CN114436835B - 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 17
- 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 9
- 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 9
- 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 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 85
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 56
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims abstract description 50
- 238000001704 evaporation Methods 0.000 claims description 58
- 230000008020 evaporation Effects 0.000 claims description 58
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 50
- 239000007788 liquid Substances 0.000 claims description 31
- 239000012074 organic phase Substances 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 28
- 238000001035 drying Methods 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 20
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 20
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 20
- 239000003513 alkali Substances 0.000 claims description 15
- 238000004821 distillation Methods 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 239000012467 final product Substances 0.000 claims description 9
- 238000005406 washing 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
- 238000001914 filtration Methods 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
- 238000007701 flash-distillation Methods 0.000 claims 1
- 239000007787 solid Substances 0.000 abstract description 46
- 239000000047 product Substances 0.000 abstract description 22
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 abstract description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 10
- 229940114081 cinnamate Drugs 0.000 abstract description 8
- 238000012216 screening Methods 0.000 abstract description 7
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- 229940121375 antifungal agent Drugs 0.000 abstract description 2
- 239000003429 antifungal agent Substances 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
- 238000002425 crystallisation Methods 0.000 description 29
- 230000008025 crystallization Effects 0.000 description 29
- 238000010438 heat treatment Methods 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 11
- 238000005119 centrifugation Methods 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 238000005070 sampling Methods 0.000 description 8
- 239000006228 supernatant Substances 0.000 description 8
- 230000004580 weight loss Effects 0.000 description 8
- 238000001514 detection method Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000004090 dissolution Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 238000004042 decolorization Methods 0.000 description 4
- KBEBGUQPQBELIU-CMDGGOBGSA-N Ethyl cinnamate Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1 KBEBGUQPQBELIU-CMDGGOBGSA-N 0.000 description 3
- 244000062241 Kaempferia galanga Species 0.000 description 3
- 235000013421 Kaempferia galanga Nutrition 0.000 description 3
- 229930016911 cinnamic acid Natural products 0.000 description 3
- 235000013985 cinnamic acid Nutrition 0.000 description 3
- -1 cinnamic acid ester Chemical class 0.000 description 3
- KBEBGUQPQBELIU-UHFFFAOYSA-N cinnamic acid ethyl ester Natural products CCOC(=O)C=CC1=CC=CC=C1 KBEBGUQPQBELIU-UHFFFAOYSA-N 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 3
- 238000005580 one pot reaction Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 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
- 238000004519 manufacturing process 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
- 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
- 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
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 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
- 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
- 238000009835 boiling Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000000694 effects Effects 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
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 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
- 230000007794 irritation Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000010413 mother solution Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002994 raw material Substances 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
- 229940045955 star anise extract Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- 238000001291 vacuum drying 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 the ethyl p-oxymethyl cinnamate by using natural product anisaldehyde as a reactant and reacting with ethyl acetate in one step, the preparation process is simple in reaction, high in safety and easy to operate, and the ethyl p-oxymethyl cinnamate can be prepared in large quantity, and finally the obtained ethyl p-oxymethyl cinnamate is a white solid, and the purity of the ethyl p-oxymethyl cinnamate can reach 99.98%.
Description
Technical Field
The invention relates to the field of compound preparation, in particular to a preparation process of ethyl p-methoxycinnamate.
Background
Cinnamic acid esters are widely applied in the fields of fine chemical industry and medicines. The p-oxymethyl cinnamic acid ethyl ester is derived from kaempferia galanga extract, has the advantages of good absorptivity in the 280-320 nm area, high absorptivity, no irritation to skin, good safety and the like, becomes an ideal sun-screening agent, has certain biological activity and has antifungal effect. Meanwhile, in life, the ethyl p-methoxycinnamate is also used as a food flavor additive due to the unique fragrance thereof, so that the ethyl p-methoxycinnamate has wide application in the fields of preparing sun-screening products, antifungal agents and food additives.
