A preparation method of 2-(hydroxyimino)acetic acid

Abstract

The present invention provides a method for preparing 2-(hydroxyimino)acetic acid. The method for preparing 2-(hydroxyimino)acetic acid comprises the following steps: mixing chloral hydrate and hydroxylamine hydrochloride to obtain the 2-(hydroxyimino)acetic acid. The method for preparing 2-(hydroxyimino)acetic acid provided by the present invention has a high yield, a simple post-processing process, can achieve scaled-up production, and has strong industrial application value.

Description

Technical Field

[0001] The invention belongs to the technical field of fine chemicals, and specifically relates to a method for preparing 2-(hydroxyimino)acetic acid. Background Art

[0002] 2-(Hydroxyimino)acetic acid, melting point 140-141°C, boiling point 333.9±25°C, is mainly used to manufacture chlorooxime acetate, which is an important pesticide and pharmaceutical intermediate. CN104610249A discloses a method for preparing divalent sulfonyl isoxazole and its derivatives with herbicidal activity by first synthesizing the intermediate 3-chloro-5,5-methyl-4,5-dihydroisoxazoline from 2-(hydroxyimino)acetic acid, and then reacting it with S-5-(4-halogenated-3-methyl-1H-pyrazole)-thioacetic acid methyl ester. The reaction formula is as follows:

[0003]

[0004] There are three main methods for preparing 2-(hydroxyimino)acetic acid reported in the literature. The reaction formula is as follows:

[0005]

[0006] WO2020240391A1 discloses a method for synthesizing 2-(hydroxyimino)acetic acid by heating and hydrolyzing methyl 2-(hydroxyimino)acetate in sodium hydroxide. The yield of the reaction is 80%. The method provided by the invention has a low yield.

[0007] AVZorin et al. used lithium diisopropylamide to remove the α hydrogen on the acetic acid molecule, and synthesized 2-(hydroxyimino)acetic acid with tetrahydrofuran as solvent and alkyl nitrite as oximation reagent, with a yield of 55%. The method provided by the invention has a lower yield (Russ. J. Gen. Chem., 2018, 88(8): 1590-1594).

[0008] The current mainstream method for synthesizing 2-(hydroxyimino)acetic acid is to react with glyoxylic acid and hydroxylamine hydrochloride as raw materials. In the method for synthesizing 2-(hydroxyimino)acetic acid using glyoxylic acid and hydroxylamine hydrochloride as raw materials disclosed in WO2007096576A1, the product yield is 68%; in the method for synthesizing 2-(hydroxyimino)acetic acid using glyoxylic acid and hydroxylamine hydrochloride as raw materials disclosed in CN104610249A, the product yield reaches 91.5%; however, the reaction time of this method is relatively long, and post-processing purification requires extraction and recrystallization; and the raw material glyoxylic acid is generally produced by oxalic acid electrolysis and stored in a 30-50% aqueous solution, which contains 2-3% oxalic acid and 1% glycolic acid, and is highly corrosive. After being placed for half a year to a year, the appearance changes from yellow to reddish brown, and it is extremely unstable when exposed to air. Therefore, the synthesis of 2-(hydroxyimino)acetic acid with glyoxylic acid is often unstable, and the purity or yield of the product fluctuates greatly.

[0009] Therefore, how to provide a preparation method for 2-(hydroxyimino)acetic acid with high yield, simple post-treatment process, and safe and stable production has become a problem to be solved urgently. Summary of the invention

[0010] In view of the shortcomings of the prior art, the object of the present invention is to provide a method for preparing 2-(hydroxyimino)acetic acid. The method for preparing 2-(hydroxyimino)acetic acid provided by the present invention has a high yield, a simple post-treatment process, and can achieve scaled-up production, and has strong industrial application value.

[0011] To achieve this object, the present invention adopts the following technical solutions:

[0012] The present invention provides a method for preparing 2-(hydroxyimino)acetic acid, which comprises the following steps: mixing chloral hydrate and hydroxylamine hydrochloride to obtain the 2-(hydroxyimino)acetic acid;

[0013] The reaction formula is as follows:

[0014]

[0015] The preparation method of 2-(hydroxyimino)acetic acid provided by the present invention has easy-to-obtain raw materials, high yield, and stable yield; the preparation method of 2-(hydroxyimino)acetic acid provided by the present invention has a simple post-processing process, and only needs to desolventize and dry the reaction system to obtain 2-(hydroxyimino)acetic acid; and can achieve scaled-up production, and has strong industrial application value.

