CN105254577B - A kind of pair of triazole substituted benzene diformic ester compound, preparation method and purposes - Google Patents
A kind of pair of triazole substituted benzene diformic ester compound, preparation method and purposes Download PDFInfo
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- CN105254577B CN105254577B CN201510484499.2A CN201510484499A CN105254577B CN 105254577 B CN105254577 B CN 105254577B CN 201510484499 A CN201510484499 A CN 201510484499A CN 105254577 B CN105254577 B CN 105254577B
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- tetrafluoro
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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
Abstract
The invention discloses a kind of pair of triazole substituted benzene diformic ester compound, preparation method and purposes, belong to agricultural insecticidal, bactericide field.The present invention is using tetrafluoro terephthalic acid (TPA) as raw material, tetrafluoro paraphthaloyl chloride is obtained with thionyl chloride reaction, then with 1,2, the reaction of 4 triazoles obtains the double triazole ketones of intermediate tetrafluoro phenylene, after obtain a kind of pair of triazole substituted benzene diformic ester compound through alcoholysis.The compound of the present invention has fabulous bacteriostatic activity to rhizoctonia cerealis, rice blast fungus and Sclerotinia sclerotiorum, and inhibiting rate reaches more than 80%, and minimal inhibitory concentration scope can be applicable to the disease prevented and treated on various crops in 8 ~ 10 μ g/mL.
Description
Technical field
The invention belongs to agricultural insecticidal, bactericide field, and in particular to a kind of new double triazoles substitution Phthalates
Compound, preparation method and the purposes as disinfectant use in agriculture.
Background technology
Azole compounds are one of most widely used antifungal drugs, in the 1980s, vapour Ba-Jia Ji companies of Switzerland
With triazole substituted imidazole, the serial ring azoles of disinfectant use in agriculture penta of SSF109, methyl cyclic-azole, etaconazole, propiconazole and wide spectrum have been synthesized
Medical antifungal agent terconazole (Ketoconazole) and Itraconazole (Itraconazole) (Heers J., Van
Custerm J.,Antinycotic R.J Med Chem,1981,24,1360；Heers J.,Hendrickx R,Van
Custerm J.J Med Chem,1983,26,611；Heeres J,Backx L.J.J.,Mostmans J H.,et al.J
Med Chem,1979,22,1003).Triazole bactericidal agent is low toxicity, the steroid biosynthesis suppression of efficient, lasting period length
Agent and systemic fungicide, are still one of widely used bactericide species (Li Lu, Tong Zeng in current medicine and pesticide field
Beast, the sweet Chinese pharmaceutical chemistry magazines of expensive, 1995,4 (5):271；Yang Guangfu, Yang Huazheng, Lu Rong key agricultural chemicals collected translations, 1996,
18(1):21；Li Xinzhi, takes charge of the emerging agricultural chemicals of ancestor, 2003,1 (42):4).Exploitation is efficient, low toxicity, low-residual new varieties, adjusts product
Structure has turned into the focus that China agricultural chemicals circle personage pays close attention to jointly.
Triazole derivative is a class internal-suction type antibacterial, bactericide, is after chemical protective agent development and hair
The novel antibacterial got up, bactericide are opened up, it not only has the advantages that wide spectrum, low toxicity, efficient, duration length and residual are few,
But also conduct and protect inside, there is good antibacterial, bactericidal activity in terms for the treatment of.
The content of the invention
The present invention is intended to provide a kind of chemistry of double triazole substituted benzene diformic ester compounds with bacteriostatic activity
Preparation method.
Technical scheme is as follows：
A kind of pair of triazole substituted benzene diformic ester compound of the invention, its structural formula is
Wherein：R can be methyl or ethyl.
The preparation method of above-mentioned a kind of pair of triazole substituted benzene diformic ester compound, reaction equation is as follows：
Wherein：R can be methyl or ethyl.
