CN113185424A - Method for removing trace DMAc in DMF (dimethyl formamide) - Google Patents
Method for removing trace DMAc in DMF (dimethyl formamide) Download PDFInfo
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 title claims abstract description 295
- 238000000034 method Methods 0.000 title claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 claims abstract description 39
- 238000004821 distillation Methods 0.000 claims abstract description 21
- 239000000725 suspension Substances 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 14
- 238000010438 heat treatment Methods 0.000 claims abstract description 13
- 238000001816 cooling Methods 0.000 claims abstract description 10
- 239000012320 chlorinating reagent Substances 0.000 claims abstract description 8
- 238000005086 pumping Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 15
- 239000007787 solid Substances 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 13
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 claims 2
- 239000004376 Sucralose Substances 0.000 abstract description 11
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 abstract description 11
- 235000019408 sucralose Nutrition 0.000 abstract description 11
- 230000007547 defect Effects 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 14
- 238000004519 manufacturing process Methods 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- 239000011521 glass Substances 0.000 description 11
- 238000010907 mechanical stirring Methods 0.000 description 11
- 239000011259 mixed solution Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 230000008569 process Effects 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000005660 chlorination reaction Methods 0.000 description 8
- -1 chloromethylene amine salt Chemical class 0.000 description 7
- 238000004321 preservation Methods 0.000 description 6
- 210000003298 dental enamel Anatomy 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 229910006124 SOCl2 Inorganic materials 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000001577 simple distillation Methods 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 238000012946 outsourcing Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FACOTAQCKSDLDE-YKEUTPDRSA-N [(2R,3R,4R,5R,6R)-6-[(2R,3S,4S,5S)-2,5-bis(chloromethyl)-3,4-dihydroxyoxolan-2-yl]oxy-3-chloro-4,5-dihydroxyoxan-2-yl]methyl acetate Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](COC(=O)C)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 FACOTAQCKSDLDE-YKEUTPDRSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012824 chemical production Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- MAGVJLLHDZWQFM-UHFFFAOYSA-N n-chloro-n-methylmethanamine Chemical compound CN(C)Cl MAGVJLLHDZWQFM-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a method for removing trace DMAc in DMF, which is characterized by comprising the following steps: (1) adding a chlorinating agent and purified DMF (dimethyl formamide) into a reaction kettle, controlling the molar ratio of the chlorinating agent to the purified DMF to be 0.1-1: 1, mixing, and then pumping into a low-temperature kettle; (2) controlling the temperature of the kettle to be between 10 ℃ below zero and 40 ℃, heating the kettle to between 40 and 90 ℃, reacting the kettle for 0.1 to 48 hours under the pressure of the vacuum degree of between 10 and 101 KPa, then cooling the kettle to between 10 and 40 ℃, and stirring the kettle to form a suspension; (3) and transferring the suspension into a distillation kettle, adding a DMF raw material to be recovered, wherein the volume of the DMF raw material is 5-100 times of that of the suspension, reacting at 10-40 ℃ for 0.1-48 h, heating to 50-80 ℃ for distillation, controlling the distillation temperature to be 50-80 ℃ and the vacuum pressure to be 0.1-50 KPa, so as to obtain purified DMF, and pumping the purified DMF into the reaction kettle through a pipeline to participate in the reaction. The invention has the advantages that: overcomes the defects that the conventional recycled DMF has high DMAc content and is difficult to prepare Vilsmeier reagent, and also avoids the problem of low yield of sucralose prepared by using the Vilsmeier reagent solution.
Description
Technical Field
The invention belongs to the technical field of chemical production, relates to high-purity DMF (dimethyl formamide) required by Vilsmeier reagent preparation, and particularly relates to a method for removing trace DMAc (dimethyl formamide) in DMF.
