DD260499A5 - METHOD FOR PRODUCING A BUCYCLO HEPTANE, OCTAN OR NONANE - Google Patents

Abstract

The invention relates to a process for the preparation of bicyclo (2.2.1) heptanes, bicyclo (2.2.2) octanes and bicyclo (2.2.3) nonanes having two or three heteroatoms in the ring, such as O, S and N. Position by a carbocyclic group, but not an alkynylphenyl group, and are substituted in the 4-position and optionally in the 3 and / or 5-position. According to the invention, compounds of the formula (I) in which, for example: R is an optionally substituted C 2-10 -alkyl, alkenyl or alkynyl group, and the like al .; R1 is a cyano, gem-dimethyl, spiro-cyclopropyl, gem-dicyan, gem-diethynyl, oxo or methylene group, and the like. al .; R2 is an optionally substituted phenyl, C5-10 cycloalkyl or cycloalkenyl group; R3 is hydrogen, an optionally substituted C1-3-alkyl, C2-3-alkenyl or alkynyl group, and the like. al .; Y and Y1 are the same or different oxygen or S (O) m ZCH2CH2 CH2CH2O, sulfur, CH2O, CH2S, and the like. a. Formula (I)

Description

Field of application of the invention

This invention relates to novel chemical compounds having activity as pesticides, to processes for their preparation, to compositions containing them and to their use for pest control. More specifically, this invention relates to a class of heterobicycloalkanes.

Characteristic of the known state of the art

The use of certain 2,6,7-trioxabicyclo (2.2.2) octanes as pesticides is described in European patent application no. 152,229.

Object of the invention

The aim of the invention is the provision of new pesticides with strong insecticidal and acaricidal activity.

Explanation of the essence of the invention

The invention has for its object to find new compounds with the desired properties that are suitable as an active ingredient in pesticides.

It has now been discovered that derivatives of 2,6,7-trioxabicyclo (2.2.2) octanes in which at least one of the ring oxygen atoms has been replaced have interesting pesticidal activity. Thus, this invention provides a compound of formula (I):

(D

wherein R is a C ₂ _io alkyl, alkenyl or alkynyl, each optionally substituted by cyano, C ^ cycloalkyl, C ₁ ^ alkoxy group or a ₁ S (0) _m R ⁴ moiety, in the group is C 1 -C 4 alkyl and m is O, 1 or 2, or substituted by halogens or methyl-substituted; or R is a C ^ o-cycloalkyl, C ^ -io-cycloalkenyl or phenyl group, each optionally substituted by a C ₁ ^ -Aikoxy, Ci_ ₃ alkyl, Ca ^ alkynyl, halogen, a cyano group or a S (O) _m R ⁴ moiety as hereinbefore defined is substituted;

wherein R ^{1 is} hydrogen, halogen, a CO ₂ R ^{4 group} in which R ^{4 is} a C ₁ ^ ₁ alkyl group, or a C ^ alkyl, C ₂ _ ₃ alkenyl or alkynyl group, the jeweMs optionally by halogen, a cyano, C ₁ ^ ₄ alkoxy, Alkylcarbalkoxygruppe having up to 6 carbon atoms, or an S (O) _m R ⁴ moiety may be substituted as has been previously defined herein or R ¹ represents a Cyan, acc. Dimethyl, spirocyclopropyl, acc. Dicyan, gem. Diethynyl, oxo or methylene group, each of which may optionally be substituted by a cyano or trifluoromethyl group, or R ^{1 represents} a C ₂ _ ₃ alkynyl group which is substituted by a tri-Ci ^ -alkylsilylgrüppe, or R ¹ and R and the carbon atoms to which they are attached form a C ^ carbocyclic ring containing from ₃ alkenyl optionally substituted by halogen, Ci_3 alkyl or alkoxy or C ₂ _;

wherein R ^{2 represents} a phenyl, C 1-10 cycloalkyl or cycloalkenyl group, each of which may optionally be substituted; wherein R ^{3 is} hydrogen, a C ^ alkyl, C ₂ _ ₃ alkenyl or alkynyl group, each of which may be optionally substituted by a cyano, C ₁ ^ alkylthio, Ci_4 alkoxy group or halogen, or R ³ represents halogen or a cyano group; and wherein Y and Y ^{1 may be the} same or different and are oxygen, S (O) _m , wherein m is 0.1 or 2; and Z is a CH ₂ CH ₂ moiety, CH ^^ O moiety, sulfur, a CH ₂ O, CH ₂ S, CHR ^1x NR ⁵ moiety, wherein R ^{lx is} hydrogen, halogen, a cyano group, a COOR ⁴ moiety, or a C ^ alkyl, C ₂ - ₃ alkenyl or alkynyl, each optionally substituted (by halogen, cyano, C ₁ ^ -AIkOXy-, Alkylcarbalkoxy having up to 6 carbon atoms, or an O S ) _m R ⁴ moiety, wherein derm and R ^{4 have} the meaning as defined hereinbefore, and R ^{6 is} hydrogen or a benzyl, C 1-4 alkyl group or C (O) R ⁶ , wherein R ⁶ is a Ci_4-alkyl, alkoxy or NR ⁷ H group in which R ^{7 is} a Ci-4-alkyl, C ₇ _8-aralkyl or phenyl group, each of which may be optionally substituted by halogen, or Z is means a-CH (oR ⁸ I-CH ₂ group, in which R ⁸ is hydrogen, a C - ^ - alkyl, C ₁ ^ -ACyI-, C ₂ _ ₇ carbamoyl or SO ₂ R ⁴ moiety represents in which R ^{4 is} a C 1-4 -alkyl group or a grouping -CH (OR ⁸ I-CH ₂ - means -COCH ₂ -; provided that (i) when Z is CHR ^1x is NR ^5, R ¹ and R ³ are hydrogen, (ii) when Y and Y ¹ are both oxygen, Z is CH ₂ O is not and (iii) R ² is not optionally substituted by a C ₂ _ ₃ alkynyl group is substituted phenyl group. In the definition of Z, the first atom is adjacent to the 4-position of the bicyclic ring system. '

Suitable groups for R are propyl, butyl, pentyl, C ₂ -5-alkenyl or alkynyl, C _5-7 -cycloalkyl or phenyl. Most suitable for R are n-propyl, η-butyl, i-butyl, sec-butyl, t-butyl, cyclopentyl, cyclohexyl or phenyl. Preferably, R represents a propyl, η-butyl, i-butyl, t-butyl or cyclohexyl group.

Suitable groups for R ¹ are hydrogen, cyano, ethynyl, methyl or ethyl, each of which may be optionally substituted by cyano, methoxy, methylthio or fluorine. Most suitable for R ¹ are hydrogen, methyl, cyano, trifluoromethyl or ethyl groups. Preferably, R ^{1 is} hydrogen or a methyl or trifluoromethyl group. When R ^{2 is} a substituted phenyl group, a C 1-6 cycloalkyl or cycloalkenyl group, suitable substituents include halogens, cyano, azide, nitro, C 1-6 alkyl or alkoxy groups, of which the latter two may be substituted by Halogen substituted, or a C ₂ _3 alkenyl group, which may optionally be substituted by halogen. When R ^{2 is} a phenyl group, it may be substituted by up to three substituents, which are preferably in the 3,4 and / or 5 position. Suitable substituents for R ² are cyclohexyl, cyclopheptyl or phenyl groups which are optionally in the 3-, 4- and / or 5-position by chlorine, bromine, iodine, cyano, azide or nitro and / or a phenyl group which in the 2- and / or 6-position optionally substituted by fluorine, are substituted. Most suitable as a substituent for R ² is a cyclohexyl or phenyl group which is optionally substituted in the 4-position by chlorine, bromine, iodine or a cyano group. Suitable substituents for R ³ are hydrogen or d-3-alkyl groups; preferably R ^{3 is} hydrogen. Suitable substituents for Z are -CH ₂ S-, -CH ₂ O- or -CH ₂ CH ₂ -; preferably, Z-CH _{2 is} S or -CH ₂ O-. Suitable substituents for Y and Y ¹ are both oxygen or both sulfur. A group of compounds of the formula (I) is that of the formula (IA):

wherein R ^a is a C ₂ _ ₇ signifies alkyl, alkenyl or alkynyl group, each of which is optionally substituted with halogen, cyano or C alkoxy groups may be substituted, or R ^a is a C3_io cycloalkyl, cycloalkenyl C4_io or phenyl group substituted by a C ₁ ^ ₁ -AIkOXy-, C ^ alkyl, C ₂ in each case optionally - may be substituted alkynyl, cyano or halogen - ^; wherein R ^{1 a is} hydrogen, a Ci_ ₃ alkyl, C ₂ _ ₃ alkenyl or alkynyl group, each optionally substituted by a cyano, C ₁ - ^ - AIkOXy-, C ^ -Alkylthio-.AIkylcarbalkoxygruppe with bis may be substituted to 6 carbon atoms or halogen, or R ^{1 a} is a cyano, acc. Dimethyl group or R ^{1 a} and R ^a and the carbon atoms to which they are attached form a carbocyclic Cs_ ₇ ring which is optionally substituted by a C _1-3 alkyl or alkoxy group; wherein R ^{2a is} a phenyl, C 1-6 cycloalkyl or cycloalkenyl group, each of which may optionally be substituted; and wherein R ^3a is hydrogen, a C-i_ ₃ alkyl, C ₂ _ ₃ alkenyl ο 'it is alkynyl, each optionally substituted by cyano, C 1-4 alkylthio, C ^ alkoxy or halogen could be;

wherein Y ^a and Y ^{1 a are the} same or different and each represents oxygen and S (0) _m ^a , wherein m ^{a is} 0,1 or 2; wherein Z is ^a CH ₂ CH _2, CH ₂ CH ₂ O, sulfur, CH ₂ O, CH ₂ S, CH ₂ NR ^4a in which R ^4a is hydrogen, C ^ alkyl or benzyl group or C (O) R ^Sa, in which R ^{5a is} a C 1-4 -alkyl or -alkoxy group, or Z ^a is a CH (OR ^6a ) CH ₂ -group, in which R ^{6a is} hydrogen, a C 1-4 -alkyl or C 1-4 -acyl group or CH (OR ^6a ) -CH ₂ means -COCH ₂ -; except when Y ^a and Y ^{1 a are} both oxygen, Z ^{a is} not CH ₂ O.

Suitable substituents for R ^a are propyl, butyl, C ^ -cycloalkyl or phenyl. Most suitable for R ^a are propyl, t-butyl, cyclopentyl or cyclohexyl and preferably R ^{a is} a propyl, t-butyl or cyclohexyl group.

Suitable substituents for R ^{1 a} are hydrogen, cyano, methyl or ethyl, which may each be optionally substituted by a cyano, methoxy, methylthio or fluorine. Most suitable for R ^1a is hydrogen, a methyl, trifluoromethyl or ethyl group. Preferably, R ^{1 a is} hydrogen or a methyl group.

When R ^{2a represents} a substituted phenyl group, a substituted C 3-10 cycloalkyl or cycloalkenyl group, suitable substituents include halogen, cyano, azido, nitro or C _1-3 alkyl groups, the latter optionally substituted by halogen, or C ₂ _ ₃ alkenyl or alkynyl groups, each optionally substituted by halogens.

Suitable substituents for R ^2a are cyclohexyl, cycloheptyl or phenyl, each of which may optionally be substituted in the 3- or 4-position by halogen, cyano, C ₂ _3 alkynyl, azide or nitro groups. Most suitable for R ^2a are cyclohexyl or phenyl, each of which may optionally be substituted at the 4-position by chlorine, bromine, a C ₂ -3 alkynyl or cyano group.

