CN113845412B - Synthesis method of ortho-cyclohexanedione - Google Patents
Synthesis method of ortho-cyclohexanedione Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 112
- 238000000034 method Methods 0.000 claims abstract description 27
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 88
- 150000001875 compounds Chemical class 0.000 claims description 87
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 58
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 48
- 238000007254 oxidation reaction Methods 0.000 claims description 43
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 40
- 239000002904 solvent Substances 0.000 claims description 39
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 239000003054 catalyst Substances 0.000 claims description 24
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- 230000003197 catalytic effect Effects 0.000 claims description 17
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 16
- 150000002085 enols Chemical class 0.000 claims description 16
- 238000006266 etherification reaction Methods 0.000 claims description 16
- 229910052710 silicon Inorganic materials 0.000 claims description 16
- 239000010703 silicon Substances 0.000 claims description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 15
- 239000007800 oxidant agent Substances 0.000 claims description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 12
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 9
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 8
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 claims description 8
- 230000001590 oxidative effect Effects 0.000 claims description 8
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
- 239000011698 potassium fluoride Substances 0.000 claims description 5
- 235000003270 potassium fluoride Nutrition 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000005695 Ammonium acetate Substances 0.000 claims description 4
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 4
- 229940043376 ammonium acetate Drugs 0.000 claims description 4
- 235000019257 ammonium acetate Nutrition 0.000 claims description 4
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 claims description 4
- 229910001634 calcium fluoride Inorganic materials 0.000 claims description 4
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 4
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000011775 sodium fluoride Substances 0.000 claims description 4
- 235000013024 sodium fluoride Nutrition 0.000 claims description 4
- 235000009518 sodium iodide Nutrition 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 238000010189 synthetic method Methods 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 16
- 238000009776 industrial production Methods 0.000 abstract description 6
- 231100000331 toxic Toxicity 0.000 abstract description 6
- 230000002588 toxic effect Effects 0.000 abstract description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000006227 byproduct Substances 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 238000000967 suction filtration Methods 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- 238000001914 filtration Methods 0.000 description 9
- 238000002390 rotary evaporation Methods 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000002274 desiccant Substances 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 239000007789 gas Substances 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 230000007935 neutral effect Effects 0.000 description 7
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 4
- 238000000605 extraction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000009987 spinning Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- JQPFYXFVUKHERX-UHFFFAOYSA-N 2-hydroxy-2-cyclohexen-1-one Natural products OC1=CCCCC1=O JQPFYXFVUKHERX-UHFFFAOYSA-N 0.000 description 1
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- OILAIQUEIWYQPH-UHFFFAOYSA-N cyclohexane-1,2-dione Chemical compound O=C1CCCCC1=O OILAIQUEIWYQPH-UHFFFAOYSA-N 0.000 description 1
- LSRPARCOXAUYNP-UHFFFAOYSA-N cyclohexylidene(oxido)oxidanium Chemical compound [O-][O+]=C1CCCCC1 LSRPARCOXAUYNP-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/29—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of organic synthesis, and provides a synthesis method of ortho-cyclohexanedione. The method provided by the invention not only can protect carbonyl, but also can improve the selectivity of the product; the raw materials used in the invention are cheap and easy to obtain, no toxic or harmful reagent is needed, the safety is good, no toxic or harmful gas is generated in the reaction process, and the method is environment-friendly; in addition, the method provided by the invention is simple to operate, few in byproducts, high in product purity, high in economic benefit and suitable for industrial production.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a synthesis method of ortho-cyclohexanedione.
Background
Ortho-cyclohexanedione is an important chemical raw material, and can be used for synthesizing fine chemicals such as perfume, medicine and the like, and can also be used as an organic chemical solvent. The ortho-cyclohexanedione is mainly prepared by cyclohexanone oxidation, and the following synthesis methods are mainly adopted at present:
(1) A selenium dioxide oxidation method; in 1875, riley et al in the paper "Selenium Dioxide aNew OxidisingAgent" published Journal ofChemical Society report that cyclohexanone is oxidized by using Selenium Dioxide as an oxidizing agent, the method comprises the steps of heating cyclohexanone to 70-80 ℃, then dropwise adding a mixed solution of Selenium Dioxide and ethanol into a bottle, heating and refluxing for 2 hours after the dropwise addition, and finally drying, separating and purifying to obtain ortho-cyclohexanedione, wherein the yield is 30-50%. The method has simple steps, but has lower yield, and the selenium dioxide has extremely toxic effect and great harm to human bodies and environment, and is not suitable for industrial production.
