CN112851543B - Preparation method of methoxyamine hydrochloride and preparation method of N-methoxyacetamide - Google Patents
Preparation method of methoxyamine hydrochloride and preparation method of N-methoxyacetamide Download PDFInfo
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- 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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- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
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Abstract
The invention relates to a preparation method of methoxyamine hydrochloride and a preparation method of N-methoxyacetamide, belonging to the technical field of organic synthesis. The preparation method of methoxyamine hydrochloride comprises the following steps: 1) Performing methylation reaction on acetohydroxamic acid and dimethyl sulfate in water to generate N-methoxyacetamide; sodium bicarbonate and sodium hydroxide are adopted in the methylation reaction process to control the pH of a reaction system to 7-9, and the molar ratio of the sodium bicarbonate to the sodium hydroxide is 0.03-0.09:1; 2) Then preparing the N-methoxyacetamide into methoxyamine hydrochloride. According to the preparation method of methoxyamine hydrochloride, sodium bicarbonate and sodium hydroxide composite alkali are adopted in the methylation reaction process, so that the conversion rate of acetohydroxamic acid can be improved, the pH value in the methylation process can be strictly controlled to 7-9, the generation of polymethyl impurities (O, N-dimethylhydroxylamine hydrochloride) is reduced, and the yield of N-methoxyacetamide is improved.
Description
Technical Field
The invention relates to a preparation method of methoxyamine hydrochloride and a preparation method of N-methoxyacetamide, belonging to the technical field of organic synthesis.
Background
Methoxyamine hydrochloride (molecular formula is CH 3 ONH 2 HCl) is an important chemical raw material for producing antibiotic medicines such as cefuroxime acid (ester) and the like and phenoxyl bacteria amine bactericides; methoxyamine hydrochloride is also a pharmaceutical product and is commonly used in surgical procedures to maintain or restore arterial pressure, particularly for the reduction of blood pressure caused by spinal anesthesia.
Although the methoxyamine hydrochloride has high application value, the method for preparing the methoxyamine hydrochloride in the prior literature or the prepared methoxyamine hydrochloride has insufficient purity or insufficient yield, and limits the popularization and application of the methoxyamine hydrochloride to a certain extent.
Disclosure of Invention
The invention aims to provide a preparation method of methoxyamine hydrochloride, which not only can improve the conversion rate of acetohydroxamic acid, but also is beneficial to improving the purity of methoxy hydrochloride.
The invention also provides a preparation method of the N-methoxy acetamide.
In order to achieve the above purpose, the preparation method of methoxyamine hydrochloride of the invention adopts the following technical scheme:
a method for preparing methoxyamine hydrochloride, comprising the following steps:
1) Performing methylation reaction on acetohydroxamic acid and dimethyl sulfate in water to generate N-methoxyacetamide; sodium bicarbonate and sodium hydroxide are adopted in the methylation reaction process to control the pH of a reaction system to 7-9, and the molar ratio of the sodium bicarbonate to the sodium hydroxide is 0.03-0.09:1;
2) Then preparing the N-methoxyacetamide into methoxyamine hydrochloride.
According to the preparation method of methoxylamine hydrochloride, sodium bicarbonate and sodium hydroxide composite alkali are adopted in the methylation reaction process, so that the conversion rate of acetohydroxamic acid can be improved, the pH value in the methylation process can be strictly controlled to 7-9, the generation of polymethyl impurities (O, N-dimethylhydroxylamine hydrochloride) is reduced, the yield of N-methoxyacetamide is improved, and the yield of methoxylamine hydrochloride and the purity of products are finally improved.
The preparation method of the methoxyamine hydrochloride is simple and easy to operate, can improve the conversion rate of the acetohydroxamic acid, is controllable in process, can effectively reduce side reactions, and improves the yield and purity of the methoxyamine hydrochloride.
Preferably, the temperature of the methylation reaction is 10-30 ℃.
The mol ratio of the acetohydroxamic acid to the dimethyl sulfate is 1:1-1.4.
