CN107540670A - A kind of preparation method of the formonitrile HCN of 1 (base of 3 chlorine pyrazolo [1,5a] 4,5,6,7 tetrahydropyridine 2) 5 methylamine pyrazoles 4 - Google Patents
A kind of preparation method of the formonitrile HCN of 1 (base of 3 chlorine pyrazolo [1,5a] 4,5,6,7 tetrahydropyridine 2) 5 methylamine pyrazoles 4 Download PDFInfo
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- CN107540670A CN107540670A CN201610470787.7A CN201610470787A CN107540670A CN 107540670 A CN107540670 A CN 107540670A CN 201610470787 A CN201610470787 A CN 201610470787A CN 107540670 A CN107540670 A CN 107540670A
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Abstract
The present invention relates to a kind of 1 (3 chlorine pyrazolos [1; 5a] 4; the base of 5,6,7 tetrahydropyridine 2) 5 methylamine pyrazoles 4 formonitrile HCN preparation method; with 1 (3 chlorine pyrazolos [1; 5a] 4,5,6; the base of 7 tetrahydropyridine 2) 5 amino-pyrazol 4 formonitrile HCN be initiation material, successively by etherification reaction, purifying, rearrangement reaction, deformylase reaction and filtration drying process.The preparation method reaction efficiency of the present invention is high, reaction condition is gentle, improve the security of production and the versatility of equipment, prepared (the 3 chlorine pyrazolos [1 of finished product 1,5a] 4,5, the base of 6,7 tetrahydropyridine 2) 5 methylamine pyrazoles 4 formonitrile HCN there is the advantages of high income, purity are high, production cost is low.
Description
Technical field
The present invention relates to a kind of preparation method of organic intermediate, and in particular to 1- (3- chlorine pyrazolo [1,5a] -4,5,6,
7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs preparation method, belong to chemical technology field.
Background technology
1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs be prepare it is double
The key intermediate of azoles oxalic acid dinitrile, 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- first
Nitrile can obtain pyraclonil through step chemical reaction again.At present, it is fresh be documented 1- (3- chlorine pyrazolo [1,5a] -4,5,
6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs preparation method, Ge Faxiang exists within 2012 years《Anhui chemical industry》Magazine
A kind of 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydrochysene pyrroles are disclosed herein in the phase " synthesis of pyraclonil " one of volume 38 the 6th
Pyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs preparation method, i.e. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridines -
2- yls) -5- amino-pyrazol -4- formonitrile HCNs and chloromethanes react, and chemical equation is：
But there is open defect and deficiency in above-mentioned prior art：First, methylating reagent is chloromethanes, chloromethanes is gas
1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- of state and price height, gaseous chloromethanes and liquid
The deficiency that reaction efficiency is low, utilization of materials is low, production cost is high be present in amino-pyrazol -4- formonitrile HCN solution reactions；It is second, above-mentioned
Chemically react for compressive reaction, to require high to production equipment, working condition, adding the security risk of production；It is third, above-mentioned
Chemical reaction can not avoid double methylated by-products, i.e. reaction can generate 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydrochysene pyrroles
Pyridine -2- bases) -5- dimethylamine pyrazoles -4- formonitrile HCNs, reduce 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2-
Base) -5- methylamine pyrazoles -4- formonitrile HCNs yield and purity, also increase subsequent purification process and separating difficulty.
The content of the invention
It is an object of the invention to provide a kind of 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- first
The preparation method of amine pyrazoles -4- formonitrile HCNs, preparation method of the invention have reaction efficiency height, high income, product purity height, production
The advantages of cost is low, while preparation method reaction condition of the present invention is gentle, it is low for equipment requirements, improve production security and
The versatility of equipment.
Realize the technical scheme is that：
Using 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- formonitrile HCNs as starting
Raw material, successively by etherification reaction, purifying, rearrangement reaction, deformylase reaction and filtration drying process, 1- is prepared
(3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs, specific chemical reaction step is such as
Under：
1) etherification reaction：By 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazols -4-
Formonitrile HCN, trimethyl orthoformate, solvent and catalyst C1 input reactor in, under 70~100 DEG C, condition of negative pressure react 6~
20h, obtain reaction solution A；
2) purify:Saturated sodium bicarbonate aqueous solution, water or 5wt% aqueous hydrochloric acid solutions are added to the reaction solution A, stir,
Stand, add anhydrous magnesium sulfate after liquid separation into organic layer again, stand, filtrate A is obtained after filtering；
3) rearrangement reaction：Catalyst C2 is added into the filtrate A, 5~12h, drop are reacted under the conditions of 100~140 DEG C
Reaction solution B is obtained after temperature；
4) deformylase reacts：Water and inorganic acid are added into the reaction solution B, react 4 under the conditions of 40~70 DEG C~
10h, obtain reaction liquid C；
5) filtration drying：The reaction liquid C is cooled to 0~5 DEG C, and filtering, filter cake is washed with water, obtains 1- (3- chlorine after drying
Pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs；
Step 1) the catalyst C1 is Bronsted acid or Lewis acid, and step 3) the catalyst C2 is tertiary amine salt, season
Ammonium salt Huo quaternary alkylphosphonium salts, the step 4) inorganic acid are sulfuric acid or nitric acid.
