CN104910075A - Bis-pyrazole schiff base compound as well as preparation method and application thereof as bactericide - Google Patents
Bis-pyrazole schiff base compound as well as preparation method and application thereof as bactericide Download PDFInfo
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- CN104910075A CN104910075A CN201510350618.5A CN201510350618A CN104910075A CN 104910075 A CN104910075 A CN 104910075A CN 201510350618 A CN201510350618 A CN 201510350618A CN 104910075 A CN104910075 A CN 104910075A
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- pyrazole
- hydrochloride
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- 239000002262 Schiff base Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title abstract description 36
- 230000000844 anti-bacterial effect Effects 0.000 title abstract description 3
- 239000003899 bactericide agent Substances 0.000 title abstract 2
- 244000000004 fungal plant pathogen Species 0.000 claims abstract description 4
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 claims description 30
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 23
- -1 pyrazole schiff bases Chemical class 0.000 claims description 19
- 239000007787 solid Substances 0.000 claims description 14
- 235000019441 ethanol Nutrition 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 7
- 238000001953 recrystallisation Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 238000000967 suction filtration Methods 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 3
- 150000008062 acetophenones Chemical class 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- 241000223218 Fusarium Species 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 241000221662 Sclerotinia Species 0.000 abstract 1
- 241001669638 Venturia nashicola Species 0.000 abstract 1
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 27
- FEKUXLUOKFSMRO-UHFFFAOYSA-N (4-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C=C1 FEKUXLUOKFSMRO-UHFFFAOYSA-N 0.000 description 8
- PCNFLKVWBDNNOW-UHFFFAOYSA-N 4-hydrazinylbenzoic acid Chemical compound NNC1=CC=C(C(O)=O)C=C1 PCNFLKVWBDNNOW-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 230000001954 sterilising effect Effects 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 150000004753 Schiff bases Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 235000014443 Pyrus communis Nutrition 0.000 description 2
- 240000001987 Pyrus communis Species 0.000 description 2
- 206010039509 Scab Diseases 0.000 description 2
- 241000221696 Sclerotinia sclerotiorum Species 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 150000003217 pyrazoles Chemical class 0.000 description 2
- 238000005728 strengthening Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
- BTIYBKZAMOAXAH-STBIYBPSSA-N Cc(cc1)ccc1-[n](cc1/C=N/C(N(c2ccccc2)NC2)=C2C#N)nc1-c1ccccc1 Chemical compound Cc(cc1)ccc1-[n](cc1/C=N/C(N(c2ccccc2)NC2)=C2C#N)nc1-c1ccccc1 BTIYBKZAMOAXAH-STBIYBPSSA-N 0.000 description 1
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 1
- 239000005869 Pyraclostrobin Substances 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000005658 Tebufenpyrad Substances 0.000 description 1
- WHDHEVMINMZADQ-UHFFFAOYSA-N [F].N1C=CC=C1 Chemical class [F].N1C=CC=C1 WHDHEVMINMZADQ-UHFFFAOYSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- TWFZGCMQGLPBSX-UHFFFAOYSA-N carbendazim Chemical compound C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 150000003008 phosphonic acid esters Chemical class 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- HZRSNVGNWUDEFX-UHFFFAOYSA-N pyraclostrobin Chemical compound COC(=O)N(OC)C1=CC=CC=C1COC1=NN(C=2C=CC(Cl)=CC=2)C=C1 HZRSNVGNWUDEFX-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- ZZYSLNWGKKDOML-UHFFFAOYSA-N tebufenpyrad Chemical compound CCC1=NN(C)C(C(=O)NCC=2C=CC(=CC=2)C(C)(C)C)=C1Cl ZZYSLNWGKKDOML-UHFFFAOYSA-N 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a bis-pyrazole schiff base derivative. The bis-pyrazole schiff base derivative is characterized by having the general formula specified in the description, wherein R1 in the structural formula is any of H, 4-CH3, 4-F and 4-Cl, and R2 is any of H, 4-CH3, 4-F and 4-Cl. Moreover, the invention discloses a preparation method thereof. The invention further discloses the content that the bis-pyrazole schiff base derivative is capable of effectively inhibiting plant pathogenic fungi. Therefore, the bis-pyrazole schiff base derivative disclosed by the invention can be used as a potential bactericide. The bis-pyrazole schiff base derivative disclosed by the invention disclosed by the invention has the beneficial effect of an obvious inhibition effect on gibberella, sclerotinia sclerotiorun and venturia nashicola.