Preferably, the methylation reaction is carried out by adding dimethyl sulfate, sodium hydroxide and ammonium bicarbonate into an aqueous solution of acetohydroxamic acid. The dimethyl sulfate has a fast decomposition rate under the reaction condition, and the side reaction rate is equivalent to the main reaction rate, so as to control the side reaction and improve the raw material conversion rate, and preferably, the methylation reaction is carried out by adding dimethyl sulfate, sodium hydroxide and sodium bicarbonate into an acetohydroxamic acid aqueous solution in batches.
Preferably, the mass fraction of the acetohydroxamic acid in the acetohydroxamic acid aqueous solution is 29-40%.
Preferably, dimethyl sulfate, sodium hydroxide and sodium bicarbonate are added into an acetohydroxamic acid aqueous solution in three batches for reaction; the mole ratio of the dimethyl sulfate to the acetohydroxamic acid added in the first batch is 0.85-1:1, the mole ratio of the dimethyl sulfate to the acetohydroxamic acid added in the second batch is 0.05-0.15:1, and the mole ratio of the dimethyl sulfate to the acetohydroxamic acid added in the third batch is 0.10-0.25:1. Further preferably, the reaction time of the first batch of dimethyl sulfate with the acetohydroxamic acid is 0.5-1h after the addition of the first batch of dimethyl sulfate, the reaction time of the second batch of dimethyl sulfate with the acetohydroxamic acid is 0.5-1h after the addition of the second batch of dimethyl sulfate, and the reaction time of the third batch of dimethyl sulfate with the acetohydroxamic acid is 0.5-2h after the addition of the third batch of dimethyl sulfate.
Preferably, sodium hydroxide and sodium bicarbonate are added to the aqueous acetohydroxamic acid solution as a mixed aqueous solution of the two. Preferably, in the mixed aqueous solution, the mass fraction of sodium hydroxide is 29.7-40.3%, and the mass fraction of sodium bicarbonate is 2.4-5.4%. Further preferably, the mixed aqueous solution is obtained by mixing a solid of sodium hydroxide and sodium bicarbonate with water. Preferably, the mixed aqueous solution is added dropwise to the aqueous solution of acetohydroxamic acid. Further preferably, the molar ratio of sodium hydroxide to sodium bicarbonate in the mixed solution is 1:0.03-0.09.
Preferably, dimethyl sulfate is added dropwise to the aqueous acetohydroxamic acid solution during the methylation reaction. Further preferably, when dimethyl sulfate, sodium hydroxide and sodium bicarbonate are added into an aqueous solution of acetohydroxamic acid in three batches for reaction, the first batch of dimethyl sulfate is added dropwise from 1 to 3 hours.
Since dimethyl sulfate can react with acetohydroxamic acid to form monomethyl sulfate, monomethyl sulfate reacts with alkali to form sulfate and methanol to consume alkali, neutralization of the surrounding alkali reduces the pH in a small range, resulting in a reduction in the conversion of the raw material. In order to reduce the reaction of dimethyl sulfate with a base and to improve the conversion rate of acetohydroxamic acid, preferably, the mixed aqueous solution is added dropwise to the acetohydroxamic acid aqueous solution simultaneously with the dropwise addition of dimethyl sulfate during the methylation reaction.
Preferably, the preparation of methoxyacetamide to methoxyamine hydrochloride comprises the steps of: adding acid into the reaction system after the methylation reaction in the step 1) to carry out acidolysis on N-methoxyacetamide, separating to remove acetic acid, adding an alcohol solvent to disperse, then adjusting the system to be alkaline, then distilling, collecting a methoxyamine fraction, adding hydrochloric acid into the fraction to adjust the pH value to be less than 2, then evaporating to dryness to obtain a solid, dissolving the solid with an organic good solvent of methoxyamine hydrochloride, carrying out solid-liquid separation, and drying to obtain the N-methoxyacetamide.
