CN1644582A - Pyrazole contained diheterocyclic compound, its preparation and use - Google Patents
Pyrazole contained diheterocyclic compound, its preparation and use Download PDFInfo
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- CN1644582A CN1644582A CN 200410093331 CN200410093331A CN1644582A CN 1644582 A CN1644582 A CN 1644582A CN 200410093331 CN200410093331 CN 200410093331 CN 200410093331 A CN200410093331 A CN 200410093331A CN 1644582 A CN1644582 A CN 1644582A
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- compound
- ethyl
- pyrazole
- methyl
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Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 51
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 36
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 claims description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000012295 chemical reaction liquid Substances 0.000 claims description 14
- 239000012141 concentrate Substances 0.000 claims description 14
- 238000001035 drying Methods 0.000 claims description 14
- 230000007935 neutral effect Effects 0.000 claims description 14
- 239000012074 organic phase Substances 0.000 claims description 14
- 238000005406 washing Methods 0.000 claims description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 claims description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000004440 column chromatography Methods 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 229960001701 chloroform Drugs 0.000 claims description 5
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 4
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 10
- 241001414720 Cicadellidae Species 0.000 abstract description 3
- 241000894006 Bacteria Species 0.000 abstract 1
- 240000008067 Cucumis sativus Species 0.000 abstract 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 abstract 1
- 240000007594 Oryza sativa Species 0.000 abstract 1
- 235000007164 Oryza sativa Nutrition 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 230000004071 biological effect Effects 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 235000009566 rice Nutrition 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 35
- -1 Pyrazole compound Chemical class 0.000 description 14
- 238000000034 method Methods 0.000 description 14
- 238000013019 agitation Methods 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000000749 insecticidal effect Effects 0.000 description 8
- 230000000855 fungicidal effect Effects 0.000 description 7
- 230000003449 preventive effect Effects 0.000 description 7
- 241000123650 Botrytis cinerea Species 0.000 description 6
- 241000223195 Fusarium graminearum Species 0.000 description 6
- 241000409991 Mythimna separata Species 0.000 description 6
- 241000233616 Phytophthora capsici Species 0.000 description 6
- 241000209140 Triticum Species 0.000 description 6
- 235000021307 Triticum Nutrition 0.000 description 6
- DSUKUFGNCZKNGB-UHFFFAOYSA-N 2H-1,3-thiazol-2-ide 1-oxide Chemical compound S1([C-]=NC=C1)=O DSUKUFGNCZKNGB-UHFFFAOYSA-N 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 5
- 241001330975 Magnaporthe oryzae Species 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 4
- OCVLSHAVSIYKLI-UHFFFAOYSA-N 3h-1,3-thiazole-2-thione Chemical compound SC1=NC=CS1 OCVLSHAVSIYKLI-UHFFFAOYSA-N 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- 241000221785 Erysiphales Species 0.000 description 4
- 241000358422 Nephotettix cincticeps Species 0.000 description 4
- 244000061456 Solanum tuberosum Species 0.000 description 4
- 235000002595 Solanum tuberosum Nutrition 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 231100000331 toxic Toxicity 0.000 description 4
- 230000002588 toxic effect Effects 0.000 description 4
- LFPRWNRZQORQRI-UHFFFAOYSA-N 4-bromo-5-ethyl-2-methylpyrazole-3-carboxylic acid Chemical compound CCC1=NN(C)C(C(O)=O)=C1Br LFPRWNRZQORQRI-UHFFFAOYSA-N 0.000 description 3
- NXAIFVHVBHMNJS-UHFFFAOYSA-N 4-chloro-5-ethyl-2-methylpyrazole-3-carboxylic acid Chemical compound CCC1=NN(C)C(C(O)=O)=C1Cl NXAIFVHVBHMNJS-UHFFFAOYSA-N 0.000 description 3
- NWFDDRJCLWSJNP-UHFFFAOYSA-N 5-ethyl-2-methyl-4-nitropyrazole-3-carboxylic acid Chemical compound CCC1=NN(C)C(C(O)=O)=C1[N+]([O-])=O NWFDDRJCLWSJNP-UHFFFAOYSA-N 0.000 description 3
- AYPCLZDGADHRDL-UHFFFAOYSA-N 5-ethyl-2-methylpyrazole-3-carboxylic acid Chemical compound CCC=1C=C(C(O)=O)N(C)N=1 AYPCLZDGADHRDL-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 241001425390 Aphis fabae Species 0.000 description 2
- 241001480061 Blumeria graminis Species 0.000 description 2
- 241001012098 Omiodes indicata Species 0.000 description 2
- 241000813090 Rhizoctonia solani Species 0.000 description 2
- 238000007598 dipping method Methods 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 230000001018 virulence Effects 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000221696 Sclerotinia sclerotiorum Species 0.000 description 1
- 241001454293 Tetranychus urticae Species 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical group [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A compound containing pyrazol double heterocyclic ring with biological activity, its production and use are disclosed. The production is carried out by: 1-methyl-3-ethyl group-4-substituting-5-pyrazol formyl chlorine-nitric condensing reacting with heterocyclic ring under action of acid catching agent in 0-20deg.C organic solvent, and after-processing to obtain the products. It achieves insect-killed activity for leafhopper, and prevention for rice blast germina and cucumber gray mold bacteria.