Description
Technical field
The present invention relates to double pyrazole schiff base compound and preparation method thereof and purposes.
Background technology
Schiff bases analog derivative has sterilization, anticancer, the biological activity widely such as weeding and plant growth regulating, and it is the focus of heterocyclic chemistry area research always.Heterogeneous ring compound contains the hydrogen bond in the heterocyclic atoms such as O, N, S and organism formation because of it is closely bound up, and with coenocorrelation, there is affinity, occur in vivo to interact thus caused the superposition of active factor, therefore heterocyclic group being incorporated into the biological activity likely strengthening compound in schiff bases.
Pyrazoles and derivative thereof are because containing atom N in its structure, and be a kind of important heterogeneous ring compound, it has biological activity widely.Because of this compounds have efficiently, low toxicity, and the multi-faceted conversion of its ring substituents, is widely used in the field such as medicine, agricultural chemicals.Find that pyrazole compound has sterilization, sterilization, desinsection, antiviral isoreactivity after deliberation.In recent years, the commercialization in succession of many novel pyrazoles medicine, as: pyraclostrobin, tebufenpyrad, fluorine azoles bacterium acid amides etc., become one of focus of current medicinal design study on the synthesis to the further investigation of pyrazole compound.We do bridge two pyrazole groups with schiff bases and connect, to strengthening the biological activity of compound.
Compare with current pyrazoles schiff base compounds, double pyrazole is introduced in this patent innovation, hopes and develops new derivatives that is more efficient, low toxicity.The exploitation comparing with other single heterocyclic compound that two Hete rocyclic derivatives is used for various medicine has great importance.It is furtherd investigate there is certain theory and actual value, especially on the basis of synthesizing series novel double pyrazole Schiff bases biology, systematic research tool is carried out to their biological activity and be of great significance.
Summary of the invention
The object of the present invention is to provide a kind of novel double pyrazole schiff base compounds and their preparation method and purposes.
Technical scheme of the present invention is as follows:
A kind of pyrazoles schiff bases analog derivative, is characterized in that it has following general formula:
R in structural formula
1for: H, 4-CH
3, any one in 4-F, 4-Cl; R
2for: H, 4-CH
3, any one in 4-F, 4-Cl.
Prepare a method for above-mentioned pyrazoles schiff bases analog derivative, it is made up of the following step:
Step 1: 1:30-1:35 will replace phenylhydrazine hydrochloride and suitable quantity of water mixing in molar ratio, regulate pH to be 7-8 with mineral alkali, add same volume ethanol, stir and make it to dissolve completely, add Ethoxymethylenemalononitrile again, reflux, TLC spike is reacted, cooling reaction solution, be cooled with an ice bath again, filter, dry thick product, ethyl alcohol recrystallization to solid 1;
Step 2: in reaction vessel, 4:5:430 adds substituted acetophenone, replaces phenylhydrazine hydrochloride and appropriate organic solvent in molar ratio, stirs and makes it to dissolve, then add appropriate bases, heating reflux reaction for some time, follow the tracks of reaction with TLC.After cooling, suction filtration obtains thick product, and ethyl alcohol recrystallization obtains product 2;
Step 3: the solid 2 being dissolved in DMF is dropped to DMF and POCl of ice bath 30min in advance by 1:3:7 in molar ratio
3in, recover stirring at normal temperature for some time, to 20-100 DEG C of stirring reaction for some time, after being cooled to normal temperature, pour in frozen water, adjust PH to 7-9 with inorganic alkali solution, suction filtration also washes 3 times, obtains solid 3 after oven dry;
Step 4: by the solid 1 and 3 of synthesis in molar ratio 1:1 be dissolved in organic solvent, reacting by heating for some time (TLC detection reaction carries out degree), after completion of the reaction cooling separate out solids.Recrystallization can obtain object product and pyrazoles schiff bases analog derivative.
