CN101973946B - Phenazine-1-carboxylic acids derivative and preparation method thereof - Google Patents
Phenazine-1-carboxylic acids derivative and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a phenazine-1-carboxylic acids derivative and a preparation method thereof in the field of biotechnology. In the derivative, chemical groups, containing hydrophilic groups, hydrophobic groups, linear structure groups, cyclic structure groups and aromatic structure groups are introduced into 1-locus carboxyl of phenazine-1-carboxylic acid. The preparation method comprises the following steps of: reflowing and distilling the phenazine-1-carboxylic acid separated from pseudomonas in a thionyl chloride solution to obtain an activated intermediate; dissolving the activated intermediate into dichloromethane, and adding an amino compound and triethylamine under an ice bath; then reacting at room temperature to stay overnight, and following the reaction by using a thin layer chromatography; and rotatably evaporating, extracting, drying and purifying to obtain a target compound. The derivative is used as an active ingredient of a pesticide formulation for fighting fruit and vegetables and crop diseases and insect pests as well as rice sheath blight. In the invention, antifungal activity tests are carried out by utilizing a plate method, and the compound with better activity is obtained.
Description
Technical field
The present invention relates to verivate of a kind of biological technical field and preparation method thereof, particularly a kind of have anti-mycotic activity compound phenazine-1-carboxylic acid series derivates and preparation method thereof.
Background technology
Shanghai Communications University takes the lead in using Pseudomonas fluorescens strain M18 exploitation to have wide spectrum, efficient, safety and can effectively control the biological pesticide of fungoid root-rot and stem rot; Name and be " Shen piperazine mycin "; Its staple is a phenazine-1-carboxylic acid; Since then, the chronic disease that the climing rot of the blight of cucumber and watermelon, muskmelon, the gourd, fruit and vegetables such as root rot of capsicum are difficult to cure has had the jinx, and phenazine-1-carboxylic acid is from crop rhizosphere soils, to filter out isolated microbiotic in many strains autotrophic bacteria; Can wide spectrum suppress various crop disease fungal pathogenses, than other medicament the high-efficiency prevention and control disease arranged, promote the high crop yield high-quality, advantage such as preserve the ecological environment.The related patent U.S. Patent No. document is following:
Patent of invention title: growth-promoting antagonistic bacterium M 18 for biologic agricultural chemical and preparation method thereof, patent documentation publication number: CN1340609.This patent for invention technical project has also been used new efficient screening, cultivation program, from plant rhizosphere soil, prepares to have simultaneously to promote plant-growth and broad spectrum to suppress the growth-promoting antagonistic bacterium M 18 for biologic agricultural chemical of plant epiphyte venereal disease evil.The product of this patent for invention can suppress various plants pathogen growth such as melon didymella bryoniae, Rhizoctonia solani Kuhn and cucumber fusarium axysporum effectively, and the growth of plant seedlings is had obvious facilitation.
Patent of invention title: utilize antagonizing bacteria M 18 strain to prepare the method for sterilant, patent documentation publication number: CN1802927.This patent for invention technology is under substratum of optimizing and culture condition; Utilize derivative strain M18G and the M18R of growth-promoting antagonistic bacterium M18; Produce the fermented liquid of high-content phenazine-1-carboxylic acid and pyoluteorin respectively; Respectively M18G fermented liquid and M18R fermented liquid are prepared into dry powder again; And be that 90%～10% and 10%～90% to carry out physics composite with the weight percent of the pyoluteorin in phenazine-1-carboxylic acid in the M18G dry powder and the M18R dry powder, be prepared into the microbial source sterilant of high-efficiency prevention and control Plant diseases.The sterilant that this patent for invention provides is to be wettable powder but not the active bacteria formulation of activeconstituents with the microbial metabolites; Thereby has a high stability; Its drug effect is not subject to the influence of envrionment conditions; Simultaneously under the prerequisite that low dosage uses, the multiple diseases of plant had higher control effect.
Patent of invention title: the RNA rapid extracting method of pseudomonas M 18, patent documentation publication number: CN101302508.The rapid extracting method of this patent for invention technology comprises that step is following: collects 106～107 cell pseudomonas M 18s, adds sex change liquid and chloroform, and mixing, centrifugal, bacterium liquid is divided into three layers in pipe; Draw 500 μ l supernatant liquids and be transferred in the silicon fiml post, and add Virahol, centrifugal; Add in ethanol to the silicon fiml post, centrifugal; Repeat a step; Centrifugal again, guarantee absence of liq in the silicon fiml post; Add in distilled water, elutriant to the silicon fiml post; Centrifugal, collect elutriant with a clean centrifuge tube.Extraction time of the present invention shortens greatly, and from the method for extracting RNA, can find out: the time of extraction is within 6min; There is not DNA to pollute; Leaching process is easy to robotization.After crossing column condition optimization, the RNA purity that extracts is very high; Its light absorption value of the RNA A260/A280=1.93 that extracts through spectrophotometric determination.