Preferably, the pure solvent is ethanol. The volume of the alcohol solvent adopted for each 90-120g of the acetohydroxamic acid is 500mL.
The distillation is atmospheric distillation. The fraction collected is a fraction collected at 80-95deg.C. Preferably, the acid is concentrated sulfuric acid. The mass fraction of the concentrated sulfuric acid is 85-98%.
Preferably, the acidolysis temperature is 73-76 ℃. The acidolysis reaction time is 3-8h.
Preferably, the organic good solvent is isopropanol. Preferably, the quality of the organic good solvent adopted for every 90-120g of the acetohydroxamic acid is 60g.
The preparation method of the N-methoxy acetamide adopts the following technical scheme:
a method for preparing N-methoxy acetamide, comprising the following steps: performing methylation reaction on acetohydroxamic acid and dimethyl sulfate in water to generate N-methoxyacetamide; sodium bicarbonate and sodium hydroxide are adopted in the methylation reaction process to control the pH value of a reaction system to be 7-9; the molar ratio of the sodium bicarbonate to the sodium hydroxide is 0.03-0.09:1.
According to the preparation method of the N-methoxyacetamide, sodium bicarbonate and sodium hydroxide composite alkali are adopted, so that not only can the conversion rate of acetohydroxamic acid be improved, but also the pH value in the methylation process can be strictly controlled to 7-9, the generation of the polymethyl impurity (O, N-dimethylhydroxylamine hydrochloride) is reduced, and the yield of the N-methoxyacetamide is improved.
Preferably, the temperature of the methylation reaction is 10-30 ℃.
Preferably, the methylation reaction is carried out by adding dimethyl sulfate, sodium hydroxide and ammonium bicarbonate into an aqueous solution of acetohydroxamic acid. Further preferably, the methylation reaction is carried out by adding dimethyl sulfate, sodium hydroxide and sodium bicarbonate to an aqueous solution of acetohydroxamic acid in batches.
Preferably, dimethyl sulfate, sodium hydroxide and sodium bicarbonate are added into an acetohydroxamic acid aqueous solution in three batches for reaction; the mole ratio of the dimethyl sulfate to the acetohydroxamic acid added in the first batch is 0.85-1:1, the mole ratio of the dimethyl sulfate to the acetohydroxamic acid added in the second batch is 0.05-0.15:1, and the mole ratio of the dimethyl sulfate to the acetohydroxamic acid added in the third batch is 0.10-0.25:1. Further preferably, the reaction time of the first batch of dimethyl sulfate with the acetohydroxamic acid is 0.5-1h after the addition of the first batch of dimethyl sulfate, the reaction time of the second batch of dimethyl sulfate with the acetohydroxamic acid is 0.5-1h after the addition of the second batch of dimethyl sulfate, and the reaction time of the third batch of dimethyl sulfate with the acetohydroxamic acid is 0.5-2h after the addition of the third batch of dimethyl sulfate.
Preferably, sodium hydroxide and sodium bicarbonate are added to the aqueous acetohydroxamic acid solution as a mixed aqueous solution of the two.
Preferably, in the mixed aqueous solution, the mass fraction of sodium hydroxide is 29.7-40.3%, and the mass fraction of sodium bicarbonate is 2.4-5.4%. Further preferably, the molar ratio of sodium hydroxide to sodium bicarbonate in the mixed solution is 1:0.03-0.09.
Preferably, the mixed aqueous solution is added dropwise to the aqueous solution of acetohydroxamic acid. The dimethyl sulfate is dropwise added into the acetohydroxamic acid aqueous solution in a dropwise manner. The mixed aqueous solution was added dropwise to an aqueous acetohydroxamic acid solution simultaneously with the dropwise addition of dimethyl sulfate.
Further preferably, when dimethyl sulfate, sodium hydroxide and sodium bicarbonate are added into an aqueous solution of acetohydroxamic acid in three batches for reaction, the first batch of dimethyl sulfate is added dropwise from 1 to 3 hours.
