CN106831637A - Thiazole amide compound and preparation method and application - Google Patents
Thiazole amide compound and preparation method and application Download PDFInfo
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- CN106831637A CN106831637A CN201710047210.XA CN201710047210A CN106831637A CN 106831637 A CN106831637 A CN 106831637A CN 201710047210 A CN201710047210 A CN 201710047210A CN 106831637 A CN106831637 A CN 106831637A
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- AEVRNPYRZJIZNH-UHFFFAOYSA-N CCOC(CCC(Nc1nc2ccccc2[s]1)=O)=O Chemical compound CCOC(CCC(Nc1nc2ccccc2[s]1)=O)=O AEVRNPYRZJIZNH-UHFFFAOYSA-N 0.000 description 1
- BNUQIHXVYZORMO-UHFFFAOYSA-N OC(CC(CNc1ncc[s]1)C=O)=O Chemical compound OC(CC(CNc1ncc[s]1)C=O)=O BNUQIHXVYZORMO-UHFFFAOYSA-N 0.000 description 1
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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
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—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
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- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of thiazole amide compound and preparation method and application.The thiazole amide compound, its general structure is shown in formula I.Related activity tests result shows that compound shown in Formulas I has brassinosteroid related activity in plant, can be further used as plant growth regulator application.
Description
Technical field
The invention belongs to plant growth regulator field, it is related to a kind of thiazole amide compound and preparation method thereof and answers
With.
Background technology
Brassinosteroid, also known as brassin lactones (BRs), is the class endogenous plant growth regulating by synthesizing in plant
Agent.It can adjust plant various enzymes and hormone required in itself, give full play to plant itself potential and growth vigor, enhancing life
Life vigor and the waterlogging ability of drought resisting.In view of the content in plant such as brassin lactones is extremely low (to be less than 10-6) and it is used as plant ppm
The excellent physiologically active that thing hormone is shown in agricultural crops, its synthesis and transformation research are constantly subjected to scientists from all over the world
Favor.But and internal metabolism site with high costs for brassinosteroid synthesis be more, easily metabolic inactivation problem but beam
Hand finds new target drone acceptor and carries out the exploration of analog exploitation and increasingly cause people to pay close attention to without plan.
US6667278 (2003) is reported and has been copied first kind non-steroidal analog according to the structure and unit of BL, and is sieved
Choosing obtains high activity BM1 (pM grades), but high concentration (more than nM) is shown as without physiologically active, and must be cooperateed with IAA (5 μM)
Can play a role.
The content of the invention
It is an object of the invention to provide a kind of thiazole amide compound and preparation method and application.
The present invention provide thiazole amide compound, its general structure shown in formula I,
In the Formulas I, R1It is hydrogen, phenyl or 6- tolyls；
R2For butyric acid base, methyl butyrate base, Boc- glutamic acid base, Boc- asparagines acidic group, p-methoxyphenyl, to methoxy
Phenethyl or methyl benzoate base.
Specifically, compound shown in the Formulas I is any one in following compound：
4- (thiazole -2- amino) -4- ketobutyric acids
4- (thiazole -2- amino) -4- oxobutyrates
4- (thiazole -2- amino) -4- oxobutyrics
N2- (tertbutyloxycarbonyl)-N5- (thiazole -2- amino) glutamine
N2- (tertbutyloxycarbonyl)-N4- (thiazole -2- amino) asparagine
4- methoxyl groups-N- (thiazole -2- amino) benzoic acid
4- methoxyl groups-N- (thiazole -2- amino) phenylacetic acid
4- methoxycarbonyl groups-N- (thiazole -2- amino) benzoic acid
4- [(phenyl-[d] thiazole) -2- amino)] -4- oxobutyrics
4- [(6- tolyls-[d] thiazole) -2- amino] -4- oxobutyrics.
The method of compound, comprises the following steps shown in the formula I that the present invention is provided：
Compound shown in Formula II and reactant III are carried out into acylation reaction, reaction is finished and obtains chemical combination shown in the Formulas I
Thing；
In the Formula II, R1Definition it is identical with claim 1；
The reactant III be reactant III1, reactant III2 or
The reactant III1 is
The reactant III2 is
In the above method, the mol ratio of the reactant II and reactant III is 1:(0.9-1.2), concretely 1:
1.1；
The reaction is carried out in a solvent；The solvent is chosen in particular from tetrahydrofuran, dichloromethane, ethyl acetate, acetone
With at least one in acetonitrile；
When the reactant III is reactant III1, the acylation reaction is carried out in -5 DEG C -5 DEG C or room temperature；Reaction
Time is 2-3h；
The reactant III isWhen, the reaction temperature of the acylation reaction is the backflow of solvent for use
Temperature；Reaction time is 1-6h, specially 2-3h；
When the reactant III is reactant III2, the reaction temperature of the acylation reaction is room temperature；Reaction time is
6-24h, specially 12h.