Application for a patent for invention title: utilize engineering bacterial strain M 18 G to carry plasmid pME 6032 Phz to produce the method for phenazine-1-carboxylic acid, patent documentation publication number: CN101705265A.This application for a patent for invention discloses and from growth-promoting antagonistic bacterium M18 genome, has amplified the biosynthetic encoding sox fragment of phenazine-1-carboxylic acid phzA1-G1; And with among this gene fragment insertion expression plasmid pME6032; Place under the control of strong promoter Ptac, be built into recombinant plasmid pME6032Phz; Then this recombinant plasmid is imported among the derivative strain M18G of growth-promoting antagonistic bacterium M18, be built into engineering strain M18G/pME6032Phz.Engineering bacillus strain realizes the high efficiency stable expression of encoding sox in the copy number of amplification phenazine-1-carboxylic acid biosynthesizing encoding sox.At last engineering strain M18G/pME6032Phz is cultivated in the analysis for soybean powder nutrient solution, produce phenazine-1-carboxylic acid efficiently and stably, significantly improve the output of phenazine-1-carboxylic acid.Utilize high-yield genetic engineering bacterium strain of the present invention to prepare phenazine-1-carboxylic acid, it produces instinct and reaches this requirement of farming that is applied to prevent and treat rice sheath blight disease, can be used for the preparation of sterilant Shen piperazine mycin, on a large scale controlling plant diseases.
In order to improve the activity of phenazine-1-carboxylic acid, reduce using dosage, it is current this problem that technology improves and development faces that further searching has stronger active compound than phenazine-1-carboxylic acid.
Summary of the invention
The objective of the invention is to overcome deficiency of the prior art, a kind of phenazine-1-carboxylic acid series derivates and preparation method thereof is provided.The present invention carries out structural modification to phenazine-1-carboxylic acid, utilizes the reactivity of its 1 carboxyl, carries out condensation with different aminocompounds; Can obtain the verivate of a series of phenazine-1-carboxylic acids; Then, utilize flat band method to carry out the anti-mycotic activity test, obtained to have better active compound.
The present invention realizes through following technical scheme:
The present invention relates to the phenazine-1-carboxylic acid series derivates; Through on 1 carboxyl of phenazine-1-carboxylic acid, introducing the chemical group that comprises hydrophilic radical, hydrophobic grouping, linear structure group and ring texture group, aromatic structure group, obtain having the title product of anti-mycotic activity through condensation reaction:
The compound 1-19 structural formula that generates is following:
Described chemical group comprises: methoxy ethamine, N-acetylethylenediamine, 3-alanine, N-(2 '-amino-ethyl) tetramethyleneimine; 3-(propylamine of 2 '-oxo-pyrrolidine-1 '-yl), 3-(1H-imidazoles-1-yl) propylamine, 2-(ethamine of pyridine-2 '-yl), 2; The 4-difluoroaniline, 2-phenyl-ethyl amine, suberane amine, 2-[2-(2-amino ethoxy) oxyethyl group] ethamine; 2-(4 '-p-methoxy-phenyl) ethamine, 2-(4 '-amino-sulfonyl phenyl) ethamine, pentamethylene amine, amantadine; Benzylamine, cyclooctylamine, amino propylene of 3-and 3-(diethylamino) propylamine.
Described compound 1-19 through on 1 carboxyl of phenazine-1-carboxylic acid, introducing hydrophilic chemical group, obtains having the active compound of stronger anti-rice sheath blight disease germ.
Described compound 1-19 through on 1 carboxyl of phenazine-1-carboxylic acid, introducing the hydrophilic ring texture group that has, obtains having the active compound of stronger anti-rice sheath blight disease germ.
The invention still further relates to the preparation method of aforesaid phenazine-1-carboxylic acid series derivates, may further comprise the steps:
1. will from pseudomonas, in sulfur oxychloride solution, reflux and distill by isolated phenazine-1-carboxylic acid, obtain activated intermediate.
Described backflow and distillation, return time are 6 hours, and return time is to remove sulfur oxychloride with distillating method after 6 hours.
2. be dissolved in methylene dichloride to activated intermediate, ice bath adds aminocompound and triethylamine down; Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.
Described aminocompound is an equivalent or 0.5 equivalent; Described triethylamine is four equivalents.
3. with revolving steaming, extraction, drying and purifying, obtain target compound.
