CN112961121A - Synthesis process of cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane - Google Patents
Synthesis process of cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane Download PDFInfo
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- CN112961121A CN112961121A CN202110150705.1A CN202110150705A CN112961121A CN 112961121 A CN112961121 A CN 112961121A CN 202110150705 A CN202110150705 A CN 202110150705A CN 112961121 A CN112961121 A CN 112961121A
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- epoxy
- menthoxypropane
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- QSPXTBSJQJHAPF-UHFFFAOYSA-N 2-[(1-methyl-4-propan-2-ylcyclohexyl)oxymethyl]oxirane Chemical compound C1CC(C(C)C)CCC1(C)OCC1OC1 QSPXTBSJQJHAPF-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 25
- 239000002826 coolant Substances 0.000 title claims abstract description 17
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 72
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims abstract description 32
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229940041616 menthol Drugs 0.000 claims abstract description 32
- 238000009835 boiling Methods 0.000 claims abstract description 30
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims abstract description 11
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 claims abstract description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 34
- 238000010438 heat treatment Methods 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000007788 liquid Substances 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- 239000003208 petroleum Substances 0.000 claims description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000006276 transfer reaction Methods 0.000 claims description 14
- 239000008367 deionised water Substances 0.000 claims description 11
- 229910021641 deionized water Inorganic materials 0.000 claims description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 8
- 238000009833 condensation Methods 0.000 claims description 8
- 230000005494 condensation Effects 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- -1 alkyl hydrocarbon Chemical class 0.000 claims description 7
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 7
- 239000004215 Carbon black (E152) Substances 0.000 claims description 6
- 229930195733 hydrocarbon Natural products 0.000 claims description 6
- 239000011259 mixed solution Substances 0.000 claims description 6
- 239000003444 phase transfer catalyst Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 238000004321 preservation Methods 0.000 claims description 5
- LRWZZZWJMFNZIK-UHFFFAOYSA-N 2-chloro-3-methyloxirane Chemical compound CC1OC1Cl LRWZZZWJMFNZIK-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims 8
- 238000001704 evaporation Methods 0.000 claims 1
- 239000011261 inert gas Substances 0.000 abstract description 8
- 238000004821 distillation Methods 0.000 abstract description 6
- 239000012046 mixed solvent Substances 0.000 abstract description 6
- 239000006227 byproduct Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 2
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 239000013076 target substance Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 7
- 238000005086 pumping Methods 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- 238000007599 discharging Methods 0.000 description 3
- 238000007142 ring opening reaction Methods 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 235000019504 cigarettes Nutrition 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- IMVMIMWLBYHMBW-UHFFFAOYSA-N 1-chloro-3-(1-methyl-4-propan-2-ylcyclohexyl)oxypropan-2-ol Chemical compound CC(C)C1CCC(C)(OCC(O)CCl)CC1 IMVMIMWLBYHMBW-UHFFFAOYSA-N 0.000 description 1
- MDVYIGJINBYKOM-UHFFFAOYSA-N 3-[[5-Methyl-2-(1-methylethyl)cyclohexyl]oxy]-1,2-propanediol Chemical compound CC(C)C1CCC(C)CC1OCC(O)CO MDVYIGJINBYKOM-UHFFFAOYSA-N 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 235000015218 chewing gum Nutrition 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 235000015094 jam Nutrition 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 235000013622 meat product Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 235000019633 pungent taste Nutrition 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940034610 toothpaste Drugs 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Epoxy Compounds (AREA)
Abstract
The invention discloses a synthesis process of cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane, which adopts menthol, epichlorohydrin, tetrabutylammonium bromide and other raw materials, abandons inert gas, does not need a pressure-bearing reaction kettle, the 1, 2-epoxy-3-L-menthoxypropane is synthesized by a one-pot method, the reaction time is short, and the menthol raw material is completely converted into a target substance without byproducts, so that the purification steps are reduced, low temperature is not needed, the energy consumption is reduced, the inert gas is replaced by a linear boiling difference mixed solvent external circulation technology, then 1, 2-epoxy-3-L-menthoxypropane with the purity of more than 99 percent is obtained through simple reduced pressure distillation, the primary yield can reach more than 98.5 percent, and the process is environment-friendly and safe.
Description
Technical Field
The invention relates to the technical field of cooling agents, and particularly belongs to a synthesis process of a cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane.
