CN105541634A - Synthetic method of homosalate - Google Patents
Synthetic method of homosalate Download PDFInfo
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- CN105541634A CN105541634A CN201410619254.1A CN201410619254A CN105541634A CN 105541634 A CN105541634 A CN 105541634A CN 201410619254 A CN201410619254 A CN 201410619254A CN 105541634 A CN105541634 A CN 105541634A
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- sodium
- homosalate
- cyclonol
- wintergreen oil
- salicylate
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- WSSJONWNBBTCMG-UHFFFAOYSA-N CC(C1)CC(C)(C)CC1OC(c(cccc1)c1O)=O Chemical compound CC(C1)CC(C)(C)CC1OC(c(cccc1)c1O)=O WSSJONWNBBTCMG-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a method for synthesizing homosalate through an ester exchange reaction of methyl salicylate or ethyl salicylate and 3,3,5-trimethylcyclohexanol under the catalysis of an alkali. The method has the advantages of simple operation, high conversion rate, economy, environmental protection, and suitableness for industrial production.
Description
Technical field
The present invention relates to the synthetic method of uv-absorbing agent homosalate.
Technical background
The ultraviolet contained in sunlight, educational circles of Dermatology Department is divided into the long wave ultraviolet (UVA) of 320nm-400nm, the medium wavelength ultraviolet (UVB) of 280nm-320nm, the short wave ultraviolet (UVC) of 200nm-280nm.The ultraviolet of below 280mn is absorbed by ozonosphere, can not arrive ground, and the ultraviolet arriving ground can bring various impact to the skin of people, wherein UVB can cause skin to produce erythema or water scar, promote that melanochrome is formed, make skin chromogenesis calm, cause the formation of foxiness.Once thought that UVA can not produce large impact to skin in the past, but all prove that accepting excessive UVA irradiation can bring certain impact to skin by electron microscope or histochemical method, UVA section UV-light is different from UVB, its energy can reach dermal layer of the skin, brings change slowly to the spandex fiber in vessel wall or conjunctive tissue.Thus cause the brown of skin, make the flexibility decrease of skin, what promote wrinkle makes people sharply aging, can also promote that erythematous response even causes phototoxicity or photosensitized reaction in addition.Sensitive skin can also make immunity degradation by damage dna continuously across the radiation of UVB, UVA in the sunlight, even brings out skin carcinoma.So defend excessive UVA, UVB irradiates protection human body and escapes injury, and delaying senility seems becomes more and more important.The uv-absorbing agent of research both at home and abroad divides by structure and is broadly divided into following a few class at present: salicylate class, benzophenone class, benzotriazole category, group-substituted acrylonitrile, triazines and other classes.
Homosalate (Homosalate) has another name called former film and to fall apart ester; it is a kind of typical salicylic acid uv-absorbing agent; chemistry by name 3; 3; 5-trimethylcyclohexyl salicylate, can absorb the ultraviolet of UVB295 ~ 315nm wave band, is used for sun-proof daily use chemicals product by U.S. FDA, Europe, Japan, Australia's approval; protection skin, not by UVB irradiation damage, is widely used in makeup and the garment material etc. such as sunscreen, skin toner liquid.
Homosalate (Homosalate) structure
The synthesis of this compound has no bibliographical information.In existing routine techniques, ester compound can by being that Carboxylic acid and alcohol dewaters synthesis under acid catalysis, also can carboxylic acid halides (as acyl chlorides) and alcohol synthesize accordingly, or synthesize with carboxylate salt and halohydrocarbon, consider raw material sources and production cost problem, latter two method is not suitable for the suitability for industrialized production of this product.Through contriver's test, adopt Whitfield's ointment and 3,3, the esterification under acid (as sulfuric acid, tosic acid etc.) catalysis of 5-cyclonol, temperature of reaction needs more than 180 DEG C, and low conversion rate, reactant color is dark, and aftertreatment waste water is many, is also not suitable for suitability for industrialized production.
