CN101955466A - Synthesis method of 5-trifluoromethyluracil - Google Patents
Synthesis method of 5-trifluoromethyluracil Download PDFInfo
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- CN101955466A CN101955466A CN2009100575883A CN200910057588A CN101955466A CN 101955466 A CN101955466 A CN 101955466A CN 2009100575883 A CN2009100575883 A CN 2009100575883A CN 200910057588 A CN200910057588 A CN 200910057588A CN 101955466 A CN101955466 A CN 101955466A
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- uridylic
- trifluoromethyl
- cf3i
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- trifluoromethyluracil
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Abstract
The invention relates to a practical synthesis method of 5-trifluoromethyluracil, which mainly solves the technical problem of high cost caused by multiple synthesis steps or excessive use of expensive raw materials in the traditional synthesis method. Uracil is used as a raw material and reacts with a water solution of trifluoroiodomethane, hydrogen peroxide and ferric sulfate under the environment of fluoboric acid by heating to obtain high-yield 5-trifluoromethyluracil. The chemical reaction formula is disclosed in the specifications.
Description
Technical field:
The present invention relates to the simple and practical synthetic method of 5-trifluoromethyl uridylic.
Background technology:
Uridylic is a base important in the human body.The alkyl that modification contains a plurality of fluorine atoms on uridylic or similar base is at medicine and pharmaceutical intermediate, and all there is important use aspects such as agricultural chemicals.And trifluoromethyl is proved to be a very useful modification group, and the uridylic that trifluoromethyl is modified is the key intermediate of some anticarcinogens.Many bibliographical informations have been arranged the at present preparation of 5-trifluoromethyl uridylic.Mainly contain following several method:
1) 2-trifluoromethyl acrylate and urea element generate 5 with iodine under sulphuric acid catalysis in DMSO, and 6-dihydro-5-trifluoromethyl uridylic is reoxidised into 5-trifluoromethyl uridylic.
2) trifluoromethyl mercury and uridylic under the AIBN effect in the reaction 100h, productive rate 54%.
3) 5-iodouracil and two fluoro-2-fluorosulfonyl methyl acetates prepare under cupric iodide catalysis.
4) methyl uracil becomes 5-trichloromethyl-2 with chlorinated with chlorine earlier, the 4-dichloro pyrimidine, and again at butter of antimony, antimony pentachloride and anhydrous hydrofluoric acid effect generate 5-trifluoromethyl uridylic down.
5) uridylic and CF3I are under acidic conditions, and the effect of superoxide and molysite is preparation down.
This several method relatively, preceding four kinds owing to relate to polystep reaction and some special reagents, be not suitable for large-scale industrial production.The 5th kind of method once go on foot can higher yields preparation 5-trifluoromethyl uridylic, but need use the CF3I of excessive (3-6 equivalent), and this reagent is expensive difficult preparation gas, with the method in the document, cost is higher.
Summary of the invention:
The simple and practical synthetic method that the purpose of this invention is to provide a kind of 5-trifluoromethyl uridylic, the mainly technical problem that synthesis step is many or the excessive use of expensive raw material causes the cost height to be looked forward to of the existing synthetic method existence of solution.The present invention is primarily aimed at the method for trifluoromethyl methyl iodide and has optimized experiment condition, has developed a kind of synthesis technique of practicality, thereby has reduced cost effectively.
Technical scheme of the present invention:
The synthesis technique of 5-trifluoromethyl uridylic of the present invention is as follows:
The present invention is raw material with the uridylic, and under the fluoroboric acid environment, with CF3I, hydrogen peroxide and ferric sulfate aqueous solution reacting by heating just can higher yields obtains 5-trifluoromethyl uridylic.
The consumption of CF3I is 1 equivalent, and the consumption of hydrogen peroxide is 2 equivalents, and the ferric sulfate aqueous solution consumption is 0.3 equivalent.Temperature of reaction is 60-70 ℃, reacts under this temperature 1～3 hour.
Beneficial effect of the present invention: synthesis technique of the present invention is succinct, and method for purifying and separating is easy, with the preparation of the CF3I higher yields of low equivalent 5-trifluoromethyl uridylic, productive rate can reach more than 54%, has reduced cost effectively.The present invention can apply to a large amount of synthetic of 5-trifluoromethyl uridylic.
Embodiment:
Embodiment one
The preparation of 2mol/L CF3I solution:
Tool mouth at 500mL receives the dimethyl sulfoxide (DMSO) that adds 400mL in the test tube, and weighing is also write down gross weight.The frozen water cooling is stirred down.Inlet end connects the CF3I steel cylinder, and exit end connects a same tool mouth that the 40mL dimethyl sulfoxide (DMSO) is housed and receives test tube as the tail gas receiving trap.Open the valve of steel cylinder at ambient temperature, CF3I gas is slowly fed in the dimethyl sulfoxide (DMSO).Speed is as the criterion can't see bubble in the receiving bottle.Waiting first to receive when the test tube total mass has increased by 160 grams stops.This solution is 2mol/L CF3I solution.
The operation of this technology:
(27.5g 0.25mol) adds the 1000mL there-necked flask that constant pressure funnel is housed to uridylic, adds the 500mL dmso solution, system nitrogen replacement three times.Inject the fluoborate solution of 50mL 42%.Then inject the DMSO solution of the 2mol/L CF3I of 125mL.Reaction flask is placed the frozen water system, slowly inject the ferric sulfate aqueous solution of 75mL 3mol/L.The aqueous hydrogen peroxide solution of 50mL 30% injects constant pressure funnel, splashes into system in 15 minutes.Stirred 15 minutes, and directly reaction flask was moved in the oil bath that is heated to 70 ℃ then.Stir, afterreaction blackening gradually in 20 minutes continues to stir 2 hours, and the some plate detects to be found no longer to change.Stopped reaction.Cool to room temperature, pour into sodium sulfite aqueous solution (1mol/L, 1000mL) be quenched to light yellow.With ethyl acetate extraction (10 * 500mL).Organic layer wash with water (2 * 200mL), anhydrous sodium sulfate drying.Filter, concentrate and obtain product (24.5g, productive rate: 55.6%).
HNMR(d-DMSO)δppm：11.59(S，2H)，8.02(S，1H).
FNMR(d-DMSO)δppm：-61.58.
Embodiment two
The operation of this technology:
(27.5g 0.25mol) adds the 1000mL there-necked flask that constant pressure funnel is housed to uridylic, adds the 500mL dmso solution, system nitrogen replacement three times.Inject the fluoborate solution of 50mL 42%.Then inject the DMSO solution of the 2mol/L CF3I of 125mL.Reaction flask is placed the frozen water system, slowly inject the ferric sulfate aqueous solution of 75mL 3mol/L.The aqueous hydrogen peroxide solution of 50mL 30% injects constant pressure funnel, splashes into system in 15 minutes.Stirred 15 minutes, and directly reaction flask was moved in the oil bath that is heated to 60 ℃ then.Stir, reacted blackening gradually in 20 minutes, continue to stir 3 hours, the some plate detects to be found no longer to change.Stopped reaction.Cool to room temperature, pour into sodium sulfite aqueous solution (1mol/L, 1000mL) be quenched to light yellow.With ethyl acetate extraction (10 * 500mL).Organic layer wash with water (2 * 200mL), anhydrous sodium sulfate drying.Filter, concentrate and obtain product (24.1g, productive rate: 54.5%).
Embodiment three
The operation of this technology:
(27.5g 0.25mol) adds the 1000mL there-necked flask that constant pressure funnel is housed to uridylic, adds the 500mL dmso solution, system nitrogen replacement three times.Inject the fluoborate solution of 50mL 42%.Then inject the DMSO solution of the 2mol/L CF3I of 125mL.Reaction flask is placed the frozen water system, slowly inject the ferric sulfate aqueous solution of 75mL 3mol/L.The aqueous hydrogen peroxide solution of 50mL 30% injects constant pressure funnel, splashes into system in 15 minutes.Stirred 15 minutes, and directly reaction flask was moved in the oil bath that is heated to 65 ℃ then.Stir, reacted blackening gradually in 20 minutes, continue to stir 2.5 hours, the some plate detects to be found no longer to change.Stopped reaction.Cool to room temperature, pour into sodium sulfite aqueous solution (1mol/L, 1000mL) be quenched to light yellow.With ethyl acetate extraction (10 * 500mL).Organic layer wash with water (2 * 200mL), anhydrous sodium sulfate drying.Filter, concentrate and obtain product (24.5g, productive rate: 55.6%).
Embodiment four
The operation of this technology:
(27.5g 0.25mol) adds the 1000mL there-necked flask that constant pressure funnel is housed to uridylic, adds the 500mL dmso solution, system nitrogen replacement three times.Inject the fluoborate solution of 50mL 42%.Then inject the DMSO solution of the 2mol/L CF3I of 125mL.Reaction flask is placed the frozen water system, slowly inject the ferric sulfate aqueous solution of 75mL 3mol/L.The aqueous hydrogen peroxide solution of 50mL 30% injects constant pressure funnel, splashes into system in 15 minutes.Stirred 15 minutes, and directly reaction flask was moved in the oil bath that is heated to 67 ℃ then.Stir, reacted blackening gradually in 20 minutes, continue to stir 1.5 hours, the some plate detects to be found no longer to change.Stopped reaction.Cool to room temperature, pour into sodium sulfite aqueous solution (1mol/L, 1000mL) be quenched to light yellow.With ethyl acetate extraction (10 * 500mL).Organic layer wash with water (2 * 200mL), anhydrous sodium sulfate drying.Filter, concentrate and obtain product (25.1g, productive rate: 56.8%).
Claims (2)
1. the synthetic method of a 5-trifluoromethyl uridylic, may further comprise the steps, by uridylic is raw material, with CF3I under acidic conditions, and superoxide, the molysite reaction obtains, and it is characterized in that: the described acid of acidic conditions is fluoroboric acid, superoxide is a hydrogen peroxide, and molysite is a ferric sulfate aqueous solution.
2. the synthetic method of 5-trifluoromethyl uridylic according to claim 1, it is characterized in that, the consumption of CF3I is 1 equivalent, the consumption of hydrogen peroxide is 2 equivalents, the ferric sulfate aqueous solution consumption is 0.3 equivalent, temperature of reaction is 60-70 ℃, reacts under this temperature 1～3 hour, and reaction formula is:
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| CN2009100575883A CN101955466A (en) | 2009-07-13 | 2009-07-13 | Synthesis method of 5-trifluoromethyluracil |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014076085A1 (en) * | 2012-11-13 | 2014-05-22 | Boehringer Ingelheim International Gmbh | Novel process for the manufacture of 2,4-dichloro-5-trifluoromethyl-pyrimidine |
| CN103880760A (en) * | 2014-04-18 | 2014-06-25 | 南京安源生物医药科技有限公司 | Synthesis method of 5-(trifluoromethyl) uracil |
| CN106892873A (en) * | 2017-04-16 | 2017-06-27 | 内蒙古佳瑞米精细化工有限公司 | A kind of preparation method of 5 trifluoromethyl uracil |
-
2009
- 2009-07-13 CN CN2009100575883A patent/CN101955466A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014076085A1 (en) * | 2012-11-13 | 2014-05-22 | Boehringer Ingelheim International Gmbh | Novel process for the manufacture of 2,4-dichloro-5-trifluoromethyl-pyrimidine |
| CN103880760A (en) * | 2014-04-18 | 2014-06-25 | 南京安源生物医药科技有限公司 | Synthesis method of 5-(trifluoromethyl) uracil |
| CN106892873A (en) * | 2017-04-16 | 2017-06-27 | 内蒙古佳瑞米精细化工有限公司 | A kind of preparation method of 5 trifluoromethyl uracil |
| CN106892873B (en) * | 2017-04-16 | 2019-11-15 | 内蒙古佳瑞米精细化工有限公司 | A kind of preparation method of 5- trifluoromethyl uracil |
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Application publication date: 20110126 |