CN108395409A - Application of the stripper in dichloro pyrimidine purifying - Google Patents
Application of the stripper in dichloro pyrimidine purifying Download PDFInfo
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- CN108395409A CN108395409A CN201810552509.5A CN201810552509A CN108395409A CN 108395409 A CN108395409 A CN 108395409A CN 201810552509 A CN201810552509 A CN 201810552509A CN 108395409 A CN108395409 A CN 108395409A
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- Prior art keywords
- dichloro pyrimidine
- pyrimidine
- organic phase
- stripper
- dichloro
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention provides the methods that stripper purifies dichloro pyrimidine, include the following steps：A after) dihydroxy-pyrimidine carries out chlorination reaction, dichloro pyrimidine reaction mixture is obtained；B) reaction mixture is added water and is hydrolyzed, or ice water is added and carries out ice solution, is then extracted using organic solvent, obtains the organic phase of the crude product containing dichloro pyrimidine；C) organic phase of the crude product containing dichloro pyrimidine enters stripper from top or top, and vapor enters stripper from bottom or lower part, carries out punching steaming to the organic phase of the crude product containing dichloro pyrimidine, obtains the organic phase of the sterling containing dichloro pyrimidine；D) the organic phase of the sterling containing dichloro pyrimidine, decompression or air-distillation concentration, decrease temperature crystalline, centrifugation or filtering obtain dichloro pyrimidine sterling.The present invention uses reverse vapor stripper, dichloro pyrimidine crude product, with the state of drop, directly to be contacted with vapor in a manner of being added dropwise or spray so that purifying is efficient, and refined yield is greatly improved, and is suitble to industrialized production and application.
Description
Technical field
The present invention relates to the application of chemical field more particularly to stripper in dichloro pyrimidine purifying.
Background technology
2,4- dichloro pyrimidines, 2,5- dichloro pyrimidines, 4,6- dichloro pyrimidines, 2- amino -4,6- dichloro pyrimidines are used as and apply
Multi items pesticide, medicine etc. it is medicinal synthesis chemistry intermediate, be by hydroxy pyrimidine by chlorination reaction synthesize come.2,4- bis-
Hydroxy pyrimidine synthesizes 2,4- dichloro pyrimidines, and 2,5- dihydroxy-pyrimidines synthesize 2,5- dichloro pyrimidines, and 4,6- dihydroxy-pyrimidines synthesize 4,
6- dichloro pyrimidines.Because its structure is similar, so its chemical property is substantially similar, the chemical reaction of synthesis and chlorination are located with rear
Reason is also similar.By taking 4,6- dichloro pyrimidines as an example：
4,6- dichloro pyrimidines are the important intermediates for synthesizing sulfa drugs and fungicide Fluoxastrobin.Preparation method can divide
For phosphorus oxychloride chloridising and solid phosgene chloridising.Wherein the step of phosphorus oxychloride chloridising, is：By 4,6- dihydroxy-pyrimidines
It is reacted under tertiary amine effect with phosphorus oxychloride, obtains the reaction mixture of the dichloro pyrimidine Han 4,6-；The mixture passes through purifying,
Obtain pure 4,6- dichloro pyrimidines.
There are mainly two types of the purification process.The first purification process is：It will be mixed containing the reaction of 4,6- dichloro pyrimidines
Object is evaporated under reduced pressure, and is recycled phosphoryl chloride phosphorus oxychloride, is poured into ice water, is adjusted pH value to neutrality, is extracted with organic solvent, recycles organic layer, wash
It washs, dry, filter, be evaporated under reduced pressure, obtain 4,6- dichloro pyrimidines (Yang Guiqiu, Peng Ligang, the conjunction of .4, the 6- dichloro pyrimidine such as field Shanxi
At technical study [J] Shenyang Institute of Chemical Technology journals, 2009,23 (2)：118-120).Second of purification process be：4 will be contained,
The reaction mixture of 6- dichloro pyrimidines recycles phosphoryl chloride phosphorus oxychloride, is poured into ice water, sodium hydroxide is added to neutralize, dichloromethane extraction, water
It washes, dry, obtaining 4,6- dichloro pyrimidines after precipitation, (study on the synthesis [J] of the chlorine pyrimidines such as Peng Jun, Liu Weidong, Yong Lanzhi is fine
Chemical intermediate, 2009,39 (6)：14-17).
