CN103848797B - 2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide compound salifying method and application - Google Patents

2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide compound salifying method and application Download PDF

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CN103848797B
CN103848797B CN201410091119.4A CN201410091119A CN103848797B CN 103848797 B CN103848797 B CN 103848797B CN 201410091119 A CN201410091119 A CN 201410091119A CN 103848797 B CN103848797 B CN 103848797B
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acid
amido
ethyl
algae
phenyl thiazole
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CN103848797A (en
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徐效华
刘奇声
陶园园
谢龙观
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Nankai University
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Nankai University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • 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
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles

Abstract

The present invention relates to the salifying method of a kind of 2-(1-amido-ethyl)-N-phenyl thiazole-4-Carbox amide and derivative thereof and the application in control algae thereof.Compound shown in general structure; Wherein, X is HCl, H 2sO 4, H 3pO 4, toxilic acid, fumaric acid, tosic acid, citric acid, oxalic acid, oxysuccinic acid, acetic acid, tartrate etc.; R, R 1, R 2, R 3for H, halogen, C2 ~ C5 alkyl, sulfonic group, alkoxyl group, nitro, amino, the amino etc. of replacement; This compounds salifying method synthesis technique is comparatively easy, is applicable to suitability for industrialized production, has the potentiality being developed to efficient algicide.To fresh water algae Chlorophyta microcystic aeruginosa, scenedesmus obliquus, Chlorella pyrenoidesa etc., there is excellent wide spectrum algicdal activity, compared with traditional algicide, there is high reactivity, environmental friendliness, feature to aspects such as non-target organism toxicity are low, synthetic method is simple, is the of great value algicide lead compound of a class.

