CN108558857A - A kind of thiazole piperidines furanone derivatives and its preparation method and application - Google Patents
A kind of thiazole piperidines furanone derivatives and its preparation method and application Download PDFInfo
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- 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
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Abstract
The present invention provides a kind of thiazole piperidines furanone derivatives and its preparation method and application, and the present invention relates to thiazole piperidines Furanones compound, its its chemical structure of general formula is shown in 7 1g of formula：
Description
Technical field
Technical scheme of the present invention is related to the derivative of the furanone of piperidines containing thiazole.
Background technology
Furanone be witchweed lactone important activity structure (Dieckmann et al.J.Organ.Chem., 2018,
83(1)：125-135), witchweed lactone is widely present in many unifacial leaves and the root juice of dicotyledon, is a kind of
Novel plant hormone.The witchweed lactone of natural source is unstable, extraction is difficult, fully synthetic difficulty is big, is based on witchweed alcohol
(Strigol) it carries out structure to simplify derivative A- ring structure aromatization products GR24 being metastable active analogue thereof, often quilt
Positive control (Modi S, et al.Scientific Reports, 2017,7 (1) as activity comparison：17606-
17617).Thiazole piperidines have a plurality of types of bioactivity and extensive purposes (Pasteris R J, et
al.WO 2008091580.2008-07-31).The medicinal activity for reporting such compound for the first time in 2004, can not only change
Become blood vessel tension, also can effectively treat the disease caused by the imbalance of blood vessel endothelium growth factor regulative mechanism and EP3 by
The disease of body control, also has remarkable effect (Knox P, et al.WO to the treatment of tumour and mullerianosis illness
2004058750.2004-07-15).In pesticide field, E.I.Du Pont Company is obtained by the structure optimization in high flux screening and later stage
There are the thiazole -2- piperidines fluorine thiazole pyrrole ethyl ketones of specific action to downy mildew and late blight, this compound is to a variety of works
Oomycete pathogen on object has excellent fungistatic effect, and (Yang Ji's spring waits pesticides, 2013,52 (1)：50-52).2016,
Hiroshi reports the 11 membered rings-thiazole -2- piperidine compounds of a kind of efficient sterilizing, to the bacteriostatic activity of potato immunological disease
Reach 100% (15832228 9.2017-06-21 of Wada H, et al.EP)；Applicant seminar, which has also carried out, is based on thiazole
The New pesticides discovery of piperidines is studied.
For find and find ultra high efficiency, wide spectrum, low toxicity, low ecological risk and with the new guide of existing pesticide no interactions resistance
Compound, the present invention utilize the principle of pesticide molecule design, design to synthesize the derivative of a kind of furanone based on thiazole piperidines
Object has been carried out at the same time the screening and evaluation of the bioactivity of system, to provide new candidate chemical combination for preventing and kill off for disease pest and weed
Object.
Invention content
The technical problem to be solved by the present invention is to：The synthetic method of a new class of thiazole piperidines furanone derivatives is provided
And its regulation and control agricultural, gardening, health and forestry pest, plant seed germination, the bioactivity of the phytopathy original and its measurement side
Method, while application of these compounds in agriculture field, horticultural field, field of forestry and health field being provided.
Technical solution is used by the present invention solves the technical problem：With agriculture field, horticultural field, field of forestry
The chemical structure of general formula of the thiazole piperidines Furanones compound of desinsection, bactericidal activity, seed development regulation activity is shown in formula 7-1g：
Wherein, R1It is selected from：Hydrogen, C1-C6Alkyl, C1-C6Halogenated alkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6
Alkenyl, C2-C6Halogenated alkenyl, C2-C6Alkynyl, C2-C6Halo alkynyl, hydroxyl, C3-C6Naphthenic base, substituted piperidin-1-yl, quilt
The phenyl or C that substituted morpholine -1- bases, substituted nafoxidine -1- bases, phenyl or halogen replaces1-C6It is alkyl-substituted
Phenyl or C1-C6The phenyl or C of halogenated alkyl substitution3-C6The phenyl of naphthenic base substitution or the phenyl or C of nitro substitution2-C6Alkene
The phenyl or C of base substitution2-C6The phenyl or C of halogenated alkenyl substitution3-C6The phenyl or C of cycloalkenyl group substitution2-C6Alkynyl substituted
Phenyl or C2-C6The phenyl or C of halo alkynyl substitution3-C6Phenyl, pyridyl group or the pyridine of halogen substitution of cycloalkynyl radical substitution
Base or C1-C6Alkyl-substituted pyridyl group or C1-C6The pyridyl group or C of halogenated alkyl substitution3-C6The pyridine of naphthenic base substitution
Base or the pyridyl group or C of nitro substitution2-C6The pyridyl group or C of alkenyl substitution2-C6The pyridyl group or C of halogenated alkenyl substitution3-
C6The pyridyl group or C of cycloalkenyl group substitution2-C6The pyridyl group or C of alkynyl substituted2-C6The pyridyl group or C of halo alkynyl substitution3-C6
The pyrimidine radicals or C that pyridyl group, pyrimidine radicals or the halogen of cycloalkynyl radical substitution replace1-C6Alkyl-substituted pyrimidine radicals or C1-C6Halogen
The pyrimidine radicals or C of substituted alkyl substitution3-C6The pyrimidine radicals of naphthenic base substitution or the pyrimidine radicals or C of nitro substitution2-C6Alkenyl takes
The pyrimidine radicals or C in generation2-C6The pyrimidine radicals or C of halogenated alkenyl substitution3-C6The pyrimidine radicals or C of cycloalkenyl group substitution2-C6Alkynyl takes
The pyrimidine radicals or C in generation2-C6The pyrimidine radicals or C of halo alkynyl substitution3-C6Cycloalkynyl radical substitution pyrimidine radicals, it is substituted contain 1 or
Five yuan of 2 N atoms or six membered heteroaryl, substituted five yuan containing 1 or 2 S atom or six membered heteroaryl contain 1 or 2
Substituted five yuan of a O atom or six membered heteroaryl, substituted five yuan or hexa-atomic miscellaneous containing 1 N atom and 1 S atom
Aryl, substituted five yuan or six membered heteroaryl, the quilt containing 2 N atoms and 1 S atom containing 1 N atom and 1 O atom
Five yuan or six membered heteroaryl, substituted five yuan or six membered heteroaryl containing 2 N atoms and 1 O atom of substitution；Above-mentioned five
Member or six membered heteroaryl are selected from：Substituted furyl, thienyl, pyrrole radicals, imidazole radicals, pyrazolyl, thiazolyl, isothiazole
Ji, oxazolyl, isoxazolyl, oxadiazolyls, thiadiazolyl group, pyridyl group, pyridazinyl, pyrimidine radicals, pyrazinyl, triazine radical, tetrazine
Base, indyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazole base, benzothiazolyl, benzo
Thiadiazolyl group, benzoxazolyl, the quinolyl of isomerization, the isoquinolyl of isomerization, phthalazinyl, quinoxalinyl, quinazolyl,
The silicon substrate of cinnoline base or naphthyridines base, alkyl or alkenyl substitution；
Halogen is fluorine, chlorine, bromine or iodine in above-mentioned definition；
The alkyl, alkenyl or alkynyl are straight chain or branch alkyl；Alkyl itself or portion as other substituent groups
It is selected from methyl, ethyl, propyl, butyl, amyl, hexyl and its isomers, isomers is selected from isopropyl, isobutyl group, Zhong Ding
Base, tertiary butyl, isopentyl or tertiary pentyl；
The halogenated alkyl group is selected from the group containing one or more identical or different halogen atoms, the alkyl halide
Base is selected from CH2Cl、CHCl2、CCl3、CH2F、CHF2、CF3、CF3CH2、CH3CF2、CF3CF2Or CCl3CCl2；
Described naphthenic base itself or as other substituent groups part be selected from cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl；
Described alkenyl itself or as other substituent groups part be selected from vinyl, allyl, 1- acrylic, butene-2-
Base, butylene -3- bases, amylene -1- bases, amylene -3- bases, hexene -1- bases or 4- methyl-3-pentenyls；
Described alkynyl itself or as other substituent groups part be selected from acetenyl, propine -1- bases, propine -2- bases, fourth
Alkynes -1- bases, crotonylene-base, 1- methyl -2- butynyls, hexin -1- bases or 1- ethyl -2- butynyls；
The enantiomeric form and its mixture of thiazole piperidines furanone derivatives 7-1g, the optical isomer are pair
Reflect isomers or cis-trans-isomer；
The geometric isomer of thiazole piperidines furanone derivatives 7-1g, i.e. (R)-(S) isomery and its mixture；
The atropisomer and its mixture of thiazole piperidines furanone derivatives 7-1g.
