CN100503563C - Arylpyrrole N-oxalate derivatives and their preparation and application as insecticides - Google Patents

Abstract

This invention relates to the method for synthesizing the derivates of pyrrole-aryl N- oxalic ester and its application. Its structure shows as formula (I) (see the specification of each group in the directions). The described compound has a favorable insecticidal activity widely used in pest control for the crops. The insecticide has a broad prospect.

Description

Arylpyrrole N-oxalate derivatives and their preparation and application as insecticides

technical field

The present invention relates to insecticides, especially arylpyrrole N-oxalate derivatives and their preparation and application.

Background technique

In 1987, researchers from CR2anamid isolated dioxapR2rrolomR2cin from the metabolites of StreptomR2cesfumanus, and found that it had moderate insecticidal and acaricidal activity. Subsequently, the American Cyanamid Company developed a structurally new insecticide and acaricide 2-arylpyrrole insecticide chlorfenapr (chlorfenapR2r) through in-depth research on this natural antibiotic. Addor R.R3.; Babcock T.J.; Black B.C. et al.SR2nthesis and ChemistrR2 of Agrochemincals III, ACS SR2mp.504, pp283-297.(1992);

In 1992, the American cyanamide company (CR2anamid) synthesized N-substituted pyrrole derivatives of the aminoalkyl carboxylate structure, such as Ia and Ib, and the lethality of 10 mg/L to southern armyworm was 100%. Kuhn D.G.; Donovan S.F.; Furch J.A. US 5,286,743 (1992).

In 1992, the American cyanamide company (CR2anamid) synthesized N-cycloalkyl carboxylate pyrrole derivatives II, such as IIa and IIb, 10mg/L against southern armyworm, corn leaf beetle and aphid nightworm, 100mg/L The lethality rate of spider mites against organophosphorus resistant strains was 100%. Kuhn, D.G.; Donovan, S.F.; Furch, J.A. US 5,232,980 (1992).

In 1993, the American cyanamide company (CR2anamid) synthesized III, such as IIIa and IIIb, which have excellent activity against adults and eggs of western potato leafhoppers and organophosphorus resistant strains of spider mites, with a lethality of 100% at 100 mg/L. Kuhn D.G.; Kames R3aran V. US 5,302,383 (1993).

In 1993, BaR2er company reported that N-carbamate substituted arylpyrrole derivatives, such as IVa and IVb, had a lethality of 98% at 100 mg/L to organophosphorus resistant strains of spider mites, which was higher than that of chlorfenapyr (80% fatality rate). Uhr H.; Erdelen C.; R3achendorff-Neumann U., Stendel R3. US 5521211 (1993).

Contents of the invention

The object of the present invention is to provide an arylpyrrole N-oxalate derivative and its preparation and application. The compound has excellent insecticidal activity.

The present invention is the arylpyrrole N-oxalate derivatives whose general chemical formula is (I):

In the formula, R ₁ represents hydrogen, Cl, Br or CF ₃ ; R ₂ represents Cl, Br, CF ₃ , CN or NO ₂ ; R ₃ represents CN, NO ₂ or S(O ₂ ) CF ₃ ; R ₄ represents hydrogen , Cl, Br or CF ₃ ; Y represents O, S or N; R represents 1-6 carbon alkoxy, 1-6 carbon haloalkoxy, 1-6 carbon alkoxyalkoxy, 3-6 carbon alkene oxygen Base, 3-6 halocarbenyloxy, 3-6 carbonyneoxy, 3-7 carboncycloalkoxy, 3-6 carbon cyanoalkoxy, phenoxy, benzyloxy, hydroxyl, 1 -4-carbon alkoxyalkyl, 1-4-carbon alkyl, phenyl, naphthyloxy or benzene ring is substituted by one or more of the following groups: halogen, 1-4-carbon alkyl, 1-4-carbon alkoxy Base, 1-4 carbon haloalkyl, 1-4 carbon haloalkoxy, 1-4 carbon alkoxyalkyl, 1-4 carbon alkylthio, 1-4 carbon alkylsulfinyl, 1-4 carbon alkyl Sulfonyl, nitro, cyano, hydroxyl, carboxyl, 1-4 carbon alkylcarbonyl, 1-4 carbon alkoxycarbonyl or imino.

