CN1245638A - 1,2-alkyl (aryl) acyl aroyl hydrazines insect growth regulator and its preparation and application - Google Patents

Abstract

The present invention discloses a 1,2-alkyl (aryl) acyl aroyl hydrazines insect growth regulator, its preparation and application. Said invention also provides the structural formula, and invented compound has strong toxic effect against armyworm, its LC 50 is up to 6-8 ppm. It can be extensively used for control of insect pests in crops, and is simple in preparation process and easy to implement.

Description

1,2-alk(aryl)acylaroylhydrazine insect growth regulator and its preparation and application

The invention relates to an insect growth regulator and its preparation method and application, in particular to an alk(aroyl)acyl aroylhydrazine compound and its preparation method and application.

With the development of agricultural production, the role of pesticides is becoming more and more significant, but the problem of traditional pesticide residues has always troubled people. Therefore, the research and development of a new generation of high-efficiency, low-toxicity, pollution-free and environmentally friendly pesticides is in front of scientists. As the third generation of pesticides, insect growth regulators have the characteristics of high efficiency, low toxicity and strong selectivity. It mainly destroys the normal growth and development or reproduction of insects, so as to achieve the purpose of inhibiting insects. It is a new generation of insecticides that are environmentally friendly. The creative work in this field is an important research and development direction of new pesticides in the 21st century.

U.S. Patent No. 5,424,333,4,814,349 disclose a class of insect growth regulators-inhibitory hydrazine (RH-5849), that is, 2-benzoyl-1-tert-butylbenzohydrazine, which is Xu Jidong of Rohm-Haas Company (Hsu, Adam Chi Tung) developed and commercialized insect growth regulators for the first time. It is a non-steroidal compound that mimics the structure of 20-hydroxysteroid ecdysone, which has the activity of ecdysone, inhibits feeding on Lepidoptera, Coleoptera, and Diptera larvae, accelerates molting and reduces oviposition The role of pests is mainly stomach poisoning, strong systemic, rapid action, significant control effect on cotton, vegetables and other crops, but low toxicity to humans, livestock, poultry, fish, so It is a new type of pesticide with low residue and no pollution. Once RH-5849 was successfully developed, it aroused great attention from people, and they used RH-5849 as the parent to modify its structure in an all-round way in order to improve its activity and expand its insecticidal spectrum. Among them, the products with remarkable efficacy include RH-5992 and RH-2485. In addition, some modifications have been made to the hydrazide bridge and some compounds with better activity and potential commercial value have been found. However, the above-mentioned compounds have disadvantages such as poor solubility and slow effect after medication. Therefore, new insect growth regulators must be researched and developed as soon as possible to meet people's needs.

One of the purposes of the present invention is to disclose a class of 1,2-alk(aroyl)acylaroylhydrazine compounds with better solubility and quicker effect after administration;

The second object of the present invention is to disclose the preparation method of said compound;

The third object of the present invention is to disclose the use of said compounds as insect growth regulators.

Design of the present invention is such:

Taking di(aryl)hydrazide as the lead compound, introducing active groups in different positions, such as ester group, aryloxyacetyl group and tert-butyl group, etc., to form a new class of compounds—1,2-alk(aryl) Acylaroylhydrazine compounds. The introduction of these groups can enhance its ester solubility and improve its biological activity.

或

Its structural general formula of said compound of the present invention is shown in formula (1) or (2):

or

Where: W ₁ , W ₂ is one of alkyl, aryl or aryloxymethyl, such as tert-butyl, phenyl, 4-ethylphenyl, 3,5-dimethylphenyl, 3- Methylphenyl and phenoxymethyl, etc.;

Y, Z are hydrogen;

A is tert-butyl;

B is alkoxycarbonylmethyl, such as ethoxycarbonylmethyl, methoxycarbonylmethyl and the like.