When Z ^a contains a heteroatom, it is adjacent to the carbon atom of the bicyclooctane ring having the substituent R ^2a .

Suitable moieties for Z ^a are -CH ₂ S-, -CH ₂ CH ₂ O- or -CH ₂ CH ₂ -. Suitable substituents for Y ^a and Y ^{1 a} are each oxygen. Another group of compounds of formula (IA) consists of those as defined above, except that in addition to the meanings already mentioned, R ^{6a may be} a C _1-7 -carbamoyl group.

Preferred compounds are u. a.

1- (4-bromophenyl) -4-i-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-bromophenyl) -4-i-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-chlorophenyl) -4-s-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-s-butyl-1-cyclohexyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-bromophenyl) -3-methyl-4-propyl-2,6-dioxa-7-ttiiabicyclo [2.2.2] octane;

1-cyclohexyl-5-propyl-2,7,8-trioxabicyclo [2.2.2] nonane;

1-cyclohexyl-5-propyl-2,7,8-trioxabicyclo [2.2.2] nonane;

1- (4-chlorophenyl) -4-propyl-2,6-dioxabicyclo [2.2.2] octane;

1- (4-bromophenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-t-Butyl-1- (4-chlorophenyl) -2,6-dioxabicyclo [2.2.2] octane; .

1- (4-chlorophenyl) -8-methoxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane;

1- (4-chlorophenyl) -8-methoxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane;

T- (4-chlorophenyl) -8-oxo-4-propyl-2,6-dioxabicyclo [2.2.2] octane;

i-W-BromphenylM-t-butyl ^ e-dioxa ^ ^^ -thiabicyclol Ioctan;

4-t-Butyl-1- (4-chlorophenyl) -2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-iodophenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-t-butyl-1-cyclohexyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-t-butyl-1-cycloheptyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-chlorophenyl) -4-i-butyl-2-oxa-6,7-dithiabicyclo [2.2.2] octane;

1-cyclohexyl-4-propyl-2,6,7-trithiabicyclo [2.2.2] octane;

1-cyclohexyl-8-methyl-4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-bromophenyl) -4-i-butyl-8-methyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-bromophenyl) -8-methyl-4-propyl-2,6-dioxane-7-thia-bicyclo [2.2.2] octane;

1- (4-bromophenyl) -4-n-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-bromophenyl) -4-propyl-2-oxa-6,7-dithiabicyclo [2.2.2] octane; ,

In a further embodiment, this 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 to use any method known in the art for the preparation of analogous compounds, eg in the case where the compound of formula (I) contains three heteroatoms, a compound of formula (II) an orthocarboxylate of the formula R ² C (OR ⁹ J _{3 is} condensed

(II)

HY *

wherein R to R ³ are as hereinbefore defined, R ^{9 is} a C 1-4 alkyl, phenyl or C ₇ , aralkyl group, Y ² and Y ^{3 may be the} same or different and each is oxygen mean or sulfur and Z ¹ is a group CH ₂ CH ₂ OH, SH, CH ₂ OH, CH ₂ SH or CHR ^lx NHR ^5, except that Y ² and Y ³ is not intended to mean both oxygen when Z 'is a CH ₂ OH grouping is.

This reaction is usually carried out at elevated temperature, for example between 50 and 200 ⁰ C, more preferably between 120 and 170 ° C, in the presence of a base, for. As an amine such as triethylamine, or a mineral acid, eg. Hydrochloric acid or a sulfonic acid derivative, e.g. As toluene sulfonic acid, or an acidic resin. The reaction is best carried out in the absence of a solvent, but a solvent may be added if desired. The preparation of compounds of the formula (II) is carried out by methods which are known to the person skilled in the art for the preparation of compounds of analogous structure. Examples of such methods are presented in the Schemes. The compounds of the formula (I) in which Z is a CH ₂ CH _{2 group} and Y and Y ^{1 are} each oxygen can be prepared by removal of protective groups and ring closure of compounds of the formula (III).

R ¹⁰ O

wherein R and R ² are as hereinbefore defined, Q is hydrogen, the groups R ^{10 are} protecting groups for hydroxyl groups, and R ^{11 is} a C 1-4 alkyl group. The best are the groups R ¹⁰ connected to each other to z. To form an isopropylidene group, however, all other groups which protect the hydroxyl groups in the preparation of the compound of formula (III) and are readily cleaved to close the ring to the compound of formula (I) are suitable. This ring closure is usually carried out in the presence of a dilute acid which splits off the R ¹⁰ protecting group, e.g. In the presence of a dilute mineral acid such as hydrochloric acid. The reaction usually takes place at room temperature. The preparation of compounds of the formula (III) is shown in the diagram. The compounds of the formula (I) in which Z represents an OH (OR ⁸ ) CH _{2 group} and Y and Y ¹ each represent oxygen, can be prepared by a similar deprotection and a similar ring closure of a compound of formula (III), in the Q represents an OH group are prepared, wherein first a compound of formula (I) is prepared having an 8-hydroxyl group, which can then be converted into a group OR ⁸ , for example by reaction with an R ⁸ -Ha ! ogenid in the presence of a base. Compounds of formula (III) in which Q is a hydroxyl group can be prepared in an analogous manner as the compounds of formula (III) in which Q is hydrogen. The compounds of the formula (I) in which Z is a CHR ^{1 x} NR ⁵ grouping and Y and Y ^{1 are} each oxygen are preferably prepared by ring closure of a compound of the formula (IV) (Scheme 3):

(IV)

wherein R, R ² , R ^lx and R ^{5 have} the meaning as already defined herein. This ring closure is carried out in the presence of a Lewis acid as an acidic catalyst. Etn particularly preferred acidic catalyst for this ring closure is boron trifluoride etherate; the reaction is usually carried out in an inert solvent, e.g. As a halogenated hydrocarbon, preferably methylene chloride, at temperatures below room temperature, for example between -100 and 0 ⁰ C, usually carried out between -70 and -50 ° C.

The compounds of the formula (IV) can be prepared by reacting compounds of the formula (V) and of the formula (VI):

R.

(V)

-C-L

ii

(Vl)

wherein R, R ² , R ^lx and R ⁵ are as hereinbefore defined, and wherein L is a leaving group, e.g. As halogen, means. This reaction is best carried out in an inert solvent in the presence of a base at non-extreme temperatures. Halogenated ^ hydrocarbons, eg. As methylene chloride, are particularly suitable solvents, pyridine is a preferred base and the reaction is best carried out at temperatures between -50 and 100 ⁰ C, preferably at 0 ⁰ C performed.

The compounds of the formula (V) can in turn be prepared from compounds of the formula (VII) by reaction with an amine (R ⁵ NH ₂ ) and with sodium cyanoborohydride in a polar solvent, for example an alcohol, such as methanol:

(VII)

The compound of the formula (VII) is prepared by oxidation of the corresponding hydroxyl compound, for example by using oxalyl chloride, dimethyl sulfoxide and triethylamine. The hydroxy compound can in turn be prepared from compounds of the formula (II) in which R ¹ and R ^{3 are} hydrogen, Y ² and Y ^{3 are} oxygen and Z ^{1 is} a CH ₂ OH group, these with diethyl carbonate in the presence of a strong base , z. As potassium hydroxide, in a polar solvent, for. As an alcohol such as methanol, at elevated temperature, for example between 50 and 100 ⁰ C, are reacted.

The compounds of formula (I) can be used to control arthropods such as insecticides or acarine pests. This invention thus provides a method of controlling arthropods consisting in administering to the arthropod or its environment an arthropod-effective amount of a compound of formula (I). This invention also provides a method of controlling and / or eradicating arthropod infestation in mammals (including humans) which consists of applying to the animal an effective amount of a compound of formula (I). This invention further provides the compounds of formula (I) for use in human and veterinary medicine for the control of arthropod pests.

The compounds of formula (I) may be used for such purposes by applying the compounds themselves or in diluted form in a known manner as a dipping agent, spray, lacquer, foam, dust, powder, aqueous suspension, paste, gel, shampoo, fat, flammable Solid, evaporative sheets, wettable powder, granules, aerosol, emulsifiable concentrate, oily suspension, oily solutions, pressure packs, impregnated articles or pourable formulations. Dipping concentrates are not used as such but are diluted with water and the animals are placed in such a dipping bath containing the dipping detergent. Sprays can be applied by hand or with the help of a spray arch or spray bar. The animal, plant or surface to be treated can be saturated with the spray liquor by applying a large volume or can only be coated on the surface by using the spray in small or very small volumes. Aqueous suspensions may be applied in the same manner as sprays or dips. Dusts may be used with the help of dust collectors or, in the case of animals, by incorporation in permeable bags attached to trees or rubbish bars. Pastes, shampoos or fats can be applied by hand or they can be spread over the surface of an inert material against which the animals rub and thus transfer the composition to their skin. Casting formulations are provided in the form of a small volume fluid unit which is distributed to the back of the animals so that all or most of the fluid remains on the animals.

The compounds of formula (I) may be formulated as ready-to-use compositions for the animals, plants or surfaces or as compositions requiring further dilution prior to use. However, both types of formulations represent a compound of formula (I) in intimate admixture with one or more carriers or diluents. The carriers may be liquid, solid or gaseous, or they may be a mixture of such substances. The compound of formula (I ) can be used in a concentration of 0.025 to 99%. The amount depends on whether the composition should be further diluted. Dusts, powders and granules are intimate admixture of a compound of formula (I) with a powdered, solid, inert carrier, e.g. with suitable clays, kaolin, talc, mica, lime, gypsum, vegetable carriers, starch and diatomaceous earth.

Sprays containing a compound of formula (I) may comprise a solution thereof in an organic solvent (eg those listed below) or an emulsion in water (dip wash or spray wash) at the point of use of an emulsifiable concentrate (also as with water miscible oil) is prepared, which can also be used for diving purposes. The concentrate preferably constitutes a mixture of the active ingredient with or without organic solvent and with one or more emulsifiers. Solvents may be present within wide limits, but preferably in an amount between 0 and 90% of the composition. They may be selected from kerosene, ketones, alcohols, xylene, aromatic petroleum fractions and other solvents known in the art. The concentration of emulsifiers can be adjusted within wide limits, but is preferably in the range between 5 and 25%. The emulsifiers are usually nonionic surfactants, e.g. Polyoxyalkylene esters of alkylphenols and polyoxyethylene derivatives of hexane anhydrides, and anionic surfactants, e.g. Sodium lauryl sulfate, fatty alcohol ether sulfates, sodium and calcium salts of alkylaryl sulfonates and alkyl sulfosuccinates.

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

Emulsifiable concentrates include emulsifiers and often an organic solvent such as kerosene, ketones, alcohols, xylenes, aromatic petroleum fractions and other solvents known in the art. Wettable powders and emulsifiable concentrates usually contain from 5 to 95% by weight of the active ingredient and are diluted prior to use, e.g. with water. Varnishes are a solution of the active ingredient in an organic solvent which also contains a resin and optionally a plasticizer. Immersion baths can be prepared not only from emulsifiable concentrates, but also from wettable powders, soap-based baths and aqueous suspensions containing a compound of formula (I) in intimate admixture with a dispersing aid and one or more surfactants.

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

Fats or ointments may be made from vegetable oils, synthetic esters of fatty acids or wool fat together with an inert base, e.g. As a soft paraffin. A compound of formula (I) is preferably evenly distributed in solution or suspension in this mixture. Fats can also be made from emulsifiable concentrates by diluting them with an ointment base.

