CN106632109A - Method for preparing N-isopropypl-1H-1,2,4-triazole-3,5-diamine - Google Patents
Method for preparing N-isopropypl-1H-1,2,4-triazole-3,5-diamine Download PDFInfo
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- CN106632109A CN106632109A CN201611263717.0A CN201611263717A CN106632109A CN 106632109 A CN106632109 A CN 106632109A CN 201611263717 A CN201611263717 A CN 201611263717A CN 106632109 A CN106632109 A CN 106632109A
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- triazole
- diamines
- isopropyls
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- hydrazine hydrate
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- 0 CCC*C(NNC(N)N)=C Chemical compound CCC*C(NNC(N)N)=C 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/14—Nitrogen atoms
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing N-isopropypl-1H-1,2,4-triazole-3,5-diamine. An N-isopropypl-1H-1,2,4-triazole-3,5-diamine product is synthesized by two-step reaction of raw materials dimethyl N-cyanodithioiminocarbonate, propylamine and hydrazine hydrate at 20 to 25 DEG C under a reflux condition by adopting alcohol as a solvent. The preparation method is easy to operate and high in product purity, and the obtained product has purity capable of reaching 99 percent or higher, and has broad market prospect and high economic value.
Description
Technical field
The present invention relates to paraquat emetic synthesis field, more particularly to a kind of N- isopropyls -1H-1,2,4- triazoles -
The preparation method of 3,5- diamines.
Background technology
Paraquat emetic is also known as triazole pyrimidone (IUPAC) abbreviation PP796, emetic, triazolo pyrimidine ketone, enemy's grass
Hurry up/Methomyl emetic etc., chemical name is：Methyl -4- n-propyl -4,5- dihydros-[1,2,4] triazole-of 2- amino -6 [1,
5] and pyrimidine -5- ketone, it is white crystalline solid, molecular formula is：C9H13N5O, molecular weight 207.2, CAS NO:27277-00-5,
Being dissolved in dimethylformamide, dichloromethane, methyl alcohol, to be slightly dissolved in ethyl acetate, dichloroethanes, toluene insoluble molten in petroleum ether, water
Solution degree 2g/l, chloroform 83g/l, ethanol 6g/l, DMSO13g/l are unstable under strong alkaline condition.It is important organic synthesis and doctor
Medicine intermediate, can synthesize many derived products, be also important medical and for animals active emetic composition.
N- isopropyl -1H-1,2,4- triazole -3,5- diamines is the key for synthesizing paraquat emetic triazole pyrimidone
Raw material, is currently that with 5- amino -3- sulfydryl -1,2,4 triazoles and iodopropane are raw material, carry out methylation reaction and obtain product,
Secondary technique is raw materials used costly, high cost, and can produce a large amount of waste water containing iodine, it is difficult to process, industrialization amplification is limited
System.
Based on this, there is provided a kind of new N- isopropyl -1H-1,2,4- triazole -3,5- diamines synthetic methods, reduces cost
While reduce pollution, just seem particularly necessary.
The content of the invention
To solve the problems, such as above-mentioned prior art, it is an object of the invention to provide a kind of N- isopropyls -1H-1,2,
The preparation method of 4- triazole -3,5- diamines.Preparation method is simple to operate, product purity is high, and products therefrom purity may be up to
More than 99%, with good market prospects and economic worth.
To reach above-mentioned purpose, the technical scheme is that：
A kind of N- isopropyls -1H-1,2,4- triazole -3, the preparation method of 5- diamines, with cyanogen amino curing carbonic acid two
Methyl esters, n-propylamine and hydrazine hydrate are raw material, using alcohol as solvent, under 20-25 DEG C and counterflow condition, are synthesized in two steps
Yield is >=93%, the N- isopropyl -1H-1 of content (HPLC) >=99%, 2,4- triazole -3, the amine products of 5- bis-.Its is specific
Chemical equation is：
Further, the mol ratio of cyanogen amino carbon disulfide dimethyl phthalate of the present invention and n-propylamine be 0.9～
0.93:1.Wherein, the ratio of cyanogen amino carbon disulfide dimethyl phthalate and n-propylamine is too low, then raw material reaction not exclusively causes raw material
Waste, ratio is too high, and directive/guide causes impurity to produce final product purity to be reduced.