But there are many problems in actual production in both purification process, such as (1) extracts mode with organic solvent,
Because there are a large amount of byproducts of reaction, therefore product purity is not high, needs the further processing steps such as crystallization, reduces product
Yield；(2) mode is distilled, the distillation process time is long, and energy consumption is excessively high, and remaining salinity steps up in kettle, vapo(u)rizing temperature phase
It should increase, product is caused to decompose, while inorganic salt concentration is high in kettle, equipment damage rate is high.
Likewise, there is also above for the preparation of 2,4- dichloro pyrimidines, 2,5- dichloro pyrimidines, 2-amino-4,6-dichloropyrimidine
Problem.
Invention content
In view of this, the technical problem to be solved in the present invention is to provide application of the stripper in dichloro pyrimidine purifying,
It is easy to operate using stripper, there is higher yield and purity.
In order to solve the above technical problems, the application the present invention provides stripper in dichloro pyrimidine purifying.
Stripper is applied in the purifying of dichloro pyrimidine by the present invention, reduces material long-time high-temperature heating and causes
The side reactions such as degradation, polymerization, improve material and steam contacting efficiency, so the vaporizing extract process of stripper is than other stripping modes
It is more efficient, yield higher.
The present invention provides the methods that stripper purifies dichloro pyrimidine, include the following steps：
A after) dihydroxy-pyrimidine carries out chlorination reaction, dichloro pyrimidine reaction mixture is obtained；
B) reaction mixture is added water and is hydrolyzed, or ice water is added and carries out ice solution, is then extracted using organic solvent
It takes, obtains the organic phase of the crude product containing dichloro pyrimidine；
C) organic phase of the crude product containing dichloro pyrimidine enters stripper from top or top, and vapor enters from bottom or lower part
Stripper carries out punching steaming to the organic phase of the crude product containing dichloro pyrimidine, obtains the organic phase of the sterling containing dichloro pyrimidine；
D) the organic phase of the sterling containing dichloro pyrimidine, decompression or air-distillation concentration, decrease temperature crystalline, centrifugation or filtering obtain two
Chlorine pyrimidine sterling.
In the present invention, the dihydroxy-pyrimidine can be dihydroxy-pyrimidine well known to those skilled in the art, such as 2,4- bis-
Hydroxy pyrimidine, 2,5- dihydroxy-pyrimidines, 4,6- dihydroxy-pyrimidines or 2- amino -4,6- dihydroxy-pyrimidines.It is corresponding, preparation
Dichloro pyrimidine is respectively 2,4- dichloro pyrimidines, 2,5- dichloro pyrimidines, 4,6- dichloro pyrimidines or 2- amino -4,6- dichloro pyrimidines.
The present invention is not particularly limited the chlorinating agent of the chlorination reaction, can be well known to those skilled in the art three
Chlorethoxyfos, phosphorus trichloride, phosphorus pentachloride, Lucas (Lucas) reagent, concentrated hydrochloric acid and anhydrous zinc chloride mixture,
Vilesmier-Haack reagents, thionyl chloride, sulfonic acid chloride, chlorinated with chlorine sulfoxide etc..
The present invention is also not particularly limited the system of the chlorination reaction, no matter whether has depositing for organic solvent in system
, after reaction, direct hydrolysis or ice solution after can cooling down.
That is, in dichloro pyrimidine reaction mixture, water is added in the reaction system in the hydrolysis.