Description
(1) technical field
The present invention relates to a kind of pyrazole contained diheterocyclic compound, preparation method and application.
(2) background technology
Pyrazole compound is being played the part of important role in heterocyclic pesticide.Because that pyrazole compound shows is efficient, low toxicity and diversity structure, thereby has boundless research and development prospect.Synthetic and the bioactivity research of bis-heterocyclic compounds has become an important directions of heterocyclic pesticide.Before the present invention makes, after the nineties, there is the pesticide patent of relevant two heterocycle structures to occur abroad, two heterocycles are connected pyrazoles by groups such as methylene radical, sulfuryls in the patent report with nitrogen heterocyclic ring.Domestic Lee rectifies name etc. pyrazoles directly is connected with heterocycle, obtains the bis-heterocyclic compounds of a series of biologically actives; Liu Zhao outstanding persons etc. have synthesized the acid amides series bis-heterocyclic compounds of a class biologically active.
(3) summary of the invention
The object of the invention is to provide a kind of pyrazole contained diheterocyclic compound, preparation method and application thereof of biologically active.
Described bis-heterocyclic compounds is suc as formula shown in (I):
Wherein X represents H or electron-withdrawing group, is preferably one of following: H, NO
2, Cl, Br; Y, Z independently represent O or S separately.
A kind of preparation method of above-mentioned pyrazole contained diheterocyclic compound, comprise the steps: suc as formula the 1-methyl shown in (II)-3-ethyl-4-replacement-5-pyrazol formyl chloride and suc as formula the nitrogen heterocyclic ring shown in (III) under the acid-capture agent effect, carry out condensation reaction at 0～20 ℃ in organic solvent, aftertreatment gets product;
Wherein X, Y, Z define the same.
Based on the consideration of productive rate and cost, the described reaction times was good with 1～50 hour.
Described 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride: nitrogen heterocyclic ring: the molar ratio of acid-capture agent is preferably 1: 1.0～and 1.5: 1.0～2.0, described consumption of organic solvent is preferably 20～60 times of nitrogen heterocyclic ring quality.
It is one of following that described acid-capture agent is preferably: triethylamine, pyridine, lutidine, Anhydrous potassium carbonate.
It is one of following that described organic solution is preferably: tetrahydrofuran (THF), ethyl acetate, toluene, chlorobenzene, trichloromethane.
Described aftertreatment can be: use dilute hydrochloric acid washing reaction liquid to neutral, and layering, the organic phase drying is filtered, and concentrates, and column chromatography for separation gets described pyrazole contained diheterocyclic compound.
The preparation method of described pyrazole contained diheterocyclic compound recommends to be undertaken by following parameter:
Described 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride: nitrogen heterocyclic ring: the molar ratio of acid-capture agent is 1: 1.0～1.1: 1.2～1.4, and described consumption of organic solvent is 30～50 times of nitrogen heterocyclic ring quality; Setting-up point is 5～15 ℃, and the reaction times is 10～20 hours.
Described 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride can adopt following method to make: 1-methyl-3-ethyl-4-replacement-5-pyrazole carboxylic acid and excess chlorination sulfoxide are joined in the 100mL there-necked flask, back flow reaction under agitation, reaction finishes, concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride transparent liquid.Use method for preparing 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride, yield generally reaches more than 90%.