The preparation side of a kind of pair of triazole substituted benzene diformic ester compound of the present invention with bacteriostatic activity
Method, is carried out as steps described below：
(1) with 1,2- dichloroethanes for solvent, under heated reflux condition, tetrafluoro terephthalic acid (TPA) reacts with thionyl chloride
Obtain tetrafluoro paraphthaloyl chloride；Tetrafluoro paraphthaloyl chloride is obtained under catalyst with the reaction of 1H-1,2,4- triazoles
The double triazole ketones of intermediate tetrafluoro phenylene.
(2) the double triazole ketones of the tetrafluoro phenylene obtained by step are taken, are reacted with ROH, the double triazoles of double fluorine are made to benzene
Diformic ester compound.
In the step (1), the double triazole terephthalic acid (TPA) methyl esters used catalysts of the double fluorine of synthetic intermediate are triethylamine,
The mol ratio of tetrafluoro terephthalic acid (TPA) and thionyl chloride is 1:2.1；Mole of tetrafluoro terephthalic acid (TPA) and 1H-1,2,4- triazoles
Than for 1:4；The mol ratio of tetrafluoro terephthalic acid (TPA) and triethylamine is 1:2.5, every 0.1 mole of tetrafluoro terephthalic acid (TPA) correspondence 1,
2- dichloroethanes 90mL.
The double triazole ketones of tetrafluoro phenylene and ROH mol ratio are 1 in the step (2):(1.12×103)~1:
(1.68×103), wherein R can be methyl or ethyl.
The temperature of solvent thermal reaction is 100~150 DEG C in the step (2), and the pressure of reaction is 1.5Mpa.
A kind of pair of triazole of the present invention with bacteriostatic activity replaces the purposes of phthalic acid methyl ester, described one
Plant the preventing and treating that double triazole substituted benzene diformic ester compounds with bacteriostatic activity can be used for fungus-caused plant disease.
A kind of purposes of double triazole substituted benzene diformic ester compounds with bacteriostatic activity of the present invention, its
It is characterised by：A kind of described double triazole substituted benzene diformic ester compounds with bacteriostatic activity can be used for wheat line withered
Germ, rice blast fungus, the preventing and treating of Sclerotinia sclerotiorum and wheat powdery mildew.
A kind of double triazoles with bacteriostatic activity of the present invention replace the synthetic method of phthalic acid methyl ester, operation
Convenient, favorable reproducibility.The antibacterial data display of sample has to rhizoctonia cerealis, rice blast fungus and Sclerotinia sclerotiorum
Fabulous bacteriostatic activity, inhibiting rate reaches more than 80%, and minimal inhibitory concentration scope is in 8~10 μ g/mL, in agricultural chemicals and life
Scientific domain will produce huge application value.
Embodiment
Experimental example 1
(1) synthesis of the double triazole ketones of intermediate tetrafluoro phenylene：47.60g is sequentially added in 500mL four-hole boiling flasks
50.00g chlorinations are added dropwise in tetrafluoro terephthalic acid (TPA), 0.5mL DMFs and 180mL 1,2- dichloroethanes, room temperature
Sulfoxide, time for adding about 1h.Room temperature is cooled to after return stirring 4h.1,2- dichloroethanes is reclaimed in air-distillation, and nitrogen is protected simultaneously
Cooling.
The addition 150mL tetrahydrofuran stirring and dissolvings into above-mentioned reactant, addition 55.20g 1H-1,2,4- triazoles, in
50.59g triethylamines are slowly added dropwise under the conditions of ice-water bath, nitrogen protection is lower to be continued to react 24h, is warming up to after 50 DEG C and is incubated 1h, steams
Distillation goes to obtain yellow solid 62.05g after solvent, washing filtering, and yield is 91.26%.
