Preparation method of alkoxy amine hydrochloride

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of alkoxyamine hydrochloride, dibasic anhydride is used as a starting material, the alkoxyamine hydrochloride is obtained through aminolysis, alkylation and hydrolysis, C1-C4 alkoxyamine hydrochloride can be prepared through the preparation method provided by the invention, and the alkoxyamine hydrochloride can be prepared by adopting a shrinkage process. The compound II is not separated, the aqueous solution of the compound II is directly used for the next step, the compound III is also directly used for the next step of reaction in a solution form, the process operation is simple, the period is short, the solvent is convenient to recycle and reuse, the waste water is less, and the method has the advantage of industrial popularization.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for preparing alkoxyamine hydrochloride. Background Art

[0002] Alkoxyamine hydrochloride is a widely used and expensive organic chemical intermediate. It is used as an alkoxyamination reagent in organic synthesis. In medicine, it is used to synthesize cefuroxime drugs. In pesticides, it is used to synthesize herbicides such as clethodim and benzophenone. It can also be used as an intermediate in the field of medicine and new pesticide creation, and has broad application prospects.

[0003] At present, the main synthetic routes of alkoxyamine hydrochloride are as follows:

[0004] 1) Using ketone or aldehyde (taking benzaldehyde as an example) as the starting material, alkoxyamine hydrochloride is prepared through oximation, alkylation and hydrolysis with hydroxylamine hydrochloride:

[0005]

[0006] Since oximation and hydrolysis are reversible reactions, the overall yield of this route is not high.

[0007] 2) Sodium nitrite and sodium bisulfite are used as raw materials, sulfur dioxide is introduced to obtain sulfinate, and then alkylation and hydrolysis are performed to obtain alkoxyamine hydrochloride:

[0008]

[0009] Although this route uses cheap industrial-grade inorganic salts to greatly reduce costs, the reaction is violent and prone to explosion, and a large amount of three wastes is produced.

[0010] 3) Using carboxylic acid ester (taking ethyl acetate as an example) as the starting material, alkoxyamine hydrochloride is obtained through aminolysis, alkylation and hydrolysis:

[0011]

[0012] The carboxylate route has cheap raw materials and mild reactions, making it a relatively economical route. However, the ethanol, ethyl acetate, and acetic acid produced by this route are not conducive to solvent recovery and reuse, and the hydroxylamine hydrochloride in the aminolysis step cannot be completely converted, resulting in the derived N,O-dialkylhydroxylamine impurity, which affects the purity of the alkoxyamine hydrochloride and results in a low yield. Summary of the invention

[0013] The purpose of the present invention is to provide a method for preparing alkoxyamine hydrochloride, which uses dibasic acid anhydride as a starting material and obtains the alkoxyamine hydrochloride through aminolysis, alkylation and hydrolysis.

[0014] In order to achieve the above object, the technical solution adopted by the present invention is:

[0015] A method for preparing an alkoxyamine hydrochloride, the chemical structure of which is shown in Formula I below: Wherein R is an alkane group from C1 to C4, and its synthesis route is as follows:

[0016] Wherein R1 is a hydrocarbon group of C2 or more;

[0017] The preparation method comprises the following steps:

[0018] S1. Amine solution: Hydroxylamine hydrochloride is freed with an aqueous solution of an alkali, and then reacted with an acid anhydride in an organic solvent. Water is separated during the reaction. After the reaction is completed, it is extracted with water to obtain an aqueous solution of compound II;

[0019] S2. Alkylation: The aqueous solution of compound II is O-alkylated using an alkylating agent, and the solution of compound III is obtained after post-treatment for the next reaction;

[0020] S3. Hydrolysis: The solution of compound III is hydrolyzed under acidic conditions. After the hydrolysis is completed, the reaction solution is adjusted to a strong alkaline state, the alkoxyamine is evaporated and absorbed with concentrated hydrochloric acid to obtain the alkoxyamine hydrochloride.

