CN105906575B - A kind of synthesis technique of 1,2,4 triazoles of 1H - Google Patents
A kind of synthesis technique of 1,2,4 triazoles of 1H Download PDFInfo
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- CN105906575B CN105906575B CN201610280722.6A CN201610280722A CN105906575B CN 105906575 B CN105906575 B CN 105906575B CN 201610280722 A CN201610280722 A CN 201610280722A CN 105906575 B CN105906575 B CN 105906575B
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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
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract
The invention discloses a kind of synthesis technique of 1,2,4 triazoles of 1H, its synthesis step are as follows：(1) formic acid esters, hydrazine hydrate and ammonium salt are sequentially added into autoclave, in the case where sealing stirring, reaction kettle is pressurizeed and is to slowly warm up to reaction temperature, after reaction, slowly reduce reaction temperature and steam by-product carbinol using waste heat, obtain white " milky " thing.(2) the white " milky " thing is transferred in reaction kettle, add ethanol, heating reflux reaction obtains mixed liquor, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, separates out white crystal, after centrifugation, 1,2,4 triazoles of 1H are can obtain through hot-air oven drying.The direct ammonolysis of ammonia that the present invention is decomposed by formic acid esters and ammonium salt under high-temperature and high-pressure conditions obtains formamide and hydration hydrazine reaction, effectively raises whole chemical reaction velocity, reduces reaction temperature, improve product yield, overall synthesis technique is simple, and energy consumption is low, and three waste discharge is few.
Description
Technical field
The present invention relates to organic synthesis field, more particularly to a kind of 1H-1, the synthesis technique of 2,4- triazoles.
Background technology
1,2,4- triazole sterling is white crystal, and industrial goods are pink or brown solid, and fusing point is 119 DEG C -121
DEG C, decomposition temperature is soluble easily in water more than 220 DEG C, is slightly soluble in ethyl acetate, acetone, insoluble in chloroform, benzene.
Since J.A.Bladin in 1885 synthesizes 1,2,4- triazoles first, the heterocyclic compound containing 1,2,4- triazole
Thing undergoes an unusual development rapidly.Global chemical research person has synthesized a large amount of compounds containing 1,2,4- triazoles, and finds such
Material contains various physiological activity, therefore after the century-old development of experience, 1,2,4- triazole is still subject to entirely
The attention of the expert of international drugs synthesis, organic synthesis, material containing azoles etc..
In the 1960s, the N.V-Pnlipn Dnphan companies of Holland have synthesized first 1,2,4- triazole and have killed
The spirit of microbial inoculum prestige bacterium, this is the triazole pesticide that the mankind use earliest.Beyer Co., Ltd in 1973, which is proposed first, has chirality
The commercialization fungicide triazolone of carbon.20th century the eighties listing product have：Flutriafol, the phenyl ether methyl cyclic of listing in 1980
Azoles；The tetraconazole of production in 1984；The alcohol of azoles, the Cyproconazole of listing in 1986；Olefin conversion of listing in 1988 etc..20 generation
Record the nineties, the nitrile bacterium azoles of listing in 1991：Bromuconazole, the triticonazole of listing in 1992；The Flusilazole and Tebuconazole of 1993；
The kind bacterium azoles of listing in 1994, Flusilazole, glyoxalin etc..21st century, the Flusilazole of listing in 2002 etc..With science and technology
Development, researcher, which furthers investigate, to be found, some triazole compounds not only have bactericidal activity, is also had desinsection, mite killing, is removed
Grass, plant growth regulation.
In more than ten years in past, the various medical products of triazole are also developed, for the every field of medicine, example
Such as antimycotic bacterium drug field, field of antineoplastic medicaments, antiviral drugs field, anti-psychoactive drugs field, in addition
Also constantly there is triazole type medical product to be developed in anti-hypertension, contraception, antiallergy, hypnosis, anti-bronchiectasis etc.
Come.Wherein most typical several prods are the rizatriptan benzoates for treating antimigraine；For treating the next bent of advanced breast cancer
Azoles；Treat mycotic voriconazole；Nucleotide antiviral agent virazole etc..