[0016] In the present invention, the molar ratio of hydroxylamine hydrochloride to chloral hydrate is (0.5-2):1, for example, it can be 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, etc.; preferably, it is (0.98-1.02):1, for example, it can be 0.98:1, 0.99:1, 1:1, 1.01:1, 1.02:1, etc.

[0017] In the present invention, the temperature of the mixed reaction is 50-100°C, for example, it can be 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, etc.; preferably 50-80°C, 50°C, 55°C, 60°C, 65°C, 70°C, 75°C, 80°C, etc.

[0018] In the present invention, the mixing reaction time is 1-10 h, for example, it can be 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, etc.

[0019] In the present invention, the mixing reaction is carried out in a solvent.

[0020] Preferably, the solvent comprises water.

[0021] In the present invention, the weight ratio of the solvent to chloroacetaldehyde hydrate is (1-10):1, for example, it can be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc.

[0022] In the present invention, desolventizing and drying are required after the mixing reaction.

[0023] In the present invention, the desolventizing is carried out by concentrating under reduced pressure.

[0024] Preferably, the pressure of the reduced pressure concentration is 3000-3500Pa, for example, it can be 3000Pa, 3050Pa, 3100Pa, 3150Pa, 3200Pa, 3250Pa, 3300Pa, 3350Pa, 3400Pa, 3450Pa, 3500Pa, etc.; the temperature of the reduced pressure concentration is 50-80°C, for example, it can be 50°C, 52°C, 54°C, 56°C, 58°C, 60°C, 62°C, 64°C, 66°C, 68°C, 70°C, 72°C, 74°C, 76°C, 78°C, 80°C, etc.

[0025] In the present invention, the drying is carried out by drying.

[0026] Preferably, the drying temperature is 50-80°C, for example, it can be 50°C, 52°C, 54°C, 56°C, 58°C, 60°C, 62°C, 64°C, 66°C, 68°C, 70°C, 72°C, 74°C, 76°C, 78°C, 80°C, etc.; the drying time is 10-20h, for example, it can be 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h, 19h, 20h, etc.

[0027] The preparation method of 2-(hydroxyimino)acetic acid provided by the present invention has a simple post-treatment process. Under preferred reaction conditions, after the reaction is completed, it is only necessary to desolventize the reaction system to obtain a wet solid, and then dry the wet solid to obtain the 2-(hydroxyimino)acetic acid.

[0028] As a preferred technical solution of the present invention, the preparation method of 2-(hydroxyimino)acetic acid comprises the following steps: mixing hydroxylamine hydrochloride, chloroacetaldehyde hydrate and water (1-10) times the weight of chloroacetaldehyde hydrate in a molar ratio of (0.98-1.02):1, reacting at 50-80°C for 1-10h, concentrating under reduced pressure at 3000-3500Pa and 50-80°C, and then drying at 50-80°C for 10-20h to obtain the 2-(hydroxyimino)acetic acid;

[0029] The reaction formula is as follows:

[0030]

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The method for preparing 2-(hydroxyimino)acetic acid provided by the present invention has a yield of more than 95% and a stable yield;

[0033] (2) The preparation method of 2-(hydroxyimino)acetic acid provided by the present invention has a simple post-processing process, and only needs to desolventize and dry the reaction system to obtain 2-(hydroxyimino)acetic acid;

[0034] (3) The method for preparing 2-(hydroxyimino)acetic acid provided by the present invention can realize scale-up production and has strong industrial application value. DETAILED DESCRIPTION

[0035] The technical solution of the present invention is further described below by specific implementation methods. It should be understood by those skilled in the art that the embodiments are only to help understand the present invention and should not be regarded as specific limitations of the present invention.

[0036] All raw materials in the following examples are conventional products that can be purchased through regular channels.

[0037] Example 1

[0038] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0039] 334.2 g of water, 70.6 g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 3000 Pa and 50°C, and then dried at 50°C for 20 h to obtain 88.1 g of white crystals.

[0040] 1 H NMR (DMSO-d6, 300MHz) δ7.60(s,1H,CH),12.62(s,1H,OH),13.88(s, 1H,COOH).ESI-HRMS[M+H] + calcd for C2H4NO3:90.0186,found:90.0191.

[0041] Example 2

[0042] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0043] 501.3 g of water, 69.1 g (purity 98.5%, 0.98 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 60° C. and stirred for 6 h, concentrated under reduced pressure at 3100 Pa at 60° C., and then dried at 60° C. for 20 h to obtain 88.0 g of white crystals.

