CN104292165B - Fluorine-containing alkenes compounds with azacyclo-and its production and use - Google Patents

Fluorine-containing alkenes compounds with azacyclo-and its production and use Download PDF

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CN104292165B
CN104292165B CN201410134330.XA CN201410134330A CN104292165B CN 104292165 B CN104292165 B CN 104292165B CN 201410134330 A CN201410134330 A CN 201410134330A CN 104292165 B CN104292165 B CN 104292165B
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nmr
cdcl
alkenes compounds
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CN104292165A (en
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曹松
熊扬
黄涛
吴伟
金观毅
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East China University of Science and Technology
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    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/60—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
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    • C07D209/04—Indoles; Hydrogenated indoles
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    • 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
    • C07D231/12—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Abstract

The present invention relates to a kind of fluorine-containing alkenes compounds with azacyclo-and its production and use.Described alkenes compounds is compound shown in Formulas I, or its isomer or acceptable salt in Pesticide Science.Compound shown in Formulas I is prepared by containing reacting together with difluoro alkenes compounds and nitrogen heterocyclic ring (containing NH) compounds of aromatic ring.The alkenes compounds that the present invention provides is as the application of crop bactericide.In Formulas I, R1～R4It is respectively and independently selected from: hydrogen, C1～C3Alkyl, C1～C3Alkoxyl, a kind of in halogen；Or R1～R4The phenyl being combined as bivalence of middle arbitrary neighborhood two or oxygen containing five yuan or the hexa-member heterocycle heterocyclic radical of bivalence, remaining is H；A is nitrogenous five yuan or hexa-atomic heterocycle, by the substituted heterocycle containing N five yuan or hexa-atomic of thienyl, or is replaced by phenyl or the heterocycle containing N five yuan or hexa-atomic of benzo；The hetero atom number of described heterocycle is 1～3.

Description

Fluorine-containing alkenes compounds with azacyclo-and its production and use
Technical field
The present invention relates to alkenes compounds of a kind of fluorine-containing and azacyclo-and its production and use, specifically, Relate to one (E)-N-α-fluorine-containing and alkenes compounds of azacyclo-and selectivity synthesis should (E)-N-under metal salt-free is catalyzed The method of α-fluorine-containing alkenes compounds with azacyclo-.
Background technology
Fluorine containing olefine compounds is the framing structure of organic synthesis, organic chemical industry's intermediate and the activity that a class is important Group, they are widely used to medicine, pesticide and polypeptide compounds.See document (a) I.Manca, A.Mastinu, F.Olimpieri,M.Falzoi,M.Sani,et al.,Eur.J.Med.Chem.2013,62,256；(b)S.Alexande, WO2004005268A1,2004；(c)K.Steert,I.El-Sayed,P.Van der Veken,A.Krishtal, C.V.Alsenoy,et al.,Bioorg.Med.Chem.Lett.2007,17,6563.Although existing many documents report is fluorine-containing The preparation method of alkene, but some severe reaction conditions, complex steps；The fluorination reagent used having is expensive；Some use gas Body brings operation inconvenience.See document (a) A.K.Ghosh, S.Banerjee, S.Sinha, S.B.Kang, B.Zajc, J.Org.Chem.2009,74,3689；(b)X.Lei,G.Dutheuil,X.Pannecoucke,J.Quirion, Org.Lett.,2004,6(13),2101。
It is relatively fewer that the synthetic method of nitrogenous heterocyclic alkenes compounds is reported.Most common and maximally effective synthesis contains The method of azacyclo-alkenes compounds is nitrogen heterocyclic ring (containing NH) and the iodide of alkene, bromide, the chloride of copper catalysis There is the reaction of Ullmann type, but this reaction is generally required for the long period under the conditions of higher temperature and metal salt catalyst Complete.See document (a) H.Wang, Y.Li, F.Sun, Y.Feng, K.Jin, X.Wang, J.Org.Chem.2008,73, 8639-8642;(b)R.A.Altman,S.L.Buchwald,Org.Lett.2006,8,2779-2782。
In consideration of it, provide, a kind of step is succinct, reaction condition is gentle and without metal salt catalyst and have high selection The nitrogenous heterocyclic alkenes compounds of preparing of (isomer is less) becomes the main technical issues that need to address of the present invention.
Summary of the invention
The present inventor it has been investigated that: using is initiation material together with difluoro alkenes compounds, not only can be in nothing Under metal salt catalyst existence condition, the most advantageously obtain fluorine-containing and azacyclo-alkenes compounds, and product is the most single One (i.e. there is higher three-dimensional selection).
The present invention has designed and synthesized the alkenes compounds of the fluorine-containing of a series of novel structure and azacyclo-, and finds to be somebody's turn to do Fluorine-containing and azacyclo-the alkenes compounds of class has bactericidal activity.
