CN116854561A - Method for preparing 1, 3-adamantanediol - Google Patents
Method for preparing 1, 3-adamantanediol Download PDFInfo
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- CN116854561A CN116854561A CN202310537093.0A CN202310537093A CN116854561A CN 116854561 A CN116854561 A CN 116854561A CN 202310537093 A CN202310537093 A CN 202310537093A CN 116854561 A CN116854561 A CN 116854561A
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- adamantanediol
- dichloroadamantane
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- MOLCWHCSXCKHAP-UHFFFAOYSA-N adamantane-1,3-diol Chemical compound C1C(C2)CC3CC1(O)CC2(O)C3 MOLCWHCSXCKHAP-UHFFFAOYSA-N 0.000 title claims abstract description 107
- 238000000034 method Methods 0.000 title claims abstract description 40
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 17
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims abstract description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 71
- 238000006243 chemical reaction Methods 0.000 claims description 71
- DZLCQHWJVJXVES-UHFFFAOYSA-N 1,3-dichloroadamantane Chemical compound C1C(C2)CC3CC1(Cl)CC2(Cl)C3 DZLCQHWJVJXVES-UHFFFAOYSA-N 0.000 claims description 68
- 239000012043 crude product Substances 0.000 claims description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
- 238000002390 rotary evaporation Methods 0.000 claims description 39
- 239000000706 filtrate Substances 0.000 claims description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- 238000000746 purification Methods 0.000 claims description 32
- 239000012065 filter cake Substances 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- 239000007787 solid Substances 0.000 claims description 25
- 238000000967 suction filtration Methods 0.000 claims description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 21
- 238000004519 manufacturing process Methods 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- 238000004090 dissolution Methods 0.000 claims description 19
- 238000010992 reflux Methods 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- 239000012295 chemical reaction liquid Substances 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- CJJMAWPEZKYJAP-UHFFFAOYSA-N 3-hydroxyadamantane-1-carboxylic acid Chemical compound C1C(C2)CC3CC2(O)CC1(C(=O)O)C3 CJJMAWPEZKYJAP-UHFFFAOYSA-N 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 11
- 239000005457 ice water Substances 0.000 claims description 10
- 239000003208 petroleum Substances 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 239000012071 phase Substances 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- 239000012074 organic phase Substances 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 abstract description 6
- 239000007858 starting material Substances 0.000 abstract description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 abstract description 3
- 235000019253 formic acid Nutrition 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000001514 detection method Methods 0.000 description 14
- 239000007788 liquid Substances 0.000 description 12
- 238000003828 vacuum filtration Methods 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- DWPIPTNBOVJYAD-BQKDNTBBSA-N (5s,7r)-3-aminoadamantan-1-ol Chemical compound C([C@H](C1)C2)[C@@H]3CC2(N)CC1(O)C3 DWPIPTNBOVJYAD-BQKDNTBBSA-N 0.000 description 3
- VQHPRVYDKRESCL-UHFFFAOYSA-N 1-bromoadamantane Chemical compound C1C(C2)CC3CC2CC1(Br)C3 VQHPRVYDKRESCL-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- HLWZKLMEOVIWRK-UHFFFAOYSA-N 1,3-dibromoadamantane Chemical compound C1C(C2)CC3CC1(Br)CC2(Br)C3 HLWZKLMEOVIWRK-UHFFFAOYSA-N 0.000 description 1
- -1 acetone-water-silver sulfate Chemical compound 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- ADZWSOLPGZMUMY-UHFFFAOYSA-M silver bromide Chemical compound [Ag]Br ADZWSOLPGZMUMY-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 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
- C07C17/361—Preparation of halogenated hydrocarbons by reactions involving a decrease in the number of carbon atoms
- C07C17/363—Preparation of halogenated hydrocarbons by reactions involving a decrease in the number of carbon atoms by elimination of carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
- C07C2603/74—Adamantanes
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing 1, 3-adamantane diol, which belongs to the technical field of chemical synthesis, and adopts 3-hydroxy-1-adamantane formic acid as a starting material to carry out chlorination reaction under the action of thionyl chloride and then to prepare the 1, 3-adamantane diol through alkaline hydrolysis reaction.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a method for preparing 1, 3-adamantanediol by taking 3-hydroxy-1-adamantanecarboxylic acid as a starting raw material.
