CN110183428A - A kind of furans bamic acid esters compound of the tetrazole containing 1,2,3,4- and its preparation method and application - Google Patents

A kind of furans bamic acid esters compound of the tetrazole containing 1,2,3,4- and its preparation method and application Download PDF

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CN110183428A
CN110183428A CN201910473201.6A CN201910473201A CN110183428A CN 110183428 A CN110183428 A CN 110183428A CN 201910473201 A CN201910473201 A CN 201910473201A CN 110183428 A CN110183428 A CN 110183428A
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furans
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CN110183428B (en
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崔紫宁
何敏
姜珊
李宇豪
向绪稳
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South China Agricultural University
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/713—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with four or more nitrogen atoms as the only ring hetero atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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Abstract

The invention discloses furans bamic acid esters compounds of a kind of tetrazole containing 1,2,3,4- and its preparation method and application.The structure of the compound such as formula (III) is described；Wherein, the R is selected from hydrogen, halogen, nitro, hydroxyl, C1~4Alkyl, C1~4Halogenated alkyl, C1~4Alkoxy or C1~4One of halogenated alkyl is a variety of.Contain tetrazole heterocycle structure and 5- phenyl -2- furan ring structure in the compound structure simultaneously, its structure novel, compound all has good inhibiting effect, IC for rice leaf spot bacteria Xanthomonas oryzae pv.oryzae and/or xanthomonas oryzae pv. oryzicola X.oryzae pv.oryzicola simultaneously50Value is even significantly lower than Yekuzuo and Thiodiazole-copper, reduces 18~25 times, and the prevention and treatment and/or treatment in the plant disease that prevention and treatment is caused by above two pathogen have great application prospect, can be prepared as bactericide and is applied；Meanwhile the preparation method of compound of the present invention is simple, quick, and yield is high, convenient for being prepared on a large scale.

Description

A kind of furans bamic acid esters compound of the tetrazole containing 1,2,3,4- and its preparation Methods and applications
Technical field
The invention belongs to heterocyclic compound application field, in particular to a kind of thio first of furans for containing 1,2,3,4- tetrazoles Acid esters compound and the preparation method and application thereof.
Background technique
Tetrazole heterocyclic compound is the five-membered heteroaromatic compounds of the nitrogen-atoms containing there are four, this is one kind in organic conjunction The extremely important intermediate in can be used to synthesize the product that the fields such as medicine, pesticide and industry use.
In azoles farm chemicals, current existing azimsulfuron class, tetrazolinone herbicides have monocotyledon The four azole plant growth regulator of triazole methyl mercapto of obvious effect, the fungicide such as simeconazoles, benomyl and Fipronil, triazole The insecticides such as phosphorus, these pesticides all have the advantages of efficient, less toxic, to safety of human and livestock, and are widely used in agricultural production ((a) Feng,G.-R.；Huo,A.-X.；Zhang,S.-X.；Wang,H.-R.；Wang,H.-Q.J.Nanjing Normal Univ. (Nat.Sci.Ed.)2007,30,71.(b)Li,W.；Zhang,Y.-M.；Wei,T.-B.；Gao,L.- M.Chin.J.Org.Chem.2008,28,454.(c)Luo,Y.-P.；Yang,G.-F.J.Heterocycl.Chem.2007, 44,937.(d)Luo,Y.-P.；Yang,G.-F.Bioorg.Med.Chem.2007,15,1716.).
And in recent years, the status that tetrazole heterocyclic compound occupies in novel high-efficiency environment friendly pesticides discovery is increasingly Height, to find the biologically active compound of structure novel, the various tetrazole heterocyclic compounds of design and synthesis are very heavy A kind of approach wanted.
Summary of the invention
The purpose of the present invention is to provide a kind of furans bamic acid esters compounds of tetrazole containing 1,2,3,4-.This hair In the bright compound structure simultaneously contain tetrazole heterocycle structure and 5- phenyl -2- furan ring structure, structure novel, together When compound for rice leaf spot bacteria Xanthomonas oryzae pv.oryzae and/or xanthomonas oryzae pv. oryzicola X.oryzae pv.oryzicola all has good inhibiting effect, IC50Value is even significantly lower than Yekuzuo and Thiodiazole-copper, Prevention and treatment and/or treatment in the plant disease that prevention and treatment is caused by above two pathogen have great application prospect, can make The standby bactericide that becomes is applied.
