CN111747863A - Method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by one-pot method - Google Patents
Method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by one-pot method Download PDFInfo
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- 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 the field of organic synthesis, in particular to a method for preparing 0-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by a one-pot method, which comprises the following steps: s1 acetylation: mixing hydroxylamine hydrochloride with water and methyl acetate, and dripping sodium hydroxide solution under stirring at room temperature to obtain intermediate acetyl hydroxylamine; s2 alkylation: dripping an alkylating reagent into the reaction kettle at normal temperature, and then heating for reaction; s3 hydrolysis purification: adding concentrated sulfuric acid after the reaction is qualified, heating for hydrolysis, adding caustic soda flakes or liquid caustic soda after the reaction is qualified, adjusting the pH to 12, distilling at normal pressure, acidifying with hydrochloric acid, cooling for crystallization, centrifuging and drying to obtain a final product; the invention selects methyl acetate as acetyl protective agent, and compared with ethyl acetate, the invention has the following advantages: good water solubility, small reaction steric hindrance, sufficient protection, less impurities, low price and cost and the like; meanwhile, the product has high purity, simple and convenient process operation, easily obtained raw materials, simple wastewater components and relatively friendly environment, and is suitable for industrial production.
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by a one-pot method.
Background
The O-alkoxyamino hydrochloride series compounds are mainly used for synthesizing alkoxyamino reagents to generate oxime with ketone. The pesticide has wide application in medical pesticides: such as the pesticides benzoxydim, clethodim, sethoxydim, and the like; the cefuroxime sodium and cefuroxime axetil are mainly used in medicine; and bactericide phenoxy ester. And can also be used as an intermediate of functional dye. The N, O-dialkyl hydroxylamine hydrochloride is mainly used for synthesizing medicines, pesticides and optical material compounds, wherein the N, O-dimethyl hydroxylamine hydrochloride is used for preparing Weinreb amide.
The use of O-alkyl hydroxylamine hydrochloride is also widely studied, and currently, the following synthetic routes are mainly used: 1. hydroxylamine hydrochloride and acetone or butanone are used for generating ketoxime, then the ketoxime is obtained by rectification and purification, the pure product is obtained and reacts with chloralkane and strong base in an anhydrous polar solvent under high pressure, and after the reaction is finished, the acetone or butanone is separated by adding hydrochloric acid for rectification after multi-step purification. The process needs to be separated for many times, the last step of hydrolysis is an equilibrium reaction, and the separation difficulty of acetone and raw material acetone oxime methyl ether or butanone oxime methyl ether is large. US5382685A and US5557013A representative of processes basf; CN103282344 and CN101503375A of Ningbo Europe. 2. Sodium bisulfite sulfur dioxide is used as a raw material, and alkylation, hydrolysis, neutralization and distillation are carried out. The method has multiple steps and adopts sulfur dioxide toxic gas for reaction. Meanwhile, the process is safe and hidden from explosion danger. Quaternary Never (chemical and adhesive, 2001, 5, 200- & 202) and Chin 109160908 by Fine Chemicals, Inc., of Siping. 3. Liwencellu et al (fine chemical raw material and intermediate, 2007, 22-23) describe the synthesis of ethoxyamine hydrochloride by reacting ethyl acetate with hydroxylamine hydrochloride under alkaline conditions, then reacting with diethyl sulfate, and performing multi-step purification treatment. The alkylamine hydrochloride was synthesized by the chemical of qingquan (CN101357895) and the university of chinese pharmacy (CN106800580) by a similar route. In the route, the ethyl acetate has low solubility in water, and needs relatively high temperature for a long time to react, so that the ester is hydrolyzed by itself more, and impurities in subsequent reaction steps are more and are not easy to separate. The 1.1 to 1.4 equivalents of ester used in the literature do not fulfill the process requirements. Meanwhile, the reaction intermediate needs to be separated and purified additionally, the process is complicated, the cost is high, and impurities are difficult to remove.
The synthesis of N, O-dialkyl hydroxylamine hydrochloride is not disclosed in many documents, and the following methods are mainly adopted:
1. the purification from the O-alkyl hydroxylamine hydrochloride byproduct is difficult. Qi-An Sun (Eur.J.org.chem.2018, 3920-3927) was isolated by reacting O-alkylhydroxylamine hydrochloride with benzenesulfonyl chloride, followed by reaction with An alkyl halide. Are difficult to industrialize.
