CN116102454A - Preparation method of 2- (hydroxyimino) acetic acid - Google Patents
Preparation method of 2- (hydroxyimino) acetic acid Download PDFInfo
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- CN116102454A CN116102454A CN202111324191.3A CN202111324191A CN116102454A CN 116102454 A CN116102454 A CN 116102454A CN 202111324191 A CN202111324191 A CN 202111324191A CN 116102454 A CN116102454 A CN 116102454A
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- C07C249/00—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C249/04—Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes
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Abstract
The invention provides a preparation method of 2- (hydroxyimino) acetic acid. The preparation method of the 2- (hydroxyimino) acetic acid comprises the following steps: mixing chloral hydrate and hydroxylamine hydrochloride to react, and obtaining the 2- (hydroxyimino) acetic acid. The preparation method of the 2- (hydroxyimino) acetic acid provided by the invention has the advantages of higher yield, simple post-treatment process, realization of amplified production and stronger industrial application value.
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of 2- (hydroxyimino) acetic acid.
Background
2- (hydroxyimino) acetic acid, with a melting point of 140-141 ℃ and a boiling point of 333.9 + -25 ℃, is mainly used for preparing chlorooximido acetate, and the chlorooximido acetate is an important pesticide and medical intermediate. CN104610249a discloses a method for preparing a bivalent sulfonyl isoxazole and its derivatives with herbicidal activity by synthesizing an intermediate 3-chloro-5, 5-methyl-4, 5-dihydro-isoxazoline from 2- (hydroxyimino) acetic acid, and then reacting with S-5- (4-halo-3-methyl-1H-pyrazole) -thioacetate methyl ester, wherein the reaction formula is shown as follows:
the preparation methods for synthesizing 2- (hydroxyimino) acetic acid reported in the current literature mainly comprise three methods, and the reaction formulas are shown as follows:
WO2020240391A1 discloses a process for the thermal hydrolysis of methyl 2- (hydroxyimino) acetate in sodium hydroxide to 2- (hydroxyimino) acetic acid in a reaction yield of 80% which provides a process with a lower yield.
The method provided by the invention has low yield (Russ.J.Gen.chem., 2018,88 (8): 1590-1594).
The current mainstream method for synthesizing 2- (hydroxyimino) acetic acid is to react glyoxylate and hydroxylamine hydrochloride as raw materials. In the method for synthesizing 2- (hydroxyimino) acetic acid by taking glyoxylic acid and hydroxylamine hydrochloride as raw materials disclosed in WO2007096576A1, the product yield is 68%; the product yield in the synthesis method for synthesizing 2- (hydroxyimino) acetic acid by taking glyoxylic acid and hydroxylamine hydrochloride as raw materials disclosed in CN104610249A reaches 91.5%; however, the method has longer reaction time, and the post-treatment purification needs extraction and recrystallization; the raw material glyoxylate is generally produced by an oxalic acid electrolysis method, is stored in 30-50% aqueous solution, contains 2-3% oxalic acid and 1% glycolic acid, has strong corrosiveness, changes from yellow to reddish brown in appearance after being placed for half a year to one year, and is extremely unstable in air contact. Therefore, the synthesis of 2- (hydroxyimino) acetic acid with glyoxylate tends to be unstable, and the product purity or yield fluctuates greatly.
Therefore, how to provide a preparation method with higher yield, simple post-treatment process and capability of realizing safe and stable production of 2- (hydroxyimino) acetic acid is a problem to be solved at present.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a preparation method of 2- (hydroxyimino) acetic acid. The preparation method of the 2- (hydroxyimino) acetic acid provided by the invention has the advantages of higher yield, simple post-treatment process, realization of amplified production and stronger industrial application value.
To achieve the purpose, the invention adopts the following technical scheme:
the invention provides a preparation method of 2- (hydroxyimino) acetic acid, which 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 preparation method of the 2- (hydroxyimino) acetic acid provided by the invention has the advantages of easily available raw materials, higher yield and stable yield; the preparation method of the 2- (hydroxyimino) acetic acid provided by the invention has simple post-treatment process, and the 2- (hydroxyimino) acetic acid can be obtained only by desolventizing and drying the reaction system; but also can realize the amplified production and has stronger industrial application value.
In the present invention, the molar ratio of hydroxylamine hydrochloride to chloral hydrate is (0.5-2): 1, and may be, for example, 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 (0.98-1.02): 1, for example, 0.98:1, 0.99:1, 1:1, 1.01:1, 1.02:1, etc. are possible.
