CN109627232A - A kind of quinolines and its preparation method and application - Google Patents
A kind of quinolines and its preparation method and application Download PDFInfo
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- CN109627232A CN109627232A CN201811379208.3A CN201811379208A CN109627232A CN 109627232 A CN109627232 A CN 109627232A CN 201811379208 A CN201811379208 A CN 201811379208A CN 109627232 A CN109627232 A CN 109627232A
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- isobutyl group
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
The invention discloses a kind of quinolines and its preparation method and application.The structure of the compound as shown in formula (i) or formula (ii), wherein R1For H, C1‑4Alkyl, C1‑4Halogenated alkyl, C1‑4Alkoxy or C1‑4One or more of halogenated alkoxy.Compound structure of the present invention is novel, and there is good bacteriostasis, there is good inhibiting effect for the pathogen of plant disease, especially there is good inhibiting effect to botrytis cinerea pers, cotton-wilt fusarium, fusarium graminearum and peanut Cercospora bacteria, bacteriostasis is substantially better than Fluoxastrobin；Fungicide be can be used as preventing and treating and/or treating phytopathogen, the compound has broad application prospects in the prevention and treatment of plant disease and/or therapy field.
Description
Technical field
The present invention relates to technical field of farm chemical bactericides, more particularly, to a kind of quinolines and its preparation side
Method and application.
Background technique
Quinolines are very important one kind compounds in nitrogen-containing heterocycle.In health care and plant protection side
Face, the compound of many ring structures containing quinoline, which is shown, to be widely applied and development prospect.In terms of health care, quinolines medicine
Object is widely used in the prevention and treatment of the diseases such as malaria, ulcer, cancer, inhibition of HIV and schizophrenia.Quinine and chloroquine are people
Class more early for preventing and treating the drug of malaria, is used till today always.Nearest relevant report shows chloroquine to SARS virus
There is certain inhibiting effect；Inverase (saquinavir) is the protease inhibitors of first listing treatment AIDS；A Li
Piperazine azoles (aripiprazole) is suitable for the treatment of various acute and chronic schizophrenia and schizoaffective disorder.
In terms of plant protection, quinolines also show efficient fungicide and herbicide.Quinoxyfen is very
Effectively kill powdery mildew agent；Gram barnyard grass spirit is chloroquine acid herbicides, can thoroughly prevent and kill off barnyard grass in paddy field and effective to advanced age barnyard grass, should
Medicine is low as herbicides for use in paddy dosage, and application is convenient, to live streaming and transplanting rice safety.As pesticide research, quinolines chemical combination
Object is that the new world has been opened up in the development of chemistry of pesticide, provides new approach to find the new pesticide of high-efficiency low-toxicity.
The common side of one kind that other active groups are the new quinoline fungicide of research is introduced in chinoline backbone
Reported in method, such as patent CN201510796235.0 by 1,2,3,4- tetrahydroquinoline in conjunction with pyrazolecarboxamide, be prepared into
To a kind of compound with bactericidal activity.But there are still before wide research for the bactericidal activity and fungicidal spectrum of quinoline
Scape.
Summary of the invention
The purpose of the present invention is to provide a kind of quinolines.The present invention has pyrrole by modifying in quinoline structure
The benzyloxy of azoles substituent group is prepared for the quinoline compound of a kind of structure novel, and the compound has good antibacterial work
With, for plant disease pathogen have good inhibiting effect, especially to botrytis cinerea pers, cotton-wilt fusarium,
Fusarium graminearum and peanut Cercospora bacteria have good inhibiting effect, and bacteriostasis is substantially better than Fluoxastrobin；Describedization
Closing object can be used as fungicide for preventing and treating and/or treating plant disease.
Another object of the present invention is to provide the preparation methods of the quinolines.
A further object of the present invention is to provide the quinolines to prevent and treat and/or treat answering in plant disease
With.