It is desired to provide a process for efficiently and easily preparing O-alkylhydroxylamine hydrochloride and N, O-dialkylhydroxylamine hydrochloride, respectively. Meanwhile, the product has high purity, low cost, environmental protection and industrialization suitability.
Disclosure of Invention
The invention aims to provide a method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by a one-pot method, so as to solve the problems in the background technology.
In order to achieve the purpose, the invention provides the following technical scheme: a method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by a one-pot method is characterized by comprising the following steps:
s1 acetylation step: mixing hydroxylamine hydrochloride with water and methyl acetate, dropwise adding a sodium hydroxide solution under stirring at 10-40 ℃, dropwise adding for 1-8 hours, reacting for 1-4 hours, and obtaining an intermediate aqueous solution of acetylhydroxylamine after the reaction is qualified;
s2 alkylation stage: dropwise adding dimethyl sulfate or diethyl sulfate into the reaction kettle at 10-40 ℃ for 1-5 hours, or adding halogenated compounds such as chloropropane and the like, heating for reaction for 5-10 hours, monitoring until the reaction is qualified, and directly carrying out the next reaction without separation;
s3 hydrolysis purification stage: adding concentrated sulfuric acid, heating to 40-80 deg.C, hydrolyzing for 0.5-7 hr, adding caustic soda flakes or liquid caustic soda to regulate pH to 12, and distilling O-alkyl hydroxylamine or N, O-dialkyl hydroxylamine at normal pressure; acidifying with hydrochloric acid gas, cooling, crystallizing, centrifuging and drying to obtain the O-alkyl hydroxylamine hydrochloride or N, O-dialkyl hydroxylamine hydrochloride.
Preferably, the molar ratio of the hydroxylamine hydrochloride to the water to the methyl acetate to the sodium hydroxide solution in the acetylation step reaction in the step S1 is 1 to (1.0-8.0) to (1.0-2.0) to (1.1-5.0); the mass fraction of the sodium hydroxide solution is 5-50%.
Preferably, the molar ratio of the hydroxylamine hydrochloride, the water, the methyl acetate and the sodium hydroxide solution is 1 to (1.0-5.0) to (1.0-1.4) to (1.5-2.8).
Preferably, in the alkylation stage reaction of step S2, halogenated compounds such as dimethyl sulfate, diethyl sulfate and chloropropane are generally called alkylating agents, and if O-alkyl hydroxylamine hydrochloride is synthesized, the molar ratio of the alkylating agent to hydroxylamine hydrochloride is: (0.8-1.9) to 1; if the N, O-dialkyl hydroxylamine hydrochloride is synthesized by simultaneously dripping liquid alkali or adding flake alkali, the mol ratio of the alkylating reagent, the liquid alkali and the hydroxylamine hydrochloride is as follows: (2.0-4.0) to 1; wherein the alkylating reagent is dimethyl sulfate, diethyl sulfate, 1-chloropropane, 1-chlorobutane, 1-chloropropene, 1-bromopropane, 1-bromobutane, 1-bromopropylene and the like, and the concentration of the liquid alkali is 5-50%.
Preferably, if O-alkylhydroxylamine hydrochloride is synthesized, the molar ratio of alkylating agent to hydroxylamine hydrochloride is: (0.9-1.2) to 1; if the N, O-dialkyl hydroxylamine hydrochloride is synthesized by simultaneously dripping liquid alkali or adding flake alkali, the mol ratio of the alkylating reagent, the liquid alkali and the hydroxylamine hydrochloride is as follows: (2.0-2.4) to 1; wherein the concentration of the liquid caustic soda is 30-50%.
Preferably, in the hydrolysis purification stage reaction of step S3, the molar ratio of concentrated sulfuric acid to caustic soda flakes and hydroxylamine hydrochloride is: 0.2-2.0: 1.5-4.0: 1.
Preferably, the molar ratio of the concentrated sulfuric acid to the caustic soda flakes and the hydroxylamine hydrochloride is as follows: 0.5-1.0: 2.0-3.0: 1.