Another object of the present invention is to provide the furans bamic acid esters compounds of the tetrazole containing 1,2,3,4- Preparation method.
A further object of the present invention is to provide answering for the furans bamic acid esters compound of the tetrazole containing 1,2,3,4- With.
Above-mentioned purpose of the invention is achieved by following scheme:
One kind containing the furans bamic acid esters compound of 1,2,3,4- tetrazoles, the structure of the compound such as formula (III) It is described:
Wherein, the R is selected from hydrogen, halogen, nitro, hydroxyl, C1~4Alkyl, C1~4Halogenated alkyl, C1~4Alkoxy or C1~4Halogen One of substituted alkyl is a variety of.
Preferably, the R be selected from hydrogen, fluorine, chlorine, bromine, nitro, hydroxyl, methyl, ethyl, n-propyl, isopropyl, normal-butyl, Isobutyl group, sec-butyl, tert-butyl, methoxyl group, ethyoxyl, positive propoxy, isopropoxy, trifluoromethyl, trifluoromethoxy or three One of fluoro ethyl is a variety of.
Preferably, the R is selected from hydrogen, 2- nitro, 3- nitro, 4- nitro, 2- fluorine, 3- fluorine, 4- fluorine, 2- bromine, 3- bromine, 4- Bromine, 2- chlorine, 3- chlorine, 4- chlorine, 2,4- difluoro, 2,6- difluoro, 2- methyl, 3- methyl, 4- methyl, 2- methoxyl group, 3- methoxyl group, 4- Methoxyl group, 2- trifluoromethyl, 3- trifluoromethyl or 4- trifluoromethyl.Its structure is with one of flowering structure:
It is highly preferred that the R is selected from 2- fluorine, 4- fluorine, 4- bromine, 2- chlorine, 3- chlorine, 4- chlorine, 2,4- difluoro or 2,6- difluoro.Its Structure is with one of flowering structure:
It is highly preferred that the R is selected from 4- chlorine, 4- fluorine or 2,4- difluoro.Its structure is with one of flowering structure:
The present invention also protects the preparation side of the furans bamic acid esters compound of the tetrazole containing 1,2,3,4- simultaneously Method includes the following steps:
S1. in the presence of a diluent, compound shown in formula I and SOCl2It reacts under reflux condition, preparation formula II is changed Close object；
S2. under diluent and inorganic base existence condition, N- methyl-5-mercapto-1,2,3,4-tetrazole is in stirring at normal temperature Under become sulphur anion, then reacted with formula (II) described compound, formula (III) the target chemical combination can be prepared Object:
Preferably, in step S1, the temperature of the reflux is 80~120 DEG C；Return time is 3~6h；It is highly preferred that institute The temperature for stating reflux is 80~90 DEG C；Return time is 3~4h.
Preferably, in step S2, the temperature of reaction is 20~30 DEG C；Reaction time is 0.5~1h.
Preferably, in step S2, the diluent be selected from benzene,toluene,xylene, chlorobenzene, dichloro-benzenes, petroleum ether, hexane, Hexamethylene, methylene chloride, chloroform, carbon tetrachloride, ether, diisopropyl ether, dioxanes, tetrahydrofuran, glycol dimethyl ether, second two Diethylene glycol diethyl ether, acetone, butanone, methylisobutylketone, acetonitrile, propionitrile, butyronitrile, N,N-dimethylformamide, N, N- dimethylacetamide Amine, N- methyl-formailide, N-Methyl pyrrolidone, hexamethylphosphoramide, methyl acetate, ethyl acetate, dimethyl are sub- Sulfone, methanol, ethyl alcohol, normal propyl alcohol, isopropanol, glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether or diethylene glycol One of single ether is a variety of.
It is highly preferred that the diluent is selected from one of acetonitrile, acetone or tetrahydrofuran or a variety of.
Preferably, the inorganic base is selected from sodium hydroxide, potassium carbonate, sodium carbonate, sodium ethoxide, sodium bicarbonate or potassium acetate It is one or more.
It is highly preferred that the inorganic base is one or both of sodium hydroxide or potassium carbonate.