Above-mentioned purpose of the invention is achieved by following scheme:
A kind of quinolines, the structure of the compound as shown in formula (i) or formula (ii):
Wherein R1For H, C1-4Alkyl, C1-4Halogenated alkyl, C1-4Alkoxy or C1-4One or more of halogenated alkoxy.
Preferably, the R1For H, C1-2Alkyl, C1-2Halogenated alkyl, C1-2Alkoxy or C1-2One in halogenated alkoxy
It is a.
Preferably, the R1For H, methyl, ethyl, trifluoromethyl, methoxyl group, ethyoxyl or trifluoromethoxy.
Preferably, the R1For trifluoromethyl or trifluoromethoxy.
The present invention also protects the preparation method of the quinolines simultaneously, comprising the following steps:
S1. using 2- isobutyl group -4- methoxyacetophenone as Material synthesis 2- isobutyl group -4-hydroxyacetophenone；It is again that 2- is different
Butyl -4-hydroxyacetophenone, 2- halogen methyl quinoline, carbonate is miscible reacts in organic solvent, and 2- isobutyl group -4- is prepared
(2- quinoline) methoxyacetophenone；
S2. 2- isobutyl group -4- (2- quinoline) methoxyacetophenone, DMF and DMA hybrid reaction are obtained into (E) -3- (N, N-
Dimethyl) -1- (2- isobutyl group -4- (2 methoxy quinoline) phenyl) -2- propylene -1- ketone；It is again that itself and hydrazine is miscible molten in polarity
It is reacted in agent, 2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline is prepared；
S3. finally by 2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline, R1Substituted benzyl bromine compounds and carbon
Target product can be prepared in the miscible reaction in organic solvent of hydrochlorate.
Preferably, 2- isobutyl group -4-hydroxyacetophenone, 2- halogen methyl quinoline and carbonate molar ratio is 1 ︰ in step S1
1.1~1.5 ︰ 0.2~0.5；The organic solvent is DMF, and the carbonate is potassium carbonate, sodium carbonate or cesium carbonate；Reaction temperature
Degree is 50~60 DEG C, and the reaction time is 8~14h.
It is highly preferred that 2- halogen methyl quinoline described in step S1 is 2- methyl fluoride quinoline, 2- chloromethyl quinoline, 2- bromomethyl
Quinoline；It is further preferred that being 2- chloromethyl quinoline.
It is highly preferred that 2- isobutyl group -4-hydroxyacetophenone, 2- chloromethyl quinoline and carbonate molar ratio is in step S1
1 ︰, 1.1 ︰ 0.5；The carbonate is cesium carbonate；Reaction temperature is 60 DEG C, reaction time 12h.
Preferably, 2- isobutyl group -4-hydroxyacetophenone preparation process in step S1 are as follows: 2- isobutyl group -4- methoxybenzene
Ethyl ketone is dissolved in organic solvent, and maintains the temperature at 0 DEG C, and Boron tribromide is then added dropwise, is reacted at room temperature, can be prepared
Obtain 2- isobutyl group -4-hydroxyacetophenone.
It is highly preferred that the molar ratio of 2- isobutyl group -4- methoxyacetophenone and Boron tribromide is 48 ︰ 0.5；It is wherein organic molten
Agent is methylene chloride；Reaction time is 12h.
(E) -3- (N, N- dimethyl) -1- (2- isobutyl group -4- (2 methoxy quinoline) phenyl) -2- propylene-in step S2
1 ︰ 0.5~1 of molar ratio of 1- ketone and hydrazine；The polar organic solvent is ethyl alcohol；The reaction condition is heated to reflux；Reaction time
For 6~12h；
It is highly preferred that hydrazine described in step S2 is hydrazine hydrochloride；(E) -3- (N, the N- dimethyl) -1- (2- isobutyl group -4-
(2 methoxy quinoline) phenyl) molar ratio of -2- propylene -1- ketone and hydrazine is 1 ︰ 0.5；Reaction time is 12h.
Preferably, (E) -3- (N, N- dimethyl) -1- (2- isobutyl group -4- (2 methoxy quinoline) benzene is prepared in step S2
Base) -2- propylene -1- ketone reaction temperature be 100 DEG C, reaction time 12h.