Compared with the prior art, the method for preparing the O-alkyl hydroxylamine hydrochloride and the N, O-dialkyl hydroxylamine hydrochloride by the one-pot method disclosed by the invention has the following advantages: 1. the price of the selected methyl acetate is low, the price is only half of that of the ethyl acetate, the molecular weight is small, the dosage is small, the water solubility is better than that of the ethyl acetate, the reaction is faster, the amino protection is more sufficient, the impurities in the subsequent reaction are less, and the byproduct methanol is easy to carry out biochemical treatment; 2. the process is a one-pot method, and the alkylamine is not separated except the final product of distillation, so that the process is time-saving and simple; 3. the process can simply adjust the dosage of the alkylating reagent to respectively prepare O-alkyl hydroxylamine hydrochloride or N, O-dialkyl hydroxylamine hydrochloride with high qualified purity and yield.
Drawings
FIG. 1 is a chemical reaction scheme of O-alkylhydroxylamine hydrochloride of the present invention;
FIG. 2 is a chemical reaction scheme of N, O-dialkylhydroxylamine hydrochloride of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Referring to fig. 1-2, the present invention provides a technical solution: a method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by a one-pot method is characterized by comprising the following steps:
s1 acetylation step: mixing hydroxylamine hydrochloride with water and methyl acetate, dropwise adding a sodium hydroxide solution under stirring at 10-40 ℃, dropwise adding for 1-8 hours, reacting for 1-4 hours, and obtaining an intermediate aqueous solution of acetylhydroxylamine after the reaction is qualified;
s2 alkylation stage: dropping dimethyl sulfate or diethyl sulfate into the reaction kettle at 10-40 ℃ for 1-5 hours without separation, or adding halogenated compounds such as chloropropane and the like, heating for reaction for 5-10 hours, monitoring until the reaction is qualified, and directly carrying out the next reaction without separation;
s3 hydrolysis purification stage: adding concentrated sulfuric acid, heating to 40-80 deg.C, hydrolyzing for 0.5-7 hr, adding caustic soda flakes or liquid caustic soda to regulate pH to 12, and adding O-alkyl hydroxylamine or N, O-dialkyl hydroxylamine. Acidifying with hydrochloric acid gas, cooling for crystallization, and centrifuging and drying to obtain the O-alkyl hydroxylamine hydrochloride or the N, O-dialkyl hydroxylamine hydrochloride.
Further, the S1) acetylation reaction is carried out, wherein the molar ratio of the hydroxylamine hydrochloride, the water, the methyl acetate and the sodium hydroxide solution is 1 to (1.0-8.0) to (1.0-2.0) to (1.1-5.0); the mass fraction of the sodium hydroxide solution is 5-50%.
Further, the S1) acetylation reaction is carried out, wherein the molar ratio of the hydroxylamine hydrochloride, the water, the methyl acetate and the sodium hydroxide solution is 1 to (1.0-5.0) to (1.0-1.4) to (1.5-2.8); the mass fraction of the sodium hydroxide solution is 30-50%
Further, in the alkylation reaction of S2), if O-alkyl hydroxylamine hydrochloride is synthesized, the molar ratio of the alkylating agent to the hydroxylamine hydrochloride is: (0.8-1.9) to 1. If the N, O-dialkyl hydroxylamine hydrochloride is synthesized by simultaneously dripping liquid alkali or adding flake alkali, the molar ratio of the alkylating reagent, the liquid alkali and the hydroxylamine hydrochloride is as follows: (2.0-4.0) to 1. Wherein the alkylating agent is dimethyl sulfate, diethyl sulfate, 1-chloropropane, 1-chlorobutane, 1-chloropropene, 1-bromopropane, 1-bromobutane, 1-bromopropylene, etc., and the concentration of the liquid alkali is 5-50%
Further, in the alkylation reaction of S2), if O-alkyl hydroxylamine hydrochloride is synthesized, the molar ratio of the alkylating agent to the hydroxylamine hydrochloride is: (0.9-1.2) to 1. If the N, O-dialkyl hydroxylamine hydrochloride is synthesized by simultaneously dripping liquid alkali or adding flake alkali, the molar ratio of the alkylating reagent, the liquid alkali and the hydroxylamine hydrochloride is as follows: 2.O-2.4: 2.0-2.4: 1. Wherein the alkylating agent is dimethyl sulfate, diethyl sulfate, 1-chloropropane, 1-chlorobutane, 1-chloropropene, 1-bromopropane, 1-bromobutane, 1-bromopropylene, etc., and the concentration of the liquid alkali is 30-50%
Further, in the hydrolysis purification reaction of S3), the molar ratio of the concentrated sulfuric acid to the caustic soda flakes and the hydroxylamine hydrochloride is: 0.2-2.0: 1.5-4.0: 1.
