DD257429A5 - PROCESS FOR PREPARING A TRIOXABIZYKLO (2,2,2) -ECTANE - Google Patents

Abstract

The invention relates to a process for the preparation of a Trioxabicyclo & 2,2,2! -Oktans for the fight against Schaedlingen. The aim of the invention is the provision of new compounds with strong insecticidal and acaricidal activity. According to the invention, novel 3-substituted 2,6,7-trioxabicyclo & 2,2,2 octanoates of the formula (I) are prepared in which, for example: R is optionally substituted C 2-10 -alkyl, alkenyl or alkynyl; R1 is a cyano group, spirocyclopropyl, oxo or methylene group, and the like. al .; R2 is phenyl, C5-10cycloalkyl or cycloalkenyl; R3 is optionally substituted hydrogen, C1-13-alkyl, C2-3-alkenyl or alkynyl u. a. The compounds are prepared, for example, by condensation of an ortho carboxylate with an appropriately substituted 2-hydroxymethylpropane-1,3-diol. Formula (I)

Description

(I)

manufactured,

wherein RC _{2 is} -io-alkyl, alkenyl or alkynyl, each optionally substituted by or methyl, substituted by a cyano group, C 1-6 cycloalkyl, halo group, C 1-4 alkoxy group or a group S (0) m R ⁴ , wherein R ⁴ is Ci_4-alkyl and m is 0.1 or or R C3_i ₀ -Zykloalkyl, Cno-cycloalkenyl or phenyl, each optionally substituted by a C ₁ ^ -AIkOXy-, CI_ ₃ alkyl-C2-4-alkynyl , Halo, cyano or a group S (O) _m R ⁴ as defined above; R ^{1 is} a halo group,

l, C ₂ -3 alkenyl or alkynyl, each optionally substituted by a halo, cyano, C 1-4 alkoxy, alkylcarboxy group having up to 6 carbon atoms, a group S (O) m R ⁴ as defined above or alkynyl substituted by tri-C 1-4 -alkylsilyl or R ^{1 is} a cyano group, spiro-cyclopropyl, gem-dimethyl, gem-dicyano group, gem-diethynyl, oxo group or methylene optionally substituted by a cyano group, or C 1 _ ₃ -alkyl optionally substituted by fluorine, or R ¹ and R and the carbon atoms to which they are attached form a Cs_7-carbocyclic ring, optionally substituted by a halo group, Ci_ ₃ -alkyl or an alkoxy group or C ₂ _ ₃ -alkenyl ; R ² is phenyl, C ₅ -I ₀ -Zykloalkyl or cycloalkenyl is, each optionally substituted, and R ³ is hydrogen, Ci_3 alkyl, C ₂ _ ₃ alkenyl or alkynyl each optionally substituted by a cyano group, C ₁ ^ ₄ - Alkylthio, C ^ alkoxy or halo group, or R ^{3 is} a cyano or halo group.

A suitable R is propyl, butyl, pentyl, C ₂ -6 alkenyl or alkynyl, C ^ -Zykloalkyl or phenyl, each optionally substituted by one to three fluoro, chloro or Bromogruppen. The most suitable R is η-butyl, n-propyl, i-butyl, s-butyl, t-butyl, cyclopentyl or cyclohexyl, and preferably R is n-propyl, η-butyl, i-butyl, t-butyl or cyclohexyl. A suitable R ¹ is a cyano group, ethynyl or methyl or ethyl, optionally substituted by a cyano, methoxy, methylthio or fluoro group. The most suitable R ¹ is methyl, cyano, ethynyl, trifluoromethyl or ethyl. Preferably, R ^{1 is} methyl, trifluoromethyl, a cyano group or ethynyl.

When R ^{2 is} a substituted phenyl, Cs_io-cycloalkyl or cycloalkenyl group, suitable substituents include a halo, cyano, azido, tetrazolyl group, a group SO ₂ R ⁵ wherein R ^{5 is} an amino or di-C ₁ - ^ AI kylaminogruppe is, a group COR ⁶ , wherein R ^{6 is} a C ^ alkoxy, Bezyloxy-, amino or di-C ^ alkylamino group, a nitro group, Ci_ ₃ alkyl, optionally substituted by a halo group, cyano group or alkynyl, or C ₂ _ ₃ alkenyl or alkynyl, each optionally substituted by a halo group or tri-C 1-6 alkyl silyl. When R ^{2 is} phenyl, C 1-8 cycloalkyl or cycloalkenyl substituted by an acidic or basic group, salts may be formed from the compounds having the formula (I). The invention includes salts of the compounds of the formula (I). The preparation of these salts is carried out by the methods generally known in the art. Typical salts include acid addition salts, such as those formed by mineral acids, and basic salts, such as those formed by the alkaline earth metals.

A suitable R ² is cyclohexyl, cycloheptyl, cyclooctyl or phenyl at the 3, 4 and / or 5 position optionally substituted by a halo, cyano, C ₂ _ ₃ alkynyl, azido or nitro group and / or an the 2- and / or 6-position by a fluoro group. The most suitable R ² is cyclohexyl or phenyl optionally substituted at the 3, 4 and / or 5 position by a chloro, bromo, iodo, cyano or ethynyl. Preferably, R ^{2 is} phenyl, substituted at position 4 by chlorine, bromine, ethynyl or a cyano group

A suitable R ³ is hydrogen or methyl

Preferably, R ^{3 is} hydrogen

 Suitable compounds of formula (I) include those of formula (IA),

_E 3a R ^a 1.

(IA)

R ^2a

wherein R ^{a is} C ₂ ^ ₁ alkyl, alkenyl or alkynyl, C ^ o-cycloalkyl or phenyl, each optionally substituted by cyano or Ci_4-alkoxy, R ^{1 a is} a cyano group or Ci_3-alkyl, C ₂ _ ₃ -Alkeny I or alkynyl each optionally substituted by one cyanosis, Ci-4-alkoxy, C ^ alkylthio or halo group, or R ^1a is a cyano group, gem-dimethyl, or R ^1a and R ^a and the carbon atoms to which they are attached are, form a C ^ -carbocyclic ring, optionally substituted by Ci_ ₃ alkyl or an alkoxy group; R ^2a is phenyl, Cs-io-cycloalkyl or cycloalkenyl, optionally substituted, and R ^3a is hydrogen, CI_ ₃ alkyl, C ₂ _ ₃ alkenyl or alkynyl each optionally substituted by one cyanosis, Ci-4 alkylthio , Ci-4-alkoxy or halo group.

A suitable R ^a is propyl, butyl, Cs-7-cycloalkyl or phenyl. The most suitable R ^a is n-propyl, butyl, cyclopentyl or cyclohexyl, and preferably R ^{a is} propyl, butyl or cyclohexyl.

A suitable R ^{1 a} is a cyano group, methyl or ethyl, optionally substituted by a cyano, methoxy, methylthio or fluoro group. Preferably, R ^{1a is} methyl or ethyl.

Suitable substituents for R ^2a include Halog-, cyanosis, azido, nitro, CI_ ₃ alkyl optionally substituted by halo group, or C ₂ _ ₃ alkenyl or alkynyl each optionally substituted by a halo group.

Suitable R ^2a are cyclohexyl, cycloheptyl or phenyl optionally substituted at the 3- or 4-position by a halo, cyano, azido or nitro group. The most suitable R ^2a is cyclohexyl or phenyl, optionally substituted at the 4-position by chlorine, bromine or a cyano group.

Preferred compounds of the present invention include:

1- (4-bromophenyl) -4-cyclohexyl-3-methyl-2,6,7-trioxabicyclo [2,2,2] octane,

1- (4-chlorophenyl) -3-methyl-4-isopropyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -3-methyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-chlorophenyl) -3-methyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1-cyclohexyl-3-methyl-4-isopropyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-Brornophenyl) -4-t-butyl-3-methyl-2,6,7-trioxabizyklo [2,2,2] octane,

1,4-Dizyklohexyl-3-methyl-2,6,7-trioxabizyklo [2,2,2] octane,

4-t-Butyl-1- (4-chlorophenyl) -3-methyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-Ethynylphenyl) -3-methyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

3-Methyl-4-n-propyl- [4- (2-trimethylsilylethynyl) -phenyl] -2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-ethynylphenyl) -4-n- propyl 3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 4-n-propyl-3-trifluoromethyl-1- [4- (2-trimethylsilylethynyl) -phenyl] 2,6,7 trioxabicyclo [2.2.2] octane, 1- (4-chlorophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4- Bromophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, i - ^ - chlorophenylM-cyclohexyl-S-trifluoromethyl-ej-trioxabicyclo ^^ loctane, 1- (4-Bromophenyl) -4-cyclohexyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -3-ethenyl-4-n-propyl-2, 6,7-trioxabicyclo [2,2,2] octane, 1-cyclohexyl-4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl ) -3-cyano-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 3-cyano-1- (4-ethynylphenyl) -4-n-propyl-2,6, 7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl) -4-cyclohexyl-3-methoxymethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1-cyclohexyl-3 methyl-4-n-propyl-2,6,7-Triox Abicyclo [2,2,2] octane, 1- (4-bromophenyl) -4-t-butyl-3-ethyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-t-butyl 1-zykJohexyl-3-methyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-Bromophenyl) -3,5-dimethyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1-cyclohexyl-3,5-dimethyl-4-n propyl 2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-cyanophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 3-cyano-1- (4-cyanophenyl) -4-isopropyl-2,6,7-trioxabicyclo [2,2,2] octane, 4-t-butyl-3-cyano-1- (4-iodophenyl ) -2,6,7-trioxabicyclo [2,2,2] octane and 4-t-butyl-3-cyano-1- [4- (2-trimethylsilylethynyl) -phenyl] -2,6,7-trioxabicyclo [ 2,2,2] octane, 1- (4-bromophenyl) -4-n-butyl-3-methyl-2,6,7-trioxabicyclo [2,2,2] octane, 4-n-butyl-1 (4-chlorophenyl) -3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-t-butyl-3-cyano-1- (4-ethynylphenyl) -2,6,7- trioxabicyclo [2,2,2] octane, 1- (4-cyanophenyl) -3-ethynyl-4-isopropyl-2,6,7-trioxabicyclo [2,2,2] octane, i-bromo-S ^ - dichlorophenylM-n-propyl-S-trifluoromethyl-ej-trioxabicyclo [10-] loctane, 1- (4-bromo-3-chlorophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2, 2,2] octane. Particularly preferred compounds include:

1- (4-bromophenyl) -3-methyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -4-cyclohexyl-3-methyl 2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-chlorophenyl) -3-methyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -4-t-butyl-3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-chlorophenyl) -4-t-butyl-3- Methyl 2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-ethynylphenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-ethynylphenyl) -3-methyl-4- n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-cyanophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2 _/ 2] octane, 1- (4-bromophenyl) -4-n-butyl-3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-n-butyl-1- (4-chlorophenyl ) -3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-t-butyl-3-cyano-1- (4-ethynylphenyl) -2,6,7-trioxabicyclo [2, 2,2] octane, 1- (4-cyanophenyl) -3-ethynyl-4-isopropyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-bromo-3-chlorophenyl) 4 -n-propyl-3-tr ifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane or 4-n-butyl-1- (4-bromophenyl) -3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 4-n-butyl-1- (4-iodophenyl) -3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-n-butyl-3-methyl-1- (4 - (2-trimethylsilylethynyl) phenyl) -2,6,7-trioxabicyclo [2,2,2] octane, 4-n-butyl-1- (4-ethynylphenyl) -3-methyl-2,6,7-trioxabicyclo [2,2,2] octane, 4-t-butyl-3-cyano-1-cyclohexyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl) -3-cyano -4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

3-cyano-1- (4-iodophenyl) -4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane, 3-cyano-4-n-propyl-1- (4- (4-yl) 2-methylmethylsilylethynyl) phenyl) -2,6,7-trioxabicyclo [2,2,2] octane or 3-cyano-1- (4-ethynyl-phenyl) -4-n-propyl-2,6,7-trioxabicyclo [2 2,2] octane.

In another aspect, the invention provides a process for the preparation of a compound of formula (I). The process for the preparation of a compound of formula (I) may be a method known in the art for the preparation of analogous compounds, e.g. By condensation of a triol of formula (II) with an ortho-carboxylate of formula R ² (C (OR ⁷ ) ₃ .

(II)

wherein R to R ^{3 are} as defined above and R ^{7 is} Ci_4-alkyl, phenyl or C ₇ _8-aralkyl. Suitable for R ⁷ are methyl or ethyl, preferably methyl. The Raktion is usually carried out in the presence of an acid, for example a mineral acid, preferably hydrochloric acid, or a sulfonic acid derivative, for example toluenesulfonic acid, or an acid resin or in the presence of a trialkylamine, for example a triethylamine, at elevated temperature,

for example between 5O ⁰ C and 200 ⁰ C, typically between 12O ⁰ C and 170 ° C. The reaction can be advantageously carried out in the absence of a solvent, if desired, but also a suitable solvent can be added.