[0044] Example 3

[0045] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0046] 1671 g of water, 72.0 g (purity 98.5%, 1.02 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 70°C and stirred for 4 h, concentrated under reduced pressure at 70°C at 3200 Pa, and then dried at 70°C for 15 h to obtain 88.1 g of white crystals.

[0047] Example 4

[0048] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0049] 3342 g of water, 706 g (purity 98.5%, 10 mol) of hydroxylamine hydrochloride and 1671 g (purity 99.0%, 10 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 80°C at 3300 Pa, and then dried at 80°C for 10 h to obtain 880.3 g of white crystals.

[0050] Example 5

[0051] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0052] 334.2 g of water, 141.1 g (purity 98.5%, 2 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction flask, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 3400 Pa and 60°C, and then dried at 60°C for 20 h to obtain 158.6 g of white crystals.

[0053] Example 6

[0054] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0055] 334.2 g of water, 84.7 g (purity 98.5%, 1.2 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 70°C at 3500 Pa, and then dried at 70°C for 15 h to obtain 103.5 g of white crystals.

[0056] Example 7

[0057] This embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0058] 334.2 g of water, 67.0 g (purity 98.5%, 0.95 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 50° C. and stirred for 10 h, concentrated under reduced pressure at 80° C. at 3000 Pa, and then dried at 80° C. for 10 h to obtain 85.6 g of white crystals.

[0059] Example 8

[0060] The present embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0061] 334.2 g of water, 35.3 g (purity 98.5%, 0.5 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were put into a reaction bottle in sequence, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 3000 Pa and 50°C, and then dried at 50°C for 20 h to obtain 52.1 g of white crystals.

[0062] Example 9

[0063] The present embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0064] 334.2 g of water, 70.6 g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 45°C and stirred for 12 h, concentrated under reduced pressure at 3200 Pa and 50°C, and then dried at 50°C for 20 h to obtain 83.1 g of white crystals.

[0065] Example 10

[0066] The present embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0067] 334.2 g of water, 70.6 g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 100° C. and stirred for 1 h, concentrated under reduced pressure at 3300 Pa and 70° C., and then dried at 60° C. for 10 h to obtain 74.3 g of white crystals.

[0068] Embodiment 11

[0069] The present embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0070] 334.2 g of water, 70.6 g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 105° C. and stirred for 50 min, concentrated under reduced pressure at 3300 Pa and 60° C., and then dried at 50° C. for 20 h to obtain 91.0 g of white crystals.

[0071] Example 12

[0072] The present embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0073] 334.2 g of pure methanol, 70.6 g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 3300 Pa and 50°C, and then dried at 50°C for 10 h to obtain 121.7 g of white crystals.

[0074] Example 13

[0075] The present embodiment provides a method for preparing 2-(hydroxyimino)acetic acid, and the method for preparing 2-(hydroxyimino)acetic acid comprises the following steps:

[0076] 334.2 g of 50 vol% methanol aqueous solution, 70.6 g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1 g (purity 99.0%, 1 mol) of chloroacetaldehyde hydrate were sequentially put into a reaction bottle, heated to 50°C and stirred for 10 h, concentrated under reduced pressure at 3500 Pa and 50°C, and then dried at 50°C for 10 h to obtain 96.6 g of white crystals.

[0077] Test Case

[0078] Test sample: White crystals obtained after drying in Example 1-13

[0079] Test method: The purity of 2-(hydroxyimino)acetic acid in the test sample was tested by HPLC external standard method; the yield of the reaction was calculated according to the feed amount of raw material hydroxylamine hydrochloride. The test results are shown in Table 1:

[0080] Table 1

[0081]

[0082] As can be seen from the data in Table 1, by adopting the preparation method of 2-(hydroxyimino)acetic acid provided by the present invention (Examples 1-13), the solid obtained after the reaction system is desolventized and dried, the purity of 2-(hydroxyimino)acetic acid is between 3.3-99.0% measured by HPLC external standard method, and the recovery rate is between 4.5-99.1% based on hydroxylamine hydrochloride; by adopting the preparation method of 2-(hydroxyimino)acetic acid provided by the preferred technical scheme of the present invention (Examples 1-3), the solid obtained after the reaction system is desolventized and dried, the purity of 2-(hydroxyimino)acetic acid is between 98.2-99.0% measured by HPLC external standard method, and the recovery rate is between 95.2-99.1% based on hydroxylamine hydrochloride.

[0083] By comparing Example 1 and Example 4, it can be seen that when the feed amount is increased by 10 times, the purity and yield of 2-(hydroxyimino)acetic acid in the obtained product will not be affected, indicating that the preparation method of 2-(hydroxyimino)acetic acid provided by the present invention can be applied to scale-up preparation.