Step is revolved steaming, extraction, drying and purifying described in 3., and its method is following:
A, with revolve steam to remove desolvate after, add ETHYLE ACETATE in the solid product and extremely dissolve fully with water;
Organic layer is obtained in b, extraction repeatedly;
C, add anhydrous sodium sulfate drying in the organic layer and spend the night;
D, remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound through column chromatography purification; Through characterizing compounds, confirm as target compound.
Described ETHYLE ACETATE and water, its volume ratio is: 2: 1.
The invention still further relates to the application of aforesaid phenazine-1-carboxylic acid series derivates:
Application one, phenazine-1-carboxylic acid series derivates are used as the active ingredient of anti-gourd, fruit and vegetable and diseases and pests of agronomic crop pesticide preparation;
Application two, phenazine-1-carboxylic acid series derivates are used as the active ingredient of the pesticide preparation of anti-rice sheath blight disease.
The present invention adopts flat band method to carry out the anti-mycotic activity test.With the comparatively serious rice sheath blight disease germ (Rhizoctonia solani Kuhn) of influence in the farm crop is example, carries out active testing.Its implementation process is following:
1) preparation of bacterium piece to be measured: the PDA substratum that will dissolve is evenly poured in sterilized a few cover petridish and is processed flat board; Get one of germ bacterial classification, it is central to put into above-mentioned petridish with aseptic technique picking one fritter, is inverted in 28 ℃ of incubators and cultivates, and mycelia is covered with flat board, can supply to use (noticing that cell age is consistent) this moment.
2) mother liquor configuration: in anhydrous ethanol solvent, concentration is arranged to Geometric Sequence with sample dissolution, about five.
3) times dilution methods such as preparing method's one substratum of pastille culture medium flat plate: get the mother liquor of equivalent, add 60mL PDA substratum, pour into after fully shaking up in the three cover petridish, the preparation pastille is dull and stereotyped; Get the not PDA substratum of pastille of 50mL again, evenly pour three cover petridish into, make blank.
4) connecing bacterium measures: after treating the substratum cooled and solidified, insert the pathogenic bacteria bacterium cake of diameter 0.8cm; The petridish that connects kind is inverted in 28 ℃ the incubator and cultivates; After treating that blank covers with (about about 42h), measure the colony diameter that each is handled, calculate bacteriostasis rate then with the right-angled intersection method.
5) data processing: the method for calculation of bacteriostasis rate: bacteriostasis rate=1-(D
t/ D
Ck), D
tExpression specimen flat-plate bacterial colony diameter, D
CkExpression blank flat-plate bacterial colony diameter; Half-inhibition concentration waits the regression equation calculation of the bacteriostasis rate of specific concentration to draw according to five.
The present invention is an example with the rice sheath blight disease germ, enumerates the Mlc (seeing table 1) of part of compounds.Cited compound has all showed certain activity, and wherein compound 7,9, and 10 have shown better biological activity.These will be as the further verivate synthetic of the present invention foundation.Table 1 phenazine-1-carboxylic acid verivate anti-mycotic activity is following:
Can obviously find out from last table, compound 7,9,10 have shown better anti-rice sheath blight disease germ activity.With compound 10 is example, its anti-rice sheath blight disease germ IC
50Be 0.003 μ M, and phenazine-1-carboxylic acid is 0.068 μ M, the latter is the former more than 20 times.That is to say that will reach same anti-rice sheath blight disease germ effect, the dosage of compound 10 only needs 1/20th of phenazine-1-carboxylic acid.Therefore, compare phenazine-1-carboxylic acid, the activity of compound 10 improves greatly, and the using dosage that reaches same antimycotic effectiveness just can reduce greatly.
In all former document of biomaterial pseudomonas that the present invention relates to and rice sheath blight disease germ more report is arranged.Pseudomonas, lifting one piece is example, Xu Yuquan at the FEMS MICROBIOLOGY LETTERS of 2004 publication the 237th volume, just once set forth the mechanism of pseudomonas metabolism phenazine-1-carboxylic acid as the communication author in the 41-47 page or leaf.Sheath and culm blight of rice germ, lifting one piece is example, Soil Biology&Biochemistry the 38th volume 923-930 page or leaf that Yulianti T etc. published in 2006 was just once set forth the rice sheath blight disease germ.