Pastes and shampoos are also semi-solid compositions in which a compound of formula (I) is used as a uniform dispersion in a suitable base, e.g. soft or liquid paraffin, or in a non-greasy basis with glycerine, vegetable glues or a suitable soap. Since fats, shampoos and pastes are normally used without further dilution, they should contain the appropriate amount of the compound of formula (I) needed for the treatment.

Aerosols can be used as a simple solution of the active ingredient in the aerosol propellant and a common solvent, e.g. As halogenated alkanes or the above-mentioned solvents, are produced. Casting compositions may be prepared as a solution or suspension of a compound of formula (I) in a liquid medium. A host or mammalian host may also be protected from attack by acarine ectoparasites by carrying a suitably shaped plastic article impregnated with a compound of formula (I). Such articles include, but are not limited to, impregnated collars, strips, bands, sheets, and tags attached to appropriate body parts

The concentration of a compound of formula (I) applied to an animal will depend on the compound selected, the intervals between treatments, the nature of the composition and the likely infestation, but in general between 0.001 and 20.0% should be used. and preferably between 0.01 and 10% of the compound in the composition used. The amount of the compound applied to an animal is dependent upon the mode of application, the size of the animal, the concentration of the compound in the composition used, the factor with which the composition is diluted, and the type composition, but generally ranges between 0.0001% and 0.5%, except in the case of undiluted compositions. Example of casting compositions, which are generally applied in a concentration in the range between 0.1 and 20.0%, preferably between 0.1 and 10%.

The compounds of formula (I) can also be used for the protection and treatment of plant species. In these cases, an effective amount of the active ingredient is used as an insecticide or acaricide. The amount used depends on the compound selected, the type of composition, the mode of application, the plant species, the planting density and probable infestation, and other similar factors, but generally a suitable amount for agricultural crops is in the range of 0.001 to 3 kg / ha, preferably between 0.01 and 1 kg / ha. Typical compositions for use in agriculture contain between 0.0001% and 50% of a compound of formula (I) and most preferably between 0.1 and 15% by weight of a compound of formula (I).

Cultures to which the compounds of formula (I) can be applied include i.a. Cotton, wheat, corn, rice, millet, soybeans, wine, tomatoes, potatoes, fruit trees and firs.

Dusts, greases, pastes and aerosol compositions are generally applied in random distribution as described above, and concentrations of 0.001 to 20% of a compound of formula (I) can be used in the composition employed.

It has been found that the compounds of formula (I) are active against the common housefly (Musca domestica). In addition, various other compounds of formula (I) have activity against other arthropod pests, i.a. against Tetranychus urticae, Plutella xylostella, Culex spp. and Blatella germanica. The compounds of formula (I) are thus suitable for controlling arthropods, for. B. for controlling insects and acarines in any environment where they occur as pests, z. In agriculture, livestock, health and the home.

Insect pests belong to u. a. to the orders Coleoptera (eg Anobium, Tribolium, Sitophilus, Diabrotica, Anthonomus or Anthrenus spp.), Lepidoptera (eg Ephestia, Plutella, Chilo, Heliothis, Spodoptera or Tineola spp.), Diptera (eg Musca, Aedes, Culex, Glossina, Stomoxys, Haematobia, Tabanus, Hydrotaea, Lucilia, Chrysomia, Callitroga, Dermatobia, Hypoderma, Liriomyza and Melophagus spp.), Phthiraptera (Malophaga, eg Damalina spp., And Anopiura, eg Linognathus and Haematopinus spp ), Hemiptera (eg Aphis, Bemisia, Aleurodes, Nilopavata, Nephrotetix or Cimex spp), Orthoptera (e.g.

Schistocerca or Acheta spp.), Dictyoptera (e.g., Blatella, Periplaneta or Blatta spp.), Hymenoptera (e.g., Solenopsis or Monomorium spp.), Isoptera (e.g., Reticulitermes spp.), Siphonaptera (e.g. Ctenocephalides or Pulex spp.), Thysanura (e.g.

Le.pisma spp.), Dermaptera (eg Forficula spp.) And Pscoptera (eg Peripsocus spp.).

Acarine pests are u. a. Ticks of the genera Boophilus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Haemaphysalis, Dermocentor and Anocentor and Bilbes and Rays such as Tetranychus, Psoroptes, Notoedres, Psorergates, Chorioptes and Demodex spp.

The compounds of the invention may be combined with one or more other active ingredients (e.g., pyrethroids, carbamates and organophosphorus compounds) and / or with attractants and the like. Furthermore, it has been found that the effectiveness of the compounds of the invention can be enhanced when a synergist or potentiator is added, e.g. A synergist from the class of oxidase inhibitors such as piperonyl butoxide or propyl 2-propynylphenyl phosphonate; a second compound of the invention; or a pyrethroid-active compound suitable for pest control. When a synergist of the class of oxidase inhibitors is present in a composition of the invention, the ratio of synergisti compound of formula (I) should be in the range of 25: 1 to 1:25, e.g. about 10: 1 lie. Stabilizers for preventing a chemical degradation, which may occur in compounds of formula (I) are, for. Antioxidants (eg, tocopherols, butylhydroxyanisole and butylhydroxytoluene) and scavengers (e.g.

Epichlorohydrin).

The following examples illustrate, in a non-limiting manner, preferred embodiments of the invention.

All temperatures are in degrees Celsius. As used herein, the term ether refers to diethyl ether.

embodiment example 1

1 - {4-Chlorophenyl) -4-ethyl-2,6-dioxabicyclo [2.2.2.] Octane

1- (4-chlorophenyl) propyl-2,6-dioxabicyclo -4-[2.2.2.] Octän

(i) 15 ml of methanesulfonyl chloride were added to 33,0g 2,2-dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane dropwise with stirring in 100 ml of dry pyridine at 0 ⁰ C. The mixture was stirred at room temperature for two hours and then 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. 39 g of 2,2-dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane methanesulfonate were obtained as a colorless oil, which solidified on standing. The compound was used without further purification.

Gas-liquid chromatography (GLC) on OV-210 at 15O ⁰ C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks): 4.40; 2H; s; 3.70; 4H, s; 3:10; 3H, s; 1.50; 8H, m; 0.90; 3H, m.

(ii) A mixture of 6.0 g of 2,2-dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane methanesulfonate and 9.0 g of sodium iodide in methyl ethyl ketone was refluxed with stirring for 48 hours. The solvent was removed in vacuo and the resulting oil poured into water. The aqueous mixture was extracted with ether. The ether extracts were washed with 5% sodium thiosulfate solution and then with water. The ether extracts were dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue was purified by column chromatography on silica gel,

eluting with 1:10 ether: hexane. There was obtained 5.0 g of 2,2-dimethyi-5-ethyl-5-iodomethyl-1,3-dioxane as a colorless oil.

Gas-liquid chromatography (GLC) with OV-210 at 150 ⁰ C gave a peak.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

3.75; 4H, s; 3.45; 2H, s; 1.20; 8H, m; 0.90; 3H, m. '

(iii) and (iva) 5.3ml to a 1.6M solution of n-butyllithium in hexane were added with stirring to 1.5g of 4-chloroacetophenone-N, N-dimethylhydrazone (bp = 80-82 ° C / 0.05mm given) in 50ml dry tetrahydrofuran at -70 ⁰ C under nitrogen. The mixture was stirred at -70 ⁰ C for 30 minutes. To this solution a solution of 2.4 g of 2,2-dimethyl-5-ethyl-5-iodomethyl-1,3-dioxane in 20 ml of dry Tetahydrofuran at -7O ⁰ C was added with stirring. The mixture was slowly warmed to room temperature. The mixture was stirred at room temperature for 24 hours. Thereafter, water was added and the mixture was extracted with ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue (2.9 g) and 40 ml of 2N hydrochloric acid were stirred at room temperature for 24 hours. This aqueous mixture was extracted 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 gel eluting with ether hexane 1:20. There were obtained 0.6 g of 1- (4-chlorophenyl) -4-ethyl-2,6-dioxabicyclo [2.2.2] octane as colorless crystals (F = 78 ⁰ C). Gas-liquid chromatography (GLC) at OV-210 to 210 ° C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, JHz):

7.40,2H, d, 8; 7.30,2Ή, d, 8; 4.00,4H, 's; 2.20, 2H, m; 1.90,2H; m; 1.20,2H, m; 0,90,3H, m.

IR spectrum (Nujol): 1130 (s), 1100 (m), 1090 (m), 1070 (m), 1020 (s).

Mass Spectrum (MS): Chemical Ionization: M-M = 253

b) 1- (4-chlorophenyl) -4-propyl-2,6-dioxabicyclo [2.2.2.] octane (F = 94 ⁰ C) was prepared in an analogous manner, by 2,2-Dimethyl-5- propyl 5-hydroxymethyl-1,3-dioxane was replaced by 2,2-dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane.

Gas-liquid chromatography (GLC) on OV-210 at 185 ° C gave a peak.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.10; 4H, m; 3.80; 4H, s; 1.90; 2H, m; 1.70; 2H, m; 1.00; 4H, m; 0.80, 3H, m.

Infrared spectrum (IR) in Nujol: 1130 (s), 1080 (m), 1020 (s).

Mass spectrum (MS), chemical ionization: M + 1 = 267.

Example 2

1- (4-bromophenyl) -4-ethyl-2,6-dioxa-7-thiabicyclo [2.2.2.] Octane

1- (4-bromophenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2.] Octane

(i) 340 mg of a 50% dispersion of sodium hydride in paraffin oil was added cautiously with stirring to a solution of 500 mg of thioacetic acid in 100 ml of dimethylformamide at 2O ⁰ C. After 30 minutes, 2.0 g of 2,2-dimethyl-5-ethyl-5-iodomethyl-1,3-dioxane was added. The mixture was refluxed for two hours with stirring. The mixture was cooled and poured into water. The aqueous mixture was extracted with ether. The ether extracts were washed with water and dried over anhydrous magnesium sulfate. The solution was evaporated in vacuo. The residue was purified by column chromatography using silica gel and etherhexane as 1: 4 as eluent.

There were obtained 1.5 g of acetylthiomethyl-5-ethyl-2,2-dimethyl-1,3-dioxane as a pale yellow oil.

Gas-liquid chromatography (GLC) on OV-210 at 150 ^° C. gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, JHz): · 3.70.4H, s; 3.20, 2H, s; 2.45.3H, s; 1.50, 8H, m; 0.90, 3H, m.

(ii) and (iii) were 2.0 g of 5-acetylthiomethyl-5-ethyl-2,2-dimethyl-1,3-dioxane for 24 hours at 20 ⁰ C in 2.0 ml of a 10% sodium hydroxide solution and 20 ml of methanol under Nitrogen atmosphere stirred. The mixture was neutralized with 0.5 ml concentrated hydrochloric acid. To this was added 1.0 g of Dowex 50 × 8-200 ion exchanger (H ⁺ form) and this mixture was refluxed for 4 hours while stirring under nitrogen atmosphere. The mixture was filtered and the filtrate evaporated in vacuo. To the residue was added toluene and the mixture was evaporated in vacuo. There was obtained 1.0 g of 2,2-di (hydroxymethyl) butanethiol as a colorless oil which was used without further purification.

(iva) 0,5g2,2-di- (hydroxymethyl) -butanthiol, 1.0gTrimethyl-4-bromo-orthobenzoatundO, 1 ml triethylamine was heated for 45 minutes with a nitrogen stream to 130 ⁰ C. The volatile components were removed at 140 ^° C. in vacuo (2.00 mm).