Pyrazoles schiff bases analog derivative of the present invention has obvious restraining effect to gibberella, Sclerotinia sclerotiorum and Pear scab.Therefore pyrazoles schiff base compound of the present invention can do potential sterilization pesticide.
Embodiment
Embodiment one: the preparation of compound 1
3.6g (0.025mol) phenylhydrazine hydrochloride is dissolved in 15mL water, regulate pH to be 8 with 10% sodium hydroxide solution, add 15mL ethanol, stir and make it entirely molten, add 3.25g (0.025mol) Ethoxymethylenemalononitrile again, reflux 2h.Naturally cool to ice bath cooling 2h after room temperature, filter, washing, dry, yellow crystals 1.
Methyl phenyl ketone (20mmol), phenylhydrazine hydrochloride (25mmol), anhydrous sodium acetate (30mmol) and 100mL ethanol is added in 250mL single necked round bottom flask, magnetic agitation, 50-60 DEG C of reaction 3h (TLC detection reaction carries out degree).Be spin-dried for by reaction solution after completion of the reaction, add water washing, be extracted with ethyl acetate (3 × 40mL), merge organic layer and use anhydrous sodium sulfate drying, underpressure distillation obtains crude product 2.By DMF and POCl
3(5mL) mix ice bath 30min, then above-mentioned solid be dissolved in 4mL DMF and drop in above-mentioned mixed solution, proceeding to stirring at normal temperature one hour gradually, be heated to 70-80 DEG C of reaction 5h.After being cooled to normal temperature, pour in frozen water, adjust pH to 7-8 with 50%NaOH, suction filtration also washes 3 times, obtains solid 3 after oven dry.Respectively get 1mmol gained solid 1 and 3, be dissolved in ethanol (10mL), back flow reaction 2h (TLC detection reaction carries out degree) cools after completion of the reaction and separates out solids.Ethyl alcohol recrystallization can obtain light yellow pure compound 4.
Productive rate 66%, mp:159-161 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.12 (d, J=0.5Hz, 1H), 8.57 (d, J=0.5Hz, 1H), 7.89 (s, 1H), 7.85 – 7.74 (m, 4H), 7.69 – 7.60 (m, 2H), 7.57 – 7.44 (m, 7H), 7.43 – 7.36 (m, 2H) .MS (ESI): 415.16 (C
26h
18n
6, [M+H]
+) .Anal.Calcd for C
26h
18n
6: C, 75.35; H, 4.38; N, 20.28; Found:C, 75.55; H, 4.31; N, 19.52.
Embodiment two: the preparation of compound 2
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride.Obtain yellow crystalline target compound.Productive rate 72%, mp:161-163 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.11 (s, 1H), 8.57 (s, 1H), 7.87 (s, 1H), 7.83 – 7.73 (m, 4H), 7.55 – 7.43 (m, 7H), 7.42 – 7.36 (m, 1H), 7.28 (s, 1H), 7.26 – 7.24 (m, 1H), 2.42 (s, 3H) .MS (ESI): 428.94 (C
27h
20n
6, [M+H]
+) .Anal.Calcdfor C
27h
20n
6: C, 75.68; H, 4.70; N, 19.61; Found:C, 75.35; H, 4.43; N, 19.73.