Methods described also comprises the following steps：It is described after completion of the reaction, reaction system is purified；
The method of the purifying is specially recrystallization or solvent mashing；
In the re-crystallization step, solvent for use is specially ethanol or ethyl acetate；
In the solvent mashing step, solvent for use is specially ethanol or is 2 by volume ratio:1 ethyl acetate and oil
The mixed liquor of ether composition；
The solvent mashing step is specifically included：To mashing solvent for use is added in the reaction system, stir to product
Separate out, suction filtration；The reaction system is specially 1g with the amount ratio of solvent mashing step solvent for use：5mL.
In addition, the invention described above provide Formulas I described in compound coordinate plant growth activity in application and contain formula I
The plant growth active regulator of compound, falls within protection scope of the present invention.
Specifically, coordinate plant growth activity for it is following any one：
1) plant growth is promoted；
2) promote cane elongation and/or increase thick；
3) seed germination rate is improved；
4) yield is improved；
5) improving quality；
6) plant lodging tolerance is strengthened；
7) anti-adversity of plant is strengthened；
The plant growth active regulator is at least one conditioning agent with following function：
1) plant growth is promoted
2) promote cane elongation and/or increase thick；
3) seed germination rate is improved；
4) yield is improved；
5) improving quality；
6) plant lodging tolerance is strengthened；
7) anti-adversity of plant is strengthened；
The anti-adversity of the enhancing plant is specially the resistance to salt stress ability of enhancing plant；
The plant is specially paddy rice, corn or wheat.
In addition, application of the compound in weeding and the weeding containing type I compound described in the Formulas I of the invention described above offer
Agent, falls within protection scope of the present invention.
Specifically, the grass is grassy weed；Specially wild oat, Triticum tauschii, barnyard grass, herba setariae viridis grass or goatweed；
The formulation of the plant growth active regulator or herbicide is water dispersible granules, suspending agent, aqueous emulsion, tablet or microcapsules.
Carrier in above-mentioned formulation can be various common carriers, as long as ensureing that it is easy to after being prepared with compound shown in formula I
Pending site is applied to, for example, can be plant, seed or soil；Or be conducive to storing, transport or operating.Carry
Body can be solid or liquid, or usually gas but the material of boil down to liquid.
The compound of present invention design synthesis is the special thiazole amide brassinosteroid analogs of a class formation, is passed through
Relevant biological activity verifies that there is discovery some of which compound special brassinosteroid to react, and such as promotes plan south in dark
Mustard mutant det2-1 hypocotyl elongations, rice leaf inclination increase, strengthen ability of the resistance to salt stress of corn etc..Individual compound
Just there is response very high in low concentration, in addition in the case of high concentration, moreover it is possible to suppress the plant height of wheat, retarding of growing is carried
Its ability resistant to lodging high.Have on the grassy weeds such as control of wild oats, Triticum tauschii, barnyard grass, herba setariae viridis grass, goatweed simultaneously
There is good prevention effect.Prepared by the series compound easy, and with low cost, agriculture application and popularization value is high, is worth follow-up
Further investigation exploitation.
Specific embodiment
With reference to specific embodiment, the present invention is further elaborated, but the present invention is not limited to following examples.Institute
State method and be conventional method unless otherwise instructed.The raw material can be obtained from open commercial sources unless otherwise instructed.
The preparation of embodiment 1, compound 1a：
Reaction scheme is shown below：
In 100mL round-bottomed flasks, thiazolamine (10mmol) and succinic anhydride (12mmol), 15mL tetrahydrochysene furans are added
Mutter (solvent orange 2 A) stirring and dissolving, temperature rising reflux carries out acylation reaction for 2 hours, cooling down separates out solid, filters to obtain solid, second
Alcohol recrystallization purifying.Recrystallizing specific method is：In to 1g head products to be recrystallized, ethanol 3mL is added dropwise over, is heated to reflux,
Until head product all dissolves, continue the 10min that flows back, rear slow cooling separates out solid, and suction filtration obtains clean product.