Further, N- isopropyls -1H-1 of the present invention, 2,4- triazole -3,5- diamines preparation methods specifically include following
Step：
7) under a nitrogen atmosphere, cyanogen amino carbon disulfide dimethyl phthalate is utilized into solvent uniform dissolution；
8) 20-25 DEG C (being less than 20 DEG C, reaction is slow, the reaction time extends, and higher than 25 DEG C, reaction can produce impurity)
Under, n-propylamine is slowly added dropwise, stir after completion of dropping；
9) 20 DEG C are less than 20-25 DEG C of insulation reaction half an hour, reaction is slow, the reaction time extends, higher than 25 DEG C, reaction
Impurity can be produced), then heat to backflow；
10) hydrazine hydrate at reflux, is slowly added dropwise, the completion of dropping in 2-3 hours；Wherein, wt：80%-85%
Hydrazine hydrate, is the wt of cyanogen amino carbon disulfide dimethyl phthalate consumption：1.02-1.05 again)
11) 20-25 DEG C of insulation reaction 2-3 hour at reflux, less than 20 DEG C, reaction is slow, and raw material reaction is not complete
Entirely, higher than 25 DEG C, reaction can produce impurity, and then vacuum distillation goes out 80% alcoholic solvent.
12) and then residue is cooled to 5-10 DEG C, filter, filtrate collect after reuse, filter cake washes with water, obtains after being dried
Target compound.
Further, the solvent described in step (1) is selected from any one in isopropanol or methyl alcohol.
Further, in step (4), the hydrazine hydrate solution concentration is 80wt%.
Further, products therefrom purity >=99%.
Relative to prior art, beneficial effects of the present invention are：
Preparation N- isopropyl -1H-1 provided by the present invention, 2,4- triazole -3, the method for 5- diamines, products obtained therefrom is received
Rate is high, and purity is high, and low cost, products therefrom purity may be up to more than 99%, with good market prospects and economic worth.It is suitable
For industrial amplification production.
Specific embodiment
Technical solution of the present invention is described in further detail with reference to specific embodiment：
With reference to embodiment, the present invention is described further, described below, is only the preferable enforcement to the present invention
Example, not does the restriction of other forms to the present invention, and any those skilled in the art are possibly also with the disclosure above
Technology contents be changed to the Equivalent embodiments of equal change.It is every without departing from the present invention program content, according to the present invention
Technical spirit any simple modification that following examples are made or equivalent variations, all fall within protection scope of the present invention.
A kind of N- isopropyls -1H-1,2,4- triazole -3, the preparation method of 5- diamines, with cyanogen amino curing carbonic acid two
Methyl esters, n-propylamine and hydrazine hydrate are raw material, using alcohol as solvent, under 20-25 DEG C and counterflow condition, are synthesized in two steps
Yield is >=93%, the N- isopropyl -1H-1 of content (HPLC) >=99%, 2,4- triazole -3, the amine products of 5- bis-.Its is specific
Chemical equation is：
Further, the mol ratio of cyanogen amino carbon disulfide dimethyl phthalate of the present invention and n-propylamine be 0.9～
0.93:1.Wherein, the ratio of cyanogen amino carbon disulfide dimethyl phthalate and n-propylamine is too low, then raw material reaction not exclusively causes raw material
Waste, ratio is too high, and directive/guide causes impurity to produce final product purity to be reduced.
