CS207650B2 - Method of making the noew n-/1,3,4-thiadiazol-2-yl/benzamides - Google Patents

Description

The present invention relates to a process for the preparation of a group of novel N- (1,3,4-thiadiazol-2-yl) benzamides containing a phenyl, naphthyl or heteroaryl residue in the 5-position of the thiadiazole ring, the phenyl core of which is substituted at the 2 and 6 positions which compounds are useful as insecticides.

Insect control was one of the first problems that stood ahead of agrochemical research, and the solution to this problem is being intensively continued. Insect pests of numerous orders and species attack utility plants of all types, cause hygiene problems and contaminate food and feed. The damage caused by insects is incalculable and the control of harmful insects is a matter of paramount importance.

Recently, research into new and improved insecticides has been prompted by the withdrawal of old residues leaving insecticides from use. ^:

Although the compounds of formula (I) below are novel substances in organic chemistry, some of the prior art works are, however, of interest. For example, Cebalo, in U.S. Pat. No. 3,726,892, discloses herbicidally active 1,3,4-thiadiazol-2-ylureas.

Rao in Indian J. Chem. 8, 509-513 (1970) describes a process for the synthesis of 2-amino-1,3,4-thiadiazoles, which are intermediates for the preparation of the compounds of the invention.

Wellinga and Mulder in U.S. Patent 3,748,356 disclose the herbicidal and insecticidal activity of N-benzoyl-N--phenylureas.

The invention is in the field of agrochemistry and describes a process for the preparation of the novel thiadiazolylbenzamides of the general formula I,

in which

R is a radical of formula

207850

where

X represents oxygen or sulfur, one of R ¹ and R ² is hydrogen and the other is fluorine, chlorine, bromine, trifluoromethyl or methoxy group, one of R ³ and R ⁴ is hydrogen and the other is methoxy or trifluoromethyl; one of R ⁵ and R ⁶ is hydrogen and the other is chlorine, bromine or fluorine, trifluoromethyl or hydrogen and one of R ⁷ and R ⁸ is hydrogen and the other is C 1 -C 2 alkoxy, substituted with 1 to 5 fluorine atoms, characterized in that the compound of formula (II) and ( ₂₎ are cyclized

E-NH-C-NH-C

OCH, (II) in which

E represents the remainder of the formula

O

II

R = C-NH- where

R is as defined in formula I by the action of a dehydrating agent.

The invention also relates to insecticidal compositions containing, as active ingredients, the aforementioned compounds of the formula I as well as methods for controlling insect pests using such compositions and active ingredients.

Throughout the text, all temperatures are in degrees Celsius, all parts and percentages are parts and percentages by weight, and the term "halogen atom" refers to fluorine, chlorine, bromine and iodine atoms.

The compounds of formula (I) are prepared by methods known per se or analogous to those known per se.

All compounds of formula (I) may be prepared by cyclizing a compound of formula (II) with a dehydrating agent.

Suitable dehydrating agents include phosphoric acid, formic acid, phosphorus pentachloride, phosphorus pentoxide in the presence of a strong acid, benzoic acid chlorides and anhydrides and alkanoic acids. Preferred dehydrating agents are strong acids, especially methanesulfonic acid and concentrated sulfuric acid.

The dehydration cyclization is carried out at a temperature of from 20 to 80 ° C, preferably at room temperature. If desired, solvents can be used for this reaction, including halogenated benzenes and halogenated alkanes such as dichlorobenzene and methyldichloride, as well as chloroform, although it is usually preferred to carry out the reaction without a solvent.

All of the starting materials used in the preparation of the compounds of the invention are readily obtainable by conventional methods.

The invention is illustrated by the following non-limiting examples. The examples illustrate the synthesis of typical compounds of the invention and the examples labeled "preparation" illustrate the synthesis of typical starting materials. In all cases, compounds were identified by NMR spectroscopy, elemental microanalysis, and in some cases by IR and mass spectroscopy. Preparation 1

1- (4-pentafluoroethoxybenzoyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide

To 10 ml of tetrahydrofuran is added 0.54 g of ammonium thiocyanate, the mixture is heated to reflux and 1.5 g of 2,6-dimethoxybenzoyl chloride dissolved in another 10 ml of tetrahydrofuran are added. The mixture was stirred at reflux for 20 minutes, then cooled to room temperature and a solution of 1.5 g of 4-pentafluoroethoxybenzoylhydrazine in 20 ml of tetrahydrofuran was added dropwise. The reaction mixture was stirred at room temperature for 1.5 hours, then evaporated to dryness in vacuo and the residue was washed with diethyl ether. The ether was evaporated in vacuo and the residue was recrystallized to give 1.1 g of the title compound, m.p. 184-186 ° C.