Description

2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide compound salifying method and application
Technical field
The present invention relates to a kind of 2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide compound salifying method and killing the application of water-bloom algae aspect.
Background technology:
Bacillamide4 just assigned to as far back as 1976 from a kind of thermophilic actinomyces (ThermoactinomycesstrainTM-64).Regrettably, less owing to being separated the amount obtaining compound, their biological activity does not all obtain paying close attention to and research for a long time.Our seminar achieves first for Bacillamide4 that it is complete synthesis, by to Bacillamide4 composition optimizes, find that a class has the algicdal activity compound (Xie Longguan of application prospect, the thiazolium compoundss such as Xu Xiaohua, Wei Zhigang kill algae aspect application Chinese invention patent CN201210112982.4 algae).
Utilizing the natural product with allelopathy to become pesticide new product as lead compound exploitation is the new trend occurred at present.Compared with conventional inorganic cupric ion algicide, natural product has easy degraded, environmentally friendly, low to non-target organism toxicity, the feature of killing the algae spectrum aspect such as wide as agricultural chemicals.
Before our seminar on working foundation, considering that algicide is finally applied is at aquatic ecosystem, and (2-(1-amido-ethyl)-N-phenyl thiazole-4-Carbox amide salify have not been reported.
Summary of the invention
The object of this invention is to provide a kind of salifying method of thiazole compound.By salify will (2-(1-amido-ethyl)-N-phenyl thiazole-4-Carbox amide be prepared into water soluble salt, stability and the algicdal activity of compound can be improved on the one hand, on the other hand for the green formulation of developing water dissolubility in future lays the foundation.The present invention studies the various salifying method of this compounds, have chosen three kinds of typical single-cell algae class testings (biological activitys of 2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide type series derivates such as microcystic aeruginosa, Chlorella pyrenoidesa, scenedesmus obliquus.And propose these type of chemicals and can be used for preventing and treating wawter bloom algae.Biological activity determination after thiazole compound salify in the present invention shows that it has the potential being developed to efficient algicide.
Thiazole compound provided by the invention has the compound shown in general structure (I):
Wherein, X is HCl, H 2sO 4, H 3pO 4, toxilic acid, fumaric acid, tosic acid, citric acid, oxalic acid, oxysuccinic acid, acetic acid, tartrate etc.;
R, R 1, R 2, R 3for H, halogen, C2 ~ C5 alkyl, sulfonic group, alkoxyl group, nitro, amino, the amino etc. of replacement;
Reported (CN101119723A) in the patent that the series derivates synthetic method that the different group of compound 2-(1-amido-ethyl)-N-phenyl thiazole-4-methane amide phenyl ring replaces had been delivered before our seminar, no longer specifically set forth at this.The step that the method for one-tenth hydrochloride is concrete is:
2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide compound is fully dissolved in dehydrated alcohol, build hydrochloric acid generating unit, anhydrous NaCl and strong sulfuric acid response, import in above-mentioned ethanolic soln after producing hydrogen chloride gas drying, there is crystallization gradually until saturated, be spin-dried for solvent and obtain solid.
The salifying method of compound 2-provided by the invention (1-amido-ethyl)-N-phenyl thiazole-4-carboxamides derivatives, and measure it respectively and killing the application in algae, compared with traditional algicide, it has high reactivity, easily degraded, feature to aspects such as non-target organism toxicity are low; Synthetic method is simple, is the of great value algicide lead compound of a class.
Embodiment
The detailed synthetic method of the compound that the present invention relates to is shown in the ChinChemLett that this seminar has delivered, 2009,20,1195-1197.
Reported (CN101119723A) in the patent that the series derivates synthetic method that the different group of compound 2-(1-amido-ethyl)-N-phenyl thiazole-4-methane amide phenyl ring replaces had been delivered before our seminar.
Pass into the hydrogen chloride gas crystallization of existing system in the ethanol solution of body compound 2-(1-amido-ethyl)-N-phenyl thiazole-4-methane amide before the synthesis, its hydrochloride can be prepared easily.
The series derivates synthesized when R is different substituents is called after M-1 ~ M-5 respectively:
Substitutive derivative when table 1R is different functional groups
Its biological activity to three kinds of algaes such as scenedesmus obliquus (Scenedesmusobliquus), Chlorella pyrenoidesa (Chlorellapyrenoidose), microcystic aeruginosas (Microcystisaeruginosa) is tested respectively when R is different substituents:
Determination of activity experiment is carried out in the Erlenmeyer flask of 100mL, specifies that final algae liquid cumulative volume is 40mL.Measure the density X of algae kind, calculating initial algae density is the algae kind volume YmL that 5.5 × 105/mL needs, getting YmL algae kind adds in 100mL triangular flask, adding substratum again makes cumulative volume be 40mL, substratum medicine 20ulDMSO dissolves, be added in algae culture system, drug concentration is the ultimate density of supporting in algae in system.Arrange control group, control group is the algae kind only adding 20ulDMSO process simultaneously.Each concentration process arranges 2 repetitions, and each replicate measurement 10 secondary data, each concentration obtains 20 results altogether.20 secondary data each concentration obtained are averaged light absorption value corresponding to the algae kind density that namely obtains each concentration, obtain the algae kind density of algae kind carrying out converting afterwards.
Note: add algae kind volume computing formula: Y=5.5 × 105 × 40/X
Data processing and evaluation method: by medicine to the curve of logarithmic value (Lg (the C)) gained of the relatively set medicine series concentration of the inhibiting rate IR% of algae and corresponding equation, solve the half effect concentration value EC of medicine to experiment algae 72h 50, 72h.Medicine is to the growth inhibiting half effect concentration EC of algae 50value is the drug concentration of instigating experiment algae to suppress 50%.EC 50be worth less, the rejection ability of medicine to algae is stronger.
Note: inhibiting rate formula is: IR (%)=(1-N/N 0) × 100
Wherein: IR-inhibiting rate; N-adds medicine group algae density; N 0-control group algae density
Table 2 different substituents is to the determination of activity EC of three kinds of algaes 50(mg/L)
The compound M-2 choosing above-mentioned synthesis carries out into the embodiment 1 of hydrochloride method:
The systematic naming method of compound M-2 (2-(1-amido-ethyl)-N-(the bromo-phenyl of 4-)-thiazole-4-carboxamide (English: 2-(1-aminoethyl)-N-(4-bromophenyl) thiazole-4-carboxamide, and it is as follows to be made hydrochloride method:
S-1 becomes the preparation method of hydrochloride: in 50ml round-bottomed flask precise lmmol series derivates and add 25ml dehydrated alcohol and fully dissolve, build hydrochloric acid generating unit: take about 30g anhydrous NaCl and be positioned in there-necked flask, and drip the vitriol oil wherein gradually, after producing hydrogen chloride gas gradually, import in ethanolic soln by after hydrogen chloride gas drying, have crystallization gradually until saturated.Be spin-dried for solvent and obtain solid.
The series salt hydrochlorate S-1 ~ S-5 synthesized when R1-R4 is different substituents is as follows
Several derivant hydrochloric acid salt of table 3
The biological activity determination data of the series salt hydrochlorate synthesized when R is different substituents to scenedesmus obliquus, Chlorella pyrenoidesa, microcystic aeruginosa are as follows:
Table 4 different substituents is to the determination of activity EC of three kinds of algaes 50(mg/L)
Choose the compound M-2 of above-mentioned synthesis and the embodiment 2 of different acid (organic acid and mineral acid) salifying method:
In 50ml round-bottomed flask precise lmmol series derivates and add 25ml dehydrated alcohol and fully dissolve, build hydrochloric acid generating unit: the oxalic acid adding 1.2mmol wherein, have crystallization gradually until saturated.Be spin-dried for solvent and obtain solid.
Table 5X is that band derivative got by different organic acids salt
When X be different organic acids salt replace time synthesis series salt Y-1 ~ Y-8, measure that it is as follows to the biological activity determination data of scenedesmus obliquus, Chlorella pyrenoidesa, microcystic aeruginosa respectively:
Biological activity test method is identical with the activity test method of above-mentioned M series derivates, is not described in detail in this.
Table 6 different organic acids salt compound is to the determination of activity EC of three kinds of algaes 50(mg/L)
Experimental result shows: the solvability not only increasing water, and substantially increases algicdal activity, and current Inorganic Copper ion algicide is to the EC of microcystic aeruginosa 50for 1.5mg/L, but because it is to hydrobiological high toxicity and the high residue in water body, current Inorganic Copper ion algicide prohibits the use.And our series compound of synthesis can replace cupric ion algicide completely.

