CN102408428B - 1,2-oxinane pyrazolidone compounds and preparation method and applications thereof - Google Patents
1,2-oxinane pyrazolidone compounds and preparation method and applications thereof Download PDFInfo
- Publication number
- CN102408428B CN102408428B CN201110210322.5A CN201110210322A CN102408428B CN 102408428 B CN102408428 B CN 102408428B CN 201110210322 A CN201110210322 A CN 201110210322A CN 102408428 B CN102408428 B CN 102408428B
- Authority
- CN
- China
- Prior art keywords
- formula
- phosphine
- compound
- compound shown
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 0 CCCC(N(CC#C*(C1*C1)C(C)[C@]1*)NC1c1cc*(*)c*1)=O Chemical compound CCCC(N(CC#C*(C1*C1)C(C)[C@]1*)NC1c1cc*(*)c*1)=O 0.000 description 3
- URLKBWYHVLBVBO-UHFFFAOYSA-N Cc1ccc(C)cc1 Chemical compound Cc1ccc(C)cc1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 1
Abstract
The invention discloses 1,2-oxinane pyrazolidone compounds and a preparation method and applications thereof. The 1,2-oxinane pyrazolidone compounds are shown in a formula III or a formula IV. The preparation method comprises the following steps: uniformly mixing a compound shown in a formula I and a compound shown in a formula II in a solvent and reacting in the presence of a phosphine catalyst to obtain the compounds shown in the formula III or the formula IV. The invention provides a new, simple and feasible method for synthesizing the 1,2-oxinane pyrazolidone compounds; the synthesized compounds are new compounds which are not reported in literatures; in the method disclosed by the invention, the cycloaddition reaction is adopted and the method belongs to the atom economic reaction; and the method uses organic phosphine as the catalyst rather than a transition metal catalyst, thus the product does not have heavy metal residual pollutants and has weeding effect on crabgrass and barnyard grass.
Description
Technical field
The invention belongs to organic synthesis and Pesticide Science field, relate to a kind of 1,2-Azacyclooctane Activity of Pyrazolidinones and preparation method thereof and application.
background technology
1,2-Azacyclooctane Activity of Pyrazolidinones and analogue (formula 1) have multifarious biological activity, in fields such as medicine, agricultural chemicals, there is great researching value, be used as weedicide, sterilant, acetyl-CoA carboxylase inhibitor etc. and be studied, these compounds have received the more concern of agricultural chemicals circle with its significant weeding activity.Although these are 1 years old, 2-Azacyclooctane Activity of Pyrazolidinones and analogue are being played the part of key player in bioactive molecules research, but more successful synthetic method is also more rare, therefore, develop synthetic these compounds of simple and practical high-efficiency synthesis method and study its biological activity and enjoy attention always.
Formula 1
The intermolecular cycloaddition reaction of nucleophilic organic phosphine catalysis is one of the most effective instrument of synthetic carbocyclic ring and heterogeneous ring compound, utilize this class cycloaddition reaction can be very compactly from carbocyclic ring and the heterogeneous ring compound of the raw material composite structure complexity that is cheaply easy to get.At present, the cycloaddition reaction of nucleophilic organic phosphine catalysis has been used to synthetic cyclopentenes, tetrahydrobenzene, cyclopropane, furans, furanone, tetrahydropyridine, pyrrolin, dihydro pyrone, dihydro-isoxazole, chroman, benzopyrone, Dihydrobenzofuranes, pyrazoles, 1, carbocyclic ring and the heterogeneous ring compounds such as 3-dioxane play an important role in building diversity compound library.
Summary of the invention
The object of this invention is to provide a kind of 1,2-Azacyclooctane Activity of Pyrazolidinones and preparation method thereof and application.
Provided by the invention 1,2-Azacyclooctane Activity of Pyrazolidinones, as shown in formula III or formula IV,
In described formula III and formula IV, R is any one in naphthyl, furyl, pyrryl, pyridyl, pyranyl and the total number of carbon atoms that the total number of carbon atoms is the phenyl that replaces of the alkyl, benzyl, phenyl, halogen of 1-20, the phenyl that nitro replaces, phenyl that alkyl that the total number of carbon atoms is 1-20 replaces, alkoxyl group that the total number of carbon atoms is 1-20 replace phenyl, naphthyl, halogen replace cycloalkyl that is 1-20.
In the naphthyl that the phenyl that described halogen replaces and halogen replace, described halogen is all selected from least one in fluorine, chlorine, bromine and iodine; In the phenyl that described halogen replaces, the number of halogenic substituent is 1-5, is preferably 1-3; In the naphthyl that described halogen replaces, the number of halogenic substituent is 1-7, is preferably 1-3;
In the phenyl that described nitro replaces, the number of nitro is 1-5, is preferably 1-3; In the naphthyl that described nitro replaces, the number of nitro is 1-7, is preferably 1-3;
Described the total number of carbon atoms is that in the phenyl of alkyl replacement and the phenyl of the alkoxyl group replacement that the total number of carbon atoms is 1-20 of 1-20, the total number of carbon atoms in alkyl and alkoxyl group is 1-20, is preferably 1-6; Described the total number of carbon atoms is that in the phenyl that replaces of the alkyl of 1-20, the number of alkyl is 1-5, is preferably 1-3; Described the total number of carbon atoms is that in the phenyl that replaces of the alkoxyl group of 1-20, the number of alkoxyl group is 1-5, is preferably 1-3.