Embodiment three: the preparation of compound 3
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 75%, mp:184-185 DEG C;
1h NMR (400MHz, CDCl
3) δ 9.17 – 9.10 (m, 1H), 8.56 (s, 1H), 7.87 (s, 1H), 7.84 – 7.74 (m, 4H), 7.63 – 7.56 (m, 2H), 7.56 – 7.37 (m, 8H) .MS (ESI): 448.94 (C
26h
17clN
6, [M+H]
+) .Anal.Calcd for C
26h
17clN
6: C, 69.56; H, 3.82; N, 18.72; Found:C, 69.35; H, 3.45; N, 18.93.
Embodiment four: the preparation of compound 4
Preparation method is with embodiment one.Step 2 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 68%, mp:167-173 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.11 (s, 1H), 8.51 (s, 1H), 7.89 (s, 1H), 7.83 – 7.73 (m, 4H), 7.69 – 7.59 (m, 2H), 7.54 – 7.38 (m, 6H), 7.24 – 7.14 (m, 2H) .MS (ESI): 433.15 (C
26h
17fN
6, [M+H]
+) .Anal.Calcd for C
26h
17fN
6: C, 72.21; H, 3.96; N, 19.43; Found:C, 72.56; H, 4.21; N, 19.86.
Embodiment five: the preparation of compound 5
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 69%, mp:159-165 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.10 (s, 1H), 8.51 (s, 1H), 7.87 (s, 1H), 7.8 – 7.73 (m, 4H), 7.53 – 7.46 (m, 5H), 7.28 (s, 1H), 7.26 – 7.15 (m, 3H), 2.42 (s, 3H) .MS (ESI): 447.15 (C
27h
19fN
6, [M+H]
+) .Anal.Calcd for C
27h
19fN
6: C, 72.63; H, 4.29; N, 18.82; Found:C, 72.98; H, 4.46; N, 19.21.
Embodiment six: the preparation of compound 6
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 72%, mp:179-183 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.14 (s, 1H), 8.54 (s, 1H), 7.87 (s, 1H), 7.83 – 7.73 (m, 4H), 7.63 – 7.36 (m, 8H), 7.20 – 7.10 (m, 2H) .MS (ESI): 433.15 (C
26h
17fN
6, [M+H]+) and .Anal.Calcd for C
26h
17fN
6: C, 72.21; H, 3.96; N, 19.43; Found:C, 72.64; H, 4.35; N, 19.69.
Embodiment seven: the preparation of compound 7
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 74%, mp:171-174 DEG C.
1h NMR (400MHz, CDCl
3) δ 10.06 (s, 1H), 8.49 (s, 1H), 7.92 – 7.70 (m, 6H), 7.63 – 7.40 (m, 5H), 7.25 – 7.12 (m, 3H) .MS (ESI): 433.15 (C
26h
16f
2n
6, [M+H]
+) .Anal.Calcdfor C
26h
16f
2n
6: C, 69.33; H, 3.58; N, 18.66; Found:C, 69.65; H, 3.94; N, 19.02.
Embodiment eight: the preparation of compound 8
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 72%, mp:160-168 DEG C.
1h NMR (400MHz, CDCl
3) δ 10.06 (d, J=1.5Hz, 1H), 8.49 (d, J=4.7Hz, 2H), 7.94 – 7.68 (m, 6H), 7.62 – 7.36 (m, 5H), 7.25 – 7.15 (m, 3H) .MS (ESI): 467.11 (C
26h
16clFN
6, [M+H]
+) .Anal.Calcd for C
26h
16clFN
6: C, 66.88; H, 3.45; N, 18.00; Found:C, 67.21; H, 3.84; N, 18.43.
Embodiment nine: the preparation of compound 9
Preparation method is with embodiment one.Step 2 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride.Obtain yellow crystalline target compound.Productive rate 69%, mp:144-148 DEG C.
