JPS5851922B2 - Satsuchi Yuzai Oyobi Sono Seizouhou - Google Patents

Description

[Detailed description of the invention] The present invention relates to insecticides.

More specifically, this is a pyrethrin-type synthetic insecticide,
It relates to processes for their production, compositions containing them and the use of such compounds and compositions for insecticidal purposes.

For many years, research has been carried out in the field of synthetic analogs of pyrethrins in an effort to discover synthetic alternatives that have superior properties to the natural products.

The research initially aims to improve the toxicity or stability of natural products, while at the same time maintaining an acceptable balance of other suitable properties such as cost, ease of manufacture, mammalian toxicity, etc. The problem was to modify the acid and/or alcohol moieties of the ester molecule.

In recent years, attention has begun to be focused on the knockdown properties of synthetic pyrethroids as well as their toxicity.

And many synthetic analogs have been developed for their knockdown properties, along with or in lieu of their toxicity to insects.

Such knockdown agents may be used as single active agents if they have high toxicity to insects or in combination with another insecticidal compound selected for its toxicity. They are becoming increasingly important in household insecticides where they are used.

The present invention relates to a new system of synthetic pyrethroids, some of which have excellent knockdown properties and others that are highly toxic to insects.

The present invention is based on the general formula (wherein X represents -0-C- or -5-C-, Y represents -O- or -S-, and Z represents Hl-CH3゜-C
represents N or -C3CH, Zl and z2 are the same or different and represent norogen (e.g. chlorine), methyl, respectively, n is 0, 1 or 2, and at C1 and C3 on the cyclopropane ring The hydrogen configuration is substantially all cis or substantially all trans.

The esters of the present invention can be structurally considered as esters of 3-monosubstituted 2,2-dimethylcyclopropanecarboxylic acids and alcohols.

However, although it is convenient to describe these esters structurally in these terms, as explained in detail below, these esters can be prepared by methods other than esterification of acids with alcohols, and In fact, this is usually the case.

The acids from which the esters of the invention are structurally derived are 3
3-mono-substituted-2,2-dimethylcycloprononecarboxylic acids in which the -substituent is a 2-oxo-3-oxa-cyclopentylidenemethyl or 2-oxo-3thia-cyclopentylidenemethyl group.

The alcohols from which the esters of the invention are structurally derived are essentially 3-phenoxybenzyl and 3-phenylthio-benzyl alcohols, but these alcohols may optionally be α of the benzyl alcohol residue.
- may be substituted on the carbon atom by a methyl group or a cyano or ethynyl group.

The alcohol may also be optionally substituted with up to two chlorine and/or methyl groups on one or both aromatic rings.

Specific examples of alcohols from which the ester of the present invention can be structurally derived include 3-phenoxybenzyl alcohol, α-cyano-3-phenoxybenzyl alcohol,
α-ethynyl-3-phenoxybenzyl alcohol, α
-Methyl-3-phenoxybenzyl alcohol, 3-phenylthiobenzyl alcohol, α-cyano 3-
Examples include phenylthio-benzyl alcohol.

The esters of the present invention exhibit geometric and optical isomerism.

They can therefore be produced either as optically active forms that can later be mixed together or as racemic mixtures that can later be resolved into optically active forms.

Optically active forms or racemic mixtures can be separated into individual geometric isomers.

In addition to the geometric isomerism arising from the coordination between the substituents on the cyclopropane ring and the ring and the stereoisomerism around the double bond in the 3-substituent, if 2 does not represent hydrogen, There is also the possibility of optical isomers arising from the asymmetry of the alpha carbon atom of the benzyl alcohol residue.

The esters of the present invention can be prepared by esterification involving the reaction of a cyclopropanecarboxylic acid of formula 1 or a derivative thereof with an alcohol of formula 2 or a derivative thereof.

(where Q and COP are functional groups or atoms that react together to form an ester bond; X, YlZlz
l, Z2 and n are as defined above) In practice, an acid or an acid chloride is converted into an alcohol (c
op is C0OH or C0-Hal and Q is O
(H) or with a no-rogen compound (Q
=)・rogen) is a carboxylic acid salt (COP is COOMC
It is usually convenient to react with alkali: whose M is, for example, a silver or triethylammonium cation.

Alternatively, some of the esters are lower, alkyl esters of acids (COP is COOalkyl and the alkyl group contains 1 to 4 carbon atoms) and Q=
It can be produced by ester rearrangement (transesterification) using alcohol (1) of OH.

This ester rearrangement can be activated with base catalysis and is a convenient method to employ when the carboxylic acid derivative is prepared in the form of a lower alkyl ester, as discussed in more detail below. be.