(2) An isoamyl nitrite oxidation process; in 2014, wangwei et al in Zhejiang chemical journal published paper, "research on oxidation of cyclohexanone by isoamyl nitrite to prepare 1, 2-cyclohexanedione", wherein isoamyl nitrite is adopted to oxidize cyclohexanone, the method comprises dissolving cyclohexanone in sulfuric acid solution, dropwise adding isoamyl nitrite under ice bath condition, reacting for 3h, extracting with dichloromethane after reaction, and anhydrous MgSO 4 Drying, filtering, separating, purifying and rectifying to obtain the ortho-cyclohexanedione, wherein the yield is 60-80%. The method has moderate yield, but the reaction needs to use a large amount of diethyl ether and acid to generate a large amount of waste liquid, has great harm to the environment and is not suitable for industrial production.
(3) A hydrogen peroxide oxidation process; in 2020, a method for preparing ortho-cyclohexanedione by using hydrogen peroxide as cyclohexanone oxide is reported in patent CN 112441891A by Nanjing New Material research institute, china Steel group, and is characterized in that cyclohexanone, a catalyst and a ligand are uniformly stirred in a nitrogen atmosphere, hydrogen peroxide is dropwise added at room temperature, after the reaction is finished, water is used for washing, liquid separation is carried out, and an organic layer is subjected to reduced pressure rectification to obtain the ortho-cyclohexanedione, wherein the yield is about 95%. The method has higher yield, but the beta-diketone imine ligand is required to be used, is not easy to obtain, needs to be synthesized by oneself, has a complex preparation process and is not suitable for large-scale production.
In summary, the existing preparation method of ortho-cyclohexanedione has the defects of complex preparation steps, high cost and poor environmental protection, and is not suitable for industrial production.
Disclosure of Invention
In view of this, the present invention provides a method for synthesizing ortho-cyclohexanedione. The method provided by the invention has the advantages of simple steps, low raw material price, wide sources, no toxic and harmful waste residue and gas in the reaction process, good environmental protection, high product yield, higher economic benefit and suitability for industrial production.
In order to achieve the above object, the present invention provides the following technical solutions:
a method for synthesizing ortho-cyclohexanedione, comprising the following steps:
(1) Mixing cyclohexanone, trimethylchlorosilane, an alkaline agent and a catalyst to perform enol silicon etherification reaction to obtain a compound with a structure shown in a formula I;
(2) Mixing the compound with the structure shown in the formula I with m-chloroperoxybenzoic acid to perform oxidation reaction to obtain a compound with the structure shown in the formula II;
(3) Mixing the compound with the structure shown in the formula II with a desilication reagent to perform desilication reaction to obtain a compound with the structure shown in the formula III;
(4) Mixing the compound with the structure shown in the formula III, a catalyst and an oxidant for catalytic oxidation reaction to obtain ortho-cyclohexanedione;
preferably, the alkaline agent is one or more of potassium carbonate, sodium hydroxide, potassium hydroxide, triethylamine and pyridine;
the catalyst in the step (1) is one or more of potassium iodide, sodium iodide, iodine simple substance, sodium methoxide, potassium tert-butoxide and triethylamine;
the solvent for the enol silicon etherification reaction is one or more of toluene, dioxane, N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran.
Preferably, the molar ratio of the cyclohexanone to the trimethylchlorosilane is 1 (1-3); the dosage of the catalyst in the step (1) is 1-10% of the weight of cyclohexanone; the dosage of the alkaline agent is 50-200% of the weight of the cyclohexanone.
Preferably, the temperature of the enol silicon etherification reaction is 50-100 ℃ and the time is 2-10 h.
Preferably, the mol ratio of the compound with the structure shown in the formula I to the m-chloroperoxybenzoic acid is (1-4): 1;
the solvent for oxidation reaction is one or more of cyclohexane, cyclopentane, n-hexane or petroleum ether.
Preferably, the temperature of the oxidation reaction is-20-0 ℃ and the time is 1-5 h.
Preferably, the desilication agent is one or more of potassium fluoride, sodium fluoride, calcium fluoride and hydrofluoric acid; the mol ratio of the compound with the structure shown in the formula II to the desilication reagent is 1 (1-5);
the solvent for desilication reaction is one or more of dichloromethane, chloroform, methanol, ethanol, acetonitrile and tetrahydrofuran.
Preferably, the desilication reaction is carried out at a temperature of 20-40 ℃ for 1-4 hours.
Preferably, the catalyst in the step (4) is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonium acetate and triethylamine;
the oxidant is any one of phosphorus pentoxide, dimethyl sulfoxide (DMSO), ferric chloride or manganese dioxide;
the solvent for catalytic oxidation reaction is one or more of dichloromethane, N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran.
Preferably, the molar ratio of the compound with the structure shown in the formula III to the oxidant is 1 (1-4); the dosage of the catalyst in the step (4) is 20-80% of the weight of the compound with the structure shown in the formula III;
the temperature of the catalytic oxidation reaction is-5 ℃ and the time is 0.5-6 h.