Background
The 1, 3-adamantane diol is white crystal, slightly soluble in water, soluble in methanol, ethanol and tetrahydrofuran, and is used as an important adamantane disubstituted derivative, and has general application in the fields of organic synthesis, pharmaceutical chemical industry and functional molecular materials. The chemical structural formula of the 1, 3-adamantanediol is as follows:
。
at present, the synthesis methods of the 1, 3-adamantane diol mainly comprise the following steps: method one, a process for producing 1, 3-adamantanediol by hydrolysis of 1, 3-dibromoadamantane. In the Chinese patent publication No. CN113717314A, a method for preparing 1, 3-adamantanediol from l, 3-dibromoadamantane is disclosed, and the three-necked flask is filled with l, 3-dibromoadamantane, ag 2 SO 4 Acetone and water, heating and refluxing, wherein a large amount of light yellow silver bromide is generated, heating and refluxing until l, 3-dibromoadamantane completely reacts, filtering while the mixture is hot, and cooling filtrate to separate out 1, 3-adamantane diol; in the acetone-water-silver sulfate system, a large amount of noble metal silver and acetone are used in the reaction process, so that the method can only stay in a laboratory stage, and the actual production benefit is poor.
In the second method, 3-amino-1-adamantanol is used as a starting material, for example, chinese patent publication No. CN113372190A discloses a method for preparing 1, 3-adamantanediol from 3-amino-1-adamantanol, which comprises dissolving 3-amino-1-adamantanol in water and adding concentrated hydrochloric acid to produce hydrochloride; adding a proper amount of concentrated nitric acid into the obtained water solution to reach a certain concentration; heating to proper temperature for reaction for a certain time, then carrying out alkalization reaction and centrifugal separation to obtain 1, 3-adamantane diol, wherein a large amount of concentrated hydrochloric acid, concentrated nitric acid and high-concentration sodium hydroxide solution are used in the reaction process, the industrialization difficulty is high,
。
and a third method: 1-bromoadamantane is taken as a starting material, for example, chinese patent publication No. CN112159304A discloses a method for preparing 1, 3-adamantane diol by taking 1-bromoadamantane as the starting material, dissolving 1-bromoadamantane in an organic solvent, adding concentrated sulfuric acid and nitric acid for nitration reaction, and obtaining an organic solution phase; and mixing the obtained organic solution phase with water solution of strong alkali, and carrying out hydrolysis reaction to obtain the 1, 3-adamantanediol. The method has high operation risk coefficient and high production cost due to the adoption of a large amount of high-concentration mixed acid and strong alkali solution, is not suitable for industrial production,
。
disclosure of Invention
The invention aims to overcome the problems of difficult industrial production caused by dangerous and uneconomical reaction reagents, long reaction period, low yield, difficult post-treatment and severe operation environment in the process of preparing 1, 3-adamantane diol in the prior art, and provides a method for preparing 1, 3-adamantane diol by taking 3-hydroxy-1-adamantane formic acid as a starting material, wherein the high-purity 1, 3-adamantane diol is obtained through cheaper chlorination reagents and simple reaction steps, no dangerous reagent is used in the reaction process, and the method is environment-friendly, suitable to operate, high in yield and purity and has the potential of industrial production.
In order to solve the technical problems, the present invention provides a method for preparing 1, 3-adamantanediol, comprising the steps of:
step A, chlorination reaction: adding 3-hydroxy-1-adamantane carboxylic acid into a solvent M under the condition of room temperature and stirring, slowly dropwise adding thionyl chloride, setting the reaction temperature to be 10-100 ℃ and the reaction time to be 2-7 hours, and obtaining a reaction solution containing 1, 3-dichloroadamantane;
step B, alkaline hydrolysis reaction: adding water, an alkaline reagent N and 1, 3-dichloroadamantane into a reactor, setting the reaction temperature to be 50-150 ℃ and the reaction time to be 3-10 hours, so as to obtain a reaction solution containing 1, 3-adamantane diol;
the solvent M in the step A is one or more of dichloromethane, toluene and petroleum ether;
and B, wherein the alkaline reagent N is one or more of triethylamine, benzylamine, dimethyl sulfoxide, acetone, sodium hydroxide and potassium hydroxide.
As a further improvement of the present invention, the above-mentioned process for preparing 1, 3-adamantanediol, wherein the mass ratio of thionyl chloride to 3-hydroxy-1-adamantanecarboxylic acid in step A is 3-14:1, the reaction temperature is 30-50 ℃ and the reaction time is 2-5 hours.
As a further improvement of the present invention, the above-mentioned process for preparing 1, 3-adamantanediol, wherein the solvent M in the step A is petroleum ether.
As a further improvement of the present invention, in the above method for preparing 1, 3-adamantane diol, the basic agent N in the step B is triethylamine, and the mass ratio of the basic agent N to 1, 3-dichloroadamantane is 2-8:1, the reaction temperature is 100-150 ℃ and the reaction time is 6-7 hours.
