Preparation method of 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanediol

Abstract

The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanediol. The method comprises the following steps: (1) stirring nickel salt and a ligand in an organic solvent I to react under an inert gas condition to obtain a nickel catalyst; wherein the ligand is any one of L1, L2 and L3: # imgabs0 # (2) adding a nickel catalyst, 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanedione and alkali into a solvent II, and carrying out a hydrogenation reaction to obtain the 2, 2, 4, 4-tetramethyl-1, 3-cyclobutanediol. The method is mild in reaction condition and high in product yield (98%), and CBDO (cis: trans = 93: 7) with a high cis-form ratio can be obtained without isomer separation of the product. The used nickel catalyst has the advantages of high catalytic activity and good selectivity of a traditional supported noble metal catalyst and low price of a supported transition metal catalyst. The method is expected to be widely applied to the field of organic synthesis.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol. Background Art

[0002] 2,2,4,4-Tetramethylcyclobutane-1,3-diol (CBDO) is often used as a monomer for polyester. Compared with bisphenol A monomer, polyester synthesized using CBDO has advantages such as higher glass transition temperature, excellent weather resistance and hydrolytic stability, and does not have the disadvantages of bisphenol A monomer such as estrogen mimicry and harm to human health. Therefore, the synthesis and development of CBDO monomer raw materials are of great significance to improving the competitiveness of polyester products.

[0003] CBDO is obtained by reducing 2,2,4,4-tetramethylcyclobutanone (CBDK). However, the hydride reduction or catalytic hydrogenation reaction of CBDK usually produces a mixture of cis- and trans-CBDO, and the isomers need to be separated by recrystallization, column chromatography, etc. to obtain cis-CBDO and trans-CBDO. Polyesters with different properties can be prepared by adjusting the ratio of cis- and trans-isomers of CBDO. Compared with trans-CBDO or a mixture of the two isomers, cis-CBDO gives polyesters higher thermal stability and toughness. In order to achieve the preparation of high cis-trans ratio 2,2,4,4-tetramethyl-1,3-cyclobutanediol, CN117820078A discloses a method for preparing cis-2,2,4,4-tetramethyl-1,3-cyclobutanediol, using 2,2,4,4-tetramethyl-1,3-cyclobutanedione and hydrogen as raw materials, reacting under the action of a metal catalyst to obtain a crude 2,2,4,4-tetramethyl-1,3-cyclobutanediol, and then passing the crude product through a chromatography column filled with β-cyclodextrin polyamide filler, eluting with a first eluent, and obtaining cis-2,2,4,4-tetramethyl-1,3-cyclobutanediol with a purity higher than 98.5%. This preparation process requires further chromatography column process after the reaction is completed, and the preparation process is relatively complicated. CN107001198A and CN107001204A report the isomerization process of preparing cis-CBDO in batches. The method uses a mixture of cis- and trans-CBDO as a raw material, dissolves it in a suitable solvent system, and uses a Ru-based catalyst in an intermittent reactor under hydrogen conditions to isomerize it into a CBDO product with a cis-trans ratio between 2 and 25. The ruthenium-based supported catalyst used in this method is often expensive and difficult to be widely used. CN110124674A discloses a method for hydrogenating CBDK to obtain CBDO using an Fe, Co or Ni-based catalyst. This catalyst includes a main active metal element, a metalloid element, and an auxiliary active metal element. Not only does it use more than two metals, but the CBDO prepared by it has a low cis-trans ratio (0.6-1.5). Therefore, it is of great significance to develop a method for synthesizing CBDO by hydrogenating CBDK in one step with simple process, low cost and high selectivity for cis products. Summary of the invention

[0004] In view of the above technical problems, the present invention provides a method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol.

[0005] To achieve the above object, the technical solution of the present invention is implemented as follows:

[0006] A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol, comprising the following steps:

[0007] (1) Under inert gas conditions, a nickel salt and a ligand are stirred in an organic solvent I to react to obtain a nickel catalyst; wherein the ligand is any one of L1, L2 and L3:

[0008]

[0009] (2) The nickel catalyst obtained in step (1), 2,2,4,4-tetramethyl-1,3-cyclobutanedione and a base are added to solvent II, hydrogen is introduced, and 2,2,4,4-tetramethyl-1,3-cyclobutanediol is obtained by hydrogenation reaction.

[0010] The specific reaction formula is as follows:

[0011]

[0012] In the above step (1), the molar ratio of nickel salt to ligand is 1:(1.1-1.5).

[0013] The stirring reaction temperature in the above step (1) is 40-80°C and the time is 4-8h.

