CN114436835A - Preparation process of ethyl p-methoxycinnamate - Google Patents
Preparation process of ethyl p-methoxycinnamate Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- DHNGCHLFKUPGPX-UHFFFAOYSA-N ethyl 4-methoxycinnamate Natural products CCOC(=O)C=CC1=CC=C(OC)C=C1 DHNGCHLFKUPGPX-UHFFFAOYSA-N 0.000 title claims abstract description 12
- XTZZULGXHUQOEN-UHFFFAOYSA-N ethyl p-methoxycinnamate Natural products CCOC1=CC=C(C=CC(=O)OC)C=C1 XTZZULGXHUQOEN-UHFFFAOYSA-N 0.000 title claims abstract description 12
- DHNGCHLFKUPGPX-RMKNXTFCSA-N ethyl trans-p-methoxycinnamate Chemical compound CCOC(=O)\C=C\C1=CC=C(OC)C=C1 DHNGCHLFKUPGPX-RMKNXTFCSA-N 0.000 title claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims abstract description 88
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 60
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims abstract description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 11
- 238000001704 evaporation Methods 0.000 claims description 64
- 230000008020 evaporation Effects 0.000 claims description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 50
- 239000007788 liquid Substances 0.000 claims description 40
- 238000002425 crystallisation Methods 0.000 claims description 29
- 230000008025 crystallization Effects 0.000 claims description 29
- 239000012074 organic phase Substances 0.000 claims description 28
- 238000001035 drying Methods 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 26
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 21
- 238000004821 distillation Methods 0.000 claims description 21
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 21
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 238000005119 centrifugation Methods 0.000 claims description 17
- 239000003513 alkali Substances 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 10
- 230000003472 neutralizing effect Effects 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 239000012467 final product Substances 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- -1 ethyl oxymethylene Chemical group 0.000 claims description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 claims 1
- 235000013372 meat Nutrition 0.000 claims 1
- 239000007787 solid Substances 0.000 abstract description 46
- 239000000047 product Substances 0.000 abstract description 23
- 238000012216 screening Methods 0.000 abstract description 7
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 239000003429 antifungal agent Substances 0.000 abstract description 2
- 229940121375 antifungal agent Drugs 0.000 abstract description 2
- 239000002778 food additive Substances 0.000 abstract description 2
- 235000013373 food additive Nutrition 0.000 abstract description 2
- 229930014626 natural product Natural products 0.000 abstract description 2
- 239000000376 reactant Substances 0.000 abstract description 2
- 238000002474 experimental method Methods 0.000 description 9
- 239000013078 crystal Substances 0.000 description 8
- 238000005070 sampling Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 230000004580 weight loss Effects 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000004042 decolorization Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 244000062241 Kaempferia galanga Species 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229940114081 cinnamate Drugs 0.000 description 2
- 229930016911 cinnamic acid Natural products 0.000 description 2
- 235000013985 cinnamic acid Nutrition 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 239000000498 cooling water Substances 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 2
- 238000005580 one pot reaction Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- AFDXODALSZRGIH-QPJJXVBHSA-N (E)-3-(4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1 AFDXODALSZRGIH-QPJJXVBHSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- KBEBGUQPQBELIU-CMDGGOBGSA-N Ethyl cinnamate Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1 KBEBGUQPQBELIU-CMDGGOBGSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 235000007265 Myrrhis odorata Nutrition 0.000 description 1
- 240000004760 Pimpinella anisum Species 0.000 description 1
- 235000012550 Pimpinella anisum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- KBEBGUQPQBELIU-UHFFFAOYSA-N cinnamic acid ethyl ester Natural products CCOC(=O)C=CC1=CC=CC=C1 KBEBGUQPQBELIU-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000004032 superbase Substances 0.000 description 1
- 150000007525 superbases Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C67/54—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Crystallography & Structural Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The ethyl p-methoxycinnamate has wide application in the fields of preparing sun-screening products, antifungal agents and food additives. The invention provides a preparation process for synthesizing ethyl p-oxymethylcinnamate by using a natural product anisic aldehyde as a reactant to react with ethyl acetate in one step, the preparation process is simple in reaction, high in safety and easy to operate, the ethyl p-oxymethylcinnamate can be prepared in a large amount, and the finally obtained ethyl p-oxymethylcinnamate is a white solid with the purity of 99.98%.