Therefore need to study the economic environmental protection of a kind of homosalate of invention, applicable industrial synthetic method.
Summary of the invention
Difficult and not enough for overcoming prior art, the present inventor attempts under acid or base catalysis, synthesizing homosalate with Whitfield's ointment lower alkyl esters and 3,3,5-cyclonol through transesterification reaction, low alkyl group wherein refers to the alkyl of C1-C6, as methyl, ethyl, propyl group, sec.-propyl etc.
Through test, with acid (as sulfuric acid, methylsulfonic acid, tosic acid etc.) for catalyzer, even if temperature of reaction brings up to 180-195 DEG C, time lengthening by 35 hours, wintergreen oil and 3,3, the ester interchange conversion rate of 5-cyclonol, not more than 50%, does not have commercialization to be worth yet.Through large quantifier elimination, the present inventor finds Whitfield's ointment lower alkyl esters and 3, the transesterification reaction of 3,5-cyclonol can be carried out under the catalysis of alkali, particularly load-type solid demonstrate catalytic efficiency high, be convenient to from reaction system be separated, reusable advantage.Therefore, of the present invention focusing on provides a kind of method taking alkali as catalyst Whitfield's ointment lower alkyl esters and 3,3,5-cyclonol and carry out transesterify synthesis homosalate.For detection reaction carries out degree, adopt the content of main raw material in gc analysis reaction system.
The present invention realizes by following steps:
To Whitfield's ointment lower alkyl esters and 3,3,5-cyclonols in add appropriate alkali as a catalyst, then heat up carry out transesterify, ceaselessly steam the low-boiling point alcohol of generation, question response reaches balance, obtains homosalate easily through underpressure distillation.
Whitfield's ointment lower alkyl esters in described step is salicylic C1-C6 alkyl ester, as wintergreen oil, salicylic ether, propyl salicylate, isopropyl salicylate; From cost and the angle facilitating product separation, preferred wintergreen oil, salicylic ether.
The mol ratio of the Whitfield's ointment lower alkyl esters in described step and the charging capacity of 3,3,5-cyclonol can be 0.5: 1 to 1: 5.0, preferably 0.8: 1 to 1: 1.5.
The alkali making catalyzer in described step is mineral alkali or organic bases, include but not limited to basic metal, the inorganic salt of alkaline-earth metal, basic metal, the organic salt of alkaline-earth metal, C1-C50 organic amine and quaternary ammonium salt thereof, particularly ammoniacal liquor, calcium oxide, magnesium oxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammoniacal liquor, salt of wormwood, sodium carbonate, calcium carbonate, sodium bicarbonate, sodium phosphate, sodium hydride, hydrolith, triethylamine, diisopropylamine, pyridine, Tetrabutyl amonium bromide, trimethyl benzyl ammonia chloride, palmityl trimethyl ammonium chloride, sodium methylate, sodium ethylate, potassium tert.-butoxide, sodium salicylate, the mixture of one or two or more kinds in potassium salicylate, or the substrate composed load-type solid such as these alkali and aluminum oxide, zirconium white, gac, resin, as NaOH-aluminum oxide, CaO-aluminum oxide, NaOH-gac, KF-aluminum oxide, MgO-zirconium white, Na-NaOH-aluminum oxide, strongly basic anion ion exchange resin etc.An apparent advantage of working load type solid alkali is that reaction terminates to remove catalyzer easily by the method for filtering, and catalyzer likely recovery.
In described step, the charging capacity of catalyzer can be the 0.01-100% of Whitfield's ointment lower alkyl esters quality, preferably 0.1-20%, further preferred 0.1-10%.
Transesterification reaction in described step completes in a heated condition, and temperature of reaction can be 20-200 DEG C, preferably 100-180 DEG C, further preferably 120-160 DEG C.