Etherification reaction, rearrangement reaction, the chemical equation of deformylase reaction are：
Etherification reaction formula is:
Rearrangement reaction formula is：
Deformylase reaction equation is:
Preferably, the step 1) solvent is ethylbenzene, dimethylbenzene, trimethylbenzene or chlorobenzene, and the boiling point of the solvent is all 130
More than DEG C, there is larger difference on boiling point with etherification reaction Methanol product (64 DEG C of boiling point), dereaction is removed under condition of negative pressure
On etherification reaction system without influence during the methanol of generation.
Preferably, step 1) the catalyst C1 be benzene sulfonic acid, p-methyl benzenesulfonic acid, p-chlorobenzenesulfonic acid, m-nitrobenzene sulfonic acid,
Methanesulfonic acid, zinc chloride, zinc acetate, copper chloride, copper acetate, ferric trichloride, ferrous chloride or alchlor, catalyst can promote instead
It should occur, and accelerate reaction process, shorten the reaction time.
Preferably, the vacuum of the step 1) negative pressure is 0.05~0.07MPa.It is true with vacuum pumping during etherification reaction
Sky, is formed and the vacuum in maintenance reaction kettle is between 0.05~0.07MPa.
Preferably, step 1) the trimethyl orthoformate dosage is 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydrochysene pyrroles
Pyridine -2- bases) 2~5 times of -5- amino-pyrazol -4- formonitrile HCN molal quantitys, the catalyst C1 dosages be 1- (3- chlorine pyrazolo [1,
5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- formonitrile HCN molal quantitys 1~5%, the dosage of the solvent is 1-
5~10 times of (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- formonitrile HCN weight.
Preferably, step 3) the tertiary amine salt is trimethylamine hydrochloride, trimethylamine hydrobromate, triethylamine hydrochloride, three
Ethylamine hydrobromide, tripropyl amine (TPA) hydrochloride, tripropyl amine (TPA) hydrobromate, tri-n-butylamine hydrochloride, tri-n-butylamine hydrobromate, pyridine hydrochloric acid
One or more in salt, pyridine hydrobromide salt, 2- methyl pyridinium chlorides or 2- picoline hydrobromates, the quaternary ammonium salt
For tetramethylammonium hydrochloride, tetramethylammonium hydrobromate, etamon hydrochloride, etamon hydrobromate, tetrapropylammonium hydrochloride, tetrapropylammonium
Hydrobromate, tetrabutylammonium salt hydrochlorate, tetrabutylammonium hydrobromate, benzyltrimethylammon.um hydrochloride, benzyltrimethylammon.um hydrobromate,
Benzyl triethyl ammonium ammonium salt hydrochlorate, benzyl triethyl ammonium ammonium hydrobromate, benzyl tripropyl ammonium salt hydrochlorate, benzyl tripropyl ammonium hydrobromic acid
Salt, benzyl tributyl ammonium hydrochloride, benzyl tributyl ammonium hydrobromate, N- benzyl pyridines hydrochloride, N- benzyl pyridine hydrobromic acids
One or more in salt, N- benzyl -2- methyl pyridinium chlorides or N- benzyl -2- picoline hydrobromates, the quaternary phosphine
Salt is four methyl phosphonium chlorides, four methyl bromide Phosphonium, tetraethyl phosphonium chloride, four ethyl phosphonium bromide Phosphonium, tetrapropyl phosphonium chloride, tetrapropyl bromine
Hua Phosphonium, 4-butyl phosphonium chloride, Si butyl phosphonium bromide, benzyl trimethyl phosphonium chloride, benzyl trimethyl phosphonium bromide, benzyl triethyl ammonium chlorine
Hua Phosphonium, Bian base triethyl groups phosphonium bromide, benzyl tripropyl phosphonium chloride, benzyl tripropyl phosphonium bromide, benzyl tributyl phosphonium chloride, benzyl
One or more in San butyl phosphonium bromides.Catalyst promotes reaction, and accelerates reaction process, shortens the reaction time.
