CN108264471A - A kind of synthetic method of pharmaceutical intermediate Allyl thiourea - Google Patents
A kind of synthetic method of pharmaceutical intermediate Allyl thiourea Download PDFInfo
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- CN108264471A CN108264471A CN201611268422.2A CN201611268422A CN108264471A CN 108264471 A CN108264471 A CN 108264471A CN 201611268422 A CN201611268422 A CN 201611268422A CN 108264471 A CN108264471 A CN 108264471A
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- solution
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- allyl thiourea
- synthetic method
- dehydrating agent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C331/00—Derivatives of thiocyanic acid or of isothiocyanic acid
- C07C331/02—Thiocyanates
- C07C331/04—Thiocyanates having sulfur atoms of thiocyanate groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
- C07C335/10—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of an unsaturated carbon skeleton
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A kind of synthetic method of pharmaceutical intermediate Allyl thiourea, mainly includes the following steps：5L sodium chloride solutions are added in reaction vessel, the 3 methylisothiocyanate benzene of 4mol, raising solution temperature is to 60 65 DEG C, the allylamine of 5-6mol and 6L acetone solns are added in, flow back 90 120min, stratification, take out oil reservoir, it is washed 5-7 times with potassium bromide solution, obtains propenyl mustard oil, dehydrating agent dehydration, filtering, filtrate decompression is distilled, and is collected 80-86 DEG C of fraction, is obtained thiocyanic acid acrylic ester；The thiocyanic acid acrylic ester of gained is added to 5-6mol phenyl acetamides, add in 2L aqueous solutions, solution temperature is increased to 50-60 DEG C, reacts 50-70min, reduces solution temperature to 10-15 DEG C, crystal is precipitated, filtering, toluene solution washing, butanone solution washing, dehydrating agent is dehydrated, and obtains finished product Allyl thiourea.
Description
Technical field
The present invention relates to a kind of synthetic methods of pharmaceutical intermediate Allyl thiourea.
Background technology
Allyl thiourea is mainly used as preservative, and external used medicine for plastic surgery, eliminates scar, and cosmetics eliminate skin
Skin microscratch；Cyanide-free copper electroplating additive；Organic synthesis raw material.It is used for inhibiting nitration reaction in sewage experiment.But existing synthesis
Method does reactant using sodium sulfocynanate mostly, and process is more complicated, and ultimate yield is simultaneously not bery high, therefore, it is necessary to propose one
Kind new synthetic method, this quality and yield for further improving product, reducing by-products content has important economy
Meaning.
Invention content
The purpose of the present invention is to provide a kind of synthetic methods of pharmaceutical intermediate Allyl thiourea, include the following steps：
(i) 5L sodium chloride solutions are added in reaction vessel, the 3- methylisothiocyanate benzene of 4mol, raising solution temperature is extremely
60--65 DEG C, the allylamine of 5-6mol and 6L acetone solns are added in, flow back 90-120min, and stratification takes out oil reservoir, uses bromine
Change potassium solution to wash 5-7 times, obtain propenyl mustard oil, dehydrating agent dehydration is filtered, and filtrate decompression distillation collects 80-86 DEG C
Fraction, obtain thiocyanic acid acrylic ester；The thiocyanic acid acrylic ester of gained is added to 5-6mol phenyl acetamides, adds in 2L aqueous solutions,
Solution temperature is increased to 50-60 DEG C, reacts 50-70min, reduces solution temperature to 10-15 DEG C, crystal, filtering, first is precipitated
Benzole soln washs, butanone solution washing, and dehydrating agent dehydration obtains finished product Allyl thiourea；Wherein, the sodium chloride described in step (i)
Liquid quality fraction is 10-16%, and acetone soln mass fraction described in step (i) is 15-20%, subtracting described in step (i)
Pressure residing for pressure distillation is 20--30kPa, and the toluene solution mass fraction described in step (i) is 70-80%, and step (i) is described
Butanone solution mass fraction for 85-90%, the dehydrating agent described in step (i) is Anhydrous potassium carbonate, appointing in dead plaster
Meaning is a kind of.
Entire reaction process can be represented with following reaction formula：
The invention has the advantages that：Reduce the intermediate link of reaction, shorten the reaction time, improve reaction yield.
Specific embodiment
With reference to specific implementation example, the invention will be further described：
A kind of synthetic method of pharmaceutical intermediate Allyl thiourea,
Example 1：
It is 10% sodium chloride solution that 5L mass fractions are added in reaction vessel, and the 3- methylisothiocyanate benzene of 4mol rises
High solution temperature is to 60 DEG C, and it is 15% acetone soln to add in the allylamine of 5mol and 6L mass fractions, and flow back 90min, stands and divides
Layer takes out oil reservoir, is washed 5 times with potassium bromide solution, obtains propenyl mustard oil, and dehydrating agent dehydration is filtered, and filtrate 20kPa subtracts
Pressure distillation collects 80 DEG C of fraction, obtains thiocyanic acid acrylic ester；The thiocyanic acid acrylic ester of gained is added to 5mol phenyl acetamides,
2L aqueous solutions are added in, raising solution temperature reacts 50min to 50 DEG C, reduces solution temperature to 10 DEG C, and crystal, filtering, matter is precipitated
It measures score to wash for 70% toluene solution, mass fraction is washed for 85% butanone solution, and the dehydration of Anhydrous potassium carbonate dehydrating agent is obtained into
Product Allyl thiourea 408.32g, yield 88%.
Example 2：
It is 13% sodium chloride solution that 5L mass fractions are added in reaction vessel, and the 3- methylisothiocyanate benzene of 4mol rises
High solution temperature is to 62 DEG C, and it is 17% acetone soln to add in the allylamine of 5.5mol and 6L mass fractions, and flow back 110min, stands
Layering is taken out oil reservoir, is washed 6 times with potassium bromide solution, obtains propenyl mustard oil, dehydrating agent dehydration, filtering, filtrate 25kPa
Vacuum distillation collects 83 DEG C of fraction, obtains thiocyanic acid acrylic ester；The thiocyanic acid acrylic ester of gained is added to 5.5mol phenylacetyls
Amine adds in 2L aqueous solutions, and raising solution temperature reacts 60min to 55 DEG C, reduces solution temperature to 12 DEG C, crystal, mistake is precipitated
Filter, mass fraction are washed for 75% toluene solution, and mass fraction is washed for 87% butanone solution, and dead plaster dehydrating agent takes off
Water obtains finished product Allyl thiourea 426.88g, yield 92%.
Example 3：
It is 16% sodium chloride solution that 5L mass fractions are added in reaction vessel, and the 3- methylisothiocyanate benzene of 4mol rises
High solution temperature is to 65 DEG C, and it is 20% acetone soln to add in the allylamine of 6mol and 6L mass fractions, and flow back 120min, stands and divides
Layer takes out oil reservoir, is washed 7 times with potassium bromide solution, obtains propenyl mustard oil, and dehydrating agent dehydration is filtered, and filtrate 30kPa subtracts
Pressure distillation collects 86 DEG C of fraction, obtains thiocyanic acid acrylic ester；The thiocyanic acid acrylic ester of gained is added to 6mol phenyl acetamides,
2L aqueous solutions are added in, raising solution temperature reacts 70min to 60 DEG C, reduces solution temperature to 15 DEG C, and crystal, filtering, matter is precipitated
It measures score to wash for 80% toluene solution, mass fraction is washed for 90% butanone solution, and the dehydration of Anhydrous potassium carbonate dehydrating agent is obtained into
Product Allyl thiourea 436.16g, yield 94%.
Claims (4)
1. a kind of synthetic method of pharmaceutical intermediate Allyl thiourea, which is characterized in that mainly include the following steps：
(i) 5L sodium chloride solutions, the 3- methylisothiocyanate benzene of 4mol, raising solution temperature to 60-- are added in reaction vessel
65 DEG C, the allylamine of 5-6mol and 6L acetone solns are added in, flow back 90-120min, and stratification takes out oil reservoir, uses potassium bromide
Solution washs 5-7 times, obtains propenyl mustard oil, and dehydrating agent dehydration is filtered, and filtrate decompression distillation, 80-86 DEG C of collection evaporates
Point, obtain thiocyanic acid acrylic ester；The thiocyanic acid acrylic ester of gained is added to 5-6mol phenyl acetamides, adds in 2L aqueous solutions, raising
Solution temperature reacts 50-70min to 50-60 DEG C, reduces solution temperature to 10-15 DEG C, crystal is precipitated, filter, toluene is molten
Liquid washs, butanone solution washing, and dehydrating agent dehydration obtains finished product Allyl thiourea；Wherein, the sodium chloride solution described in step (i)
Mass fraction is 10-16%, and the acetone soln mass fraction described in step (i) is 15-20%, and the decompression described in step (i) is steamed
It is 20--30kPa to evaporate residing pressure.
A kind of 2. synthetic method of pharmaceutical intermediate Allyl thiourea according to claim 1, which is characterized in that step (i)
The toluene solution mass fraction is 70-80%.
A kind of 3. synthetic method of pharmaceutical intermediate Allyl thiourea according to claim 1, which is characterized in that step (i)
The butanone solution mass fraction is 85-90%.
A kind of 4. synthetic method of pharmaceutical intermediate Allyl thiourea according to claim 1, which is characterized in that step (i)
The dehydrating agent is any one in Anhydrous potassium carbonate, dead plaster.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611268422.2A CN108264471A (en) | 2016-12-31 | 2016-12-31 | A kind of synthetic method of pharmaceutical intermediate Allyl thiourea |
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| CN201611268422.2A CN108264471A (en) | 2016-12-31 | 2016-12-31 | A kind of synthetic method of pharmaceutical intermediate Allyl thiourea |
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| CN108264471A true CN108264471A (en) | 2018-07-10 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112827659A (en) * | 2021-01-03 | 2021-05-25 | 中南大学 | Reagent and method for selective flotation separation of galena and sphalerite |
-
2016
- 2016-12-31 CN CN201611268422.2A patent/CN108264471A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112827659A (en) * | 2021-01-03 | 2021-05-25 | 中南大学 | Reagent and method for selective flotation separation of galena and sphalerite |
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| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180710 |
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| WD01 | Invention patent application deemed withdrawn after publication |