In the present invention, the temperature of the mixing reaction is 50 to 100℃and may be, for example, 50℃55℃60℃65℃70℃75℃80℃85℃90℃95℃100℃or the like; preferably 50-80deg.C, 50deg.C, 55deg.C, 60deg.C, 65deg.C, 70deg.C, 75deg.C, 80deg.C, etc.
In the present invention, the mixing reaction time is 1 to 10 hours, and may be, for example, 1 hour, 2 hours, 3 hours, 4h, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, etc.
In the present invention, the mixing reaction is performed in a solvent.
Preferably, the solvent comprises water.
In the present invention, the weight ratio of the solvent to chloral hydrate is (1-10): 1, and may be, for example, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc.
In the present invention, desolventizing and drying are also required after the mixing reaction.
In the present invention, the desolventizing is performed by concentrating under reduced pressure.
Preferably, the pressure of the reduced pressure concentration is 3000-3500Pa, for example, 3000Pa, 3050Pa, 3100Pa, 3150Pa, 3200Pa, 3250Pa, 3300Pa, 3350Pa, 3400Pa, 3450Pa, 3500Pa, etc.; the reduced pressure concentration temperature is 50-80deg.C, such as 50deg.C, 52deg.C, 54 deg.C, 56 deg.C, 58 deg.C, 60 deg.C, 62 deg.C, 64 deg.C, 66 deg.C, 68 deg.C, 70 deg.C, 72 deg.C, 74 deg.C, 76 deg.C, 78 deg.C, 80 deg.C, etc.
In the invention, the drying is performed by drying.
Preferably, the temperature of the drying is 50-80 ℃, for example, 50 ℃, 52 ℃, 54 ℃, 56 ℃, 58 ℃, 60 ℃, 62 ℃, 64 ℃, 66 ℃, 68 ℃, 70 ℃, 72 ℃, 74 ℃, 76 ℃, 78 ℃, 80 ℃ and the like; the drying time is 10-20h, for example, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 17h, 18h, 19h, 20h, etc.
The preparation method of the 2- (hydroxyimino) acetic acid provided by the invention has the advantages that the post-treatment process is simple, under the preferable reaction condition, after the reaction is finished, the reaction system is only required to be desolventized to obtain a wet solid, and then the wet solid is dried to obtain the 2- (hydroxyimino) acetic acid.
As a preferred technical scheme of the invention, the preparation method of the 2- (hydroxyimino) acetic acid comprises the following steps: mixing hydroxylamine hydrochloride, chloral hydrate and water with the weight portion of (1-10) times of chloral hydrate with the molar ratio of (0.98-1.02), reacting for 1-10 hours at 50-80 ℃, concentrating under reduced pressure at the pressure of 3000-3500Pa and 50-80 ℃, and drying for 10-20 hours at the temperature of 50-80 ℃ to obtain the 2- (hydroxyimino) acetic acid;
the reaction formula is as follows:
compared with the prior art, the invention has the following beneficial effects:
(1) According to the preparation method of the 2- (hydroxyimino) acetic acid, the yield of the preferable technical scheme reaches more than 95%, and the yield is stable;
(2) The preparation method of the 2- (hydroxyimino) acetic acid provided by the invention has simple post-treatment process, and the 2- (hydroxyimino) acetic acid can be obtained only by desolventizing and drying the reaction system;
(3) The preparation method of the 2- (hydroxyimino) acetic acid provided by the invention can realize the amplified production and has a relatively high industrial application value.
Detailed Description
The technical scheme of the invention is further described by the following specific embodiments. It will be apparent to those skilled in the art that the examples are merely to aid in understanding the invention and are not to be construed as a specific limitation thereof.
The starting materials in the examples below are all conventional products commercially available through regular channels.
Example 1
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 70.6g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 3000Pa pressure of 50℃and then dried at 50℃for 20 hours, whereby 88.1g of white crystals were obtained.
1 H NMR(DMSO-d 6 ，300MHz)δ7.60(s,1H,CH),12.62(s,1H,OH),13.88(s， 1H,COOH).ESI-HRMS[M+H] + calcd for C 2 H 4 NO 3 :90.0186,found:90.0191.
