CN114380671B - Neotame key intermediate and preparation method thereof - Google Patents
Neotame key intermediate and preparation method thereof Download PDFInfo
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- CN114380671B CN114380671B CN202210088287.2A CN202210088287A CN114380671B CN 114380671 B CN114380671 B CN 114380671B CN 202210088287 A CN202210088287 A CN 202210088287A CN 114380671 B CN114380671 B CN 114380671B
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- 239000004384 Neotame Substances 0.000 title claims abstract description 21
- HLIAVLHNDJUHFG-HOTGVXAUSA-N neotame Chemical compound CC(C)(C)CCN[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 HLIAVLHNDJUHFG-HOTGVXAUSA-N 0.000 title claims abstract description 21
- 235000019412 neotame Nutrition 0.000 title claims abstract description 21
- 108010070257 neotame Proteins 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 25
- LTNUSYNQZJZUSY-UHFFFAOYSA-N 3,3-dimethylbutanal Chemical compound CC(C)(C)CC=O LTNUSYNQZJZUSY-UHFFFAOYSA-N 0.000 claims abstract description 19
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 12
- NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 6
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 6
- 230000003301 hydrolyzing effect Effects 0.000 claims abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 21
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 19
- 238000002156 mixing Methods 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 10
- 238000010533 azeotropic distillation Methods 0.000 claims description 9
- 239000007788 liquid Substances 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 8
- 239000012295 chemical reaction liquid Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 claims description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 238000007323 disproportionation reaction Methods 0.000 claims description 2
- 238000004886 process control Methods 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 13
- 239000012043 crude product Substances 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 5
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical class CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- -1 3, 3-dimethylbutyl Chemical group 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- LQYKCNXSTNSOMI-UHFFFAOYSA-N (1-chloro-3,3-dimethylbutyl) acetate Chemical compound CC(=O)OC(Cl)CC(C)(C)C LQYKCNXSTNSOMI-UHFFFAOYSA-N 0.000 description 1
- XGCKOSFYXBAPQM-UHFFFAOYSA-N 1-chloro-3,3-dimethylbutane Chemical compound CC(C)(C)CCCl XGCKOSFYXBAPQM-UHFFFAOYSA-N 0.000 description 1
- DUXCSEISVMREAX-UHFFFAOYSA-N 3,3-dimethylbutan-1-ol Chemical compound CC(C)(C)CCO DUXCSEISVMREAX-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000007036 catalytic synthesis reaction Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 239000008123 high-intensity sweetener Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 235000013615 non-nutritive sweetener Nutrition 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/293—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/42—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by hydrolysis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/80—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/78—Separation; Purification; Stabilisation; Use of additives
- C07C45/81—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
- C07C45/82—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation
- C07C45/84—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation by distillation by azeotropic 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 invention relates to a neotame key intermediate and a preparation method thereof, and belongs to the technical field of neotame intermediate synthesis. The invention relates to a synthesis process of a key intermediate of neotame, which comprises the steps of taking tert-butyl chloride and vinyl acetate as raw material systems, adding the raw material systems into a system consisting of a solvent and a catalyst, reacting at the temperature of minus 35 ℃ to minus 20 ℃, then distilling, hydrolyzing and rectifying to obtain 3, 3-dimethylbutyraldehyde. The neotame key intermediate has higher purity; the invention also provides a simple and feasible preparation method, and has the advantages of low production cost, high yield and environmental protection.
Description
Technical Field
The invention relates to a neotame key intermediate and a preparation method thereof, and belongs to the technical field of neotame intermediate synthesis.
Background
Neotame (N- [ N- (3, 3-dimethylbutyl) -L-alpha-aspartic acid ] -L-phenylalanine-1-methyl ester) in the sweetener is a high-power sweetener developed by Neotabe's Utility company, has the advantages of high sweetness, low calorie, high stability and the like, is safe and harmless to human bodies, is a non-nutritive high-intensity sweetener with excellent performance, has huge market potential, and 3, 3-dimethylbutyraldehyde is an important intermediate of neotame, and the product price cannot be reduced due to the high market price, so that a method for preparing the intermediate economically and specially is required to be studied. 3, 3-dimethylbutyraldehyde has the chemical structural formula shown below:
。
there are many methods for preparing 3, 3-dimethylbutyraldehyde:
in CN101311151, ethylene gas is used as raw material for preparation, however, the ethylene gas has higher requirements on transportation, storage, production equipment and the like, the preparation method has longer flow and high energy consumption, and the preparation method is obtained by mixing and gasifying 3, 3-dimethylbutanol and water by using inert gas as carrier gas at the high temperature of more than 300 ℃ and then carrying out catalytic dehydrogenation in the presence of noble metal.
