CN105801484A - Preparation method of pyrazolyl acrylonitrile compound - Google Patents
Preparation method of pyrazolyl acrylonitrile compound Download PDFInfo
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Abstract
The invention belongs to the field of organic synthesis, and concretely relates to a preparation method of a pyrazolyl acrylonitrile compound. A pyrazole carboxylic ester compound and p-tert-butylphenylacetonitrile are shown in a general formula (II), in the existence of an organic solvent and alkali, a reaction is carried out at 60-160 DEG C, 2-(4-(tert-butyl)phenyl)-1-(1-ethyl-3-methyl-1hydrogen-5-pyrazolyl)-2-cyan vinyl alcohol sodium salt or kali salt is obtained as shown in a general formula (III), a reaction is directly carried out between the obtained compound (III) and pivaloyl chloride at 60-160 DEG C, and the pyrazolyl acrylonitrile compound as shown in a general formula (I) is obtained. The method has the advantages of high yield of the target compound, low 'three wastes (waste gas, waste water and industrial residue)' discharge, and simple operation; and the method is suitable for large scale industrial production.
Description
Technical field
The invention belongs to organic synthesis field, more particularly to the preparation method of a pyrazolyl acrylonitrile compound.
Background technology
Pyrazolyl acrylonitrile compound shown in logical formula I is that a class has the parasite killing of excellence, acaricidal activity, can be used for preventing and treating
Insect pest, the compound of demodicid mite evil.
Patent WO2010124617A1 discloses the synthetic method of this compounds.By the pyrazole carboxylic acid shown in logical formula II
Ester type compound with to tert-butyl benzene acetonitrile, normal heptane, ethylene glycol monoethyl ether mixed solvent in, the Feldalat NM of dropping 20%
Methanol solution, reaction terminate after, be poured into after cooling in water, add ethyl acetate extraction, aqueous phase with concentrated hydrochloric acid adjust pH to 2～3,
Being extracted with ethyl acetate 3 times, organic facies is scrubbed, is concentrated to give hydroxy nitrile intermediate shown in logical formula IV after drying,
Single step yield 37～79%.Intermediate shown in logical formula IV again with pivaloyl chloride, in dichloromethane, in the presence of triethylamine,
Reaction obtains target compound single step yield 12～51% shown in logical formula I.
Patent CN102898373A is with hydroxy nitrile compounds shown in logical formula IV as initiation material, at toluene or chlorobenzene
In, in the presence of inorganic base, react with pivaloyl chloride, prepare target compound shown in logical formula I.
The preparation method of above-mentioned logical formula I, is required to synthesize through hydroxy nitrile intermediate shown in logical formula IV.
And the synthesis yield of this intermediate is low, post processing is complicated, uses multiple alkali and multi-solvents, and quantity of three wastes is big.
Therefore it is badly in need of a kind of yield height, low cost, is suitable to the synthetic method of large-scale industrial production.
Summary of the invention
The present invention provides the preparation method of a kind of pyrazolyl acrylonitrile compound.
For achieving the above object, the present invention uses the technical scheme to be:
A kind of pyrazolyl acrylonitrile (Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl)
Pivalic acid vinyl acetate) preparation method of compounds, reaction equation is as follows,
In formula: R1Selected from H, methyl, CN or halogen, R2Selected from C1-C5Alkyl；
Lead to the pyrazole carboxylic acid ester compound shown in formula II and to tert-butyl benzene acetonitrile, in the presence of alkali and organic solvent,
React 3-8 hour in 60-160 DEG C, course of reaction constantly separates by-product alcohol, obtain logical 2-(4-(tertiary fourth shown in formula III
Base) phenyl)-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl)-2-cyano vinyl sodium alkoxide or the suspension of potassium salt, gained compound
(III) suspension directly reacts 1-3 hour at 60-160 DEG C with pivaloyl chloride, obtains pyrazolyl propylene shown in logical formula I
Nitrile compounds.
Pyrazole carboxylic acid ester compound shown in described logical formula II, with to tert-butyl benzene acetonitrile reaction, separates the mistake of by-product alcohol
Journey can be by the method for rectification, constantly add solvent and constantly steam the method for solvent or steam the method for demixing of solvents and be able to
Remove by-product alcohol.
Described compound (III) reacts with pivaloyl chloride after terminating, and removes, by the way of washing or filtration, the salt that reaction generates,
Again by the way of distillation or crystallization, prepare pyrazolyl acrylonitrile compound shown in logical formula I.