One of the preparation methods of said compound of the present invention is as follows:

Using 1-tert-butyldiarylhydrazide as a raw material, carry out N-alkylation reaction with hydrocarbyl haloacetate in a solvent under the condition of the presence of basic substances to obtain the target product of the present invention——1,2 -alk(aromatic)acyl aroyl hydrazine compound, its reaction equation is as shown in (3):

Wherein: X is halogen; R ¹ and R ² are one of halogen, alkyl, hydrogen, alkoxy, nitro or cyano; R ³ is one of alkyl, alkenyl or aryl;

Said 1-tert-butyldiarylhydrazide can be prepared by the technology disclosed in US Patent No. 4,814,349;

Said hydrocarbyl haloacetate is ethyl bromoacetate;

Said solvent can be a kind of in hydrocarbons, toluene, benzene, acetonitrile, dimethylformamide or tetrahydrofuran or their mixture, and preferred solvent is a kind of in tetrahydrofuran, dimethylformamide or acetonitrile;

Said base can be inorganic bases such as potassium hydroxide, sodium hydroxide, sodium hydride or potassium hydride, or organic bases such as n-butyllithium and tert-butyl potassium;

The process conditions of the reaction are as follows:

The reaction temperature is 40°C-100°C, preferably 40-70°C; the reaction time is 4-8 hours.

After the reaction is finished, the target product can be obtained by using conventional separation methods.

Two of the preparation method of said compound of the present invention are as follows:

Using alkane(aryl)oxyacetylhydrazine as raw material, carry out acylation reaction with acid chloride to obtain the target product of the present invention——1,2-alk(aryl)acyl aroylhydrazine compounds, the reaction equation is as shown in (4) :

Wherein: R ⁴ is aryl; R ⁵ is aryl or alkyl; L is hydroxyl or chlorine;

The reaction time is 3 to 6 hours, and the reaction temperature is 80°C to 120°C;

The raw material alkane (aryl) oxyacetylhydrazide can be prepared by the technology disclosed in the national patent US4814349;

The compounds of the present invention can be used as insect growth regulators, and can be used by conventional methods.

The compound of the present invention has strong activity of poisoning and killing armyworms, and its LC ₅₀ reaches 6-8 ppm. The invention can be widely used in insect control of crops, and the preparation process is simple and easy, and is an insect growth regulator with broad application prospects.

Determination of insecticidal activity:

1. Selection of live test worms:

The 2nd instar larvae of corn armyworm were selected as the test objects.

2. Bioassay method

Take an appropriate amount of the original medicine and dissolve it in an organic solvent to make a solution, add a little emulsifier in aqueous solution to make a medicine solution with a concentration of 1-100ppm, immerse the newly cut corn leaves in the medicine solution, and take out the cold water after the infiltration is complete. Dry.

Put 10 2nd instar larvae of corn armyworm into the beaker, put the above-mentioned corn leaves soaked in the medicine into the beaker, and take medical gauze to seal it. Each concentration of medicinal solution was placed in three replicates for observation. Observe that the percentage of the total number of test insects that have completely died is the kill rate.

Below in conjunction with embodiment further clarifies content of the present invention, but these embodiments do not limit protection scope of the present invention.

Example 1

The synthesis of 1-tert-butyl-1-(3,5-dimethylbenzoyl)-2-(ethoxycarbonylmethyl)-2-(4-ethylbenzoyl)hydrazine, the reaction equation is as follows :

Add 1.057g (3mmol) 1-tert-butyl-1-(3,5-dimethylbenzoyl)-2-(4-ethylbenzoyl)hydrazine and 15mL anhydrous DMF to a dry three-necked flask , 0.128g (3.2mmol) 60% sodium hydride, at room temperature, after stirring for 2 hours, add dropwise 5mL DMF solution of 0.534g (3.2mmol) ethyl bromoacetate, react at 47°C for 3 hours, then heat up to 70°C React for 3 hours. A small amount of sodium hydride and ethyl bromoacetate can be added here. After the reaction was completed, most of the DMF was evaporated under reduced pressure, the residue was poured into 10mL water, extracted with chloroform (3×10mL), washed with water until neutral, the organic layer was dried with anhydrous magnesium sulfate, the solution was concentrated, and the residue was washed with silica gel After separation by column chromatography, the eluent was petroleum ether: ethyl acetate = 5:1 (V/V) and finally 0.63 g of white crystals was obtained, with a yield of 48.0%. mp116.4～117.2℃. ¹ H NMR, δ(ppm): 7.92～6.84 (7H, m, Ar-H), 4.13～3.83 (4H, m, CH ₂ CO ₂ CH ₂ ), 2.61～2.60 (2H, q, Ar-CH ₂ ), 2.32 (6H, s, Ar-CH ₃ ), 1.70 (9H, s, (CH ₃ ) ₃ C), 1.20~1.17 (3H, t, ArCH ₂ CH ₃ ), 1.07~1.04 (3H, t, _{OCH2CH3 )} . MS, 439[M ⁺ -1-CO2CH2CH3] _, 383(29.2 ₎ [M ⁺⁺ 2-( _CH3 ) _3C ], ₃₆₆ (68.7)[M ⁺⁺ _{1 -} CO2CH2CH ₃ ], 133(82.5)[M ⁺ -C ₁₇ H ₂₅ N ₂ O ₃ ], 105(30.4) [M ⁺ -C ₁₈ H ₂₅ N ₂ O ₄ ] elemental analysis