Further, in the hydrolysis purification reaction of S3), the molar ratio of the concentrated sulfuric acid to the caustic soda flakes and the hydroxylamine hydrochloride is: 0.5-1 to 2.0-3.0 to 1.
Example 1: preparation of N, O-dimethylhydroxylamine hydrochloride
Firstly, mixing 35.0g of hydroxylamine hydrochloride, 36.0g of water and 37.0g of methyl acetate, stirring at 25 ℃, dropwise adding 113.3g of 30% sodium hydroxide solution, dropwise adding for 2 hours, reacting for 1 hour, after passing the detection, dropwise adding 160.0g of dimethyl sulfate into a reaction kettle at 25 ℃, dropwise adding 104.3g of 50% sodium hydroxide solution for 5 hours, reacting for passing the reaction, dropwise adding 49g of concentrated sulfuric acid, heating to 76 ℃, hydrolyzing for 5 hours, slowly adding 80g of 50% liquid alkali after passing the detection, adjusting the pH to 12, steaming N, O-dimethylhydroxylamine under normal pressure, and collecting the distillate at 43-70 ℃. Acidifying with hydrochloric acid gas, cooling for crystallization, filtering, washing with 20ml of cold ethanol twice, and drying to obtain 37.1g of N, O-dimethylhydroxylamine hydrochloride, with yield of 76.1%, white crystal, melting point of 113.2-114.4 deg.C, infrared spectrum consistent with standard spectrum, water content of 0.45%, and purity of 98.5% (titration).
Example 2: preparation of N, O-diethylhydroxylamine hydrochloride
Firstly, 70.0g of hydroxylamine hydrochloride, 72.0g of water and 80.0g of methyl acetate are mixed, stirred at 30 ℃, 240.0g of 30% sodium hydroxide solution is dripped, the dripping time is 1 hour, the reaction is carried out for 3 hours, after the detection is qualified, 323.4g of diethyl sulfate is dripped into a reaction kettle at 35 ℃, 200.5g of 50% sodium hydroxide solution is dripped at the same time, after the dripping time is 2 hours and the reaction is qualified, 98.0g of concentrated sulfuric acid is dripped, the temperature is raised to 80 ℃, the hydrolysis is carried out for 3 hours, 87.0g of caustic soda flakes are slowly added after the detection is qualified, the pH value is adjusted to 12, N, O-diethylhydroxylamine is steamed under normal pressure, and the distillate at. Acidifying with hydrochloric acid gas, cooling for crystallization, filtering and drying to obtain N, O-diethyl hydroxylamine hydrochloride 98.2g with yield of 78.2%, white crystal with melting point of 123.4-125.2 deg.C, infrared spectrum consistent with standard spectrum, water content of 0.31%, and purity of 98.7% (titration).
Example 3: preparation of N, O-dipropylhydroxylamine hydrochloride
Firstly, 700.0g of hydroxylamine hydrochloride, 800.0g of water and 810.0g of methyl acetate are mixed, stirred at 20 ℃, 2200.0g of 40% sodium hydroxide solution is dripped, the dripping time is 2.3 hours, the reaction is carried out for 1.5 hours, after the detection is qualified, 3075g of 1-bromopropane is added into a reaction kettle, 400.0g of sodium hydroxide flake alkali is simultaneously added, the reflux reaction is carried out for 8 hours, after the detection is qualified, the cooling is carried out, 980.0g of concentrated sulfuric acid is dripped, the temperature is increased to 60 ℃, the hydrolysis is carried out for 7 hours, after the detection is qualified, 1200.0g of flake alkali is slowly added, the pH value is adjusted to 12, N, O-dipropylhydroxylamine is steamed under normal pressure, and fractions at. Acidifying with hydrochloric acid gas, cooling for crystallization, filtering and drying to obtain 1246.5g of N, O-dipropyl hydroxylamine hydrochloride, the yield is 81.1%, the white crystal has the melting point of 146.2-148.1 ℃, the infrared spectrum is consistent with the standard spectrum, the water content is 0.48%, and the purity is 98.3% (titration).