Example 2
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
501.3g of water, 69.1g (purity: 98.5%, 0.98 mol) of hydroxylamine hydrochloride and 167.1g (purity: 99.0%, 1 mol) of chloral hydrate were successively charged into a reaction flask, heated to 60℃and stirred for 6 hours, concentrated under reduced pressure at 60℃under 3100Pa, and then dried at 60℃for 20 hours, to obtain 88.0g of white crystals.
Example 3
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
1671g of water, 72.0g (purity 98.5%, 1.02 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate are put into a reaction flask in sequence, heated to 70 ℃ and stirred for 4 hours, concentrated under reduced pressure at 70 ℃ under the pressure of 3200Pa, and then dried at 70 ℃ for 15 hours, to obtain 88.1g of white crystals.
Example 4
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
3342g of water, 706g (purity 98.5%, 10 mol) of hydroxylamine hydrochloride and 1671g (purity 99.0%, 10 mol) of chloral hydrate were put into a reaction flask in this order, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 3300Pa pressure of 80℃and then dried at 80℃for 10 hours to give 880.3g of white crystals.
Example 5
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 141.1g (purity 98.5%, 2 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were put into a reaction flask in this order, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 60℃under a pressure of 3400Pa, and then dried at 60℃for 20 hours to obtain 158.6g of white crystals.
Example 6
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 84.7g (purity 98.5%, 1.2 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 70℃under a pressure of 350Pa, and then dried at 70℃for 15 hours, whereby 103.5g of white crystals were obtained.
Example 7
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 67.0g (purity 98.5%, 0.95 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 80℃under 3000Pa, and then dried at 80℃for 10 hours, to obtain 85.6g of white crystals.
Example 8
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 35.3g (purity 98.5%, 0.5 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 3000Pa pressure of 50℃and then dried at 50℃for 20 hours, to obtain 52.1g of white crystals.
Example 9
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 70.6g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 45℃and stirred for 12 hours, concentrated under reduced pressure at a pressure of 3200Pa and 50℃and then dried at 50℃for 20 hours, whereby 83.1g of white crystals were obtained.
Example 10
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 70.6g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 100℃and stirred for 1h, concentrated under reduced pressure at 70℃under 3300Pa, and then dried at 60℃for 10h, to obtain 74.3g of white crystals.
Example 11
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of water, 70.6g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were put into a reaction flask in this order, heated to 105℃and stirred for 50 minutes, concentrated under reduced pressure at 60℃under 3300Pa, and then dried at 50℃for 20 hours to obtain 91.0g of white crystals.
Example 12
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of pure methanol, 70.6g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 50℃under 3300Pa, and then dried at 50℃for 10 hours, to obtain 121.7g of white crystals.
Example 13
This example provides a process for the preparation of 2- (hydroxyimino) acetic acid, comprising the steps of:
334.2g of 50vol% aqueous methanol solution, 70.6g (purity 98.5%, 1 mol) of hydroxylamine hydrochloride and 167.1. 167.1g (purity 99.0%, 1 mol) of chloral hydrate were successively put into a reaction flask, heated to 50℃and stirred for 10 hours, concentrated under reduced pressure at 50℃under 3500Pa, and then dried at 50℃for 10 hours, whereby 96.6g of white crystals were obtained.
Test case
Test sample: white crystals obtained after drying of examples 1 to 13
The testing method comprises the following steps: the purity of 2- (hydroxyimino) acetic acid in the test sample is tested by adopting an HPLC external standard method; the yield of the reaction was calculated from the feed amount of the raw hydroxylamine hydrochloride, and the test results are shown in table 1:
TABLE 1
As can be seen from the data in Table 1, the purity of 2- (hydroxyimino) acetic acid measured by HPLC external standard method in the solid obtained by desolventizing and drying the reaction system by the preparation method of 2- (hydroxyimino) acetic acid provided by the invention (examples 1-13) is 3.3-99.0%, and the yield is 4.5-99.1% based on hydroxylamine hydrochloride; by adopting the preparation method of the 2- (hydroxyimino) acetic acid provided by the preferred technical scheme (examples 1-3), the purity of the 2- (hydroxyimino) acetic acid is 98.2-99.0% as measured by an HPLC external standard method in the solid obtained after the reaction system is desolventized and dried, and the yield is 95.2-99.1% as calculated by hydroxylamine hydrochloride.
