Method for synthesizing alkoxyamine hydrochloride by oxime ether hydrolysis

Abstract

The invention belongs to the technical field of chemical synthesis, and provides a method for synthesizing alkoxyamine hydrochloride by oxime ether hydrolysis. The method for synthesizing the alkoxyamine hydrochloride by oxime ether hydrolysis comprises the following steps: adding a solvent into a hydrolysis system of oxime ether and hydrochloric acid, uniformly mixing, and carrying out reduced pressure hydrolysis. According to the present invention, the specific type of the solvent is added to the hydrolysis system of the oxime ether and the hydrochloric acid, such that the oxime ether and the hydrochloric acid can be completely mixed, the acidification is complete, the hydrolysis is easily performed, the side reaction is reduced, the yield of the alkoxyamine hydrochloride is improved, the yield reaches more than 80%, and the purity reaches more than 90%.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, and in particular to a method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether. Background Technology

[0002] Alkoxyamine hydrochloride is an important organic synthesis intermediate with wide applications in pharmaceuticals, pesticides and other fields. It is usually prepared by hydrolysis of oxime ethers.

[0003] CN101357895B discloses a method for synthesizing methoxyamine hydrochloride. In this method, ethyl acetate and hydroxylamine hydrochloride are added to a reaction vessel, followed by the dropwise addition of a 10-30% (w / w) NaOH solution for oxime reaction. Then, dimethyl sulfate and a 10-30% (w / w) NaOH solution are added for methylation reaction. Subsequently, the mixture is cooled and cold water is added, followed by extraction with a haloalkane solvent. The haloalkane solvent is recovered under reduced pressure at 30-50°C, and the resulting product is added to an inorganic acid solution for hydrolysis. After hydrolysis, hydrochloric acid is used to form the product methoxyamine hydrochloride. CN113402416A discloses a method for preparing methoxyamine hydrochloride, including etherification, distillation separation, hydrolysis, and crystallization drying steps. First, acetone oxime reacts with chloromethane and caustic soda under a catalyst to generate acetone oxime methyl ether, followed by hydrolysis under dilute hydrochloric acid conditions to generate the product methoxyamine hydrochloride. CN110922341A discloses a method for preparing methoxyamine hydrochloride, in which methyl ketone oxime, dimethyl sulfoxide, triethylamine, and a methylating agent are added to a reaction vessel to carry out a methylation reaction to generate methyl ketone oxime methyl ether; then, 30-35% hydrochloric acid is added to the methyl ketone oxime methyl ether for acidification to obtain methoxyamine hydrochloride. CN119143625A discloses a method for preparing alkoxyamine hydrochloride, in which the compound after O-alkylation treatment is hydrolyzed under acidic conditions (temperature 65-90℃), and after hydrolysis, the reaction solution is adjusted to strong alkalinity (pH value adjusted to 13-14), the alkoxyamine is distilled off, and absorbed by concentrated hydrochloric acid to obtain alkoxyamine hydrochloride. Both of these patents simply mention that the hydrolysis stage involves mixing oxime ether with hydrochloric acid, but oxime ether itself has poor water solubility, and when mixed with hydrochloric acid aqueous solution, obvious stratification easily occurs, and side reactions are prone to occur, resulting in poor hydrolysis efficiency and low yield of methoxyamine hydrochloride.

[0004] To address the above shortcomings, this invention provides a method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether. This method ensures thorough mixing of oxime ether and hydrochloric acid aqueous solution, resulting in more complete acidification, which facilitates hydrolysis, effectively reduces side reactions, and improves the yield of alkoxyamine hydrochloride. Summary of the Invention

[0005] The purpose of this invention is to provide a method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether, addressing the shortcomings of existing technologies.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides a method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ethers, comprising the following steps: Add solvent to the hydrolysis system of oxime ether and hydrochloric acid, mix well, and then perform depressurized hydrolysis.

[0007] Preferably, the solvent comprises one or more of methanol, anhydrous ethanol, propanol, isopropanol, tert-butanol, and acetone.

[0008] Preferably, the mass ratio of the oxime ether to the solvent is 1:1~2.

[0009] Preferably, the molar ratio of the oxime ether to HCl in the hydrochloric acid is 1:0.5~4.

[0010] Preferably, the hydrochloric acid has a mass fraction of 5-25%.

[0011] Preferably, the temperature of the depressurized hydrolysis is 5~50℃, and the vacuum degree of the depressurized hydrolysis is -0.1~-0.088MPa.

[0012] Preferably, the oxime ether is a ketoxime methyl ether.