The method of preparing compound shown in compound shown in formula III and formula IV provided by the invention, comprise the steps: under phosphine catalyst exists, by compound shown in compound shown in formula I and formula II, (be also 2,3-divinyl acetoacetic ester) mix and in solvent, carry out cycloaddition reaction reaction, react the complete compound shown in described formula III and formula IV that obtains;
In described formula I, R is any one in naphthyl, furyl, pyrryl, pyridyl, pyranyl and the total number of carbon atoms that the total number of carbon atoms is the phenyl that replaces of the alkyl, benzyl, phenyl, halogen of 1-20, the phenyl that nitro replaces, phenyl that alkyl that the total number of carbon atoms is 1-20 replaces, alkoxyl group that the total number of carbon atoms is 1-20 replace phenyl, naphthyl, halogen replace cycloalkyl that is 1-20.Wherein, in the naphthyl that the phenyl that described halogen replaces and halogen replace, described halogen is all selected from least one in fluorine, chlorine, bromine and iodine; In the phenyl that described halogen replaces, the number of halogenic substituent is 1-5, is preferably 1-3; In the naphthyl that described halogen replaces, the number of halogenic substituent is 1-7, is preferably 1-3; In the phenyl that described nitro replaces, the number of nitro is 1-5, is preferably 1-3; In the naphthyl that described nitro replaces, the number of nitro is 1-7, is preferably 1-3; Described the total number of carbon atoms is that in the phenyl of alkyl replacement and the phenyl of the alkoxyl group replacement that the total number of carbon atoms is 1-20 of 1-20, the total number of carbon atoms in alkyl and alkoxyl group is 1-20, is preferably 1-6; Described the total number of carbon atoms is that in the phenyl that replaces of the alkyl of 1-20, the number of alkyl is 1-5, is preferably 1-3; Described the total number of carbon atoms is that in the phenyl that replaces of the alkoxyl group of 1-20, the number of alkoxyl group is 1-7, is preferably 1-3.
This reaction is [3+2+3] cycloaddition reaction between the azomethine imines of nucleophilic organic phosphine catalysis and connection alkene ester, and its reaction equation is as follows:
In aforesaid method, compound shown in described formula I is 1-(α-tolylene)-3-oxo-dihydro pyrazoles inner salt, 1-[(4-aminomethyl phenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt, 1-[(4-nitrophenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt or 1-[(2-chloro-phenyl-) methylene radical]-3-oxo-dihydro pyrazoles inner salt;
Described phosphine catalyst is selected from least one in trialkyl phosphine, alkyl diaryl phosphine, two (diarylphosphino) alkane, dialkyl aryl phosphine and triaryl phosphine; Wherein, described trialkyl phosphine is selected from least one in trimethyl-phosphine, triethyl phosphine, tripropyl phosphine, tri isopropyl phosphine, tributylphosphine, tri-butyl phosphine and tricyclohexyl phosphine; Described alkyl diaryl phosphine is selected from least one in methyldiphenyl base phosphine, ethyl diphenylphosphine, propyl group diphenylphosphine, isopropyl diphenyl base phosphine, butyl diphenyl phosphine, tert-butyl diphenyl phosphine and cyclohexyl diphenylphosphine; Described two (diarylphosphino) alkane is selected from two (diphenylphosphino) methane, 1,2-bis-(diphenylphosphino) ethane, 1,3-bis-(diphenylphosphino) propane, 1,4-bis-(diphenylphosphino) butane, 1, at least one in 5-bis-(diphenylphosphino) pentane and 1,6-bis-(diphenylphosphino) hexane; Described dialkyl aryl phosphine is selected from least one in dimethylphenylphosphine, diethyl phenyl phosphine, dipropyl Phenylphosphine, diisopropyl phenyl phosphine, dibutyl Phenylphosphine, di-tert-butyl-phenyl phosphine and dicyclohexyl Phenylphosphine; Described triaryl phosphine is selected from least one in triphenylphosphine, three (4-aminomethyl phenyl) phosphine, three (4-fluorophenyl) phosphine and three (pentafluorophenyl group) phosphine, preferably at least one in trimethyl-phosphine, tri isopropyl phosphine, tributylphosphine and tricyclohexyl phosphine.
Described solvent is selected from least one in chloroform, methylene dichloride, ethylene dichloride, benzene and toluene, preferred methylene dichloride or the mixed solvent being formed by methylene dichloride and benzene, in the described mixed solvent being formed by methylene dichloride and benzene, the volume ratio of methylene dichloride and benzene is arbitrary proportion, specifically can be 3-4: 1-2.
Shown in described formula I and formula II, the molar ratio of compound is 1: 2-4, specifically can be 1: 2.0-2.2,1: 2.2-2.4,1: 2.0-2.4,1: 2.0-3,1: 2.2-3 or 1: 2.4-3, is preferably 1: 2.4; The mole dosage that feeds intake of described phosphine catalyst is the feed intake 1-20% of mole dosage of compound shown in formula I, specifically can be 5-20%, 5-10% or 10-20%, preferably 20%.In described reactions steps, the time is 1 hour-150 hours, specifically can be 80-150 hour, 80-130 hour, 80-120 hour, 120-150 hour, 120-130 hour or 130-150 hour, is preferably 120 hours; Temperature is-20 ℃-110 ℃, specifically can be-5 ℃ to 0 ℃, 0 ℃ to 25 ℃ or-5 ℃ to 25 ℃, preferably 0 ℃.