At present, the synthetic method for synthesizing the ethyl p-oxymethyl cinnamate mainly comprises the following steps of firstly synthesizing cinnamic acid by utilizing a Perkin condensation reaction or a Knoevenagle reaction, and then obtaining cinnamic acid ester by an esterification reaction, wherein the two reactions are all required to prepare the cinnamic acid ester by two-step reaction, and the esterification rate is low; secondly, the patent CN 107602384A prepares the light yellow solid, namely the ethyl p-oxymethylbenzoate, from the p-oxymethylbenzaldehyde and diethyl malonate under the action of solid super alkali. However, the heating temperature in the preparation process of the solid super alkali used in the reaction is up to 500-600 ℃, and active metal sodium is needed, and the preparation process is complex in operation and low in safety. Therefore, the development of a preparation process of the ethyl p-oxymethyl cinnamate, which has the advantages of simple reaction, high safety and easy operation and can be prepared in large quantities, is very necessary.
Disclosure of Invention
The p-methoxy ethyl cinnamate is an extract of agricultural product kaempferia galanga, and because the price is high in recent years, and the content of the p-methoxy ethyl cinnamate in the agricultural product kaempferia galanga is low, the p-methoxy ethyl cinnamate only accounts for 1.2-14% of the total components, the extraction difficulty is high, and the cost is high, so that the natural p-methoxy ethyl cinnamate is synthesized by adopting natural anisic aldehyde (star anise extract) and natural ethyl acetate which are low in price and wide in source as main raw materials.
The inventor finds that the laboratory synthesizes small batches of ethyl p-methoxy cinnamate, the crude product made by 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 production is amplified is brown solid, and the pure white solid cannot be obtained by decolorization and crystallization.
Therefore, in order to solve the problems, the invention provides a preparation process for synthesizing the p-oxymethyl ethyl cinnamate by using natural product anisaldehyde as a reactant and ethyl acetate through one-step reaction, the preparation process only needs one-step reaction, and meanwhile, active alkali metal is not used in the reaction, so that the process safety is improved. The reaction temperature is low, the reaction energy consumption is reduced, and the preparation cost is reduced. The preparation of the ethyl p-oxymethyl cinnamate 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:
the preparation process of the ethyl p-methoxycinnamate mainly comprises the following steps: adding ethyl acetate, anisaldehyde and sodium ethoxide into cyclohexane, reacting at 40-60 ℃ to generate the p-oxymethyl ethyl cinnamate, and decolorizing the p-oxymethyl ethyl sarcosilicate by adopting 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. the reaction: adding anisaldehyde dropwise while stirring, controlling the reaction temperature to be 40-60 ℃, and finishing the reaction;
3. Washing and flash evaporation treatment: adding water into a reaction kettle, adding acid to neutralize alkali, adding water to remove salt in an organic phase, separating liquid, transferring the organic phase into a distillation kettle to remove solvent, and sending the organic phase into a flash evaporation kettle to flash to obtain flash evaporation feed liquid;
4. Crystallizing, centrifuging and drying: and 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 for stirring, and then sodium ethoxide is added. When sodium ethoxide is added, the reaction kettle needs to be opened for vacuum so as to prevent dust from overflowing.
Further, the molar ratio of anisaldehyde to sodium ethoxide is: 0.6 to 0.9:1, preferably 0.7:1.
Further, the molar ratio of cyclohexane to anisaldehyde is: 2.0 to 3.0:1, preferably 2.3:1.
Wherein, the mass ratio between the ethyl acetate and the anisic aldehyde in the step 1 and the step 2 is as follows: 2.5-10:1.
In the technical scheme of the invention, the anisaldehyde in the step 2 is placed in a high-level tank, a valve of a dropping hopper of the high-level tank is opened during reaction, dropping speed is controlled, the anisaldehyde is quickly dropped into a reaction kettle (the dropping time is determined by the specific kettle temperature) within about one hour, 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 exceeds the preset temperature, the dripping can be stopped, and the jacket cooling water is started. After the dripping is finished, the temperature is kept at 40-45 ℃ for one hour, and sampling is carried out to detect whether the reaction is complete.
In the step 3 of the technical scheme of the invention, after the reaction is finished, water is firstly added into the reaction kettle to further react with unreacted sodium ethoxide, sodium ethoxide is removed, then acid liquor is added to neutralize generated sodium hydroxide by acid, and meanwhile, a cooling water jacket is adopted to control the reaction temperature not to exceed 45 ℃ in the neutralization process.