The residue was purified by chromatography on alumina (Alumi.ia Woelm TSC) eluting with dichloromethane: hexane as 1: 6, saturated with ammonia. There were obtained 80 mg of 1- (4-bromophenyl) -4-ethyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane as colorless crystals.

Gas-liquid chromatography (GLC) on OV-210 at 200 ^° C gave a peak.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.50,4H, s; 4.20, 4H, m; 3.15, 2H, s; 1.40, 2H, m; 1.00, 3H, m.

Infrared spectrum (IR) in Nujol: 1090 (s), 1035 (m), 1022 (w).

Mass spectrum (MS), chemical ionization: M + 1: 315, 317

(ivb) Using an analogous method as in (iva) (see above), 2,2-di- (hydroxymethyl) -pentane-1-thiol and trimethyl-4-bromo-orthobenzoate were reacted together to give 1- (4- Bromophenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2.] Octane.

Gas-liquid chromatography (GLC) on OV-210 at 200 ^° C gave a peak.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.50; 4H, s; 4.20; 4H, m; 3.20; 2H, m; 1.40; 4H, m; 1.00; 3H, m.

Infrared spectrum (IR) in Nujol: 1080 (s), 1040 (s), 1020 (m).

Mass spectrum (MS), chemical ionization: M + 1: 329.331

Examples

1-Cyclohexyl-5-propyl-2,7,8-trioxabicyclo [3.2.2.] Nonane

(i) 7.5 g of an 80% dispersion of sodium hydride in oil was added with stirring to a solution of 52 g of diethyl-propylmalonate in 200 ml of dry benzene at room temperature. The mixture was then refluxed for one hour with stirring, the mixture was cooled and 42 g of ethyl bromoacetate added dropwise The reaction mixture was refluxed for 3 hours with stirring The reaction mixture was cooled, poured into water and the aqueous mixture washed with ether The ether extracts were washed with water, dried over anhydrous magnesium sulfate and the solvent removed in vacuo.

By distillation, 58 g of diethyl 2-ethoxycarbonyl-2-propylsuccinate were obtained as a colorless oil (bp = 130-6 ⁰ C,

Gas-liquid chromatography (GLC) on OV-210 at 15O ⁰ C gave a peak.

The nuclear magnetic resonance spectrum was as follows: ¹ H (ppm with TMS as standard in CDCb, integral, number of peaks, JHz):

4.25; 6H, m; 3.00; 2H, s; 2.00; 2H, m; 1,50-0,80,14H, m.

(ii) 55,8g 2-ethoxycarbonyl-2-propyl-succinic acid diethyl ester in 50 ml of dry ether were la ^ ngsafn and current stirring to a suspension of 14.7 g lithium aluminum hydride in 150 ml of dry ether at 0 ⁰ C under a nitrogen given.

The mixture was stirred at room temperature for three hours and then refluxed for four hours with stirring.

To the cooled reaction mixture was then added a solution of 30.0 g potassium hydroxide, 22.0 g potassium dihydrogen phosphate and 22.0 g dipotassium hydrogen phosphate in 200 ml water. The pH was adjusted to 5.0 with glacial acetic acid. The solid was filtered off and washed with 40 ml of water. The combined filtrate and washings were evaporated in vacuo. The residue was washed with 3 × 100 ml acetone. The acetone washings were evaporated in vacuo. The residue was washed 3 χ with 100 ml of chloroform and the washings were evaporated in vacuo.

Toluene was then added and the residue was evaporated in vacuo. 3,3-Di (hydroxymethyl) hexan-1-ol was obtained as a colorless oil and used without further purification.

(iii) From 750 mg of 3,3-di- (hydroxymethyl) -hexan-1-ol and!, OgTrimethyl-ortboxyclohexyl-carboxylate ³ were prepared according to the in Example

2 described method obtained 50 mg of 1-cyclohexyl-5-propyl-2,7,8-trioxabicyclo [3.2.2.] Nonane as a colorless oil. Gas-liquid chromatography (GLC) on OV-210 at 190 ° C gave a peak.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

3.80; 6H, m; 2.00 to 0.80; 2OH, m _r

Infrared spectrum (IR) as liquid film: 1114 (s), 1070 (s), 1040 (s), 1010 (m) cm ^-1 .

Mass spectrum (MS), chemical ionization: M + 1: 255

Example 4

4-t-butyl-1- (4-chlorophenyl) -2,6-dioxabicyclo [2.2.2.] Octane

A mixture of 150 ml of cyclohexanone, 17.5 g of 5-t-butyl-2,2-dimethyl-5-hydroxymethyl-1,3-dioxane-methanesulfonate (see synthesis of 2,2-dimethyl-5-ethyl-5-hydroxymethyl- 1,3-dioxane methanesulfonate and reference 4) and 12 g of sodium iodide were refluxed for 24 hours with stirring. The solvent was removed in vacuo and the resulting oil poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with 5% aqueous sodium thiosulfate solution and then with water. The ether extracts were dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue was purified by column chromatography on silica gel using hexane as an eluent. There was obtained 14 g of 3-t-butyl-3-iodomethyl- (1,5-dioxaspiro [5.5.] Undecane) as a colorless oil.

Gas-liquid chromatography on OV-210 at 185 ° C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, JHz):

3.80; 2H, d; 3.50; 2H, d, 10; 3.40; 2H, s; 1.50; 10H, m; 0.90, 9H, s.

A mixture of 3.5 g of 3-tert-butyl-3-iodomethyl- (1,5-dioxaspiro [5.5.] Undecane), 0.5 g of p-toluenesulfonic acid and 200 ml of acetone was refluxed for 36 hours. The mixture was cooled and 2.0 g of sodium bicarbonate added. The solvent was removed in vacuo and the resulting oil poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and then evaporated in vacuo. There was obtained 2.3 g of 5-t-butyl-2,2-dimethyl-5-iodomethyl-1,3-dioxane as a colorless oil which was used without further purification.

Gas-liquid chromatography (GLC) on OV-210 at 170 ° C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, JHz):

3.70; 2H, d, 10; 3.50; 2H, d, 10; 3.30; 2H, s; 1.20; 6H, s; 0.80; 9H, s.

4-t-Butyl-1- (4-chlorophenyl) -2,6-dioxa-bicyclo [2.2.2.] Octane was prepared from 5-t-butyl-2,2-dimethyl-5-iodomethyl-1,3- dioxane according to the method described for the synthesis of 1- (4-chlorophenyl) -4-ethyl-2,6-dioxabicyclo [2.2.2.] octane.

Physical Data: Gas-liquid chromatography (GLC) on OV-210 at 200 ^° C gave a peak. Melting point: 155 ^° C. The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks): 7.25.4H, m; 4.10; 4H, m; 2.10; 2H, m; 2.00; 2H, rri; 1.00; 9H, s. The infrared spectrum (IR) in Nujol: 1130 (s), 1100 (s), 1015 (s). The mass spectrum (MS), chemical ionization: M + 1: 281.

Example 5

1- (4-chlorophenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo [2.2.2.] Octane and 1- (4-chlorophenyl) -4-ethyl-8-hydroxy-2,6-dioxabicyclo [2.2.2.] octane

33g 2,2-Dimethyl-5-ethyl-5-hydroxymethyl-1,3-dioxane was added under stirring to a suspension of pyridinium chlorochromate 122,6g and 7.8 g of anhydrous sodium acetate in 200ml of dry methylene chloride at 0 ^0C under a nitrogen stream. The mixture was stirred at room temperature for 6 hours. Thereafter, the mixture was diluted with 500 ml of dry ether and the organic solution was decanted off. The oily residue was extracted with ether and the combined extracts were evaporated in vacuo. The residue was purified by chromatography on silica gel using etherhexane as 1: 3 as eluent. There were obtained 30 g of 2,2-dimethyl-5-ethyl-5-formyl-1,3-dioxane as a colorless oil.

Gas-liquid chromatography (GLC) on OV-210 at 13O ⁰ C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as a standard in CDCl ₃ , integral, number of peaks, JHz):

9.6; 1 H, s; 4.2; 2H, d, 12; 3.8; 2H, d, 12; 1.4; 8H, m; 0.85, 3H, t, 6.

In an analogous manner, 2,2-dimethyl-5-formyl-5-propyl-1,3-dioxane was prepared from 2,2-dimethyl-5-hydroxymethyl-5-propyl-1,3-dioxane.

29ml of a 1.6M solution of n-butyllithium in hexane was added with stirring to a solution of 9.0 g 4-chloroacetophenone-N, N-dimethyl hydrazone in 100 ml of dry tetrahydrofuran at -7O ⁰ C under a nitrogen atmosphere. The mixture was stirred at -7O ⁰ C for 30 minutes. A solution of 9.5 g was then 2,2-dimethyl-5-formyl-5-propyl-1,3-dioxane in 20 ml of dry tetrahydrofuran at -7O ⁰ C. The mixture was slowly warmed to room temperature and then stirred for 5 days at room temperature. Thereafter, water was added and the mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue (16 g) and 50 ml of 2N hydrochloric acid were stirred at room temperature for 24 hours.

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 eluted by chromatography on silica gel eluting with ethenehexane 1: 2. There was obtained 3.5 g of 1- (4-chlorophenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo [2.2.2.] Octane as a waxy solid.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.30; 4H, m; 3.90; 5H, m; 3.00 to 1.70; 3H, m; 1.40 to 0.70; 7H, m.

The infrared spectrum (IR) in Nujol: 3470 (s and br), 1130 (m), 1100 (s), 1030 (s).

Mass spectrum (MS), chemical ionization: M + 1: 283

1- (4-Chlorophenyl) -4-ethyl-8-hydroxy-2,6-dioxabicyclo [2.2.2] octane was prepared in a similar manner.

Physical data: Melting point 97 ° C.

The nuclear magnetic resonance spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.35; 4H, m; 4.00; 5H, m; 3.00 to 1.70; 3H, m; 1.30; 2H, m; 0.90; 3H, m.

Infrared spectrum (IR) in Nujol: 3450 (s and br), 1130 (m), 1100 (s), 1 080 (s), 1 020 (m).

Mass spectrum (MS), chemical ionization: M + 1: 269

Example 6 1- (4-Chloro-phenyl) -8-methoxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane

440μΙ of a 1.6M solution of n-butyllithium in hexane was added with stirring to a solution of 200mg of 1- (4-chlorophenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane in 10 ml dry tetrahydrofuran under a stream of nitrogen at ^{0 0} C given. The mixture was stirred for 30 minutes and then 200 μΙ methyl iodide was added. The mixture was stirred for two days under nitrogen flow at room temperature. Thereafter, water was 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 column chromatography on silica gel, eluting with 1: 10 ethenehexane. There were obtained 66 mg of 2- (4-chlorophenyl) -8-methoxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane as a colorless solid.

The nuclear resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.30; 4H, m; 4.40 to 3.40; 5H, m; 3.30; 3H, s; 2.80 to 1.80; 2H, m; 1.50 to 0.80; 7H, m.

Mass spectrum (MS), chemical ionization: M + 1: 297

Example 7 8-Acetoxy-1- (4-chlorophenyl) -4-propyl-2,6-dioxabicyclo [2.2.2] octane

A solution of 500mg of 1- (4-chlorophenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane and 296μΙ of triethylamine in 20 ml of dry ether was stirred at ⁰ ° C. 125 μl of acetyl chloride were added and the mixture was stirred at room temperature for 24 hours. The mixture was poured into water and the aqueous mixture extracted with diethyl ether. The.