R1It preferably is selected from：Hydrogen, allyl, propargyl, goes back propyl at methyl.
The synthetic method of the thiazole piperidines furanone derivatives 7-1g of the present invention is as follows：
Wherein, substituent R1It is defined as described above；The synthesis step of general formula compound is as follows：
A. the preparation of intermediate 7-16：
Intermediate 7-16 under starting material 7-15 and diethyl carbonate by reacting preparation；Starting material 7-15 and intermediate 7-
Substituent R in 161It is defined as described above；
B. the preparation of intermediate 7-17：
Intermediate 7-17 reacts preparation with bromoethyl acetate by intermediate 7-16；Substituent R in intermediate 7-171Determine
It is adopted as previously described；
C. the preparation of intermediate 7-18：
Intermediate 7-18 is prepared in alcohol solvent by sodium borohydride reduction by intermediate 7-17, in the intermediate 7-18
Substituent R1It is defined as described above；Reducing agent sodium borohydride can be substituted by other reducing agents, and etoh solvent can be corresponding by other
Solvent substitute；
D. the preparation of intermediate 7-19：
Intermediate 7-19, which is reacted by intermediate 7-18 under the action of EDC and copper chloride, to be made, in the intermediate 7-19
Substituent R1It is defined as described above；
E. the preparation of thiazole piperidines furanone derivatives 7-1g：
Thiazole piperidines furanone derivatives 7-1g by intermediate 7-19 in the presence of diisopropylamino lithium with Ethyl formate
It reacts and is made under potassium carbonate and N-Methyl pyrrolidone effect with bromo- -2 (5H) -one of 3- methylfurans of 5- again after reaction, it is described
Substituent R in thiazole piperidines furanone derivatives 7-1g1It is defined as described above.
Work as R1For Boc when, the specific thiazole piperidines furanone derivatives 7-1g in part of the invention synthetic route citing such as
Under：
The present invention the synthesis of thiazole piperidines furanone derivatives 7-1g and the specific method of biological activity determination be divided into
Lower step：F. the preparation of compound 7-16：
The method of reference literature improves (Sakurai H, et al.Tetrahedron Letters, 1980,21 (20)：
1967-1970)；By 0.10 gram of compound 7-15,0.32 mM is dissolved in 15 milliliters of diethyl carbonate, under condition of ice bath to
0.02 gram of sodium hydride is added in reaction system, 0.48 mM, ice bath is removed after addition, is heated to reflux under 95 degrees Celsius
3 hours, the reaction was complete for TLC detections；20 milliliters of saturated ammonium chloride solution, 3 × 20 milli of ethyl acetate extraction is added to reaction system
It rises, ethyl acetate layer is washed with saturated sodium-chloride again, merges organic phase, anhydrous sodium sulfate drying.It filters, be concentrated under reduced pressure, through column
Chromatograph VPetroleum ether∶VEthyl acetatePurify to obtain target product 7-16 at=5: 1；Yellow oily, yield：90%；Amount prepared by compound 7-16 and
The volume of reaction vessel is expanded or shunk by corresponding proportion.
G. the preparation of compound 7-17：
The method of reference literature improves (Zhang G, et al.J.American Chem.Soc., 2016,138 (25)：
7932-7938)；By 0.40 gram of compound 7-16,1.05 mMs are dissolved in 25 milliliters of dry THF, under condition of ice bath to
0.06 gram of sodium hydride is added in reaction bulb, 1.57 mMs, continues stirring 10 minutes, then 0.26 gram of bromoacetate is added dropwise,
It 1.57 mMs, flows back 3 hours in 90 degrees Centigrades, the reaction was complete for TLC detections；It is molten that saturated ammonium chloride is added to reaction system
20 milliliters of liquid, ethyl acetate extract 3 × 20 milliliters, and ethyl acetate layer is washed with saturated sodium-chloride again, merge organic phase, anhydrous sulphur
Sour sodium drying.It filters, be concentrated under reduced pressure, through column chromatography, VPetroleum ether∶VEthyl acetatePurify to obtain target product 7-17 at=6: 1；Yellow oily, production
Rate：92%；The volume of amount and reaction vessel prepared by compound 7-17 is expanded or shunk by corresponding proportion.
H. the preparation of compound 7-18：
By 0.24 gram of compound 7-17,0.51 mM is dissolved in 15 milliliters of absolute ethyl alcohol, to reaction bulb under condition of ice bath
In be added portionwise 0.03 gram of sodium borohydride, 0.77 mM, after addition, continue stirring 10 minutes, TLC detection reaction knots
Beam；20 milliliters of saturated sodium bicarbonate is added into reaction system to be quenched, ethyl acetate extracts 3 × 25 milliliters, and ethyl acetate layer is again
It is washed with saturated sodium-chloride, merges organic phase, anhydrous sodium sulfate drying；It filters, be concentrated under reduced pressure, through column chromatography, VPetroleum ether∶VEthyl acetate
Purify to obtain target compound 7-18 at=3: 1；Colorless oil, yield：85%；The body of amount and reaction vessel prepared by compound 7-16
Product is expanded or shunk by corresponding proportion.
I. the preparation of compound 7-19：
The method of reference literature improves (Sakurai H, et al.Tetrahedron Letters, 1980,21 (20)：
1967-1970)；By 0.11 gram of compound 7-18,0.24 mM is dissolved in 15 milliliters of toluene, then successively to reaction system
Addition 1- ethyls-(3- dimethylaminopropyls) carbodiimide, 0.08 gram of abbreviation EDC, 0.48 mM, 0.02 gram of copper chloride,
It 0.12 mM, after addition, flows back 4 hours in 80 degree Celsius of -100 degrees Centigrade, the reaction was complete for TLC detections.Directly
Suction filtered through kieselguhr, reduced pressure, through column chromatography, VPetroleum ether∶VEthyl acetatePurify to obtain target compound 7-19 at=5: 1；Yellow oily, production
Rate：89%；The volume of amount and reaction vessel prepared by compound 7-16 is expanded or shunk by corresponding proportion.
J. the preparation of thiazole piperidines furanone derivatives 7-1g：
The method of reference literature improves (Brooks D W, et al.J.Organ.Chem., 1985,50 (5)：628-
632)；Compound 7-19 is dissolved in 10 milliliters of dry tetrahydrofuran for 0.24 mM, it is anti-to be placed in -70 degrees Celsius of low temperature
It answers in slot, then 0.36 milliliter of the dropwise addition diisopropylamino lithium (LDA) into reaction system, 0.72 mM, after being added dropwise, after
After continuous stirring 3 hours, then 0.18 gram of Ethyl formate is added dropwise into reaction bulb, i.e., 2.4 mMs, after addition, is warming up to room
Temperature is stirred overnight；15 milliliters of saturated ammonium chloride solution is added after the reaction was complete in TLC detections, and ethyl acetate extracts 3 × 15 milliliters,
Ethyl acetate layer is washed with saturated sodium-chloride again, merges organic phase, anhydrous sodium sulfate drying；It filters, be concentrated under reduced pressure, obtain thick centre
Body, the crude intermediate directly cast single step reaction；
By in 0.21 mM of N-Methyl pyrrolidone (NMP) for being dissolved in 4 milliliters of crude intermediate, bromo is then sequentially added
Bromo- -2 0.42 mM of (5H) -one of 3- methylfurans of compound 5-, 0.15 gram of Anhydrous potassium carbonate, i.e., 1.05 mMs, have been added
It is stirred at room temperature 3 hours after finishing, TLC detection reactions terminate, and 20 milliliters of water, 3 × 25 milli of ethyl acetate extraction is added to reaction system
It rises, ethyl acetate layer is washed with saturated sodium-chloride again, merges organic layer, anhydrous sodium sulfate drying；It filters, be concentrated under reduced pressure, through column layer
Analysis, VPetroleum ether∶VEthyl acetatePurify to obtain target product 7-1g, yellow oily, yield at=5: 1：75%；Amount prepared by compound 7-16 and
The volume of reaction vessel is expanded or shunk by corresponding proportion.