Further, in step 3, the purpose of adding water again is to wash out acids, bases, salts, etc. in the organic phase with water. Wherein the resulting organic phase is a reddish brown clear solution.
Further, the purpose of transferring the organic phase into the distillation still in the step 3 is to remove ethanol generated after cyclohexane and ethyl acetate and the first water addition, and the cyclohexane and ethyl acetate in the system are separated by controlling the temperature of the distillation still, so as to recover the solvent.
Further, the temperature of the distillation still in the step 3 is 85-90 ℃.
Further, in step 3, the low boiling point product (< 100 ℃) under vacuum is removed by a water ring vacuum pump before the flash evaporation operation, and then the high vacuum flash evaporation is directly started, wherein the flash evaporation temperature is 110-125 ℃.
In the step 3, the acid is an inorganic acid, and in the technical scheme of the invention, the inorganic acid is one or more of sulfuric acid, phosphoric acid and hydrochloric acid, and in the specific embodiment of the 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, preferably ethanol.
Further, in the step 4, when the solvent is ethanol, the ethanol concentration is 85% -100%, preferably 95%.
In the embodiment of the invention, after the flash evaporation material liquid in the step 4 is fully dissolved by ethanol, insoluble matters (a small amount of inorganic salts) are filtered, the crystallization temperature is 0-10 ℃, and the crystallization process is accompanied by slow stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. The mother solution needs to recycle the ethanol, and the recycled ethanol can be directly used, and part of the product can be concentrated and recrystallized, or can be rectified to improve the content and then crystallized.
Wherein, the drying condition is 40 ℃, the vacuum drying is carried out for 8 hours till no weight loss, the 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-oxymethyl cinnamate, and compared with the Perkin condensation reaction or the Knoevenagle reaction, the invention has less reaction steps, high yield and more than 85 percent of reaction yield.
2. Compared with laboratory synthesis, the crude product made 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 production is amplified is brown solid, and the product cannot be made into pure white solid by decolorization and crystallization. Therefore, the rapid distillation and decoloration (flash evaporation) process is added, the color of the product crystallized by the rapid distillation of the crude product belongs to 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, and the catalytic efficiency and the synthesis yield can be improved.
4. The invention recovers and reutilizes the solvent, reduces the preparation cost and has little environmental hazard.
5. The method does not adopt dangerous reagent, is safe and reliable and is easy to operate.
Detailed Description
The technical scheme of the invention will be described in conjunction with specific embodiments of the invention.
The reagents and apparatus used in the present invention are conventional products commercially available.
Examples 1 to 4
Examples 1 to 4 are the solvent screening experiments in step 1, which are specifically performed as follows: 1. feeding, namely adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of solvent into a reaction kettle, and stirring;
2. the reaction: 200Kg of anisaldehyde is added dropwise while stirring, the reaction temperature is controlled to be about 45 ℃, after the dropwise addition is finished, the temperature is kept at 40-45 ℃ for one hour, sampling and detection are carried out, and the reference content product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: the flash evaporation material liquid obtained above is added with 1.2 times of 95% ethanol by mass by heating, and after full dissolution (possibly with slight heating), insoluble substances are filtered out, and the solution is placed at 0-10 ℃ for crystallization, and the crystallization process is accompanied by slow stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. The solvents and reaction yields used in examples 1 to 4, step 1, are shown in Table 1.
TABLE 1 influence of solvent on reaction yield in step 1
| Examples | Using solvents | Reaction yield (average of three experiments) |
| Example 1 | Cyclohexane | 86％ |
| Example 2 | Toluene (toluene) | 80％ |
| Example 3 | Acetic acid ethyl ester | 72％ |
| Example 4 | Dichloromethane (dichloromethane) | 61％ |
Examples 5 to 8
Examples 5 to 8 are: when the solvent in the step 1 is cyclohexane, the effect of the feeding ratio of cyclohexane to anisaldehyde on the reaction yield is achieved.
