HUT68462A - Process for producing pesticidal compounds, compositions containing the compounds and process for using of the compositions - Google Patents

Abstract

The present invention describes a compound of formula (I), wherein n and n' are the same or different and are each 0, 1 or 2; R is hydrogen or methyl, R' is methyl ethyl or cyclopropyl, R<2> and R<3> are the same or different and are each hydrogen or methyl; R<a> is hydrogen or methyl, R<b> is cyano or R<a> and R<b> are linked to form a group CH2S(O)m where m is 0, 1 or 2. A method for preparing the compounds of formula (I), pesticidal formulations containing the compounds and their use in controlling pests are also described.

Description

The present invention relates to novel pesticidal chemical compounds, to processes for their preparation, to compositions containing them and to their use for controlling pests. More particularly, the invention relates to a group of sulfur-containing heterocyclic compounds.

European Patent Nos. 216625, 216624 and 300797 disclose 2,6,7-tritiabicyclo [2.2.2] octanes; the main difference between the compounds disclosed is in the nature of the 1-substituents.

European Patent Applications 294229, 294228 and 372816 relate to 1,3-dithianic pesticides which

In the 5-position they contain a rather narrow range of alkyl groups.

It has been found that a general class of these previously described compounds includes a novel class of compounds having beneficial insecticidal activity, such as flies and / or cockroaches, and this property is coupled with low toxicity and / or good stability in mammals.

Accordingly, the present invention provides compounds of formula I wherein n and n 'are the same or different and each is 0, 1 or 2:

R is hydrogen or methyl,

R ^{1 is} methyl, ethyl or cyclopropyl,

R ² and R ^{3 are the} same or different and each is hydrogen or methyl;

• · · ♦

R ^is hydrogen or methyl,

You are a cyano group R ^b

R ^a and R ^b together form a group -CH ₂ S (O) _m - wherein m is 0, 1 or 2.

Preferably R is hydrogen.

When R ^a and R ^{b are} -CH ₂ S (O) _m -,

R ^{1 is} preferably ethyl,

Preferably R ² and R ³ are hydrogen, m, n and n 'are preferably 0.

When R ^is hydrogen or methyl and R ^{b is} cyano:

Preferably R ¹ , R ² and R ³ are each methyl.

A preferred group of compounds of formula I are compounds of formula II wherein R, m, n and n 'are as defined above and R ¹ is as defined above, preferably ethyl.

Another preferred group of compounds of formula (I) are compounds of formula (III) wherein R ¹ , R ¹ , R ² , R ³ , R ^a , n and n 'are as defined above.

The compounds of formula (III) may exist in many stereoisomeric forms; the present invention also encompasses mixtures of isomers and the isomers themselves. The present invention encompasses radiolabeled compounds of Formula I, particularly those wherein one carbon atom is replaced by ¹⁴ C or one or more hydrogen atoms.

Preferred compounds of formula I include:

- 4's

1- (3,3-dimethyl-butyl) -4- (n-propyl) -2,6,7-trithiabicyclo [2.2.2] octane

1- (3,3-dimethyl-butyl) -4- (n-propyl) -2,6,7-trithiabicyclo [2.2.2] octane-2-oxide

5- (tert-butyl) -2-cyano- (3,3-dimethylbutyl) -1,3-dithiane

1- (3,3-dimethylbutyl) -4-ethyl-2,6,7-trithiabicyclo [2.2.2] octane.

Compounds of formula (I) may be prepared (i) from an anion of a compound of formula (IV) with an alkylating agent. Suitable alkylating agents include a

3,3-dimethylbutyl halides such as iodide. Suitably, the anion of the compound of formula IV is prepared in situ from the compound of formula IV. The reaction is carried out in the presence of a sufficiently strong base such as butyllithium in an inert solvent such as ether such as tetrahydrofuran at a temperature of -100 ° C to 20 ° C, preferably -80 ° C to -20 ° C.

Compounds of formula (IV) wherein RT ^a and Rb together form -CH2S (O) _m - may be synthesized as described in European Patent Application 300797.

Compounds of formula IV wherein R ^{b is a} cyano group are prepared by converting appropriate compounds which contain an aldehyde group instead of a cyano group. For this conversion, the aldehyde is reacted with a suitable reagent such as Ο, Ν-bis (trifluoroacetyl) hydroxylamine. This aldehyde, in turn, is formed from a 2-unsubstituted dithiane or oxathane with a formylating agent, · · · · · · ·

With dimethylformamide in the presence of a strong base such as butyllithium.

(ii) When a compound of formula (II) is required, a compound of formula (V)

a) with a tert-BuCH 2 CH 2 X compound in which X is activated in the presence of an activated carboxy group such as carboxylic acid chloride, Lewis acid such as aluminum trichloride or boron trifluoride etherate. The reaction is conveniently carried out in an inert solvent such as a halogenated hydrocarbon such as dichloromethane, at a temperature of, for example, -100 ° C and 50 ° C, preferably -60 ° C, under an inert gas such as nitrogen;

b) reacting with tert-BuCH2CH2CN in the presence of a suitable acid such as hydrogen chloride gas. The reaction is suitably carried out in an inert solvent such as an aromatic hydrocarbon, a chlorinated hydrocarbon or an ether, preferably toluene, dichloromethane or tetrahydrofuran, at a temperature of from -70 ° C to 70 ° C, preferably 0 ° C.