Background
The Vilsmeier reagent is a V-type reagent for short, and the specific structure is chloromethylene amine salt; the Vilsmeier reagent has unique structure and characteristics in the aspects of medicine, pesticide, dye and the likeHas good application prospect. It is an important formylation reagent, can generate electrophilic substitution and nucleophilic substitution reaction to synthesize various aldehyde compounds, and can also generate a series of reactions such as condensation, cyclization, aromatic cyclization, chlorination, heterocycle and the like with beta-diketone, unsaturated ketone, epoxy ketone, heterocycle, amide, polyene and the like. Due to its excellent reactivity, its structure, properties and application fields are continuously researched and developed. At present, Vilsmeier reagent is used in the largest amount in the process of preparing sucralose, and thionyl chloride (SOCl) is mostly adopted in production2) Vilsmeier reagent was prepared.
In the Vilsmeier reagent application process, the N-substituted amide recovered after the reaction is typically recovered from the reaction product mixture, and this recovered N-substituted amide is then recycled for use as a reaction vehicle for recycling and green production purposes. However, due to the complex chlorination reaction, the recovered N-substituted amide may produce a small amount of process by-product, such as a small amount of byproduct DMAc in DMF, i.e., the recovered DMF may be contaminated with a small amount of byproduct DMAc. When the recovered DMF is recycled, the DMAc content is continuously enriched and finally the whole reaction is seriously affected.
After a large number of experiments, the Vilsmeier reagent is difficult to form solid Vilsmeier reagent when the content of DMAc in DMF is higher than 0.2 percent and the Vilsmeier reagent solution is used for carrying out chlorination reaction of sucrose-6-acetate, and the yield is obviously reduced. Both CN102482201B and CN103965069B mention about a 10% reduction in yield per 1% by weight of DMAc present in DMF during the chlorination of sucrose-6-acetate. And the solution proposed in both patents is to add solid Arnold reagent to DMF solution containing DMAc and then distill to obtain purified DMF. The disadvantage of this process is that the solid Arnold reagent is very sensitive to moisture and cumbersome to transport and handle, and that it is expensive to purchase and unsuitable for industrial production. Therefore, it is very necessary to develop a simple, easy-to-operate and cheap method for purifying DMF by removing DMAc, to expand the application range of Vilsmeier reagent, improve the chlorination process level of sucralose and increase the industrialization capability.
Disclosure of Invention
The invention aims to solve the defects (the reagent is sensitive to water, the transportation and the operation are troublesome, the outsourcing price is high, and the reagent is not suitable for industrialized production) in the DMF distillation purification method disclosed in the patent publication Nos. CN102482201B and CN103965069B, and provides a method for removing trace DMAc in DMF; the method is simple, easy to operate and low in cost.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a method for removing trace DMAc in DMF comprises a reaction kettle, a low-temperature kettle and a distillation kettle, and is characterized in that: the outlet of the distillation kettle is connected to a reaction kettle through a pipeline;
the method comprises the following steps:
(1) vilsmeier reagent was prepared beforehand: adding a chlorinating agent and purified DMF (a purchased pure product or a product obtained after preliminary rectification in production) into a reaction kettle, controlling the molar ratio of the chlorinating agent to the purified DMF to be 0.1-1: 1, fully mixing, and then pumping into a low-temperature kettle;
(2) controlling the temperature of the low-temperature kettle at-10-40 ℃, then heating to 40-90 ℃ and the pressure of 10-101 KPa, reacting for 0.1-48 h, cooling to 10-40 ℃ after reaction, separating out a large amount of solid Vilsmeier reagent, and stirring to form a suspension;
(3) and (3) transferring the suspension liquid prepared in the step (2) into a distillation kettle, adding a DMF raw material (the DMAc content is less than 5.0%) to be recovered, the volume of the suspension liquid is 5-100 times, reacting at 10-40 ℃ for 0.1-48 h, heating to 50-80 ℃ for distillation, controlling the distillation temperature to be 50-80 ℃ and the vacuum pressure to be 0.1-50 KPa, obtaining purified DMF (the DMAc content is 0.01-0.5%), and pumping the purified DMF into the reaction kettle through a pipeline to participate in the reaction.
If the DMAc content in the DMF is too high, more Vilsmeier reagent is needed, so that the cost is too high, the DMF with the DMAc content reduced can be obtained by firstly carrying out pretreatment by using cheap and effective methods such as distillation and the like, and then the DMF with the quality requirement is obtained by adopting the method for treatment.
