CN106631690A - Preparation method of 1-adamantanol - Google Patents
Preparation method of 1-adamantanol Download PDFInfo
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- CN106631690A CN106631690A CN201611039864.XA CN201611039864A CN106631690A CN 106631690 A CN106631690 A CN 106631690A CN 201611039864 A CN201611039864 A CN 201611039864A CN 106631690 A CN106631690 A CN 106631690A
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- adamantanol
- water
- temperature
- mixed system
- bromoadamantane
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- VLLNJDMHDJRNFK-UHFFFAOYSA-N adamantan-1-ol Chemical compound C1C(C2)CC3CC2CC1(O)C3 VLLNJDMHDJRNFK-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims abstract description 51
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 25
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 24
- VQHPRVYDKRESCL-UHFFFAOYSA-N 1-bromoadamantane Chemical compound C1C(C2)CC3CC2CC1(Br)C3 VQHPRVYDKRESCL-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000012043 crude product Substances 0.000 claims abstract description 19
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims abstract description 13
- 229940001584 sodium metabisulfite Drugs 0.000 claims abstract description 13
- 235000010262 sodium metabisulphite Nutrition 0.000 claims abstract description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000004321 preservation Methods 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 238000000967 suction filtration Methods 0.000 claims abstract description 9
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 239000000706 filtrate Substances 0.000 claims abstract description 8
- 239000012046 mixed solvent Substances 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 8
- 238000010438 heat treatment Methods 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000011534 incubation Methods 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 5
- 238000004821 distillation Methods 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 4
- 239000011259 mixed solution Substances 0.000 abstract description 2
- 229910001573 adamantine Inorganic materials 0.000 abstract 1
- 238000003889 chemical engineering Methods 0.000 abstract 1
- 238000004817 gas chromatography Methods 0.000 description 10
- 230000009286 beneficial effect Effects 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229940052761 dopaminergic adamantane derivative Drugs 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- -1 carbonium compound Chemical class 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000002826 coolant Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000171 quenching effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- OHCMANJUZNNOQW-UHFFFAOYSA-N 2,4,4-trimethylcyclohexene-1-carbaldehyde Chemical compound CC1=C(C=O)CCC(C)(C)C1 OHCMANJUZNNOQW-UHFFFAOYSA-N 0.000 description 1
- CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- QPHBUJJTFKRYHM-UHFFFAOYSA-N adamantane-1-sulfonic acid Chemical class C1C(C2)CC3CC2CC1(S(=O)(=O)O)C3 QPHBUJJTFKRYHM-UHFFFAOYSA-N 0.000 description 1
- GRXIPYKONIZFLN-UHFFFAOYSA-N adamantane;nitric acid Chemical compound O[N+]([O-])=O.C1C(C2)CC3CC1CC2C3 GRXIPYKONIZFLN-UHFFFAOYSA-N 0.000 description 1
- LZCDAPDGXCYOEH-UHFFFAOYSA-N adapalene Chemical compound C1=C(C(O)=O)C=CC2=CC(C3=CC=C(C(=C3)C34CC5CC(CC(C5)C3)C4)OC)=CC=C21 LZCDAPDGXCYOEH-UHFFFAOYSA-N 0.000 description 1
- 229960002916 adapalene Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- 229910001429 cobalt ion Inorganic materials 0.000 description 1
- XLJKHNWPARRRJB-UHFFFAOYSA-N cobalt(2+) Chemical compound [Co+2] XLJKHNWPARRRJB-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000012776 electronic material Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920002120 photoresistant polymer Polymers 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- YPNVIBVEFVRZPJ-UHFFFAOYSA-L silver sulfate Chemical compound [Ag+].[Ag+].[O-]S([O-])(=O)=O YPNVIBVEFVRZPJ-UHFFFAOYSA-L 0.000 description 1
- 229910000367 silver sulfate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 1
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- 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
- C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
- C07C29/12—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of esters of mineral acids
- C07C29/124—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of esters of mineral acids of halides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/093—Preparation of halogenated hydrocarbons by replacement by halogens
- C07C17/10—Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 1-adamantanol and belongs to the technical field of chemical engineering. The preparation method comprises steps as follows: (1), adamantine is added to a bromine and water mixed system and subjected to heat preservation at three temperature stages in sequence, 1-bromoadamantane is produced through the reaction, and a mixed system containing 1-bromoadamantane is obtained; (2), the mixed system containing 1-bromoadamantane in the step (1) is subjected to atmospheric distillation, excessive bromine is separated out, temperature of the mixed system is controlled, an aqueous solution of sodium metabisulfite is dropwise added, a heat preservation reaction is performed, and a 1-adamantanol crude product is prepared; (3), the 1-adamantanol crude product prepared in the step (2) is added to a mixed solvent prepared from water and an organic solvent mutually soluble with water, activated carbon is added, the mixed solution is heated and filtered, filtrate is crystallized and subjected to suction filtration, and 1-adamantanol is obtained. The preparation method is simple to operate, has low safety risk and few three wastes, and is high in yield and suitable for industrial production.