Compounds of formula (V) may be prepared from the corresponding compound of formula (VI) wherein R is a C 1-4 alkylsulfonyl or arylsulfonyl group such as methanesulfonyl or ptoluenesulfonyl;

(a) by reaction with sodium trithiocarbonate followed by acid hydrolysis and reduction. Reaction with sodium trithiocarbonate in a solvent such as dipolar aprotic solvent such as dimethylformamide, 4 · 4 · 4 · 4

4 ··· · 4 ····

6 is performed at a non-extreme temperature, for example between 10 ° C and 150 ° C, and preferably between 20 ° C and 130 ° C. The acid hydrolysis is suitably carried out with a dilute mineral acid such as dilute sulfuric acid or hydrochloric acid at a non-extreme temperature such as 0 ° C to 100 ° C and suitably 20 ° C to 30 ° C. The reduction is carried out with a reducing agent such as a metal hydride such as lithium aluminum hydride in a non-reactive solvent such as an ether such as diethyl ether at an extreme temperature such as 0 ° C to 100 ° C and suitably 30 ° C to 60 ° C. implementing it;

b) by reaction with potassium thiocyanate to give the trithiocyanate intermediate, which is then hydrolyzed alkaline and reduced. The thiocyanate reaction is suitably carried out in a non-reactive solvent, such as a dipolar aprotic solvent such as dimethylformamide, at elevated temperatures, for example 50 ° C to 180 ° C and suitably 120 ° C to 170 ° C. Suitably, the alkaline hydrolysis is carried out with an alkali metal hydroxide such as sodium hydroxide in an aqueous solvent system containing a water miscible solvent such as ethanol, suitably at 0 ° C to 70 ° C, for example 20 ° C to 30 ° C. The reduction is carried out with a reducing agent such as zinc, suitably zinc powder and hydrogen chloride, suitably concentrated hydrochloric acid, in a hydrocarbon solvent such as toluene, at a non-extreme, preferably elevated temperature such as 70 ° C to 120 ° C;

c) reacting with sodium sulfide and sulfur to form bis (dithiolane disulfide), which is then reduced to a compound of formula VI with a reducing agent such as zinc and hydrochloric acid. The first reaction is conveniently carried out in a protic solvent such as a C 1 -C 4 alkanol such as ethanol at a non-extreme temperature such as 0 ° C to 100 ° C and 60 ° C to 85 ° C, respectively. The reduction is conveniently carried out with zinc powder and concentrated hydrochloric acid in a hydrocarbon solvent such as toluene at a suitably elevated temperature, for example between 70 ° C and 120 ° C.

Compounds of formula I wherein one or more of m, n and n 'are other than O can be prepared by oxidation of the corresponding lower oxidation compound.

This oxidation is generally carried out in an inert solvent such as acetonitrile or a halogenated hydrocarbon such as chloroform at a non-extreme temperature such as 0 ° C to 100 ° C, preferably 20 ° C to 30 ° C. Suitable oxidizing agents are, for example, peracids such as m-chloroperbenzoic acid. The oxidation is preferably carried out in the presence of a buffer such as anhydrous sodium acetate. Compounds wherein m is 2 and n and n · are 0 are compounds of formula I wherein m is 0 or 1 with potassium permanganate in a ketone such as acetone, not extreme, e.g. -30 ° C to 100 ° C preferably by oxidation at a temperature of -10 ° C to 30 ° C.

The compounds of formula (I) are pesticides.

4 · «44 ··· Φ

8 as agents for controlling arthropods such as insects and mites, helminths such as nematodes and molluscs such as naked snails. Thus, in accordance with the process of the present invention, arthropods, helminths and / or molluscs can be controlled by treating the arthropods, helminths and / or molluscs or their environment with an effective amount of a compound of formula (I). The present invention can reduce or eliminate infestation by humans and animals, plants, including trees, and / or arthropods, nematodes and / or molluscs, such that humans or animals or their habitat are (I). ) with an effective amount of a compound of the formula. The present invention also encompasses the use of the compounds of formula I for use in the control of arthropods, helminths and / or molluscs in human and veterinary medicine, in public health and in agriculture.

Compounds of formula I are particularly valuable in arable, fodder, greenhouses, orchards and vineyards, ornamental and tree plantations, and in woods such as cereals such as corn, wheat, rice and sorghum, cotton, salads such as beans, kale, lettuce, onions, tomatoes and peppers, arable crops such as potatoes, sugar beet, peanuts, soybeans, rapeseed, sugar cane, pasture and feed such as corn, sorghum, alfalfa, planting, tea, -, cocoa, banana, oil palm, t ···:

- 9 X \

such as coconut, rubber and spice plantations, orchards and groves. for example, protection of deciduous and evergreen forest trees of stone fruits and seeds, citrus fruits, kiwifruit, avocados, mangoes, olives and nuts, flowers and shrubs in vineyards, ornamental plants, greenhouses, gardens and parks, forests, plantations and nurseries.

The compounds of the present invention also have valuable properties against wood such as live and felled trees, processed wood, lumber or building materials against leaf bark, such as Urocerus, or other beetles such as scolytides, platypodides, lyctides, bostrychides, cerambycides and anabolics.

The compounds of the invention may also be used to protect stored products, such as cereals, fruits, nuts, spices and tobacco, in whole, ground or processed form, against butterflies, beetles and mites. The compounds may be used to protect stored animal products, such as skins, hair, wool and feathers, in natural or modified form, such as rugs or textiles, against butterflies and beetles, and stored meat and fish against insects, mites and flies.

The compounds of the formula I are also very effective against arthropods, helminths and molluscs which are harmful to human and animal health or are vectors or carriers of disease of humans and pets, such as the aforementioned pests, and in particular ticks, mites, lice, fleas, mosquitoes: ··· »

- ίο and the spicy, unpleasant larvae and snails.

The compounds of formula (I) may be used alone or in diluted form for known purposes such as baths, sprays, mists, coatings, foams, dusts, spray powders, aqueous suspensions, pastes, gels, creams, shampoos, ointments, evaporative formulations, flammable rolls, baits, nutritional supplements, wettable powders, granules, aerosols, emulsifiable concentrates, oily suspensions, oily solutions, pressurized preparations, impregnated products, pourable or other standard formulations well known to those skilled in the art. The bath concentrates are not diluted in the form as prepared but diluted with water and the animals are immersed in a bath containing this liquid. The spray can be applied by hand or with various machine or air-operated equipment to the desired location. The animal, soil, plant, or surface to be treated may be spray-saturated or applied at low or ultra-low volume on the surface with high volume application. Aqueous suspensions may be used in a manner similar to sprays and baths. Dusts are dispersed by means of a dust application device and, in the case of animals, suspended in perforated bags on trees or rods to which animals are attached. Pastes, shampoos and ointments may be applied by hand or dispersed on the surface of an inert material, to which animals are rubbed and applied to their skin. The dressing composition is applied in small amounts of fluid to the back of the animals such that all or most of the fluid remains on the animal.