Description
Technical Field
The invention relates to the field of compound preparation, and in particular relates to a preparation process of ethyl p-methoxycinnamate.
Background
The cinnamic acid lipid has wide application in the fields of fine chemical engineering and medicine. The ethyl p-oxymethylcinnamate is derived from a kaempferia galangal extract, is an ideal sun-screening agent due to the advantages of good absorptivity in a 280-320 nm region, high absorptivity, no irritation to skin, good safety and the like, and has certain biological activity and antifungal effect. Meanwhile, in life, ethyl p-methoxycinnamate is also used as a food flavor additive due to the unique fragrance of the ethyl p-methoxycinnamate, so that the ethyl p-methoxycinnamate is widely applied to the fields of preparing sun-screening products, antifungal agents and food additives.
At present, the synthesis method for synthesizing ethyl p-oxymethylcinnamate mainly comprises the following steps of synthesizing cinnamic acid by utilizing a Perkin condensation reaction or a Knoevenagle reaction, and then obtaining cinnamate by an esterification reaction, wherein the cinnamate is prepared by two steps of reactions in both reactions, and the esterification rate is low; secondly, patent CN 107602384A prepares p-oxymethylbenzaldehyde and diethyl malonate into light yellow solid under the action of solid super-alkali, namely p-oxymethyl ethyl benzoate. However, the heating temperature in the preparation process of the solid super base used in the reaction is as high as 500-600 ℃, and active metal sodium is required, and the preparation process is complex to operate and low in safety. Therefore, the development of a preparation process of the p-oxymethyl ethyl cinnamate, which has the advantages of simple reaction, high safety and easy operation and can be prepared in large scale, is necessary.
Disclosure of Invention
The ethyl p-methoxycinnamate is an extract of the kaempferia galangal as an agricultural product, and because the price is high in recent years, and the content of the ethyl p-methoxycinnamate in the kaempferia galangal as an agricultural product is low and only accounts for 1.2-14% of the total components, the extraction difficulty is high, and the cost is high, the natural p-methoxycinnamate is synthesized by adopting the raw materials of natural anisic aldehyde (an anise extract) and natural ethyl acetate which are low in price and wide in source as main raw materials.
The inventor finds that a small batch of ethyl p-methoxycinnamate is synthesized in a laboratory, a crude product made in the laboratory is a yellow solid, a white crystalline solid can be obtained by adding activated carbon for decolorization and ethanol for crystallization, but a product produced in an enlarged mode is a brown solid, and the product cannot be made into a pure white solid by decolorization and crystallization.
Therefore, aiming at the problems, the invention provides a preparation process for synthesizing ethyl p-oxymethylcinnamate by using a natural product anisic aldehyde as a reactant to react with ethyl acetate in one step, the preparation process only needs one-step reaction, active alkali metal is not used in the reaction, and the process safety is improved. The reaction temperature is low, the reaction energy consumption is reduced, and the preparation cost is reduced. The ethyl p-oxymethylcinnamate prepared by the process has the characteristics of high yield and high purity.
The synthesis reaction of the invention is as follows:
the invention adopts the following technical scheme:
a preparation process of ethyl p-methoxycinnamate mainly comprises the following steps: adding ethyl acetate, anisic aldehyde and sodium ethoxide into cyclohexane, reacting at 40-60 ℃ to generate ethyl p-oxymethylcinnamate, and decolorizing the ethyl p-oxymethylcinnamate by a flash evaporation process.