Preferably, step 3) the catalyst C2 dosages be 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridines -
2- yls) -5- amino-pyrazol -4- formonitrile HCN molal quantitys 5~15%.
Preferably, step 3) is cooled to 40~60 DEG C, and the temperature after cooling is roughly the same with deformylase reaction temperature.
Preferably, the dosage of the step 4) inorganic acid be 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridines -
2- yls) 1.5~2 times of -5- amino-pyrazol -4- formonitrile HCN molal quantitys.
Preferably, step 5) filter cake is washed with water to more than pH5, such as pH5.0, pH5.1, pH5.2, pH5.5.
Compared with prior art, the beneficial effects of the present invention are:
1st, the present invention is with 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- first
Nitrile is initiation material, successively by etherification reaction, rearrangement reaction, deformylase reaction prepare 1- (3- chlorine pyrazolo [1,5a] -4,
5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs, three-step reaction is liquid, liquid reaction, and reaction efficiency is high, this hair
Finished product 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- prepared by bright preparation method
Formonitrile HCN has the advantages of high income, purity are high, production cost is low.
2nd, the present invention can avoid 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazols -
The double methylated by-products of 4- formonitrile HCNs, that is, avoid generating 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5-
Dimethylamine pyrazoles -4- formonitrile HCNs, improve the purity and yield of finished product, while it also avoid later separation purification procedures.
3rd, etherification reaction of the present invention is negative reaction, and condition of negative pressure is advantageous to except the methanol of dereaction generation, driving a reaction
Progress, improve the speed of reaction；Solvent used in etherification reaction of the present invention is ethylbenzene, dimethylbenzene, trimethylbenzene or chlorobenzene, institute
Stating solvent neither influences subsequent chemical reaction, and has larger difference on boiling point with etherification reaction Methanol product, in negative pressure bar
Methanol can be effectively removed under part, and does not reduce solvent used in etherification reaction, the synergy of condition of negative pressure and solvent, is pushed away jointly
Dynamic reaction is smoothed out.
4th, etherification reaction negative reaction of the invention, rearrangement reaction, deformylase reaction are synthesis under normal pressure, reaction condition temperature
With improve the security of production, reduce the particular/special requirement to equipment, improve the versatility of equipment.
5th, etherification reaction of the present invention uses tertiary amine salt, season using Bronsted acid or Lewis acid as catalyst, rearrangement reaction
Ammonium salt Huo quaternary alkylphosphonium salts make catalyst, above-mentioned to promote reaction, and accelerate reaction process, shorten the reaction time.
6th, the inorganic acid that deformylase reaction uses is high boiling sulfuric acid or nitric acid, and volatility is small, when reaction temperature control
For system at 40~70 DEG C, inorganic acid volatilization is few, and environmental pollution is small.
Embodiment
To allow those skilled in the art to be better understood from the present invention and can be practiced, with reference to specific implementation
The present invention is further elaborated for example.
First, part of the embodiment of the present invention
Embodiment 1
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, ethylbenzene 132g, trimethyl orthoformate 53g and m-nitrobenzene sulfonic acid monohydrate 0.22g, stirring
Under be warming up to 70~80 DEG C, react 20h under suction to 0.05Mpa, obtain reaction solution A；
2) purify：Saturated sodium bicarbonate aqueous solution 100ml is added into reaction solution A, stirs 10min, stands 30min, point
Liquid discards water layer, adds anhydrous magnesium sulfate 10g in organic layer, is filtered after standing 5h, obtain filtrate A；
3) rearrangement reaction：Tri-n-butylamine hydrochloride 1.1g is added into filtrate A, 100~110 DEG C of reaction 12h, is cooled to 40
DEG C, obtain reaction solution B；
4) deformylase reacts：Water 70ml is first added into reaction solution B, adds 98wt% sulfuric acid 15g, 40~50 DEG C
10h is reacted, obtains reaction liquid C；
5) filtration drying：Reaction liquid C cools to 0 DEG C, and filtering, filter cake is washed with water to pH5.5,90~100 DEG C of vacuum of filter cake
8h is dried, obtains 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs 23.5g.