Take weedicide, sterilant or acetyl-CoA carboxylase inhibitor and formula III and the application of formula IV compound in preparing weedicide, sterilant or acetyl-CoA carboxylase inhibitor that above-mentioned formula III provided by the invention and formula IV compound be activeconstituents, also belong to protection scope of the present invention.Grass in described weedicide is preferably lady's-grass and/or barnyard grass.Described formula III and formula IV compound are preferably formula V to compound shown in formula XII:
Preferred, the serve as reasons composition of compound shown in described formula III and formula IV and solvent composition of described weedicide, the total concn of compound shown in described formula III and formula IV is 0.078-100 μ g/mL, this total concn specifically can be 1-100 μ g/mL, 1.25-100 μ g/mL, 0.312-100 μ g/mL, 5-100 μ g/mL, 20-100 μ g/mL, 80-100 μ g/mL, 5-80 μ g/mL, 20-80 μ g/mL, 5-20 μ g/mL, 1.25-80 μ g/mL, 1.25-20 μ g/mL, 1.25-80 μ g/mL, 0.312-80 μ g/mL, 0.312-20 μ g/mL or 0.078-0.312 μ g/mL, the mixed solution that the acetone that described solvent is is 1: 59 by volume ratio and liquid agar form.
The present invention provides a kind of simple novel method for synthesizing 1,2-Azacyclooctane Activity of Pyrazolidinones; The synthetic compound document of the present invention has no report, is new compound; Method provided by the invention adopts the mode of cycloaddition to react, and belongs to atom economic reaction; The present invention adopts organic phosphine as catalyzer, and without transition-metal catalyst, can not have heavy-metal residual pollutent in product; New compound has certain weeding activity.
Embodiment
Compound 1-(α-tolylene)-3-oxo-dihydro pyrazoles inner salt shown in formula I used in following embodiment, 1-[(4-aminomethyl phenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt, 1-[(4-nitrophenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt, 1-[(2-chloro-phenyl-) methylene radical]-3-oxo-dihydro pyrazoles inner salt is all according to document (a) Journal of the American Chemical Society, 2003, 125:10778. (b) Journal of the American Chemical Society, 2005, 127:11244. (c) Journal of the American Chemical Society, 2006, 128:6330. the method for report is prepared and is obtained, concrete synthetic method is as follows:
Add pyrazolidine-3-ketone (5mmol) in the solution of 1 ml methanol in aldehyde (5mmol), the mixture obtaining at room temperature stirs 1-24 hour (the concrete reaction times is by thin-layer chromatography Monitoring and Controlling), then with 20 milliliters of ether dilutions, leach precipitation, with 5 milliliters of ether washings, under vacuum, be drying to obtain corresponding azomethine imines (shown in I), productive rate is 70-90%.
Compound 2 shown in formula II used in following embodiment, 3-divinyl acetoacetic ester is according to document (a) Journal of the American Chemical Society, 2007,129:5843-5845, (b) Organic Letters, 2010,12:2570-2573 and (c) Journal of Organic Chemistry, 2002, the method of 67:2837-2847 report is prepared and is obtained, and concrete synthetic method is as follows:
Under argon shield, the 2-of 34.8g (0.1mol) (triphenylphosphine fork base) ethyl acetate is dissolved in the mixed solvent of 300 milliliters of methylene dichloride and 100 milliliters of pentanes, be cooled to 0 ℃.Under agitation condition, the triethylamine of 14.8 milliliters was slowly added in 1 hour to above-mentioned solution by syringe pump, then at room temperature stir and spend the night.The suspension producing filters with the Büchner funnel that silica gel is housed, then at 0 ℃, pass through Rotary Evaporators concentrated filtrate, then add 300 milliliters of pentanes in the resistates of gained, stir 30 minutes, cross and filter out triphen oxygen phosphorus, filtrate concentrates by Rotary Evaporators at 0 ℃.Under reduced pressure, distillation residue obtain colorless oil product (shown in II), and productive rate is 61%.
Shown in embodiment 1, formula V and VI 1,2-Azacyclooctane Activity of Pyrazolidinones synthetic
By compound 1-(α-tolylene)-3-oxo-dihydro pyrazoles inner salt (0.125mmol) shown in 0.0218g formula I, 4mL methylene dichloride, compound 2 shown in 1mL benzene and 0.0280g formula II, 3-divinyl acetoacetic ester (0.250mmol) is put in the Shrek pipe of the 15mL crossing with oven drying, add phosphine catalyst tricyclohexyl phosphine 0.025mmol to mix and carry out cycloaddition reaction, in this reaction system, 1-(α-tolylene)-3-oxo-dihydro pyrazoles inner salt and 2, the mol ratio of 3-divinyl acetoacetic ester is 1: 2.0, the molar content that tricyclohexyl phosphine accounts for 1-(α-tolylene)-3-oxo-dihydro pyrazoles inner salt is 20%, at 0 ℃, stir 120 hours, with crossing post (ethyl acetate: sherwood oil=10: 1 after Rotary Evaporators concentration of reaction solution, v/v), obtain 40.3mg product, mixture for compound shown in formula V and VI, yield 81%, by nucleus magnetic hydrogen spectrum, calculating the mol ratio of compound shown in formula V and VI in deuterochloroform is 34: 46.(V) be a pair of tautomer that cannot be separated with (VI).