Preferably, the mass fraction of the acetohydroxamic acid in the acetohydroxamic acid aqueous solution is 29-40%. Preferably, the molar ratio of the acetohydroxamic acid to the dimethyl sulfate is 1:1-1.4.
Detailed Description
The technical scheme of the invention is further described below in connection with the specific embodiments.
Examples 1 to 3 below are examples of the process for preparing methoxy hydrochloride and examples 4 to 6 are examples of the process for preparing N-methoxyacetamide.
Example 1
The preparation method of methoxyamine hydrochloride in the embodiment comprises the following steps:
1) Adding 0.10mol of sodium bicarbonate and 3.52mol of sodium hydroxide into 200g of water, and uniformly mixing to obtain a composite aqueous alkali solution (namely a mixed aqueous solution);
2) 108g (1.44 mol) of acetohydroxamic acid and 200g of water are added into a reaction bottle and uniformly mixed to obtain a reaction solution, the temperature of the reaction solution is controlled to be 10 ℃, 181.6g (1.44 mol) of dimethyl sulfate is added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH value of a reaction system is controlled to be 7.0-7.5,2 hours after the dropwise addition, and the dimethyl sulfate is stirred for 0.5 hour after the dropwise addition. Then, 27.2g (0.22 mol) of dimethyl sulfate is added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH value of the reaction system is controlled to be 7.0-7.5, bi Jiaoban is controlled to be 0.5h, then 45.4g (0.36 mol) of dimethyl sulfate is added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH value of the reaction system is controlled to be 7.0-7.5, the mixture is stirred for 0.5h after the completion of TLC monitoring reaction, and a reaction product liquid is obtained.
3) Heating the reaction product liquid to 60 ℃, preserving heat for 1 hour (quenching dimethyl sulfate), cooling to room temperature, and dripping 141g of concentrated sulfuric acid (containing H) with the mass fraction of 98 percent 2 SO 4 1.41 mol), at 73 deg.C for 3 hours, then evaporating acetic acid under reduced pressure at 60 deg.C, adding 500g of ethanol to disperse the residue, adding alkali to adjust pH to 10, stirring for 0.5 hours, filtering, distilling the filtrate at normal pressure, collecting fraction at 80-95 deg.C, and adding 115g of 30% by mass concentrated hydrochloric acid to adjust pH<2, evaporating to dryness, then adding 60g of isopropanol, stirring at room temperature for half an hour, filtering, and drying the obtained solid at 50 ℃ to obtain 115.5g of finished product, wherein the yield is 95.3%, and the gas phase detection purity is 99.2%.
Example 2
The preparation method of methoxyamine hydrochloride in the embodiment comprises the following steps:
1) Adding 0.2mol of sodium bicarbonate and 2.3mol of sodium hydroxide into 200g of water, and uniformly mixing to obtain a composite aqueous alkali solution (namely a mixed aqueous solution);
2) 108g (1.44 mol) of acetohydroxamic acid and 252g of water are added into a reaction bottle and uniformly mixed to obtain a reaction liquid, the temperature of the reaction liquid is controlled to be 20 ℃, 163.4g (1.30 mol) of dimethyl sulfate is added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH=7.5-8.0,2 hours of the reaction system is controlled, and after the dropwise addition of the dimethyl sulfate is completed, the mixture is stirred for 0.5 hour. Then continuously dripping 18.1g (0.14 mol) of dimethyl sulfate, simultaneously dripping composite alkaline water solution, controlling the pH value of a reaction system to be 7.5-8.0, dripping Bi Jiaoban for 0.5h, then dripping 27.2g (0.22 mol) of dimethyl sulfate, simultaneously dripping composite alkaline water solution, controlling the pH value of the reaction system to be 7.5-8.0, stirring for 0.5h after dripping, and carrying out TLC monitoring on the reaction to obtain a reaction product liquid.