Background
The natural menthol has important application in daily chemical industry, food, medicine and cigarette products as a freshener, but the menthol has short and strong cooling effect due to high volatility and irritation, even causes harm to human skin and eyes, and the special mint smell of the menthol further limits the wide application of the menthol in daily chemical products. The novel water-soluble cooling agent ws-10 (3-L-menthoxypropane-1, 2-diol) has the characteristics of strong water solubility, refreshing property, durability, freshness, no pungent taste and no bitter taste. Can be widely used for products such as chewing gum, toothpaste, candy, jelly, jam, starch food, meat products, cigarettes, medicines and the like, so that the synthesis research of the 1, 2-epoxy-3-L-menthoxypropane of the WS-10 intermediate has practical significance.
The 1, 2-epoxy-3-L-menthoxypropane is obtained by using menthol, 1, 2-epoxy-3-chloropropane and a phase transfer catalyst to react, but the existing reaction is carried out in two steps under the protection of inert gas, the menthol and the 1, 2-epoxy-3-chloropropane in the first step respectively carry out ring opening reaction in anhydrous aluminum trichloride or zinc chloride, distillation is carried out to obtain 1-chlorine-3-L-menthoxy-2-propanol, and the 1-chlorine-3-L-menthoxy-2-propanol carries out phase transfer reaction and distillation to obtain the 1, 2-epoxy-3-L-menthoxypropane. In the first step of ring-opening reaction, anhydrous aluminum trichloride or zinc chloride is required to react under the condition of inert gas, menthol cannot react completely, unreacted menthol is separated by distillation to obtain 1-chloro-3-L-menthoxy-2-propanol, and meanwhile, 1, 2-epoxy-3-chloropropane is easy to decompose in the ring-opening process, so that byproducts are generated, the subsequent purification difficulty is high, and the yield is low; the second step phase transfer needs to control the oxygen content under the strict inert gas condition, reduces the influence of air on the phase transfer reaction, has strict requirements on a phase transfer catalyst, is easy to cause incomplete phase transfer and yield reduction, causes excessive waste liquid, gradually increases the cost, reduces the profit margin, and is not beneficial to the current environmental protection and economic harmonious development.
Disclosure of Invention
The invention aims to provide a synthesis process of a cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane, which overcomes the defects that the traditional synthesis process method has incomplete reaction of raw material menthol, overlong reaction time and more byproducts, the aftertreatment needs distillation for purification, partial byproducts are removed, and meanwhile, a pressure-bearing reaction kettle is adopted to introduce inert gas, the reaction conditions are harsh, and the industrial production is not facilitated.
In order to solve the problems, the technical scheme adopted by the invention is as follows:
the synthesis process of the cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane comprises the following steps:
s1, adding menthol, toluene, an organic reagent with a boiling range of 30-60 ℃, tetrahydrofuran, ethyl acetate and cyclohexane into a reaction kettle, heating and stirring until the menthol is completely dissolved, then adding aluminum trichloride to raise the temperature in the reaction kettle to 45-50 ℃, stirring, performing condensation reflux reaction, stopping condensation, heating part of the solvent to evaporate out of the reaction kettle, continuing condensation reflux reaction, simultaneously dropwise adding a mixed solution into the reaction system, and continuing heating and heat preservation after dropwise adding is finished to completely convert the menthol;
s2, adding deionized water dropwise into the reaction system after menthol is completely converted, stirring, standing for layering, separating out lower-layer water in the reaction kettle, and then adding alkali liquor and a phase transfer catalyst into the reaction kettle to perform phase transfer reaction;
s3, starting heating to evaporate part of the solvent out of the reaction kettle by heating, and then carrying out condensation reflux reaction until the phase transfer reaction is finished;
s4, adding deionized water into the reaction kettle after the phase transfer reaction is finished until the turbidity in the reaction kettle disappears, stirring and standing, separating out a lower water layer, and then recovering the solvent in the reaction kettle to obtain the 1, 2-epoxy-3-L-menthoxypropane.
Preferably, the mass ratio of the menthol, the toluene, the organic reagent with the boiling range of 30-60 ℃, the tetrahydrofuran, the ethyl acetate and the cyclohexane is 500:192:20:15:5: 5.
Preferably, the organic agent with a boiling range of 30-60 ℃ is petroleum ether with a boiling range of 30-60 ℃.