Preferably, in step S2, compound shown in the diluent, the formula (II), N- methyl -5- sulfydryl -1,2,3, The mass ratio of the material of 4- tetrazole and inorganic base is 300~600:1~2:1~1.5:1~3.
It is highly preferred that compound, N- methyl-5-mercapto-1,2,3,4-tetrazole shown in the diluent, the formula (II) The mass ratio of the material with inorganic base is 400:1:1:2.
The furans bamic acid esters compound of the tetrazole containing 1,2,3,4- is in preparing control of plant disease drug Application also within protection scope of the present invention.
Preferably, the control of plant disease drug is plant disease fungicide.
It is highly preferred that it is rice leaf spot bacteria that the plant disease fungicide, which is by pathogen for plant disease, Xanthomonas oryzae pv.oryzae and/or xanthomonas oryzae pv. oryzicola X.oryzae pv.oryzicola causes Plant disease.
Compared with prior art, the invention has the following advantages:
Contain tetrazole heterocycle structure and 5- phenyl -2- furan ring structure in compound structure of the present invention simultaneously, Its structure novel, while compound is for rice leaf spot bacteria Xanthomonas oryzae pv.oryzae and/or rice Xanthomonas campestris PV.oryzicola X.oryzae pv.oryzicola all has good inhibiting effect, IC50Value is even significantly lower than leaf Withered azoles and Thiodiazole-copper reduce 18~25 times, prevention and treatment in the plant disease that is caused by above two pathogen of prevention and treatment and/or Treatment has great application prospect, can be prepared as bactericide and is applied；
Meanwhile the preparation method of compound of the present invention is simple, quick, and yield is high, convenient in actual production process Large batch of preparation.
Specific embodiment
The present invention is made combined with specific embodiments below and further being elaborated, the embodiment is served only for explaining this Invention, is not intended to limit the scope of the present invention.Test method as used in the following examples is normal unless otherwise specified Rule method；Used material, reagent etc., unless otherwise specified, for the reagent and material commercially obtained.
The synthesis of 1 compound III -1 of embodiment
The specific preparation process of compound III -1 is as follows:
0.44g 5- (2- chlorphenyl) -2- furancarboxylic acid (2.0mmol) is sequentially added in 50mL single port bottle, 5mL dichloro is sub- Sulfone；It is heated to reflux 3 hours, stops heating, be cooled to room temperature to reaction solution, remove remaining thionyl chloride under reduced pressure, both obtain furans Formyl chloromethylated intermediate, the intermediate are directly used in next step without purifying；
Separately take addition 0.12g (2.0mmol) N- methyl-5-mercapto-1,2,3,4-tetrazole, 0.55g in 50mL single port bottle Potassium carbonate (4.0mmol), 20mL acetonitrile, stirring at normal temperature 0.5h；The acetonitrile solution of furoyl chloride is added dropwise in room temperature, after being added dropwise React at room temperature 1h；Monitored using thin-layer chromatography (TLC), to after completion of the reaction, reaction solution filtering, filtrate be spin-dried for brown slightly produces Object, crude product are isolated and purified through silica gel column chromatography (methylene chloride/V: methanol/V=100:1), are obtained isolated light yellow solid Body compound 0.519g, yield: 81%.1H NMR (400MHz, Chloroform-d) δ 7.98 (dd, J=7.7,1.8Hz, 1H), 7.53 (dd, J=7.9,1.4Hz, 1H), 7.49 (d, J=3.9Hz, 1H), 7.46-7.38 (m, 2H), 7.36 (d, J= 3.9Hz,1H),4.13(s,3H).
Identified, the structure of compound III -1 is as follows:
The synthesis of 2 compound III -2 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (3- fluorophenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain dark yellow solid III -2.
1H NMR (400MHz, Chloroform-d) δ 7.79 (q, J=1.4Hz, 1H), 7.73-7.68 (m, 1H), 7.47 (d, J=3.8Hz, 1H), 7.44-7.40 (m, 2H), 6.94 (d, J=3.8Hz, 1H), 4.13 (s, 3H)
The synthesis of 3 compound III -3 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (4- chlorphenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain light yellow solid III -3.
1H NMR (400MHz, Chloroform-d) δ 7.76 (d, J=8.6Hz, 2H), 7.51-7.42 (m, 3H), 6.90 (d, J=3.8Hz, 1H), 4.13 (s, 3H)
Embodiment 4: the synthesis of compound III -4
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (2- fluorophenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain white solid III -4.