Description
Technical Field
The invention relates to a preparation method of 1-adamantanol, belonging to the technical field of chemical industry.
Background
1-adamantanol, chemical name 1-tricyclo [3.3.1.1(3.7)]Decanol, molecular formula C10H16O, melting point>Is soluble in organic solvent at 240 ℃, insoluble in water, sublimable and has the following structural formula:
1-adamantanol, an important fine chemical, has wide applications in the fields of medicine, electronic materials and cosmetics, such as monomers for producing synthetic adamantane derivatives and adapalene, monomers for producing photoresists, photochromic compounds.
There are many reports about the synthesis of the intermediate at home and abroad, and the method mainly comprises the following four methods:
the method comprises the following steps: hydrolysis of bromides
The second method comprises the following steps: direct oxidation process
The third method comprises the following steps: hydrolysis of adamantane sulfonates
The method four comprises the following steps: hydrolysis of adamantane nitrate
The above method has the following disadvantages:
in the first method, the synthesis and post-treatment processes of bromoadamantane reported in patent CN101492348A are complicated, a pressure reaction is required in a hydrolysis process, the requirement on equipment is higher, and potential safety hazards exist, which are not favorable for large-scale production of 1-adamantanol. Expensive silver sulfate catalysis was used in j.org.chem.,26.2207(1961) to adversely reduce synthesis.
In the second method, EP0844228A reports that NHPI and cobalt ions catalyze adamantane to react with oxygen to prepare 1-adamantanol, and the method has poor selectivity, generates polyhydroxy adamantane, has a complex product separation process and expensive catalyst, and has great potential safety hazard when oxygen is used for oxidation. In Japanese patent No. 510654, the use of expensive chromium trioxide as a catalyst results in high cost, difficulty in disposing chromium-containing waste, and serious environmental pollution.
In the third method, in each of Japanese patent No. 3998966, Japanese unexamined patent publication No. 1-283236 and Chinese patent No. CN101891570A, a large amount of fuming sulfuric acid and acetonitrile are used, a large amount of strongly acidic high COD waste water (containing a large amount of acetonitrile) is generated by the reaction, and the treatment is difficult, and moreover, the use of a large amount of a carbonium compound such as tert-butyl alcohol and tert-butyl chloride and an organic nitrile compound increases the synthesis cost.
In the fourth method, 1-adamantanol is obtained by hydrolyzing nitrate ester of adamantane in Chinese patent CN102276375, and the method has poor selectivity and is easy to generate polyhydroxy adamantane.
In view of the above, there is a need to provide a new method for preparing 1-adamantanol, so as to solve the deficiencies of the prior art.
Disclosure of Invention
The invention aims to solve the technical problems of poor selectivity, high safety risk, serious pollution, high cost and the like of the preparation method of the 1-adamantanol in the prior art, and provides the preparation method of the high-purity 1-adamantanol, which has the advantages of high selectivity, safety, less three wastes, high yield and convenience for industrial production.
The present inventors have made intensive studies to achieve the above object and as a result, have found that the above object can be achieved by subjecting the quenched reaction solution to hydrolysis treatment at normal pressure after the adamantane is reacted in a mixed solution containing bromine and water, and have completed the present invention.