1hNMR (400MHz, CDCl
3) δ 10.05 (s, 1H), 8.50 (s, 1H), 7.90 – 7.75 (m, 4H), 7.67 (d, J=8.4Hz, 3H), 7.56 – 7.39 (m, 5H), 7.31 (d, J=8.5Hz, 3H), 2.42 (s, 3H) .MS (ESI): 429.17 (C
27h
20n
6, [M+H]
+) .Anal.Calcd forC
27h
20n
6: C, 75.68; H, 4.70; N, 19.61; Found:C, 75.97; H, 4.96; N, 19.98.
Embodiment ten: the preparation of compound 10
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride.Obtain yellow crystalline target compound.Productive rate 68%, mp:152-158 DEG C.
1h NMR (400MHz, CDCl
3) δ 10.05 (s, 1H), 8.50 (s, 1H), 7.85 – 7.78 (m, 3H), 7.72 – 7.64 (m, 3H), 7.54 – 7.43 (m, 5H), 7.31 (d, J=8.0Hz, 3H), 2.42 (s, 6H) .MS (ESI): 443.19 (C
28h
22n
6, [M+H]
+) .Anal.Calcd for C
28h
22n
6: C, 76.00; H, 5.01; N, 18.99; Found:C, 76.43; H, 5.36; N, 19.41.
Embodiment 11: the preparation of compound 11
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride.Obtain yellow crystalline target compound.Productive rate 65%, mp:145-149 DEG C.
1h NMR (400MHz, CDCl
3) δ 10.05 (s, 1H), 8.50 (s, 1H), 7.88 – 7.74 (m, 3H), 7.71 – 7.58 (m, 3H), 7.55 – 7.40 (m, 5H), 7.31 (d, J=8.1Hz, 3H), 2.42 (s, 3H) .MS (ESI): 463.14 (C
27h
19clN
6, [M+H]
+) .Anal.Calcd for C
27h
19clN
6: C, 70.05; H, 4.14; N, 18.15; Found:C, 70.42; H, 4.41; N, 18.54.
Embodiment 12: O, O ' preparation of-diethyl-α-(4-chloro-phenyl-) amino-(1-phenyl-3-rubigan)-4-pyrazolylmethyl phosphonic acid ester (compound 12)
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride.Obtain yellow crystalline target compound.Productive rate 66%, mp:150-153 DEG C.
1h NMR (400MHz, CDCl
3) δ 10.05 (s, 1H), 8.51 (s, 1H), 7.86 – 7.78 (m, 3H), 7.67 (d, J=8.5Hz, 3H), 7.57 – 7.43 (m, 5H), 7.31 (d, J=8.2Hz, 3H), 2.42 (s, 3H) .MS (ESI): 447.17 (C
27h
19fN
6, [M+H]
+) .Anal.Calcd for C
27h
19fN
6: C, 72.63; H, 4.29; N, 18.82; Found:C, 72.98; H, 4.64; N, 19.21.
Embodiment 13: the preparation of compound 13
Preparation method is with embodiment one.Step 2 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 68%, mp:167-170 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.12 (s, 1H), 8.54 (s, 1H), 7.89 (s, 1H), 7.79 – 7.74 (m, 4H), 7.63 (d, J=7.4Hz, 2H), 7.47 (m, 8H), 2.42 (s, 3H) .MS (ESI): 448.12 (C
26h
17clN
6, [M+H]
+) .Anal.Calcd for C
26h
17clN
6: C, 69.56; H, 3.82; N, 18.72; Found:C, 69.95; H, 4.24; N, 19.01
Embodiment 14: the preparation of compound 14
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-hydrazinobenzoic acid hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 67%, mp:120-125 DEG C.
1h NMR (400MHz, CDCl
3) δ 10.06 (s, 1H), 8.52 (s, 1H), 7.87 – 7.72 (m, 5H), 7.63 (s, 1H), 7.56 – 7.43 (m, 6H), 7.40 – 7.31 (m, 2H), 2.42 (s, 3H) .MS (ESI): 463.14 (C
27h
19clN
6, [M+H]+) and .Anal.Calcd for C
27h
19clN
6: C, 70.05; H, 4.14; N, 18.15; Found:C, 70.42; H, 4.43; N, 18.51.