The invention provides a synthesis method of ortho-cyclohexanedione, which adopts cyclohexanone as a raw material, and obtains a final product ortho-cyclohexanedione through enol silicon etherification, oxidation, desilication and catalytic oxidation reactions. The method provided by the invention adopts trimethylsilyl to protect carbonyl in cyclohexanone, then introduces carbonyl groups at the ortho position through oxidation reaction, removes trimethylsilyl through desilication, and finally oxidizes hydroxyl into carbonyl through catalytic oxidation reaction, thereby obtaining ortho-cyclohexanedione. The method provided by the invention not only can protect carbonyl, but also can improve the selectivity of the product; the raw materials used in the invention are cheap and easy to obtain, no toxic or harmful reagent is needed, the safety is good, no toxic or harmful gas is generated in the reaction process, and the method is environment-friendly; in addition, the method provided by the invention is simple to operate, few in byproducts, high in product purity, high in economic benefit and suitable for industrial production.
Drawings
FIG. 1 is a gas chromatograph of a compound having the structure shown in formula I prepared in example 1;
FIG. 2 is a gas chromatograph of the compound having the structure shown in formula II prepared in example 1;
FIG. 3 is a gas chromatograph of a compound having a structure shown in formula III prepared in example 1;
FIG. 4 is a schematic illustration of ortho-cyclohexanedione prepared in example 1 1 H-NMR chart.
Detailed Description
The invention provides a synthesis method of ortho-cyclohexanedione, which comprises the following steps:
(1) Mixing cyclohexanone, trimethylchlorosilane, an alkaline agent and a catalyst to perform enol silicon etherification reaction to obtain a compound with a structure shown in a formula I;
(2) Mixing the compound with the structure shown in the formula I with m-chloroperoxybenzoic acid to perform oxidation reaction to obtain a compound with the structure shown in the formula II;
(3) Mixing the compound with the structure shown in the formula II with a desilication reagent to perform desilication reaction to obtain a compound with the structure shown in the formula III;
(4) Mixing the compound with the structure shown in the formula III, a catalyst and an oxidant for catalytic oxidation reaction to obtain ortho-cyclohexanedione;
in the invention, the synthesis route of the ortho-cyclohexanedione is shown as a formula A:
the following is a detailed description of formula A.
The invention mixes cyclohexanone, trimethylchlorosilane, alkaline agent and catalyst to carry out enol silicon etherification reaction, and the compound with the structure shown in the formula I is obtained. In the invention, the alkaline agent is preferably one or more of potassium carbonate, sodium hydroxide, potassium hydroxide, triethylamine and pyridine; the catalyst for the enol silicon etherification is preferably one or more of potassium iodide, sodium iodide, iodine simple substance, sodium methoxide, potassium tert-butoxide and triethylamine; the preferable solvent for the enol silicon etherification reaction is one or more of toluene, dioxane, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and tetrahydrofuran.
In the present invention, the molar ratio of cyclohexanone to trimethylchlorosilane is preferably 1 (1-3), more preferably 1 (1.5-2.5); the catalyst is preferably used in an amount of 1 to 10% by weight, more preferably 3 to 8% by weight, based on cyclohexanone; the amount of the alkaline agent is preferably 50 to 200% by weight, preferably 100 to 150% by weight, based on cyclohexanone.
In the present invention, the temperature of the enol silicon etherification reaction is preferably 50 to 100 ℃, more preferably 60 to 80 ℃, and the time of the enol silicon etherification reaction is preferably 2 to 10 hours, more preferably 3 to 8 hours.
In the specific embodiment of the invention, cyclohexanone, an alkaline agent, a catalyst and a solvent are preferably mixed, the obtained mixed solution is heated to the temperature of enol silicon etherification, then trimethylchlorosilane is dropwise added into the mixed solution, and after the dropwise addition is finished, the mixed solution is subjected to heat preservation for reaction; the time of the enol silicon etherification reaction is counted from the completion of the dropwise addition of the trimethylchlorosilane; in particular embodiments of the present invention, TLC is preferably used to monitor the progress of the reaction.
After the enol silicon etherification reaction is finished, the obtained product feed liquid is cooled to room temperature, filtered, filter cakes are washed by diethyl ether, the obtained filtrate is washed by 5 weight percent of HCl solution, 5 weight percent of sodium bicarbonate solution, saturated NaCl solution and distilled water in sequence, and the organic solvent in the washed filtrate is evaporated to dryness, so that the compound with the structure shown in the formula I is obtained.
After the compound with the structure shown in the formula I is obtained, the compound with the structure shown in the formula I and m-chloroperoxybenzoic acid (m-CPBA) are mixed for oxidation reaction to obtain the compound with the structure shown in the formula II. In the present invention, the molar ratio of the compound having the structure represented by formula I to m-chloroperoxybenzoic acid is preferably (1 to 4): 1, more preferably (1.5 to 3.5): 1; the oxidation reaction solvent is preferably one or more of cyclohexane, cyclopentane, n-hexane or petroleum ether.
In the present invention, the temperature of the oxidation reaction is preferably-20 to 0 ℃, more preferably-10 to-5 ℃, and the time of the oxidation reaction is preferably 1 to 5 hours, more preferably 2 to 4 hours.