The acid of formula ■ (COP=COOH) is the alcohol of formula ■ (
It is a known compound like Q=OH).

Acids of formula 11 may conveniently be prepared by a Witteig reaction involving a phosphorane or ylide of formula (1) and a cis or trans caronaldehyde of formula (2) or a lower alkyl ester thereof.

Triphenyl-substituted phosphoranes of formula IV are described in the chemical literature.

Since the stability of the triphenylphosphorus oxide produced as a by-product in the Witteig reaction is particularly high, it is preferred to use triphenyl-substituted phosphoranes, which favors the completion of the Witteig reaction.

However, in principle any other organic group can be used in place of this phenyl group.

Calonaldehyde or its ester can be produced by ozonolysis of folic acid or its ester, respectively.

If caronaldehyde is prepared in the form of an ester or in the form of a trans-coordinated free acid, the reaction components are of the formula (II) as described above.

However, if it is desired to use the free acid in the form of the cis isomer, this is most conveniently reacted internally as the miasyral form.

During the Uiteitzig reaction, this hemiacyal ring is cleaved and the aldehyde functionality then participates in the Uiteitzig reaction to give the Uiteitzog reaction product in the cis form.

Phosphorane I and aldehyde V are preferably reacted in substantially equimolar ratios, conveniently in a solvent such as an aromatic hydrocarbon such as benzene, or a polar solvent such as dimethyl sulfoxide or tetrahydrofuran, or a chlorinated hydrocarbon such as dichloromethane. I am forced to do it.

This product can be improved if the reaction is carried out under an inert atmosphere, such as nitrogen.

The esters of the invention can also be prepared directly by a Witteig reaction of the type described above.

In this variant, phosphorane ■ is converted to formula ■ (wherein Y,
z, z1, Z2 and n are as defined above) of caronaldehyde.

Esters of formula (1) can be prepared by esterifying caronaldehyde or an esterifiable derivative thereof with an alcohol of formula (2) or an esterifiable derivative thereof or by ozonolysis of a suitable ester of folic acid.

Alcohols of the formula (2) in which 2 represents CN or C3CH or CH3 can be prepared from the corresponding aldehydes by conventional methods.

i.e. the desired 3-phenoxy- or 3-phenyl-
The thio-benzaldehyde can be reacted (a) with HCN (conveniently generated in situ from KCN and an acid), with addition of HCN occurring to form a cyanohydrin, or (b) with a metal acetylide. derivative or (c
) can be reacted with Grignard reagent.

One or more of the insecticidal esters of the invention can be formulated with an inert carrier or diluent to form insecticidal compositions, and these include, for example, dusts and granular solids, wettable powders, mosquito coils, etc. and other solid formulations or as emulsions, emulsifiable concentrates, sprays and aerosols, and other liquid formulations with the addition of suitable solvents, diluents and surfactants.

Pyretolum synergists such as piperonyl butoxide or tropital can be added to these compositions.

The insecticidal composition may also include naturally occurring or other synthetic pyrethrins to improve or synergize the insecticidal and/or knockdown properties of the pyrethrins in the composition.

The novel esters of the invention or insecticidal compositions containing them can be used to control insects on a domestic or agricultural scale by treating the insects themselves or environments susceptible to insect attack with the compounds or compositions of the invention. It can be used for the purpose of

The following examples are given to illustrate the invention.

Experiments 1-4 describe the preparation of the intermediate acid or its lower alkyl ester.

In the following examples and experiments, the stereochemistry of the acid is (
River-Sys (IR・3S) or (Ta-Trans (IR・3S)
3R).

These compounds are substantially pure optically and geometrically isomers, and we hereby identify IR-cis and I
The nomenclature of R-trans is based on the sequence rules of Khan et al.
g, Chem, Int, Ed, 5.385 (196
6) is proposed as a convenient alternative to strict naming based on

According to this proposal, (-+)-cis(IR・3S
) and (river-trans (IR·3R)) can also be written as (IRcis] and [1Rtrans], respectively.

Experiment 1 (cursis-(IR・3S)-3-((2-oxo-3
-oxa-cyclopentylidene)-methyl]-2,2-
Dimethylcyclopropanecarboxylic acid (2-oxo-3-
Oxa-cyclopentylidene)-triphenylphosphorane (He1v, Cbem.

Prepared according to Acta 46.1580 (1963) l (2,4f), intramolecularly from (-+)-cis-(IR-38) calonaldehyde acid to miacyral (0,9
f) and tetrahydrofuran (125 mJ) were refluxed under nitrogen for 6 hours.

The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane.

The organic phase was thoroughly extracted with sodium carbonate solution.