The synthesis of thiazole piperidines furanone derivatives and the specific method of biological activity determination of the present invention is divided into following
Step：
K. the bactericidal activity of thiazole piperidines furanone derivatives 7-1g of the invention and intermediate measures：
The sterilization of the thiazole piperidines furanone derivatives 7-1g and intermediate of the present invention or bacteriostatic activity use thalli growth
Rate measuring method, the specific steps are：1.8 milligrams of samples are taken to be dissolved in 2 drop n,N-Dimethylformamide, then with containing a certain amount of
The aqueous solution of polysorbas20 emulsifier is diluted to the medicament of 500 mcg/mls, and reagent agent is aseptically respectively drawn to 1 milli
It rises in culture dish, then is separately added into 9 milliliters of PDA culture mediums, 50 mcg/ml drug containing tablets are made after shaking up, with 1 milli of addition
The tablet for rising aqua sterilisa does blank control, cuts bacterium disk along mycelia outer rim with 4 millimeters of card punch of diameter, moves to drug containing tablet
On, in equilateral triangle to put, often processing is repeated 3 times, and culture dish is placed on culture in 24 ± 1 degrees Celsius of constant incubators, is waited for
Control colony diameter investigates each processing bacterium disk extension diameter after expanding to 2-3 centimetres, average, calculated compared with blank control
Opposite bacteriostasis rate, for trying the kind that strain is most of typical plant pathogen that field actually occurs in China's agricultural production,
Its code name and title are as follows：AS：Tomato early blight bacterium, Latin are entitled：Alternaria solani、BC：Gray mold of cucumber
Bacterium, Latin are entitled：Botrytis cinerea、CA：Peanut Cercospora bacteria, Latin are entitled：Cercospora
arachidicola、GZ：Fusarium graminearum, Latin are entitled：Gibberella zeae、PI：Phytophthora infestans,
Latin is entitled：Phytophthora infestans(Mont.)de Bary、PP：Botryosphaeria berengeriana f. sp, Latin are entitled：
Physalospora piricola、PS：Rhizoctonia solani Kuhn, Latin are entitled：Pellicularia sasakii、RC：Cereal
Rhizoctonia, Latin are entitled：Rhizoctonia cerealis、SS：Sclerotinia sclerotiorum, Latin are entitled：Sclerotinia
sclerotiorum。
L. the measurement of witchweed lactone derivatives 7-1g of the invention to Seed Germination：
The mother liquor of each compound of 1 mg/ml configured is added to according to 1 ‰ ratio in MS culture mediums, system
At the MS tablets of 1 mcg/ml of final compound concentration, using the processing of solvent alternative compounds as blank control；Take appropriate examination
Required arabidopsis seed is tested, is placed it in 1.5 milliliters of centrifuge tubes；Following operation is carried out in superclean bench；By 1 milliliter
75% ethyl alcohol, which is added to, to be filled in seed-bearing centrifuge tube, and liquid is removed after shaking washing 30 seconds；Add 1 milliliter of sterile water washing 3~4
It is secondary and remove liquid；Add 1 milliliter of 15%NaClO, shake 8 minutes and removes liquid；Then 1 milliliter of sterile water washing 3~4 times again
And remove liquid；Arabidopsis seed after washing is planted in MS solid plates；Seed is placed in 4 degrees Celsius of refrigerator spring
It is observed after being cultivated 2 days in 21 ± 2 degrees Celsius, illumination in 16 hours, 8 hours dark environment after changing processing 3 days and counts seed
Sprouting situation calculates inhibition of seed germination rate.
The present invention beneficial effect be：Guide's optimization is carried out to thiazole piperidines furanone derivatives, and to thiazole piperidines furan
It mutters the screening for having carried out bacteriostatic activity and anti-phytoviral activity and inducing anti-disease activity of ketone derivatives 7-1g and intermediate.
The present invention illustrates that thiazole piperidines furanone derives by the way that specific preparation and biological activity determination embodiment are more specific
The synthesis of object 7-1g and intermediate and bioactivity and application, the embodiment are only used for illustrating the present invention and unrestricted
Invention, especially bioactivity is merely illustrative of, and unrestricted this patent, specific implementation mode are as follows：
Embodiment 1：The synthesis of compound 7-16：
The method of reference literature improves (Sakurai H, et al.Tetrahedron Letters, 1980,21 (20)：
1967-1970)；By 0.10 gram of compound 7-15,0.32 mM is dissolved in 15 milliliters of diethyl carbonate, under condition of ice bath to
0.02 gram of sodium hydride is added in reaction system, 0.48 mM, ice bath is removed after addition, is heated to reflux under 95 degrees Celsius
3 hours, the reaction was complete for TLC detections；20 milliliters of saturated ammonium chloride solution, 3 × 20 milli of ethyl acetate extraction is added to reaction system
It rises, ethyl acetate layer is washed with saturated sodium-chloride again, merges organic phase, anhydrous sodium sulfate drying.It filters, be concentrated under reduced pressure, through column
Chromatograph VPetroleum ether∶VEthyl acetatePurify to obtain target product 7-16 at=5: 1；Yellow oily, yield：90%.1H NMR (400MHz, CDCl3)δ
8.05 (s, 1H), 4.24-4.06 (m, 4H), 3.98 (s, 2H), 3.15-3.03 (m, 1H), 2.79-2.90 (m, 2H), 2.10-
2.08 (m, 2H), 1.72-1.62 (m, 2H), 1.41 (s, 12H), 1.18 (t, J=7.1Hz, 3H)13C NMR (100MHz,
CDCl3) δ 187.62,174.79,167.69,154.68,153.38,125.36,79.77,61.23,47.05,40.48,
32.14,28.44,14.13.HRMS (ESI-TOF) m/z calcd for C18H26N2NaO5S[M+Na+] 405.1460, found
405.1458；The volume of amount and reaction vessel prepared by compound 7-9 is expanded or shunk by corresponding proportion..
Embodiment 2：The synthesis of compound 7-17：
The method of reference literature improves (Zhang G, et al.Journal of the American Chemical
Society, 2016,138 (25)：7932-7938)；By 0.40 gram of compound 7-16,1.05 mMs are dissolved in dry THF
In 25 milliliters, 0.06 gram of sodium hydride is added under condition of ice bath into reaction bulb, 1.57 mMs, continues stirring 10 minutes, then drip
Add 0.26 gram of bromoacetate, 1.57 mMs, flow back 3 hours in 90 degrees Centigrades, the reaction was complete for TLC detections；To reaction
20 milliliters of saturated ammonium chloride solution is added in system, and ethyl acetate extracts 3 × 20 milliliters, and ethyl acetate layer is washed with saturated sodium-chloride again
It washs, merges organic phase, anhydrous sodium sulfate drying.It filters, be concentrated under reduced pressure, through column chromatography, VPetroleum ether∶VEthyl acetatePurify to obtain target at=6: 1
Product 7-17；Yellow oily, yield：92%.1H NMR (400MHz, CDCl3) δ 8.14 (s, 1H), 4.97-4.93 (m, 1H),
4.25-4.09 (m, 6H), 3.19-3.04 (m, 2H), 2.98-2.87 (m, 3H), 2.11 (d, J=12.3Hz, 2H), 1.80-
1.70 (m, 2H), 1.48 (s, 9H), 1.24 (t, J=7.1Hz, 3H), 1.17 (t, J=7.1Hz, 3H)13C NMR (100MHz,
CDCl3) δ 188.88,174.61,171.20,169.27,154.66,153.00,125.79,79.74,61.48,61.00,
51.27,40.41,32.76,32.12,32.07,28.43,14.11,14.00.HRMS (ESI-TOF) m/z calcd for
C22H32N2NaO7S[M+Na+] 491.1828, found 491.1825.
Embodiment 3：The synthesis of compound 7-18：
By 0.24 gram of compound 7-17,0.51 mM is dissolved in 15 milliliters of absolute ethyl alcohol, to reaction bulb under condition of ice bath
In be added portionwise 0.03 gram of sodium borohydride, 0.77 mM, after addition, continue to stir 10min, TLC detection reactions terminate.