[0014] The nickel salt in the above step (1) is Ni(acac)2, NiCl2, NiBr2, NiI2, Ni(NTf2)2, Ni(BF4)2, Ni(OAc)2·4H2O, Ni(NO3)2, NiSO4, Ni(OTs)2 or Ni(ClO4)2.

[0015] In the above step (1), the organic solvent I is any one of tetrahydrofuran, benzene, toluene, p-xylene, 1,4-dioxane, dimethyl sulfoxide, 1,2-dichloroethane, ether, cyclohexane, chloroform, dichloromethane and petroleum ether.

[0016] In the above step (2), the molar ratio of the nickel catalyst to the base is 1:(0.1-2); the mass percentage of the nickel catalyst to 2,2,4,4-tetramethyl-1,3-cyclobutanedione is 5-50wt%.

[0017] In the above step (2), the base is any one of K2CO3, KHCO3, NaOtBu, CF3CO2Na, K3PO4, Na2CO3, Cs2CO3, CsF, LiOH, NaOH, NaHCO3, tBuOK and KOAc.

[0018] In the above step (2), the solvent II is any one of tetrahydrofuran, 1,4-dioxane, benzene, toluene, p-xylene, chlorobenzene, dichloromethane, chloroform and ether.

[0019] In the above step (2), the pressure of hydrogen is 3MPa-4.5Mpa; the temperature of hydrogenation reaction is 100-125°C, and the time is 8-11h.

[0020] 2,2,4,4-tetramethyl-1,3-cyclobutanediol prepared by the above preparation method.

[0021] The nickel catalyst is prepared by combining phosphorus-nitrogen multidentate ligands with abundant metal nickel. Under the electron-donating effect of the ligand, the electron density of the nickel center is greatly increased and activated. The activated nickel center is greatly improved in combining with hydrogen and catalytic hydrogenation reaction, which can effectively improve the reaction yield and reduce the reaction conditions. At the same time, due to the chelating effect between cis-2,2,4,4-tetramethyl-1,3-cyclobutanediol and the nickel center (trans-2,2,4,4-tetramethyl-1,3-cyclobutanediol does not have this chelation due to its spatial configuration), it is stabilized and can gain an advantage in the equilibrium transformation shown in the figure below, so the reaction can obtain 2,2,4,4-tetramethyl-1,3-cyclobutanediol with a high cis ratio.

[0022]

[0023] The beneficial effects produced by the present invention are:

[0024] (1) The present invention provides a method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol. Under the action of hydrogen and a nickel catalyst, 2,2,4,4-tetramethyl-1,3-cyclobutanedione is used as a raw material to react to obtain 2,2,4,4-tetramethyl-1,3-cyclobutanediol. The method has mild reaction conditions and a high product yield (98%). In addition, CBDO with a high cis ratio (cis:trans=93:7) can be obtained without isomer separation of the product.

[0025] (2) The nickel catalyst used in the present invention comprises a nickel salt and a ligand (any one of L1, L2 and L3), which has the advantages of high catalytic activity and good selectivity of a conventional supported noble metal catalyst and low price of a supported transition metal catalyst. The method is expected to be widely used in the field of organic synthesis. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0027] Figure 1 2,2,4,4-tetramethyl-1,3-cyclobutanediol prepared by the present invention 1 H NMR spectrum.

[0028] Figure 2 2,2,4,4-tetramethyl-1,3-cyclobutanediol prepared by the present invention 13 C NMR spectrum. DETAILED DESCRIPTION

[0029] The technical solution of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Example 1

[0031] A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol in this embodiment comprises the following steps:

[0032] (1) Synthesis of ligand L1

[0033] Add 5g of compound I to a flask containing 100mL of tetrahydrofuran (THF), replace the air in the flask with nitrogen three times, and pass nitrogen protection. Place the system in a 0℃ ice-water bath, add 6mL of triethylamine and 5g of chlorodiisopropylphosphine to the flask in sequence, stir and react at room temperature for 1h, cool the system to -78℃, add 3mL of n-butyllithium, stir and react at room temperature for 1h, then raise the system temperature to 60℃ and continue to react for 12h. After the reaction is completed, extract the reaction mixture three times with 100mL of toluene, combine the extracts, and evaporate the extracts to dryness to obtain 7g of ligand L1, with a yield of 81%. 1 H NMR (500MHz, CDCl3) δ7.73 (d, J = 1.7Hz, 1H), 7.66-7.58 (m, 2H), 7.49 (t, J = 7.8Hz, 1H), 6.86 (dd, J = 7.9, 1.3Hz, 1H), 6.47 (dd, J=3.8, 1.8Hz, 1H), 5.69 (s, 1H), 2.20 (hept, J=6.0Hz, 2H), 1.03 (d, J=6.1Hz, 11H). 13 CNMR(125MHz,CDCl3)δ154.94,154.85,153.61,153.58,142.44,138.87,13 8.71,126.62,111.05,110.95,108.45,104.63,36.77,36.59,18.48,18.39.