[0013] The beneficial effects of this invention are: This invention improves the yield of alkoxyamine hydrochloride by adding a specific type of solvent to the hydrolysis system of oxime ether and hydrochloric acid, thereby enabling the oxime ether and hydrochloric acid to mix thoroughly, resulting in more complete acidification, better hydrolysis, reduced side reactions, and increased yield of alkoxyamine hydrochloride to over 80% and purity to over 90%. Detailed Implementation

[0014] This invention provides a method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ethers, comprising the following steps: Add solvent to the hydrolysis system of oxime ether and hydrochloric acid, mix well, and then perform depressurized hydrolysis.

[0015] In this invention, the solvent preferably comprises one or more of methanol, anhydrous ethanol, propanol, isopropanol, tert-butanol, and acetone.

[0016] In this invention, the mass ratio of the oxime ether to the solvent is preferably 1:1 to 2, more preferably 1:1.2 to 1.8, and even more preferably 1:1.5.

[0017] In this invention, the molar ratio of the oxime ether to HCl in the hydrochloric acid is preferably 1:0.5~4, more preferably 1:1~3.5, and even more preferably 1:1.5~3.

[0018] In this invention, the mass fraction of the hydrochloric acid is preferably 5-25%, more preferably 10-20%, and even more preferably 15%.

[0019] In this invention, the temperature of the vacuum hydrolysis is preferably 5~50℃, more preferably 10~40℃, and even more preferably 20~30℃; the vacuum degree of the vacuum hydrolysis is preferably -0.1~-0.088MPa, more preferably -0.095~-0.089MPa, and even more preferably -0.09MPa.

[0020] In this invention, the method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether preferably further includes adding water to the system; The water replenishment preferably includes replenishing water to the hydrolysis system before depressurization hydrolysis, or replenishing water directly during depressurization hydrolysis.

[0021] In this invention, the oxime ether is preferably a ketoxime methyl ether.

[0022] In this invention, the ketoxime methyl ether preferably comprises one or more of butanone oxime methyl ether, 2-pentanone oxime methyl ether, 3-pentanone oxime methyl ether, methyl isopropyl ketone oxime methyl ether, methyl isobutyl ketone oxime methyl ether, 2-hexanone oxime methyl ether, 3-hexanone oxime methyl ether, 2-heptanone oxime methyl ether, 3-heptanone oxime methyl ether, and 4-heptanone oxime methyl ether.

[0023] In this invention, the ketoxime methyl ether is preferably synthesized by conventional methods.

[0024] In this invention, the alkoxyamine hydrochloride has the general formula RONH2·HCl, wherein R is preferably a C1~C5 alkyl group.

[0025] In this invention, the alkoxyamine hydrochloride preferably comprises one or more of O-methylhydroxylamine hydrochloride, O-butylhydroxylamine hydrochloride, O-pentylhydroxylamine hydrochloride, O-(4-methylpentyl)hydroxylamine hydrochloride, O-hexylhydroxylamine hydrochloride, and O-heptylhydroxylamine hydrochloride.

[0026] In this invention, the depressurized hydrolysis is preferably terminated when no solvent or other components are distilled off.

[0027] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0028] Example 1

[0029] 50 g of butanone oxime methyl ether and 270 g of 10% hydrochloric acid were added to a hydrolysis reactor to form a hydrolysis system (the molar ratio of butanone oxime methyl ether to HCl was 1:1.5). 50 g of methanol was added to the hydrolysis system, and the mixture was stirred thoroughly for 2 hours to ensure homogeneity. Subsequently, vacuum hydrolysis was carried out at -0.089 MPa until no solvent or ketone was distilled off, yielding a hydrolysate. During vacuum hydrolysis, the temperature was controlled within the range of 5–50 °C, and 50 g of water was added as needed. The hydrolysate was cooled to -5 °C at a rate of 1 °C / min and crystallized at -5 °C for 2 hours. The resulting solution was then filtered to obtain alkoxyamine hydrochloride.

[0030] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 83.31%. The methoxyamine content was determined to be 90.31% by potentiometric titration.

[0031] Example 2

[0032] The difference from Example 1 is that 75g of methanol was added to the hydrolysis system.

[0033] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 85.56%. The methoxyamine content was determined to be 91.39% by potentiometric titration.

[0034] Example 3

[0035] The difference from Example 1 is that 100g of methanol was added to the hydrolysis system.

[0036] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 87.27%. The methoxyamine content was determined to be 92.11% by potentiometric titration.

[0037] Example 4

[0038] The difference from Example 1 is that 50g of anhydrous ethanol was added to the hydrolysis system.

[0039] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 84.73%. The methoxyamine content was determined to be 90.27% by potentiometric titration.

[0040] Example 5

[0041] The difference from Example 1 is that 50g of acetone was added to the hydrolysis system.

[0042] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 82.73%. The methoxyamine content was determined to be 90.74% by potentiometric titration.

[0043] Example 6

[0044] The difference from Example 1 is that 50g of tert-butanol was added to the hydrolysis system.