The triol of formula (II) may be prepared: (i) from the corresponding triol in which R ¹ and / or R ^{3 are} hydrogen via a protected aldehyde which is reacted with a reagent, for example a Grignard reagent is suitable for the extension of the carbon chain after the removal of the protection, ie, as shown in Scheme 1.

In certain cases, it may be advantageous to prepare triol derivatives in which R ¹ , R ^{3 is} hydrogen and one of the hydroxy groups is protected by reduction of an ester of the formula (III):

'R ⁹ OOC

COOR

wherein R ^{8 is} a protecting group such as benzyl and R ^{9 is} C 1-4 alkyl. This reduction is advantageously carried out by a complex hydride such as lithium aluminum hydride in a carry solvent, preferably an ether. The compound of the formula (III) can be prepared from the corresponding compound RCH (CO ₂ R ⁹ ) 2 by reaction with a compound XCH ₂ OR ⁸ in which X is a residual group such as a halogen in the presence of a strong base, for example of sodium hydride.

(ii) When a compound of formula (I) is to be prepared in which R ^{3 is} hydrogen by the reduction of a compound of formula (IV):

wherein R, R ¹ and R ^{9 are} as defined above. This reduction is advantageously carried out by a complex hydride, for example lithium aluminum hydride, in a carrying solvent such as an ether, for example diethyl ether.

When R and R ¹ are bonded together to form a carbocyclic ring, the compound of the formula (IV) is advantageously prepared by the reaction of a compound of the formula (V)

(V)

with a compound Hal-CO ₂ R ⁹ , wherein R, R ¹ and R ^{9 are} as defined above and Hal is a halogen, for example chlorine. This reaction is advantageously carried out in the presence of a Grignard reagent, for example ethylmagnesium bromide, in a solvent such as ether, for example tetrahydrofuran. Other compounds of formula (IV) are advantageously prepared by the reaction of a compound RCH (CO ₂ R ⁹ J ₂ with a compound Hal-CO.R ¹ , wherein R, R ¹ , R ⁹ and Hal are as defined above, or This reaction is advantageously carried out in the presence of a strong base, for example a metal hydride, in a non-polar solvent, for example an aromatic hydrocarbon, such as benzene or toluene

 The compounds of the formula (I) can also be prepared by cyclization of a compound of the formula (VI)

RR ¹

(Vl)

wherein R to R ^{3 are} as defined above in the presence of an acid catalyst. Boron trifluoride etherate is a particularly preferred acid catalyst for the cyclization, and are generally in an inert solvent, for example a halogenated hydrocarbon, preferably dichloromethane, at a temperature below the environmental temperature temperature, for example between -100 ⁰ C and O ⁰ C and advantageously between -7O ⁰ C and -50 ° C is performed.

The compounds of the formula (VI) can be prepared by the reaction of compounds of the formula (VII) and (VIII):

RR

, _ ^ _v K C yy

0 OH ^wf

wherein R ^{10 is} a group R ¹ and R to R ^{3 are} as defined above and L is a residual group, for example a halo group. This reaction is advantageously carried out in an inert solvent in the presence of a base at a non-extreme temperature. Halogenated hydrocarbons, for example dichloromethane, are particularly suitable solvents, pyridine is a preferred base, and the reaction is advantageously carried out at a temperature between -5O ⁰ C and 100 ⁰ C, preferably at ^{0 0} C.

The compounds of formula (VII), in turn, can be prepared from compounds of formula (II) by reaction with diethyl carbonate in the presence of a strong base, for example potassium hydroxide, in a polar solvent such as an alcohol, for example ethanol, at elevated temperature, for example between 50 ⁰ C and 100 ⁰ C. This is a preferred method for the preparation of compounds of formula (VII) wherein R ¹ = R ¹⁰ = CF ₃ .

Alternatively, the compounds of formula (VII) may be prepared by the reaction of a Grignard reagent R ¹ MgHaI or a C ₂ -4 alkynyllithium compound or a sodium cyanide with a compound of formula (IX)

(IX)

wherein R, R ¹ and R ^{3 are} as defined above and Hal is a halogen atom, for example, bromine or iodine. This reaction is advantageously carried out in an inert solvent, suitable is an ether, for example diethyl ether or dioxane, at a non-extreme temperature, for example -5O ⁰ C and 5O ⁰ C and preferably between -10 ⁰ C and 1O ⁰ C. The alkynyllithium is advantageously present as a complex, for example with ethylenediamine. The sodium cyanide is advantageously added as an aqueous solution. The compounds of formula (IX) may be prepared by the oxidation of compounds of formula (VII) wherein R ^{10 is} hydrogen, using oxalyl chloride and dimethyl sulfoxide in an inert solvent such as a halogenated hydrocarbon, for example dichloromethane, followed by a base such as triethylamine, or using pyridine chlorochromate in an inert solvent such as a halogenated hydrocarbon, for example, dichloromethane.

The compounds of formula (VII) wherein R ^{10 is} hydrogen may be prepared in analogous manner to prepare compounds of formula (VII) wherein trifluoromethyl is from compounds of formula (II). A compound of the formula (I) can be converted into another compound of the formula (I) by known methods. Thus, the compounds of formula (I) wherein R ^{2 is} an ethynylphenyl group can be prepared from the corresponding iodophenyl group via the intermediate trimethylsilylethynylphenyl.

The compounds of formula (I) can be used to control arthropods such as insects and acarine pests. Thus, in another aspect, the invention provides a method of controlling arthropods in animals which consists in administering to the animal an arthropodially effective amount of a compound of formula (I). The compounds of formula (I) may be used for these purposes by applying the compounds directly or in diluted form in known manner as dipping agents, sprays, lacquers, foams, dust, powders, aqueous suspensions, pastes, gels, shampoos, lubricants, combustible solid, evaporation emanator such as an evaporating mat, wettable powder, granules, aerosol, emulsifiable concentrate, oil suspensions, oil solutions, impregnated product or infusion composition. Dipping concentrates are not used as such, but diluted with water, and the animals are immersed in a dip with the dipping agent. Sprays can be introduced by hand or via a spray or spray arch or with Raumsprühanlagen. The animal, plant or surface being treated can be saturated by a high volume application with the spray or superficially coated with the spray through easy or extremely low volume application. Aqueous suspensions may be applied in the same manner as spraying or dipping. Dust can be used by a powder application device or in animals in hole pouches attached to trees or friction poles. Pastes, shampoos and lubricants can be applied by hand or spread over the surface of a sluggish material on which the animals rub and thus transfer the material to their skin. Spotting compositions are distributed as a low volume liquid unit on the back of the animals so that all or almost all of the liquid adheres to the animals. The compounds of formula (I) can be prepared either as ready-to-use compositions for animals, plants or surfaces, as room sprays or aerosols or as compositions which must be diluted before use, but both types of compositions contain a compound of the formula ( I) in close admixture with one or more carriers or diluents. The carriers can be liquid, solid or gaseous or consist of mixtures of these substances, and the compound of the formula (I) can be used in a concentration of 0.025 to 99% w / v. depending on whether further dilution is required. Dust, powder and granules consist of the compound of formula (I) in intimate admixture with a powdered, solid, inert carrier, for example suitable clays, kaolin, silica, talc, mica, gypsum, vegetable carriers, starch and diatomaceous earths.

Sprays of a compound of formula (I) may consist of a solution in an organic solvent (eg those listed below) or an emulsion in water (dip wash or spray wash) made in situ from an emulsifiable concentrate (also known as water miscible oil ), which can also be used for diving purposes. The concentrate preferably consists of a mixture of the active ingredient with or without an organic solvent and one or more emulsifying agents. Solvents can be present within wide limits, but preferably in an amount of 1 to 90% by weight / volume. of the composition, and they may be selected from kerosenes, ketones, alcohols, xylene, aromatic naphtha, aromatic and aliphatic esters, and other solvents known in the art. The concentration of the emulsifying agent can be varied widely, but is preferably in the range of 0.5 to 25% w / v, and the emulsifying agents are advantageously nonionic surfactants including the polyoxyalkylene esters of alkylphenols and the polyoxyethylene derivatives of hexitol anhydrides and anionic surfactants including sodium lauryl sulfate, fatty alcohol ether sulfate, Na and Ca salts of alkylaryl sulfonates and alkyl sulfosuccinates.

Wettable powders include an inert, solid carrier, one or more surfactants, and optionally stabilizers and / or antioxidants.

Wettable powders and emulsifiable concentrates normally contain between 1 and 95% by weight of the active ingredient and are diluted before use, for example with water.

Paints consist of a solution of the active ingredient in an organic solvent, together with a resin and optionally a plasticizer.

Dipping washes can be prepared not only from emulsifiable concentrates but also from wettable powders, soap-based scavengers and aqueous suspensions consisting of a compound of formula (I) in intimate admixture with a dispersant and one or more surface-active agents.

Aqueous suspensions of a compound of formula (I) may consist of a suspension in water together with suspending, stabilizing or other agents. The suspensions or solutions may be used as such or in a diluted form prepared in a known manner.

Lubricants (or ointments) can be made from vegetable oils, synthetic esters of fatty acids or wool fat, along with a slow-acting base, for example soft paraffin. A compound of formula (I) is preferably uniformly distributed in solution or suspension in the mixture. Lubricants may also be prepared from emulsifiable concentrates by dilution with an ointment base.

Pastes and shampoos are also semi-solid preparations in which a compound of formula (I) may be present as a uniform dispersion in a suitable base such as soft or liquid paraffin, or made on a fat-free basis with glycerin, mucus or a suitable soap. Since lubricants, shampoos and pastes are generally applied without further dilution, they should contain the appropriate percentage of the compound of formula (I) needed for the treatment.

Aerosol sprays can be prepared as a simple solution of the active ingredient in the aerosol propellant and co-solvent, such as halogenating alkanes, or the aforementioned solvents. Infusion compositions may be prepared as a solution or suspension of a compound of formula (I) in a liquid medium. A bird or mammalian host may also be protected from attack by ectopic acarinic parasites by carrying appropriately contoured articles made of plastic impregnated with a compound of formula (I). These articles include impregnated neck rings, pendants, bands, foils and strips that are conveniently attached to appropriate parts of the body.

The concentration of the compound of the formula (I) applied to an animal will vary depending on the compound selected, the interval between treatments, the type of composition and the probable infestation, but generally should be 0.001 to 20.0 % W / v and preferably 0.01 to 10% of the compound is present in the applied composition. The amount of composition applied to an animal will vary according to the method of application, the size of the animal, the concentration of compound in the composition used, the factor by which the composition is diluted, and the nature of the composition, but is generally within the range from 0.0001% to 0.5%, except for undiluted compositions such as infusion compositions generally applied at a concentration in the range of from 0.1 to 20.0%, and preferably from <0.1 to 10%.

The compounds of formula (I) are also useful in the protection and treatment of plant species, in which case an insecticidal or acaricidal amount of the active ingredient is applied. The rate of application will vary according to the compound chosen, the nature of the composition, the mode of application, plant species, planting density and probable infestation and the like factors, generally a useful application rate for agricultural crops is 0.001 to 3 kg / ha and preferably between 0, 01 and 1 kg / ha. Typical compositions for agricultural use contain from 0.0001% to 50% of a compound of the formula (I) and advantageously between 0.1 and 15% by weight of a compound of the formula (I).

The special crops include cotton, wheat, corn, rice, sorghum (sorghum), vines, tomatoes, potatoes, fruit trees and spruces.

Dust, lubricants, pastes, surface and room sprays and aerosol compositions are generally applied randomly as described above and may be used at concentrations of 0.001 to 20% w / v. the compound of the formula (I) can be worked in the composition used.

It has been found that the compounds of formula (I) are active against the common housefly (Musca domestica).

In addition, compounds of formula (I) are active against other arthropod pests, including Tetranychusurticai Plutella xylostella, Culex spp. and Blatella germanica. Thus, the compounds of formula (I) are useful in the control of arthropods, e.g. Insects and acarines, in any environment where these are pests, e.g. In agriculture, domestic animals, public health and the household.

Insect pests are members of the orders Coleoptera (eg Anobium, Tribolium, Sitophilus, Diabrotica, Anthonomus or Anthrnus spp.), Lepidoptera (eg Ephestia, Plutella, Chilo, Heliothis, Spodoptera or Tineola spp.), Diptera (e.g. B. Musca, Aedes,

Culex, Glossina, Stomoxys, Haematobia, Tabanus, Hydrotaea, Lucilia, Chrysomia, Callitroga, Dermatobia, Hypoderma,

Liriomyza and Melophagus spp.), Phthiraptera (Malophagosa B. Damalina spp., And Anoplura, eg Pediculus humanus capitis,

Pediculus humanus humanus, Phythirus pubis Linognathus and Haematopinus spp.), Hemiptera (eg Aphis, Bemisia, Aleurodes, Nilopavata, Nephrotetix or Cimes spp.), Orthoptera (eg Sehistocerca or Acheta spp.), Dictyoptera (e.g. B.

