CN113045451A - Method for preparing methoxylamine hydrochloride by adopting microreactor - Google Patents
Method for preparing methoxylamine hydrochloride by adopting microreactor Download PDFInfo
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- CN113045451A CN113045451A CN202110266863.3A CN202110266863A CN113045451A CN 113045451 A CN113045451 A CN 113045451A CN 202110266863 A CN202110266863 A CN 202110266863A CN 113045451 A CN113045451 A CN 113045451A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C239/00—Compounds containing nitrogen-to-halogen bonds; Hydroxylamino compounds or ethers or esters thereof
- C07C239/08—Hydroxylamino compounds or their ethers or esters
- C07C239/20—Hydroxylamino compounds or their ethers or esters having oxygen atoms of hydroxylamino groups etherified
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- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
Abstract
The invention belongs to the field of fine chemical intermediate synthesis, and discloses a method for preparing methoxylamine hydrochloride by adopting a microreactor. The method comprises the following specific steps: the preparation method comprises the steps of preparing acetyl hydroxylamine, preparing acetyl methoxyamine and preparing methoxyamine hydrochloride, wherein the preparation process of the acetyl hydroxylamine and the acetyl methoxyamine is carried out in a microreactor. Specifically, a hydroxylamine hydrochloride solution, ethyl acetate and an alkali liquor are pumped into a microchannel reaction module A, mixed in a microchannel, pumped into a microchannel reaction module B together with dimethyl sulfate and an alkali liquor, and subjected to mixing reaction, collection, hydrolysis, distillation, neutralization, salification, concentration and other processes to obtain the methoxylamine hydrochloride. Compared with the prior art, the method effectively improves the yield of the methoxylamine hydrochloride by using the microreactor, reduces the generation of three wastes, shortens the reaction time and reduces the production cost.
Description
Technical Field
The invention belongs to the field of fine chemical intermediate synthesis, and particularly relates to a method for preparing methoxylamine hydrochloride by using a microreactor.
Background
Methoxylamine hydrochloride is an important chemical raw material and is widely applied to the preparation and synthesis of low-toxicity pesticides, novel herbicides, medicines and functional dyes. In the field of pesticides, methoxylamine hydrochloride is mainly used for synthesizing efficient and low-toxicity phenoxy methyl; in the field of medicine, the method is applied to the synthesis of cefuroxime serving as a second-generation cephalosporin product and the synthesis of neonomamine, propargylamine, hydroxyurea and the like. The foreign methoxylamine hydrochloride is mainly produced in India, the production process is relatively laggard, the operation safety needs to be improved, and a large amount of three wastes are easily generated in the preparation process. The domestic producers of methoxylamine hydrochloride also have the problems of high production cost, more three wastes and the like.
The micro-reactor, i.e. micro-channel reactor, utilizes some precise processing techniques to make the characteristic dimension of the reactor reach micron level, so that the internal structure thereof has extremely large specific surface area which may be hundreds of times or even thousands of times of that of some stirred tanks. When materials enter the micro-reactor, the micro-reactor can provide excellent mass and heat transfer capacity for the whole reaction, thereby realizing the instant uniform mixing and high-efficiency heat transfer of the materials. At present, the microreactor is widely applied to the fields of pesticide intermediate preparation, medical intermediate synthesis, nano material preparation, daily chemicals and the like.
Application number 200910096865.1 discloses a method for synthesizing methoxylamine hydrochloride, which comprises the steps of firstly adding butanone oxime, water, sodium hydroxide and a phase transfer catalyst into a reaction vessel; then adding a methylating agent after cooling; standing for layering, distilling at normal temperature, and mixing with hydrochloric acid solution; finally, rectifying, evaporating and dehydrating to obtain the methoxylamine hydrochloride concentrated solution. The preparation method has the advantages of mild reaction conditions, high product yield and the like. However, a phase transfer catalyst needs to be added during the reaction process, and a large amount of organic reagents such as butanone and methanol are used, which easily causes environmental pollution.
Application number 201510810069.5 discloses a preparation method of methoxylamine hydrochloride, which is characterized in that sulfur dioxide gas, sodium nitrite, sodium hydroxide and dimethyl sulfate are subjected to a series one-pot reaction in a water phase to prepare methoxylamine hydrochloride. The preparation method is simple and convenient to operate and low in production cost. However, sulfur dioxide and sodium nitrite used in the reaction process belong to toxic substances, and are easy to cause serious pollution to the environment.