Further, N- isopropyls -1H-1 of the present invention, 2,4- triazole -3,5- diamines preparation methods specifically include following
Step：
13) under a nitrogen atmosphere, cyanogen amino carbon disulfide dimethyl phthalate is utilized into solvent uniform dissolution；
14) 20-25 DEG C (being less than 20 DEG C, reaction is slow, the reaction time extends, and higher than 25 DEG C, reaction can produce impurity)
Under, n-propylamine is slowly added dropwise, stir after completion of dropping；
15) 20 DEG C are less than 20-25 DEG C of insulation reaction half an hour, reaction is slow, the reaction time extends, higher than 25 DEG C, instead
Impurity should be produced), then heat to backflow；
16) hydrazine hydrate at reflux, is slowly added dropwise, the completion of dropping in 2-3 hours；Wherein, wt：80%-85%
Hydrazine hydrate, is the wt of cyanogen amino carbon disulfide dimethyl phthalate consumption：1.02-1.05 again)
17) 20-25 DEG C of insulation reaction 2-3 hour at reflux, less than 20 DEG C, reaction is slow, and raw material reaction is not complete
Entirely, higher than 25 DEG C, reaction can produce impurity, and then vacuum distillation goes out 80% alcoholic solvent.
18) and then residue is cooled to 5-10 DEG C, filter, filtrate collect after reuse, filter cake washes with water, obtains after being dried
Target compound.
Further, the solvent described in step (1) is selected from any one in isopropanol or methyl alcohol.
Further, in step (4), the hydrazine hydrate solution concentration is 80wt%.
Further, products therefrom purity >=99%.
Embodiment 1
Reactor is carried out after nitrogen displacement, adds 6Kg isopropanols, 1.2Kg cyanogen amino carbon disulfide dimethyl phthalates to stir molten
Xie Hou, is warmed to room temperature naturally, and under 25 DEG C of stirrings, then slow liter is added dropwise 538g n-propylamines, and it is little that time for adding is maintained at 1.5
When, then at this temperature after insulation reaction half an hour, 83 DEG C are warming up to flowing back, the hydrazine hydrate of 1.224Kg is then added dropwise
(wt：80%), time for adding is maintained at 2 hours, and then reactant liquor is cooled to 35 DEG C, and vacuum distillation goes out 4.8Kg isopropanols, remaining
Thing is cooled to 10 DEG C, filters, and filter cake is washed with water, and after being dried off-white powder 1.075Kg, as N- isopropyls -1H-1 are obtained,
2,4- triazole -3,5- diamines, the detection of Jing liquid chromatographs, liquid content is 99.2%.
Embodiment 2
Reactor is carried out after nitrogen displacement, adds 3Kg isopropanols, 0.61Kg cyanogen amino carbon disulfide dimethyl phthalates, stirring
After dissolving, it is warmed to room temperature naturally, under 21 DEG C of stirrings, then slow liter is added dropwise 268g n-propylamines, and it is little that time for adding is maintained at 2
When, then at this temperature after insulation reaction half an hour, 83 DEG C are warming up to flowing back, the hydrazine hydrate of 0.612Kg is then added dropwise
(wt：83%), time for adding is maintained at 2.5 hours, and then reactant liquor is cooled to 30 DEG C, and vacuum distillation goes out 2.4Kg isopropanols, remains
Excess is cooled to 10 DEG C, filters, and filter cake is washed with water, and after being dried off-white powder 0.54Kg, as N- isopropyls -1H- are obtained
1,2,4- triazole -3,5- diamines, the detection of Jing liquid chromatographs, liquid content is 99.1%.
Embodiment 3
Reactor is carried out after nitrogen displacement, adds 6.4Kg isopropanols, 1.21Kg cyanogen amino carbon disulfide dimethyl phthalates to stir
After mixing dissolving, it is warmed to room temperature naturally, under 20 DEG C of stirrings, then slow liter is added dropwise 539g n-propylamines, and time for adding is maintained at 1.8
Hour, then at this temperature after insulation reaction half an hour, 83 DEG C are warming up to flowing back, the hydrazine hydrate of 1.3Kg is then added dropwise
(wt：85%), time for adding is maintained at 3 hours, and then reactant liquor is cooled to 38 DEG C, and vacuum distillation goes out 4Kg isopropanols, residue
It is cooled to 5 DEG C, filters, filter cake is washed with water, obtains off-white powder 0.98Kg, as N- isopropyls -1H-1 after being dried, 2,4-
Triazole -3,5- diamines, the detection of Jing liquid chromatographs, liquid content is 99.5%.