Embodiment 2
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, dimethylbenzene 265g, trimethyl orthoformate 53g and zinc chloride 0.68g, it is warming up to 90 under stirring~
100 DEG C, 10h is reacted under suction to 0.06Mpa, obtains reaction solution A；
2) purify：Water 100ml is added into reaction solution A, stirs 10min, stands 30min, liquid separation discards water layer, organic layer
Middle addition anhydrous magnesium sulfate 10g, filtered after standing 5h, obtain filtrate A；
3) rearrangement reaction：TBAB 3.2g is added into filtrate A, 130~140 DEG C of reaction 5h, is cooled to 50 DEG C,
Obtain reaction solution B；
4) deformylase reacts：Water 70ml is first added into reaction solution B, adds 60wt% nitric acid 21g, 50~60 DEG C
4h is reacted, obtains reaction liquid C；
5) filtration drying：Reaction liquid C cools to 1 DEG C, and filtering, filter cake is washed with water to pH5.0,90~100 DEG C of vacuum of filter cake
10h is dried, obtains 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs
24.6g。
Embodiment 3
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, chlorobenzene 150g, trimethyl orthoformate 21.2g and copper acetate monohydrate 0.6g, rise under stirring
Temperature reacts 15h under suction to 0.07Mpa, obtains reaction solution A to 80~90 DEG C；
2) purify：Water 100ml is added into reaction solution A, stirs 10min, stands 30min, liquid separation discards water layer, organic layer
Middle addition anhydrous magnesium sulfate 10g, filtered after standing 8h, obtain filtrate A；
3) rearrangement reaction：Benzyltrimethylammonium chloride 1.86g is added into filtrate A, 120~130 DEG C of reaction 10h, is cooled
To 60 DEG C, reaction solution B is obtained；
4) deformylase reacts：Water 70ml is first added into reaction solution B, adds 98wt% sulfuric acid 20g, 60~70 DEG C
8h is reacted, obtains reaction liquid C；
5) filtration drying：Reaction liquid C cools to 0 DEG C, and filtering, filter cake is washed with water to pH5.2,90~100 DEG C of vacuum of filter cake
8h is dried, obtains 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs 25.1g.
Embodiment 4
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, dimethylbenzene 160g, trimethyl orthoformate 31.8g and p-methyl benzenesulfonic acid 0.51g, stir lower heat up
To 70~80 DEG C, 8h is reacted under suction to 0.07Mpa, obtains reaction solution A；
2) purify：5wt% aqueous hydrochloric acid solution 100ml are added into reaction solution A, stir 10min, stand 30min, liquid separation is abandoned
Water layer is removed, anhydrous magnesium sulfate 10g is added in organic layer, is filtered after standing 5h, obtain filtrate A；
3) rearrangement reaction：Tetraethyl chlorination squama 1.82g is added into filtrate A, 110~120 DEG C of reaction 8h, is cooled to 50
DEG C, obtain reaction solution B；
4) deformylase reacts：Water 100ml is first added into reaction solution B, adds 98wt% sulfuric acid 18g, 50~60
DEG C reaction 7h, obtain reaction liquid C；
5) filtration drying：Reaction liquid C cools to 5 DEG C, and filtering, filter cake is washed with water to pH5.1,90~100 DEG C of vacuum of filter cake
8h is dried, obtains 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs 23.3g.
Embodiment 5
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, mesitylene 200g, trimethyl orthoformate 42.4g and ferric trichloride 0.32g, stir lower heat up
To 80~90 DEG C, 6h is reacted under suction to 0.06Mpa, obtains reaction solution A；
2) purify：5wt% aqueous hydrochloric acid solution 100ml are added into reaction solution A, stir 10min, stand 30min, liquid separation is abandoned
Water layer is removed, anhydrous magnesium sulfate 10g is added in organic layer, is filtered after standing 5h, obtain filtrate A；
3) rearrangement reaction：Bromination N- benzyl pyridines 3.75g is added into filtrate A, 130~140 DEG C of reaction 6h, is cooled to 40
DEG C, obtain reaction solution B；
4) deformylase reacts：Water 80ml is first added into reaction solution B, adds 60wt% nitric acid 15.8g, 40~45
DEG C reaction 5h, obtain reaction liquid C；
5) filtration drying：Reaction liquid C cools to 0 DEG C, and filtering, filter cake is washed with water to pH5.1,90~100 DEG C of vacuum of filter cake
8h is dried, obtains 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs 25.4g.