Further, the chlorinating agent in the step (1) is SOCl2(thionyl chloride), COC12(phosgene), phosgene, triphosgene or phthalein chloride.
Further, the content of DMAc in the DMF purified in the step (1) is 0.01-0.5 percent, and the water content is 0.001-0.1 percent.
Further, the content of DMAc in the DMF purified in the step (1) is 0.05-0.2 percent, and the water content is 0.001-0.01 percent.
Further, the DMAc content in the DMF raw material to be recovered in the step (3) is about 0.1-5%. (preferably less than 1%, most preferably less than 0.5%)
Further, the DMAc content in the DMF raw material to be recovered in the step (3) is about 0.1-1%.
Further, the DMAc content in the DMF raw material to be recovered in the step (3) is about 0.1-0.5%.
Further, the distillation temperature in the step (3) is 50-70 ℃, and the vacuum pressure is 0.3-10 KPa.
Research shows that the Vilsmeier reagent prepared newly is not easy to store and use, comprises suction filtration, washing, packaging, transportation, weighing and addition, is easy to decompose after being contacted with air, emits toxic gas, is harmful to operators, is not beneficial to field operation, and probably is the main reason that the Vilsmeier reagent is not sold basically in the market. It was also found that if the chlorination agent is added directly and then distilled, i.e. a certain amount of chlorination agent is added to the raw material DMF containing a small amount of DMAc, the raw material DMF will immediately change color, and then the distilled DMF is significantly acidic (mainly HCl produced by the reaction) and contains a small amount of dimethylaminochloride, which affects the subsequent reaction. The invention can prepare Vilsmeier reagent suspension liquid meeting the requirement in advance by adding a bypass system in a DMF distillation purification system, directly transferring and adding the Vilsmeier reagent suspension liquid into a distillation kettle, adding a small amount of DMAc-containing raw material DMF, allowing the Vilsmeier reagent to react with DMAc, and then distilling DMF reaction liquid to obtain the purified DMF without DMAc.
The invention has the advantages that:
1. the Vilsmeier reagent suspension is prepared in advance by adopting a bypass technology, solid-liquid separation is not needed, the Vilsmeier reagent suspension can be directly added into a distillation kettle, an intermediate separation step is omitted, operation is greatly simplified, and the preparation method is suitable for industrial production; the method not only overcomes the defect that Vilsmeier reagent is difficult to prepare due to the high DMAc content in the conventional circulating DMF, but also avoids the problem of low yield of sucralose prepared by using the Vilsmeier reagent solution.
2. Compared with a solid Arnold reagent method, the method can effectively solve the problems of inconvenient transportation, troublesome operation, high price, unsuitability for industrial production and the like of the solid Arnold reagent;
3. the obtained purified DMF is recovered by vacuum distillation, the DMAc content is as low as 0.1%, the DMAc content is recovered and reused in a sucralose chlorination working section, the sucralose yield can be improved (from the original 50-70% to 65-80%), and the yield is obviously improved (5-12%) when the purified DMF obtained by removing the DMAc is applied to a sucralose synthesis reaction and compared with the conventional DMF with the DMAc content of about 0.4%; the remainder of the raffinate was treated to recover DMF and enriched DMAc.
Drawings
FIG. 1 is a schematic diagram of a process for removing traces of DMAc from DMF.