Example 4: preparation of O-methylhydroxylamine hydrochloride
Firstly, mixing 35.0g of hydroxylamine hydrochloride, 36.0g of water and 37.0g of methyl acetate, stirring at 20 ℃, dropwise adding 153.3g of 30% sodium hydroxide solution for 2 hours, reacting for 1 hour, after passing the detection, dropwise adding 88.3g of dimethyl sulfate into a reaction kettle at 20 ℃, dropwise adding 5 hours, after passing the reaction, dropwise adding 39.2 g of concentrated sulfuric acid, heating to 75 ℃, hydrolyzing for 5 hours, after passing the detection, slowly adding 40g of caustic soda flakes to adjust the pH value to 12, steaming the O-methylhydroxylamine at normal pressure, and collecting the fraction at 40-67 ℃. Acidifying with hydrochloric acid gas, cooling for crystallization, filtering, and oven drying to obtain O-methyl hydroxylamine hydrochloride 30.2g with yield of 72.5%, white crystal with melting point of 151.2-152.1 deg.C, infrared spectrum consistent with standard spectrum, water content of 0.35%, and purity of 98.5% (titration).
Example 5: preparation of O-ethylhydroxylamine hydrochloride
Mixing 7.0kg of hydroxylamine hydrochloride with 10.0kg of water and 8.0kg of methyl acetate, stirring at 34 ℃, dropwise adding 17.6kg of 50% sodium hydroxide solution for 4 hours, reacting for 1.5 hours, after the detection is qualified, dropwise adding 23.1kg of diethyl sulfate into a reaction kettle at 40 ℃, dropwise adding for 4 hours, after the reaction is qualified, dropwise adding 7.8kg of concentrated sulfuric acid, heating to 60 ℃, hydrolyzing for 8 hours, slowly adding 20.0kg of 40% liquid alkali to adjust the pH value to 12 after the detection is qualified, steaming the O-ethylhydroxylamine at normal pressure, and collecting 60-70 ℃ fractions. Acidifying with hydrochloric acid gas, cooling for crystallization, centrifuging, and oven drying to obtain O-ethylhydroxylamine hydrochloride 7.2kg with yield of 74.2%, white crystal, melting point of 131.4-133.6 deg.C, infrared spectrum consistent with standard spectrum, water content of 0.29%, and purity of 99.1% (titration).
Example 6: preparation of O-propylhydroxylamine hydrochloride
Firstly, 3.5g of hydroxylamine hydrochloride, 6g of water and 3.7g of methyl acetate are mixed, the mixture is stirred at 10 ℃, 12.5g of 35% sodium hydroxide solution is dripped, the dripping time is 1 hour, the reaction is carried out for 2 hours, after the detection is qualified, 8.0g of 1-chloropropane is added into a reaction kettle, the reflux reaction is carried out for 6 hours, after the detection is qualified, the mixture is cooled, 3.9g of concentrated sulfuric acid is dripped, the temperature is raised to 60 ℃, the hydrolysis is carried out for 5 hours, after the detection is qualified, 5.0 pieces of alkali are slowly added to adjust the pH value to 12, the O-propylhydroxylamine is steamed at normal pressure, and. Acidifying with hydrochloric acid gas, cooling for crystallization, filtering, and oven drying to obtain O-propyl hydroxylamine hydrochloride 3.7g, yield 66.4%, white crystal, melting point 155.1-157.0 deg.C, infrared spectrum consistent with standard spectrum, water content 0.43%, and purity 98.2% (titration).
Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that changes, modifications, substitutions and alterations can be made in these embodiments without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (7)
1. A method for preparing O-alkyl hydroxylamine hydrochloride and N, O-dialkyl hydroxylamine hydrochloride by a one-pot method is characterized by comprising the following steps:
s1 acetylation step: mixing hydroxylamine hydrochloride with water and methyl acetate, dropwise adding a sodium hydroxide solution under stirring at 10-40 ℃, dropwise adding for 1-8 hours, reacting for 1-4 hours, and obtaining an intermediate aqueous solution of acetylhydroxylamine after the reaction is qualified;
s2 alkylation stage: dropwise adding dimethyl sulfate or diethyl sulfate into the reaction kettle at the temperature of 10-40 ℃ for 1-5 hours; or adding halogenated compounds such as chloropropane and the like, heating for reaction for 5-10 hours, monitoring until the reaction is qualified, and directly carrying out the next reaction without separation;
s3 hydrolysis purification stage: adding concentrated sulfuric acid, heating to 40-80 deg.C, hydrolyzing for 0.5-7 hr, adding caustic soda flakes or liquid caustic soda to regulate pH to 12, and steaming O-alkyl hydroxylamine or N, O-dialkyl hydroxylamine under normal pressure; acidifying with hydrochloric acid gas, cooling, crystallizing, centrifuging and drying to obtain the O-alkyl hydroxylamine hydrochloride or N, 0-dialkyl hydroxylamine hydrochloride.