Described organic solvent is aromatic hydrocarbon.Preferably organic solvent is benzene,toluene,xylene, chlorobenzene and dichloro-benzenes.Described two
Toluene or dichloro-benzenes can be dimethylbenzene or the dichloro-benzenes of mixing (o-, m-, to)
Described alkali is selected from C1-C5Sodium alkoxide or potassium alcoholate.
The addition of alkali is shown in logical formula II 0.7-1.5 times of the amount of combinations of materials；To the addition of tert-butyl benzene acetonitrile it is
Shown in logical formula II 0.7-1.5 times of the amount of combinations of materials；The addition of pivaloyl chloride is compound thing shown in logical formula II
0.7-1.5 times of the amount of matter.The addition of organic solvent is so that reactant mixture can well stir is advisable.
Preferred version is, described alkali is selected from Feldalat NM, Sodium ethylate, sodium tert-butoxide or potassium tert-butoxide；Described organic solvent is selected from first
Benzene, dimethylbenzene or chlorobenzene；
The addition of alkali is shown in logical formula II 0.9-1.3 times of the amount of combinations of materials；To the addition of tert-butyl benzene acetonitrile it is
Shown in logical formula II 0.9-1.3 times of the amount of combinations of materials；The addition of pivaloyl chloride is compound thing shown in logical formula II
0.9-1.3 times of the amount of matter.
Compound shown in described logical formula II is 80-150 DEG C with to the reaction temperature of tert-butyl benzene acetonitrile；Shown in logical formula III
Compound is 100-150 DEG C with the reaction temperature of pivaloyl chloride.
Suitable phase transfer catalyst can also be added in some cases in reaction system.
The preparation method of logical pyrazole carboxylic acid ester compound shown in formula II see WO2010124617A1 and
CN1626520A。
In the definition of formula given above (I, II, III) compound and organic solvent, collect term used and typically define such as
Under: halogen refers to fluorine, chlorine, bromine, iodine.Alkyl refers to straight or branched form, such as: methyl, ethyl, n-pro-pyl, different
The groups such as propyl group, normal-butyl, isobutyl group, sec-butyl, tertiary butyl, 2-methyl butyl, n-pentyl, isopentyl.
The present invention compared with prior art have the advantage that:
In prior art, dicyandiamide solution is that (alkane purpose is for separating by-products alcohol, ethers purpose with ethers mixed solvent for alkane
In order to regulate polarity), by the way of azeotropic and layering, remove by-product alcohol, intermediate is that hydroxy nitrile (IV) needs to pass through
Be acidified, extract, the mode such as washing separates and purifies, and this intermediate bad dispersibility, content are low, need in course of reaction
Four kinds of solvents, two or more alkali just can obtain target product (I).And the sodium salt that intermediate of the present invention is hydroxy nitrile or
Potassium salt, it need not separation can directly carry out next step reaction, and this intermediate good dispersion, content are high.In preparation process with
Aromatic hydrocarbon is solvent, removes by-product alcohol by the method for rectification, can high yield obtain intermediate (III), without isolation,
By " one kettle way ", it is to avoid cause the decomposition of intermediate, and then synthesis targeted during post processing washing and acid-base neutralization
Compound Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) pivalic acid vinyl esters
Compound, two-step reaction has only to a kind of alkali and a kind of solvent, and total recovery increases substantially.Intermediate need not separate, and directly uses
React in next step, it is to avoid post processing and the purification step such as intermediate washing, extraction, decrease " three wastes " discharge, reduce
Cost, and energy resource consumption.Two-step reaction is carried out continuously, and is suitable to large-scale industrial production.
Detailed description of the invention
The preparation method of pyrazolyl acrylonitrile compound shown in logical formula I is further described below by enumerating embodiment,
But the present invention is not limited only to these embodiments.
Embodiment 1
Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) pivalic acid vinyl acetate (table
Compound 1 in 1) synthesis
Equipped with in the reaction bulb of rectifying column, add 43.7g (0.8mol) Feldalat NM, 140g (0.8mol) to tert-butyl benzene second
Nitrile and 900g toluene, be warmed up to 60 DEG C.It is slowly added dropwise 170g (1.0mol) 1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazole carboxylic acid first
Ester and the solution of 300 toluene, dripped off with about 1 hour.After completion of dropwise addition, it is warmed up to backflow, during reaction, constantly by tower top
Separate the boiling point low-boiling-point substance less than 65 DEG C, react 5 hours, obtain 2-(4-(tert-butyl group) phenyl)-1-(-1-ethyl-3-methyl isophthalic acid hydrogen
-5-pyrazolyl) the toluene suspension liquid of-2-cyano vinyl sodium alkoxide.