2nd, comparative example part
Comparative example 1
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, mesitylene 200g, trimethyl orthoformate 42.4g, are warming up to 80~90 DEG C under stirring, take out true
Reciprocal of duty cycle obtains reaction solution A to 6h is reacted under 0.06Mpa；
2) purify：5wt% aqueous hydrochloric acid solution 100ml are added into reaction solution A, stir 10min, stand 30min, liquid separation is abandoned
Water layer is removed, anhydrous magnesium sulfate 10g is added in organic layer, is filtered after standing 5h, obtain filtrate A；
3) rearrangement reaction：Bromination N- benzyl pyridines 3.75g is added into filtrate A, 130~140 DEG C of reaction 6h, is cooled to 40
DEG C, obtain reaction solution B；
4) deformylase reacts：Water 80ml is first added into reaction solution B, adds 60wt% nitric acid 15.8g, 40~45
DEG C reaction 5h, obtain reaction liquid C；
5) filtration drying：Reaction liquid C cools to 0 DEG C, and nodeless mesh separates out.
Comparative example 2
1) etherification reaction：1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- is added in reactor
Amino-pyrazol -4- formonitrile HCNs 26.5g, mesitylene 200g, trimethyl orthoformate 42.4g and ferric trichloride 0.32g, stir lower heat up
To 80~90 DEG C, 6h is reacted under suction to 0.06Mpa, obtains reaction solution A；
2) purify：5wt% aqueous hydrochloric acid solution 100ml are added into reaction solution A, stir 10min, stand 30min, liquid separation is abandoned
Water layer is removed, anhydrous magnesium sulfate 10g is added in organic layer, is filtered after standing 5h, obtain filtrate A；
3) rearrangement reaction：Filtrate A reacts 6h at 130~140 DEG C, is cooled to 40 DEG C, obtains reaction solution B；
4) deformylase reacts：Water 80ml is first added into reaction solution B, adds 60wt% nitric acid 15.8g, 40~45
DEG C reaction 5h, obtain reaction liquid C；
5) filtration drying：Reaction liquid C cools to 0 DEG C, and nodeless mesh separates out.
3rd, experimental sections
Product analysis prepared by the embodiment of the present invention 1~5 of experimental example 1 and comparative example 1~2
(3- chlorine pyrazolo [the 1,5a] -4,5,6,7- four of product 1- prepared by the embodiment of the present invention 1~5 and comparative example 1~2
Pyridinium hydroxide -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs quality and yield respectively by weighing and being calculated, its purity analysis is adopted
Use high performance liquid chromatography.The testing result that embodiment 1~5 and comparative example 1~2 prepare product is shown in Table 1.
The embodiment 1~5 of table 1 and comparative example 1~2 prepare product detection result
The reaction liquid C of comparative example 1~2 cools to 0 DEG C, and nodeless mesh separates out, and high performance liquid chromatography does not detect in reaction liquid C
To 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs, i.e. yield is 0；This hair
Bright embodiment 1~5 prepare product 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamines pyrazoles -
For the yield of 4- formonitrile HCNs between 84.3%~91.9%, for product purity between 98%~99%, high income, purity are high, obtain
Unexpected experimental result；Study and find simultaneously, reaction product 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydrochysene pyrroles
Pyridine -2- bases) in -5- methylamine pyrazoles -4- formonitrile HCNs, high performance liquid chromatography be not detected by disubstituted product 1- (3- chlorine pyrazolo [1,
5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- dimethylamine pyrazoles -4- formonitrile HCNs, avoid interference of the homologue impurity to finished product.
Claims (10)
- A kind of 1. preparation of 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs Method, it is characterised in that comprise the following steps：1) etherification reaction：By 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- first In nitrile, trimethyl orthoformate, solvent and catalyst C1 input reactors, 6~20h is reacted under 70~100 DEG C, condition of negative pressure, Obtain reaction solution A；2) purify:Saturated sodium bicarbonate aqueous solution, water or 5wt% aqueous hydrochloric acid solutions are added to the reaction solution A, stirring, is stood, Add anhydrous magnesium sulfate after liquid separation into organic layer again, stand, filtrate A is obtained after filtering；3) rearrangement reaction：Catalyst C2 is added into the filtrate A, 5~12h is reacted under the conditions of 100~140 DEG C, after cooling Obtain reaction solution B；4) deformylase reacts：Water and inorganic acid are added into the reaction solution B, 4~10h is reacted under the conditions of 40~70 DEG C, Obtain reaction liquid C；5) filtration drying：The reaction liquid C is cooled to 0~5 DEG C, and filtering, filter cake is washed with water, obtains 1- (3- chlorine pyrazoles after drying And [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrazoles -4- formonitrile HCNs；Step 1) the catalyst C1 is Bronsted acid or Lewis acid, and step 3) the catalyst C2 is tertiary amine salt, quaternary ammonium salt Huo quaternary alkylphosphonium salts, the step 4) inorganic acid are sulfuric acid or nitric acid.