C% H% N%

Theoretical value: 71.20 7.81 6.39

Measured value: 70.78 7.85 6.36 Armycidal activity: 250 ppm 96.7%, LC ₅₀ =8 ppm.

Example 2

The synthesis of 1-tert-butyl-1-benzoyl-2-(ethoxycarbonylmethyl)-2-benzoylhydrazine, the reaction equation is as follows:

The preparation method is the same as in Example 1, wherein the raw material is 1-tert-butyl-1-benzoyl-2-benzoylhydrazine, and the yield is 41.2%. mp: 84-84.5°C. ¹ H NMR, δ(ppm): 7.98～6.78 (10H, m, Ar-H), 4.08～3.81 (4H, m, CH ₂ CO ₂ CH ₂ ), 1.69 (9H, s, (CH ₃ ) ₃ C ), 1.03-1.00 (3H, t, OCH ₂ CH ₃ ). MS, 382(13.2)[M ⁺ ], 326(3.82)[M ⁺⁺ 1-( _CH3 ) _3C ], 308(100.0)[M ⁺ -1- _{CO2CH2CH3 ]} , 105( _15.5 )[M ⁺ -C ₁₅ H ₂₁ N ₂ O ₃ ]. Elemental analysis

C% H% N%

Theoretical value: 69.09 6.85 7.32

Measured value: 68.84 6.83 7.21 Armyworm killing activity: 1000ppm 50.2%.

Example 3

The synthesis of 1-tert-butyl-1-(3,5-dimethylbenzoyl)-2-(methoxycarbonylmethyl)-2-(4-ethylbenzoyl)hydrazine, the reaction equation is as follows :

Add 1.057g (3mmol) 1-tert-butyl-1-(3,5-dimethylbenzoyl)-2-(4-ethylbenzoyl)hydrazine and 15mL anhydrous DMF to a dry three-necked flask , 0.128g (3.2mmol) 60% sodium hydride, at room temperature, after stirring for 2 hours, dropwise added 5mL DMF solution of 0.489g (3.2mmol) methyl bromoacetate, reacted at 40～45°C for 2 hours, then heated up to 65 °C for another 3 hours. A small amount of sodium hydride and methyl bromoacetate can be added here. After the reaction was completed, most of the DMF was evaporated under reduced pressure, the residue was poured into 10mL water, extracted with chloroform (3×10mL), washed with water until neutral, the organic layer was dried with anhydrous magnesium sulfate, the solution was concentrated, and the residue was washed with silica gel After separation by column chromatography, the eluent was petroleum ether: ethyl acetate = 5:1 (V/V) and finally 0.57 g of white solid was obtained with a yield of 44.8%. mp116.4～117.2℃. ¹ H NMR, δ(ppm): 7.90~6.85 (7H, m, Ar-H), 4.06~3.84 (2H, q, CH ₂ CO), 3.44 (3H, s, OCH ₃ ) 2.63~2.57 (2H, q, Ar-CH ₂ CH ₃ , 2.30 (6H, s, Ar-CH ₃ ), 1.67 (9H, s, (CH ₃ ) ₃ C), 1.19～1.16 (3H, t, ArCH ₂ CH ₃ ), MS , 425 (1.1) [M ⁺ +1], 351 (15.0) [M ⁺ -CH ₂ CO ₂ CH ₃ ], 133 (100) [M ⁺ -C ₁₆ H ₂₃ N ₂ O ₃ ], 105 (9.6) [M ⁺ -C ₁₇ H ₂₃ N ₂ O ₄ ].Elemental analysis:

C% H% N%

Theoretical value: 70.73 7.60 6.60

Measured value: 70.68 7.64 6.59 Armycidal activity: 15 ppm 83.3%, LC ₅₀ =6 ppm.