In described step, reaction terminates, and makes target product and raw material, separation of by-products, obtain highly purified homosalate by underpressure distillation, while the recoverable such as by product lower alcohol.
Effect of the present invention is: with Whitfield's ointment lower alkyl esters and 3.5-cyclonol, transesterify under alkali particularly supported solid base catalysis prepares homosalate, substantially " three wastes " are not had to discharge, preference Raw transformation efficiency can reach 95-98%, finished product purity can reach on 99%, salicylic acid content is lower than 0.5%, other foreign matter contents, lower than 0.2%, have simple to operate, economy, environmental protection, are suitable for industrial production.
Embodiment
Specifically, the present invention can be explained by following examples, but scope of the present invention is not limited only to these embodiments.
Embodiment 1
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 14.0g, mixes, and adds salt of wormwood 5.0g, is warming up to 120-130 DEG C of reaction 10h, and gas-chromatography monitoring wintergreen oil transformation efficiency is 85.6%.Underpressure distillation, obtains water white homosalate 12.2g, and yield 70.8%, GC purity is greater than 99%.
Embodiment 2
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 23.3g, salt of wormwood 0.50g, Tetrabutyl amonium bromide 0.1g, be warming up to 180 DEG C of reaction 13h, in gas chromatographic detection reaction system, wintergreen oil transformation efficiency is 97.2%.Change vacuum distillation apparatus into, front-end volatiles reclaim to be waited to apply mechanically, and obtains water white homosalate 13.98g, and yield 81.1%, GC purity is greater than 99%.
Embodiment 3
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 18.7g, sodium hydroxide 0.20g, potassium salicylate 0.1g, be warming up to 160 DEG C of reaction 8h, gas-chromatography monitoring wintergreen oil transformation efficiency is 94.8%.
Embodiment 4
Add salicylic ether 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 7.5g, 60% sodium hydrogen 0.10g, 70 DEG C of insulation 2h, are then warming up to 140 DEG C of reactions and spend the night.Gas-chromatography monitoring 3,5-3-methyl cyclohexanol alcohol conversion is 86.2%.
Embodiment 5
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 14.0g, sodium methylate 0.80g, be warming up to 180 DEG C of reaction 5h, gas-chromatography monitoring wintergreen oil transformation efficiency is 94.7%.
Embodiment 6
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 13.1g, calcium oxide 0.70g, be warming up to 170 DEG C of reaction 8h and generate, gas-chromatography monitoring wintergreen oil transformation efficiency is 87.1%.
Embodiment 7
Add salicylic ether 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 19.0g, sodium phosphate 10.0g, be warming up to 130-140 DEG C of reaction 15h, gas-chromatography monitoring salicylic ether transformation efficiency is 81.2%.
Embodiment 8
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 14.0g, calcium carbonate 0.20g, Tetrabutyl amonium bromide 0.5g, be warming up to 150-160 DEG C of reaction 5.5h and generate homosalate.Gas-chromatography monitoring wintergreen oil transformation efficiency is 94.6%, underpressure distillation, yield 77.1%.
Embodiment 9
Wintergreen oil 10.0g is added, 3,3 in 250ml there-necked flask; 5-cyclonol 19.0g; Na-NaOH-Al2O3 solid super base 0.4g, the lower stirring at room temperature 2h of drying nitrogen protection, being then progressively warming up to 150-160 DEG C of reaction spends the night; gas-chromatography monitoring wintergreen oil transformation efficiency is 96.1%; be cooled to less than 60 DEG C, filtration catalizer, filtrate decompression is distilled; obtain water white homosalate, yield 92%.。
Embodiment 10
Salicylic ether 200.0g is added, 3,3,5-cyclonol 500.0g in 5000ml there-necked flask, sodium salicylate 20g, ten hexamethyl trimethylammonium bromide 5g, be warming up to 150-160 DEG C of reaction and spend the night, gas-chromatography monitoring salicylic ether transformation efficiency is 90.16%, underpressure distillation, yield 74.62%
Embodiment 11
Wintergreen oil 10.2kg is added, 3,3,5-cyclonol 18.0kg in 50L reactor, sodium bicarbonate 700g, benzyltrimethylammonium bromide 50g, be warming up to 100 DEG C of reaction 18h, gas-chromatography monitoring wintergreen oil transformation efficiency is 79.4%, underpressure distillation, yield 63%.