[0021] Furthermore, the acid anhydride in S1 is a cyclic anhydride, specifically one of succinic anhydride, glutaric anhydride, phthalic anhydride, and maleic anhydride; the base used for free hydroxylamine hydrochloride is one of an inorganic base, sodium hydroxide or sodium carbonate; and the organic solvent used is toluene or xylene.

[0022] Furthermore, the hydrocarbonating agent is a halogenated hydrocarbon or a sulfate, and the acid-binding agent used in the hydrocarbonating reaction is an organic base or an inorganic base.

[0023] Furthermore, the reaction temperature during the hydrolysis process is 65-90°C, the pH of the reaction solution is adjusted to 13 to 14 after hydrolysis, and the fractions above 50°C are collected to obtain an alkoxyamine aqueous solution, which is absorbed with concentrated hydrochloric acid to obtain an alkoxyamine hydrochloride aqueous solution, and concentrated to remove water to precipitate alkoxyamine hydrochloride.

[0024] The advantages of the present invention are as follows: the preparation method provided by the present invention can prepare C1 to C4 alkoxyamine hydrochlorides, and a telescoping process is adopted, compound II is not separated, the aqueous solution of compound II is directly used in the next step, and compound III is also directly used in the next step reaction in the form of a solution, the process operation is simple and the cycle is short, the solvent is easy to recover and reuse, and less wastewater is produced, which has the advantage of being industrially popularizable. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The present invention discloses a gas phase spectrum of methoxyamine hydrochloride prepared by the preparation method of the present invention. DETAILED DESCRIPTION

[0026] Example

[0027] A method for preparing an alkoxyamine hydrochloride, the chemical structure of which is shown in Formula I below: Wherein R is an alkane group from C1 to C4, and its synthesis route is as follows:

[0028] Wherein R1 is a hydrocarbon group of C2 or more;

[0029] The preparation method comprises the following steps:

[0030] S1. Amine solution: Hydroxylamine hydrochloride is freed with an aqueous solution of an alkali, and then reacted with an acid anhydride in an organic solvent. Water is separated during the reaction. After the reaction is completed, it is extracted with water to obtain an aqueous solution of compound II;

[0031] S2. Alkylation: The aqueous solution of compound II is O-alkylated using an alkylating agent, and the solution of compound III is obtained after post-treatment for the next reaction;

[0032] S3. Hydrolysis: The solution of compound III is hydrolyzed under acidic conditions. After the hydrolysis is completed, the reaction solution is adjusted to a strong alkaline state, the alkoxyamine is evaporated and absorbed with concentrated hydrochloric acid to obtain the alkoxyamine hydrochloride.

[0033] Furthermore, the acid anhydride in S1 is a cyclic anhydride, specifically one of succinic anhydride, glutaric anhydride, phthalic anhydride, and maleic anhydride; the base used for free hydroxylamine hydrochloride is one of an inorganic base, sodium hydroxide or sodium carbonate; and the organic solvent used is toluene or xylene.

[0034] Furthermore, the hydrocarbonating agent is a halogenated hydrocarbon or a sulfate, and the acid-binding agent used in the hydrocarbonating reaction is an organic base or an inorganic base.

[0035] Furthermore, the reaction temperature during the hydrolysis process is 65-90°C, the pH of the reaction solution is adjusted to 13 to 14 after hydrolysis, and the fractions above 50°C are collected to obtain an alkoxyamine aqueous solution, which is absorbed with concentrated hydrochloric acid to obtain an alkoxyamine hydrochloride aqueous solution, and concentrated to remove water to precipitate alkoxyamine hydrochloride.

[0036] Specific experimental examples

[0037] In the following experimental cases, the reaction was monitored by TLC and visualized using ethanolic phosphomolybdic acid solution.