(V) mixture and (VI): IR (film) v
max2980,1716,1699,1662,1567,1541,1491,1417,1396,1366,1241,1201,1098,1039,760,736,705,668cm
-1; HRMS (ESI) C
22h
27n
2o
5 +[M+H]
+calculated value is 399.1914, finds 399.1918.
(VI) (main isomer):
1h NMR (300MHz, CDCl
3) δ 7.43-7.07 (m, 4H), 6.13 (dd, J=5.0,3.6Hz, 1H), 5.48 (s, 1H), 4.68 (dd, J=18.3,3.6Hz, 1H), 4.34-4.26 (m, 2H), 4.10-3.95 (m, 2H), 3.85-3.71 (m, 1H), 3.39 (ddd, J=37.9,20.0,15.5Hz, 1H), 2.74 (ddd, J=16.8,12.2,9.0Hz, 1H), 2.35-2.17 (m, 1H), 2.15 (s, 3H), (1.35 t, J=7.1Hz, 3H), (1.18 t, J=7.1Hz, 3H);
13c NMR (75MHz, CDCl
3) δ 173.0,168.8,164.4,146.4,141.0,135.0,133.7,128.3,127.9,126.7,125.8,71.5,61.2,60.8,53.2,43.6,30.5,22.7,14.2,14.0.
(V) (less important isomer):
1h NMR (300MHz, CDCl
3) δ 6.81 (s, 1H), 5.14 (s, 1H), 2.65-2.45 (m, 1H), 2.07 (s, 3H), 1.31 (t, J=7.1Hz, 3H), 1.10 (t, J=7.1Hz, 3H);
13c NMR (75MHz, CDCl
3) δ 167.8,165.5,137.2,136.1,127.4,127.3,61.3,60.6,30.7,14.1,13.8.
As from the foregoing, products therefrom structure is correct, is compound shown in formula III and formula IV.
Embodiment 2, formula (VII) and (VIII) shown in 1,2-Azacyclooctane Activity of Pyrazolidinones synthetic
By compound 1-[(4-aminomethyl phenyl shown in 0.0235g formula I) methylene radical]-3-oxo-dihydro pyrazoles inner salt (0.125mmol), 3mL methylene dichloride, compound 2 shown in 2mL benzene and 0.0308g formula II, 3-divinyl acetoacetic ester (0.275mmol) is put in the Shrek pipe of the 15mL crossing with oven drying, add phosphine catalyst trimethyl-phosphine 0.0125mmol to mix and carry out cycloaddition reaction, in this reaction system, 1-[(4-aminomethyl phenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt and 2, the mol ratio of 3-divinyl acetoacetic ester is 1: 2.2, trimethyl-phosphine accounts for 1-[(4-aminomethyl phenyl) methylene radical] molar content of-3-oxo-dihydro pyrazoles inner salt is 10%, at-5 ℃, stir 130 hours, with crossing post (ethyl acetate: sherwood oil=10: 1 after Rotary Evaporators concentration of reaction solution, v/v), obtain 33.0mg product, for formula (VII) with the mixture of compound (VIII), yield 64%, (VII): (VIII) be 39: 61 (mol ratios in deuterochloroform, by nucleus magnetic hydrogen spectrum, calculate).(VII) be a pair of tautomer that cannot be separated with (VIII).
(VII) mixture and (VIII): IR (film) v
max2980,1716,1699,1652,1557,1541,1508,1417,1395,1366,1240,1200,1097,1040,762,668cm
-1; HRMS (ESI) C
23h
29n
2o
5 +[M+H]
+calculated value is 413.2071, finds 413.2081.
(VIII) (main isomer):
1h NMR (300MHz, CDCl
3) δ 7.33-6.94 (m, 1H), 6.18 (dd, J=5.1,4.0Hz, 2H), 5.40 (s, 1H), 4.63 (dd, J=17.9,3.9Hz, 1H), 4.35-4.18 (m, 2H), 4.17-3.95 (m, 2H), 3.91-3.64 (m, 2H), 3.37 (ddd, J=11.6,8.9,2.3Hz, 1H), 2.88-2.64 (m, 1H), 2.27 (s, 3H), 2.26-2.19 (m, 1H), 2.13 (s, 3H), (1.36 t, J=7.2Hz, 3H), (1.20 t, J=7.1Hz, 3H);
13c NMR (75MHz, CDCl
3) δ 173.0,168.9,164.5,145.4,137.9,136.3,135.4,133.6,129.0,128.7,125.9,71.4,61.2,60.8,52.9,43.6,30.5,22.7,21.0,14.1,13.8.
(VII) (less important isomer):
1h NMR (300MHz, CDCl
3) δ 6.82 (s, 1H), 5.05 (s, 1H), 2.65-2.45 (m, 1H), 2.32 (s, 3H), 2.06 (s, 3H), 1.31 (t, J=7.2Hz, 3H), 1.13 (t, J=7.1Hz, 3H);
13c NMR (75MHz, CDCl
3) δ 173.0,168.9,164.5,137.0,136.1,134.1,127.1,61.3,60.7,30.8,21.0,14.1,13.8.
