CN108047094A - A kind of O- methyl-isoureas Methylsulfate novel preparation method - Google Patents
A kind of O- methyl-isoureas Methylsulfate novel preparation method Download PDFInfo
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- CN108047094A CN108047094A CN201711378295.6A CN201711378295A CN108047094A CN 108047094 A CN108047094 A CN 108047094A CN 201711378295 A CN201711378295 A CN 201711378295A CN 108047094 A CN108047094 A CN 108047094A
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- methylsulfate
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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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/24—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfuric acids
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Abstract
The invention discloses a kind of O methyl-isoureas Methylsulfate novel preparation methods, comprise the following steps：Into tri- mouthfuls of reaction bulbs of 500mL, a certain amount of dimethyl suflfate is added in, adds in quantitative urea by several times, after reaction solution is limpid, insulation reaction is for a period of time to get product O methyl-isourea Methylsulfates.The present invention uses urea and dimethyl suflfate to be reacted for raw material under microwave action and prepares O methyl-isourea Methylsulfates.The advantage is that can promote reaction to be smoothed out in a low temperature of conventional method is difficult to happen, and greatly shorten the reaction time, improve reaction efficiency and product purity；Control 45 70 DEG C of temperature；The reduction of reaction temperature can not only reduce security risk, moreover it is possible to reduce the side reaction in production process so that product yield is increased to more than 80%.
Description
Technical field
The invention belongs to technical field of chemistry, are related to a kind of O- methyl-isoureas Methylsulfate novel preparation method.
Background technology
O- methyl-isoureas (can abbreviation OMIU) are a kind of in medicine, pesticide and Material Field have the synthesis of extensive use
Mesosome.The substance be clear crystal, molecular formula C2H6N2O, molecular weight 74.08,44-45 DEG C of fusing point can absorb water in air
Point and carbon dioxide.O- methyl-isoureas are very unstable, therefore the form for being often made into salt is sold and used.In view of it is special
Molecular structure, O- methyl-isoureas are the good " forerunners for synthesizing guanidine, imidazoles, (urea) miazines and its derivative
Object ", and this few class substance much all has good bioactivity, so O- methyl-isoureas (salt) are facilitated in medicine, pesticide
The extensive use in the fields of grade.
O- methyl-isourea Methylsulfates are one kind of O- methyl-isourea salt, molecular formula C2H6N2OCH3OSO3H, point
Son amount 186.2, the substance can directly react obtained with dimethyl suflfate and urea, but it is difficult to from urea and dimethyl suflfate
It is separated in reaction mixture, mixed system room temperature is in viscous liquid.Common O- Methyl Isourea Sulfates, O- methyl are different
Urea-sulfuric acid hydrogen salt etc. is all that it is all by further solid matter obtained from reaction, the active ingredient that they participate in reaction
" O- methyl-isoureas ".The method for preparing O- methyl-isourea salt is more, the most commonly used is cyanamide method and urea method, in addition with lime
Nitrogen method.Since cyanamide is toxic in cyanamide method, stability is poor and expensive etc., the low grade of lime nitrogen method products therefrom purity is not
The puzzlement of sharp factor, urea method isourea salt technique are increasingly becoming mainstream synthesis technology.
Patent of invention (publication number 102432506A) discloses one kind using dimethyl carbonate as methylating reagent in urea method
The method for preparing O- methyl-isoureas under highly basic effect with urea, but the O- methyl-isourea stability obtained by the method is poor, it is unfavorable
In storage and transport.In addition, dimethyl carbonate cost is higher, it is unfavorable for the popularization of the technique.
The existing report of synthesis technology of O- methyl-isourea salt is prepared using dimethyl suflfate as methylating agent and urea reaction at present
Road simultaneously has an industrialization device, but the prior art either there are the reaction time is long otherwise reaction temperature height there are security risks
And reaction yield it is generally relatively low the defects of.In conventional method, reaction temperature is low, and raw material reaction speed is slow even hardly to react,
In order to promote being smoothed out for reaction, reaction temperature need to be improved to 70 DEG C or more, but high temperature causes system stability to reduce, system
Temperature drastically raises and easily triggers security risk, while during pyroreaction, side reaction significantly increases, and product yield declines.It is existing
Common process controlling reaction temperature is at 70-120 DEG C, and product yield is 64% or so.