He did

N- [5- (4-pentafluoroethoxyphenyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide

To 5 g of methanesulfonic acid was slowly added 1 g of the intermediate prepared in "Preparation 1" and the mixture was stirred at room temperature for 5 hours, then poured slowly onto 100 g of ice and mixed thoroughly. The pH of the aqueous mixture was adjusted to 8.5 by addition of concentrated ammonium hydroxide, the solid material was filtered off and recrystallized from aqueous ethanol to give 0.6 g of crude product. This product was purified by silica gel chromatography eluting with 70% toluene and 30% ethyl acetate. After purification, 200 mg of the title product melting at 227-229 ° C is obtained.

Example 2

N- [5- (4-Trifluoromethoxyphenyl) -1,3,4-thiadiazol-yl] -2,6-dimethoxybenzamide

Following the procedure described in Example 1, 1- (4-trifluoromethoxybenzoyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide with methanesulfonic acid was prepared by melting at 201-203 ° C.

Example 3

N- [5- (6-methoxy-2-benzo [b] furyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide

The title compound, melting at 215-217 ° C, is obtained as described in Example 1 by reacting 1- (6-methoxy-2-benzo [b] furylcarbonyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide with methanesulfonic acid.

Example 1 a d 4

N- [5- (2-indenyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide

Following the procedure described in Example 1, reaction of 1- (2-indenocarbonyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide with methanesulfonic acid afforded the title compound, melting at 230-232 ° C.

Example 1 a d 5

N- [5- (5-methoxy-2-benzo [b] furyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide

Using the procedure described in Example 1, methanesulfonic acid was reacted with

1- (5-Methoxy-2-benzo [b] furylcarbonyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide to give the title compound, m.p. 255-257 ° C.

Example 1 a d 6

N- [5- (5-Trifluoromethyl-2-benzo [b] furyl] -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide

Following the procedure described in Example 1, reaction of 1- (5-trifluoromethyl-2-benzo [b] furylcarbonyl) -4- (2,6-dimethoxybenzoyl) thiosemylcarbazide with methanesulfonic acid gave the title compound, m.p. 242-245 ° C.

Example 1 a d 7

N- [5- (6-Trifluoromethyl-2-benzo [b] furyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide

Using the general procedure described in Example 1, reaction of 1- (6-trifluoromethyl-2-benzo b) furylcarbonyl) -4- (2,6-dimethoxybenzoyl) thiosemylcarbazide with methanesulfonic acid affords the title compound, m.p. 206 DEG-208 DEG.

Example 8

N- [5- (5-fluoro-2-benzo [b] furyl-1,3,4-thiadiazol-2-yl) -2,6-dimethoxybenzamide]

Following the procedure described in Example 1, 1- (5-fluoro-2-benzo [b] furylcarbonyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide was reacted with methanesulfonic acid to give the title compound, melting at 244-245 ° C. C.

In order to determine the insecticidal activity, the compounds of the formula I were subjected to a series of tests against live insects. Typical tests are described below and the results of these tests are presented.

In many cases, tests with a specific application rate are repeated and the average of the results obtained in these tests is calculated. Blank spaces in the tabulated data indicate that the test was not performed at the indicated application rate. The active substances are indicated by the numbers of the preparation examples.

Test 1

Efficacy test against Epilachna varivestis and Spodoptera eridania

Each of the test compounds is made into an active agent by dissolving 10 mg of the test compound in 1 ml of a solvent consisting of equal parts of anhydrous ethanol and acetone, containing 23 g of Toximul R and 13 g of To207650 ximul S (Toximul R). and Toximul S are surfactants consisting of a mixture of sulfonate and non-ionic surfactants) and the solution is mixed with 9 mL of water so that the resulting formulation contains the test drug at a concentration of 1000 ppm. The resulting dispersion is then diluted with water to the desired lower concentration if necessary.

The resultant dispersion is then evenly sprayed with bean plants 10 days old and the treated plants are allowed to dry. Leaves are then removed from the plants and the cut ends are covered with cotton soaked water. Two leaves are each placed in a 100 mm diameter petri dish, and five Epilachna varivestis larvae (2nd or 3rd instar and 5 larvae of Spodoptera eridania (2nd or 3rd instar) are added to each dish. The plates are kept for 3 days at a temperature of about 25 ° C and a relative humidity of 51%, followed by a first evaluation of the inisecticidal activity, and some of the plates are kept in the air-conditioned chamber for a further 3 days, followed by further evaluation. .

