CN1100753C - Process for preparing crystal 0-methyl-isourea acetate - Google Patents
Process for preparing crystal 0-methyl-isourea acetate Download PDFInfo
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- CN1100753C CN1100753C CN98107901A CN98107901A CN1100753C CN 1100753 C CN1100753 C CN 1100753C CN 98107901 A CN98107901 A CN 98107901A CN 98107901 A CN98107901 A CN 98107901A CN 1100753 C CN1100753 C CN 1100753C
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- methyl
- isourea
- described methods
- acetate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention provides a method for producing a high-purity crystalline methylisourea hydrochloride which comprises: (a) A methanol solution or suspension of O-methyliso urea hydrochloride is reacted with an alkali metal acetate at -10 to 65 DEG C, (b) a precipitated alkali metal chloride is removed from the reaction mixture in a temperature range based on the process (a) and (c) the reaction system is cooled to -50 to 30 DEG C to crystallize O-methylisourea acetate, which is separated by an ordinary method. O-Methylisourea acetate can be obtained in a crystal form in an extremely excellent yield and purity.
Description
A kind of method for preparing high-purity O-methyl-isourea acetate of theme of the present invention.
The O-methyl-isourea salt of strong inorganic acid is easy to obtain by methyl alcohol, cyanamide and the reaction of a kind of strong inorganic acid usually.Typical example is O-Methyl Isourea Sulfate or O-methyl-isourea hydrochloride.
Yet, with weak acid for example the reaction of acetic acid be impossible because the undercapacity of acid is with activation cyanamide molecule.Therefore, can not directly obtain faintly acid O-methyl-isourea salt.
O-methyl-isourea salt for example can prepare guanidinesalt as the amidination agent.Here the corresponding guanidinesalt of O-methyl-isourea salt and amine reaction becoming.
Many medicine or activation of plant preservatives components with guanidine structure contain acetate as negatively charged ion.In order to prepare these active ingredients by corresponding amine, need to use the O-methyl-isourea acetate as the amidination agent, could directly obtain required pair anion because have only by this way.
Prior art is (referring to Chemical Abstracts Vol.106; Referat-Nr.32380) the O-methyl-isourea acetate for preparing aqueous solution form is only disclosed, wherein make cyanamide, methyl alcohol and sulfuric acid reaction become O-methyl-isourea hydrosulfate in the first step, it is mixed with moisture calcium hydroxide in second step, isolate the calcium sulfate of formation, and the filtrate and the acetic acid reaction that contain free isourea alkali become a kind of O-methyl-isourea acetate solution.The shortcoming of this method is that free O-methyl-isourea alkali and O-methyl-isourea acetate all are unsettled in the aqueous solution.
Between synthesis phase, O-methyl-isourea hydrolysis becoming methyl alcohol and urea, the latter is difficult to separate and removes.When the O-methyl-isourea aqueous solution concentrates, decompose, thereby can only obtain containing the O-methyl-isourea acetate of many impurity with the yield of extreme difference.
Can not obtain pure crystal 0-methyl-isourea acetate by concentrated aqueous solution.In addition, the shortcoming of described method is that solid calcium sulphate precipitates with superfine form usually, thereby must filter and cause higher loss of yield for a long time.
Therefore, the objective of the invention is to, develop a kind of method for preparing the O-methyl-isourea acetate, this method does not have corresponding shortcoming in the prior art, and can be with simple prepared high yield and highly purified salt.
This task can be solved by following mode by the present invention, wherein
A) methanol solution of O-methyl-isourea hydrochloride or suspension are reacted under-10 to 65 ℃ of temperature with alkali metal acetate,
B) under the temperature of step a), from reaction mixture, remove sedimentary alkali metal chloride and
C) make the crystallization of O-methyl-isourea acetate by being cooled to-50 to 30 ℃, and separate according to a conventional method.
The fact proves unexpectedly, can prepare the O-crystallization isourea acetate of crystalline form with very high productive rate and very high purity.
The first step of the inventive method a) in, the methanol solution of O-methyl-isourea hydrochloride or suspension are at-10 to 65 ℃, react with alkali metal acetate under preferred 20 to the 65 ℃ temperature, and under this temperature stirred reaction mixture, make its reaction 5 minutes to 24 hours, preferred reaction 1 to 8 hour.
Preferably the alkali metal acetate that uses with the anhydrous solid form at first can be Lithium Acetate, sodium-acetate or Potassium ethanoate.For the reason of price, preferably use sodium-acetate.