The content of the invention
It is an object of the invention to overcome above-mentioned technology there are the defects of, a kind of O- methyl-isoureas Methylsulfate system is provided
Standby new method, O- methyl-isourea Methylsulfates prepared by this method, property is stablized, convenient for storing and transporting.
A kind of O- methyl-isoureas Methylsulfate novel preparation method, comprises the following steps：
Into tri- mouthfuls of reaction bulbs of 500mL, a certain amount of dimethyl suflfate is added in, quantitative urea is added in by several times, treats reaction solution
After limpid, insulation reaction is for a period of time to get product O- methyl-isourea Methylsulfates.
Further, the input molar ratio of dimethyl suflfate and urea is 0.9:1.0~1.0:1.0, urea divides 2~3 times and adds
Enter.
Further, it is smoothed out using microwave assisted reaction.
Further, three mouthfuls of reaction bulbs are located in microwave reactor, set 47-50 DEG C of the temperature of microwave controller, open
Stirring.Temperature is 51 DEG C after 23min, and the limpid no solid of reaction system continuously adds urea reaction, system is clear again after 18min
It is bright, insulation reaction 30min.Microwave temperature control is adjusted at 59-61 DEG C, stirring heat preservation 1h (microwave power set 165W) is obtained
Crude product O- methyl-isourea Methylsulfates, liquid chromatographic detection content are 80.01%.
Compared with prior art, beneficial effects of the present invention are：
The present invention uses urea and dimethyl suflfate to be reacted for raw material under microwave action and prepares O- methyl-isourea methyl sulphur
Hydrochlorate.The advantage is that can promote reaction to be smoothed out in a low temperature of conventional method is difficult to happen, and greatly shorten the reaction time,
Improve reaction efficiency；45-70 DEG C of controlling reaction temperature, the reaction temperature of the more current common process of the temperature have obtained notable drop
Low, the reduction of reaction temperature can not only substantially reduce security risk, improve reaction controllability, moreover it is possible to substantially reduce in production process
Side reaction so that product yield is increased to more than 80% by 64% or so of popular response.Reaction yield significantly improves, greatly
The big purity for improving reaction product without isolation, improve O- methyl-isourea Methylsulfates directly as reaction raw materials
Participate in the suitability reacted downstream.
Specific embodiment
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below
The present invention is further explained for specific example.
Embodiment
Into microwave reactor in tri- mouthfuls of reaction bulbs of 500mL, 126.0g dimethyl suflfates are added in, 30.5g urea is set micro-
47-50 DEG C of the temperature of wave controller, power 165W open stirring.The limpid no solid (51 DEG C of temperature) of system after reaction 23min,
30.5g urea reactions are continuously added, system is limpid again after 18min, insulation reaction 30min.Microwave temperature control is adjusted in 59-
61 DEG C, stirring heat preservation 1h, crude product O- methyl-isourea Methylsulfates are obtained, liquid chromatographic detection content is 80.01%.
Reference examples 1
Into tri- mouthfuls of reaction bulbs of 500mL, 126.0g dimethyl suflfates, 30.5g urea are added in, heating water bath sets water-bath
Temperature 50 C opens stirring.System is soon limpid (51 DEG C of system temperature) after reacting 4h, continuously adds 30.5g urea, continues anti-
Should, system is limpid again after 30min, keeps the temperature 50 DEG C of reaction 30min.60 DEG C of insulation reaction 1h are warming up to, it is different to obtain crude product O- methyl
Urea Methylsulfate, liquid chromatographic detection content are 64.91%.
Reference examples 2
Dimethyl suflfate 405kg is put into 500L enamel reaction stills, starts stirring, heating steam is opened and is progressively warming up to
90 DEG C, start evenly to be continuously added to urea 200kg substantially, urea adds time 56min, system temperature during urea adds
At 86~95 DEG C, urea finishes follow-up continuation of insurance temperature and reacts 60min at 88~92 DEG C for control.Insulation reaction finishes, and samples sticky
Liquid, liquid chromatographic detection obtain O- methyl-isourea methylsulfuric acids salt content as 63.77%.
The above is only best mode for carrying out the invention, and any one skilled in the art is in the present invention
In the technical scope of disclosure, the simple change or equivalence replacement of the technical solution that can be become apparent to each fall within the present invention's
In protection domain.