As from the foregoing, products therefrom structure is correct, is compound shown in formula III and formula IV.
Embodiment 3, formula (IX) and (X) shown in 1,2-Azacyclooctane Activity of Pyrazolidinones synthetic
By compound 1-[(4-nitrophenyl shown in 0.0274g formula I) methylene radical]-3-oxo-dihydro pyrazoles inner salt (0.125mmol), compound 2 shown in 5mL methylene dichloride and 0.0336g formula II, 3-divinyl acetoacetic ester (0.300mmol) is put in the Shrek pipe of the 15mL crossing with oven drying, add phosphine catalyst tributylphosphine 0.00625mmol to mix and carry out cycloaddition reaction, in this reaction system, 1-[(4-nitrophenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt and 2, the mol ratio of 3-divinyl acetoacetic ester is 1: 2.4, tributylphosphine accounts for 1-[(4-nitrophenyl) methylene radical] molar content of-3-oxo-dihydro pyrazoles inner salt is 5%, at 25 ℃, stir 80 hours, with crossing post (ethyl acetate: sherwood oil=10: 1 after Rotary Evaporators concentration of reaction solution, v/v), obtain 29.0mg product, for formula (IX) with the mixture of compound (X), yield 58%, (IX): (X) be 19: 81 (mol ratios in deuterochloroform, by nucleus magnetic hydrogen spectrum, calculate).(IX) be a pair of tautomer that cannot be separated with (X).
(IX) mixture and (X): IR (film) v
max2918,1715,1698,1652,1541,1521,1473,1456,1418,1396,1347,1243cm
-1; HRMS (ESI) C
22h
26n
3o
7 +[M+H]
+calculated value is 444.1765, finds 444.1744.
(X) (main isomer):
1h NMR (300MHz, CDCl
3) δ 8.10-7.98 (m, 2H), 7.62 (dd, J=9.0,1.1Hz, 2H), 6.05 (dd, J=4.7,2.8Hz, 1H), 5.64 (s, 1H), 4.87 (dd, J=19.2,2.8Hz, 1H), 4.37 (q, J=7.1Hz, 2H), 4.05-3.87 (m, 3H), 3.66 (dd, J=19.2,4.7Hz, 1H), 3.57-3.45 (m, 1H), 2.71 (ddd, J=16.7,12.7,9.0Hz, 1H), 2.30 (dd, J=15.1,7.5Hz, 1H), 2.22 (s, 3H), 1.40 (t, J=7.1Hz, 3H), 1.14 (dd, J=10.0,4.3Hz, 3H).
(IX) (less important isomer):
1h NMR (300MHz, CDCl
3) δ 8.20 (d, J=8.9Hz, 2H), 7.52-7.19 (m, 2H), 6.78 (t, J=3.5Hz, 1H), 5.43 (s, 1H), 4.30-4.20 (m, 2H), 4.12 (m, 3H), 2.61-2.38 (m, 1H), 2.18 (s, 3H), 1.32 (t, J=7.1Hz, 3H), 1.18 (t, J=7.1Hz, 3H).
As from the foregoing, products therefrom structure is correct, is compound shown in formula III and formula IV.
Embodiment 4, formula (XI) and (XII) shown in 1,2-Azacyclooctane Activity of Pyrazolidinones synthetic
By the chloro-phenyl-of compound 1-[(2-shown in the formula I of 0.0261g) methylene radical]-3-oxo-dihydro pyrazoles inner salt (0.125mmol), compound 2 shown in 5mL trichloromethane and 0.042g formula II, 3-divinyl acetoacetic ester (0.375mmol) is put in the Shrek pipe of the 15mL crossing with oven drying, add phosphine catalyst tricyclohexyl phosphine 0.025mmol to mix and carry out cycloaddition reaction, in this reaction system, 1-[(2-chloro-phenyl-) methylene radical]-3-oxo-dihydro pyrazoles inner salt and 2, the mol ratio of 3-divinyl acetoacetic ester is 1: 3, tricyclohexyl phosphine accounts for 1-[(2-chloro-phenyl-) methylene radical] molar content of-3-oxo-dihydro pyrazoles inner salt is 20%, at 0 ℃, stir 150 hours, with crossing post (ethyl acetate: sherwood oil=10: 1 after Rotary Evaporators concentration of reaction solution, v/v), obtain 48.7mg product, for formula (XI) with the mixture of compound (XII), yield 90%, (XI): (XII) be 24: 76 (mol ratios in deuterochloroform, by nucleus magnetic hydrogen spectrum, calculate).(XI) be a pair of tautomer that cannot be separated with (XII).
(XI) mixture and (XII): IR (film) v
max2932,1715,1541,1508,1458,1396,1366,1252,1199,1097,1042,864,748,668cm
-1; HRMS (ESI) C
22h
26clN
2o
5 +[M+H]
+calculated value is 433.1525, finds 433.1534.