The compounds of formula (I) can be formulated into formulations that can be used directly on animals, plants or surfaces, or formulations that need to be diluted prior to use, but both are formulated with one or more carriers or diluents. in the form of an intimate mixture. The carriers may be liquid, solid, or gaseous, or mixtures thereof, and the compound of Formula I may be present in amounts of 0.025 to 99% w / v, depending on whether or not further dilution is required.

Dusts, dispersible powders and granules, and other solid formulations of the compound of formula I are pulverized with a solid, inert carrier such as clays, kaolin, bentonite, attapulgite, adsorbent carbon, talc, mica, limestone, gypsum, tricalcium phosphate. in the form of an intimate mixture of cork, magnesium silicate, vegetable carriers, starch and diatomaceous earth. Such solid compositions are generally prepared by impregnating the solid diluents with a solution of the compound of formula (I) in a volatile solvent, evaporating the solvent, optionally grinding the product to powder and optionally granulating, compressing or encapsulating the product.

Φ · • • · * * «« «· · · ·

- 12 A spray containing a compound of formula (I) consisting of a solution or an aqueous emulsion (bath or spray) of any of the organic solvents described below, is prepared in situ from an emulsifiable concentrate (otherwise known as a water miscible oil). can also be used for bathing purposes. Preferably, the concentrate comprises the active ingredient with or without an organic solvent and one or more emulsifiers. The solvents may be present in a wide range, but preferably in amounts of 0 to 90% w / v, and may be selected from petroleum, ketones, alcohols, xylenes, aromatic gasoline and other solvents customary in the art of formulation. The concentration of the emulsifiers ranges over a wide range, but is preferably between 5 and 25% (w / v), and the emulsifiers are suitably nonionic surfactants which include polyoxyalkylene esters of alkylphenols and polyoxyethylene of hexitol anhydrides. and anionic surfactants such as sodium lauryl sulfate, fatty alcohol ether sulfates, alkylarylsulfonates and alkylsulfosuccinates. Examples of cationic emulsifiers are benzalkonium chloride and quaternary ammonium ethosulfates.

Amphoteric emulsifiers include carboxymethylated oleinimidazoline and alkyldimethyl betaine.

The evaporator formulation generally consists of a mixture of cotton and cellulose, which is pressed into boards of approximately 35 x 22 x 3 mm and treated with a concentrate of up to 0.3 ml containing the active ingredient in an organic solvent solution and optionally with antioxidant, paint and fragrance. . The insecticide is evaporated using a heat source, such as an electric heater.

Flammable solids generally consist of sawdust and binder mixed with the active ingredient, and this mixture is generally formed into rolls of rolls. A coloring agent and a fungicide may be added.

Wettable powders may contain an inert solid carrier and one or more surfactants and, if desired, stabilizers and / or antioxidants.

Emulsifiable concentrates consist of emulsifiers and often organic solvents such as petroleum, ketones, alcohols, xylenes, aromatic gasolines and other solvents known in the art.

Wettable powders and emulsifiable concentrates generally contain from 5 to 95% by weight of the active ingredient and are diluted with, for example, water before use.

The coated agents consist of a solution of the active ingredient in an organic solvent containing a resin and optionally a plasticizer.

Bathing fluids may also be prepared from aqueous suspensions containing not only emulsifiable concentrates, but also wettable powders, soap based baths and an intimate mixture of the compound of formula (I) with a dispersant and one or more surfactants.

Aqueous suspensions of the compound of formula (I) may also contain suspending, stabilizing or other agents. The suspensions or solutions may be used in their original form or diluted in a known manner.

Ointments may be prepared from vegetable oils, synthetic esters of fatty acids, or wool grease with an inert base such as soft paraffin. Preferably, a compound of formula (I) is uniformly distributed in solution or suspension by stirring. Ointments may also be prepared from emulsifiable concentrates by dilution with an ointment base.

Pastes and shampoos are also semi-solid compositions in which the compound of formula (I) is present in a uniform dispersion in a suitable base such as soft or liquid paraffin or is formulated with a non-ointment glycerol, gum or suitable soap. Because ointments, shampoos, and pastes are generally applied undiluted, these compositions should contain a percentage of the compound of formula I required for treatment.

Aerosol sprays are prepared by simply dissolving the active ingredient in an aerosol carrier and co-solvent, such as halogenated alkanes and the aforementioned solvents. The pourable compositions are prepared in the form of a solution or suspension of the compound of formula I in a liquid medium. A pathogen-carrying bird or mammal can also be protected from infections caused by mite ectoparasites by placing on its body a suitable molded plastic object impregnated with a compound of formula (I). Examples of such items are an impregnated collar, label, ribbon, plate or strip. The plastic is suitably polyvinyl chloride (PVC).

The concentration of the compound of formula (I) applied to the animal, indoors or outdoors will depend on the compound chosen, the duration of treatment, the nature of the composition and the likely infection, but will generally be 0.001 to 20.0% w / v, preferably 0.01%. The compound should be present in an amount of from about 10% to about 10%. The amount of compound administered to the animal will vary with the mode of application, the size of the animal, the concentration of the compound in the composition used, the dilution factor of the composition and the nature of the composition, but will generally range from 0.0001 to 0.5% wt. pourable compositions which are generally employed in a concentration of 0.1 to 20.0%, preferably 0.1 to 10%. The amount of compound to be used for stored products will generally range from 0.1 to 20 ppm. When spraying a confined space, the average initial concentration of the compound of formula (I) should be between 0.001 and 1 mg per cubic meter of treated air.

The compounds of formula (I) may also be used for the protection and treatment of plant species, wherein an effective amount of the active ingredient is used as an insecticide, acaricide, nematocide or molluscicide. The rate of application depends on the compound chosen, the nature of the preparation, the mode of application, the plant species, the depth of planting and the probable infestation and other factors, but generally in the agricultural areas 0.001 and 3 kg / ha, preferably 0.01 and 1 kg / ha. if it changes between. Typical agricultural formulations contain from 0.0001 to 50%, preferably from 0.1 to 15% by weight, of the compound of formula (I).

Dusts, ointments, pastes and aerosol formulations are generally used as described above and in a form containing from 0.001 to 20% w / v of the compound of formula I.