3) Heating the reaction product liquid to 60 ℃, preserving heat for 1 hour (quenching dimethyl sulfate), cooling to room temperature, and dropwise adding 156.8g of concentrated sulfuric acid (containing H) with the mass fraction of 90 percent 2 SO 4 1.44 mol), at 73 deg.C for 3 hours, then evaporating acetic acid under reduced pressure at 60 deg.C, adding 500g of ethanol to disperse the remainder, adding alkali to adjust pH to 10, stirring for 0.5 hours, filtering, distilling the filtrate at normal pressure, collecting fraction at 80-95 deg.C, and adding 115g of 30% by mass concentrated hydrochloric acid to adjust pH<2, evaporating to dryness, then adding 60g of isopropanol, stirring for half an hour at room temperature, filtering, and drying the obtained solid at 50 ℃ to obtain 116.4g of finished product, wherein the yield is 96.3%, and the gas phase detection purity is 99.5%.
Example 3
The preparation method of methoxyamine hydrochloride in the embodiment comprises the following steps:
1) Adding 0.15mol of sodium bicarbonate and 3.0mol of sodium hydroxide into 200g of water, and uniformly mixing to obtain a composite aqueous alkali solution (namely a mixed aqueous solution);
2) 108g (1.44 mol) of acetohydroxamic acid and 162g of water are added into a reaction bottle and uniformly mixed to obtain a reaction liquid, the temperature of the reaction liquid is controlled to be 30 ℃, 154.3g (1.22 mol) of dimethyl sulfate is added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH of a reaction system is controlled to be 8-9, after 2 hours of dropwise addition, the mixture is stirred for 0.5 hour after dropwise addition of the dimethyl sulfate. Then, 9.1g (0.08 mol) of dimethyl sulfate is continuously added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH value of the reaction system is controlled to be 8-9, bi Jiaoban is added dropwise for 0.5h, then 18.1g (0.14 mol) of dimethyl sulfate is added dropwise, meanwhile, a composite alkaline water solution is added dropwise, the pH value of the reaction system is controlled to be 8-9, the mixture is stirred for 0.5h after the dropwise is finished, and a reaction product liquid is obtained after TLC monitoring reaction.
3) Heating the reaction product liquid to 60 ℃, preserving heat for 1 hour (quenching dimethyl sulfate), cooling to room temperature, and dropwise adding 166g of concentrated sulfuric acid (containing H) with the mass fraction of 85 percent 2 SO 4 1.44 mol), at 73 deg.C for 3 hours, then evaporating acetic acid under reduced pressure at 60 deg.C, adding 500g of ethanol to disperse the remainder, adding alkali to adjust pH to 10, stirring for 0.5 hours, filtering, distilling the filtrate at normal pressure, collecting fraction at 80-95 deg.C, and adding 115g of 35% by mass of concentrated hydrochloric acid to adjust pH<2, evaporating to dryness, then adding 60g of isopropanol, stirring at room temperature for half an hour, filtering, and drying the obtained solid at 50 ℃ to obtain 113.6g of finished product, wherein the yield is 93.5%, and the gas phase detection purity is 99.0%.
Example 4
The preparation method of the N-methoxyacetamide comprises the following steps:
1) Step 1) as in example 1;
2) Step 2) of example 1;
3) Heating the reaction product liquid obtained in the step 2) to 60 ℃, preserving heat for 1 hour (quenching dimethyl sulfate), reducing the temperature to room temperature, performing reduced pressure distillation, desalting, extracting with ethyl acetate, and evaporating the solvent under reduced pressure to obtain an N-methoxyacetamide product with the purity of 96%.
The content of the acetohydroxamic acid, the N-methoxyacetamide and the polymethylated impurity in the reaction product liquid at the end of the reaction is analyzed by an HPLC method (namely a high performance liquid chromatography), and the conversion rate of the acetohydroxamic acid is 98.4%, the yield of the N-methoxyformamide is 96.2% and the yield of the polymethylated impurity is 0.2% through calculation.