(XII) (main isomer):
1h NMR (300MHz, CDCl
3) δ 7.73 (dd, J=7.7, 1.5Hz, 1H), 7.47-7.31 (m, 1H), 7.27-7.09 (m, 2H), 6.61 (dd, J=6.7, 4.9Hz, 1H), 5.57 (s, 1H), 4.46 (dd, J=16.0, 4.9Hz, 1H), 4.28 (qd, J=7.1, 4.9Hz, 2H), 4.16 (dd, J=16.1, 6.6Hz, 1H), 4.07-3.81 (m, 2H), 3.63 (td, J=11.9, 8.0Hz, 1H), 3.30-3.18 (m, 1H), 3.09 (ddd, J=16.3, 12.1, 8.4Hz, 1H), 2.25 (ddd, J=16.3, 7.9, 1.6Hz, 1H), 2.04 (s, 3H), 1.33 (t, J=7.1Hz, 3H), 1.19-1.09 (m, 3H),
13c NMR (75MHz, CDCl
3) δ 173.6,168.1,164.2,142.8,138.6,138.1,133.2,132.9,130.5,130.2,129.4,128.2,126.1,69.1,61.1,60.9,53.4,43.2,30.6,22.0,14.2,13.9.
(XI) (less important isomer):
1h NMR (300MHz, CDCl
3) δ 6.99 (s, 1H), 5.01 (s, 1H), 2.02 (s, 3H), 1.32 (t, J=7.1Hz, 3H), 1.00 (t, J=7.1Hz, 3H);
13c NMR (75MHz, CDCl
3) δ 167.6,165.1,129.8,128.8,126.4,61.2,60.6,30.9,14.1,13.7.
As from the foregoing, products therefrom structure is correct, is compound shown in formula III and formula IV.
The Herbicidal of compound shown in embodiment 5, formula III and formula IV
The mixture that adds embodiment 1 to prepare gained formula III and IV compound (being also compound shown in formula V and formula VI) in 2mL volumetric flask is total to 0.012g, with acetone solution constant volume, obtains the solution that concentration is 6mg/mL;
Pipetting this concentration is the acetone soln 0.05mL of 6mg/mL again, then adds acetone and obtain to constant volume in 5mL volumetric flask the acetone soln that concentration is 0.06mg/mL;
Pipetting this concentration is the solution 0.05mL of 0.06mg/mL again, then adds acetone and obtain to constant volume in 5mL volumetric flask the acetone soln that concentration is 0.0006mg/mL.
Get respectively again each 1.0mL of acetone soln that above-mentioned 3 concentration are respectively 6mg/mL, 0.06mg/mL and 0.0006mg/mL, join the solution of making respectively 60mL in the liquid agar of 59mL, the concentration of the mixture of final formula III and IV compound is respectively 100 μ g/mL, 1 μ g/mL and 0.01 μ g/mL.
According to upper identical method, only formula III and formula IV compound are replaced with to acetochlor, the liquid agaroid that the ultimate density that obtains acetochlor is respectively 100 μ g/mL, 1 μ g/mL and 0.01 μ g/mL in contrast.
According to upper identical method, only prepared by embodiment 1 to gained formula III and IV compound (being also compound shown in formula V and formula VI) and replaces with respectively that embodiment 2-4 prepares gained formula III and IV compound (being also compound shown in compound, formula XI and formula XII shown in compound, formula IX and formula X shown in formula VII and formula VIII) carries out weeding activity test.
In table 2, measured mixture and formula XI and the inhibiting rate of formula XII compound under more concentration of formula IX and formula X, adopt in test method and table 1 just the same.
Measuring method: adopt Activities, in the agar liquid of above-mentioned different concns, add respectively 10 lady's-grass and barnyard grass seed, then insert in the artificial lighting incubator of 27 ± 0.5 ℃ and cultivate, rear 7d is processed in test, it is index that the target root growth of take suppresses, the inhibiting rate of working sample to target, inhibiting rate=[(it is long that blank root long is processed root)/blank root is long] * 100%.Each compound is distinguished replicate(determination) 3 times under different concns, and inhibiting rate is averaged.The weeding activity of compound shown in gained formula III and IV as shown in Tables 1 and 2.
Table 1, to the weeding activity of lady's-grass and barnyard grass (inhibiting rate, %)
The mixture of the mixture of table 2, formula IX and formula X and formula XI and formula XII to the weeding activity of lady's-grass and barnyard grass (inhibiting rate, %)
From table 1 and table 2, compound shown in formula III and formula IV has certain inhibition activity to lady's-grass and barnyard grass, can be used as weedicide and further develops.
Claims (8)
1. tautomer compound shown in formula III and formula IV,
In described formula III and formula IV, R is phenyl, p-methylphenyl, p-nitrophenyl or Chloro-O-Phenyl.
