CN101245037B - Process for producing oxygen methyl isourea acetate - Google Patents
Process for producing oxygen methyl isourea acetate Download PDFInfo
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- CN101245037B CN101245037B CN2008100593586A CN200810059358A CN101245037B CN 101245037 B CN101245037 B CN 101245037B CN 2008100593586 A CN2008100593586 A CN 2008100593586A CN 200810059358 A CN200810059358 A CN 200810059358A CN 101245037 B CN101245037 B CN 101245037B
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Abstract
The invention discloses a preparation method of oxymethylisourea acetate, which comprises the following steps: 1) the methanol solution of the oxymethylisourea bisulfate is reacted with sodium acetate and sodium hydroxide at the temperature of 10 to 65 DEG C for 2 to 10 hours; the molar ratio of the oxymethylisourea bisulfate to the sodium hydroxide and the menthol is 1:1:6 to 10 and the molar ratio of the oxymethylisourea bisulfate to the sodium acetate and the sodium hydroxide is 1:0.8 to 1.5:0.8 to 1.50; 2) the precipitated sodium sulfate is removed from the reaction mixture at the temperature of the step 1); 3) the reaction solution is condensed by the distillation of the menthol and the condensation temperature is 40 to 80 DEG C; 4) the concentrated solution of the oxymethylisourea acetate is cooled, crystallized and centrifugally separated. The synthesized product of the invention is high in purity, high in yield and simple in technique; the method is especially suitable for the application of industrial scale.
Description
Technical field
The present invention relates to a kind of preparation method of oxygen methyl isourea acetate.
Background technology
The oxygen methyl-isourea salt of strong inorganic acid can be by urea and methyl-sulfate reaction, through obtaining after acidolysis, the hydrolysis.Typical example is a methoxyl-isourea hydrosulfate.
Yet methoxyl-isourea hydrosulfate and acetic acid can not react because the intensity of acetic acid too a little less than, can not directly obtain faintly acid oxygen methyl-isourea salt.
Its effective ingredient oxygen methyl-isourea of oxygen methyl isourea acetate is the important intermediate of synthetic Ro 2-9757 series antineoplastic medicament.Also can be used as the reaction of amidination agent and amine and generate corresponding guanidinesalt.Many medicines with guanidine structure or activation of plant preservatives component contain acetate and make negatively charged ion, need with oxygen methyl isourea acetate as the amidination agent, as oxygen methyl isourea acetate and amino dodecane reaction generation dodine.
Clear 61-180760 report, methoxyl-isourea hydrosulfate mixes with moisture calcium hydroxide in the aqueous solution, isolates the calcium sulfate of formation, and contains the filtrate and the acetic acid reaction generation oxygen methyl isourea acetate solution of free oxygen methyl-isourea alkali.The shortcoming of this method is: oxygen methyl-isourea hydrolysis becoming methyl alcohol and urea, the latter is difficult to separate and removes, and decomposes when the oxygen methyl-isourea aqueous solution concentrates, thereby can only obtain containing the oxygen methyl isourea acetate of many impurity with the yield of extreme difference.
CN1198434A (1998) report, oxygen methyl-isourea hydrochloride and sodium-acetate react in methanol solution and generate oxygen methyl isourea acetate.The shortcoming of this method is: byproduct sodium chloride has certain solubleness in methyl alcohol, is difficult to remove fully.
Liaoning chemical industry 2003.01 reports, oxygen methyl-isourea hydrogen salt are dissolved in the organic solvent and generate free oxygen methyl-isourea with the sodium hydroxide reaction.In free oxygen methyl-isourea and the acetic acid and generate oxygen methyl isourea acetate.The shortcoming of this method is: oxygen methyl-isourea hydrogen salt and sodium hydroxide reaction are incomplete, and the ratio that acetic acid drips is difficult to control.
Summary of the invention
The objective of the invention is to overcome the shortcoming of prior art, a kind of preparation method of oxygen methyl isourea acetate is provided.
The preparation method of oxygen methyl isourea acetate comprises the steps:
1) methanol solution of methoxyl-isourea hydrosulfate reacts with sodium-acetate and sodium hydroxide under 10 ℃ to 65 ℃ temperature, reaction times is 2 hours to 10 hours, the mol ratio of methoxyl-isourea hydrosulfate and sodium hydroxide, methyl alcohol is 1: 1: 6～10, and the mol ratio of methoxyl-isourea hydrosulfate and sodium-acetate, sodium hydroxide is 1: 0.8～1.5: 0.8～1.50;
2) under the temperature of step 1), from reaction mixture, remove sedimentary sodium sulfate;
3) come concentration of reaction solution by distillating carbinol, thickening temperature is 40 ℃ to 80 ℃;
4) oxygen methyl isourea acetate concentrated solution cooling, crystallization, centrifugation gets final product.
The mol ratio of described methoxyl-isourea hydrosulfate and sodium-acetate, sodium hydroxide is preferably 1: 1.0～and 1.2: 1.0～1.2.Described step 1) temperature of reaction is preferably 0 ℃ to 50 ℃, and the reaction times is preferably 3 hours to 8 hours.The thickening temperature of described step 3) is preferably 50 ℃ to 70 ℃.
Product purity height (〉=98%) after the present invention is synthetic, productive rate height, single batch of synthetic yield are 70～75%, and mother liquor reclaims back productive rate＞90%.Technology is simple, and method of the present invention is particularly suitable for industrial scale applications.