Above-mentioned pyrazole contained diheterocyclic compound is as the application of insectofungicide.
Adopt toxic potato agar substratum (PDA) method that the fungicidal activity that the synthetic compound has carried out Pyricularia oryzae (Pyricularia oryzae), fusarium graminearum (Gibberella zeae), Phytophthora capsici germ (Phytophthora capsici) and botrytis cinerea pers (Botrytis cinerea) is measured, adopt potted plant stem and leaf of Wheat to preserve the spore method fungicidal activity that the synthetic compound has carried out wheat powdery mildew (Blumeria graminis) is measured.The result shows that described pyrazole contained diheterocyclic compound does not have preventive effect effect (X=NO substantially to fusarium graminearum, Phytophthora capsici germ
2, Y=S, Z=O and X=NO
2, except the Y=S, the formula of Z=S (I) compound), and rice blast fungus, botrytis cinerea pers, wheat powdery mildew are had different preventive effect effects.
Adopt the Potter spray method that the synthetic compound has been carried out the insecticidal activity assay of mythimna separata (Mythimna separata), adopt dipping plant method the synthetic compound to be carried out the insecticidal activity assay of green rice leafhopper (Nephotettix cincticeps).The result shows that described pyrazole contained diheterocyclic compound does not have insecticidal activity substantially to mythimna separata, and leafhopper is had certain insecticidal activity, and is best with formula (I) compound effect of X=Br especially.
(4) embodiment
Below by embodiment the present invention is further specified, but protection scope of the present invention is not limited to this.
Embodiment 1
19mmol 1-methyl-3-ethyl-4-nitro-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-nitro-5-pyrazol formyl chloride transparent liquid.
2.06g (20mmol) 2-thiazolidone and 2.4g (24mmol) triethylamine are joined in the 40mL chloroform soln, drip 1-methyl-3-ethyl-4-nitro-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 20h then in about 7 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, ethyl alcohol recrystallization obtains yellow solid.Yield is 89%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.36(t，2H，N-CH
2-C)，3.79(s，3H，N-CH
3)，3.48(t，2H，S-CH
2-C)，2.95(q，2H，CH
2-C)，1.29(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1723，1677
Embodiment 2
19mmol 1-methyl-3-ethyl-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, and under agitation back flow reaction 3h reacts and finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-5-pyrazol formyl chloride transparent liquid.
2.06g (20mmol) 2-thiazolidone and 2.0g (22mmol) lutidine are joined in the 40mL toluene solution, ice bath stirs down and drips 1-methyl-3-ethyl-5-pyrazol formyl chloride, and it is complete that 40min drips, and reacts 10h then in about 3 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 32%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；6.45(s，1H，heterocyclic?H)，4.18(t，2H，N-CH
2-C)，4.00(s，3H，N-CH
3)，3.36(t，2H，S-CH
2-C)，2.65(q，2H，CH
2-C)，1.23(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1712，1674
Embodiment 3
19mmol 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-chloro-5-pyrazol formyl chloride transparent liquid.
2.06g (20mmol) 2-thiazolidone and 1.85g (23mmol) pyridine are joined in the 40mL ethyl acetate solution, drip 1-methyl-3-ethyl-4-chloro-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 15h then in about 10 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 67%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.22(t，2H，N-CH
2-C)，3.99(s，3H，N-CH
3)，3.46(t，2H，S-CH
2-C)，2.72(q，2H，CH
2-C)，1.34(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1716，1675
Embodiment 4
19mmol 1-methyl-3-ethyl-4-bromo-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-bromo-5-pyrazol formyl chloride transparent liquid.
2.06g (20mmol) 2-thiazolidone and 1.85g (23mmol) pyridine are joined in the 40mL chlorobenzene solution, drip 1-methyl-3-ethyl-4-bromo-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 16h then in about 6 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 64%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.12(t，2H，N-CH
2-C)，3.91(s，3H，N-CH
3)，3.40(t，2H，S-CH
2-C)，2.62(q，2H，CH
2-C)，1.23(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1717，1677
Embodiment 5
The trichloromethane consumption changes 50 times of 2-thiazolidone quality into, and other is operated with embodiment 1.Yield is 89%.