[0038] A method for preparing alkoxyamine hydrochloride, the specific detailed preparation steps are as follows:

[0039] 1. Preparation of Compound II:

[0040] Preparation of compound II-a:

[0041] Method 1:

[0042]

[0043] Add hydroxylamine hydrochloride (24.8 g, 0.356 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator. Dissolve caustic soda flakes (14.27 g, 0.356 moL) in 15 g of water and then add dropwise. Add succinic anhydride (35 g, 0.349 moL) and 135 g of toluene. Raise the temperature to 105 to 110°C for reaction. Release the lower layer of water in the water separator during the reaction. After 8 hours, TLC detection (developing agent methanol: water: glacial acetic acid = 30:1:1) shows that there is no obvious residue of hydroxylamine hydrochloride. Cool to 30 to 40°C, extract with 60 g of water × 3 to obtain compound II-a, i.e., N-hydroxysuccinimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0044] Method 2:

[0045] The difference between method 2 and method 1 is that xylene is used as solvent, the reaction temperature is increased, and the reaction time is shortened.

[0046]

[0047] Add hydroxylamine hydrochloride (24.5 g, 0.353 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator. Dissolve caustic soda flakes (14.2 g, 0.355 moL) in 15 g of water and then add dropwise. Add succinic anhydride (35 g, 0.349 moL) and 130 g of xylene. Heat to 130°C for reaction. Release the water in the lower layer of the water separator during the reaction. After 5 hours, TLC detection (developing solvent methanol: water: glacial acetic acid = 30:1:1) showed that the hydroxylamine hydrochloride was completely converted. Cool to 30 to 40°C, extract with 60 g of water × 3 to obtain compound II-a, i.e., N-hydroxysuccinimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0048] Method 3:

[0049]

[0050] Method 3 differs from method 1 in that sodium carbonate is used as a base to free hydroxylamine hydrochloride.

[0051] Add hydroxylamine hydrochloride (24.28 g, 0.350 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator. Dissolve sodium carbonate (20.39 g, 0.192 moL) in 50 g of water and add dropwise. After the addition is complete, add succinic anhydride (35 g, 0.349 moL) and 130 g of toluene. Raise the temperature to 110°C for reaction. Release the lower layer of water in the water separator during the reaction. After 9 hours, TLC detection (developing solvent methanol: water: glacial acetic acid = 30:1:1) shows that the hydroxylamine hydrochloride is completely converted. Cool to 30 to 40°C, extract with 70 g of water × 3 times to obtain compound II-a, i.e., N-hydroxysuccinimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0052] Preparation of compound II-b:

[0053] Method 1:

[0054]

[0055] Add hydroxylamine hydrochloride (24.89 g, 0.358 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator, dissolve caustic soda flakes (14.56 g, 0.364 moL) in 15 g of water and then add dropwise, add maleic anhydride (35 g, 0.357 moL) and 135 g of toluene, and heat to 105 to 110°C for reaction. During the reaction, release the water in the lower layer of the water separator. After 8 hours, perform TLC detection (developing agent methanol: water: glacial acetic acid = 30:1:1), use phosphomolybdic acid for color development, and the hydroxylamine hydrochloride is completely converted. Cool to 30 to 40°C, extract with 60 g of water × 3 times, and obtain compound II-b, i.e., N-hydroxysuccinimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0056] Method 2:

[0057]

[0058] Method 2 differs from method 1 in that inorganic base sodium carbonate is used to free hydroxylamine hydrochloride.

[0059] Add hydroxylamine hydrochloride (25.8 g, 0.371 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator, dissolve sodium carbonate (20.1 g, 0.189 moL) in 50 g of water and then add dropwise, add maleic anhydride (35 g, 0.357 moL) and 135 g of toluene, and heat to 105 to 110°C for reaction. During the reaction, release the lower layer of water in the water separator. After 8 hours, perform TLC detection (developing agent methanol: water: glacial acetic acid = 30:1:1), use phosphomolybdic acid for color development, and the hydroxylamine hydrochloride is completely converted. Cool to 30 to 40°C, extract with 60 g of water × 3 times, and obtain compound II-b, i.e., N-hydroxymaleimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0060] Preparation of compound II-c:

[0061]

[0062] Add hydroxylamine hydrochloride (16.6 g, 0.239 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator, dissolve caustic soda flakes (9.55 g, 0.238 moL) in 15 g of water and then add dropwise, add phthalic anhydride (34.9 g, 0.236 moL) and 135 g of toluene, raise the temperature to 105 to 110°C for reaction, separate the lower layer of water during the reaction, and perform TLC detection after 8 hours (developing agent methanol: water: glacial acetic acid = 30:1:1), use phosphomolybdic acid for color development, and observe a small amount of residual hydroxylamine hydrochloride. Cool to 40 to 50°C, extract with 80 g of water × 3, and obtain compound II-c, i.e., N-hydroxyphthalimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0063] Preparation of compound II-d:

[0064]

[0065] Add hydroxylamine hydrochloride (21.25 g, 0.306 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator, dissolve caustic soda flakes (12.39 g, 0.31 moL) in 15 g of water and then add dropwise, add glutaric anhydride (34.8 g, 0.306 moL) and 135 g of toluene, and heat to 105 to 110° C. for reaction. During the reaction, release the water in the lower layer of the water separator. After 8 hours, perform TLC detection (developing agent methanol: water: glacial acetic acid = 30:1:1), use phosphomolybdic acid for color development, and the hydroxylamine hydrochloride residue is not obvious. Cool to 40 to 50° C., extract with 80 g of water × 3 times, and obtain compound II-d, i.e., N-hydroxyglutarimide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0066] Preparation of compound II-e:

[0067]

[0068] Add hydroxylamine hydrochloride (19.63 g, 0.278 moL) into a glass bottle equipped with a stirrer, a thermometer and a water separator, dissolve caustic soda flakes (11.14 g, 0.278 moL) in 15 g of water and then add dropwise, add adipic anhydride (39 g, 0.306 moL) and 140 g of xylene, and heat to 130°C for reaction. During the reaction, release the water in the lower layer of the water separator. After 6 hours, perform TLC detection (developing agent methanol: water: glacial acetic acid = 30:1:1), use phosphomolybdic acid for color development, and the hydroxylamine hydrochloride is completely converted. Cool to 40 to 50°C, extract with 80 g of water × 3 times, and obtain compound II-e, i.e., N-hydroxyadipic imide aqueous solution, which is directly used in the next hydrocarbonization reaction.

[0069] 2. Preparation of Compound III:

[0070] Preparation of compound III-a1:

[0071] Method 1:

[0072]

[0073] Add an aqueous solution of compound II-a (prepared from 35 g of succinic anhydride) to a glass bottle equipped with a stirrer and a thermometer. Add caustic soda (15.4 g, 0.384 moL) in an ice-water bath to dissolve it, then add iodomethane (59.57 g, 0.419 moL) dropwise. After the addition is complete, raise the temperature to 35 to 40°C and react for 12 hours. TLC detection (developing solvent: dichloromethane: methanol = 4:1) shows that compound II-a is completely converted. If there is any residue, add an appropriate amount of iodomethane to complete the conversion. After the reaction is complete, cool to room temperature, add 20 g of 10% sodium thiosulfate aqueous solution, wash until the reaction solution is colorless, and use it for the next hydrolysis step.

[0074] Method 2:

[0075] Method 2 differs from Method 1 in that dimethyl sulfate is used for alkylation.

[0076]

[0077] Add an aqueous solution of compound II-a (prepared from 35 g of succinic anhydride) to a glass bottle equipped with a stirrer and a thermometer. Add caustic soda (14.2 g, 0.355 moL) in an ice-water bath and stir to dissolve. Warm to room temperature and drop dimethyl sulfate (41.8 g, 0.331 moL) for 2 to 3 hours. During the addition, control the internal temperature at 20 to 30°C. After the addition is complete, continue stirring at room temperature for 3 hours. TLC detection (developing solvent: dichloromethane: methanol = 4:1) shows that compound II-a is completely converted. If there is any residue, add an appropriate amount of dimethyl sulfate to complete the conversion. After the reaction is complete, cool to room temperature and use it directly in the next hydrolysis step.