(2) synthesis of the double triazole dimethyl terephthalate (DMT)s of double fluorine：Weigh double three nitrogen of tetrafluoro phenylene prepared by 0.30g
Azoles ketone, 40mL methanol are placed in 100mL stainless steel autoclave, and it is 1.5Mpa stirring reactions that pressure is maintained at 120 DEG C
Room temperature is cooled to after 6h, solvent is removed under reduced pressure and obtains light yellow viscous liquid, add 5% sodium bicarbonate aqueous solution 50mL, often
Temperature stirring 1h, then through suction filtration, dry white solid 0.22g, yield is 64.47%., hydrogen infrared to product progress is composed, carbon is composed,
Elementary analysis and X-ray single crystal diffraction are characterized, and concrete outcome is as follows：
Main infrared absorption peak (KBr)：3116.6cm–1, 2925.0cm–1, 1715.4cm–1, 1614.5cm–1,
1506.3cm–1, 1389.3cm–1, 956.3cm–1, 704.8cm–1；
Nuclear-magnetism footpath hydrogen spectrum1H NMR(500MHz,CD3OD)δ：8.52(s,2H),8.39(s,2H),3.62(s,6H)；
Nuclear-magnetism carbon is composed13C NMR(75MHz,CD3OD)δ：169.28,160.59,152.41,149.72,122.07,
117.58,51.96.
The double triazole dimethyl terephthalate (DMT)s of the double fluorine of 0.05g are dissolved in 6mL methanol, after room temperature is volatilized 6 days, obtain colourless
Bulk crystals.Crystal structure determination uses Bruker Apex II CCD diffractometers, under 293K, with through graphite monochromatised Mo
K alpha raysPoint diffraction is collected with ω scan modes, the data of collection are used in combination by SAINT programe reductions
SADABS methods carry out semiempirical absorption correction.Structure elucidation and refine be respectively adopted SHELXTL programs SHELXS and
SHELXL is completed, by complete matrix least square method to F2It is modified the coordinate and anisotropy for obtaining whole non-hydrogen atoms
Parameter.All hydrogen atoms are fixed on parent during structure refinement by theory, are assigned more slightly larger than parent displacement parameter
The isotropism displacement parameter of (C-H, 1.2 times).Detailed axonometry data are shown in Table 1.
The predominant crystal data of the double triazole dimethyl terephthalate (DMT)s of 1 pair of fluorine of table
Experimental example 2
The synthesis of the double triazole dimethyl terephthalate (DMT)s of double fluorine：Weigh the double triazoles of tetrafluoro phenylene prepared by 0.30g
Ketone, 40mL methanol are placed in 100mL stainless steel autoclave, and pressure is maintained at 100 DEG C for after 1.5Mpa stirring reactions 6h
Room temperature is cooled to, solvent is removed under reduced pressure and obtains light yellow viscous liquid, add 5% sodium bicarbonate aqueous solution 50mL, normal temperature is stirred
Mix 1h, then through suction filtration, dry white solid 0.14g, yield is 43.53%.
Experimental example 3
The synthesis of the double triazole dimethyl terephthalate (DMT)s of double fluorine：Weigh the double triazoles of tetrafluoro phenylene prepared by 0.30g
Ketone, 40mL methanol are placed in 100mL stainless steel autoclave, and pressure is maintained at 150 DEG C for after 1.5Mpa stirring reactions 6h
Room temperature is cooled to, solvent is removed under reduced pressure and obtains light yellow viscous liquid, add 5% sodium bicarbonate aqueous solution 50mL, normal temperature is stirred
Mix 1h, then through suction filtration, dry white solid 0.18g, yield is 56.01%.
Experimental example 4
The synthesis of the double triazole diethyl terephthalates of double fluorine：Weigh the double triazoles of tetrafluoro phenylene prepared by 0.21g
Ketone, 60mL ethanol are placed in 100mL stainless steel autoclave, and it is 1.5Mpa stirring reactions 6h that pressure is maintained at 120 DEG C
After be cooled to room temperature, remove solvent under reduced pressure and obtain light yellow viscous liquid, add 5% sodium bicarbonate aqueous solution 50mL, normal temperature
1h is stirred, then through suction filtration, dry white solid 0.17g, yield is 49.09%.Product is carried out infrared, hydrogen spectrum, carbon spectrum and
Elementary analysis, concrete outcome is as follows：
Main infrared absorption peak (KBr)：3102.8cm–1, 2965.0cm–1, 2932.3cm–1,1709.8cm–1,
1600.9cm–1, 1545.3cm–1, 1424.7cm–1, 1395.1cm–1, 1266.5cm–1, 948.8cm–1, 705.3cm–1；
Nuclear-magnetism footpath hydrogen spectrum1H NMR(500MHz,CD3OD)δ：8.58(s,2H),8.46(s,2H),4.35–4.15(m,4H,
CH2),1.63–1.42(m,6H)；
Nuclear-magnetism carbon is composed13C NMR(75MHz,CD3OD)δ：166.39,157.83,151.26,148.53,125.08,
119.74,55.29,16.58.
