CN109836424A - A kind of method that the sodium salt methylation of environment-friendly type theophylline prepares caffeine - Google Patents
A kind of method that the sodium salt methylation of environment-friendly type theophylline prepares caffeine Download PDFInfo
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- CN109836424A CN109836424A CN201910184371.2A CN201910184371A CN109836424A CN 109836424 A CN109836424 A CN 109836424A CN 201910184371 A CN201910184371 A CN 201910184371A CN 109836424 A CN109836424 A CN 109836424A
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Abstract
The present invention is a kind of method that the sodium salt methylation of environment-friendly type theophylline prepares caffeine.Method includes the following steps: theophylline sodium salt, DMC is added to reaction kettle, methanol reacts 1-5 hours under 100-180 DEG C, stirring；It is separated after cooling by rotary evaporation, obtained solid i.e. crude caffeine.The present invention greatly improves the reaction efficiency of theophylline sodium salt Yu DMC methylation reaction, and by simple purification step, crude caffeine obtained is purified；Caffeine yield reaches as high as 97.3%.
Description
Technical field:
The present invention relates to a kind of organic synthesis fields, more particularly, to a kind of synthetic method of caffeine.
Background technique:
Caffeine is a kind of astragalus alkaloid compound, and entitled 1,3, the 7- trimethyl xanthine of chemistry, normality is in white
Color or yellowish green, the needle-shaped crystalline hydrate for having mercerising, molecular formula C8H10N4O2·(H2O), molecular weight is
212.2059.The distillation of one Caffeine Hydrate can be refining to obtain hexagonal prism shape anhydrous crystalline, molecular formula C8H10N4O2, point
Son amount is 194.19.
Caffeine is a kind of central nervous excitation agent, has selective excitement effect, drive that can be temporary to cerebral cortex
It walks sleepiness and regains one's vigor, clinically for treating neurasthenia and stupor recovery, and a kind of important antipyretic-antalgic agent.
The production method of caffeine mainly has extraction method, biological synthesis process and chemical synthesis.Corpse fourth in 1820
Pelletier extracts caffeine from coffee for the first time.And since 1899 annual fee She Er chemical synthesis caffeines, chemistry
Synthetic method, which prepares caffeine just, becomes the main source of caffeine.
Currently, the synthetic route of caffeine manufacturing enterprise is almost the same, i.e., using cyanoacetic acid and dimethyl urea as initial
Raw material is prepared through multistep reactions such as condensation, cyclization, nitrosation, reduction, phthalein, methylations, and wherein a particularly critical step is
The final step of synthetic caffeine is the methylation reaction of theophylline sodium salt.Whether this step also has clearly concerning entire synthetic route
The characteristic of clean production or environmental protection production.
Typical methylating reagent such as iodomethane, the majority such as smell methane, dimethyl suflfate, chloromethanes are due to it is with toxicity
It is restricted in production and application.But in the prior art, the methylation reaction reagent of caffeine is still dimethyl suflfate
(DMS), the waste water for reacting generation is not only measured greatly, also to pass through extremely complex post-processing, and dimethyl suflfate before discharging
Use and its reaction after the carcinogenicity by-product methyl sulfate that generates, also do not meet the development trend of green chemistry chemical technology.
Summary of the invention:
The purpose of the present invention is provide a kind of environment-friendly type theophylline sodium salt methylation preparation for deficiency existing for current techniques
The method of caffeine.This method uses methanol as solvent, any catalyst is not used, using the technique side of solid-liquid two phase reaction
Method greatly improves the reaction efficiency of theophylline sodium salt Yu DMC methylation reaction, and by simple purification step, will be obtained thick
Caffeine is savored to be purified.
The technical solution of the present invention is as follows:
A kind of method that the sodium salt methylation of environment-friendly type theophylline prepares caffeine, comprising the following steps:
Theophylline sodium salt, DMC is added to reaction kettle, methanol reacts 1~5 hour under 100~180 DEG C, stirring；It is cooled to
After room temperature, it is evaporated in 50~70 DEG C of rotary evaporation to solvents, obtained solid i.e. crude caffeine.
Wherein, molar ratio is theophylline sodium salt: dimethyl carbonate (DMC)=1:1~20.