In the specific embodiment of the invention, the temperature of the solvent is preferably reduced to the oxidation reaction temperature, then the compound with the structure shown in the formula I is added into the solvent, then the m-chloroperoxybenzoic acid is added into the feed liquid for a plurality of times, the m-chloroperoxybenzoic acid is kept at the oxidation reaction temperature for reaction after being added, and the mixture is preferably stirred for 2 hours at room temperature after the reaction is completed at the oxidation reaction temperature, so that the oxidation is more thorough; in the present invention, the mass of each addition of m-chloroperoxybenzoic acid is preferably 10 to 30% of the total mass of m-chloroperoxybenzoic acid.
After the oxidation reaction is finished, the obtained product feed liquid is preferably filtered, and the obtained filtrate is subjected to rotary evaporation to obtain the compound with the structure shown in the formula II.
After obtaining the compound with the structure shown in the formula II, the invention mixes the compound with the structure shown in the formula II with a desilication reagent to carry out desilication reaction, thus obtaining the compound with the structure shown in the formula III. In the invention, the desilication reagent is preferably one or more of potassium fluoride, sodium fluoride, calcium fluoride and hydrofluoric acid; the molar ratio of the compound having the structure shown in the formula II to the desilication reagent is preferably 1 (1-5), more preferably 1 (1.1-4), and even more preferably 1 (1.5-2); the solvent for desilication reaction is preferably one or more of dichloromethane, chloroform, methanol, ethanol, acetonitrile and tetrahydrofuran.
In the present invention, the temperature of the desilication reaction is preferably 20 to 40 ℃, more preferably 25 to 35 ℃, and the time of the desilication reaction is preferably 1 to 4 hours, more preferably 2 to 3 hours.
In a specific embodiment of the present invention, it is preferable to add the compound having the structure shown in formula II and the desilication reagent to a solvent, and to perform the reaction at the temperature of the desilication reaction.
After the desilication reaction is finished, the pH value of the obtained product feed liquid is preferably adjusted to be neutral, then the product feed liquid with the pH value adjusted is extracted by using methylene dichloride to obtain a methylene dichloride phase, the methylene dichloride phase is dried by using anhydrous sodium sulfate, a drying agent is removed by filtration after the drying is finished, the dried methylene dichloride phase is subjected to rotary evaporation, and the solvent in the dried methylene dichloride phase is removed to obtain the compound with the structure shown in the formula III.
After the compound with the structure shown in the formula III is obtained, the compound with the structure shown in the formula III, a catalyst and an oxidant are mixed for catalytic oxidation reaction, so that the ortho-cyclohexanedione is obtained. In the invention, the catalyst for catalytic oxidation reaction is preferably one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonium acetate and triethylamine; the oxidant is preferably one or more of phosphorus pentoxide, dimethyl sulfoxide, ferric chloride or manganese dioxide, and more preferably a mixture of phosphorus pentoxide and dimethyl sulfoxide; in the invention, the phosphorus pentoxide is an electrophile, and can activate dimethyl sulfoxide, so that the product yield is improved; the solvent for catalytic oxidation is preferably one or more of dichloromethane, N-Dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and tetrahydrofuran.
In the present invention, the molar ratio of the compound having the structure represented by formula III to the oxidizing agent is preferably 1 (1 to 4), more preferably 1 (2 to 3); the catalyst is preferably used in an amount of 20 to 80% by weight, more preferably 30 to 60% by weight, based on the compound having the structure represented by formula III.
In the present invention, the temperature of the catalytic oxidation reaction is preferably-5 to 5 ℃, more preferably-3 to 3 ℃, and the time of the catalytic oxidation reaction is preferably 0.5 to 6 hours, more preferably 1 to 5 hours.
In the specific embodiment of the present invention, it is preferable to dissolve the compound having the structure shown in formula III in a solvent, then add a catalyst and an oxidizing agent to the solution, and cool the temperature of the mixed solution to the temperature of catalytic oxidation reaction to perform the reaction.
After the catalytic oxidation reaction is finished, the invention preferably adopts hydrochloric acid solution to quench the reaction, and then the obtained product feed liquid is sequentially filtered, washed, dried and distilled with solvent to obtain ortho-cyclohexanedione; the mass fraction of the hydrochloric acid solution is preferably 10%; the washing detergent is preferably a solvent for catalytic oxidation reaction, and the drying agent used for drying is preferably anhydrous sodium sulfate.
The technical solutions of the present invention will be clearly and completely described in the following in connection with the embodiments of the present invention.