Ether extracts were washed with water, dried over anhydrous magnesium sulfate and the solution was evaporated in vacuo. The residue was purified by column chromatography on silica gel, eluting with diethyl ether: hexane as 1: 6. There were obtained 100 mg of 8-acetoxy-1- (4-chlorophenyl) -4-propyl-2,6-dioxabicyclo [2.2.2] octane as a waxy solid.

The nuclear magnetic resonance spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7.40; 4H, m; 5.20; 1H, d, 8; 4.40 to 3.80; 4H, m; 3.00 to 2.50; 2H, m; 2.20, 3H, s; 1.40-0.8, 7 H, m.

Mass spectrum (MS), chemical ionization: M + 1: 325.

Example 8 1- (4-Chloro-phenyl) -8-oxo-4-propyl-2,6-dioxabicyclo [2.2.2] octane

500 mg V (4-Chlorophenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane were added to a stirred suspension of pyridinium chlorochromate 955mg and 270mg of anhydrous sodium acetate in 20 ml of dry methylene chloride at 0 C ⁰ added under a stream of nitrogen. The mixture was stirred at room temperature for six hours. The mixture was then diluted with 50 ml of diethyl ether and the organic layer was decanted off. The oily residue was treated with diethyl ether and the combined extracts were evaporated in vacuo. The residue was purified by column chromatography on silica gel with diethyl etherhexane as 1: 3 as eluent. There were obtained 240 mg of 1- (4-chlorophenyl) -8-oxo-4-propyl-2,6-dioxabicyclo [2.2.2] octane as a colorless solid (F = 96 ⁰ C).

Gas-liquid chromatography (GLC) on OV-210 at 185 ° C gave a peak. The nuclear magnetic resonance spectrum was as follows: ¹ H (ppm, with TMS as standard in CDCl ₃ , integral, number of peaks): 7.40; 4H, m; 4.20; 4H, s; 3.00; 2H, s; 1.50; 4H, m; 1.00; 3H, m

 Infrared spectrum (IR) in Nujol: 1750 (s), 1 130 (m), 1100 (m), 1 030 (m), 1 010 (m). Mass spectrum (MS), chemical ionization: M + 1: 281.

Example 9 1- (4-Chlorophenyl) -4-propyl-2,6-dioxabicyclo [2.2.2] oct-8-yl methanesulfonate

With stirring, 164 μM methanesulfonyl chloride was added to a solution of 500 mg of 1- (4-chlorophenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo [2.2.2] octane in 2.0 mL of dry pyridine. The mixture was stirred at room temperature for six hours. Thereafter, the mixture was poured into water, and the aqueous mixture was extracted with diethyl ether. The ether extracts were washed with 1N hydrochloric acid. The ether extracts were then washed with a saturated aqueous sodium bicarbonate solution. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was washed with diethyl ether and the remaining solid dried in air. There was obtained 220 mg of 1- (4-chlorophenyl) -4-propyl-2,6-dioxabicyclo [2.2.2] oct-8-yl methanesulfonate as a colorless solid.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks): 7.40; 4H, m; 5.10; 1H, d, 6; 4.30 to 3.8; 4H, m; 3,10, 3H, s; 3.00-2.40; 2H, m; 1.50; 4H, m; 1.00; 3H, m. Mass spectrum (MS), chemical ionization: M + 1: 361

Example 10 1- (4-Bromophenyl) -4-isobutyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane

1) 22.0 g of diethyl isobutylmalonate were added with stirring to a suspension of 4.8 g of a 50% dispersion of sodium hydride in oil in 200 ml of dry toluene under a nitrogen atmosphere. The mixture was stirred at 80 ^° C. for one hour. The mixture was cooled and 16.0 g of benzyl chloromethyl thioether added ⁵ in 50 ml of dry toluene and the mixture stirred for two hours at 80 ⁰ C. The mixture was cooled and then poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. 32.0 g of diethyi-2-benzylthiomethyl-2-isobutylmalonate were obtained as a yellow oil and used without further purification.

2) 32.0 g of diethyl 2-benzylthiomethyl-2-isobutyl malonate in 60 ml of dry diethyl ether were added with stirring to a suspension of 7.0 g of lithium aluminum hydride in 400 ml of dry diethyl ether at ⁰ ° C. under a nitrogen atmosphere. The mixture was stirred for three hours at room temperature and then refluxed with stirring for a further three hours. The mixture was cooled and very carefully added 25 ml of 10% sodium hydroxide solution. The mixture was filtered and the solid washed with ether. The filtrates were dried over anhydrous magnesium sulfate and evaporated in vacuo. 20 g of 2-benzylthiomethyl-2-isobutyl-propane-1,3-diol were obtained as a colorless solid and used without further purification.

3) 7.0 g of 2-benzylthiomethyl-2-isobutyl-propane-1,3-diol in 150 ml of dry diethyl ether were added at -70 ⁰ C to 150 ml of liquid ammonia. To the solution was added 1.8 g of sodium with stirring. It was stirred for another hour at -70 ^0C. Thereafter, the mixture was warmed to -30 ⁰ C and 10 g of solid ammonium chloride carefully added. The ammonia was removed from the reaction mixture by a stream of nitrogen. The residue was washed with dry methylene chloride and the filtrates evaporated in vacuo. There was obtained 2.5 g of 2,2-dihydroxymethyl-4-methylpentane-1-thiol as a colorless, odorous oil which was used without further purification.

4) 1,2,2-Dihydroxymethyl-4-methylpentane-1-thiol and trimethyl-4-bromo-orthobenzoate were prepared using the procedure described in Example 2 but with one drop of concentrated hydrochloric acid as catalyst in place of triethylamine, 90 mg of 1- (4-bromophenyl) -4-isobutyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane was prepared as a colorless solid after recrystallization from hexane.

Analogously, 2,2-dihydroxymethyl-3-methylbutane-1-thiol or 2,2-dihydroxymethyl-3-methylpentane-1-thiol and trimethyl-4-bromo-orthobenzoate or trimethyl-4 were prepared chloro-orthobenzoate or trimethylorthocyclohexylcarboxylate, the following compounds are prepared: 1- (4-bromophenyl) -4-isopropyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane,

1- (4-chlorophenyl) -4-s-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane,

4-s-butyl-1-cyclohexyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane.

3,3-Dihydroxymethyl-hexane-2-thiol and 3,3-dihydroxymethyl-5-methylhexane-2-thiol were prepared in an analogous manner from diethylpropyl malonate and diethyl isobutyl malonate and benzyl 1-chloroethyl thioether ⁶ .

3,3-Dihydroxymethyl-hexane-2-thiol or 3,3-di-hydroxymethyl-5-methylhexane-2-thiol were reacted with trimethyl 4-bromoorthobenzoate ² or trimethyl orthocyclohexylcarboxylate ³ in an analogous manner and thereby the following Made connections:

1- (4-bromophenyl) -8-methyl-4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1-cyclohexyl-8-methyl-4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

1- (4-bromophenyl) -4-i-butyl-8-methyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane.

2,2-Dihydroxymethylhexan-1-thiol was prepared in an analogous manner from diethyl n-butylmalonate and converted to 2,2-dihydroxymethyl-4-methylpentan-1-thiol.

By analogy with the compounds described above, trimethyl 4-bromoorthobenzoate ² and 2,2-dihydroxymethylhexane-1-thiol were 1- (4-bromophenyl) -4-n-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane (F = 110-112 ⁰ C).

Example 11 1- (4-Bromophenyl) -4-t-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane

i) With stirring, 1.25 g of a 50% dispersion of sodium hydride in oil was added to a solution of 3.2 ml of benzylmercaptan in 75 ml of dry dimethylformamide at ⁰ ° C. under a stream of nitrogen. It was stirred for a further 30 minutes. To this was then added 7.5 g of 5-t-butyl-2,2-dimethyl-5-hydroxymethyl-1,3-dioxane methanesulfonate and the mixture was stirred at 130 ^° C. for 7 hours. The reaction mixture was cooled and poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and then evaporated in vacuo. There were obtained 7.0 g of 5-benzylthiomethyl-5-t-butyl-2,2-dimethyl-1,3-dioxane as a light oil and used further without further purification.

-14- 260 49S

ii) 7.0 g of δ-benzylthiomethyl-St-butyl ^^ -dimethyl-i, -dioxane and 0.6 g of Dowex 50 χ 8-200 ion exchange resin (fT-form) in 100 ml of methanol and 10 ml of water were stirred for 3 hours cooked at reflux. The mixture was filtered and the filtrate evaporated in vacuo. There was obtained 5.0 g of benzylthiomethyl-2-hydroxymethyl-3,3-dimethylbutan-1-ol as a colorless oil which was used without further purification.

iii) 5.0 g of 2-benzylthiomethyl-2-hydroxymethyl-3,3-dimethyl-butan-1-ol in dry diethyl ether was added at -7O ⁰ C to 250 ml of liquid ammonia. To the solution 2.0 g of sodium were stirred with stirring and then added a further hour at -7O ⁰ C. The mixture was then warmed to room temperature while passing nitrogen over it. Then, 20.0 g of solid ammonium chloride was added. The mixture was filtered and the solid washed with 100 ml of methanol. The filtrates were evaporated in vacuo. The resulting solid was washed with 500 ml of chloroform.

The washings were evaporated in vacuo. There was obtained 4.0 g of 2,2-dihydroxymethyl-3,3-dimethylbutan-1-thiol as a crystalline solid.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

4.00; 4H, s; 3.20 to 2.90; 4H, m; 1.90; 1H, t, 7; 1.10; 9H, s.

Mass spectrum (MS), chemical ionization: M + 1: 179.

From 2,2-dihydroxymethyl-3,3-dimethylbutane-1-thiol and trimethyl 4-bromoorthobenzoate, trimethyl 4-chloroorthobenzoate, trimethyl orthocyclohexylcarboxylate and trimethyl orthocycloheptylcarboxylate, the following compounds were prepared using the method described above:

1- (4-bromophenyl) -4-t-butyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-t-Butyl-1- (4-chlorophenyl) -2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-tert-butyl-1-cyclohexyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane;

4-tert-butyl-1-cycloheptyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane.

Examples 1- (4-Chloro-henyl) -4-isobutyl-2-oxa-6,7-dithiabicyclo [2.2.2] octane

i) 26.0 ml of methanesulfonyl chloride were added dropwise, with stirring, to a solution of 41.6 g of 2-benzyloxymethyl-2-hydroxymethyl-4-methylpentan-1-ol (prepared from diethyl isobutyl malonate in a manner analogous to that used for the Preparation of 2-benzyloxymethyl-2-cyclohexyl-propane-1,3-diol described in Example 16) and 30 ml of dry pyridine in 300 ml of dry diethyl ether at 0 ° C. The mixture was stirred at room temperature for 24 hours, after which the mixture was poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with 1N hydrochloric acid, then with saturated sodium bicarbonate solution and finally with water. The ether extracts were dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by chromatography on silica gel, eluting with diethyl ether: hexane as 1: 1. There were obtained 23 g of 2-benzyloxymethyl-hydroxymethyl-methylpentan-i-bis-bismethanesurfonate as an oil.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

7.40; 5H, s; 4.60; 2H, s; 4.30; 4H, s; 3.60; 2H, s; 3:10; 6H, s; 2.20 to 1.00; 9H, m.