One purpose of the present invention is, it is provided that the fluorine-containing alkenes compounds with azacyclo-of a kind of novel structure, described Alkenes compounds is compound shown in Formulas I, or its isomer or acceptable salt in Pesticide Science:
In Formulas I, R1～R4It is respectively and independently selected from: hydrogen (H), C1～C3Alkyl, C1～C3Alkoxyl, halogen (F, Cl, Br or I) Middle one；Or R1～R4Middle arbitrary neighborhood two is (such as R1And R2、R2And R3, or R3And R4) the phenyl being combined as bivalence (it is with female Ring phenyl be " and " relation) or oxygen-containing (O) five yuan of bivalence or hexa-member heterocycle heterocyclic radical (its with female ring phenyl for " and " relation), Remaining is H；
A is nitrogenous (N) five yuan or hexa-atomic heterocycle, by the substituted heterocycle containing N five yuan or hexa-atomic of thienyl, or by phenyl Replace or the heterocycle containing N five yuan or hexa-atomic of benzo；The hetero atom number of described heterocycle is 1～3.
It is another object of the present invention to provide a kind of method of compound shown in formula I, the main step of described method Suddenly: under having alkali existence condition, anti-in organic aprotic polar solvent with compound shown in formula III by compound shown in Formula II Should, obtain object (compound shown in Formulas I)
R in formula II and III1～R4And the definition of A is identical with described previously, the preparation of compound shown in formula II sees document C.S.Thomoson,H.Martinez,W.R.Dolbier,Jr.,J.Fluorine Chem.2013,150,53。
Further object of the present invention is, discloses compound shown in a kind of Formulas I, or its isomer or can connect in Pesticide Science The purposes of the salt being subject to, i.e. compound shown in Formulas I, or its isomer or its in Pesticide Science acceptable salt as crops (as Semen Tritici aestivi or Fructus Cucumidis sativi etc.) the application of antibacterial.
Detailed description of the invention
In one preferred technical scheme of the present invention, R1～R4It is respectively and independently selected from: H, methyl, methoxyl group, Cl, Br or I Middle one, or R1～R4Middle arbitrary neighborhood two is (such as R1And R2、R2And R3, or R3And R4) the phenyl being combined as bivalence (it is with female Ring phenyl be " and " relation) or bivalence oxygen-containing quinary heterocyclic radical (its with female ring phenyl for " and " relation), remaining is H；
Further preferred technical scheme is: R1～R4It is respectively and independently selected from: H, methyl, methoxyl group, in Cl, Br or I one Kind, or R2And R3Be combined as bivalence benzene (its with female ring phenyl be " and " relation) or oxygen-containing five yuan (itself and female ring phenyl of bivalence For " and " relation), R1And R4It is H.
In presently preferred technical scheme, A is the five-ring heterocycles of nitrogenous (N), substituted containing N by thienyl Five-ring heterocycles, or replaced by phenyl or the five-ring heterocycles containing N of benzo；Hetero atom (N) number of the described five-ring heterocycles containing N is 1～3；
Further preferred technical scheme is: group in formula IUnder (wherein curve mark is for replacing position, lower same) is One in row group:
In a further preferred technical solution of the present invention, during compound shown in Formula II reacts with compound shown in formula III Alkali used can be organic base: such as trialkylamine (conventional is triethylamine) or the aliphatic sodium alkoxide of side chain or straight chain or potassium；Also Can be inorganic base: such as the oxysalt of IA metallic element that race comprises or hydroxide in the periodic table of elements；
Further preferred technical scheme is: the alkali that compound shown in Formula II is used in reacting with compound shown in formula III By inorganic base: such as the oxysalt of IA metallic element that race comprises or hydroxide in the periodic table of elements；The present invention recommends Inorganic base be the phosphate of the comprised metallic element of IA race in the periodic table of elements, such as potassium phosphate etc..
Additionally, organic aprotic polar solvent that the present invention recommends is DMF (DMF) or acetonitrile.
Fluorine-containing and azacyclo-the alkenes compounds that the present invention provides has higher bactericidal activity, wherein part chemical combination Thing under 50ug/mL concentration to fusarium graminearum (Fusarium graminearum) and botrytis cinerea pers (Bocrytis Cinerea Pers) still show preferable bactericidal activity.And prepare the of the present invention fluorine-containing and olefines chemical combination of azacyclo- The method of thing has that step is simple, reaction condition is gentle and the advantage such as easy and simple to handle, has potential commercial application value.
Below by embodiment, the invention will be further described, and its purpose is only that and is best understood from present disclosure. Therefore, protection scope of the present invention is not limited by the cases cited.
Embodiment one
(E) synthesis of-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-imidazoles (compound Ia):
To by compound IIa (0.204 gram, 1.2mmol), K3PO4(0.424 gram, 2mmol) and 2mLDMF composition mixed In compound, dropping, by compound IIIa (0.068 gram, 1mmol) and 2mLDMF composition mixture, is stirred at room temperature 12 hours. Stop stirring, filter, filtrate adds suitable quantity of water, and respectively with the CH of 10mL2Cl2Extract 3 times.Collect organic facies, and with anhydrous MgSO4It is dried.Filter, be spin-dried for filtrate, obtain thick product.Thick product is by silicagel column column chromatography for separation (normal hexane: dichloromethane =10:1(v/v)) obtain 0.198 gram of white solid (compound Ia), fusing point 93.5-94.5 DEG C, productivity 91%.