Methanol aqueous solution or the suspension of implementing the required O-methyl-isourea hydrochloride of the inventive method can obtain in a different manner:
1. by dissolving in anhydrous methanol or suspend crystal 0-methyl isourea hydrochloride pure.
2. by making the reaction of cyanamide and methyl alcohol and aqueous hydrochloric acid, isolate the product that obtains and dissolve or be suspended in the anhydrous methanol.
3. by making cyanamide and anhydrous methanol and gas hcl reaction.
4. by making the reaction of cyanamide and methyl alcohol and chloromethane amidine hydrochloride.
The concentration of O-methyl-isourea hydrochloride in methanol solution or suspension of using can change in very wide scope, but has proved that particularly advantageous is that every mole of O-methyl-isourea hydrochloride uses 1 to 20 mole, preferred 2 to 10 mole, of methanol.
The amount of the alkali metal acetate that adds is preferably every mole of O-methyl-isourea hydrochloride with 0.5 to 2, particularly 0.8 to 1.2 mole.
The temperature of reaction of a) regulating in reactions steps and the amount of methyl alcohol are preferential to be selected like this, and its makes the alkali metal chloride that forms precipitate as much as possible, and the O-methyl-isourea acetate is then almost completely stayed in the solution.
Reactions steps a) finish after, at reactions steps b) in preferably from the reaction mixture that obtains, isolate sedimentary alkali metal chloride by means of separating centrifuge or suction filter.
Here importantly, carry out under the temperature that is separated in step a) of alkali metal chloride for the present invention.This mode can guarantee that reaction soln is substantially free of alkali metal chloride, and the O-methyl-isourea acetate is almost completely stayed in the solution.Isolated alkali metal chloride is preferably used methanol wash, and the separate collection methanol solution.
Corresponding to step c), preferably make methanol solution be cooled to-50 to 30 ℃ by means of a crystallizer, preferred-30 to 20 ℃.According to preferred embodiment, temperature be adjusted to one be lower than reactions steps a) or b) under the temperature of temperature 20 to 50 Kelvin degrees.
Reaction mixture stirred under this temperature 0.5 to 24 hour, preferred 1 to 12 hour, made the crystallization of solid O-methyl-isourea acetate.
The O-methyl-isourea acetate that crystallizes out preferably keep under the temperature of reaction of step c), according to known method with use known equipment for example whizzer or suction filter separate, and use pure methanol wash where necessary.
The reaction product that obtains is for example dry under vacuum in common mode, needn't further handle to reach high purity.
In order to improve total productive rate, the also further mother liquor that obtains of processing reaction step c).For this reason, under decompression and reactions steps temperature a), from the mother liquor that obtains, distill out a large amount of methyl alcohol, the feasible suspension that forms a kind of alkali metal chloride, the O-methyl-isourea acetate that contains then almost completely is retained in the solution.
Make this suspension then through processing step b) and c), obtain the second section of crystal 0-methyl-isourea acetate.
As mentioned above, this product equally can be also dry under vacuum condition where necessary with pure methanol wash.
Scheme as an alternative, also can make spissated by distilling out methyl alcohol, still contain muriatic mother liquor of solid alkali metal and next batch reaction mixture.
Can be by the mother liquor that circulation obtains so that productive rate is maximum and residuals is minimum.
Because the technology that productive rate height (the highest by 85%) and purity height (〉=98%) and reaction are carried out is simple, method of the present invention is particularly suitable for industrial scale applications.
Further specify the present invention with embodiment below.
Embodiment
Embodiment 1
168.2kg (4k mole) solid cyanamide (99.6%) is dissolved under 20 ℃ of temperature in 545kg (17k mole) methyl alcohol.Under 20 ℃ of temperature, added 145.8kg (4k mole) gas chlorination hydrogen to this solution, and continue to stir 24 hours at 20 ℃ through 8 hours.
The solution that obtains is heated to 40 ℃, adds 328.1kg (4k mole) solid water-free sodium-acetate in 4 hours, and continues to stir 8 hours at 40 ℃.The suspension that obtains carries out centrifugation at 40 ℃, uses the 200kg methanol wash, the separate collection wash filtrate.