2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline, R in step S31Substituted benzyl bromine compounds and carbon
The molar ratio of hydrochlorate is 1 ︰, 1.2~2.0 ︰ 1.4~3；The organic solvent is DMF, DMA or DMSO, and the carbonate is carbonic acid
Potassium, sodium carbonate or cesium carbonate；Reaction temperature is 40~60 DEG C, and the reaction time is 8~14h.
It is highly preferred that 2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline, R in step S31Substituted benzyl bromination
The molar ratio for closing object and carbonate is 1 ︰, 1.67 ︰ 2；The organic solvent is DMF, and the carbonate is cesium carbonate；Reaction temperature
It is 50 DEG C, reaction time 12h.
The application in plant disease is being prevented and treated and/or treated to the quinolines also in protection scope of the present invention
It is interior.
It is highly preferred that the application is to prevent and treat and/or treat botrytis cinerea pers, cotton-wilt fusarium, wheat scab
The application of bacterium and peanut Cercospora bacteria.
The present invention also protects the quinolines in the application being prepared into fungicide simultaneously.
Compared with prior art, the invention has the following advantages:
Compound structure of the present invention is novel, and has good bacteriostasis, has for the pathogen of plant disease
There is good inhibiting effect, especially to botrytis cinerea pers, cotton-wilt fusarium, fusarium graminearum and peanut Cercospora bacteria
With good inhibiting effect, bacteriostasis is substantially better than Fluoxastrobin；Fungicide be can be used as preventing and treating and/or treating plant
Pathogen, the compound have broad application prospects in the prevention and treatment of plant disease and/or therapy field.
Specific embodiment
The present invention is made combined with specific embodiments below and further being elaborated, the embodiment is served only for explaining this
Invention, is not intended to limit the scope of the present invention.Test method as used in the following examples is normal unless otherwise specified
Rule method；Used material, reagent etc., unless otherwise specified, for the reagent and material commercially obtained.
Instrument and reagent used in following embodiment are as follows:
1H NMR uses Bruker Furier 300MHz Nuclear Magnetic Resonance, CD3OD is solvent, and TMS is internal standard compound；LC-MS
Use Agilent 6100；HPLC uses Agilent 1260.
Agents useful for same is that commercially available analysis is pure unless otherwise specified.
The preparation process of compound is schematically as follows in following embodiment:
The preparation of embodiment 1 compound 7a and 8a
Compound 7a:2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazole-3-yl) Phenoxymethyl)
Quinoline；
Compound 8a:2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazoles -5- base) Phenoxymethyl)
Quinoline.
The structure of compound 7a and 8a are as follows:
Specific preparation process is as follows:
(1) it is different that 10g (48mmol) 2- 2- isobutyl group -4-hydroxyacetophenone (compound 2) preparation: is added in reaction flask
Butyl -4- methoxyacetophenone (compound 1) and 100mL methylene chloride, are cooled to 0 DEG C, then 45mL (0.5mol) is added dropwise
Boron tribromide.It is stirred to react 12h at room temperature, TLC shows fully reacting.After adding water quenching to go out, methylene chloride extraction is added
(100mL × 3) collect organic phase, are concentrated to give 8.8g colourless oil liquid compound 2 (i.e.) 2- isobutyl after anhydrous sodium sulfate is dry
Base -4-hydroxyacetophenone), yield 96%.LC-MS, m/z:193.2 [M+H]+.
(2) it the preparation of 2- isobutyl group -4- (2- quinoline) methoxyacetophenone (compound 3): is sequentially added in reaction flask
8.8g (46mmol) compound 2,9.1g (51mmol) 2- chloromethyl quinoline, 7.5g (23mmol) cesium carbonate and 100mLDMF.
12h is stirred to react at 50 DEG C.TLC shows fully reacting.It is concentrated to give crude product after removal solvent, then obtains 11.7g through column chromatography for separation
Colourless oil liquid compound 3, yield 76%.LC-MS, m/z:334.2 [M+H]+.