20 milliliters of saturated sodium bicarbonate is added into reaction system to be quenched, ethyl acetate extracts 3 × 25 milliliters, and ethyl acetate layer is again with full
And NaCl, merge organic phase, anhydrous sodium sulfate drying；It filters, be concentrated under reduced pressure, through column chromatography, VPetroleum ether∶VEthyl acetate=3: 1
Purify to obtain target compound 7-18；Colorless oil, yield：85%.1H NMR (400MHz, CDCl3) δ 7.09 (s, 1H), 5.07-
5.04 (m, 1H), 4.26-4.00 (m, 5H), 3.72 (dd, J=7.0,1.1Hz, 1H), 3.46-3.41 (m, 1H), 3.13-3.08
(m, 1H), 2.92-2.82 (m, 2H), 2.70-2.56 (m, 2H), 2.10-2.01 (m, 2H), 1.75-1.64 (m, 2H), 1.47
(s, 9H), 1.30-1.07 (m, 6H)13C NMR (100MHz, CDCl3) δ 174.83,173.08,171.78,156.02,
154.70,113.90,79.65,70.93,60.92,60.77,47.39,40.50,33.02,32.28,28.44,14.14,
14.07.
Embodiment 4：The synthesis of compound 7-19：
The method of reference literature improves (Sakurai H, et al.Tetrahedron Letters, 1980,21 (20)：
1967-1970)；By 0.11 gram of compound 7-18,0.24 mM is dissolved in 15 milliliters of toluene, then successively to reaction system
Addition 1- ethyls-(3- dimethylaminopropyls) carbodiimide, 0.08 gram of abbreviation EDC, 0.48 mM, 0.02 gram of copper chloride,
It 0.12 mM, after addition, flows back 4 hours in 80 degree Celsius of -100 degrees Centigrade, the reaction was complete for TLC detections.Directly
Suction filtered through kieselguhr, reduced pressure, through column chromatography, VPetroleum ether∶VEthyl acetatePurify to obtain target compound 7-19 at=5: 1；Yellow oily, production
Rate：89%.1H NMR (400MHz, CDCl3) δ 7.13 (s, 1H), 4.18-3.98 (m, 6H), 3.83-3.64 (m, 1H), 3.11-
3.00 (m, 1H), 2.92-2.71 (m, 3H), 2.67-2.40 (m, 2H), 2.05-1.95 (m, 2H), 1.70-1.52 (m, 2H),
1.40 (s, 9H), 1.19-1.14 (m, 6H)13C NMR (100MHz, CDCl3) δ 175.44,171.68,171.14,154.69,
152.89,152.37,116.50,116.29,116.00,79.68,61.41,61.23,60.87,60.75,57.45,48.55,
47.47,40.65,40.57,33.31,32.19,31.46,28.45,14.14,14.10.HRMS (ESI-TOF) m/z calcd
for C22H33ClN2NaO6S[M+Na+] 511.1646, found 511.1645.
Embodiment 5：The synthesis of compound 7-1g：
The method of reference literature improve (Brooks D W, et al.The Journal of Organic Chemistry,
1985,50 (5)：628-632)；Compound 7-19 is dissolved in 10 milliliters of dry tetrahydrofuran for 0.24 mM, is placed in -70
Degree Celsius low temperature reaction vessel in, then into reaction system be added dropwise LDA0.36 milliliters, 0.72 mM, after being added dropwise, after
After continuous stirring 3 hours, then 0.18 gram of Ethyl formate is added dropwise into reaction bulb, i.e., 2.4 mMs, after addition, is warming up to room
Temperature is stirred overnight；15 milliliters of saturated ammonium chloride solution is added after the reaction was complete in TLC detections, and ethyl acetate extracts 3 × 15 milliliters,
Ethyl acetate layer is washed with saturated sodium-chloride again, merges organic phase, anhydrous sodium sulfate drying；It filters, be concentrated under reduced pressure, obtain thick centre
Body, the crude intermediate directly cast single step reaction；
Crude intermediate is dissolved in 4 milliliters of N-Methyl pyrrolidone for 0.21 mM, bromo chemical combination is then sequentially added
Bromo- -2 0.42 mM of (5H) -one of 3- methylfurans of object 5-, 0.15 gram of Anhydrous potassium carbonate, i.e., 1.05 mMs, after addition
It is stirred at room temperature 3 hours, TLC detection reactions terminate, and 20 milliliters of water are added to reaction system, ethyl acetate extracts 3 × 25 milliliters, second
Ethyl acetate layer is washed with saturated sodium-chloride again, merges organic layer, anhydrous sodium sulfate drying；It filters, be concentrated under reduced pressure, through column chromatography,
VPetroleum ether∶VEthyl acetatePurify to obtain target product 7-1g, yellow oily, yield at=5: 1：75%；Elemental analysis result found
(calcd.)：525.1678(525.1671[M+Na]+)；1H NMR (400MHz, CDCl3) δ 8.46 (d, J=0.9Hz, 1H),
7.87 (d, J=0.8Hz, 1H), 7.12-7.05 (m, 1H), 6.56 (s, 1H), 4.48-4.40 (m, 2H), 4.22 (br, 2H),
3.36-3.20 (m, 1H), 2.98-2.85 (m, 2H), 2.20-2.15 (m, 3H), 1.90-1.78 (m, 3H), 1.48 (s, 9H),
1.43 (t, J=7.1Hz, 4H)13C NMR (100MHz, CDCl3) δ 177.16,165.87,154.59,150.49,141.68,
135.11,130.03,119.76,109.92,98.57,79.84,77.25,61.51,41.45,32.01,28.46,14.34,
10.80.The volume of amount and reaction vessel prepared by compound 7-1g is expanded or shunk by corresponding proportion；Wherein, bromo compound
Substituent R2It is defined as described above.
Embodiment 6：The thiazole piperidines furanone derivatives 7-1g of the present invention and the Antibacterial Activity result of intermediate：
The code name and title for the frequently seen plants disease fungus that the present invention tests are as follows：AS：Tomato early blight bacterium, latin name
For：Alternaria solani、BC：Botrytis cinerea pers, Latin are entitled：Botrytis cinerea、CA：Peanut foxiness
Germ, Latin are entitled：Cercospora arachidicola、GZ：Fusarium graminearum, Latin are entitled：Gibberella
zeae、PI：Phytophthora infestans, Latin are entitled：Phytophthora infestans(Mont.)de Bary、PP：Apple
Fruit Target spot pathogen, Latin are entitled：Physalospora piricola、PS：Rhizoctonia solani Kuhn, Latin are entitled：
Pellicularia sasakii、RC：Rhizoctonia cerealis, Latin are entitled：Rhizoctonia cerealis、SS：Sclerotina Sclerotiorum in Winter Rape
Core germ, Latin are entitled：Sclerotinia sclerotiorum, these strains have representativeness well, can represent
The kind for most of pathogen that field occurs in agricultural production.
Thalli growth rate method measurement result is shown in Table 1, and table 1 shows in 50 mcg/ml, the thiazole piperazine that the present invention synthesizes
Pyridine furanone derivatives 7-1g and intermediate have different degrees of bactericidal activity.Compound 7-1g to tomato early blight bacterium AS and
The activity of phytophthora infestans PI is more than 20%, and positive control medicament GR24 is to the no activity of the two bacterium.Compound 7-
It is more than 10% to the activity of botrytis cinerea pers BC that 1g is higher by positive control medicament GR24 to the activity of botrytis cinerea pers BC.Change
It closes object 7-17 and 7-1g and work of the positive control medicament GR24 to peanut Cercospora bacteria CA is higher by the activity of peanut Cercospora bacteria CA
Property is more than 10%.Compound 7-17 and 7-1g is higher by positive control medicament GR24 to rice line to the activity of Rhizoctonia solani Kuhn PS
The activity of blight bacterium PS is more than 10%.Compound 7-1g is higher by positive control medicament GR24 to standing grain to the activity of Rhizoctonia cerealis RC
The activity of phizoctonia cerealis RC is more than 20%.Compound 7-17 and 7-1g is higher by positive control drug to the activity of Sclerotinia sclerotiorum SS
Agent GR24 is more than 20% to the activity of Sclerotinia sclerotiorum SS.Therefore, the compound of the present invention is compared with positive control GR24, by
In the difference of molecular structure and substituent group, unexpected high bactericidal activity is achieved.