Claims (5)

1. a salt for 2-(1-amido-ethyl)-N-phenyl thiazole-4-Carbox amide, is characterized in that it is the compound with following general structure:
Wherein, R substituent is Br, F, Cl, time, R 1, R 2, R 3be H, X is HCl;
R 2when substituting group is Br, R, R 1, R 3be H, X is H 2sO 4, H 3pO 4, toxilic acid, fumaric acid, tosic acid, citric acid, oxalic acid, oxysuccinic acid, acetic acid, tartrate.
2. a pesticide composition, is characterized in that: containing salt according to claim 1 at agriculturally acceptable salt as activeconstituents and it is at agriculturally acceptable carrier.
3. a salt salifying method for 2-according to claim 1 (1-amido-ethyl)-N-phenyl thiazole-4-Carbox amide, is characterized in that comprising the following steps:
1) precursor compound 2-(1-amido-ethyl)-N-phenyl thiazole-4-methane amide is synthesized;
2) pass into the hydrogen chloride gas crystallization of existing system, prepare its hydrochloride.
4. salt according to claim 1 is for the preparation of the application killing algae medicine aspect.
5. application according to claim 4, is characterized in that: described algae is scenedesmus obliquus, Chlorella pyrenoidesa, microcystic aeruginosa.
CN201410091119.4A 2014-03-13 2014-03-13 2-(1-amido-ethyl)-N-phenyl thiazole-4-benzamide compound salifying method and application Active CN103848797B (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4365989A (en) * 1982-01-27 1982-12-28 Chevron Research Company 2-Thiocyanomethylthio-4,4-dialkyl-5-substituted-thiazoline fungicides
CN1646506A (en) * 2002-02-04 2005-07-27 拜尔农作物科学股份公司 Difluoromethyl thiazolyl carboxanilides
CN102633741A (en) * 2012-04-18 2012-08-15 南开大学 Application of thiazole compounds in aspect of killing fresh water algae

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10167911A (en) * 1996-12-03 1998-06-23 Takeda Chem Ind Ltd Algicide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4365989A (en) * 1982-01-27 1982-12-28 Chevron Research Company 2-Thiocyanomethylthio-4,4-dialkyl-5-substituted-thiazoline fungicides
CN1646506A (en) * 2002-02-04 2005-07-27 拜尔农作物科学股份公司 Difluoromethyl thiazolyl carboxanilides
CN102633741A (en) * 2012-04-18 2012-08-15 南开大学 Application of thiazole compounds in aspect of killing fresh water algae

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
(-)-Bacillamide C: the convergent approach;Wang wei et al;《Organic & Biomolecular Chemistry》;20091126;第8卷;第529-532页 *
Tryptamine derived amides with thiazole ring system from Thermoactinomyces strain TA66-2;Cagla Akmemis Korkmaz et al;《Magnetic Resonance in Chemistry》;20071126;第46卷;第80-83页 *

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