Embodiment 12
Add salicylic ether 10.0kg in 50L reactor, 3,3,5-cyclonol 18.0kg, paratoluenesulfonic acid sodium salt 500g, be warming up to 140 DEG C of reaction 15h, gas-chromatography monitoring salicylic ether transformation efficiency is 82.6%, underpressure distillation, yield 75%.
Embodiment 13
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 14.0g, mixes, and adds activated carbon supported sodium hydroxide 2.0g, is warming up to 140-150 DEG C of reaction and spends the night, and gas-chromatography monitoring wintergreen oil transformation efficiency is 98.8%.Filtration catalizer, filtrate decompression is distilled, and obtains water white homosalate, yield 94%.
Embodiment 14
Wintergreen oil 10.0g is added, 3,3 in 250ml there-necked flask; 5-cyclonol 17.0g, CaO-Al2O3 solid super base 0.7g, the lower stirring at room temperature 2h of drying nitrogen protection; then be progressively warming up to 150-160 DEG C of reaction to spend the night, gas-chromatography monitoring wintergreen oil transformation efficiency is 97.7%.Be cooled to less than 60 DEG C, filtration catalizer, filtrate decompression is distilled, and obtains water white homosalate, yield 93%.
Embodiment 15
Wintergreen oil 10.0g is added, 3,3 in 250ml there-necked flask, 5-cyclonol 15.0g, strong basic ion exchange resin (styrene type) 2.0g, is warming up to 150-160 DEG C of reaction and spends the night, and gas-chromatography monitoring wintergreen oil transformation efficiency is 93.4%.Be cooled to less than 60 DEG C, filtration catalizer, filtrate decompression is distilled, and obtains water white homosalate, yield 88%.
Embodiment 16
Add wintergreen oil 10.0g in 250ml there-necked flask, 3,3,5-cyclonol 15.0g, the CaO-Al2O3 solid super base 0.6g of recovery, be warming up to 150-160 DEG C of reaction and spend the night, gas-chromatography monitoring wintergreen oil transformation efficiency is 95.4%.Be cooled to less than 60 DEG C, filtration catalizer, filtrate decompression is distilled, and obtains water white homosalate, yield 89%.
Claims (1)
1. a synthetic method for homosalate, is characterized in that wintergreen oil or salicylic ether and 3,3,5-cyclonol heat under base catalysis and carries out transesterification reaction, then obtain homosalate through underpressure distillation, alkali wherein as catalyzer is selected from mineral alkali or organic bases, as basic metal, the inorganic salt of alkaline-earth metal, basic metal, the organic salt of alkaline-earth metal, C1-C50 organic amine and quaternary ammonium salt thereof, special calcium oxide, magnesium oxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, ammoniacal liquor, salt of wormwood, sodium carbonate, calcium carbonate, sodium bicarbonate, Sodium phosphate dibasic, triethylamine, diisopropylamine, pyridine, Tetrabutyl amonium bromide, trimethyl benzyl ammonia chloride, palmityl trimethyl ammonium chloride, sodium hydride, hydrolith, sodium methylate, sodium ethylate, potassium tert.-butoxide, sodium salicylate, the mixture of one or two or more kinds in potassium salicylate or these alkali and aluminum oxide, zirconium white, gac, the substrate composed load-type solid such as resin, the charging capacity of catalyzer is the 0.1-20% of salicylate quality, the mol ratio of the charging capacity of wintergreen oil or salicylic ether and 3,3,5-cyclonol is 0.8: 1 to 1: 1.5, transesterification reaction temperature is 100-180 DEG C.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749165A (en) * | 2017-03-24 | 2017-05-31 | 山东永浩新材料科技有限公司 | A kind of preparation method of butylene sulfite |