Embodiment 6
19mmol 1-methyl-3-ethyl-4-bromo-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-bromo-5-pyrazol formyl chloride transparent liquid.
2.38g (20mmol) 2-thiazole thione and 3.59g (26mmol) Anhydrous potassium carbonate are joined in the 40mL chlorobenzene solution, drip 1-methyl-3-ethyl-4-bromo-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 16h then in about 6 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 84%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.52(t，2H，N-CH
2-C)，3.89(s，3H，N-CH
3)，3.52(t，2H，S-CH
2-C)，2.59(q，2H，CH
2-C)，1.23(t，3H，C-CH
3)
IR(KBr，V)cm
-1；1686(CO)，1227(CS)
Embodiment 7
19mmol 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-chloro-5-pyrazol formyl chloride transparent liquid.
2.38g (20mmol) 2-thiazole thione and 3.59g (26mmol) Anhydrous potassium carbonate are joined in the 40mL tetrahydrofuran solution, drip 1-methyl-3-ethyl-4-chloro-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 10h then in about 6 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, use ethyl alcohol recrystallization, obtain yellow crystals.Yield is 87%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.52(t，2H，N-CH
2-C)，3.90(s，3H，N-CH
3)，3.50(t，2H，S-CH
2-C)，2.60(q，2H，CH
2-C)，1.22(t，3H，C-CH
3)
IR(KBr，V)cm
-1；1680(CO)，1149(CS)
Embodiment 8
19mmol 1-methyl-3-ethyl-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, and under agitation back flow reaction 3h reacts and finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-5-pyrazol formyl chloride transparent liquid.
2.38g (20mmol) 2-thiazole thione and 2.4g (24 mmol) triethylamine are joined in the 40mL tetrahydrofuran solution, drip 1-methyl-3-ethyl-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 10h then in about 6 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 43%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；6.45(s，1H，heterocyclic?H)，4.47(t，2H，N-CH
2-C)，3.97(s，3H，N-CH
3)，3.46(t，2H，S-CH
2-C)，2.63(q，2H，CH
2-C)，1.23(t，3H，C-CH
3)
IR(KBr，V)cm
-1；1686(CO)，1157(CS)
Embodiment 9
19mmol 1-methyl-3-ethyl-4-nitro-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-nitro-5-pyrazol formyl chloride transparent liquid.
2.38g (20mmol) 2-thiazole thione and 2.0g (22mmol) lutidine are joined in the 50mL chloroform soln, drip 1-methyl-3-ethyl-4-nitro-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 15h then in about 12 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, use ethyl alcohol recrystallization, obtain yellow crystals.Yield is 92%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.77(t，2H，N-CH
2-C)，3.77(s，3H，N-CH
3)，3.59(t，2H，S-CH
2-C)，2.93(q，2H，CH
2-C)，1.27(t，3H，C-CH
3)
IR(KBr，V)cm
-1；1685(CO)，1210(CS)
Embodiment 10
19mmol 1-methyl-3-ethyl-4-nitro-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-nitro-5-pyrazol formyl chloride transparent liquid.
1.74g (20mmol) 2-oxazolidone and 2.0g (22mmol) lutidine are joined in the 40mL chlorobenzene solution, drip 1-methyl-3-ethyl-4-nitro-5-pyrazol formyl chloride under ice bath stirs, 30min drips complete, reacts 15h then in about 12 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, use ethyl alcohol recrystallization, obtain yellow crystals.Yield is 92%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.40(t，2H，O-CH
2-C)，4.05(t，2H，N-CH
2-C)，3.80(s，3H，N-CH
3)，2.53(q，2H，CH
2-C)，1.14(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1791，1682
Embodiment 11
19mmol 1-methyl-3-ethyl-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, and under agitation back flow reaction 3h reacts and finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-5-pyrazol formyl chloride transparent liquid.
1.74g (20mmol) 2-oxazolidone and 2.3g (23mmol) triethylamine are joined in the 40mL toluene solution, drip 1-methyl-3-ethyl-5-pyrazol formyl chloride under ice bath stirs, 35min drips complete, reacts 1lh then in about 8 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 45%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；6.60(s，1H，heterocyclic?H)，4.48(t，2H，O-CH
2-C)，4.14(t，2H，N-CH
2-C)，4.02(s，3H，N-CH
3)，2.66(q，2H，CH
2-C)，1.24(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1790，1677
Embodiment 12
19mmol 1-methyl-3-ethyl-4-chloro-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-chloro-5-pyrazol formyl chloride transparent liquid.