Mixture of ice and water is added in the ice solution in the reaction system.
Then organic solvent is added to be extracted, the organic phase of the crude product containing dichloro pyrimidine is obtained.
The organic solvent be preferably one kind in alkane, aromatic hydrocarbons, chloralkane, chlorinated aromatic hydrocarbons and alkyl-substituted aromatic hydrocarbon or
It is a variety of.More preferably toluene or dichloroethanes.Further preferably toluene.
In the organic phase of the crude product containing dichloro pyrimidine, the mass ratio of organic solvent and dichloro pyrimidine crude product is preferably 0.1
~20：1, further preferably 1~2:1.
The present invention is after the extraction, it is preferred that is washed to organic phase, neutralisation treatment.
It is purified subsequently into stripper.
It is currently preferred, before entering stripper, the organic phase of the crude product containing dichloro pyrimidine is concentrated, preferably
, make a concentration of saturated concentration under room temperature of dichloro pyrimidine crude product.
Concentration of the product in organic phase is controlled, steam stripping efficiency can be improved, while energy consumption can be reduced.
The present invention is to the type of the stripper and is not particularly limited, and can be packed tower or non-packed tower.
The organic phase of the crude product containing dichloro pyrimidine enters stripper from top (or top), and vapor is from bottom (under or
Portion) enter stripper, punching steaming is carried out to the organic phase of the crude product containing dichloro pyrimidine, vapor carries out convection current stripping, material with material
It can be detached, obtained pure containing dichloro pyrimidine with impurity such as three chlorophosphates by azeotropic separation mode with vapor short-time contact
The organic phase of product.
In some specific embodiments of the present invention, the stripper schematic diagram is as shown in Figure 1, stripper top (on or
Portion) it is provided with feed inlet, bottom (or lower part) is provided with vapor air inlet, filler can be arranged in tower, or be not provided with filler,
Discharge port is for collecting product.
The present invention enters the mode of stripper to the organic phase of the crude product containing dichloro pyrimidine and is not particularly limited, and can adopt
With titration, or by misty droplet spray into etc. it is well known to those skilled in the art in a manner of.
In the stripper, the rate of addition of the organic phase of dichloro pyrimidine crude product and go out liquid velocity balance.
Pressure in the stripper is preferably normal pressure, and temperature is preferably 100 DEG C.
It is currently preferred, after stripping, obtained organic phase is concentrated, decrease temperature crystalline, centrifugation or filtering, obtain high
The dichloro pyrimidine product of purity.
The method of the concentration can be the condensing modes well known to those skilled in the art such as vacuum distillation or air-distillation.
Purification process provided by the invention reduces the pairs such as degradation, the polymerization of the dichloro pyrimidine that conventional distil-lation mode is brought
Reaction, distillation efficiency is high, and product purity is high, can effectively reduce quantity of three wastes, reduces the pollution to environment, and energy consumption is greatly reduced,
Effectively reduce cost.The experimental results showed that product purification yield of the present invention is 98% or more, product purity is up to 99% or more.
In addition, the present invention uses reverse vapor stripper, dichloro pyrimidine crude product is in a manner of being added dropwise or spray, with drop
State, directly contacted with vapor so that purifying is more effective, and the purity and yield of product are greatly improved, and reduces
Target product degradation that conventional distil-lation mode is brought is consumed energy the problems such as big, and industrialized production and application are suitble to.
Description of the drawings
Fig. 1 is the schematic device of stripper of the present invention.
Specific implementation mode
In order to further illustrate the present invention, stripper provided by the invention is purified in dichloro pyrimidine with reference to embodiment
In application be described in detail.