Example 5
The preparation method of the N-methoxyacetamide comprises the following steps:
1) Step 1) of example 2;
2) Step 2) as in example 2;
3) Heating the reaction product liquid obtained in the step 2) to 60 ℃, preserving heat for 1 hour (quenching dimethyl sulfate), reducing the temperature to room temperature, performing reduced pressure distillation, desalting, extracting with ethyl acetate, and evaporating the solvent under reduced pressure to obtain an N-methoxyacetamide product with the purity of 95 percent.
The content of the acetohydroxamic acid, the N-methoxyacetamide and the polymethylation impurity in the reaction product liquid at the reaction end point is analyzed by adopting an HPLC method, and the conversion rate of the acetohydroxamic acid is 99.0%, the yield of the N-methoxyformamide is 98.3% and the yield of the polymethylation impurity is 0.3% through calculation.
Example 6
The preparation method of the N-methoxyacetamide comprises the following steps:
1) Step 1) of example 3;
2) Step 2) of example 3;
3) Heating the reaction product liquid obtained in the step 2) to 60 ℃, preserving heat for 1 hour (quenching dimethyl sulfate), reducing the temperature to room temperature, performing reduced pressure distillation, desalting, extracting with ethyl acetate, and evaporating the solvent under reduced pressure to obtain an N-methoxyacetamide product with the purity of 96%.
The content of acetohydroxamic acid, N-methoxyacetamide and the content of the methylated impurities in the reaction product liquid at the end point of the reaction are analyzed by adopting an HPLC method, and the conversion rate of the acetohydroxamic acid is 97.5%, the yield of the N-methoxyformamide is 95.8% and the yield of the methylated impurities is 0.3% through calculation.
Comparative example
The preparation methods of N-methoxyacetamides of comparative examples 1 to 11 were different from the preparation method of N-methoxyacetamides of example 5 only in that the complex aqueous alkali of step 1) of example 5 was replaced, the preparation methods of N-methoxyacetamides of comparative examples 12 to 25 were different from the preparation method of N-methoxyacetamides of example 5 only in that the complex aqueous alkali of step 1) of example 5 and the solvent (i.e., water) used in the preparation of the reaction solution of step 2) were replaced, the aqueous alkali and the solvent specifically used in each comparative example were as shown in Table 1, and the contents of acetohydroxamic acid, N-methoxyacetamides and the multi-methylated impurities in the reaction product solutions at the reaction end points of each comparative examples were analyzed by HPLC method, and the conversion rate of acetohydroxamic acid, the yield of N-methoxyacetamides and the yield of multi-methylated impurities were calculated as shown in Table 1.
TABLE 1 conversion of acetohydroxamic acid, yield of N-methoxyacetamide and yield of polymethylated impurities by aqueous alkali and solvent used in the preparation method of N-methoxyacetamides of comparative examples 1 to 26
Comparing examples 4-6 with comparative examples 1-25, it can be seen that:
1) The solvent effect is generated in the methylation reaction process, water is the optimal solvent for the methylation reaction, and the impurity content of the acetone and the ethanol serving as solvents is obviously higher than that of the water serving as the solvents.
2) In the methylation reaction process, ion effect exists, calcium and alkali do not react, and the conversion rate of potassium alkali is higher than that of sodium alkali raw materials, so that more product impurities are generated.
3) After the phase transfer catalyst cetyl trimethylammonium bromide was added in comparative example 2, the conversion of acetohydroxamic acid was increased as compared with comparative example 1, but the selectivity of N-methoxyacetamide was decreased, and the impurity content was increased, which was detrimental to the reaction.
4) The preparation method of the N-methoxyacetamide adopts the composite alkali solution of sodium bicarbonate and sodium hydroxide, so that the conversion rate is high, and the impurity content is low.