1.74g (20mmol) 2-oxazolidone and 1.85g (23mmol) pyridine are joined in the 40mL ethyl acetate solution, drip 1-methyl-3-ethyl-4-chloro-5-pyrazol formyl chloride under ice bath stirs, 40min drips complete, reacts 13h then in about 5 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 77%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.43(t，2H，O-CH
2-C)，4.09(t，2H，N-CH
2-C)，3.86(s，3H，N-CH
3)，2.63(q，2H，CH
2-C)，1.24(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1791，1683
Embodiment 13
19mmol 1-methyl-3-ethyl-4-bromo-5-pyrazole carboxylic acid and 200mmol sulfur oxychloride are joined in the 100mL there-necked flask, back flow reaction 3h under agitation, reaction finishes, and concentrating under reduced pressure gets light yellow 1-methyl-3-ethyl-4-bromo-5-pyrazol formyl chloride transparent liquid.
1.74g (20mmol) 2-oxazolidone and 1.85g (23mmol) pyridine are joined 40mL tetrahydrochysene fluorine mutters in the solution, drip 1-methyl-3-ethyl-4-bromo-5-pyrazol formyl chloride under ice bath stirs, 40min drips complete, reacts 16h then in about 10 ℃, reaction is finished, extremely neutral with diluted hydrochloric acid aqueous solution washing reaction liquid, layering, organic phase drying, filter, concentrate, column chromatography [V (sherwood oil): V (ethyl acetate)=2: 1] separates, and obtains pure product.Yield is 74%.
This compound
1H NMR and IR are as described below,
1H?NMR(CDCl
3)δppm；4.58(t，2H，O-CH
2-C)，4.27(t，2H，N-CH
2-C)，3.82(s，3H，N-CH
3)，2.96(q，2H，CH
2-C)，1.29(t，3H，C-CH
3)
IR(KBr，V
CO)cm
-1；1793，1703
The test of embodiment 14 fungicidal activities
Adopt toxic potato agar substratum (PDA) method that the fungicidal activity that embodiment 1～13 synthetic compound has carried out Pyricularia oryzae (Pyricuiaria oryzae), fusarium graminearum (Gibberella zeae), Phytophthora capsici germ (Phytophthora capsici) and botrytis cinerea pers (Botrytiscinerea) is measured, general sieve concentration is 25ppm; Adopt the toxic potato agar substratum of excised leaf (PDA) method that the fungicidal activity that the synthetic compound has carried out Rhizoctonia solani Kuhn (Rhizoctoniasolani) is measured, general sieve concentration is 500ppm; Adopt potted plant toxic potato agar substratum (PDA) method that the fungicidal activity that the synthetic compound has carried out Sclerotinia sclerotiorum (Sclerotoniasclerotiorum) is measured, general sieve concentration is 500ppm; Adopt potted plant stem and leaf of Wheat to preserve the spore method fungicidal activity that the synthetic compound has carried out wheat powdery mildew (Blumeria graminis) is measured, general sieve concentration is 500ppm.Test result sees Table 1.