- 2. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that the step 1) solvent is ethylbenzene, dimethylbenzene, trimethylbenzene or chlorobenzene.
- 3. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that step 1) the catalyst C1 is benzene sulfonic acid, p-methyl benzenesulfonic acid, to chlorobenzene sulphur Acid, m-nitrobenzene sulfonic acid, methanesulfonic acid, zinc chloride, zinc acetate, copper chloride, copper acetate, ferric trichloride, ferrous chloride or tri-chlorination Aluminium.
- 4. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that the vacuum of the step 1) negative pressure is 0.05~0.07MPa.
- 5. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that step 1) the trimethyl orthoformate dosage be 1- (3- chlorine pyrazolo [1, 5a] -4,5,6,7- tetrahydropyridine -2- bases) 2~5 times of -5- amino-pyrazol -4- formonitrile HCN molal quantitys, the catalyst C1 dosages are The 1~5% of 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- formonitrile HCN molal quantitys, institute The dosage for stating solvent is 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- formonitrile HCN weights 5~10 times of amount.
- 6. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that step 3) the tertiary amine salt be trimethylamine, triethylamine, tripropyl amine (TPA), tri-n-butylamine, Pyridine, 2- picolines hydrochloride or hydrobromate in one or more, the quaternary ammonium salt be tetramethylammonium, etamon, four Third ammonium, tetrabutylammonium, benzyltrimethylammon.um, benzyl triethyl ammonium ammonium, benzyl tripropyl ammonium, benzyl tributyl ammonium, N- benzyl pyridines, N- One or more in the hydrochloride or hydrobromate of benzyl -2- picolines, the quaternary alkylphosphonium salt are chlorination or bromination tetramethyl Phosphonium, Si Yi Ji Phosphonium, Si Bing Ji Phosphonium, 4-butyl-phosphonium, Bian base San Jia Ji Phosphonium, Bian base San Yi Ji Phosphonium, benzyl San Bing Ji Phosphonium, the fourth of benzyl three One or more in Ji Phosphonium.
- 7. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that step 3) the catalyst C2 dosages be 1- (3- chlorine pyrazolo [1,5a] -4, 5,6,7- tetrahydropyridine -2- bases) -5- amino-pyrazol -4- formonitrile HCN molal quantitys 5~15%.
- 8. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that step 3) is cooled to 40~60 DEG C.
- 9. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that the dosage of the step 4) inorganic acid be 1- (3- chlorine pyrazolo [1,5a] -4, 5,6,7- tetrahydropyridine -2- bases) 1.5~2 times of -5- amino-pyrazol -4- formonitrile HCN molal quantitys.
- 10. 1- (3- chlorine pyrazolo [1,5a] -4,5,6,7- tetrahydropyridine -2- bases) -5- methylamine pyrroles according to claim 1 The preparation method of azoles -4- formonitrile HCNs, it is characterised in that step 5) filter cake is washed with water to more than pH5.
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| CN112724131A (en) * | 2020-12-30 | 2021-04-30 | 湖北相和精密化学有限公司 | Aminopyrazole and purification treatment process of mother liquor material in preparation process thereof |
| CN113773288A (en) * | 2021-09-30 | 2021-12-10 | 南京林业大学 | Heterocyclic ring-containing dehydroabietyl formamide compounds and preparation method and application thereof |
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| CN1225635A (en) * | 1996-07-18 | 1999-08-11 | 赫彻斯特-舍林农业发展有限公司 | Substituted pyrazolyl-pyrazole derivatives, process for their prepn. and their use as agents with herbicidal effect |
| CN1060478C (en) * | 1992-10-12 | 2001-01-10 | 先灵公司 | Substituted pyrazole derivatives |
| CN105001221A (en) * | 2015-08-25 | 2015-10-28 | 湖北相和精密化学有限公司 | Synthetic method of pyraclonil |
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| CN112724131A (en) * | 2020-12-30 | 2021-04-30 | 湖北相和精密化学有限公司 | Aminopyrazole and purification treatment process of mother liquor material in preparation process thereof |
| CN113773288A (en) * | 2021-09-30 | 2021-12-10 | 南京林业大学 | Heterocyclic ring-containing dehydroabietyl formamide compounds and preparation method and application thereof |
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