Insecticidal activity is expressed on a scale of 0 to 3, compared to control experiments in which plants are treated with solvent only and not treated at all. The individual values of the above scale have the following meaning:

= no effect, - 1 to 7 larvae killed,

- 8 to 14 larvae killed, = 15 larvae killed.

The results of the activity test of typical compounds of the invention are summarized in the following table:

Table 1

Compound Applied Epilachna varivestis Spodpptera eridania from example dose in ppm 4 days 7 days 4 days 7 din number

1000

100 (1000

100 ALIGN!

1000

100 ALIGN!

1000

100 ALIGN!

1000

100 ALIGN!

1000

100 ALIGN!

1000

100 o

o o

o o

o o

O

The compound of Example 2 was further tested in the same manner, but at different application rates, where the number of insect larvae killed was not expressed on a 0 to 3 scale but as a% mortality. In a 4-day test against Spodoptera eridania larvae, this compound shows 100% mortality at 5 ppm and in a 7-day test 100% mortality at 2.5 ppm. In the test against Epilachna varivestis, the above-mentioned compound shows 100% mortality at 5 ppm at 4 days and 80% at 2.5 ppm at 7 days.

The above data demonstrates the high insecticidal activity of the compounds of formula (I). It is understood that the compounds of the invention can be used extensively to combat insects of various orders harmful to mankind for both health and economic reasons.

For example, the disclosed compounds kill the following harmful insects:

order of beetles (Coleoptera), such as Anthonomus grandis (flowering flower), Crambus caliginosellus (grass grass, Oulema imelanopus,

Leptinotarsa decemlineata,

Hypera postica,

Anthrenus scrophulariae, Trlbolium confusum,

Lyctidae spec. (bump heads),

Agriotesspec. (click beetles),

Sitophilus oryzae (rice weevil), Nodonota puncticollis and Coinotrachelus neruphar, diptera order, such as Musea domestica [house fly], Stomloxys calcitrans (stalk thistle), Haematobia irritans,

Phormia regina,

Hylemyia brassicae and Psila rosae, Butterfly order (Lepidopteraj, such as Laspeyresia pomonella, Euxoa spec.),

Fruits of interpunctella, Tartricidae spec.,

Heliothis zea

Ostrinia nubilalis,

Hellula rogatalis,

Trichoplusia ni,

Thyridopteryx ephemeraeformis,

Malacosoma americanum and the Spodoptera frugiperda, order Orthoptera, such as Blattella germanica and Periplaneta americana.

The compounds of the present invention can be used to reduce insect populations by applying an insecticidally effective amount of any of these compounds to the insect-eating agent.

Insects can ingest the active ingredient by applying it to any material that eats the insect. For example, insect-infesting plants can be controlled by applying the active ingredient to those parts of the plant which eat the insects, in particular to the leaves of the plant. Insect pests infesting and feeding on textiles, paper, wood products, etc. can be easily controlled by applying the active ingredient to these materials and products. Similarly, the disclosed compounds can be effectively used to protect stored grain or seed.

Remarkably, the disclosed compounds prevent the emergence of the following developmental stages of the insects that ingested them. For example, when the compounds of the invention ingest adult adult insects, such adults are virtually unaffected, but lay sterile eggs. If the active substance is ingested by a larva, it will die without imetamorphosis at the next larval stage. The larvae in the last larval stage, which ingest the active substance, pupa, but die in the umbilical form.

it will be understood that the use of a compound of Formula I does not necessarily result in the destruction of the entire insect population. In some cases, however, the entire pupulation is killed, but in other cases only part of the insect is killed and the remaining part survives by application of the active substance. The size of the part of the population that the active ingredient kills depends on the type of insect, the active ingredient used, the dose applied, the viability and condition of the insects, the weather conditions, and other factors known to those skilled in the art. The term 'reduction of insect populations' means, therefore, a reduction in the number of live insect specimens which, in some but not all cases, results in the disappearance of the treated insect population. The extent of reduction of insect populations using a given compound will, of course, depend upon the dose of the compound administered. In all cases, at least an insecticidally effective amount of the compound is required. The term "insecticidally effective amount" is used to describe an amount that is capable of causing a measurable reduction in the treated insect population. Insecticidally effective amounts generally range from 1 to 1000 ppm.

It should be emphasized that the application rates of insecticides are usually expressed as the concentration of insecticide in the dispersion used for application. The application rate is measured and expressed in this manner because it is most useful to apply an amount of dispersion sufficient to cover the sheets or other treated materials with a thin film of dispersion. Thus, the amount of dispersion to be applied depends on the surface area of the insect-treated material to be treated and the amount of active ingredient depends on its concentration in the applied dispersion.