1H NMR(400MHz,CDCl3)δ7.50(s,1H),7.08(s,1H),6.96(s,1H),7.67(s,4H),6.16 (d,J=10.0Hz,1H),3.66(s,3H);
19F NMR(376MHz,CDCl3)δ-86.8(d,J=10.0Hz);
13C NMR(101MHz,CDCl3)δ159.4(d,4JCF=1.4Hz),143.9(d,1JCF=259.3Hz),136.8, 130.4,129.1(d,3JCF=3.4Hz),122.5(d,3JCF=7.1Hz),118.2(d,3JCF=2.8Hz),114.4,103.6(d ,2JCF=33.7Hz),55.2;
HRMS(EI)calcd for C12H11FN2O[M]+218.0855,found218.0840.
Embodiment two
(E) synthesis of-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-pyrazoles (compound Ib):
Except with in addition to compound IIIa in compound IIIb alternate embodiment one, remaining step is identical with enforcement one, obtains 0.202 gram of white solid (compound Ib), fusing point 95.0-96.0 DEG C, productivity 93%.
1H NMR(400MHz,CDCl3)δ7.76(d,J=1.6Hz,1H),7.47(d,J=2.5Hz,1H),6.70(s,4H), 6.38-6.37(m,1H),6.28(d,J=8.0Hz,1H),3.71(s,3H);
19F NMR(376MHz,CDCl3)δ-88.2(d,J=8.9Hz);
13C NMR(101MHz,CDCl3)δ159.3,146.2(d,1JCF=260.5Hz),142.6,131.4(d,4JCF= 1.7Hz),129.3(d,3JCF=3.4Hz),123.0(d,3JCF=6.6Hz),114.1,107.9,104.6(d,2JCF=34.8Hz), 55.2;
HRMS(EI)calcd for C12H11FN2O[M]+218.0855,found218.0856.
Embodiment three
(E) conjunction of-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-2-phenyl-1H-benzimidazole (compound Ic) Become:
Except with in addition to compound IIIa in compound IIIc alternate embodiment one, remaining step is identical with enforcement one, obtains 0.299 gram of white solid (compound Ic), fusing point 128.1-129.1 DEG C, productivity 87%.
1H NMR(400MHz,CDCl3)δ7.89-7.87(m,3H),7.41-7.34(m,6H),6.59(s,4H),6.52 (d,J=8.0Hz,1H),3.63(s,3H);
19F NMR(376MHz,CDCl3)δ-83.9(d,J=8.3Hz);
13C NMR(101MHz,CDCl3)δ159.5(d,4JCF=1.8Hz),152.0(d,4JCF=2.9Hz),143.3(d,1JCF=262.6Hz),143.2,134.6(d,3JCF=4.2Hz),130.4,129.1,128.9(d,3JCF=3.5Hz),128.6, 128.4,124.4,124.0,122.4(d,3JCF=6.6Hz),120.3,114.3,110.8,108.9(d,2JCF=36.4Hz), 55.1;
HRMS(EI)calcd for C22H17FN2O[M]+344.1325,found344.1319.
Embodiment four
(E) synthesis of-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-indole (compound Id):
Except with in addition to compound IIIa in compound IIId alternate embodiment one, remaining step is identical with enforcement one, obtains 0.238 gram of white solid (compound Id), fusing point 124.5-125.5 DEG C, productivity 89%.
1H NMR(400MHz,CDCl3)δ7.72-7.70(m,1H),7.41-7.39(m,1H),7.28-7.26(m,2H), 7.14-7.13(m,1H),6.77-6.70(m,5H),6.40(d,J=8.0Hz,1H),3.75(s,3H);
19F NMR(376MHz,CDCl3)δ-84.0(d,J=8.5Hz);
13C NMR(101MHz,CDCl3)δ159.0,146.2(d,1JCF=261.2Hz),135.1(d,3JCF=3.9Hz), 129.1(d,3JCF=3.4Hz),129.0,126.7(d,4JCF=3.2Hz),123.6(d,3JCF=7.2Hz),123.4,121.6, 121.1,114.1,111.5,106.1,103.8(d,2JCF=39.0Hz),55.2;
HRMS(EI)calcd for C17H14FNO[M]+267.1059,found267.1058.
Embodiment five
(E) synthesis of-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-BTA (compound Ie):
Except with in addition to compound IIIa in compound IIIe alternate embodiment one, remaining step is identical with enforcement one, obtains 0.229 gram of white solid (compound Ie), fusing point 126.6-127.5 DEG C, productivity 85%.
1H NMR(400MHz,CDCl3)δ8.14-8.12(m,1H),7.48-7.36(m,3H),6.72-6.69(m,3H), 6.62(d,J=8.8Hz,2H),3.66(s,3H);19F NMR(376MHz,CDCl3)δ-89.7(d,J=8.8Hz);
13C NMR(101MHz,CDCl3)δ159.7(d,4JCF=1.6Hz),145.4,142.3(d,1JCF=263.6Hz), 132.2(d,4JCF=2.8Hz),129.4(d,3JCF=3.4Hz),129.3,125.0,121.9(d,3JCF=6.2Hz),120.3, 114.2,110.0,108.7(d,2JCF=33.3Hz),55.1;
HRMS(EI)calcd for C15H12FN3O[M]+269.0964,found269.0965.
Embodiment six
(E) synthesis of-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-1,2,4-triazole (compound If):
Except with in addition to compound IIIa in compound IIIf alternate embodiment one, remaining step is identical with enforcement one, obtains 0.197 gram of white solid (compound If), fusing point 96.0-97.1 DEG C, productivity 90%.