[0045] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 80.73%. The methoxyamine content was determined to be 90.53% by potentiometric titration.

[0046] Example 7

[0047] The difference from Example 1 is that 50g of butanone oxime methyl ether and 270g of 5% hydrochloric acid (the molar ratio of butanone oxime methyl ether to HCl is 1:0.75) are added to the hydrolysis reactor to form a hydrolysis system.

[0048] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 88.93%. The methoxyamine content was determined to be 91.20% by potentiometric titration.

[0049] Example 8

[0050] The difference from Example 1 is that 50g of butanone oxime methyl ether and 270g of 15% hydrochloric acid (the molar ratio of butanone oxime methyl ether to HCl is 1:2.25) are added to the hydrolysis reactor to form a hydrolysis system.

[0051] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 85.31%. The methoxyamine content was determined to be 90.87% by potentiometric titration.

[0052] Example 9

[0053] The difference from Example 1 is that 50g of butanone oxime methyl ether and 270g of 20% hydrochloric acid (the molar ratio of butanone oxime methyl ether to HCl is 1:3) are added to the hydrolysis reactor to form a hydrolysis system.

[0054] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 83.58%. The methoxyamine content was determined to be 90.33% by potentiometric titration.

[0055] Example 10

[0056] The difference from Example 1 is that 50g of butanone oxime methyl ether and 270g of 25% hydrochloric acid (the molar ratio of butanone oxime methyl ether to HCl is 1:3.75) are added to the hydrolysis reactor to form a hydrolysis system.

[0057] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 82.71%. The methoxyamine content was determined to be 90.16% by potentiometric titration.

[0058] Example 11

[0059] The difference from Example 1 is that 50g of butanone oxime methyl ether and 360g of 10% hydrochloric acid (the molar ratio of butanone oxime methyl ether to HCl is 1:2) are added to the hydrolysis reactor to form a hydrolysis system.

[0060] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 83.97%. The methoxyamine content was determined to be 91.23% by potentiometric titration.

[0061] Example 12

[0062] The difference from Example 1 is that 50g of butanone oxime methyl ether and 540g of 10% hydrochloric acid (the molar ratio of butanone oxime methyl ether to HCl is 1:3) are added to the hydrolysis reactor to form a hydrolysis system.

[0063] The alkoxyamine hydrochloride obtained in this embodiment is methoxyamine hydrochloride, with a yield of 84.13%. The methoxyamine content was determined to be 91.77% by potentiometric titration.

[0064] Comparative Example 1

[0065] The difference from Example 1 is that methanol is not added.

[0066] The alkoxyamine hydrochloride obtained in this comparative example was methoxyamine hydrochloride, with a yield of 60.31%. The methoxyamine content was determined to be 65.71% by potentiometric titration.

[0067] Comparative Example 2

[0068] The difference from Example 1 is that 75g of water was added to the hydrolysis system.

[0069] The alkoxyamine hydrochloride obtained in this comparative example was methoxyamine hydrochloride, with a yield of 63.58%. The methoxyamine content was determined to be 69.74% by potentiometric titration.

[0070] As can be seen from the above embodiments, the present invention provides a method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether. Adding a specific type of solvent to the hydrolysis system of oxime ether and hydrochloric acid can increase the solubility of oxime ether in hydrochloric acid, allowing oxime ether and hydrochloric acid to mix thoroughly, increasing the contact area, making acidification more complete, and facilitating hydrolysis. At the same time, the presence of the solvent increases the stability of the hydrolysis system, making the product alkoxyamine hydrochloride less prone to decomposition, reducing the occurrence of side reactions, and improving the yield of alkoxyamine hydrochloride to over 80% and a purity of over 90%.

[0071] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether, characterized in that, It includes the following steps: Add solvent to the hydrolysis system of oxime ether and hydrochloric acid, mix well, and then perform depressurized hydrolysis.

2. The method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether according to claim 1, characterized in that, The solvent comprises one or more of methanol, anhydrous ethanol, propanol, isopropanol, tert-butanol, and acetone.

3. The method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether according to claim 1 or 2, characterized in that, The mass ratio of the oxime ether to the solvent is 1:1~2.

4. The method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether according to claim 3, characterized in that, The molar ratio of the oxime ether to HCl in the hydrochloric acid is 1:0.5~4.

5. The method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether according to claim 4, characterized in that, The hydrochloric acid has a mass fraction of 5-25%.

6. The method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether according to claim 4 or 5, characterized in that, The temperature of the depressurized hydrolysis is 5~50℃, and the vacuum degree of the depressurized hydrolysis is -0.1~-0.088MPa.

7. The method for synthesizing alkoxyamine hydrochloride by hydrolysis of oxime ether according to claim 6, characterized in that, The oxime ether is a ketoxime methyl ether.