At present, the dominating process route of 1,2,4- triazole of the synthesis synthesis of document report has following several：
(1) 3- amino-1,2,4-triazols diazonium deamination method.Synthesis route is as follows, and pertinent literature includes：
Hydrogen cyanide chemistry.6.Cyanogen condensation with cyanide,Wiley,D.W.et
al.,Journal of Organic Chemistry,1976；The 1-(or 4-)[2-dialkylaminoethyl]-1,2,
4-triazoles.Preparation and pharmacodynamics results,Henichart,Jean P.et al.,
Chimica Therapeutica,1973.1,2,4-Triazole,Ainsworth,C.Organic Syntheses,1960.
The aminoguanidine that this method is obtained first with hydrazine hydrate and cyanamide reaction, then react with formic acid to obtain 3- amino -1,2,4- tri-
Nitrogen azoles, then obtains 1H-1,2,4- triazoles by diazotising deamination.This method W-response mild condition, high income.But
Reactions steps are cumbersome, and overall the cost is relatively high.
(2) 1,3,5-triazines and hydrazonium salt are blended in reflux in absolute ethyl alcohol and obtain 1,2,4- triazoles, synthesis route
As follows, (pertinent literature includes Triazines.XVI.A new synthesis for 1,2,4-
triazoles.Grundmann,Christoph and Ratz,Rudi.Journal of Organic Chemistry,
1956.) this method due to cost of material it is higher, be not suitable for large-scale industrial production.
(3) it is hydrated Hydrazinecarboxamidederivatives method.Synthesis route is as follows, and (pertinent literature includes：1,2,4-Triazole,
Beer, Hans. European patent, 44438,1982；Direct preparation for 1,2,4-triazole from
Hydrazine and formamide.Petree, Harris E.et al. United States Patent (USP) U.S4267347,1981) this method
Hydrazine hydrate is added dropwise in 170-180 DEG C of formamide, thermal dehydration obtains 1,2,4- triazoles when being added dropwise.This is the country 1,2,
The technique mainly taken of 4- triazoles production, but since formamide is difficult to that the reaction was complete during the reaction, recycling and separation are tired
It is difficult.
(4) formic acid, hydrazine hydrate, ammonia method.Synthesis route is as follows, and pertinent literature includes：Process for
preparation of 1,2,4-triazole with minimum formation of 4-amino-1,2,4-
Triazole.Bhanuchandra, Shah Dipakkumar., indian patent, 2009MU01331,2010；1 hydrogen -1,2,4-
The preparation of triazole, Guo Qingming etc., Chinese patent, CN 86100562A；The preparation of granular 1,2,4-triazole sodium salt, Gao Jian
Merit et al., Chinese patent, CN 102212038A, this method are that formic acid is passed through ammonia at 130 DEG C, are added after being warming up to 155 DEG C
Enter hydrazine hydrate, can also finally obtain 1,2,4- triazoles.This raw materials technology is simple, but formic acid is larger to equipment corrosion,
Later stage dehydration energy under 155 degrees celsius is high.
HCOOH+NH3→HCOONH4
(5) bishydrazide, ammonia method.Synthesis route is as follows, and pertinent literature includes：Nuclear
Substituted β-Aminoethyl-1,2,4trazoles, Ainsworth, et al.J.Am.Chem.Soc.1955, the party
Method using bishydrazide and liquefied ammonia 200 degrees Celsius of reaction under high pressures 24 are small in water heating kettle when, obtain triazole.Yield is usually
70%-80%.This technique avoids the high energy consumption shortcoming in corrosion and dehydration of the formic acid to equipment, but reaction temperature
High and pressure is big, higher to equipment requirement.It is difficult to large-scale industrial production.
(6) first and second ketazine formamide methods.Synthesis route is as follows, and pertinent literature includes：Method of
producing1,2,4-triazole by the cyclocondensation reaction of formamide with
ketazines in the presence of water with distillative removal of the ketone
Byproduct.Nagata, Nobuhiro et al. United States Patent (USP)s, U.S.6002015,1999；Triazole catalysts
and methods of making and using the same.Elgammal,Ramez A.and Foister,
Shane.PCT patents, 2011035064,2011, the first and second ketazines and water are added dropwise to 170 degrees centigrades by this method together
In formamide, byproduct methyl ethyl ketone recycles, and can obtain the triazole of high yield.First and second ketazines are the centres of hydrazine hydrate production
Product, the methyl ethyl ketone of recycling is to synthesize the intermediate raw material of the first and second ketazines, so integrated artistic energy consumption is relatively low, but this method technique
Complexity, equipment requirement are higher.
