CN101054366B - Method of synthesizing 1-methyl hydantoin - Google Patents
Method of synthesizing 1-methyl hydantoin Download PDFInfo
- Publication number
- CN101054366B CN101054366B CN2007100556900A CN200710055690A CN101054366B CN 101054366 B CN101054366 B CN 101054366B CN 2007100556900 A CN2007100556900 A CN 2007100556900A CN 200710055690 A CN200710055690 A CN 200710055690A CN 101054366 B CN101054366 B CN 101054366B
- Authority
- CN
- China
- Prior art keywords
- reaction
- minutes
- add
- zassol
- heated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The present invention relates to a synthetic method of 1-methyl hydantoin, which belongs to synthetic method of compounds. The synthetic method includes following steps, adding 46.5g 30% aminomethane water solution, 106g 10% sodium carbonate water solution and 87.5g 20% 500ml 4-opening flasksodium monochloracetate water solution to react for 3 to 5hr at 50 to 70 DEG C; vaporizing to remove aminomethane and regulating pH value to 2; Heating to 100DEG C, dropping 91g 8% sodium cyanate water solution, agitating and reacting 30 minutes, adding 7.3g sodium cyanate solid to react 90 minutes, then cooling it to 5 DEG C, adding 25g concentrated sulfuric acid, heating to 100 DEG C and reflux reacting 2hr, generating crude product by vacuum distilling. The present invention is characterized in that it implement green chemical because of avoiding using hypertoxic medicine of hydroxy acetonitrile and enhance the safety of operation, and its synthesis cost is low, entire syntheticroute is more simple, which is suitable for large scale industrial production.
Description
Technical field
The invention belongs to the synthetic method of compound, be specifically related to the synthetic method of 1-methyl hydantoin.
Background technology
The 1-methyl hydantoin is a kind of of glycolylurea analog derivative, and it has pharmacological action very widely, and for example anti-inflammatory resists low serum protein mass formed by blood stasis, eliminate activity oxygen and free radical etc.The synthetic method bibliographical information of 1-methyl hydantoin is less, 1-benzyl-5-alkoxyl group glycolylurea, 1-amino-2 are arranged at present, the synthetic route of related compounds such as 4-glycolylurea, 5-(substituted naphthyl) glycolylurea, wherein the synthetic method of 1-benzyl-5-alkoxyl group glycolylurea has been used the hypertoxic drug hydroxyacetonitrile, therefore do not meet Green Chemistry, and 1-amino-2, the synthetic method productive rate of 4-glycolylurea is lower.
Summary of the invention
The invention provides a kind of synthetic method of 1-methyl hydantoin, to solve the use hypertoxic drug that exists in synthetic, the problem of complex synthetic route.The technical scheme that the present invention takes is:
In the 500ml four-necked bottle, add 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 50 ℃～70 ℃ reaction 3～5hr.Steaming removes methylamine and regulates the pH value is 2.Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, stirring reaction is after 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃ of back flow reaction 2hr, evaporated under reduced pressure gets crude product.
The present invention is with synthetic product chloroform recrystallization purifying.
The present invention is methylamine and sodium chloroacetate at first, is solvent with water, is 50～70 ℃ in temperature of reaction, and the reaction times is that reaction makes N-methylamino-sodium acetate under 3～5 hours conditions; Further reacting with Zassol under acidic conditions then, is to heat cyclization under 100 ℃ of conditions to obtain the 1-methyl hydantoin with reacted product in temperature of reaction.
The invention has the advantages that: owing to avoid using the hypertoxic drug hydroxyacetonitrile, thus realized Green Chemistry, improved the security of operation; Selected sodium chloroacetate simultaneously, methylamine, the inexpensive raw material that is easy to get such as Zassol, thereby reduce and synthesize cost, and last 1-methyl hydantoin yield can reach 60～63%, is higher than the productive rate of bibliographical information, has obtained good effect, make that whole synthetic route is more simple, be fit to industrialized production.
Embodiment
Embodiment 1
In the 500ml four-necked bottle, add 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 50 ℃ of reaction 4hr.Steaming removes methylamine and regulates the pH value is 2.Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, behind the stirring reaction 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃ of back flow reaction 2hr, evaporated under reduced pressure gets crude product 9.85g (59.4%).With synthetic product chloroform recrystallization purifying, the product after purified detects purity through high performance liquid phase and can reach more than 99%.
Embodiment 2
In the 500ml four-necked bottle, add 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 60 ℃ of reaction 4hr.Steaming removes methylamine and regulates the pH value is 2.Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, behind the stirring reaction 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃, back flow reaction 2hr, evaporated under reduced pressure gets crude product 10.77g (62.5%).With synthetic product chloroform recrystallization purifying, the product after purified detects purity through high performance liquid phase and can reach more than 99%.
Embodiment 3
In the 500ml four-necked bottle, add 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 70 ℃ of reaction 4hr.Steaming removes methylamine and regulates the pH value is 2.Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, behind the stirring reaction 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃, back flow reaction 2hr, evaporated under reduced pressure gets crude product 10.18g (61.4%).With synthetic product chloroform recrystallization purifying, the product after purified detects purity through high performance liquid phase and can reach more than 99%.