Embodiment 4
Reactor is carried out after nitrogen displacement, adds 2Kg methyl alcohol, 0.41Kg cyanogen amino carbon disulfide dimethyl phthalates to stir molten
Xie Hou, is warmed to room temperature naturally, and under 24 DEG C of stirrings, then slow liter is added dropwise 180g n-propylamines, and time for adding is maintained at 2 hours,
Then at this temperature after insulation reaction half an hour, 65 DEG C are warming up to flowing back, the hydrazine hydrate (wt of 0.4Kg is then added dropwise：
80%), time for adding is maintained at 3 hours, and then reactant liquor is cooled to 38 DEG C, and vacuum distillation goes out 1.6Kg methyl alcohol, residue cooling
To 3 DEG C, filter, filter cake is washed with water, after being dried off-white powder 358g, as N- isopropyls -1H-1,2,4- tri- nitrogen are obtained
Azoles -3,5- diamines, the detection of Jing liquid chromatographs, liquid content is 99.8%.
Embodiment 5
Reactor is carried out after nitrogen displacement, adds 2Kg methyl alcohol, 0.41Kg cyanogen amino carbon disulfide dimethyl phthalates to stir molten
Xie Hou, is warmed to room temperature naturally, and under 14 DEG C of stirrings, then slow liter is added dropwise 180g n-propylamines, and time for adding is maintained at 2 hours,
Then at this temperature after insulation reaction half an hour, 65 DEG C are warming up to flowing back, the hydrazine hydrate (wt of 0.4Kg is then added dropwise：
80%), time for adding is maintained at 3 hours, and then reactant liquor is cooled to 38 DEG C, and vacuum distillation goes out 1.6Kg methyl alcohol, residue cooling
To 3 DEG C, filter, filter cake is washed with water, after being dried off-white powder 280g, as N- isopropyls -1H-1,2,4- tri- nitrogen are obtained
Azoles -3,5- diamines, the detection of Jing liquid chromatographs, liquid content is 98.2%.
Embodiment 6
Reactor is carried out after nitrogen displacement, adds 2Kg methyl alcohol, 0.41Kg cyanogen amino carbon disulfide dimethyl phthalates to stir molten
Xie Hou, is warmed to room temperature naturally, and under 35 DEG C of stirrings, then slow liter is added dropwise 180g n-propylamines, and time for adding is maintained at 2 hours,
Then at this temperature after insulation reaction half an hour, 65 DEG C are warming up to flowing back, the hydrazine hydrate (wt of 0.4Kg is then added dropwise：
80%), time for adding is maintained at 3 hours, and then reactant liquor is cooled to 38 DEG C, and vacuum distillation goes out 1.6Kg methyl alcohol, residue cooling
To 3 DEG C, filter, filter cake is washed with water, after being dried off-white powder 300g, as N- isopropyls -1H-1,2,4- tri- nitrogen are obtained
Azoles -3,5- diamines, the detection of Jing liquid chromatographs, liquid content is 97.8%.
From above-described embodiment it can be seen that in the range of reaction temperature 20-25 DEG C, product purity is kept at more than 99%,
Can even be up to 99.8% (see embodiment 4), and temperature too high (embodiment 6) or too low (embodiment 5) can not reach as
This high purity, and cause the waste of raw material.
The above, the only specific embodiment of the present invention, but protection scope of the present invention is not limited thereto, any
The change or replacement expected without creative work, all should be included within the scope of the present invention.Therefore, it is of the invention
The protection domain that protection domain should be limited by claims is defined.