1H NMR (400MHz, Chloroform-d) δ 7.99 (td, J=7.7,1.5Hz, 1H), 7.49 (d, J=3.8Hz, 1H), 7.48-7.40 (m, 1H), 7.34-7.29 (m, 1H), 7.22 (dd, J=10.9,8.6Hz, 1H), 7.09 (t, J= 3.6Hz,1H),4.13(s,3H).
The synthesis of 5 compound III -5 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (3- fluorophenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain yellow solid III -5.
1H NMR(400MHz,Chloroform-d)δ7.63–7.59(m,1H),7.54–7.44(m,3H),7.15(tdd, J=8.4,2.6,0.9Hz, 1H), 6.94 (d, J=3.8Hz, 1H), 4.13 (s, 3H)
Embodiment 6: the synthesis of compound III -6
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (4- fluorophenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain light yellow solid III -6.
1H NMR (400MHz, Chloroform-d) δ 7.87-7.78 (m, 2H), 7.47 (d, J=3.8Hz, 1H), 7.23- 7.14 (m, 2H), 6.86 (d, J=3.8Hz, 1H), 4.13 (s, 3H)
The synthesis of 7 compound III -7 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorine using 5- (2,4- difluorophenyl) -2 furoyl chloride Phenyl) -2 furoyl chloride, obtain light yellow solid III -7.
1H NMR (400MHz, Chloroform-d) δ 7.98 (td, J=8.6,6.3Hz, 1H), 7.49 (d, J=3.8Hz, 1H),7.13–6.91(m,3H),4.13(s,3H).
The synthesis of 8 compound III -8 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorine using 5- (2,6- difluorophenyl) -2 furoyl chloride Phenyl) -2 furoyl chloride, obtain brown solid III -8.
1H NMR (600MHz, Chloroform-d) δ 7.47 (d, J=3.8Hz, 1H), 7.44-7.39 (m, 1H), 7.10- 7.05(m,3H),4.12(s,3H).
The synthesis of 9 compound III -9 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (2- nitrobenzophenone) -2 furoyl chloride Base) -2 furoyl chloride, obtain pale white solid III -9.
1H NMR (400MHz, Chloroform-d) δ 7.90 (dd, J=8.1,1.1Hz, 1H), 7.82 (dd, J=7.8, 1.4Hz, 1H), 7.74 (td, J=7.6,1.3Hz, 1H), 7.65 (td, J=7.8,1.5Hz, 1H), 7.45 (d, J=3.8Hz, 1H), 6.89 (d, J=3.8Hz, 1H), 4.12 (s, 3H)
The synthesis of 10 compound III -10 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (3- nitrobenzophenone) -2 furoyl chloride Base) -2 furoyl chloride, obtain yellow solid III -10.
1H NMR (400MHz, Chloroform-d) δ 8.64 (t, J=1.9Hz, 1H), 8.30 (ddd, J=8.2,2.2, 1.0Hz, 1H), 8.20-8.13 (m, 1H), 7.72 (t, J=8.0Hz, 1H), 7.52 (d, J=3.8Hz, 1H), 7.08 (s, 1H)
The synthesis of 11 compound III -11 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (4- nitrobenzophenone) -2 furoyl chloride Base) -2 furoyl chloride, obtain light yellow solid III -11.
1H NMR(400MHz,Chloroform-d)δ8.39–8.32(m,2H),8.02–7.96(m,2H),7.51(d,J =3.9Hz, 1H), 7.12 (d, J=3.8Hz, 1H), 4.14 (s, 3H)
The synthesis of 12 compound III -12 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (4- bromophenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain light yellow solid III -12.
1H NMR(400MHz,Chloroform-d)δ7.72–7.66(m,2H),7.65–7.60(m,2H),7.47(d,J =3.8Hz, 1H), 6.92 (d, J=3.8Hz, 1H), 4.13 (s, 3H)
The synthesis of 13 compound III -13 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorobenzene using 5- (4- aminomethyl phenyl) -2 furoyl chloride Base) -2 furoyl chloride, obtain light yellow solid III -13.