Example 1
(1) 9.8g of cyclohexanone, 21mL of triethylamine and 20mL of DMF are added into a flask and uniformly mixed, the mixture is heated to 80 ℃, 15mL of trimethylchlorosilane is added dropwise into the solution, the reaction is kept at 80 ℃ for 2 hours, the TCL monitors the reaction progress, the solution is cooled to room temperature after the reaction is finished, suction filtration is carried out, diethyl ether (20 mL multiplied by 3) is used for washing filter cakes, filtrate is respectively 10mL 5%HCl,10mL 5 percent of sodium bicarbonate solution, 10mL of saturated NaCl solution and 10mL of distilled water are used for washing for 3 times, and finally, the solvent is distilled off by spin to obtain the compound with the structure shown in the formula I, the yield is 91.2 percent, and the purity is 95.2 percent.
(2) 15mL of cyclohexane was added to the reaction flask, the temperature of the reaction flask was maintained at-15 ℃,5g of a compound having a structure represented by formula I was added to the flask, 2.5-g m-CPBA was added thereto a small amount of a plurality of times after stirring and dissolution, and after the addition was completed, the reaction was carried out for 1 hour, and then the reaction flask was left to stand at room temperature with stirring for 2 hours. And (3) carrying out suction filtration after the reaction is finished, removing filter residues, and carrying out rotary evaporation on the filtrate to obtain the compound with the structure shown in the formula II, wherein the yield is 86%, and the purity is 94.5%.
(3) 15mL of methylene chloride, 3g of a compound having a structure represented by formula II and 1.5g of potassium fluoride were charged into the flask, and reacted at 30℃for 2 hours, and the TCL was monitored for progress of the reaction. After the reaction, the pH was adjusted to neutral, the resulting dichloromethane phase was dried over anhydrous sodium sulfate using a dichloromethane extraction solution, and then the drying agent was removed by filtration, and the solvent was spin-evaporated to give a compound having the structure shown in formula III in a yield of 87% and a purity of 94.1%.
(4) 4mL of DMSO and 0.1g of phosphorus pentoxide were sequentially added to a solution of 2g of a compound having a structure represented by formula III in 20mL of methylene chloride, reacted at-5℃for 1 hour, and 2mL of triethylamine was added dropwise to the reaction flask, followed by further reaction for 1 hour. After the reaction is finished, the reaction is quenched by 10% hydrochloric acid, and then the solvent is filtered, washed, dried and distilled in turn to obtain the ortho-cyclohexanedione with the yield of 82.5% and the purity of 95%.
FIG. 1 is a gas chromatograph of a compound having the structure shown in formula I prepared in this example;
FIG. 2 is a gas chromatograph of the compound having the structure shown in formula II prepared in this example;
FIG. 3 is a gas chromatograph of a compound having a structure shown in formula III prepared in this example;
FIG. 4 shows the ortho-cyclohexanedione prepared in this example 1 H-NMR chart.
As can be seen from FIGS. 1 to 4, the products obtained in steps 1 to 4 of the present invention conform to the expected structure.
Example 2
(1) 98g of cyclohexanone, 100mL of 30% NaOH solution, 1g of potassium iodide and 200mL of DMF are added into a flask, the mixture is uniformly mixed, the mixture is heated to 70 ℃, 150mL of trimethylchlorosilane is added dropwise into the solution, the reaction is kept at 70 ℃ for 3 hours, TCL monitors the reaction progress, the solution is cooled to room temperature after the reaction is finished, suction filtration is carried out, diethyl ether (50 mL multiplied by 3) is used for washing filter cakes, filtrate is respectively 50mL 5%HCl,50mL 5% sodium bicarbonate solution, 50mL of saturated NaCl solution and 50mL of distilled water are used for washing 3 times, and finally the solvent is distilled off in a spinning way to obtain the compound with the structure shown in the formula I, the yield is 88.9%, and the purity is 95.7%.
(2) 100mL of cyclohexane was added to the reaction flask, the temperature of the reaction flask was maintained at-15 ℃, 65g of a compound having a structure represented by formula I was added to the flask, 20g m-CPBA was added thereto a small amount of a plurality of times after stirring and dissolution, and after the addition was completed, the reaction was carried out for 2 hours, and then the reaction flask was left to stand at room temperature with stirring for 3 hours. And (3) carrying out suction filtration after the reaction is finished, removing filter residues, and carrying out rotary evaporation on the filtrate to obtain the compound with the structure shown in the formula II, wherein the yield is 88.2%, and the purity is 95.8%.
(3) 150mL of methylene chloride, 30g of the compound having the structure shown in formula II and 10g of sodium fluoride were charged into the flask, reacted at 30℃for 3 hours, and the TCL was monitored for progress of the reaction. After the reaction, the pH is adjusted to be neutral, the dichloromethane is extracted, the dichloromethane phase is dried and dehydrated by anhydrous sodium sulfate, then the drying agent is removed by filtration, and the solvent is evaporated by spin drying to obtain the compound with the structure shown in the formula III, wherein the yield is 89%, and the purity is 93.7%.