At 80-90 DEG C, upwards step reactant mixture drips 98g (0.8mol) pivaloyl chloride, drip in 30 minutes
Finish.After completion of dropwise addition, it is stirred for reacting 1 hour.After reaction terminates, cool to room temperature, wash twice, each 800 grams,
Separating water layer, organic layer removed under reduced pressure toluene solvant, still is residual obtains 258g Z-2-(4-(tert-butyl group) benzene through recrystallized from acetonitrile
Base)-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) pivalic acid vinyl acetate white solid, content 99.0%, yield
65%, fusing point 92-93 DEG C.
Its1H NMR(300MHz,CDCl3):
7.32(d,2H),7.07(d,2H),6.18(s,1H),3.56(q,2H),2.28(s,3H),1.35(s,9H),1.27(s,9H),1.01(t,3H)。
Embodiment 2
Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) pivalic acid vinyl acetate (table
Compound 1 in 1) synthesis
Equipped with in the reactor of rectifying column, add 11Kg (20.2mol) Feldalat NM and 180Kg toluene, be warmed up to 100 DEG C.
It is slowly added dropwise 33Kg (189mol) to tert-butyl benzene acetonitrile, 30Kg (177mol) 1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazole carboxylic acid
Methyl ester and the solution of 50Kg toluene, dripped off with about 1.5 hours.After completion of dropwise addition, be warmed up to backflow, during reaction, constantly by
The tower top separation boiling point low-boiling-point substance less than 65 DEG C, reacts 6 hours, obtains 2-(4-(tert-butyl group) phenyl)-1-(-1-ethyl-3-methyl isophthalic acid
Hydrogen-5-pyrazolyl) the toluene suspension liquid of-2-cyano vinyl sodium alkoxide.
At 100-105 DEG C, upwards step reactant mixture drips 24Kg (197mol) pivaloyl chloride, drip in 30 minutes
Complete.After completion of dropwise addition, it is stirred for reacting 1 hour.After reaction terminates, cool to room temperature, wash twice, each 150Kg,
Separating water layer, organic layer removed under reduced pressure toluene solvant, still is residual obtains 52.4Kg Z-2-(4-(tert-butyl group) through recrystallized from acetonitrile
Phenyl)-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) pivalic acid vinyl acetate white solid, content 99.3%, receive
Rate 74.9%, fusing point 92-93 DEG C.
Embodiment 3
Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(the chloro-1 hydrogen-5-pyrazolyl of 1-ethyl-3-methyl-4-) pivalic acid vinyl acetate
The synthesis of (compound 5 in table 1)
Equipped with in the reaction bulb of rectifying column, add 54.6g (1.0mol) Feldalat NM and 900g toluene, be warmed up to 80 DEG C.
It is slowly added dropwise 205g (1.0mol) 4-chloro-1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazole carboxylic acid methyl ester, 175g (1.0mol) to the tert-butyl group
Benzene acetonitrile and the solution of 300 toluene, dripped off with about 2 hours.After completion of dropwise addition, be warmed up to backflow, during reaction, constantly by
The tower top separation boiling point low-boiling-point substance less than 65 DEG C, reacts 3 hours, obtains 2-(4-(tert-butyl group) phenyl)-1-(4-chloro-1-ethyl-3-
Methyl isophthalic acid hydrogen-5-pyrazolyl) the toluene suspension liquid of-2-cyano vinyl sodium alkoxide.