The specific operation is as follows: 1. feeding, namely adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and a certain amount of cyclohexane into a reaction kettle, and stirring;
2. The reaction: 200Kg of anisaldehyde is dropwise added under stirring, the reaction temperature is controlled to be about 45 ℃, after the dropwise addition is finished, the temperature is kept at 40-45 ℃ for one hour, sampling detection is carried out, and the reference content product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: the flash evaporation material liquid obtained above is added with 1.2 times of 95% ethanol by mass by heating, and after full dissolution (possibly with slight heating), insoluble substances are filtered out, and the solution is placed at 0-10 ℃ for crystallization, and the crystallization process is accompanied by slow stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. Wherein, in examples 5 to 8, the feeding ratio of cyclohexane and anisaldehyde in step 1 and the reaction yield are shown in Table 2.
TABLE 2 influence of the feed ratio of cyclohexane to anisaldehyde on the reaction yield
Examples 9 to 12
Examples 9 to 12 are the alkali screening experiments in step 1, which are specifically performed as follows: 1. feeding, namely adding 500Kg of ethyl acetate, 140Kg of alkali and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. The reaction: 200Kg of anisaldehyde is dropwise added while stirring, the reaction temperature is controlled to be about 45 ℃, after the dropwise addition is finished, the temperature is kept at 40-45 ℃ for one hour, sampling detection is carried out, and the reference content product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: the flash evaporation material liquid obtained above is added with 1.2 times of 95% ethanol by mass by heating, and after full dissolution (possibly with slight heating), insoluble substances are filtered out, and the solution is placed at 0-10 ℃ for crystallization, and the crystallization process is accompanied by slow stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. Wherein, the alkali and reaction yield used in the step 1 in examples 9 to 12 are shown in Table 3.
TABLE 3 influence of the base species in step 1 on the reaction yield
| 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 anisaldehyde on the reaction yield, and the specific operation is as follows: 1. feeding, namely adding 500Kg of ethyl acetate, a certain amount of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. The reaction: 200Kg of anisaldehyde is dropwise added while stirring, the reaction temperature is controlled to be about 45 ℃, after the dropwise addition is finished, the temperature is kept at 40-45 ℃ for one hour, sampling detection is carried out, and the reference content product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: the flash evaporation material liquid obtained above is added with 1.2 times of 95% ethanol by mass by heating, and after full dissolution (possibly with slight heating), insoluble substances are filtered out, and the solution is placed at 0-10 ℃ for crystallization, and the crystallization process is accompanied by slow stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. Wherein, the ratio of sodium ethoxide to anisaldehyde and the reaction yield of examples 13-16 are shown in Table 4.
TABLE 4 experiment of influence of the ratio of Aniline aldehyde to sodium ethoxide on reaction yield
Examples 17 to 21
Examples 17 to 21 are reaction temperature screening experiments in step 2, which are specifically performed as follows: 1. feeding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. the reaction: 200Kg of anisaldehyde is added dropwise while stirring, the reaction temperature is controlled to be 30-60 ℃, the temperature is maintained at 40-45 ℃ for one hour after the dropwise addition is finished, sampling and detection are carried out, and the reference content of the product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: the flash evaporation material liquid obtained above is added with 1.2 times of 95% ethanol by mass by heating, and after full dissolution (possibly with slight heating), insoluble substances are filtered out, and the solution is placed at 0-10 ℃ for crystallization, and the crystallization process is accompanied by slow stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. The reaction temperatures and reaction yields used in examples 17 to 21 and step 2 are shown in Table 5.
TABLE 5 experiment of influence of reaction temperature on reaction yield in step2
Examples 22 to 26
Examples 22 to 26 are solvent screening experiments for use in the crystallization in step 4, which are specifically performed as follows: 1. feeding, namely adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. the reaction: 200Kg of anisaldehyde is added dropwise while stirring, the reaction temperature is controlled to be about 45 ℃, after the dropwise addition is finished, the temperature is kept at 40-45 ℃ for one hour, sampling and detection are carried out, and the reference content product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: adding a certain amount of 95% ethanol into the flash evaporation liquid, dissolving thoroughly (possibly with slightly heating), filtering to remove insoluble substances, crystallizing at 0-10deg.C, and slowly stirring to prevent excessive crystal growth. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. The solvents and reaction yields used for crystallization in examples 22 to 26 and step 4 are shown in Table 6.