[0084] By comparing Example 1 with Examples 5-8, it can be seen that when the molar ratio of hydroxylamine hydrochloride to chloroacetaldehyde hydrate is outside the preferred range (1.98-1.02), the purity and yield of 2-(hydroxyimino)acetic acid in the obtained product will be seriously affected; when hydroxylamine hydrochloride is relatively excessive, a large amount of hydroxylamine hydrochloride will remain in the product; when chloroacetaldehyde hydrate is relatively excessive, a large amount of chloroacetaldehyde will remain in the product.

[0085] By comparing Example 1 with Examples 9-11, it can be seen that the reaction temperature affects the purity and yield of 2-(hydroxyimino)acetic acid in the obtained product. When the reaction temperature is too low, the progress of the reaction of chloral hydrate and hydroxylamine hydrochloride will be affected, and most of the obtained white crystals are hydroxylamine hydrochloride; when the reaction temperature is too high, the imine in the product is unstable, which will lead to the decomposition of 2-(hydroxyimino)acetic acid.

[0086] By comparing Example 1 with Examples 12-13, it can be seen that the reaction yield is higher when water is used as the solvent, because the raw materials need to be dissolved in water and water participates in the reaction. Most of the white crystals obtained in Example 12 are hydroxylamine hydrochloride and trichloroacetaldehyde.

[0087] The applicant declares that the present invention illustrates a method for preparing 2-(hydroxyimino)acetic acid of the present invention through the above-mentioned embodiments, but the present invention is not limited to the above-mentioned embodiments, that is, it does not mean that the present invention must rely on the above-mentioned embodiments to be implemented. Those skilled in the art should understand that any improvement of the present invention, equivalent replacement of various raw materials of the product of the present invention, addition of auxiliary components, selection of specific methods, etc., all fall within the protection scope and disclosure scope of the present invention.

Claims

1. A method for preparing 2-(hydroxyimino)acetic acid, characterized in that: The preparation method of 2-(hydroxyimino)acetic acid comprises the following steps: mixing chloral hydrate and hydroxylamine hydrochloride to react to obtain the 2-(hydroxyimino)acetic acid; The reaction formula is as follows: The molar ratio of hydroxylamine hydrochloride to chloral hydrate is (0.5-1.9):1; The temperature of the mixed reaction is 50-100°C; The mixed reaction is carried out in a solvent; The solvent contains at least water.

2. The method for preparing 2-(hydroxyimino)acetic acid according to claim 1, wherein The molar ratio of the hydroxylamine hydrochloride to the chloral hydrate is (0.98-1.02):

1.

3. The method for preparing 2-(hydroxyimino)acetic acid according to claim 1, characterized in that The temperature of the mixed reaction is 50-80°C.

4. The method for preparing 2-(hydroxyimino)acetic acid according to claim 1, characterized in that: The mixing reaction time is 1-10h.

5. The method for preparing 2-(hydroxyimino)acetic acid according to claim 1, characterized in that: The weight ratio of the solvent to chloroacetaldehyde hydrate is (1-10):

1.

6. The method for preparing 2-(hydroxyimino)acetic acid according to claim 1, characterized in that: After the mixed reaction, desolventizing and drying are required.

7. The method for preparing 2-(hydroxyimino)acetic acid according to claim 6, characterized in that: The desolventizing is carried out by concentrating under reduced pressure.

8. The method for preparing 2-(hydroxyimino)acetic acid according to claim 7, characterized in that: The pressure of the reduced pressure concentration is 3000-3500Pa, and the temperature of the reduced pressure concentration is 50-80°C.

9. The method for preparing 2-(hydroxyimino)acetic acid according to claim 6, characterized in that: The drying is carried out by oven drying.

10. The method for preparing 2-(hydroxyimino)acetic acid according to claim 9, characterized in that: The drying temperature is 50-80° C., and the drying time is 10-20 hours.

11. The method for preparing 2-(hydroxyimino)acetic acid according to claim 1, characterized in that: The preparation method of 2-(hydroxyimino)acetic acid comprises the following steps: mixing hydroxylamine hydrochloride, chloroacetaldehyde hydrate and water in a molar ratio of (0.5-1.9):1, reacting at 50-100° C. for 1-10 hours, concentrating under reduced pressure at 3000-3500 Pa and 50-80° C., and then drying at 50-80° C. for 10-20 hours to obtain the 2-(hydroxyimino)acetic acid; The reaction formula is as follows:

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