Blattella, Periplaneta or Baltta spp.), Hymenoptera (eg Solenopsis or Monomorium spp.), Isoptera (eg Reticulitermes spp.), Siphonaptera (eg Ctenocephalides or Pulexspp.), Thysanura (e.g. Lepisma spp.), Dermaptera (eg Forficula spp.) And Pscoptera (eg Peripsocus spp.).

The acarine pests include ticks, ζ. B. members of the genes Boophilus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermocentor and Anocentor, and mites and mange such as Sarcoptesscabiei and Tetranychus, Psoroptes, Notoedres, Psorergates, Chorioptes and Demodex spp.

Compounds of the invention may be combined with one or more other active ingredients (e.g. pyrethroids, carbamates and organophosphates) and / or with attractants and / or with fungicides and the like.

In addition, it has been found that the activity of the compounds of the invention can be enhanced by the addition of a synergistic or enhancing agent, for example a synergistic oxidase inhibitor such as piperonyl butoxide or NIA 16388; a second compound of the invention or a pyrethroid pesticidal compound. When a synergistic oxidase inhibitor agent is present in one form of the invention, the ratio of synergistic agent to compound of formula (I) is in the range of 25: 1 to 1:25, e.g. at about 10: 1.

Stabilizers to prevent chemical degradation that may occur in the compounds of the invention include, for example, antioxidants (such as tocopherols, butylhydroxyanisole and butylhydroxytoluene) and deoxidants (such as epichlorohydrin).

It is believed that the invention extends in its claim to:

(a) compounds of formula (I);

(b) Process for the preparation of compounds of formula (I);

(c) insecticidal and acaricidal compositions consisting of a compound of formula (I) in admixture with a carrier;

(d) methods for the preparation of such pesticidal compositions;

(e) methods of controlling arthropod pests, such as insects or acarin pests, which consist in the application of a compound of formula (I) to the pests or their environment;

(f) synergistic pesticidal compositions comprising a compound of formula (I), and

(g) potentiating or non-potentiating mixtures of a compound of formula (I) and another pesticidal compound

(h) novel intermediates in the preparation of compounds of formula (I).

embodiment

The following examples illustrate, in a nonlimiting manner, preferred aspects of the invention.

The physical data for each of the compounds of formula (I) are given in the tables according to the examples. All temperatures are in ⁰ C.

Example A: 1-Cyclohexyl-4-ethyl-3-methyl-2,6,7-trioxabicyclo [2.2.2] octane

(i) Sodium hydride (24g, 50% dispersion in oil) was added to a stirred solution of diethyl ethyl malonate (94g) in dry benzene (300ml) at room temperature. The mixture was kept at 60 ° C with stirring for one hour. The mixture was cooled, to which acetyl chloride (36 ml) was added and the reaction stirred at room temperature for three hours. The reaction mixture was poured into ice, and the aqueous mixture was extracted with ether. The ether extracts were washed with water, dried over magnesium sulfate and the solvent removed in vacuo.

Distillation gave diethyl 2-acetyl-2-ethylmalonate (54g), a colorless oil (bp 94 ⁰ C, 1.5 mm).

The following nuclear magnetic resonance spectrum was determined: (NMR) Ή (particles / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 4.25, 4H, q, 6; 2.36.3 H, s; 2.2, 2H, m; 1,4, 6H, t, 6; 1.0, 3H, t, 6.

(ii) Lithium aluminum hydride (8.0 g) in dry diethyl ether (200ml) was stirred at 0 ⁰ C under a stream of dry nitrogen. Diethyl 2-acetyl-2-ethylmalonate (30g) in dry ether (50ml) was added and the mixture stirred at room temperature for three hours. Then, the mixture was subjected to reflux treatment for 8 hours with stirring. To the cooled reaction mixture was carefully added a solution of sodium hydroxide (20 g) and potassium hydrogen phosphate (20 g) in water (150 ml). The pH was adjusted to 5.0 with glacial acetic acid. The solid was removed by filtration and washed with water (20 ml). The combined filtrates and washes were evaporated in vacuo. The residue was washed with acetone (3 × 100 ml). The acetone washes were evaporated in yacuo.

The residue was washed with chloroform (3 × 100 ml) and the washings were evaporated in vacuo. 2-Ethyl-2-hydroxymethylbutan-1,3-diol was obtained as a pale yellow oil (8.0g). The following nuclear magnetic resonance spectrum (NMR) was determined: Ή (particles per millimeter, from TMS to CDCl ₃ , integral, number of peaks, Jh ₂ ): 4,2,3H, broad singlet; 4,1,1 H, m; 3,8,4H, m; 1,4, 5H, m; 1,0,3H, m.

(iii) Trimethyl orthocyclohexylcarboxylate (1.1 g) was added to 2-ethyl-2-hydroxymethylbutan-1,3-diol (0.75 g). One drop of concentrated hydrogen chloride was added and the mixture held under a stream of nitrogen at 13O ⁰ C for one hour.

The volatile components were removed in vacuo (3.0 mm) at 130 ^° C.

The residue was purified by chromatography on alumina (Alumina Woelm TSC) eluting 1: 4 dichloromethane: hexane saturated with ammonia. There was obtained 1-cyclohexyl-1-ethyl-2,6,7-trioxabicyclo 2,2,2-octane as a colorless oil

Gas-liquid chromatography (glc) OV210 at 150 ° C gave a peak.

In the same way but starting from diethyl n-propyl malonate, diethyl i-propyl manolate or diethyl n-butyl malonate and acetyl chloride, propionyl chloride, butyryl chloride or methoxyacetyl chloride, as appropriate, and carrying out the final condensation with trimethyl orthocyclohexyl carboxylate, trimethyl-4 Chloroorthobenzoate or trimethyl-4-bromoorthobenzoate, the following compounds were prepared:

- 1U -

1- (4-chlorophenyl) -4-ethyl-3-methyl-2,6,7-trioxabicyclo [2.2 _; 2] octane

1- (4-bromophenyl) -4-ethyl-3-methyl-2,6,7-trioxabizyklo [2,2,2,] - octane,

1- (4-chlorophenyl) -4-n-propyl-3-methyl-2,6,7-trioxabizyklo- [2,2,2] octane,

1-cyclohexyl-n-propyl-S-methyl-ej-trioxabicyclo [2,2,2,] -octane

1-cyclohexyl-4-n-propyl-3-methyl-2,6,7-trioxybizyklo [2,2,2,] - octane,

1-cyclohexyl-4-i-propyl-3-methyl-2,6,7-trioxabizyklo [2,2,2,] - octane,

1- (4-bromophenyl) -4-n-propyl-3-methyl-2,6,7-trioxabizyklo- [2,2,2] octane,

1- (4-chlorophenyl) -4-i-propyl-3-methyl-2,6,7-trioxybizyklo [2,2,2] octane,

1- (4-bromophenyl) -3-ethyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1-cyclohexyl-3-methyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -3-ethyl-4-i-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -3-n-propyl-4-i-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1-Zyklohexy-3-n-propyl-4-i-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -3-methoxymethyl-4-i-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1-cyclohexyl-3-methoxymethyl-4-n-propyl-2, 6,7-trioxabizyklo [2,2,2] octane,

1- (4-Bromophenyl) -3-methoxymethyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1-cyclohexyl-3-methoxymethyl-4-i-propyl-2, 6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -1-cyclohexyl-3-methoxymethyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -4-n-butyl-3-methyl-2,6,7-trioxabicyclo [2,2,2] octane,

4-n-Butyl-1- (4-chlorophenyl) -3-methyl-2,6,7-trioxabizyklo [2,2,2] octane.

Example B: 1-Cyclohexyl-3,4-diethyl-2,6,7-trioxabicyclo [2.2.2] octane

(i) 2-Ethyl-2-hydroxymethylpropane-1,3-diol (34g), acetone (37ml) and p-toluenesulfonic acid (0.5g) were refluxed in benzene (140ml) and the water was washed with removed from a Dean and Stark apparatus. After ten hours of refluxing, the mixture was cooled and washed with saturated aqueous sodium hydrogen carbonate solution. The benzene solution was dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. Distillation gave 2,2-dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane (35g) as a colorless oil (b.p. 80 ° C-82 ° C, 0.9 mm).

The following nuclear magnetic resonance spectrum (NMR) was determined: Ή (particle / millimeter of TMS in CDCl, integral, number of peaks, J _Hz ): 3.90, 2H, d, 6; 3,85,4H, s; 3,10,1 H, 6, t; 1.60, 6H, s; 1,55,2H, m; 1.05, 3H, m.

(ii) 2,2-Dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane (33g) was added to a stirred suspension of pyridinechlorochromate (122.6g) and anhydrous sodium acetate (7.8g) in dry dichloromethane (200ml ) at 0 ^° C under a stream of nitrogen. The mixture was stirred at room temperature for six hours. The mixture was diluted with dry ether (500 ml) and the organic solution was decanted. The oily residue was treated with ether and the combined extracts were evaporated in vacuo. The residue was purified by chromatography on silica, eluting at a ratio of 1: 3 from ether to hexane. 2,2-Dimethyl-5-ethyl-5-formyl-1,3-dioxane (30g) was obtained as a colorless oil. The gas-liquid chromatography (glc) OV2I0 at 130 ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (part / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 9.6.1 H, s; 4,2,2H, d, 12; 3.8, 2H, d, 12; 1,4, 8H, m; 0.85.3H, t, 6.

(iii) A solution of ethylmagnesium bromide (70 mL, 1.3 M in tetrahydrofuran) was stirred at 0 ^° C under nitrogen. 2,2-Demethyl-5-ethyl-5-formyl-1,3-dioxane (10.3g) in dry tetrahydrofuran (20ml) was added and the mixture was added. Room temperature for three hours. The mixture was then refluxed with stirring for one hour. Saturated aqueous ammonium chloride solution was added to the cooled reaction mixture. The aqueous mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography on silica gel, eluting with 40% etherhexane. 2,2-Dimethyl-5-ethyl-5- (1-hydroxypropyl) -1,3-dioxane was obtained as a colorless oil (10.0 g).

The gas-liquid chromatography (glc) OV210 at 140 ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / mill. Of TMS in CDCl ₃ , integral, number of peaks, J c ₂ ): 3.70, 5 H, m; 2,20,1H, d, 6; 1,40,1OH, m; 1,00,6H, m.

(iv) 2,2-dimethyl-5-ethyl-5- (1-hydroxypropyl) -1,3-dioxane (10g) and Dowex 50χ 8-200 ion exchange resin (H ⁺ form) (1.0g) in Methanol (200 ml) containing water (40 ml) was refluxed with stirring for three hours. The mixture was filtered and the filtrate removed in vacuo. 2-Ethyl-2-hydroxymethylpentane-1,3-diol (6.0 g) was recovered as a colorless, viscous oil.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / mil of TMS in CDCl ₃ , integral, number of peaks, cw): 3.80, 5 H, m; 3.00.3 H, m; 1.8 to 0.8, 10H, m.

(v) From 2-ethyl-2-hydroxymethylpentane-1,3-diol (0.7 g), using the method described in Example A, 1-cyclohexyl-3,4-diethyl-2,6,7-trioxabicyclo [ 2,2,2] octane (0.3g) as a colorless oil. The gas-liquid chromatography (glc) OV210 at 180 ⁰ C gave a peak.

1- (4-chlorophenyl) -3,4-diethyl-2,6,7-trioxabicyclo [2.2.2] octane was recovered in an analogous manner when trimethyl orthocyclohexyl carboxylate was replaced in the final condensation with trimethyl 4-chloroorthobenzoate.

1-Cyclohexyl-4-t-butyl-3-methyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl) -4-t-butyl-3-methyl-2, 6,7-trioxabicyclo [2,2,2] octane, 4-t-butyl-1- (4-chlorophenyl) -3-methyl-2,6,7-trioxabicyclo [2,2,2] octane and 1- 4-bromophenyl) -4-t-butyl-3-ethyl-2,6,7-trioxabizyklo [2,2,2] octane

were prepared by an analogous procedure starting from 2-t-butyl-2-hydroxymethylpropane-1,3-diol. 1- (4-bromophenyl) -3-ethenyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane

was prepared in an analogous manner by using vinylmagnesium bromide instead of ethylmagnesium bromide in step (iii) and using triethylamine in place of hydrochloric acid in step (v).