1H NMR(400MHz,CDCl3)δ8.10(d,J=8.0Hz,2H),6.69(s,4H),6.41(d,J=8.0Hz,1H), 3.70(s,3H);19F NMR(376MHz,CDCl3)δ-91.4(d,J=9.1Hz);
13C NMR(101MHz,CDCl3)δ159.8,153.5,145.1,142.9(d,1JCF=262.3Hz),129.3(d,3JCF=3.3Hz),121.9(d,3JCF=6.1Hz),114.5,107.2(d,2JCF=31.3Hz),55.3;
HRMS(EI)calcd for C11H10FN3O[M]+219.0791,found219.0791.
Embodiment seven
(E)-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-5-(thiophene-2-base)-1H-pyrroles (Compound Ig per) Synthesis:
Except with in addition to compound IIIa in compound IIIg alternate embodiment one, remaining step is identical with enforcement one, obtains 0.279 gram of white solid (Compound Ig per), fusing point 100.3-101.5 DEG C, productivity 93%.
1H NMR(400MHz,CDCl3)δ7.46-7.44(m,2H),7.33-7.31(m,1H),7.10-7.08(m,1H), 6.87-6.74(m,4H),6.60(d,J=4.0Hz,1H),6.31(d,J=8.0Hz,1H),3.75(s,3H);19F NMR (376MHz,CDCl3)δ-88.9(d,J=8.9Hz);
13C NMR(101MHz,CDCl3)δ159.4(d,4JCF=1.4Hz),149.8,146.0(d,1JCF=261.1Hz), 135.3,133.0(d,4JCF=1.7Hz),129.5(d,3JCF=3.3Hz),127.6,125.8,125.2,123.0(d,3JCF= 6.4Hz),114.2,105.3(d,4JCF=0.9Hz),104.6(d,2JCF=34.7Hz),55.2;
HRMS(EI)calcd for C16H13FN2OS[M]+300.0733,found300.0735.
Embodiment eight
(E)-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-indazole (compound Ih) and (E)-1-(fluoro-2-of 1- (4-methoxyphenyl) vinyl) synthesis of-2H-indazole (compound Ih '):
Except with in addition to compound IIIa in compound IIIh alternate embodiment one, remaining step is identical with enforcement one, respectively To 0.126 gram of yellow oil (compound Ih) and 0.070 gram of yellow oil (compound Ih '), productivity is respectively 47% He 26%。
1H NMR(400MHz,CDCl3)δ7.95(d,J=0.6Hz,1H),7.71-7.69(m,1H),7.53(d,J= 8.0Hz,1H),7.29-7.25(m,1H),7.06-7.03(m,1H),6.64-6.58(m,4H),6.38(d,J=8.0Hz,1H), 3.63(s,3H);
19F NMR(376MHz,CDCl3)δ-88.8(d,J=9.7Hz);
13C NMR(101MHz,CDCl3)δ159.5,150.3,146.6(d,1JCF=261.1Hz),129.5(d,3JCF= 3.3Hz),127.9,125.2,123.2,122.6(d,3JCF=6.5Hz),121.9,120.8,118.6,114.2,105.2(d,2JCF=32.4Hz),55.2;HRMS(EI)calcd for C16H13FN2O[M]+268.1012,found268.1013.
1H NMR(400MHz,CDCl3)δ8.19(d,J=1.0Hz,1H),7.70-7.67(m,1H),7.28-7.24(m, 1H),7.17-7.14(m,2H),6.64-6.62(m,2H),6.55-6.53(m,2H),6.43(d,J=8.0Hz,1H),3.60 (s,3H);
19F NMR(376MHz,CDCl3)δ-87.8(d,J=8.0Hz);
13C NMR(101MHz,CDCl3)δ159.2,145.2(d,1JCF=262.8Hz),139.4(d,4JCF=3.1Hz), 138.1,129.3(d,3JCF=3.4Hz),128.0,124.5,123.2(d,3JCF=6.6Hz),122.5,121.2,114.1(d,3JCF=21.5Hz),110.4,106.2(d,2JCF=37.3Hz),55.1;
HRMS(EI)calcd for C16H13FN2O[M]+268.1012,found268.1011.
Embodiment nine
(E)-1-(the fluoro-2-of 1-(4-methoxyphenyl) vinyl)-1H-benzimidazole (compound Ii) and (Z)-1-(1- Fluoro-2-(4-methoxyphenyl) vinyl) synthesis of-1H-benzimidazole (compound Ii '):
Except with in addition to compound IIIa in compound IIIi alternate embodiment one, remaining step is identical with enforcement one, respectively To 0.196 gram of white solid (compound Ii), 121.7-122.6 DEG C and 0.032 gram white solid (compound Ii ') of fusing point, molten Point 134.0-135.0 DEG C, productivity is respectively 73% and 12%.