The compounds of formula (I) have been found to be effective against common housefly (Musca domestica). In addition, certain compounds of formula I are active against other arthropod pests, including Myzus persicae, Tetranychus urticae, Plutella xylostella, Culex spp. , Tribolium castaneum, Sitophilus granarius, Periplaneta americana and Blattela germanica. The compounds of formula (I) are thus useful in combating arthropods, such as insects and mites, in any environment where they occur as pests, such as in agriculture, animal husbandry, public health and around the house.

Insect pests include the order Coleoptera (e.g., Anobium, Ceutorhynchus, Rhynchophorus, Cosmopolites, Lissorhoptrus, Meligethes, Hypothenemus, Hylesinus,

Acalymma, Lema, Psylliodes, Leptinotarsa, Gonocephalum,

Agriotes, Dermolepida, Heteronychus, Phaedon, Tribolium,

Sitophlus, Diabrotica, Anthonomus or Anthrenus spp.),

Lepidoptera Order (e.g., Ephestia, Mamestra, Earias, Pectinophora, Ostrinia, Trichoplusia, Pieris, Laphygma, Agrotis, Amathes, Wiseana, Tryporyza, Diatraea, Sporganot- his, Cydia, Archips, Plutella, Chilo, Heliothis, Spodoptera

or Tineola spp.), the order of Diptera (e.g. Musca, Aedes,

Anopheles, Culex, Glossina, Simulium, Stomoxys, Haematobia, Tabanus, Hydrotaea, Lucilia, Chrysomia, Callitroga, Dermatobia, Gasterophilus, Hypoderma, Hylemyia, Atherigona, Chlorops, Phytomyza, Ceratitis, Malaghspha, Liriomyza, and Melagia. e.g. Damalina spp. and Anoplura e.g. Linognathus and Haematopinus spp.), Hemiptera order (e.g. Aphis, Bemisia, Phorodon, Aeneolamia, Empoasca, Parkinsiella, Pyrilla, Aonidiella, Coccus, Pseudococcus, Helopeltis, Lygus, Dysdercus, , Triatoma, Rhodnius, Psylla, Myzus, Megoura, Phylloxera, Adelyes, Niloparvata, Nephrotettix or Cimex spp.), Orthoptera order (e.g. Locusta, Gryllus, Schistocerca or Acheta spp.); The order of Dictyoptera (e.g. Blattella, Periplaneta or Blatta spp.), The order of Hymenoptera (e.g. Athalia, Cephus, Atta Lasius, Solenopsis or Monomorium spp.), Isoptera (e.g. Odontotermes and Reticulitermes spp.); Siphonaptera (e.g., Ctenocephalides or Pulex spp.); Thysanura (e.g. Lepisma spp.), Dermaptera order (e.g. Forficula spp.), Psocoptera order (e.g. Peripsocus spp.) And Thysanoptera order (e.g. Thrips taba18 ci).

For example, mite pests can be ticks such as

Members of the genus Boophilus, Ornithodorus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermacentor and Anocentor, mites and mites, such as Acarus, Tetranychus, Psoroptes, Notoednes, Sarcoptes, Psorergates, Psorergates, Chori , Blaniulus, Polyphagotarsonemus, Scutigerella and Onis cus.

Among the worms which directly attack crops and trees of agricultural, forestry and horticultural interest or that spread bacterial, viral, mycoplasma or fungal infections of the plants are:

Meloidogyne spp., e.g. M.

incognita; doboderma spp., such as G. rostochiensis; the

Heterodera spp.

for example, H. avenae; Radopholus spp., such as R. similis; Pratylenchus spp., such as P.

pratensis; Belonolaimus spp., such as B. gracilis; the

Tylenchulus spp., Such as T. semipenetrans; Rotylenchu lus spp., such as T. reniformis; Rotylenchus spp., such as R. robustus; Helicotylenchus spp., such as H. multicinctus; Hemicycliophora spp., such as H. gracilis;

Criconemoides spp., such as C. similis; Trichodorus spp., such as T. primitivus; Xiphinema spp., such as X. diversicaudatum; Longidorus spp., such as L. elongatus; Hoplolaimus spp., such as H. coronatus; Aphelenchoides spp., such as A. ritzemabosi, A. besseyi; Ditylenchus spp., such as D. dipsaci.

J • · · *

- 19 Molluscan pests attacking crops, trees and plants of importance to agriculture, forestry and horticulture include snails such as Deroceras spp., Such as D. reticulatum; the Arion group; Milax spp .; Helix spp. and Planorbis spp. Among mollusc pests that carry human and pet diseases, Bulinus spp., Physopsis spp., Planorbis spp. and Oricomelania spp. It can be mentioned.

The compounds of the invention may be combined with one or more other pesticidal agents, such as pyrethroids, carbamates and organic phosphates, and / or attractive, repellent, bacteriocidal, fungicidal, nematocidal, antelmintic and the like. It has also been found that the compounds of the present invention have synergistic or potentiating effects, such as piperonyl butoxide or propyl 2-propynylphenylphosphonate belonging to one of the synergist oxidase inhibitors; a second compound of the invention; or by adding a pyrethroid pesticide. When an oxidase inhibitor synergist is present in the composition of the invention, the ratio of the synergist to the compound of formula I ranges from 25: 1 to 1:25, for example 10: 1.

Anti-oxidants such as tocopherols, butylhydroxyanisole and butylhydroxytoluene, as well as traps such as epichlorohydrin and organic or inorganic bases such as trialkylamines such as • ·

There are 20 triethylamines which can act as both a basic stabilizer and a scavenger.

The following examples illustrate the advantages of the invention without limiting the invention thereto.

Example 1

1- (3,3-Dimethyl-butyl) -4- (n-propyl) -2,6,7-trithiabicyclo [2.2.2] octane (i) 28.0 g of 2- (hydroxymethyl) -2 To a solution of (n-propyl) -propane-1,3-diol (European Patent Application 216624) in dry pyridine (200 ml) was added dropwise methanesulfonyl chloride (74.0 g) at 0 ° C over 30 minutes. The mixture was allowed to warm to room temperature and stirred for 18 hours. The reaction mixture was poured into water (200 ml) and extracted with chloroform (2 x 200 ml). The chloroform extract was washed with water (2 x 100 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo. The brown solid residue was stirred with 200 mL of dry diethyl ether to give 70.0 g of 2- (hydroxymethyl) -2- (n-propyl) propane-1,3-diol trimethanesulfonate as a white solid, m.p. 103-106 ° C. They are C's.