Preferably, the mixed liquid is a mixture of epichlorohydrin and alkyl hydrocarbon.
Preferably, the mass ratio of the mixture of the epichlorohydrin and the alkyl hydrocarbon is 412: 5.
Preferably, the alkyl hydrocarbon is petroleum ether with a boiling range of 60-90 ℃.
Preferably, the alkali solution is 41.2 wt% sodium hydroxide aqueous solution.
Preferably, the phase transfer catalyst is tetrabutylammonium bromide.
Preferably, the time for heating part of the solvent to evaporate out of the reaction kettle is 10 min.
Compared with the prior art, the invention has the following implementation effects:
1. the synthesis technology adopts the raw materials of menthol, 1, 2-epoxy-3-chloropropane, tetrabutylammonium bromide and the like, abandons inert gas, does not need a pressure-bearing reaction kettle, synthesizes the 1, 2-epoxy-3-L-menthoxypropane by one-pot operation, has short reaction time and no by-product, completely converts the raw materials of the menthol into a target product, reduces the purification steps, does not need low temperature, reduces the energy consumption, adopts a linear boiling difference mixed solvent technology to replace the inert gas, then obtains the 1, 2-epoxy-3-L-menthoxypropane with the purity of more than 99 percent by simple reduced pressure distillation, has the primary yield of more than 98.5 percent, and is relatively environment-friendly and safe.
2. The invention uses toluene, petroleum ether with boiling range of 30-60 ℃, tetrahydrofuran, ethyl acetate and cyclohexane to form a linear boiling difference mixed solvent, when the solvent is heated and evaporated, the low boiling point solvent can discharge most of air in a reaction kettle, so that the space of the reaction kettle is filled with solvent gas, the dripping epichlorohydrin is kept not decomposed, part of petroleum ether with boiling range of 60-90 ℃ is added into the mixed solution, and the petroleum ether with boiling range of 60-90 ℃ and the insolubility of the epichlorohydrin are utilized, so that the petroleum ether with boiling range of 60-90 ℃ can seal the contact of the epichlorohydrin and the air at the upper layer, thereby greatly improving the product yield, ensuring that the product quality is not changed, being simple to operate and having good economy.
3. The process method finally adds deionized water to make the turbidity disappear, so that tetrabutylammonium bromide is completely dissolved, and the recovery of the solvent is facilitated.
4. The process method is convenient to operate, is easy to obtain the 1, 2-epoxy-3-L-menthoxypropane product with higher purity, reduces the danger of industrial production, and has double meanings of economy and environmental protection.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Firstly, a tower section and a condenser are arranged on a 2000L reaction kettle to form an external circulation channel, then 500kg of menthol is weighed in the reaction kettle, 192kg of toluene, 20kg of petroleum ether with a boiling range of 30-60 ℃, 15kg of tetrahydrofuran, 5kg of ethyl acetate and 5kg of cyclohexane are added to form a series of mixed solvents with linear boiling points, stirring is started, and heating is started to ensure that the menthol in the kettle is completely dissolved at the temperature of 41 ℃; then adding 0.15kg of aluminum trichloride, automatically raising the temperature in the reaction kettle to 49 ℃, stirring for 30min, opening an outer circulation channel outwards, allowing part of evaporated solvent liquid to flow out of the whole reaction system for 10min, closing the outer circulation channel, returning the circulation liquid to the reaction kettle, pumping 412kg of epoxy chloropropane and 5kg of petroleum ether with the boiling range of 60-90 ℃ into a head tank to form a semi-mixed liquid, wherein most of the petroleum ether with the boiling range of 60-90 ℃ is on the upper layer; the heating temperature of the reaction kettle is controlled at 45 ℃, the mixed solution is dripped, and the dripping speed is controlled at about 10L/min; after the dripping is finished, continuously heating and preserving heat for 1h, after the complete conversion and heat preservation of the menthol is finished, dripping 100kg of deionized water into the kettle, and continuously stirring for 30 min; stopping stirring, standing, and separating out lower-layer water;
then, 750kg of 41.2% sodium hydroxide aqueous solution is pumped into the kettle, 0.3kg of tetrabutylammonium bromide is added, stirring is started for 30min, and phase transfer reaction is carried out; starting heating, wherein an external circulation channel is opened outwards, part of liquid flows out of the whole reaction system for 10min, then the external circulation channel is closed, the circulation liquid flows back into the kettle, and the temperature in the kettle is controlled at 77 ℃; keeping the temperature for 2.5h, after the phase transfer reaction is completed, pumping 300kg of deionized water into the reaction kettle, and removing turbidity in the reaction kettle; stirring for 10min, standing, and discharging lower layer water; vacuumizing the reaction kettle to-0.098 Mpa, recovering solvent under reduced pressure, and stopping heating until the temperature in the kettle reaches 87 ℃ to obtain 671kg of 1, 2-epoxy-3-L-menthoxypropane with the purity of 99.3 percent and the one-time yield of 98.75 percent.