1H NMR(400MHz,CDCl3)δ7.81-7.76(m,2H),7.29-7.24(m,3H),6.64-6.56(m,4H), 6.38(d,J=8.0Hz,1H),3.59(s,3H);
19F NMR(376MHz,CDCl3)δ-87.8(dd,J=9.0,2.9Hz);
13C NMR(101MHz,CDCl3)δ159.5(d,4JCF=1.5Hz),143.3,143.1(d,1JCF=264.6Hz), 141.9,132.1(d,3JCF=3.9Hz),129.1(d,3JCF=3.4Hz),124.7,123.8,122.4(d,3JCF=6.8Hz), 120.7,114.4,111.2(d,4JCF=1.2Hz),105.8(d,2JCF=35.1Hz),55.2;
HRMS(EI)calcd for C16H13FN2O[M]+268.1012,found268.1013.
1H NMR(400MHz,CDCl3)δ8.02(s,1H),7.76(d,J=8.0Hz,1H),7.52(d,J=8.0Hz,1H), 7.45(d,J=8.0Hz,2H),7.32-7.25(m,2H),6.87(d,J=8.0Hz,2H),5.84(d,J=32.0Hz,1H), 3.76(s,3H);
19F NMR(376MHz,CDCl3)δ-95.4(dd,J=31.1,2.7Hz);
13C NMR(101MHz,CDCl3)δ159.5,143.7(d,1JCF=270.7Hz),143.4,141.3,132.7(d,3JCF=3.0Hz),130.0(d,3JCF=7.4Hz),129.8,124.6,123.7,120.8,114.3,111.2(d,4JCF= 2.4Hz),102.0(d,2JCF=15.6Hz),55.3;
HRMS(EI)calcd for C16H13FN2O[M]+268.1012,found268.1010.
Embodiment ten
(E)-1-(the fluoro-2-of 1-(4-aminomethyl phenyl) vinyl)-1H-benzimidazole (compound Ij) synthesis:
Except with in addition to compound IIa in compound IIb alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.217 Gram white solid (compound Ij), fusing point 122.4-123.7 DEG C, productivity 86%.
1H NMR(400MHz,CDCl3)δ7.90-7.88(m,2H),7.44-7.35(m,3H),6.97(d,J=8.0Hz, 2H),6.72(d,J=8.0Hz,2H),6.51(d,J=8.0Hz,1H),2.25(s,3H);19F NMR(376MHz,CDCl3)δ- 86.8(d,J=9.1Hz);
13C NMR(101MHz,CDCl3)δ143.9(d,1JCF=263.6Hz),143.3,141.8(d,4JCF=2.6Hz), 138.3(d,4JCF=1.6Hz),132.1(d,3JCF=3.9Hz),129.6,127.7(d,3JCF=3.4Hz),127.3(d,3JCF= 6.9Hz),124.7,123.8,120.7,111.2(d,4JCF=1.4Hz),105.9(d,2JCF=34.6Hz),21.1;
HRMS(EI)calcd for C16H13FN2[M]+252.1063,found252.1064.
Embodiment 11
(E) conjunction of-1-(2-(3,4-(methylene-dioxy) phenyl)-1-is fluoride-based)-1H-benzimidazole (compound Ik) Become:
Except with in addition to compound IIa in compound IIc alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.265 Gram white solid (compound Ik), fusing point 126.5-127.5 DEG C, productivity 94%.
1H NMR(400MHz,CDCl3)δ7.91(s,1H),7.88-7.85(m,1H),7.37(m,3H),6.61(d,J= 8.0Hz,1H),6.44(d,J=8.0Hz,1H),6.41-6.39(m,1H),6.18(d,J=1.7Hz,1H),5.84(s,2H);
19F NMR(376MHz,CDCl3)δ-87.4(d,J=9.1Hz);
13C NMR(101MHz,CDCl3)δ148.1,147.6(d,4JCF=1.6Hz),143.5(d,1JCF=262.6Hz), 143.3,141.8(d,4JCF=2.6Hz),132.1(d,3JCF=4.0Hz),124.7,124.0(d,3JCF=7.0Hz),123.8, 122.4(d,3JCF=4.0Hz),120.8,111.1(d,4JCF=1.3Hz),108.7,107.4(d,4JCF=3.0Hz),105.9(d ,2JCF=35.8Hz),101.3;
HRMS(EI)calcd for C16H11FN2O2[M]+282.0805,found282.0806.
Embodiment 12
(E)-1-(the fluoro-2-of 1-(naphthalene-1-base) vinyl)-1H-benzimidazole (compound Il) and (Z)-1-(fluoro-2-of 1- (naphthalene-1-base) vinyl) synthesis of-1H-benzimidazole (compound Il '):
Except with in addition to compound IIa in compound IId alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.233 Gram white solid (compound Il), fusing point 120.7-122.0 DEG C, productivity 81%；With 0.032 gram of white solid (compound Il '), Fusing point 136.0-137.0 DEG C, productivity 11%.
1H NMR(400MHz,CDCl3)δ7.86(d,J=8.0Hz,1H),7.66-7.62(m,2H),7.53-7.50(m, 2H),7.36-7.32(m,2H),7.26-7.24(m,1H),7.16-7.07(m,2H),6.96-6.92(m,1H),6.79(d,J= 8.0Hz,1H),6.71(d,J=8.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-87.4(d,J=8.6Hz);
13C NMR(101MHz,CDCl3)δ146.2(d,1JCF=262.3Hz),143.1,141.7(d,4JCF=1.6Hz), 133.6,132.3(d,3JCF=3.7Hz),131.6(d,3JCF=3.6Hz),128.9,127.5,127.4,126.9,126.4, 125.9(d,4JCF=1.9Hz),125.6,124.6,123.7,123.6,120.7,111.4(d,3JCF=2.5Hz),101.6(d,J =33.0Hz);
HRMS(EI)calcd for C19H13FN2[M]+288.1063,found288.1062.