It is that formamide first generates formylhydrazine and ammonia with hydration hydrazine reaction, formylhydrazine is again from the mechanism of triazole synthesis
Nucleophilic addition occurs with formamide and intermolecular dehydration cyclization obtains triazole.Its reaction temperature and the speed of dehydration are whole anti-
The key condition of process is answered, therefore relative energy consumption is higher on the whole for existing process, also just because of this, 1H-1,2,4- triazoles close
Into technique still need to further optimization and improve.
The content of the invention
The purpose of the present invention is to overcome above-mentioned the deficiencies in the prior art, there is provided one kind feeds intake simplicity, and side reaction is few, production
Cost is low, can realize the 1H-1 of industrialized production, the new technique for synthesizing of 2,4- triazoles.
To achieve these goals, inventor is finally obtained following technology by a large number of experiments research and persistent exploration
Scheme：
A kind of 1H-1, the synthesis technique of 2,4- triazoles, synthesis step are as follows：
(1) formic acid esters, hydrazine hydrate and ammonium salt are sequentially added into autoclave, in the case where sealing stirring, will be reacted
Kettle pressurizes and is to slowly warm up to reaction temperature, after reaction, slowly reduces reaction temperature and steams accessory substance first using waste heat
Alcohol, obtains white " milky " thing.
(2) the white " milky " thing is transferred in reaction kettle, adds ethanol, heating reflux reaction obtains mixed liquor, will
Mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, separates out white crystal, after centrifugation,
1H-1,2,4- triazoles are can obtain through hot-air oven drying.
Preferably, the concentration of hydrazine hydrate is 85% in the step (1)；
Preferably, the ammonium salt in the step (1) is ammonium chloride, sulfate of ammoniac or ammonium hydrogen carbonate；
It is further preferred that the ammonium salt in the step (1) is ammonium chloride.
Preferably, the formic acid esters in the step (1) is methyl formate, Ethyl formate or butyl formate；
It is further preferred that the formic acid esters in the step (1) is methyl formate；
Preferably, the mass ratio that feeds intake of formic acid esters, hydrazine hydrate and ammonium salt is (4-6) in the step (1):2:(1-2)；
It is further preferred that the mass ratio that feeds intake of formic acid esters, hydrazine hydrate and ammonium salt is 5 in the step (1):2:1.3；
Preferably, reaction temperature is 120-130 DEG C in the step (1), when the reaction time is 1-2 small；
It is further preferred that when the reaction time is 1.5 small in the step (1)；
Preferably, the volume fraction of ethanol is 95% in the step (2), and the ethanol is thrown with formic acid esters in step (1)
It is 1 to expect volume ratio:1；
Preferably, the temperature of the hot-air oven drying is 80-85 DEG C.
Preferably, the formic acid esters, hydrazine hydrate, ammonium salt and ethanol are that chemistry is pure.
Present invention process route is as follows：
The present invention hydrolyzes generation formic acid and phase using formic acid esters under hot conditions in alkaline conditions by autoclave
Ammonium salt decomposition is answered to come out ammonia generation formamide, formamide and hydrazine hydrate condensation dehydration generation triazole.The water of abjection is joined again at the same time
With the hydrolysis of methyl formate so that whole reaction system is carried out to triazole direction.W-response mechanism is as follows：
Formic acid esters reacted away while formic acid is provided condensation course generation water, improve benzoic acid amidesization reaction and
The speed of triazole cyclization reaction, effectively prevent the problem of link high energy consumption is dehydrated in existing process.
Ammonium chloride provides the partial amidesization ammonia that reaction needs by thermally decomposing in the reaction system, while molten in hydrazine hydrate
The ammonia produced in liquid with reaction forms stable weakly alkaline environment, is carried out beneficial to stablizing for formic acid ester hydrolysis reaction.