The method specifically comprises the following steps:
1. feeding: adding ethyl acetate, sodium ethoxide and cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding anisic aldehyde while stirring, controlling the reaction temperature to be 40-60 ℃, and waiting for the reaction to be finished;
3. washing and flash evaporation treatment: adding water into a reaction kettle, adding acid, neutralizing alkali, adding water, removing salt in an organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing a solvent, and feeding into the flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid;
4. crystallization, centrifugation and drying: and (3) adding a solvent into the flash evaporation feed liquid while the flash evaporation feed liquid is hot, dissolving, filtering, crystallizing, centrifuging and drying to obtain a final product.
In the technical scheme of the invention, in the step 1, ethyl acetate and cyclohexane can be added into a reaction kettle to be stirred, and then sodium ethoxide is added. When sodium ethoxide is added, the vacuum of the reaction kettle needs to be opened to prevent the dust from overflowing.
Further, the molar ratio of anisic aldehyde to sodium ethoxide is: 0.6-0.9: 1, preferably 0.7: 1.
Further, the molar ratio of cyclohexane to anisic aldehyde is: 2.0-3.0: 1, preferably 2.3: 1.
Wherein the mass ratio of the ethyl acetate to the anisic aldehyde in the steps 1 and 2 is as follows: 2.5-10: 1.
In the technical scheme of the invention, the anisic aldehyde in the step 2 is placed in an elevated tank, a valve of a dropping hopper of the elevated tank is opened during reaction, the dropping speed is controlled, the anisic aldehyde is rapidly dropped into a reaction kettle within about one hour (the dropping time depends on the specific kettle temperature), the temperature is increased during the dropping process, the dropping can be directly started at room temperature, and the kettle temperature is kept at 40-60 ℃, preferably 45 ℃. If the temperature is over-temperature, the dripping can be suspended, and the jacket cooling water is started at the same time. After the dropwise addition is finished, keeping the temperature at 40-45 ℃ for one hour, and sampling to detect whether the reaction is complete.
In the technical scheme of the invention, in step 3, after the reaction is finished, water is firstly added into a reaction kettle for further reaction of the water and unreacted sodium ethoxide to remove the sodium ethoxide, then acid liquor is added for neutralizing the generated sodium hydroxide by acid, and a cooling water jacket is adopted for controlling the reaction temperature not to exceed 45 ℃ in the neutralization process.
Further, in step 3, water is again added for the purpose of washing off acids, bases, salts and the like in the organic phase with water. Wherein the organic phase obtained is a reddish brown clear solution.
Further, the organic phase in step 3 is transferred to a distillation still for the purpose of removing ethanol produced by the first addition of water and cyclohexane and ethyl acetate, and the solvent is recovered by separating cyclohexane and ethyl acetate in the system by controlling the temperature of the distillation still.
Further, the temperature of the distillation kettle in the step 3 is 85-90 ℃.
Further, in the step 3, before the flash evaporation operation, a water ring vacuum pump is used for removing low-boiling-point products under vacuum (<100 ℃), and then high-vacuum flash evaporation is directly started, wherein the flash evaporation temperature is 110-125 ℃.
In a further step 3, the acid is an inorganic acid, in the technical scheme of the present invention, the inorganic acid is one or more of sulfuric acid, phosphoric acid, and hydrochloric acid, and in a specific embodiment of the present invention, sulfuric acid is selected.
Further, the acid concentration is 10 to 15%.
In the technical scheme of the invention, in the step 4, the solvent is one of methanol, ethanol and acetone, and ethanol is preferred.
Further, in the step 4, when the solvent is ethanol, the concentration of ethanol is 85% to 100%, preferably 95%.
In the embodiment of the invention, after the flash evaporation feed liquid in the step 4 is fully dissolved by ethanol, insoluble substances (a small amount of inorganic salt) are filtered, the crystallization temperature is 0-10 ℃, and the crystal is prevented from being overlarge along with slow stirring in the crystallization process. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. The mother liquor needs to recover ethanol, the recovered ethanol can be directly used, and meanwhile, a part of products (can be concentrated and crystallized again, and can also be crystallized after being rectified to improve the content) exist.