Example 2
Firstly, a tower section and a condenser are arranged on a 2000L reaction kettle to form an external circulation channel, then 500kg of menthol is weighed in the reaction kettle, 192kg of toluene, 20kg of petroleum ether with a boiling range of 30-60 ℃, 15kg of tetrahydrofuran, 5kg of ethyl acetate and 5kg of cyclohexane are added to form a series of mixed solvents with linear boiling points, stirring is started, and heating is started to ensure that the menthol in the kettle is completely dissolved at the temperature of 45 ℃; then adding 0.15kg of aluminum trichloride, automatically raising the temperature in the reaction kettle to 50 ℃, stirring for 30min, opening an outer circulation channel outwards, allowing part of evaporated solvent liquid to flow out of the whole reaction system for 10min, closing the outer circulation channel, returning the circulation liquid to the reaction kettle, pumping 412kg of epoxy chloropropane and 5kg of petroleum ether with the boiling range of 60-90 ℃ into a head tank to form a semi-mixed liquid, wherein most of the petroleum ether with the boiling range of 60-90 ℃ is on the upper layer; the heating temperature of the reaction kettle is controlled at 54 ℃, the mixed solution is dripped, and the dripping speed is controlled at about 10L/min; after the dripping is finished, continuously heating and preserving heat for 1h, after the complete conversion and heat preservation of the menthol is finished, dripping 100kg of deionized water into the kettle, and continuously stirring for 30 min; stopping stirring, standing, and separating out lower-layer water;
then, 750kg of 41.2% sodium hydroxide aqueous solution is pumped into the kettle, 0.3kg of tetrabutylammonium bromide is added, stirring is started for 30min, and phase transfer reaction is carried out; starting heating, wherein an external circulation channel is opened outwards, part of liquid flows out of the whole reaction system for 10min, then the external circulation channel is closed, the circulation liquid flows back into the kettle, and the temperature in the kettle is controlled at 78 ℃; keeping the temperature for 2.5h, after the phase transfer reaction is completed, pumping 300kg of deionized water into the reaction kettle, and removing turbidity in the reaction kettle; stirring for 10min, standing, and discharging lower layer water; vacuumizing the reaction kettle to-0.098 Mpa, recovering the solvent under reduced pressure, stopping heating when the temperature in the reaction kettle reaches 87 ℃, and thus obtaining 669.1kg of 1, 2-epoxy-3-L-menthoxypropane with the purity of 99.6 percent and the one-time yield of 98.47 percent.
Example 3
Firstly, a tower section and a condenser are arranged on a 2000L reaction kettle to form an external circulation channel, then 500kg of menthol is weighed in the reaction kettle, 192kg of toluene, 20kg of petroleum ether with a boiling range of 30-60 ℃, 15kg of tetrahydrofuran, 5kg of ethyl acetate and 5kg of cyclohexane are added to form a series of mixed solvents with linear boiling points, stirring is started, and heating is started to ensure that the menthol in the kettle is completely dissolved at the temperature of 45 ℃; then adding 0.15kg of aluminum trichloride, automatically raising the temperature in the reaction kettle to 47 ℃, stirring for 30min, opening an outer circulation channel outwards, allowing part of evaporated solvent liquid to flow out of the whole reaction system for 10min, closing the outer circulation channel, returning the circulation liquid to the reaction kettle, pumping 412kg of epoxy chloropropane and 5kg of petroleum ether with the boiling range of 60-90 ℃ into a head tank to form a semi-mixed liquid, wherein most of the petroleum ether with the boiling range of 60-90 ℃ is on the upper layer; the heating temperature of the reaction kettle is controlled at 53 ℃, the mixed solution is dripped, and the dripping speed is controlled at about 10L/min; after the dripping is finished, continuously heating and preserving heat for 1h, after the complete conversion and heat preservation of the menthol is finished, dripping 100kg of deionized water into the kettle, and continuously stirring for 30 min; stopping stirring, standing, and separating out lower-layer water;
then, 750kg of 41.2% sodium hydroxide aqueous solution is pumped into the kettle, 0.3kg of tetrabutylammonium bromide is added, stirring is started for 30min, and phase transfer reaction is carried out; starting heating, wherein an external circulation channel is opened outwards, part of liquid flows out of the whole reaction system for 10min, then the external circulation channel is closed, the circulation liquid flows back into the kettle, and the temperature in the kettle is controlled at 85 ℃; keeping the temperature for 2.5h, after the phase transfer reaction is completed, pumping 300kg of deionized water into the reaction kettle, and removing turbidity in the reaction kettle; stirring for 10min, standing, and discharging lower layer water; vacuumizing the reaction kettle to-0.098 Mpa, recovering solvent under reduced pressure, and stopping heating until the temperature in the kettle reaches 89 ℃ to obtain 670.0kg of 1, 2-epoxy-3-L-menthoxypropane with the purity of 99.70% and the one-time yield of 98.60%.