The aqueous extract was acidified to yield the crude product.

This was extracted with dichloromethane and dried (Na25
o4).

When evaporated, a colorless solid (0,35P, m, p, 144~
149°C) was obtained.

NMR showed this to be the title compound.

Experiment 2 (-+)-) Lance-(IR・3R)-3-C(2-
Oxo-3-oxa-cyclopentylidene)-methyl]
-2,2-dimethylcyclopropanecarboxylic acid (→-trans-calonaldehyde acid (1, (1) [(
→-trans-(1'R・3R)-obtained from folic acid], (
2-oxo-3-oxa-cyclopentylidene)triphenylphosphorane (2,=1) and tetrahydrofuran (12 od) were refluxed for 6 hours.

After work-up as described in Experiment 1, the crude acid was isolated as a viscous liquid (nd2o=1.5104) (0,64f).

NMR identified this as the title compound.

Experiment 3 (-1-)-trans-(IR・3R)-3-[(2
-oxo-3-thia-cyclopentylidene)-methy+
J-2.2-Dimethylcyclopropanecarphonic acid Experiment 20 Calonaldehyde acid (0,Fl), (2-oxo-3-thia-cyclopentylidene) triphenylphosphorane [Tetrahedron Letters 52.5435 (1
(1,1') prepared according to 968) and tetrahydrofuran were refluxed under nitrogen for 6 hours.

After treatment as described in Experiment 1, the acid was isolated as a dark brown viscous semisolid (0,42'?).

This was identified as the title compound by NMR.

Experiment 4 (+)-cis-(IR・3S)-3-((2-oxo-
3-thia-cyclopentylidene)-methyl]2,2-dimethylcyclopropanecarboxylic acid Experiment 10 Hemiacyal (0,51), (3-oquino-3-thia-cyclopentylidene)triphenyl in the molecule of caronaldehyde acid Phosphorane (1, oL?) and tetrahydrofuran (6
0 m was refluxed under nitrogen for 6 hours.

After treatment as described in Experiment 1, a colorless solid (0,5
2P, m, p.

153-155°C) was obtained.

This was identified as the title compound by NMR.

Example 1 3-phenoxybenzyl
-((2-oxo-3-thiacyclopentylidene)-methyl]-2,2-dimethylcyclopropanecarboxylate (Compound A) To the acid prepared in Experiment 4 (300 rv) in dry dichloromethane (10 ml), Pyridine (105Wu2/10
7 μl) and thiolyl chloride (158771p/9
6 μl) was added.

This mixture was allowed to stand for 3 hours, at which point dichloromethane (
3-phenoxybenzyl alcohol (2
65m9) and pyridine (1057n9/107μ,
e) was added.

The mixture was left at room temperature overnight and the solvent was evaporated.

The residue was chromatographed on neutral alumina (sy) using benzene as solvent.

When evaporated, the indicated ester (0,39P, nd2o1
．． 5848 and a molecular weight of 408 by mass spectrometry.

Using the acids from Experiments 1 to 3 instead of the acid from Experiment 4, perform the following 3 experiments.
-Phenoxybenzylcyclopropanecarboxylic acid ester was similarly prepared.

Compound B (+)-trans-(IR・3R)-3-1: (2-oxo-3-thiacyclopentylidene-methyl), nd2
0 1.5796, molecular weight 408° Compound C (i)-trans-(IR・3R)-3-((2-oxo-3-oxa-cyclopentylidene)-methyl)-
nd2o 1.5634, molecular weight 392° Compound D (Ta-cis-(IR・3S)-3((2-oxo-3-
oxa-cyclopentyritin)-methyl], na20
1.5618, molecular weight 392°. The structures of all compounds A to D were confirmed by NMR and mass spectra.

The insecticidal activity of the esters of the invention was evaluated against house fly and mustard beetle using the following method.

Iy<-1'l (Musca domestic
The thoracic cavities of test performance flies in a) were treated with 1 μl drop of insecticide dissolved in acetone.

Two sets of 15 flies each were used at each dose ratio, and six doses per test compound were used.

After treatment, flies were kept within a temperature of 20°C ± 1° and insecticidal activity was evaluated 24 and 48 hours after treatment.

The LD5o value is calculated in μr of insecticide per fly;
And relative toxicity was calculated from the inverse ratio of LD5o values (W
HO Buretein 35.893 (1966) and En
tomologia and Exp, Appl
, Yotomo, 253 (1967)].

Mustard beetle (Phaedon cochle)
An acetone solution of the test compound was applied to the abdomen of an adult mustard beetle using a microdrop applicator.

The treated insects were allowed to stand for 48 hours, after which the insecticidal properties were evaluated.