Wherein, the drying condition is 40 ℃, the vacuum drying is carried out for 8 hours continuously until no weight loss exists, white solid is obtained, and the purity of the product reaches 99.98 percent.
The invention has the beneficial effects that:
1. the invention adopts one-step reaction to synthesize the ethyl p-oxymethylcinnamate, and compared with Perkin condensation reaction or Knoevenagle reaction, the invention has the advantages of less reaction steps, high yield and reaction yield of over 85 percent.
2. Compared with the laboratory synthesis, the crude product prepared in the laboratory is yellow solid, white crystalline solid can be obtained by adding activated carbon for decolorization and ethanol crystallization, but the product after the large-scale production is brown solid, and the product cannot be pure white solid by decolorization and crystallization. Therefore, the process of quick distillation and decoloration (flash evaporation) is added, the color of the product crystallized after the crude product is quickly distilled belongs to a pure white solid, and the purity is higher and can reach more than 99.98 percent.
3. In the technical scheme of the invention, cyclohexane is used as a solvent, so that the solubility of sodium ethoxide in a reaction system can be increased, the catalytic efficiency is improved, and the synthesis yield is improved.
4. The invention recovers and reuses the solvent, reduces the preparation cost and has little environmental hazard.
5. The method does not adopt dangerous reagents, and is safe, reliable and easy to operate.
Detailed Description
The technical solution of the present invention will be described below with reference to specific embodiments of the present invention.
The reagents and apparatus used in the present invention are conventional products commercially available.
Examples 1 to 4
Examples 1 to 4 are solvent screening experiments in step 1, which were specifically performed by: 1. feeding, adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of solvent into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be about 45 ℃, keeping the temperature to be 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, wherein the reference content product is about 95%, namely the reaction is finished;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase to a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase to a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding 1.2 times of 95% ethanol into the flash evaporation liquid, dissolving completely (heating slightly if necessary), filtering out insoluble substances, crystallizing at 0-10 deg.C, and slowly stirring to prevent oversize crystals. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. The drying condition is 40 ℃, the vacuum drying is carried out for 8 hours continuously until no weight loss exists, and the analysis is qualified. In examples 1 to 4, the solvent and reaction yield used in step 1 are shown in Table 1.
TABLE 1 Effect of solvent on reaction yield in step 1
| Examples | Using solvents | Reaction yield (average of three experiments) |
| Example 1 | Cyclohexane | 86％ |
| Example 2 | Toluene | 80％ |
| Example 3 | Ethyl acetate | 72％ |
| Example 4 | Methylene dichloride | 61％ |
Examples 5 to 8
Examples 5 to 8 are: when the solvent in step 1 is cyclohexane, the effect of the feed ratio of cyclohexane to anisaldehyde on the reaction yield.
The specific operation is as follows: 1. feeding, adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and a certain amount of cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be about 45 ℃, keeping the temperature to be 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, and controlling the reference content product to be about 95%, namely finishing the reaction;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase to a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase to a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding 1.2 times of 95% ethanol by mass into the flash evaporation liquid, fully dissolving (possibly slightly heating), filtering out insoluble substances, crystallizing at 0-10 deg.C, and slowly stirring to prevent crystal oversize. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. The drying condition is 40 ℃, the vacuum drying is carried out for 8 hours continuously until no weight loss exists, and the analysis is qualified. In examples 5 to 8, the charge ratio and reaction yield of cyclohexane and anisic aldehyde in step 1 are shown in table 2.