The technical scheme for solving the technical problems is as follows: a preparation method of 1-adamantanol comprises the following steps:
(1) adding adamantane into a mixed system of bromine and water, and carrying out heat preservation reaction in three temperature stages in sequence to generate 1-bromoadamantane to obtain a mixed system containing 1-bromoadamantane; wherein,
the three temperature stages are sequentially: at 40-60 deg.C, 70-90 deg.C, 100 deg.C and 120 deg.C;
the molar ratio of the bromine to the adamantane is 1.1-1.9:1, and the mass ratio of the water to the adamantane is 0.05-0.3: 1;
(2) distilling the mixed system containing the 1-bromoadamantane prepared in the step (1) at the normal pressure of 30-60 ℃ until no bromine is dripped, controlling the temperature of the mixed system, dripping aqueous solution of sodium metabisulfite, carrying out heat preservation reaction to prepare a 1-adamantanol crude product, wherein,
the mass percentage concentration of the sodium metabisulfite aqueous solution is 10-40%;
the molar ratio of the sodium metabisulfite to the adamantane in the step (1) is 0.1-0.5;
(3) and (3) adding the 1-adamantanol crude product prepared in the step (2) into a mixed solvent consisting of water and an organic solvent mutually soluble with water, adding activated carbon, heating, filtering, crystallizing the filtrate, and performing suction filtration to obtain the 1-adamantanol.
The 1-adamantanol prepared by the preparation method has the total yield of 88-93 percent (calculated by adamantane), the HPLC purity of more than 99.5 percent, can be directly used for synthesizing adamantane derivatives, has the advantages of simple and convenient operation, high safety coefficient, high yield, low cost, few three wastes and suitability for industrial production.
On the basis of the technical scheme, the invention can be further improved as follows.
Further, the temperature of the mixed system is controlled to be 30-80 ℃ in the step (2).
The adoption of the further beneficial effects is as follows: if the temperature of the mixed system is lower than 30 ℃, the quenching reaction system is too viscous, the product is easy to agglomerate, bromine is included, and quenching is not thorough; if the temperature of the mixing system is higher than 80 ℃, the purity of the product is reduced.
Further, the temperature of the heat preservation reaction in the step (2) is 30-80 ℃, and the time is 3-4 hours.
The adoption of the further beneficial effects is as follows: if the reaction time is kept below 3 hours, the reaction quenching is not thorough; if the reaction time is maintained for more than 4 hours, the purity of the product is reduced.
Further, the water-miscible organic solvent in the step (3) is one of THF, methanol, ethanol, n-propanol, isopropanol and n-butanol, and the mass ratio of the water to the water-miscible organic solvent is 5: 80-95.
The adoption of the further beneficial effects is as follows: improve the recrystallization efficiency and obviously improve the product purity.
Further, the heating temperature in the step (3) is 30-85 ℃, and the time is 1-3 hours.
The adoption of the further beneficial effects is as follows: at too low a temperature, the crude product is not completely dissolved.
Further, the temperature of the filtration in the step (3) is 30-60 ℃.
The adoption of the further beneficial effects is as follows: the heat filtration temperature is low, and products are separated out and lost; the heat filtration temperature is high, the loss of the organic solvent is serious, and the proportion of the refined solvent is influenced.
Further, the crystallization process conditions of the filtrate in the step (3) are as follows: stirring for 1-3 hours at the temperature of 10-30 ℃.
The adoption of the further beneficial effects is as follows: can ensure that the product is fully separated out.
The invention has the beneficial effects that:
(1) the total yield of the 1-adamantanol prepared by the preparation method is 88-93 percent (calculated by adamantane), the HPLC purity can reach more than 99.5 percent, and the 1-adamantanol can be directly used for synthesizing adamantane derivatives.
(2) The preparation process of the 1-bromoadamantane does not use expensive catalysts, but improves the reaction selectivity by controlling the reaction temperature, so that the reaction stays at the stage of the 1-bromoadamantane.
(3) The preparation method disclosed by the invention is simple and convenient to operate, small in safety risk, less in three wastes and high in yield, and is suitable for industrial production.
Detailed Description
The principles and features of this invention are described below in conjunction with specific embodiments, which are set forth merely to illustrate the invention and are not intended to limit the scope of the invention.
Example 1
The method for producing 1-adamantanol of this example includes the steps of:
(1) adding 400.0g (2.94mol) of adamantane into a mixed system of 517.6g (3.24mol) of bromine and 20.0g of water in a 2L three-necked bottle at room temperature, gradually dissolving white adamantane solid after adding the bromine, quickly filling the system with brownish red gas, installing a reflux condenser tube (low-temperature ethanol is used as a cooling medium), slowly performing stepwise temperature rise reaction, performing heat preservation reaction in three temperature stages in sequence, wherein each 3 hours is one stage, the first stage is 40 ℃, the second stage is 70 ℃, the third stage is 120 ℃, performing sampling GC test, stopping the reaction, and reacting to generate 1-bromoadamantane to obtain the mixed system containing 1-bromoadamantane.