Filtrate is sent in the other container,, continued to stir 4 hours at 4 hours internal cooling to 10 ℃.Form a kind of thick crystal slurries, centrifugation under 10 ℃ of temperature, and use the 50kg methanol wash.After vacuum-drying under 50 ℃ of temperature, obtaining 322kg (60%) purity is the O-methyl-isourea acetate of 99.5% (cation chromatography).
Pure crystal 0-methyl-isourea acetate has following feature: ultimate analysis: C 35.59%, H7.74%, N 20.86% (theoretical value: C 35.82%, H 7.51%, N 20.88%); 119.7 ℃ of fusing points (kapillary), IR spectrum: 1718s, 1600sh, 1560s, 1451w, 1407vs, 1341w, 1212m, 1189w, 1150m, 1083m, 1017w, 924w, 886w, 829b, 713m, 657m, 611m, 541m;
1H-NMR-spectrum: 1.895ppm (CH3); 3.992ppm (CH
3O); 5.085 (NH
2).
In first and second step with centrifugal separation with the washing soln mother liquor of purifying.Under 40 ℃ and vacuum condition, distill out 400kg methyl alcohol from the 680kg that obtains.The 20kg methanol wash is used in the 280kg sodium-chlor suspension centrifugation under 40 ℃ of temperature that stays, and is cooled to 10 ℃, stirs to make its complete crystallization in 4 hours.The crystal slurries that obtain centrifugation under 10 ℃ of temperature, and use the 20kg methanol wash.Obtain 129kg (24%) purity after the drying and be the second section of 99% solid O-methyl-isourea acetate.
Embodiment 2
The solid O-methyl-isourea hydrochloride that 442.2kg (4k mole) is pure is dissolved in 464kg (14.5k mole) methyl alcohol.
Solution is heated to 40 ℃, in 30 minutes, adds 328.1kg (4k mole) solid sodium-acetate, and stirred 5 hours at 40 ℃.The suspension that obtains carries out centrifugation under 40 ℃ of temperature.
Filtrate is cooled to 0 ℃, stirs 2 hours with complete crystallization.The product that obtains takes out by centrifugation at 0 ℃, and is dry under 50 ℃ of temperature.Obtain 317.3kg (59.1%) purity and be 98% O-methyl-isourea acetate.
Embodiment 3
84.1kg (2k mole) solid cyanamide is dissolved in 750kg (23.4k mole) methyl alcohol.Add 229.9kg (2k mole) solid chloromethane amidine hydrochloride to this solution, and under 20 ℃ of temperature, stirred this reaction mixture 20 hours.
Solution is heated to 30 ℃, in 30 minutes, adds 328.1kg (4k mole) solid sodium-acetate, and stirred 5 hours at 30 ℃.The suspension that obtains carries out centrifugation under 30 ℃ of temperature.
Filtrate is cooled to-18 ℃, stirs 2 hours with complete crystallization.The product that obtains carries out centrifugation at-18 ℃, and vacuum-drying under 50 ℃ of temperature.Obtain 352.2kg (65.6%) purity and be 98% O-methyl-isourea acetate.
Embodiment 4
168.2kg (4k mole) solid cyanamide is dissolved in 896kg (28k mole) methyl alcohol.Under 30 ℃ of temperature, added 145.8kg (4k mole) gas chlorination hydrogen to this solution, and continue reaction 20 hours through 3 hours.
In 20 ℃ and 30 minutes, add 328.1kg (4k mole) solid sodium-acetate, and stirred 5 hours at 20 ℃.The suspension that obtains carries out centrifugation under 20 ℃ of temperature.
Filtrate is cooled to-15 ℃, stirs 2 hours with complete crystallization.The product that obtains carries out centrifugation at-15 ℃, is cooled to-15 ℃ methanol wash and vacuum-drying under 50 ℃ of temperature with 100kg.Obtain 303kg (56.5%) purity and be 99.5% O-methyl-isourea acetate.
Claims (16)
1. the preparation method of high-purity crystals O-methyl-isourea acetate is characterized in that,
A) methanol solution of O-methyl-isourea hydrochloride or suspension are reacted under-10 to 65 ℃ of temperature with alkali metal acetate,
B) under the temperature of step a), from reaction mixture, remove sedimentary alkali metal chloride and
C), make the crystallization of O-methyl-isourea acetate, and separate according to a conventional method by being cooled to-50 to 30 ℃.
2. in accordance with the method for claim 1, it is characterized in that, use sodium-acetate as alkali metal acetate.