Embodiment 15: the preparation of compound 15
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 74%, mp:196-199 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.14 (d, J=0.5Hz, 1H), 8.54 (s, 1H), 7.88 (s, 1H), 7.81 – 7.74 (m, 4H), 7.61 – 7.56 (m, 2H), 7.54 – 7.47 (m, 5H), 7.45 – 7.41 (m, 2H) .MS (ESI): 483.08 (C
26h
16cl
2n
6, [M+H]
+) .Anal.Calcd for C
26h
16cl
2n
6: C, 64.61; H, 3.34; N, 17.39; Found:C, 64.98; H, 3.75; N, 17.65.
Embodiment 16: the preparation of compound 16
Preparation method is with embodiment one.Step 1 replaces the phenylhydrazine hydrochloride in example one with 4-fluorophenyl hydrazine hydrochloride, and step 2 replaces the phenylhydrazine hydrochloride in example one with 4-chlorophenylhydxazine hydrochloride.Obtain yellow crystalline target compound.Productive rate 71%, mp:160-161 DEG C.
1h NMR (400MHz, CDCl
3) δ 9.14 (s, 1H), 8.52 (s, 1H), 7.88 (s, 1H), 7.82 – 7.72 (m, 4H), 7.65 – 7.57 (m, 2H), 7.55 – 7.44 (m, 5H), 7.19 – 7.11 (m, 2H), 1.56 (s, 3H) .MS (ESI): 467.11 (C
26h
16clFN
6, [M+H]
+) .Anal.Calcd for C
26h
16clFN
6: C, 66.88; H, 3.45; N, 18.00; Found:C, 67.13; H, 3.76; N, 18.35.
Embodiment 17: pyrazoles schiff bases analog derivative antibacterial activity in vitro research
Experiment adopts mycelial growth to suppress the pyrazoles schiff bases analog derivative of method to synthesis to carry out plant pathogenic fungi biotic resistance mensuration.
Aseptically, be dissolved in acetone by the target compound of synthesis, dilute for 100mg/mL is as storing solution, the test liquid 1mL getting configuration, in the 10mL test tube of sterilizing, adds the PDA substratum of 9mL about 50 DEG C, is poured in culture dish after mixing.Another 1mL acetone as blank, using derosal as positive control.
Choose the bacterium colony circle being in same growth potential, obtain bacterium cake with punch tool, bacterium cake is inverted on the substratum of above-mentioned dosing substratum, each repetition 5 times.Cultivate in incubator under 25 ± 1 DEG C of conditions, within 3 days, measure bacterium colony loop diameter by right-angled intersection method afterwards, average as experimental result, calculate inhibiting rate.
Inhibiting rate=[(contrast colony diameter-process colony diameter)/contrast colony diameter] * 100%
Pyrazoles schiff base compounds listed by table 1 the present invention to plant pathogenic fungi: the activity of gibberella, Sclerotinia sclerotiorum and Pear scab is surveyed
Claims (3)
1. a double pyrazole schiff bases analog derivative, is characterized in that, has following general formula:
R in structural formula
1for: H, 4-CH
3, any one in 4-F, 4-Cl; R
2for: H, 4-CH
3, any one in 4-F, 4-Cl.