TABLE 2 Effect of cyclohexane and anisaldehyde charge ratio on reaction yield
Examples 9 to 12
Examples 9 to 12 are alkali screening experiments in step 1, which were specifically performed by: 1. feeding, adding 500Kg of ethyl acetate, 140Kg of alkali and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be about 45 ℃, keeping the temperature to be 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, and controlling the reference content product to be about 95%, namely finishing the reaction;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase to a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase to a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding 1.2 times of 95% ethanol into the flash evaporation liquid, dissolving completely (heating slightly if necessary), filtering out insoluble substances, crystallizing at 0-10 deg.C, and slowly stirring to prevent oversize crystals. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. The drying condition is 40 ℃, the vacuum drying is carried out for 8 hours continuously until no weight loss exists, and the analysis is qualified. In examples 9 to 12, the base used in step 1 and the reaction yield are shown in Table 3.
TABLE 3 influence of base species on reaction yield in step 1
| Examples | Alkali | Reaction yield (average of three experiments) |
| Example 9 | Sodium methoxide | 78％ |
| Example 10 | Sodium ethoxide | 86％ |
| Example 11 | Sodium hydroxide | 56％ |
| Example 12 | Potassium carbonate | 12％ |
Examples 13 to 16
Examples 13 to 16 are experiments on the influence of the ratio of sodium ethoxide to anisic aldehyde on the reaction yield, and the specific operations are as follows: 1. feeding, adding 500Kg of ethyl acetate, a certain amount of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be about 45 ℃, keeping the temperature to be 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, and controlling the reference content product to be about 95%, namely finishing the reaction;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salts in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase into a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding 1.2 times of 95% ethanol into the flash evaporation liquid, dissolving completely (heating slightly if necessary), filtering out insoluble substances, crystallizing at 0-10 deg.C, and slowly stirring to prevent oversize crystals. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. The drying condition is 40 ℃, the vacuum drying is carried out for 8 hours continuously until no weight loss exists, and the analysis is qualified. In examples 13 to 16, the ratio and reaction yield of sodium ethoxide to anisic aldehyde are shown in table 4.
TABLE 4 Effect of anisic aldehyde to sodium ethoxide ratio on reaction yield
Examples 17 to 21
Examples 17 to 21 are reaction temperature screening experiments in step 2, which were specifically performed by: 1. feeding, namely adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be 30-60 ℃, keeping the temperature to be 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, wherein the reference content product is about 95%, namely the reaction is finished;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase to a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase to a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding 1.2 times of 95% ethanol into the flash evaporation liquid, dissolving completely (heating slightly if necessary), filtering out insoluble substances, crystallizing at 0-10 deg.C, and slowly stirring to prevent oversize crystals. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. Drying at 40 deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. In examples 17 to 21, the reaction temperature and the reaction yield used in step 2 are shown in Table 5.
TABLE 5 influence of reaction temperature on reaction yield in step 2
Examples 22 to 26
Examples 22 to 26 are screening experiments of the solvent used in the crystallization in step 4, and the specific operations are as follows: 1. feeding, adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be about 45 ℃, keeping the temperature to be 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, wherein the reference content product is about 95%, namely the reaction is finished;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase to a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase to a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding a certain amount of 95% ethanol into the flash evaporation liquid, fully dissolving (possibly slightly heating), filtering out insoluble substances, crystallizing at 0-10 deg.C, and slowly stirring to prevent oversize crystals. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. Drying at 40 deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. In examples 22 to 26, the solvents used for the crystallization in step 4 and the reaction yields are shown in Table 6.