Embodiment
Below embodiments of the invention are elaborated: following examples are being to implement under the prerequisite with technical scheme of the present invention; Detailed embodiment and process have been provided; But protection scope of the present invention is not limited to following embodiment; Chemical group as introducing includes but not limited to hydrophilic radical, hydrophobic grouping, linear structure group and ring texture group, aromatic structure group; The chemical group of introducing includes but not limited to methoxy ethamine, N-acetylethylenediamine, 3-alanine, N-(2 '-amino-ethyl) tetramethyleneimine; 3-(propylamine of 2 '-oxo-pyrrolidine-1 '-yl), 3-(1H-imidazoles-1-yl) propylamine, 2-(ethamine of pyridine-2 '-yl), 2; The 4-difluoroaniline, 2-phenyl-ethyl amine, suberane amine, 2-[2-(2-amino ethoxy) oxyethyl group] ethamine; 2-(4 '-p-methoxy-phenyl) ethamine, 2-(4 '-amino-sulfonyl phenyl) ethamine, pentamethylene amine, amantadine; Benzylamine, cyclooctylamine, amino propylene of 3-and 3-(diethylamino) propylamine; The chemical group of 1 carboxyl introducing includes but not limited to hydrophilic radical, hydrophobic grouping, linear structure group and ring texture group, aromatic structure group.
In following examples, the experimental technique of unreceipted actual conditions, usually according to normal condition, or the condition of advising according to manufacturer.
Embodiment 1
Synthesizing of compound N-(2 '-methoxy ethyl) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down methoxy ethamine (equivalent, 150.2mg, 0.170mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(2 '-methoxy ethyl) azophenlyene-1-methane amide 338.2mg through column chromatography purification, productive rate is 60.1%.Yellow solid .mp:98-99 ℃ .IR (KBr compressing tablet): 3441,3263,2964,2921,2810,1666,1557,1416,1347,1263,1193,1118,1087,1028,875,841,796,747,694cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.35 (m, 1H), 9.00 (m, 1H), 8.38 (m, 1H), 8.25 (m, 2H), 7.94 (m, 3H), 3.89 (m, 2H), 3.75 (m, 2H) and 3.55 (s, 3H).
13C NMR (100MHz, DMSO-d
6): δ 163.7,142.3,142.2,140.6,139.7,134.1,132.9,132.0,131.4,130.0,129.3,129.0,128.6,70.4,58.0.HRMS (ESI positive mode): theoretical value [M+H]
+282.1243, experimental value 282.1239.
Embodiment 2
Synthesizing of compound N-(2 '-kharophen ethyl) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down the N-acetylethylenediamine (equivalent, 204mg, 0.232mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(2 '-kharophen ethyl) azophenlyene-1-methane amide 301.6mg through column chromatography purification, productive rate is 48.9%.Yellow powder .Mp:156-157 ℃ .IR (KBr compressing tablet): 3447,2960,2927,2077,1651,1562,1416,1262,1096,1025,803,752,661,591cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.25 (m, 1H), 8.97 (m, 1H), 8.41 (m, 1H), 8.28 (m, 2H), 7.95 (m, 3H), 6.60 (m, 1H), 3.84 (m, 2H), 3.65 (m, 2H) and 2.01 (s, 3H).
13C NMR (100MHz, CDCl
3): δ 170.7,166.2,143.3,143.0,141.2,140.5,135.3,134.0,131.9,131.1,129.8,129.7,129.0,128.5,40.8,39.5,23.3.HRMS (ESI positive mode): theoretical value [M+H]
+309.1352, experimental value 309.1342.
Embodiment 3
Synthesizing of compound N-(3 '-carboxyl propyl group) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down the 3-alanine (equivalent, 103mg) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(3 '-carboxyl propyl group) azophenlyene-1-methane amide 105.0mg through column chromatography purification, productive rate is 17.0%.Yellow solid .Mp:141-142 ℃ .IR (KBr compressing tablet): 3443,2925,2859,1719,1645,1561,1464,1415,1261,1225,1095,1023,861,801,751,669cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.20 (m, 1H), 8.97 (m, 1H), 8.53 (m, 1H), 8.30 (m, 2H), 7.98 (m, 3H), 3.78 (m, 2H), 2.60 (t, J=4.2,2H) and 2.15 (m, 2H).
13C NMR (100MHz, CDCl
3): δ 176.8,165.9,143.9,142.7,141.1,137.3,135.0,133.2,131.7,131.1,130.2,129.9,129.4,127.9,39.0,31.9,25.1.HRMS (ESIpositive mode): theoretical value [M+H]
+310.1192, experimental value 310.1199.
Embodiment 4
Compound N-[2 '-(tetramethyleneimine-1 "-yl) ethyl] azophenlyene-1-methane amide synthetic
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down N-(2 '-amino-ethyl) tetramethyleneimine (equivalent, 228mg, 0.253mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, through column chromatography purification obtain target compound N-[2 '-(tetramethyleneimine-1 "-yl) ethyl] azophenlyene-1-methane amide 527.7mg, productive rate is 82.4%.Yellow powder .Mp:126-127 ℃ .IR (KBr compressing tablet): 3445,2959,2795,1653,1562,1526,1416,1349,1266,1021,798,750,702cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.35 (m, 1H), 9.00 (m, 1H), 8.39 (m, 1H), 8.29 (m, 2H), 7.94 (m, 3H), 3.86 (m, 2H), 2.95 (m, 2H), 2.78 (m, 4H) and 1.93 (m, 4H).
13C NMR (100MHz, CDCl
3): δ 164.7,143.4, and 142.9,141.4,140.9,135.1,133.4,131.3 130.9,130.0,129.6,129.3,129.1,54.9,54.1,39.1,23.7.HRMS (ESI positive mode): theoretical value [M+H]
+321.1715, experimental value 321.1730.
Embodiment 5
Compound N-[3 '-(2 "-oxo-pyrrolidine-1 "-yl) propyl group] azophenlyene-1-methane amide synthetic
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 3-(propylamine of 2 '-oxo-pyrrolidine-1 '-yl) (and an equivalent, 284.4mg, 0.280mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, through column chromatography purification obtain target compound N-[3 '-(2 "-oxo-pyrrolidine-1 "-yl) propyl group] azophenlyene-1-methane amide 637.4mg, productive rate is 91.5%.Brown solid .Mp:101-102 ℃ .IR (KBr compressing tablet): 3445,3228,2925,2921,2810,1736,1674,1649,1524,1462,1428,1376,1346,1262,1155,1094,1024,809,752,692cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.18 (s, 1H), 8.98 (m, 1H), 8.54 (m, 1H), 8.38 (m, 1H), 8.26 (m, 1H), 7.93 (m, 3H), 3.68 (m, 2H), 3.54 (t, J=3.6,2H), 3.46 (t, J=3.9,2H) 2.42 (t, J=7.8,2H) and 2.02 (m, 4H).
13C NMR (100MHz, CDCl
3): δ 175.2,164.7,143.0,142.7,141.3,140.5,134.9,133.4,131.5,130.8,129.6,129.3,129.2,128.9,47.0,40.2,37.0,30.8,27.2,17.8.HRMS (ESI positive mode): theoretical value [M+H]
+349.1665, experimental value 349.1667.
Embodiment 6
Synthesizing of compound N-[3 '-(1H-imidazoles-1-yl) propyl group] azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 3-(1H-imidazoles-1-yl) propylamine (equivalent, 250mg, 0.236mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-[3 '-(1H-imidazoles-1-yl) propyl group] azophenlyene-1-methane amide 547.2mg through column chromatography purification, productive rate is 82.6%.Yellow powder .Mp:136-137 ℃ .IR (KBr compressing tablet): 3444,2960,1651,1560,1520,1415,1266,1230,1082,1027,902,799,748,696,662,624cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.12 (m, 1H), 9.00 (m, 1H), 8.41 (m, 1H), 8.26 (m, 2H), 7.96 (m, 3H), 7.60 (s, 1H), 7.06 (d, J=20.7,2H), 4.17 (t, J=3.9,2H), 3.67 (m, 2H) and 3.30 (m, 2H).
13C NMR (100MHz, CDCl
3): δ 164.9,143.1,142.7,140.8,140.3,137.0,135.2,133.6,131.7,130.8,129.7,129.5,129.4,128.5,128.4,118.7,44.4,36.6,30.9.HRMS (ESI positive mode): theoretical value [M+H]
+332.1511, experimental value 332.1521.
Embodiment 7
Compound N-[2 '-(pyridine-2 "-yl) ethyl] azophenlyene-1-methane amide synthetic
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 2-(ethamine of pyridine-2 '-yl) (and an equivalent, 244.3mg, 0.238mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, through column chromatography purification obtain target compound N-[2 '-(pyridine-2 "-yl) ethyl] azophenlyene-1-methane amide 634.2mg, productive rate is 96.6%..Mp:83-84 ℃ of .IR of red-brown solid (KBr compressing tablet): 3445,2960,2103,1659,1589,1561,1523,1470,1426,1351,1263,1096,1024,870,805,750,702,671,507cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.14 (s, 1H), 8.99 (m, 1H), 8.63 (m, 1H), 8.35 (m, 1H), 8.24 (m, 1H), 7.93 (m, 4H), 7.59 (m, 1H), 7.29 (s, 1H), 7.16 (m, 1H), 4.13 (m, 2H) and 3.29 (t, J=3.6,2H).
13C NMR (100MHz, CDCl
3): δ 164.6,159.5,149.3,143.1,142.6,141.0,140.5,136.4,135.1,133.3,131.2,130.7,129.8,129.4,128.9,123.4,121.4,39.3,37.7.HRMS (ESI positive mode): theoretical value [M+H]
+329.1402, experimental value 329.1409.