Wherein, 5~30ml methanol is added in every 0.01 mole of theophylline sodium salt.The purification step packet of the crude caffeine
It includes:
Obtained crude caffeine is dissolved into ultrapure water, 1~3 hour of low temperature crystallization, then takes advantage of at 0~10 DEG C
Cold suction filtration obtains solid and is put into vacuum drying oven, and 60 DEG C are dried in vacuo 2~4 hours；
Wherein, the thick caffeine of mass ratio: water=1:1~10.
Substantive distinguishing features of the invention are as follows:
Current theophylline sodium salt methylation is prepared in the related patents of caffeine, and catalyst, and common solvent have been used
For water, method is complicated, and separation is difficult, and by-product is more.And the present invention does not use any catalyst, and organic phase methanol is used only
Making solvent can be completed theophylline sodium salt methylation reaction, and reaction system and method are all relatively easy, and product separates also than simpler
It is single, and yield is also relatively high, has reached 97.3%.
The invention has the benefit that
1. the present invention does not need to greatly reduce production cost using any catalyst.
2. document report and actual production process illustrate, the product yield of DMS technique is 90% or so.And the application
DMC technique caffeine yield reach as high as 97.3%, it is evident that improve the utilization rate of raw material theophylline sodium salt.
3. this technology purifies caffeine using washing lowering temperature crystallization, avoids use and limit the use of product chloroform and methylene chloride.
4. and DMS technics comparing, this technology can mentioned using DMC methylation reaction system, the by-product carbinol sodium of generation
Pure procedure is converted into the methanol/water solution of sodium hydroxide.
5. the DMC methylation reaction process system effects of energy saving and emission reduction of the application is obvious to sum up with DMS technics comparing.
Specific embodiment:
Below with reference to embodiment the present invention is described in detail, but embodiment should not limit the scope of the invention.
Theophylline sodium salt and DMC methylation reaction equation are as follows:
Embodiment 1
The theophylline sodium salt of 0.01mol is separately added into the liner with cover of 100ml Hastelloy reaction kettle, 0.1mol's
The methanol of DMC, 20ml.3 hours of confined reaction at 160 DEG C.It is cooled to room temperature, mixture in kettle is rotated to steaming at 60 DEG C
It is sent to solvent to be evaporated, obtains crude caffeine.A certain amount of sample preparation solution is taken, is detected using HPLC, obtaining reaction yield is
90.9%.
Embodiment 2
The theophylline sodium salt of 0.01mol is separately added into the liner with cover of 100ml Hastelloy reaction kettle, 0.1mol's
The methanol of DMC, 20ml.4 hours of confined reaction at 160 DEG C.Solvent is steamed after cooling, obtains crude caffeine.Take one
Quantitative sample preparation solution, is detected using HPLC, and obtaining reaction yield is 94.0%.
Embodiment 3
The theophylline sodium salt of 0.01mol is separately added into the liner with cover of 100ml Hastelloy reaction kettle, 0.05mol's
The methanol of DMC, 20ml.3 hours of confined reaction at 160 DEG C.Solvent is steamed after cooling, obtains crude caffeine.Take one
Quantitative sample preparation solution, is detected using HPLC, and obtaining reaction yield is 85.4%.
Embodiment 4
The theophylline sodium salt of 0.01mol is separately added into the liner with cover of 100ml Hastelloy reaction kettle, 0.06mol's
The methanol of DMC, 10ml.3 hours of confined reaction at 160 DEG C.Solvent is steamed after cooling, obtains crude caffeine.Take one
Quantitative sample preparation solution, is detected using HPLC, and obtaining reaction yield is 97.3%.
Embodiment 5
Crude caffeine 2g in above-described embodiment 4 is put into 100ml beaker, 20ml room temperature ultrapure water is added, will burn
Cup is put into 5 DEG C of refrigerator, 1 hour of low temperature crystallization, takes advantage of cold suction filtration, solid is put into vacuum drying oven, 60 DEG C of vacuum drying 3 are small
When.A certain amount of sample preparation solution is taken, is detected using HPLC, measuring caffeine purity is 99.0%.
The mechanism of purification is to obtain the coffee of higher degree by the way that the method that a certain amount of water carries out decrease temperature crystalline is added
Cause.