[0078] Preparation of compound III-a2:

[0079]

[0080] In a glass bottle equipped with a stirrer and a thermometer, an aqueous solution of compound II-a (prepared from 35 g of succinic anhydride) was added, and caustic soda (13.8 g, 0.345 moL) was added under an ice-water bath, stirred to dissolve, and ethyl bromide (45.73 g, 0.419 moL) was added dropwise. After the addition was complete, the temperature was raised to 40°C and the reaction was allowed to proceed for 15 h. According to TLC detection (developing solvent: dichloromethane: methanol = 4:1), compound II-a was completely converted. The mixture was cooled to room temperature, and 20 g of a 10% aqueous sodium thiosulfate solution was added to wash until the reaction solution was colorless for use in the next hydrolysis step.

[0081] Preparation of compound III-b1:

[0082]

[0083] Add an aqueous solution of compound II-b (prepared from 35 g of maleic anhydride) into a glass bottle equipped with a stirrer and a thermometer, add caustic soda (15.5 g, 0.39 moL) under an ice-water bath, stir to dissolve, add iodomethane (61 g, 0.43 moL) dropwise, and after the addition is complete, heat to 40°C in a dark environment and react for 15 h. TLC detection (developing solvent: dichloromethane: methanol = 4:1) shows that compound II-b is completely converted. Cool to room temperature, add 30 g of 10% sodium thiosulfate aqueous solution, wash until the reaction solution is colorless, and cool to room temperature to obtain a solution of compound III-b1 for the next hydrolysis step.

[0084] Preparation of compound III-b2:

[0085]

[0086] In a glass bottle equipped with a stirrer and a thermometer, an aqueous solution of compound II-b (prepared from 35 g of maleic anhydride) was added, and caustic soda (15.2 g, 0.38 moL) was added under an ice-water bath, stirred to dissolve, and ethyl bromide (46.67 g, 0.428 moL) was added dropwise. After the addition was complete, the temperature was raised to 40°C and the reaction was allowed to proceed for 15 h. According to TLC detection (developing solvent: dichloromethane: methanol = 4:1), compound II-b was completely converted. The mixture was cooled to room temperature, and 30 g of 10% sodium thiosulfate aqueous solution was added to wash until the reaction solution was colorless. The temperature was lowered to room temperature for the next hydrolysis step.

[0087] Preparation of compound III-c:

[0088]

[0089] Add an aqueous solution of compound II-c (prepared from 35 g of phthalic anhydride) into a glass bottle equipped with a stirrer and a thermometer, add caustic soda (9.56 g, 0.239 moL) under an ice-water bath, stir to dissolve, add ethyl bromide (28.32 g, 0.259 moL) dropwise, and after the addition is complete, raise the temperature to 40°C and react for 18 hours. TLC detection (developing solvent: dichloromethane: methanol = 4:1) shows that compound II-c is completely converted, and cool to room temperature for the next hydrolysis step.

[0090] Preparation of compound III-d:

[0091]

[0092] Add an aqueous solution of compound II-d (prepared from 35 g of phthalic anhydride) into a glass bottle equipped with a stirrer and a thermometer, add flake caustic soda (14.18 g, 0.354 moL) under an ice-water bath, stir to dissolve, add bromopropane (31.9 g, 0.26 moL) dropwise, and after the addition is complete, raise the temperature to 65°C and react for 8 hours. TLC detection (developing solvent: dichloromethane: methanol = 4:1) shows that compound II-d is completely converted, and cool to room temperature to obtain an aqueous solution of compound III-d for the next hydrolysis step.