2. prepare a method for above-mentioned double pyrazole schiff bases analog derivative, it is made up of the following step:
Step 1: 1:30-1:35 will replace phenylhydrazine hydrochloride and suitable quantity of water mixing in molar ratio, regulate pH to be 7-8 (pH is scope preferably) with mineral alkali, add same volume ethanol, stir and make it to dissolve completely, add Ethoxymethylenemalononitrile again, reflux, TLC spike is reacted, cooling reaction solution, be cooled with an ice bath again, filter, dry thick product, ethyl alcohol recrystallization to solid 1; Step 2: in reaction vessel, 4:5:430 adds substituted acetophenone, replaces phenylhydrazine hydrochloride and appropriate organic solvent in molar ratio, stirs and makes it to dissolve, then add appropriate bases, heating reflux reaction for some time, follow the tracks of reaction with TLC.After cooling, suction filtration obtains thick product, and ethyl alcohol recrystallization obtains product 2;
Step 3: the solid 2 being dissolved in DMF is dropped to DMF and POCl of ice bath 30min in advance by 1:3:7 in molar ratio
3in, recover stirring at normal temperature for some time, to 20-100 DEG C of stirring reaction for some time, after being cooled to normal temperature, pour in frozen water, adjust PH to 7-9 with inorganic alkali solution, suction filtration also washes 3 times, obtains solid 3 after oven dry;
Step 4: by the solid 1 and 3 of synthesis in molar ratio 1:1 be dissolved in organic solvent, reacting by heating for some time (TLC detection reaction carries out degree), after completion of the reaction cooling separate out solids.Recrystallization can obtain object product and pyrazoles schiff bases analog derivative.
3. the application of a class double pyrazole schiff bases analog derivative according to claim 1 in control plant pathogenic fungi.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105481747A (en) * | 2015-12-15 | 2016-04-13 | 南京农业大学 | Carbonic ester derivative of phenylpyrrole dipyrroline ketone, preparation method and application |
| CN108147997A (en) * | 2018-02-27 | 2018-06-12 | 淮阴师范学院 | Pyrazoles aldehyde anil schiff base compounds and its preparation method and application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101475523A (en) * | 2009-01-12 | 2009-07-08 | 南京农业大学 | 3-acyl pyrroline-2-ketoxime ether compound, and preparation and use thereof |
| WO2013138617A1 (en) * | 2012-03-16 | 2013-09-19 | Axikin Pharmaceuticals, Inc. | 3,5-diaminopyrazole kinase inhibitors |
| CN104402819A (en) * | 2014-09-22 | 2015-03-11 | 安徽农业大学 | Preparation and application of bispyrazole carboxamide derivative to the control of rice black streaked dwarf disease |
-
2015
- 2015-06-23 CN CN201510350618.5A patent/CN104910075B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101475523A (en) * | 2009-01-12 | 2009-07-08 | 南京农业大学 | 3-acyl pyrroline-2-ketoxime ether compound, and preparation and use thereof |
| WO2013138617A1 (en) * | 2012-03-16 | 2013-09-19 | Axikin Pharmaceuticals, Inc. | 3,5-diaminopyrazole kinase inhibitors |
| CN104402819A (en) * | 2014-09-22 | 2015-03-11 | 安徽农业大学 | Preparation and application of bispyrazole carboxamide derivative to the control of rice black streaked dwarf disease |
Non-Patent Citations (3)
| Title |
|---|
| SAMIR BONDOCK等: "Synthesis and antimicrobial activity of some new thiazole, thiophene and", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| SWARNKAR, DEEPAK等: "Microwave-assisted synthesis of some pyrazole derivatives via Vilsmeier-Haack formylation and their biological activity", 《WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES》 * |
| VORA, JABALI J.DENG 等: "Synthesis and antimicrobial activity of some new 4-(substituted\aryl)-[[(1,3-diphenyl-1H-pyrazole-4-yl)methylene]amino]-1,5-dimethyl-2-phenyl-3-pyrazolidinone derivatives", 《INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105481747A (en) * | 2015-12-15 | 2016-04-13 | 南京农业大学 | Carbonic ester derivative of phenylpyrrole dipyrroline ketone, preparation method and application |
| CN105481747B (en) * | 2015-12-15 | 2018-03-27 | 南京农业大学 | A kind of carbonates derivative of phenylpyrrole connection pyrrolinone, preparation method and application |
| CN108147997A (en) * | 2018-02-27 | 2018-06-12 | 淮阴师范学院 | Pyrazoles aldehyde anil schiff base compounds and its preparation method and application |
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