Embodiment 7：Measurement knots of the witchweed lactone derivatives 7-1g and its intermediate of the present invention to Seed Germination
Fruit：
Under 1 μ g/mL concentration, the Seed Germination of Arabidopsis Pumila rate of blank control has reached 97%, the compound of the present invention 7-
The seed of arabidopsis is sprouted degree and is significantly reduced after 1g and its intermediate are handled, and only 10% or so seed can be sprouted, and big
Partial seed cannot be sprouted, and the phenomena of mortality occurs in seedling, have inhibition of seed germination activity very outstanding.This row chemical combination
Object also has certain inhibiting effect to the sprouting of China's Common Farmland Weeds seed.China's Common Farmland Weeds are selected from grass recklessly
Green pepper, hemp, artillery plant, volume stem smartweed, chenopodium ambrosiodies, small lamb's-quarters, it is miscellaneous with lamb's-quarters, summer cypress, alternanthera philoxeroides, Lindernia procumbens, concave head
Amaranth, North America amaranth, white amaranth, conjunction are by amaranth, long awns amaranth, water chestnut leaf amaranth, thorn amaranth, Amaranthus retroflexus, wrinkle fruit amaranth, amaranthus caudatus, feather cockscomb, four-o'clock, U.S.
Continent Phytolacca acinosa, Talinum crassifolium, fall certain herbaceous plants with big flowers potato, cerastium glomeratum, the seed of cowherb, water quality grass, charlock, land cress, bird's-pepper (pl. bird's-peppers), Nasturtium officinale,
Radix Isatidis, penny cress, coffee senna, Cassia, sensitive plant, Brazilian sensitive plant, medicago hispida, alfalfa, yellow sweet clover, white vanilla
Wooden slippers, white clover, red clover, Vicia Saliva L, window box oxalis, Carolina Cranesbill Herb, the fissure root of Beijing euphorbia, hairy euphorbia, America
Bright and beautiful grass, Euphorbia maculata, flowerofanhour root or herb, Herba Malvastri Coromandeliani, passion plant, passionflower, Opuntia ficus, single thorn cactus, cactus, safflower water
Amaranth, careless dragon, cicely, eryngo, field bindweed, Ipomoea cairica, Pharbitis purpurea, pharbitis nilChoisy, lantana, false Verbena officinalis, cloves sieve
The western eggplant of Le, datura, datura flower, solanum rostratum, noise made in coughing or vomiting, water eggplant, false acid pulp, henbane seed, broomwort, wall speedwell, Arab
Veronica, Veronica, feltwort, Plantago virginica, ribwort, Ambrosia trifida, folium artemisiae argyi artemisiifolia, Aster subulatus, Ageratum conyzoides,
Alpine yarrow, big bur beggar-ticks, bidens pilosa, Horseweed Herb, Soviet Union door white wine chrysanthemum, wild crowndaisy chrysanthemum, wild pool wormwood artemisia, Qiu Ying, Eupatorium adenophorum, annual fleabane herb,
Fragrant eupatorium herb, bidentis, smallflower galinsoga herb, coarse wool smallflower galinsoga herb, jerusalem artichoke, Mikania micrantha, guayule rubber, Solidago Canadensis, golden waist arrow, Europe
Climbing groundsel, sowthistle, sonchus oleraceus, maidenhair, marigold, spends more Zinnia, is plumage awns chrysanthemum, Wedelia trilobata, smooth grey teasel root chrysanthemum
Ear, Italian Siberian cocklebur, spiny cocklebur, Triticum tauschii, wild oat, carpetweed, field brome grass, rescuebrome, downy brome, sandbur, few flower
Sandbur, Paspalum distichum, lolium temulentum, Paspalum conjugatum, Panicum repens, Sorghum halepense, sudangrass, big drift, Eichhornia crassipes.The compound of the present invention 7-
1g and its intermediate do not have inhibiting effect to crop seed, and the crop is selected from：Paddy, wheat, barley, oat, corn, height
Fine strain of millet, sweet potato, potato, cassava, soybean, garden pea, broad bean, pea, mung bean, red bean, cotton, silkworm and mulberry, peanut, sesame, Xiang
Certain herbaceous plants with big flowers, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal hemp, tobacco, tomato, capsicum, radish, cucumber,
Chinese cabbage, celery, hot pickled mustard tuber, rape, green onion, garlic, watermelon, muskmelon, "Hami" melon, pawpaw, apple, citrus, peach, tea, wild vegetables, bamboo
Bamboo shoot, hops, pepper, banana, papaya, orchid, potted landscape.
Embodiment 8：Witchweed lactone derivatives 7-1g and its intermediate the answering in preparing composition pesticide of the present invention
With：
The witchweed lactone derivatives 7-1g and intermediate of the present invention can prepare composition pesticide, and the composition includes this
For the witchweed lactone derivatives 7-1g and its intermediate of invention as active constituent, the content of active constituent is 0.1 to 99.9%
The surfactant of weight, the solid or liquid adjuvants of 99.9 to 0.1% weight and optional 0 to 25% weight.
Embodiment 9：The thiazole piperidines furanone derivatives 7-1g and intermediate of the present invention is planted with antimicrobial combination in prevention
The application of object disease：
Any one in the thiazole piperidines furanone derivatives 7-1g and intermediate and commodity fungicide of the present invention or two
Kind combination forms bactericidal composition and is selected from for preventing agricultural and forestry and gardening plant disease, the commodity fungicide：Benzene
And thiadiazoles, tiadinil, it is abbreviated as TDL, tisocromide, first thiophene and lures amine, 4- methyl-1s, 2,3- thiadiazoles -5- formic acid, 4- first
Base -1,2,3- thiadiazoles -5- sodium formates, 4- methyl-1s, 2,3- thiadiazoles -5- Ethyl formates, DL- beta-aminobutyric acids, different thiophene bacterium
Amine, English are general entitled：Isotianil, 3,4-, bis- chloroisothiazole -5- formic acid, 3,4-, bis- chloroisothiazole -5- sodium formates, 3,
Bis- chloroisothiazole -5- Ethyl formates of 4-, virazole, antofine, Ningnanmycin or salicylic acid, cymoxanil, thiram, ziram,
Mancozeb, aliette, thiophanate-methyl, Bravo, enemy can pine, procymidone, fenpropidin, thiophanate methyl, thiophanate, smart first
White spirit, flumorph, dimethomorph, mefenoxam, benalaxyl-M, double chlorine zarilamid, flusulfamide, first flusulfamide, thiophene fluorine bacterium
Amine, flutolanil, tecloftalam, ring propionyl bacterium amine, cyflufenamid, fenhexamid, zarilamid, Silthiopham, furametpyr, pyrrole thiophene bacterium
Amine, mandipropamid, zoxamide, fenfuram, carboxin, chlozolinate, iprodione, Fluoxastrobin, dimoxystrobin, fluoxastrobin,
Kresoxim-methyl, SSF 126, orysastrobin, ZEN 90160, pyraclostrobin, trifloxystrobin, Enestroburin, alkene oxime amine, oxygen ring azoles, chaff
Bacterium azoles, Cyproconazole, difenoconazole, olefin conversion, efficient olefin conversion, epoxiconazole, benzoxazole, Fluquinconazole, Flusilazole, powder azoles
Alcohol, hexaconazole, glyoxalin, kind bacterium azoles, metconazole, nitrile bacterium azoles, penconazole, propiconazole, prothioconazoles, simeconazoles, Tebuconazole, four
Fluorine ether azoles, Triadimenol, triticonazole, bitertanol, probenazole, furidazol, imazalil, efficient imazalil, Prochloraz, fluorine bacterium
The white spirit of azoles, cyazofamid, Fenamidone, Evil imidazoles, pefurazoate, famoxadones, oxazole, hymexazo, Evil, Guardian, soil
Bacterium spirit, octhilinone, benthiozole, dodemorph, butadiene morpholine, tridemorph, fenpiclonil, fludioxonil, fluazinam, pyridine spot
It is oxime, ring pyridine bacterium amine, Boscalid, fluopicolide, pyridine bacterium amine, cyprodinil, fluorine mepanipyrim, ferimzone, mepanipyrim, phonetic mould
Amine, Fenarimol, nuarimol, chinomethionat, dithianon, ethoxyquin, oxyquinoline, the third oxygen quinoline, quinoxyfen,
Diethofencarb, iprovalicarb, benzene metsulfovax, Propamocarb, methasulfocarb, edifenphos, different rice blast net, pyrazophos, tolelofos-methyl, pest of going out