The dispersions used to administer the compounds of the present invention are prepared from conventional isosicidal compositions which are novel in the present case since the new compounds of the present invention are present therein. Most commonly, aqueous dispersions prepared by mixing a small amount of concentrated insecticidal composition with an appropriate amount of water are used to achieve the desired concentration of active ingredient in the applied dispersion. Such concentrated water dispersible compositions generally containing from 5 to 90% active ingredient are usually in the form of emulsifiable concentrates, wettable powders or suspensions.

Wettable powders consist of an intimate blend of the active ingredient with an inert carrier which is a mixture of inert powder material and surfactants. The concentration of active ingredient is usually from 10 to 90% by weight. The inert powder material is usually selected from the group of attapulgite clays, montmorillonite clays, infusorio clays and purified silicates. Active surfactants which are present in the wettable powder in an amount of 0,5 to 10% | % are usually sulfoinated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates and nonionic surfactants such as ethylene oxide adducts of alkylphenol.

Typical emulsifiable concentrates contain the active compound according to the invention in a suitable concentration, such as in an amount of 50-500 grams per liter of liquid (corresponding to a concentration of 5-50%) dissolved in an inert carrier which is a mixture of a water-immiscible organic solvent and emulsifiers. Suitable organic solvents include aromatic hydrocarbons, especially xylenes, and petroleum fractions, especially the high-boiling niaphthalenic and olefinic petroleum fractions. However, other organic solvents, such as terpenic solvents and

287650 more complex alcohols such as 2-ethoxyethanol. Emulsifiers suitable for the preparation of emulsifiable concentrates are selected from the same types and concentrations of surfactants as wettable powders.

The suspensions according to the invention consist of an active substance in the form of a finely divided powder suspended in a suitable liquid non-solvent at a concentration similar to that of emulsifiable concentrates. The most suitable liquid non-solvent is a mixture of water and surfactants. The same types of surfactants are used for the preparation of suspensions as for the preparation of wettable powders. In many cases, small amounts of inert diluents are used to improve suspendability.

Such inert diluents include swellable clays such as attapulgite and montronorillonite, starches, and in particular purified silicates.

If desired for any reason, it is equally possible to apply the active compound according to the invention in the form of a solution in a suitable, organic solvent, usually in petroleum oil, as in spraying alleys widely used in agrochemistry.

Further, the compounds of the invention may be applied in the form of dusts and aerosol formulations. Dusts consist of the active ingredient in finely powdered form dispersed in a powdered inert carrier. The carrier is usually powdered clay, such as pyrophyllite, bentonite, volcanic sediment or montrnoirillonite. Dusts usually contain the active ingredient in a concentration of from 0.1 to 10 why.

The aerosol formulations consist of a compound of formula (I) dissolved or dispersed in an inert carrier which is a propellant propellant and is enclosed in a container from which the mixture is discharged through an atomizing valve. The propellant blends are either low boiling hydrocarbons or suitable suspensions pressurized with internal gaseous hydrocarbons.

Claims (3)

OBJECT OF THE INVENTION A process for the preparation of the novel N- (1,3,4-thiadiazol-2-yl) benzamides of the general formula I, in which: R is a radical of formula wherein X represents oxygen or sulfur, one of R ¹ and R ² is hydrogen and the other is fluorine, chlorine, bromine, trifluoromethyl or methoxy group, one of R ³ and R ⁴ is hydrogen and the other is methoxy or trifluoromethyl; one of R ⁵ and R ⁶ is hydrogen and the other is chlorine, bromine or fluorine, trifluoromethyl or hydrogen and one of R ⁷ and R ⁸ is hydrogen and the other is C 1 -C 2 alkoxysikiupine, substituted with 1 to 5 fluorine atoms, characterized in that a compound of formula (II) in which is cyclized is cyclized E represents the remainder of the formula O II R = C-NH- where R is as defined in formula I by the action of a dehydrating agent. 2. The process of item 1, for the preparation of N- [5- (4-trifluoromethoxyphenyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide, characterized in that 1- ( 4-Trifluoromethoxybenzoyl-4- (2,6-dimethoxybenzoyl) thiosemicarbazide is cyclized by treatment with methanesulfonic acid. 3. The process of item 1, for the preparation of N- [5- (4-pentafluoroethoxyphenyl) -1,3,4-thiadiazol-2-yl] -2,6-dimethoxybenzamide, characterized in that 1- [4-] 4- pentafluoroethoxybenzoyl) -4- (2,6-dimethoxybenzoyl) thiosemicarbazide is cyclized by treatment with methanesulfonic acid.