1H NMR (400MHz, Chloroform-d) δ 7.72 (d, J=8.2Hz, 2H), 7.45 (d, J=3.8Hz, 1H), 7.29 (d, J=8.0Hz, 2H), 6.86 (d, J=3.8Hz, 1H), 4.12 (s, 3H), 2.42 (s, 3H)
The synthesis of 14 compound III -14 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorine using 5- (4- methoxyphenyl) -2 furoyl chloride Phenyl) -2 furoyl chloride, obtain yellow solid III -14.
1H NMR (600MHz, Chloroform-d) δ 7.79-7.74 (m, 2H), 7.44 (d, J=3.8Hz, 1H), 7.01- 6.97 (m, 2H), 6.78 (d, J=3.8Hz, 1H), 4.11 (s, 3H), 3.87 (s, 3H)
The synthesis of 15 compound III -15 of embodiment
Method is with embodiment 1, except that substituting 5- (2- chlorphenyl) -2- furan using 5- phenyl -2 furoyl chloride It mutters formyl chloride, obtains yellow solid III -15.
1H NMR(600MHz,Chloroform-d)δ7.85–7.81(m,1H),7.70–7.67(m,2H),7.65–7.60 (m, 2H), 7.52-7.48 (m, 1H), 7.46 (d, J=3.8Hz, 1H), 6.91 (d, J=3.8Hz, 1H), 4.12 (s, 3H)
The results are shown in Table 1 for structure, appearance, mass spectrum and the elemental analysis of compound III -1~III -15.
Structure, appearance, mass spectrum and the elemental analysis result of 1 compound III -1~III -15 of table
The bactericidal activity of 16 compound III -1~III -15 of embodiment
Use for examination pathogen for rice leaf spot bacteria (Xoo) and xanthomonas oryzae pv. oryzicola (Xoc).This examination Testing pathogen used is to adopt from field crops, booth vegetable and the site of pathological change sampling for storing fruit from by sick position Cause of disease is taken, inoculation and purifying, are identified as rice leaf spot bacteria Xoo (Xanthomonas on corresponding culture medium Oryzae pv.oryzae) and xanthomonas oryzae pv. oryzicola Xoc (X.oryzae pv.oryzicola).
(1) bactericidal activity of the test compound to rice leaf spot bacteria (Xoo)
The test concentrations of compound: untested compound and control fungicide Yekuzuo raw medicine, Thiodiazole-copper raw medicine dissolve respectively In DMSO, 200 μ gmL are diluted to the aseptic aqueous solution of 0.1% polysorbas20-1With 100 μ gmL-1.Test strain is rice Leaf spot bacteria (Xanthomonas oryzae pv.oryzae).
By 15 compounds in table 1, i.e. compound III -1~III -15, using turbidimetry, for Xoo (Xanthomonas oryzae pv.oryzae) carries out the screening test of in vitro bactericidal activity: to the NB fluid nutrient medium of 4mL The middle culture solution that 1mL testing sample solution and 40 μ L thallus containing Xoo is added, 180r/min culture 36~48 is small under the conditions of 28 DEG C When.The bacterium solution of each concentration is measured to OD value (OD in microplate reader595), DMSO does negative control.Bacteriostasis rate calculation formula is such as Under:
Inhibiting rate (%)=(blank group OD595Experimental group OD595)/blank group OD595×100
Each concentration of every kind of compound repeats test three times, measure that the results are shown in Table 2, then according to measuring As a result, the concentration gradient of adjustment compound, EC of the test compound to Xoo50Value, measuring the results are shown in Table shown in 2.
The data measured are evaluated using Logistic model analysis, analyze to obtain mesh using analysis of statistical data processing system Compound is marked to the EC of Xoo50Value, the results are shown in Table 2.
In vitro antibacterial activity of 2 compound of table to Xoo
From table 2 it can be seen that the bactericidal activity of -15 couples of Xoo of compound III -1~III is above Yekuzuo and Thiodiazole-copper, Middle compound III -1, III -3, III -4, III -6, III -7, III -8 show antibacterial work very under the concentration of 200 μ g/mL Property, under the concentration of 100 μ g/mL, compound III -3, III -6, III -7 still show inhibiting rate very.Half inhibits dense Spend (EC50) show the bacteriostatic activities of all compounds better than Yekuzuo (94.35 ± 1.95 μ g/mL) and Thiodiazole-copper (124.83 ± 3.66μg/mL)；Wherein, compound III -3 (4.83 ± 0.52 μ g/mL), III -6 (5.83 ± 0.66 μ g/mL) and III -7 (6.35 ± 0.81 μ g/mL) show apparent bacteriostatic activity, EC50Value reduces 18~25 times compared with Yekuzuo and Thiodiazole-copper.