(4) 20mL of DMSO and 0.5g of phosphorus pentoxide were sequentially added to a 150mL of methylene chloride solution containing 20g of the compound having the structure represented by formula III, reacted at-5℃for 2 hours, and 10mL of triethylamine was added dropwise to the reaction flask, followed by further reaction for 2 hours. After the reaction is finished, the reaction is quenched by 10% hydrochloric acid, filtered, washed and dried, and the solvent is distilled to obtain the ortho-cyclohexanedione with the yield of 87.5% and the purity of 92.5%.
Example 3
(1) 9.8g of cyclohexanone, 21mL of 30% potassium carbonate solution, 0.3g of sodium iodide and 20mL of DMSO are added into a flask, the mixture is uniformly mixed, the mixture is heated to 80 ℃, 15mL of trimethylchlorosilane is added dropwise into the solution, the reaction is kept at 80 ℃ for 2 hours, TCL monitors the reaction progress, after the reaction is finished, the solution is cooled to room temperature, suction filtration is carried out, anhydrous acetonitrile (20 mL multiplied by 3) is used for washing filter cakes, filtrate is respectively 10mL 5%HCl,10mL 5% sodium bicarbonate solution, 10mL of saturated NaCl solution and 10mL of distilled water for 3 times, and finally, the solvent is distilled off in a spinning way to obtain the compound with the structure shown in the formula I, the yield is 83.1%, and the purity is 90.3%.
(2) 15mL of cyclopentane is added into a reaction bottle, the temperature of the reaction bottle is kept at-15 ℃,5g of a compound with a structure shown in a formula I is added into the bottle, 2.5-g m-CPBA is added into the bottle for a small amount of times after stirring and dissolving, the reaction is carried out for 1h after the addition, and then the mixture is placed at room temperature and stirred for 2h. And (3) carrying out suction filtration after the reaction is finished, removing filter residues, and carrying out rotary evaporation on the filtrate to obtain the compound with the structure shown in the formula II, wherein the yield is 72%, and the purity is 89.6%.
(3) Into a flask, 15mL of ethanol, 3g of a compound having a structure represented by formula II and 1.5g of calcium fluoride were charged, and reacted at 30℃for 2 hours, and TCL was monitored for progress of the reaction. After the reaction, the pH is adjusted to be neutral, the dichloromethane extraction solution is dried and dehydrated by anhydrous sodium sulfate, then the drying agent is removed by filtration, and the solvent is evaporated by spin drying to obtain the compound with the structure shown in the formula III, wherein the yield is 70%, and the purity is 88.7%.
(4) 3g of manganese dioxide was sequentially added to a solution of 2g of a compound of formula III in 20mL of methylene chloride, reacted at-5℃for 1 hour, 2mL of ammonium acetate was added dropwise to the reaction flask, and the reaction was continued for 1 hour. After the reaction is finished, the reaction is quenched by 10% hydrochloric acid, filtered, washed and dried, and the solvent is distilled to obtain the ortho-cyclohexanedione with the yield of 51.5% and the purity of 85%.
Example 4
(1) 50g of cyclohexanone, 100mL of pyridine, 5g of potassium tert-butoxide and 100mL of tetrahydrofuran are added into a flask, the mixture is uniformly mixed, the mixture is heated to 85 ℃, 90mL of trimethylchlorosilane is added dropwise into the solution, the reaction is kept at 85 ℃ for 4h, TCL monitors the reaction progress, the solution is cooled to room temperature after the reaction is finished, suction filtration is carried out, diethyl ether (40 mL multiplied by 3) is used for washing filter cakes, filtrate is respectively 50mL 5%HCl,50mL 5% sodium bicarbonate solution, 50mL of saturated NaCl solution and 50mL of distilled water are used for washing 3 times, and finally the solvent is distilled off in a spinning way to obtain the compound with the structure shown in the formula I, the yield is 96.6%, and the purity is 95.7%.
(2) 80mL of petroleum ether was added to the reaction flask, the temperature of the reaction flask was maintained at 0 ℃,30g of a compound having a structure represented by formula I was added to the flask, 10g m-CPBA was added thereto a small amount of a plurality of times after stirring and dissolution, reacted for 2 hours after the addition was completed, and then left to stand at room temperature for 3 hours with stirring. And (3) carrying out suction filtration after the reaction is finished, removing filter residues, and carrying out rotary evaporation on the filtrate to obtain the compound with the structure shown in the formula II, wherein the yield is 91.7%, and the purity is 94.9%.
(3) Into a flask, 75mL of a chloroform solution, 10g of a compound having a structure represented by formula II and 8g of hydrofluoric acid were charged, and reacted at 40℃for 2 hours, and TCL was used to monitor the progress of the reaction. After the reaction, the pH is adjusted to be neutral, the dichloromethane is extracted, the dichloromethane phase is dried and dehydrated by anhydrous sodium sulfate, then the drying agent is removed by filtration, and the solvent is evaporated by spin to obtain the compound with the structure shown in the formula III, wherein the yield is 85%, and the purity is 94.3%.