Embodiment 1
It in the four-hole bottle equipped with reflux condensing tube, heats up, 4,6- dihydroxy-pyrimidines are added with constant pressure funnel in stirring
228g, content 98%, phosphorus oxychloride 633g contents 97%.It is warming up to 40~45 DEG C and triethylamine 408g contents 99% is added dropwise, be added dropwise
It finishes, temperature rises to 100~105 DEG C, keeps the temperature 2 hours.HPLC (efficient liquid phase) analyzes 4,6- dihydroxy-pyrimidines and is less than 0.2%,
Reaction finishes.880g toluene is added, is cooled to 0~5 DEG C, mixture of ice and water 800g is added, ice solution to room temperature decomposes organic phase water
Solution, water layer extract (200ml toluene), merge organic phase, neutrality is washed till with buck.Concentrate toluene.Obtain 697g toluene dichloro pyrimidines
Solution, 4,6- dichloro pyrimidine purity are 97.3%, content 39.91%.Crude yield is 92%.
697g crude product solutions are divided into three parts of 240g, 240g, 217g, 1,2,3 is denoted as respectively, does rectifying experiment：Steam is filled out
Material top of tower temperature requirement reaches 94 DEG C~96 DEG C, starts that the organic phase after concentration, control charging speed is added dropwise after temperature reaches
Degree, adjustment prevent the cold tower of stripper；Obtained organic phase, water phase quality and 4,6- dichloro pyrimidines purity and concentration are shown in
Table 1 will obtain the product of high-purity after organic phase concentration, cooling, crystallization, centrifugation or the filtering of gained.Refined yield is up to
98% or more, appearance is the crystal of white, and experimental result is as shown in table 1.
Fig. 1 is the schematic device of above-mentioned stripper.
1 embodiment of table, 1 experimental result summarizes
Embodiment 2
It in the four-hole bottle equipped with reflux condensing tube, heats up, 2- amino -4,6- bis- is added with constant pressure funnel in stirring
Hydroxy pyrimidine 510g (content 98%, 4mol) and phosphorus oxychloride 1428g (content 99%).It is warming up to 40~45 DEG C of three second of dropwise addition
Amine 810g (content 99%), is added dropwise, and temperature rises to 85~90 DEG C, keeps the temperature 2 hours.HPLC (efficient liquid phase) analyzes 2- ammonia
Base -4,6- dihydroxy-pyrimidine is less than 1%, and reaction finishes.3000g toluene is added, is cooled to 0~10 DEG C, mixture of ice and water is added
3000g, low temperature hydrolysis are warmed to room temperature, layering.Water layer is extracted 2 times with 400g toluene, is merged organic phase, is used aqueous sodium carbonate
It washes, then is washed to neutrality.Concentration organic phase simultaneously recycles toluene 1800g.Obtaining high concentration toluene solution 2668g, HPLC survey purity is
96.8%, content is 22.58% (external standard method), crude yield 92%.
2668g crude product solutions are divided into three parts of 668g, 1000g, 1000g, 4,5,6 is denoted as respectively, does rectifying experiment：Steam
Filler head temperature requires to reach 94 DEG C~96 DEG C, starts that the organic phase after concentration, control charging speed is added dropwise after temperature reaches
Degree, adjustment prevent the cold tower of stripper；Obtained organic phase, water phase quality and 4,6- dichloro pyrimidines purity and concentration are shown in
Table 2 will obtain the product of high-purity after organic phase concentration, cooling, crystallization, centrifugation or the filtering of gained.Refined yield is up to
98% or more.Experimental result is as shown in table 2.
2 embodiment of table, 2 experimental result summarizes
By above-described embodiment it is found that the present invention purifies dichloro pyrimidine using stripper, higher yield and purity are obtained.
The explanation of above example is only intended to facilitate the understanding of the method and its core concept of the invention.It should be pointed out that pair
For those skilled in the art, without departing from the principle of the present invention, the present invention can also be carried out
Some improvements and modifications, these improvement and modification are also fallen within the protection scope of the claims of the present invention.
Claims (9)
1. application of the stripper in dichloro pyrimidine purifying.