[0034] The reaction formula is as follows:

[0035]

[0036] (2) Preparation of nickel catalyst

[0037] In a nitrogen atmosphere, add 1.3g (0.01mol) of NiCl2 and 3.4g (0.012mol) of ligand L1 to a flask containing 100mL of toluene, place the flask on a stirrer, and stir the reaction at 55°C for 8h to obtain a solution containing a nickel catalyst. After the solution is cooled to room temperature, add 25mL of ether, and a large amount of solid precipitates. After filtering and drying, 3.8g of a nickel catalyst with a structure shown in the figure below is obtained, and the yield is 95%.

[0038]

[0039] (3) Synthesis of CBDO

[0040] Into the autoclave, 10 g of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, 0.4 g (0.0025 mol) of cesium carbonate, 0.5 g (0.00125 mol) of the nickel catalyst obtained in step (2) and 55 mL of tetrahydrofuran were added in sequence, and the air in the autoclave was replaced with nitrogen three times, and then replaced with nitrogen once. Hydrogen was introduced, the temperature was controlled at 120°C, the hydrogen pressure was 3.5 MPa, and the reaction was kept warm for 8 hours. After the reaction was completed, the system was cooled to room temperature, and 9.66 g of CBDO was obtained after removing the toluene solvent and the nickel catalyst, with a yield of 94% and a cis-trans ratio of 92:8. Preparation of 2,2,4,4-tetramethyl-1,3-cyclobutanediol 1 H NMR spectra and 13 C NMR spectrum Figure 1 and Figure 2 shown.

[0041] Example 2

[0042] A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol in this embodiment comprises the following steps:

[0043] (1) Synthesis of ligand L2

[0044] a. Add 5 g of o-fluorobenzaldehyde and 2 mL of ethylenediamine to a flask containing 150 mL of ethanol, replace the air in the flask with nitrogen three times, pass nitrogen protection, place the flask in an ice-water bath at 0°C, stir and react for 1.5 h, then slowly add 3 g of sodium cyanoborohydride to the flask in batches, stir and react at room temperature for 2 h, and after TLC shows that the reaction is complete, end the reaction, add 50 mL of 15 wt% sodium hydroxide solution to quench the reaction, let stand and stratify, extract three times with 250 mL of dichloromethane, combine the organic phases, wash the organic phases with saturated sodium chloride solution, dry over anhydrous sodium sulfate, and spin dry to obtain a crude product. The crude product is purified by column chromatography (5% ammonia water, methanol: dichloromethane = 0-1:20) to obtain 5.4 g of compound II with a yield of 87%.

[0045] b. Add 7.5g of diphenylphosphine and 1.6g of potassium hydride to a flask containing 100mL of tetrahydrofuran (THF), stir at room temperature for 25min, add 6.2g of compound II, stir and react at 80°C for 12h, monitor the reaction by TLC, and terminate the reaction after the reaction is complete. Add 100mL of water to the reaction mixture to quench the reaction, let stand for stratification, extract three times with 100mL of dichloromethane, combine the organic phases, dry the organic phases over anhydrous sodium sulfate, spin dry the solvent to obtain a crude product, and recrystallize the crude product in a solvent (toluene: n-hexane = 1:3) to obtain 7.2g of ligand L2, with a yield of 92%. 1 H NMR (500MHz, CDCl3) δ7.60-7.53(m,1H),7.38-7.24(m,9H),7.17(dt,J=6.4,3.9Hz,1H), 7.12-7.03(m,4H),3.99(d,J=5.9Hz,2H),2.80-2.73(m,2H),2.55(tt,J=5.9,4.1Hz,1H). 13 C NMR (125MHz, CDCl3) δ138.86,138.20,136.83,133.90,133.82,129.94,128.49,128.05,126.81,126.56,52.87,47.09.

[0046] The reaction formula is as follows:

[0047]

[0048] (2) Preparation of nickel catalyst

[0049] In a nitrogen atmosphere, 1.1 g (0.005 mol) of NiBr2 and 4.6 g (0.0075 mol) of ligand L2 were added to a flask containing 100 mL of tetrahydrofuran, and the flask was placed on a stirrer and stirred at 55°C for 8 h to obtain a solution containing a nickel catalyst. After cooling, 25 mL of ether was added to precipitate a large amount of solids, which were filtered and dried to obtain 3.6 g of a nickel catalyst with a structure shown in the figure below, with a yield of 87%.