The preparation of embodiment 2, compound 1b：
Reaction scheme is shown below：
In 100mL round-bottomed flasks bottle, thiazolamine (10mmol), succinic anhydride (12mmol), 15mL tetrahydrochysenes are added
Furans stirring and dissolving, back flow reaction 3h carries out acylation reaction, and cooling down separates out solid, filters to obtain solid, ethyl alcohol recrystallization
Purify to obtain intermediate product.Intermediate product (10mmol) is taken, methyl alcohol 3ml dissolvings, ice salt bath is cooled to 0 DEG C, and constant temperature is added dropwise produced
Obtain the 5ml tetrahydrofuran solutions of thionyl chloride, 30min completion of dropping；Continue to react 5 hours, reactant mixture pours into 150mL ice
In water, ethyl acetate extracts (3x100mL), saturated common salt water washing (3x100mL), anhydrous Na2SO4Dry, filtering and concentrating, slightly
Product is purified by re-crystallizing in ethyl acetate.Recrystallizing specific method is：In to 1g head products to be recrystallized, acetic acid is added dropwise over
Ethyl ester 3mL, is heated to reflux, until head product all dissolves, continues the 10min that flows back, and rear slow cooling separates out solid, and suction filtration obtains pure
Net product.
The preparation of embodiment 3, compound 1d：
Reaction scheme is shown below：
In 100mL round-bottomed flasks, thiazolamine (10mmol), 3mL (20mmol) triethylamine, 15ml tetrahydrochysene furans are added
Mutter stirring and dissolving, separately add TBTU (3.531g, 11mmol) and Boc- amino acid (10mmol).Reactant mixture be stirred at room temperature into
Row acylation reaction 12h, TLC detection reaction process.After reaction terminates, concentrate and dissolved with dichloromethane (50mL), 1M NaOH
PH to 10 is adjusted, after system layering, phase of fetching water, 1M HCl are acidified to pH=3, ethyl acetate extraction (3x100mL), saturated aqueous common salt
Washing (3x100mL), anhydrous Na2SO4Dry, filtering and concentrating, crude product is purified by ethyl alcohol recrystallization.Recrystallization specific method
For：In to 1g head products to be recrystallized, ethanol 3mL is added dropwise over, be heated to reflux, until head product all dissolves, continue to flow back
10min, rear slow cooling separates out solid, and suction filtration obtains clean product.
According to upper identical method, the compound of listed remaining the ownership Formulas I of table 1 can be prepared.
The structure and yield of synthesis compound of table 1. (1a-1j)
Embodiment 4, Arabidopsis Mutants det2-1 hypocotyl elongation activity tests
Arabidopsis Mutants det2-1 seeds with 70% ethanol disinfection 1min, while 1% sodium hypochlorite 15min, sterilized water
Clean and be seeded in 1/2MS (compound of 0.8% agar, 1% sucrose and prescribed concentration)；4 DEG C of refrigerator vernalization 3 days, then transfer
To dark condition, 22 DEG C are cultivated 7 days, and after whole strain is taken pictures, ImageJ softwares measure its hypocotyl length, all compound tests
Result is as shown in table 2.
The comparison medicament Hypocotyls Elongation of Arabidopsis measurement result of table 2
The Hypocotyls Elongation of Arabidopsis measurement result of table 3
From table 2,3 as can be seen that 24-epiBL has activity very high, in 1 μM of concentration, hypocotyl length reaches 0.9413
± 0.0748cm, and the non-steroidal brassinosteroid analogs Bikinin for having reported extends activity and is better than 24- at 40 μM
EpiBL, reaches 1.1086 ± 0.0684cm；It is all design synthesis compounds in, 1b, 1c, 1h to Arabidopsis Mutants all
With elongation activity very high, maximum reaches 0.8054 ± 0.0380cm, because compound is with low cost, in square one
Under, with value very high.
Embodiment 5, Rice laminae inclination is tested
Paddy rice (Nipponbare) seed 10%H2O2Sterilization 20min, sterilized water is cleaned, and is sprouted 3 days in 30 DEG C of incubators, children
Bud illumination cultivation 5-6 days, when its length is to 11 heart of leaf, interception Leaf inclination position is placed in various concentrations under 28 DEG C of dark conditions
48h is cultivated in liquid, protractor measurement Leaf inclination, all compound test results are as shown in table 3.
Influence of the comparison medicament of table 4 to Rice laminae inclination angle
Table 5 synthesizes influence of the compound to Rice laminae inclination angle
From table 4,5 as can be seen that 24-epiBL has activity very high, in 10 μM of concentration, blade pitch angle reaches 125
± 9 °, and Bikinin is in 100 μM of Cmax, activity is not so good as 24-epiBL, can only achieve 75 ± 8 °；Closed in all designs
Into compound in, 1b, 1c, 1h have certain concentration dependant activity to blade lean, and maximum reaches 51 ± 7 °.Activity
The performance of compound is consistent with Hypocotyls Elongation of Arabidopsis experiment, shows that compound has brassinosteroid related activity, while
Design compound is with low cost, under square one, with value very high.