1H NMR(400MHz,CDCl3)δ8.23(s,1H),8.00(d,J=8.0Hz,1H),7.91-7.85(m,4H), 7.70(d,J=8.0Hz,1H),7.56-7.53(m,3H),7.43-7.39(m,2H),6.63(d,J=32.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-95.4(d,J=29.1Hz);
13C NMR(101MHz,CDCl3)δ145.8(d,1JCF=269.7Hz),143.6,141.0,133.7,132.4, 131.3,128.9,128.8(d,4JCF=0.8Hz),127.3(d,3JCF=8.6Hz),127.2(d,3JCF=4.8Hz),126.7, 126.1,125.5,124.8,123.9,123.5,121.0,111.4(d,3JCF=2.6Hz),97.8(d,2JCF=16.3Hz);
HRMS(EI)calcd for C19H13FN2[M]+288.1063,found288.1064.
Embodiment 13
(E)-1-(2-(2-bromophenyl)-1-is fluoride-based)-1H-benzimidazole (compound Im) and (Z)-1-(2-(2-bromine Phenyl)-1-is fluoride-based) synthesis of-1H-benzimidazole (compound Im '):
Except with in addition to compound IIa in compound IIe alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.174 Gram white solid (compound Im), fusing point 119.8-121.0 DEG C, productivity 55%；With 0.120 gram of white solid (compound Im '), Fusing point 134.2-135.1 DEG C, productivity 38%.
1H NMR(400MHz,CDCl3)δ7.82-7.80(m,2H),7.59(d,J=8.0Hz,1H),7.37-7.32(m, 3H),7.07-7.03(m,1H),6.97-6.93(m,1H),6.65(d,J=8.0Hz,1H),6.60-6.58(m,1H);
19F NMR(376MHz,CDCl3)δ-86.4(d,J=8.4Hz);
13C NMR(101MHz,CDCl3)δ145.9(d,1JCF=263.9Hz),143.1,141.4(d,4JCF=2.0Hz), 133.0,132.0(d,3JCF=3.5Hz),129.7,128.9,128.8,127.8,124.8,124.3(d,3JCF=5.0Hz), 123.8,120.7,111.3(d,4JCF=2.1Hz),104.0(d,2JCF=36.5Hz);
HRMS(EI)calcd for C15H10BrFN2[M]+316.0011,found316.0010.
1H NMR(400MHz,CDCl3)δ8.08(s,1H),7.77-7.73(m,2H),7.61-7.59(m,1H),7.54- 7.52(m,1H),7.32-7.27(m,3H),7.07-7.06(m,1H),6.29(d,J=32.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-95.1(d,J=31.0Hz);
13C NMR(101MHz,CDCl3)δ145.9(d,1JCF=271.5Hz),143.7,140.6,133.0,132.0, 131.1(d,3JCF=5.9Hz),130.0(d,3JCF=11.0Hz),129.4(d,4JCF=1.3Hz),127.7,124.9,124.0, 123.9(d,4JCF=1.8Hz),121.0,111.4(d,4JCF=2.5Hz),99.0(d,2JCF=13.0Hz);
HRMS(EI)calcd for C15H10BrFN2[M]+316.0011,found316.0010.
Embodiment 14
(E)-1-(2-(3-bromophenyl)-1-is fluoride-based)-1H-benzimidazole (compound In) and (Z)-1-(2-(3-bromine Phenyl)-1-is fluoride-based) synthesis of-1H-benzimidazole (compound In '):
Except with in addition to compound IIa in compound IIf alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.148 Gram white solid (compound In), fusing point 115.4-116.6 DEG C, productivity 47%；With 0.126 gram of white solid (compound In '), Fusing point 138.2-139.1 DEG C, productivity 40%.
1H NMR(400MHz,CDCl3)δ7.88-7.86(m,2H),7.37-7.28(m,4H),7.12-7.11(m,1H), 6.97-6.93(m,1H),6.61(d,J=8.0Hz,1H),6.42(d,J=8.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-83.9(d,J=8.6Hz);
13C NMR(101MHz,CDCl3)δ145.2(d,1JCF=265.0Hz),143.3,141.4(d,4JCF=2.4Hz), 132.5(d,3JCF=7.6Hz),131.8(d,3JCF=3.8Hz),131.3(d,3JCF=3.9Hz),131.2(d,4JCF=1.2Hz), 130.4,125.7(d,4JCF=2.9Hz),124.9,124.0,122.9,120.9,111.2(d,4JCF=1.5Hz),104.2(d,2JCF=35.9Hz);
HRMS(EI)calcd for C15H10BrFN2[M]+316.0011,found316.0010.