As a further improvement of the present invention, the above method for preparing 1, 3-adamantane diol further comprises a first purification step of purifying 1, 3-dichloroadamantane prepared in the step a, the first purification step comprising the steps of:
step C: adding the reaction solution containing 1, 3-dichloroadamantane prepared in the step A into ice water, vigorously stirring, vacuum filtering, separating phases of filtrate, rotationally evaporating an organic phase by using a rotary evaporator to obtain a solid, and merging filter cakes to obtain a 1, 3-dichloroadamantane crude product;
step D: and C, adding the crude product of the 1, 3-dichloroadamantane prepared in the step C into a solvent U for dissolution, adopting heating reflux or ultrasonic wave to promote the dissolution, carrying out vacuum suction filtration, and carrying out rotary evaporation on the filtrate by a rotary evaporator to obtain the 1, 3-dichloroadamantane.
As a further improvement of the invention, the solvent U in the step D is one or more of absolute methanol, absolute ethanol, methylene dichloride, petroleum ether, toluene, acetone, ethyl acetate and tetrahydrofuran.
As a preferred measure of the present invention, the above-mentioned process for preparing 1, 3-adamantanediol, wherein the solvent U in the step D is preferably methylene chloride.
As another improvement of the present invention, the above method for preparing 1, 3-adamantane diol further comprises a second purification step of purifying the 1, 3-dichloroadamantane prepared in the step a, the second purification step comprising the steps of:
step E: adding the reaction solution containing 1, 3-dichloroadamantane prepared in the step A into ice water, vigorously stirring for 1-3 hours, vacuum filtering by using a vacuum pump, collecting a filter cake, performing rotary evaporation on the filtrate by using a rotary evaporator to obtain a solid, and merging the filter cakes to obtain a 1, 3-dichloroadamantane crude product;
step F: and E, adding the 1, 3-dichloroadamantane crude product obtained in the step E into dichloromethane, carrying out vacuum suction filtration by using a vacuum pump, and carrying out rotary evaporation on filtrate by using a rotary evaporator to obtain the 1, 3-dichloroadamantane.
As a further improvement of the present invention, the above method for preparing 1, 3-adamantanediol further comprises a purification step three of purifying the 1, 3-adamantanediol prepared in step B, the purification step three comprising the steps of:
step G: c, performing rotary evaporation on the reaction solution containing the 1, 3-adamantane diol prepared in the step B by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product;
step H: and D, adding the 1, 3-adamantane diol crude product prepared in the step G into a solvent Q for dissolution, adopting heating reflux or ultrasonic wave to promote the dissolution, carrying out vacuum suction filtration, and carrying out rotary evaporation on filtrate by a rotary evaporator to obtain the 1, 3-adamantane diol.
As a further improvement of the present invention, in the above-mentioned process for producing 1, 3-adamantanediol, in the step H, the solvent Q used is one or more of tetrahydrofuran, anhydrous methanol and anhydrous ethanol.
As another improvement of the present invention, the above method for preparing 1, 3-adamantanediol further comprises a purification step four of purifying the 1, 3-adamantanediol prepared in the step B, the purification step four comprising the steps of:
step I: c, performing rotary evaporation on the reaction liquid containing the 1, 3-adamantane diol prepared in the step B by using a rotary evaporator to obtain a crude product of the 1, 3-adamantane diol;
step J: and (3) adding the crude product of the 1, 3-adamantane diol prepared in the step (I) into absolute methanol serving as a solvent for dissolution, carrying out vacuum suction filtration by using a vacuum pump, and carrying out rotary evaporation on filtrate by using a rotary evaporator to obtain the 1, 3-adamantane diol.
As another improvement of the present invention, the above method for preparing 1, 3-adamantanediol further comprises a purification step five of purifying the 1, 3-adamantanediol prepared in the step B, wherein the purification step five comprises the following steps:
step K: c, performing rotary evaporation on the reaction liquid containing the 1, 3-adamantane diol prepared in the step B by using a rotary evaporator to obtain a crude product of the 1, 3-adamantane diol;
step L: and D, adding a proper amount of alkali liquor into the 1, 3-adamantanediol crude product prepared in the step K, carrying out vacuum suction filtration, and collecting a filter cake to obtain the 1, 3-adamantanediol.
As a further improvement of the present invention, the above-mentioned method for preparing 1, 3-adamantanediol, wherein the alkali solution is one of 5-10% sodium hydroxide solution or 5-10% potassium hydroxide solution.