Compared with prior art, synthesis technique of the present invention has the advantages that：
(1) present invention is with using autoclave, using formic acid esters under hot conditions under high-temperature and high-pressure conditions with it is corresponding
Ammonium salt decomposition comes out ammonia generation formamide, formamide and hydrazine hydrate condensation dehydration generation triazole.The water of abjection participates in again at the same time
The hydrolysis of methyl formate so that whole reaction system is carried out to triazole direction.Reaction temperature is reduced, simplifies synthesis technique
The step of, reduce the generation of side reaction, ensure that product to quality, improves yield, reaction yield is higher than in terms of hydrazine hydrate
90%；
(2) present invention is raw material using methyl formate and ammonium chloride, small toxicity low relative to traditional handicraft cost of material,
Reaction process is simple and less energy consumption, and discharging of waste liquid is few, is easy to industrialized production, greatly reduces production cost；
(3) whole reaction carries out in the reaction system of closing, react the hydrolysis methanol of generation can recycle to
Methyl formate is produced, the ethanol that purifying technique uses can be recycled by steaming again, almost non-wastewater discharge, and it is dirty to reduce environment
Dye, environmental protection.
Brief description of the drawings
Fig. 1 is 1 synthetic product of embodiment1H NMR spectras；
Fig. 2 is the FTIR spectrograms of 1 synthetic product of embodiment；
Fig. 3 is the high-efficient liquid phase chromatogram of 1 synthetic product of embodiment；
Fig. 4 is the high-efficient liquid phase chromatogram of 1 synthetic product of comparative example.
Embodiment
It is the specific embodiment of the present invention below, technical scheme is done and is further described, but it is of the invention
Protection domain be not limited to these embodiments.It is every to be included in this hair without departing substantially from the change of present inventive concept or equivalent substitute
Within bright protection domain.
Embodiment 1
(1) sequentially added into reaction kettles of the 10L with mechanical agitator methyl formate 4.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium chloride 2.0Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 1 is small after, natural cooling and slowly opening is put
The organic gas such as the methanol in air valve condensation recycling kettle.Temperature is down to room temperature, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 3.5Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, can obtain 1H-1,2,4- triazole 2.1Kg, with hydration under the conditions of 83 DEG C through hot-air oven drying
Hydrazine rate of collecting is 90%.
Embodiment 2
(1) sequentially added into reaction kettles of the 10L with mechanical agitator methyl formate 5.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium chloride 1.3Kg, in the case where sealing stirring, is to slowly warm up to 130 DEG C, when reaction 1.5 is small after, natural cooling is simultaneously slowly opened
The organic gas such as the methanol in vent valve condensation recycling kettle.Temperature is down to room temperature, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 4.1Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.2Kg, with hydrazine hydrate are can obtain under the conditions of 82 DEG C through hot-air oven drying
Rate of collecting is 94%.
Embodiment 3
(1) sequentially added into reaction kettles of the 10L with mechanical agitator methyl formate 6.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium chloride 1.5Kg, in the case where sealing stirring, is to slowly warm up to 124 DEG C, when reaction 1.3 is small after, natural cooling is simultaneously slowly opened
The organic gas such as the methanol in vent valve condensation recycling kettle.Temperature is down to room temperature, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 4.5Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.1Kg, with hydrazine hydrate are can obtain under the conditions of 85 DEG C through hot-air oven drying
Rate of collecting is 90%.
Embodiment 4
(1) sequentially added into reaction kettles of the 10L with mechanical agitator Ethyl formate 4.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium chloride 1Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 1.5 is small after, natural cooling and slowly opening is put
The organic gas such as the methanol in air valve condensation recycling kettle.Temperature is down to room temperature, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 3.8Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.0Kg, with hydrazine hydrate are can obtain under the conditions of 80 DEG C through hot-air oven drying
Rate of collecting is 85%.
Embodiment 5
(1) sequentially added into reaction kettles of the 10L with mechanical agitator Ethyl formate 6.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium chloride 2Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 1.5 is small after, natural cooling and slowly opening is put
The organic gas such as the ethanol in air valve condensation recycling kettle.Temperature is down to room temperature, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 5.0Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.0Kg, with hydrazine hydrate are can obtain under the conditions of 82 DEG C through hot-air oven drying
Rate of collecting is 85%.