Example C: 1- (4-Bromo-phenyl) -4-cyclohexyl-3-methyl-2,6,7-trioxabicyclo [2.2.2] octane

(i) Diethyl cyclohexyl malonate (18.7 g) was added to a stirred suspension of sodium hydride (4.8 g, 50% dispersion in oil) in dry tetrahydrofuran (50 mL) under nitrogen. The mixture was refluxed for one hour with stirring. The mixture was cooled and benzyl chloromethyl ether (13.9g) in dry tetrahydrofuran (50ml) was added and the mixture stirred under reflux for three hours. The mixture was cooled and poured into water. The aqueous mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. Diethyl 2-benzyloxymethyl-2-cyclohexyl malonate (30g) was recovered as a brown oil and continued to be used without further purification.

(ii) Diethyl 2-benzyloxymethyl-2-cyclohexyl malonate (2g) was added to a suspension of lithium aluminum hydride (0.63g) in dry ether (30ml) at 0 ° C under nitrogen. The mixture was stirred at room temperature for twelve hours. Water (5 ml) was added carefully, and the mixture was stirred for ten minutes. Add 10% sulfuric acid solution (10 ml) and extract the mixture with 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 1: 1 ether: hexane. There was recovered 2-benzyloxymethyl-2-cyclohexylpropene-1,3-diol as a colorless oil (1.0 g).

Gas-liquid chromatography (glc) OV210 at 23O ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 7.35, 5H, s; 4,55, 2H, s; 3.75, 4H, d, 6; 3,60, 2H, s; 2,90, 2H, t; 2,00-0,90,11 H, m.

(iii) 2-Benzyloxymethyl-2-cyclohexylpropane-1,3-diol (3g), 2,2-dimethoxypropane (8ml), p-toluenesulfonic acid (150mg) and molecular sieves (Type 4A) were prepared in refluxing dry toluene (50ml ) heated for four hours. The mixture was cooled and filtered. The filtrate was diluted with ether, and the ethereal solution was extracted with aqueous sodium hydrogen carbonate solution. The ethereal solution was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica, eluting with 1: 5 ether: hexane. 5-Benzyloxymethyl-5-cyclohexyl-2,2-dimethyl-1,3-dioxane (3.0 g) was obtained as a colorless

The gas-liquid chromatography (glc) OV210 at 230 ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, number of peaks): 7.30, 5H, s; 4.50, 2H, s; 3,70,4H, s; 3,60, 2H, s; 2,00-0,9,17 H, m.

(iv) 5-benzyloxymethyl-5-cyclohexyl-2,2-dimethyl-1,3-dioxane (3.0g) in dry ether (10ml) was added at -70 ⁰ C liquid ammonia (100 ml). To the stirred solution was added Natrim (0.5g). Was allowed to warm to 3O ⁰ C, the mixture, and it was added solid ammonium chloride (2.0g) was added. The ammonia was removed from the reaction mixture under a stream of nitrogen. Water was added and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo.

5-Cyclohexyl-2,2-dimethyl-5-hydroxymethyl-1,3-dioxane was obtained as a creamy solid (2.15 g) which was used without further purification.

The gas-liquid chromatography (glc) OV210 at 200 ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / millimeter of TMS in CDCl ₃ , integral, number of peaks): 3.80, 2 H, s; 3,65,4H, s; 2,30,1 H, s, wide; 2,00-0,8,17 H, m.

(v) 5-Cyclohexyl-2,2-dimethyl-5-hydroxymethyl-1,3-dioxane (2.2 g) was added to a stirred suspension of pyridine chlorochromate (6.1 g) and anhydrous sodium acetate (3.0 g) in dry Dichloromethane (50 ml) was added at ^{0 0} G under a stream of nitrogen. The mixture was stirred at room temperature for six hours. The mixture was diluted with dry ether (100 ml) and the organic solution was decanted. The oily residue was treated with ether and the combined extracts were evaporated in vacuo. 5-Cyclohexyl-2,2-dimethyl-5-formyl-1,3-dioxane was recovered as a pale yellow oil (1.8 g) and used without further purification.

The following nuclear magnetic resonance (NMR) spectrum was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 9.80.1 H, s; 4.25, 2H, d, 12; 3.90, 2H, d, 12; 2,00-0,8,17 H, m.

Infrared spectrum (IR), (liquid film): v173Om " ¹ .

(vi) Methylmagnesium iodide (3.0 mL, 3M solution in ether) was added to a solution of 5-cyclohexyl-2,2-dimethyl-5-formyl-1,3-dioxane (1.8 g) in dry ether (50 mL) , The mixture was refluxed for two hours with stirring, cooled and poured into a mixture of 2N hydrochloric acid solution in ice. The aqueous mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. 5-Cyclohexyl-2,2-dimethyl-5- (1-hydroxy-ethyl) -1,3-dioxane was obtained as a creamy solid (1.5 g).

The gas-liquid chromatography (glc) OV210 at 170 ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 4.15.1 H, q, 6; 3,90-3,50,4H, m; 3,10 1 H, s wide; 2,00-0,9,2OH, m.

(vii) 5-Cyclohexyl-2,2-dimethyl-5- (1-hydroxyethyl) -1,3-dioxane (1.5 g) and Dowex 50 χ 8-200 (H ⁺ -form) ion exchange resin (1.0 g) in methanol (30 ml) and water (10 ml) were refluxed for six hours with stirring. The mixture was filtered and the filtrate was evaporated in vacuo. 2-Cyclohexyl-2-hydroxymethylbutan-1,3-diol was recovered as a pale yellow oil (1.2 g) and used without further purification.

Gas-liquid chromatography (glc) OV210 at 160 ° C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 4.30.1 H, m; 4,00, 2H, s; 3.95, 2H, s; 3,20, 3H, s wide; 2,00-0,90,14H, m.

(Vii) From 2-cyclohexyl-2-hydroxymethylbutan-1,3-diol (0.27 g) and trimethyl 4-bromobenzoorthobenzoate, 1- (4-bromophenyl) -4-cyclohexyl was used, using the method described in Example A. 3-Methyl-2,6,7-trioxabicyclo [2,2,2] octane, a colorless solid recovered (0.14g).

The gas-liquid chromatography (glc) OV210 at 240 ⁰ C gave a peak.

1,4-Dicyclohexyl-3-methyl-2,6,7-trioxabicyclo [2,2,2] octane was prepared in an analogous manner using trimethyl orthocyclohexyl carboxylate instead of trimethyl 4-bromobenzo-tobenzoate in the final condensation reaction.

-12- 257 492

Example D:

2- (4-bromophenyl) -4,4 a, 5,6,7,8,8 a, heptahydro-2,4 a-epoxymethanobenzo-1,3-dioxin

(i) A tetrahydrofuran solution (30ml) of ethylmagnesium bromide was prepared from bromomethane (7.05g) and magnesium (1.5g). The solution was cooled to OX and 2-carbethoxycyclohexanone (10.0g) was added carefully. The

The reaction mixture was stirred at room temperature for 30 minutes, and under nitrogen was added dropwise ethylchloroate

(7.0 g) added. It formed a white precipitate. Sulfuric acid solution (80 ml, 1%) was added and the aqueous

Extracted mixture with ether. The ether extracts were washed with dilute aqueous sodium hydrogen carbonate solution / water and then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The

Distillation gave 2,2-Dikarbethoxyzyklohexanon (7.8g) a colorless oil (b.p. 98-102 ⁰ C, 0.9 mm).

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / mill, from TMS to CDCl ₃ , integral number of peaks, cw): 4,3,4H, q, 6; 2.5, 4H, m; 1,8,4H, m; 1,4,6H, t, 6.

(ii) A solution of 2,2-dicarbethoxycyclohexanone (3.0g) in dry ether (15ml) was added dropwise to a stirred suspension of lithium aluminum hydride (1.4g) in dry ether (50ml) at ⁰ ° C under nitrogen. The mixture was refluxed for six hours with stirring. To the stirred mixture was added potassium hydroxide (6g) in water (TOOmI). Dipotassium hydrogen phosphate (4.2 g) and potassium dihydrogen phosphate (3.3 g) in water (50 ml) were added; the ether was removed by passing a nitrogen stream through the mixture. The resulting slurry was acidified with glacial acetic acid and the solid was filtered off. The filtrate was evaporated in vacuo. The residue was extracted with acetone and the solution evaporated in vacuo. 2,2-di- (hydroxymethyl) -cyclohexanol was obtained

(1.2 g) as a pale yellow oil. '

Gas-liquid chromatography (glc) OV210 at 150 ° C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / milliliter of TMS in CDCl 3, integral, number of peaks, J _Hz ): 4,6,3H, s; 4.00-3.70, 5H, m; 1,800-0,9,8H, m.

(iii) 2,2-Di- (hydroxymethyl) -cyclohexanol (0.76g) was added to trimethyl 4-bromoorthobenzoate (T, 1g). It was added one drop of concentrated hydrochloric acid and the mixture heated at 14O ⁰ C for three hours. The volatile components were removed at 15O ⁰ C in vacuo (3.0 mm). The residue was purified by chromatography on alumina (Alumina-Woehm, TSC) eluting with 1: 1 dichloromethane: hexane saturated with ammonia.

There was recovered 2- (4-bromophenyl) -4,4a, 5,6,7,8,8a-heptahydro-2,4a-epoxymethanobenzo-1,3-dioxin as a colorless oil (0.27g).

In an analogous manner, 2-cyclohexyl-4,4a, 5,6,7,8,8a-heptahydro-2,4a-epoxymethanobenzo-1,3-dioxane was prepared.

Example E: 1- (4-Chlorophenyl) -3,5-dimethyl-4-ethyl-2,6,7-trioxabicyclo [2.2.2] octane

(i) 2,2-Dimethyl-5-ethyl-hydroxymethyl-1,3-dioxane (10g) was added to a stirred suspension of sodium hydride (2.4g, 50% dispersion in oil) in dry tetrahydrofuran (80ml). The mixture was subjected to a reflux treatment for one hour with stirring. Benzyl chloride (9.2 ml) was added and the mixture was refluxed with stirring for three hours, then the mixture was poured into water and the aqueous mixture extracted with ether.

The ethereal extract was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo.

5-Benzyloxymethyl-2,2-dimethyl-5-ethyl-1,3-dioxane was recovered as a pale brown oil (15g) and used without further purification.

(ii) 5-Benzyloxymethyl-2,2-dimethyl-5-ethyl-1,3-dioxane (15.0 grams) and Dowex 50 χ 8-200 (H ⁺ form) ion exchange resin (2.0 grams) in methanol (250ml) containing 50ml of water was refluxed with stirring for three hours. The mixture was filtered and the filtrate was evaporated in vacuo. 2-Benzyloxymethyl-2-hydroxymethylbutan-1-ol was recovered as a yellow oil (9.7 g).

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 7.35, 5H, s; 4.55, 2H, s; 3,65,4Hm s; 1.40, 2H, m; 0.90, 3H, t, 6.

(iii) 2-Benzyloxymethyl-2-hydroxymethylbutan-1-ol (9.7g) was added to a stirred suspension of pyridinechlorochromate (9.7g) and anhydrous sodium acetate (2.0g) in dry dichloromethane (200ml) at ⁰ ° C Nitrogen flow added. The mixture was stirred at room temperature for six hours. The mixture was diluted with dry ether (200 ml) and the organic solution was decanted. The oily residue was treated with ether and the combined extracts were evaporated in vacuo. The residue was purified by chromatography on silica, eluting with 1: 2 ether: hexane.

2-Benzyloxymethyl-2-ethylpropanedial was obtained as a pale brown oil (3.3 g) which was used immediately.

Infrared spectrum (liquid film): ν 1720cm " ¹ .

(iv) Methylmagnesium iodide (16 mL, 3 M solution in ether) was added to a solution of 2-benzyloxymethyl-2-ethylpropanedial (3.2 g) in dry ether (70 mL). The mixture was refluxed for two hours with stirring and cooled. Aqueous ammonium chloride solution was added (30 ml, 10%) and the aqueous mixture extracted with ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo.

The residue was purified by chromatography on silica, eluting with ether. 3-Benzyloxymethyl-3-ethylpentane-2,4-diol was obtained as a pale yellow oil (2.1 g).

The gas-liquid chromatography (glc) OV210 at 185 ⁰ C exhibited a peak.

The following nuclear magnetic resonance spectrum (N MR) was determined: ¹ H (particles / millimeter of TMS in CDCl ₃ , integral, number of peaks: 7.40, 5H, s, 4.60, 2H, s, 4.40- 3.40, 6H, m, 1.60-0.75, 11H, m.

(v) 3-Ethyl-3-hydroxymethylpentane-2,4-diol was prepared from 3-benzyloxymethyl-3-ethylpentane-2,4-diol using the method described in step (iv) of Example C. 3-Ethyl-3-hydroxymethylpentane-2,4-diol was obtained as a pale brown

Gas-liquid chromatography (glc) OV210 at 170 ° C gave a peak.

The following nuclear magnetic resonance (NMR) spectrum was determined: ¹ H (particles / millimeter of TMS in CDCl ₃ , integral number of peaks): 4.60-3.50, 7H, m; 180-0,70,11 H, m.

(vi) 1- (4-Chloro-phenyl) -3,5-dimethyl-4-ethyl-2,6,7-trioxabicyclo [2.2.2] olctane (0.21g), a colorless oil, became from 3 Ethyl 3-hydroxymethylpentane-2,4-diol (0.7 g) was prepared using the method described in step (iii) of Example A.

The gas-liquid chromatography (glc) OV210 at 220 ⁰ C gave a peak.

In an analogous manner, the following compounds were prepared:

1-cyclohexyl-3,5-dimethyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-bromophenyl) -3,5-dimethyl-4-n-propyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-chlorophenyl) -3,5-dimethyl-4-n-propyl-2 _/ 6,7-trioxabicyclo [2.2.2] octane.

Example F: 1- (4-Chlorophenyl) -4n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2 _/ 2,2] octane Sodium hydride (8.0g, 60% dispersion in oil) was stirred Solution of diethyl n-propylmalonate (40g) in dry benzene (200ml). The mixture was kept under stirring for one hour at 6O ⁰ C. The mixture was cooled and trifluoroacetic anhydride (28 ml) was added carefully. The mixture was stirred at room temperature for two hours.

Water was added and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo.

Distillation gave 2-n-propyl-2-trifluorazetylmalonat, a colorless oil (bp 73 ⁰ C, 0.2mm) (35g).

A gas-liquid chromatography (glc) OV210 at 130 ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / milliliters of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 4.30, 4H, 1, 8; 2.00, 2H, m; 1.50 to 0.70, 11 H, m.

3,3-Di (hydroxymethyl) -1,1,1-trifluorohexan-2-ol was prepared from diethyl 2-n-propyl-2-trifluoroacetylmalonate using the procedure described for the preparation of 2-ethyl-2-hydroxymethylbutane-1 , 3-diol method described (Example A [A1]).

1- (4-chlorophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, i-cyclohexylM-n-propyl-S-trifluoromethyl-2,6, 7-trioxabicyclo [2,2,2] octane and 1- (4-bromophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane were obtained from 3 , 3-di- (hydroxymethyl) -1,1,1-trifluorohexan-2-ol prepared by an analogous method to Example A (step [ii]).

Using similar techniques, 1- (4-chlorophenyl) -4-cycloxyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1,4-dicyclohexyl-3-trifluoromethyl-2,6 , 7-trioxabicyclo [2,2,2] octane and 1- (4-bromophenyl) -4-cyclohexyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane.

When diethyl n-propyl malonate was replaced by diethyl prop-2-enyl malonate or diethyl 2-methylprop-2-enyl malonate, the following compounds were prepared:

1- (4-bromophenyl) -4-prop-2-enyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1-cyclo-4-prop-2-enyl-3-ol trifluoromethyl-2,6,7-trioxabizyklo [2,2,2] octane,

1- (4-Bromophenyl) -4- (2-methylprop-2-enyl) -3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1-cyclohexyl-4- (2-methylprop -2-enyl) -3-trifluoromethyl-2,6,7-trioxabizyklo [2,2,2] octane.

Example G: 1- (4-Ethynylphenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane

(i) A mixture of 3,3-di (hydroxymethyl) -1,1,1-trifluorohexan-2-one (2.8g), diethyl carbonate (1.6ml), potassium hydroxide (0.1g) and dry ethanol ( 4.0 ml) was subjected to a gentle reflux treatment (oil bath, 110 ° C) under a stream of nitrogen for a period of thirty minutes. Then, the ethanol was removed by distillation. The distillation would yield 3- (1-hydroxy-2,2,2-trifluoroethyl) -3n-propyloxetane (1.7g), a colorless oil (boiling point 112 ⁰ C, 20 to 25mm).

The gas-liquid chromatography (glc) OV210 at 120 ⁰ C would result in a peak.

Infrared (IR) spectrum (liquid film): 3450 (s, br), 1,300 (s), 1170 (s), 1130 (s), 1045 (s).

(ii) A solution of 4-iodobenzoylchloride (2.1 g) in dry dichloromethane (25 ml) was added to a stirred solution of 3- (1-hydroxy-2,2,2-trifluoroethyl) -3-n-propyloxetane (1 , 55g) and pyridine (1.0ml) in dry dichloromethane at ⁰ ° C.

The reaction mixture was stirred at room temperature for 24 hours. The mixture was poured into water, and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica, eluting with 1% triethylamine in hexane.

There was recovered 3- [1- (4-iodobenzoyloxy) -2,2,2-trifluoroethyl] -3-n-propyloxetane as a colorless oil (2.4 g).

Gas-liquid chromatography (glc) OV210 at 200 ° C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / milliliters of TMS in CDCl ₃ , integral, number of peaks): 7.70, 4H, m; 4,80-4,20, 5H, m; 2.20 to 0.80, 7H, m.

(iii) To a stirred solution of 3- [1- (4-Jodobenzoyloxy) -2,2,2-trifluoroethyl] -3-n-propyloxetane (2.3g) was dissolved in dry dichloromethane (50ml) at -7O ⁰ C Bortrilfluoridetherat (0.54 ml) added. The mixture was allowed to warm slowly to room temperature and then stirred for 12 hours. Triethylamine (1.0 ml) was added and the mixture was poured into water. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on alumina eluting with 1: 4 dichloromethane: hexane saturated with ammonia.

There was recovered 1- (4-iodophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane as a colorless solid (0.53 grams).

Gas-liquid chromatography (glc) OV210 at 22O ⁰ C gave a peak.

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / milliliters of TMS in CDCl ₃ , integral, number of peaks, J _Hz ): 7.70, 2H, d, 8; 7.30, 2H, d, 8; 4.80-3.80, 5H, m; 1,40,4H, m; 1,00,3H, m.

 t- (4-cyanophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane was used in an analogous manner by using 4-cyanobenzoyl chloride instead of 4-iodobenzoyl chloride instead of 4-iodobenzoyl chloride prepared in step (ii).

1- (4-Bromo-3,5-dichlorophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane and 1- (4-bromo-3-chlorophenyl ) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane were prepared in an analogous manner by using 4-bromo-3,5-dichlorobenzoyl chloride and 4-bromo-3, respectively chlorobenzoyl chloride instead of 4-iodobenzoyl chloride in step (ii).

(iv) bis-triphenylphosphinepalladium dichloride (20 mg) and copper (I) iodide (5 mg) were added to a stirred solution of 1- (4-iodophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [ 2,2,2] octane (0.5g) and trimethylsilylacetylene (0.24ml) in dry diethylamine (20ml). The mixture was stirred at room temperature for twelve hours. The mixture was evaporated in vacuo and the residue was then dissolved in diethyl ether. The ethereal solution was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on alumina eluting with 1: 4 dichloromethane: hexane saturated with ammonia. 4-n-Propyl-3-trifluoromethyl-1- [4- (2-trimethylsilylethynyl) phenyl] -2,6,7-trioxabicyclo [2,2,2] octane was obtained as a pale brown solid (0.36g).

Gas-liquid chromatography (glc) OV210 at 23O ⁰ C gave a peak.

(v) Tetrabutylammonium fluoride solution (0.84 mL, 1M solution in tetrahydrofuran) was added to a stirred solution of 4-n-propyl-3-trifluoromethyl-1- [4- (2-trimethylsilylethynyl) phenyl] -2,6,7- trioxabicyclo [2.2.2] octane (0.28g) in dry tetrahydrofuran (5ml). The mixture was stirred at room temperature for 30 minutes. The solvent was removed in vacuo and the residue was dissolved in dry diethyl ether. The ethereal solution was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was recrystallized from hexane. 1- (4-Ethynylphenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane was obtained as a pale yellow solid (70 mg).

Gas-liquid chromatography (glc) OV210 23O ⁰ C gave a peak.

Example H:

1- {4-Ethynylphenyl) -3-methyl-4-propyl-2,6,7-trioxabizyklo [2,2,2] octane

(i) A mixture of 2,2-di- (hydroxymethyl) -pentan-1-ol (24.6 grams), diethylcarboxylate (20.1 ml), potassium hydroxide (0.3 g) and dry ethanol (2 ml) was added A nitrogen stream for 30 minutes on gentle reflux (oil bath, 11O ⁰ C to 120 ⁰ C). After this time, the ethanol formed was removed by distillation at atmospheric pressure (oil bath 130 ° C-140 ° C, distillation head temperature 76 ° C). The pressure was reduced to 20 mm Hg and the oil bath temperature adjusted to 230 ⁰ C. It S-hydroxymethyl-Sn-propyloxetane was distilled as a colorless liquid (16.7 g, Coptemperatur 120 ° C-126 ⁰ C).

The gas-liquid chromatograph (glc) Ov-210 at 12O ⁰ C gave a peak. The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, multiplicity): 4.35.4H, s; 3,60,2H, m; 180 to 0.7.7 H, m.

(ii) A solution of dimethyl sulfoxide (12ml) in dry dichloromethane (4.0 mL) was added to a solution of oxalyl chloride (7,4ml) was added in dichloromethane (25 ml) with stirring at -7O ⁰ C under nitrogen. After completion of the addition the resulting mixture for another five minutes at -7O ⁰ C was stirred before a solution of S-hydroxymethyl-Sn-propyloxetane (10.0g) in dichloromethane (25 ml) was tropic dropwise over a period of 10 minutes , The resulting mixture was stirred for a further 30 minutes, then pure triethylamine (54 ml) was added over about 30 minutes. The reaction mixture was allowed to warm to room temperature over 3 hours, after which it was poured into water. The organic phase was separated and the aqueous layer was further extracted with fresh dichloromethane. The combined organic extracts were washed with dilute hydrochloric acid, saturated sodium bicarbonate and brine. The resulting organic phase was dried over anhydrous magnesium sulfate and evaporated in vacuo to give 3-formyl-3-n-propyloxetane (10.5 g) as a yellow oil.

Gas-liquid chromatography (glc) OV-210 at 12O ⁰ C gave a peak.

Infrared spectrum (IR) (liquid film): 1730 cm ^-1 .

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, multiplicity, J _Hz ): 9.0.1 H, s; 4,90, 2H, d, 6; 4, 60, 2H, d, 6; 2.30-1.0, 7H, m.

(iii) A solution of S-formyl-Sn-propyloxetane (10g) in dry ether (50ml) was dissolved in ether (100 ml) at 0 ⁰ C under nitrogen a stirred solution of methylmagnesium iodide (0.078 mole). The reaction mixture was allowed to warm to room temperature and stirred for an additional three hours. Thereafter, it was cooled to 0 ^° C. and a sufficient amount of saturated ammonium chloride solution was added slowly to dissolve the resulting precipitate. The organic phase was separated and the aqueous layer reextracted with fresh ether. The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue was purified by column chromatography on silica, gradient annealing with hexane-ether mixtures.

Elution with pure ether gave 3- (1-hydroxyethyl) -3-n-propyloxetane as an oil (2.5g).

Gas-liquid chromatography (glc) OV-210 at 120 ° C gave a peak.

Infrared spectrum (IR) (liquid film): 3420 (s, br), 1470 (s), 1120 (s), 985 (s) cm ^-1 .

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particle / millimeter of TMS in CDCl ₃ , integral, multiplicity, JH _Z ): 4.65, 2H, d, 6; 4.35, 2H, d, 6; 3,9,1 H, q 6; 1,15,3H, d, 6; 1.9-0.8.7H, m.

(iv) A solution of 4-iodobenzoyl chloride (3.5g) in dry ether (25ml) was added to a stirred solution of 3- (1-hydroxyethyl) -3-n-propyloxetane (1.7g) and pyridine (1.8ml) in Ether (50ml) added at ⁰ ° C. The resulting mixture was stirred at room temperature for 24 hours. Thereafter, the mixture was washed with water and brine. The organic extracts were dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue was purified by column chromatography on silica (pre-eluted with 1% triethylamine in hexane) eluting with hexane-ether mixtures. 3- [1- (4-iodobenzoyloxy) ethyl] -3-n-propyloxetane was obtained as a colorless oil (1.8 g).

Gas-liquid chromatography (glc) OV: 210, programmed from 12O ⁰ C to 25O ⁰ C, gave a peak.

Infrared spectrum (IR) (liquid film): 1,730 (s), 1 285 (s), 1115 (s), 1020 (s), 770 (s) cm ^-1 .

The following nuclear magnetic resonance spectrum (NMR) was determined: ¹ H (particles / mill. Of TMS in CDCl ₃ , integral, multiplicity): 7.8, H, s; 5.4.1 H, q; 4,85-4,35,4H, m; 1.9-0.8 ,, 10H, m.

(v) 3- [1- (4-iodobenzoyloxy) ethyl] -3-n-propyloxetane was dissolved in 1- (4-ethynylphenyl) -3-methyl-4-propyl-2,6,7-trioxabicyclo [2.2 , 2] octane by a method which is exactly the same in Example G, steps (iii), (iv) and (v), and the corresponding intermediates were isolated and characterized.

Gas-liquid chromatography (glc) on the final product oV-17 at 24O ⁰ C gave a peak.

Example I: 4-t-Butyl-3-cyano-1- {4-ethynylphenyl) -2,6,7-trioxabicyclo [2.2.2] octane

(i) To a stirred solution of pyridinechlorochromate (6.5g) in dry dichloromethane (50ml) under a nitrogen atmosphere was added 3-t-butyl-3-hydroxymethyloxetane (2.9g) in dichloromethane (10ml). The mixture was stirred overnight and dry diethyl ether (100 ml) was added. The mixture was filtered through a Fluorosil column. The column was washed with further ether portions (2 × 50 ml). The combined filtrates were evaporated in vacuo. 3-t-Butyl-3-formyloxetane was recovered as a colorless solid (2.3 g).

The following nuclear magnetic resonance spectrum (NMR) was determined: 'H'f particles / Mill of TMS in CDCl ₃ , integral, number of peaks): 9.90.1 H, s; 4.70 ^ 4.40 (4H, q); 1.05, 9H, s.

(ii) To a stirred solution of 3-t-butyl-3-formyloxetane (1.0g) and 4-iodobenzoyl chloride (2.6g) in dry diethyl ether (35ml) under nitrogen was added a solution of sodium cyanide (1.25g) in water (1.0ml) added. The mixture was stirred overnight. The mixture was poured into water (50 ml) and the aqueous mixture was extracted with diethyl ether. The ethereal solution was dried over anhydrous sodium sulfate and then evaporated in vacuo. The residue was chromatographed on silica pretreated with triethylamine, eluting with hexane: chloroform 1: 3. The 4-iodobenzoate of 3-t-butyl-3- (cyanohydroxymethyl) oxetane was recovered as a colorless solid (2.54 g). The following nuclear magnetic resonance (NMR) spectrum was determined: ¹ H (particles / millimeter of TMS in CDCl ₃ , integral number of peaks): 7.90-7.70, m 4 H, q; 5.80.1 H, s; 4,80-4,60,4H, m; 1,10, 9 H, s.

4-t-Butyl-3-cyano-1- [4- (2-trimethylsilylethynyl) phenyl] -2,6,7-trioxabicyclo [2.2.2] octane was obtained from the 4-iodobenzoate of 3-t-butyl -3- (cyanohydroxymethyl) oxetane using the procedure described in Example G. A mixture of 4-t-butyl-3-cyano-1- [4- (2-trimethylsilylethylnyl) -phenyl] -2,6,7-trioxabicyclo [2.2.2] octane (1.3 g) and anhydrous potassium carbonate in dry methanol (125 milliliters) was stirred under dry nitrogen for two hours. The resulting solution was evaporated in vacuo. The residue was taken up in diethyl ether and the ethereal solution washed with water. The ethereal solution was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by chromatography on alumina eluting with hexane: dichloromethane 4: 1, saturated with ammonia. 4-t-Butyl-3-cyano-1- (4-ethynylphenyl) -2,6,7-trioxabicyclo [2.2.2] octane was obtained as pale yellow needles (600 mg).

From 3-formyl-3-isopropyloxetane and 4-cyanobenzoyl chloride, 3-cyano-1- (4-cyanophenyl) -4-isopropyl-2,6,7-trioxabicyclo [2.2.2] octane was obtained using the procedure described above manufactured.

Example J:

1- (4-Zyanophenyl) -3-ethynyl-4-isopropyl-2,6,7-trioxabizyklo [2,2,2] octane

To a stirred suspension of lithium azetylidene-ethylene diamine complex (2.76g) in dry dioxane (25ml) under nitrogen was added at ⁰ ° C a solution of 3-formyl-3-isopropyloxetane (2.56g) in dry dioxane (10ml). The mixture was allowed to warm to room temperature. After three hours, nuclear magnetic resonance analysis showed that 3-formyl-3-isopropyloxetane was still present. An additional portion of the lithium azetylidene diamine diamines complex (3.0 g) was added and stirring continued overnight. The mixture was poured into ice-shifted water, and the aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water and dried over anhydrous sodium sulfate. The ethereal solution was evaporated in vacuo. 3- (1-Hydroxyprop-2-ynyl) -3-isopropyloxetane was recovered as an orange oil (0.8g).

The following nuclear magnetic resonance (NMR) spectrum was determined: ¹ H (particles / mill. Of TMS in CDCl ₃ , integral, number of peaks): 4.45.1 H, s; 4.70-4.40, 4H, m; 2.50.1 H, s; 2.5.1 H, s; 2,10,1 H, m; 1.10-1.00, 6H, m.

3- (1-Hydroxyprop-2-ynyl) -3-isopropyloxetane and 4-cyanobenzoyl chloride were synthesized using the procedure described in Example G 1- (4-cyanophenyl) -3-ethynyl-4-isopropyl-2,6,7- trioxabicyclo [2,2,2] octane.

The data on the mass spectra, infrared spectra and nuclear magnetic resonance spectra for the compounds given in the examples are given in Table I.

Table 1

No. R. R R enamel Mass spectrum infrared spectrum 1 100 (s), 1080 (m), 1020 (m) Method off point ( ⁰ C) Chem. Ionization 1 105 (s), 1080 (w), 1020 (s), example M + 1 1 005 (w) 1 4-CI-phenyl et me 48-50 269 1080 (s), 1010 (), 975 (m) A 2 4-Br-phenyl et me 53-54 313315 1110 (s), 1 100 (s), 1025 (s), A 1010 (s) 3 c. Hex. et me oil 241 1080 (s), 1020 (s), 970 (m) A 4 4-CI-phenyl et et 73-74 283 1110 (s), 1025 (s), 1000 (s) B 1100 (s), 1080 (w), 1020 (s), 5 c. Hex. 'Et et oil 255 1 000 (m) B 6 4-CI-phenyl n-pr me 39-41 283 1087 (s), 1017 (s), 975 (m) A 7 4-Br-phenyl n-pr me 40 327 329 1100 (s), 1075 (w), 1020 (s) A 1 090 (w), 1 055 (m), 1 020 (s), 8th c. Hex. n-pr me oil 255 975 (w) A 9 4-CI-phenyl i-pr me oil 283 A 10 c. Hex. i-pr me oil 255 1080 (m), 1060 (m), 1015 (s), A 970 (s) 11 4-Br-phenyl -CH ₂ CH 2CH2CH2 " solid fuel 325,327 D 12 c. Hex. -CH ₂ CH 2Ch ^ CHj ^- 43-46 253 D 13 4-Br-phenyl c. Hex. 'Me solid fuel 367 369 C

No. R ² R R ¹ enamel mass spectrum infrared spectrum Method off: j ; F point ( ⁰ C) Chem. Ionization example F! a j 14 4-Br-phenyl t-Bu me 104-113 341 343 1085 (m), 1060 (w), 1010 (s) B: G; G F 1.5 4-Br-phenyl t-Bu et 122-128 355357 1090 (m), 1060 (w), 1 020 (s) B; F j 16 c hex. c. Hex. me 55-56 295 1 090 (m), 1 020 (s) C G Q: 18 4-CI-phenyl t-Bu me 96-98 297 1140 (s), 1 100 (s), 1025 (s) B; i F 19 4-Br-phenyl nPr CHCH ₂ solid fuel 339341 1620 (w), 1 1105 (s), 1020 (s) B i A! 20 c. Hex. nPr CF ₃ 48-49 309 1 170 (s), 1 140 {s), 1090 (m), F j G ^! B 1 030 (s) A 21 4-Br-phenyl nPr CF ₃ 54-56 381 383 1170 (s), 1 135 (m), 1 120 (m) F! H j A 1050 (m), 1025 (m) Hi 22 4-CI-phenyl nPr CF ₃ 71-73 337 1170 (s), 1140 (m), 1 120 (m), F \ , I A 1 045 (s), 1 020 {s) H : A 23 4-Br-phenyl c. Hex. CF ₃ solid fuel 421 423 1 180 (s), 1 145 (s), 1 115 (s), F A A 1045 (m), 1025 (s) A 24 4-CI-phenyl c. Hex. CF ₃ Solid ....... 377. " 1070 (s), 1 100 (s), 1120 (s) A 25 4-Ethynylphenyl nPr CF ₃ solid fuel 3 310 (w), 1 172 (s), 1 130 (m), A 1 115 (m) 26 4- [2- (trimethyl- nPr CF ₃ solid fuel silyl) ethynyl] phenyl 27 4-Br-phenyl c. Hex. MeOCH ₂ solid fuel 397 399 1 100 (s), 120 (s) 28 4-l-phenyl nPr CF ₃ solid fuel 1180 (s), 1 145 (s), 1 120 (s), 1 025 (s) 29 4-Ethynylphenyl nPr me solid fuel 273 30 4- [2- (trimethyl- nPr me solid fuel 345 sylyl) ethynyl] phenyl 31 4-l-phenyl nPr me 58-63 375 1110 (s), 1020 (s), 830 (s) F 35 4-Br-phenyl iPr nPr waxy 355357 1 105 (s), 1085 (m), 1020 (s) HI solid fuel H j 36 c. Hex. iPr nPr oil 283 1050 (m), 1020 (s), 980 (m) 37 4-CN-phenyl nPr CF ₃ solid fuel 328 2 250 (m), 1170 (s), 1140 (s), H ! 1110 (s), 1050 (s), 1015 (s) I 38 4-Br-phenyl 2-methyl- CF ₃ solid fuel 393395 1 185 (s), 1065 (m) 1 110 (s), prop-2-enyl 1 020 (s) 39 c. Hex. 2-methyl- CF ₃ oil 321 1160 (w), 1165 (s), 1120 (m), prop-2-enyl 1085 (m), 1030 (m) 40 c. Hex. c. Hex. CV ₃ solid fuel 349 1 180 (s), 1 100 (s), 1030 (s) 41 c. Hex. Prop-2-enyl CF ₃ oil 307 1650 (w), 1 180 (s), 1 140 (m), 1090 (m), 1030 (m) 42 4-Br-phenyl Prop-2-enyl CF ₃ solid fuel 379381 1650 (w), 1 180 (s), 1 140 (m), 1 110 (s), 1020 (s) 43 c. Hex. t-Bu me 69-71 1055 (s), 1025 (s) 44 4-Br-Phe n-pr et solid fuel 341 343 1105 (s), 1032 (s), 1020 (s) 45 c. Hex. n-pr et oil 269 1090 (m), 1062 (m), 1020 (s) 46 4-Br-phenyl i-pr. et Oily solid 341 343 1110 (m), 1020 (s) 47 4-Br-phenyl n-pr MeOCH ₂ solid fuel 357 359 1110 (m), 1020 (s) 48 c. Hex. n-pr MeOCH ₂ oil 285 1105 (m), 1080 (m), 1020 (s) 49 4-Br-phenyl i-pr MeOCH ₂ solid fuel 357 359 1140 (m), 1100 (s), 1000 (s) 50 c-hex. i-pr MeOCH ₂ oil 285 1100 (m), 1055 (m), 1025 (s) 51 4-Br-phenyl n-Bu me 341 343 1100 (s), 1010 (s), 990 (m) 52 4-CI-phenyl n-Bu me 297 1095 (s), 1015 (s), 999 (m) 53 4-CN-phenyl i-pr CN 141-143 285 54 4-CN-phenyl i-pr C = CH 84-85 284 55 4-l-phenyl t-Bu CN 155-157 400 56 4- [2-trimethylsilyl) - ethynyl] phenyl t-Bu CN. 57 4-Ethynylphenyl t-Bu CN 123-125 298 58 4-Br-3,5-di- Cl-phenyl n-pr CF ₃ solid fuel 449451 59 4-Br-3-CI-phenyl n-pr CF ₃ solid fuel 415417 60 4-Br-phenyl n-Bu CF ₃ 50-52 395397 1055 (s), 1125 (m), 1100 (m) 61 4-l-phenyl n-Bu me solid fuel 389 1005 (s) 62 4- (2-trimethyl n-Bu me solid fuel 359 silylethynyllphenyl 4-Ethynylphenyl 63, n-Bu me Solid ' 287 64 cyclohexyl t-Bu CN \ oil

No. R ² RR ¹ Melt mass spectrum Infrared spectrum Method off

point ( ⁰ C) Chem. Ionization Example

M + 1

64 cyclohexyl t-Bu CN oil H

65 4-Br-phenyl n-pr CN 116-118. I

66 4-l-phenyl n-pr CN solid I

67 4- (2-trimethyl-n-pr CN solid ·. Silyl) ethyl) phenyl

68 4-Ethynylphenyl n-pr CN solid I

c. Hex. = Cyclohexyl

t-Bu = Tertiary butyl

n-Pr = normal propyl

i-Pr = isopropyl

Nr. Nuclear Magnetic Resonance Spectrum ⁽¹ H, run in CDCI ₃ and expressed as counts / Mill. From TMS, number of protons, number of protons, number of peaks and J _H2 [shown insofar])

1, 7,55,2 H, d, 8; 7, 30, 2 H, d, 8; 4.50-3.80.5 H, m; From 1.70 to 1.90.5 H, m; 0.95.3 H, t,

2, 7.45, 4H, s, 4.40-4, 5, 5H, m, 1.7-1, 2, 5H, m, 0.9, 3H, t, 6.

3 4,00,5 H, m; 2,00-0,6,19 H, m.

4 7,50,2 H, d, 8; 7, 30, 2 H, d, 8; 4.1-3.8.5 H, m; 2.0 to 0.8.10 H, m.

5. 3.90.5 H, m; 2.0-0.9.21 H, m.

6,7,40,2 H, d; 8th; 7,65,2 H, d, 8; 4.4-3.9.5 H, m; 1.7-0.9.10 H, m.

7,7,4,4 H, s; 4.50-4.00.5 H, m; 1,40,3 H, d, 6; 1.30.4 H, m; 1,00,3 H, m.

8, 4.25-3.6.5 H, m; 2,00-0,8,21, m.

9 7, 50, 2 H, d, 7; 4.5-4.00.5 H, m; 1.80 to 1.20.4, m; 0.95.6 H, d, 6.

10 4,25,1 H, q, 6; 4.0,4 H, s; 2,00-0,8,21 H, m.

11 7.40,4H, s; 4,55,1H, dd, 8,3; 4,00,4H, m; 2,20-0,90,8H, m.

12 4,35,1 H, dd, 7,3; 3,80,4 H, m; 2,2-0,8,19 H, m.

13 7.40,4H, s; 4,55,1H, q, 6; 4,15,4H, s; 2,00-0,80,14H, m.

14 7,40,4 H, s; 4,60-4,00,5 H, m; 1.55.3 H, d, 6; 1.00,9 H, s. ·

15 7.40.4H, s; 4.40-4.00.5H, m; 2.00.2H, m; 1.20.3H, t, 6; 1.00.9H, s.

16 4,30,1 H, q, 6; 4,00,4 H, s; 2,20-0,80,25 H, m.

18 7,40,2 H, d, 8; 7,20,2 H, d, 8; 4.80-3.80.5 H, m; 1.60.3 H, d, 7; 1.00,9 H, s.

19 7,50,4H, s; 6.20-5.20.1 H, m; 4,60,2 H, m; 4.30-3.90.5 H, m; 1.40-0.70.7 H, m.

20 4.60-3.60.5 H, m; 2,20-0,80,18 H, m.

21 7,50,4 H, m; From 4.80 to 3.80. 5H, m; 1.70-0.80.7 H, m.

22, 7, 24, 2 H, d, 8; 7,35,2 H, d, 8; 4.60-3.80.5 H, m; 1.60 to 0.80.7 H, m.

23 7.50,4H, s; 4,70,1H, m; 4,20,4H, m; 2,00-0,90,11H, m.

24 7.50,2H, d, 8; 7,30,2H, d, 8; 4,80,1H, m; 4,30,4H, m; 2,00-0,90,11H, m.

25 7.40.4H, m; 4.70-3.80.5H, m; 3.05.1H, s; 1,50-0,80,7 H, m.

26 7.50,4H, m; 4,80-3,90,5H, m; 1,60-0,80,7H, m; 0,40,9H, s.

27 7.50-4 H, s; 4,80-3,50,10 H, m; 2,20-1,00,11 H, m.

28 7,40,2 H, d, 8; 7, 30, 2 H, d, 8; 4.70-3.80.5 H, m; 1.40.4 H, m; 1,00,3 H, m.

29 7.40,4H, m; 4,5-3,8,5H, m; 3,0,1 H, s; 1,3,3H, d, 6; 1.3-0.7.7 H, m.

30 7.45,4H, m; 4,4-3,9,5H, m; 1,4,3H, d, 6; 1,4-0,8,7H, m, 0,3,9H, s ,

31 7,70,2 H, d, 8; 7, 30, 2 H, d, 8; 4.5-3.9.5 H, m; 1,45,3 H, d, 6; 1.7-0.8.7 H, m.

35 7,40,4 H, s; 4,40-4,00,5 H, m; 2,00-0,75,14 H, m.

36 4.30-3.70.5 H, m; 2,20-0,70,25 H, m.

37 7.65,4 H, s; 4.80-3.80.5 H, m; 1.75-0.80.7 H, m. <

38: 7.50,4H, s; 5,05,1 H, s; 4,80,1 H, s; 4,60-4, 00, 5H, m; 2.30.1 H, d, 14; 2,20,1 H, d, 14; 1,75,3H, s.

39 4.95.1 H, s; 4,72,1 H, s; 4.40-3.70.5 H, m; 2,17,1 H, d, 14; 2.07.1 H, d, 14; 1,90-0,90,14H, m.

40 4,60-3,80,5 H, m; 2,00-0,80,22 H, m.

41 5.65.1 H, m; 5.15.2 H, m; 4.60-3.75.5 H, m; 2.35-0.90, 13H, m.

42 7.50,4H, s; 5,65,1H, m; 5,20,2H, m; 4,60-4,00,5H, m; 2,40-2,10,2H, m.

43 4.40-3.80.5 H, m; 2,0-0,95,23 H, m.

44. 7,40,4H, s; 4,20-3,80,5H, m; 1,70,2H, m; 1,40-0,90, 10H, m.

45 4.00-3.75.5 H, m; 2,00-0,80,23 H, m.

46 7, 40-4, s; 4,20,5 H, m; 1.80.3 H, m; 1.30.3 H, m; 1.00.6 H, d, 6.

47 7,40,4 H, s; 4,40-4,00,5 H, m; 3,80,2 H, d; 3,40,3 H, s; 1.40.4 H, m; 1,00,3 H, m.

48 4,40-4,00,5 H, m; 3,80,2 H, d; 3.55.3 H, s; 2,20-1,00,18 H, m.

49 7,40,4 H, s; 4,50,1 H, m; 4,20,4 H, s; 3.80.2 H, d (broad), 3.40.3 H, s; 2,00,1 H, m; 1.00.6 H, dd.

50 4,30,1 H, m; 4,00,4H, rri; 3,65,2 H, m; 3,40,3 H, s; 2.00 to 0.80.18 H, m.

51 7,50,4 H, s; 4.50-3.90.5 H, m; 1,50-0,90,12 H, m.

52 7,60,2 H, d, 7; 7, 40, 2 H, d, 7; 4.50-3.90.5 H, m; 1.50 to 0.90, 12, m.

53.7,65,4H, q; 5,05,1H, d; 4,40-4,10,4H, m; 1.95.1 H, m; 1.00.6 H, m.

54 7,75,4 H, q; 5.00.1 H, m; 4.40 - ^, 00.4 H, m; 2.55.1 H, 2 s; 1,90,1 H, m; 0.95.6 H, m.

55. 7,70-7,30,4H, q; 4,95,1H, d; 4,50-4,00,4H, m; 1,05,9H, s.

56 7.60-7.40.4 H, q; 4.95.1 H, d; 4.50-4.00.4 H, m; 1.00.9 H, s; 0,20,9 H, s.

57 7.60-7.40.4 H, q; 4.95.1 H, d; 4.50-4.00.4 H, m; 3.05.1 H, s; 1.05.9 H, s.

32 4-Br-phenyl nPr me me Oil 33 4-CI-phenyl nPr me me oil 34 c. Hex. nPr me me oil

Nuclear Magnetic Resonance Spectrum f'H, carried out in CDCl ₃ and expressed as particles / mill. from TMS, number of protons, number of protons, number of peaks and Jhz [as far as indicated])

58 · 7,60,2 H, s; 4.50.1 H, m; 4.35.1 H, m; 4,10,3H, m; 1.60 to 0.85.7 H, m.

59.7.70.1 H, d, 1.5; 7, 60, 1 H, d, 7; 7, 35, 1 H, dd, 7, a, 5; 4,50,1 H, m; 4,35,1 H, m; 4.05.3 H, m; 1.60-0.80.7 H, m. "

60 7,50,4H, s; 4,50,1 H, mgm, rmtngh, m; 4,05,3H, mgm, qmtpapmipnoh, mm.

61 umupnwh, d, 7; 7,40,2H, d, 7; 4,60-4,00,5H, m; 1,80 to 0,80,12H, m.

62 7,55,2 H, d, 7; 7, 45, 2 H, d, 7; 4.40-3.90.5 H, m; 1,40,3 H, d, 6; 1.30.6 H, m; 0.90.3 H, 6, t; 0.25.9 H, s.

63,75,2 H, d, 7; 7, 50, 2 H, d, 7; 4,35,1 H, m; 4.25-3.95.4 H, m; 3.05.1 H, s; 1.50-1.10.9 H, m; 0,95,3 H, t, 7.

64 4,75,1 H, d; 4.30-3.75.4 H, m; 1.85-1.50 / 6H, mgm, qmwpaqmppnth, m; 0.95,9H, s.

65 7.45 m 4H, m; 4,90,1 H, d; 4.40-4.05.4 H, mgm, qmrtaqmwpnrh, m; 0.95 m 3 H, t.

66 7,70,2 H, d; 7,30,2 H, d; 4,90,1 H, d; 4.55-4.05.4 H, mgm, qmrtaqmqtnrh, m; 0.95.3 H, t.

67 7,50,2 H, d; 7,45,2 H, d; 4,90,1 H, d; 4,40-4,05,4 H, m; 1.50-1.10.4 H, m; 0.95.3 H, t; 0,20,9 H, s.

68 7,50,2 H, d; 7,45,2 H, d; 4.95.1 H, d; 4.35-4.05.4 H, m; 3.05.1 H, s; 1.45-1.10.4 H, m; 0.95.3 H, t.

No. R ² R. R ¹ R ³ melt mass spec. Infrared "method

point Chem.lon. spectrum

M +1, example

17 4-CI-Phenyl Et Me Me Oil 283 1105 (s), E

1080 (w), 1025 (s), 1000 (s)

341343 E

297 1100 (s), 1027 (s) E

269 1100 (s), 1020 (s) E

No. Magnetic nuclear magnetic resonance spectrum

17 7,45,2 H, d, 8; 7,20,2 H, d, 8; 4,40,2 H, q, 6; 4,00,2 H, m; 1.30.8 H, m; 0.90.3 H, m.

32 7,50,4 H, s; 4.50-3.50.4 H, m; 1,70-0,80,13 H, m.

33 7.45,2H, d, 8; 7,35,2H, d, 8; 4,50-3,90,4H, m; 1,50 to 1,1,10,10H, m; 0,90,3H, m ,

34 4.30-3.70.4H, m; 2.00-1.00.21H, m; 0.90.3H, m.

Biological activity

The numbers given for the compounds refer to the number of the compound in the table above.

A. Deadly activity against the housefly

The activity of the compounds of the invention against the unaesthetized female muscadomestica (WRL strain) was demonstrated by the topical application of a solution of the test compound in butanone to the experimental insect.

The effect of the compound was also assessed at local application in conjunction with a synergic (6vg per piperonyl butoxide (PB)). The mortality rate was estimated after 24 and 48 hours.

The following compounds were active at less than 30pg / fly: 1,11,12,15,16,19,20,22,37,38,40,41,42,44,45,46,47,48,

49,50,17,32,33,34.

The following compounds were active at less than 1 pg / fly: 6,7,8,9,10,13,14,18,21,23,24,25,26,27,29,30.

B. Lethal activity against Blattella germania

The activity of compounds of the invention against uneaten male Blatella germanica (WRL strain) was demonstrated by the topical application of a solution of the compound to be tested in butanone to the experimental insect.

The activity of the compound was also assessed in the case of the local application of the compound in conjunction with a synergic (10 μg per piperonyl butoxide [PB] per insect), the mortality was assessed after 24 and 48 hours.

The following compounds were active at less than 50 pg / insect: 1,5,1-1,12,13,15,18,19,20,21,23,25,26,27,36,37,38,39, 40

41,42,44,48,32,33,34.

The following compounds were active at less than 5 μg / insect: 6.7, 8.9, 29.30.

C. Lethal activity against Sitophilus granarius

The activity of the compounds of the invention against S. granaruis (adult animals) was demonstrated by the addition of the compound in acetone solution to corn, which was later infected with the insects. The mortality rate was 6 days

estimated.

The following compounds were less than 200 particles / mill. Acetone solution active: 16,18,19, 20, 22,23,26,27,37,41,42,43,

44,32,33, 34.

The following compounds were less than 50 particles / mill. Acetone solution active: 6,14,15,21, 25,29.

D. Lethal activity against Culex quinquefasciatus

The activity of the compounds of the invention against adult female Culex was demonstrated by directly spraying 0.5 ml of the compound in OPD / methylene chloride. The lethality was estimated after 24 hours.

The following compounds were active at less than 1.0%: 6,12,14,15,18,19, 21, 22, 23, 24, 25, 26, 27, 37, 39, 41, 43, 33, 48, 50,

The following compound was active at less than 0.1%: 29.

E. Toxicity in mammals

Compound 15 has an LD ₅₀ value of greater than 20 mg / kg when administered orally to mice (Charles River DC1).

compositions

1. Emulsifiable concentrate

Connection 11 10.00

Ethylan KEO 20.00

Xylene 67.50

Butylated hydroxyanisole 2.50

Wettable powder 100.00 Second Connection 11 Attpulgit 25,00 Natriumisopropylbenzensulfonat 69,50 Sodium salt of condensed naphthalene 0.50 sulfonic acid Butylated hydroxytoluene 2.50 2.50 dust 100.00 Third Connection 11 Butylated hydroxyanisole 0.50 talc 0.10 99.40 bait 100.00 4th   Connection 11 powdered sugar 40,25 Butylated hydroxytoluene 59.65 0.10 paint 100.00 5th Connection 11 resin 2.5 butylated 5.0 Highly aromatic white spirit 0.5 92.0 aerosol 100.0 6th Connection 11 Butylated hydroxyanisole 0.30 1,1,1-trichloroethane 0.10 Odorless Kerosen 4.00 Arcton 11/12. Mixture 50:50 15,60 80,00 spray 100.00 7th Connection 11 butylated 0.1 xylene 0.1 Odorless Kerosen 10.0 89.8 Potential spraying agent 100.00 8th. Connection 11 piperonyl butoxide 0.1 Butylated hydroxyanisole 0.5 xylene 0.1 Odorless Kerosen 10.1 89.2

100.00

Scheme 1

Sehn 1} ζ of. one or two hydroxy groups _t

Conversion of the remaining hydroxy group (s) to aldehyde, for example by the use of pyridine chlorochromate

Reaction with the Grignard reagent R'MgHaI

Elimination of the protection of the hydroxy groups

wherein R ¹⁰ , R ^{11 are} protecting groups which can be removed under different conditions, e.g. B. by hydrogenolysis and acid hydrolysis. Advantageously, both groups R ^{10 are} joined to form an isopropyl group, and R ¹¹ is benzyl.

Claims (2)

Invention claim: Process for the preparation of a trioxabicyclo [2,2,2] octane, characterized in that a compound of the formula (I) R Λ (D wherein R is C ₂ _io-alkyl, alkenyl or alkynyl, each optionally substituted by or methyl-substituted by a cyano, C 1-6 cycloalkyl, halo, C 1-4 alkoxy group or a group S (O ⁾ m R ⁴ , wherein R ^{4 is} C ^ alkyl, and m is 0.1 or 2, or R is C3_ ₁₀ -Zykloalkyl, Cn is ₀ -Zykloalkenyl or phenyl, each optionally substituted by a Ci_4-alkoxy, C-i_ ₃ alkyl, C ₂ -4- alkynyl, halo, cyanosis, or a group S (0) mR ^4, as defined above; R ¹ is a halo group, Ci_3-alkyl, _C2 _3 alkenyl or alkynyl each optionally substituted by a halo, cyano -, Ci_4-alkoxy, Alkylkarbalkoxygruppe having up to 6 carbon atoms, a group S (0) mR ⁴ , as defined above, or alkynyl, substituted by tri-Ci ^ -alkylsilyl, or R ^{1 is} a cyano group, Spirozyklopropyl, Gem -Dimethyl, gem-dizyano, gem-diethynyl, oxo or methylene group, optionally substituted by a cyano group or C 1-4 alkyl, optionally substituted by ch fluorine, or R ¹ and R and the atoms of carbon to which they are attached, form a carbocyclic C ^ ring, optionally substituted by a halo, CI_ ₃ -AlkyloderAlkoxygruppeoderC ₂ _5 alkenyl; R ² is phenyl, C ^ o-cycloalkyl or cycloalkenyl each optionally substituted and R ³ is hydrogen, C ^ alkyl, C ₂ _ ₃ alkenyl or alkynyl each optionally substituted by one cyanosis, Ci-4 alkylthio -, C ₁ ^ -Aikoxy- or halo group, or R ^{3 is} a cyano or halo group, is prepared by the condensation of an orthocarboxylate having the formula R ² C (OR ⁷ ) ₃ with a triol having the formula (II). (ID OH OH OH wherein R to R ³ are as defined above and R ⁷ is Ci ^ alkyl, phenyl or C ₇ _8-aralkyl is the same, or by cyclization of a compound of formula (Vl) (Vl) wherein R to R ^{3 are} as defined above in the presence of an acidic catalyst. The method of item!, Characterized in that a compound of formula (I) is prepared in which R is propyl, butyl, pentyl, C ₂ _ ₅ alkenyl, or alkynyl, C ^ -Zykloalkyl or phenyl, each optionally substituted by one to three chloro, fluoro or bromo groups; R ^{1 is} a cyano group, ethynyl or methyl or ethyl, optionally substituted by a cyano, methoxy, methylthio or fluoro group; R ^2, C5_io-cycloalkyl, or cycloalkenyl is phenyl, each optionally substituted by a halo, cyanosis, azido, tetrazolyl or a group S (0) mR ^5, wherein m is 1 and R ⁵ is C ^ alkyl or m is 2 and R ⁵ is Ci_4-alkyl, one Amino or di-C 1-4 -alkylamino group, a group COR ⁶ in which R ^{6 is} C ₁ -, 4-alkoxy, benzyloxy, amino, or di-C ₁ - ₄ -alkylamino, nitro, C ₁ - -Alkyl group, optionally substituted by halo, cyano or ethynyl, or C ₂ _ 3 alkenyl or ethynyl, each optionally substituted by a halo group or tri-C 1-6 alkyl silyl; and R ³ is hydrogen or methyl. 3. Process according to item 1, characterized in that 1- (4-bromophenyl) -4-cyclohexyl-3-methyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-Chloro-phenyl) -3-methyl-4-iso-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -3-methyl-4-n- propyl 2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-chlorophenyl) -3-methyl-4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane, 1-cyclohexyl-3-methyl-4-iso-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -4-t-butyl-3-methyl- 2,6,7-trioxabicyclo [2,2,2] octane, 1,4-dicyclohexyl-3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-t-butyl-1 (4-chlorophenyl) -3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-ethynylphenyl) -3-methyl-4-n-propyl-2,6,7- trioxabicyclo [2,2,2] octane, 3-methyl-4-n-propyl-1- [4- (2-trimethylsilylethynyl) phenyl] -2,6,7-trioxabicyclo [2.2.2] octane, 1 - (4-Ethynyl-phenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-n-propyl-3-trifluoromethyl-1- [4- (2 -trimethylsilylethynyl) -phenyl] -2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-chlorophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2 , 2,2] octane, 1- (4-bromophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-Ch lorophenyl) -4-cyclohexyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromophenyl) -4-cyclohexyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl) -3-ethenyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1-cyclohexyl-4-n -propyl-3-trifluoromethyl-2,6,7-triox'abicyclo [2.2.2] octane, 1- (4-bromophenyl) -3-cyano-4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane, 3-cyano-1- (4-ethynylphenyl) -4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl) 4-Cyclohexyl-3-methoxymethyl-2,6,7-trioxabicyclo [2,2,2] octane, 1-cyclohexyl-3-methyl-4-n-propyl-2,6,7-trioxabicyclo [2,2 , 2] octane, 1- (4-bromophenyl) -4-t-butyl-3-ethyl-2,6,7-trioxabicyclo [2,2,2] octane, 4-t-butyl-1-cyclohexyl-3 -methyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-chlorophenyl) -3,5-dimethyl-4-n-propyl-2,6,7-trioxabicyclo [2.2 , 2] octane, 1- (4-bromophenyl) -3,5, -dimethyl-4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane, 1-cyclohexyl-3,5- Dimethyl 4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-cyanophenyl) -4-n-propyl-3-trifluoromethyl-2,6 , 7-trioxabicyclo [2,2,2] octane, 1- (4-bromophenyl) -4-n-butyl-3-methyl-2,6,7-trioxabicyclo-2,2,2] octane, 4-n-butyl -1- (4-chlorophenyl) -3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-t-butyl-3-cyano-1- (4-ethynylphenyl) -2,6 , 7-trioxabicyclo [2,2,2] octane, 1- (4-cyanophenyl) -3-ethynyl-4-isopropyl-2,6,7-trioxabicyclo [2.2.2] octane, 3-cyano-1 - {4-cyanophenyl) -4-isopropyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-t-butyl-3-cyano-1- (4-iodophenyl) -2,6,7 trioxabicyclo [2.2.2] octane, 4-t-butyl-3-cyano-1- [4- (2-trimethylsilylethynyl) phenyl] -2,6,7-trioxabicyclo [2,2,2] octane, 1- (4-Bromo-3,5-dichlorophenyl) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane, 1- (4-bromo-3-chlorophenyl ) -4-n-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane or 4-n-butyl-1- (4-bromophenyl) -3-trifluoromethyl-2,6,7 trioxabicyclo [2.2.2] octane, 4-n-butyl-1- (4-iodophenyl) -3-methyl-2,6,7-trioxabicyclo [2.2.2] octane, 4-n-butyl 3-methyl-1- (4- (2-trimethylsilylethynyl) phenyl) -2,6,7-trioxabicyclo [2,2,2] octane, 4-n-butyl-1- (4-ethynylphenyl) - 3-m ethyl 2,6,7-trioxabicyclo [2,2,2] octane, 4-t-butyl-3-cyano-1-cyclohexyl-2,6,7-trioxabicyclo [2,2,2] octane, 1 (4-Bromophenyl) -3-cyano-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane, 3-cyano-1- (4-iodophenyl) -4-n-propyl 2,6,7-trioxabicyclo [2,2,2] octane, 3-cyano-4-n-propyl-1- (4- (2-trimethylsilylethynyl) phenyl) -2,6,7-trioxabicyclo [2.2 , 2] octane or 3-cyano-1- (4-ethynylphenyl) -4-n-propyl-2,6,7-trioxabicyclo [2,2,2] octane. 4. The method according to item 1, characterized in that a compound of the formula (IA) 3a is prepared wherein R ^a is C ₂ _4 alkyl, alkenyl or alkynyl, C ^ o-cycloalkyl or phenyl, each optionally substituted by cyanosis or Ci ^ alkoxy group, R ^1a is a cyano group or C ₁ -S--alkyl, C ₂ _3 alkenyl or alkynyl, each optionally substituted by a cyano, C ₁ ^ ₁ alkoxy, CI ^ ₁ alkylthio or halo group, or R ^{1a is} a cyano group, Gem dimethyl or R ^1a and R ^a and the carbon atoms to which they are attached form a carbocyclic CS_ ₇ ring form, which is optionally substituted by CI_ ₃ alkyl or an alkoxy group; R ^2a is phenyl, C ₅ -I ₀ -Zykloalkyl oderZykloalkenyl, each optionally substituted and R ^3a is hydrogen, CI_ ₃ alkyl, C ₂ _3 alkenyl or alkynyl each optionally substituted by one cyanosis, Ci ^ alkylthio , - or halo group. Field of application of the invention The invention relates to a process for the preparation of novel chemical compounds with pesticidal activity, compositions in which they are contained, and their use in the control of pests. In particular, the invention relates to a class of 1,3,4-trisubstituted 2,6,7-trioxabicyclo [2,2,2] octanes. Characteristic of the known technical solutions The use of certain 2,6,7-trioxabicyclo [2,2,2] octanes as pesticides is described in European Patent Application 152229. Object of the invention The aim of the invention is to provide novel compounds with strong pesticidal activity, which can be used for controlling pests. Explanation of the essence of the invention The invention has for its object to find new compounds with the desired properties and processes for their preparation. It has now been found that derivatives of 2,6,7-trioxabicyclo [2,2,2] octanes having substituents in the 3-position have an interesting pesticidal activity. Accordingly, according to the invention, compounds of the formula (I)