As a preferred measure of the invention, the above-mentioned process for preparing 1, 3-adamantanediol, the lye is 5% sodium hydroxide solution.
Compared with the prior art, the invention has the beneficial effects that: (1) The invention uses 3-hydroxy-1-adamantanecarboxylic acid as raw material, uses solvents such as methylene dichloride, toluene and petroleum ether, has no dangerous operation in the reaction process, has no potential safety hazard, can realize large-scale production, and has strong operability; (2) The method uses the sulfoxide chloride as the chlorinating agent, does not need a catalyst, has high chlorination reaction rate and high purity, can improve the production efficiency and reduces the production cost; (3) The method has the advantages of simple reaction route, short reaction time, proper and controllable reaction conditions, simple and convenient post-treatment, high yield and purity and industrialized production conditions.
Drawings
FIG. 1 is a synthetic route diagram of the present invention.
Description of the embodiments
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention. All materials are commercially available unless otherwise specified. The GC detection is gas chromatography detection.
Example 1: a process for preparing 1, 3-adamantanediol as shown in figure 1, comprising the steps of: step A, chlorination reaction, step B, alkaline hydrolysis reaction, and purification step I and purification step III.
Step A, chlorination reaction: 5g of 3-hydroxy-1-adamantane carboxylic acid is added into a four-neck flask filled with 25ml of dichloromethane at room temperature under stirring, a condensing reflux device is built, a sodium hydroxide solution is used as tail gas absorption liquid, 15g of thionyl chloride is slowly added dropwise, after the dropwise addition is finished, the reaction liquid is light yellow homogeneous liquid, the reaction temperature is controlled to be 10 ℃, and the reaction liquid containing 1, 3-dichloroadamantane is obtained after 7 hours of reaction.
Pouring the reaction solution containing 1, 3-dichloroadamantane into 100ml of ice water, vigorously stirring, absorbing tail gas, using sodium hydroxide solution with proper concentration, carrying out vacuum filtration by using a vacuum pump when no gas is emitted and a large amount of small particles of white solid appears, carrying out vacuum filtration, separating filtrate phases, collecting filter cakes, carrying out rotary evaporation on an organic phase by using a rotary evaporator to obtain solid, merging the filter cakes, and drying the filter cakes in a vacuum oven at 60 ℃ for 10 hours to obtain a 1, 3-dichloroadamantane crude product; adding the 1, 3-dichloroadamantane crude product into 30ml of absolute methanol, accelerating solid dissolution by using an ultrasonic crushing mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, and performing rotary evaporation on the filtrate by using a rotary evaporator to obtain 4.8g of 1, 3-dichloroadamantane, wherein the yield is 92%, and the GC detection purity is 99.3%.
Step B, alkaline hydrolysis reaction: adding 100ml of water, 9.6g of triethylamine and 4.8g of 1, 3-dichloroadamantane into a 300ml reaction kettle, controlling the reaction temperature to be 50 ℃ and reacting for 6 hours to obtain a reaction solution containing 1, 3-adamantanediol; performing rotary evaporation on the reaction solution containing 1, 3-dichloroadamantane by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product; adding the crude product containing 1, 3-adamantane diol into 30ml of absolute methanol, accelerating solid dissolution by using an ultrasonic crushing mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, and performing rotary evaporation on the filtrate by using a rotary evaporator to obtain 3.57g of 1, 3-adamantane diol, wherein the yield is 91%, and the GC detection purity is 99.2%.
Example 2: a process for preparing 1, 3-adamantanediol comprising the steps of: step A, chlorination reaction, step B, alkaline hydrolysis reaction, and purification step I and purification step IV.
Step A, chlorination reaction: 5g of 3-hydroxy-1-adamantane carboxylic acid is added into a four-neck flask filled with 25ml of toluene at room temperature under the condition of stirring, a condensing reflux device is built, a sodium hydroxide solution is used as a tail gas absorption liquid, 70g of thionyl chloride is slowly added dropwise, after the dropwise addition is finished, the reaction liquid is light yellow homogeneous liquid, the reaction temperature is controlled to be 100 ℃, and the reaction liquid containing 1, 3-dichloroadamantane is obtained after 2 hours of reaction.