Embodiment
Embodiment 1
With 292.4Kg (1.7Kmol) methoxyl-isourea hydrosulfate (95.5%) and 150Kg (1.83Kmol) sodium-acetate and 68Kg (1.7Kmol) sodium hydroxide in 446Kg (14Kmol) methyl alcohol, and under 30 ℃ of temperature, stir 5 hours after-filtration, the a spot of washed with methanol of filter residue, filtrate enters in the concentration kettle, and under 60 ℃ of temperature vacuum concentration, solution after concentrating enters the crystallization kettle crystallization, the crystallization after-filtration that finishes, product obtains 165Kg (75.9%) purity and is 98% oxygen methyl isourea acetate after vacuum-drying under 50 ℃ of temperature.
Embodiment 2
With 292.4Kg (1.7Kmol) methoxyl-isourea hydrosulfate (95.5%) and 145Kg (1.77Kmol) sodium-acetate and 70Kg (1.75Kmol) sodium hydroxide in 446Kg (17Kmol) methyl alcohol, and under 40 ℃ of temperature, stir 8 hours after-filtration, the a spot of washed with methanol of filter residue, filtrate enters in the concentration kettle, and under 70 ℃ of temperature vacuum concentration, solution after concentrating enters the crystallization kettle crystallization, the crystallization after-filtration that finishes, product obtains 160Kg (73.6%) purity and is 98% oxygen methyl isourea acetate after vacuum-drying under 50 ℃ of temperature.
Embodiment 3
With 292.4Kg (1.7Kmol) methoxyl-isourea hydrosulfate (95.5%) and 140Kg (1.7Kmol) sodium-acetate and 70Kg (1.75Kmol) sodium hydroxide in 446Kg (14Kmol) methyl alcohol, and under 20 ℃ of temperature, stir 4 hours after-filtration, the a spot of washed with methanol of filter residue, filtrate enters in the concentration kettle, and under 65 ℃ of temperature vacuum concentration, solution after concentrating enters the crystallization kettle crystallization, the crystallization after-filtration that finishes, product obtains 155Kg (71.3%) purity and is 98% oxygen methyl isourea acetate after vacuum-drying under 50 ℃ of temperature.
Embodiment 4
With 292.4Kg (1.7Kmol) methoxyl-isourea hydrosulfate (95.5%) and 112Kg (1.37Kmol) sodium-acetate and 56Kg (1.4Kmol) sodium hydroxide in 357Kg (11Kmol) methyl alcohol, and under 15 ℃ of temperature, stir 2 hours after-filtration, the a spot of washed with methanol of filter residue, filtrate enters in the concentration kettle, and under 60 ℃ of temperature vacuum concentration, solution after concentrating enters the crystallization kettle crystallization, the crystallization after-filtration that finishes, product obtains 100Kg (46%) purity and is 85% oxygen methyl isourea acetate after vacuum-drying under 50 ℃ of temperature.
Embodiment 5
With 292.4Kg (1.7Kmol) methoxyl-isourea hydrosulfate (95.5%) and 210Kg (2.56Kmol) sodium-acetate and 105Kg (2.63Kmol) sodium hydroxide in 446Kg (14Kmol) methyl alcohol, and under 65 ℃ of temperature, stir 10 hours after-filtration, the a spot of washed with methanol of filter residue, filtrate enters in the concentration kettle, and under 80 ℃ of temperature vacuum concentration, solution after concentrating enters the crystallization kettle crystallization, the crystallization after-filtration that finishes, product obtains 160Kg (73.6%) purity and is 67% oxygen methyl isourea acetate after vacuum-drying under 50 ℃ of temperature.
Claims (2)
1. the preparation method of an oxygen methyl isourea acetate is characterized in that comprising the steps:
1) methanol solution of methoxyl-isourea hydrosulfate reacts with sodium-acetate and sodium hydroxide under 10 ℃ to 65 ℃ temperature, reaction times is 2 hours to 10 hours, the mol ratio of methoxyl-isourea hydrosulfate and sodium hydroxide, methyl alcohol is 1: 1: 6～10, and the mol ratio of methoxyl-isourea hydrosulfate and sodium-acetate is 1: 0.8～1.5;
2) under the temperature of step 1), from reaction mixture, remove sedimentary sodium sulfate;
3) come concentration of reaction solution by distillating carbinol, thickening temperature is 40 ℃ to 80 ℃;
4) oxygen methyl isourea acetate concentrated solution cooling, crystallization, centrifugation gets final product.
2. according to the preparation method of the described a kind of oxygen methyl isourea acetate of claim 1, the thickening temperature that it is characterized in that described step 3) is 50 ℃ to 70 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100593586A CN101245037B (en) | 2008-01-25 | 2008-01-25 | Process for producing oxygen methyl isourea acetate |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100593586A CN101245037B (en) | 2008-01-25 | 2008-01-25 | Process for producing oxygen methyl isourea acetate |
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| Publication Number | Publication Date |
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| CN101245037A CN101245037A (en) | 2008-08-20 |
| CN101245037B true CN101245037B (en) | 2011-12-21 |
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| CN2008100593586A Expired - Fee Related CN101245037B (en) | 2008-01-25 | 2008-01-25 | Process for producing oxygen methyl isourea acetate |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113603617A (en) * | 2021-08-05 | 2021-11-05 | 宁夏恒钛科技有限公司 | Preparation method of O-methyl-N-nitroisourea |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1198434A (en) * | 1997-05-05 | 1998-11-11 | Skw特罗斯特贝格股份公司 | Process for preparing crystal 0-methyl-isourea acetate |
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- 2008-01-25 CN CN2008100593586A patent/CN101245037B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1198434A (en) * | 1997-05-05 | 1998-11-11 | Skw特罗斯特贝格股份公司 | Process for preparing crystal 0-methyl-isourea acetate |
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