1H NMR(400MHz,CDCl3)δ8.07(s,1H),7.80-7.78(m,1H),7.69-7.68(m,1H),7.57- 7.55(m,1H),7.45-7.43(m,1H),7.39-7.35(m,1H),7.34-7.31(m,2H),7.23(d,J=8.0Hz, 1H),5.87(d,J=32.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-92.1(d,J=30.6Hz);
13C NMR(101MHz,CDCl3)δ146.1(d,1JCF=263.2Hz),143.6,140.8,133.3(d,3JCF= 6.1Hz),132.2,131.4(d,3JCF=8.0Hz),131.1(d,4JCF=2.1Hz),130.4,127.1(d,3JCF=7.2Hz), 124.8,124.0,123.0,121.0,111.3(d,4JCF=2.8Hz),99.8(d,2JCF=14.7Hz);
HRMS(EI)calcd for C15H10BrFN2[M]+316.0011,found316.0012.
Embodiment 15
(E)-1-(2-(4-bromophenyl)-1-is fluoride-based)-1H-benzimidazole (compound Io) and (Z)-1-(2-(4-bromine Phenyl)-1-is fluoride-based) synthesis of-1H-benzimidazole (compound Io '):
Except with in addition to compound IIa in compound IIg alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.218 Gram white solid (compound Io), fusing point 118.3-119.4 DEG C, productivity 69%；With 0.073 gram of white solid (compound Io '), Fusing point 138.7-139.8 DEG C, productivity 23%.
1H NMR(400MHz,CDCl3)δ7.90-7.87(m,2H),7.38-7.30(m,5H),6.70(d,J=8.0Hz, 2H),6.47(d,J=8.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-84.4(d,J=8.7Hz);
13C NMR(101MHz,CDCl3)δ144.7(d,1JCF=264.5Hz),143.3,141.4(d,3JCF=2.5Hz), 132.2,131.8(d,3JCF=3.9Hz),129.4,129.3,124.9,124.0,122.3(d,4JCF=1.6Hz),120.9, 111.2,104.8(d,2JCF=35.8Hz);
HRMS(EI)calcd for C15H10BrFN2[M]+316.0011,found316.0013.
1H NMR(400MHz,CDCl3)δ8.06(s,1H),7.79-7.77(m,1H),7.55-7.54(m,1H),7.48- 7.46(m,2H),7.39-7.37(m,2H),7.34-7.30(m,2H),5.87(d,J=32.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-92.8(d,J=30.8Hz);
13C NMR(101MHz,CDCl3)δ145.4(d,1JCF=271.6Hz),143.5,140.8,132.3(d,4JCF= 2.8Hz),132.1,130.2(d,3JCF=6.1Hz),130.1(d,3JCF=7.5Hz),124.8,123.9,122.1(d,3JCF= 3.4Hz),121.0,111.3(d,4JCF=2.7Hz),100.4(d,2JCF=14.9Hz);
HRMS(EI)calcd for C15H10BrFN2[M]+316.0011,found316.0012.
Embodiment 16
(E)-1-(2-(3-chlorphenyl)-1-is fluoride-based)-1H-benzimidazole (compound Ip) and (Z)-1-(2-(3-chlorine Phenyl)-1-is fluoride-based) synthesis of-1H-benzimidazole (compound Ip '):
Except with in addition to compound IIa in compound IIh alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.155 Gram white solid (compound Ip), fusing point 107.4-108.5 DEG C, productivity 57%；With 0.090 gram of white solid (compound Ip '), Fusing point 125.8-126.9 DEG C, productivity 33%.
1H NMR(400MHz,CDCl3)δ7.78-7.75(m,2H),7.26-7.21(m,3H),7.02(d,J=8.0Hz, 1H),6.92-6.88(m,1H),6.82(s,1H),6.47(d,J=8.0Hz,1H),6.32(d,J=8.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-84.0(d,J=8.7Hz);
13C NMR(101MHz,CDCl3)δ145.2(d,1JCF=264.9Hz),143.4,141.5,134.8,132.2(d,3JCF=7.6Hz),130.1,128.4,128.3,128.2,125.4(d,3JCF=2.9Hz),124.9,124.0,120.9,111.2 (d,4JCF=1.2Hz),104.3(d,2JCF=35.9Hz);
HRMS(EI)calcd for C15H10ClFN2[M]+272.0517,found272.0512.
1H NMR(400MHz,CDCl3)δ8.11(s,1H),7.85-7.83(m,1H),7.61-7.57(m,2H),7.44- 7.29(m,5H),5.90(d,J=32.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-92.4(d,J=30.8Hz);
13C NMR(101MHz,CDCl3)δ145.8(d,1JCF=272.1Hz),143.5,140.8,134.7,133.0(d,3JCF=6.0Hz),132.2(d,4JCF=2.6Hz),130.1,128.4(d,3JCF=8.0Hz),128.1(d,4JCF=2.0Hz), 126.7(d,3JCF=7.2Hz),124.8,123.9,120.9,111.3(d,4JCF=2.9Hz),99.7(d,2JCF=14.5Hz);
HRMS(EI)calcd for C15H10ClFN2[M]+272.0517,found272.0515.
Embodiment 17
(E)-1-(2-(3-iodophenyl)-1-is fluoride-based)-1H-benzimidazole (compound Iq) and (Z)-1-(2-(3-iodine Phenyl)-1-is fluoride-based) synthesis of-1H-benzimidazole (compound Iq '):
Except with in addition to compound IIa in compound IIi alternate embodiment nine, remaining step is identical with enforcement nine, obtains 0.218 Gram white solid (compound Iq), fusing point 96.1-97.0 DEG C, productivity 60%；With 0.106 gram of white solid (compound Iq '), melt Point 110.2-111.3 DEG C, productivity 29%.