This is because containing a certain amount of by-product carbinol sodium in crude caffeine, sodium methoxide is reacted with water to be generated
Methanol and sodium hydroxide, and according to the difference of data caffeine, sodium hydroxide solubility in water, so the present invention is in crude product coffee
A certain amount of water is added to caffeine decrease temperature crystalline in coffee because in, takes advantage of cold filtering purification caffeine.
Wherein, the quality of thick caffeine and water is 1:1~1:10 than range.
Sterling caffeine and the sodium hydroxide solubility at each temperature in water
Unaccomplished matter of the present invention is well-known technique.
Claims (2)
1. a kind of method that the sodium salt methylation of environment-friendly type theophylline prepares caffeine, it is characterized in that method includes the following steps:
Theophylline sodium salt, DMC is added to reaction kettle, methanol reacts 1 ~ 5 hour under 100 ~ 180 DEG C, stirring；It is cooled to room temperature
Afterwards, it is evaporated in 50 ~ 70 DEG C of rotary evaporation to solvents, obtained solid i.e. crude caffeine；
Wherein, molar ratio is theophylline sodium salt: dimethyl carbonate (DMC)=1:1 ~ 20；5 ~ 30ml is added in every 0.01 mole of theophylline sodium salt
Methanol.
2. the method that environment-friendly type theophylline sodium salt methylation as described in claim 1 prepares caffeine, it is characterized in that described is thick
The purification step for savoring caffeine includes:
Obtained crude caffeine is dissolved into ultrapure water, 1 ~ 3 hour of low temperature crystallization, then takes advantage of cold pumping at 0 ~ 10 DEG C
Filter obtains solid and is put into vacuum drying oven, and 60 DEG C are dried in vacuo 2 ~ 4 hours；
Wherein, the thick caffeine of mass ratio: water=1:1 ~ 10.
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| CN201910184371.2A CN109836424B (en) | 2019-03-12 | 2019-03-12 | Method for preparing caffeine by methylation of environment-friendly theophylline sodium salt |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112724143A (en) * | 2021-02-07 | 2021-04-30 | 河北工业大学 | Method for preparing theobromine by methylating 3-methylxanthine |
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| CN104892611A (en) * | 2015-05-19 | 2015-09-09 | 青岛科技大学 | Synthetic method of caffeine |
| CN105294691A (en) * | 2015-11-23 | 2016-02-03 | 青岛科技大学 | Preparation process for environment-friendly semisynthetic caffeine |
| CN106046004A (en) * | 2016-06-06 | 2016-10-26 | 上海佰特因医药科技有限公司 | Total synthesis method for theacrine |
| CN106496227A (en) * | 2016-08-31 | 2017-03-15 | 安徽省润生医药股份有限公司 | A kind of preparation method and its usage of istradefylline |
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2019
- 2019-03-12 CN CN201910184371.2A patent/CN109836424B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892611A (en) * | 2015-05-19 | 2015-09-09 | 青岛科技大学 | Synthetic method of caffeine |
| CN105294691A (en) * | 2015-11-23 | 2016-02-03 | 青岛科技大学 | Preparation process for environment-friendly semisynthetic caffeine |
| CN106046004A (en) * | 2016-06-06 | 2016-10-26 | 上海佰特因医药科技有限公司 | Total synthesis method for theacrine |
| CN106496227A (en) * | 2016-08-31 | 2017-03-15 | 安徽省润生医药股份有限公司 | A kind of preparation method and its usage of istradefylline |
Non-Patent Citations (2)
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| 李兴泰等: ""伊曲茶碱合成工艺改进"", 《药学研究》 * |
| 胡彦汝: ""1，3-二甲基黄嘌呤甲基化的合成工艺优化"", 《中国优秀硕士学位论文全文数据库(电子期刊) 工程科技Ⅰ辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112724143A (en) * | 2021-02-07 | 2021-04-30 | 河北工业大学 | Method for preparing theobromine by methylating 3-methylxanthine |
| CN112724143B (en) * | 2021-02-07 | 2022-04-15 | 河北工业大学 | Method for preparing theobromine by methylating 3-methylxanthine |
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