(2) Distilling excessive bromine out of the mixed system containing 1-bromoadamantane prepared in the step (1) at the temperature of 30-60 ℃ under normal pressure, stopping distillation when no bromine steam is evaporated, controlling the temperature of the mixed system to be 30-80 ℃, dropwise adding an aqueous solution of sodium metabisulfite, removing residual bromine, dropwise adding the sodium metabisulfite, keeping the temperature at 30 ℃ and stirring for 3.5 hours, cooling to room temperature (20-35 ℃), and performing suction filtration to prepare 500.0g of 1-adamantanol crude product (including water, wherein the yield of the crude product is larger than the theoretical yield). The GC purity of the 1-adamantanol crude product is 93.8%.
(3) Adding the 1-adamantanol crude product prepared in the step (2) into a mixed solvent composed of water and methanol according to a mass ratio of 5:95, adding activated carbon for decoloring, heating at 45 ℃ for 2 hours, filtering at 30 ℃, stirring at 10 ℃ for 1 hour for filtrate crystallization, and performing suction filtration to obtain 394.1g of the 1-adamantanol. The yield of 1-adamantanol was 88.1% and the GC purity was 99.5%, which was a white crystalline solid.
Example 2
The method for producing 1-adamantanol of this example includes the steps of:
(1) adding 400.0g (2.94mol) of adamantane into a mixed system of 720.0g (4.51mol) of bromine and 40.0g of water in a 2L three-necked bottle at room temperature, gradually dissolving white adamantane solid after adding the bromine, quickly filling the system with brownish red gas, installing a reflux condenser tube (low-temperature ethanol is used as a cooling medium), slowly performing stepwise temperature rise reaction, performing heat preservation reaction in three temperature stages in sequence, wherein each 3 hours is one stage, the first stage is 50 ℃, the second stage is 80 ℃, the third stage is 110 ℃, performing sampling GC test, stopping the reaction, and reacting to generate 1-bromoadamantane to obtain the mixed system containing 1-bromoadamantane.
(2) Distilling the mixed system containing the 1-bromoadamantane prepared in the step (1) at the temperature of 30-60 ℃ under normal pressure to remove excessive bromine, stopping distillation when no bromine steam is evaporated, controlling the temperature of the mixed system to be 30-80 ℃, dropwise adding an aqueous solution of sodium metabisulfite, removing residual bromine, dropwise adding the sodium metabisulfite, keeping the temperature at 70 ℃ and stirring for 3.5 hours, cooling to room temperature (20-35 ℃), and performing suction filtration to prepare 470.5g of 1-adamantanol crude product (including water, wherein the yield of the crude product is larger than the theoretical yield). The GC purity of the 1-adamantanol crude product is 95.5%.
(3) Adding the 1-adamantanol crude product prepared in the step (2) into a mixed solvent composed of water and THF according to a mass ratio of 5:80, adding activated carbon for decoloring, heating at 55 ℃ for 1-3 hours, filtering at 40 ℃, stirring at 20 ℃ for 2 hours for filtrate crystallization, and performing suction filtration to obtain 402.8g of the 1-adamantanol. The yield of 1-adamantanol was 90.1% and the GC purity was 99.6%, which was a white crystalline solid.
Example 3
The method for producing 1-adamantanol of this example includes the steps of:
(1) adding 400.0g (2.94mol) of adamantane into a mixed system of 894.1g (5.61mol) of bromine and 120.0g of water at room temperature in a 2L three-necked bottle, gradually dissolving white adamantane solid after the bromine is added, quickly filling the system with brownish red gas, installing a reflux condenser tube (low-temperature ethanol is used as a cooling medium), slowly performing stepwise temperature rise reaction, performing heat preservation reaction in three temperature stages in sequence, wherein each 3 hours is one stage, the first stage is 60 ℃, the second stage is 90 ℃, the third stage is 120 ℃, sampling GC (gas chromatography) testing is performed, the remaining amount of adamantane is less than 2.5 percent, stopping the reaction, and generating 1-bromoadamantane to obtain the mixed system containing 1-bromoadamantane.
