CN116621675A - Method for synthesizing cis-1, 4-cyclohexanediol in high selectivity - Google Patents
Method for synthesizing cis-1, 4-cyclohexanediol in high selectivity Download PDFInfo
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- VKONPUDBRVKQLM-UHFFFAOYSA-N cyclohexane-1,4-diol Chemical compound OC1CCC(O)CC1 VKONPUDBRVKQLM-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 20
- 238000006243 chemical reaction Methods 0.000 claims abstract description 31
- 239000003054 catalyst Substances 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- DCZFGQYXRKMVFG-UHFFFAOYSA-N cyclohexane-1,4-dione Chemical compound O=C1CCC(=O)CC1 DCZFGQYXRKMVFG-UHFFFAOYSA-N 0.000 claims abstract description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 12
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052707 ruthenium Inorganic materials 0.000 claims abstract description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 239000003513 alkali Substances 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 238000011049 filling Methods 0.000 claims description 8
- 238000001914 filtration Methods 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 2
- LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 claims description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 235000011181 potassium carbonates Nutrition 0.000 claims description 2
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 3
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 5
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PMMYEEVYMWASQN-IMJSIDKUSA-N cis-4-Hydroxy-L-proline Chemical compound O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- BFPOIBUGVNVNKU-UHFFFAOYSA-N 2,3-dioxabicyclo[2.2.2]octane Chemical compound C1CC2CCC1OO2 BFPOIBUGVNVNKU-UHFFFAOYSA-N 0.000 description 1
- VKONPUDBRVKQLM-IZLXSQMJSA-N O[C@H]1CC[C@H](O)CC1 Chemical class O[C@H]1CC[C@H](O)CC1 VKONPUDBRVKQLM-IZLXSQMJSA-N 0.000 description 1
- 241000276425 Xiphophorus maculatus Species 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000004973 liquid crystal related substance Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
- C07C29/145—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones with hydrogen or hydrogen-containing gases
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/24—Phosphines, i.e. phosphorus bonded to only carbon atoms, or to both carbon and hydrogen atoms, including e.g. sp2-hybridised phosphorus compounds such as phosphabenzene, phosphole or anionic phospholide ligands
- B01J31/2404—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
- B01J31/2409—Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring with more than one complexing phosphine-P atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/74—Separation; Purification; Use of additives, e.g. for stabilisation
- C07C29/76—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment
- C07C29/78—Separation; Purification; Use of additives, e.g. for stabilisation by physical treatment by condensation or crystallisation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/60—Reduction reactions, e.g. hydrogenation
- B01J2231/64—Reductions in general of organic substrates, e.g. hydride reductions or hydrogenations
- B01J2231/641—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes
- B01J2231/643—Hydrogenation of organic substrates, i.e. H2 or H-transfer hydrogenations, e.g. Fischer-Tropsch processes of R2C=O or R2C=NR (R= C, H)
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/80—Complexes comprising metals of Group VIII as the central metal
- B01J2531/82—Metals of the platinum group
- B01J2531/821—Ruthenium
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07C2601/14—The ring being saturated
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Abstract
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing cis-1, 4-cyclohexanediol with high selectivity. The method takes 1, 4-cyclohexanedione as a raw material, adopts a ruthenium catalyst with large steric hindrance to control the reaction selectivity, takes hydrogen as a hydrogen source, and synthesizes cis-1, 4-cyclohexanediol in one step. The method has the advantages of high yield, few reaction steps, high selectivity, environment friendliness, easiness in large-scale preparation and the like.
Description
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a method for synthesizing cis-1, 4-cyclohexanediol with high selectivity.
Background
1, 4-cyclohexanediols are divided into trans-1, 4-cyclohexanediols and cis-1, 4-cyclohexanediols as shown in the following figures. The melting point and the boiling point of the trans-1, 4-cyclohexanediol are 416K and 423K respectively, and the trans-1, 4-cyclohexanediol is soluble in ethanol and water and is a platy solid at normal temperature. The cis-1, 4-cyclohexanediol has a melting point of 386K, is easily dissolved in water, ethanol and acetone, and is in a prismatic crystallization state at normal temperature.
Cis-1, 4-cyclohexanediol is an important pharmaceutical intermediate and can be used for synthesizing new materials such as liquid crystal electro-mechanical materials, which have very important value and unique properties in chiral reagents and polymers. At present, domestic production is low, especially high-purity cis-form or trans-form domestic production is low. In recent years, research on a synthetic method of cis-1, 4-cyclohexanediol has been attracting more and more attention. The synthesis method of cis-1, 4-cyclohexanediol mainly comprises the following steps:
(1) In Journal of Organic Chemistry,1989,54 (22), 5292-5302, the authors have expressed 2, 3-dioxabicyclo [2.2.2]Octane is taken as raw material, deuterated dichloromethane is taken as solvent, and RuCl is taken as solvent 2 (PPh 3 ) 3 Under the catalysis, cis-1, 4-cyclohexanediol is synthesized. The method has the advantages of difficult acquisition of raw materials and lower reaction yield.
(2) In patent CN 107759446A, the authors used 4- (hydrocarbyloxy) cyclohexanone as the starting material, synthesized diastereoisomers by reduction, separated the cis intermediate by column chromatography, and finally hydrolyzed to obtain cis-1, 4-cyclohexanediol. The method has complicated steps, only 50% of intermediates are utilized, the atom economy is low, and the method is not suitable for large-scale preparation due to separation by column chromatography.
(3) In Chemistry-A European Journal,2009,15 (28), 6953-6963, the authors prepared a 1, 4-cyclohexanediol mixture with hydroquinone as the starting material and Ru/C as the catalyst, after reaction at 90 degrees for 24 hours under a hydrogen atmosphere at 10 atmospheres, with the cis-trans ratio of the product being 75:25. The method has simple synthetic route, but can not effectively prepare the 1, 4-cyclohexanediol with high cis-trans ratio.
(4) In Bioorganic & Medicinal Chemistry Letters,2015,25 (3), 695-700, the authors prepared 1, 4-cyclohexanediol mixtures starting from cyclohexanone of ethylene glycol protected carbonyl by reduction to give the corresponding alcohol, followed by removal of the protecting groups in aqueous hydrochloric acid.
(5) In Tetrahedron Letters,2014,55,128-132, the authors hydrogenated 1, 4-cyclohexanediols under the action of ruthenium catalysts, unfortunately the resulting mixtures, failed to give products of a single configuration.
In summary, the reported methods have mainly the following disadvantages: complicated steps, long reaction time, high cost, difficult obtainment of raw materials, difficult separation of obtained mixtures and the like.
Disclosure of Invention
Aiming at the technical problems existing in the prior art, the invention aims to provide a synthesis method of cis-1, 4-cyclohexanediol, which has the advantages of few reaction steps, easily available raw materials, high product purity and suitability for mass production.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a method for synthesizing cis-1, 4-cyclohexanediol with high selectivity comprises the following synthetic route:
the synthesis steps are as follows: adding 1, 4-cyclohexanedione, a catalyst, alkali and a solvent into a reaction kettle, replacing with nitrogen for 3 times, filling hydrogen to a certain pressure, stirring at 50-110 ℃ for reaction for 10-40 h, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol.
Preferably, the catalyst is a large-steric-hindrance ruthenium catalyst, and the structural formula of the catalyst is one of the formulas L1-L12:
preferably, the molar ratio of the 1, 4-cyclohexanedione to the catalyst is from 100 to 900:1.
Preferably, the base is sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium ethoxide, butyllithium, tert-butyllithium, or lithium diisopropylamide.
Preferably, the molar ratio of the 1, 4-cyclohexanedione to the alkali is 1:5-20.
Preferably, the solvent is dichloromethane, chloroform, toluene, xylene, tetrahydrofuran, 2-methyltetrahydrofuran, N-dimethylformamide, methanol, ethanol or dimethylsulfoxide.
Preferably, the concentration of 1, 4-cyclohexanedione in the solvent is from 0.1 to 5mol/L (abbreviated as M).
Preferably, the pressure is 10 to 80 atmospheres.
The beneficial effects are that: the invention uses the ruthenium catalyst with large steric hindrance to control the reaction selectivity, and the cis-1, 4-cyclohexanediol is obtained by one-step synthesis with high cis-trans ratio, and the method has the advantages of high yield, few reaction steps, high selectivity, environmental protection, easy large-scale preparation and the like.
Drawings
FIG. 1 is a chart showing the nuclear magnetic resonance hydrogen spectrum of cis-1, 4-cyclohexanediol, which is a target product obtained in example 1 of the present invention.
FIG. 2 is a chart showing nuclear magnetic resonance of cis-1, 4-cyclohexanediol, which is a target product obtained in example 1 of the present invention.
Detailed Description
The present invention will be described in detail with reference to examples, but the scope of the present invention is not limited to the examples.
Example 1
A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity: adding 1, 4-cyclohexanedione (molar equivalent 1), a catalyst L1 (molar equivalent 0.01) and sodium tert-butoxide as alkali (molar equivalent 20) and a solvent dichloromethane (0.2M) into a reaction kettle, replacing 3 times with nitrogen, filling hydrogen to 10 atmospheres, stirring at 50 ℃ for reaction for 40 hours, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol with the yield of 90%.
And (3) carrying out nuclear magnetic characterization on a target product, wherein the result is as follows:
1 HNMR(400MHz,[D 6 ]DMSO):δ4.29(s,2H),3.51(m,2H),1.59-1.36(m,8H)；
13 CNMR(400MHz,[D 6 ]DMSO):δ65.89,30.37。
the melting point of the target product is 98-100 ℃ and the density is 1.156g/cm 3 。
Example 2
A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity: adding 1, 4-cyclohexanedione (molar equivalent 1), a catalyst L4 (molar equivalent 0.01) and potassium tert-butoxide as alkali (molar equivalent 10) and solvent toluene (0.5M) into a reaction kettle, replacing 3 times with nitrogen, finally filling hydrogen to 20 atmospheres, stirring at 100 ℃ for reaction for 30 hours, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol with the yield of 89%.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 3
A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity: adding 1, 4-cyclohexanedione (molar equivalent 1), a catalyst L7 (molar equivalent 0.005) and sodium methoxide as alkali (molar equivalent 5) and solvent xylene (2M) into a reaction kettle, replacing with nitrogen for 3 times, filling hydrogen to 40 atmospheres, stirring at 80 ℃ for reaction for 20 hours, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol with the yield of 92%.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 4
A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity: adding 1, 4-cyclohexanedione (molar equivalent 1), a catalyst L9 (molar equivalent 0.007), potassium hydroxide which is alkali (molar equivalent 15) and a solvent tetrahydrofuran (0.1M) into a reaction kettle, replacing the mixture with nitrogen for 3 times, filling hydrogen to 50 atmospheres, stirring at 60 ℃ for reaction for 10 hours, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol, wherein the yield is 95%.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 5
A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity: adding 1, 4-cyclohexanedione (molar equivalent 1), a catalyst L11 (molar equivalent 0.006) and cesium carbonate as alkali (molar equivalent 10) and a solvent N, N-dimethylformamide (5M) into a reaction kettle, replacing 3 times with nitrogen, filling hydrogen to 60 atmospheres, stirring at 110 ℃ for reaction for 24 hours, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol with the yield of 78%.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Example 6
A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity: adding 1, 4-cyclohexanedione (molar equivalent 1), a catalyst L12 (molar equivalent 0.009), potassium bicarbonate which is alkali (molar equivalent 18) and a solvent chloroform (1M) into a reaction kettle, replacing 3 times with nitrogen, finally filling hydrogen to 80 atmospheres, stirring at 50 ℃ for reaction for 36h, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering by diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol, wherein the yield is 95%.
The nuclear magnetic data, melting point and density of the target product of this example are the same as those of example 1.
Claims (8)
1. A method for synthesizing cis-1, 4-cyclohexanediol with high selectivity, which is characterized in that: adding 1, 4-cyclohexanedione, a catalyst, alkali and a solvent into a reaction kettle, replacing with nitrogen for 3 times, filling hydrogen to a certain pressure, stirring at 50-110 ℃ for reaction for 10-40 h, cooling to room temperature after the reaction is finished, slowly releasing hydrogen, filtering with diatomite, concentrating, and removing an organic solvent to obtain cis-1, 4-cyclohexanediol.
2. The method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1, characterized in that: the catalyst is a large-steric-hindrance ruthenium catalyst, and the structural formula of the catalyst is one of the formulas L1 to L12:
3. the method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1 or 2, characterized in that: the molar ratio of the 1, 4-cyclohexanedione to the catalyst is 100-900:1.
4. The method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1, characterized in that: the alkali is sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium methoxide, potassium ethoxide, butyl lithium, tert-butyl lithium or lithium diisopropylamide.
5. The method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1 or 4, characterized in that: the molar ratio of the 1, 4-cyclohexanedione to the alkali is 1:5-20.
6. The method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1, characterized in that: the solvent is dichloromethane, chloroform, toluene, xylene, tetrahydrofuran, 2-methyltetrahydrofuran, N-dimethylformamide, methanol, ethanol or dimethyl sulfoxide.
7. The method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1 or 6, characterized in that: the concentration of the 1, 4-cyclohexanedione in the solvent is 0.1-5 mol/L.
8. The method for synthesizing cis-1, 4-cyclohexanediol with high selectivity according to claim 1, characterized in that: the pressure is 10-80 atmospheres.
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