Embodiment 8
Synthesizing of compound N-(2 ', 4 '-difluorophenyl) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 2,4 difluorobenzene amine (equivalent, 258mg, 0.202mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(2 ', 4 '-difluorophenyl) azophenlyene-1-methane amide 118.6mg through column chromatography purification, productive rate is 17.7%.Yellow powder .Mp:212-213 ℃ .IR (KBr compressing tablet): 3443,2964,1679,1618,1565,1425,1259,1095,1023,961,841,803,752,725cm
-1.
1H NMR (300MHz, CDCl
3): δ 9.05 (m, 1H), 8.77 (m, 1H), 8.45 (m, 1H), 8.33 (m, 2H), 7.98 (m, 4H), 7.00 (m, 2H).
13CNMR (100MHz, DMSO-d
6): δ 163.2,162.6,143.0,142.8,142.6,134.0,132.9,132.8,132.0,131.9,131.2,130.7,129.4,129.2,128.0,125.0,122.2,111.1,104.2.HRMS (ESI positive mode): theoretical value [M+H]
+336.0948, experimental value 336.0942.
Embodiment 9
Synthesizing of compound N-phenylethyl azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down the 2-phenyl-ethyl amine (equivalent, 242mg, 0.251mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-phenylethyl azophenlyene-1-methane amide 464.9mg through column chromatography purification, productive rate is 71.0%.Yellow powder .Mp:93-94 ℃ .IR (KBr compressing tablet): 3454,3235,3059,2964,2925,2878,1657,1616,1551,1520,1346,1263,1204,1164,1093,1029,960,924,862,818,747,697,664,578,519cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.02 (s, 1H), 9.01 (m, 1H), 8.30 (m, 2H), 7.89 (m, 3H), 7.65 (m, 1H), 7.34 (m, 5H), 4.03 (m, 2H) and 3.10 (d, J=3.6,2H).
13C NMR (100MHz, CDCl
3): δ 164.6,143.1,142.7,140.9,140.5,139.5,135.2,133.4,131.2,130.8,129.8,129.4,129.0,128.9,128.8,128.6,126.3,40.7,35.7.HRMS (ESI positive mode): theoretical value [M+H]
+328.1450, experimental value 328.1458.
Embodiment 10
Synthesizing of compound N-suberane base azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down suberane amine (equivalent, 226mg, 0.255mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-suberane base azophenlyene-1-methane amide 564.7mg through column chromatography purification, productive rate is 88.4%.Yellow powder .Mp:126-127 ℃ .IR (KBr compressing tablet): 3445,3257,2922,2853,1658,1619,1554,1523,1455,1417,1349,1263,1210,1098,1022,805,745,676cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.11 (m, 1H), 9.00 (m, 1H), 8.37 (m, 1H), 8.29 (m, 1H), 8.20 (m, 1H), 7.94 (m, 3H), 4.44 (m, 1H), 2.15 (m, 2H) and 1.84 (m, 10H).
13C NMR (100MHz, CDCl
3): δ 163.2,143.6,142.7,141.0,140.7,135.1,133.2,131.4,130.7,129.9,129.5,129.2,128.7,50.5,34.7,28.1,24.1.HRMS (ESI positive mode): theoretical value [M+H]
+320.1763, experimental value 320.1766.
Embodiment 11
Compound 1,2-two (N-phenazinyl carbonyl-2 '-amino ethoxy) ethane synthetic
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 2-[2-(2-amino ethoxy) oxyethyl group] ethamine (0.5 equivalent, 148.2mg, 0.147mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound 1 through column chromatography purification, 2-two (N-phenazinyl carbonyl-2 '-amino ethoxy) ethane 139.3mg, productive rate is 12.4%..Mp:112-113 ℃ of .IR of red-brown solid (KBr compressing tablet): 3444,2962,2913,2817,1655,1546,1468,1414,1346,1261,1097,1024,867,801,751,699,602cm
-1.
1H NMR (300MHz, CDCl
3): δ 11.10 (s, 2H), 8.75 (m, 4H), 8.13 (m, 2H), 7.82 (m, 4H), 7.70 (m, 2H), 7.57 (m, 2H) and 3.88 (m, 12H).
13C NMR (100MHz, CDCl
3): δ 164.3,142.4,141.9,140.4,139.7,134.8,133.3,131.0,130.6,129.4,128.8,128.7,128.2,70.7,70.1,39.6.HRMS (ESI positive mode): theoretical value [M+H]
+561.2250, experimental value 561.2241.