(ii) To a solution of 12.0 g of 2- (hydroxymethyl) -2- (n-propyl) -propane-1,3-diol trimethanesulfonate in 100 ml of dimethylformamide, 18.0 g of sodium trithiocarbonate are obtained. J. Org. Chem. 1968, 33, 1275] in 25 ml of water. The mixture was stirred for 4 hours

Reflux at 130 ° C and allow to cool to room temperature. After stirring for a further 18 hours, dilute sulfuric acid (50 ml) was added slowly over 30 minutes. The mixture was extracted with chloroform. The extract was dried over anhydrous magnesium sulfate and concentrated in vacuo. THE • · · · *

• · • · · ······ «

To 21 residual brown liquids was added hexane (200 mL) and the mixture was washed with water (3 x 50 mL). After drying over anhydrous magnesium sulfate and evaporation, 6.8 g of an amber oil are obtained. A solution of 6.4 g of crude oil in 10 ml of diethyl ether is added dropwise to a suspension of 3.0 g of lithium aluminum hydride in 100 ml of dry diethyl ether at a rate sufficient to maintain the source. After the addition was complete, the mixture was stirred for 4 hours and then carefully added with 3 ml of water. After addition of dilute sulfuric acid (3 ml), water (3 ml) was added again, the solid was filtered off and washed with diethyl ether (50 ml). The combined filtrates were dried over anhydrous magnesium sulfate and concentrated in vacuo. 5.3 g of 2- (mercaptomethyl) -2- (n-propyl) propane-1,3-dithiol are obtained in the form of a pale yellow oil.

(iii) 4.0 g of 2- (mercaptomethyl) -2- (n-propyl) -propane-1,3-dithiol and 3.6 g of ethyl orthoformate in 120 ml of dry 1.0 g

Amberlyst is boiled under stirring and reflux in toluene containing 15 branded resins. The mixture was cooled and filtered. The filtrate was evaporated in vacuo and the residue was purified by chromatography on alumina adsorbent, eluting with a 1:10 mixture of dichloromethane and hexane. 3.1 g of 4- (n-propyl) -2,6,7-tritiabicyclo [2.2.2] octane are obtained in the form of a colorless solid, m.p. 139 ° C.

(iv) Starting from 3,3-dimethylbutan-1-ol (Aldrich) and 1 equivalent of methanesulfonyl chloride and following the procedure described in step (i), 3,3-dimethylbutyl methanesulfonate is prepared.

φ · i

«· · · • · · · · ··· ······

A mixture of 22 (ν) 13.6 g of 3,3-dimethylbutyl methanesulfonate and 50 g of sodium iodide in 175 ml of butanone is stirred and refluxed for 1 hour. The solvent was then removed in vacuo and the residue partitioned between diethyl ether and water. The organic layer was separated, washed with water and brine, then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 10.7 g

3,3-Dimethylbutyl iodine was obtained as a yellow liquid.

(vi) To a solution of 2.2 g of 4- (n-propyl) -2,6,7-trityiabicyclo [2.2.2] octane in 75 ml of dry tetrahydrofuran with stirring at -70 ° C and 8.0 ml of nitrogen stream A 1.6 molar solution of n-butyllithium in hexane was added dropwise. The resulting solution was stirred at -70 ° C for 45 minutes and then 2.72 g of 3,3-dimethylbutyl iodide were added and stirring was continued at -70 ° C for 2 hours. The mixture was then allowed to warm to 20 ° C and stirred at 20 ° C for 18 hours, then water was carefully added and the aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica eluting with a 1:10 mixture of dichloromethane and hexane. 2.0 g of 1- (3,3-dimethylbutyl) -4- (n-propyl) -2,6,7-tritiabicyclo [2.2.2] octane are thus obtained in the form of a colorless solid.

Similarly, 1- (3,3-dimethylbutyl) -4-ethyl-2,6,7-trithiabicyclo [2.2.2] octane was prepared.

In steps (vii), (viii) and (ix) below, the 2- (mercap!

• · · · · · · · · · · · · · · · ·

An improved process for the preparation of -23-to-methyl) -2- (n-propyl) -propane-1,3-dithiol is described.

(vii) To a stirred suspension of 300 g of 2- (hydroxymethyl) -2- (n-propyl) propane-1,3-diol trimethylsulfonate in 2000 ml of dry dimethylformamide was added 900 g of potassium thiocyanate. The mixture was stirred at 140 ° C for 16 hours. It is then cooled and its volume is distilled (dimethylformamide) (head temperature 50 ° C, pressure 2 kPa) to ca. to one third. The residue was cooled and 2000 ml of water and 2000 ml of toluene were added. The mixture was vigorously stirred and the layers were separated. The aqueous layer was further extracted with toluene (3 x 1000 mL). The combined toluene extracts were washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give 140.0 g of 2- (n-propyl) -2- (thiocyanato-methyl) -1,3-dithiocyanato-propane as a dark oil.

(viii) 20 g of 2- (n-propyl) -2- (thiocyanato-methyl) -1,3-dithiocyanato-propane are dissolved in 100 ml of toluene and 800 ml of water are added. The aqueous mixture was stirred and after the addition of 20 g of sodium hydroxide, it was refluxed for 8 hours. After standing overnight, the toluene layer was separated and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give 17.0 g of 4- (mercaptomethyl) -4- (n-propyl) -1,2-dithiolane as a dark oil.

(ix) A solution of 36.0 g of 4- (mercaptomethyl) -4- (n-propyl) -1,2-dithiolane in 200 ml of toluene is stirred vigorously!

• · · · · ·· «· ·« * «« 4

- 24 and 60 g of zinc powder and 1000 ml of 1: 1 dilute hydrochloric acid are added over 1 hour under nitrogen. The mixture was refluxed for 3 hours, then cooled and extracted with toluene (500 mL). The toluene layer was dried over anhydrous magnesium sulfate and the solvent removed in vacuo. 36.0 g of 2- (mercaptomethyl) -2- (n-propyl) propane-1,3-dithiol are obtained in the form of a pale yellow oil.