(2) Distilling the mixed system containing 1-bromoadamantane prepared in the step (1) at 30-60 ℃ under normal pressure to remove excessive bromine, stopping distillation when no bromine steam is evaporated, controlling the temperature of the mixed system to be 30-80 ℃, dropwise adding an aqueous solution of sodium metabisulfite to remove residual bromine, dropwise adding the sodium metabisulfite, keeping the temperature at 80 ℃ and stirring for 3.5 hours, cooling to room temperature (20-35 ℃), and performing suction filtration to obtain 490.3g of 1-adamantanol crude product (including water, wherein the yield of the crude product is larger than the theoretical yield). The GC purity of the 1-adamantanol crude product is 95.7%.
(3) Adding the 1-adamantanol crude product prepared in the step (2) into a mixed solvent composed of water and isopropanol according to a mass ratio of 5:90, adding activated carbon for decoloring, heating at 75 ℃ for 1-3 hours, filtering at 60 ℃, stirring at 105 ℃ for 3 hours for filtrate crystallization, and performing suction filtration to obtain 416.3g of the 1-adamantanol. The yield of 1-adamantanol was 93.0% and the GC purity was 99.5%, which was a white crystalline solid.
Therefore, the 1-adamantanol prepared by the preparation method has the total yield of 88-93 percent (calculated by adamantane) and the HPLC purity of over 99.5 percent, and can be directly used for synthesizing adamantane derivatives.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (7)
1. A preparation method of 1-adamantanol is characterized by comprising the following steps:
(1) adding adamantane into a mixed system of bromine and water, and carrying out heat preservation reaction in three temperature stages in sequence to generate 1-bromoadamantane to obtain a mixed system containing 1-bromoadamantane; wherein,
the three temperature stages are sequentially: at 40-60 deg.C, 70-90 deg.C, 100 deg.C and 120 deg.C;
the molar ratio of the bromine to the adamantane is 1.1-1.9:1, and the mass ratio of the water to the adamantane is 0.05-0.3: 1;
(2) distilling the mixed system containing the 1-bromoadamantane prepared in the step (1) at the normal pressure of 30-60 ℃ until no bromine is dripped, controlling the temperature of the mixed system, dripping aqueous solution of sodium metabisulfite, carrying out heat preservation reaction to prepare a 1-adamantanol crude product, wherein,
the mass percentage concentration of the sodium metabisulfite aqueous solution is 10-40%;
the molar ratio of the sodium metabisulfite to the adamantane in the step (1) is 0.1-0.5;
(3) and (3) adding the 1-adamantanol crude product prepared in the step (2) into a mixed solvent consisting of water and an organic solvent mutually soluble with water, adding activated carbon, heating, filtering, crystallizing the filtrate, and performing suction filtration to obtain the 1-adamantanol.
2. The process for producing 1-adamantanol according to claim 1, wherein the temperature of the mixed system in the step (2) is controlled to 30 to 80 ℃.
3. The method for preparing 1-adamantanol according to claim 1, where in the step (2) the incubation is performed at 30 to 80 ℃ for 3 to 4 hours.
4. The method for preparing 1-adamantanol according to claim 1, where in the step (3), the water-miscible organic solvent is one of THF, methanol, ethanol, n-propanol, isopropanol and n-butanol, and the mass ratio of the water to the water-miscible organic solvent is 5: 80-95.
5. The method of claim 1, wherein the heating in step (3) is carried out at a temperature of 30 to 85 ℃ for 1 to 3 hours.
6. The process for producing 1-adamantanol according to claim 1, wherein the temperature for the filtration in the step (3) is 30 to 60 ℃.
7. The method for preparing 1-adamantanol according to claim 1, wherein the crystallization process conditions of the filtrate in the step (3) are as follows: stirring for 1-3 hours at the temperature of 10-30 ℃.
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| CN112159304A (en) * | 2020-10-26 | 2021-01-01 | 四川众邦制药有限公司 | Method for preparing 1, 3-adamantanediol by using 1-bromoadamantane as starting material |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101492348A (en) * | 2009-02-26 | 2009-07-29 | 泸州万联化工有限公司 | Method for producing 1-adamantane ethanol |
-
2016
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| CN101492348A (en) * | 2009-02-26 | 2009-07-29 | 泸州万联化工有限公司 | Method for producing 1-adamantane ethanol |
Non-Patent Citations (1)
| Title |
|---|
| 孙爱春等: "1-溴代金刚烷的合成", 《浙江师范大学学报(自然科学版)》 * |
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|---|---|---|---|---|
| CN112159304A (en) * | 2020-10-26 | 2021-01-01 | 四川众邦制药有限公司 | Method for preparing 1, 3-adamantanediol by using 1-bromoadamantane as starting material |
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