Experimental example 5
The synthesis of the double triazole diethyl terephthalates of double fluorine：Weigh the double triazoles of tetrafluoro phenylene prepared by 0.21g
Ketone, 40mL ethanol are placed in 100mL stainless steel autoclave, and it is 1.5Mpa stirring reactions 6h that pressure is maintained at 100 DEG C
After be cooled to room temperature, remove solvent under reduced pressure and obtain light yellow viscous liquid, add 5% sodium bicarbonate aqueous solution 50mL, normal temperature
1h is stirred, then through suction filtration, dry white solid 0.09g, yield is 26.01%.
Experimental example 6
The synthesis of the double triazole diethyl terephthalates of double fluorine：Weigh the double triazoles of tetrafluoro phenylene prepared by 0.21g
Ketone, 40mL ethanol are placed in 100mL stainless steel autoclave, and it is 1.5Mpa stirring reactions 6h that pressure is maintained at 150 DEG C
After be cooled to room temperature, remove solvent under reduced pressure and obtain light yellow viscous liquid, add 5% sodium bicarbonate aqueous solution 50mL, normal temperature
1h is stirred, then through suction filtration, dry white solid 0.15g, yield is 43.34%.
The isolated measuring of experimental example 7 is studied the bacteriostasis property of compound：
Use colony growth diameter method.The double triazole substituted benzene diformic ester compounds of testing compound are dissolved in respectively molten
High concentration mother liquor is prepared in agent, and mother liquor is added in 40~50 DEG C of PSA culture mediums, it is 10 μ g/mL's to be prepared into mass concentration
Pastille culture medium.The fresh mycelia block of rhizoctonia cerealis, rice blast fungus and Sclerotinia sclerotiorum is inoculated with after 8h respectively, often
Plant medicament to be repeated 4 times, 24 DEG C are cultivated 3 days, measure colony growth radius, calculate mycelial growth inhibition rate.As a result this pair of fluorine is found
Double triazole terephthalic acid ester compounds to the inhibiting rates of rhizoctonia cerealis more than 90%, to rice blast fungus
Inhibiting rate more than 80%, to the inhibiting rate of Sclerotinia sclerotiorum up to 100%.Minimal inhibitory concentration scope is in 8~10 μ g/
mL。
The living body measurement of experimental example 8 is studied the bacteriostasis property of compound
Measure object is wheat powdery mildew, and assay method uses and trembles conidia powder inocalation method.First by ρ, (double triazoles replace
Phthalates compound)=1000 μ g/mL N, N-dimethyl formamide solution is uniformly sprayed on two leaf stage wheat, 1
After it, the Fresh spores of wheat powdery mildew are collected, are uniformly shaken off with writing brush on for examination plant, on 24 DEG C of daytime, evening 20
DEG C culture 8 days, every kind of medicament is repeated twice, check first piece of blade of wheat lesion area.As a result find that such compound is equal
To the inhibiting rate of wheat powdery mildew up to more than 80%.
Claims (7)
1. a kind of pair of triazole substituted benzene diformic ester compound, it is characterised in that its structural formula is
, wherein：R can be methyl or ethyl.