3. according to claim 1 or 2 described methods, it is characterized in that every mole of O-methyl-isourea hydrochloride uses 1 to 20 mole, of methanol.
4. according to claim 1 or 2 described methods, it is characterized in that every mole of O-methyl-isourea hydrochloride uses 2 to 10 mole, of methanol.
5. according to claim 1 or 2 described methods, it is characterized in that every mole of O-methyl-isourea hydrochloride uses 0.5 to 2 mole of alkali metal acetate.
6. according to claim 1 or 2 described methods, it is characterized in that every mole of O-methyl-isourea hydrochloride uses 0.8 to 1.2 mole of alkali metal acetate.
7. according to claim 1 or 2 described methods, it is characterized in that,, prepare the methanol solution or the suspension of O-methyl-isourea hydrochloride by making pure crystal 0-methyl isourea hydrochloride dissolving or being suspended in the anhydrous methanol.
8. according to claim 1 or 2 described methods, it is characterized in that,, separate the product obtain and dissolve or be suspended in the anhydrous methanol, prepare the methanol solution or the suspension of O-methyl-isourea hydrochloride by making the reaction of cyanamide and methyl alcohol and aqueous hydrochloric acid.
9. according to claim 1 or 2 described methods, it is characterized in that,, prepare the methanol solution or the suspension of O-methyl-isourea hydrochloride by making cyanamide and anhydrous methanol and gas hcl reaction.
10. according to claim 1 or 2 described methods, it is characterized in that,, prepare the methanol solution or the suspension of O-methyl-isourea hydrochloride by making the reaction of cyanamide and methyl alcohol and chloromethane amidine hydrochloride.
11., it is characterized in that reactions steps a) is carried out according to claim 1 or 2 described methods under 20 to 65 ℃ of temperature.
12., it is characterized in that reactions steps c according to claim 1 or 2 described methods) crystallization under-30 to 20 ℃ of temperature, carry out.
13., it is characterized in that reactions steps c according to claim 1 or 2 described methods) temperature than reactions steps a) or low 20 to 50 Kelvin degrees of temperature b).
14., it is characterized in that according to claim 1 or 2 described methods, come the mother liquor of concentration response step c) by distillating carbinol, then make methanol suspension experience reactions steps b) and c).
15., it is characterized in that according to claim 1 or 2 described methods, come the mother liquor of concentration response step c) by distillating carbinol, then make methanol suspension and next batch reaction mixture.
16. the purity that is obtained by the described method of one of claim 1 to 15 is the crystal 0-methyl-isourea acetate more than 98%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19719024.3 | 1997-05-05 | ||
| DE1997119024 DE19719024A1 (en) | 1997-05-05 | 1997-05-05 | Preparation of crystalline O-methyl-isourea acetate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1198434A CN1198434A (en) | 1998-11-11 |
| CN1100753C true CN1100753C (en) | 2003-02-05 |
Family
ID=7828722
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98107901A Expired - Fee Related CN1100753C (en) | 1997-05-05 | 1998-05-04 | Process for preparing crystal 0-methyl-isourea acetate |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPH10316646A (en) |
| CN (1) | CN1100753C (en) |
| DE (1) | DE19719024A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101245037B (en) * | 2008-01-25 | 2011-12-21 | 巨化集团公司 | Process for producing oxygen methyl isourea acetate |
| US9670149B2 (en) * | 2013-06-17 | 2017-06-06 | 3M Innovative Properties Company | Process for preparing guanidino-functional monomers |
| DE102017004596B4 (en) | 2017-05-13 | 2021-02-11 | Alzchem Trostberg Gmbh | Process for the production of phenylguanidines or their salts |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61180760A (en) * | 1985-02-05 | 1986-08-13 | Dainippon Ink & Chem Inc | Production of o-methylisourea acetic acid salt |
-
1997
- 1997-05-05 DE DE1997119024 patent/DE19719024A1/en not_active Withdrawn
-
1998
- 1998-05-01 JP JP12217298A patent/JPH10316646A/en active Pending
- 1998-05-04 CN CN98107901A patent/CN1100753C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61180760A (en) * | 1985-02-05 | 1986-08-13 | Dainippon Ink & Chem Inc | Production of o-methylisourea acetic acid salt |
Also Published As
| Publication number | Publication date |
|---|---|
| DE19719024A1 (en) | 1998-11-12 |
| JPH10316646A (en) | 1998-12-02 |
| CN1198434A (en) | 1998-11-11 |
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