Mass spectrum (MS), chemical ionization: M + 1: 409.

ii) 1-Benzyloxy-2,2-bis- (benzylthiomethyl) -4-methyl-pentane was prepared from S-benzyloxymethyl-hydroxymethyl-methyl-pentane-1-ol and dimethanesulfonate by a method analogous to that used for the synthesis of Benzylthiomethyl-5-tert-butyl-2,2-dimethyl-1,3-dioxane.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J ₂ ):

7.10; 15H, m; 4.40; 2H, s; 3.60; 4H, s; 3.30; 2H, s; 2.50; 4H, s; 1.80 to 0.80; 9H.

Mass spectrum (MS), chemical ionization: M + 1: 465.

2-Isobutyl-2-hydroxymethyl-propane-1,3-thiol was prepared from 1-benzyloxy-2,2-bis (benzylthiomethyl) -4-methyl-pentane by a method similar to that used for the synthesis of 2, 2-bis- (hydroxymethyl-3,3-dimethyl-1-butanediol.

1- (4-Chloro-phenyl) -4-isobutyl-2-oxa-6,7-dithiabicyclo [2.2.2] octane was prepared from 2-isobutyl-2-hydroxymethyl-propane-1,3-thiol and 4-chloro trimethyl ortho-benzoate was prepared by a method described above.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

7.65; 2H, d, 7; 7, 45; 2H, d, 7; 4.25; 2H, s; 3:10; 4H, m; 1.75,1 H, m; 1.30, 2H, d, 6; 1.00, 6H, d, 6.

Mass spectrum (MS), chemical ionization: M + 1: 315

2-hydroxymethyl-2-propyl-propane-1,3-thiol was reacted by an analogous procedure to 2-losbutyl-2-hydroxymethyl-propane-1,3-dithiol, whereby 2-benzyloxymethyl-2-propyl-propane 1,3-diol was assumed.

1- (4-Bromo-phenyl) -4-propyl-2-oxa-6,7-dithiabicyclo [2.2.2] octane was obtained from trimethyl 4-bromo-orthobenzoate and 2-hydroxymethyl-2-propyl-propane-1 , 3-dithiol produced.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

7.50; 4H, m; 4.20; 2H, m; 3:10; 4H, m; 1.35; 4H, m; 0.95; 3H, m.

Mass spectrum (MS), chemical ionization: M + 1: 347.

Example 13 1-Cyclohexyl-4-propyl-2,6,7-trithiabicyclo [2.2.2] octane

Starting from 2-hydroxymethyl-2-propyl-propane-1,3-diol and using a reaction procedure analogous to that in Example 12, 1-cyclohexyl-4-propyl-2,6,7-trithiabicyclo [2.2. 2] octane produced as a clear oil. ,

The nuclear magnetic resonance spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

3.00; 6H, s; 2.00 to 0.80; 18H, m.

Mass spectrum (MS), chemical ionization: M + 1: 289.

Example 14

i) 14.2 g of 2-benzylthiomethyl-2-propyl-propane-1,3-diol (prepared from propylmalonic acid diethyl ester by a method analogous to that used for the synthesis of 2-benzylthiomethyl-2-isobutyl-propane 1,3-diol used in Example 10) in 100 ml of dry tetrahydrofuran were stirred at 0 ^° C. under a stream of nitrogen. To the solution, 2.7 g of a 50% dispersion of sodium hydride in oil was carefully added, and the mixture was stirred at 20 ° C for one hour. 9.6 g of benzyl bromide were added carefully and the reaction mixture was refluxed with stirring for 12 hours. The mixture was cooled and poured into water. The aqueous mixture was extracted with diethyl ether. The ether extracts were washed with water, dried over anhydrous magnesium sulfate and then evaporated in vacuo. 22g 2-Benzyloxymethyl-2-benzylthiomethyl-pentane-1-oil was obtained as a pale yellow oil and used without further purification.

ii) 5 g of 2-benzyloxymethyl-2-benzylthionnethylpentan-1-ol were added with stirring to a suspension of 5 g of pyridinium chlorochromate and 3.0 g of anhydrous sodium acetate in 20 ml of dry methylene chloride at ⁰ ° C. under a stream of nitrogen. The mixture was stirred at room temperature for three hours. The reaction mixture was then diluted with 100 ml of diethyl ether and the organic solution was decanted off. Ether was added to the oily residue and the combined extracts were evaporated in vacuo. The residue was chromatographed on silica gel, eluting with ethyl acetate: hexane as 1:10. There were obtained 1.9 g of 2-benzyloxymethyl-2-benzylthiomethyl-pentanal as a colorless oil.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

9.50,1H, s; 7,30,10H, s; 4.50, 2H, s; 3.80, 2H, s; 3.65, 2H, s; 2.95, 2 H, s; 1.80-0.80, 7H, m.

Infrared spectrum (IR) as liquid film: ν 1735cm " ¹ .

Mass spectrum (MS), chemical ionization: M + 1: 343.

iii) 4.0 ml of a 3 M solution of methylmagnesium iodide in ether was added to a solution of 2.6 g of 2-benzyloxymethyl-2-benzylthiomethylpentanal in 50 ml of dry diethyl ether at ⁰ ° C. The mixture was refluxed with stirring for 2 hours. The mixture was cooled and poured into 1 N hydrochloric acid in ice. 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 chromatographed on silica gel, eluting with diethyl ether. There were obtained 0.7 g of 3-benzyloxymethyl-3-benzylthiomethyl-hexan-2-ol as a colorless oil.

Gas-liquid chromatography (GLC) on OV-101 at 250 ° C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm, with TMS as standard in CDCl ₃ , integral, number of peaks):

7,30,10H, s; 4.40, 2H, m; 4.00-3.00, 6H, m; 2.95-2.40, 2H, m; 1,60-0,70,10H, m.

Mass spectrum (MS), chemical ionization: M + 1: 359.

iv) and v) 1- (4-Bromo-phenyl) -3-methyl-4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane (oil) was prepared from 3-benzyloxymethyl-3-benzylthiomethyl hexane-2-ol and trimethyl 4-bromo-orthobenzoate were prepared using the method of steps iii) and iv) of Example 10.

The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7,40,4H, s; 4,60-3,90,3H, m; 3,00,2H, m; 1.60-0.80, 10H, m. ;

Mass spectrum (MS), chemical ionization: M + 1: 343, 345.

Example 15 1- (4-iodo-phenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane

i) 16 ml of a 1.6M solution of butyllithium in hexane were added with stirring to a solution of 1.7 g of 1- (4-bromo-phenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] given octane in 150 ml of dry diethyl ether at -70 ⁰ C under nitrogen. The reaction mixture was slowly warmed to room temperature, with the progress of the reaction monitored by GLC analysis. After all of the starting material had been consumed, 6.6 g of iodine in 50 ml of dry diethyl ether were added, followed immediately by an aqueous solution of 10 g of sodium thiosulfate in 70 ml of water. The mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo. The residue was purified by chromatography on alumina (Alumina Woelm TSC) eluting with methylene chloride: hexane as 1:10 saturated with ammonia. There were obtained 0.8 g of 1- (4-iodo-phenyl) -4-propyl-2,6-dioxa-7-thiabicyclo [2.2.2] octane as colorless crystals (F = 128-132 ° C).

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ): 7.70, 2H, d, 7; 7, 40, 2H, d, 7; 4,15,4H, m; 3,10, 2H, m; 1.30, 4H, m; 0.95, 3H, m. Mass spectrum (MS), chemical ionization: M + 1: 377.

Example 16 1- {4-Cyano-phenyl) -4-cyclohexyl-7-methyl-2,6-dioxa-7-azabicyclo [2.2.2] octane

i) 18.7 g of diethyl cyclohexylmalonate were added with stirring to a suspension of 4.8 g of a 50% dispersion of sodium hydroxide in oil and 50 ml of dry tetrahydrofuran under a nitrogen atmosphere. The mixture was refluxed for one hour. The mixture was cooled and 13.9 g of benzyl chloromethyl ether in 50 ml of dry tetrahydrofuran were added and the mixture was then refluxed for three hours with stirring. The mixture was then 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. There were thus obtained 30 g of diethyl 2-benzyloxymethyl-2-cyclohexyl-malonate as a brown oil and used without further purification, ii) 2 g of 2-benzyloxymethyl-2-cyclohexyl-malonsäurediethylester were at ^{0 0} C to a suspension of 0.63 g Lithium aluminum hydride in 30 ml of dry ether under nitrogen atmosphere. The mixture was stirred at room temperature for 12 hours. Then 5 ml of water were then added carefully and the mixture was then stirred for 10 minutes. To this was added 10 ml of 10% sulfuric acid and the mixture was extracted 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 gel, eluting with ether: hexane = 1: 1. There was obtained 1.0 g of 2-benzyloxymethyl-2-cyclohexyl-propane-1,3-diol as a colorless oil.

Gas-liquid chromatography (GLC) on OV-210 at 23O ⁰ C gave a peak.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, Jh _z ):

7:35, 5H, s; 4,55, 2H, s; 3.75, 4h, d, 6; 3,60, 2H, s; 2.90, 2H, t, 6; 2,00-0,90,11 H, m.

iii) 5,5g2-benzyloxymethyl-2-cyclohexyl-propane-1,3-diol in 50 ml dry diethyl ether was added at-70 ⁰ C to 200 ml of liquid ammonia. To the solution was added 2.5 g of sodium while stirring. It was stirred for another hour at -70 ^0C. The reaction mixture was then warmed to 0 ⁰ C and added 15 g of solid Ammoniumchiorid cautiously. The ammonia was removed from the reaction mixture by a stream of nitrogen. To the mixture was added 25 ml of methanol to destroy unconsumed sodium. 400 ml of methylene chloride were then added and the mixture was filtered. The filtrates were evaporated in vacuo. There were obtained 3.2 g of 2-cyclohexyl-2-hydroxymethyl-propane-1,3-diol as a colorless solid. The nuclear magnetic resonance spectrum (NMR) was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

3,80, 6H, s; 3.30, 3H, s; 2,00-0,80,11 H, m.

iv) A mixture of 3.76 g of 2-cyclohexyl-2-hydroxymethyl-propane-1,3-diol, 2.42 ml of ethyl carbonate and 0.1 ml of a solution of 5 g of potassium hydroxide in 25 ml of ethanol was refluxed for 20 minutes. The apparatus was then converted to distillation. The ethanol is removed (78-8O ⁰ C at 760 mm Hg) was removed by distillation. After all of the ethanol had been distilled off, the residue was distilled under reduced pressure to distill 3-cyclohexyl-3-hydroxy-oxetane as a colorless oil.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

4,50,4H, s; 3,75,2H, d, 6; 2,6,1 H, t, 6; 2,00-1,00,11 H, m. Infrared spectrum (IR) as liquid film: 3400 (s and br), 1150 (s),

Mass spectrum (MS), chemical ionization: M + 1: 171.

v) 7.0 g of S-cyclohexyl-S-hydroxymethyloxetane were dissolved in 20 ml of dry methylene chloride and added dropwise to a solution of 1.1 equivalents (4 ml) of oxalyl chloride in 15 ml of dry methylene chloride. At -70 ⁰ C a solution of 7.15 ml of dimethyl sulfoxide was added 10 ml Methyienchlorid. After 30 minutes at -7O ⁰ C was stirred, 29 ml of triethylamine were added within 30 minutes: Within three hours the reaction mixture was slowly warmed to room temperature and then the reaction was stopped by pouring into water. Extraction with methylene chloride followed by washing with dilute hydrochloric acid, saturated sodium bicarbonate solution and brine and finally drying over magnesium sulfate gave a solution which was evaporated to give 3-cyclohexyl-3-formyloxetane as a colorless oil.