Pouring the reaction solution containing 1, 3-dichloroadamantane into 100ml of ice water, vigorously stirring, absorbing tail gas, using sodium hydroxide solution with proper concentration, carrying out vacuum filtration by using a vacuum pump when no gas is emitted and a large amount of small particles of white solid appears, carrying out vacuum filtration, separating filtrate phases, collecting filter cakes, carrying out rotary evaporation on an organic phase by using a rotary evaporator to obtain solid, merging the filter cakes, and drying the filter cakes in a vacuum oven at 60 ℃ for 9 hours to obtain a 1, 3-dichloroadamantane crude product; adding the 1, 3-dichloroadamantane crude product into 30ml of absolute ethyl alcohol, accelerating solid dissolution by using a heating reflux mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, and performing rotary evaporation on the filtrate by a rotary evaporator to obtain 4.8g of 1, 3-dichloroadamantane, wherein the yield is 92%, and the GC detection purity is 99.3%.
Step B, alkaline hydrolysis reaction: adding 100ml of water, 38.4g of acetone and 4.8g of 1, 3-dichloroadamantane into a 300ml reaction kettle, controlling the reaction temperature to be 150 ℃ and reacting for 3 hours to obtain a reaction solution containing 1, 3-adamantane diol; performing rotary evaporation on the reaction solution containing 1, 3-dichloroadamantane by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product; adding the crude product containing the 1, 3-adamantane diol into 30ml of absolute methanol, accelerating solid dissolution by using a heating reflux mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, and performing rotary evaporation on the filtrate by a rotary evaporator to obtain 3.57g of the 1, 3-adamantane diol, wherein the yield is 91%, and the GC detection purity is 99.2%.
Example 3: a process for preparing 1, 3-adamantanediol comprising the steps of: step A, chlorination reaction, step B, alkaline hydrolysis reaction, and purification step I and purification step V.
Step A, chlorination reaction: 10g of 3-hydroxy-1-adamantane carboxylic acid is added into a four-neck flask filled with 50ml of petroleum ether at room temperature under the condition of stirring, a condensing reflux device is built, a sodium hydroxide solution is used as tail gas absorption liquid, 80g of thionyl chloride is slowly added dropwise, after the dropwise addition is finished, the reaction liquid is light yellow homogeneous liquid, the reaction temperature is controlled to be 60 ℃, and the reaction liquid containing 1, 3-dichloroadamantane is obtained after the reaction is carried out for 5 hours.
Pouring the reaction solution containing 1, 3-dichloroadamantane into 200ml of ice water, vigorously stirring, absorbing tail gas, using sodium hydroxide solution with proper concentration, carrying out vacuum filtration by using a vacuum pump when no gas is emitted and a large amount of small particles of white solid appears, separating filtrate phases, collecting filter cakes, rotationally steaming an organic phase by using a rotary evaporator to obtain solid, merging the filter cakes, and placing the filter cakes in a vacuum oven at 60 ℃ for drying for 10 hours to obtain a 1, 3-dichloroadamantane crude product; the crude product of 1, 3-dichloroadamantane is added into 70ml of dichloromethane, the solid dissolution is accelerated by using a heating reflux mode, then the vacuum suction filtration is carried out by using a vacuum pump, the filtrate is collected, the filtrate is subjected to rotary evaporation by a rotary evaporator, 9.7g of 1, 3-dichloroadamantane is obtained, the yield is 93%, and the GC detection purity is 99.4%.
Step B, alkaline hydrolysis reaction: 200ml of water, 48.5g of triethylamine and 9.7g of 1, 3-dichloroadamantane are added into a 600ml reaction kettle, the reaction temperature is controlled to be 100 ℃, and the reaction is carried out for 5 hours, so as to obtain a reaction liquid containing 1, 3-adamantanediol; performing rotary evaporation on the reaction solution containing 1, 3-dichloroadamantane by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product; adding the crude product containing 1, 3-adamantane diol into 70m of 0% sodium hydroxide solution, accelerating solid dissolution by using a heating reflux mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, and performing rotary evaporation on the filtrate by a rotary evaporator to obtain 7.2g of 1, 3-adamantane diol, wherein the yield is 92%, and the GC detection purity is 99.1%.
Example 4: a process for preparing 1, 3-adamantanediol comprising the steps of: step A, chlorination reaction; and B, alkaline hydrolysis reaction, a second purification step and a third purification step.
Step A, chlorination reaction: 5g of 3-hydroxy-1-adamantane carboxylic acid is added into a four-neck flask filled with 25ml of petroleum ether at room temperature under the condition of stirring, a condensing reflux device is built, a sodium hydroxide solution is used as tail gas absorption liquid, 50g of thionyl chloride is slowly added dropwise, after the dropwise addition is finished, the reaction liquid is light yellow homogeneous liquid, the reaction temperature is controlled to be 70 ℃, and the reaction liquid containing 1, 3-dichloroadamantane is obtained after the reaction is carried out for 5 hours.