Example 4

The synthesis of 1-tert-butyl-1-(4-fluorobenzoyl)-2-(ethoxycarbonylmethyl)-2-(4-fluorobenzoyl)hydrazine, the reaction equation is as follows:

The preparation method is the same as in Example 1, wherein the raw material is 1-tert-butyl-1-(4-fluorobenzoyl-2-(4-fluorobenzoyl)hydrazine, the yield is 42.5%, mp: 74-75°C. ¹ H NMR, δ(ppm): 8.06-6.96 (8H, m, Ar-H), 4.24-3.92 (4H, m, CH ₂ CO ₂ CH ₂ ), 1.67 (9H, s, (CH ₃ ) ₃ C ), 1.08～1.05 (3H, t, OCH ₂ CH ₃ ). MS, 419 (10.5) [M ⁺ +1], 345 (100.0) [M ⁺ -CO ₂ CH ₂ CH ₃ ], 123 (33.3) [ M ⁺ -C ₁₅ H ₂₀ FN ₂ O ₃ ], 95 (11.3) [M ⁺ -C ₁₆ H ₂₀ FN ₂ O ₄ ]. Elemental analysis:

C% H% N%

Theoretical value: 63.15 5.78 6.69

Measured value: 62.60 5.85 6.68 Armyworm killing activity: 500ppm 35.3%.

Example 5

The synthesis of 1-tert-butyl-1-(4-chlorobenzoyl)-2-(ethoxycarbonylmethyl)-2-(4-chlorobenzoyl)hydrazine, the reaction equation is as follows:

The preparation method was the same as in Example 1, wherein the raw material was 1-tert-butyl-1-(4chloro-benzoyl-2-(4-chlorobenzoyl)hydrazine, the yield was 52.3%, glassy substance. ¹ H NMR , δ (ppm): 7.95~6.83 (8H, m, Ar-H), 4.24~3.82 (4H, m, CH ₂ CO ₂ CH ₂ ), 1.66 (9H, s, (CH ₃ ) ₃ C), 1.04 ~1.02 (3H, t, OCH ₂ CH ₃ ).Myxocidal activity: 1000ppm 86.7%.

Example 6

The synthesis of 1-tert-butyl-1-benzoyl-2-(methoxycarbonylmethyl)-2-(4-ethylbenzoyl)hydrazine, the reaction equation is as follows:

The preparation method is the same as in Example 1, wherein the raw material is 1-tert-butyl-1-benzoyl-2-(4-ethylbenzoyl)hydrazine, the yield is 51.2%, glassy substance, ¹ H NMR, δ( ppm): 7.96~6.71 (9H, m, Ar-H), 4.09~3.79 (4H, m, CH ₂ CO ₂ CH ₂ ) 2.58~2.53 (2H, q, Ar-CH ₂ ), 1.68 (9H, s , (CH ₃ ) ₃ C), 1.16-1.13 (3H, t, ArCH ₂ CH ₃ ), 1.08-1.05 (3H, t, OCH ₂ CH ₃ ). Armycidal activity: 31.3ppm73.3%.

Example 7

The synthesis of 1-tert-butyl-1-(3-methylbenzoyl-2-(methoxycarbonylmethyl)-2-(4-ethylbenzoyl)hydrazine, the reaction equation is as follows:

The preparation method is the same as in Example 1, wherein the raw material is 1-tert-butyl-1-(3-methylbenzoyl)-2-(4-ethylbenzoyl)hydrazine, and the yield is 54.5%, glassy substance. ¹ H NMR, δ(ppm): 7.93~6.77 (8H, m, Ar-H), 4.07~3.84 (4H, m, CH ₂ CO ₂ CH ₂ ) 2.60~2.56 (2H, q, Ar-CH ₂ ) , 2.30 (3H, s, ArCH ₃ ) 1.68 (9H, s, (CH ₃ ) ₃ C) 1.18～1.15 (3H, t, ArCH ₂ CH ₃ ), 1.04～1.01 (3H, t, OCH ₂ CH ₃ ) . Armyworm activity: 15.6ppm 76.6%.