[0050]

[0051] (3) Synthesis of CBDO

[0052] Into the autoclave, 10 g of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, 1.17 g (0.0036 mol) of cesium carbonate, 1.5 g (0.0018 mol) of the nickel catalyst obtained in step (2), and 50 mL of p-xylene were added in sequence, and the air in the autoclave was replaced three times with nitrogen, and then replaced with hydrogen once. Hydrogen was introduced, the temperature was controlled at 115° C., the hydrogen pressure was 3 MPa, and the reaction was kept warm for 10 hours. After the reaction was completed, the system was cooled to room temperature, and after removing the tetrahydrofuran solvent and the nickel catalyst, 9.46 g of CBDO was obtained, with a yield of 92% and a cis-trans ratio of 91:9.

[0053] Example 3

[0054] A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol in this embodiment comprises the following steps:

[0055] (1) Synthesis of ligand L3

[0056] a. Add 20.8g of pyridine-2,6-dicarboxylic acid to a flask containing 200mL of methanol, add 59g of thionyl chloride, stir and react at 70°C for 5h, TLC shows that the reaction is over, and add water to quench. Let stand for stratification, extract with 250mL of dichloromethane, and combine the organic phases. The above organic phase is washed with saturated sodium chloride solution, then dried over anhydrous sodium sulfate, and spin-dried to obtain a crude product. The above crude product is purified by column chromatography (ethyl acetate: petroleum ether = 1:5) to obtain 23.6g of compound III, with a yield of 97%.

[0057] b. Add 24.3g of compound III and 200mL of tetrahydrofuran (THF) to the flask. After evacuating nitrogen three times, introduce nitrogen protection. In an ice-water bath, add 9.5g of lithium aluminum tetrahydride in batches, slowly warm up to room temperature, and stir to react for 0.5h; then warm up to 60°C and stir to react for 5h. After TLC shows that the reaction is complete, add 100mL of water and 50mL of 1M hydrochloric acid aqueous solution to quench the reaction. Filter the reaction solution with diatomaceous earth, rinse with tetrahydrofuran, dry with anhydrous sodium sulfate, and spin dry to obtain a crude product. The obtained crude product was purified by silica gel column chromatography (5% triethylamine, methanol: dichloromethane = 1:10) to obtain 15.4g of compound IV with a yield of 89%.

[0058] c. Add 17.3 g of compound IV, 13.9 g of selenium dioxide and 100 mL of 1,4-dioxane to the reaction flask, stir and reflux at 100 ° C for 5 h. After TLC shows that the reaction is complete, vacuum filter and spin dry the filtrate to obtain 16.5 g of compound V with a yield of 98%.

[0059] d. To a reaction flask containing 200 mL of acetonitrile, 23.6 g of compound V and 50 g of aniline were added in sequence, and the reaction was stirred at 60 ° C for 4 h. After TLC showed that the reaction was completed, vacuum filtration was performed, washed with methanol, and vacuum dried to obtain 42.7 g of ligand L3, with a yield of 78%. 1 H NMR (500MHz, CDCl3) δ8.52 (s, 1H), 8.46 (s, 1H), 7.74-7.65 (m, 4H), 7.50-7.38 (m, 11H), 7.09 (tt, J = 7.2, 1.6Hz, 3H). 13 C NMR (125MHz, CDCl3) δ162.70,155.66,150.48,137.41,129.45,126.49,122.58,122.03.

[0060] The reaction formula is as follows:

[0061]

[0062] (2) Preparation of nickel catalyst

[0063] In a nitrogen atmosphere, 4.2 g (0.015 mol) of Ni(OAc)2·4H2O and 4.8 g (0.0165 mol) of ligand L3 were added to a flask containing 100 mL of toluene, and the flask was placed on a stirrer. The reaction was stirred at 80°C for 5 h to obtain a solution containing a nickel catalyst. After the solution was cooled to room temperature, 25 mL of ether was added to produce a large amount of precipitate. After filtration and drying, 6.3 g of a nickel catalyst with a structure shown in the figure below was obtained, with a yield of 92%.