Embodiment 12
Synthesizing of compound N-(4 '-p-methoxy-phenyl ethyl) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 2-(4 '-p-methoxy-phenyl) ethamine (equivalent, 302.4mg, 0.293mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(4 '-p-methoxy-phenyl ethyl) azophenlyene-1-methane amide 502.8mg through column chromatography purification, productive rate is 70.3%.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ10.99(s，1H)，9.00(m，1H)，8.35(m，1H)，8.23(m，1H)，7.88(m，3H)，7.63(m，1H)，7.29(m，2H)，6.86(m，2H)，4.03(dd，J1＝12.3，J2＝6.3，2H)，3.79(s，3H)and?3.02(t，J＝6.3，2H)。
Embodiment 13
Synthesizing of compound N-(4 '-amino-sulfonyl phenylethyl) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 2-(4 '-amino-sulfonyl phenyl) ethamine (equivalent, 400.6mg) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(4 '-amino-sulfonyl phenylethyl) azophenlyene-1-methane amide 802.8mg through column chromatography purification, productive rate is 98.7%.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ11.08(s，1H)，8.99(m，1H)，8.38(m，5H)，7.95(m，5H)，7.59(m，2H)，4.04(m，2H)and?3.17(m，2H)。
Embodiment 14
Synthesizing of compound N-pentamethylene base azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down pentamethylene amine (equivalent, 170.4mg, 0.198mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-pentamethylene base azophenlyene-1-methane amide 467.2mg through column chromatography purification, productive rate is 80.2%.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ11.14(m，1H)，9.00(d，J＝7.2，1H)，8.26(m，3H)，7.93(m，3H)，4.61(m，1H)，2.16(m，2H)and?1.86(m，6H)。
Embodiment 15
Synthesizing of compound N-(1-adamantyl) azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down amantadine (equivalent, 175.4mg) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-(1-adamantyl) azophenlyene-1-methane amide 344.3mg through column chromatography purification, productive rate is 48.2%.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ11.14(m，1H)，8.96(m，1H)，8.25(m，3H)，7.96(m，3H)，2.35(s，6H)，2.20(s，3H)and?1.80(m，6H)。
Embodiment 16
Synthesizing of compound N-benzyl azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down benzylamine (equivalent, 214.3mg, 0.219mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-benzyl azophenlyene-1-methane amide 571.2mg through column chromatography purification, productive rate is 91.1%.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ11.42(s，1H)，9.03(m，1H)，8.31(m，2H)，7.93(m，4H)，7.45(m，5H)and?4.90(d，J＝5.1，2H)。
Embodiment 17
Synthesizing of compound N-ring octyl group azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down cyclooctylamine (equivalent, 254.5mg, 0.280mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-ring octyl group azophenlyene-1-methane amide 570.2mg through column chromatography purification, productive rate is 85.5%.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ11.14(m，1H)，8.99(m，1H)，8.26(m，3H)，7.93(m，3H)，4.42(m，1H)and?1.91(m，14H)。
Embodiment 18
Compound N-(propylene-3 '-yl) azophenlyene-1-methane amide is synthetic
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down the amino propylene of 3-(equivalent, 114.2mg, 0.150mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, (azophenlyene-1-methane amide 390.3mg of propylene-3 '-yl), productive rate is 74.1% to obtain target compound N-through column chromatography purification.Yellow powder.
1H?NMR(300MHz，CDCl
3)：δ11.13(m，1H)，9.01(m，1H)，8.28(m，3H)，7.94(m，3H)，6.15(m，1H)，5.48(m，1H)，5.29(m，1H)and?4.34(s，2H)。
Embodiment 19
Synthesizing of compound N-[3 '-(diethylamino) propyl group] azophenlyene-1-methane amide
448.4mg phenazine-1-carboxylic acid refluxes after 6 hours in 20mL sulfur oxychloride solution, distillation method is removed sulfur oxychloride, obtains the sulfoxide activated intermediate.Be dissolved in the 5mL methylene dichloride to activated intermediate, ice bath add down 3-(diethylamino) propylamine (equivalent, 260.5mg, 0.318mL) and as the triethylamine of acid scavenger (four equivalents, 1.12mL).Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction.Steam except that after desolvating with revolving, in solid product, add ETHYLE ACETATE and water (volume ratio 2: 1) dissolving extremely fully.Extract repeatedly three times, get organic layer.Adding anhydrous sodium sulfate drying in the organic layer spends the night.Remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound N-[3 '-(diethylamino) propyl group] azophenlyene-1-methane amide 540.4mg through column chromatography purification, productive rate is 80.3%.Yellow solid.