Claims (9)
1. A preparation method of methoxyamine hydrochloride is characterized in that: the method comprises the following steps:
1) Carrying out methylation reaction on acetohydroxamic acid and dimethyl sulfate in water to generate N-methoxyacetamide, wherein the molar ratio of the acetohydroxamic acid to the dimethyl sulfate is 1:1-1.4; sodium bicarbonate and sodium hydroxide are adopted in the methylation reaction process to control the pH value of a reaction system to be 7-9, and the molar ratio of the sodium bicarbonate to the sodium hydroxide is 0.03-0.09:1;
2) Preparing methoxyamine hydrochloride from N-methoxyacetamide; the preparation of methoxyacetamide into methoxyamine hydrochloride comprises the following steps: adding acid into the reaction system after the methylation reaction in the step 1) to carry out acidolysis on N-methoxyacetamide, separating to remove acetic acid, adding an alcohol solvent to disperse, then adjusting the system to be alkaline, then distilling, collecting a methoxyamine fraction, adding hydrochloric acid into the fraction to adjust the pH value to be less than 2, then evaporating to dryness to obtain a solid, dissolving the solid with an organic good solvent of methoxyamine hydrochloride, carrying out solid-liquid separation, and drying to obtain the N-methoxyacetamide.
2. The method for preparing methoxyamine hydrochloride according to claim 1, wherein: the methylation reaction is carried out by adding dimethyl sulfate, sodium hydroxide and sodium bicarbonate into an acetohydroxamic acid aqueous solution in batches.
3. The process for the preparation of methoxyamine hydrochloride according to any one of claims 1 or 2, characterized in that: sodium hydroxide and sodium bicarbonate are added into the aqueous solution of acetohydroxamic acid in a mixed aqueous solution of the sodium hydroxide and the sodium bicarbonate; in the mixed aqueous solution, the mass fraction of sodium hydroxide is 29.7-40.3%, and the mass fraction of sodium bicarbonate is 2.4-5.4%; the mass fraction of the acetohydroxamic acid in the acetohydroxamic acid aqueous solution is 29-40%.
4. A process for the preparation of methoxyamine hydrochloride according to claim 3, characterized in that: the mixed aqueous solution is added into the acetohydroxamic acid aqueous solution in a dropwise manner; the dimethyl sulfate is dropwise added into an acetohydroxamic acid aqueous solution in a dropwise manner; the mixed aqueous solution was added dropwise to an aqueous acetohydroxamic acid solution simultaneously with the dropwise addition of dimethyl sulfate.
5. A preparation method of N-methoxyacetamide is characterized by comprising the following steps: the method comprises the following steps: performing methylation reaction on acetohydroxamic acid and dimethyl sulfate in water to generate N-methoxyacetamide; sodium bicarbonate and sodium hydroxide are adopted in the methylation reaction process to control the pH value of a reaction system to be 7-9; the molar ratio of the sodium bicarbonate to the sodium hydroxide is 0.03-0.09:1.
6. The process for producing N-methoxyacetamide as claimed in claim 5, wherein: dimethyl sulfate, sodium hydroxide and sodium bicarbonate are added into an acetohydroxamic acid aqueous solution in batches for reaction.
7. The process for producing N-methoxyacetamide as claimed in claim 5 or 6, wherein: sodium hydroxide and sodium bicarbonate are added into the aqueous solution of acetohydroxamic acid in a mixed aqueous solution of the sodium hydroxide and the sodium bicarbonate; in the mixed aqueous solution, the mass fraction of sodium hydroxide is 29.7-40.3%, and the mass fraction of sodium bicarbonate is 2.4-5.4%.
8. The process for producing N-methoxyacetamide as claimed in claim 7, wherein: the mixed aqueous solution is added into the acetohydroxamic acid aqueous solution in a dropwise manner; the dimethyl sulfate is dropwise added into an acetohydroxamic acid aqueous solution in a dropwise manner; the mixed aqueous solution was added dropwise to an aqueous acetohydroxamic acid solution simultaneously with the dropwise addition of dimethyl sulfate.
9. The method for producing N-methoxyacetamide as claimed in claim 8, wherein: the mass fraction of the acetohydroxamic acid in the acetohydroxamic acid aqueous solution is 29-40%.
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