The nuclear magnetic resonance (NMR) spectrum was as follows: ¹ H (ppm with TMS in CDCl ₃ , integral, number of peaks, J _Hz ):

9,80,1 H, s; 4.68, 2H, d, 6; 4.50, 2H, d, 6; 2.05-1.00.11 H, m. Infrared spectrum (IR) as liquid film: 1 720 (s), 980 (s).

vi) 1.7 g of S-cyclohexyl-S-formyloxetan were dissolved at 25 ⁰ C in 10 mL of methanol. Successively, 3.3 g of anhydrous sodium acetate, 3.4 g of methylamine hydrochloride and 630 mg of sodium cyanoborohydride were added, followed by another 30 ml of methanol. The mixture was stirred overnight and then basified with 22 ml of 1N sodium hydroxide solution and a pH of 9 was set. Extraction with ether, washing and drying followed by evaporation gave S-cyclohexyl-S-methylaminomethyloxetane as a colorless oil.

The nuclear magnetic resonance (NMR) spectrum was as follows: - (ppm with TMS in CDCl ₃ , integral, number of peaks, J _Hz ):

4, 49, 2H, d, 5; 4.35, 2H, d, 5; 2.75, 2H, s; 2.50, 3H, s; 2.05-1, 10, 11H, m.

Infrared spectrum (IR) as liquid film: 3300 (w) and (br), 980 (s).

Mass spectrum (MS), chemical ionization: M + 1: 184.

vii) 0,166g 4-cyanobenzoyl chloride in 5 ml of methylene chloride were added with stirring to a solution of 0,183g 3-cyclohexyl-3-methylaminomethyl-oxetane and 0,42ml triethylamine in 5 ml of methylene chloride at 0 ^0C. After being stirred overnight, the reaction mixture was poured into saturated sodium bicarbonate solution. Extraction with ether gave a crude product, which was purified by chromatography on alumina, eluting with methylene chloride: hexane as 1: 1, saturated with ammonia. 3- [N- (4-cyanobenzoyl) -N-methylaminomethyl] -3-cyclohexyl-oxetane was obtained as a colorless oil.

The nuclear magnetic resonance spectrum (NMR) was as follows: - (ppm, with TMS as standard in CDCl ₃ , integral, number of peaks, J _Hz ):

7, 75, 2H, d, 8; 7:50, 2 H, d, 8; 4,54,4H, s; 3.73, 2H, s; 3.09 3H, s; 2,05-0,95,1 VH ₁ m.

Infrared spectrum (IR) as liquid film: 2200 (s), 1640 (s), 1070 (m), 980 (m).

Mass spectrum (MS), chemical ionization: M + 1: 313.

viii) With stirring were 37,2μΙ -N-methylaminomethyll-3-cyclohexyl-oxetane in 3 ml of methylene chloride at -70 ⁰ C under a nitrogen atmosphere, boron trifluoride etherate (to a solution of 281 mg 3- [N- 4-cyanobenzoyl) ,

After being stirred overnight, additional 110μΙ boron trifluoride etherate was added to the mixture. After being stirred for a further 24 hours, the mixture was poured into 20 ml of methylene chloride saturated with ammonia.

By nitriding and evaporation, 1- (4-cyanophenyl) -4-cyclohexyl-7-methyl-2,6-dioxa-7-azabicyclo [2.2.2] octane was obtained as pale yellow crystals.

The nuclear magnetic resonance (NMR) spectrum was as follows: - (ppm with TMS as standard in CDCl ₃ , integral, number of peaks):

7,60,4H, s; 3,95,4H, s; 2,95, 2H, s; 2,04, 3H, s; 1,90-1,00,11 H, m.

Infrared Spectrum (IR) in Nujol: 2220 (s), 1,140 (m), 1,080 (s), 1,030 (m), 990 (m).

Mass spectrum (MS), chemical ionization: M + 1: 313.

Literature:

1. V. Gash, J. Org. Chem. 37, 2197 (1972) _;

1 a. W. E. Conrad, L. A. Levasseur, R. F. Murphy, N. LHare, H. E. Conrad, J. Org. Chem., 27, 2227 (1962).

2. S.M. McElvain, J. T. Venerable, J. Amer. Chem. Soc. 72,1661 (1950)

3. S.M. McElvain, R.E. Stam, J. Amer. Chem. Soc. 77, 4571 (1955)

4. Y.Ozoe, M.Eto, Agric. Biol. Chem. 46,411 (1982)

5. J.L. Wood, V. duVigneaud, J. Biol. Chem. 131, 267 (1939)

6. I.VIattas, L.D. Vecchia, J.J. Fitt, J. Org. Chem. 38, 3749 (1973)

17- 260 499 Y ¹ Y Z R • et R ¹ R ² R ³ F masses 297 281 infrared spectrum Syntheses. Data for characterizing a series of compounds according to the invention are given in the following table: spectrum Wax 325 example No. d. Pr. Chem. Ioni 96 361 Cpd. et ( ⁰ C) sation pr (M + 1) firmly 343.345 O O CH ₂ CH ₂ pr H 4-Clphenyl H 78 253 1 130 (s), 1 100 (m), 1090 (m), 1 135- 329.331 1 070 (m), 1020 (s) 1 O O CH ₂ CH ₂ t-Bu H 4-Clphenyl H 94 267 138 343.345 1130 (s), 1080 (m), 1020 (s) 1 S O CH ₂ O et H 4-Brphenyl H firmly 315.317 firmly 299 1090 (s), 1035 (m), 1022 (w) 2 CM S O CH ₂ O H 4-Brphenyl H firmly 329.331 firmly 271 1080 (s), 1040 (s), 1020 (m) 2 - 3 O O CH ₂ CH ₂ O pr H cyclohexyl H oil 255 firmly 343.345 1114 (s), 1070 (s), 1040 (s), 3 4 firmly 1010 (m) 5 O O CH ₂ CH ₂ pr H 4-Clphenyl H 155 281 120- 271 1 130 (s), 1 100 (s), 1015 (s) 4 O O CHOHCH ₂ pr H 4-Clphenyl H 97 269 121 357.359 3450 (s, br), 1 130 (m) 5 6 pr oil 1 100 (s), 1080 (s), 1020 (m) 7 O O CHOHCH ₂ H 4-Clphenyl H Wax 283 101- 343.345 3470 (s, br), 1 130 (m) 5 pr 102 1 100 (s), 1030 (s) 8th O O CHOMeCH ₂ H 4-Clphenyl H firmly 193- 299 6 O O CHOAcCH ₂ Bu H 4-Clphenyl H 195 7 9 O O COCH ₂ H 4-Clphenyl H 162- 271 1750 (s), 1 130 (m), 1 100 (m), 8th 10 iPr 164 1030 (m), 1010 (m) 11 O O CH (OSO ₂ - sBu H 4-Clphenyl H 140- 285 9 Me) CH ₂ sBu 141 12 S O CH ₂ O sBu H 4-Brphenyl H 142- 315 10 nPr 143 345.347 13 S O CH ₂ O H 4-Brphenyl H firmly 289 10 s O CH ₂ O nPr H 4-Brphenyl H firmly 1080 (m), 1045 (s), 1020 (m) 10 14 S. O CH ₂ O Bu H 4-Clphenyl H oil 343.345 1 045 (s) 10 15 S O CH ₂ O H cyclohexyl H ' 343.345 1 035 (s) 10 16 S O CH ₂ O Bu me 4-brphenyl H oil 1 090 (s), 1032 (s), 1 020 (s) 10 17 110- 377 18 S O CH ₂ O Bu me cyclohexyl H 112 1080 (m), 1060 (s), 1030 (s) 10 S O CH ₂ O me 4-Brphenyl H 128 313 1 090 (s), 1 050 (s), 1 025 (s) 10 19 Bu 132 20. S O CH ₂ O H 4-Brphenyl H firmly 1095 (m), 1045 (s), 1020 (s) 11 Bu 21 S O CH ₂ O H 4-Clphenyl H 1 100 (m), 1 043 (s), 1028 (s) 11 Bu 22 S O CH ₂ O nPr H cyclohexyl H 1090 (m), 1040 (s), 1012 (s) , 11 hPr 23 S O CH ₂ O H cyclo H 1080 (m), 1020 (m), 995 (s) 11 nPr heptyl 24 S O CH ₂ S nBu H 4-Clphenyl H 12 S O CH ₂ S H 4-Brphenyl H 12 25 S S CH ₂ S nPr H cyclo H 13 26 hexyl 27 S O CH ₂ O cyclo H 4-Brphenyl me 1070 (s), 1010 (s) 14 S O CH ₂ O hexyl H 4-Brphenyl H 10 28. 29 S O CH ₂ O H 4-lphenyl H 15 30 O NMe CH ₂ O H 4-CN H 2 220 (s), 1 140 (m), 1 C30 (s), 16 phenyl 1030 (m), 990 (m) 31

Biological activity A. Lethale activity against house flies

The activity of compounds according to the invention against unanesthetized female houseflies (WRL strain) was determined by applying a solution of the test compound in butanone to the surface of the test insect.

The activity of the compound to be tested was also found in conjunction with the synergist piperonyl butoxide (6 μg PB per insect). The killing rate was determined after 24 and 48 hours.

The following compounds had less than 30 μg / fly activity: 2,3,6, 8,11,14,17,18,19, 20,23, 27,29,30.

The following compounds exhibited activity at less than 1 pg / av: 4.13, 15, 21, 22, 24, 25, 28.

B. Lethale activity against Blattella germanica

The activity of compounds of the invention against unanesthetized male Blattella germanica (WRL strain) was determined by applying a solution of the compound of interest in butanone to the surface of the test insect. The activity of the compound to be tested was determined in conjunction with the synergist piperonyl butoxide (10 μg / insect). The killing rate was determined after 24 and 48 hours.

The following compounds had activity at less than 50 μg / insect: 2,3,8,9,14,15,17,18,19,20,21,22,23. The following compounds had activity at less than 5 μg / insect: 4.13.

C. Lethale activity against Sitophilus granarius

The activity of compounds of the invention against adult S. granarius was demonstrated by the addition of an acetonic solution of the compound to grains, which were later presented to the insects. The killing rate was determined after 6 days.

The following compounds had activity of less than 200 ppm acetone solution: 4,15,16,17,18,19,20,21,22,23,

The following compounds exhibited activity with less than 50 ppm acetone solution: 13, 14, 25.

D. Lethale's activity against Culex quinquefasciatus' "

The activity of compounds of the invention against female Culex adults was demonstrated by direct spraying with O, 5 ml of the compound in OPD / methylene chloride. The killing rate was determined after 24 hours. The following compounds had less than 1% activity: 4,5,13,14,15,16,19, 21,22,25,27,28,30.

E. Toxicity in mammals

Compound 4 has an LD ₅₀ rate of greater than 200 mg / kg when administered orally to mice (Charles River CD 1). The following schemes are illustrative of the synthesis of intermediates used in the preparation of compounds of this invention

Alk = alkyl, R, R ¹ , R ² , etc. have the meaning as in the description.

Claims (7)

claims: 1. A process for the preparation of a bicycloheptane, octane or nonane, characterized in that a compound of formula J
R E ³ (I) wherein R is a C ₂ _io-alkyl, alkenyl or alkynyl group, each of which may optionally be substituted by a cyano, C3 ^ -cycloalkyl-vCi_4-alkoxy group or halogen or methyl-substituted, or by a group S (0) _m R ⁴ , wherein R ^{4 is} a C 1-4 alkyl group and m is 0.1 or 2, or wherein R is a C 1-6 cycloalkyl, C 1-6 cycloalkenyl or phenyl group, each optionally substituted by a C 1-4 alkoxy -, Ci_3-alkyl, C ₂ -4 alkenyl, C ₂ -4 alkynyl, cyano, halogen or an S (0) _m R ⁴ moiety, which is as defined above, is substituted; R ¹ is hydrogen, halogen, a grouping COOR ^4, wherein R ⁴ is a C | _4 alkyl group, a CI_ ₃ alkyl, C ₂ _3 alkenyl or alkynyl group, each in turn substituted by halogen, cyano or Ci ^ Alkoxy group is optionally substituted, an alkylcarbalkoxy group having up to 6 carbon atoms, an S (O) _m R ⁴ moiety as hereinbefore defined, or R ¹ is a cyano, gem-dimethyl, spiro-cyclopropyl , gem-dicyan, gem-diethynyl, oxo or methylene group, each of which may optionally be substituted by a cyano or CF ₃ group, or R ¹ is a C ₂ _ ₃ alkynyl group which is represented by a tri C ¹ -C 4 -alkylsilyl group, or R ¹ and R and the carbon atoms to which they are attached form a C 1 -C 4 -carbocyclic ring optionally substituted by halogen, C 1-3 -alkyl or -alkoxy or C ₂ _ _3- alkenyl group is substituted; R ^{2 represents} a phenyl, Cs ^ cycloalkyl or cycloalkenyl group, each of which may be substituted; R ³ is hydrogen, C ^ alkyl, C ₂ _ ₃ alkenyl or alkynyl group, by a cyano, Ci ^ alkylthio, in each case optionally C - ^ - alkoxy group may be substituted or halogen, or R ³ represents a cyano group or halogen; { Y and Y ^{1 may be the} same or different and may denote oxygen or S (O) _m , wherein m is 0.1 or 2; Z is CH ₂ CH ₂ , CH ₂ CH ₂ O, sulfur, CH ₂ O, CH ₂ S, CHR ^{1 x} NR ⁵ , where R ^{1 is} hydrogen, halogen, a cyano, a COOR ⁴ group or a C _1-3 - Alkyl group, C ₂ _ ₃ alkenyl or alkynyl group, each optionally substituted by halogen, a cyano, C ₁ ^ -AIkOXy-, Alkylcarbalkoxygruppe having up to 6 carbon atoms or an S (0) _m R ⁴ moiety, wherein m and R ^{4 are} as previously defined and R ^{5 is} hydrogen, benzyl, C 1-4 alkyl, C (O) R ⁶ group wherein R ^{6 is} C 1-4 alkyl, alkoxy or NHR ⁷ moiety, wherein R ⁷ is a C ^ alkyl, C ₇ _8-aralkyl or phenyl group may be, which may be substituted by halogen, or Z is a-CO · CH ₂ -or-CH (oR ⁸ ) CH ₂ group, wherein R ⁸ is hydrogen, C ^ alkyl, C ₁ or C ₂ _7 ^ -ACyI--carbamoyl group or a SO ₂ R ⁴ moiety, wherein R ⁴ is a C ^ -Alkyjgruppe, and wherein the atom first named in the definition of Z is the 4-position of bicyclic adjacent ring system is adjacent;
on condition that (i) when ZCHR ^1x NR ⁵ , R ¹ and R ³ must be hydrogen; (H) if both YaIs and Y ^{1 are} oxygen, Z does not mean CH ₂ O; (iii) R ² does not denote a phenyl group represented by an optionally substituted C ₂ _ ₃ - Alkynyl group is substituted;
is made by a) when X contains a heteroatom, an orthocarboxylic acid ester of the formula R ² C (OR ⁹ I _{3 is} condensed with a compound of formula (Ij):
"" R. ~~ \ : ·. , (in wherein R, R ¹ , R ² and R ³ are as hereinbefore defined, R ^{9 is} a C 1-4 alkyl, phenyl or C ₇ _g aralkyl group, Y ² and Y ³ , the same or different each O or S and Z ^{1 is} a group CH ₂ CH ₂ OH, SH, CH ₂ OH, CH ₂ SH or CHR ^1x NHR ⁵ , wherein R ¹ and R ^{5 have} the meaning as already defined in claim 1 with the proviso that both Y ² and Y ^{3 are} not oxygen when Z ^{1 is} a CH ₂ OH moiety; or when Z is a CH ₂ CH ₂ moiety and both Y and Y ^{1 are} oxygen, a compound of the formula wherein R, R ¹ and R ^{2 are} as defined above, R ^{10 is} a protecting group for hydroxyl groups and R ^{11 is} a Ci_4-alkyl group, after cleavage of protective groups is cyclized; or when Z is a CH (OR ⁸ ) CH _{2 group} and Y and Y ^{1 are} each oxygen, a compound of the formula (III A) (MA) wherein R, R ¹ and R ^{2 are} as defined above, R ^{10 is} a protective group for hydroxyl groups and R ^{11 is} a C 1-4 -alkyl group, after cleavage of the protective groups to a compound of formula (I) is cyclized, this 8 -OH substituent, and this 8-OH group is converted to an 8-OR ⁸ grouping; or when both Y and Y ^{1 are} oxygen and Z is a CH ₂ R ³ NHR ⁵ grouping, a compound of the formula (IV) (IV) wherein R, R ² , R ³ and R ^{5 are} as defined above, cyclized in the presence of an acidic catalyst. 2. The method according to claim 1, characterized in that R represents an n-propyl, η-butyl, i-butyl, t-butyl or cyclohexyl group. 3. The method according to claim 1 or 2, characterized in that R ^{1 is} hydrogen, a methyl or trifluoromethyl group. 4. The method according to any one of the preceding claims, characterized in that R ^{2 is} a phenyl, cyclohexyl or cycloheptyl, which optionally in the positions 3,4 and / or 5 at least once by chlorine, bromine, iodine, cyano, azide - or nitro groups may be substituted, or that R ^{2 is} a phenyl group which is substituted in the 2- and / or 6-position by fluorine. 5. The method according to any one of the preceding claims, characterized in that R ^{3 is} hydrogen or a methyl group. ; 6. The method according to any one of the preceding claims, characterized in that Y is oxygen, Y ¹ oxygen and Z is CH ₂ O or CH ₂ S mean. 7. The method according to claim 1, characterized in that the compound prepared is a compound of formula (I A): _R 3a R ^{a Z} I (IA) wherein R ^a is a C ₂ _ ₇ alkyl, alkenyl or alkynyl group which is substituted in each case optionally substituted by halogen, cyano or _C1 ^ ₁ -Al koxygru ρ pe, or R ^a is a C3_i ₀ cycloalkyl, C ^ o-cycloalkenyl or phenyl, each optionally substituted by a C ₁ ^ -AIkOXy-, CI_ ₃ alkyl, C ₂ ^ rAlkinyl-cyano group or halogen substituted; R ^{1 a is} hydrogen, a C ^ alkyl, C ₂ _ ₃ alkenyl or alkynyl group, each optionally substituted by a cyano, C ^ alkoxy, C ₁ ^ alkylthio, alkyl-cärbalkoxygruppe with up to 6 carbon atoms, or halogen, or R ^{1 a} represents a cyano or gem-dimethyl, or R ^1a and R ^a and the carbon atoms to which they are attached form a C ^ ₇ carbocyclic ring optionally substituted by a Ci- Substituted 3-alkyl or alkoxy group; R ^{2a represents} a phenyl, C _5-10 cycloalkyl or cycloalkenyl group, each of which may optionally be substituted; R ^{3a is} hydrogen, a Ci_ ₃ alkyl, C ₂ _ ₃ alkenyl or alkynyl group, which may be substituted by a cyano, Ci ^ alkylthio, Ci ^ -AI koxygru ρ pe or halogen optionally substituted; Y ^a and Y ^{1 a are the} same or different and are both oxygen and S (O) _m ^a , where m ^{a can be} 0.1 or 2; Z ^{a represents} a CH ₂ CH ₂ , CH ₂ CH ₂ O group, sulfur, CH ₂ O, CH ₂ S or a CH ₂ NR ^4a group in which R ^{4a represents} hydrogen, a benzyl, C 1-4 alkyl group, one C (O) R ^5a moiety, wherein R ^5a is a C ^ alkyl or alkoxy group, group, or Z is a-CO · CH ₂ - or -CH (oR ^6a) CH ₂ group, in which R ^6a denotes hydrogen, a C 1-4 -alkyl or C 1-4 -acyl group, with the proviso that in the case of Y ^a and Y ^1a both mean oxygen, Z ^{a is} not CH ₂ O-grouping. 8. The method according to claim 1, characterized in that the compound prepared 1- (4-bromo-phenyl) -4-i-butyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 1- ( 4-Bromo-phenyl) -4-i-propyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 1- (4-bromo-phenyl) -4-s-butyl-2,6- dioxa-7-thiabicyclo- (2.2.2) octane, 1- (4-chlorophenyl) -4-s-butyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 4-s Butyl-1-cyclohexyl-2,6-dioxa-7-thiabicyclo (2.2.2) octane,
1- (4-Bromo-phenyl) -3-methyl-4-propyl-2,6-dioxa-7-thiabicyclo (2.2.2) octane, 1-cyclohexyl-5-propyl-2,7,8-trioxabicyclo ( 2.2.2) nonane,
1- (4-chloro-phenyl) -4-propyl-2,6-dioxabicyc! O (2.2.2) -octane,
1- (4-Bromophenyl) -4-propyl-2,6-dioxa-7-thiabicyclo (2.2.2) octane, 4-t-butyl-1- (4-chloro-phenyl) -2,6-dioxabicyclo ( 2.2.2) octane,
1- (4-Chloro-phenyl) -8-hydroxy-4-propyl-2,6-dioxabicyclo (2.2.2) octane, 1- (4-chloro-phenyl) -8-methoxy-4-propyl-2 , 6-dioxabicyclo (2.2.2) octane, 1- (4-chloro-phenyl) -8-oxo-4-propyl-2,6-dioxabicyclo (2.2.2) octane, 1- (4-bromo-phenyl) 4-t-butyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 4-t-butyl-1- (4-chloro-phenyl) -2,6-dioxa-7-thiabicyclo ( 2.2.2) octane, 1- (4-iodo-phenyl) -4-propyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 4-t-Butyl-1-cyclohexyl-2,6-dioxa-7-thiabicyclo (2.2.2) octane, 4-t-butyl-1-cycloheptyl-2,6-dioxa-7-thiabicyclo (2.2.2 ) octane, 1- (4-chlorophenyl) -4-i-butyl-2-oxa-6,7-dithiabicyclo- (2.2.2) octane, 1-cyclohexyl-4-propyl-2,6 , 7-trithiabicyclo (2.2.2) octane, 1-Cyclohexyl-8-methyl-4-propyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 1- (4-bromophenyl) -4-i-butyl-8-methyl-2 , 6-dioxa-7-thiabicyclo (2.2.2) octane, i- (4-bromo-phenyl) -8-methyl-4-propyl-2,6-dioxa-7-thiabicyclo (2.2.2) octane, 1 - (4-Bromo-phenyl) -4-n-butyl-2,6-dioxa-7-thiabicyclo- (2.2.2) octane, 1- (4-bromo-phenyl) -4-propyl-2-oxa 6,7-dithiabicyclo- (2.2.2) octane,