1HNMR(300MHz，CDCl
3)：
11.01(m，1H)，9.00(m，1H)，8.30(m，3H)，7.95(m，3H)，3.71(m，2H)，2.69(m，2H)，2.59(m，4H)1.97(m，2H)?and?1.04(t，J＝7.2，6H)。
Claims (7)
1. fen piperazine – 1 a – carboxylic acid series derivates is characterized in that, said fen piperazine – 1 – carboxylic acid series derivates is selected from the compound shown in the following structural formula 1-19:
2. the preparation method of fen piperazine – 1 a – carboxylic acid series derivates according to claim 1 is characterized in that, may further comprise the steps:
1. will from pseudomonas, in sulfur oxychloride solution, reflux and distill by isolated phenazine-1-carboxylic acid, obtain activated intermediate;
2. be dissolved in methylene dichloride to activated intermediate, ice bath adds aminocompound and triethylamine down; Then, room temperature reaction spends the night, and uses thin layer chromatography to follow the tracks of reaction;
3. with revolving steaming, extraction, drying and purifying, obtain target compound.
3. the preparation method of Fen Qin – 1 – carboxylic acid series derivates according to claim 2 is characterized in that, backflow and the distillation of step described in 1., and return time is 6 hours, return time is to remove sulfur oxychloride with distillating method after 6 hours.
4. the preparation method of Fen Qin – 1 – carboxylic acid series derivates according to claim 2 is characterized in that, the aminocompound of step described in 2. is an equivalent or 0.5 equivalent; Described triethylamine is four equivalents.
5. the preparation method of Fen Qin – 1 – carboxylic acid series derivates according to claim 2 is characterized in that, step is revolved steaming, extraction, drying and purifying described in 3., and its method is following:
A, with revolve steam to remove desolvate after, add ETHYLE ACETATE in the solid product and extremely dissolve fully with water, the volume ratio of ETHYLE ACETATE and water is: 2:1;
Organic layer is obtained in b, extraction repeatedly;
C, add anhydrous sodium sulfate drying in the organic layer and spend the night;
D, remove by filter siccative, use Rotary Evaporators to remove to desolvate and obtain bullion, obtain target compound through column chromatography purification; Through characterizing compounds, confirm as target compound.
6. the application of fen piperazine – 1 a – carboxylic acid series derivates according to claim 1 is characterized in that, fen piperazine – 1 – carboxylic acid series derivates is used as the active ingredient of the pesticide preparation of antimycotic gourd, fruit and vegetable that causes and diseases and pests of agronomic crop.
7. the application of fen piperazine – 1 a – carboxylic acid series derivates according to claim 1 is characterized in that, fen piperazine – 1 – carboxylic acid series derivates is used as the active ingredient of the pesticide preparation of anti-rice sheath blight disease.
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| CN103155926B (en) * | 2011-12-18 | 2014-04-23 | 深圳诺普信农化股份有限公司 | Sterilization composite based on phenazino-1-carboxylicacid |
| CN103155925B (en) * | 2011-12-18 | 2014-04-23 | 深圳诺普信农化股份有限公司 | Sterilization composite containing phenazino-1-carboxylic acid |
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| CN103360329B (en) * | 2013-07-18 | 2015-11-18 | 中国科学院南海海洋研究所 | One class compound phenazine and preparing the application in antitumor drug |
| CN103343150B (en) * | 2013-07-22 | 2015-10-07 | 上海农乐生物制品股份有限公司 | A kind of preparation method of azophenlyene-1-formyl hydrazine biological bactericide |
| CN104829544B (en) * | 2014-02-08 | 2017-12-26 | 上海泰禾国际贸易有限公司 | A kind of method for preparing the carboxylic acid of azophenlyene 1 |
| CN104045601A (en) * | 2014-06-23 | 2014-09-17 | 南京工业大学 | Method for synthesizing phenazine-1-carboxylic acid |
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| CN107880035B (en) * | 2017-11-07 | 2021-05-28 | 华南农业大学 | Preparation method and application of 1,3, 4-thia (oxa) diazole-phenazine-1-formamide compound |
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| EP0115394A2 (en) * | 1983-01-21 | 1984-08-08 | Merck Frosst Canada Inc. | Phenothiazone derivatives and analogs |
| EP0172744A2 (en) * | 1984-08-16 | 1986-02-26 | Development Finance Corporation Of New Zealand | Phenazinecarboxamide compounds |
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| EP0115394A2 (en) * | 1983-01-21 | 1984-08-08 | Merck Frosst Canada Inc. | Phenothiazone derivatives and analogs |
| EP0172744A2 (en) * | 1984-08-16 | 1986-02-26 | Development Finance Corporation Of New Zealand | Phenazinecarboxamide compounds |
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