Embodiment 6
(1) sequentially added into reaction kettles of the 10L with mechanical agitator butyl formate 5.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium sulfate 1.5Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 2 is small after, natural cooling and slowly opening is put
The organic gas such as the butanol in air valve condensation recycling kettle.Room temperature is down to, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 4.5Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 1.9Kg, with hydrazine hydrate are can obtain under the conditions of 80 DEG C through hot-air oven drying
Rate of collecting is 84%.
Embodiment 7
(1) sequentially added into reaction kettles of the 10L with mechanical agitator methyl formate 5.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium sulfate 1.6Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 1.5 is small after, natural cooling is simultaneously slowly opened
The organic gas such as the methanol in vent valve condensation recycling kettle.Room temperature is down to, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 4.5Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.1Kg, with hydrazine hydrate are can obtain under the conditions of 85 DEG C through hot-air oven drying
Rate of collecting is 90%.
Embodiment 8
(1) sequentially added into reaction kettles of the 10L with mechanical agitator methyl formate 5.0Kg, 85% hydrazine hydrate 2.0Kg,
30% ammonium chloride 1.3Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 2 is small after, natural cooling is simultaneously slowly beaten
The organic gas such as methanol, ammonia in open air valve condensation recycling kettle.Room temperature is down to, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 5Kg, heating reflux reaction
Mixed liquor is obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.2Kg, with hydrazine hydrate are can obtain under the conditions of 80 DEG C through hot-air oven drying
Rate of collecting is 94%.
Embodiment 9
(1) sequentially added into reaction kettles of the 10L with mechanical agitator methyl formate 5.0Kg, 85% hydrazine hydrate 2.0Kg,
Ammonium hydrogen carbonate 2.0Kg, in the case where sealing stirring, is to slowly warm up to 120 DEG C, when reaction 1.5 is small after, it is naturally cold and slowly open
The organic gas such as methanol, carbon dioxide in vent valve condensation recycling kettle.Room temperature is down to, obtains white " milky " thing；
(2) the white " milky " thing is transferred in 50L glass reaction kettles, adds 95% ethanol 4.8Kg, be heated to reflux anti-
Mixed liquor should be obtained, mixed liquor is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, it is brilliant to separate out white
Body, after centrifugation, 1H-1,2,4- triazole 2.1Kg, with hydrazine hydrate are can obtain under the conditions of 85 DEG C through hot-air oven drying
Rate of collecting is 90%.
Comparative example 1
(1) 14Kg formamides and the anhydrous formic acid of 2Kg are added in 50L glass reaction kettles, after being heated to 180 DEG C, is being stirred
The hydrazine hydrate that mass concentration is 85% is slowly added dropwise in the state of mixing, and is slowly added dropwise and is produced to avoid white cigarette, and temperature drops in reaction process
It is low, stop that hydrazine hydrate is added dropwise when temperature drops to 145 DEG C or so, installation distilling apparatus carries out distillation water removal.When temperature recovery arrives
More than 180 DEG C start second and hydrazine hydrate are added dropwise.The rate of addition of hydrazine hydrate is controlled, hydrazine hydrate 10.0Kg, drop is added dropwise altogether twice
Add hydrazine hydrate and reaction 30 minutes is stirred more than 180 DEG C, then stop heating, allow reactant natural cooling at room temperature, obtain
To white solid.
(2) 95% ethanol 25.0Kg is added in a kettle, and heating reflux reaction obtains mixed liquor in 30 minutes, by mixed liquor
Through filter cylinder heat filtering to crystallization kettle, filtrate is cooled to room temperature in crystallization kettle, white crystal is separated out, after centrifugation, at 80 DEG C
Under the conditions of through hot-air oven drying i.e. can obtain 1H-1,2,4- triazole 9.5Kg, using hydrazine hydrate rate of collecting as 81%.
The result shows that：Technical solution synthesis 1H-1,2,4- triazoles using the present invention are obvious in comprehensive yield and cost
Better than the existing synthesis technique using formic acid and formamide as raw material, embodiment illustrates the technology of the present invention side compared with comparative example
It is anti-with hydrazine hydrate that the core of case is that the direct ammonolysis of ammonia that formic acid esters and ammonium salt decompose under high-temperature and high-pressure conditions obtains formamide
Should, while the dehydrating agent that formic acid esters can be reacted as follow-up cyclization, whole chemical reaction velocity is effectively raised, is reduced
Reaction temperature, improves product yield.