Embodiment 6, compound controls growth test to wheat seedling
Wheat (winter wheat Jimai 22) seed is cleaned and is seeded in 1% fine jade with 10% dioxygen water sterilization 15-20min, sterilized water
The compound of fat and prescribed concentration), 25 DEG C of incubator dark germination 2 days, under subsequent 100% illumination, 65% damp condition, 26 DEG C
Culture 6 days, measures the plant height of wheat, statistic analysis result.
Statistical experiment result is as shown in table 6,7：
Influence of the comparison medicament of table 6 to Plant Height in Wheat
Table 7 synthesizes influence of the compound to Plant Height in Wheat
From the data in table 6,7 it is known that some compounds prepared by the present invention have to wheat seedling retarding of growing
Good effect, such as 1b, 1e, 1f, 1j；Wherein 1f controls plant height minimum value reaches 2.09 ± 0.44cm, similar to Bikinin；
The normal growth development of plant is not contained simultaneously.In the extreme circumstances, these effects help to prevent the lodging of wheat from occurring, and protect
Barrier wheat stable yields and normal economic benefit.
Influence experiment of the embodiment 7, compound to Maize Seedling Under Salt Stress biomass
Selection full seed, in the same size, nothing are gone mouldy, the corn seed (Zheng Dan 958) of no disease and pests harm, with control 24-
EpiBL (1.0mg/L), Bikinin (40mg/L) and medicament to be measured (40mg/L) normal temperature seed soaking 24h, after the completion of seed soaking, with sterilizing
Filter paper suck dry moisture is standby.The seed of seed soaking is placed in the germination box for being covered with quartz sand, add 150mM in every box
NaCl solution 10mL, the vernalization at 28 DEG C in incubator, per 25, box, if 3 repetitions, (CK) is processed as control with clear water,
(daytime is cultivated in illumination box：18h, 26 DEG C；100% illumination, night：6h, 20 DEG C).Treatment fluid is changed daily, and germination is extremely
At the 8th day, 10 plants of biomass of seedling of random measurement (weigh seedling fresh weight, after be placed in 48h dried in 80 DEG C of baking ovens, weigh dry weight
Amount).
Experimental result is as shown in table 8：
The influence of the comparison medicament of table 8 and compound to corn seedling biomass
From the data in table 8 it is known that some compounds of present invention preparation are to the biology under corn seedling salt stress
Amount accumulation has certain effect, and wherein 1b, 1c, 1h performance is excellent, actual similar to Bikinin significantly beyond clear water control,
Promote the germination under stress simultaneously.In the extreme circumstances, these effects are assisting in slight maize under NaCl stress just
It is frequently grown and develops, ensures the economic benefit of corn.
Embodiment 8, compound is tested weed seed Inhibiting germination
The liquid of the 80mg/L configured with 1b, 1c, 1f, 1h is carried out to weeds (wild oat, herba setariae viridis grass, goatweed) seed
Culture dish is soaked seed 24h, and sterilized water is cleaned and is seeded in bottom and is lined with the 6cm batch cultur wares of two layers of filter paper, uniformly put per ware
Big full and uniform 20, the seed of appropriate grain is put, 3 repetitions process (CK) as control, trained during experiment with clear water
Support ware filter paper and be always maintained at moistening.Dark culturing (daytime in incubator：18h, 25 DEG C；Night：6h, 20 DEG C), count 3 days and germinate
Gesture and 7 days germination percentages.
Experimental result is as shown in table 9：
Inhibiting germination activity of the compound of table 9 to weeds
From the results shown in Table 9, under the drug concentration of 80mg/L, the kind of herba setariae viridis grass, goatweed and wild oat
Son germination is all subject to a certain degree of suppression.In herba setariae viridis grass, suppress most preferably 1f, inhibiting rate has reached 47.7%；Its
Secondary is 1h, has reached 16.2%.In goatweed, suppress best still 1f, inhibiting rate has reached 50.7%；Next to that 1h, reaches
To 22.3%.Suppression of the 1f to wild oat is also best, has reached 43.2%；Next to that 1b, has reached 15.4%；
1h also has 13.3% inhibiting rate.With the raising of concentration, drug effect may be more preferable, and wherein 1f has application value very high,
It is worth follow-up developmental research.