[0093] Preparation of compound III-e:

[0094]

[0095] Add an aqueous solution of compound II-d (prepared from 35 g of phthalic anhydride) into a glass bottle equipped with a stirrer and a thermometer, add flake caustic soda (14.18 g, 0.354 moL) under an ice-water bath, stir to dissolve, add bromopropane (31.9 g, 0.26 moL) dropwise, and after the addition is complete, raise the temperature to 65°C and react for 8 hours. TLC detection (developing solvent: dichloromethane: methanol = 4:1) shows that compound II-d is completely converted, and cool to room temperature to obtain an aqueous solution of compound III-d for the next hydrolysis step.

[0096] 3. Preparation of alkoxyamine hydrochloride:

[0097] 1. Preparation of methoxyamine hydrochloride:

[0098] Method 1: Preparation by hydrolysis of compound III-a1

[0099]

[0100] To a solution of compound III-a1 (prepared from 35 g of the starting material succinic anhydride), add 57 g of concentrated hydrochloric acid, raise the temperature to 80 to 90 ° C and react for 4 hours, then cool to room temperature, adjust the pH to 14 with liquid alkali, start atmospheric distillation, collect the 50 to 95 ° C fraction, which is a methoxyamine aqueous solution, absorb it with 31 g of concentrated hydrochloric acid to obtain a methoxyamine hydrochloride aqueous solution, concentrate and remove the solution volume to about 1 / 4, continue stirring at 5 ° C for 30 min, filter to obtain methoxyamine hydrochloride, filter and dry with air to obtain 18.6 g of solid, with a molar yield of 64.1%.

[0101] Method 2: Preparation by hydrolysis of compound III-b1

[0102]

[0103] To the solution of compound III-b1 (prepared from 35 g of starting material maleic anhydride), add 57 g of concentrated hydrochloric acid, raise the temperature to 65°C for reaction for 7 h, cool to room temperature, adjust the pH to 14 with liquid alkali, start atmospheric distillation, collect the fraction from 50 to 95°C, which is the methoxyamine aqueous solution, absorb it with 31 g of concentrated hydrochloric acid to obtain methoxyamine hydrochloride aqueous solution, concentrate and remove the solution volume to about 1 / 4, continue to stir at 5°C, filter to obtain methoxyamine hydrochloride, filter and dry with air to obtain 20.6 g of solid with a molar yield of 69.2%.

[0104] Method 3: Preparation by hydrolysis of compound III-e:

[0105]

[0106] To the solution of compound III-e (prepared from 35 g of starting material adipic anhydride), add 48 g of concentrated hydrochloric acid, raise the temperature to 65°C, react for 7 h, cool to room temperature, adjust the pH to 14 with liquid alkali, start atmospheric distillation, collect the 50 to 95°C fraction, which is the methoxyamine aqueous solution, absorb it with 28 g of concentrated hydrochloric acid to obtain methoxyamine hydrochloride aqueous solution, concentrate and remove the solution volume to about 1 / 4, cool to 0 to 5°C, stir, filter, and obtain methoxyamine hydrochloride. After filtration, dry it with air to obtain 16.7 g of solid, with a molar yield of 73.6%.

[0107] 2. Preparation of ethoxyamine hydrochloride:

[0108] Method 1: Preparation of ethoxyamine hydrochloride by hydrolysis of compound III-b2

[0109]

[0110] To a solution of compound III-b2 (prepared from 35 g of starting material maleic anhydride), add 60 g of concentrated hydrochloric acid, raise the temperature to 65 ° C for reaction for 7 h, cool to room temperature, adjust the pH to 14 with liquid alkali, start atmospheric distillation, collect the 50 to 105 ° C fraction, which is an ethoxyamine aqueous solution, absorb it with 33 g of concentrated hydrochloric acid to obtain a methoxyamine hydrochloride aqueous solution, concentrate and remove the solution volume to about 1 / 4, continue to cool to 0 to 5 ° C with stirring, filter to obtain ethoxyamine hydrochloride, filter and air dry to obtain 22.78 g of solid, with a molar yield of 65.3%.