Claims (4)
1. a kind of O- methyl-isoureas Methylsulfate novel preparation method, which is characterized in that comprise the following steps：
Into tri- mouthfuls of reaction bulbs of 500mL, a certain amount of dimethyl suflfate is added in, quantitative urea is added in by several times, treats that reaction solution is limpid
Afterwards, insulation reaction is for a period of time to get product O- methyl-isourea Methylsulfates.
2. O- methyl-isoureas Methylsulfate novel preparation method according to claim 1, which is characterized in that dimethyl suflfate
Input molar ratio with urea is 0.9:1.0~1.0:1.0,2~3 additions of urea point.
3. O- methyl-isoureas Methylsulfate novel preparation method according to claim 2, which is characterized in that promoted using microwave
Into reaction progress and reduce the generation of side reaction.
4. O- methyl-isoureas Methylsulfate novel preparation method according to claim 3, which is characterized in that three mouthfuls of reaction bulbs
Middle addition reaction raw materials, are placed in microwave reactor, set 47-50 DEG C of the temperature of microwave controller, open stirring；Treat reactant
It is limpid no solid, continuously adds urea reaction, treats limpid again, insulation reaction 30min；Microwave temperature control is adjusted in 59-
61 DEG C, stirring heat preservation 1h obtains crude product O- methyl-isourea Methylsulfates, its content of liquid chromatographic detection.
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| CN201711378295.6A CN108047094B (en) | 2017-12-19 | 2017-12-19 | Novel preparation method of O-methyl isourea methyl sulfate |
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| CN201711378295.6A CN108047094B (en) | 2017-12-19 | 2017-12-19 | Novel preparation method of O-methyl isourea methyl sulfate |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303045A (en) * | 2019-11-25 | 2020-06-19 | 温州大学 | Production process of 2-ethoxy-4, 6-difluoropyrimidine |
| CN112979502A (en) * | 2021-02-24 | 2021-06-18 | 武汉青江化工黄冈有限公司 | Novel oxymethylisourea hydrogen sulfate and preparation method and application thereof |
| CN113387843A (en) * | 2021-04-15 | 2021-09-14 | 上海凌凯医药科技有限公司 | Method for synthesizing O-methyl isourea hydrogen sulfate |
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| JPS61180760A (en) * | 1985-02-05 | 1986-08-13 | Dainippon Ink & Chem Inc | Production of o-methylisourea acetic acid salt |
| CN1263088A (en) * | 1998-11-23 | 2000-08-16 | Basf公司 | Preparation of o-alkyl isourea |
| CN103483273A (en) * | 2013-09-12 | 2014-01-01 | 浙江工业大学 | 6-methyl-5-fluorine-2,4-pyrimidinediamine compound and preparation and application thereof |
| CN105669496A (en) * | 2016-03-04 | 2016-06-15 | 湖南化工研究院有限公司 | Preparation method of O-methyl isourea sulphate |
| CN106632080A (en) * | 2016-08-25 | 2017-05-10 | 宿迁市万和泰化工有限公司 | Flucytosine manufacturing process |
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Patent Citations (5)
| 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 |
| CN1263088A (en) * | 1998-11-23 | 2000-08-16 | Basf公司 | Preparation of o-alkyl isourea |
| CN103483273A (en) * | 2013-09-12 | 2014-01-01 | 浙江工业大学 | 6-methyl-5-fluorine-2,4-pyrimidinediamine compound and preparation and application thereof |
| CN105669496A (en) * | 2016-03-04 | 2016-06-15 | 湖南化工研究院有限公司 | Preparation method of O-methyl isourea sulphate |
| CN106632080A (en) * | 2016-08-25 | 2017-05-10 | 宿迁市万和泰化工有限公司 | Flucytosine manufacturing process |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111303045A (en) * | 2019-11-25 | 2020-06-19 | 温州大学 | Production process of 2-ethoxy-4, 6-difluoropyrimidine |
| CN112979502A (en) * | 2021-02-24 | 2021-06-18 | 武汉青江化工黄冈有限公司 | Novel oxymethylisourea hydrogen sulfate and preparation method and application thereof |
| CN113387843A (en) * | 2021-04-15 | 2021-09-14 | 上海凌凯医药科技有限公司 | Method for synthesizing O-methyl isourea hydrogen sulfate |
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