2. a method of preparing formula III and formula IV compound described in claim 1, under the condition that comprises the steps: to exist at phosphine catalyst, compound shown in compound shown in formula I and formula II is mixed and in solvent, carries out cycloaddition reaction, react the complete compound shown in formula III and formula IV described in claim 1 that obtains;
Compound shown in described formula I is 1-(α-tolylene)-3-oxo-dihydro pyrazoles inner salt, 1-[(4-aminomethyl phenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt, 1-[(4-nitrophenyl) methylene radical]-3-oxo-dihydro pyrazoles inner salt or 1-[(2-chloro-phenyl-) methylene radical]-3-oxo-dihydro pyrazoles inner salt;
Described phosphine catalyst is selected from least one in trialkyl phosphine, alkyl diaryl phosphine, two (diarylphosphino) alkane, dialkyl aryl phosphine and triaryl phosphine; Wherein, described trialkyl phosphine is selected from least one in trimethyl-phosphine, triethyl phosphine, tripropyl phosphine, tri isopropyl phosphine, tributylphosphine, tri-butyl phosphine and tricyclohexyl phosphine; Described alkyl diaryl phosphine is selected from least one in methyldiphenyl base phosphine, ethyl diphenylphosphine, propyl group diphenylphosphine, isopropyl diphenyl base phosphine, butyl diphenyl phosphine, tert-butyl diphenyl phosphine and cyclohexyl diphenylphosphine; Described two (diarylphosphino) alkane is selected from two (diphenylphosphino) methane, 1,2-bis-(diphenylphosphino) ethane, 1,3-bis-(diphenylphosphino) propane, 1,4-bis-(diphenylphosphino) butane, 1, at least one in 5-bis-(diphenylphosphino) pentane and 1,6-bis-(diphenylphosphino) hexane; Described dialkyl aryl phosphine is selected from least one in dimethylphenylphosphine, diethyl phenyl phosphine, dipropyl Phenylphosphine, diisopropyl phenyl phosphine, dibutyl Phenylphosphine, di-tert-butyl-phenyl phosphine and dicyclohexyl Phenylphosphine; Described triaryl phosphine is selected from least one in triphenylphosphine, three (4-aminomethyl phenyl) phosphine, three (4-fluorophenyl) phosphine and three (pentafluorophenyl group) phosphine;
Described solvent is selected from least one in chloroform, methylene dichloride, ethylene dichloride, benzene and toluene;
Shown in described formula I and formula II, the molar ratio of compound is 1:2-4; The mole dosage that feeds intake of described phosphine catalyst is the feed intake 1-20% of mole dosage of compound shown in described formula I;
In described reactions steps, the time is 80-150 hour, and temperature is-5 ℃ to 25 ℃.
3. method according to claim 2, is characterized in that: described phosphine catalyst is selected from least one in trimethyl-phosphine, tri isopropyl phosphine, tributylphosphine and tricyclohexyl phosphine;
The mixed solvent that described solvent is selected from methylene dichloride or is comprised of methylene dichloride and benzene;
Shown in described formula I and formula II, the molar ratio of compound is 1:2.4; The mole dosage that feeds intake of described phosphine catalyst is 20% of the mole dosage that feeds intake of compound shown in described formula I.
4. take the weedicide that formula III and formula IV compound are activeconstituents described in claim 1.
5. weedicide according to claim 4, is characterized in that: tautomer compound shown in described formula III and formula IV is formula V to a pair of tautomer in formula XII:
The serve as reasons composition of compound shown in described formula III and formula IV and solvent composition of described weedicide, the total concn of compound shown in described formula III and formula IV is 0.078-100 μ g/mL, the mixed solution that the acetone that described solvent is is 1:59 by volume ratio and liquid agar form.
6. formula III and the application of formula IV compound in preparing weedicide described in claim 1.
7. application claimed in claim 6, is characterized in that: the grass in described weedicide is lady's-grass and/or barnyard grass.
8. according to the application described in claim 6 or 7, it is characterized in that: the serve as reasons composition of compound shown in described formula III and formula IV and solvent composition of described weedicide, the total concn of compound shown in described formula III and formula IV is 0.078-100 μ g/mL, the mixed solution that the acetone that described solvent is is 1:59 by volume ratio and liquid agar form.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110210322.5A CN102408428B (en) | 2011-07-26 | 2011-07-26 | 1,2-oxinane pyrazolidone compounds and preparation method and applications thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110210322.5A CN102408428B (en) | 2011-07-26 | 2011-07-26 | 1,2-oxinane pyrazolidone compounds and preparation method and applications thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102408428A CN102408428A (en) | 2012-04-11 |
| CN102408428B true CN102408428B (en) | 2014-01-15 |
Family
ID=45910814
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110210322.5A Expired - Fee Related CN102408428B (en) | 2011-07-26 | 2011-07-26 | 1,2-oxinane pyrazolidone compounds and preparation method and applications thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102408428B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105669678B (en) * | 2016-03-08 | 2017-11-03 | 中国农业大学 | A kind of phthalazines and azoles and preparation method thereof |