[0111] Method 2: Preparation of ethoxyamine hydrochloride by hydrolysis of compound III-c

[0112]

[0113] To a solution of compound III-c (prepared from 35 g of phthalic anhydride as the starting material), add 41 g of concentrated hydrochloric acid, heat to 65 ° C for reaction for 7 h, cool to room temperature, adjust the pH to 14 with liquid alkali, start atmospheric distillation, collect the 50 to 105 ° C fraction, which is an ethoxyamine aqueous solution, absorb it with 24 g of concentrated hydrochloric acid to obtain an ethoxyamine hydrochloride aqueous solution, concentrate and remove the solution volume to about 1 / 4, continue to cool to 0 to 5 ° C, stir, filter, and obtain ethoxyamine hydrochloride. After filtration, air dry to obtain 15.47 g of ethoxyamine hydrochloride with a molar yield of 67.2%.

[0114] 3. Preparation of propoxylamine hydrochloride:

[0115]

[0116] To the solution of compound III-d (prepared from 35 g of the starting material phthalic anhydride), add 42 g of concentrated hydrochloric acid, raise the temperature to 65 ° C for reaction for 7 h, cool to room temperature, adjust the pH to 14 with liquid alkali, start atmospheric distillation, collect the 50 to 120 ° C fraction, which is the propoxylamine aqueous solution, absorb it with 24 g of concentrated hydrochloric acid to obtain an aqueous solution of propoxylamine hydrochloride, concentrate and remove the solution volume to about 1 / 4, continue to cool to 0 to 5 ° C, stir, filter, obtain propoxylamine hydrochloride, filter and air dry to obtain 12.1 g of propoxylamine hydrochloride, with a molar yield of 68.4%.

Claims

1. A method for preparing an alkoxyamine hydrochloride, characterized in that: Its chemical structure is shown in the following formula I: Wherein R is an alkane group from C1 to C4, and its synthesis route is as follows: Wherein R1 is a hydrocarbon group of C2 or more; The preparation method comprises the following steps: S1. Amine solution: Hydroxylamine hydrochloride is freed with an aqueous solution of an alkali, and then reacted with an acid anhydride in an organic solvent. Water is separated during the reaction. After the reaction is completed, it is extracted with water to obtain an aqueous solution of compound II; S2. Alkylation: The aqueous solution of compound II is O-alkylated using an alkylating agent, and the solution of compound III is obtained after post-treatment for the next reaction; S3. Hydrolysis: The solution of compound III is hydrolyzed under acidic conditions. After the hydrolysis is completed, the reaction solution is adjusted to a strong alkaline state, the alkoxyamine is evaporated and absorbed with concentrated hydrochloric acid to obtain the alkoxyamine hydrochloride.

2. The method for preparing an alkoxyamine hydrochloride according to claim 1, wherein: The acid anhydride in S1 is a cyclic anhydride, specifically one of succinic anhydride, glutaric anhydride, phthalic anhydride and maleic anhydride; the base used for free hydroxylamine hydrochloride is one of an inorganic base, sodium hydroxide or sodium carbonate; and the organic solvent used is toluene or xylene.

3. The method for preparing the alkoxyamine hydrochloride according to claim 1, characterized in that: The hydrocarbonating agent is a halogenated hydrocarbon or a sulfate, and the acid-binding agent used in the hydrocarbonating reaction is an organic base or an inorganic base.

4. The method for preparing the alkoxyamine hydrochloride according to claim 3, characterized in that: The reaction temperature during the hydrolysis process is 65-90°C. After the hydrolysis, the pH of the reaction solution is adjusted to 13 to 14, and the fractions above 50°C are collected to obtain an alkoxyamine aqueous solution, which is absorbed with concentrated hydrochloric acid to obtain an alkoxyamine hydrochloride aqueous solution, and concentrated to remove water to precipitate the alkoxyamine hydrochloride.

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