Element, kasugarnycin, polyoxin, Polyoxin, valida, jinggangmeisu, streptomysin, metalaxyl, furalaxyl, M 9834,
Ofurace, mebenil, carbendazim, benomyl, thiophanate-methyl, triazolone, bupirimate, dimethirimol, ethirimol, enemy
Bacterium pellet, captan, folpet, vinclozolin, fluoromide, dimethachlon, Bravo, Isoprothiolane, kitazine, Yekuzuo,
Pentachloronitrobenzene, Propineb, phosethyl-Al, sulphur, Bordeaux mixture, copper sulphate, copper oxychloride, cuprous oxide, Kocide SD,
Metrafenone, Pencycuron, diclomezin, Rabcide, pyroquilon, volution bacterium amine, tricyclazole, triforine, more fruit pyridines, the pungent salt of biguanides,
Iminoctadine, botran, benzene flusulfamide, toluene flusulfamide, K-281, fenaminosulf, oxolinic acide, probenazole, bronopol, iodine
Methane, enemy's line ester, dazomet, nemamort, lythidathion, fensulfothion, thionazin, dichlofenthion, fosthietan, kills line at metham-sodium
Prestige, vikane, dichloropropylene, dichloro-isonicotinic acid, allyl isothiazole；The present invention thiazole piperidines furanone derivatives 7-1g and in
Total mass percentage of the mesosome in the bactericidal composition is 1%-90%, and thiazole piperidines furanone of the invention derives
The ratio of object 7-1g and intermediate and aforementioned commodity fungicide is mass percent 1%: 99% to 99%: 1%；The sterilization group
The dosage form for closing object processing is selected from：Seed treatment emulsion, aqueous emulsion, big granula, microemulsion, water-soluble granule, soluble thick agent, water
Dispersive granule, poison grain, aerosol, blocky poison bait, sustained-release block, dense poison bait, CG/Encapsulated granule, micro-capsule suspension, Waterless Seed Dressing powder
Agent, missible oil, electrostatic spray agent, water-in-oil emulsion, oil in water emulsion, smoke candle, granula subtilis, smoke candle, smoke cartridge, smog stick,
Seed treatment suspending agent, smog piece, smog ball, granular poison bait, thermal fog, medicine paint, fine granule, oil suspending agent, oil-dispersing property pulvis,
Sheet poison bait, dense jelly sprinkle and pour agent, seed coat agent, liniment, suspended emulsion, film forming finish, soluble powder, seed treatment water
Soluble powder, ultra-low volume suspending agent, tracking pulvis, ultra low volume liquids, any one in wet-mixing kind water-dispersible powder；
The plant disease of the bactericidal composition prevention is selected from：Seedling blight of rice, tomato root rot, the late blight of potato, the black shin of tobacco
Disease, millet powdery mildew, downy mildew of garpe, downy mildew of lettuce, cucumber downy mildew, cucumber anthracnose；The bactericidal composition is applicable in
Plant be selected from：Paddy, wheat, barley, oat, corn, sorghum, sweet potato, potato, cassava, soybean, garden pea, broad bean, pea
Beans, mung bean, red bean, cotton, silkworm and mulberry, peanut, sesame, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut palm
Son, oil palm, sisal hemp, tobacco, tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tuber, rape, green onion, garlic, watermelon, muskmelon, Kazakhstan
Close melon, pawpaw, apple, citrus, peach, tea, wild vegetables, bamboo shoots, hops, pepper, banana, papaya, orchid, potted landscape.
Embodiment 10：The thiazole piperidines furanone derivatives 7-1g and intermediate of the present invention is with combinations of herbicides in prevention grass
Harmful application：
The present invention the present invention thiazole piperidines furanone derivatives 7-1g and intermediate with it is arbitrary in Commercial herbicides
One or two combination forms Herbicidal combinations for preventing agricultural and forestry and gardening plant crop smothering：Phenoxy carboxylic acid weeding
Agent such as 2,4-D butyl esters, 2 first, 4 chlorine；Aromatic oxygen-phenoxy group propionates class herbicide such as quizalofop-ethyl surely kills, cover grass energy；Dinitrobenzene
Amine herbicide such as trefanocide, Pendimethalin；Triazine such as Simanex, atrazine, prometryn, ametryn, bladex；Acyl
Amine herbicide such as alachlor, Acetochlor, pretilachlor, butachlor, propisochlor, isopropyl methoxalamine；Phenyl ureagroup herbicides are such as
Diuron, linuron, chlortoluron, isoproturon；Diphenyl ether herbicide for example acifluorfen, fomesafen, lactofen,
Fluoroglycofen-ethyl；The careless spirits of cyclic imide class herbicide such as Evil, Flumiclorac pentyl, flumioxazin；Sulfonylurea herbicide such as benzyl is phonetic
Sulphur is grand, tribenuron-methyl, monosulfmeturon, single phonetic sulphur ester, pyrazosulfuron, azoles Sulfometuron Methyl；Chloropropham such as benthiocarb, grass
Up to going out；Organic phosphates herbicide such as glyphosate, glufosinate-ammonium；Brominal, the ioxynil of other classification herbicide such as nitriles, benzoic acid
The Mediben of class herbicide, Imazethapyr, the imazamox of imidazolinone herbicide, the pyrimidine of pyrimidinylthiobenzoate herbicides
Salicylic acid, Nong Meili, sethoxydim, clethodim of cyclohexenone analog herbicide etc., Bentazon, the dichloroquinoline of heterocycle herbicide
Sour, clomazones, fluroxypramide, the dosage form of composition processing are selected from seed treatment emulsion, aqueous emulsion, big granula, microemulsion, water-soluble
Property granula, soluble thick agent, water-dispersible granules, poison grain, aerosol, blocky poison bait, sustained-release block, dense poison bait, CG/Encapsulated granule, micro-
Capsule suspension, Waterless Seed Dressing pulvis, missible oil, electrostatic spray agent, water-in-oil emulsion, oil in water emulsion, smoke candle, granula subtilis, cigarette
Mist candle, smoke cartridge, smog stick, seed treatment suspending agent, smog piece, smog ball, granular poison bait, thermal fog, medicine paint, fine granule,
Oil suspending agent, oil-dispersing property pulvis, sheet poison bait, dense jelly, sprinkle pour agent, seed coat agent, liniment, suspended emulsion, film forming finish, can
Soluble powder, seed treatment water solube powder, ultra-low volume suspending agent, tracking pulvis, ultra low volume liquids, wet-mixing kind are water-dispersed
Any one in property pulvis；The total mass percentage of the compound of the present invention in the composition is 1%-90%, this hair
Bright thiazole piperidines furanone derivatives 7-1g and the ratio of intermediate and commercially available agricultural chemical are that mass percent 1%: 99% arrives
99%: 1%；The control effect of medicament is good, these compositions have synergistic effect and summation action, do not find with antagonistic action
Composition.Above-mentioned medicament can be watered spraying and use；The applicable controlling object of these compositions is what China was planted extensively
The crop of the monocotyledon weed and broadleaf weed that crop field occurs, the crop field is selected from paddy, wheat, barley, oat, paddy
Son, sorghum, sweet potato, potato, cassava, soybean, broad bean, pea, garden pea, mung bean, red bean, cotton, crudefiber crop, silkworm and mulberry, peanut,
Rape, sesame, soybean, sunflower, beet, sugarcane, coffee, cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal hemp and flower
Grass, oil plant, sugar material, Chinese medicine, tea, vegetables, wild vegetables, bamboo shoots, flowers, ornamental plant, hops, pepper, seedling and tobacco leaf,
Flue-cured tobacco, air-curing of tobacco leaves, suncured tabacco, tomato, capsicum, radish, cucumber, Chinese cabbage, celery, hot pickled mustard tuber, beet, green onion, garlic, watermelon, muskmelon, "Hami" melon,
Pawpaw, potato, corn, rice, fruit tree, banana, citrus, peach, papaya, orchid, potted landscape.