Pouring the reaction solution containing 1, 3-dichloroadamantane into 100ml of ice water, vigorously stirring for 1 hour, absorbing tail gas by using sodium hydroxide solution with proper concentration, carrying out vacuum filtration by using a vacuum pump until no gas is emitted and a large amount of small-particle white solid appears, collecting filter cakes, carrying out rotary evaporation on the filter liquor by using a rotary evaporator to obtain solid, merging the filter cakes, and drying the filter cakes for 10 hours at 60 ℃ in a vacuum oven to obtain a 1, 3-dichloroadamantane crude product; adding the 1, 3-dichloroadamantane crude product into 30ml of dichloromethane, carrying out vacuum suction filtration by using a vacuum pump, and carrying out rotary evaporation on filtrate by a rotary evaporator to obtain the 1, 3-dichloroadamantane 4.9g, wherein the yield is 94%, and the GC detection purity is 99.1%.
Step B, alkaline hydrolysis reaction: adding 100ml of water, 24g of triethylamine and 4.9g of 1, 3-dichloroadamantane into a 300ml reaction kettle, controlling the reaction temperature to be 100 ℃, and reacting for 4 hours to obtain a reaction solution containing 1, 3-adamantane diol; performing rotary evaporation on the reaction solution containing 1, 3-dichloroadamantane by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product; adding the crude product containing the 1, 3-adamantane diol into 30ml of tetrahydrofuran, accelerating solid dissolution by using a heating reflux mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, performing rotary evaporation on the filtrate by a rotary evaporator, and collecting filter cakes to obtain the 1, 3-adamantane diol 3.68 g, wherein the yield is 92%, and the GC detection purity is 99.3%.
Example 5: a process for preparing 1, 3-adamantanediol comprising the steps of: step A, chlorination reaction; and B, alkaline hydrolysis reaction, a purification step II and a purification step IV.
Step A, chlorination reaction: 5g of 3-hydroxy-1-adamantane carboxylic acid is added into a four-neck flask filled with 25ml of petroleum ether at room temperature under the condition of stirring, a condensing reflux device is built, a sodium hydroxide solution is used as tail gas absorption liquid, 45g of thionyl chloride is slowly added dropwise, after the dropwise addition is finished, the reaction liquid is light yellow homogeneous liquid, the reaction temperature is controlled to be 80 ℃, and the reaction liquid containing 1, 3-dichloroadamantane is obtained after the reaction is carried out for 6 hours.
Pouring the reaction solution containing 1, 3-dichloroadamantane into 100ml of ice water, vigorously stirring for 3 hours, absorbing tail gas by using sodium hydroxide solution with proper concentration, carrying out vacuum filtration by using a vacuum pump until no gas is emitted and a large amount of small-particle white solid appears, collecting filter cakes, carrying out rotary evaporation on the filter liquor by using a rotary evaporator to obtain solid, merging the filter cakes, and drying the filter cakes for 10 hours at 60 ℃ in a vacuum oven to obtain a 1, 3-dichloroadamantane crude product; the crude product of 1, 3-dichloroadamantane is added into 30ml of dichloromethane, vacuum suction filtration is carried out by using a vacuum pump, and the filtrate is subjected to rotary evaporation by a rotary evaporator, so that 4.75g of 1, 3-dichloroadamantane is obtained, the yield is 91%, and the GC detection purity is 99.5%.
Step B, alkaline hydrolysis reaction: adding 100ml of water, 24g of sodium hydroxide and 4.75g of 1, 3-dichloroadamantane into a 300ml reaction kettle, controlling the reaction temperature to be 100 ℃, and reacting for 5 hours to obtain a reaction solution containing 1, 3-adamantane diol; performing rotary evaporation on the reaction solution containing 1, 3-dichloroadamantane by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product; adding the crude product containing 1, 3-adamantane diol into 80ml sodium hydroxide solution with mass fraction of 5%, accelerating solid dissolution by using a heating reflux mode, enabling triethylamine hydrochloride contained in the crude product to react with sodium hydroxide to generate sodium chloride and triethylamine, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, performing rotary evaporation on the filtrate by a rotary evaporator, and collecting filter cakes to obtain 3.61g of 1, 3-adamantane diol, wherein the yield is 93%, and the GC detection purity is 99.5%.
Example 6: a process for preparing 1, 3-adamantanediol comprising the steps of: step A, chlorination reaction; and B, alkaline hydrolysis reaction, a purification step II and a purification step V.