1H NMR(400MHz,CDCl3)δ7.86-7.83(m,2H),7.35-7.30(m,4H),7.46(d,J=8.0Hz, 1H),6.80-6.77(m,1H),6.60(d,J=8.0Hz,1H),6.38(d,J=8.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-84.0(d,J=8.7Hz);
13C NMR(101MHz,CDCl3)δ145.0(d,1JCF=265.0Hz),143.2,141.3(d,4JCF=2.4Hz), 137.2(d,3JCF=3.9Hz),137.1(d,4JCF=1.3Hz),132.5(d,3JCF=7.4Hz),131.7(d,3JCF=3.8Hz), 130.5,126.2(d,4JCF=2.8Hz),124.9,124.0,120.9,111.2(d,4JCF=1.5Hz),104.0(d,2JCF= 35.8Hz),94.6;
HRMS(EI)calcd for C15H10FIN2[M]+363.9873,found363.9872.
1H NMR(400MHz,CDCl3)δ8.12(s,1H),7.92-7.91(m,1H),7.85-7.83(m,1H),7.65- 7.62(m,2H),7.53(d,J=8.0Hz,1H),7.39-7.36(m,2H),7.15-7.11(m,1H),5.87(d,J= 32.0Hz,1H);
19F NMR(376MHz,CDCl3)δ-92.4(d,J=30.5Hz);
13C NMR(101MHz,CDCl3)δ145.7(d,1JCF=272.1Hz),143.5,140.8,137.2(d,3JCF= 7.8Hz),137.0(d,4JCF=2.2Hz),133.4(d,3JCF=6.1Hz),132.2(d,4JCF=2.6Hz),130.5,127.7 (d,3JCF=7.5Hz),124.8,124.0,121.0,111.3(d,4JCF=2.8Hz),99.6(d,2JCF=14.6Hz),94.7;
HRMS(EI)calcd for C15H10FIN2[M]+363.9873,found363.9872.
Embodiment 18
The mensuration of bactericidal activity:
(1) preparation of drug solution
By the candidate drug of 10mg, it is made into the mother solution of 10mg/mL respectively with DMF, then it is standby that mother solution is made into 50ug/mL concentration With.
(2) making of culture medium
PDA culture medium: Rhizoma Solani tuber osi (200g), glucose (20g), agar (15-20g), water (1000mL).Preparation 1L PDA Culture medium is standby.With the culture dish of 6cm, each culture dish falls the culture medium of 10mL, cools down standby.Respectively to red mould and grey mold two Individual bacterium carries out the test of inhibition zone, and each medicine arranges two repetitions.
(3) in vitro fungistatic effect test (inhibition zone method)
A) making of mensuration flat board
In advance by melt and dissolved for bacterium culture medium microwave-oven-heating to be determined, then it is incubated in 45-50 DEG C of thermostat water bath； Additionally in having cultivated strain inclined plane or plate, add 5-l0mL sterilized water, scraping surface bacterium layer, make bacterium suspension or spore Suspension, in the culture medium being incubated in advance, shakes up gently, be subsequently poured into plate before carefully bacterium solution being poured into, makes mensuration bacterium and puts down Plate.
B) general paper dish method
With tweezers, sterilizing filter paper (6mm) is dipped in upper Streptomycin Solution (avoiding contaminating antibacterial), after it is the most dry, by filter paper Sheet impregnates in the medicinal liquid prepared, and drains unnecessary medicinal liquid, connects at a certain distance and be affixed on containing on bacterium flat board after medicinal liquid is the most dry. Put mensuration bacteria growing preference temperature and cultivate 48h, then take out and determine fungistatic effect with kind of calliper antibacterial circle diameter.
(4) data process
According to the diameter of the inhibition zone surveyed, average.Concrete outcome is shown in Table 1:
Table 1

Claims (6)

1. an alkenes compounds for fluorine-containing and azacyclo-, described alkenes compounds is compound shown in Formulas I, or its Acceptable salt in Pesticide Science:
In formula I, R1～R4It is respectively and independently selected from: hydrogen, C1～C3Alkyl, C1～C3One in alkoxy or halogen；Or, R2And R3Group It is combined into the phenyl of bivalence, R1And R4It is H；GroupFor a kind of in following groups:
2. a fluorine-containing alkenes compounds with azacyclo-, described alkenes compounds is compound shown in Formulas I k, or its Acceptable salt in Pesticide Science:
3. the method preparing alkenes compounds as claimed in claim 1 or 2, it has main steps that: with the presence of alkali bar Under part, compound shown in Formula II react in organic aprotic polar solvent with compound shown in formula III, obtain object:
Wherein, R1～R4And groupDefinition identical with described in claim 1, wherein said alkali is IA race in the periodic table of elements The phosphate of comprised metallic element or hydroxide.
4. method as claimed in claim 3, it is characterised in that wherein said organic aprotic polar solvent is N, N-dimethyl Methanamide.
5. alkenes compounds as claimed in claim 1 or 2 is as the application of crop bactericide.
Apply the most as claimed in claim 5, it is characterised in that wherein said crops are Semen Tritici aestivi or Fructus Cucumidis sativi.
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