrous magnesium sulfate, stir and dry for 60 minutes; remove the magnesium sulfate by suction filtration, and concentrate the organic phase using a rotary evaporator, the water bath temperature is not higher than 30°C, and the vacuum degree is not lower than 100 mbar; separate the target product by reduced pressure distillation to obtain a golden liquid. The target product is confirmed by the results of nuclear magnetic resonance hydrogen spectrum; the calculated yield of cyclooctatetraene is 16.00g, and the molar yield is 46%.

[0075] The amount of raw materials input in this example is 21 times the amount in the test in Example 1, which is a very large test. The results show that the yield of the very large test is not much different from the yield of the small test (Example 1), indicating that the invention has the potential for industrial production.

[0076] Example 3

[0077] Cyclooctatetraene was synthesized according to the method of Example 1, except that 5.46 g CuSO 4 Replace 4.60gCuCl 2 In a 100 mL reaction bottle, 0.63 g of cyclooctatetraene was obtained with a molar yield of 39%.

[0078] Example 4

[0079] Cyclooctatetraene was synthesized according to the method of Example 1, except that 4.06 g NiCO 3 Replace 4.60gCuCl 2 In a 100 mL reaction bottle, 1.00 g of cyclooctatetraene was obtained with a molar yield of 62%.

[0080] Example 5

[0081] Cyclooctatetraene was synthesized according to the method of Example 1, except that 3.78 g Cu 2 (OH) 2 CO 3 Replace 4.60 g CuCl 2 In a 100 mL reaction bottle, 0.57 g of cyclooctatetraene was obtained with a molar yield of 35%.

[0082] Example 6

[0083] Cyclooctatetraene was synthesized according to the method of Example 1, except that 2.2 equivalents of FeCl 3 Replace 4.60gCuCl 2 In a 100 mL reaction bottle, 0.11 g of cyclooctatetraene was obtained with a molar yield of 6.85%.

[0084] Example 7

[0085] Cyclooctatetraene was synthesized according to the method of Example 1, except that 2.2 times the equivalent of Co(NO 3 ) 2 Replace 4.60 g CuCl 2 In a 100 mL reaction bottle, 0.033 g of cyclooctatetraene was obtained with a molar yield of 2.04%.

[0086] Example 8

[0087] Cyclooctatetraene was synthesized according to the method of Example 1, except that 2.2 equivalents of MnCl were added. 2 Replace 4.60 g CuCl 2 In a 100 mL reaction bottle, 0.015 g of cyclooctatetraene was obtained with a molar yield of 0.93%.

[0088] The invention uses 1,5-cyclooctadiene as a starting material, sequentially adds n-butyl lithium and tetramethylethylenediamine for reaction, and synthesizes cyclooctatetraene under the oxidation of a transition metal salt. The invention has the advantages of high safety, low cost and less toxicity.

[0089] The present invention is described in detail with reference to specific embodiments and / or exemplary examples and drawings, but these descriptions cannot be understood as limiting the present invention. It is understood by those skilled in the art that, without departing from the spirit and scope of the present invention, various equivalent substitutions, modifications or improvements may be made to the technical solution and its implementation methods of the present invention, all of which fall within the scope of the present invention. The scope of protection of the present invention shall be subject to the attached claims.

Claims

1. A method for synthesizing cyclooctatetraene, wherein 1,5-cyclooctadiene is used as a raw material, and a lithiation reaction and an oxidation reaction of a transition metal salt are sequentially performed to synthesize cyclooctatetraene.

2. The method according to claim 1, characterized in that The transition metal salt is selected from one or more of the fourth period transition metal salts, preferably selected from one or more of the metal salts of copper, nickel, iron, cobalt and manganese, more preferably copper salt and / or nickel salt.

3. The method according to claim 1, characterized in that The method specifically comprises the following steps: Step 1, adding 1,5-cyclooctadiene and a lithiation reagent into a solvent, stirring to obtain a mixed solution; Step 2, adding the mixed solution into the transition metal salt solution, stirring and reacting to obtain a reaction solution; Step 3: post-treating the reaction solution to obtain cyclooctatetraene.

4. The method according to claim 3, characterized in that In step 1, The lithiation agent 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, more preferably n-butyl lithium. The molar ratio of the 1,5-cyclooctadiene to the lithiation agent is (0.6-1.4):3, preferably (0.8-1.2):3, and more preferably (0.9-1.1):

3.

5. The method according to claim 3, characterized in that: In step 1, The solvent is selected from one or more of alkane and ether solvents, preferably one or more of pentane, n-hexane, diethyl ether and tetrahydrofuran. The molar volume ratio of the 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.

6. The method according to claim 3, characterized in that In step 1, a tertiary amine is also added to the solution containing 1,5-cyclooctadiene and a lithiation agent. The tertiary amine is added to a solution containing 1,5-cyclooctadiene and a lithiation agent at -10 to -5°C, preferably -15 to -8°C, After adding the tertiary amine, the temperature of the reaction solution naturally rises to 15-30° C., and the reaction is stirred for 35-60 hours, preferably 40-55 hours, to obtain a mixed solution.

7. The method according to claim 3, characterized in that In step 2, The solvent is selected from one or more alkane solvents, preferably one or more alkane solvents with a carbon number of C3-C8, more preferably n-hexane. 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.

8. The method according to claim 3, characterized in that In step 2, 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.

9. The method according to claim 3, characterized in that: In step 3, the post-treatment includes washing the organic layer, drying, removing the solvent and distilling under reduced pressure.

10. Cyclooctatetraene obtained by the process according to any one of claims 1 to 9.

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