(3) (E) -3- (N, N- dimethyl) -1- (2- isobutyl group -4- (2 methoxy quinoline) phenyl) -2- propylene -1- ketone
The preparation of (compound 4): sequentially adding 11.7g (35mmol) compound 3 and 200mLDMF/DMA in reaction flask, at 100 DEG C
It is stirred to react 12h.TLC shows fully reacting.It is concentrated to give crude product after removal solvent, then obtains 9.5g colorless oil through column chromatography for separation
Liquid compound 4, yield 70%.LC-MS, m/z:389.1 [M+H]+.
(4) preparation of 2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline (compound 5): in reaction flask according to
Secondary addition 9.5g (24.5mmol) compound 4,12.9g (12.3mmol) hydrazine hydrochloride and 120mL ethyl alcohol, back flow reaction 12h.
TLC shows fully reacting.Quenching reaction is concentrated to give crude product after removing solvent, then obtains 7.3g white solid through column chromatography for separation
Close object 5, yield 84%.LC-MS, m/z:358.2 [M+H]+.
(5) 2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazole-3-yl) Phenoxymethyl) quinoline
(7a) and 2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazoles -5- base) Phenoxymethyl) quinoline (8a)
Preparation: the adjacent trifluoromethoxy benzyl of 214mg (0.6mmol) compound 5,255mg (1.0mmol) is sequentially added in 30mL reaction flask
Bromine (compound 6), 391mg (1.2mmol) cesium carbonate and 10mLDMF are heated to 50 DEG C, react 12h, and TLC display has been reacted
Entirely.After removing solvent, methylene chloride extraction (20mL × 3) is added, collects organic phase, after anhydrous sodium sulfate is dry, filters, concentration
Obtain crude product.
57mg 2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazole-3-yl) is prepared into through HPLC
Phenoxymethyl) quinoline (7a), yield 18% and 38mg 2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H-
Pyrazoles -5- base) Phenoxymethyl) quinoline (8a), yield 12%.
2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazole-3-yl) Phenoxymethyl) quinoline (7a):
1H NMR (CDCl3,300MHz), δ: 8.18 (d, J=8.5Hz, 1H), 8.09 (d, J=8.4Hz, 1H), 7.83 (d, J=
8.1Hz, 1H), 7.78-7.64 (m, 2H), 7.55 (t, J=7.5Hz, 1H), 7.42 (d, J=2.2Hz, 1H), 7.40~7.30
(m, 2H), 7.13 (d, J=7.5Hz, 2H), 7.04 (s, 1H), 6.90~6.87 (m, 2H), 6.35 (d, J=2.2Hz, 1H),
5.42 (s, 2H), 5.35 (s, 2H), 2.65 (d, J=7.1Hz, 2H), 1.77~1.64 (m, 1H), 0.73 (d, J=6.6Hz,
6H)；LC-MS, m/z:532.2 [M+H]+, tR=1.97min；HPLC, 100% (214nm), 100% (254nm), tR=
6.74min.
2- (3- isobutyl group -4- (1- ((2- trifluoromethoxy) benzyl) -1H- pyrazoles -5- base) Phenoxymethyl) quinoline (8a):
1H NMR (CD3OD, 300MHz), δ: 8.36 (d, J=8.6Hz, 1H), 8.05 (d, J=8.4Hz, 1H), 7.94 (d, J=
8.1Hz, 1H), 7.79 (t, J=7.1Hz, 1H), 7.73~7.68 (m, 2H), 7.61 (t, J=7.5Hz, 1H), 7.45~7.39
(m, 1H), 7.34 (d, J=8.0Hz, 1H), 7.29 (d, J=8.1Hz, 2H), 7.12 (d, J=6.5Hz, 1H), 6.94~6.89
(m, 2H), 6.36 (d, J=2.2Hz, 1H), 5.45 (s, 2H), 5.39 (s, 2H), 2.59 (d, J=7.2Hz, 2H), 1.66~
1.52 (m, 1H), 0.63 (d, J=6.6Hz, 6H)；LC-MS, m/z:532.3 [M+H]+, tR=2.03min；HPLC, 99%
(214nm).