The compound of the general formula (Ia) shows particularly excellent insecticidal activity, wherein R represents 1-6 carbon alkoxy, 1-6 carbon haloalkoxy, 1-6 carbon alkoxyalkoxy, 3-6 Carbenyloxy, 3-6 halocarbenyloxy, 3-6 carbonyneoxy, 3-7 carbon cycloalkoxy, 3-6 carbon cyanoalkoxy, phenoxy, benzyloxy, Hydroxy, 1-4 carbon alkoxyalkyl, 1-4 carbon alkyl, phenyl, naphthyloxy or benzene ring are substituted by one or more of the following groups: halogen, 1-4 carbon alkyl, 1-4 Carbon alkoxy, 1-4 carbon haloalkyl, 1-4 carbon haloalkoxy, 1-4 carbon alkoxyalkyl, 1-4 carbon alkylthio, 1-4 carbon alkylsulfinyl, 1-4 Carbon alkylsulfonyl, nitro, cyano, hydroxyl, carboxyl, 1-4 carbon alkylcarbonyl, 1-4 carbon alkoxycarbonyl or imino.

The compound of general formula (I) of the present invention can be prepared according to the following method one: compound A and B are in organic solvent, make acid-binding agent with inorganic base or organic base (the mol ratio of compound A and compound B and acid-binding agent is 1:1:1-2), react at -10-80°C for 2-12 hours, separate the organic phase, remove the organic solvent under reduced pressure, and then purify it with a silica gel column. The organic solvent is toluene, benzene, cyclohexane, acetonitrile, acetone, tetrahydrofuran, ether, dioxane, DMF (\, \dimethylformamide) or DMSO (dimethyl sulfoxide); the inorganic base is NaOH, KOH, Na ₂ CO ₃ , K ₂ CO ₃ , NaHCO ₃ , KHCO ₃ ; the organic base is pyridine, triethylamine or 4-N, N-dimethylaminopyridine.

method one:

X is Cl or Br.

Put compound A and oxalic acid in organic solvent, use inorganic base or organic base as acid-binding agent (the molar ratio of compound A, oxalic acid and acid-binding agent is 1:1:1-2), react at -10-80°C for 2 -12 hours, the organic phase was separated, and the organic solvent was removed under reduced pressure to obtain compound C. Compound C was chlorinated with sulfoxide, oxalyl chloride or phosgene, and then reacted with alcohol, phenol or oxime to obtain compound I. The organic solvent is toluene, benzene, cyclohexane, acetonitrile, acetone, tetrahydrofuran, ether, dioxane, DMF or DMSO (dimethyl sulfoxide); the inorganic base is NaOH, KOH, Na ₂ CO ₃ , K ₂ CO _3. NaHCO ₃ , KHCO ₃ ; the organic base is pyridine, triethylamine or 4-N,N-dimethylaminopyridine.

Method Two:

X is Cl or Br.