From the point of view of the structure and activity data of the compound described in table 2, electron-withdrawing group (such as chlorine, fluorine) is introduced on phenyl ring It is advantageous to the activity of compound, improve its bacteriostatic activity；And it introduces electron donating group (such as methyl, methoxyl group) and is unfavorable for its suppression The active raising of bacterium；Meanwhile same substituent group also has shadow to the activity of compound when different location replaces on phenyl ring It rings, wherein its position of substitution on phenyl ring puts in order according to active height are as follows: the contraposition ortho position > > meta position.
(2) activity of the test compound to xanthomonas oryzae pv. oryzicola (Xoc).
The test concentrations of compound: untested compound and control fungicide Yekuzuo, Thiodiazole-copper are dissolved in DMSO, use The aseptic aqueous solution of 0.1% polysorbas20 is diluted to 200 μ g/mL and 100 μ g/mL；Test strain is xanthomonas oryzae pv. oryzicola Xoc(X.oryzae pv.oryzicola)。
By 15 compounds in table 1, i.e. compound III -1~III -15, using turbidimetry, for Xoc (X.oryzae Pv.oryzicola it) carries out the screening test of in vitro bactericidal activity: 1mL sample to be tested being added into the NB fluid nutrient medium of 4mL The culture solution of solution and 40 μ L thallus containing Xoc, 180r/min is cultivated 36~48 hours under the conditions of 28 DEG C.By the bacterium solution of each concentration OD value (OD is measured in microplate reader595), DMSO does blank control.Bacteriostasis rate calculation formula is as follows:
Inhibiting rate (%)=(blank group OD595Experimental group OD595)/blank group OD595×100
Each concentration of each compound repeats test three times, according to gained inhibiting rate, utilizes Logistic model analysis Evaluation, the EC for obtaining target compound to Xoc is analyzed using analysis of statistical data processing system50Value；It the results are shown in Table 3.
In vitro antibacterial activity of 3 compound of table to Xoc
From table 3 it can be seen that the Antifungal Activity in Vitro of -15 couples of Xoc of compound III -1~III is above Yekuzuo and thiophene bacterium Copper, wherein compound III -1, III -3, III -4, III -6, III -7, III -8 show suppression very under the concentration of 200 μ g/mL Bacterium activity, under the concentration of 100 μ g/mL, compound III -3, III -6, III -7 still show inhibiting rate very.Half suppression Concentration (EC processed50) show that the bacteriostatic activity of all compounds is superior to Yekuzuo (166.78 ± 4.38 μ g/mL) and Thiodiazole-copper (254.76±6.52μg/mL)；Wherein, compound III -3 (9.88 ± 0.73 μ g/mL), III -6 (12.67 ± 1.25 μ g/mL), III -7 (24.39 ± 1.26 μ g/mL), III -8 (36.78 ± 2.03 μ g/mL) show apparent bacteriostatic activity, EC50Value and leaf Withered azoles is compared with Thiodiazole-copper reduces 18~25 times.
From the point of view of the structure and activity data of the compound described in table 3, electron-withdrawing group (such as chlorine, fluorine) is introduced on phenyl ring It is advantageous to the activity of compound, improve its bioactivity；And it introduces electron donating group (such as methyl, methoxyl group) and is unfavorable for its work The raising of property；Meanwhile same substituent group also has an impact to the activity of compound when different location replaces on phenyl ring, In, the position of substitution on phenyl ring puts in order according to active height are as follows: the contraposition ortho position > ≈ meta position.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention The limitation of shield range can also be made on the basis of above description and thinking for those of ordinary skill in the art Other various forms of variations or variation, there is no necessity and possibility to exhaust all the enbodiments.It is all of the invention Made any modifications, equivalent replacements, and improvements etc., should be included in the protection of the claims in the present invention within spirit and principle Within the scope of.