(4) 8.5g of ferric chloride was sequentially added to 80mL of a tetrahydrofuran solution containing 6g of the compound having the structure represented by formula III, reacted at-5℃for 1.5 hours, 10mL of triethylamine was added dropwise to the reaction flask, and the reaction was continued for 3 hours. After the reaction is finished, the reaction is quenched by 10% hydrochloric acid, filtered, washed and dried, and the solvent is distilled off to obtain the ortho-cyclohexanedione with the yield of 81.7% and the purity of 96%.
Example 5
(1) 1000g of cyclohexanone, 2000mL of triethylamine and 2000mL of DMF are added into a reaction kettle and uniformly mixed, the mixture is heated to 80 ℃, 1500mL of trimethylchlorosilane is added dropwise into the solution, the reaction is kept at 80 ℃ for 5h, the TCL monitors the reaction progress, the solution is cooled to room temperature after the reaction is finished, the solution is filtered and washed by diethyl ether (500 mL multiplied by 3), and the filtrate is subjected to rotary evaporation to obtain the compound with the structure shown in the formula I, wherein the yield is 94.8% and the purity is 97.2%.
(2) 1500mL of cyclohexane was added to the reactor, the reactor temperature was maintained at-15 ℃, 500g of a compound having the structure represented by formula I was added to the flask, 250g m-CPBA was added thereto a small amount of a plurality of times after stirring and dissolution, and reacted for 5 hours after the addition was completed, and then left to stand at room temperature for 3 hours with stirring. Filtering after the reaction is finished, removing filter residues, and performing rotary evaporation on the filtrate to obtain the compound with the structure shown in the formula II, wherein the yield is 93%, and the purity is 97.5%.
(3) 1500mL of methylene chloride, 300g of a compound having a structure represented by formula II and 150g of potassium fluoride were charged into the reactor, reacted at room temperature for 5 hours, and the TCL was monitored for progress of the reaction. After the reaction, the pH value is adjusted to be neutral, the dichloromethane extraction solution is dried and dehydrated by anhydrous sodium sulfate, then the drying agent is removed by filtration, and the solvent is evaporated by spin drying to obtain the compound with the structure shown in the formula III, wherein the yield is 95.3%, and the purity is 96.1%.
(4) 100mL of DMSO and 2g of phosphorus pentoxide were sequentially added to a solution of 200g of a compound having a structure represented by formula III in 2000mL of methylene chloride, reacted at-5℃for 5 hours, 200mL of triethylamine was added to the reaction flask, and the reaction was continued for 3 hours. After the reaction is finished, the reaction is quenched by 10% hydrochloric acid, filtered, washed and dried, and the solvent is distilled off to obtain the ortho-cyclohexanedione with the yield of 83.5% and the purity of 97%.
Comparative example 1
(1) 9.8g of cyclohexanone and 21mL of sodium hydroxide solution are added into a flask, 20mL of DMF is uniformly mixed, the mixture is heated to 80 ℃, 15mL of trimethylchlorosilane is added dropwise into the solution, the reaction is kept at 80 ℃ for 2h, the TCL monitors the reaction progress, the solution is cooled to room temperature after the reaction is finished, suction filtration is carried out, diethyl ether (20 mL multiplied by 3) is used for washing filter cakes, filtrate is respectively washed by 10mL 5%HCl,10mL 5% of sodium bicarbonate solution, 10mL of saturated NaCl and 10mL of distilled water for 3 times, and finally the solvent is distilled off in a rotary manner to obtain the compound with the structure shown in the formula I, the yield is 64.3%, and the purity is 85.2%.
Steps (2), (3) and (4) are the same as in example 1.
Comparative example 2
(1) The procedure is as in step (1) of example 1.
(2) 15mL of cyclohexane was added to the reaction flask, the reaction flask was left at room temperature, 5g of a compound having a structure represented by formula I was added to the flask, and after stirring and dissolution, 2.5. 2.5g m-CPBA was added thereto a small amount of a plurality of times, and after the addition was completed, the reaction was carried out for 3 hours. And (3) carrying out suction filtration after the reaction is finished, removing filter residues, and carrying out rotary evaporation on the filtrate to obtain the compound with the structure shown in the formula II, wherein the yield is 34%, and the purity is 67%.
Steps (3), (4) are the same as in example 1.
Comparative example 3
(1) The procedure is as in step (1) of example 1.
(2) The procedure is as in step (2) of example 1.
(3) 15mL of methylene chloride, 3g of a compound having a structure represented by formula II and 1.5g of potassium chloride were charged into the flask, and reacted at 30℃for 2 hours, and the TCL was monitored for progress of the reaction. After the reaction, the pH is adjusted to be neutral, the solution is extracted by dichloromethane, the dichloromethane phase is dried and dehydrated by anhydrous sodium sulfate, then the drying agent is removed by filtration, and the solvent is evaporated by spin drying. No corresponding product was obtained.
(4) The procedure is as in step (4) of example 1.
Comparative example 4
Steps (1), (2) and (3) are the same as in example 1.