The preparation of embodiment 9, compound 1b water dispersible granules (10%)
1b 10g, wetting dispersing agent fatty alcohol sulfate salt 6g, disintegrant ammonium sulfate 3g, carrier kaolin is weighed to complement to
100g, is sufficiently mixed uniform, and wettable powder is ground into through airslide disintegrating mill, in adding fluidized bed drying comminutor, with containing
The aqueous solution of adhesive polyethylene glycol 2g, in the fluidized bed prilling of (50 DEG C -70 DEG C), dries in drying machine, is obtained after screening
10%1b water dispersible granules products.
The water dispersible granules of other general formula compounds can be prepared by the above method.
The preparation of embodiment 10, compound 1c aqueous suspension agents (25%)
Weigh 1c 25g, emulsifying agent NPEPO44.8g, desugar lignosulfonates 1.2g, together with adding water, total amount 70g is added
Barreling is carried out in sand milling kettle, after 1h, thickener xanthans 0.15g, antifreeze glycol 4g and remaining water 100% is supplied,
In addition system, it is modulated, obtains the homogeneous aqueous suspension agent of 1c (25%) whites.
The aqueous suspension agent of other general formula compounds can be prepared by the above method.
The preparation of embodiment 11, compound 1f aqueous emulsions (5%)
Weigh 1f 5g and emulsifying agent agriculture breast 501#2.8g, co-emulsifier agriculture breast 601#7.2g is added together, and makes to be dissolved into
Even oil phase.Water, antifreeze ethylene glycol 5g are mixed, as homogeneous water phase.Under normal temperature and high-shear emulsion machine stirring,
Water is added to oil phase, well dispersed aqueous emulsion is formed.
The aqueous emulsion of other general formula compounds can be prepared by the above method.
The preparation of embodiment 12, compound 1h effervescent tablets (1%)
Weigh after 1h 1g are dried 24 hours at 80 DEG C and pack, oxalic acid 30g, sodium acid carbonate 30g mechanical crushings are arrived
100 mesh, diatomite 0.1g, lactose 3g, white carbon 31g and talcum powder 5g mixing and stirrings, are crushed to 800 mesh, with 1h mixed
Close mixer in stirring 10 minutes after be pressed into effervescent tablet, pack product.
The tablet of other general formula compounds can be prepared by the above method.
Embodiment 13, the 20 μm of preparations of microcapsules (3%) of compound 1i particle diameters
Weigh 2.0g shitosans and 1.0g gelatin is dissolved in the acetum of 100ml 2%, by 2ml Sorbitans acid potassium list
Laurate is slowly added into above-mentioned solution under 800rpm stirrings, persistently stirs 20min.Again by 1.0ml fatty alcohol polyoxies
Vinethene mixes with 2.0ml 7.5%1i ethanol solutions, stirring and emulsifying 10min under 1000rpm.Then, the emulsion of 1i is existed
It is slowly added into the acetum of the shitosan and gelatin for having emulsified under 1200rpm stirrings, continues to stir 45min until mixed
Close liquid dispersed.Finally by obtained mixed liquor in the spray dryer that inlet temperature is 135 DEG C, outlet temperature is 85 DEG C
Solidification drying is carried out, gained powder is 1i slow-release microcapsules.After measured, medicine encystation rate 83%, carrying drug ratio 3.0%, averagely
20.5 μm of particle diameter.
The microcapsules of other general formula compounds can be prepared by the above method.
The influence (Hypocotyls Elongation of Arabidopsis experiment) of embodiment 14, different 1c compound formulations to drug effect
Arabidopsis Mutants det2-1 seeds with 70% ethanol disinfection 1min, while 1% sodium hypochlorite 15min, sterilized water
Clean and be seeded in 1/2MS (0.8% agar, 1% sucrose and certain density 3h compound formulations)；4 DEG C of refrigerator vernalization 3 days, with
After be transferred under dark condition, 22 DEG C cultivate 7 days, after whole strain is taken pictures, ImageJ softwares measure its hypocotyl length.Formulation concentrations
It is 0.02mg/g (20mg/L) that compound method is, by the concentration indicated, to add water the preparation of various concentration or DMSO is diluted to institute
The concentration for needing.
Result of the test
All compound test results are as shown in table 10.