In the method disclosed in CN1301247a, 3-dimethylbutyl chloride is used as a raw material, the cost of the raw material is high, and dimethyl sulfide compounds which generate malodor in the production process have heavy environmental pollution, and the pollution is treated with high production cost, so that the industrial production is not suitable.
In US5994593, 1-dichloro-3, 3-dimethane is prepared by hydrolysis, and this preparation method has the disadvantage of expensive raw materials and is not suitable for large-scale industrial production.
In US5856584, 1-chloro-3, 3-dimethylbutane is prepared by oxidation, which has disadvantages in that iodide is used as a catalyst, which is expensive and not easily recovered, and in that the reaction produces malodorous dimethyl sulfide by-products, which are costly to treat.
CN 201110233967.0 is prepared by using vinyl acetate and tert-butyl chloride as raw materials and catalyzing with aluminum trichloride, adding reactants one by one, and after the reaction is finished, adding deionized water into a reaction kettle, so that the reaction in the first half stage has severe heat release, is very dangerous, has higher difficulty in controlling temperature, low yield and inconvenient operation; the hydrochloric acid is introduced again to catalyze the hydrolysis, so that the efficiency is low, and the equipment corrosion is accelerated.
Disclosure of Invention
The invention aims to solve the technical problems of overcoming the defects in the prior art and providing a neotame key intermediate with higher purity; the invention also provides a simple and feasible preparation method, and has the advantages of low production cost, high yield and environmental protection.
The invention relates to a synthesis process of a key intermediate of neotame, which comprises the steps of taking tert-butyl chloride and vinyl acetate as raw material systems, adding the raw material systems into a system consisting of a solvent and a catalyst, reacting at the temperature of minus 35 ℃ to minus 20 ℃, then distilling, hydrolyzing and rectifying to obtain 3, 3-dimethylbutyraldehyde.
The synthesis process of the neotame key intermediate preferably comprises the following steps of:
(1) Pre-mixing tert-butyl chloride and vinyl acetate to form a system I;
(2) Cooling an anhydrous aluminum trichloride catalyst and a methylene dichloride solvent to-35 ℃ to-20 ℃ in a liquid nitrogen low-temperature device, and mixing to form a system II;
(3) Dropwise adding the mixed system I into the mixed system II, and maintaining the reaction temperature at minus 35 ℃ to minus 20 ℃;
(4) Adding the intermediate product 1-chloro 3, 3-dimethylbutyl acetate into water for washing, and removing aluminum trichloride;
(5) Distillation hydrolysis treatment is carried out to obtain crude butyraldehyde;
(6) Adding water into the distillate in the step (5), and carrying out azeotropic distillation on an organic phase and water to obtain the 3, 3-dimethylbutyraldehyde.
Preferably, the mixing mass ratio of the tert-butyl chloride, the vinyl acetate, the anhydrous aluminum chloride and the methylene dichloride is (4-5): 3-4: (6-7): (10-20).
Preferably, the dripping time of the mixed system I to the mixed system II is controlled to be 0.5-12 hours.
Preferably, in the step (2) and the step (3), the temperature is-35 ℃ to-31 ℃.
Preferably, in the step (4), the whole process control temperature is-10-10 ℃ during water washing.
Preferably, in the step (5), after the methylene dichloride is distilled out at the temperature of 45-55 ℃, water with the mass of 1-3 times is added for refluxing for 2-5 hours, the hydrolysis and disproportionation are carried out at the temperature of 45-55 ℃, and crude butyraldehyde at the temperature of 45-100 ℃ is taken.
Preferably, in the step (6), sodium bicarbonate is added to the distillate in the step (5) for neutralization.