Steps (x) and (xi) describe an alternative route for the preparation of 1- (3,3-dimethylbutyl) -4- (n-propyl) -2,6,7-tritiabicyclo [2.2.2] octane.

(x) Slow hydrogen chloride gas is passed through 100 ml of dry toluene at 0 ° C for 5 minutes. A solution of 1.8 g of 2- (mercaptomethyl) -2- (n-propyl) propane-1,3-dithiol in 20 ml of dry toluene was added followed by 1.1 g of 4,4-dimethylvaleronitrile (GM Whitesides, JP Sevenair and RW Goetz, J. Amer. Chem. Soc. 1967, 89, 1135) are added with 20 ml of dry toluene. After 3 days at 0 ° C, the mixture was poured into water and the aqueous mixture was extracted with toluene. The toluene extracts were washed with water and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residual solid was washed with methanol and air-dried to give 0.70 g of 1- (3,3-dimethyl-4- (n-propyl) -2,6,7-tritiabicyclo [2.2.2] octane) as a colorless solid.

(xi) to a suspension of 0.57 g of aluminum chloride in 10 ml of dichloromethane at -70 ° C under nitrogen, 0.84 g of 2- (mercaptomethyl) -2- (n-propyl) propane-1, A solution of 3-dithiol in 5 mL of dichloromethane was added with stirring. After 5 minutes, 0.7 g of 4,4-dimethylpentanoyl chloride (G.M.

• «

Whitesides, J.P. Sevenair and R.W. Goetz, J. Amer. Chem. Soc. 1967, 89, 1135) are added dropwise over 10 minutes with 10 ml of methylene chloride. The reaction mixture was allowed to warm to -20 ° C over 2 hours and then to 20 ° C overnight. After addition of 100 ml of diethyl ether, the mixture is extracted with further portions of diethyl ether. The combined ether extracts were washed with water, dried over anhydrous magnesium sulfate and concentrated in vacuo. Recrystallization from acetone gave 1- (3,3-dimethyl-butyl) -4- (n-propyl) -2,6,7-tritiabicyclo [2.2.2] octane as a continuous solid.

In the following steps (xii), (xiii) and (xiv), a further improved preparation for the preparation of 2- (mercaptomethyl) -2-propane-1,3-dithiol is described.

(xii) 12 kg of 2- (hydroxymethyl) -2- (n-propyl) propane-1,3-diol is added to a solution of 51 kg of p-toluenesulfonyl chloride in 60 liters of pyridine in a 410 liter reactor. pyridine solution was added over 2 hours while maintaining the internal temperature at 40-45 ° C. After the addition was complete, the mixture was cooled to 20 ° C and stirred overnight at 20 ° C. It is then cooled to 5-10 ° C and a mixture of 90 L of concentrated hydrochloric acid and 90 L of water is added over 30 minutes while maintaining the internal temperature below 30 ° C. After stirring for 30 minutes, the reaction mixture is centrifuged. The wet solid is then re-slurried with 120 L of water and centrifuged again. The solid was washed with additional water to neutral and dried under vacuum at 40 ° C to less than 1% moisture. 47.0 kg of colorless 2-hydroxymethyl-2- (n-propyl) propane-1,3-diol tri (p-toluenesulfonate) are obtained, m.p. 170-171 ° C. are.

(xiii) To a stirred suspension of 10.5 kg of sulfur in 150 liters of ethanol in a 410 liter reactor was added 21.6 kg of sodium sulfide trihydrate followed by 25 kg of 2- (hydroxymethyl) -2- (n-propyl) propane. -1,3-diol tri (p-toluenesulfonate) was added. The mixture is slowly heated to reflux and refluxed for 6 hours. The reaction mixture was cooled to 20-25 ° C and water (12 L) was added followed by toluene (80 L). The mixture was stirred rapidly for 15 minutes and allowed to stand overnight. The lower aqueous layer was transferred to an adjacent 410 L reactor. This aqueous layer was extracted with 2 x 80 L of toluene and the aqueous layer was discarded. The toluene extracts were combined in a 410 L reactor and washed with 3 x 50 L water. Toluene was removed by vacuum distillation [55 to 60 ^° C, 15 kPa (150 mbar), 120 l] from the organic layer. The resulting bis (4-propyl-1,2-dithiolan-4-ylmethyl) disulfide solution was used without further purification.

(xiv) A solution of 1.2 liters of bis (4-propyl-1,2-dithiolan-4-ylmethyl) disulfide prepared in the preceding step is added to zinc powder under vigorous stirring and under a stream of nitrogen. The mixture was heated to 85 ° C and

Concentrated hydrochloric acid (3.1 L) was added dropwise over 3-4 hours while the mixture was slightly boiling. After the addition was complete, the mixture was stirred at 90 ° C for 1-2 hours, then cooled and the zinc residue removed by filtration. Wash the organic layer twice with water and then toluene »·· <·· *

- Distill in a vacuum of 27. This gives 2- (mercaptomethyl) -2- (n-propyl) -propane-1,3-dithiol in quantitative yield in the form of a pale yellow oil.

In steps (xv) and (xvi), another process for the preparation of 4,4-dimethylpentanenitrile is described.

(xv) 1547 g of 3,3-dimethyl-1-butene in a catalytic amount of ca. Hydrogen bromide was bubbled under stirring at a temperature below 40 ° C with 0.5 g AIBN. The orange reaction mixture was allowed to cool and allowed to stand overnight. Water (600 mL) was added and stirred for 15 minutes. The layers were separated and the organic layer was washed with water (2 x 600 mL) and stirred with saturated aqueous potassium bicarbonate (600 mL) for 15 min. The layers were separated, and the organic layer was washed with water (600 mL) and brine (500 mL). 2580 g of 1-bromo-3,3-dimethylbutane are thus obtained in the form of an almost colorless liquid.