Application No. 201210505588.7 discloses a method for preparing methoxyamine hydrochloride, which comprises the steps of preparing acetyl hydroxylamine, preparing acetyl methoxyamine and preparing methoxyamine hydrochloride. The preparation method can avoid the toxic substances such as sulfur dioxide, sodium nitrite and the like used in the existing production process of methoxyamine hydrochloride, and reduce the emission of waste gas such as nitrogen oxide and the like. However, the yield and purity of the methoxyamine hydrochloride produced by the preparation method are not very high.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for preparing methoxylamine hydrochloride by adopting a microreactor, which comprises the steps of pumping a hydroxylamine hydrochloride solution, ethyl acetate and an alkali liquor into a microchannel reaction module A, mixing the hydroxylamine hydrochloride solution, the ethyl acetate and the alkali liquor in a microchannel, pumping the mixture, dimethyl sulfate and the alkali liquor into a microchannel reaction module B again, carrying out mixing reaction, collecting, hydrolyzing, distilling, neutralizing, salifying, concentrating and the like to obtain methoxylamine hydrochloride, effectively improving the yield of methoxylamine hydrochloride, reducing the generation of three wastes, shortening the reaction time and reducing the production cost; and the methoxylamine hydrochloride can be continuously prepared on line in large batch, and has wide application prospect in the fields of pesticides and medicines.
In order to solve the problems of the prior art, the invention adopts the technical scheme that:
a method for preparing methoxylamine hydrochloride by adopting a microreactor sequentially comprises the steps of preparing acetyl hydroxylamine, preparing acetyl methoxylamine and preparing methoxylamine hydrochloride, wherein the preparation processes of the acetyl hydroxylamine and the acetyl methoxylamine are carried out in the microreactor; specifically, a hydroxylamine hydrochloride solution, ethyl acetate and an alkali liquor are pumped into a microchannel reaction module A, mixed in a microchannel, pumped into a microchannel reaction module B together with dimethyl sulfate and an alkali liquor, and subjected to mixing reaction, collection, hydrolysis, distillation, neutralization, salification and concentration to obtain the methoxylamine hydrochloride.
The method for preparing methoxyamine hydrochloride by adopting the microreactor comprises the following steps:
step 1, constructing a micro-reactor, wherein the micro-reactor consists of a batching system, a feeding system, a micro-reaction system and a post-processing system, and the micro-reaction system consists of a micro-channel reaction module A and a micro-channel reaction module B;
step 3, pumping the solution a, dimethyl sulfate and alkali liquor into a microchannel reaction module B respectively, and carrying out mixed reaction to obtain a solution B;
and 4, collecting the solution b, and performing hydrolysis, distillation, neutralization, salification and concentration processes to obtain the methoxylamine hydrochloride.
The improvement is that the concentration of the hydroxylamine hydrochloride solution in the step 2 is 1-1000 mg/mL, and the mass of the hydroxylamine hydrochloride solution is 10-500 g; the mass of the ethyl acetate is 20-1000 g; the alkali liquor has a mass concentration of 10-31% and a mass of 60-3000g, and is specifically sodium hydroxide solution or potassium hydroxide.
The improvement is that the mass of the dimethyl sulfate in the step 3 is 10-1000 g; the alkali liquor has a mass concentration of 10-31% and a mass of 60-3000g, and is specifically sodium hydroxide solution or potassium hydroxide.
The improved material of the microchannel reaction module A and the microchannel reaction module B is one or more of stainless steel, glass, ceramic or polydimethylsiloxane (for example, the combination of stainless steel material at the front end and ceramic material at the back end).
The improved structure is that the diameter of the channel of the micro-channel reaction module A and the diameter of the channel of the micro-channel reaction module B are both 5-500 μm.
The improved structure is that the length of the channels of the micro-channel reaction module A and the micro-channel reaction module B is 5-200 cm.
Has the advantages that:
compared with the prior art, the method for preparing methoxylamine hydrochloride by adopting the microreactor has the following advantages:
(1) the production process of the methoxylamine hydrochloride is full-automatic, the control precision is very accurate, the reaction process is safe and easy to operate, the production cost is lower, and the yield of the obtained methoxylamine hydrochloride is higher;
(2) the microreactor used by the invention has good mass transfer performance, so that the methoxylamine hydrochloride can be continuously prepared on line in large scale, and has wide application prospect in the fields of pesticide and medicine;
(3) the production process of the methoxylamine hydrochloride reduces energy consumption, improves product selectivity, reduces byproducts, reduces solid wastes, does not use toxic substances such as sulfur dioxide, sodium nitrite and the like, does not use organic reagents, generates less three wastes, and is environment-friendly.
Drawings
The microreactor means employed in the example of FIG. 1-feed tank, 2-constant flow pump, 3-microchannel reaction module, 4-storage tank, 5-collection tank;
FIG. 2 is a chromatogram of methoxyamine hydrochloride prepared in example 1.
Detailed Description
As shown in fig. 1, the micro-reactor device of the present invention is formed by connecting a raw material tank 1, a constant flow pump 2, a microchannel reaction module 3 (including a microchannel reaction module a and a microchannel reaction module B), a storage tank 4 and a collection tank 5 in series in sequence through a pipeline. The head tank 1 (5), holding vessel 4 are connected with constant flow pump 2 (6) through the pipeline, and constant flow pump 2 rethread pipeline and microchannel module 3 (2) intercommunication are connected with 5 collection tanks through the pipeline at last.
EXAMPLE 1 preparation of methoxyamine hydrochloride
According to the connection mode of figure 1, a micro-reactor is built for reaction:
(1) weighing 10g of hydroxylamine hydrochloride, adding the hydroxylamine hydrochloride into 100mL of water, stirring to obtain a hydroxylamine hydrochloride solution, adding 20 g of ethyl acetate and 60g of 20% sodium hydroxide solution into a material tank respectively, pumping into a microchannel reaction module A through a constant flow pump, and reacting to obtain a solution a;
(2) respectively pumping 190g of the solution a, 10g of dimethyl sulfate and 60g of 20% sodium hydroxide solution into a microchannel reaction module B, and reacting to obtain a solution B;
(3) taking out the solution b from the collection tank, adding hydrochloric acid (hydrolysis step), and refluxing at 65 ℃ for 1 h; then distilling at 65 ℃ under normal pressure (distillation step), and cooling the solution to 40 ℃ by using circulating water and brine ice; adding sodium hydroxide solution to make pH value of the solution reach about 7.0 (neutralization step), and stirring for 10 min; adding water into the solution, adjusting the pH value to 14.0 by using alkali liquor, heating and distilling at normal pressure, adding hydrochloric acid to absorb a distillate (salifying step), and discharging the waste water into a sewage treatment system after kettle residues are dissolved by water; the distillate obtained in the above step was distilled under reduced pressure to obtain 11.2g of a concentrated solution of methoxylamine hydrochloride (concentration step). The yield of methoxyamine hydrochloride was 93% [11.2 (actual output) ÷ 12 (theoretical output) =93.3% ], and the chromatogram was as shown in FIG. 2.
EXAMPLE 2 preparation of methoxyamine hydrochloride
(1) Weighing 500g of hydroxylamine hydrochloride, adding the hydroxylamine hydrochloride into 500mL of water, stirring to obtain a hydroxylamine hydrochloride solution, adding 1000g of ethyl acetate and 3000g of 10% sodium hydroxide solution into a material tank respectively, pumping into a microchannel reaction module A through a constant flow pump, and reacting to obtain a solution a;
(2) respectively pumping 5000g of the solution a, 1000g of dimethyl sulfate and 3000g of 10% sodium hydroxide solution into a microchannel reaction module B, and reacting to obtain a solution B;
(3) 9000g of solution b was taken out of the collection tank, hydrochloric acid was added (hydrolysis step), and reflux was carried out at 65 ℃ for 1 hour; then distilling at 65 ℃ under normal pressure (distillation step), and cooling the solution to 40 ℃ by using circulating water and brine ice; adding sodium hydroxide solution to make pH value of the solution reach about 7.0 (neutralization step), and stirring for 10 min; adding water into the solution, adjusting the pH value to 14.0 by using alkali liquor, heating and distilling at normal pressure, adding hydrochloric acid to absorb a distillate (salifying step), and discharging the waste water into a sewage treatment system after kettle residues are dissolved by water; and (4) distilling the distillate in the previous step under reduced pressure to obtain a methoxylamine hydrochloride concentrated solution (concentration step). The yield of methoxyamine hydrochloride was 92%.
EXAMPLE 3 preparation of methoxyamine hydrochloride
(1) Weighing 250g of hydroxylamine hydrochloride, adding the hydroxylamine hydrochloride into 500mL of water, stirring to obtain a hydroxylamine hydrochloride solution, adding the hydroxylamine hydrochloride solution, 500g of ethyl acetate and 1000g of 10% sodium hydroxide solution into a material tank respectively, pumping the solution into a microchannel reaction module A through a constant flow pump, and reacting to obtain a solution a;
(2) pumping 22500g of the solution a, 500g of dimethyl sulfate and 1000g of a 31% sodium hydroxide solution into a microchannel reaction module B respectively to react to obtain a solution B;
(3) 3750g of the solution b was taken out of the collection tank, added with hydrochloric acid (hydrolysis step), and refluxed at 65 ℃ for 1 hour; then distilling at 65 ℃ under normal pressure (distillation step), and cooling the solution to 40 ℃ by using circulating water and brine ice; adding sodium hydroxide solution to make pH value of the solution reach about 7.0 (neutralization step), and stirring for 10 min; adding water into the solution, adjusting the pH value to 14.0 by using alkali liquor, heating and distilling at normal pressure, adding hydrochloric acid to absorb a distillate (salifying step), and discharging the waste water into a sewage treatment system after kettle residues are dissolved by water; and (4) distilling the distillate in the previous step under reduced pressure to obtain a methoxylamine hydrochloride concentrated solution (concentration step). The yield of methoxyamine hydrochloride was 95%.