Embodiment 11：The thiazole piperidines furanone derivatives 7-1g and intermediate of the present invention is combined with plant growth regulator
Application in coordinate plant growth：
The thiazole piperidines furanone derivatives 7-1g and intermediate and commodity plant growth regulator of the present invention of the present invention
In the combination of any one or two kinds form Herbicidal combinations for adjusting agricultural and forestry and the growth of gardening plant：It is described
Plant growth regulator is selected from 2,4,5- tears (2,4,5-T), 2,4,5- tears propionic acid, 2,4-D- butyric acid, 2,4-D- propionic acid, 2- first-
4- chloro-butyric acids, 6- benzylaminopurines, 8-hydroxyquinoline, 8-hydroxyquinoline citrate, ABT root-inducing powders, CO-11, GA4+7,
The red palm antistaling agent of H2-06 environment-friendly highly efficients, S abscisic acids, Ah not 1618, short Feng Ling, cycocel, cycocel, Idall receipts, ammonia chlorine pyrrole
Pyridine acid, diethyl aminoethyl hexanoate, paraquat, Bravo, benzimidazole, benzene pyridazine acid, benomyl, benayl aminopurine, glyphosate, super quick egg
In vain, gibberellic acid 3, gibberellic acid 4, gibberellic acid 7, growth-promoting ester, dextropropoxyphene, cyanamide, Isoprothiolane, diquat dibromide, diuron, dinoseb,
Daminozide, daminozide, to bromobenzene fluoroacetic acid, benzac, paclobutrazol, acardite, two Kai Gula acid sodium, Chemox PE, anti-fall
Element, cycloheximide, rich pyridine alcohol, Feng Guole, mefluidide, mefluidide, flumetralim, humic acid, the agent of olive absciss layer, coronatine,
Guofengling, glyodin, sugar content increase of fruits agent, succinic acid, ancymidol, cyclanilide, cycloheximide, the spirit of sulphur grass, sulphur bacterium
Prestige, kinetin, chitosan, Duraset, alachlor, methyl cyclopropene, methyl imazalil, first chlorine nitre pyrazoles, carbaryl,
First piperazine, metoxuron, chaff adenine phosphate, inabenfide, TrinexAN_SNacethyl, ascorbic acid, control soul, waxy Bacillus, zeatin, grain weight
Guarantor, union II phenylurea, Luoyang Chouzhibao chlorpropham, chlorophenoxyacetic acid, chloropyuril, choline chloride, phosphonium chloride, magron,
Mediben methyl esters, hymexazos, ancymidol, jasmonic, methyl jasmonate, naphthyloxyacetic acid, naphthyloxyacetic acid, methyl α-naphthyl acetate, methyl α-naphthyl acetate, naphthalene
It is fresh that methyl acetate, naphthalene ethyl acetate, naphthalene ethyl acetate, naphthaleneacetamide, naphthaleneacetamide, allantoin, piperazine strengthen element, hydroxy ethyl hydrazine, blueness
Element, Thidiazuron, dimethipin, probenazole, Triiodobenzoic acid, Triiodobenzoic acid, three fourth benzyl chlorides, trifluorobutyrate, trichloro-benzenes
Oxygen propionic acid, triacontanol, triacontanol, triazolone, ioxynil, sintofen, supernatural power element, undecenoic acid, tridecanol, oil
Growth regulator, gaultherolin, tetcyclacis, rosin diene, mepiquat chloride, glycidic acid, dikegulac, adjusts tartaric acid, adjusts ring salicylic acid
Acid adjusts peace, adjusts silicon, adjusts the real health of phosphine, flurprimidol, support, abscisic acid, De-Green, disleave phosphine, Thidiazuron, steady early rich, fluorenes fourth
Acid, fluorenes butyric acid amine, the basic element of cell division, sevin, uniconazole P, olefin conversion, adenine, niacinamide, transplanting spirit, triapenthenol, second two
Phosphonic acids, glyoxime, ethylene silicon, ethephon (CEPHA),2-(chloroethyl) phosphonic acid, ethoxyquin, acetylsalicylic acid, isopentenyl gland purine, maleic hydrazide, suckering ether, suppression
Bud azoles, endothal, indolepopionic acid, indolebutyric acid, heteroauxin, heteroauxin, 'Inshuzhi ', 'Inshuzhi ', corn ripener, corn
Element, chloretazate, study on brassinolide, study on brassinolide, increase production of amines, production increasing agent, Yield-increasing Hormone, heptopargil, glyphosine, glyphosine, increasing
Tryptamines, fluoridamid, chlorflurenol, morphactin, Decanol, butralin, the agent of ramie control flower, Zhuang Feng An, cloxyfonac, composition processing
Dosage form be selected from seed treatment emulsion, aqueous emulsion, big granula, microemulsion, water-soluble granule, soluble thick agent, water-dispersible granules,
Poison grain, aerosol, blocky poison bait, sustained-release block, dense poison bait, CG/Encapsulated granule, micro-capsule suspension, Waterless Seed Dressing pulvis, missible oil, electrostatic
Spray, water-in-oil emulsion, oil in water emulsion, smoke candle, granula subtilis, smoke candle, smoke cartridge, smog stick, seed treatment suspend
It is agent, smog piece, smog ball, granular poison bait, thermal fog, medicine paint, fine granule, oil suspending agent, oil-dispersing property pulvis, sheet poison bait, dense
Jelly sprinkles and pours agent, seed coat agent, liniment, suspended emulsion, film forming finish, soluble powder, seed treatment water solube powder, surpasses
Low capacity suspending agent, tracking pulvis, ultra low volume liquids, any one in wet-mixing kind water-dispersible powder；The change of the present invention
It is 1%-90% to close object total mass percentage in the composition, thiazole piperidines furanone derivatives 7-1g of the invention and
The ratio of intermediate and commodity plant growth regulator is mass percent 1%: 99% to 99%: 1%；These compositions have
Synergistic effect and summation action do not find the composition with antagonistic action.Above-mentioned medicament can be watered spraying and use；These
The applicable crop of composition is paddy, wheat, barley, oat, millet, sorghum, sweet potato, potato, cassava, soybean, broad bean, pea
Beans, garden pea, mung bean, red bean, cotton, crudefiber crop, silkworm and mulberry, peanut, rape, sesame, soybean, sunflower, beet, sugarcane, coffee,
Cocoa, ginseng, fritillaria, rubber, coconut, oil palm, sisal hemp and flowers, oil plant, sugar material, Chinese medicine, tea, vegetables, wild vegetables, bamboo
It is bamboo shoot, flowers, ornamental plant, hops, pepper, seedling and tobacco leaf, flue-cured tobacco, air-curing of tobacco leaves, suncured tabacco, tomato, capsicum, radish, cucumber, white
Dish, celery, hot pickled mustard tuber, beet, green onion, garlic, watermelon, muskmelon, "Hami" melon, pawpaw, potato, corn, rice, fruit tree, banana, mandarin orange
Tangerine, peach, papaya, orchid, potted landscape.