2. The one-pot process for the preparation of 0-alkylhydroxylamine hydrochloride and N, 0-dialkylhydroxylamine hydrochloride according to claim 1, wherein: the molar ratio of the hydroxylamine hydrochloride, the water, the methyl acetate and the sodium hydroxide solution in the acetylation step of the step S1 is 1: 1.0-8.0: 1.0-2.0: 1.1-5.0; the mass fraction of the sodium hydroxide solution is 5-50%.
3. The one-pot process for the preparation of O-alkylhydroxylamine hydrochloride and N, O-dialkylhydroxylamine hydrochloride according to claim 2, wherein: the molar ratio of the hydroxylamine hydrochloride, the water, the methyl acetate and the sodium hydroxide solution is 1: 1.0-5.0: 1.0-1.4: 1.5-2.8.
4. The one-pot process for the preparation of O-alkylhydroxylamine hydrochloride and N, 0-dialkylhydroxylamine hydrochloride according to claim 1, wherein: in the alkylation stage reaction of step S2, halogenated compounds such as dimethyl sulfate, diethyl sulfate, and chloropropane are generally referred to as alkylation reagents, and if O-alkyl hydroxylamine hydrochloride is synthesized, the molar ratio of the alkylation reagent to hydroxylamine hydrochloride is: (0.8-1.9) to 1; if the N, O-dialkyl hydroxylamine hydrochloride is synthesized by simultaneously dripping liquid alkali or adding flake alkali, the mol ratio of the alkylating reagent, the liquid alkali and the hydroxylamine hydrochloride is as follows: (2.0-4.0) to 1; wherein the alkylating reagent is dimethyl sulfate, diethyl sulfate, 1-chloropropane, 1-chlorobutane, 1-chloropropene, 1-bromopropane, 1-bromobutane, 1-bromopropylene and the like, and the concentration of the liquid alkali is 5-50%.
5. The one-pot process for the preparation of O-alkylhydroxylamine hydrochloride and N, 0-dialkylhydroxylamine hydrochloride according to claim 4, wherein: if O-alkylhydroxylamine hydrochloride is synthesized, the molar ratio of the alkylating agent to hydroxylamine hydrochloride is: (0.9-1.2) to 1; if the N, O-dialkyl hydroxylamine hydrochloride is synthesized by simultaneously dripping liquid alkali or adding flake alkali, the mol ratio of the alkylating reagent, the liquid alkali and the hydroxylamine hydrochloride is as follows: (2.0-2.4) to 1; wherein the concentration of the liquid caustic soda is 30-50%.
6. The one-pot process for the preparation of O-alkylhydroxylamine hydrochloride and N, O-dialkylhydroxylamine hydrochloride according to claim 1, wherein: in the hydrolysis purification stage reaction of step S3, the molar ratio of concentrated sulfuric acid to caustic soda flakes and hydroxylamine hydrochloride is: 0.2-2.0: 1.5-4.0: 1.
7. The one-pot process for the preparation of 0-alkylhydroxylamine hydrochloride and N, O-dialkylhydroxylamine hydrochloride according to claim 6, wherein: the molar ratio of concentrated sulfuric acid to caustic soda flakes and hydroxylamine hydrochloride is as follows: 0.5-1.0: 2.0-3.0: 1.
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| CN114181107A (en) * | 2021-11-08 | 2022-03-15 | 宁波睿田科技有限公司 | Synthesis method of benzyloxy amine hydrochloride |
| CN114920665A (en) * | 2022-05-24 | 2022-08-19 | 山东师范大学 | Method for separating methoxylamine hydrochloride and N-methylmethoxylamine hydrochloride |
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