The preparation of embodiment 2 compound 7b and 8b
Compound 7b:2- (3- isobutyl group -4- (1- ((3- trifluoromethoxy) benzyl) -1H- pyrazole-3-yl) Phenoxymethyl)
Quinoline；
Compound 8b:2- (3- isobutyl group -4- (1- ((3- trifluoromethoxy) benzyl) -1H- pyrazoles -5- base) Phenoxymethyl)
Quinoline.
The structure of compound 7b and 8b are as follows:
The preparation process of compound 7b and 8b are with compound 7a and 8a, the difference is that using 3- trifluoro in step (5)
Methoxybenzyl bromine substitutes adjacent trifluoromethoxy benzyl bromine and is reacted, and compound 7b and 8b can be prepared.
2- (3- isobutyl group -4- (1- ((3- trifluoromethoxy) benzyl) -1H- pyrazole-3-yl) Phenoxymethyl) quinoline (7b),
Yield 21%.1H NMR (CD3OD, 300MHz), δ: 8.36 (d, J=8.6Hz, 1H), 8.05 (d, J=8.4Hz, 1H), 7.94
(d, J=8.1Hz, 1H), 7.79 (t, J=7.6Hz, 1H), 7.75~7.65 (m, 2H), 7.61 (t, J=7.6Hz, 1H), 7.47
~7.37 (m, 1H), 7.34 (d, J=7.8Hz, 1H), 7.29 (d, J=8.0Hz, 2H), 7.12 (d, J=7.5Hz, 1H), 6.94
~6.89 (m, 2H), 6.36 (d, J=2.0Hz, 1H), 5.45 (s, 2H), 5.39 (s, 2H), 2.59 (d, J=7.2Hz, 2H),
1.68~1.51 (m, 1H), 0.63 (d, J=6.6Hz, 6H)；LC-MS, m/z:532.3 [M+H]+, tR=2.03min；HPLC,
99% (214nm), 99% (254nm), tR=6.00min.
2- (3- isobutyl group -4- (1- ((3- trifluoromethoxy) benzyl) -1H- pyrazoles -5- base) Phenoxymethyl) quinoline (8b),
Yield 14%.1H NMR (CD3OD, 300MHz), δ: 8.37 (d, J=8.4Hz, 1H), 8.05 (d, J=8.4Hz, 1H), 7.95
(d, J=8.3Hz, 1H), 7.86~7.69 (m, 3H), 7.62 (t, J=7.5Hz, 1H), 7.44 (t, J=8.0Hz, 1H), 7.29
(d, J=8.4Hz, 1H), 7.27~7.16 (m, 2H), 7.10 (s, 1H), 7.00~6.88 (m, 2H), 6.37 (d, J=2.3Hz,
1H), 5.41 (s, 2H), 5.40 (s, 2H), 2.59 (d, J=7.2Hz, 2H), 1.64~1.51 (m, 1H), 0.63 (d, J=
6.6Hz,6H)；LC-MS, m/z:532.3 [M+H]+, tR=2.00min；HPLC, 95% (214nm), 94% (254nm), tR=
5.92min.
Embodiment 3
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that 2- isobutyl group-in step (2)
The preparation of 4- (2- quinoline) methoxyacetophenone (compound 3), detailed process is as follows:
8.8g (46mmol) compound 2,9.1g (51mmol) 2- chloromethyl quinoline, 3g are sequentially added in reaction flask
(9.2mmol) cesium carbonate and 100mLDMF.12h is stirred to react at 50 DEG C.TLC shows fully reacting.It is concentrated after removal solvent
Crude product is obtained, then obtains 10.7g colourless oil liquid compound 3, yield 70% through column chromatography for separation.LC-MS, m/z:334.2 [M+H]
+。
Embodiment 4
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that 2- isobutyl group-in step (2)
The preparation of 4- (2- quinoline) methoxyacetophenone (compound 3), detailed process is as follows:
8.8g (46mmol) compound 2,9.1g (51mmol) 2- chloromethyl quinoline, 7.5g are sequentially added in reaction flask
(23mmol) cesium carbonate and 100mLDMF.12h is stirred to react at 60 DEG C.TLC shows fully reacting.It is concentrated to give after removal solvent
Crude product, then 9.5g colourless oil liquid compound 3, yield 62% are obtained through column chromatography for separation.LC-MS, m/z:334.2 [M+H]+.