[0064]

[0065] (3) Synthesis of CBDO

[0066] Into the autoclave, 10 g of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, 0.15 g (0.001 mol) of potassium carbonate, 5.0 g (0.0108 mol) of the nickel catalyst obtained in step (2), and 50 mL of p-xylene were added in sequence, and the air in the autoclave was replaced three times with nitrogen, and then replaced with hydrogen once. Hydrogen was introduced, the temperature was controlled at 125°C, the hydrogen pressure was 4.5 MPa, and the reaction was kept warm for 11 hours. After the reaction was completed, the system was cooled to room temperature, and 9.75 g of CBDO was obtained after removing the toluene solvent and the nickel catalyst, with a yield of 98% and a cis-trans ratio of 93:7.

[0067] Example 4

[0068] A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol in this embodiment comprises the following steps:

[0069] (1) The synthesis method of ligand L1 is the same as that of Example 1.

[0070] (2) Preparation of nickel catalyst

[0071] In a nitrogen atmosphere, add 1.3g (0.01mol) of NiCl2 and 3.4g (0.012mol) of ligand L1 to a flask containing 100mL of toluene, place the flask on a stirrer, and stir the reaction at 40°C for 4h to obtain a solution containing a nickel catalyst. After the solution is cooled to room temperature, add 25mL of ether, and a large amount of solid precipitates. After filtering and drying, 3.5g of a nickel catalyst with a structure shown in the figure below is obtained, and the yield is 88%.

[0072]

[0073] (3) Synthesis of CBDO

[0074] Into the autoclave, 10 g of 2,2,4,4-tetramethyl-1,3-cyclobutanedione, 0.4 g (0.0025 mol) of cesium carbonate, 0.5 g (0.00125 mol) of the nickel catalyst obtained in step (2), and 55 mL of tetrahydrofuran were added in sequence, and the air in the autoclave was replaced with nitrogen three times, and then replaced with nitrogen once. Hydrogen was introduced, the temperature was controlled at 100°C, the hydrogen pressure was 3.5 MPa, and the reaction was kept warm for 8 hours. After the reaction was completed, the system was cooled to room temperature, and 9.35 g of CBDO was obtained after removing the toluene solvent and the nickel catalyst, with a yield of 90% and a cis-trans ratio of 89:11.

[0075] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol, characterized in that: Here are the steps: (1) Under inert gas conditions, a nickel salt and a ligand are stirred in an organic solvent I to react to obtain a nickel catalyst; wherein the ligand is any one of L1, L2 and L3: (2) The nickel catalyst obtained in step (1), 2,2,4,4-tetramethyl-1,3-cyclobutanedione and a base are added to solvent II, hydrogen is introduced, and 2,2,4,4-tetramethyl-1,3-cyclobutanediol is obtained by hydrogenation reaction.

2. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 1, characterized in that: The molar ratio of the nickel salt to the ligand in the step (1) is 1:(1.1-1.5).

3. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 2, characterized in that: The stirring reaction in step (1) is carried out at a temperature of 40-80° C. and for a time of 4-8 hours.

4. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to any one of claims 1 to 3, characterized in that: The nickel salt in step (1) is Ni(acac)2, NiCl2, NiBr2, NiI2, Ni(NTf2)2, Ni(BF4)2, Ni(OAc)2·4H2O, Ni(NO3)2, NiSO4, Ni(OTs)2 or Ni(ClO4)2.

5. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to any one of claims 1 to 3, characterized in that: In the step (1), the organic solvent I is any one of tetrahydrofuran, benzene, toluene, p-xylene, 1,4-dioxane, dimethyl sulfoxide, 1,2-dichloroethane, ether, cyclohexane, chloroform, dichloromethane and petroleum ether.

6. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 5, characterized in that: In the step (2), the molar ratio of the nickel catalyst to the base is 1:(0.1-2); the mass percentage of the nickel catalyst to 2,2,4,4-tetramethyl-1,3-cyclobutanedione is 5-50wt%.

7. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 6, characterized in that: The base in step (2) is any one of K2CO3, KHCO3, NaOtBu, CF3CO2Na, K3PO4, Na2CO3, Cs2CO3, CsF, LiOH, NaOH, NaHCO3, tBuOK and KOAc.

8. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 7, characterized in that: In the step (2), the solvent II is any one of tetrahydrofuran, 1,4-dioxane, benzene, toluene, p-xylene, chlorobenzene, dichloromethane, chloroform and ether.

9. The method for preparing 2,2,4,4-tetramethyl-1,3-cyclobutanediol according to claim 8, characterized in that: In the step (2), the pressure of hydrogen is 3MPa-4.5Mpa; the temperature of the hydrogenation reaction is 100-125°C, and the time is 8-11h.

10. 2,2,4,4-tetramethyl-1,3-cyclobutanediol prepared by the preparation method according to claim 1.

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