(4) 4mL of DMSO was added to a solution of 2g of the compound of formula III in 20mL of methylene chloride, and the mixture was reacted at-5℃for 1 hour, and 2mL of triethylamine was added dropwise to the reaction flask, followed by further reaction for 1 hour. After the reaction is finished, the reaction is quenched by 10% hydrochloric acid, filtered, washed and dried, and the solvent is distilled to obtain the ortho-cyclohexanedione with the yield of 42.5% and the purity of 75%.
As can be seen from the comparative examples, the catalyst in the step (1) of the present invention can promote the reaction, accelerate the reaction rate, and improve the yield and purity of the product; the step (2) of the invention needs to be carried out under the condition of low temperature, if the reaction is placed at room temperature, the reaction is incomplete, the product yield and purity are reduced, and the reaction is not facilitated; in the step (3) of the invention, a desilication reagent is needed, and the potassium chloride cannot cause desilication reaction; when DMSO is used as an oxidant in the step (4), electrophiles such as phosphorus pentoxide and the like are required to be added for activation, otherwise, the yield and purity of the product are low.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (8)
1. A method for synthesizing ortho-cyclohexanedione, which is characterized by comprising the following steps:
(1) Mixing cyclohexanone, trimethylchlorosilane, an alkaline agent and a catalyst to perform enol silicon etherification reaction to obtain a compound with a structure shown in a formula I;
(2) Mixing the compound with the structure shown in the formula I with m-chloroperoxybenzoic acid to perform oxidation reaction to obtain a compound with the structure shown in the formula II;
(3) Mixing the compound with the structure shown in the formula II with a desilication reagent to perform desilication reaction to obtain a compound with the structure shown in the formula III;
(4) Mixing the compound with the structure shown in the formula III, a catalyst and an oxidant for catalytic oxidation reaction to obtain ortho-cyclohexanedione;
the alkaline agent in the step (1) is one or more of potassium carbonate, sodium hydroxide, potassium hydroxide, triethylamine and pyridine; the catalyst in the step (1) is one or more of potassium iodide, sodium iodide, iodine simple substance, sodium methoxide, potassium tert-butoxide and triethylamine; the temperature of the enol silicon etherification reaction is 50-100 ℃ and the time is 2-10 h;
in the step (2), the temperature of the solvent is firstly reduced to the oxidation reaction temperature, then a compound with a structure shown in a formula I is added into the solvent, then m-chloroperoxybenzoic acid is added into the feed liquid for a plurality of times, after the m-chloroperoxybenzoic acid is added, the reaction is carried out at the oxidation reaction temperature in a heat-preserving way, after the reaction is completed at the oxidation reaction temperature, the reaction is stirred for 2 hours at room temperature; the mass of the m-chloroperoxybenzoic acid added each time is 10-30% of the total mass of the m-chloroperoxybenzoic acid;
the desilication reagent is one or more of potassium fluoride, sodium fluoride, calcium fluoride and hydrofluoric acid; the mol ratio of the compound with the structure shown in the formula II to the desilication reagent is 1 (1-5); the desilication reaction is carried out at the temperature of 20-40 ℃ for 1-4 hours;
the catalyst in the step (4) is one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonium acetate and triethylamine; the dosage of the catalyst in the step (4) is 20-80% of the weight of the compound with the structure shown in the formula III; the temperature of the catalytic oxidation reaction is between-5 and 5 ℃ and the time is between 0.5 and 6 hours 。
2. The synthetic method according to claim 1, wherein the solvent for the enol silicon etherification is one or more of toluene, dioxane, N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran.
3. The synthesis method according to claim 1 or 2, wherein the molar ratio of cyclohexanone to trimethylchlorosilane is 1 (1-3); the dosage of the catalyst in the step (1) is 1-10% of the weight of cyclohexanone; the dosage of the alkaline agent is 50-200% of the weight of the cyclohexanone.
4. The synthesis method according to claim 1, wherein the molar ratio of the compound having the structure shown in formula I to m-chloroperoxybenzoic acid is (1-4): 1;
the solvent for oxidation reaction is one or more of cyclohexane, cyclopentane, n-hexane or petroleum ether.
5. The method according to claim 1 or 4, wherein the oxidation reaction is carried out at a temperature of-20 to 0 ℃ for a time of 1 to 5 hours.
6. The method according to claim 1, wherein the solvent for desilication reaction is one or more of dichloromethane, chloroform, methanol, ethanol, acetonitrile and tetrahydrofuran.
7. The method according to claim 1, wherein the oxidizing agent in the step (4) is any one of phosphorus pentoxide, dimethyl sulfoxide, ferric chloride or manganese dioxide;
the solvent for catalytic oxidation reaction is one or more of dichloromethane, N-dimethylformamide, dimethyl sulfoxide and tetrahydrofuran.
8. The synthesis method according to claim 1, wherein the molar ratio of the compound having the structure represented by formula III to the oxidizing agent is 1 (1-4).
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