Embodiment 5
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that 2- isobutyl group-in step (2)
The preparation of 4- (2- quinoline) methoxyacetophenone (compound 3), detailed process is as follows:
8.8g (46mmol) compound 2,9.1g (51mmol) 2- chloromethyl quinoline, 3.2g are sequentially added in reaction flask
(23mmol) potassium carbonate and 100mLDMF.12h is stirred to react at 50 DEG C.TLC shows fully reacting.It is concentrated to give after removal solvent
Crude product, then 8.1g colourless oil liquid compound 3, yield 53% are obtained through column chromatography for separation.LC-MS, m/z:334.2 [M+H]+.
Embodiment 6
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that 2- isobutyl group-in step (2)
The preparation of 4- (2- quinoline) methoxyacetophenone (compound 3), detailed process is as follows:
8.8g (46mmol) compound 2,9.1g (51mmol) 2- chloromethyl quinoline, 1.3g are sequentially added in reaction flask
(9.2mmol) potassium carbonate and 100mLDMF.12h is stirred to react at 50 DEG C.TLC shows fully reacting.It is concentrated after removal solvent
Crude product is obtained, then obtains 7.5g colourless oil liquid compound 3, yield 49% through column chromatography for separation.LC-MS, m/z:334.2 [M+H]
+。
Embodiment 7
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that step (4) 2- (3- isobutyl group-
4- (3- pyrazolyl) Phenoxymethyl) quinoline (compound 5) preparation, detailed process is as follows:
Sequentially added in reaction flask 9.5g (24.5mmol) compound 4,12.9g (12.3mmol) hydrazine hydrochloride and
120mL ethyl alcohol, back flow reaction 6h.TLC shows fully reacting.Quenching reaction is concentrated to give crude product after removing solvent, then chromatographs through column
Separate to obtain 4.5g compound as white solid 5, yield 52%.LC-MS, m/z:358.2 [M+H]+.
Embodiment 8
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that step (4) 2- (3- isobutyl group-
4- (3- pyrazolyl) Phenoxymethyl) quinoline (compound 5) preparation, detailed process is as follows:
Sequentially added in reaction flask 9.5g (24.5mmol) compound 4,12.9g (12.3mmol) hydrazine hydrochloride and
120mL ethyl alcohol, back flow reaction 10h.TLC shows fully reacting.Quenching reaction is concentrated to give crude product after removing solvent, then through column layer
Analysis separates to obtain 6.6g compound as white solid 5, yield 76%.LC-MS, m/z:358.2 [M+H]+.
Embodiment 9
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that step (4) 2- (3- isobutyl group-
4- (3- pyrazolyl) Phenoxymethyl) quinoline (compound 5) preparation, detailed process is as follows:
Sequentially added in reaction flask 9.5g (24.5mmol) compound 4,25.8g (24.5mmol) hydrazine hydrochloride and
120mL ethyl alcohol, back flow reaction 10h.TLC shows fully reacting.Quenching reaction is concentrated to give crude product after removing solvent, then through column layer
Analysis separates to obtain 6.1g compound as white solid 5, yield 70%.LC-MS, m/z:358.2 [M+H]+.