Preferably, in step (6), the temperature of azeotropic distillation is 80-86 ℃.
And (3) all the steps (1) to (6) adopt nitrogen protection to prevent oxidation of the product.
A key intermediate of neotame is prepared by the preparation method.
The invention takes a liquid nitrogen low-temperature device as a refrigeration source, takes tert-butyl chloride and vinyl acetate as raw materials, and carries out anhydrous aluminum trichloride catalytic synthesis, and the key is that reactants of tert-butyl chloride and vinyl acetate are premixed in advance to form a system I, methylene dichloride solvent and anhydrous aluminum trichloride are mixed to form a system II, after the temperature of the system II is sufficiently reduced, the system I is added to obtain a reactant of 1-chloro-3, 3-dimethylbutyl acetate, and after the product is added into a water system to carry out water washing, aluminum trichloride is washed out, hydrochloric acid is generated by the product to catalyze hydrolysis without adding acid; adding water in the distillation process of the organic phase to achieve azeotropy and improve the product yield; the whole process adopts nitrogen protection to prevent oxidation of the product; and the middle distillate is rectified to obtain more pure 3, 3-dimethylbutyraldehyde, so that the product yield is improved.
Compared with the prior art, the invention has the following beneficial effects:
(1) The mixed system is adopted, the system is uniform, and the exothermic reaction and the reaction speed are controlled, so that the reaction is safer and more efficient;
(2) The dropping temperature is controlled at minus 35 ℃ to minus 20 ℃, so that the problems of severe reaction temperature release and incapability of stable control of reaction in the reaction process are solved, and the yield and purity of the product are improved;
(3) The aluminum trichloride catalyst is removed by adopting a water washing mode, and the water washing process has an exothermic process, and the method adopts a mode of dropwise adding reactants into water, so that severe reaction is prevented, potential safety hazards are eliminated, and the catalyst is separated;
(4) Adding water at 45-55 ℃ for azeotropic reflux to obtain an organic phase containing butyraldehyde, and refluxing at low temperature to avoid oxidation of the product, so that the purity of the product is obviously improved;
(5) The organic phase of butyraldehyde is subjected to azeotropic distillation with water, so that the distillation boiling point can be reduced by about 20 ℃, the oxidation of the product is prevented, the pure 3, 3-dimethylbutyraldehyde is obtained, and the yield is obviously improved;
(6) Based on the characteristic that 3, 3-dimethylbutyraldehyde is easy to oxidize, nitrogen protection is adopted in the whole process to prevent oxidation of the product, so that the purity of the product is improved.
Drawings
FIG. 1 is a gas chromatogram of 3, 3-dimethylbutyraldehyde produced according to the present invention.
Detailed Description
The present invention is further described below with reference to examples, but the scope of the present invention is not limited thereto, and modifications made by those skilled in the art to the technical scheme of the present invention should fall within the scope of the present invention.
All the raw materials used in the examples are commercially available unless otherwise specified.
The following processes were all carried out under nitrogen protection.
Example 1
Mixing 640 g of dichloromethane solvent and 380 g of aluminum trichloride into a system II, cooling to-31 ℃ by a liquid nitrogen low-temperature device, mixing 250 g of chlorobutane and 190 g of vinyl acetate into a system I, dropwise adding the system I into the system II for 5 hours, reacting for 10 hours, keeping the reaction temperature at-31 ℃, preparing 1425g of water, dropwise adding the reaction liquid into the water, controlling the reaction temperature at 5+/-2 ℃, extracting an organic phase, distilling the dichloromethane at 50+/-5 ℃, adding 950 g of water, refluxing for 3 hours, recovering a 45-100 ℃ distillate crude product, adding 332g of water, azeotropically rectifying at 84+/-2 ℃ to obtain the 3, 3-dimethylbutyraldehyde with the purity of 98.5% and the molar yield of 98%.