(xvi) To a stirred solution of 456 g of sodium cyanide in 1 liter of water is added 210 g of tetrabutylphosphonium bromide, 1.5 l of toluene and 1023 g of 1-bromo-3,3-dimethylbutane. The mixed emulsion is heated to 50 ° C and then carefully (exothermic between 50 ° C and 63 ° C) to 85-88 ° C. The reaction mixture was maintained at this temperature for 6.5 hours, then cooled and stirred overnight. The organic layer was washed with water (3 x 700 mL), 2M sodium hydroxide solution (2 x 500 mL), water (2 x 500 mL), and brine (500 mL). 1052 g of a 4,4-dimethylpentanenitrile solution in toluene are obtained. Toluene was removed by distillation at ambient pressure and the product was removed under reduced pressure [b.p. 80-82 ° C, 2 kPa (15 mm Hg)]. 4,4-Dimethylpentanenitrile was obtained in 75% yield.

Example 2

1- (3,3-Dimethyl-butyl) -4- (n-propyl) -2,6,7-trithiabicyclo [2.2.21] octane-2-oxide

0.6 g of 1- (3,3-dimethylbutyl) -4- (n-propyl) -2,6,7-tritiabicyclo [2.2.2] octane, 0.45 g of 80-90% purity. A mixture of chloroperbenzoic acid (Aldrich) and 0.8 g of anhydrous sodium acetate in 30 ml of acetonitrile was stirred at 20 ° C for 24 hours. The solvent was removed in vacuo and the residue partitioned between water and ethyl acetate. The organic layer was separated, washed with sodium bicarbonate solution and saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo and the residue was chromatographed on silica. Elution with hexane: ethyl acetate (1: 1) gave 0.23 g of 1- (3,3-dimethylbutyl) -4- (n-propyl) -2,6,7-trityl bicyclo [2.2.2]. octane-2-oxide was obtained as a colorless solid.

Example 3

5- (tert-Butyl) -2-cyano-2- (3,3-dimethylbutyl) -1,3-dithiane (i) 5 g of 5- (tert-butyl) -1,3-dithiane (EL Eliel et al., J. Amer. Chem. Soc. 1976, 98, 3583) To a stirred solution of tetrahydrofuran (50 mL) was added 17.75 mL of a 1.6 M solution of n-butyllithium in hexane at -30 ° C. The mixture is stirred for an additional hour, ·

- 29 then transferred to a syringe and added dropwise to 10 ml of pure dimethylformamide cooled to -10 ° C. The mixture was stirred for 1 hour at -10 ° C and allowed to stand overnight at 0 ° C. The reaction mixture was poured into ice-water (100 ml) and extracted with hexane. The aqueous layer was neutralized with dilute hydrochloric acid and re-extracted with diethyl ether. The ether extracts were dried over anhydrous magnesium sulfate and then concentrated in vacuo. 3.1 g of a white solid remain. The resulting 5- (tert-butyl) -2-formyl-1,3-dithiane is highly present as a dimer.

(ii) 1 g of 5- (tert-butyl) -2-formyl-1,3-dithiane was heated to melt under a nitrogen atmosphere and then allowed to cool. The viscous oil thus formed was taken up in 100 ml of dry benzene containing 0.78 g of pyridine. To the solution

1.1 g of Ο, Ν-bis (trifluoroacetyl) hydroxylamine (J. H. Pomeroyn et al., J. Amer. Chem. Soc. 1959, 81 6340) are added and the mixture is refluxed for 2 hours. After cooling, diethyl ether and water were added and the organic layer was separated. The aqueous layer was extracted with fresh diethyl ether, the combined organic extracts dried over anhydrous magnesium sulfate and concentrated in vacuo. The yellow solid residue was purified by silica gel column chromatography. Gradient elution with hexane / dichloromethane afforded 0.38 g of 5- (tert-butyl) -1-cyano-1,3-dithiane as a white solid.

(iii) To a solution of 0.5 g of 5- (tert-butyl) -2-cyano-1,3-dithiane in 15 ml of tetrahydrofuran and cooled to -50 ° C under a nitrogen atmosphere was added 2.0 ml of 1.6 molar n-butyllithium in hexane. solution. After 2 hours at -40 ° C, 1.6 g of 3,3-dimethylbutyl iodide are added. The reaction mixture was allowed to warm to room temperature overnight. Diethyl ether and water were then added. The organic layer was separated and the aqueous layer was extracted with fresh diethyl ether. The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent: ethyl acetate / hexane = 1: 6). 0.33 g of 5- (tert-butyl) -2-cyano-2- (3,3-dimethylbutyl) -1,3-dithiane is isolated as a white solid.

Biological effect

The following examples illustrate, without limitation, the pest control activity of the compounds of formula (I).

Spray tests

A 5% solution of the compounds of the invention in acetone was diluted with 94.5% water and 0.5% Synperonic to give an aqueous emulsion. This was used to treat the following insects.

Musca domestica

20 female Musca were placed in a cardboard cylinder and sealed at both ends with gauze. A solution of the compound was sprayed onto the insects thus closed and mortality was assessed after 25 hours at 25 ° C.

The following compounds were active at concentrations below 200 ppm: 1, 2, 3, 4,

Plutella xvlostella

Leaf plates were placed on 7 Plutella larvae and sprayed with a solution of the compound. Mortality was assessed after 2 days at 25 ° C.

The following compounds were active at concentrations below 1000 ppm: 1, 4.

Mvzus persicae

10 adult insects were placed on discs made of Chinese cabbage leaves. After 24 hours, the disk was sprayed with a solution of the compound. Mortality was assessed after 2 days at 25 ° C.

The following compounds were active at concentrations below 1000 ppm: 1, 3.

The following compound was active at concentrations below 200 ppm:.

Diabrotica undecimpunctata

Filter paper and feed were sprayed with a solution of the compound. The filter paper was then infected with 10 second-stage larvae. Mortality was assessed after 48 hours.

The following compounds were active at concentrations below 1000 ppm: 1, 2, 3, 4.

Local application

The compounds of the present invention were tested against male Periplaneta americana on anesthetized insects using a butanone solution of the compound. Mortality was assessed 6 days later.

Compounds showing activity of less than 50 µg / insect were: 1, 3, 4.

The compounds of the invention were tested against the female Musca domestica (WRL strain) using a butanone solution of the compounds topically in insects. Mortality was assessed 48 hours later.

The following compounds were effective at less than 1 Mg / insect: 1, 2, 3, 4.