Step A, chlorination reaction: under the condition of room temperature and stirring, 20g of 3-hydroxy-1-adamantane formic acid is added into a four-neck flask filled with 100ml of dichloromethane, a condensing reflux device is built, a sodium hydroxide solution is used as tail gas absorption liquid, 160g of thionyl chloride is slowly added dropwise, after the dropwise addition is finished, the reaction liquid is light yellow homogeneous liquid, the reaction temperature is controlled to be 45 ℃, and the reaction liquid containing 1, 3-dichloroadamantane is obtained after the reaction is carried out for 5 hours.
Pouring the reaction solution containing 1, 3-dichloroadamantane into 400ml of ice water, vigorously stirring for 3 hours, absorbing tail gas by using sodium hydroxide solution with proper concentration, carrying out vacuum filtration by using a vacuum pump until no gas is emitted and a large amount of small-particle white solid appears, collecting filter cakes, carrying out rotary evaporation on the filter liquor by using a rotary evaporator to obtain solid, merging the filter cakes, and drying the filter cakes for 15 hours at 60 ℃ in a vacuum oven to obtain a 1, 3-dichloroadamantane crude product; the crude product of 1, 3-dichloroadamantane is added into 150ml of dichloromethane, vacuum suction filtration is carried out by using a vacuum pump, and the filtrate is subjected to rotary evaporation by a rotary evaporator, thus obtaining 19.8g of 1, 3-dichloroadamantane, the yield is 95%, and the GC detection purity is 99.5%.
Step B, alkaline hydrolysis reaction: 400ml of water, 50g of triethylamine and 19.8g of 1, 3-dichloroadamantane are added into a 1000ml reaction kettle, the reaction temperature is controlled to be 90 ℃, and the reaction is carried out for 10 hours, so as to obtain a reaction liquid containing 1, 3-adamantane diol; performing rotary evaporation on the reaction solution containing 1, 3-dichloroadamantane by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product; adding the crude product containing 1, 3-adamantane diol into 150ml of absolute methanol, accelerating solid dissolution by using a heating reflux mode, performing vacuum suction filtration by using a vacuum pump, collecting filtrate, and performing rotary evaporation on the filtrate by using a rotary evaporator to obtain 14g of 1, 3-adamantane diol, wherein the yield is 90%, and the GC detection purity is 99.2%.
The invention has been described in detail with reference to the drawings, but the invention is not limited to the embodiments described above, and it will be apparent to those skilled in the art that modifications and improvements can be made without departing from the scope of the invention.
Claims (14)
1. A process for preparing 1, 3-adamantanediol, characterized in that it comprises the steps of:
step A, chlorination reaction: adding 3-hydroxy-1-adamantane carboxylic acid into a solvent M under the condition of room temperature and stirring, slowly dropwise adding thionyl chloride, setting the reaction temperature to be 10-100 ℃ and the reaction time to be 2-7 hours, and obtaining a reaction solution containing 1, 3-dichloroadamantane;
step B, alkaline hydrolysis reaction: adding water, an alkaline reagent N and 1, 3-dichloroadamantane into a reactor, setting the reaction temperature to be 50-150 ℃ and the reaction time to be 3-10 hours, so as to obtain a reaction solution containing 1, 3-adamantane diol;
the solvent M in the step A is one or more of dichloromethane, toluene and petroleum ether;
and B, wherein the alkaline reagent N is one or more of triethylamine, benzylamine, dimethyl sulfoxide, acetone, sodium hydroxide and potassium hydroxide.
2. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the mass ratio of the thionyl chloride to the 3-hydroxy-1-adamantanecarboxylic acid in the step A is 3-14:1, the reaction temperature is 30-50 ℃ and the reaction time is 2-5 hours.
3. A process for the preparation of 1, 3-adamantanediol according to claim 2, characterized in that: the solvent M in the step A is petroleum ether.
4. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the alkaline reagent N in the step B is triethylamine, and the mass ratio of the alkaline reagent N to the 1, 3-dichloroadamantane is 2-8:1, the reaction temperature is 100-150 ℃ and the reaction time is 6-7 hours.
5. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the method also comprises a first purification step of purifying the 1, 3-dichloroadamantane prepared in the step A, wherein the first purification step comprises the following steps of:
step C: adding the reaction solution containing 1, 3-dichloroadamantane prepared in the step A into ice water, vigorously stirring, vacuum filtering, separating phases of filtrate, rotationally evaporating an organic phase by using a rotary evaporator to obtain a solid, and merging filter cakes to obtain a 1, 3-dichloroadamantane crude product;
step D: and C, adding the crude product of the 1, 3-dichloroadamantane prepared in the step C into a solvent U for dissolution, adopting heating reflux or ultrasonic wave to promote the dissolution, carrying out vacuum suction filtration, and carrying out rotary evaporation on the filtrate by a rotary evaporator to obtain the 1, 3-dichloroadamantane.