Example 8

The synthesis of 1-(2,4-dichlorobenzoyl)-2-(4-chlorophenoxyacetyl)hydrazine, the reaction equation is as follows:

Add 3g (15mmol) p-chlorophenoxyacetylhydrazide and 40mL tetrahydrofuran into a 100mL round bottom flask, stir, add water 10mL, sodium bicarbonate 2.5g, stir evenly, then add 3.13g (15mmol) 2,4-dichlorobenzene Formyl chloride was slowly added dropwise to the reaction solution within 1.5 hours, stirred at room temperature for 3.5 hours, and the solvent was evaporated to obtain 5.4 g of white powder with a yield of 96.0%. mp: 165.9-167.0°C. ¹ H NMR, δ (ppm): 7.62～7.08 (m, 7H, Ar-H), 4.72 (s, 2H, CH ₂ O) Elemental analysis:

C% H% N%

Theoretical value: 48.22 2.96 7.49

Measured value: 48.08 2.72 7.33

Armycidal activity: 62.5ppm 96.7%, LC ₅₀ =32ppm.

Example 9 Synthesis of 1-(2,4-dichlorobenzoyl)-2-(4-chlorophenoxyacetyl)hydrazine, the reaction equation is as follows:

The preparation method is the same as in Example 8, wherein the raw materials are 4-dichlorobenzoic acid and m-methylphenoxyacetylhydrazide, the yield is 68.2%, mp: 173.4°C-175.0°C, and the armycidal activity: LC ₅₀ =30ppm.

The following compounds can be conveniently prepared in a similar manner: 1-tert-butyl-1-(4-methylbenzoyl)-2-(methoxycarbonylmethyl)-2-(4-methylbenzoyl) Hydrazine, mp: 97.0～97.3℃; 1-tert-butyl-1-(3-methylbenzoyl)-2-(methoxycarbonylmethyl)-2-(3-methylbenzoyl)hydrazine , mp: 91.0～92.2℃; 1-tert-butyl-1-(4-ethylbenzoyl)-2-(methoxycarbonylmethyl)-2-(4-ethylbenzoyl)hydrazine, mp: 100.4～101.2℃; 1-tert-butyl-1-(3,5-dimethylbenzoyl)-2-(methoxycarbonylmethyl)-2-(3,5-methylbenzoyl) Acyl)hydrazine, mp: 123.6～123.7℃; 1-tert-butyl-1-(4-ethylbenzoyl)-2-(methoxycarbonylmethyl)-2-(benzoyl)hydrazine, mp : 100.4～101.2℃; 1-tert-butyl-1-(3,5-dimethylbenzoyl)-2-(methoxycarbonylmethyl)-2-(benzoyl)hydrazine, mp: 133.0 ~134.1°C; 1-tert-butyl-1-(4-ethylbenzoyl)-2-(methoxycarbonylmethyl)-2-(3,5-dimethylbenzoyl)hydrazine, mp : 92.4～93.2℃; 1-tert-butyl-1-(4-bromobenzoyl)-2-(methoxycarbonylmethyl)-2-(4-bromobenzoyl)hydrazine, glassy substance; 1-(tert-pentanoyl)-2-(4-fluorophenoxyacetyl)hydrazine, mp: 104.0-105.1℃; 1-(3,5-dimethylbenzoyl)-2-(4-fluorobenzene Oxyacetyl)hydrazine, mp: 196.4-197.0℃; 1-(3-trifluoromethylbenzoyl)-2--(4-chlorophenoxyacetyl)hydrazine, mp: 142.1-143.0℃; 1- (4-bromobenzoyl)-2-(2,4-dichlorophenoxyacetyl)hydrazine, mp: 207.0-208.2°C; 1-(2,4-dichlorobenzoyl)-2-(2 -Chlorophenoxyacetyl)hydrazine, mp: 180.9-183.0℃; 1-(3-trifluoroacetyl)-2-(2,4-dichlorophenoxyacetyl)hydrazine, mp: 174.8-176.0℃; 1-(6-chloropicolyl)-2-(3-trifluoromethylphenoxyacetyl)hydrazine, mp: 132.0-133.1℃; 1-(3,5-Dimethylbenzoyl)-2- (3-methylphenoxyacetyl)hydrazine, mp: 170.0-171.1℃; 1-(phenylacryloyl)-2-(4-chlorophenoxyacetyl)hydrazine, mp: 188.1-190.2℃; 1-( Phenylacryloyl)-2-(3-trifluoromethylphenoxyacetyl)hydrazine, mp: 196.1-196.9℃; 1,2-bis(2,4-dichlorophenoxyacetyl)hydrazine, mp: 133.1 -133.8°C. 1-(2,4-dichlorophenoxyacetyl)-2-(3-trifluoromethylphenoxyacetyl)hydrazine, mp: 217.0-218.2℃1-(tert-valeryl)-2-(4-chloro Phenoxyacetyl)hydrazine, mp: 123.5-125.0°C 1-(2-fluorobenzoyl)-2-(2,4-dichlorophenoxyacetyl)hydrazine, mp: 142.6-142.8°C 1-(tert Pentanoyl)-2-(2,4-dichlorophenoxyacetyl)hydrazine, mp: 95.3-96.5°C.