Table 1 pyrazole contained diheterocyclic compound is to the restraining effect of germ
| The embodiment title | Formula (I) compound | Concentration (ug/ml) | Fusarium graminearum | The Phytophthora capsici germ | Rice blast fungus | Botrytis cinerea pers | Concentration (ug/ml) | Wheat powdery mildew | ||
| ??X | ??Y | ??Z | Preventive effect (%) | Preventive effect (%) | Preventive effect (%) | Preventive effect (%) | Preventive effect (%) | |||
| Embodiment 3 | ?Cl | ??S | ??O | ????25 | ????0 | ????0 | ????13.3 | ????9.3 | ????500 | ????20.0 |
| Embodiment 7 | ?Cl | ??S | ??S | ????25 | ????0 | ????0 | ????17.8 | ????35.8 | ????500 | ????20.0 |
| Embodiment 12 | ?Cl | ??O | ??O | ????25 | ????0 | ????0 | ????17.8 | ????18.5 | ????500 | ????30.0 |
| Embodiment 2 | ?H | ??S | ??O | ????25 | ????0 | ????0 | ????4.4 | ????15.9 | ????500 | ????20.0 |
| Embodiment 8 | ?H | ??S | ??S | ????25 | ????0 | ????0 | ????8.9 | ????15.9 | ????500 | ????10.0 |
| Embodiment 11 | ?H | ??O | ??O | ????25 | ????0 | ????0 | ????17.8 | ????6.6 | ????500 | ????15.0 |
| Embodiment 1 | ?NO 2 | ??S | ??O | ????25 | ????29.9 | ????28.0 | ????40.0 | ????15.9 | ????500 | ????10.0 |
| Embodiment 9 | ?NO 2 | ??S | ??S | ????25 | ????14.9 | ????10.8 | ????40.0 | ????22.5 | ????500 | ????30.0 |
| Embodiment 10 | ?NO 2 | ??O | ??O | ????25 | ????0 | ????0 | ????8.9 | ????5.3 | ????500 | ????10.0 |
| Embodiment 4 | ?Br | ??S | ??O | ????25 | ????12.0 | ????0 | ????14.0 | ????0 | ????500 | ????15.0 |
| Embodiment 6 | ?Br | ??S | ??S | ????25 | ????4.5 | ????0 | ????10.5 | ????0 | ????500 | ????15.0 |
| Embodiment 13 | ?Br | ??O | ??O | ????25 | ????4.5 | ????0 | ????35.1 | ????0 | ????500 | ????5.0 |
The test of embodiment 15 insecticidal activities
Adopt the Potter spray method that embodiment 1～13 synthetic compound has been carried out the insecticidal activity assay of mythimna separata (Mythimnaseparata), working concentration is 1000mg/L; Adopt leaf worm with soaking method the synthetic compound to be carried out the insecticidal activity assay of black bean aphid (Aphis fabae), working concentration is 500mg/L; Adopt dipping plant method that the synthetic compound has been carried out the insecticidal activity assay of green rice leafhopper (Nephotettixcincticeps), working concentration is 500mg/L; Adopt leaf worm with the method for soaking the synthetic compound to be carried out two-spotted spider mite (Tetranchus urticae), working concentration is 500mg/L.Test result sees Table 2.
Mortality ratio is being the A level more than 90%, is the B level between 70～90%, is the C level between 50～70%, is the D level between 0～50%.
Table 2 pyrazole contained diheterocyclic compound is to the killing action of insect
| The embodiment title | Formula (I) compound | Leafhopper | Mythimna separata | ||||
| ????X | ????Y | ????Z | Mortality ratio (%) | The virulence rank | Mortality ratio (%) | The virulence rank | |
| Embodiment 3 | ????Cl | ????S | ????O | ????0 | ????9.09 | ????D | |
| Embodiment 7 | ????Cl | ????S | ????S | ????0 | ????0 | ||
| Embodiment 12 | ????Cl | ????O | ????O | ????0 | ????0 | ||
| Embodiment 2 | ????H | ????S | ????O | ????0 | ????0 | ||
| Embodiment 8 | ????H | ????S | ????S | ????0 | ????13.64 | ????D | |
| Embodiment 11 | ????H | ????O | ????O | ????0 | ????0 | ||
| Embodiment 1 | ????NO 2 | ????S | ????O | ????0 | ????0 | ||
| Embodiment 9 | ????NO 2 | ????S | ????S | ????0 | ????0 | ||
| Embodiment 10 | ????NO 2 | ????O | ????O | ????20.00 | ????D | ????0 | |
| Embodiment 4 | ????Br | ????S | ????O | ????53.57 | ????C | ????0 | |
| Embodiment 6 | ????Br | ????S | ????S | ????47.12 | ????D | ????0 | |
| Embodiment 13 | ????Br | ????O | ????O | ????53.57 | ????C | ????0 |
Claims (10)
1, suc as formula the pyrazole contained diheterocyclic compound shown in (I):
Wherein X represents H or electron-withdrawing group, and Y, Z independently are O or S separately.