Embodiment 4
In the 500ml four-necked bottle, add 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 60 ℃ of reaction 3hr.Steaming removes methylamine and regulates the pH value is 2.Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, behind the stirring reaction 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃, back flow reaction 2hr, evaporated under reduced pressure gets crude product 10.21g (61.6%).With synthetic product chloroform recrystallization purifying, the product after purified detects purity through high performance liquid phase and can reach more than 99%.
Embodiment 5
In the 500ml four-necked bottle, add 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 60 ℃ of reaction 5hr.Steaming removes methylamine and regulates the pH value is 2.Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, behind the stirring reaction 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃, back flow reaction 2hr, evaporated under reduced pressure gets crude product 9.75g (58.8%).With synthetic product chloroform recrystallization purifying, the product after purified detects purity through high performance liquid phase and can reach more than 99%.
Claims (2)
1. the synthetic method of a 1-methyl hydantoin, it is characterized in that comprising the following steps: in the 500ml four-necked bottle, adding 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 50 ℃～70 ℃ reaction 3～5hr; Steaming removes methylamine and regulates the pH value is 2; Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, stirring reaction is after 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃ of back flow reaction 2hr, evaporated under reduced pressure gets crude product.
2. the synthetic method of 1-methyl hydantoin according to claim 1, it is characterized in that comprising the following steps: in the 500ml four-necked bottle, adding 30% aqueous methylamine solution 46.5g, 10% aqueous sodium carbonate 106g, 20% sodium chloroacetate aqueous solution 87.5g, 50 ℃ of reaction 4hr; Steaming removes methylamine and regulates the pH value is 2; Be heated to 100 ℃, drip 8% Zassol aqueous solution 91g under the reflux state again, behind the stirring reaction 30 minutes, add Zassol solid 7.3g and continue reaction after 90 minutes, be cooled to 5 ℃, add 98% vitriol oil 25g, be heated to 100 ℃ of back flow reaction 2hr, evaporated under reduced pressure gets crude product 9.85g (59.4%), and with synthetic product chloroform recrystallization purifying, the product after purified detects purity through high performance liquid phase and can reach more than 99%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100556900A CN101054366B (en) | 2007-05-28 | 2007-05-28 | Method of synthesizing 1-methyl hydantoin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007100556900A CN101054366B (en) | 2007-05-28 | 2007-05-28 | Method of synthesizing 1-methyl hydantoin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101054366A CN101054366A (en) | 2007-10-17 |
| CN101054366B true CN101054366B (en) | 2010-06-23 |
Family
ID=38794439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100556900A Expired - Fee Related CN101054366B (en) | 2007-05-28 | 2007-05-28 | Method of synthesizing 1-methyl hydantoin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101054366B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103360320B (en) * | 2013-07-30 | 2015-12-02 | 邱智东 | The preparation method of 1-methyl-2,4-imidazolidinedione |
-
2007
- 2007-05-28 CN CN2007100556900A patent/CN101054366B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN101054366A (en) | 2007-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106810426B (en) | Method for synthesizing cannabidiol | |
| CN111892507B (en) | Synthesis method of dopamine hydrochloride | |
| CN104974060A (en) | Method for preparing sodium, 8-(2-hydroxybenzamido)octanoate | |
| CN104945299B (en) | A kind of high-efficiency synthesis method of vildagliptin | |
| CN110590635A (en) | Preparation method of levetiracetam and intermediate thereof | |
| CN112592356A (en) | Method for synthesizing lornoxicam | |
| CN112062712A (en) | Preparation method of 2- (5-bromo-3-methylpyridin-2-yl) acetic acid hydrochloride | |
| CN103664923B (en) | The preparation method of Nifuratel | |
| CN102485723A (en) | Semi-synthesis of vinpocetine through one kettle way and preparation of water-soluble vinpocetine salt | |
| CN101054366B (en) | Method of synthesizing 1-methyl hydantoin | |
| CN112574049A (en) | Novel method for preparing phenylglycine by using hydrocyanic acid | |
| CN101333175A (en) | Method for preparing D-asparagine and D-homoserine | |
| CN114181117B (en) | Preparation method of peramivir intermediate | |
| CN114702425A (en) | Preparation method of (S) -2-amino- (S) -3- [ pyrrolidone-2' ] alanine derivative and intermediate | |
| CN107879979A (en) | A kind of preparation method of Dexmedetomidine | |
| CN102010345A (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
| CN109836344B (en) | Method for producing glycine by organic solvent | |
| CN101492388A (en) | Method for synthesis of Miqujing medicament material | |
| CN111961077A (en) | Preparation method of beta sodium glycerophosphate containing crystal water | |
| CN108203396B (en) | Synthesis of enkephalinase inhibitor | |
| CN104496833A (en) | Gabapentin synthesis technology | |
| CN111662233B (en) | Method for synthesizing 4-chloro-1H-imidazole-2-carboxylic acid ethyl ester by one-step method | |
| CN108101852A (en) | A kind of preparation method of olaparib | |
| CN116655481B (en) | Industrial synthesis method of levocarnitine | |
| CN103265616A (en) | N(2)-L-alanyl-L-glutamine synthesis method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100623 Termination date: 20130528 |