| CN109772464A (en) * | 2017-11-14 | 2019-05-21 | 中国石油化工股份有限公司 | A kind of solid base and its preparation method and application |
| CN112321434A (en) * | 2020-10-10 | 2021-02-05 | 马鞍山科思化学有限公司 | Preparation method of salicylate green synthesis process |
| CN114682306A (en) * | 2022-03-30 | 2022-07-01 | 山东新和成维生素有限公司 | Regeneration method of weak base catalyst for synthesizing raw membrana de-enzymic ester |
| CN114956994A (en) * | 2021-02-27 | 2022-08-30 | 大加香料技术(天津)有限公司 | Preparation method of salicylate |
| CN115894224A (en) * | 2022-11-14 | 2023-04-04 | 山东新和成维生素有限公司 | Method for preparing raw film bulk ester by adopting micro-channel continuous flow reactor |
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| BR8905636A (en) * | 1989-10-30 | 1991-04-30 | Rhodia | PROCESS OF OBTAINING SALICYLIC AND ODORIFERAL COMPOSITES THAT CONTAIN THEM |
| CN1746151A (en) * | 2004-09-07 | 2006-03-15 | 花王株式会社 | Process for producing salicylic esters |
| CN104045561A (en) * | 2014-05-21 | 2014-09-17 | 江苏德峰药业有限公司 | Synthetic method for 3,3,5-trimethylcyclohexanol salicylate |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4624802A (en) * | 1984-01-07 | 1986-11-25 | Henkel Kommanditgesellschaft Auf Aktien | Salicylic acid esters of carbocyclic alcohols as perfumes or scenting agents, perfumery compositions and salicylic acid esters |
| BR8905636A (en) * | 1989-10-30 | 1991-04-30 | Rhodia | PROCESS OF OBTAINING SALICYLIC AND ODORIFERAL COMPOSITES THAT CONTAIN THEM |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106749165A (en) * | 2017-03-24 | 2017-05-31 | 山东永浩新材料科技有限公司 | A kind of preparation method of butylene sulfite |
| CN106749165B (en) * | 2017-03-24 | 2019-04-09 | 山东永浩新材料科技有限公司 | A kind of preparation method of butylene sulfite |
| CN109772464A (en) * | 2017-11-14 | 2019-05-21 | 中国石油化工股份有限公司 | A kind of solid base and its preparation method and application |
| CN112321434A (en) * | 2020-10-10 | 2021-02-05 | 马鞍山科思化学有限公司 | Preparation method of salicylate green synthesis process |
| CN112321434B (en) * | 2020-10-10 | 2024-03-15 | 马鞍山科思化学有限公司 | Preparation method of salicylate through green synthesis process |
| CN114956994A (en) * | 2021-02-27 | 2022-08-30 | 大加香料技术(天津)有限公司 | Preparation method of salicylate |
| CN114956994B (en) * | 2021-02-27 | 2024-02-02 | 大加香料技术(天津)有限公司 | Preparation method of salicylate |
| CN114682306A (en) * | 2022-03-30 | 2022-07-01 | 山东新和成维生素有限公司 | Regeneration method of weak base catalyst for synthesizing raw membrana de-enzymic ester |
| CN114682306B (en) * | 2022-03-30 | 2023-12-12 | 山东新和成维生素有限公司 | Regeneration method of weak base catalyst for synthesizing crude membrane bulk ester |
| CN115894224A (en) * | 2022-11-14 | 2023-04-04 | 山东新和成维生素有限公司 | Method for preparing raw film bulk ester by adopting micro-channel continuous flow reactor |
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Application publication date: 20160504 |