TABLE 6 screening experiments with solvents used in the crystallization in step 4
Examples 27 to 30
Examples 27 to 30 are experiments of the influence of the water content of ethanol on the reaction yield in the case of selecting ethanol as the solvent in step 4. The specific operation is as follows: 1. feeding, namely adding 500Kg of ethyl acetate, 140Kg of sodium ethoxide and 280Kg of cyclohexane into a reaction kettle, and stirring;
2. The reaction: 200Kg of anisaldehyde is added dropwise while stirring, the reaction temperature is controlled to be 45 ℃, after the dropwise addition is finished, the temperature is kept at 40-45 ℃ for one hour, sampling and detection are carried out, and the reference content product is about 95%, namely the reaction is finished;
3. Washing and flash evaporation treatment: water and then 13% sulfuric acid are added into the reaction kettle to neutralize the alkali. Adding water, removing salt in the organic phase, separating liquid, transferring the organic phase into a distillation kettle, removing solvent at the temperature of 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. Crystallizing, centrifuging and drying: adding 1.2 times of 85% -100% ethanol by mass into the flash evaporation material liquid by heating, fully dissolving (possibly slightly heating), filtering insoluble substances, crystallizing at 0-10deg.C, and slowly stirring to prevent oversized crystals. After crystallization, the supernatant is pumped out, the solid is transferred into a centrifuge for full centrifugation to obtain near-dry solid, the solid content is analyzed, and the solid is transferred into drying after being qualified. Drying at 40deg.C under vacuum for 8 hr until no weight loss occurs, and analyzing to obtain the final product. The ethanol water content (ethanol concentration) and the reaction yield used for crystallization in step 4 in examples 27 to 30 are shown in Table 7.
TABLE 7 influence of the moisture 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 relatively low, and the content requirement of enterprises is not met.
The foregoing is a further detailed description of the invention in connection with specific embodiments, and it is not intended that the invention be limited to those specific embodiments. It will be apparent to those skilled in the art that several deductions or substitutions may be made without departing from the spirit of the invention, and these shall be considered to be within the scope of the invention.
Claims (10)
1. The preparation process of the ethyl p-methoxycinnamate is characterized by comprising the following steps of:
(1) Feeding: adding ethyl acetate, sodium ethoxide and cyclohexane into a reaction kettle, and stirring;
(2) The reaction: adding anisaldehyde dropwise while stirring, controlling the reaction temperature to be 45 ℃, and finishing the reaction;
(3) Washing and flash evaporation treatment: adding water into a reaction kettle, adding acid to neutralize alkali, adding water to remove salt in an organic phase, separating liquid, transferring the organic phase into a distillation kettle to remove solvent, and sending the organic phase into a flash evaporation kettle to flash to obtain flash evaporation feed liquid;
(4) Crystallizing, centrifuging and drying: adding 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;
The molar ratio of anisic aldehyde to sodium ethoxide is 0.7:1;
The molar ratio of cyclohexane to anisaldehyde was 2.3:1.
2. The preparation process according to claim 1, wherein the mass ratio between ethyl acetate and anisaldehyde is: 2.5-10:1.
3. The process according to claim 1, wherein in the step (3), the temperature in the flash distillation vessel is 110 to 125℃and the temperature of the liquid in the distillation vessel is 85 to 90 ℃.
4. The process according to claim 1, wherein in step (3), the acid is selected from inorganic acids.
5. The process according to claim 4, wherein the acid is one or more of sulfuric acid, hydrochloric acid and phosphoric acid.
6. The process according to claim 5, wherein the concentration of the acid is 10% to 15%.
7. The process according to claim 1, wherein in step (4), the solvent is one of methanol, ethanol and acetone.
8. The process of claim 7, wherein the solvent is ethanol.
9. The process of claim 8, wherein the ethanol concentration is 85% to 100%.
10. The process of claim 8, wherein the concentration of ethanol is 95%.
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