The above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations；Although with reference to the foregoing embodiments
The present invention is described in detail, it will be understood by those of ordinary skill in the art that：It still can be to foregoing each implementation
Technical solution described in example is modified, or carries out equivalent substitution to which part technical characteristic；And these modification or
Replace, the essence of appropriate technical solution is departed from the scope of various embodiments of the present invention technical solution.
Claims (11)
1. a kind of 1H-1, the synthesis technique of 2,4- triazoles, it is characterised in that synthesis step is as follows：
（1）Formic acid esters, hydrazine hydrate and ammonium salt are sequentially added into autoclave, in the case where sealing stirring, by reaction kettle plus
Press and be to slowly warm up to reaction temperature, after reaction, slowly reduce reaction temperature and steam by-product carbinol using waste heat, obtain
To white " milky " thing；
（2）The white " milky " thing is transferred in reaction kettle, adds ethanol, heating reflux reaction obtains mixed liquor, will mix
Liquid is cooled to room temperature through filter cylinder heat filtering to crystallization kettle, filtrate in crystallization kettle, white crystal is separated out, after centrifugation, through heat
Wind oven drying can obtain 1H-1,2,4- triazoles；
The step（1）In ammonium salt be ammonium chloride, ammonium sulfate or ammonium hydrogen carbonate；
The step（1）In formic acid esters be methyl formate, Ethyl formate or butyl formate.
2. synthesis technique as claimed in claim 1, it is characterised in that the step（1）The concentration of middle hydrazine hydrate is 85%.
3. synthesis technique as claimed in claim 1, it is characterised in that the ammonium salt is ammonium chloride.
4. synthesis technique as claimed in claim 1, it is characterised in that the formic acid esters is methyl formate.
5. synthesis technique as claimed in claim 1, it is characterised in that the quality that feeds intake of the formic acid esters, hydrazine hydrate and ammonium salt
Than for (4-6):2:(1-2).
6. synthesis technique as claimed in claim 5, it is characterised in that the quality that feeds intake of the formic acid esters, hydrazine hydrate and ammonium salt
Than for 5:2:1.3.
7. synthesis technique as claimed in claim 1, it is characterised in that the step（1）Middle reaction temperature is 120-130 DEG C,
When reaction time is 1-2 small.
8. synthesis technique as claimed in claim 7, it is characterised in that when the reaction time is 1.5 small.
9. synthesis technique as claimed in claim 1, it is characterised in that the step（2）The volume fraction of middle ethanol is 95%,
Feed intake volume and the step of the ethanol（1）Middle formic acid esters feeds intake volume ratio as 1:1.
10. synthesis technique as claimed in claim 1, it is characterised in that the temperature of the hot-air oven drying is 80-85 DEG C.
11. synthesis technique as claimed in claim 1, it is characterised in that the formic acid esters, hydrazine hydrate, ammonium salt and ethanol are
Chemistry is pure.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3328835A1 (en) * | 1983-08-10 | 1985-02-21 | Dynamit Nobel Ag, 5210 Troisdorf | Process for the preparation of 1H-1,2,4-triazole |
| CN102485715A (en) * | 2010-12-03 | 2012-06-06 | 刘志敏 | Synthesizing technology of triazole derivative |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3328835A1 (en) * | 1983-08-10 | 1985-02-21 | Dynamit Nobel Ag, 5210 Troisdorf | Process for the preparation of 1H-1,2,4-triazole |
| CN102485715A (en) * | 2010-12-03 | 2012-06-06 | 刘志敏 | Synthesizing technology of triazole derivative |
Non-Patent Citations (2)
| Title |
|---|
| 1,2,4-三氮唑的合成方法;张扬;《四川化工》;20051231;第8卷(第2期);18-20 * |
| 甲酰胺法合成1H-1，2，4-三氮唑;李文风等;《精细化工中间体》;20090228;第39卷(第1期);27-29 * |
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