Embodiment 10
The preparation process of compound described in the present embodiment is with embodiment 1, the difference is that step (4) 2- (3- isobutyl group-
4- (3- pyrazolyl) Phenoxymethyl) quinoline (compound 5) preparation, detailed process is as follows:
Sequentially added in reaction flask 9.5g (24.5mmol) compound 4,25.8g (24.5mmol) hydrazine hydrochloride and
120mL ethyl alcohol, back flow reaction 12h.TLC shows fully reacting.Quenching reaction is concentrated to give crude product after removing solvent, then through column layer
Analysis separates to obtain 6.4g compound as white solid 5, yield 73%.LC-MS, m/z:358.2 [M+H]+.
11 biological activity determination of embodiment
Synthesized compound 7a, 7b, 8a and 8b is surveyed according to international pesticides discovery Engineering Technical Research Centre bioactivity
S.O.P. (SOP) is determined, with botrytis cinerea pers, cotton-wilt fusarium, fusarium graminearum and peanut Cercospora bacteria
Bactericidal activity measurement is carried out for material to be tested.General sieve mass concentration is 50mg/L, and Fluoxastrobin (azoxystrobin) is comparison medicine
Agent.The bactericidal activity measurement result of compound is shown in Table 1.
The bactericidal activity (inhibiting rate/%) of 1 compound of table
| Compound | Botrytis cinerea pers | Cotton-wilt fusarium | Fusarium graminearum | Peanut Cercospora bacteria |
| 7a | 28.4 | 59.7 | 46.7 | 90.2 |
| 8a | 25.3 | 61.3 | 49.2 | 89.1 |
| 7b | 30.1 | 57.4 | 43.5 | 92.4 |
| 8b | 26.9 | 58.6 | 42.1 | 90.9 |
| Fluoxastrobin | 19.4 | 56.3 | 37.6 | 81.2 |
Biological activity determination the result shows that, 4 kinds of synthesized quinoline compounds containing pyrazole ring, i.e. compound 7a, 8a, 7b
And 8b, have at the concentration tested to botrytis cinerea pers, cotton-wilt fusarium, fusarium graminearum and peanut Cercospora bacteria
Excellent bactericidal activity is significantly better than that control drug Fluoxastrobin；In 4 kinds of phytopathogens, compound is for peanut foxiness
The bactericidal activity of germ is best, followed by cotton-wilt fusarium；And in 4 compounds, it is brown to botrytis cinerea pers and peanut
Most preferably compound 7b, inhibiting rate have respectively reached 30.1% and 92.4% for the bactericidal effect of pinta bacterium；It is withered to cotton
Most preferably compound 8a, inhibiting rate have respectively reached 61.3% He for the bactericidal effect of germ and fusarium graminearum
49.2%.
To sum up, compound of the present invention has good inhibiting effect for 4 kinds of phytopathogens, and effect is obvious excellent
In control drug Fluoxastrobin, it can be used as bactericide and carry out using in the prevention and treatment of plant disease and/or therapy field with wide
Wealthy application prospect.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of shield range can also be made on the basis of above description and thinking for those of ordinary skill in the art
Other various forms of variations or variation, there is no necessity and possibility to exhaust all the enbodiments.It is all of the invention
Made any modifications, equivalent replacements, and improvements etc., should be included in the protection of the claims in the present invention within spirit and principle
Within the scope of.
Claims (10)
1. a kind of quinolines, which is characterized in that the structure of the compound as shown in formula (i) or formula (ii):
；
Wherein R1For H, C1-4Alkyl, C1-4Halogenated alkyl, C1-4Alkoxy or C1-4One or more of halogenated alkoxy.
2. quinolines according to claim 1, which is characterized in that the R1For H, C1-2Alkyl, C1-2Halogenated alkyl,
C1-2Alkoxy or C1-2One in halogenated alkoxy.
3. quinolines according to claim 2, which is characterized in that the R1For H, methyl, ethyl, trifluoromethyl, first
Oxygroup, ethyoxyl or trifluoromethoxy.
4. quinolines according to claim 3, which is characterized in that the R1For trifluoromethyl or trifluoromethoxy.
5. the preparation method of any quinolines of Claims 1 to 4, which comprises the following steps:
S1. using 2- isobutyl group -4- methoxyacetophenone as Material synthesis 2- isobutyl group -4-hydroxyacetophenone；Again by 2- isobutyl
Base -4-hydroxyacetophenone, 2- halogen methyl quinoline, carbonate is miscible reacts in organic solvent, and 2- isobutyl group -4- is prepared
(2- quinoline) methoxyacetophenone；
S2. 2- isobutyl group -4- (2- quinoline) methoxyacetophenone, DMF and DMA hybrid reaction are obtained into (E) -3- (N, N- diformazan
Base) -1- (2- isobutyl group -4- (2 methoxy quinoline) phenyl) -2- propylene -1- ketone；It is again that itself and hydrazine is miscible organic molten in polarity
It is reacted in agent, 2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline is prepared；
S3. finally by 2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline, R1Substituted benzyl bromine compounds and carbonate
Target product can be prepared in the miscible reaction in organic solvent.
6. preparation method according to claim 5, which is characterized in that 2- isobutyl group -4-hydroxyacetophenone, 2- halogen in step S1
The molar ratio of methylquinoline and carbonate is 1 ︰, 1.1~1.5 ︰ 0.2~0.5；The organic solvent is DMF, and the carbonate is
Potassium carbonate, sodium carbonate or cesium carbonate；Reaction temperature is 50~60 DEG C, and the reaction time is 8~14h；
(E) -3- (N, N- dimethyl) -1- (2- isobutyl group -4- (2 methoxy quinoline) phenyl) -2- propylene -1- ketone in step S2
With 1 ︰ 0.5~1 of molar ratio of hydrazine；The polar organic solvent is ethyl alcohol；The reaction condition is heated to reflux；Reaction time is 6
~12h；
2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline, R in step S31Substituted benzyl bromine compounds and carbonate
Molar ratio is 1 ︰, 1.2~2.0 ︰ 1.4~3；The organic solvent is DMF, DMA or DMSO, and the carbonate is potassium carbonate, carbonic acid
Sodium or cesium carbonate；Reaction temperature is 40~60 DEG C, and the reaction time is 8~14h.
7. preparation method according to claim 5, which is characterized in that 2- isobutyl group -4-hydroxyacetophenone, 2- chlorine in step S1
The molar ratio of methylquinoline and carbonate is 1 ︰, 1.1 ︰ 0.5；The carbonate is cesium carbonate；Reaction temperature is 60 DEG C, when reaction
Between be 12h；
(E) -3- (N, N- dimethyl) -1- (2- isobutyl group -4- (2 methoxy quinoline) phenyl) -2- propylene -1- ketone in step S2
Molar ratio with hydrazine is 1 ︰ 0.5；Reaction time is 12h；
2- (3- isobutyl group -4- (3- pyrazolyl) Phenoxymethyl) quinoline, R in step S31Substituted benzyl bromine compounds and carbonate
Molar ratio is 1 ︰, 1.67 ︰ 2；The organic solvent is DMF, and the carbonate is cesium carbonate；Reaction temperature is 50 DEG C, the reaction time
For 12h.
8. the application in plant disease is being prevented and treated and/or treated to any quinolines of Claims 1 to 4.
9. any quinolines of Claims 1 to 4 are in the application being prepared into fungicide.
10. applying according to claim 8, which is characterized in that the application be prevent and treat and/or treatment botrytis cinerea pers,
The application of cotton-wilt fusarium, fusarium graminearum and peanut Cercospora bacteria.
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| CN101098866A (en) * | 2005-01-07 | 2008-01-02 | 辉瑞产品公司 | Heteroaromatic quinoline compounds and their use as pde10 inhibitors |
| CN106632318A (en) * | 2016-11-04 | 2017-05-10 | 广东环境保护工程职业学院 | Tetrahydropyridopyrimidine compound, preparation method therefor and application of tetrahydropyridopyrimidine compound |
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| CN106632318A (en) * | 2016-11-04 | 2017-05-10 | 广东环境保护工程职业学院 | Tetrahydropyridopyrimidine compound, preparation method therefor and application of tetrahydropyridopyrimidine compound |
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