| CN114394971B (en) * | 2022-01-24 | 2023-01-31 | 云南大学 | Preparation method of indole carbazole compound |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3126395A (en) * | 1964-03-24 | Chj czhs | ||
| EP0202794A1 (en) * | 1985-04-30 | 1986-11-26 | Eli Lilly And Company | 7-Substituted-2,3-(Dihydro) bicyclic pyrazolidinones |
| EP0508126A1 (en) * | 1991-03-21 | 1992-10-14 | Bayer Ag | 3-Hydroxy-4-aryl-5-oxo-pyrazolin derivatives |
| CN1283191A (en) * | 1997-11-21 | 2001-02-07 | 巴斯福股份公司 | Benzylidene pyrazolones and its preparation and use |
| CN100482666C (en) * | 2003-07-14 | 2009-04-29 | 拜尔农作物科学股份公司 | Hetaryl-substituted pyrazolidindione derivatives with pesticidal characteristics |
-
2011
- 2011-07-26 CN CN201110210322.5A patent/CN102408428B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3126395A (en) * | 1964-03-24 | Chj czhs | ||
| EP0202794A1 (en) * | 1985-04-30 | 1986-11-26 | Eli Lilly And Company | 7-Substituted-2,3-(Dihydro) bicyclic pyrazolidinones |
| EP0508126A1 (en) * | 1991-03-21 | 1992-10-14 | Bayer Ag | 3-Hydroxy-4-aryl-5-oxo-pyrazolin derivatives |
| CN1283191A (en) * | 1997-11-21 | 2001-02-07 | 巴斯福股份公司 | Benzylidene pyrazolones and its preparation and use |
| CN100482666C (en) * | 2003-07-14 | 2009-04-29 | 拜尔农作物科学股份公司 | Hetaryl-substituted pyrazolidindione derivatives with pesticidal characteristics |
Non-Patent Citations (2)
| Title |
|---|
| C.Cucurou,等.Mechanisms of Inactivation of Lipoxygenases by Phenidone and BW755C.《Biochemistry》.1991,第30卷(第37期),第8964-8970页. |
| Mechanisms of Inactivation of Lipoxygenases by Phenidone and BW755C;C.Cucurou,等;《Biochemistry》;19910930;第30卷(第37期);第8964-8970页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102408428A (en) | 2012-04-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Fourgeaud et al. | Oxaphospholene and oxaphosphinene heterocycles via RCM using unsymmetrical phosphonates or functional phosphinates | |
| CN103570600B (en) | A kind of chiral alpha methylene beta-lactam class compound and its preparation method and application | |
| CN102408428B (en) | 1,2-oxinane pyrazolidone compounds and preparation method and applications thereof | |
| AU2004309054B2 (en) | Process for the preparation of pyridine derivatives | |
| Shcherbakov et al. | Transformations of 3-acyl-4H-polyfluorochromen-4-ones under the action of amino acids and biogenic amines | |
| Ghelfi et al. | Synthesis of 5-methoxylated 3-pyrrolin-2-ones via the rearrangement of chlorinated pyrrolidin-2-ones | |
| CN102741237A (en) | Beta-dihydrofuran deriving compound, method for producing beta-dihydrofuran deriving compound or beta-tetrahydrofuran deriving compound, beta-glycoside compound, method for producing beta-glycoside compound, and method for producing 4'-ethynyl d4t and analogue comp | |
| CN107286192B (en) | A kind of alkynyl phosphate synthesis method | |
| Jung et al. | Synthesis of aza-derivatives of tetrahydrofuran lignan natural products | |
| Langer et al. | Synthesis of Functionalized 2‐Alkylidenetetrahydrofurans by Cyclization of 1, 3‐Bis (trimethylsilyloxy)‐1, 3‐butadienes with Epoxides | |
| Çiftçi et al. | Structural and fluorescence properties of the 2, 2′-methylenediphenoxy and 1, 1′-methylenedi-2-naphthoxy cyclotriphosphazene derivatives | |
| CN104844651A (en) | Method for preparing six fluorine phosphonic acid ester base fe organism derivatives | |
| Palacios et al. | Diastereoselective hydrophosphonylation of imines using (R, R)-TADDOL phosphite. Asymmetric synthesis of α-aminophosphonic acid derivatives | |
| JPWO2007080837A1 (en) | Method for producing substituted benzene | |
| Kotali et al. | Synthesis of novel dehydroacetic acid N-aroylhydrazone-derived boron heterocycles | |
| Wilton-Ely et al. | Hydrogen-bonded networks:(phosphine) gold (I) 4-amino-2-pyrimidine-thiolates | |
| Nongbri et al. | Arene ruthenium β-diketonato triazolato derivatives: Synthesis and spectral studies (β-diketones: 1-phenyl-3-methyl-4-benzoyl pyrazol-5-one, acetylacetone derivatives) | |
| CN102260267A (en) | Pyrazolidone-tetrahydropyrazole compounds and synthesis method thereof | |
| Xue et al. | Diethyl phosphite mediated reductive [1+ 4] annulation of α-ketoesters with α, β-unsaturated ketones and synthesis of polysubstituted 2, 3-dihydrofurans | |
| TWI739789B (en) | Process for preparing substituted 2-arylethanols | |
| Yavari et al. | Synthesis of Highly Functionalized Stable Heterocyclic Phosphorus Ylides. Cycloaddition Reaction between Conjugated Phosphorus Ylides and Alkyl Propiolates | |
| Bahri et al. | One-pot synthesis of new highly substituted allylic phosphorodiamidates | |
| CN105777757B (en) | Tetrahydrochysene diazepine and quinazoline compounds and preparation method thereof | |
| Kędzia et al. | Efficient syntheses of 3-phosphorylquinolin-4-ones and 3-phosphoryl-1, 8-naphthyridin-4-ones | |
| Borse et al. | Synthetic utility of Kabachnik–Fields reaction: A convenient one-pot three-component synthesis of N-phenyl isoquinolone-1-phosphonates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140115 Termination date: 20150726 |
|
| EXPY | Termination of patent right or utility model |