Detailed Description
The invention is further illustrated with reference to fig. 1:
a method for removing trace DMAc in DMF comprises the following specific implementation steps:
example 1 SOCl2Method for preparing Vilsmeier reagent
(1) 150L of pure DMF (N, N-dimethylformamide containing 0.1% DMAc and 0.03% water) purchased from outsourcing is added into a 500L glass lining reaction kettle provided with a mechanical stirring device, a reflux condenser and a temperature measuring thermometer, and 60Kg of SOCl is slowly dripped into the reaction kettle at the temperature of 0-5 DEG C2(thionyl chloride), after the dropwise addition, heating to 70 ℃ for reaction for 2h, and then decompressing (vacuum degree of 50 KPa) for reaction for 2 h; then cooling to 0 ℃, stirring and preserving heat until a large amount of white solid appears to form Vilsmeier reagent suspension;
(2) to 10m equipped with a mechanical stirring, reflux condenser and temperature thermometer3Adding DMF (including DMF) in production line into glass lining reaction kettleDMAc0.9%, moisture 0.05%) 5m3Stirring and preserving heat, and slowly adding the prepared Vilsmeier reagent suspension at 10 ℃ to obtain a mixture;
(3) the mixture was directly heated to 70 ℃ and distilled under reduced pressure (degree of vacuum 100 KPa) to obtain DMF 4.2m with DMAc content of 0.1% or less3The residual liquid is hydrolyzed to obtain about 0.7m3The mixed solution of DMF and DMAc (the content of DMAc is about 5 percent), and the mixed solution is concentrated and then used for simple distillation separation to recover DMF and DMAc, wherein the recovery rate of DMF is higher than 90 percent.
EXAMPLE 2 preparation of Vilsmeier reagent from triphosgene
(1) Adding 150L of the purified DMF obtained in the example 1 into a 500L glass lining reaction kettle provided with a mechanical stirring device, a reflux condenser and a temperature measuring thermometer, slowly adding 50Kg of triphosgene at the temperature of 0-5 ℃, slowly heating to 65 ℃ after the addition, reacting for 2h, and then reducing the pressure (the vacuum degree is 50 KPa) for reacting for 2 h; then cooling to 0 ℃, stirring and preserving heat until a large amount of white solid appears to form Vilsmeier reagent suspension;
(2) will be 10m equipped with a mechanical stirring, reflux condenser and thermometer3DMF (containing DMAc0.4% and water 0.03%) in production line (7 m) is added into a glass lining reaction kettle3Slowly adding the prepared Vilsmeier reagent suspension under the conditions of stirring and heat preservation at 10 ℃ to obtain a mixture;
(3) the mixture was directly heated and distilled under reduced pressure (degree of vacuum 100 KPa) to obtain DMF 6.4m with DMAc content of 0.1% or less3The residual liquid is hydrolyzed to obtain about 0.4m3The mixed solution of DMF and DMAc (the content of DMAc is about 6 percent), and the mixed solution is concentrated and then used for simple distillation separation to recover DMF and DMAc, and the recovery rate of DMF is higher than 93 percent.
Example 3 isolation of solid Vilsmeier reagent for use
(1) Adding 150L of the purified DMF obtained in the example 2 into a 500L glass lining reaction kettle provided with a mechanical stirring device, a reflux condenser and a temperature measuring thermometer, and slowly dropwise adding 60Kg of SOCl at the temperature of 0-5 DEG C2After the dropwise addition, the temperature is raised to 75 ℃ for reaction for 2 hours, and then the pressure is reduced (the vacuum degree is 50 KPa) for reaction for 2 hours; then cooling to 0 ℃, stirring and preserving heatUntil a large amount of white solid appears, carrying out suction filtration to obtain 180Kg of solid Vilsmeier reagent;
(2) will be 10m equipped with a mechanical stirring, reflux condenser and thermometer3DMF (containing DMAc0.9% and water 0.05%) in production line is added into a glass lining reaction kettle to form a mixture with the thickness of 5m3Slowly adding the prepared Vilsmeier reagent into the mixture under the conditions of stirring and heat preservation at 10 ℃ to obtain a mixture;
(3) the mixture was heated and distilled under reduced pressure (degree of vacuum 100 KPa) to obtain DMF 3.2m with DMAc content of 0.1% or less3The residual liquid is hydrolyzed to obtain about 1.7m3The mixed solution of DMF and DMAc (the content of DMAc is about 3 percent), and the mixed solution is concentrated and then used for simple distillation separation and recovery of DMF and DMAc, and the recovery rate of DMF is higher than 85 percent.
Example 4 SOCl2Direct distillation process
Will be equipped with mechanical stirring, reflux condenser and 10m of thermometer3DMF (containing DMAc0.9% and water 0.05%) in production line is added into enamel glass reaction kettle to form 5m solution3Stirring and keeping the temperature at 10 ℃, and slowly dripping 120Kg of SOCl2Then, the mixture was distilled under reduced pressure (degree of vacuum: 100 KPa) while raising the temperature to obtain DMF 4.0m having a DMAc content of 0.1% or less3The product contains 0.2% of dimethylamino acyl chloride, cannot meet the production requirement of sucralose, has more side reactions, and reduces the yield by 2-5%.
Example 5 without purified DMF
(1) Adding 150L DMF (containing DMAc0.9% and water 0.05%) in production line into 500L enamel glass reaction kettle equipped with mechanical stirring and reflux condenser, and slowly dripping 60Kg SOCl at 0-5 deg.C2After the dropwise addition, the temperature is raised to 75 ℃ for reaction for 2 hours, and then the pressure is reduced (the vacuum degree is 50 KPa) for reaction for 2 hours; then cooling to 0 ℃, stirring and preserving heat, and only a small amount of white solid appears;
(2) 10m equipped with mechanical stirring, reflux condenser and thermometer3DMF (containing DMAc0.9% and water 0.05%) in production line is added into enamel glass reaction kettle to form 5m solution3Slowly adding the prepared Vilsmeier reagent suspension under the conditions of stirring and heat preservation at 10 ℃ to obtain a mixture;
(3) the mixture was directly heated and distilled under reduced pressure (degree of vacuum 100 KPa) to obtain DMF 3.0m with DMAc content of 0.1% or less3However, the content of 0.1% of dimethylamino acyl chloride in the solution can not meet the production requirement of sucralose, so that the side reactions are more, and the yield is reduced by 1-3%.
EXAMPLE 6 concentrated Vilsmeier reagent preparation method
(1) 3000L of DMF (containing DMAc0.1% and water 0.03%) prepared in advance is added into a 5000L enamel glass reaction kettle provided with a mechanical stirring device, a reflux condenser and a temperature measuring thermometer, and 1200Kg of SOCl is slowly dripped at the temperature of 0-5 DEG C2After the dropwise addition, the temperature is raised to 70 ℃ for reaction for 2 hours, and then the pressure is reduced (the vacuum degree is 50 KPa) for reaction for 2 hours; then cooling to 0 deg.C, stirring and holding until a large amount of white solid appears to form a Vilsmeier reagent suspension 3800L, which can be used for about 100m3The on-line DMF treatment of (1);
(2) to 10m equipped with a mechanical stirring, reflux condenser and temperature thermometer3DMF (containing DMAc0.9% and water 0.05%) in production line is added into enamel reactor to form 5m solution3Stirring and preserving heat, and slowly adding 180-200L of the prepared Vilsmeier reagent suspension liquid at 10 ℃ to obtain a mixture;
(3) heating the mixture to 70 deg.C directly, and distilling under reduced pressure (vacuum degree of 100 KPa) to obtain DMF 4.0m with DMAc content below 0.1%3The above; centralized treatment of residual liquid;
(4) repeating the above steps (2) and (3), and treating successively for about 100m3To obtain DMF 85m with DMAc content below 0.1%3Above, the residual liquid is collected and hydrolyzed to obtain about 15m3The DMF and DMAc are mixed (the DMAc content is about 5 percent), and the DMF and the DMAc are separated and recovered by simple distillation, and the DMF recovery rate is higher than 95 percent.
Example 7 treatment of DMF for sucralose Synthesis
The synthesis process of sucralose is as follows:
(1) in a 5M apparatus equipped with a mechanical stirrer, condenser and thermometer33500L 1, 1, 2-trichloroethane is added into a glass lining reaction kettle,cooling with low temperature water to below 0 deg.C, adding dropwise 650L thionyl chloride, controlling the temperature below 0 deg.C, stirring at 0 deg.C for 1 hr;
(2) slowly dripping 1000L of sucrose-6-acetate DMF solution (prepared from 350 Kg of sucrose) into the above solution, controlling the dripping temperature below 0 deg.C, slowly heating to 70 deg.C (about 1 hr during heating), stirring for 1 hr under heat preservation; slowly heating to 90 ℃ (the temperature rise process is about 1 hour), and stirring for 1 hour under the condition of heat preservation; finally, slowly heating to 110 ℃ (the temperature rise process is about 1 h), and reacting for 2h under the condition of heat preservation;
(3) after the reaction is finished, putting the mixed solution into a low-temperature reaction kettle, cooling the mixed solution to below 10 ℃ by using low-temperature water, dropwise adding 20% ammonia water until the pH value is 9, finally neutralizing the mixed solution to be neutral by using a dilute hydrochloric acid solution, and stirring the mixed solution for about 30 min;
(4) distilling the mixed solution in vacuum to remove most of the solvent, adding 1000L of water twice, evaporating to dryness, adding 4000L of water, decocting at 80 deg.C, vacuum filtering, washing the filter cake with ethyl acetate, and extracting the filtrate with ethyl acetate (1000L × 4);
(5) and combining the ethyl acetate layers, carrying out rotary evaporation on most of ethyl acetate, adding activated carbon for decolorization, filtering, concentrating the filtrate to obtain a light yellow concentrated solution, recrystallizing with ethyl acetate to obtain sucralose-6-acetate, and calculating the yield.
Claims (8)
1. A method for removing trace DMAc in DMF comprises a reaction kettle, a low-temperature kettle and a distillation kettle, and is characterized in that: the outlet of the distillation kettle is connected to a reaction kettle through a pipeline;
the method comprises the following steps:
(1) vilsmeier reagent was prepared beforehand: adding a chlorinating agent and purified DMF (dimethyl formamide) into a reaction kettle, controlling the molar ratio of the chlorinating agent to the purified DMF to be 0.1-1: 1, fully mixing, and then pumping into a low-temperature kettle;
(2) controlling the temperature of the low-temperature kettle at-10-40 ℃, then heating to 40-90 ℃ and the pressure of 10-101 KPa, reacting for 0.1-48 h, cooling to 10-40 ℃ after reaction, separating out a large amount of solid Vilsmeier reagent, and stirring to form a suspension;
(3) and (3) transferring the suspension liquid prepared in the step (2) into a distillation kettle, adding a DMF raw material to be recovered, wherein the volume of the DMF raw material is 5-100 times of that of the suspension liquid, reacting for 0.1-48 h at 10-40 ℃, then heating to 50-80 ℃ for distillation, controlling the distillation temperature to be 50-80 ℃ and the vacuum pressure to be 0.1-50 KPa, obtaining purified DMF, and pumping the purified DMF into the reaction kettle through a pipeline to participate in the reaction.
2. The method of claim 1, wherein the removal of traces of DMAc from DMF comprises: the chlorinating agent in the step (1) is thionyl chloride, phosgene, diphosphine, triphosgene or phthalein chloride.
3. The method of claim 1, wherein the removal of traces of DMAc from DMF comprises: the content of DMAc in the DMF purified in the step (1) is 0.01-0.5 percent, and the water content is 0.001-0.1 percent.
4. The method of claim 1, wherein the removal of traces of DMAc from DMF comprises: the content of DMAc in the DMF purified in the step (1) is 0.05-0.2 percent, and the water content is 0.001-0.01 percent.
5. A method according to any one of claims 1-4, wherein the removal of traces of DMAc from DMF is carried out by: the DMAc content in the DMF raw material to be recovered in the step (3) is about 0.1-5%.
6. A method according to any one of claims 1-4, wherein the removal of traces of DMAc from DMF is carried out by: the DMAc content in the DMF raw material to be recovered in the step (3) is about 0.1-1%.
7. A method according to any one of claims 1-4, wherein the removal of traces of DMAc from DMF is carried out by: the DMAc content in the DMF raw material to be recovered in the step (3) is about 0.1-0.5%.
8. A method according to any one of claims 1-4, wherein the removal of traces of DMAc from DMF is carried out by: the distillation temperature in the step (3) is 50-70 ℃, and the vacuum pressure is 0.3-10 KPa.
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