Claims (7)
1. a kind of N- isopropyls -1H-1,2,4- triazole -3, the preparation method of 5- diamines, it is characterised in that with the sulphur of cyanogen amino two
It is raw material to change dimethyl carbonate, n-propylamine and hydrazine hydrate, using alcohol as solvent, under 20-25 DEG C and counterflow condition, in two steps
The amine products of N- isopropyl -1H-1,2,4- triazoles -3,5- two being synthesized；Its specific chemical equation is：
2. a kind of N- isopropyls -1H-1 according to claim 1,2,4- triazole -3, the preparation method of 5- diamines, it is special
Levy and be, described cyanogen amino carbon disulfide dimethyl phthalate and the mol ratio of n-propylamine is 0.9～0.93:1.
3. a kind of N- isopropyls -1H-1 according to claim 2,2,4- triazole -3, the preparation method of 5- diamines, it is special
Levy and be, the method specifically includes following steps：
1) under a nitrogen atmosphere, cyanogen amino carbon disulfide dimethyl phthalate is utilized into solvent uniform dissolution；
2) at 20-25 DEG C, n-propylamine is slowly added dropwise, is stirred after completion of dropping；
3) 20-25 DEG C of insulation reaction half an hour, backflow is then heated to；
4) hydrazine hydrate at reflux, is slowly added dropwise, the completion of dropping in 2-3 hours；
Wherein, wt：80%-85% hydrazine hydrates；
5) 20-25 DEG C of insulation reaction 2-3 hour at reflux, then vacuum distillation goes out 80% alcoholic solvent；
6) and then by residue 5-10 DEG C is cooled to, is filtered, reuse after filtrate collection, filter cake is washed with water, and after being dried mesh is obtained
Mark compound.
4. a kind of N- isopropyls -1H-1 according to claim 3,2,4- triazole -3, the preparation method of 5- diamines, it is special
Levy and be, step 1) described in solvent in isopropanol or methyl alcohol any one.
5. a kind of N- isopropyls -1H-1 according to claim 3,2,4- triazole -3, the preparation method of 5- diamines, it is special
Levy and be, step 4) in, the hydrazine hydrate solution concentration is 80wt%.
6. a kind of N- isopropyls -1H-1 according to claim 3,2,4- triazole -3, the preparation method of 5- diamines, it is special
Levy and be, the step 4) in hydrazine hydrate consumption for cyanogen amino carbon disulfide dimethyl phthalate consumption wt：1.02-1.05 again.
7. a kind of N- isopropyls -1H-1 according to claim 3,2,4- triazole -3, the preparation method of 5- diamines, it is special
Levy and be, products therefrom purity >=99%.
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| CN201611263717.0A CN106632109A (en) | 2016-12-30 | 2016-12-30 | Method for preparing N-isopropypl-1H-1,2,4-triazole-3,5-diamine |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6570014B1 (en) * | 2002-04-30 | 2003-05-27 | Sinon Corporation | Process for preparing triazolopyrimidine derivatives |
| CN1463974A (en) * | 2002-06-10 | 2003-12-31 | 兴农股份有限公司 | Method for preparation of Triazolo pyrimidine derivative |
| JP3958109B2 (en) * | 2002-05-10 | 2007-08-15 | 興農股▲ふん▼有限公司 | Method for producing triazolopyrimidine derivative |
-
2016
- 2016-12-30 CN CN201611263717.0A patent/CN106632109A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6570014B1 (en) * | 2002-04-30 | 2003-05-27 | Sinon Corporation | Process for preparing triazolopyrimidine derivatives |
| JP3958109B2 (en) * | 2002-05-10 | 2007-08-15 | 興農股▲ふん▼有限公司 | Method for producing triazolopyrimidine derivative |
| CN1463974A (en) * | 2002-06-10 | 2003-12-31 | 兴农股份有限公司 | Method for preparation of Triazolo pyrimidine derivative |
Non-Patent Citations (1)
| Title |
|---|
| 程春生等: "Catalytic Synthesis Methods for Triazolopyrimidine Derivatives", 《CHINESE JOURNAL OF CHEMISTRY》 * |
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