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (9)
1. The synthesis process of the cooling agent intermediate 1, 2-epoxy-3-L-menthoxypropane is characterized by comprising the following steps: the method comprises the following steps:
s1, adding menthol, toluene, an organic reagent with a boiling range of 30-60 ℃, tetrahydrofuran, ethyl acetate and cyclohexane into a reaction kettle, heating and stirring until the menthol is completely dissolved, then adding aluminum trichloride to raise the temperature in the reaction kettle to 45-50 ℃, stirring, performing condensation reflux reaction, stopping condensation, heating part of the solvent to evaporate out of the reaction kettle, continuing condensation reflux reaction, simultaneously dropwise adding a mixed solution into the reaction system, and continuing heating and heat preservation after dropwise adding is finished to completely convert the menthol;
s2, adding deionized water dropwise into the reaction system after menthol is completely converted, stirring, standing for layering, separating out lower-layer water in the reaction kettle, and then adding alkali liquor and a phase transfer catalyst into the reaction kettle to perform phase transfer reaction;
s3, starting heating to evaporate part of the solvent out of the reaction kettle by heating, and then carrying out condensation reflux reaction until the phase transfer reaction is finished;
s4, adding deionized water into the reaction kettle after the phase transfer reaction is finished until the turbidity in the reaction kettle disappears, stirring and standing, separating out a lower water layer, and then recovering the solvent in the reaction kettle to obtain the 1, 2-epoxy-3-L-menthoxypropane.
2. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 1, wherein: the mass ratio of the menthol, the toluene, the organic reagent with the boiling range of 30-60 ℃, the tetrahydrofuran, the ethyl acetate and the cyclohexane is 500:192:20:15:5: 5.
3. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 1 or 2, characterized in that: the organic reagent with the boiling range of 30-60 ℃ is petroleum ether with the boiling range of 30-60 ℃.
4. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 1, wherein: the mixed liquid is a mixture of epoxy chloropropane and alkyl hydrocarbon.
5. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 4, wherein: the mass ratio of the mixture of the epichlorohydrin to the alkyl hydrocarbon is 412: 5.
6. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 4 or 5, characterized in that: the alkyl hydrocarbon is petroleum ether with a boiling range of 60-90 ℃.
7. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 1, wherein: the alkali liquor is 41.2 wt% sodium hydroxide aqueous solution.
8. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 1, wherein: the phase transfer catalyst is tetrabutylammonium bromide.
9. The process for synthesizing 1, 2-epoxy-3-L-menthoxypropane, which is a cooling agent intermediate, according to claim 1, wherein: the time for heating and evaporating part of the solvent out of the reaction kettle is 10 min.
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| JP2010280706A (en) * | 2010-08-13 | 2010-12-16 | Takasago Internatl Corp | Process for producing 3-1-menthoxypropane-1,2-diol |
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| US20100279997A1 (en) * | 2009-05-04 | 2010-11-04 | Lindsay Burns Barbier | Analgesic that binds filamin a |
| JP2010280706A (en) * | 2010-08-13 | 2010-12-16 | Takasago Internatl Corp | Process for producing 3-1-menthoxypropane-1,2-diol |
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