2. the method that stripper purifies dichloro pyrimidine, includes the following steps：
A after) dihydroxy-pyrimidine carries out chlorination reaction, dichloro pyrimidine reaction mixture is obtained；
B) reaction mixture is added water and is hydrolyzed, or ice water is added and carries out ice solution, is then extracted, is obtained using organic solvent
To the organic phase of the crude product containing dichloro pyrimidine；
C) organic phase of the crude product containing dichloro pyrimidine enters stripper from top or top, and vapor enters stripping from bottom or lower part
Tower carries out punching steaming to the organic phase of the crude product containing dichloro pyrimidine, obtains the organic phase of the sterling containing dichloro pyrimidine；
D it is phonetic that the) organic phase of the sterling containing dichloro pyrimidine, decompression or air-distillation concentration, decrease temperature crystalline, centrifugation or filtering obtain dichloro
Pyridine sterling.
3. according to the method described in claim 2, it is characterized in that, the stripper is packed tower or non-packed tower.
4. according to the method described in claim 2, it is characterized in that, the dichloro pyrimidine is 2,4- dichloro pyrimidines, 2,5- dichloros
Pyrimidine, 4,6- dichloro pyrimidines or 2- amino -4,6- dichloro pyrimidines.
5. according to the method described in claim 2, it is characterized in that, the organic solvent is alkane, aromatic hydrocarbons, chloralkane, chlorine
For one or more in aromatic hydrocarbons and alkyl-substituted aromatic hydrocarbon.
6. according to the method described in claim 5, it is characterized in that, the organic solvent is toluene or dichloroethanes.
7. according to the method described in claim 2, it is characterized in that, in the organic phase of the crude product containing dichloro pyrimidine, You Jirong
The mass ratio of agent and dichloro pyrimidine crude product is 0.1~20：1.
8. according to the method described in claim 2, it is characterized in that, in the stripper, the organic phase of the crude product containing dichloro pyrimidine
Rate of addition and liquid outlet quantity balance.
9. according to the method described in claim 2, it is characterized in that, the pressure in the stripper is normal pressure, vapor (steam) temperature is
100℃。
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723612A (en) * | 1995-06-02 | 1998-03-03 | Dsm Chemie Linz Gmbh | Process for the preparation of pure 4,6-dihloropyrimidine |
| CN102675216A (en) * | 2012-03-20 | 2012-09-19 | 河北临港化工有限公司 | Novel purifying treatment process for 4,6-dichloropyrimidine |
| CN103450094A (en) * | 2013-09-13 | 2013-12-18 | 重庆紫光化工股份有限公司 | Method for purifying 4, 6-dichloro pyrimidine |
| CN103539747A (en) * | 2013-09-24 | 2014-01-29 | 重庆紫光化工股份有限公司 | Preparation method of 4,6-dichloropyrimidine |
-
2018
- 2018-05-31 CN CN201810552509.5A patent/CN108395409A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723612A (en) * | 1995-06-02 | 1998-03-03 | Dsm Chemie Linz Gmbh | Process for the preparation of pure 4,6-dihloropyrimidine |
| CN102675216A (en) * | 2012-03-20 | 2012-09-19 | 河北临港化工有限公司 | Novel purifying treatment process for 4,6-dichloropyrimidine |
| CN103450094A (en) * | 2013-09-13 | 2013-12-18 | 重庆紫光化工股份有限公司 | Method for purifying 4, 6-dichloro pyrimidine |
| CN103539747A (en) * | 2013-09-24 | 2014-01-29 | 重庆紫光化工股份有限公司 | Preparation method of 4,6-dichloropyrimidine |
Non-Patent Citations (2)
| Title |
|---|
| 崔明珍: "蒸馏与汽提", 《废弃物化学组分的毒理和处理技术》 * |
| 张顺泽等: "汽提塔及汽提塔的设计", 《分离工程》 * |
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Application publication date: 20180814 |