Claims (10)

1. the furans bamic acid esters compound that one kind contains 1,2,3,4- tetrazoles, which is characterized in that the knot of the compound Structure such as formula (III) is described:
Wherein, the R is selected from hydrogen, halogen, nitro, hydroxyl, C1~4Alkyl, C1~4Halogenated alkyl, C1~4Alkoxy or C1~4Alkyl halide One of base is a variety of.
2. containing the furans bamic acid esters compound of 1,2,3,4- tetrazoles according to claim 1, which is characterized in that institute It states R and is selected from hydrogen, fluorine, chlorine, bromine, nitro, hydroxyl, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, uncle One of butyl, methoxyl group, ethyoxyl, positive propoxy, isopropoxy, trifluoromethyl, trifluoromethoxy or trifluoroethyl or It is a variety of.
3. containing the furans bamic acid esters compound of 1,2,3,4- tetrazoles according to claim 2, which is characterized in that institute State R be selected from hydrogen, 2- nitro, 3- nitro, 4- nitro, 2- fluorine, 3- fluorine, 4- fluorine, 2- bromine, 3- bromine, 4- bromine, 2- chlorine, 3- chlorine, 4- chlorine, 2,4- difluoro, 2,6- difluoro, 2- methyl, 3- methyl, 4- methyl, 2- methoxyl group, 3- methoxyl group, 4- methoxyl group, 2- trifluoromethyl, 3- trifluoromethyl or 4- trifluoromethyl.
4. containing the furans bamic acid esters compound of 1,2,3,4- tetrazoles according to claim 3, which is characterized in that institute It states R and is selected from 2- fluorine, 4- fluorine, 4- bromine, 2- chlorine, 3- chlorine, 4- chlorine, 2,4- difluoro or 2,6- difluoro.
5. the preparation method of any furans bamic acid esters compound containing 1,2,3,4- tetrazoles of Claims 1-4, It is characterized by comprising the following steps:
S1. in the presence of a diluent, compound shown in formula I and SOCl2It reacts under reflux condition, II compound of preparation formula；
S2. under diluent and inorganic base existence condition, N- methyl-5-mercapto-1,2,3,4-tetrazole becomes under stirring at normal temperature It at sulphur anion, is then reacted with formula (II) described compound, formula (III) described target compound can be prepared:
6. the preparation method of the furans bamic acid esters compound containing 1,2,3,4- tetrazoles according to claim 5, It is characterized in that, in step S1, the temperature of the reflux is 80~120 DEG C；Return time is 3~6h；
In step S2, the temperature of reaction is 20~30 DEG C；Reaction time is 0.5~1h；
In step S2, the diluent is selected from benzene,toluene,xylene, chlorobenzene, dichloro-benzenes, petroleum ether, hexane, hexamethylene, dichloro Methane, chloroform, carbon tetrachloride, ether, diisopropyl ether, dioxanes, tetrahydrofuran, glycol dimethyl ether, ethylene glycol diethyl ether, third Ketone, butanone, methylisobutylketone, acetonitrile, propionitrile, butyronitrile, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, N- methyl-first Anilide, N-Methyl pyrrolidone, hexamethylphosphoramide, methyl acetate, ethyl acetate, dimethyl sulfoxide, methanol, ethyl alcohol, One in normal propyl alcohol, isopropanol, glycol monoethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether or diethylene glycol monoethyl ether Kind is a variety of；
The inorganic base is selected from the one or more of sodium hydroxide, potassium carbonate, sodium carbonate, sodium ethoxide, sodium bicarbonate or potassium acetate.
7. the preparation method of the furans bamic acid esters compound containing 1,2,3,4- tetrazoles according to claim 5, It is characterized in that, in step S2, compound shown in the diluent, the formula (II), N- methyl -5- sulfydryl -1,2,3,4- tetra- nitrogen The mass ratio of the material of azoles and inorganic base is 300~600:1~2:1~1.5:1~3.
8. the furans bamic acid esters compound of any tetrazole containing 1,2,3,4- of Claims 1-4 is in preparation plant Application in disease control drug.
9. applying according to claim 8, which is characterized in that the control of plant disease drug is plant disease fungicide.
10. applying according to claim 9, which is characterized in that the plant disease fungicide is by disease for plant disease Opportunistic pathogen is rice leaf spot bacteria Xanthomonas oryzae pv.oryzae and/or xanthomonas oryzae pv. oryzicola The plant disease that X.oryzae pv.oryzicola causes.
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