2, pyrazole contained diheterocyclic compound as claimed in claim 1 is characterized in that described X representative is one of following: H ,-NO
2, Cl, Br.
3, pyrazole contained diheterocyclic compound as claimed in claim 2 is characterized in that described X representative-NO
2
4, pyrazole contained diheterocyclic compound as claimed in claim 2 is characterized in that described X represents Br.
5, a kind of preparation method of pyrazole contained diheterocyclic compound according to claim 1, it is characterized in that comprising the steps: suc as formula the 1-methyl shown in (II)-3-ethyl-4-replacement-5-pyrazol formyl chloride and suc as formula the nitrogen heterocyclic ring shown in (III) under the acid-capture agent effect, carry out condensation reaction at 0～20 ℃ in organic solvent, aftertreatment gets product;
Wherein X represents H or electron-withdrawing group, and Y, Z independently are O or S separately.
6, the preparation method of pyrazole contained diheterocyclic compound as claimed in claim 5, it is characterized in that described 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride: nitrogen heterocyclic ring: the molar ratio of acid-capture agent is 1: 1.0～1.5: 1.0～2.0, described consumption of organic solvent is 20～60 times of nitrogen heterocyclic ring quality, and the described reaction times is 1～50 hour.
7, the preparation method of pyrazole contained diheterocyclic compound as claimed in claim 5, it is characterized in that described acid-capture agent is one of following: triethylamine, pyridine, lutidine, Anhydrous potassium carbonate, described organic solution are one of following: tetrahydrofuran (THF), ethyl acetate, toluene, chlorobenzene, trichloromethane.
8,, it is characterized in that described aftertreatment is as the preparation method of the described pyrazole contained diheterocyclic compound of one of claim 5～7: extremely neutral with dilute hydrochloric acid washing reaction liquid, layering, the organic phase drying is filtered, and concentrates, column chromatography for separation gets described pyrazole contained diheterocyclic compound.
9, as the preparation method of the described pyrazole contained diheterocyclic compound of one of claim 5～7, it is characterized in that described 1-methyl-3-ethyl-4-replacement-5-pyrazol formyl chloride: nitrogen heterocyclic ring: the molar ratio of acid-capture agent is 1: 1.0～1.1: 1.2～1.4, and described consumption of organic solvent is 30～50 times of nitrogen heterocyclic ring quality; Setting-up point is 5～15 ℃, and the reaction times is 10～20 hours.
10, the described pyrazole contained diheterocyclic compound of claim 1 is as the application of insectofungicide.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093344A (en) * | 2011-03-17 | 2011-06-15 | 南京工业大学 | N-substituted acetoxy pyrazole compound containing thiazole thione or oxazolidinone, preparation method and application |
| CN103554089A (en) * | 2013-11-26 | 2014-02-05 | 黑龙江大学 | Diheterocyclic compound as well as synthesis method and application thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR241812A1 (en) * | 1983-08-02 | 1992-12-30 | American Cyanamit Company | New hydroimidiazole pyrrolopyrines, or vynolines, thiene-y furo ¡2,3b¿ pyridines dihydrothiene-y-furo ¡2,3b¿ pyridines, thiene-y furo ¡3,2b¿ pyridines and tautomeres thereof. |
| CN1091239A (en) * | 1993-02-16 | 1994-08-31 | 南开大学元素有机化学研究所 | Plant growth regulating agent of cell division factor type |
| FR2707295A1 (en) * | 1993-06-07 | 1995-01-13 | Rhone Poulenc Agrochimie | Pyrazole fungicides substituted at position 3 by a heterocycle. |
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2004
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102093344A (en) * | 2011-03-17 | 2011-06-15 | 南京工业大学 | N-substituted acetoxy pyrazole compound containing thiazole thione or oxazolidinone, preparation method and application |
| CN102093344B (en) * | 2011-03-17 | 2012-09-26 | 南京工业大学 | N-substituted acetoxy pyrazole compound containing thiazole thione or oxazolidinone, preparation method and application |
| CN103554089A (en) * | 2013-11-26 | 2014-02-05 | 黑龙江大学 | Diheterocyclic compound as well as synthesis method and application thereof |
| CN103554089B (en) * | 2013-11-26 | 2015-04-08 | 黑龙江大学 | Diheterocyclic compound as well as synthesis method and application thereof |
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