Bactericidal activities of the thiazole piperidines furanone derivatives 7-1g and intermediate of 1 present invention of table under 50mg/L concentration
(%)
The influence (1 μ g/mL) that the thiazole piperidines furanone derivatives 7-1g and intermediate of 2 present invention of table sprouts seed
Claims (10)
1. a kind of thiazole piperidines furanone derivatives, it is characterised in that：With the general structure as shown in formula 7-1g：
Wherein：R1、R2It is hydrogen, C1-C6Alkyl, C1-C6Halogenated alkyl, C1-C6Alkoxy, C1-C6Halogenated alkoxy, C2-C6Alkenyl,
C2-C6Halogenated alkenyl, C2-C6Alkynyl, C2-C6Halo alkynyl, hydroxyl, C3-C6Naphthenic base, is substituted substituted piperidin-1-yl
Morpholine -1- bases, substituted nafoxidine -1- bases, phenyl or halogen substitution phenyl or C1-C6Alkyl-substituted phenyl
Or C1-C6The phenyl or C of halogenated alkyl substitution3-C6The phenyl of naphthenic base substitution or the phenyl or C of nitro substitution2-C6Alkenyl takes
The phenyl or C in generation2-C6The phenyl or C of halogenated alkenyl substitution3-C6The phenyl or C of cycloalkenyl group substitution2-C6The benzene of alkynyl substituted
Base or C2-C6The phenyl or C of halo alkynyl substitution3-C6The pyridyl group of phenyl, pyridyl group or halogen substitution that cycloalkynyl radical replaces,
Or C1-C6Alkyl-substituted pyridyl group or C1-C6The pyridyl group or C of halogenated alkyl substitution3-C6The pyridyl group of naphthenic base substitution,
Or the pyridyl group or C of nitro substitution2-C6The pyridyl group or C of alkenyl substitution2-C6The pyridyl group or C of halogenated alkenyl substitution3-C6
The pyridyl group or C of cycloalkenyl group substitution2-C6The pyridyl group or C of alkynyl substituted2-C6The pyridyl group or C of halo alkynyl substitution3-C6Ring
The pyrimidine radicals or C that pyridyl group, pyrimidine radicals or the halogen of alkynyl substituted replace1-C6Alkyl-substituted pyrimidine radicals or C1-C6It is halogenated
Alkyl-substituted pyrimidine radicals or C3-C6The pyrimidine radicals of naphthenic base substitution or the pyrimidine radicals or C of nitro substitution2-C6Alkenyl replaces
Pyrimidine radicals or C2-C6The pyrimidine radicals or C of halogenated alkenyl substitution3-C6The pyrimidine radicals or C of cycloalkenyl group substitution2-C6Alkynyl substituted
Pyrimidine radicals or C2-C6The pyrimidine radicals or C of halo alkynyl substitution3-C6The pyrimidine radicals of cycloalkynyl radical substitution substituted contains 1 or 2
Five yuan of a N atoms or six membered heteroaryl, substituted five yuan containing 1 or 2 S atom or six membered heteroaryl contain 1 or 2
Substituted five yuan of a O atom or six membered heteroaryl, substituted five yuan or hexa-atomic miscellaneous containing 1 N atom and 1 S atom
Aryl, substituted five yuan or six membered heteroaryl, the quilt containing 2 N atoms and 1 S atom containing 1 N atom and 1 O atom
Five yuan or six membered heteroaryl, substituted five yuan or six membered heteroaryl containing 2 N atoms and 1 O atom of substitution；Above-mentioned five
Member or six membered heteroaryl are selected from：Substituted furyl, thienyl, pyrrole radicals, imidazole radicals, pyrazolyl, thiazolyl, isothiazole
Ji, oxazolyl, isoxazolyl, oxadiazolyls, thiadiazolyl group, pyridyl group, pyridazinyl, pyrimidine radicals, pyrazinyl, triazine radical, tetrazine
Base, indyl, benzothienyl, benzofuranyl, benzimidazolyl, indazolyl, benzotriazole base, benzothiazolyl, benzo
Thiadiazolyl group, benzoxazolyl, the quinolyl of isomerization, the isoquinolyl of isomerization, phthalazinyl, quinoxalinyl, quinazolyl,
The silicon substrate of cinnoline base or naphthyridines base, alkyl or alkenyl substitution；
Halogen is fluorine, chlorine, bromine or iodine in above-mentioned definition；
The alkyl, alkenyl or alkynyl are straight chain or branch alkyl；Alkyl itself or as other substituent groups part select
From methyl, ethyl, propyl, butyl, amyl, hexyl and its isomers, isomers is selected from isopropyl, isobutyl group, sec-butyl, uncle
Butyl, isopentyl or tertiary pentyl；
The halogenated alkyl group is selected from the group containing one or more identical or different halogen atoms, the halogenated alkyl choosing
From CH2Cl、CHCl2、CCl3、CH2F、CHF2、CF3、CF3CH2、CH3CF2、CF3CF2Or CCl3CCl2；
Described naphthenic base itself or as other substituent groups part be selected from cyclopropyl, cyclobutyl, cyclopenta or cyclohexyl；
Described alkenyl itself or as other substituent groups part be selected from vinyl, allyl, 1- acrylic, butene-2-base, fourth
Alkene -3- bases, amylene -1- bases, amylene -3- bases, hexene -1- bases or 4- methyl-3-pentenyls；
Described alkynyl itself or as other substituent groups part be selected from acetenyl, propine -1- bases, propine -2- bases, butine -1-
Base, crotonylene-base, 1- methyl -2- butynyls, hexin -1- bases or 1- ethyl -2- butynyls；
The enantiomeric form and its mixture of thiazole piperidines furanone derivatives 7-1g, the optical isomer are that mapping is different
Structure body or cis-trans-isomer；
The geometric isomer of thiazole piperidines furanone derivatives 7-1g, i.e. (R)-(S) isomery and its mixture；
The atropisomer and its mixture of thiazole piperidines furanone derivatives 7-1g.
2. thiazole piperidines furanone derivatives 7-1g according to claim 1：
R1It preferably is selected from：Hydrogen, methyl；R2It preferably is selected from：Hydrogen, allyl, propargyl, 3- methylfurans -2 (5H) -one -5- bases.
3. according to the thiazole piperidines furanone derivatives 7-1g of the claims 1 or 2, compound therein is：
(Z) -4- (4- (3- (carbethoxyl group) -4- ((4- methyl -5- oxygen -2,5-dihydrofuran -2- bases) oxygen) butyl- 3- alkene -1- alkynes -
1- yls) thiazol-2-yl) piperidines -1- carboxylic acid tert-butyl esters.
4. according to the synthetic method of any one of the claim 1-3 thiazole piperidines furanone derivatives 7-1g, specific route is such as
Under：
The substituent R1Definition it is as described in claim 1；Specific synthetic method is divided into following steps：
A. the preparation of intermediate 7-16：
Intermediate 7-16 under starting material 7-15 and diethyl carbonate by reacting preparation；In starting material 7-15 and intermediate 7-16
Substituent R1Definition it is as described in claim 1；
B. the preparation of intermediate 7-17：
Intermediate 7-17 reacts preparation with bromoethyl acetate by intermediate 7-16；Substituent R in intermediate 7-171Definition such as
Described in claim 1；
C. the preparation of intermediate 7-18：
Intermediate 7-18 is prepared in alcohol solvent by sodium borohydride reduction by intermediate 7-17, is replaced in the intermediate 7-18
Base R1Definition it is as described in claim 1；Reducing agent sodium borohydride can be substituted by other reducing agents, and etoh solvent can be by other phases
The solvent answered substitutes；
D. the preparation of intermediate 7-19：
Intermediate 7-19, which is reacted by intermediate 7-18 under the action of EDC and copper chloride, to be made, and is replaced in the intermediate 7-19
Base R1Definition it is as described in claim 1；
E. the preparation of thiazole piperidines furanone derivatives 7-1g：
Thiazole piperidines furanone derivatives 7-1g is reacted in the presence of diisopropylamino lithium with Ethyl formate by intermediate 7-19
It reacts and is made under potassium carbonate and N-Methyl pyrrolidone effect with bromo- -2 (5H) -one of 3- methylfurans of 5- again afterwards, the thiazole
Substituent R in piperidines furanone derivatives 7-1g1Definition it is as described in claim 1.
5. a kind of composition pesticide, it includes claim 1-3 any one of them thiazole piperidines furanone derivatives 7-1g and
Intermediate can prepare composition pesticide, and the composition is spread out comprising claim 1-3 any one of them thiazole piperidines furanones
As active constituent, the content of active constituent is 0.1 to 99.9% weight, 99.9 to 0.1% weight for biological 7-1g and its intermediate
The surfactant of the solid or liquid adjuvants of amount and optional 0 to 25% weight.
6. the use of thiazole piperidines furanone derivatives 7-1g and its intermediate in preparing fungicide described in claim 1-3
On the way.
7. the thiazole piperidines furanone derivatives 7-1g and its intermediate described in claim 1-3 are preparing plant seed germination suppression
Purposes in preparation.
8. the use of thiazole piperidines furanone derivatives 7-1g and its intermediate in preparing herbicide described in claim 1-3
On the way.
9. a kind of pesticide complex composition, it includes claim 1-3 any one of them thiazole piperidines furanone derivatives 7-
1g and its intermediate and other fungicide, herbicide, plant growth regulator compounding are as active constituent, thiazole piperidines furanone
Derivative 7-1g and its intermediate and other fungicide, herbicide, plant growth regulator ratio be mass percent 1%:
99% to 99%: 1%, the content of active constituent is 1 to 99% weight, the solid or liquid adjuvants of 99 to 1% weight.
10. the purposes of pesticide complex composition according to claim 9, for being prevented in agricultural, forestry and gardening
Pathogen, the harm of weeds or the growth of adjusting plant.
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