The compound of general formula (Ia) of the present invention can be prepared as follows: 2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (D) and equimolar Acetylaminomethylene acetate was dissolved in tetrahydrofuran, in the presence of 1-1.5 moles of sodium hydride, refluxed for 8 hours, cooled, filtered, the filtrate was concentrated, and the residue was chromatographed on a silica gel column under reduced pressure to obtain a white Crystalline 1-acetylaminomethylene-2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (E), compound E and 1-1.5 moles After mixing the phosphorus oxyhalide, the temperature was raised to reflux, and after reflux reaction for 1 hour, it was cooled, the reaction mixture was poured into ice water, extracted with ethyl acetate, the organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate, and filtered The solvent was precipitated under reduced pressure, and the obtained solid was recrystallized from a mixed solvent of ethyl acetate and petroleum ether to obtain compound F. Compounds F and G are reacted in an organic solvent with an inorganic base or an organic base as an acid-binding agent (the molar ratio of compound F to compound G to acid-binding agent is 1:1:1-2), and react at -10-80°C After 2-12 hours, the organic phase was separated, the organic solvent was removed under reduced pressure, and then purified by silica gel chromatography. The organic solvent is toluene, benzene, cyclohexane, acetonitrile, acetone, tetrahydrofuran, ether, dioxane, DMF or DMSO; the inorganic base is NaOH, KOH, Na ₂ CO ₃ , K ₂ CO ₃ , NaHCO ₃ , KHCO ₃ ; The organic base is pyridine, triethylamine or 4-N, N-dimethylaminopyridine.

X = Cl, Br.

Compound D is either commercially available or prepared by known methods (see US5777132).

The invention can also be illustrated by the compounds listed in Table 1, but the invention is not limited.

The compound of the general formula (I) of the present invention has excellent properties and can be used for controlling pests of Lepidoptera, Arthoptera, Heteroptera, Diptera, Orthoptera and Homoptera.

The insecticidal activity of some compounds of the general formula (I) of the present invention is equivalent to that of the commercialized variety chlorfenapyr.

The compound of the general formula (I) of the present invention can be used directly, can also be used with an agriculturally acceptable carrier, and can also be used in combination with other insecticides and (or) acaricides.

Detailed ways

Further illustrate the present invention below in conjunction with embodiment:

Example 1:

Acetylaminomethylene acetate

Dissolve 9.0 g (0.1 mol) of N-hydroxymethylene-acetamide in 25 g (0.25 mol) of acetic anhydride, add 10 drops of pyridine dropwise, stir at room temperature overnight, concentrate under reduced pressure, add 50 mL of toluene and distill the residual vinegar under reduced pressure. All the anhydrides were taken out and cooled to obtain 13.0 g of white solids, Yield: 99.2%, mp: 32-35° C. ¹ H NMR: δ: 2.04 (s, 3H, CH3); 2.08 (s.3H.CH3); 5.23 ( d, 2H, J=7.5HR1, CH2); 6.95 (s, 1H, br, NH). Anal. Calcd. (%) for C ₅ H ₉ NO ₃ : C: 45.80; H: 6.92; N: 10.68. found(%): C: 45.70; H: 6.92; N: 10.57.

Example 2:

1-Acetamidomethylene-2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (E)

Dissolve 17.5 g (0.05 mol) of 2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (D) in 50 mL of tetrahydrofuran dried over sodium metal , add 4.32g (50%, 0.09mol) of sodium hydride, heat up to reflux, after 30min of reflux reaction, cool to room temperature, add 9.65g (0.074mol) acetamidomethylene acetate, heat up to reflux, TLC tracking reaction , after refluxing for 8 hours, cooling, filtering, and concentrating the filtrate, the residue was subjected to silica gel column chromatography under reduced pressure, and the eluent was a mixed solvent of ethyl acetate and petroleum ether to obtain 8.0 g of white crystals, and 2.58 g of raw materials were recovered, Yield: 44.7%, mp: 149-151°C. ¹ Anal. Calcd. (%) for C ₁₅ H ₁₀ BrClF ₃ N ₃ O: C: 42.83; H: 2.40; N: 9.99. found (%): C: 42.86; H: 2.41; N: 9.82.

Example 3:

1-Halomethylene-2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (F)

2.9 mmol of 1-acetylaminomethylene-2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (E) and 8.2 mmol of trihalooxy After the phosphorus was mixed, the temperature was raised to reflux, and after reflux reaction for 1 hour, cooled, the reaction mixture was poured into ice water, extracted with ethyl acetate, the organic layer was washed with water in turn, washed with saturated brine, dried over anhydrous sodium sulfate, filtered and precipitated under reduced pressure , the resulting solid was recrystallized from a mixed solvent of ethyl acetate and petroleum ether.

F _a : X=Cl, Yield: 60.1%, mp: 131-133°C. ¹ H NMR: δ: 5.60 (s, 2H, CH2); 7.56 (dd, J=9HR1, Ph).Anal.Calcd.( %) for C ₁₃ H ₆ BrCl ₂ F ₃ N ₂ : C: 39.23; H: 1.52; N: 7.04.found (%): C: 39.04; H: 1.80; N: 7.21.F _b : X=Br, Yield: 80.2%, mp: 136-138°C. ¹ H NMR: δ: 5.61 (s, 2H, CH ₂ ); 7.57 (dd, J=9HR1, Ph). Anal. Calcd.(%) for C ₁₃ H ₆ Br ₂ ClF ₃ N ₂ : C: 35.29; H: 1.37; N: 6.33. Found (%): C: 35.32; H: 1.54; N: 6.57.

Example 4:

Potassium tert-butoxyoxalate

Add 16.0g (0.5mol) of methanol dropwise to 61.25g (0.5mol) of freshly distilled oxalyl chloride at room temperature, stir at room temperature for 2h, after the reaction is complete, distill at normal pressure, collect fractions at 119-125°C to obtain colorless Liquid methyl chlorooxalate 122.15g, Yield: 36.2%.

Dissolve 4.74g (64.05mmol) tert-butanol in 100mL of anhydrous ether, add 5.06g (64.05mmol) pyridine, add 5.0g (40.8mmol) methyl chlorooxalate dropwise to the above solution, and stir at room temperature for 1h After that, it was washed with water, saturated sodium bicarbonate and water successively, dried over anhydrous sodium sulfate, and desolvated under reduced pressure to obtain 3.36 g of tert-butyl methoxyoxalate as a colorless oily liquid, Yield: 51.4%. ¹ H NMR: δ: 1.56 (s, 9H, C(CH ₃ ) ₃ ); 3.87 (s, 3H, CH ₃ )

Dissolve 3.22g (20.1mmol) of tert-butyl methoxalate in 10mL of acetonitrile and 10mL of water, grind 1.373g (82%, 20.1mmol) of potassium hydroxide into powder, add it to the above solution, and stir at room temperature for 2h until Potassium hydroxide was completely dissolved, and vacuum precipitation gave 3.18 g of colorless crystal tert-butoxyoxalate potassium salt, Yield: 86.0%. ¹ H NMR: δ(D ₂ O): 1.41(9H, C(CH ₃ ) ₃ ).

Example 5:

Alkoxyoxalic acid

Under cooling in an ice bath, slowly add 5 mL of water dropwise to 7 mmol of alkyl chlorooxalate. After the drop is complete, adjust the reaction solution to pH = 2 with dilute hydrochloric acid, extract with ether, dry over anhydrous sodium sulfate, and precipitate under reduced pressure. An oily liquid was obtained.

G1: R=CH ₃ , Yield: 77.9%. ¹ H NMR: δ: 3.96 (s, 3H, CH ₃ ); 9.17 (s, 1H, COOH).

G2: R=C ₂ H ₅ , Yield: 75.8%. ¹ H NMR: δ: 1.40 (t, 3H, J=7.5HR1, CH ₃ ); 4.40 (q, 2H, J=7.5HR1, CH ₂ ); 9.03(s, 1H, COOH).

G3: R=nC ₄ H ₉ . Yield: 77.0%. ¹ H NMR: δ: 0.96 (t, 3H, J=7.5HR1, CH ₃ ); 1.37～1.50 (m, 2H, CH ₂ CH ₃ ); 1.70 ~1.80 (m, 2H, OCH ₂ CH ₂ ); 4.35 (t, 3H, J=7.5HR1, OCH ₂ ); 9.52 (s, 1H, COOH).

Embodiment 6:

Synthesis of target compound I:

Dissolve 0.227 mmol of 1-bromomethylene-2-(4-oxo-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (Fb) in 3 mL of toluene, add 0.681 1 mmol of aqueous sodium hydroxide solution (1 mL of water), 0.681 mmol of alkoxyoxalic acid, and catalytic amount of tetra-n-butylammonium bromide were stirred overnight at room temperature. After the reaction was completed, 15 mL of ethyl acetate was added to dilute the reaction solution, washed with water, and anhydrous sulfuric acid The sodium was dried overnight, filtered, and the filtrate was precipitated under reduced pressure. The obtained solid was recrystallized from a mixed solvent of petroleum ether and diethyl ether to obtain a white solid.

Embodiment 7:

Synthesis of target compound I:

Dissolve 0.227 mmol of 1-chloromethylene-2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole (F _a ) in 3 mL of toluene, room temperature Add dropwise 0.678 mmol of an aqueous solution of potassium alkoxyoxalate (1 mL of water), add a catalytic amount of tetra-n-butylammonium bromide, stir at room temperature for 8 h, follow the reaction by TLC, and when the reaction is complete, add 15 mL of ethyl acetate to dilute the reaction solution. Wash with water, dry overnight with anhydrous sodium sulfate, filter, and precipitate the filtrate under reduced pressure. The obtained solid is recrystallized from a mixed solvent of petroleum ether and diethyl ether to obtain a white solid.

Likewise, other compounds of the invention can be synthesized. See Table 1:

The present invention has carried out the mensuration of insecticidal activity, and mensuration procedure is as follows:

The insects tested were southern armyworm [MR2thimna (=Pseudaletia) separata (R3alker), a normal colony reared indoors on corn leaves. The armyworm adopts the method of soaking leaves. The samples are prepared into solutions of different concentrations with acetone, soaked in corn leaves at the seedling stage, dried and placed in a 7cm petri dish, inserted into the 4th instar larvae, and repeated 2-4 times. As a control, larvae were raised by soaking corn leaves with acetone solution.

Table 1 is the test result of part compound:

Claims (7)

1. An arylpyrrole N-oxalate derivative, characterized in that it has the structure shown in the following general formula (I):

In the formula, R ₁ represents hydrogen, Cl, Br or CF ₃ ; R ₂ represents Cl, Br, CF ₃ , CN or NO ₂ ; R ₃ represents CN, NO ₂ or S(O ₂ ) CF ₃ ; R ₄ represents hydrogen , Cl, Br or CF ₃ ; Y represents O or S; R represents 1-6 carbon alkoxy, 1-6 carbon haloalkoxy, 3-6 carbenyloxy, 3-6 halocarbenyloxy, 3-6 carbon alkynyloxy, 3-7 carbon cycloalkoxy, 3-6 carbon cyanoalkoxy, phenoxy, benzyloxy, hydroxyl, 1-4 carbon alkyl, phenyl, naphthyloxy Or a benzene ring substituted by one or more of the following groups: halogen, 1-4 carbon alkyl, 1-4 carbon alkoxy, 1-4 carbon haloalkoxy, 1-4 carbon haloalkoxy, 1-4 Carbon alkylthio, 1-4 carbon alkylsulfinyl, 1-4 carbon alkylsulfonyl, nitro, cyano, hydroxyl, carboxyl, 1-4 carbon alkylcarbonyl or 1-4 carbon alkoxycarbonyl . 2. The arylpyrrole N-oxalate derivatives according to claim 1, characterized in that R ₁ represents CF ₃ ; R ₂ represents Br; R ₃ represents CN; R ₄ represents oxygen; Y represents O; R represents 1-6 carbon alkoxy, 1-6 carbon haloalkoxy, 3-6 carbon alkenyloxy, 3-6 halocarbenyloxy, 3-6 carbon alkynyloxy, 3-7 carbon cycloalkoxy , 3-6 carbon cyanoalkoxy, phenoxy, benzyloxy, hydroxyl, 1-4 carbon alkyl, phenyl, naphthyloxy or benzene ring substituted by one or more of the following groups: halogen , 1-4 carbon alkyl, 1-4 carbon alkoxy, 1-4 carbon haloalkyl, 1-4 carbon haloalkoxy, 1-4 carbon alkylthio, 1-4 carbon alkylsulfinyl, 1 -4-carbon alkylsulfonyl, nitro, cyano, hydroxyl, carboxyl, 1-4-carbon alkylcarbonyl or 1-4-carbon alkoxycarbonyl. 3. The preparation method of arylpyrrole N-oxalate derivatives according to claim 1, characterized in that it comprises the following steps: Put compound A and B in an organic solvent, use inorganic base or organic base as acid-binding agent, the molar ratio of compound A and compound B to acid-binding agent is 1:1:1-2, and react at -10-80°C for 2 -12 hours, separate the organic phase, remove the organic solvent under reduced pressure, and then purify with a silica gel chromatographic column;

X is Cl or Br, Y is O or S. 4. The preparation method of arylpyrrole N-oxalate derivatives according to claim 1, characterized in that it comprises the following steps: Put compound A and oxalic acid in an organic solvent, use inorganic base or organic base as acid-binding agent, the molar ratio of compound A, oxalic acid and acid-binding agent is 1:1:1-2, react at -10-80°C for 2- After 12 hours, the organic phase was separated, and the organic solvent was removed under reduced pressure to obtain compound C. Compound C was chlorinated with thionyl chloride or oxalyl chloride or phosgene, and then reacted with alcohol or phenol to obtain compound I;

X is Cl or Br, R is 1-6 carbon alkoxy, 1-6 carbon haloalkoxy, 3-6 carbenyloxy, 3-6 halocarbenyloxy, 3-6 carbonyneoxy, 3-7 carbon cycloalkoxy, 3-6 carbon cyanoalkoxy, phenoxy or benzyloxy. 5. The preparation method of arylpyrrole N-oxalate derivatives according to claim 2, characterized in that it comprises the following steps: Dissolve 2-(4-chloro-phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole D and equimolar acetamidomethylene acetate in tetrahydrofuran at 1-1.5 In the presence of a mole of sodium hydride, reflux for 8 hours, cool, filter, and concentrate the filtrate. The residue is chromatographed on a silica gel column under reduced pressure to obtain 1-acetylaminomethylene-2-(4-chloro- Phenyl)-3-cyano-4-bromo-5-trifluoromethyl-pyrrole E, after mixing compound E and 1-1.5 moles of phosphorus oxyhalide, the temperature is raised to reflux, and after 1 hour of reflux reaction, cooling, The reaction mixture was poured into ice water, extracted with ethyl acetate, the organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, filtered and precipitated under reduced pressure, and the obtained solid was recrystallized from a mixed solvent of ethyl acetate and petroleum ether. To obtain compound F, put compound F and G in an organic solvent, use an inorganic base or an organic base as an acid-binding agent, and the molar ratio of compound F and compound G to the acid-binding agent is 1:1:1-2, -10-80 React at ℃ for 2-12 hours, separate the organic phase, remove the organic solvent under reduced pressure, and then purify with a silica gel column;

X = Cl, Br. 6. According to the preparation method of arylpyrrole N-oxalate derivatives according to claim 3, 4 or 5, it is characterized in that the organic solvent is toluene, benzene, cyclohexane, acetonitrile, acetone, tetrahydrofuran, Diethyl ether, dioxane, N,N-dimethylformamide or dimethyl sulfoxide; the inorganic base is NaOH, KOH, Na ₂ CO ₃ , K ₂ CO ₃ , NaHCO ₃ or KHCO ₃ ; organic The base is pyridine, triethylamine or 4-N,N-dimethylaminopyridine. 7. The application of the arylpyrrole N-oxalate derivatives according to claim 1, characterized in that it is used as an insecticide to control Lepidoptera, Coleoptera, Heteroptera and Diptera , Orthoptera or Homoptera insects.