6. The method for producing 1, 3-adamantanediol as claimed in claim 5, wherein: and D, wherein the solvent U is one or more of absolute methanol, absolute ethanol, methylene dichloride, petroleum ether, toluene, acetone, ethyl acetate and tetrahydrofuran.
7. The method for producing 1, 3-adamantanediol according to claim 6, wherein: the solvent U in the step D is preferably dichloromethane.
8. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the method also comprises a second purification step of purifying the 1, 3-dichloroadamantane prepared in the step A, wherein the second purification step comprises the following steps of:
step E: adding the reaction solution containing 1, 3-dichloroadamantane prepared in the step A into ice water, vigorously stirring for 1-3 hours, vacuum filtering by using a vacuum pump, collecting a filter cake, performing rotary evaporation on the filtrate by using a rotary evaporator to obtain a solid, and merging the filter cakes to obtain a 1, 3-dichloroadamantane crude product;
step F: and E, adding the 1, 3-dichloroadamantane crude product obtained in the step E into dichloromethane, carrying out vacuum suction filtration by using a vacuum pump, and carrying out rotary evaporation on filtrate by using a rotary evaporator to obtain the 1, 3-dichloroadamantane.
9. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the method also comprises a purification step III for purifying the 1, 3-adamantane diol prepared in the step B, wherein the purification step III comprises the following steps:
step G: c, performing rotary evaporation on the reaction solution containing the 1, 3-adamantane diol prepared in the step B by using a rotary evaporator to obtain a 1, 3-adamantane diol crude product;
step H: and D, adding the 1, 3-adamantane diol crude product prepared in the step G into a solvent Q for dissolution, adopting heating reflux or ultrasonic wave to promote the dissolution, carrying out vacuum suction filtration, and carrying out rotary evaporation on filtrate by a rotary evaporator to obtain the 1, 3-adamantane diol.
10. A process for preparing 1, 3-adamantanediol according to claim 9, characterized in that: in the step H, the solvent Q is one or more of tetrahydrofuran, absolute methanol and absolute ethanol.
11. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the method also comprises a purification step IV for purifying the 1, 3-adamantane diol prepared in the step B, wherein the purification step IV comprises the following steps:
step I: c, performing rotary evaporation on the reaction liquid containing the 1, 3-adamantane diol prepared in the step B by using a rotary evaporator to obtain a crude product of the 1, 3-adamantane diol;
step J: and (3) adding the crude product of the 1, 3-adamantane diol prepared in the step (I) into absolute methanol serving as a solvent for dissolution, carrying out vacuum suction filtration by using a vacuum pump, and carrying out rotary evaporation on filtrate by using a rotary evaporator to obtain the 1, 3-adamantane diol.
12. A process for the preparation of 1, 3-adamantanediol according to claim 1, characterized in that: the method also comprises a purification step five for purifying the 1, 3-adamantane diol prepared in the step B, wherein the purification step five comprises the following steps:
step K: c, performing rotary evaporation on the reaction liquid containing the 1, 3-adamantane diol prepared in the step B by using a rotary evaporator to obtain a crude product of the 1, 3-adamantane diol;
step L: and D, adding a proper amount of alkali liquor into the 1, 3-adamantanediol crude product prepared in the step K, carrying out vacuum suction filtration, and collecting a filter cake to obtain the 1, 3-adamantanediol.
13. A process for preparing 1, 3-adamantanediol according to claim 12, characterized in that: the alkali liquor is one of 5-10% sodium hydroxide solution or 5-10% potassium hydroxide solution.
14. A process for preparing 1, 3-adamantanediol as claimed in claim 13, wherein: the alkali liquor is 5% sodium hydroxide solution.
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| Title |
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| LISA CANDISH ET AL: ""Catalytic Access to Alkyl Bromides, Chlorides and lodides via Visible Light-Promoted Decarboxylative Halogenation"", 《CHEM.EUR.J》, vol. 22, 8 July 2016 (2016-07-08), pages 9971 - 9974 * |
| MOISEEV, I. K ET AL: ""Synthesis and properties of dioximes of the adamantine series"", 《ZHURNAL ORGANICHESKOI KHIMII》, vol. 22, 31 December 1986 (1986-12-31), pages 2292 - 6 * |
| ZHENTAO WANG ET AL: ""Silver-Catalyzed Decarboxylative Chlorination of Aliphatic Carboxylic Acids"", 《J.AM.CHEM.SOC》, vol. 134, 8 February 2012 (2012-02-08), pages 4258 - 4263 * |
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