2. the preparation method of a kind of pair of triazole substituted benzene diformic ester compound described in claim 1, it is characterised in that
Carry out as steps described below：
（1）With 1,2- dichloroethanes for solvent, under heated reflux condition, tetrafluoro terephthalic acid (TPA) is obtained with thionyl chloride reaction
Tetrafluoro paraphthaloyl chloride；Tetrafluoro paraphthaloyl chloride obtains centre under catalyst with the reaction of 1H-1,2,4- triazoles
The double triazole ketones of body tetrafluoro phenylene,
（2）The double triazole ketones of the tetrafluoro phenylene obtained by step are taken, are reacted with ROH, double triazole substitution phthalic acids are made
Ester type compound.
3. the preparation method of a kind of pair of triazole substituted benzene diformic ester compound according to claim 2, its feature
It is the step（1）In, the double triazole ketone used catalysts of synthetic intermediate tetrafluoro phenylene are triethylamine, and tetrafluoro is to benzene
The mol ratio of dioctyl phthalate and thionyl chloride is 1:2.1；The mol ratio of tetrafluoro terephthalic acid (TPA) and 1H-1,2,4- triazoles is 1:4；
The mol ratio of tetrafluoro terephthalic acid (TPA) and triethylamine is 1:2.5, the 1 of every 0.1 mole of 90 mL of tetrafluoro terephthalic acid (TPA) correspondence,
2- dichloroethanes.
4. the preparation method of a kind of pair of triazole substituted benzene diformic ester compound according to claim 2, its feature
It is the step（2）The double triazole ketones of middle tetrafluoro phenylene and ROH mol ratio are 1:(1.12×103)~1:(1.68×
103), wherein R can be methyl or ethyl.
5. the preparation method of a kind of pair of triazole substituted benzene diformic ester compound according to claim 2, its feature
It is the step（2）The temperature of middle solvent thermal reaction is 100 ~ 150 DEG C, and the pressure of reaction is 1.5Mpa.
6. the purposes of a kind of pair of triazole substituted benzene diformic ester compound described in claim 1, it is characterised in that：It is a kind of
Double triazole substituted benzene diformic ester compounds are used for the preventing and treating of fungus-caused plant disease.
7. the purposes of a kind of pair of triazole substituted benzene diformic ester compound described in claim 1, it is characterised in that：It is a kind of
Double triazole substituted benzene diformic ester compounds are used for rhizoctonia cerealis, rice blast fungus, Sclerotinia sclerotiorum and small
The preventing and treating of wheat powdery mildew bacterium.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1141037A (en) * | 1993-11-25 | 1997-01-22 | 拜尔公司 | Derivatives of 2,3,5,6-tetrafluorobenzoic acid and their use in combating pests |
| CN1923819A (en) * | 2006-10-12 | 2007-03-07 | 青岛科技大学 | compound containing aromatic ether and ditriazole and use thereof |
| CN101445488A (en) * | 2007-11-27 | 2009-06-03 | 西南大学 | Triazoles compounds with antimicrobial activity and preparation method and pharmaceutical use thereof |
| WO2011020579A1 (en) * | 2009-08-20 | 2011-02-24 | Bayer Cropscience Ag | Method for producing 1-phenyl-1,2,4-triazoles |
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| WO2014163934A1 (en) * | 2013-03-13 | 2014-10-09 | Dow Agrosciences Llc | Preparation of 1,3-(substituted-diaryl)-1,2,4-triazoles |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1141037A (en) * | 1993-11-25 | 1997-01-22 | 拜尔公司 | Derivatives of 2,3,5,6-tetrafluorobenzoic acid and their use in combating pests |
| CN1923819A (en) * | 2006-10-12 | 2007-03-07 | 青岛科技大学 | compound containing aromatic ether and ditriazole and use thereof |
| CN101445488A (en) * | 2007-11-27 | 2009-06-03 | 西南大学 | Triazoles compounds with antimicrobial activity and preparation method and pharmaceutical use thereof |
| WO2011020579A1 (en) * | 2009-08-20 | 2011-02-24 | Bayer Cropscience Ag | Method for producing 1-phenyl-1,2,4-triazoles |
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