As can be seen from comparison of example 1 and example 4, when the dosage is increased by 10 times, the purity and yield of the 2- (hydroxyiminoacetic acid in the obtained product are not affected, which indicates that the preparation method of the 2- (hydroxyiminoacetic acid provided by the invention can be applied to the enlarged preparation.
As is evident from a comparison of example 1 and examples 5-8, when the molar ratio of hydroxylamine hydrochloride to chloral hydrate is outside the preferred range (1.98-1.02), the purity of 2- (hydroxyimino) acetic acid in the resulting product and its yield are severely affected; when the hydroxylamine hydrochloride is relatively excessive, a large amount of hydroxylamine hydrochloride remains in the product; when the chloral hydrate is relatively excessive, a large amount of chloral remains in the product.
As is evident from a comparison of example 1 and examples 9-11, the reaction temperature affects the purity of 2- (hydroxyimino) acetic acid and its yield in the resulting product, and when the reaction temperature is too low, it affects the progress of the reaction of chloral hydrate with hydroxylamine hydrochloride, and the resulting white crystals are mostly hydroxylamine hydrochloride; when the reaction temperature is too high, the imine in the product is unstable, resulting in decomposition of 2- (hydroxyiminoacetic acid).
As is evident from a comparison of example 1 and examples 12-13, the yield of the reaction was higher by using water as the solvent, since the starting material required water to be dissolved and water to participate in the reaction, the white crystals obtained in example 12 were mostly hydroxylamine hydrochloride and chloral.
The applicant states that the present invention is illustrated by the above examples as a method for preparing 2- (hydroxyimino) acetic acid, but the present invention is not limited to the above examples, i.e. it is not meant that the present invention must be carried out in dependence on the above examples. It should be apparent to those skilled in the art that any modification of the present invention, equivalent substitution of raw materials for the product of the present invention, addition of auxiliary components, selection of specific modes, etc., falls within the scope of the present invention and the scope of disclosure.
Claims (10)
1. A process for the preparation of 2- (hydroxyimino) acetic acid, characterized in that the process for the preparation of 2- (hydroxyimino) acetic acid comprises the steps of: mixing chloral hydrate and hydroxylamine hydrochloride to react to obtain the 2- (hydroxyimino) acetic acid;
the reaction formula is as follows:
2. the process for the preparation of 2- (hydroxyimino) acetic acid according to claim 1, characterized in that the molar ratio of hydroxylamine hydrochloride to chloral hydrate is (0.5-2): 1, preferably (0.98-1.02): 1.
3. The process for the preparation of 2- (hydroxyimino) acetic acid according to claim 1 or 2, characterized in that the temperature of the mixing reaction is 50-100 ℃, preferably 50-80 ℃.
4. A process for the preparation of 2- (hydroxyimino) acetic acid according to any of the claims 1-3, characterized in that the mixing reaction takes from 1 to 10 hours.
5. The method for producing 2- (hydroxyimino) acetic acid according to any one of claims 1 to 4, wherein the mixing reaction is carried out in a solvent;
preferably, the solvent comprises water.
6. The process for producing 2- (hydroxyimino) acetic acid according to claim 5, wherein the weight ratio of the solvent to chloral hydrate is (1-10): 1.
7. The method for producing 2- (hydroxyimino) acetic acid according to any one of claims 1 to 6, wherein the mixing reaction is followed by desolventizing and drying.
8. The method for producing 2- (hydroxyimino) acetic acid according to claim 7, wherein the desolventizing is performed by vacuum concentration;
preferably, the pressure of the reduced pressure concentration is 3000-3500Pa, and the temperature of the reduced pressure concentration is 50-80 ℃.
9. The method for producing 2- (hydroxyimino) acetic acid according to claim 7, wherein the drying is performed by oven drying;
preferably, the temperature of the drying is 50-80 ℃, and the drying time is 10-20h.
10. The method for producing 2- (hydroxyimino) acetic acid according to any one of claims 1 to 9, characterized in that the method for producing 2- (hydroxyimino) acetic acid comprises the steps of: mixing hydroxylamine hydrochloride, chloral hydrate and water in the molar ratio of (0.5-2) 1 to (1-10) times of chloral hydrate, reacting for 1-10 hours at 50-100 ℃, concentrating under reduced pressure at the pressure of 3000-3500Pa at 50-80 ℃, and drying for 10-20 hours at 50-80 ℃ to obtain the 2- (hydroxyimino) acetic acid;
the reaction formula is as follows:
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