TABLE 6 screening experiment of solvents used in crystallization in step 4
Examples 27 to 30
Examples 27 to 30 are experiments on the influence of the water content of ethanol on the reaction yield when ethanol is used as a solvent in step 4. The specific operation is as follows: 1. feeding, adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. reaction: dropwise adding 200Kg of anisic aldehyde while stirring, controlling the reaction temperature to be 45 ℃, keeping the temperature at 40-45 ℃ for one hour after the dropwise adding is finished, sampling and detecting, wherein the reference content product is about 95%, namely the reaction is finished;
3. washing and flash evaporation treatment: adding water into the reaction kettle, adding 13% sulfuric acid, and neutralizing alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase to a distillation kettle, removing the solvent when the temperature of the distillation kettle is not more than 90 ℃, and sending the organic phase to a flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid, wherein the temperature of the flash evaporation kettle is 110-125 ℃;
4. crystallization, centrifugation and drying: adding ethanol with the mass of 85% -100% 1.2 times of that of the flash evaporation feed liquid into the flash evaporation feed liquid, filtering out insoluble substances after the flash evaporation feed liquid is fully dissolved (the solution is possibly heated slightly), and crystallizing at 0-10 ℃, wherein the crystals are prevented from being oversize along with slow stirring in the crystallization process. After crystallization, supernatant liquid is firstly pumped out, the solid is transferred to a centrifugal machine for full centrifugation to obtain a solid which is close to dry, the solid content is analyzed, and the solid is transferred to drying after being qualified. The drying condition is 40 ℃, the vacuum drying is carried out for 8 hours continuously until no weight loss exists, and the analysis is qualified. In examples 27 to 30, the water content (ethanol concentration) and reaction yield of ethanol used for crystallization in step 4 are shown in table 7.
TABLE 7 influence of the Water content of ethanol used in the crystallization in step 4 on the product quality
The unqualified product quality means that the content of the p-methoxybenzaldehyde in the product is lower and does not meet the content requirement of enterprises.
The foregoing is a more detailed description of the present invention with reference to specific embodiments thereof, which should not be taken to limit the invention to the specific embodiments thereof. It will be apparent to those skilled in the art that various changes, substitutions and alterations can be made without departing from the spirit and scope of the invention.
Claims (10)
1. A preparation process of ethyl p-methoxycinnamate comprises the following steps:
adding ethyl acetate, anisic aldehyde and sodium ethoxide into cyclohexane, and reacting at 40-60 ℃ to generate ethyl p-oxymethylcinnamate.
2. The process of claim 1, wherein the ethyl oxymethylene meat silicate is decolorized by a flash evaporation process.
3. The process according to claim 1, comprising the following steps:
(1) feeding: adding ethyl acetate, sodium ethoxide and cyclohexane into a reaction kettle, and stirring;
(2) reaction: dropwise adding anisic aldehyde while stirring, controlling the reaction temperature to be 40-60 ℃, and waiting for the reaction to be finished;
(3) washing and flash evaporation treatment: adding water into a reaction kettle, adding acid, neutralizing alkali, adding water, removing salt in an organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing a solvent, and feeding into the flash evaporation kettle for flash evaporation to obtain flash evaporation feed liquid;
(4) crystallization, centrifugation and drying: and (3) adding a solvent into the flash evaporation feed liquid while the flash evaporation feed liquid is hot, dissolving, filtering, crystallizing, centrifuging and drying to obtain a final product.
4. The process of claim 1, wherein the molar ratio of anisaldehyde to sodium ethoxide is: 0.6-0.9: 1, preferably 0.7: 1.
5. The process of claim 1, wherein the molar ratio of cyclohexane to anisaldehyde is: 2.0-3.0: 1, preferably 2.3: 1.
6. The process according to claim 1, wherein the mass ratio between ethyl acetate and anisic aldehyde is: 2.5-10: 1.
7. The process according to claim 3, wherein in the step (2), the reaction temperature is preferably 45 ℃.
8. The process according to claim 3, wherein in the step (3), the temperature in the flash evaporation kettle is 110 to 125 ℃, and the temperature in the distillation kettle is 85 to 90 ℃.
9. The process according to claim 3, wherein in the step (3), the process according to claim 1, wherein in the step (3), the acid is selected from the group consisting of inorganic acids; further, the acid is one or more of sulfuric acid, hydrochloric acid and phosphoric acid; further, the acid concentration is 10% -15%.
10. The preparation process according to claim 3, wherein in the step (4), the solvent is one of methanol, ethanol and acetone; preferably ethanol; further, the ethanol concentration is 85% to 100%, preferably 95%.
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