The Hypocotyls Elongation of Arabidopsis measurement result of table 10
From the data in table 10 it is known that the 1c compound formulations that prepare of the present invention to the drug effect of arabidopsis hypocotyl all
It is better than the treatment of pure medicament.Wherein water dispersible granules, aqueous suspension agent, aqueous emulsion and microcapsules are demonstrated by activity higher,
It is better than tablet and 1c under the concentration of 20mg/L, preparation has been highlighted to improving the generally effect of drug effect, for the application study in later stage
There is provided certain directive significance.
Attached all characterization of compound data
4- (thiazole -2- amino) -4- ketobutyric acids (1a)
1H NMR(300MHz,DMSO-d6) δ 12.14 (s, 2H), 7.45 (d, J=3.6Hz, 1H), 7.18 (d, J=
3.5Hz, 1H), 2.66 (ddd, J=7.1,6.0,1.3Hz, 2H), 2.55 (ddd, J=7.4,6.0,1.3Hz, 2H)13C NMR
(75MHz,DMSO-d6)δ173.71,170.38,158.16,137.70,113.34,30.03,28.59.HRMSm/z:
201.0331(M+H+,calcd for C7H8N2O3S, 201.0328) fusing point:188.1-189.8℃
4- (thiazole -2- amino) -4- oxobutyrates (1b)
1H NMR(300MHz,DMSO-d6) δ 12.15 (s, 1H), 7.45 (d, J=3.6Hz, 1H), 7.19 (d, J=
3.6Hz,1H),3.60(s,3H),2.77-2.58(m,4H).13C NMR(75MHz,DMSO-d6)δ172.75,170.10,
137.70,113.37,51.59,29.87,28.27.HRMSm/z:215.0486(M+H+,calcd for C8H11N2O3S,
215.0485) fusing point:160.9-162.6℃
4- (thiazole -2- amino) -4- oxobutyrics (1c)
1H NMR(300MHz,DMSO-d6) δ 12.14 (s, 1H), 7.45 (d, J=3.7Hz, 1H), 7.19 (dd, J=3.6,
0.7Hz, 1H), 4.05 (q, J=7.1Hz, 2H), 2.76-2.56 (m, 4H), 1.17 (t, J=7.1Hz, 3H)13C NMR
(75MHz,DMSO-d6)δ172.19,170.11,158.10,137.67,113.33,60.13,29.88,28.50,
14.18.HRMS m/z:229.0642(M+H+,calcd for C9H13N2O3S, 229.0641) fusing point:138.4-139.3℃
N2- (tertbutyloxycarbonyl)-N5- (thiazole -2- amino) glutamine (1d)
1H NMR(300MHz,DMSO-d6) δ 12.16 (s, 2H), 7.48 (d, J=3.6Hz, 1H), 7.22 (d, J=
3.6Hz, 2H), 4.19 (d, J=7.2Hz, 1H), 2.28 (s, 2H), 1.90-1.84 (m, 2H), 1.38 (s, 9H)13C NMR
(75MHz,DMSO-d6)δ173.91,170.58,158.10,155.72,137.67,113.35,78.25,53.05,31.62,
28.36,26.22.HRMS m/z:330.1119(M+H+,calcd for C13H20N3O5S, 330.1118) fusing point:196.3-
197.5℃
N2- (tertbutyloxycarbonyl)-N4- (thiazole -2- amino) asparagine (1e)
1H NMR(300MHz,DMSO-d6) δ 12.36 (s, 1H), 12.16 (s, 1H), 7.48 (d, J=3.6Hz, 1H),
7.22 (d, J=3.6Hz, 2H), 4.54 (d, J=7.8Hz, 1H), 4.35 (t, J=5.1Hz, 1H), 3.44 (qd, J=7.0,
5.1Hz,2H),2.77–2.53(m,2H),1.38(s,9H).13C NMR(75MHz,DMSO-d6)δ171.46,170.27,
158.09,155.35,137.84,113.78,78.67,56.26,51.13,36.13,28.34,18.73.HRMS m/z:
316.0964(M+H+,calcd for C12H18N3O5S, 316.0962) fusing point:110.4-111.4℃
4- methoxyl groups-N- (thiazole -2- amino) benzoic acid (1f)
1H NMR(300MHz,CDCl3- d) δ 8.30-8.18 (m, 2H), 7.52 (d, J=4.2Hz, 1H), 7.16-7.01
(m,3H),3.92(s,3H).13C NMR(75MHz,DMSO-d6)δ164.41,163.12,160.03,135.15,135.10,