Example 2
Mixing 750 g of dichloromethane solvent and 300 g of aluminum trichloride into a system II, cooling to-35 ℃ by utilizing a liquid nitrogen low-temperature device, mixing 230 g of chlorobutane and 200g of vinyl acetate into a system I, dropwise adding the system I into the system II, reacting for 10 hours, keeping the reaction temperature at-35 ℃, preparing 1500g of water, dropwise adding the reaction liquid into the water, controlling the reaction temperature at-8+/-2 ℃, extracting an organic phase, distilling dichloromethane at 50+/-5 ℃, adding 1000 g of water, refluxing for 3 hours, recovering 45-100 ℃ distillate crude products, adding 2g of sodium bicarbonate, adding 350g of water, azeotropically rectifying, rectifying at 82+/-2 ℃ to obtain crude products, azeotropically rectifying with water to obtain 3, 3-dimethylbutyraldehyde with 99.5% of purity and 99% of molar yield.
Example 3
Mixing 820 g of dichloromethane solvent and 280g of aluminum trichloride into a system II, cooling to-20 ℃ by using a liquid nitrogen low-temperature device, mixing 200g of chlorobutane and 160 g of vinyl acetate into a system I, dropwise adding the system I into the system II, reacting for 10 hours, keeping the reaction temperature at-20 ℃, preparing 1200g of water, dropwise adding the reaction liquid into the water, controlling the reaction temperature at 8+/-2 ℃, extracting an organic phase, distilling dichloromethane at 50+/-5 ℃, adding 800 g of water, refluxing for 3 hours, recycling a 45-100 ℃ distillate crude product, obtaining a crude product, carrying out azeotropic distillation with water, adding 280g of water, carrying out azeotropic distillation, and obtaining the 3, 3-dimethylbutyraldehyde with the purity of 98.4% and the molar yield of 98.5 percent.
Comparative example 1
Mixing 750 g of dichloromethane solvent and 300 g of aluminum trichloride to form a system II, cooling to-28 ℃ by utilizing a liquid nitrogen low-temperature device, adding 230 g of tert-butyl chloride into the system II, then adding 200g of vinyl acetate, reacting for 10 hours, preparing 1500g of water, dripping the reaction liquid into the water, controlling the reaction temperature to be minus 8+/-2 ℃, extracting an organic phase, distilling dichloromethane at 50+/-5 ℃, adding 1000 g of water, refluxing for 3 hours, recovering a fraction crude product at 45-100 ℃, adding 350g of water, azeotropically rectifying at a rectifying temperature of 82+/-2 ℃ to obtain the crude product and water, and obtaining the 3, 3-dimethylbutyraldehyde with the purity of 97.2% and the molar yield of 94%.
Comparative example 2
Mixing 750 g of dichloromethane solvent and 300 g of aluminum trichloride into a system II, cooling to-28 ℃ by using a liquid nitrogen low-temperature device, mixing 230 g of chlorobutane and 200g of vinyl acetate into a system I, dropwise adding the system I into the system II, reacting for 10 hours, preparing 1500g of water, adding water drops into a reaction liquid, controlling the reaction temperature to be minus 8+/-2 ℃, extracting an organic phase, distilling dichloromethane at 50+/-5 ℃, adding 1000 g of water, refluxing for 3 hours, recovering a 45-100 ℃ distillate crude product, adding 350g of water, carrying out azeotropic distillation, and obtaining the crude product with the azeotropic distillation temperature of 82+/-2 ℃ to obtain the 3, 3-dimethylbutyraldehyde with the purity of 96.5 percent and the molar yield of 93 percent.
Comparative example 3
Mixing 750 g of dichloromethane solvent and 300 g of aluminum trichloride into a system II, cooling to-28 ℃ by using a liquid nitrogen low-temperature device, mixing 230 g of chlorobutane and 200g of vinyl acetate into a system I, dropwise adding the system I into the system II, reacting for 10 hours, preparing 1500g of water, dropwise adding the reaction liquid into the water, controlling the reaction temperature to be minus 8+/-2 ℃, extracting an organic phase, distilling dichloromethane at 50+/-5 ℃, adding 1000 g of water, refluxing for 3 hours, recovering a 45-100 ℃ distillate crude product, directly rectifying, and obtaining 3, 3-dimethylbutyraldehyde with the rectification temperature of 103+/-3 ℃ to obtain the 3, 3-dimethylbutyraldehyde with the purity of 95.0% and the molar yield of 90.0%.