At 105-110 DEG C, upwards step reactant mixture drips 122g (1.0mol) pivaloyl chloride, drip in 30 minutes
Complete.After completion of dropwise addition, it is stirred for reacting 2 hours.After reaction terminates, cool to room temperature, wash twice, each 900 grams,
Separating water layer, organic layer removed under reduced pressure toluene solvant, still is residual obtains 306g Z-2-(4-(tert-butyl group) benzene through recrystallized from acetonitrile
Base)-2-cyano group-1-(the chloro-1 hydrogen-5-pyrazolyl of 1-ethyl-3-methyl-4-) pivalic acid vinyl acetate white solid, content 99.3%, receive
Rate 70.9%, fusing point 93-94 DEG C.Its1H NMR(300MHz,CDCl3):7.29(d,2H),7.06(d,2H),3.81-3.41(m,2H),
2.25(s,3H),1.35(s,9H),1.27(s,9H),0.99(t,3H)。
Embodiment 4
Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(the chloro-1 hydrogen-5-pyrazolyl of 1-ethyl-3-methyl-4-) pivalic acid vinyl acetate
The synthesis of (compound 5 in table 1)
Equipped with in the reaction bulb of rectifying column, add 113.5g (1.0mol) potassium tert-butoxide and 1200g o-Dimethylbenzene, be warmed up to
120℃.It is slowly added dropwise 219g (1.0mol) 4-chloro-1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazole carboxylic acid ethyl ester, 175g (1.0mol)
To tert-butyl benzene acetonitrile and the solution of 300 o-Dimethylbenzenes, dripped off with about 1 hour.After completion of dropwise addition, it is warmed up to backflow, reaction
Period, constantly it is less than the low-boiling-point substance of 85 DEG C by tower top separation boiling point, reacts 3 hours, obtain 2-(4-(tert-butyl group) phenyl)-1-(4-
Chloro-1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) the o-Dimethylbenzene suspension of-2-cyano vinyl alcohol potassium salt.
At 140-144 DEG C, upwards step reactant mixture drips 183g (1.5mol) pivaloyl chloride, drip in 30 minutes
Complete.After completion of dropwise addition, it is stirred for reacting 2 hours.After reaction terminates, cool to room temperature, wash twice, each 900 grams,
Separating water layer, organic layer removed under reduced pressure o-Dimethylbenzene solvent, still is residual obtains 297g Z-2-(4-(tert-butyl group) through recrystallized from acetonitrile
Phenyl)-2-cyano group-1-(the chloro-1 hydrogen-5-pyrazolyl of 1-ethyl-3-methyl-4-) pivalic acid vinyl acetate white solid, content 99.5%,
Yield 69%.
Embodiment 5
Z-2-(4-(tert-butyl group) phenyl)-2-cyano group-1-(the chloro-1 hydrogen-5-pyrazolyl of 1-ethyl-3-methyl-4-) pivalic acid vinyl acetate
The synthesis of (compound 5 in table 1)
Equipped with in the reaction bulb of rectifying column, add ethanol solution and the 900g chlorobenzene of 295g (1.3mol) 30% Sodium ethylate,
It is warmed up to 75 DEG C.It is slowly added dropwise 205g (1.0mol) 4-chloro-1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazole carboxylic acid methyl ester, 227.5g (1.3
Mol) to tert-butyl benzene acetonitrile and the solution of 300 chlorobenzenes, dripped off with about 1 hour.After completion of dropwise addition, it is warmed up to backflow, reaction
Period, constantly it is less than the low-boiling-point substance of 80 DEG C by tower top separation boiling point, reacts 3 hours, obtain 2-(4-(tert-butyl group) phenyl)-1-(4-
Chloro-1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) the chlorobenzene suspension of-2-cyano vinyl sodium alkoxide.
At 120-130 DEG C, upwards step reactant mixture drips 158.5g (1.3mol) pivaloyl chloride, drip in 30 minutes
Add complete.After completion of dropwise addition, it is stirred for reacting 2 hours.After reaction terminates, cool to room temperature, wash twice, each 800
Gram, separating water layer, organic layer removed under reduced pressure chlorobenzene solvent, still is residual obtains 319g Z-2-(4-(tert-butyl group) through recrystallized from acetonitrile
Phenyl)-2-cyano group-1-(the chloro-1 hydrogen-5-pyrazolyl of 1-ethyl-3-methyl-4-) pivalic acid vinyl acetate white solid, content 99.1%,
Yield 73.8%.
Also can prepare table 1 according to above-mentioned method lists Z-2-shown in partial Formula (I) (4-(tert-butyl group) phenyl) simultaneously
-2-cyano group-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-pyrazolyl) pivalic acid vinyl esters compound.
The structure of table 1. partial Formula (I) compound
| Compound | R1 | Fusing point DEG C |
| 1 | H | White solid (92-93 DEG C) |
| 2 | CH3 | |
| 3 | CN | |
| 4 | F |
| 5 | Cl | White solid (93-94 DEG C) |
| 6 | I |
Claims (6)
1. a preparation method for pyrazolyl acrylonitrile compound shown in logical formula I, reaction equation is as follows,
In formula: R1Selected from H, methyl, CN or halogen, R2Selected from C1-C5Alkyl；
Lead to the pyrazole carboxylic acid ester compound shown in formula II and to tert-butyl benzene acetonitrile, in the presence of alkali and organic solvent,
2-(4-(tert-butyl group) phenyl)-1-(1-ethyl-3-methyl isophthalic acid hydrogen-5-shown in logical formula III within 3-8 hour, is obtained in 60-160 DEG C of reaction
Pyrazolyl)-2-cyano vinyl sodium alkoxide or the suspension of potassium salt, the suspension of gained compound (III) and pivaloyl chloride are at 60-160 DEG C
React 1-3 hour, obtain logical formula I compound.