Claims (8)

1. one kind 1,2-alkane (virtue) acyl group aroyl hydrazine class compound is characterized in that: chemical structure of general formula is suc as formula shown in (1) or the formula (2): Or Wherein:

W ₁, W ₂A kind of in alkyl, aryl or the aryloxy methyl;

Y, Z are hydrogen;

A is the tert-butyl group;

B is the hydrocarbon carbonyl oxygen methyl.

2. compound as claimed in claim 1 is characterized in that:

W ₁, W ₂Be the tert-butyl group, phenyl, 4-ethylphenyl, 3, a kind of in 5-3,5-dimethylphenyl, 3-aminomethyl phenyl and the Phenoxymethyl;

B is ethoxycarbonylmethyl group or methoxycarbonyl group methyl.

3. one kind 1, the preparation method of 2-alkane (virtue) acyl group aroyl hydrazine class compound is characterized in that comprising:

With the 1-tert-butyl group two fragrant hydrazides is raw material, with the halogenated acetic acids hydrocarbyl carbonate in solvent, under the condition that alkaline matter exists, carry out the N-alkylated reaction, its reaction equation is as follows:

Wherein: X is a halogen; R ¹, R ²A kind of in halogen, alkyl, hydrogen, alkoxyl, nitro or the cyano group; R ³A kind of in alkyl, thiazolinyl or the aryl;

Said solvent is a kind of and composition thereof in hydro carbons, toluene, benzene, acetonitrile, dimethyl formamide or the oxolane;

Said alkali is inorganic base or organic base;

Reaction temperature is 40 ℃～100 ℃, and the reaction time is 4～8 hours;

After reaction finishes, adopt conventional method to separate, can obtain target product of the present invention---1,2-alkane (virtue) acyl group aroyl hydrazine class compound.

4. preparation method as claimed in claim 3 is characterized in that:

Said halogenated acetic acids hydrocarbyl carbonate is a bromoethyl acetate.

5. preparation method as claimed in claim 3 is characterized in that:

Said alkali is a kind of in potassium hydroxide, sodium hydroxide, sodium hydride, hydrofining, n-BuLi or the tert-butyl group potassium.

6. preparation method as claimed in claim 3 is characterized in that:

Preferred solvent is a kind of in oxolane, dimethyl formamide or the acetonitrile.

7. as claim 3, or 4, or 5, or 6 described preparation methods, it is characterized in that:

Preferred reaction temperature is 40～70 ℃.

8. as claim 1, or 2 described application of compound, it is characterized in that: can be used as insect growth regulator, IGR.