130.55,123.80,114.16,55.75.HRMSm/z:235.0536(M+H+,calcd for C11H11N2O2S,
235.0536) fusing point:159.0-160.5℃
4- methoxyl groups-N- (thiazole -2- amino) phenylacetic acid (1g)
1H NMR(300MHz,DMSO-d6) δ 12.28 (s, 1H), 7.46 (d, J=3.5Hz, 1H), 7.38-7.20 (m,
2H), (s, the 2H) of 7.19 (dd, J=3.6,0.7Hz, 1H), 6.95-6.83 (m, 2H), 3.73 (s, 3H), 3.6813C NMR
(75MHz,DMSO-d6)δ169.64,158.40,158.26,137.77,130.42,127.07,114.01,113.53,
55.18,41.01.HRMS m/z:249.0695(M+H+,calcd for C12H13N2O2S, 249.0692) fusing point:158.3-
159.9℃
4- methoxycarbonyl groups-N- (thiazole -2- amino) benzoic acid (1h)
1H NMR(300MHz,DMSO-d6)δ12.85(s,1H),8.25–8.15(m,2H),8.14–8.04(m,2H),
(s, the 3H) of 7.58 (d, J=3.6Hz, 1H), 7.31 (d, J=3.6Hz, 1H), 3.9013C NMR(75MHz,DMSO-d6)δ
165.70,164.68,159.00,137.40,136.54,132.86,129.32,128.67,114.10,52.56.HRMS m/
z:263.0488(M+H+,calcd for C12H11N2O3S, 263.0485) fusing point: 166.8-168.2℃
4- [(phenyl-[d] thiazole) -2- amino)] -4- oxobutyrics (1i)
1H NMR(300MHz,CDCl3- d) δ 12.40 (s, 1H), 7.97 (ddd, J=7.9,1.3,0.6Hz, 1H), 7.74
(ddd, J=8.1,1.2,0.6Hz, 1H), 7.43 (ddd, J=8.2,7.3,1.3Hz, 1H), 7.36-7.24 (m, 1H), 4.07
(q, J=7.1Hz, 2H), 2.78 (td, J=6.2,5.4,1.2Hz, 2H), 2.50 (p, J=1.9Hz, 4H), 1.18 (t, J=
7.1Hz,3H).13C NMR(75MHz,DMSO-d6)δ172.12,171.19,157.95,148.68,131.57,126.12,
123.52,121.70,120.57,60.14,30.19,28.37,14.14.HRMS m/z:279.0802(M+H+,calcd for
C13H15N2O3S, 279.0798) fusing point:174.3-175.4℃
4- [(6- tolyls-[d] thiazole) -2- amino] -4- oxobutyrics (1j)
1H NMR(300MHz,CDCl3- d) δ 12.32 (s, 1H), 7.75 (dt, J=1.9,0.6Hz, 1H), 7.62 (d, J=
8.2Hz, 1H), 7.29-7.19 (m, 1H), 4.06 (q, J=7.1Hz, 2H), 2.82-2.58 (m, 4H), 2.50 (p, J=
1.8Hz,5H),1.24–1.11(m,3H).13C NMR(75MHz,DMSO-d6)δ172.12,171.03,157.07,146.64,
132.99,131.70,127.44,121.31,120.21,60.13,30.14,28.37,21.03,14.15.HRMS m/z:
293.0954(M+H+,calcd for C14H17N2O3S, 293.0954) fusing point:175.4-176.9℃.
Claims (10)
1. compound shown in Formulas I,
In the Formulas I, R1It is hydrogen, phenyl or 6- tolyls；
R2For butyric acid base, methyl butyrate base, Boc- glutamic acid base, Boc- asparagines acidic group, p-methoxyphenyl, to methoxy benzene second
Base or methyl benzoate base.
2. compound according to claim 1, it is characterised in that：During compound shown in the Formulas I is following compound
Any one：
4- (thiazole -2- amino) -4- ketobutyric acids,
4- (thiazole -2- amino) -4- oxobutyrates,
4- (thiazole -2- amino) -4- oxobutyrics,
N2- (tertbutyloxycarbonyl)-N5- (thiazole -2- amino) glutamine,
N2- (tertbutyloxycarbonyl)-N4- (thiazole -2- amino) asparagine,
4- methoxyl groups-N- (thiazole -2- amino) benzoic acid,
4- methoxyl groups-N- (thiazole -2- amino) phenylacetic acid,
4- methoxycarbonyl groups-N- (thiazole -2- amino) benzoic acid,
4- [(phenyl-[d] thiazole) -2- amino)] -4- oxobutyrics and 4- [(6- tolyls-[d] thiazole) -2- amino] -
4- oxobutyrics.