2. the preparation method as described in claim 1, it is characterised in that: described organic solvent is aromatic hydrocarbon.
3. the preparation method as described in claim 1, it is characterised in that: described organic solvent is benzene,toluene,xylene, chlorine
Benzene, dichloro-benzenes.
4. the preparation method as described in claim 1, it is characterised in that: described alkali is selected from C1-C5Sodium alkoxide or potassium alcoholate；Adding of alkali
Entering amount is shown in logical formula II 0.7-1.5 times of the amount of combinations of materials；Addition to tert-butyl benzene acetonitrile is logical formula II
0.7-1.5 times of the amount of shown combinations of materials；The addition of pivaloyl chloride is the amount of combinations of materials shown in logical formula II
0.7-1.5 times.
5. the preparation method as described in claim 3, it is characterised in that: described alkali is selected from Feldalat NM, Sodium ethylate, sodium tert-butoxide
Or potassium tert-butoxide；Described organic solvent is selected from toluene, dimethylbenzene or chlorobenzene；The addition of alkali is compound shown in logical formula II
0.9-1.3 times of the amount of material；Addition to tert-butyl benzene acetonitrile is the 0.9-1.3 of the amount of combinations of materials shown in logical formula II
Times；The addition of pivaloyl chloride is shown in logical formula II 0.9-1.3 times of the amount of combinations of materials.
6. the preparation method as described in claim 1, it is characterised in that: compound shown in described logical formula II with to the tert-butyl group
The reaction temperature of benzene acetonitrile is 80-150 DEG C；Shown in logical formula III, compound is 100-150 DEG C with the reaction temperature of pivaloyl chloride.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109553577A (en) * | 2018-12-20 | 2019-04-02 | 西安近代化学研究所 | A kind of pyrazole compound and preparation method and application |
| CN110003111A (en) * | 2018-01-04 | 2019-07-12 | 浙江省化工研究院有限公司 | A kind of preparation method of 2- aryl -3- ether -3- pyrazoles acrylonitrile compound |
| CN114702409A (en) * | 2022-04-08 | 2022-07-05 | 大连理工大学 | Method for synthesizing homoallylnitrile compound by using allyl alcohol and acetonitrile |
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| CN1216530A (en) * | 1996-04-25 | 1999-05-12 | 日产化学工业株式会社 | Ethylene derivatives and pest controlling agents |
| CN101875633A (en) * | 2009-04-29 | 2010-11-03 | 中国中化股份有限公司 | Pyrazolyl acrylonitrile compound and application thereof |
| CN102898373A (en) * | 2011-07-25 | 2013-01-30 | 中国中化股份有限公司 | Preparation method of Z-3-acyloxy-3-(1-ethylpyrazolyl)acrylonitrile compounds |
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2014
- 2014-12-29 CN CN201410838114.3A patent/CN105801484B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1216530A (en) * | 1996-04-25 | 1999-05-12 | 日产化学工业株式会社 | Ethylene derivatives and pest controlling agents |
| CN101875633A (en) * | 2009-04-29 | 2010-11-03 | 中国中化股份有限公司 | Pyrazolyl acrylonitrile compound and application thereof |
| CN102898373A (en) * | 2011-07-25 | 2013-01-30 | 中国中化股份有限公司 | Preparation method of Z-3-acyloxy-3-(1-ethylpyrazolyl)acrylonitrile compounds |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110003111A (en) * | 2018-01-04 | 2019-07-12 | 浙江省化工研究院有限公司 | A kind of preparation method of 2- aryl -3- ether -3- pyrazoles acrylonitrile compound |
| CN110003111B (en) * | 2018-01-04 | 2020-11-13 | 浙江省化工研究院有限公司 | Preparation method of 2-aryl-3-ether-3-pyrazole acrylonitrile compound |
| CN109553577A (en) * | 2018-12-20 | 2019-04-02 | 西安近代化学研究所 | A kind of pyrazole compound and preparation method and application |
| CN114702409A (en) * | 2022-04-08 | 2022-07-05 | 大连理工大学 | Method for synthesizing homoallylnitrile compound by using allyl alcohol and acetonitrile |
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