The foregoing is merely exemplary embodiments of the present invention, and specific structures and features that are well known in the art are not described in detail herein. It should be noted that modifications and improvements can be made by those skilled in the art without departing from the structure of the present invention, and these should also be considered as the scope of the present invention, which does not affect the effect of the implementation of the present invention and the utility of the patent. The protection scope of the present application shall be subject to the content of the claims, and the description of the specific embodiments and the like in the specification can be used for explaining the content of the claims.
Claims (7)
1. A synthesis process of a neotame key intermediate is characterized by comprising the following steps of: adding a system formed by solvent and catalyst into a raw material system of tert-butyl chloride and vinyl acetate, reacting at-35 ℃ to-20 ℃, then distilling and hydrolyzing, and rectifying to obtain 3, 3-dimethylbutyraldehyde;
the method comprises the following steps:
(1) Pre-mixing tert-butyl chloride and vinyl acetate to form a system I;
(2) Cooling an anhydrous aluminum trichloride catalyst and a methylene dichloride solvent to-35 ℃ to-20 ℃ in a liquid nitrogen low-temperature device, and mixing to form a system II;
(3) Dropwise adding the mixed system I into the mixed system II, and maintaining the reaction temperature at minus 35 ℃ to minus 20 ℃;
(4) Dropwise adding the reaction liquid obtained in the step (3) into water for washing to remove aluminum trichloride;
(5) Distillation hydrolysis treatment is carried out to obtain crude butyraldehyde;
(6) Adding water into the distillate in the step (5) to carry out azeotropic distillation to obtain the 3, 3-dimethylbutyraldehyde;
in the step (6), the azeotropic distillation temperature is 80-86 ℃.
2. The process for synthesizing the neotame key intermediate according to claim 1, wherein the process is characterized in that: the mixing mass ratio of the tert-butyl chloride, the vinyl acetate, the anhydrous aluminum chloride and the methylene dichloride is (4-5): (6-7): (10-20).
3. The process for synthesizing the neotame key intermediate according to claim 1, wherein the process is characterized in that: the dripping time of the mixed system I to the mixed system II is controlled to be 0.5-12 hours.
4. The process for synthesizing the neotame key intermediate according to claim 1, wherein the process is characterized in that: in the step (4), the whole process control temperature is-10-10 ℃ during water washing.
5. The process for synthesizing the neotame key intermediate according to claim 1, wherein the process is characterized in that: in the step (5), after the methylene dichloride is distilled out at the temperature of 45-55 ℃, water with the mass of 1-3 times is added for refluxing for 2-5 hours, the temperature of 45-55 ℃ is obtained through hydrolytic disproportionation, and crude butyraldehyde at the temperature of 45-100 ℃ is obtained.
6. The process for synthesizing the neotame key intermediate according to claim 1, wherein the process is characterized in that: in the step (6), sodium bicarbonate is added to the distillate in the step (5) to neutralize the distillate.
7. The process for synthesizing the neotame key intermediate according to claim 1, wherein the process is characterized in that: and (3) all the steps (1) to (6) adopt nitrogen protection.
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| CN102295541A (en) * | 2011-08-16 | 2011-12-28 | 济南诚汇双达化工有限公司 | Preparation method of 3,3-dimethyl butyraldehyde |
| CN110283057A (en) * | 2019-06-28 | 2019-09-27 | 山东奔月生物科技股份有限公司 | Microchannel plate answers method to prepare the synthesis technology of 3,3- dimethyl butyraldehyde |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102295541A (en) * | 2011-08-16 | 2011-12-28 | 济南诚汇双达化工有限公司 | Preparation method of 3,3-dimethyl butyraldehyde |
| CN110283057A (en) * | 2019-06-28 | 2019-09-27 | 山东奔月生物科技股份有限公司 | Microchannel plate answers method to prepare the synthesis technology of 3,3- dimethyl butyraldehyde |
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| Title |
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| 郁浩然主编.《化工分离工程》.中国石化出版社出版,1995,(第1版),第127-128页. * |
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Denomination of invention: Key intermediates and preparation methods of neotame Granted publication date: 20240130 Pledgee: Weihai commercial bank Limited by Share Ltd. Dongying branch Pledgor: Shandong Benyue Biotechnology Co.,Ltd. Registration number: Y2024980022971 |