Two sets of 40-50 mustard beetles each were used at each dose level, and 3-4 dose levels were used for each compound.

CJ, Sci, Fo, who again calculated LD5o values and calculated relative toxicity against the inverse ratio of LD5o.
od Agric, 20.561 (1969)].

Relative toxicity is one of the most toxic chrysanthemum esters known to house flies and mustard beetles.
-benzyl-3-furylmethyl(i)trans-chrysansemate, and the toxicity of this comparator is about 24 times that of allethrin to house flies and of allethrin to the mustard beetle. It is 65 times more.

The following relative toxicity was obtained:

Relative compound Bacara sinus beetle 5-benzyl-3-furylmethyl (trans-chrysansemate 000 000 Pyrethrin ■ 600 Bioallethrin 0 0 Compound A 00 0 〃 B 4 0 ☆ Compound Baccaracina beetle compound C 8 2 1 6 30 70 The present invention has been described above, and the novel characteristics disclosed by the present invention are listed as follows.

1, Formula I (wherein X represents 10-C- or -5-C-, Y represents 10- or -8-, Z is H1CH3, -CN
or -CyoCH, Zl and z2 may be the same or different, each represents halogen or methyl, and n is 0.1 or 2 and the stericity of hydrogen at C1 and C3 on the cyclopropane ring The configuration is substantially all cis or substantially all trans).

0 0 2, the compound according to item 1 above, wherein X represents 10-C- or -5-C-.

3. The compound according to item 1 or 2 above, wherein Z, Z'' and Z2 each represent hydrogen.

4. The compound according to any of the above items, wherein Y represents 10-.

5, (+)-cis-(IIR・3S) also (main use-
A compound according to any of the preceding clauses, which is in the form of a trans-(IR·3R) isomer.

6, (river-cis-(IR・3S) or (trans-trans-(IR-3R)-3-((2-oxo-3-thiacyclopentyritin)-methyl)-2,2-dimethylcyclopropane Carboxylic acid or (TAcis-(IR・3S)
or (Ta-trans-(IR・3R)-3-C(2-
Oxo-3-oxa-cyclopentylidene)-methyl]
-2,2-dimethylcyclopropanecarboxylic acid or (
+)-trans-(IR.3R)-3-(cyclopentylidenemethyl)-2.2-dimethylcyclopropanecarboxylic acid 3-phenoxy-benzyl ester.

7. Cyclopropanecarboxylic acid or its derivative of the formula ■ ゝ\C-CH-CH-CH-C62 1\/ CH2-CH210\ CH3CH3 (1) and the formula ■ (where Q and COP react together to form an ester) A functional group or atom forming a bond is L-CX, Y
, Z, Zl, Z2 and n are as defined in Section 1.

) with an alcohol or a derivative thereof.

8. A carboxylic acid or its C1-C4 alkyl ester is reacted with a phosphorane or ylide of the formula ■ ☆ (where Ph is phenyl) and a caronaldehyde of the formula V or its C1-C4 alkyl ester under Witteig reaction conditions. 8. The method according to item 7, wherein the method is produced by

9. Howephoran or ylide of formula ■ is converted to formula ■ (where zl
9. The method of clause 8, wherein Zl, Z2, Y and n are as defined in clause 1) to form an ester as defined in clause 1.

10. Insecticidal or knockdown active composition comprising an active compound and also an inert diluent or carrier, wherein the active compound is a compound according to any of paragraphs 1 to 6.

11. A method for controlling insects comprising applying an active compound according to any of paragraphs 1 to 6 or a composition according to paragraph 10 to insects or environments susceptible to insect attack.

Claims (1)

[Claims] Formula 1 (wherein X represents 10-C- or -5-C-, Y represents 10- or -S-, 2 represents H, CH3,
-CN or 103CH, Zl and z2 are the same or different and each represents halogen or methyl, n is 011 or 2, and the configuration of hydrogen at C1 and C3 on the cyclopropane ring is 1. An insecticide comprising, as an active ingredient, a compound having substantially all cis or substantially all trans. Cyclopropanecarboxylic acid or a derivative thereof having the formula 2 and the formula (wherein Q and COP in the above formula are functional groups or atoms that together form an ester bond, 5-C-, Y represents 10- or -S-, Z represents H1cH3, -CN or -C3CH, Zl and Z2 are the same or different and each represents halogen or methyl, and n is 0.
1 or 2, and cl on the cyclopropane ring
and wherein the configuration of the hydrogen at C3 is substantially all cis or substantially all trans, with an alcohol or derivative thereof, wherein x, y, z, z1, z2 and n have the above meanings) as an active ingredient.