From the results of the embodiments 1 to 3, the method for preparing methoxyamine hydrochloride by using the microreactor ensures the mass transfer and heat transfer efficiency, reduces the energy consumption, improves the product selectivity, has few byproducts, few solid wastes, has high environmental friendliness, is full-automatic in reaction process, accurate in control precision, safer and beneficial to industrial production.
The above detailed description is specific to one possible embodiment of the present invention, and the embodiment is not intended to limit the scope of the present invention, and all equivalent implementations or modifications without departing from the scope of the present invention should be included in the technical scope of the present invention.
Claims (7)
1. A method for preparing methoxylamine hydrochloride by adopting a microreactor is characterized by sequentially comprising the preparation of acetyl hydroxylamine, the preparation of acetyl methoxylamine and the preparation of methoxylamine hydrochloride, wherein the preparation processes of acetyl hydroxylamine and acetyl methoxylamine are carried out in the microreactor; specifically, a hydroxylamine hydrochloride solution, ethyl acetate and an alkali liquor are pumped into a microchannel reaction module A, mixed in a microchannel, pumped into a microchannel reaction module B together with dimethyl sulfate and an alkali liquor, and subjected to mixing reaction, collection, hydrolysis, distillation, neutralization, salification and concentration to obtain the methoxylamine hydrochloride.
2. The method for preparing methoxyamine hydrochloride by using the microreactor as claimed in claim 1, which comprises the following steps:
step 1, constructing a micro-reactor, wherein the micro-reactor consists of a batching system, a feeding system, a micro-reaction system and a post-processing system, and the micro-reaction system consists of a micro-channel reaction module A and a micro-channel reaction module B;
step 2, pumping the hydroxylamine hydrochloride solution, the ethyl acetate and the alkali liquor into a microchannel reaction module A respectively, and carrying out mixed reaction to obtain a solution a;
step 3, pumping the solution a, dimethyl sulfate and alkali liquor into a microchannel reaction module B respectively, and carrying out mixed reaction to obtain a solution B;
and 4, collecting the solution b, and performing hydrolysis, distillation, neutralization, salification and concentration processes to obtain the methoxylamine hydrochloride.
3. The method for preparing methoxylamine hydrochloride by using the microreactor as claimed in claim 2, wherein the concentration of the hydroxylamine hydrochloride solution in the step 2 is 1-1000 mg/mL, and the mass of the hydroxylamine hydrochloride solution is 10-500 g; the mass of the ethyl acetate is 20-1000 g; the alkali liquor is 10-31% solution with a mass concentration of 60-3000g, specifically sodium hydroxide solution or potassium hydroxide.
4. The method for preparing methoxyamine hydrochloride by using the microreactor as claimed in claim 2, wherein the mass of the dimethyl sulfate in the step 3 is 10-1000 g; the alkali liquor is 10-31% solution with a mass concentration of 60-3000g, specifically sodium hydroxide solution or potassium hydroxide.
5. The method for preparing methoxyamine hydrochloride by using the microreactor as claimed in claim 2, wherein the material of the microchannel reaction module A and the microchannel reaction module B is one or more of stainless steel, glass, ceramic or polydimethylsiloxane.
6. The method for preparing methoxyamine hydrochloride by using the microreactor as claimed in claim 2, wherein the diameter of the channel of each of the microchannel reaction module A and the microchannel reaction module B is 5-500 μm.
7. The method for preparing methoxyamine hydrochloride by using the microreactor as claimed in claim 2, wherein the length of the channels of the microchannel reaction module A and the microchannel reaction module B is 5-200 cm.
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| CN114561435A (en) * | 2022-04-27 | 2022-05-31 | 南京科力硕生物科技有限公司 | Method for preparing 4-chloro-3-ethyl-1-methylpyrazole-5-formic acid by using magnetic carbon nanotube immobilized enzyme catalysis |
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| CN102976968A (en) * | 2012-12-01 | 2013-03-20 | 张家港市大伟助剂有限公司 | Preparation method for methoxylamine hydrochloride |
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| CN102976968A (en) * | 2012-12-01 | 2013-03-20 | 张家港市大伟助剂有限公司 | Preparation method for methoxylamine hydrochloride |
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| CN114561435A (en) * | 2022-04-27 | 2022-05-31 | 南京科力硕生物科技有限公司 | Method for preparing 4-chloro-3-ethyl-1-methylpyrazole-5-formic acid by using magnetic carbon nanotube immobilized enzyme catalysis |
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