3. a kind of method for preparing compound shown in Formulas I described in claim 1 or 2, comprises the following steps：
Compound shown in Formula II and reactant III are carried out into acylation reaction, reaction is finished and obtains compound shown in the Formulas I；
In the Formula II, R1Definition it is identical with claim 1；
The reactant III be reactant III1, reactant III2 or
The reactant III1 is
The reactant III2 is
4. method according to claim 3, it is characterised in that：The mol ratio of the reactant II and reactant III is 1:
(0.9-1.2) or 1:1.1；
The reaction is carried out in a solvent；The solvent is chosen in particular from tetrahydrofuran, dichloromethane, ethyl acetate, acetone and second
At least one in nitrile；
When the reactant III is reactant III1, the acylation reaction is carried out in -5 DEG C -5 DEG C or room temperature；Reaction time
It is 2-3h；
The reactant III isWhen, the reaction temperature of the acylation reaction is the reflux temperature of solvent for use；
Reaction time is 1-6h or 2-3h；
When the reactant III is reactant III2, the reaction temperature of the acylation reaction is room temperature；Reaction time is 6-
24h or 12h.
5. the method according to claim 3 or 4, it is characterised in that：Methods described also comprises the following steps：In the reaction
After finishing, reaction system is purified；
The method of the purifying is specially recrystallization or solvent mashing；
In the re-crystallization step, solvent for use is specially ethanol or ethyl acetate；
In the solvent mashing step, solvent for use is specially ethanol or is 2 by volume ratio:1 ethyl acetate and petroleum ether group
Into mixed liquor；
The solvent mashing step is specifically included：To mashing solvent for use is added in the reaction system, stirring to product is separated out,
Suction filtration；The reaction system is specially 1g with the amount ratio of solvent mashing step solvent for use：5mL.
6. application of the compound described in Formulas I described in claim 1 or 2 in coordinate plant growth activity；Or,
Plant growth active regulator containing any type I compound in claim 1-2.
It is 7. according to claim 6 to apply or plant growth active regulator, it is characterised in that：The coordinate plant growth
Activity for it is following any one：
1) plant growth is promoted；
2) promote cane elongation and/or increase thick；
3) seed germination rate is improved；
4) yield is improved；
5) improving quality；
6) plant lodging tolerance is strengthened；
7) anti-adversity of plant is strengthened；
The plant growth active regulator is at least one conditioning agent with following function：
1) plant growth is promoted；
2) promote cane elongation and/or increase thick；
3) seed germination rate is improved；
4) yield is improved；
5) improving quality；
6) plant lodging tolerance is strengthened；
7) anti-adversity of plant is strengthened；
The anti-adversity of the enhancing plant is specially the resistance to salt stress ability of enhancing plant；
The plant is specially paddy rice, corn or wheat.
8. application of the compound in weeding described in Formulas I described in claim 1 or 2；
Herbicide containing any type I compound in claim 1-2.
9. application according to claim 8 or herbicide, it is characterised in that：The grass is grassy weed；It is specially wild
Oat, Triticum tauschii, barnyard grass, herba setariae viridis grass or goatweed.
10., according to any described application or plant growth active regulator or herbicide in claim 6-8, its feature exists
In：The formulation of the plant growth active regulator or herbicide is water dispersible granules, suspending agent, aqueous emulsion, tablet or micro- glue
Capsule.
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| US2401522A (en) * | 1942-04-17 | 1946-06-04 | Firm Sandoz Ltd | Aromatic carboxylic acid amides and a process for their manufacture |
| AU7922191A (en) * | 1990-07-07 | 1992-01-09 | Bayer Aktiengesellschaft | 2-acylamino-7-chlorobenzothiazoles |
| WO2005049564A1 (en) * | 2003-11-14 | 2005-06-02 | Adolor Corporation | Amide derivatives and methods of their use |
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| CN104968661A (en) * | 2013-02-05 | 2015-10-07 | 先正达参股股份有限公司 | Substituted amino azoles as plant growth regulators |
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2017
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| US2401522A (en) * | 1942-04-17 | 1946-06-04 | Firm Sandoz Ltd | Aromatic carboxylic acid amides and a process for their manufacture |
| AU7922191A (en) * | 1990-07-07 | 1992-01-09 | Bayer Aktiengesellschaft | 2-acylamino-7-chlorobenzothiazoles |
| CN1870996A (en) * | 2003-10-27 | 2006-11-29 | H.隆德贝克有限公司 | N-thiazol-2-yl-benzamide derivatives |
| WO2005049564A1 (en) * | 2003-11-14 | 2005-06-02 | Adolor Corporation | Amide derivatives and methods of their use |
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