The activity of the compounds of the invention against male Blattella germanica on anesthetized insects was investigated by topical application of a butanone solution of the test compound. Mortality was assessed 6 days later.

The following compounds were effective at less than 1 mg / cockroach: 1, 2, 3, 4.

Toxicity in mice

The following compounds were non-toxic in dimethylsulfoxide at an oral dose of 200 mg / kg: 1, 2.

Studies on slugs belonging to Deroceras and Arion species

Deroceras and Arion were placed on treated filter paper in a Petri dish. Mortality was assessed after 72 hours.

The following compound was effective in less than 2 cm ³ at 6%: 1.

Table 1

Compounds and their Characteristics

Nuclear Magnetic Resonance Chemical nance spectrum

Compound Compound Op. Ionization 1H, CDCl3, TMS, number (° C) mass proton, spectrum decomposition, J (Hz)

1- (3,3-dimethylbutyl) - 0.90 9H, s; -4- (n-propyl) -2,6,7-1 144 291 0.95 3H, t, J 6; -tritiabiciklo [2.2.2] - 1.20 - 1.55 , 6H, m; octane 2.00 2 H, m;

3.00: 6H: s.

1- (3,3-dimethylbutyl) - 0.90, 9H, s; -4- (n-propyl) -2,6,7-2 167 307 0.95, 3H, t, J 6; -tritiabiciklo [2.2.2] - 1.2-1.6: m: 7H; octane-2-oxide 1.90, 2H, m; 2.35 1H, dd, J 13.2 and 1.6; 2.40 1H, dd, J 13.1 and 2.3; 2.63, 1H, dd, J 11.3 and 1, 6; 2.95 1H, dd, J 11.7 and

1.6; 3.10 1H, dd, · ·

34 J 11.3 and 2.3; 3.30

1H, dd, J 12.9 and

2.6.

5- (tert-butyl) -2-cyano-2- (3,3-dimethyl-3)

-butyl) -1,3-dithiane

159.6

286

0 95 9H, s; 1.00 9H , s ; 1 55 2 H, m; 1 65 1H, before, J 11 and 2 ; 2, 00, 2 H , m ; 2, 92 2 H, dd , J 13 and 2 / 3 05 2 H, dd, J 13 and 11th

1- (3,3-dimethylbutyl) - 0.90, 9H, s; 0.95 -4-ethyl-2,6,7-trithia-4 133.4 277 3H, t, J7 ; i , 50, bicyclo [2.2.2] octane 4 H, m; 2, 05 2 H, m; 3.00 6H, S.

Claims (18)

Claims Compounds of formula (I) wherein n and n 'are the same or different and each is 0, 1 or 2: R is hydrogen or methyl, R ^{1 is} methyl, ethyl or cyclopropyl, R ² and R ^{3 are the} same or different and each is hydrogen or methyl; R ^is hydrogen or methyl, You're a cyano group Rb R ^a and R 1 * taken together form a group -CH 2 S (O) _m - wherein m is 0, 1 or 2. Compounds according to claim 1, wherein R is hydrogen. Compounds according to claim 1 or 2, wherein R ^a and R ^b together form the group -CH 2 S (O) _m - and R ^{1 is} ethyl. Compounds according to claim 3, wherein R ² and R ^{3 are} hydrogen. Compounds according to claim 3 or 4, wherein m, n and n 'are 0. Compounds according to claim 1 or 2, wherein R ^is hydrogen or methyl and R ^{b is} cyano. Compounds according to claim 6, wherein R j, R ² and R ³ are each methyl. A compound according to claim 1: 1- (3,3-Dimethyl-butyl) -4- (n-propyl) -2,6,7-trithiabicyclo [2.2.2] octane 1- (3,3-Dimethyl-butyl) -4- (n-propyl) -2,6,7-trithiabicyclo [2.2.2] octane-2-oxide 5- (tert-butyl) -2-cyano (3,3-dimethylbutyl) -1,3-dithiane 1- (3,3-Dimethyl-butyl) -4-ethyl-2,6,7-trithiabicyclo [2.2.2] octane. 9. A process for the preparation of a compound of formula I wherein n and n 'are the same or different and each is 0, 1 or 2, R is hydrogen or methyl, R ^{1 is} methyl, ethyl or cyclopropyl, R ² and R ^{3 are the} same or different and each is hydrogen or methyl; R ^is hydrogen or methyl, You are a cyano group R ^b R ^a and R ^b together form -CH ₂ S (O) _m -, wherein m is 0, 1 or 2, characterized in that (i) reacting an anion of a compound of formula IV with an alkylating agent; or (ii) for the preparation of compounds wherein R ^a and R ^b together form -CH ₂ S (O) _m -, a compound of formula V a) tert-BuCH ₂ CH ₂ X, Lewis acid t - in the presence of 37, wherein X is an activated carboxy group, b) with tert-BuCH 2 CH 2 CN in the presence of a suitable acid. 10. A pesticidal composition according to any one of claims 1-8. A compound of formula (I) as claimed in any one of claims 1 to 6 together with one or more carriers or diluents. 11. The pesticidal composition of claim 10, further comprising a synergistic or potentiating agent. The pesticidal composition according to any one of claims 10 or 11, further comprising one or more pesticidal active ingredients, attractive or repellent, bactericidal, fungicidal and / or antelmintic. 13. A method for controlling arthropod, helminth, or mollusc pests comprising the steps of: 1-8. An effective amount of a compound according to any one of claims 1 to 3 is applied to or in the vicinity of arthropods, helminths or molluscs. 14. A method of eradicating a pest infestation of a plant comprising the steps of claims 1-8. An effective amount of a compound of formula (I) as claimed in any one of claims 1 to 6, is applied to the plant. A method of eradicating a pest infestation of a stored product, comprising: An effective amount of a compound according to any one of claims 1 to 6 is applied to the stored products. 16. A method of eradicating a pest infestation of an animal comprising the steps of (1) to (8). An effective amount of a compound of formula (I) as claimed in any one of claims 1 to 6, administered to the animal. 17. A compound of formula (I) according to any one of claims 1 to 3 for use in eradicating infestation by an animal. The use of claim 17, wherein the animal is a human. The agent shall: