DD290195A5 - PROCESS FOR THE PREPARATION OF DERIVATIVES OF 2,6,7-TRIOXABICYDO [2.2.2] -OCTANES, PESTICIDES COMPOSITION AND METHODS FOR SCHAEDLINGSBEKAFENFFUNG - Google Patents

Abstract

The invention relates to a process for the preparation of derivatives of pesticidal compositions and to a process for controlling pests. In particular, the new compounds are active against arthropods. * pesticidal composition; Pest control; arthropod}

Description

Field of application of the invention

The invention relates to a process for the preparation of derivatives of 2,6,7-trioxabicyclo [2.2.2] octanes, a persticidal composition and a pest control method.

Characteristic of the known state of the art

The use of certain 2,6,7-trioxabicyclo [2.2.2] octanes is disclosed in EP-P Nos. 152229, 211598, 2161625 and 216324. It has now been found that derivatives of these compounds have remarkable pesticidal activity.

Object of the invention

The invention is intended to provide even improved pesticides on the basis mentioned above.

Explanation of the essence of the invention

Accordingly, the invention provides a process for the preparation of a compound of general formula (I):

A-X

wherein R is a C ₂ _, _o non-aromatic hydrocarbon (hydrocarbyl) group, optionally substituted by, or methyl substituted by cyano, halogen, a C, _, - alkoxy group, optionally substituted by halogen, or a group S (O) _m R ³ , wherein R ^{3 is} a C 1-4 alkyl group optionally substituted by halogen, and m is 0.1 or 2, or R represents a phenyl group optionally substituted by a C 1-4 alkoxy group, C 1-3 alkyl group, C ₂ -4-alkynyl group, halogen, C, _, - haloalkyl group, a cyano group or an S (O) _m R ³ group.

R ¹ and R ² may be the same or different, each being hydrogen, halogen, or a J ₁ -I aliphatic group optionally substituted by halogen, cyano, a C 1 -C 4 alkoxy group, a C 1 -C 4 alkoxy group, or an S (O ) _m , R ⁴ group, wherein m 'is 0.1 or 2 and R ^{4 is} C 1 -alkyl; Cyan, gem dimethyl, or d-6-carbalkoxy or R 'and R form with the carbon atoms to which they are attached, a C ^ -carbocyclic ring, optionally substituted by halogen, or a C ,. ₃ -aliphatic group or alkoxy group;

AX contains between 3 and 20 carbon atoms, wherein A represents a C ₂ -u non-aromatic hydrocarbyl (hydrocarbyl) group optionally containing one to six heteroatoms, the same or different, each selected from oxygen, sulfur, nitrogen , Fluorine or chlorine, and optionally substituted by one or two hydroxy groups, or A represents a CH ₂ O- or CH ₂ S (O) ₁₁ -GrUpPe, wherein η is 0.1 or 2; X represents hydrogen, halogen, a group Si R ⁵ , R ⁶ , R ⁷ or Sn R ⁵ , R ", R ⁷ , wherein R ⁵ , R ^e and R ^{7 are the} same or different, and each is a hydrocarbon f HydrocarbyD group _e , containing up to 8 carbon atoms, optionally substituted by one to three halogen atoms, a C, _e -alkoxy group, a C, _e -alkylthio group, a C 1-6 -alkylsulfinyl group, a C 1-4 -alkylsulfonyl group, a cyano group, a C | _ "- acyloxy or C | _e carboxy groups, or when one or more of R ⁶ to R ⁷ alkynyl, this is optionally substituted by a silyl group substituted by three.

R ^{8 represents} C 1-4 alkyl groups, or X represents a group CR ¹⁰ wherein R ⁸ and R ^{9 are the} same or different and each is independently

R ⁹

is selected from among hydrogen, halogen, cyano, C 1 -C 4 -carboxyalkoxy, C 1 -C 4 -alkyl, optionally substituted by one to three halogen atoms, cyano, C 1 -C 4 -carboxy, C 1 -C -alkoxy, or a group S (O) _m -R " in which m is "0.1 or 2 and R" is C 1-4 -alkoxy; C 1-8 -alkoxy or S (O) _m *, R ¹² , wherein m '"is 0.1 or 2 and R ^{12 is} C 1-4 -alkyl, optionally substituted by one to three fluorine atoms, or R ⁸ and R ⁹ unr! the carbon atoms to which they are attached form a C 1-8 cycloalkyl group and R ¹⁰ is hydrogen, halogen, hydroxy, cyano, C,. ₄ alkoxy, C ^ -acyloxy, Cn-carbalkoxy, or a Ci-g-hydrocarbon (hydrocarbyl) group, optionally substituted by hydroxy, cyano, C ^ alkoxy, C | _ ₄ acyloxy, C | ^ carbalkoxy , one to three halogen atoms or a group S (O) _n , - R ¹³ , wherein m "" is 0.1 or 2, and R ' ³ is C 1-4 alkyl, or R ¹⁰ is a group S (O) _n , --- R ¹⁴ , v.orin m "'' is 0.1 or 2 and R ^{14 is} C 1-4 alkyl, optionally substituted by one to three fluorine atoms. Y and Y 'are the same or different and each is selected from oxygen and S (O) _n ' wherein n 'is 0.1 or 2, and Z is CH ₂ CH ₂ , CH ₂ O or CH ₂ S (O) _n ,, where n "is 0.1 or 2. In the event that

R ⁸ A contains no C = C fragment, X represents a group CR ¹ "wherein R ⁸ , R ⁹ and R ^{10 are} as defined above, with the

R ⁹

Exception that R ⁸ and R ^{9 is} not hydrogen.

When ^{n <?} Finition <on Z the atom first mentioned is adjacent to the 4-position of the bicyclic ring system. When R is an alkyl, alkenyl or alkynyl, cycloalkyl or cycloalkenyl group, it preferably contains up to 6 carbon atoms. When R is substituted, in the case where the substituent is fluoro, it contains up to seven substituents, in the case where the substituents are chloro or bromo, up to three substituents, or substituent other than halogen, a substituent.

Preferably, R is an aliphatic or acyclic group containing between 2 and 8 carbon atoms or a phenyl group, each optionally substituted with cyano, one to seven halogen atoms, a C 1-4 alkoxy group or a group S (O) _n , R ⁴ as above Are defined. Preferably, R is propyl, butyl, pentyl, C ₂ . ₆ alkenyl or alkynyl, cyclopropylmethyl, _{Cj_-C7} cycloalkyl or phenyl, jedbs optionally substituted by fluorine, chlorine or bromine, for example, n-propyl, n-Butyl, i-but \ ', sec-Butal, t-butyl, prop 2-enyl, 2-methylprop-2-enyl, but-3-enyl, phenyl, cyclopentyl or cyclohexyl. Preferably, R is n-propyl, η-butyl, i-butyl, t-butyl or phenyl.

Preferably, R ^{1 is} hydrogen, halogen, cyano, methyl or ethyl, each optionally substituted by cyano, methoxy, methylthio, chloro, bromo or fluoro. In particular, R ^{1 is} hydrogen, methyl, cyano, trifluoromethyl or ethyl. Preferably, R 'is hydrogen, methyl, cyano or trifluoromethyl.

Preferably, R ^{2 is} hydrogen, cyano, methyl or trifluoromethyl. In particular, R ^{2 is} hydrogen ^cΛr methyl. Preferably, R ^{2 is} hydrogen.

Preferably Z is CH ₂ S or CH ₂ O.

A suitable Y and Y ¹ are selected from oxygen or sulfur.

Preferably, A is a C ₂ . _A non-aromatic hydrocarbon (hydrocarbyl) group optionally containing one to three heteroatoms as defined above. Preferably, A is a C _M non-aromatic hydrocarbon (hydrocarbyl) group which optionally contains a heteroatom and terminates in a CsC fragment adjacent to X. Preferably, A is a (CH ₂ UC = C group, a

- \ __ y - = group, one-CH = CH (CH ₂ ) ₂ C = C group, one CH ₂ O- (CH ₂ ) ₂ CsC group, one - (CH ₂ ) ₃ CH (CH ₃ ) CsC Group, a - (CH ₂ ) ₂ -CH (CH ₃ ) CH ₂ C = C group, a -CH ₂ CH (CH ₃ ) (CH ₂ ) ₂ CsC group, a - (CH ₂ I ₂ CH = CHC = C group, or a - (CH ₂ I ₃ C = C group and X is hydrogen or C ^ alkyl, optionally substituted by a hydroxy, Ci-4-alkoxy or C ^ ₄ acyloxy or One to three halogen atoms In another preferred embodiment, A is a -CH ₂ CH ₂ -,

R ^{8 is} -Ch = CH or CsC group, and X is a C-R ' ⁰ group.

R ⁹

Preferably, R ⁸ , R ⁹ and R ^{10 are} each selected from chloro, bromo, methoxy or methyl, optionally substituted by methoxy or fluoro.

The compounds according to formula (I) may be present in a number of isomeric forms. The invention provides individual isomers of compounds according to formula (I) and mixtures thereof. The invention also includes compounds according to formula (I) containing radioisotopes, in particular those in which the carbon atom is a C ^M atom or those in which one or three hydrogen atoms are replaced by tritium.

A preferred group of compounds according to the invention are represented by formula (IA) given below:

(CaC) R ¹⁵ (Csc) JC ⁹

wherein R ¹ is Cj-io alkyl, alkenyl or alkynyl, each optionally substituted methyl substituted by cyano, halogen, C ^ cycloalkyl, optionally substituted by halogen, C ₁ ^ -alkoxy optionally substituted by halogen by or or a group S ( O) _m R ³ as defined above or R 'is Cj_, ₀ cycloalkyl, C _{4., 0} cycloalkenyl or phenyl, each optionally substituted by Ci-4-alkoxy, Ct-3 alkyl, optionally substituted by up to 3 halogen atoms, C ₂ _4-alkynyl, halogen, cyano or a group S (O) _m R ³ .

R "and R '* may be the same or different, each is hydrogen, halogen or an aliphatic group containing up to 3 carbon atoms, optionally substituted by halogen, cyano, C |. ₄ alkoxy or a group S (O) _m, R 1 is alkylcarbalkoxy containing up to 6 carbon atoms, or alkynyl substituted by tri-C 1-4 -alkylsilyl, or R "is COO-C 1-4 -alkyl, cyano, methyl, or R" and R ¹ and the carbon atoms to which they are attached form a C ^ carbocyclic ring, optionally substituted by halogen, alkyl or alkoxy or CI_ ₃ C ₂ - ₃ alkenyl;

a or R ^1S represents a single bond, a group R ¹⁵ 'wherein R ^15' represents a group - () ^a

is optionally substituted by one to five methyl groups or halogen atoms, wherein w is oxygen, a group S (O) _P , wherein ρ is 0.1 or 2 or (CH ₂ ), wherein r is ₁ , 2 or 3, and Fragment (C = C) ₁ X * is attached at the a or b position of the ring or R ¹⁵ 'is an aliphatic chain containing between 1 and 8 carbon atoms in which one or two heteroatoms are inserted, the chain and R ¹⁶ 'can optionally be substituted by one to four substituents, which may be identical or different and each is rnabhängig selected from hydroxy, oxo, halogen, C, _ ₄ -alkyl or C ₁ ^ -alkoxy, each optionally substituted by up to 3 halogen atoms, C, _ ₄ acyloxy, epoxy, a C | _ ₄ alkylidene group, a Ci-e-carbalkoxy, Cyjn, or a group S (O) _P · R ^4a wherein p 'is 0,1 or 2 and R ⁴ * C 1-4 alkyl, X 'is selected from hydrogen, halogen, C 1-10 hydrocarbyl (hydrocarbyl), optionally substituted by one Hydroxy, C 1 -4 -alkoxy or C 1 -4-acyloxy or one to three halogen atoms, or X * means a group Si R ⁵ 'R ^e> R ⁷ "or Sn R ⁵ * R ⁶ * R ⁷ *, wherein R ^5a R ⁶ 'and R ⁷ ' are the same or different and each is a hydrocarbyl (hydrocarbyl) group containing up to 6 carbon atoms optionally substituted by one to three halogen, cyano, alkoxy, alkylthio , Acyloxy or carbalkoxy groups containing up to 6 carbon atoms or X * means a group R ^ie OCO, wherein R "is C,", - alkyl, q is 0 or 1 and t is 1 or 2, provided that the sum of q and t is not greater than 2.

Y and Y ¹ are the same or different and are each selected from oxygen and S (O) _n -, where n is ¹ , 0.1 or 2; Z is CH ₂ O or CH ₂ S (O) _n -, where n "is 0, 1 or 2, except that X can not be hydrogen when q is 0.11 and R ^{1S is} a single bond.

Geian heteroatoms for insertion into the alkylene chain include oxygen, nitrogen and sulfur, which sulfur may optionally be oxidized as sulfoxide or sulfone. Oxygen and nitrogen atoms may be adjacent to each other, in which case they form an oxime group.

Preferred values for the groups R ", R '", R ² ", Y, Z and Y' correspond to the values defined above for the groups R, R ¹ , R ² , Y, Z and Y ^1. Suitably R ^{15 is} one single bond, a 1,4-cyclohexyl group or an aliphatic chain, as defined above, with 2 to 6 carbon atoms, with optionally an inserted oxygen or sulfur atom. a preferred X * is hydrogen, C, _ ₃ alkoxymethyl or a group Si R ' R "R ¹⁹ , wherein R ¹⁷ , R ¹⁸ and R ^{19 are the} same or different and each is C 1-6 -alkyl, preferably η is 0.

Another preferred compound of the compounds according to dor Formol (I) is the nachstohondor Formol (IB):

(IB) _f

wherein R ', R' ¹ , R ^jl , X ', Y, Y', Z and t have the meaning defined above and R ' ⁶ ' is a single bond or a wio above defined group R ' ⁶ ' means.

Preferably, R ^{161 is} I, -I-cyclohexyl, t is 1, and X 'is hydrogen or C 1-8 alkyl optionally substituted by a hydroxy, C 1-4 alkoxy or C ,. _4- acyloxy group or one to three halogen atoms; or R ¹⁶¹ is a single bond, t bodoutot 1 and X * is C 1-4 -alkyl optionally substituted by a hydroxy, C 1-4 alkoxy, or C 1 -4 -acyloxy group or oin to three Halogunatomo. X 'is preferably a tertiary group. Preference is given to R ^ISl cyclohexyl and X * is hydrogen or R ' ^{S |} oino means single bond and X 'means a toritäros üutvl.

Another preferred group of compounds according to the invention has the following formula (IC)

(IC).

wherein R ^{b is} a C ₂ -I ₀ non-aromatic hydrocarbon (hydrocarbyl) group, optionally substituted by cyano, halo, C 1 -C 10 alkoxy, or a group S (O) _m bR ^3b where R is ^3b C ^ alkyl, and m ^b is 0,1 or 2, odor R ^b is phenyl, optionally substituted by C ^ ₄ -alkoxy, CI_ ₃ alkyl, C ^ alkynyl, halogen, C ,. ₄ -haloalkyl, cyano or a group S (O) _m bR ^3b , as defined above.

R ^1b and R ^2b may be the same or different, each being hydrogen, halogen or a C _1-3 aliphatic group optionally substituted by halogen, cyano, C 1-6 carbalkoxy, or C 1-6 alkoxy; a group S (O) _m , R \ wherein m 'is 0, 1 or 2 and R ⁴ is C 1-4 alkyl; Cj. ₃ alkynyl, cyano, gem dimethyl, or Cn carbalkoxy, or R ^1b and R ^b and the Kohlonstoffatome to which they form form a C ₆ _ ₇ -carbocyclischon ring, optionally substituted by halogen, C, _ _: alkyl or Alkoxy or C ₂ - ₃ alkenyl.

R ⁸ and R ⁹ are as defined above and R ²⁰ is a group R ^e as defined above.

B represents a single bond, methylene or a C ₂ _ "aliphatic ketene, which may contain one or two heteroatoms and / or double bonds, but no triple bonds, inserted into the chain and which may be substituted by one to four substituents may be the same or different and each is independently selected from hydroxy, oxo, halogen, C, -4-alkyl, CN-alkoxy, C) _ ₄ acyloxy, epoxy, a Ci_4 alkylidene group, a Ci-e-Carbalkoxygruppo, a C 1-1 haloalkyl or a cyano group.

D represents a single bond or a CHjO or CH ₂ S (O) "group, wherein η is 0.1 or 2, or D represents a 1,2-cyclopropyl group.

Y and Y ¹ and Z h have the meaning described above, provided that B is not a single bond odu.

Methylene group is, if D is a single bond.

Preferably, R ^{b is} propyl, butyl, pentyl, C _2;) alkenyl or -alkynyl, C 1-6 cycloalkyl or phenyl, preferably substituted with fluoro, chloro or bromo. More preferably R ^{b is} n-propyl, η-butyl, i-butyl, sec-butyl, t-butyl, phenyl, cyclopentyl or cyclohexyl, and more preferably R ^{b is} n-propyl, η-butyl, i-butyl or t-butyl.

.V ^b is preferably hydrogen, cyano, methyl or ethyl, each optionally substituted by cyano, methoxy, methylthio, chloro, bromo or fluoro. More preferably R ' ^{b is} hydrogen, methyl, cyano, trifluoromethyl or ethyl. In particular, R ' ^{b is} hydrogen, methyl, cyano or trifluoromethyl.

Suitable heteroatoms included in B include oxygen, nitrogen and sulfur, which sulfur may optionally be oxidized to the sulfoxide or sulfone.

Preferably, R ⁸ , R ^M and R ^{9 are} selected from chloro, bromo, methoxy or methyl, optionally substituted by methoxy or fluoro.

Preferably, B is a (CH ₂ I ₂ or -CH = CH group.

D is preferably a single bond.

Goolgnoto and bavoriugto Worlo for the groups N ^lb , 7, Y and Y 'liabon dloiolbo Dodouluny, wlo supra (Or dio Qruppon H ¹ , Z, Y and Y 'described. In addition, the following are preferred (olgondo Vorbindungon:

1- (Hex-5-INVL) -4-propvl-2, e, 7-trloxabicyclo (2.2.2loctan1 · (x 4 x ΡβηΙ ΙηνΙ) x 4 x ρκ> ρνΙ · 3 · ίΗΙΚιθΓοηιο "ΙινΙ × 2, β, 7 · "ΗοχβΜονοΙο | 2.2.2 | ο <: Ιβη

- (PonM-lnylM-propyl-2, G-7 trloxnbicyclo | 2.2.2 | oclnno-3-cnrbonlUil

<1- (Cyclohoxyl) -1- (pont-4inyl) -2, e, 7-trloxablcyclo | 2.2.2 | octnn <1 (Cyctol> oxy) -1- (hox 5-lnyl) -2,6, 7trioxnblcyclo | 2.2.2 | octnn-it-bulyl-1 (hox-SlnyD ^ .GJ-trloxnblcycloU ^^ loctan4-t-butyl-1 (e-triniothymethyl) ox-5lnyl) -2,6,7-trloxnblcyclol2.2.2] octn ^ (4 x Ethynylcyclohoxyl) · 4 · · propyl 2,6,7 · ^ rloxnbicyclo | 2.2.2 | oc ^ nn

4-t-Biityi-1- (4-thylcyclohoxyl) -2,6,7-trlox-n-cyclic ol2.2.2] oclnno (clian (1 tranilsoniors) 4-t-BiUyt-1- (3,3-diol-but-1-but-1-yl) -2.e, 7-trioxablcvclo | 2.2.2 | octnn1- (3.3 x ΟίηιοΐΙιγΙ1χιΙ x 1 ΙηγΙ) <1 · · ρΓορνΙ 2.6,7 · ΐΓίοχΛ ιΙογεΙο |! 2.2.2 | θΓ (ηι \ ο ·. 3 · <: | ηΓΐ) οηίΙπΙ4-t-butyl-1- (hox 5inyl) -2,6dioxn-7-thia-bicyclo 2.2.2iGi tn..

4-t-butyl-1- | 2- (prop-2-ynylthio) othyl) -2, ß, 7-tr! Oxabicyclo | 2.2.2 | oclan 4-propyl-1- | 2- (prop-2-ynylthio) oll) yl | 2.2.2 | | -2, C, 7-trioxnbicyclo octnn

4-Propyl-1- (2- (prop-2-ynyloxy) -ethyl) -2, e, 7-trioxabicyclo [2.2.2loctano-3carbonilryl i

4-t-Butyl-1- (but-3-inyloxymothyl) -2,6,7-trioxabicyclo | 2.2.2 | octan1- (but-3-inyloxymothyl) -4-propyt-2, e, 7-trioxauicycto | 2.2.2 | octano-3-carbonitril4 · t · butyl · 1 · (hopt · β · ynyl) x 2, β, 7 · trioxabicyclo | 2.2.2 | octnn1- (hop t-6-ynyl) -4-propyl 2,6,7-trioxabicyclo (2.2 | octan4-8utyl-1- (hex-5-ynyl) -2,6,7-trioxabicyclo? |. 2.2.2] octane-3carbonitril1- (hex-5-ynyl) - 4 (2-methylprop-2-enyl) -2, e, 7-trioxabicycto | 2.2.2) octane-3-carbonitrile1- (hex-5-nyl) -4- (prop-2-enyl) -2, e , 7-trloxablcyclo [2.2.2 | octano-3carbonitrll1- (but-3-inyloxymethyl) -4- (prop-2-enyl) -2,6,7-Uioxabicyclo (2.2.2 | octano-3-carbomtril

4 (but-3-enyl) -1- (hex-5-enyl) -2,6,7-trioxabicyclo | 2.2.2 | octano-3carboni> rIL4-t-Butyl-1- (4-methylhex-5- onyl) -2,6,7-trloxabicyclo | 2.2.2] octene

1- (2- (but-3-ynyloxy) ethyl | -4-ptopyl-2,6,7-trioxabicycio | 2.2.2loctan

i-IBut-S-inylthlomethylM-propyl-.ej-trloxabicyclo ^^^ loctane 4-t-butyl-1- (but-3-inylthiomothyl) -2,6,7-trioxabicyclo [2.2.2] octane 4-butyl-1 ? - (hex-5-ynyl - oxa-6,7-dithiabicyclo | 2.2.2 | octane

1t-butyl-1- (hex-5-ynyl) -2,6,7-trioxabicyclo | 2.2.2 | octane-3-carbonitrile

4-Etloxymnthyl-1- (hox-5-yl) -2,6, -trioxabicyclo [2] -2-octano-3-carbonitrile (1-N'-ethylhex-S-yn-1-yl-propyl] ee ^ -trioxabicyclo ^^^ locian4-t-Butyl / 1- (1-methyl-5-yl) -2,6,7-trioxabicyclo | 2.2.2 | octan1 · (1-chloro-5-yl) ynyl) -4-propyl-2,6,7-trioxab; cyclo | 2.2.2 | octano-3carbonitril

Methyl 7 ^ - propyl ^ .ej-trioxablcyclotf ^^ loct-i-yl) hept-2ynoate

1- (H <tx-5-ynyl) -4-isobutyl-2-oxa-6,7-dithiabicyclo | 2.2,2loctan

1- (3-methylhex-5-ynyl) -4-propyl-2,6,7-trioxabicyclo [2.2.2] octano-3-carbonitrile 1- (2-methylhex-5-ynyl) -4-propyl-2 ', 6,7-t < 'ioxabicyclo |! 2.2.2 octano-3-carbonitrile

'' ^ loctano-S-carbonitrile »., c

4-Pfopyl-1 - [(E / Z) -6- (trimethylsilyl) hex-3-one-5-ynyl] -2, e, 7-trioxabicyclo [2.2.2] octanuc-3-carbonitrile 1 · [( Ε / Ζ) · Ηοχ · 3 βn · 5 · inyl · 4-propyl-2,6,7-trίoxabicyclo [2.2.2loclane · 3 · carlonitrile (E: Z-1: 2) i-KE / ZI 1-¢ (E / Z) -7-hydroxyhept-3-ene-5-yl-methoxyhept-S-en-B-inyll-1-propyl-1-yl-trioxabicyclo-1-yl-2-octyl-1-carbonitrile - [nyl] -4-propyl-2,6,7-trioxabicyclo | 2.2.2 | oclano-3-carbonitrile 4-t-butyl-1- | (E) -hex-1-en-5-ynyl] - 2,6,7-trioxabicyc! O | 2.2. ^ Loctano-3-carbonitrile 4-propyl-2,6,7-trioxabicyclo | 2.2.2] octane-1-carboxo Idehydoxime O- (prop-2-ynyl) ohtor

2- (Hex-5-ynyl) -4-phenyl-2-oxa-6,7-dithiabirycyclo [2.2.2loctane] propyl 1- (4-methylhex-5-ynyl) -2,6,7-trioxabicyclo [2.2.2 | octan-3-carbonitril4-ethyl-1- (hox-5-ynyl) -2,6,7-trithiabicyclo | 2.2.2 | octan1- (Hex-5-ynyl) -4-phenyl-2 , 6,7-trioxobicyclo [2.2.2ltctan-3carbonitril4-Cyclopropvlmethyl-1- (hex-D-ynyl) -2,6,7-trioxabicyclo (2.2.2loctan-3carbonitril4-isobutyl-1- (3-methylhex- 5-ynyl) -2,6,7-trioxabicyclo [2.2.2loctan-3-carbonitril1-I (S) -3-methylhex-5-inyll-4-propyl-2,6,7-trioxabicyclo (2.2.2 | octane-2-carbonitrile

1- (2-Moihvlhox-6-Invl) -4- (prop-2-one nn-2, e.7-trloxybicyclo (2.2.2) octon-3-carbitoltritol 2tBu »vl-1-0.3cllmothylbutyl) - 2,6,7-tfloxeblcYclo | 2.2.21ocien

1- (3,3-Olmethylbutyl) -4-propvl-2, e, 7-trloxkblcyclo | 2.2.2 | octane-3cerbonllrll

1- | t-1 Fliiiv-3,3-imothylbiit 1onyl) ()

1 (ΙΙθ |) Ι-5Ιι \ γΙ) Ίρ (θ |) γΙ-2,0,7 · (ποχηΙιίογοΙο | 2.2.2 | οοΐηη

With dom BogtKf "hydrocarbyl Gruppo are alkyl. Alkenyl, (including alkylcycloalkyl · alkylor Alkonyl · and by cyclisclio alkyl · and alkonyl groups eubstitulorto alkyl and Alkonylgruppon), alkynyl, aryl and Arnlkylgruppon umscliriobon. Oar boy reef "Wydrocarbyloxy" bodautot, dntt olno vorstohond ddfiniorto Hydrocarbylgruppo on Sauo.

Dor term "aliphatic" Gru,> po includes oino alkyl, alkonyl or alkynyl group.

Dor Dogrifr. Halogen "includes fluorine, chlorine, uromium or iodine.

Dio invention continues oinor Vorinhron door Horstollung oinor Vorbob demo Forniol (I). Ons Vorfnhron fur dio production oinor compound yomflß For mol (I) can | odoe in the sense) dor Tochnikbokannto ancestors for dio Horstollung analogous compounds soin, boispiolswoiso:

(i) (Y and Y ^{1 are} oxygen and Z is CH ₁ O Lodoutot:

a) by cyclization oinor Vorbindung gomttß formol (II):

A-X

(II)

wherein R to R ¹ , A and X are the first to the moiety, in Anwosonhoit oinos siturocatalyst. Bortrifluuridolho. nt is oin bosondors bovonugtor Siiurokatalysalor for dio cyclization, dio standardorwoiso in oinom inorton solvent, wio in ainom halogoniorton hydrocarbon, usuallyorwoiso dichloromothane, at odor untor ooror gooignoton tomporature, boispiolswoisozwischon -100'C jihI 50 ¹ C, gooign Morwoisoiwischon -7O'C and -25'C, is carried out. Dio Compounds according to Formol (II) are horMollbar by Roaktion of the compounds according dor Formoln (III) and (IV):

(III)

(IV)

where R to R ¹ , A and X are dioxylyhone, and L oino leaving group, wio boispiolswoiso or halogen odor oino hydroxygruppo bodoutot. The roaction becomes gooignotorwoiso untor Bodingunpp; viurchgofhrt, well-known in the art, boispiolswoiso fnlls L oin hologon is in oinom inorton solvent in Gogonwart oinor Bnso boi not oxtromor Tomporatur and if L oino Hydroxygruppo is in oinom inorton solvent in Present cinos condoms boi not oxtromor temporary. If L is a hn'ogon, wordon halogoniorto Kohlonwassorstoffo, wio, for example, dichloromothane, as goeignoto inert solvent and pyridine as bovorzugto Baso oingosout. If L is a hydroxy group, the solvent is dimethylformamide, with dicyclohoxylcarbodiimide oin gooignotos being condent centering agent. The Roaktion is boi oinor temperature zwischon -50 to 100 ⁹ C, vorzugswoiso zwischon 0 and 25 ⁰ C.

The compounds according to Formula III can be provided as described in European Patent Applications Nos. 211598 and 216624. The compounds according to formula (IV) can be obtained by processes known in the art, and the synthesis of XA-CO] H (Xa = 4-ethynylcyclohoxyl) becomes Bschiobiobon in Appendix 1.

I)) if A oln ondstSndlgos CuC fragment onthält:

ibi) by reaction of a compound HChC-X with oinoi preconditioning of formol (V):

κ ¹ , _A ₀ \ _ * »- i ^l

wherein R to R 'are dioxygen ions, A ¹ CaC forms Gruppo A and L' represents a leaving group. Gooignoto exit group includes halogonido, wio boispiolswoise bromine. The reaction is preferably a strong base, wiü boispiotawoiso Butyllithii-rr ,, lithium amide sodium amide boi odor odor performed untorhalb a suitable temperature, boispiolswoiso zwischon -70 ° C and 30 ⁰ C in oinom inorton solvent wio tetrahydrofuran or diethyl ether. When lithium amide is used as the strongo base, liquid ammonia is the appropriate solvent

 The precursors according to Formol (V) can be prepared by cyclization on the corresponding compound of formula (VI);

(Vl)

Dio compounds according to Formol (Vl) can be prepared and cyclized under analogous conditions as for the preparation and cyclization of the compounds of formula (II).

(bii) If A contains a terminal CnC fragment and X is hydrogen, by reaction of a strong base with a precursor according to Formol (VII):

R ¹

(VII) _f

where R to R ⁷ . A ', Y, Y' and Z have the abovementioned meaning and Q denotes a group which is capable of conversion into an ethynyl group, for example a CH-C (hal) Hhal) CH = CHr- or -C = CH ₂ - Group, wherein halogen is chlorine or bromine

POI ¹ IOAIk) ₂

means, and Alk is a C, _ »- alkyl group.

The reaction is carried out using methods known from the prior art methods, for example, if Q is a -CH = C (hal) _r group approximately at or below room temperature, for example between -7O ⁰ C and 25 ⁰ C, in an inert Solvent, suitably oinom ethers such as tetrahydrofuran.

As a strong base for the reaction Butyllithlum is suitable. The starting material gomaß formula (VII) can be prepared by reaction of a compound of formula (VIII)

(VIII)

with a compound according to formula (AIkO) ₃ CA ¹ CH = C (MaI) ₂ or by cyclization of a compound analogous to ionomers according to formula (VI), where L 'is a group Q.

(biii) If it is necessary to prepare a compound of formula (I) wherein -AX contains a -CH = CH-CsC-X linkage, by reaction of the corresponding compound of formula (IX)

A -CH = CH-hal

(IX)

with HCsC-X, wherein R, R ¹ , R ² , X and hai are as described above and A ^{3 is} -CH = CH-CsC-X is a group AX as described above. The reaction is carried out in the presence of a suitable palladium catalyst, as is known in the art for this type of reaction, for example with bis-triphenylphosphine palladium dichloride, a catalytic amount of copper (II) halide, for example, copper iodide. The reaction is normally carried out in the presence of a basic solvent such as diethylamine or triethylamine at a non-extreme temperature, for example between -5O ⁰ C and 100 ° C and preferably at 25 ⁰ C, if the halogen is iodine or bromine

 (c) If A contains a -CONH group, by reaction of a compound of general formula (X):

-Q-

A CO ₂ AIk

(X)

with a compound NH ₂ CH ₂ A ³ -X, wherein R, R ¹ , R ² and X have the abovementioned meaning, Alk a C _t _ «- alkyl group and A ² CONHCH ₂ A ³ -X a group as described above AX is. This reaction takes place in an inert solvent, suitably an alkanol such as methanol at a non-extreme temperature place, for example between ⁰ ° C and 100 ° C, preferably between 20 and 7O ⁰ C, preferably in the presence of a catalyst such as sodium cyanide. The compounds according to formula (X) can be prepared by means of processes known from the prior art, for example as described for analogous compounds in European patent applications Nos. 152 229 and 211598.

(d) If A contains a -COO group, by reaction of a compound according to formula (XI), 1

A ² CO ₂ H

(XI)

or an <alkali metal salt thereof, with a compound XA ³ CH ₂ Hal, wherein R, R ¹ , R ^J and X have the abovementioned meaning, and hai is a halogen, such as, for example, bromine or chlorine, and A'CO ₂ CH ₂ A ³ -X is a wio described above ie group AX. This reaction is carried out in an inorton solvent, gooignotorweiso in a dipolar u laotic solvent, wio dimethylformamide at einor not oxtromon Tomporatur, boispiolswoiso between ^{0 0} C and 180 ⁰ C, preferably between ^{0 0} C and 30 ° C.

 (e) If A contains a -CH = NO group, by reaction of a compound of formol (XII):

A ² CH = NOH

(XII)

with a compound of the formula XCsCCHj-hal, in which R, R ¹ , R ¹ , X and hai have the abovementioned meaning, and A ² C = NOCH ₂ A ³ -X is a group as described above Reaction takes place in an inert solvent, suitably an alkanol, such as a methanol, in the presence of a base, for example an alkali metal alkoxide, such as sodium methoxide, at a non-extreme temperature, for example between O ⁰ C and 8O ⁰ C, preferably between 2O ⁰ C and 30 C. The compounds of the formula (XII) are prepared by methods known from the prior art, for example as shown in Appendix 4, (f) If A contains a -COH group, by reaction of a compound of the formula ( XIII):

A ² CH ₂ OH

(XIII)

with a compound of the formula XA ³ CO ₃ H, where R, R ¹ , R 'and X have the abovementioned meaning, and A ² CH ₂ OCOA ³ -X is a group AX as described above. This reaction takes place in an inert solvent, geeignetorweise a halogenate hydrocarbon such as dichloromethane, instead, non-extreme at oinor temperature, for example between ⁰ ° C and 100 ° C, preferably between 20 ⁰ C and 3O ⁰ C. The reaction is in the presence einos coupler such as carbodiimide, for example dicyclohexylcarbodiimide, and in the presence of a catalyst, such as 4-dimethylaminopyridine. The compounds according to formula (XIII) can be prepared by methods known from the prior art, as described, for example, for analogous compounds in European patent applications Nos. 152 229 and 211 598. (ii) If n'Oist, Y ¹ = O or S

Y = O or S

Z = CH ₂ S or CH ₂ O

by reaction of a compound of formula (XIV) with a compound of formula (AIkO) ₃ CAX,, 1

(XIV)

YH

wherein R, R ¹ , R ^J , A, X, Y, Y 'and Z have the abovementioned meaning, and Alk is a C,., Ralkyl group. The condensation takes place in the presence of an acid catalyst, for example a mineral acid, such as concentrated hydrochloric acid or boron trifluoride etherate and / or p-toluenesulfonic acid. The reaction is conveniently carried out without the use of a solvent, but an inert solvent, preferably a chlorinated hydrocarbon such as dichloromethane, may be added. The crude action can also be carried out in methanol containing hydrogen chloride. The reaction is suitably carried out at a non-extreme temperature, for example between -7O ⁰ C and 15O ⁰ C and usually between -1O ⁰ C and 15O ⁰ C. The compounds of the formula (XIV) can be prepared as described in European Patent Application No. 216624 or in Annex 2. Compounds according to formula (XIV), wherein Y = Y ¹ = S, Z = CH ₂ S and R '= R ² = H, can also be prepared according to the method described by GR Franzen and G. Binsch, J. Amer. Chem. Soc., 1973, 95, 175 and DJ Martin and CRCreco, J. Org. Chem., 1968, 33, 1275. The compounds of the formula (AIkO) ₃ CAX can be prepared by a conventional method for the synthesis of orthoesters, as described by SM McElvain and RE Stam, J. Amer. Chem. Soc., 1955, 77, 4571. (iii) When Z = CH ₂ S or CH ₂ O and Y and Y ^{1 are} sulfur, by reaction of a compound of formula (XV)

(XV)

with a compound L ² AX, wherein R to R ² , A and X have the abovementioned meaning, Z ¹ is CH ₂ S or CH ₂ O and L is a leaving group, for example a halogen. Suitably the reaction in Gegenwrt a strong base such as butyl lithium, in an inert solvent such as an ether, preferably tetrahydrofuran, at a non-extreme temperature, between -70 ° C and 3O ⁰ C. The compound of the formula (XV) can be prepared by the reaction of an analogous compound of the formula (XIV) with HC (OAslk) ₃ under the conditions described for the reaction (Ii), (iv) If Y is O and Y ^{1 is} O and Z is CH ₂ CH ₂ , by reaction of a compound of formula (XVI) with acid

NMe,

(XVI)

wherein R, R ¹ , R ² , A and X have the abovementioned meaning.

The reaction is carried out in acidic conditions, suitably in silica gel, with subsequent dilute hydrochloric acid at a non-extreme temperature, for example between O ⁰ C and 100 ⁰ C, with a preferred suitable temperature between 2O ⁰ C and 30 ° C. The compounds of the formula (XVI) can be prepared as illustrated in Annex 3, (v) By interconversion of compounds of the formula (I), wherein a) contains a terminal C =C fragment and X has a meaning other than hydrogen , by reaction of the corresponding compound, wherein X is hydrogen with a compound X ¹ Hai, wherein Hal is halogen and X ^{1 has} a meaning other than hydrogen. This reaction is particularly suitable for the preparation of such compounds in which X ', wherein R ²¹ is a C ₁ ^.' Represents a Ct-4-alkyl group or a group COR ² !! "is iv.ygruppe;. Or X represents a substituted silyl or tin group, the reaction becomes

usually in an etarken base such as alkyl lithium, preferably butyllithium, in an inert solvent such as ether, for example tetrahydrofuran, at a non-extreme temperature, for example between -50 ° C and 5O ⁰ C, preferably between -10 ⁰ C and 3O ⁰ C. , carried out. The starting material, for example the unsubstituted alkynylalkylbicycloalkane, can be prepared as described above.

b) If it is desired to produce a compound according to formula (I) wherein A is saturated or contains a double bond by reduction of the corresponding compound containing a double or a triple bond, respectively. This reaction suitably takes place by hydrogenation in the presence of a catalyst, for example palladium on charcoal or, if a triple bond is to be reduced and os is required to stop the reduction at the double bond stage and not reach the fully saturated compound in the presence such a catalyst poisoned by, for example, barium sulfate. The reaction is carried out in a suitable hydrogenation solvent such as methanol or ethyl acetate. Usually, the reaction is carried out at a non-extreme temperature, for example between 5 ⁰ C and 5O ⁰ C, preferably at 25 ° C.

c) if A contains a terminal CsC fragment and X is hydrogen, by desilylation of a compound according to formula XVII)

(XVII)

wherein R, R ¹ , R ² , R ", R", R ¹⁹ , Y, Y ¹ , 2 and A ^{1 have} the abovementioned meaning. This reaction can be carried out from the state of the art by methods known, for example by reaction with Tetrabutylamrnoniumfluorid in an ether such as a tetrahydrofuran, at non-extreme temperature, for example between ⁰ ° C and 70 ° C, preferably at 25 ⁰ C.

New chemical intermediates are also an important aspect of the invention. Preferred intermediates include those of formula (II), (V), (VII), (XIV) and (XV).

The compounds according to formula (I) can be used for pest control, for example of arthropods, for example insect and acaric pests and helminths, for example nematodes. The invention therefore provides a method for the control of arthropods and / or helminths, in which the arthropod and / or helminth or its surroundings an arthropisch effective amount of a compound according to formula (I) is administered. The invention also provides a method for combating and / or eradicating arthropod and / or helminth infestations of animals (including humans) and / or plants (including trees) and / or stored products in which the animal or the locus has an effective amount a compound according to formula (I) is administered. The invention further provides compounds according to formula (I) for use in human and veterinary medicine, in public health control and in agriculture for the control of arthropod and / or helminth pests. The compounds according to formula (I) are particularly valuable for the protection of field harvests, forage, in plantations, greenhouses, orchards and vineyards, for the protection of ornamental shrubs and plantations and forest trees, for example for cereals such as corn, wheat, rice , Sorghum, cotton, tobacco, vegetables and salads (such as beans, cabbages, curcubits, lettuce, onions, tomatoes and peppers), crops (such as potatoes, sugar beets, peanuts, soya beans, seed for rapeseed oil), sugarcane, pasture and fodder ( such as corn, sorghum, alfalfa), plantings (such as tea, coffee, cocoa, bananas, oil palms, coconuts, gums, spices), orchards and groves (such as stone and pomes, citrus fruits, kiwifruit, avocados, mangoes, olives and walnuts ), Vineyards, ornamental plants, flowers and shrubs under glass and in gardens and parks, forest trees (both deciduous and evergreen trees) in forests, plantations and nurseries.

They are also valuable for the protection of trees (standing, felled, transformed, stored or structured) against attack by sawfly (for example: Urocerus) or beetles (for example: Scolytidae, Platypodids, Lyctids, Bostrychids, Cerambycids, Anobiids).

They are also used to protect stored products such as grains, fruits, nuts, spices and tobacco, either whole, or ground or compounded into products from moons, beetles and worm attacks. Similarly, stored animal products such as hides, hair, wool and feathers in natural or transformed form (for example as carpets or textiles) are protected from moths and beetles, as well as stored meat and fish from beetles, mites and flies. The compounds of general formula (I) are particularly valuable for the control of arthropods or helminths which are harmful to humans or domesticated animals or which may serve as disease carriers, for example those mentioned above and in particular for the control of ticks, worms, Lice, fleas, mosquitoes, biting flies, and other agonizing flies.

The compounds according to formula (I) can be used for such purposes by applying the compounds themselves or in diluted form in a known manner as a disinfectant bath, spray, mist, lacquer, foam, dust, powder, aqueous suspension, paste, gel, cream, shampoo, Fat, combustible solid, vaporizable material, heating coils, baits, dietary supplements, wettable powders, granules, aerosols, emulsifiable concentrates, oil suspensions, oil solutions, pressure packs, impregnated articles, or for other known compositions. Immersion concentrates are not applied per se, but diluted with water and immersed in the disinfectant bath containing the disinfectant wash solution. Sprays can

be applied manually or with the help of a spray arch. The animal, the soil, the plant or the surface can be saturated with the spray by means of high volume application or superficially coated with the spray by means of light or very low volume application. Aqueous suspensions are applicable in the same way as sprays or dips. Powders must be distributed by means of a powder dispenser or, in the case of animal application, these are placed in perforated bags attached to trees or rubbing posts. Pastes, shampoos and fats are manually applicable or are spread over the surface of an inert material so that in case the animal rubs, the material will be transferred to their skins. Compositions for infusion are distributed as low volume liquid units on the back of the animals so that most of the liquid remains on the animals.

The compounds of formula (I) may be prepared either as compositions which are ready for use in animals, plants or surfaces or as compositions which must be diluted before use. Both types of compositions comprise a compound of formula (I) in intimate admixture with one or more carriers or diluents. The carriers can be liquid, solid or gaseous or comprise mixtures of such substances. The compound of the formula (I) may be present in a concentration of 0.025 to 99% w / v, depending on whether the composition is to be further diluted.

Dusts, powders and granules and other solid compositions comprise the compound of formula (I) in intimate admixture with a powdered solid inert carrier, for example clay, kaolin, bentonite, attapulgite, adsorbent carbon black, talc, mica, chalk, gypsum, tricalcium phosphate, powdered Cork, magnesium silicate, vegetable carriers, starch and diatomaceous earth. Such solid compositions are usually prepared by impregnating the solid diluents with solutions of the compounds of formula (I) in volatile solvents with subsequent evaporation of the solvents and, if desired, grinding the products into powders and, if desired, granulating them so as to encapsulate the products or can be pulled over. Sprays of a compound according to formula (I) include a solution in an organic solvent (for example those listed below) or an emulsion in water (dipping solution or spray solution) prepared from emulsifiable concentrate (a water-soluble oil) which is also used for dipping purposes , The concentrate preferably comprises a mixture of the active ingredient, with or without an organic solvent, and one or more emulsifiers. The solvents may be present within a wide range, but preferably in an amount of 0-90% w / v, of the composition and may be selected from kerosene, ketones, alcohols, xylene, aromatic naphtha and others more well-known in the preparation of such formulations Solvent. The concentration of the emulsifiers may vary within wide ranges, but is preferably in the range of 5 to 25% w / v, the emulsifiers being preferably nonionic surfactants comprising polyoxyalkylene esters of alkylphenols and polyoxyethylene derivatives of hexitol anhydrides and anionic surfactants comprising sodium lauryl sulfate. Fatty alcohol ether sulfates, sodium and calcium salts of alkylaryl sulfonates and alkyl sulfosuccinates. Cationic emulsifiers include benzalkonium chloride and quaternary ammonium ethosuphates.

Amphoteric emulsifiers include carboxymethylated olein imidazolines and alkyl dimethyl betaine.

Evaporation mats normally comprise cotton and cellulosic blends pressed into a container of about 35mm x 22mm x 3mm and containing up to 0.3ml of the concentrate containing the active ingredients in an organic solvent and optionally an antioxidant, a dye and a Perfume are provided. The insecticide is vaporized by using a heating source such as an electric heating mat.

Combustible solids usually include wood powder and binder mixed with the active ingredient and rotated in usually helical strips. For this purpose, a dye and a fungicide may also be added. Wettable powders include an inert solid carrier, one or more surfactants, and optionally stabilizers and / or antioxidants.

Emulsifiable concentrates include emulsifying agents, and often an organic solvent such as kerosene, ketones, alcohols, xylenes, aromatic naphtha compounds and other solvents known in the art.

Wettable powders and emulsifiable concentrate usually contain 5-95% by weight of the active ingredient and are diluted, for example, with water before use.

Varnishes comprise a solution of the active ingredient in an organic solvent, together with a synthetic resin and optionally a plasticizer.

Immersion solutions can be prepared not only with emulsifiable concentrates but from wettable powders, soap-based immersion dips, and aqueous suspensions comprising a compound of formula (I) in intimate admixture with a dispersant and one or more surfactants.

Aqueous suspensions of a compound of formula (I) may contain a suspension in water together with a suspending, stabilizing or other agent. The suspensions or solutions are applicable per se or in diluted form in a known manner.

Fats (or ointments) are made from vegetable oils, synthetic esters of fatty acids or wool fat together with an inert base such as soft paraffin. Preferably, a compound according to formula (I) is uniformly distributed in the solution mixture or in the suspension mixture. Fats can 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 paraffins or on a non-greasy basis with glycerin, gum solution (glue) or a suitable soap, can be made. Since fats, shampoos and pastes are usually applied without further dilution, they should contain a suitable percentage of the compound according to formula (I) which is necessary for the treatment.

Aerosol sprays can be prepared as a simple solution of the active ingredient in the aerosol propellant and cosolvents such as halogenated alkanone and the aforementioned solvents. Preparations for pouring can be prepared as a solution or suspension of a compound of the formula (I) in a liquid medium. A mammal may also be protected against attack by acarinectoparasites by means of a suitably shaped plastic article impregnated with the compound of formula (I). Such articles include impregnated tapes, pins, sheets and strips which are suitably secured to the appropriate body locations. The plastic material is preferably made of polyvinyl chloride (PVC).

The concentration of the compound of formula (I) used for animals, land or outlying areas depends on the compound chosen, the treatment intervals, the nature of the composition and the infestation, but is usually 0.001 to 20.0 Wt / vol% (w / v) and is preferably 0.01 to 10% of the compound in the particular composition. The amount of compound to be deposited on an animal depends on the mode of administration, the size of the animal, the concentration of the compound in the composition to be administered, the factor with which the composition is to be diluted and the nature of the composition Range of 0.001 to 0.5% w / w / w / w) except for non-diluted compositions such as for infusion compositions, usually at a concentration in the range of 0.1 to 20.0%, preferably 0 , 1 to 10% are knocked down. The amount of compound to be delivered for stored products is usually in the range of 0.1 to 20 ppm. Room sprays can be used to adjust an initial average concentration of 0.0001 to 1 mg of the compound of formula (1) per cubic meter of treated space. The compounds of formula (I) are also useful for the protection and treatment of plant species, in which case an effective insecticidal acaricidal or nematocidal amount of the active ingredient is employed. The rate of administration depends on the compound chosen, the nature of the composition, route of administration, plant species, plant density, infestation and other factors, but is usually in the range of 0.001 to 3kg / ha for agricultural yield 3, and preferably between 0, 01 and 1 kg / ha. Typical compositions for agricultural use contain between 0.0001% and 50% of a compound according to formula (I) and preferably between 0.1 and 15% by weight of a compound according to formula (I).

Dusts, fats, pastes and aerosols are usually applied randomly as described above and the concentrations of a compound of formula (I) in the preparations to be used are in the range of 0.001 to 20 w / v% (w / v).

The compounds according to (I) show activity against the common house fly (Musca domestica). In addition, certain compounds of formula (I) exhibit activity against other arthropic pests including Myzusperslca / fetranychus urticae, Plutella sylostella, Culex spp. Tribolium castaneum, Sltophilus granarius, Periplaneta americana and Blattella germanlca. The compounds according to formula (I) are therefore suitable for the control of arthropods, for example insects and arcarins in any environment where these diseases can form, for example in agriculture, in animal husbandry, for public health control and in the home. Insect pests include members of the order Coleoptera:

Anobium, Ceutorhynchus, Rhynchophorus, Cosmopolites, Lissorhoptrus, Mellgethes, Hypothenemus, Hyleslnus, Acalymma, Lema, Psylliodes, Leptinotarsa, Gonocephalum, Agrlotes, Dermoleplda, Heteronychus, Phaedon, Tribolium, Sltophilus, Didbrotlca, Anthonomus Anthrenus spp.), Lepidoptera (Ephestia, Mamestra, Earias, Pectlnophora, Ostrlnia, Trichoplusla, Pieris, Laphygma, Agrotls, Amathes, Wiseana, Tryporyse, Diatraea, Sporganothls, Cydia, Archlps, Plutella, Chilo, Heliothls, Spodoptera or Tineola spp.), Diptera (Musca, Aedes, Anopheles , Culex, Glossina, Simulium, Stomoxys, Haematobia, Tabanus, Hydrotaea, Lucilia, Chrysomla, Callitroga, Dermatobla, Gasterophilus, Hypoderma, Hylemyia, Atherigona, Chlorops, Phytomyza, Ceratltis, Llriomyza and Melophagus spp.), Phthiraptera (Malophaga, Damalina spp Anoplura Linognathus haemotopinus spp.), Hemiptera (Aphis, Bemisia, Phorodon, Aenoolamina, Empoasca, Parkinslella, Pyrilla, Aonidiella, Cocus, Psaudococcus, Helopeltls, Lygus, Dysdercus, Oxycarenus, Ne zara, Aleurodes, Triatoma, Psylla, Mysus, Megoura, Phylloxera, Adelyes, Nlloparvata, Nephrotetix o Cimex spp.), Orthoptera (Locusta, Gryllus, Schistocerca or Acheta spp.), Dictyoptera (Blattella, Perlplaneta or Blatte spp.), Hymenoptera (Athalia, Cephus, Atta, Solenopsis or Monomorium spp.), Isoptera (Odontotermes and Retlculitermes spp.), Siphonaptera (eg Ctenocephalldes or Pulexspp.), Thysanura (Lepisma spp.), Dermaptera (Fort lcula spp.), Pscoptera (see also Perlpsocus spp.) And Thysanoptera (Thrips tabacl). Ascarinic delays include ticks, such as Genera boophilus, Ornithodorus, Rhiplcephalus, Amblyomma, Hyalomma, Ixodes, castaneum, Sltophilus granarius, Periplaneta amiercana and Blattella germanlca.

Nematodes, which are important for agriculture, forestry, or horticultural plants and trees, either directly or by spreading bacterial, viral mycoplasma or fungal diseases on the plants, include root-knot nematodes such as:

Meloidogyne spp. (see G. M. incognita); 'cyst' nemp'.odes Globodera spp. (G. G. rostochiensis); Herntera spp. (see G. H. avenae); Radopholi! "Snp. (e.g., R. similis); 'lesion' nematodes Pratylencous spp. (e.g., P. pratensis); Belonolaimus spp. (e.g., B. gracilis); Tylenchulus spp. (e.g., T. semlpenetrans); Rotylenchulus spp. (see R.R. reniformls); Rotylenchus spp. (e.g., R. robustus); Hellcotylenchus spp. (e.g., H. multiclnctus); Hemlcycllophora spp. (e.g., H. gracilis); Criconemoides spp. (e.g., C. similis); Trlchodorus spp. (e g g T. primitivus); daggers nematodes Xiphinema spp. (see also X. diversicaudatum) Longidorus spp. (see G. L. elongatus); Hoplolmus spp. (e.g., H, coronatus); Aphelencholdes spp. (e.g., A. ritzema-bosi, A. besseyl); 'star and bulb' Eelworms Ditylenchus spp. (e.g., D. dipsacl).

Compounds of the invention may be combined with one or more pesticidal active ingredients (e.g., pyrethroids, carbamates, and organophosphates) and / or with attractants, repellents, bactericides, fungicides, nematocides, anthelmintic agents, and the like. It has been found that the activities of the compound according to the invention can be enhanced by addition of a synergist or enhancer, for example one of the oxidase inhibitor class of synergists, such as piperonyl butoxide or propyl 2-propynylphenyl phosphonate, a second compound according to the invention or a pyrethroid pesticidal compound. When an oxidase inhibitor synergist is already present in a composition according to the invention, the ratio of synergist to compound of formula (I) is between 25: 1-1: 25, in the example about 10: 1.

Stabilizers for preventing any chemical decomposition of the compounds of the invention include e.g. As antioxidants (such as tocopherols, butylated hydroxyanisole and Butylhydi jxytoluol) and "scavengers" (such as epichlorohydrin) and organic or inorganic bases, such as trialkylamines such as triethylamine, which act as base stabilizers and as "scavengers"

 In the following the invention will be explained in more detail by means of examples.

embodiments

Example I

1- (ΡβηΙ-4-ΙηνΙ) -4 · ρΓορνΙ-2, β, 7-ΜοχβοΙογ (: Ιο [2.2.2] · οοί8η

(i) To a stirred mixture of n -valeraldehyde (172 g) and water (21) are added solid calcium hydroxide (112 g) and a formaldehyde solution (1.41% of a 40% aqueous solution). The reaction temperature is maintained below 4O ⁰ C and the addition carried out for 45 minutes. The mixture is kept for 5 hours at a temperature of 6O ⁰ C. The reaction mixture is filtered through kieselguhr and the filtrates are evaporated in vacuo. The residue is treated with hot methanol (21) and the mixture is filtered through diatomaceous earth. The filtrates are evaporated in vacuo. A viscous oily product (458 g) is obtained and purified as follows:

A solution of the crude product is stirred with acetic acid (200 ml) at room temperature. Then, acetic anhydride (1.21) is added over 4 hours. The temperature rises to 65 ^° C. Stirring is continued for a further 12 hours. The reaction mixture is added with stirring to cold water (31) over 3 hours. The mixture is then stirred for a further 3 hours. The aqueous mixture is extracted with diethyl ether. The ether extracts are washed with aqueous sodium bicarbonate solution and then with brine. The extracts are dried over anhydrous magnesium sulfate and then evaporated in vacuo.

Distillation gave 2-hydroxymethyl-2-n-propylpropane-1,3-dioltriacetat (238g), a colorless oil (boiling point 120-140 ⁰ C,

Sodium (0.5 g) is added to a stirred solution of the above triacetate (238 g) in methanol (2.5 L). The mixture is heated under reflux and with stirring for 72 hours. The mixture is evaporated in vacuo.

2-hydroxymethyl-2-n-propylpropane-1,3-diol (87 g) is obtained in the form of colorless crystals (melting point 93 ⁰ C).

Ref. W.E. Conrad, L.A. Leva ^ seur, R.F. Murphy, N.L. Hare and H.E. Conrad, J. Org. Chem. 1962, 27, 2227.

(ii) A mixture of 2-hydroxymethyl-2-n-propylpropane-1,3-diol (24.6 g), diothyl carbonate (20.1 ml), potassium hydroxide (0.3 g) and dry ethanol (2 ml) become light heated under reflux (oil bath 110-12O ⁰ C) while passing nitrogen for 30 minutes. Thereafter, the ethanol formed by distillation under atmospheric pressure (oil bath 130-140 ⁰ C,

Distillation head temperature 76 ⁰ C) removed. The pressure is reduced to 20 mm Hg and the oil bath temperature is set to 23O ⁰ C. 3-hydroxymethyl-3-n-propyloxethane is distilled as a colorless liquid (16.7 g) (top temperature 120-126 ⁰ C).

Ref: European Patent Application No. 216624.

(iii) A solution of 5-chloro-1-pentyne (Aldrich Chemical Company, 20 g) and potassium cyanide (19 g) in 20% aqueous ethanol (120 ml) are heated at reflux for 20 hours. Water (600ml) is then added and the resulting mixture extracted with diethyl ether. The combined ethereal extracts are washed with water and then with brine. The extracts are dried over anhydrous magnesium sulfate and then evaporated in vacuo.

Distillation gave 5-cyano-1-pentyne (9.9g) as a colorless oil (b.p. 67-68 ° C, 15mm Hg).

(iv) A mixture of 5-cyano-i-pentyne (9.9 g) and 10% aqueous potassium hydroxide solution (100 ml) was heated at reflux for 6 hours. The resulting solution was extracted with chloroform. The aqueous phase was acidified to pH 1 with concentrated hydrochloric acid and then back-extracted with dichloromethane. The dichloromethane extracts were washed with brine, dried over anhydrous magnesium sulfate and then evaporated in vacuo.

Distillation gave hex-5-ynoic acid (9.9 g) as a colorless liquid (b.p. 66-67 ⁰ C, 0.6 mm Hg).

(v) A mixture of hex-5-acetic acid (1 g) and thionyl chloride (1.95 ml) in benzene (25 ml) is heated with stirring for 3 hours. The resulting solution is cooled and evaporated in vacuo. The resulting acid halide is taken up in ether (5 ml) η and added dropwise to a stirred solution of 3-hydroxymethyl-3-n-propyloxyethane (1.2 g) and pyridine (0.8 ml) in dry ether (20 ml). The reaction mixture is stirred for 16 hours at room temperature. Subsequently, the organic phase is washed with water, 5% hydrochloric acid, saturated sodium bicarbonate solution and brine, evaporated before drying over anhydrous magnesium sulfate and then in vacuo. The residue is purified by chromatography on silica gel, pre-eluted with hexane containing 1% triethylamine. Elution with hexane / ether mixtures gives (3-propyloxy-3-yl) -methyl-hex-5-ynoate (1.33 g) as a colorless oil.

Gas / liquid chromatography (GLC): OV-17 at 175 ^° C gives a peak.

The nuclear magnetic resonance (NMR) spectrum gives: ¹ H (ppm from TMS in CDCl ₃ , integral number of peaks):

4,45,4H, s; 4,20,2H, s; 2,8-0,8,14H, m.

(vi) Boron trifluoride etherate (0.18 ml) is a stirred solution consisting of (3-Propyloxethan-3-yl) methyl-hex-5-ynoat (1.33g) in dry dichloromethane (25ml) at -7O ⁰ C were added , The mixture is warmed to room temperature over a period of 16 hours. Triethylamine (0.28 ml) is then added and the solvent removed in vacuo. The residue is separated (extracted by shaking) with diethyl ether and water. The organic phase is separated and further washed with water and brine prior to drying over anhydrous magnesium sulfate. The solvent is evaporated in vacuo and the residue is purified by column chromatography on alumina and elution with 1: 6 dichloromethane: hexane saturated with ammonia. i-IPenM-ynylM-propyl ^ .ej-trioxabicyclo ^^^ l-octane is crystallized as a colorless oil which triturates with hexane (0.64g).

Gas / liquid chromatography (GLC): OV-17 at 200 ^° C gives a peak.

Example Il

1- (Hex-5-lnyl) -4-propyl-2,6,7-trioxabicyclo [2.2.2] octane

(i) A solution of methanesulfonyl chloride (23.7 ml) in dry dichloromethane (25 ml) is added to a solution of hex-5-yn-i-ol (Lancaster Synthesis, 25 g) and triethylamine (47.3 ml) in dichloromethane (300 ml). added dropwise with stirring and under a nitrogen atmosphere at a temperature of -7O ⁰ C. The resulting mixture is warmed to room temperature over a period of 16 hours. The mixture is then washed with water, dilute hydrochloric acid, saturated sodium carbonate solution and brine prior to drying over anhydrous magnesium sulfate and evaporation in vacuo. Hex-5-ynylmethanesulfonate is obtained in the form of an oil (43.6 g) and used without further purification.

The nuclear magnetic resonance spectrum (NMR) yields: Ή (ppm from TMS in CDCI _3, integral, number of peaks, J _Hl):

4,15,2H, t, J _Hl 6; 3,0,3H, s; 2,4-1,4,7H, m.

(M) A mixture of hex-5-ynylmethanesulfonate (43.6g) and potassium cyanide (24g) in 20% ethanol (150ml). heated under reflux for 4 hours and then stirred overnight at room temperature. Water (600ml) is added and the mixture extracted with diethyl ether. The organic extracts are washed with water and brine prior to drying over anhydrous magnesium sulfate and evaporation in vacuo.

Distillation gives a 6-cyano-1-hexine (20.1 g) as a colorless oil (b.p. 92-95 ° C, 15 mm Hg).

Infrared Spectrum (IR) (Liquid Film): 3340, 2990, 2920, 2300, 2160, 1485, 1450, 155, 6070 cm " ¹ .

(iii) using the step (iv) method of Example 1 is converted to 6-cyano-1-hexyne in hept-6-ynoic acid (0.75 mm Hg Siedopunkt 78-82 ⁰ C).

Infrared spectrum (IR) (liquid film): 3340.2980,2160,1730,1435,1310,1255,955,660cm " ¹ .

(iv) Using the procedures described in steps (v) and (vi) of Example I, 1- (hex-binyl) -4-propyl-1-trioxabicycloxy-1-octane prepared from hept-6 acid and S-hydroxymethyl-Sn-propyloxethane.

Gas / liquid chromatography (GLC): OV-17 at 175 ° C gives a peak.

The following compound is prepared in an analogous manner: 1- (Oct-7-ynyl) -4-propyl-2,6,7-trioxabicyclo [2.2.2] octane from oct-7-yn-1-ol (Ref. Patent 969816, Chem. Abs. 1965, 62 "1571 f.)

Example III

1- (Pent-4-lnyl) -4-propyl-3-trlfluormethyl-2,6,7-trloxablcyclo [2.2.2] octane

(i) A mixture of hex-5-acetic acid (1 g) and thionyl chloride (1.95 ml) in benzene (25 ml) is heated under reflux for 2.5 hours.

The resulting solution is cooled and evaporated in vacuo. The thus-obtained acid chloride is taken up in dry diethyl ether (5 ml) and dropwise added to a stirred solution consisting of 3- (1-hydroxy-2,2,2-trifluoroethyl) -3-n-propyloxethane (1.77 g) (European Patent Application no 211 598) and pyridine (0.8 ml) in ether (20 ml). The reaction mixture is stirred overnight at room temperature. After washing with water, dilute hydrochloric acid, saturated sodium carbonate solution and brine, the organic phase is dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue is purified by chromatography on silica gel (silica) pre-eluted with hexane containing 1% triethylamine. Gradient elution with hexane / ether mixtures gives 2,2,2-trifluoro-1- (3-propyloxethan-3-yl) -ethyl-hex-5-ynoate (1.2 g) as a colorless oil.

Gas / liquid chromatography (GLC): OV-17 at 175 ⁰ C gives oinen peak.

The nuclear magnetic resonance (NMR) spectrum gave: ¹ H (ppm from TMS in CDCl ₃ , integral, number of peaks) 4.8-4.1.5 H, m; 2,7-0,8,14 H, m.

(ii) Using the procedure described in step (vi) of Example I and starting from 2,2,2-trifluoro-1- (3-propyloxethan-3-yl) -ethyl-hex-5-ynoate, 1 - ( Pent-4-ynyl) -4-propyl-3-trifluoromethyl-2,6,7-trioxabicyclo [2.2.2] octane obtained in the form of a white crystalline solid.

Gas / liquid chromatography (GLC): OV-17 at 17O ⁰ C gives a peak.

The following compound is obtained in an analogous manner from hept-6-acetic acid and 3- (1-hydroxy-2,2,2-trifluoroethyl) -3-n-propyloxyethane: 1- (hex-5-ynyl) -4-propyl -3-trifluoromethyl-2,6,7-trioxabicyclol2.2.2) octane.

Example IV

1- (Pent-4-ynyl) -4-propyl-2,6,7-trloxabicyclo [2.2.2] octane-3-carbonitrile

(i) A solution of dimethyl sulfoxide (12 ml) in dry dichloromethane (4.0 ml) is added to a solution of oxalyl chloride (7.4 ml) in dichloromethane (25 ml) stirred at -70 ° C under nitrogen, added. After complete addition, the resulting mixture is stirred for a further 5 minutes at a temperature of -70 ⁰ C before a solution of 3-hydroxymethyl-3-n-propyloxethan (10.0 g) in dichloromethane (25ml) dropwise over a period of 10 Minutes is added. The resulting mixture is stirred for an additional 30 minutes when (neat = claw, hoof) triethylamine (54 ml) is added over about 30 minutes. The reaction mixture is warmed to room temperature over 3 hours when poured into water. The organic phase is separated and the aqueous layer is further extracted with dichloromethane. The combined organic extracts are washed with dilute hydrochloric acid, saturated bicarbonate solution and brine. The resulting organic phase is dried over anhydrous magnesium sulfate and evaporated in vacuo to give 3-formyl-3-n-propyloxyethane (10.5 g) (European Patent Application No. 216624) in the form of a yellow oil.

(ii) A mixture of hex-5-acetic acid (1 g) and thionyl chloride (1.95 ml) in benzene (25 ml) is heated under reflux for 3 hours. The resulting solution is cooled and evaporated in vacuo. The acid chloride thus obtained is a stirred solution consisting OFF3-formyl-3-n-propyloxethan (1.14 g) h ^r ther (50 ml) was added, after which a solution of sodium cyanide (0.61 g) in water (1 ml) was added becomes. The resulting mixture is stirred well at room temperature for 16 hours. Thereafter, the reaction mixture is washed with water, saturated sodium bicarbonate solution and brine, and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the residue is purified by column chromatography on kieselguhr, pre-eluted with hexane containing 1% triethylamine. Gradient elution with hexane / ether mixtures gives (1-cyano-1- (3-propyloxethane-3-yl) -methyl-hex-5-ynoate as a colorless oil (1.2 g).) Gas / liquid chromatography (GLC): OV-17 at 175 ° C gives a peak

The nuclear magnetic resonance spectrum (NMR) gives the following: ¹ H (ppm from TMS in CDCl ₃ , integral number of peaks) 5, 6, 1H, s; 4.75-4.4,4H, m; 2.8-0.9.14H, m.

(iii) Boron trifluoride etherate (0.25 mL) is added to a solution of i-cyano-1-O-propyloxethane-S-yD-methyl-hex-O-ynoate (0.5 g) in dry dichloromethane (10 mL) which is at a temperature of -. 70 ° C under a nitrogen atmosphere is stirred. The resulting solution is warmed to room temperature overnight. Triethylamine (0.38 ml) is added and the solvent removed under vacuum. The residue vi. d separated (shaken out) between water and diethyl ether. The organic

Phase is separated and washed with water and brine prior to drying over anhydrous magnesium sulfate and evaporation in vacuo. The residue is purified by column chromatography on alumina by elution with 1: 4 dichloromethane: hexane saturated with ammonia. This gives the 1- (pent-4-Invl) -4-propyl-2,6,7-trioxabicyclol.2.2.2) octane-3-carbonitrile in the form of an oil (0.25 g).

Gas / liquid chromatography (GLC): OV-17 at 175 ⁰ C gives oinen Peak

 The following compounds were prepared in an analogous manner: 1- (hex-5-ynyl) -4-propyl-2,6,7-triuxabicyclo [2.2.2] octane-3-carbonitrile 4-n-butyl-1- ( hex-5-ynyl) -2,6,7-trioxabicyclol2.2.2 | octane-3-carbonitrile

4-t-butyl-1- (hex-5-ynyl) -2,6,7-trioxabicyclo2.2.2) octane-3-carbonitrile (Preparation of 2-t-butyl-2-hydroxymethyl-1,3-propanediol); ,

Y. Ozoe and M. EtO, Agric. Biol. Chem., 1982, 46, 411

4-Cyclopropylmethyl-1- (hex-5-ynyl) -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile, 1- (hex-5-ynyl) -4-phenyl-2,6 , 7-trioxabicyclo | 2.2.2) octane-3-carbonitrile, 1- (hex-5-ynyl) -4-i-butyl-2,6,7-trioxabicyclo [2.2.2l-octane-3-carbonitrile, and

1- (Hex-5-ynyl) -4- (2-methylprop-2-enyl) -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile was prepared from 3-cycloppropylmethyl-3-formyloxethane , 3-formyl-3-phenyloxyethane, 3-formyl-3-i-butoxyethane and 3-formyl-3- (2-methyl-2-propyl-2-ethoxyethane). S-cyclopropylmethyl-S-formyloxyethane, 3-formyl-3-one phenyloxyethane, 3-formyl-3-i-butyloxyethane and 3-formyl-3- (2-methylprop-2-enyl) -oxoethane were prepared from diethyl cyclopropylmethyl malonate (JA Arvin and R. Adams, J. Amer. Chem. Soc, 1928 , 50, 1985), diethylphenylmalonate (Aldrich), diethyl-i-butylmalonate (beilstoin, 2.683) and diethyl 2-methylprop-2-enylmalonate (WJ Doran and HA Shonle, J. Amer. Chem. Soc, 1937, 59, 1625) using the same procedure as described in Example V, except that toluene is used as the solvent in step (i) instead of the tetrahydrofuran.

Example V

4-cyclohexyl-1- (pent-4-lnyl) -2,6,7-trloxablcyclo [2.2.2] octane

(i) Diethylcyclohexylmalonate (18.7 g) (Rof. Beilstein 9,739) is added to a stirred suspension of sodium hydride (4.8 g, 50% igo

Dispersion in oil) in dry tetrahydrofuran (50 ml) under a nitrogen atmosphere. The mixture is over

Heated under reflux for 1 hour and stirring. The mixture is cooled and benzyl chloromethyl ether (13.9 g) (Sigma Chemical

Company) in dry tetrahydrofuran (50 ml) is added and the mixture is stirred for 3 hours under reflux with stirring

heated. The mixture is cooled and poured into water. The aqueous mixture is extracted with ether. The

Ether extracts are washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. diethyl

2-benzyloxymethyl-2-cyclohexylmalonate (30 g) is obtained in the form of a brown oil and used without further purification.

(ii) Diethyl ^ -benzyloxymethyl ^ -cyclohexylmalonate (2g) is added to a suspension of lithium aluminum hydride (0.63g) in dry ether (30ml) at 0 ° C and under a nitrogen atmosphere. The mixture is added for 12 hours

Room temperature stirred. Water (5 ml) is carefully added and the mixture is stirred for 10 minutes. A 10% Sulfuric acid solution (10 ml) is added and the mixture is extracted with ether. The ether extracts are mixed with water

washed, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue is removed by means of

Chromatography on silica gel purified by elution with 1: 1 etherhexane. 2-benzyloxymethyl-2-cyclohexyl-propane-1,3-diol

is obtained in the form of a colorless oil (1.0 g).

(iii) 2-Benzyloxymethyl-2-cyclohexyl-propane-1,3-diol (5.5 g) in dry diethyl ether (50 ml) are added to liquid ammonia (200 ml) at a temperature of -70 ° C. Na'.rium (2.5 g) is added to the stirred solution. Stirring is maintained for 1 hour at a temperature of -70 ° C. The mixture is allowed to warm to a temperature of 0 ° C, and solid ammonium chloride (15 g) is added cautiously. The ammonia is removed from the reaction mixture under a stream of nitrogen. Add 25 ml of methanol to the stirred mixture to destroy residual sodium. Dichloromethane (400 ml) is added and the mixture is filtered. The filtrates are evaporated in vacuo.

2-Cyclohexyl-2-hydroxymethylpropane-1,3-diol is obtained as a colorless solid (3.2 g).

(iv) A mixture of 2-cyclohexyl-2-hydroxymethylpropane-1,3-diol (3.76g), ethyl carbonate (2.42ml) and a solution of

Potassium hydroxide in ethanol (0.1 ml of a solution of 5 g in 25 ml) is heated at reflux for 20 minutes. The device will

converted to distillation. Ethanol is removed by distillation (78-80 ⁰ C at 760mm Hg). After all Et! irisolated, the residue is distilled under reduced pressure. S-cyclohexyl-S-hydroxymethylmethoxyethane (europ. '

Patent Application No. 216624) distils over as a colorless oil.

(v) Using the procedure outlined in steps (v) and (vi) of Example I, 4-cyclohexyl-1- (pent-4-ynyl) -2,6,7-trioxabicyclo [2.2.2] octane prepared from hex-5-acetic acid and 3-cycl'-hexyl-3-hydroxymethyloxethane.

Gas / liquid chromatography (GLC): OV-17 at 23O ⁰ C gives a peak. In an analogous manner, 4-cyclohexyl-1 - (hex-5-ynyl) -2,6,7-trioxabicyclo (2.2.2 l-octane prepared from hept-6-acetic acid. Example Vl

4-t-butyl-1- (hex-5-ynyl) -2,6,7-trioxab! Cyclo [2.2.2] octane

Method 1

Using the method described in step (vi) of Example I and adding hept-6-acetic acid and 3-t-butyl-3

Hydroxy-methylthioxethane (2-t-butyl-2-hydroxymethylpropane-1,3-diol is prepared by the method of Y. Ozoe and

M.Eto, Agric. Biol. Chem. 1982, 46, 411), 4-t-butyl-1- (hex-5-ynyl) 2,6,7-trioxabicyclo [2.2.2] octane is prepared. Gas / liquid chromatography (HLC): OV-17 at 23O ⁰ C gives a peak.

Method 2

A mixture of 2-t-butyl-2-hydroxymethylpropane-1,3-diol (0.75 g) and Trimethylorthohept-6-ynoate (0.75g) (see Example XI) was heated at 5O ⁰ C until homogeneous. A drop of concentrated hydrochloric acid is added and the mixture is heated for 10 minutes under a stream of nitrogen at 135 ° C. The mixture is cooled and chromatographed on alumina, eluting with 1: 6 dichloromethane: hexane saturated with ammonia.

4-t-Butyl-1- (hox-5-Invl) -2 _> e, 7-trioxablcyclo [2.2.2] octene is obtained as colorless crystals (0.38 g, recrystallized from hexane) orhaltone. Αυίβη8ΐοοθ \ Λ / βΐ8βννίΓα1 · (Ηθχ · 5 · ΙηνΙ) · 4 · ρΙιοηνΙ · 2, 6, 7 · «ΓΐοχβοΙονοΙο | 2.2.2 | · οο ββηου8 2 · ΗναΓθχνηιοΐΙ) νΙ · 2 · ρΙ) βηνΙρΓορβη · 1,3 · (ΙίοΙ (prepared from dimethyl-2-phonyl malonate under Verwond the same in Example V boschriobonon method) horgostollt.

Example VII

4-t-ButyM- (e-trimethylsllylhex-5-lnyl) -2,6, / - tiioxablcyclo (2.2.2] octane

n-Butyllithium (0.31 ml of a 1.6M solution in hexane) becomes a stirred solution of 4-t-butyl-1 ·················· -2, β, 7 · trioxablcyclo | 2.2.2 | - octane (100mg) added in dry tetrahydrofuran (4.0ml) at ⁰ ° C under nitrogen. The

Reaction mixture is stirred for 16 minutes at a temperature of O'C. Trimethylsilyl chloride (63μΙ) is added and gobon

the mixture is warmed to 20 ° C over a period of 2 hours over a period of 2 hours. Water (0.5 ml) is added and the solvent is removed. Then water is added and the aqueous mixture is extracted with diethyl ether. The etherischon

Extracts were washed with brine and dried over magnesium chloride magnesium sulfate. The solvent is in

vacuo away. The residue is goroinigt by chromatography on alumina (Ahmina Woelm TSC), woboi with 1: 0

Dichloromethane: Hoxan saturated with ammonia.

4-t-Butyl-1- (6-trimethylsilylhox-5-ynyl) -2, e, 7-trloxy-cyclo [2.2.2] octane is obtained as colorless crystals (60 mg) (melting point 87-90.5 ° C) ,

Gas / Liquid Chromatography (GLC): OV-17 boi 230 ^e C yields einon Poak. Example VIII

1- (4-Ethlnylcyclohexyl) -4-propyl-2,6,7-trloxablcyclo [2.2.2] octane

(i) To a stirred solution of DlmethyMAcyclohexan dicarboxylate Uog, Aldrich) in methanol (50 ml) is added

Potassium hydroxide solution (7.3 g) in methanol (75 ml) was added. The reaction mixture is heated at reflux for 16 hours. After cooling, the solvent is removed with a rotary evaporator. Dor residue is in ether and water

taken and extrahiort to remove non-reactiomed starting ester. Dio aqueous layer is used with pre-sintered

Acidified hydrochloric acid and re-extracted with ether. The ether extracts are washed with brine and dried. Dio Evaporation in vacuo gives a solid. The purification is carried out by means of recrystallization from ethylacotate and

gives 4-Methoxycarbonylcyclohex.mcarbonsäure (6.2g), mp 90.9 ⁰ C.

Ref: J.D. Roberts et al., J. Amer. Cheti. Soc, 1953, 75, 637

(ii) Thionyl chloride (3.65 ml) is added to a stirred solution of 4-mothoxycarbonylcyclohexanecarboxylic acid (5.6 g) in dry

Benzene (50ml) added. The reaction mixture is gently refluxed for 4 hours in an oil bath. Dio preserved Solution is cooled and evaporated in vacuo. The acid halide thus obtained is redissolved in Beniui and woiter in

vac jo evaporates. This material is used for the next step without further purification.

Infrared spectrum (IR) (liquid film), 1790 (s), 1720 (s) cm "'

(iii) A zinc borohydride solution (67 ml of a 0.35M solution, ref. W. J. Gensler et al., J. Amer. Cherrt. Soc, 1960, 82, 6074) and

Tetramethylethylenediamine (TMEDA) was progressively added to a stirred solution of 4- Methoxycarbonylcyclohoxylcarbonyl chloride (1.02g) in THF (18ml) at ⁰ ° C. Dio reaction mixture is used for

Stirred for 30 minutes at 0 ° C. Oio organic phase is then washed with dilute hydrochloric acid and brine before being dried over anhydrous magnesium sulfate and then evaporated in vacuo. Methyl 4-hydroxymethylcyclohexanecarboxylate is obtained in the form of a semicrystalline oil.

Infrared spectrum (IR) (Fltfssigfilm), 3400 (s, br), 1720 (s) cm "'gas / liquid Chromatographio (GLC): OV-17 at 110 ⁰ C gave zwoi Peaks (cis, trans isomers, ~ 1: 1).

(iv) Dimethyl sulfoxide (0.65ml) in dry dichloromethane (5ml) is added to a solution of oxalyl chloride (0.363ml) in

Dichloromethane (5ml) under a stream of nitrogen at -70 ⁰ C was added. After stirring for 5 minutes, a solution of Methyl ^ -hydroxymethylcyclohoxanecarboxylate (0.64 g) in dichloromethane (5 ml) was added dropwise. The reaction mixture is at

-7O ⁰ C stirred for 30 minutes. Triethylamine (2.60ml) is then added and the crude mixture is allowed to pass through

Heat to room temperature for 3 hours. After pouring into water (100ml), the organic phase with

diluted hydrochloric acid, sodium carbonate solution and brine before drying over magnesium sulfate. The

Evaporation in vacuo gave methyl ^ -formylcyclohexanecarboxylate (0.58g) as a mixture of cis and trans isomoron. Infrared Spectrum Tt) (Liquid Film) 1720cm " ¹ (s). Gas / liquid chromatography (GLC): OV-17 at 120 ° C gave only one poak. Mass spectrum (MS), chemical ionization: M + 1,171.

(v) A solution of carbon tetrabromide (1.66 g) in dry dichloromethane (10 ml) is added to a stirred solution of

Triphenylphosphine (2.62g) in dry dichloromethane (10ml) was added with cooling. To this orange-colored solution

add a solution of methyl 4-formylcyclohexanecarboxylate (0.85g) in dry dichloromethane (10ml) under a vacuum

Nitrogen stream added. The reaction mixture is stirred overnight at room temperature. The solvent then becomes

removed in vacuo. The residue is mechanically stirred for 1 hour with hexane. The filtration gives a colorless solution.

Evaporation gives a colorless oil consisting of methyl 4- (2,2-dibrororivip.yl) cyclohexane carboxylate (1.15 g) as a Mixture of cis and trans isomers. Infrared spectrum (IR) (liquid film) 1722cm " ¹ Gas / liquid chromatography (GLC): OV-17 at 155 ⁰ C gave two peaks (cis and trans isomers, ~ 1: 1). Mass Spectrum (MS), Chemical Ionization (2 peaks GLC (Ms), both M + 1.325.

(vi) Methyl 4- (2,2-dibromovinyl) cyclohexanecarboxylate (1.15 g) is added to a stirred solution of potassium hydroxide (297 mg) in

Methanol (2 ml) added. It is stirred overnight and the solvent evaporated in vacuo. The backlog will be between Diethyl ether and water distributed. The aqueous layer is separated and acidified with dilute hydrochloric acid. The extraction

with diethyl ether gives a solution which is washed with brine and then dried over anhydrous magnesium sulfate. Evaporation in vacuo gives 4- (2,2-dibromovinyl) -cyclohexanecarboxylic acid (0.86 g) as a colorless solid.

Infrared spectrum (IR) (Nujol muH), 1690 (s), cm ^-1

(vii) Thionyl chloride (0.67 mL) is added to gorührton solution of 4- (2,2-dibiominyl) -cyclohoxanecarboxylic acid (0.86 g) in dry oontol (25 mL). The Roakllonsmlechung is heated in ilnom oil bath for 4 hours under lolchtom reflux. The resulting lotion is cooled and placed in vacuo overnight. The thus obtained SMurohalogonide is re-dissolved in benzene and further evaporated in vacuo. This gives old pale yellow oil 4- (2,2-dibromovinyl) -cyclohoxanecarbonyl chloride (0.91 g). InfreroUpoktrum (IR) (liquid film), 1? 90 (i) cm ~ \

(viii) 4- (2,2-Dibromovinyl) -cyclohexanecarbonylchloride (0.91g) in dry-ion Uichloromethane (5ml) of the ozone-cooled (O'C) solution of 3-propyl-3-yl-yl-oxymotliyloxethane (0.406g The mixture is stirred overnight, and the crude mixture is heated to room tolorotirene, then dichloromethane is added, and the organic phase is washed with hydrochloric acid, gosaturated sodium carbonate, and saline The solvent is dissolved in vacuo in vacuo and the residue is triturated on silica gel using a column chromatography on silica gel, precoloured with Hoxan, 1% triethylamine, triethylamine, triethylamine, elution with Hoxan / Ethor (3: 1) 3Propyloxothnn-3 -ylmothyl-4 (2,2 · dibromovinyl-cyclohoxanecarboxylate (0.6 g) in the form of an orange mixture of cis and tronsylsinoron. Infrared Spoktrum (IR) (liquid film), 1722 (s) cm -1 '

Massonspoktrum (MS), chomischo ionization, 2 Poaks In GLC / MS in the ratio of 3: 1, boido M + 1,423. (ix) Boron trifluoride diolate (40 μL) of ozone chloride solution of 3-propyloxothan-3-ylmothyl-4- (2,2-dibromovinyl) -cyclohexanecanecarboxylate (0.57 g) in dry dichloromethane (10 mL) of boi-70'C. The mixture is allowed to warm to room temperature over 16 hours during oinos period. Subsequently, triethylamine (0.6 ml) zugegobon. Dio organic Phaso is using SaIiI? solution in front of dom drying over a water troutroiom magnesium sulphate gowaschon. The solvent is isolated in vacuo ovaporiort and the residue by columnchromatogrophio on alumina (alumina), eluent with 3: 7 dichloromethone: Hoxon saturated with ammonia. i-l / t - ^ - Dibromovinyl Dcyclohoxyll M -propyl-1-e, -trioxabicyclo (2.2.21-octane is prepared in the form of oinos colorless oil (0.34 g) orhaltone. Infrared Spoktrum (IR) (liquid film), 1060.1020 cm.

Massonspoktrum (MS), chomischo ionization, 2 Poaks in GLC / MS in oinom ratio of 3: 1, boido M + 1,423. (x) n-Butyllithium (1.6 mL or 1.1 M solution in Hoxan) is added to boi-70 * C ooror solution of 1- | 4- (2,2-dibromovinyl) cyclohoxyl-H-propyl-2,6,7- trioxabicyclo | 2.2.2 | -octane (0.25g) in dry tetrahydrofuran (5ml) under nitrogen flow. After heating to Haumtomporatur over 2 hours, ether (~ 25ml) is added. Dio otherischo solution is washed with brine and dried over wassorfroiom magnesium sulfate. The solvent is de-crystallized in vacuo and the residue is triturated on aluminum oxide using SBulenchromatographio, eluent with 3: 7 dichloromethane: Hoxan saturated with ammonia. i-t / t -ethynylcyclohexylM-propyl-i ^ ej-trioxabicycloU ^^ I-octane is in the form of oinos colorless oil (0.13g) orhalton.

Example IX

4-t-Butyl-1- (4-ethlnylcyclohexyl) -2, e, 7-trloxeblcyclo [2.2.2) octane

Method 1

(i) Untor use of the method described in step (viii) of Example VIII, starting from 4- (2,2-dibromovinyl) cyclocycloxanecarbonyl chloride and 3-t-butyl-3-hydroxymothyloxothane, 3-t-butyloxyethane-3- yl-methyl, the 4- (2,2-dibromovinyl) cyclohexanecarboxylate prepared in the form of a mixture of cis and trans-umoron.

(H) Using the method described in step (ix) of Example VIII and starting from 3-t-butyloxothan-3-imethyl, the 4- (2,2-di-vinyl) -cyclohexanecarboxylate, 4-t-butyl- 1- (4- (2,2-dibromovinyl) -cyclohoxyl | -2, e, 7-

trioxabicyclo [2.2.2] octane as a colorless oil in the form of oinor mixture of cis and trans isomers orhalton.

(iii) Untor use of the method described in Stufo (x) 'Example VIII and starting from 4-t-butyl-1- [4- (2,2-dibromovinyl) -cyclohoxyl] -2,6,7-trioxabicyclo 2.2.2 | -octane is the 4-t-butyl-1- (4-ethynylcyclohexyl) -2,6,7-trioxabicyclo [2.2.2] octane as a colorless solid (mp 125.9-131.8 ⁰ C) ) in the form of a mixture of cis and trans isomoron.

Both cis- and trans-4-t-butyl-1- (4-ethynylcyclohoxyl) -2,6,7-trio: <abicyclo | 2.2.2 | -oct8n are obtained as follows:

(a) cis- and trans-methyl-4- (2,2-dibromovinyl) cyclohexanecarboxylate

Chromatographic separation of a mixture of cis and trans isomers of methyl 4- (2,2-dibromovinyl) -cyclohoxanecarboxylate (Example VIII, step | v |) on silica gel, eluents with ether (10%) in hexane gives cis- and Trans-methyl 4- (2,2-dibromovinyl-D-cyclohexanecarboxylate as colorless oil.

(B) cls-4- (2,2-Dibromvlnyl) -cyclohexancarbonsfiure

Cis-methyl-4- (2,2-dibromovinyl) -cyclohoxannarboxylate (4g) is refluxed in a solution of hydrobromic acid (48%, 20ml) and acetic acid (40ml). After 4 hours, the solvent is evaporated under reduced pressure. Water (50ml) is added and the mixture extracted with diethyl ether. The ether extracts are extracted with sodium bicarbonate solution. The aqueous layer is acidified and back-extracted with ether. Dio ethereal layer is washed with brine and dried over anhydrous magnesium sulfate. Evaporation gives a cis-4- (2,2-dibromovinyl-D-cyclohoxanecarboxylic acid (3.6 g) in the form of a pale yellow oil.

(c) trans-4- (2,2-Dibromovinyl) cyclohexane carboxylic acid

Trans -methyl 4- (2,2-dibromovinyl) cyclohexanecarboxylate (4.2g) is stirred in a solution of potassium hydroxide (1.09g) in methanol (50ml) overnight. The solvent is then de-concentrated under reduced pressure. Water (SO 4) is added and the mixture is extracted with diethyl ether The aqueous layer is then acidified with hydrochloric acid The post-extraction with ether is followed by washing the organic layer with brine and drying over anhydrous magnesium sulfate Evaporation gives trans-4- (2, 2-dibromovinyl) -cyclohoxanecarboxylic acid (3.6 g) as a pale yellow oil. (Iv) cis- and trans-4- (2,2-dibromovinyl) -cyclohexanecarboxylic acids are then converted into the cis- and trans-4-t-butyl-1 - (4-ethynylcyclohexyl) -2,6,7-trioxabicyclo (2.2.2) octanes converted by, for example, methods are used, as for the steps (vii), (viii), (ix) and (x) of the Example VIII are described.

4-t-Butvl-1- (4-ethlnvlcvctohoxvl) -2 />, 7-trloxabicycto [2.2.2 | -octane

Method 2

(i) Dissolve dilute (44.7 ml) in dry tetrahydrofuran (400 ml) and dissolve under nitrogen and mechanical

Stirring cooled to -78'C. A solution of n-butyllithium in hexane (1.6M, 197ml) is added. After stirring for 10 minutes b <3> -78'C, a solution of dimethylcyclohexane-1,4-dicarboxylate (56.6 g, Lancaster) in tetrahydrofuran (200 ml) is added.

After further stirring for 30 minutes at -78 ⁰ C a solution of Acotylchlorid (22.5 ml) in tetrahydrofuran (200 ml) is lugegeben. The crude mixture is warmed to room temperature over a period of 3 hours. Then Wassei is lugofüge and the mixture extracted with ether. The other extracts are washed with water, with saturated sodium bicarbonate solution, before using Salistluro and saline gowaschon ¹ J, then with anhydrous magnesium sulphate

dried. Evaporation under reduced pressure gave a colorless oil which was distilled in vacuo to give dimethyl 1-acetylcyclohexane-1,4-dicarboxylate (23.3g, b.p. 114-12O ⁰ C at 0.4mm Hg).

Infrared Spoktrum (IR) (Liquid Film) 1740.1710cm " ¹

(ii) Dimotl> yl-1-acylcyclohoxane-1,4-dicarboxylate (23.3g) is added to a solution of concentrated hydrochloric acid (253m * in ethanol (126ml).) After refluxing for 1 hour, the reaction mixture is poured into water extracted with dichloromothane The organic phase is washed with saturated sodium bicarbonate solution and brine.

After Trocknon over wusserfroiem magnesium sulfate, the solvent is removed under reduced pressure to give Mothyl-4-acotylcyclohexancarboxylnt as a colorless oil. This is goreinigt by distillation (boiling point 138-145 ° C at

Infrared Spoktrum (IR) (Liquid Film) 1730,1710cm " ¹

(iii) Using the method described in step (ii) -less example XVIII and starting from methyl 4-acetylcyclohoxanecarboxylate, methyl 1- (1-chlorothiono-O-cyclohexanecarboxylate is prepared.

Infrared Spoktrum (IR) (Liquid Film) 1730cm " ¹

(iv) Using the procedure described in step (Hi) of Example XVIII and starting from methyl-4- (1-chlorothionic cyclohexanecarboxylate), 4 * (1-chlorothiazinyl cyclohexanol is prepared.

Infrared Spoktrum (IR) (Liquid Film) 3400cm " ¹

(v) Preparing the method described in step (iv) of Example XVIII and starting from 4- (1-chloroethenyl) cyclocycloxymethanol, 4-ethynylcyclohoxylmethanol is prepared.

Infrared Spoktrum (IR) (Liquid Film) 3420.3290cm ' ¹

Mass spectrum (MS), (electrononoposition), M + 1,139

(vi) By prewiring the method described in step (v) of Example XVIII and starting from 4-ethynylcyclohexanemethanol, 4-ethynylcyclohexanecarboxylic acid is prepared.

Infrared spectrum (IR) (Nujol muH), 3290,1705cm ' ¹

N'asson spectrum (MS), (electron impact), M + 1,153

Using the procedure described in Example I starting from 4-Ethinylcyclohexancarbonsäure and 3-t-BiJtyl-S-hydroxymethyloxethane is 4-t-ButyM- (4-ethynylcyclohoxyl) -2,6,7-trioxabicyclol2.2.2l-oct ; ι produced.

Utitor Using the method described in Example IV and starting from 3-formyl-3-n-propyloxethane and 4-E'hinylcyelohexanchlnrrbo acids is 1- (4-ethynylcyclohexyl) -4-n-propyl-2,6 7-trioxabicyclo ( 2.2.2l-octane-3-carbonitrile produced.

aelsplelX

4t-ButyM- (3,3-dimethylbut-1-lnyl) -2, e, 7-trloxablcyclo [2.2.2] octane

(i) Using the method prepared in step (viii) of Example VIII and starting from 4,4-dimethyl-2-pentynoyl chloride (ARKatritsky et al., J.Chem.Soc, Perkin Trans 2,1974,282) and 3 ^-t-butyl-3-f hydroxymethyloxe nan is! 3-t-Butyloxethan-3-yl) methyl-4,4-dimethylpent-2-ynoate as a solid.

Gt s / liquid chromatography (GLC): OV-17 at 180 ° C gives a peak.

(ii) Untor Prevention of the process prepared in step (ix) of Example VIII and starting from (3-t-butyloxethan-3-yl) .methyl · 4,4 · dimblyipent-2 inoate 4-t-butyl-1- (3 , 3 dίmethylbut-1-ynyl) -2,6,7-trioxabicyclo | 2.2.2] octane · (in the form of colorless crystals Schmolz point 204-206 ⁰ C).

Gas / liquid chromatography (GLC): OV-17 at 180 ° C gives a peak.

Using the procedure described in Example IV and starting from 3-formyl-3-n-propyloxothane and 3-i-butyl-3-formyloxethane, 1- (3,3-dimethylbut-1-ynyl) -4-n-propyl -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitol and 4-i-butyl-1- (3,3-dimethylbut-1-ynyl) -2,6,7-troxabicyclo [2.2 .2l-octane-3-carbonitrile obtained.

Using an analogous procedure, EitherO-dimethylbut-i-enylM-n-propyl-1-trioxabycyclo-1-methyl-3-carbonitrile and trans-1- (2-t-butylcyclopropyl) -4-n-propyl 2,6 _/ 7-trioxabicyclo [2.2.2] octane-3-carbonitrile from E-4,4-dimethylpent-2-enoic acid and ethyl trans-2-t-butylcyclopropanecarboxylate (El Foreman and SM McElvain J. Amer. Chem. Soc, 1940, 62, 1438 and IA D'yakonov et al., Chem. Abs. 70: 78062m.

Using an analogous method, 4-t-butyl-1- (3,3-dimethylbutyl) -2,6,7-trioxabioyclo [2.2.2] octane and 1- (3,3-dimethylbutyl) -4-n -propyl-2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile from 4,4-dimethylpentanoic acid (GM Whitesides et al., J. Biol.

Amer. Chem. Soc, 1967, 89, 1335).

Example Xl

(i) A stirred solution of 6-cyanohex-1-yne (4.0 g) (Synthesis: see Example II, step ii) in dry methanol (30 mL) and dry diethyl ether (30 mL) is saturated with hydrogen chloride gas and the temperature is between -100 ⁰ C and O ⁰ C maintained. The solution is diluted with dry diethyl ether (120 ml) and left at a temperature of -2O ⁰ C for 24 hours. The white crystalline solid is filtered off and dried in vacuo to give methyliminohept-6-ynoate hydrochloride.

(ii) Dry Mothanol (33ml) is added to methyliminohept-e-inoathydiochloride (38.4y) under a stream of dry nitrogen. Hexane (750 ml) is added and the mixture is stirred for L hours at a temperature of 20 ° C. The mixture is allowed to stand overnight and the supernatant hexene solution is removed by decantation and poured into

vacuo evaporates to give trimethylorthohope-6-ynoate, a colorless oil (25.0g).

(iii) Using the method described in European Patent No. 216625 and starting from trimethylorthohept-6-inoate and 2-hydroxymethyl-2-n-propylpropane-1,3-dithio (Synthesis wio described in European Pat. No. 215f 25) ), 1- (hex-5-ynyl) -4-n-propyl-2-oxa-6,7-dithiabicyclo [2.2.2] octane is prepared.

2-Hyuroxymethyl-2-n-propylpropane-1,3-dithiol is also prepared as follows:

(i) α-n-Propyloxethane-S-ylmethyl-methanesulfonate is prepared from 3-hydroxymethyl-3-n-propyloxyethane and methanesulfonyl chloride using the procedure of Example II as described in step (i).

(ii) A solution of benzylmercaptan (25.0ml) in dry dimethylformamide (100ml) is added at ⁰ ° C under a vacuum

Nitrogen stream stirred. Sodium hydride (6.0 g, 80% dispersion in oil) is added cautiously and the mixture is stirred at 0 ° C for 1 hour. Add 3-n-propytoxethan-3-ylmethyl inethanesulfonate (10.0 g) and stir the mixture for 1 hour at ⁰ ° C. The mixture is refluxed for 6 hours with stirring. The mixture is cooled and poured into water. The aqueous mixture is extracted with diethyl ether. The ethereal extracts are washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue is chromatographed

on silica gel, eluting with 1: 4 diethylethonhexane. 2,2-di- (benzylthiomethyl) -pentan-1-ol is obtained as pale gold oil (15.6 g).

Mass spectrum (chemical ionization): M + 1 361

(iii) 2,2-Di (benzylthiomethyl) -pental-1-ol (8.0g) in dry diethyl ether (150ml) is added to liquid ammonia (500ml) which is stirred under nitrogen at -70 ° C. Sodium (8.0 g) is added in small pieces and the mixture is stirred at ⁰ C for 3 hours at -7O. The mixture is allowed to 2O ⁰ C and warm added solid ammonium chloride (20g) was added. Then carefully add methanol (100 ml) to destroy excess sodium. Water (200 ml) is added and citous aqueous mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo. 2-Hydroxymethyl-2-n-propylpropane-1,3-dithiol is obtained as a colorless oil (4.6 g).

In an analogous manner, 4-n-butyl-1- (hex-5-ynyl) -2-oxa-6,7-dithiabicyclo | 2.2.2l-octane, 4-t-butyl-1- (hex-5-ynyl ) -2-oxa-6,7-dithiabicyclo [2.2.2l-octane, 4-i-butyl-1- (hex-5-ynyl) -2-oxa-b, 7-dithiabicyclo | 2.2.2l-octane; 1- (Hex-5-ynyl) 4-phenyl-2-oxa-6,7-dithiabicyc o |! 2.2.2l-octanund4-cyclopropylmethyl-1- (hex-5-ynyl) -2-oxy-6,7 -dithiabicyclo [2.2.2] octane from trimethylorthohept-6-inoate and 2-n-butyl-2-hydroxymethylpropane-1,3-dithiol ₍ 2-t-butyl-2-hydroxymethylpropane-1,3-dithiol, 2-i-butyl) 2-hydroxymethylpropane-1,3-dithiol, 2-hydroxymethyl-2-phenylpropane-1,3-dithiol and 2-cyclopropyl-2-hydroxymethylpropane-1,3-dithiol.

Example XII

1 · Ηθχ x 5 x ΙηγΙ x 4 x η · · ρΓθργΙ 2,6,7-ΙίΙΙηΙβΜον (: Ιο [2.2.2] -ο <: Ιθη

Method 1

Boron trifluoride etherate (0.20ml) is added to a stirred solution of 2-mercaptomethyl-2-n-propylpropane-1,3-dithiol (0.30g) (synthesis described in Examples XXXI) and trimethylorthohept-6-inoate (0.30g) dry dichloromethane (10ml) was added at 20 ⁰ C under a nitrogen atmosphere. The mixture is stirred at 20 ⁰ C for 5 hours, and triethylamine (1.0 ml) is added. Water is added and the aqueous mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and the solvent is removed in vacuo. The residue is chromatographed on alumina, eluting with 1:10 dichloromethane: hexane saturated with ammonia. The volatile impurity (mothyl-hept-6-ynoate) is in vacuo (130 ⁰ C, 10mm Hg).

Recrystallization of the residue from hexane gives 1- (hex-5-ynyl) -4-n-propyl-2,6,7-trithiabicyclo [2.2.2] octane as a colorless solid (10 mg).

Method 2

A solution of trimethylorthohept-6-inoate (6.0g) in dry methanol (24ml) is stirred under a nitrogen atmosphere at ⁰ ° C. Add 2-mercaptomethyl-2-n-propylpropane-1,3-dithiol (3.0 g) in dry methanol (10 mL) and then add methanol saturated with hydrogen chloride (1.0 mL). After stirring at ⁰ ° C. for 20 hours, dry triethylamine (3.0 ml) is added. Water (100 ml) is added and the mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue is chromatographed on alumina, eluting with 1:10 dichloromethane: hexane saturated with ammonia. The volatile components are removed in vacuo (Kugelrohr at 130 ° C, 0.5mm Hg). The residue is crystallized from hexane. 1- (Hex-5-ynyl) -4-n-propyl-2,6,7-tr; thiabicyclo [2.2.2] octane is obtained as colorless crystals (0.90 g). Using analogous procedures (Method 2), 4-ethyl-1 - (hex-5-ynyl) -2,6,7-trithiabicyclo [2.2.2] octane and 4-i-butyl-1- (hex-5 -inyl) -2,6,7-trithiabicyclo [2.2.2] octane from trimethylortho-hept-6-ynoate and 2-ethyl-2-mercaptomethylpropane-1,3-dithiol and 2-i-butyl-2-mercaptomethylpropane -1,3-dithiol produced.

Example XIII

4-n-Propyl-1- [2- (prop-2-ynylthio) ethyl] -2,6,7-trioxabicyclo [2.2.2] octane

(i) A solution of 3-mercaptopropionic acid (15 ml) in dry dimethylformamide (250 ml) is stirred under a nitrogen atmosphere at 0 ° C. Sodium hydride (10.2 g, 80% dispersion in oil) is added cautiously and the mixture is stirred for 1 hour at 40 ° C. The mixture is cooled to ⁰ ° C. and propargyl bromide (60 g, 80% in toluene) is added dropwise. The mixture is stirred for 3 hours at 2U ° C and then for 1 hour at a temperature of 8O ⁰ C. The mixture is cooled and poured into water. The aqueous mixture is extracted with diethyl ether and the extracts washed with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo. The resulting oil (30 g), mainly prop-2-ynyl-3- (prop-2-ynylthio) propionate, is added to a solution of sodium hydroxide (8.0 g) in water (100 ml) and methanol (100 ml) and the Mixture is stirred for 24 hours at 20 ⁰ C The mixture

is extracted with diethyl ether and the acidified aqueous solution with hydrogen chloride. The acidic mixture is extracted with diethyl ether and the ethereal extracts are dried over anhydrous magnesium sulfate. The solvent is removed in vacuo. 3- (Prop-2-ynylthio) propionic acid is obtained as a red oil (12.0g) and used without further purification.

(ii) 4-n-Pfopyl-1-l2- (prop-2-ynylthio) -ethyl-2,6 ₍ 7-trioxabicyclo- | 2.2.2l-octane is obtained from 3- (prop-2-ynylthio) -propionic acid and 3-hydroxymethyl-3-n-propyloxyethane prewired to produce an ancestral substance described in Bolsplol I. 4-t-butyl-V [2- (prop-2-ynylthio) ethyl-2,6,7-trioxabicyclo (2.2. 2] octane is prepared from 3- (prop-2-ynylthio) -propionic acid and 2-t-butyl-3-hydroxyethyl ethyloxethane using the procedure described in Example I. 4-iv-Propyl-1- [2- (propyl) 2-InyltMc ^ ethyl | -2,6,7-trioxabicyclo [2.2.2l-octane-3-carbonitrile is prepared from 3- (prop-2-ynylthio) -propionic acid and 3-formyl-3-n-propyloxy-lane Using a method described in Goisoiol IV prepared.

Example XIV

4-n-Propyl-1- [2- (prop-2-lnyloxy) -othyl] -2,6,7-trloxablcyclo [2.2.2l-octane

(i) 3- (Prop-2-ynyloxy) propionic acid is prepared from propargyl alcohol and ethyl 3-bromopropionate, with an analogon

Procedure as described for the Synthose of 3- (but-3-in-1-ylo ^v y) propionic acid (Example XIX) were prepared.

(ii) 4-n-Propyl-1- [2- (prop-2-ynyloxy) -ethyl) -2,6,7-trioxabicyclo- | 2.2.21-octane is prepared from 3- (prop-2-ynyloxy) - propionic acid and 3-hydroxymethyl-3-n-propyloxethane using oinor method described in Example I.

4-t-Butyl-1- [2- (prop-2-ynyloxy) ethyl] -2,6,7-trioxabicyclo [2.2.2] octane is prepared from 3- (prop-2-ynyloxy) propionic acid and 3 -t-butyl-3-hydroxymothyloxothane using a procedure described in Example I.

4-n-PropyM-tt-lprop ^ -inyloxy-1-yl-yl / Mrioxabicyclo-1-octane-S-carbonitrile is prepared from 3- (prop-2-ynyloxy) propionic acid and 3-formyl-3 -n-propyloxethane using an ancestor vehicle described in Example IV.

Example XV

i-IBUT-a-inyloxymethyD ^ -n-propyl ^ .ej-trioxablcycloU ^^ l-octane

(i) 2- (But-3-ynyloxy) -acetic acid is prepared from but-3-yn-1-ol and ethyl bromoacetate using an analogous procedure as described for the synthesis of 3- (but-3-ynyloxy) -propionic acid (Example XIX) is borschriobon.

(ii)! - (But-S-inyloxymethyl-n-propyl) -ej-trioxabicyclo ^^^ 1-octane is prepared from 2- (but-3-ynyloxy) -salicylic acid and 3-hydroxymethyl-3-n-propyloxyethane using prepared a method described in Example I.

4-t-Butyl- (but-3-ynyloxymethyl) -2,6,7-trioxabicyclo [2.2.2] octane is prepared from 2- (but-3-ynyloxy) -acetic acid and 3-t-butyl-3- hydroxymothyloxothane using a procedure described in Example I.

1 - (But-3-ynyloxymethyl) -4-n-propyl-2,6,7-trioxabicyclo2.2.2] octane-3-carbonitrile is prepared from 2- (but-3-ynyloxy) -acetic acid and 3-formyl-3 -n-propyloxethane using a procedure described in Example IV.

Example XVI

4-t-butyl-1 - (hopt-6-nyl) -2, e, 7-t'-ioxa-cyclo [2.2.2] octene

(i) Dissolve sodium (1.2g) in dry ethanol (200ml). Diethylmalonate (7.8 mL) is added and the mixture is stirred for 30 minutes and 9.0 g of hex-5-ynylmethanesulphonate are added. The mixture is stirred for 1 hour and heated to reflux. The mixture is cooled and the volume pre-milled in vacuo. The mixture is poured into water and the aqueous mixture is extracted with diethyl ether. The ethereal extracts are washed with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo. The crude ester is added to a solution of aqueous sodium hydroxide solution (100 ml) of a 15% solution and methanol (ROmI) and the mixture is stirred at 20 ° C for 24 hours. The mixture is extracted with diethyl ether. The wöiv. & E alkaline phase comes with

Hydrogen chloride and the mixture extracted with diethyl ether. The e'.liorischen extracts are about anhydrous Dried magnesium sulfate. The solvent is removed in vacuo. 2- (Hex-5-ynyl) -malonic acid is called a colorless solid

4.5 g) and is used without further purification.

(ii) A mixture of 2- (hex-5-ynyl) -malonic acid (2.2 g) and copper oxide (60 mg) in dry acetonitrile (40 ml) is stirred for 6 hours under a nitrogen atmosphere and heated to reflux. The solvent is removed in vacuo. 5% aqueous

Hydrochloric acid is added and the aqueous mixture is extracted with diethyl ether. The ethereal extracts are over

dried anhydrous magnesium sulfate and the solvent removed in vacuo. Oct-7-acetic acid is obtained as oil (1.5 g) and is used without further purification.

(iii) 4-t-Butyl-1- (hept-6-ynyl) -2,6,7-trioxabicyclo [2.2.2] octane is prepared from oct-7-acetic acid and 3-t-butyl-3-hydroxymethyloxethane under

Using a procedure described in Example I prepared.

1 - (Hept-6-ynyl) -4-n-propyl-2,6,7-trioxabicyclo (2.2.2) octane is prepared from oct-7-acetic acid and S-hydroxymethyl-Sn-propyloxethane using a method described in Example I. prepared procedure.

Example XVII

1- (Hex-5-ynyl) -4- (prop-2-enyl) -2,6,7-trloxabicyclo [2.2.2] octane-3-carbonltril

(i) Pont-4-enal is prepared from pent-4-en-1-ol (Aldrich) as described in Example IV, step (i).

(ii) 2-Hydroxymethyl-2- (prop-2-enyl) -propane-1,3-diol is prepared from pent-4-enal as described in Example I, step (i).

3-Formyl-3- (prop-2-enyl) -oxethane is prepared from 2-hydroxymethyl-2- (prop-2-enyl) -propane-1,3-diol as described in Examples I and IV.

1- (Hex-5-ynyl) -4- (prop-2-enyl) -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile is prepared from hept-6-acetic acid and 3-formyl- 3- (prop-2-onyl) -oxoethane as described in Example IV.

In an analogous manner, starting from 2- (but-3-ynyloxy) -acetic acid (Example XV) and 3-formyl-3- (prop-2-enyl) -oxethane,

1 - (But-3-yloxymethyl) -4- (prop-2-enyl) -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile. In an analogous way, starting from hex-5-en-1-o! (Aldrich), 4- (But-3-enyl) -1- (hex-5-ynyl) -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile.

The tril obtained from 2- (but-3-enyl) -2-hydroxymethylpropane-1,3-diol triacetate by transesterification using Sodium ethoxide in methanol contains impurities and is purified as follows:

A mixture of crude 2- (but-3-enyl) -2-hydroxymethylpropane-1,3-diol (4.6 g), acetone (30 ml) and p-toluenesulfonic acid (0.25 g) are prepared in a Dean and Stark apparatus Heated under reflux for 7 hours. The mixture is cooled and washed with aqueous sodium bicarbonate solution. The organic solution is dried over anhydrous magnesium sulfate and the solvent removed in vacuo. The residue is chromatographed on silica gel, using 1: 4

Diethylothor: Hoxan eluiort becomes. The 5- (but-3-onyl) -2,2-dimethyl-5-hydroxymethyl-1,3-dioxane is obtained as a colorless oil (1.0 g).

Mass spectrum (chemical ionization): M + 1 201

5- (But-3-enyl) -2,2-dimethyl-5-hydroxymethyl-1,3-dioxane (0.80g) and Amberlyst "15" (0.50g) in methanol (100ml) containing water (1, OmI) is heated at reflux for 6 hours under stirring and the mixture is filtered and the filtrates are poured into

vacuo oyaporiort. The 2- (but-3-enyl) -2-hydroxymethylpropyl-1,3-diol is obtained as a colorless oil (0.6 g) which solidifies on standing.

3- (But-3-enyl) -3-formyloxethane is prepared from 2- (but-3-enyl) -2-hydroxymethylpropane-1,3-diol as described in Examples I and IV.

4- (But-3-enyl) -1- (hex-5-ynyl) -2,6,7-trioxabicyclo2.2.2) octane-3-carbonitrile is prepared from hept-6-acetic acid and 3- (But-3- enyl) -3-formyloxethane, as described in Example IV.

Example XVIII

4-t-ButyM- (4-methylhex-5-ynyl) - ?, e, 7-trloxablcyclo [2.2.2] octane

(i) A mixture of diethyl 2-acetyl-2-methylhexane-1,6-dioate (16.0 g) (Chem. Ber., 1980, 13, 451), hydrochloric acid (100 ml) and ethanol is refluxed for 4 hours , The mixture is cooled, diluted with water and made alkaline with sodium bicarbonate solution. The aqueous mixture is extracted with diethyl ether. The ethereal extracts are washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo.

Ethyl 5-methyl-6-oxoheptanoate is obtained as a colorless oil (7.3 g) and used without further purification.

The aqueous alkaline extracts obtained above are acidified with hydrochloric acid and the aqueous mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and the solvent is removed in vacuo.

5-Methyl-6-oxoheptanoic acid is obtained as a yellow oil (8, Cg).

(ii) A mixture of phosphorus Ponts chloride (3.0 g), dry pyridine (4.0 ml) and benzene (30ml) is stirred under a nitrogen atmosphere at 25 ⁰ C. Ethyl 5-methyl-6-oxoheotanoate (1, 0g) in benzene (3.0 ml) is added and the mixture is refluxed for 3 hours and heated to reflux. The mixture is cooled and poured into ice and water. The aqueous mixture is extracted with diethyl ether. The ethereal extracts are washed with 1 N hydrochloric acid, sodium bicarbonate solution and finally with water. The ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting oil (800 mg) consists of ethyl 6-chloro-5-methylhept-6-enoate (70%) and ethyl 6-chloro-methylhept-5-enoate (30%) and is used without further purification.

Mass spectrum (chemical ionization):

In combination with gas / liquid chromatography, two components are determined (ratio 2: 1).

M + 1 for both components 205.

(iii) A mixture of lithium aluminum hydride (1.2 g) in dry diethyl ether (100 ml) is stirred under a nitrogen atmosphere at ⁰ ° C. The mixture of ethyl 6-chloro-5-methylhept-6-enoate and ethyl 6-chloro-5-methylhept-5-enoate (4.0 g) in dry diethyl ether (20 ml) is added and the mixture is allowed to stand for 2 hours stirred in a nitrogen atmosphere.

Aqueous sodium hydroxide solution (10 ml, 10%) is added cautiously. The supernatant ether solution is removed by decantation and the residue is washed with diethyl ether (2x50 ml). The combined ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting oil (3.5 g) consists of 6-chloro-5-methylhept-6-en-1-ol (50%) and the E and Z isomers of 6-chloro-5-methylhept-5-ene 1 oil (50%) and used without further purification.

(iv) The mixture of 6-chloro-5-methylhept-6-en-1-ol and the E and Z isomers of 6-chloro-5-methylhept-5-en-1-oil (2.8 g) is stirred in dry tetrahydrofuran (50 ml) under a nitrogen atmosphere at ⁰ ° C. An n-butyllithium (43 ml of a 1.6M solution in hexane) is added and the mixture is stirred at 20 ° C for 4 hours. Ice is added and the aqueous mixture is extracted with diethyl ether. The ethereal extracts are washed with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the resulting oil chromatographed on silica gel, eluting with 2: 5 diethyl ether of hexane.

5-Methylhept-6-in-1 oil is obtained as a colorless oil (1.2 g).

Gas / liquid chromatography (GLC): OV-17 at 120X gives a peak.

Mass spectrum (chemical ionization):

Gaseous ammonia as ionizing gas M + 18 144

(v) A solution of 5-methylhept-6-in-1-ol (1.0 g) in dry dimethylformamide (9,0ml) is stirred at 2O ⁰ C and pyridinium dichromate (10.5 g) is carefully added. The mixture is stirred at 2O ⁰ C for 24 hours. Diethyl ether (50 ml) is added and the supernatant fluid is removed by decantation. The residue is washed with further portions of diethyl ether (10x 50ml). The ethereal extracts are washed with 0.5 N hydrochloric acid solution and then with water. The ethereal extracts are dried over anhydrous magnesium sulfate and the solvent removed in vacuo.

5-Methylhept-6-acetic acid is obtained as a light brown oil (0.80 g) and used without further purification.

(vi) 4-t-butyl-1- (4-methylhex-5-ynyl) -2,6,7-trioxabicycloI2.2.2l-octane is prepared from 5-methylhept-6-enoic acid and 3-t-butyl-3 -hydroxymethyloxethane, as described in Example I.

1 - (4-Methylhex-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2l-octane-3-carbonitrile is prepared from 5-methylhept-6-acetic acid and 3-formyl-3 -n-propyloxethane using a procedure described in Example IV.

Example XIX

(I) Sodium hydride (4.6 g of a 60% dispersion in mineral oil) is added to a stirred solution of but-3-ln-1 oil (16.2 g, 0.23 mol, Lancaster) in dry toluene (200 mL ) added. After 2 hours of stirring at 25 ⁰ C, a solution of ethyl 3-bromopropionate (20.8 g, 0.115 mol, Lancaster) is added. The reaction mixture is refluxed for 7 hours while stirring. Ethyl 3- (but-3-ynyloxy) propionate (17.8 g) is obtained by quenching the cooled reaction mixture in water, extracting with ether, washing with brine, drying over anhydrous magnesium sulfate and then evaporating.

(ii) Ethyl 3- (but-3-ynyloxy) -proplonate (17.4 g) is stirred overnight with a sodium hydroxide solution (150 mL, 2 M). After extraction with ether, the aqueous layer is acidified with concentrated hydrochloric acid. The required acid is obtained by ether extraction. The organic phase is washed with brine and dried over magnesium sulfate. Evaporation gives 3- (but-3-ynyloxy) -propionic acid (8.8 g) as a colorless oil.

1- [2- (But-3-ynyloxy) ethyl] -4-n-propyl-2,6,7-trioxabicyclo [2,2,2-octane is prepared from 3- (but-3-ynyloxy) propionic acid and 3 Hydroxymethyl-3-n-propyloxyethane using a procedure described in Example I. Using the above procedure and starting from ethyl 2-bromopropionate (Lancaster Synthesis) and but-3-yn-1-ol (Lancaster Synthosis), 1- [1- (but-3-ynyloxy) ethyl] -4 -n-propyl-2,6,7-trioxabicyclo [2.2.2] octane.

Example XX

(i) a mixture of 7-chloro-methoxyhept-2-yne (8.0g) (J. Martell and E. Toruoffoff Chem Abs., 76: 24712d) and sodium cyanide (5.0g) in dimethylformamide (20ml) and Water (20ml) is stirred for 7 hours at 80 ° C. The mixture is cooled and washed with

Diluted with water. The aqueous mixture is extracted with diethyl ether. The ethereal extracts are then washed with water

washed, dried over anhydrous magnesium sulfate and evaporated in vacuo.

7-cyano-1-methoxyhept-2-yne is obtained as a yellow oil (6.0 g).

Mass spectrum (chemical ionization): M + 1 152

(ii) A mixture of 7-cyano-1-methoxyhept-2-yne (6.0 g) and an aqueous sodium hydroxide solution (100 ml, 2N) is heated with stirring and reflux for 16 hours. The mixture is cooled and extracted with diethyl ether. The aqueous alkaline solution is acidified with hydrochloric acid and the aqueous mixture extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo.

8-methoxyoct-6-acetic acid is obtained as a colorless oil (6.0 g).

1- (7-methoxyhept-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane is prepared from 8-methoxyoct-6-acetic acid and 3-hydroxymethyl-3-n propyloxethane using the same procedure as described in Example I.

Example XXI

(i) methyl-5-brompentanimidat hydrochloride (melting point: 89 ⁰ C) is prepared from 5-Bromvaler onitril described using in step (i) of Example Xl procedure.

(ii) Trimethyl 5-bromothiopentanoate (colorless liquid, b.p. 108-110 ° C, 16mm Hg) is prepared from methyl 5-bromopentanimidate hydrochloride as described in step (ii) of Example XI.

(iii) 1 - (4-bromobutyl) -4-t-butyl-2,6,7-trioxabicyclo | 2.2.2] octane (m.p. 111-5 ⁰ C.) from 5-trimethyl-2-t bromorthopentanoat and Butyl 2-hydroxymethylpropane-1,3-diol prepared using the procedure described in Method 2 of Example Vl.

Mass spectrum (chemical ionization) M + 1 307 309

(iv) Sodium (0.1 g) is added at a temperature of -7O ⁰ C under a nitrogen atmosphere a stirred solution of anhydrous liquid ammonia (70ml) and dry diethyl ether (20 ml). After 10 minutes, a ferric nitrate crystal (15 mg) is added to the dark blue solution. The reaction mixture, which changes color to gray, is allowed to warm to -30 ^{c of} cerium and a further amount of sodium (0.75 g) is added in small pieces. The mixture is stirred for 30 minutes at ⁰ C and 3O-methyl propargyl ether (2.2 g) is added. The mixture is stirred for a further hour at -3O ⁰ C and 1- (4-bromobutyl) -4-t-butyl-2,6,7-trioxabicyclo [2.2.2] octane (1.0 g) in dry diethyl ether ( 50ml) is added. The

Mixture is stirred for 1 hour at -3O ⁰ C. Solid ammonium chloride (1.7g) and then methanol (5ml)

is added and the mixture is allowed to warm to room temperature. Then water (20ml) is added and the aqueous

Extracted mixture with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and dissolved in

vacuo evaporates. The residue is chromatographed on alumina, eluting with 1: 9 dichloromethane: hexane, saturated with

Ammonia, is eluted.

4-t-Butyl- (7-methoxyhept-5-ynyl) -2,6,7-trioxabicyclol.2.2.2] octane is obtained as a colorless solid (melting point 47-49 ⁰ C, recrystallized from hexane).

Example XXII But-3-ynyl-4-n-propyl-2,6,7-trioxablcyclo [2.2.2] octane-1-carboxylate

(i) Oxalyl chloride (4.3 mL) is added to a stirred solution of but-3-yn-1 oil (3.5 g) in dry dichloromethane (75 mL) at ⁰ ° C. The solution is stirred for 30 minutes at ⁰ ° C., then a stirred solution of 3-hydroxymethyl-3-n-propyloxyethane (6.4 g) and dry pyridine (30 ml) in dry dichloromethane (75 ml) is added dropwise. The mixture is stirred for 24 hours at 20 ° C. Then water is added and the aqueous mixture is extracted with diethyl ether The ethereal extracts are washed with 5% hydrochloric acid solution, saturated sodium bicarbonate solution and finally with water The ethereal extracts are dried over anhydrous magnesium sulfate and concentrated The resulting oil is chromatographed on silica gel (pre-eluted with 1% triethylamine in hexane) and eluted with 1: 1 diethyl ether: hexane, but-3-ynyl- (3-n-propyloxethan-3-yl) -. methyl oxalate is obtained as a colorless oil (7.0 g). (ii) But-3-ynyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane-1-carboxalate is prepared from but-3 -inyl- (3-n-propyloxethan-3-yl) -methybxalate using the procedure described in Example I.

Example XXIII

N- (prop-2-lnyl) -4-n-propyl-2,6,7-trloxablcyclo [2.2.2] octane-1-carboxamld

(i) Ethyl 4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane-1-carboxylate is prepared from 3-hydroxymethyl-3n-propyloxyethane and ethyloxalylchloride (Aldrich) using the methods described in Example I. Procedure produced. This gives a colorless solid with a melting point of 7O ⁰ C.

Mass spectrum (chemical ionization) M + 1 231

(ii) A solution of ethyl ^ -n-propyl ^. ^ ^ trioxabicyclotf ^^ l-octane-i-carboxyla '. (0.12 g) and 2-propynylamine (0.5 ml) and methanol (20 ml) are allowed to stand at a temperature of 20 ° C for 4 days. The solution is evaporated in vacuo. The residue is eluted on alumina and with 2: 3 dichloromethane: hexane saturated with ammonia.

N- (prop-2-ynyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2l-octane-1-carboxamide is obtained as a pale yellow solid (0.12 g).

Example XXIV

Prop-2-lnyl-2- (4-n-propyl-2,6,7-trioxablcyclo [2.2.2] oct-1-yl) acetate

(i) Ethyl 2- (4-n-propyl-2,6,7-trioxabicyclo [2.2.2] oct-1-yl) acetate is prepared from ethyl malonyi chloride and 3-hydroxymethyl-3-n-propyloxyethane using the method described in Example 1 I described procedure produced.

(ii) A mixture of ethyl 2- (4-n-propyl-2,6,7-trioxabicyclo [2.2.2] -oct-1-yl) acetate (0.48g) and sodium hydroxide (0.35g) in methanol (10 ml) and water (2.0 ml) is stirred at 20 ° C for 3 hours. Solid carbon dioxide pellets (10 g) are added and the mixture is evaporated to dryness. The crude sodium 2- (4-n-propyl-2,6,7-trioxabicyclo [2.2.2] oct-1-yl) acetate is used without further purification.

(iii) A mixture of sodium 2- (4-n-propyl-2,6,7-trioxabicycloI2.2.2] oct-1-yl) acetate (1, og) and propargyl bromide (1.8 ml of an 80% igen solution in toluene, Aldrich) in dry dimethylformamide (30 ml) is stirred at 20 ³ C for 24 hours. Then, water is added and the aqueous mixture is extracted with diethyl ether. The ethereal extracts are washed with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the residue is chromatographed on silica gel (pre-toluene with 1: 3 dichloromethane: hexane containing 3% triethylamine) and then eluted with 1: 3 dichloromethane: hexane containing 3% triethylamine.

Prop-2-ynyl-2- (4-n-propyl-2,6,7-trioxabicyclo [2.2.2] oct-1-yl acetate is obtained as a colorless solid (0.45 g).

Example XXV

(i) But-3-ynylmethanesulfonate is prepared from but-3-yn-1-ol using the procedure described in step (i) of Example I.

(Ii) 2- (But-3-ynylthio) -salicylic acid: Method A.

Thioglycolic acid (6.0 g) is added to a stirred solution of sodium hydroxide (8.0 g) in ethanol (50 ml). But-3-ynylmethanesulfonate (7.4g) is added and the mixture is stirred at 20 ° C for 24 hours. The reaction mixture is poured into water and the aqueous mixture extracted with diethyl ether. The aqueous alkaline extracts are acidified with hydrochloric acid and the mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo. The resulting oil is stirred in dry dimethylformamide (100 ml) and anhydrous sodium carbonate (15 g) is added. Methyl iodide (7,0ml) is added and the reaction mixture stirred for 3 days at 2O ⁰ C. Water is added and the aqueous mixture extracted with diethyl ether. The ethereal extracts are washed with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the residue is chromatographed on silica gel, eluting with 1: 4 diethyl ether: hexane. Methyl 2- (but-3-ynylthio) acetate is obtained as a colorless oil (1.2 g) with a small amount of methyl 2- (but-3-yn-1-ylthio) propionate. A mixture of methyl 2- (but-3-ynylthio) acetate (0.6g) and sodium hydroxide solution (20ml, 2N, 1: 1 MethanohWasser) is stirred for 24 hours at 2O ⁰ C. Water is added and the aqueous mixture extracted with diethyl ether. The aqueous alkaline extracts are acidified with hydrochloric acid and the mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and the solvent removed in vacuo. 2- (But-3-ynylthio) acetic acid is obtained as a colorless oil (0.5 g). (A small amount of 2- (but-3-ynylthio) -propionic acid is present.)

2- (But-3-ln-1-ylthlo) acetic acid: Method B

2- (But-3-ynylthio) acetic acid is prepared from thioglycolic acid and but-3-ynylmethanesulfonate using the procedure described in step (i) of Example XIII.

(iii) 1- (But-3-ynylthiomethyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane is prepared from 2- (but-3-ynylthio) acetic acid and Hydroxymethyl-3-n-propyl-oxoethane using the procedure described in Example I.

4-t-Butyl-1- (but-3-ynylthiomethyl) -2,6,7-trioxabicycloI2.2.2] octane is prepared from 2- (but-3-ynylthio) acetic acid and 3-t-butyl-3 -hydroxymethyloxethane using the procedure described in Example I. A small amount of 4-t-butyl-1 - (but-3-yn-1-ylthio) ethyl] -2,6,7-trioxabicyclo [2.2.2] octane was also present.

Example XXVI

N- (prop-2-ynyl) -2- (4-n-propyl-2,6,7-trioxabicyclo [2.2.2] oct-1-yl) -acetamide

To a stirred solution of ethyl 2- (4-n-propyl-2,6,7-trioxabicyclo [2.2.2] oct-1-yl) acetate (300 mg) (Example XXIV) in methanol (5 ml) 2-propynylamine (2.0 ml) followed by sodium cyanide (20 mg). The mixture is stirred at 70 to 80 ° C for 12 hours. Water (10 ml) is added and the mixture extracted with ethyl acetate. The ethyl acetate extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue is purified on silica gel by chromatography with gradient elution with ethylacetatehexane mixtures containing triethylamine (1%). N- (Prop-2-ynyl) -2- (4-n-propyl-2,6,7-trioxabicyclo (2.2.2) -oct-1-yl) -acetamide was obtained as a yellowish oil (122 mg). Gas / liquid chromatography (GLC): OV-17 at 245 ^° C gave a peak.

Example XXVII

(i) Using exactly the same procedure of Example II, step (i), pent-4-ynylmethanesulfonate (37.8g) is prepared from methanesulfonyl chloride (22ml), triethylamine (44ml) and pent-4-in-1 oil (Lancaster Synthesis, 20g).

(Ii) A solution of diethyl methylmalonate (Aldrich Chemical Company, 35.6 ml) in dry tetrahydrofuran (200 ml) is added dropwise to a stirred suspension of sodium hydride (60% dispersion in mineral oil, 9.1 g) in tetrahydrofuran (50 ml) under a vacuum Nitrogen atmosphere added dropwise. After completion of the addition, the mixture is heated under gentle reflux for 1 hour and then cooled before adding a solution of pent-4-ynylmethanesulfonate (35.2 g) in tetrahydrofuran (50 ml). The resulting mixture is heated under gentle reflux for a further 2 hours. The amount of solvent is then removed in vacuo and the residue partitioned between diethyl ether and water. The organic phase is separated and washed with water and brine prior to drying with anhydrous magnesium sulfate and evaporated under reduced pressure. The distillation gives diethyl 2-methyl-2- (pent-4-ynyl) malonate (45,8g) as a colorless oil (b.p. 92-97 ⁰ C, 0.5 mm Hg).

Gas / Liquid Chromatography (GLC): OV-17 programmed from 12O ⁰ C to 21O ⁰ C gives a peak.

(iii) A mixture of diethyl 2-methyl-2- (pent-4-ynyl) malonate (11 g) and potassium hydroxide (15 g) in 95% ethanol (150 ml) is refluxed for 4 hours and then 15 hours Room temperature allowed to stand. The amount of solvent is removed in vacuo and the residue taken up in water. The resulting aqueous phase is washed with dichloromethane before being acidified to pH 1 with concentrated hydrochloric acid and further extracted with fresh dichloromethane. These organic extracts are washed with brine prior to drying over anhydrous magnesium sulfate and evaporated in vacuo. 2-Methyl-2- (pent-4-ynyl) -malonic acid is obtained as a pale yellow solid (6.7 g).

(iv) A mixture of 2-methyl-2- (pent-4-ynyl) -malonic acid (5.7 g) and copper oxide (0.22 g) in acetonitrile (150 ml) is refluxed for 4.25 hours under a nitrogen atmosphere. The solvent is removed under reduced pressure and 50 ml of water and subsequently enough concentrated hydrochloric acid are added to hydrolyze the copper salt. The resulting aqueous phase is extracted with diethyl ether and the organic extracts are washed with water and brine prior to drying over anhydrous magnesium sulfate and evaporation in vacuo. The 2-methylhept-6-acid (3.6 g) is obtained as a colorless oil after distillation (boiling point 150-165 ° C, 0.5mm Hg).

(v) Using the procedure described in steps (v) and (vi) of Example 1, 1- (1-methoxyhex-5-ynyl) -4-propyl-2,6,7-trioxabicyclo [2.2.2] octane prepared from 2-methylhept-6-acetic acid and 3-hydromethyl-3-propyloxethane.

Gas / liquid chromatography (GLC): OV-17 at 200X gives a peak.

In an analogous manner, the following compound is prepared:

4-t-Butyl-1- (1-methylhex-5-ynyl) -2,6,7-trioxabicyclo [2.2.2] octane.

Using the procedure outlined in Example IV, 1- (1-methylhex-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile is prepared.

Example XXVIII

Methyl-7- (4-n-propyl-2,6,7-trioxablcyclot2.2.2] oct-1-yl) hept-2-lnoat

(i) n-Butyllithium (5.2ml, 1.6M solution in hexane) is added to a solution of hept-6-acetic acid (0.5g) in dry tetrahydrofuran (20ml) stirred at -70 ° C under a nitrogen atmosphere , The resulting mixture is held 0.25 hours at -70 ⁰ C when methyl chloroformate (0.32 ml) is added. The solution is stirred for a further 0.5 hour at -7O ⁰ C, then allowed to warm over half an hour at room temperature. Thereafter, 5 ml of water are added and the amount of the solvent is removed under reduced pressure. The residue is diluted with water and extracted with diethyl ether. The aqueous phase is separated off, acidified with concentrated hydrochloric acid to a pH of 1 and then back-extracted with dichloromethane. The combined dichloromethane extracts are washed with brine prior to drying over anhydrous magnesium sulfate and evaporation in vacuo. The residue is purified by distillation (bubble to bubble, 0.5 mm Hg). At an oven temperature of 22O ⁰ C distilled i-Methylr.ydrogen-ie-oct ^ -indioate as a brown oil (183 mg).

Mass spectrum (sample) (chemical ionization) M + 1 185

(ii) Using the procedure described in steps (v) and (vi) of Example I, methyl 7 - (- 4-propyl-2,6,7-trioxabicyclo [2.2.2] oct-1-yl ) -hept-2-inoate-1-methylhydrogen-1,8-oct-2-indiate and 3-hydroxymethyl-5-pentyl-3n-propyloxyethane.

Example XXIX

1- (Hex-5-iny) - 3-methyl-4-n-propyl-2-oxa-6,7-dithiabicycl (i [2.2.2] octane

(i) A solution of 2,2-di- (benzylthiomethyl) -pentan-1-ol (1.0g, Example XI) in dry dichloromethane (10ml) is added to a stirred suspension of pyridinium chlorochromate (1.8g) and anhydrous Sodium acetate (0.11g) in dry dichloromethane (25ml) at ⁰ ° C under a nitrogen stream. The reaction mixture is allowed to warm to 2O ⁰ C and then stirred for 2 hours. Dry diethyl ether is added and the mixture is stirred for 30 minutes. The ethereal extracts are decanted off and the residue is washed with further portions of diethyl ether. The combined ethereal extracts are dried over anhydrous magnesium sulfate and the solvent removed in vacuo. The residue is purified by chromatography on a mixture of silica gel and charcoal eluting with diethyl ether. The 2,2-di (benzylthiomethyl) pentanal is obtained as a pale yellow oil (0.27 g).

Mass spectrum (chemical ionization) M + 1 359

(ii) A solution of 2,2-di- (benzylthiomethyl) -pentanal (3.54 g) in dry diethyl ether is added to a stirred solution of methylmagnesium iodide (prepared from methyl iodide [1.2 ml] and magnesium [0.48g]) dry diethyl ether (60 ml) was added dropwise. The reaction mixture is refluxed for 2 hours and then cooled. A saturated aqueous

Ammonium chloride solution is added. The mixture was stirred for 30 minutes and extracted with diethyl ether. The ethical extracts are dried over anhydrous magnesium sulfate and the solvent removed in vacuo. The 3,3-di- (benzylthiomethyl) -hexan-2-ol is obtained as a yellow oil (1.7 g)

 Mass spectrum (chemical ionization) M + 1 375

1- (Hex-5-ynyl) -3-methyl-4-n-propyl-2-oxa-6,7-dithiabicycloI2.2.2l-octane is prepared from 3,3-di- (benzylthiomethyl) -hexane-2- ol prepared using the procedure described in Example Xl.

Example XXX

1- (2-Methylhex-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane-3-carbonyltril (>'1,4-dimethylcyclohexy-1-ene ( 12g) (ref. Beilstein 5.74) is in dry dichloromethane (120ml) and the solution stirred at -7O ⁰ C. a Οζο actual current is passed through the solution for 3 hours. the solution is allowed to warm slightly and poured into a solution of hydrogen peroxide in water (600 ml) of a 3% solution The dichloromethane is removed in vacuo and the mixture stirred vigorously for 48 hours at 20 ^° C. The mixture is basified with saturated sodium bicarbonate solution and the aqueous mixture extracted with diethyl ether The solution is acidified with 10% hydrochloric acid solution and the mixture is extracted with diethyl ether After drying over anhydrous magnesium sulfate both ethereal extracts are evaporated in vacuo Both residues contain organic acid and aldehyde The combined residues (3.5 g) are dissolved in dry dimethylform mamid (30ml) and adding pyridinium dichromate (17.4g).

The mixture is stirred for 24 hours at 20 ° C and then diluted with diethyl ether (50ml). The ethereal extracts are decanted off and the black residue is washed repeatedly with more diethyl ether. The combined ethereal extracts are washed with dilute hydrochloric acid solution followed by water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the 3-methyl-6-oxoheptanoic acid is obtained as a yellow oil (2.45 g).

Mass spectrum (chemical ionization) M + 1 159

(ii) 3-Methyl-6-oxoheptanoic acid (2.45 g) is dissolved in dry dimethylformamide (60ml) stirred at 2O ⁰ C and anhydrous sodium carbonate (1.64g) was added. Ethyl iodide (5.4 ml) is added dropwise and the mixture is refluxed for 2 hours with stirring. The mixture is cooled, poured into water and the aqueous mixture extracted with diethyl ether. The ethereal extracts are washed with saturated aqueous sodium thiosulfate solution and then with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the residue is purified by chromatography on silica gel, eluting with 1: 4 diethyl ether: hexane. The ethyl-i'-methyl-6-oxoheptanoate is obtained as an orange oil (2.0 g).

Mass spectrum (chemical ionization) M + 1 187

(iii) Using the procedure described in Example XVIII, 3-methylhept-6-acetic acid is prepared from ethyl 3-methyl-6-oxoheptanoate.

(iv) 1- (2-Methylhex-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo (2.2.2) octane-3-carbonitrile is prepared from 3-methylhept-6-acetic acid using Starting from 3-methylhept-6-acetic acid and 3-formyl-3- (prop-2-enyl) -oxoethane (see Example XVII) and using the procedure described in Example IV, 1- (1) 2-methylhex-5-ynyl) -4- (prop-2-anyl) -2,6,7-trioxabicyclo [2.2.2] octane 3-carbonitrile.

Example XXXI

1- (but-3-inyloxymethyl) -4-n-propyl-2,6,7-trithlab! Cyclo [2.2.2] octane

(i) Methanesulfonyl chloride (74.0g) is added dropwise over 30 minutes to a solution of 2-hydroxymethyl-2-n-propylpropane-1,3-diol (28.0g) in dry pyridine (200ml) under nitrogen at ⁰ ° C , The mixture is allowed to warm to room temperature. After stirring for 18 hours, the mixture is poured into water (200 ml) and extracted with chloroform (2 × 100 ml). The chloroform extracts are washed with water (2 x 100 ml), dried over anhydrous magnesium sulfate and evaporated in vacuo to give a brown solid. This is stirred in dry diethyl ether (200 ml) and gives 2-hydroxymethyl-2-n-propylpropane-1,3-diol-trimethanesulfonate as a white solid (70.0 g) (melting point 103.6 ° C). (ii) Sodium trithiocarbonate (18.0g) (see J. Org. Chem. 1968, 33, 12, ^7, 5) in water (25ml) is dissolved in a solution of 2-hydroxymethyl-2-n-propylpropane-1,3-diol. trimethanesulfonate (12.0g) in dimethylformamide (10ml). The mixture is heated 4 hours under reflux (130 ⁰ C), after which leaves my cool to room temperature. After stirring for an additional 18 hours, dilute sulfuric acid solution (50 ml) is added slowly over a period of 30 minutes. The mixture is extracted with chloroform. The extracts are dried over anhydrous magnesium sulfate, evaporated in vacuo and give a brown liquid. Hexane (200ml) is added and the mixture washed with water (3x 50ml). Drying over anhydrous magnesium sulfate and Evapora Jones gives an amber oil (6.8 g). The crude oil (6.4 g) in diethyl ether (10 ml) is added to a suspension of lithium aluminum hydride (3.0 g) in dry diethyl ether (100 ml) so that reflux is maintained. After complete addition, the mixture is stirred for a further hour and then water (3 ml) is carefully added. Then dilute sulfuric acid (3 ml) followed by water (3 ml) is added. The mixture is filtered, the solid washed with diethyl ether (50 ml) and the combined filtrates dried over anhydrous magnesium sulfate and evaporated in vacuo to give a 2-mercaptomethyl-2-n-propylpropane-1,3-dithiol as a pale yellow oil (5.3 g ).

(iii) Hydrogen chloride gas is passed through a suspension of paraformaldehyde (4.3 g) in but-3-yn-1-ol (10.0 g) (Aldrich) and toluene dichloromethane (30 ml) for 30 minutes at -20 ° C. The mixture is allowed to warm to room temperature and stirred for a further 18 hours. Cold water (30 ml) is added and the organic layer is separated, dried over anhydrous calcium chloride and, after evaporation, gives but-3-ynyl chloromethyl ether as an amber liquid (14.2 g). (iv) 2-merc (iptomethyl-2-n-propylpropane-1,3-dithiol (2.3g) and triethylorthoformate (1.74g) are combined in dry toluene (5ml) containing p-toluenesulphonic acid (5mg). After cooling, toluene (15 ml) is added and the mixture is washed with water (2 × 10 ml) Drying over anhydrous magnesium sulfate and evaporation in vacuo gives a pale yellow oil, which is extracted with diethyl ether (50 ml) and concentrated Extracts in vacuo to give a white solid Purify by chromatography on alumina, 1:10

Dichloromethane: hexane, saturates elulert with ammonia gives 4-n-propyl-2,6,7-trithiabicyclo [2.2.2] -octane as a white solid (0.33 g, melting point 139 ⁰ C)

 Mass spectrum (chemical ionization) M + 1 207

(v) n-Butyllithium (0.3 mL, 1.6 M solution in hexane) is added to a solution of 4-n-propyl-2,6,7-trithi8bicyclo [2.2.2] octane (0.1 g) in dry Tetrahydrofuran (5 ml) was added at a temperature of -70 ° C under nitrogen. The solution is stirred for 30 minutes and but-3-inylchlormethylether (0,058g) in dry tetrahydrofuran (2.0 ml) is added and allowed the reaction mixture to 20 ⁰ C heat. 10 ml of water are added and the mixture is extracted with diethyl ether. The ethereal extracts are dried over anhydrous magnesium sulfate and the solvent is removed in vacuo. The residue is purified by chromatography on alumina eluting with 1: 10 dichloromethane: hexane saturated with ammonia. 1 - (But-3-Iriyloxymethyl) -4-n-propyl-2,6,7-trithiabicyclo [2.2.2] octane is obtained as a waxy solid (0.032 g).

Example XXXII

1 - [(E / Z) -hex-3-en-5-lnl] -4-propyl-2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile

(i) ((E / 2) -5-bromopent-4-enoic acid is prepared from diethyl malonate and 1,3-dibromopropene isomer mixture, Aldrich Chemical

Company, using the procedure described in Example XVI, steps (i) and (ii).

(ii) Using the method described in steps (ii) and (hi) of Example IV, 1-I (E / Z) -4-bromobut-3-enyl] -4-propyl-2,6,7- trioxabicyclo [2.2.2] octane-3-carbonitrile (as an oil) prepared from ((E / Z) -5-bromopent-4-enoic acid and 3-formyl-3-n-propyl-oxoethane.

Gas / liquid chromatography (GLC): OV-17 at 230 ° C gives a peak. Mass spectrum (chemical ionization) M + 1 316.318

(iii) A mixture of 1- (E / Z) -4-bromobut-3-enyl-4-propyl-2,6,7-trioxabicyclo [2.2.2l-octane-3-carbonitrile (500 mg),

Trimethylsilylacetylene (0.45ml), bis-triphenylphosphinepalladium dichloride (30mg) and copper iodide (5mg) in dry Diethylamine (10 ml) is stirred at room temperature for 4 hours under a nitrogen atmosphere. The solvent becomes

removed in vacuo. The residue is taken up in diethyl ether, washed with water and brine before drying over anhydrous magnesium sulfate and evaporation under reduced pressure. The residue is removed by means of

Column chromatography on alumina, eluting with hexane containing 15% dichloromethane Ammonia, is purified. 4-Propyl-1 - [(E / Z) -6- (trimethylsilyl) -hex-3-en-5-ynyl] -2,6,7-trioxabicyclo [2.2.2] octane-3 is obtained.

carbonitrile as a pale yellow oil (365mg).

Gas / liquid chromatography (GLC): OV-17 at 25O ⁰ C gives two peaks (E / Z isomers).

(iv) Tetrabutylammonium fluoride (1.1 ml of a 1M solution in tetrahydrofuran) is added to a stirred solution of 4-propyl-1- |

Z) -6- (trimethylsilyl) -hex-3-en-5-ynyl] -2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile (293 mg) in tetrahydrofuran (5 ml). The resulting mixture is stirred for 1 hour at room temperature and the solvent is removed under reduced pressure

away. The residue is partitioned between diethyl ether and water (extracted by shaking). The organic phase is separated, washed with water and brine, dried over anhydrous magnesium sulfate and then evaporated in vacuo. The

Residue is purified by column chromatography on alumina, eluting with hexane containing 15% dichloromethane,

saturated with ammonia, is eluted. HfE / ZJ-Hex-S-en-6-ynyl-M-propyl-.ej-trioxabicycloxide is obtained. 2.21-octane-3-carbonitrile as a colorless oil (143mg).

Gas / liquid chromatography (GLC): OV-17 at 25O ⁰ C gives a peak. In an analogous manner, the following compounds are prepared from 1-l (E / Z) -4-bromobut-3-enyl] -4-propyl-2,6,7-trioxabicyclo [2.2.2] -

octan-3-carbonitrile and the requisite terminal acetylene, called in parentheses, prepared:

1 - [(E / Z) -7-methoxyhept-3-en-5-ynyl] -4-propyl-2,6,7-trioxabityclo [2.2.2] octane-carbonitrile (methyl propargyl ether).

1 - [(E / Z) -7-hydroxyhept-3-en-5-ynyl] -4-propyl-2,6,7-irioxabicyclo [2.2.2] octane-3-carbonitrile (propargyl alcohol).

Example XXXIII

4-t-butyl-1 - [(E) -hex-1-one-5-lnyl] -2,6,7-trioKablcyclo [2.2.2] octane-3-carbonltr l!

(i) Using the method described in Example IV, step (i), pent-4-in-1-oil (Aldrich Chemical Company) is incorporated in U.S. Patent No. 4,839,866

Converted to pent-4-inal. The crude product is purified by bubble-to-bubble method (oven temperature <65 ⁰ C, 15 mm Hg). Gas / liquid chromatography (LGC): OV-17 at 8O ⁰ C gives a peak.

(ii) A mixture of pent-4-indal (1.2 g) and (carbethoxymethylene) triphenylphosphorane (5.1 g) in dichloromethane (20 ml) is stirred for 2.5 hours at room temperature. The solution is evaporated under reduced pressure and the residue is extracted with hexanes. Insoluble material is removed by filtration before the solvent is evaporated to leave a yellow oil. Is obtained ethyl (E) -hept-3-en-6-ynoate as a colorless oil (1.8g) after a bubble-to-bubble distillation (oven temperature 1-5 ⁰ C, 15mm Hg) was performed.

Gas / liquid chromatography (GLC): OV-17 at 120 ° C gives two peaks.

(iii) A solution of ethyl (E) -hept-2-en-6-ynate (1.8 g) in 50% aqueous methanol containing 5% sodium hydroxide is stirred at a suitable temperature overnight. The methanol is removed under reduced pressure and the resulting aqueous phase is extracted with dichloromethane. The aqueous phase is adjusted to pH 1 with concentrated hydrochloric acid and back-extracted with dichloromethane. These organic extracts are washed with brine, dried over anhydrous magnesium sulfate and then evaporated in vacuo to give (E) -Hept-2-en-6-acetic acid as a white solid (1.3 g).

(iv) Using the procedure described in Example IV, Steps (ii) and (iii), 4-t-butyl, - [(E) -hex-1-en-5-ynyl) -2,6,7 -trioxabir.yclo [2.2.2l-octane-3-carbonitrile of 3-t-butyl-3-formyloxethane and (E) -hept-2-ene-6-acetic acid.

Gas / Liquid Chromatography (GLC): OV-17 at 220 ^° C gives two peaks.

-32- 29p 195

Example XXXV

4-n-propyl-2, e, 7-trloxablcyclo [2.2.2] octane <1 carboxaldehydroxlmprop-2-lnylether

(i) A solution of ethyl 4-propyl-2,6,7-trioxabicyclo (2.2.2. -octan-1-carboxylate (5.0g) (Example XXIII) in anhydrous tetrahydrofuran (10ml) is added to a stirred solution of lithium aluminum hydride (1.86 g) in dry diethyl ether (100ml) was added dropwise at ⁰ ° C under nitrogen. the mixture is stirred 1.5 hours at ⁰ ° C, then 2.5 hours at room temperature. an aqueous solution of sodium hydroxide (25ml of a 10% The aqueous mixture is extracted with diethyl ether, the ethereal extracts are washed with water and brine and dried over anhydrous magnesium sulfate and then evaporated in vacuo.

The residue, 1-hydroxymethyl-4-propyl-2,6,7-trioxabicyclo [2.2.2] octane, is obtained as a white crystalline solid (3.4 g, melting point 100-101 ⁰ C).

Mass spectrum (chemical ionization) M + 1 189

(ii) 4-Propyl-2,6,7-trioxabicyclo [2.2.2] octane-1-carboxaldehyde is taken from 1-hydroxymethyl-4-propyl-2, e, 7-trioxabicyclo [2.2.2] octane a method described in Example IV, step (i).

4-propyl-2,6,7-trioxabicyclo [2.2.2l-octane-1-carboxaldehyde as a white solid (1.7 g; m.p. 117-118 ⁰ C).

Mass spectrum (chemical ionization): M + 1 187

(iii) A solution of 4-propyl-2,6,7-trioxabicyclo2.2.2] octane-1-carboxaldehyde (1.0 g) in 1,2-dimethoxyethane (15 ml) is added to a stirred mixture of hydroxylamine hydrochloride (1.51 g) and sodium carbonate (2.29 g) in water (10 mL) at 2O ⁰ C.

It is stirred for 12 hours.

The mixture is diluted with diethyl ether and the organic phase is washed with water and brine and dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue, 4-propyl-2,6,7-trioxabicyclo (2.2.2) -octane-1-carboxaldehyde oxime, is obtained as a white gummy solid (0.8 g).

Gas / liquid chromatography (GLC): OV-17 at 210 ° C gives a single peak.

Mass spectrum (chemical ionization): M + 1 202

(iv) To a stirred solution of 4-propyl-2,6,7-trioxabicyclo- (2.2.2) octane-1-carboxaldehyde oxide (0.52 g) in dry methanol (10 ml) is added propargyl bromide (0.44 ml of a 80 % solution in toluene) and subsequently sodium methoxide (0.141 g) was added. the mixture is stirred for 12 hours at 2O ⁰ C. the mixture is poured into water and the aqueous mixture was extracted with diethyl ether. the ethereal extracts are washed with water and brine, and dried over anhydrous magnesium sulfate and then evaporated in vacuo.

The residue, a yellow oil, is pretreated by chromatography on silica gel with hexane containing 1% triethylamine, purified by elution with 4: 1 ethyl acetate: hexane containing 1% triethylamine.

4-Propyl-2,6,7-trioxabicyclo [2.2.2.l-octane-1-carboxaldehyde oximeprop-2-ynyl ether is obtained as a white crystalline solid (0.085 g, mp 73-74 ° C).

Example XXXV

2- (4-n-propyl-2,6,7-trloxablcyclo [2.2.2] -ocM-yl) ethyl but-2-lnoat

(i) A solution of ethyl 2- (4-propyl-2,6,7-trioxabicyclo [2.2.2l-oct-1-yl) -acetate (5.0g) (Example XXIV) in dry tetrahydrofuran (10ml ) is added dropwise to a stirred suspension of lithium aluminum hydride (1.8 g) in dry diethyl ether (100 ml) under a nitrogen atmosphere at 0 ° C. It is stirred for a further 1.5 hours at ⁰ ° C. An aqueous solution of sodium hydroxide (25 ml of a 10% solution) are added dropwise with cooling. The mixture is extracted with diethyl ether and the ethereal extracts washed with water, followed by brine, and dried over anhydrous magnesium sulfate and then evaporated in vacuo. The residue 1- (2-hydroxyethyl) -4-propyl-2,6,7-trioxabicyclo [2.2.2] octane is obtained as a colorless oil (3.5 g) which crystallizes on standing and a low-melting waxy solid results.

Gas / liquid chromatography (GLC: OV-17 at 210 ° C gives a single peak.

(ii) To a stirred solution of 1- (2-hydroxyethyl) -4-propyl-2,6,7-trioxabicycloI2.2.2l-octane (0.5g) in dry dichloromethane (20ml) is added at ⁰ ° C 4- Dimettiylaminopyridine (55mg) and subsequently tetronic acid (210mg) were added. The mixture is stirred for 5 minutes at ⁰ ° C, then dicyclohexylcprborii'mide (520 mg) is added portionwise (100 mg) over a period of 2 hours. It is stirred for a further 12 hours at 20 ° C. Water is added and the aqueous mixture extracted with dichloromethane. The organic extracts are washed with 10% sodium bicarbonate solution, water and brine before being dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue is purified as a yellow gum and chromatographed on silica gel pretreated with hexane containing 1% triethylamine by elution with 2: 3 ethyl acetate: hexane containing 1% triethylamine.

2- (1-Propyl-2,6,7-trioxabicycloI.2.2.2] -oct-1-yl) -ethyl-but-2-ynate is obtained as a white crystalline solid (0.266 mg, mp 80-81X).

Example XXXVI

1- (Hex-5-ynyl) -4-n-propyl-2,6-dloxabicyclo [2.2.2] octane

(i) A solution of trimethylsilylacetylene (12.0 g, Aldrich) in dry tetrahydrofuran (100ml) is stirred at 0 ⁰ C under a stream of nitrogen and n-butyllithium (76,5ml of a 1.6M solution in hexane) is added dropwise. The solution is stirred for 30 minutes and a solution of 1-chloro-3-iodopropane (25.0 g) in dry tetrahydrofuran (75 ml) is added. The reaction mixture is allowed to warm to 2C ⁰ C and stirred for 18 hours. The mixture is poured into water and the aqueous mixture extracted with diethyl ether. The ethereal extracts are washed with water and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the residue is distilled. 5-Chloro-1-trimethylsilylpent-1-yne is obtained as a colorless oil (12.7 g, boiling point 67-72 ° C, 15 mm Hg).

(ii) A mixture of S-chloro-1-trimethyl-ethylpent-i-ln (13.6 g) and sodium iodide (29 g) in butanone (100 ml) is refluxed for 10 hours. Thereafter, the solvent is removed in vacuo and the residue is partitioned between diethyl ether and water. The organic phase is separated, washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent is removed under reduced pressure to give 5-iodo-trimeth-1-silylpent-1-yn as a colorless oil (19.3 g).

(IM) n-Butyllithium (19.0 mL, 1.6 M solution in hexane) is added to a stirred solution of acetone in Ν, Ν-dimethylhydrazone (2.6 g) (Ref. RH Wiloy et al., J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml) was added dropwise under a stream of nitrogen at -70 ° C. The resulting solution is stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1 -in (8.1 g) in dry tetrahydrofuran (30ml) is added dropwise and the Reaktionsmischuno stirred for 1 hour at -7O ⁰ C. The mixture is allowed to warm to 0 ° C. and stirred for a further 2 hours. The reaction mixture is abgokühlt to -70 ⁰ C and oin second Toil n-butyl lithium (19ml, 1.6M solution in hexane) is added dropwise. The mixture is stirred for 15 Minuton at -7O ⁰ C. You can orwärmen to 0 ⁰ C and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0g, European Patent No. 216625) in dry tetrahydrofuran (30 ml) is added. The mixture is stirred at ⁰ ° C. for 30 minutes and at 20 ° C. for 48 hours. The solvent is removed in vacuo and the residue poured into Wassor. The aqueous mixture is extracted with diethyl ether and the ethereal extracts washed with water and dried over anhydrous magnesium sulfate and evaporated in vacuo. Chromatography of the residue on silica gel eluting with diethyl ether: hexane 1: 9 gives a yellow oil which is 2,2-dimethyl-5- (3-oxo-9-trimethylsilylnon-8-ynyl) -5-n-pro, > yl-1,3-dioxane and 7-oxo-1-tri.nethylsilyloct-1-in in the ratio of 3: 1 (1.4 g). The above-mentioned mixture in tetrahydrofuran (25 ml) and hydrochloric acid (50 ml, 1N solution) is vigorously stirred at 20 ° C for 1 hour. The tetrahydrofuran is removed in vacuo and the residue is extracted into diethyl ether. The ethereal extracts are dried over magnesium sulfate and the solvent removed in vacuo. 4-n-Propyl-1- (6-trimethylsilylhex-5-ynyl) -2,6-dioxabicyclo [2.2.2] octane is obtained as a colorless oil (1.06 g) and is used without further purification.

Mass spectrum (chemical ionization) M + 1 309

(iv) Tetrabutylammonium fluoride solution (4.0 mL of a 1.0M solution) is added to a stirred solution of 4-n-ProDyl-1- (6-trimethylsilyl-hex-S-ynoxy) -e-dioxabicyclo [10-] 1-octane in dry Tetrahydrofuran (40 ml) at 20 ° C. and the mixture is stirred for 1 hour, the solvent is removed in vacuo and the residue is extracted into diethyl ether The ethereal extracts are dried over magnesium sulphate and the solvent is removed in vacuo 4-n-propyl- 1- (6-trimethylsilylhex-5-ynyl) -2,6-dioxabicyclo [2.2.2] octane is obtained as a colorless oil (1.06g) and is used without further purification.

Mass spectrum (chemical ionization) M + 1 309

(iv) Tetrabutylammonium fluoride solution (4.0 ml of a 1.0M solution) is added to a stirred solution of 4-n-propyl-1- (6-trimethylsilyl-hex-5-ynyl) -2,6-dioxabicyclo (2.2.2). -octane in dry tetrahydrofuran (40ml) at 20 ° C and the mixture is stirred for 1 hour The solvent is removed in vacuo and the residue extracted with diethyl ether and water The ethereal extracts are dried over anhydrous magnesium sulfate and evaporated in vacuo The residue is chromatographed on alumina, eluting with dichloromethane: hexane, 1: 9, saturated with ammonia, giving 1- (hex-5-ynyl) -4-n-propyl-2,6-dioxabicyclo (2.2 .2] octane as a colorless oil (0.4ug).

Example XXXVII

1 - [(Z) -1-fluoro-3,3-dlmothylbut-1-enyl] -4-propyl-2,6,7-trloxablcyclo [2.2.2] octane-3-carbonltrll

(i) A mixture of Ethylbromtluoracetat (25g) (Fluorochem.) and Triethylphusphit (30ml) is heated in a device, which is aligned as a fractional distillation apparatus, to 15O ⁰ C until no more bromoethane is produced. The distillation of

Residue, under reduced pressure gives Ethyldiethylphosphonfluoracetat as colorless oil (9.05g, boiling point 80-88 ° C,

(ii) n-Butyllithium (4.8ml of a 1.6M solution in hexane) is added to a stirred solution of diisopropylamine (1.1ml) in

Tetrahydrofuran (15ml) was added under nitrogen at ⁰ ° C. The resulting mixture is held at O'C for 0.5 h and

then cooled to -7O ⁰ C, when a solution of Ethyldiethylphosphonfluoracetat (1.7 g) in tetrahydrofuran (5ml) is added. After a further half hour Trimethyldcetaldehyd (0,76ml) neat at -7O ⁰ C is added and allowed to warm läßtdie resulting mixture over a period of 5 hours at room temperature. Thereafter, water (5ml) is added and the bulk of the solvent removed under reduced pressure. The backlog will be between

Diethyl ether and water distributed. The organic phase is separated with water, 10% hydrochloric acid solution and brine

washed and then dried over anhydrous magnesium sulfate. The solvent is removed in vacuo to give ethyl (Z) -2-fluoro-4,4-dimethylpent-2-enoate as a pale green oil (1.0 g).

Gas / liquid chromotography (GLC): OV-17 at 100 ° C gives a peak.

(iii) Using the procedure described in Example XXXIII, step (iii), (Z) -2-fluoro-4,4-dimethylpent-2-enoic acid is obtained from ethyl (Z) -2-fluoro-4,4- dimothylpent-2-enoate.

(iv) Using the procedure described in Example IV, Steps (ii) and (iii), 1 - [(Z) -1-fluoro-3,3-dimethylbut-1-enyl-1-propyl] -ethylene trioxabicyclo ^^ l -octane-S-carbonitrile of S-formyl-Sn-propyl-oxoethane and FZl ^ -fluoro-M-dimethylpent-2-enoic acid.

Gas / liquid chromatography (GLC): OV-17 at 250 ° C gives a peak. Example XXXVIII

4-EthoxymethyM- (hex-5-ynyl) -2,6,7-trioxablcyclo [2.2.2] octane-3-carbonitrile

(i) To a stirred solution of 5,5-di- (hydroxymethyl) -2,2-dimethyl-1,3-dioxane (5.0g) (Beilstein 19, II, 93) in dry dimethylformamide (50ml is added at 20 Sodium hydride (0.68 g, 80% dispersion in oil) was added under nitrogen to the mixture, stirred and cooled for 2 hours at 80 ° C. Ethyl iodide (4.4 g) in dry dimethylformamide (40 ml) was added and the mixture 3 heated hours at 110 ⁰ C. The mixture is cooled and poured into water, the aqueous ";... jchung is extracted with diethyl ether The ethereal extracts are washed with brine, dried over anhydrous magnesium sulphate and evaporated in vacuo 2,2-dimethyl.. 5-ethoxymethyl-5-hydroxymethyl-1,3-dioxane is obtained as a pale yellow oil (1.2 g) and is used without further purification.

(Ii) Elno Mixture consisting of α 1 -dimethyl-B-ethoxymethyl-B-hydroxymethyl-i, 3-dioxane (15.0g) and Amberlyst "15" (3.0g) in methanol (500ml), holding on water ( 10 ml), is heated under reflux for 4 hours, the mixture is filtered off and the

Ritrat evaporated in vacuo. 2-Ethoxymothyl-2-hydroxymethylpropane-1,3-dlol is obtained as a viscous oil (10.5 g) and is without

woitore cleaning used.

(II) 4-Ethoxymethyl-1- (hex-6-ynyl) -2, e _> 7-trloxabicyclo [2.2.2] octane-3-carbonitrile is prepared from 2-ethoxymothyl-2-hydroxymethylpropane-1,3-dlol using the Bechplol iv boschlobenen Vorfahrenweiso prepared.

AufanalogeWelsewlrd1- (Hex-5-lnyl) -4-methoxymethyt-2, e, 7-trioxablcyclo [2.2.2l-octan-3-c & rbonitrllhergostollt. Example XXXIX

4-t-Butyl-1- (hex-5-lnyl) -2, e-dloxa-7-thlablcyclo [2.2.2l-octane

4-t-Butyl-1- (hex-5-ynyl) -2,6-dioxa-e-thiablocyclo [2.2.2] octane is prepared from trimethylorthohope-6-ynoate and 2,2-di- (hydroxymothyl) · 3,3-dimethylbutan-1-thiol (European Pat. No. 2,166,225) was prepared by prewiring a procedure described in our European Patent No. 216625.

Example XL

(I) 2-Methylpent-4-nylmethanesulfonate is prepared from 2-methylpent-4-ln-1-ol (Ref, E.Buchta and H. Schlesinger Chem., Abs. 51: 1104i) using the procedure described in Example II, step (i) Process produced.

(ii) A solution of diethyl malonate (46 g) in dry toluene (500 ml) is stirred under a nitrogen atmosphere at ⁰ ° C.

Sodium hydride (8.6 g of an 80% dispersion in liquid paraffin) is carefully added and the mixture boiled

100 ⁰ C1 hour stirred. The mixture is cooled and 2-methylpent-4-ynyl-mothanesulfonate (10.2 g) is added and dio

Mixture is heated for 3 hours with stirring and stirring. Dio mixture is cooled, poured into water and the aqueous Mixture is extracted with diethyl ether. The ethereal extracts are washed with water, over anhydrous Dried magnesium sulfate and evaporated in vacuo. Excess Diethylmalonat is reduced by distillation boi Pressure and the residue purified by chromatography on silica gel, eluaort with 7.5% diethyl ether in hexane Diethyl (2-methylpn-4-ynyl) malonate is obtained as a colorless oil (6.5 g). Gas / liquid chromatography (GLC): OV-17 at 16O ⁰ C gives a peak. Mass spectrum (MS) (chemical ionization) M + 1 241

4-i-diethylhept-6-acetic acid is prepared from diethyl (2-methylpent-4-ynyl) malonate using the methods described in steps (Hi) and (iv) of

Example XXVII procedure described.

1 - (3-Methylhex-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo | 2.2.2l-octane-3-carbonitrile is prepared from 4-methylhept-6-acetic acid and 3-formyl-3 -n-propyl-ethane prepared using the procedure described in Example IV.

Using steps (ii) and (iii) of Example XXX and starting from (S) -4-methyl-6-oxoheptanoic acid (J.Wolinsky

and D.Chan J. Amer. Chem. Soc, 1963, 85, 937), (S) -4-methyl-hopt-6-acetic acid is prepared.

1 - | (S) -3-methylhex-5-ynyl-4-n-propyl-2,6,7-trioxabicyclo [2.2.2] octane-3-carbonitrile is prepared from (S) -4-methylheptyl 6-acid under

Using the procedure described in Example IV prepared. Starting from 3-l-butyl-3-formyloxetane and 4-methylhept-6-acetic acid, 4-l-butyl-1- (3-methylhex-5-ynyl) -2,6,7-

trioxabicyclo [2,2,2] octane-2-carbonitrile.

Example XLI

1- (t-Butylthlomethyl) -4-n-propyl-2,6,7-trloxablcyclo [2.2.2] octan-3-carbonl: rll

Using steps (i) and (ii) of Example XIII and starting from t-butyl thiol and ethyl bromoacetate

t-.lutylthioacetic acid produced.

1 (t-butylthiomethyl) -4-n-propyl-2,6,7-trioxabicyclo (2,2,2] octane-3-carbonitrile is prepared from t-butyl thiooacetic acid and 3-formyl-3-n-propyloxetane using the method described in Example 1 IV described procedure.

Example XLII HHept S inylM-n-propyl-^ ej ^ trloxablcycloß loctan

n-Butyllithium (1.7 mL, 1.6 M solution in hexane) is added a stirred solution of 1- (hex-5-ynyl) -4-n-propyl-2,6,7-trioxabicyclo [2.2.2 ] octane (0.65 g) in dry tetrahydrofuran (25 ml) was added dropwise under a stream of nitrogen at ^{0 0} C. The mixture is stirred at ⁰ ° C for 15 minutes and then added with Mothyl iodide (0.18 ml). The reaction mixture is stirred for 1 hour at ⁰ ° C. and then evaporated in vacuo. The residue is partitioned between diethyl ether and water. The ethereal extracts are dried over anhydrous magnesium sulphate and the solvents are removed in vacuo. The residue is purified by chromatography on alumina, eluting with 1:10 dichloromethanehexane saturated with ammonia. 1 - (Hept-S-ynylM-n-propyl) .ej-trioxabicyclotf ^^ loctan is obtained in the form of a colorless crystalline solid (0.23 g) (containing 15% of 1- (hex-5-ynyl) - '1n- propyl-2,6,7-trioxabicycloI2,2,2loctan).

Example XLIII

4- (2,2-Dlchlorcyclopropymethyl) -1- (Hox-5-lnyl) -2, e, 7-trloxablcyclo [2,2,2) octane

1) 2-Hydroxymethyl-2- (prop-2-enyl) propane-1,3-diol triacetate (2.2 g) (Example XVII) is heated at 130 ° C. with stirring.

Sodium trichloroacetate (5.0 g) is added over a period of 2 hours and the reaction mixture becomes

Heated at 155 ° C for 24 hours. The mixture is cooled and partitioned between diethyl ether and water (extracted by shaking).

The ethereal extracts are dried over anhydrous magnesium sulphate and evaporated in vacuo. The residue

is purified by chromatography on silica, eluting with diethylmethanehexane, 1: 4.

2- (2,2-dichlorocyclopropylmethyl) -2-hydroxymethylpropane-1,3-diol triacetate is obtained as a colorless oil (1.4 g). Mass spectrum (chemical ionization): Ammonia as ionizing gas: M + 18 372.

Using the method described in Example I, Step 1, boschriebenon procedure, 2- (2,2-dichlorocyclopropylmethyl) -2-hydroxmethylpropane-1,3-dlol is prepared from 2 x (2.2 x 01οηΙθΓονοΙορΓορν ^ θίηνΙ) · 2 · ηναΓθΧΓηβΐηνΙ · ρΓορβη · 1.3 · αίοΙΐπΒοβΐβΙ made. Using the procedure described in Example VI, Ancestors 2, 4- (2,2-dichlorocyclopropylmethyl) -1 · (hoX'5-inyl) -2, e, 7-tr ^| oxablcyclo | 2,2,2-octane prepared from 2- (2,2-dichlorocyclopropylmethyl) -? - hydroxymethylpropane-1,3-diol and trimethylorthohept-6-ynoate.

compositions

1. Emulsifiable concentrates

Compound gomaß Formol I 10,00

Ethylaneko 20.00

Xylene 67.50

ButyliortosHydroxya iisol 2.50

100.00

2. Wettable powder

Pre-binding according to Formol (I) 25.00

Attopulgite 69.50

Sodium isopropylbenzenesulfonate 0.50 sodium salt of condensed naphthalene

Sulfonic acid 2.50

ButyliortusHydroxytoluene 2.50

dust 100.00 Third Compound according to formula (I) Butylated hydroyanisole 0.50 talc 0.10 99.40 bait 100.00 4th Compound according to formula (I) Glazed sugar 40,25 Butylated hydroxytoluene 59.65 0.10 paint 100.00 5th Compound according to formula (I) piperonyl butoxide 0.10 Butylated hydroxyanisole 0.50 Highly aromatic white spirit 10.10 92,00 Erosol 100.00 6th Compound according to formula (I) Butylicrtos Hydroxyanisole 0.30 1,1,1-trichloroethane 0.10 Odorless kerosene 4.00 Arcton11 / 12:50: 50Mischung 15,60 80,00

100.00

0.10

0.10

10.00

89,80

100.00

7. Spray

Compound according to formula (I)

Butylated hydroxyanisole

Odorless kerosene

8. Potent spray Compound according to formula (I) Piperonyl butoxide Butylated hydroxyanisole Xylene

Odorless kerosene

BIOLOGICAL ACTIVITIES

The following examples nonlimitingly show the pesticidal activity of the compounds according to formula (I).

Spray tests

The activity of the compounds according to the invention are tested by dissolving the compounds in acetone (5%) and diluting in water: "Synperonic" (94.5%: 0.5%) to form a water emulsion Treatment of the following insects used.

Muscadomestica

Twenty female Musca are placed in a cardboard cylinder with a net stretched over both ends. A solution containing the compound is sprayed on the insects thus entrapped and the mortality is evaluated after Ί8 hours at 25 ° C.

The following connections are active at <1000 p. p. m .:

4,5,14,20,21,22,23,24,25, 26, 28,32,43,44,45,50,53, 54, 56, 69,71, 72, 76, 77, 82, 88.89.

The following connections are active boi <200p. pm: 6,9,10,11,12,13,15,16,17,29,30,31,33,34,46,47,48,52,57,58,59,60,61,62, 63,64,65,68,74,75,78,79,80,81,83,84,85,90.

Sitophüus granarlus and Trlbollum castaneum 20 adult Sitophüus and Tribolium are supplemented with 10 g of wheat previously treated with 2 ml of a solution containing the compounds. Mortality is assessed after 6 days at 25 ° C.

The following compounds are against Sitophilus granarlu: at <1000 p.p. m. active:

7,10,19, 22, 23, 25,26,27,32,43,44, 50, 56, 69, 82, 85,88,89,90.

The following compounds are against Sitophilus granarius at <200 p. p. m. active:

3,4, 5,6,9,12,14,15,16,17, 29,30,31,33,34,45,47,48, 53, 54,57, 58, 59,60,61, 62, 68, 72, 74, 75, 76, 77, 78.79, 80. The following compounds are resistant to Tribolium castaneum at <1000p. p. m. active:

4,6,10,14,17,33,53,57,58,65, 71, 76, 79,82,84.

The following compounds are against Tribolium castaneum at <200 p. p. m. active:

9,12,15,16,34,46,63,74,75.

Myzus perslcae

10 adult Myzus are applied to a slice of a leaf of Chinese cabbage. 24 hours later, the disc is sprayed with a solution containing the compound. The mortality is assessed after 2 days at 25 ⁰ C.

The following connections are active at <1000 p. p. m. °.

4,9,17,37,46,53,56,60,71,77,78,79,80,81,84.

The following connections are active at <200 p.p.m .:

6,45,47,48, 57, 58,59,62,63,74,75,76.

Plutella xylostella

7 Plutella larvae are sprayed with the compound containing the compound and added to a leaf of C. iina cabbage which has been similarly sprayed and dried. Alternatively, 8-10 Plutella larvae were seeded on leaf discs and sprayed with the solution containing the compound. Mortality is assessed after 2 days at 25 ° C.

The following connections are active at <1000 p. p. m .:

15,16,25, 29,31, 33,34,35,48,55,56,58,59, 65, 68,71,75, 77,78,79,80,81,83,85, the following Connections are active at <200p.pm:

9,12,13,46,47,57,74.

Tetranychus urticae

Leaf discs containing mixed populations of Tetranychus urticae are sprayed with the solution containing the compound. The mortality is assessed after 2 days at 25 ⁰ C.

The following connections are active at <1000 p.p.m .:

78,81,83,90.

The following connections are active at <200 p.p.m .:

Additional spray tests

The activities of the compounds will be further investigated. The compounds are dissolved in acetone (75%) and water (25%) is added. The solution is then sprayed with the following insects:

Aphis fabae

A mixed population of Aphis fabae is used on a nasturtium leaf.

The following connections are active at <1000p. p. m .:

4, 6, 13, 16, 17, 25, 26, 29, 30, 31, 33, 46, 47, 50, 54, 63, 65.

Macrosteies fascifrons

Adult macrosteies fascifrons are tested on wheat seedlings.

The following connections are active at <1000p. p. m .:

6,9,13,16,17,23,25,26,29,31, 33,34,46,47,63,65,68.

Tetranychus urticae

A mixed population of Tetranychus urticae is tested on bean leaves.

The following connections are active at <1000 p. p. m .:

5,9,16,30,31,33,46,47,50, 65,68.

Diabrotica undecimpunctata

3. Instar Diabrotica undecimpunctata are tested on filter paper.

The following connections are active at <1000 p. p. m .:

3,4,5,6,13,16,23,25,26,29,30,31,33,34,46,47,53,63,65,68.

local application tests

The activity of the compounds according to the invention against non-anesthetized female Miiscadomestlca (WKL strain) is demonstrated by the topical application of a solution of a test compound with piporonyl butoxide in butanone. Mortality is assessed after 48 hours.

The following compounds are active at 1 μg:

9,10,11,12,13,15,17,29,30,31,33,34,47,52,63,64,68,83,84, fc 5.

The activity of the compounds according to the invention against adult male Perlplaneta amorlcana is demonstrated by topical application of a solution of a test compound in butanone gogon i'io test insects. Dio mortality is assessed after 6 days:

The connections are active at <50; jg:

2,6,16,17,25,31,39,83.

The activity of the compounds of the present invention against anesthetized male Blatella germanlca is demonstrated by topical application to a solution of a tout compound in butanone against the test insects. The mortality is determined after 6 days,

The following connections are active at 5pg:

6,9,12,14,15,16,17,20,29,30,31, 33, 34,45,46,48, 56, 57,58, 59,60,61,62, 63, 65, 66, 67, 71, 7 2, 74, 75, 83, 84, 90.

Nematucidal activity

Meloidogyne Incognita

Selected compounds of the invention are assayed on freshly hatched Meloldogyno Incognita. The test solution contains 1% acetone with 100 p. p. m. Triton X-100. The activities are evaluated after 24 hours.

The following connections are active at <100p. p. m .:

Toxicity to mammals

The toxicity of the compounds of the invention is determined by oral intubation on Charles River CD 1 mice fixed for 3 hours. The compounds are administered as solutions in DMSO at 200mg / 10ml / kg, 20mg / 10ml / kg and 2mg / 10ml / kg. The toxicity is evaluated after a 14-day period after dosing.

The following compounds give an LDio> 200mf ^l <g ~ ¹ :,

The following compounds give an LD ₆₀ in the region of 2O-200mgkg ''

ANNEX 1

CH.

^v CO ₂ Et

(I)

Cl

CH ₂ = C-

-CO-Et

(Iv)

(Ii)

CHSC

CH ₂ OH

(Iii)

Cl

CH ₂ = C

CH ₂ OH

CH = C

(i) PCl ₅ , pyridine. (ii) LiAlH ₄ , Et ₂ O (iii) n -BuLi, Thf

(iv) pyridinium dichromate, Dmf

ANNEX 2

(I)

SH

HS

'OH

\

Ph Ph

(CHO S S

Ph Ph

SH I HS OH

(Iii)

\ Ph Ph

(i) MeSO ₂ Cl, pyridine (iii) Na, liquid NH 3 (v) MeMgI, Et ₂ O (ii) PhCH ₂ SH, NaH, dimethylformamide (iv) pyridinium chlorochromate, sodium acetate,

ANNEX 3

(I)

Cl

Me ₂ NN

Cl

SiMe,

"^ SiMe

- ^ _ LJ

NNMe,

(i) Me ₃ SiC = CH, n-BuLi, Thf (ii) NaI, MeCOEt (iii) "^ U ² n -BuLi, Thf

IJ ^ sj Me Me ^;

, n-BuLi, Thf

Me Me (vi) Thf, hydrochloric acid (1N solution)

(v) silica gel (vii) (n-Bu) ₄ NI, Thf

ANNEX 4

- -Y - (CH ₂ ) _n co ₂

(CH ₂ ) _n CHO

(Iii)

CH ₀ ) C = NOH

² "i

(i) LiAlH ₄ , Et ₂ O, 20 ° -30 °

(ii) (COCl) ₂ , CH ₂ Cl ₂ , DMSO ₁ NEt ₃ , -70 ° to 20 ° ^C

(iii) MeOCH ₂ CH ₂ OMe, NH ₂ OHHCl, Na ₃ CO ₃ , H ₀ O, 20-30

Table I - Trloxablcyclo-octanes ²

connection R No. 1 Pent-4-ynyl 2 Hex-5-ynyl 3 Pent-4-ynyl 4 Hex-5-ynyl 5 Pent-4-ynyl 6 Hex-5-ynyl 7 Pent-4-ynyl 8th Ηθχ-5-ynyl 9 Hex-5-ynyl 10 6-TRIMET! Iyl-silylhex-5-ynyl 11 4-rth ^! , iylcylohexyl 12 4-Ethinylcyclohexyl 13 3,3-dimethylbut-1-ynyl 14 3,3-dimethylbut-1-ynyl 18 2- (prop-2-ynylthio) ethyl 19 2- (prop-2-ynylthio) ethyl 20 2- (prop-2-ynylthio) ethyl 21 2- (prop-2-ynyloxy) ethyl 22 2- (prop-2-ynyloxy) ethyl 23 2- (prop-2-ynyloxy) ethyl 24 But-3-ynyloxy-methyl 25 But-3-ynyloxy-methyl 26 But-3-ynyloxy-methyl 27 Hapt-6-ynyl 28 Hept-6-ipyl 29 Hex-5-ynyl 30 Hex-5-ynyl 31 Hex-5-ynyl 32 But-3-ynyloxy-methyl 33 Hex-5-ynyl 34 4-methylhex-5-ynyl 35 2- (but-3-ynyloxy) ethyl 36 Oct-7-ynyl 37 1- (but-3-ynyloxy) ethyl 38 7-Methoxyhept-5-ynyl 39 7-Methoxyhept-5-ynyl 40 But-3-ynyloxy-carbonyl 41 N- (prop-2-ynyl) carbamoyl 42 Prop-2-ynyloxy-carbonyl-methyl 43 But-3-ynylthio-methyl 44 But-3-ynylthio-methyl 47 Hex-5-ynyl 48 Hex-5-ynyl 49 Hex-5-ynyl 50 Hex-5-ynyl 51 N-prop-2-ynyl 2-acetamido 52 1-methylhex-5-ynyl 53 1-methylhex-5-ynyl 54 1-Melhylhex-5-iny! 55 e-methoxycarbonyl-hex-ö-ynyl 56 Hex-5-ynyl 59 3-methylhex-5-ynyl

R ²

Synthetic method Example

n-Pr H n-Pr H n-Pr CF ₃ n-Pr CF ₃ n-Pr CN n-Pr CN cyclohexyl H cyclohexyl H t-Bu H t-Bu H n-Pr i (isomeric mixture) t-Bu H (isomeric mixture) t-Bu H n-Pr CN n-Pr H t-Bu H n-Pr CN n-Pr H t-Bu H n-Pr CN n-Pr H t-Bu H n-Pr CN t-Bu H n-Pr H n-Bu CN 2-methylprop CN 2-enyl Prop-2-enyl CN Prop-2-enyl CN But-3-enyl CN t-Bu H n-Pr H n-Pr H n-Pr H n-Pr H t-Bu H n-Pr H n-Pr H n-Pr H n-Pr H t-Bu H t-Bu CN IBU CN MeOCH ₂ CN EtOCH ₂ CN n-Pr H n-Pr H t-Bu H n-Pr CN n-Pr H Ph H n-Pr CN

III

IV

IV

Vl

VII

VIII

IX

XIII

XIII

XIII

XIV

XIV

XIV

XV

XV

XV

XVI

XVI

IV

IV

XVII

XVII

XVII

XVIII

XIX

Il

XIX

XX

XXI

XXII

XXIII

XXIV

XXV

XXV

IV

IV

XXXVIII

XXXVIII

XXVI

XXVII

XXVII

XXVII

XXVIII

Vl

XL

Continuation of Table I Connection R

R ²

Synthetic method Example

60 61 63 64 65 66 67 68 69 70 74 75 77 78 79

80 81 82 83 84 85 86 87 88 90 91

2-methylhex-5-ynyl

3,3-dimethylbut-1-ynyl

4-Ethinylcyclohexyl

(E / Z) -6- (trimethylsilyl) hex-3-en-5-ynyl

(E / Z) -hex-3-en-5-ynyl

(E / Z) -7-Methoxyhept-3-en-5-ynyl

(E / Z) -7-Hydroxyhept-3-en-5-ynyl

(E) -hex-1-en-5 inyl

Prop-2-methyl-ynyloxyimino

2- (But-2-ynoyloxy) -e; hyl

trans-4-ethynyl-cyclohe, 'lr

cls-4-hexyl-Ethinylcyclo

4-methylhex-5-ynyl

Hex-5-ynyl

Ηθχ-5-ynyl

3-methylhex-5-ynyl

(S) -3-methylhex-5-ynyl

2-methylhex-5-ynyl

3,3-dimethylbutyl

3,3-dimethylbutyl

E-3,3-dimethylbut-1-enyl

trans-2-t-Butylcyclopropyl

t-butylthiomethyl

Z-3,3-dimethyl-1-fluoro-but-1-enyl

Hept-5-ynyl

Hex-5-ynyl

n-Pr CN i-Bu CN n-Pr CN n-Pr CN n-Pr CN n-Pr CN n-Pr CN t-Bu CN n-Pr H n-Pr H t-Bu H t-Bu H n-Pr CN phenyl CN cyclopropyl CN methyl I-Bu CN n-Pr CN Prop-2-enyl CN t-Bu H n-Pr CN n-Pr CN n-Pr CN n-Pr CN n-Pr CN n-Pr H 2,2-Dichlorcyclo- H propyl-methyl

XXX

IX

XXXII

XXXII

XXXII

XXXII

XXXIII

XXXIV

XXXV

IX

IX

XVIII

IV

IV

XL

XL

XXX

XLI

XXXVII

XLII

XLIII

Table II - Other Bicvclo-octane

connection R R ¹ R ' X Y Z synthesis method No. example 15 Hex-5-ynyl t-Bu H S O O XXXIX 16 Hex-5-ynyl n-Pr H S S O xl 17 Hex-5-ynyl n-Pr H S S S XII 45 Hex-5-ynyl n-Bu H S S O xl 46 Hex-5-ynyl t-Bu H S S O xl 57 Hex-5-ynyl i-Bu H S S O xl 58 Hex-5-ynyl n-Pr me S S O XXIX 62 But-3-inyloxymethyl n-Pr H S S S XXXI 71 Hex-5-ynyl I-Bu H S S S XII 72 Hex-5-ynyl Ph H S S O xl 73 Hex-5-ynyl n-Pr H CH ₂ O O XXXVI 76 Hex-5-ynyl et H S S S XII 89 Hex-5-ynyl cyclo H S S O xl propyl methyl

Table III - Characteristic Sponsors of Trloxabicyclo-octanes

Compound melting point mass spectrum particle magnetic resonance spectrum no. Chemical ionization ¹ H (ppm from TMS in CDCI _3, integral, multiplicity, J _Hl)

M + 1

1 solid 225 3.90.6 H, s; 2.4-1.6.7 H, m; 1.3-0.7.7 H, m.

2 O 239 3.90.6H, s; 2.17 ₍ 2H, m; 1.95.1H ₍ t; 1.75-1.45.6H, m; 1.35-1.05H, m ;

0.95.3 H, t.

3 76 ° C 293 4,35,1H, qd; 4,15,1H, dd; 4, O-3,75,3H, m; 2,25,2H, td; 2, O-1,1,9H , m;

0.9.3 H, t.

4 '57 ⁰ C 307 4,35,1H, qd; 4,15,1H, dd; 4,0-3,75,3H, m; 2,15,2H, m; 1,95,1H, t;

1,8-1,1,10H, m; 0,9,3H, t.

5 oil 250 4,8,1 H, d; 4,2,1 H, dd; 4.05-3.85.3 H, m; 2,2,2 H, td; 1.95.1 H, t;

1.9-1.55.4 H, m; 1.45-1.15.4 H, m; 0.95.3 H, t.

6 oil 264 4,8,1 H, d; 4,2,1 H, dd; 4.05-3.8.3H, m; 2,15,2 H, m; 1,9,1 H, t;

1.85-1.1.10 H, m; 0.95.3 H, t.

7 82 ° C 265 3.95.6H, s; 2,25,2H, td; 1,9,1 H, t; 1,85-0,8,15H, m.

8 Oil 279 3.95.6 H, s; 2,2,2 H, m; 1.95.1 H, t; 1.85-0, 8, 17 H, m.

9 75 ° C 253 4.00.6 H, s; 2,20,2 H, m; 1.95.1 H, t; 1.70-1.50, ΘΗ, ηι; 0.85.9 H, s.

10 87-90.5 ⁰ C 325 4.00.6H, s; 2,20,2H, m; 1,70-1,50,6H, m; 0,85,9H, s; 0,15,9H, s.

11 Oil 265 3.92.6H, s; 2.25-1.10, 15H, m; 0.85.3H, t, J ", 5.

12 126-132 ° C 2-component translsomer: -4.01,6H, s; 2.2-1.1.11 H, m; 0,90,9H, s.

trans and ice in the ice isomer: -4.00.6 H, s; 2.2-1.1.11 H, m; 0.90.9 H, s.

Ratio4: 1

279

13 204-206T, 253 4,10,6H, s; 1,25,9H, s; 0,90,9H, s.

14 123-124'C 264 4,85,1 H, d; 4,20,1 H, m; 4.00.3 H, m; 1,30,4H, m; 1,25,9H, s;

0,95,3 H, t, 7.

18 Oil 257 3.95.6 H, s; 3,25,2 H, d, 1,5; 2,85,2 H, m; 2.00.1 H, t, 1.5; 2.05.2 H, m;

1,20,4 H, m; 0, 90.3 H, t, 7.

19 76-82 ⁰ C 271 4,00,6 H, s; 3,25,2 H, d, 1,5; 2,80,2 H, m; 2,20,1 H, t, 1,5; 2,00,2 H, m;

0.90.9 H, s.

20 oil 282 4,80,1 H, d; 4,20,1 H, m; 4.00.3 H, m; 3,25,2 H, d, 1,5; 2,80,2 H, m;

2.25.1 H, t, 1.5; 2.05.2 H, m; 1.30.4 H, m; 0,95,3H, t,. 7

21 solid 241 4,15,2 H, d; 3.90.6 H, s; 3,65,2 H, t, 6; 2,40,1 H, t; 2,00,2 H, t, 6; <35 ° C 1,20,4 H, m; 0,90,3H, t,. 6

22 Oil 255 4,15,2H, d; 4,00.6H, s; 3,65,2H, t; 2,4,1H, t; 2,05,2H, t; 1,90,9H, s.

23 Oil 266 4,80,1 H, d, 2,7; 4.2-3.9.6 H, m; 3,65,2 H, t, 5; 2.45.1 H, t; 2,2,2 H, t, 5;

1,4-1,15,4H, m; 0,9,3H, t.

24 64 ° C 241 4,00,6H, s; 3,70,2H, t, 6; 3,55,2H, s; 2,55,2H, td; 1.95.1 H, t; 1,25,4H, m;

0, 90.3 H, t, 7.

25 oil 255 4.05.6 H, s; 3,7,2 H, t; 3,55,2 H, s; 2.5.2 H, td, 1.95.1 H, t; 0.85.9 H, s.

26 67.4 ⁰ C 266 4.8 8 H, d, 2.65; 4,25,1 H, m; 4,10-3,95,3 H, m; ? 3.70, H, t; 3,60,2H, s;

2.50.2 H, td; 2,00,1 H, t; 1.45-1.20.4 H, m; 1,00,3 H, t, 7.

27 66.2 ⁰ C 267 3.95.6H, s; 2,18,2H, td; 1,94,1 H, t; 1,7-1,35,8H, m; 0,85,9H, s.

28 Oil 253 3.95.6H, s; 2.17.2H, td; 1.92.1H, t; 1.7-1.05, 12H, m; 0.88.3H, t.

29 Oil 278 4,8,1 H, d, 2,6; 4,2,1 H, m; 4,05-3,85,3 H, m; 2,2,2H, m; 1.95.1 H, t, 2.6;

1.75-1.15,12 H, m; 0,9,3 H, t, 7.

30 oil 276 5.05.1 H, d; 4,8,2 H, m; 4,23,1 H, m; 4.1-3.9.3 H, m; 2.25-2.10.4 H, m;

1.95.1 H, t; 1.75.3 H, s; 1.70-1.65.2 H, m; 1.60-1.45.4 H, m.

31 Oil 262 5.75-5.5.1 H, m; 5,20,2 H, m; 4,75,1 H, d; 4,20,1 H, dd; 4.02-3.88.3 H, m;

2,20-2,12,4 H, m; 1.95.1 H, t; 1.75-1.65.2 H, m; 1.60-1.50.4 H, m.

32 Oil 264 5,55,1 H, m; 5,22,2 H, m; 4,82,1 H, d; 4,25,1 H, dd; 4.00.3 H, m;

3.75.2 H, t; 3,60,2 H, s; 2.50.2 H, td; 2,20,2 H, d; 1,97,1 H t.

33 Oil 276 5.8-5.65.1 H, m; 5.06.2 H, m; 4,80,1 H, d; 4,20,1 H, dd; 4.05-3.90.3 Hm;

2.25-2.15.2 H, m; 2.07-1.97.2 H, m; 1.95.1 H, t; 1.75-1.65.2 H, m; 1.6-1.45.6 H, m.

34 47-51 ° C 267 4.00.6H, s; 2.38.1 H, m; 2.03.1 H, d; 1,75-1,35,6H, m; 1,17,3 H, d;

0.85.9 H, s.

35 oil 255 3.90.6 H, s; 3,60,2 H, m; 3,55,2 H, t, 7; 2.45.2 H, td, 7 and 2.6;

2,00,2 H, m; 1.95.1 H, t, 2.6; 1,15,4 H, m; 0.90.3 H, t, 6.8.

36 Oil 267 3.90.6 H, s; 2,15,2 H, td "and 2,6; 1,95,1 H, t, 2,6; 1,7-1,2,1OH, m;

1,15,4 H, m; 0.90.3 H, t, 6.8.

37 Oil 255 3.95.6 H, s; 3,83,1 H, m; 3,65,1 H, m; 3.46.1 H, m; 2.45.2 H, m;

3,46,1,95,1 H, t, 2,6; 1.20-1.15.7 H, m; 0.90.3 H, t.

38 solids 283 4,10,2H, t; 3,90,6H, s; 3,35,3H, s; 2,20,2H, m; 1,65,2H, m; 1,50,4H, m; M.p. <40 ° C 1.25.4 H, m; 0, 90.3 H, t, 7.

39 47-49 ° C 297 4,19,2 H, m; 4,00,6H, s; 3,40,3 H, s; 2,20, ?. H, m; 1.60.6H, m; 0.90.9 H, s.

40 62,1 ⁰ C 255 4,35,2 H, t; 4,10,6 H, s; 2,60,2 H, m; 2,00,1 H, t; 1,22,4H, m; 0,90,3H, t.

Table III - Characteristic Data for Trioxabicyclo Compound Melting Masses Mass. Chemical ionization

M +

octane (cont.) Nuclear magnetic resonance spectrum ¹ H (ppm of TMS in CDCI ₃ , integral, multiplicity, J ₁₁₁ )

6.70.1 H, m; 4,10,2 H, d; 4.05.6 H, s; 2.25.1 H, t; 1,20,4 H, m; 0, 90.3 H, t, 7.

4.73.2 H, d; 3.95.6 H, s; 2,80,2 H, s; 2,45,1 H, t; 1,15,4 H, m; 0.90.3 H, t. 3.95.6H, s; 2,85,2 H, t, 7; 2,80,2 H, s; 2.50.2 H, td; 2,00,1 H, t; 1.40.4 H, m; 0.90.3 H, t.

4.05.6H, s; 2,83,2 H, t, 7; 2,80,2 H, s; 2.50.2 H, td; 2,00,1 H, t; 0.85.9 H, s.

4,80,1 H, d; 4,35,1 H, m; 4,00,2 H, m; 3,85,1 H, m; 2,20,2 H, m; 1.95.1 H, t; 1.75.2 H, m; 1.45.4 H, m; 1.00,9 H, s.

4.80.1 H, d; 4.2-4.9.4 H, m; 2,2,2 H, m; 1,9,1 H, t; 1.8-1.5.6H, m; 1,3,3H, m; 1,0,6H, m.

5.00.1 H, d; 4.30-3.80.6H, m; 3,32,3 H, s; 2,20,2 H, m; 1.95.1 H, t;

1.75.2 H, m; 1,50,4 H, m.

5.02.1 H, d; 4.20-3.90.4 H, m; 3.60-3.20.4 H, m; 2,20,2 H, m; 1.95.1 H, t; 1,70,2H, m; 1,53,4H, m; 1,17,3H, t,

6,7,1H, s; 4,1,2H, d; 4,0,6H, s; 2,7,2H, s; 2.25.1 H, t; 1,20,4H, m; 0,90,3t: t.

3.9.6 H, s; 2,2,2 H, m; 1.95.1 H, t; 1.85-1.10.9 H, m; 0.95.3 H, d, 7; 0.90.3 H, t,

3,95,6H, s; 2,17,2H, m; 1.95.1 H, t; 1,8-1,35.4H, m; 1,25,1 H, m; 0.95.3 H, d, 7; 0.85.9 H, s.

4.75.1 H, d, 2.6; 4,2,1 H, dd; 4.0-3.85.3 H, m; 2,2,2 H, m; 1.95.1 H, t; 1.8-1.20.9 H, m; 0.9.6 H, m.

3,92,6H, s; 3,75,3 H, s; 2,33,2 H, t, 7; 1.75-1.45.6 H, m; 1.3-1.05.4 H, m; 0.90.3 H, t.

7.30.3 H, m; 7,15,2 H, m; 4,30,6H, s; 2,20,2 H, m; 1.95.1 H, t;

1.80.2 H, m; 1,60,4 H, m.

4,75,1 H, d; 4,15,1 H, m; 4.00-3.85.3 H, m; 2.25-2.00.2 H, m; 1.95.1 H, t; 1,80-1,15,9H, m; 1,00,6H, m.

4,80,1 H, d; 4,15,1 H. m; 3.90.3 H, m; 2,15,2 H, m; 1.95.1 H, m; 1.80-1.10.9 H, m; 0.95.6 H, m.

4,87,1 H, d; 4,25,1 H, m; 4.20-4.00.3 H, m; 1.68.1 H, heptet; 1,30,2 H, d; 1,25,9 H, s; 0.95.6 H, dd.

4,76,1 H, d; 4,18,1 H, dd; 4.01-3.80.3 H, m; 2.25-1.03.15 H, m; 0.93.3 H, t.

6.25-5.85.1 H, m; 5,50,1 H, m; 4,78,1 H, m; 4,20,1 H, m; 3.90.3 H, m; 2.50-2.15.2 H, m; 1,80,2H, m; 1.30.4 H, m; 0,95,3H, t; 0.22 and 0.19.9 H, s.

6.35-5.90.1 H, m; 5.45.1 H, m; 4,78,1 H, m; 4,20,1 H, m; 3.95.3 H, m; 3,10 and 2,80,1 H, 2 xt; 2.60-2.20.2 H, m; 1.80.2 H, m; 1.30.4 H, m; 0.95.3 H, t.

6.22-5.80.1 H, m; 5.53.1 H, m; 4,80,1 H, m; 4.30-3.80.6H, m; 3.42 and 3.38.3 H, s; 2.52-2.18.2 H, m; 1.80.2 H, m; 1.30.4 H, m; 0.90.3 H, t.

6.22-5.80.1 H, m; 5,50,1 H, m; 4,75,1 H, m; 4,40,2 H, m; 4,20,1 H, m;

3.95.3 H, m; 2.50-2.18.2 H, m; 1.80.2 H, m; 1.60.1 H, broad signal;

1.30.4 H, m; 0.95.3 H, t.

6,20,1 H, m; 5.52.1 H, d, J 15.6, Hz; 4,85,1 H, d; 4,40,1 H, dd; 4.08.2 H, m; 3.92.1 H, dd; 2.30.4 H, m; 1,98,1 H, t; 1.00,9 H, s.

7,35,1 H, s; 4,75,2 H, d; 4.05.6H, s; 2.46.1 H, t; 1.25.4 H, m; 0.95.3 M, t.

4,30,2H, t; 3,90,6H, s; 2,10,2H, t; 1,96,3H, s; 1,20,4H, m; 0,90,3H.t.

3,95,6H, s; 2.22-0.95 11H, m; 0.85.9H, s.

3,95,6H, s; 2,00,1H, m; 1,95-1,05,10H, m; 0,85,9H, s.

4.78.1 H, d; 4,20,1 H, dd; 4.10-3.85.3 H, m; 2.45.1 H, m; 2.05.1 H, d; 1,35-1,10,13H, m; 0,95,3H, t.

7.50-7.10.5 H, m; 5,15,1 H, d; 4,75,1 H, m;

4.35.2 H, m; 4,20,1 H, d; 2,20,2 H, m; 2,00,1 H, t; 1.85.2 H, m; 1,60,4 H, m.

4.90.1 H, d; 4.20-3.90.4 H, m; 2,20,2H, m; 2,00,1 H, t; 1,90-1,20,8H, m; 0.55.3 H, m; 0,15,2 H, m.

4,80,1 H, d; 4.30-3.90.4 H, m; 2,15,2 H, m; 2,00,1 H, t; 1.80-1.50.5 H, m;

1.35.3 H, m; 0.95.9 H, m.

117 ⁰ C

240

42 43 47 ⁰ C 62 ⁰ C 255 257 44 47 Oil 59 ° C 271 278 48 oil 278 49 oil 2Go 50 oil 280 51 oil 254 52 oil 253 53 oil 267 54 oil 278 55 40-45 ⁰ C 297 56 68 ° C 273 59 oil 278 60 oil 278 61 96-C 278 63 96-97 ⁰ C 290 64 65 O = O = E and Z component ratio 1: 2 334 262 66 67 68 Oil oil 75-8O ⁰ C E and Z Components Ratio 1: 2 306 EandZ Components Ratio 1: 2 292 276 69 70 74 75 77 73-74 ⁰ C 80-81 ⁰ C 184-186 ⁰ C 139-141 ° C Oil 240 269 279 279 278

Oil

Oil oil

298

276,292

81 oil 278 82 oil 276 83 84 169 ⁰ C 54 ⁰ C 257 268 85 77.5 ⁰ C 266 86 67.1 ⁰ C 280 87 88 Oil oil 286 284 90 51.2 ⁰ C 253 91 8O ⁰ C 319

Table III - Characteristic Data (Or Trloxablcyclo-octanes (continued) Pre-Bonding Melting Mass Spectrum Nuclear Magnetic Resonance Spectrum

No. Chemical ionization ¹ H (ppm of TMS in CDCI ₃ , integral, multiplicity, Jm)

M + 1

4,78,1 H, d; 4,20,1 H, m; 4,05-3,85,3H,. 2,13,2 H, m; 1.95.1 H, t; 1.80-1.10.9 H, m; 0.95.6 H, m.

5.60.1 H, m; 5,20,2 H, m; 4,75,1 H, d; 4,15,1 H, m; 4.00.3 H, m; _S 2,15,4 H, m; 2.00-1.20.6 H, m; 0.95.3 H, d. 4,00,6H, s; 1.62.2 H, m; 1.32.2 H, m; 0.87.9 H, s; 0.85.9 H, s. 4,77,1 H, d; 4,20,1 H, m; 3.95.3 H, m; 1,70,2 H, m; 1.35.6 H, m; 0.95.3 H, t; 0.85.9 H, s.

6,15,1 H, d; 5.35.1 H, d; 4,82,1 H, d; 4,23,1 H, m; 4.05.3 H, m; 1,30,4H, m; 1,00,9H, s; 0,95,3H, t.

4,78,1 H, d; 4,15,1 H, m; 4.00-3.80.3 H, m; 1.40-1.20.4 H, m; 1,10-0,90,5H, m; 0.82.9 H, s; 0.60.1 H, m; 0.42, TH, m. 4,8,1 H, m; 4,3-4,0,4H, m; 2,8,2H, s; 1,5-1,2,13H, m; 0,95,3H, m.

5.50.1 H, d, Jh, 33; 4,88,1 H, d, J _H , 3; 4.30.1 H, dd, J ₁₁ , 9 and 3; 4,06,3H, m; 1,5-1,2,4H, m; 1,15,9H, s; 0,95,3H, t, J ". 7 3,90,6H, s; 2,15,2 H, m; 1.75.3 H, t; 1.65.2 H, m; 1.50.4 H, m; 1,20,4H, m; 0,90,3H, t.

4,00,6H, s; 2,20,2H, m; 1,95,1H, t; 1.80-1.30, 11 H, m.

Table IV - Characteristic data for other bicyclooctanes

Compound melting point mass spectrum nuclear magnetic resonance spectrum no. Chemical ionization ¹ H (ppm of TMS in CDCI ₃ , integral, multiplicity, Jn <)

M + 1 4,05,4H, s; 3,00,2 H, s; 2,20,2 H, m; 1.95.1 H, t, 1.0; 1.75.2 H.m; 1.55.4 H, m; 0.90.9 H, s.

4,00,2 H, m; 3,00,4 H, m; 2,20,2 H, m; 2.00.3 H, m; 1.55.4 H, m; 1.30.4 H, m; 0,95,3 H, t, 7.

3,00,6H, s; 2,20,2 H, m; 2.00.3 H, m; 1.90-1.10.8 H, m; 0.95.3 H, t, 4.00, 2H, s; 3.05.2 H, d; 2,95,2 H, d; 2.20.2 H, m; 1.92.3 H, m; 1,60,4H, m; 1,30,6H, m; 0,90,3H, t,. 7

4.10.2 H, s; 3.05.4 H, dd; 2,18,2 H, m; 1.95.3 H, m; 1.60.4 H, m; 0.95.9 H, s.

4.05.2 H, s; 3.05.4 H, dd; 2,20,2 H, m; 2.00.3 H, m; 1,75,1 H, heptet;

1.55.4 H, m; 1,20,2 H, d; 1.00.6 H, d.

4.25.1 H, q; 3,00,4 H, m; 2,20,2 H, m; 1.95.3 H, m; 1.50.4 H, m; 1.75.7 H, m; 1.00.3 H, t.

3.85.2 H, s; 3,75,2 H, t; 3,00,6H, s; 2.50.2 H, m; 1,97,1 H, t; 1.40.4 H, m; 0.97.3 H, t.

3,10,6 H, s; 2,20,2 H, m; 2.00.3 H, m; 1.60.5 H, m; 1.40,? H, d; 1.00.6H, d.

7.35.5 M, m; 4,40,2 H, s; 3.40.4 H, m; 2,20,2 H, m; 1.95.3 H, m; 1,45,4 H, m.

3,8,4 H, m; 2,2,2 H, m; 2.0-1.9.3 H, m; 1.7-1.4.8 H, m: 1.3-1.0.4 H, m; 0.9.3 H, t.

3,00,6H, s; 2,20,2H, m; 2,00,3H, m; 1,90-1,50,6H, m; 1,00,3H, t. 4.05.2 H, s; 3,10,4 H, m; 2,20,2 H, m; 2,00,3H, m; 1.60.4 H, m; 1,25,2 H, m; 0.60.3 H, m; 0,10,2 H, m.

15 68 ⁰ C 269 16 62 ⁰ C 271 17 45 89-92 ⁰ C oil 287 285 4C 53 ⁰ C 285 57 <30 ° C 285 58 44 ⁰ C 285 62 oil 289 71 72 37.1 ⁰ C 70.2 ⁰ C 301 305 73 oil 237 76 89 Oil oil 273 283

Claims (9)

Wherein R is a C ₂ _ ₁₀ non-aromatic hydrocarbon (Hydrocaryl) group, optionally substituted by, or methyl substituted by cyano, halogen, C _1-4 -alkoxy, optionally substituted by halogen or a group S (O) _1n R ³ means, wherein R ³ is C ^ alkyl, optionally substituted by halogen, and m is 0.1 or 2, or R is phenyl optionally substituted by C, _4 alkoxy, C ^ -3-alkyl, _C2 _4-alkynyl, halogen, C Haloalkyl, cyano or a group S (O) _m R ³ as defined above, R ¹ and R ² may be the same or different and each is hydrogen, halogen or a C ^ aliphatic group optionally substituted by halogen, cyano, C ^ carbalkoxy, C ₁ ^ -alkoxy or a group S (O) _m R ⁴ , wherein m 'is 0,1 or 2 and R ^{4 is} C 1-4 alkyl; Cyan, acc. Dimethyl, or C 1 -C 4 -carboxy or R ¹ and R and the carbon atoms to which they are attached form a C ₅ -C ₇ carbocyclic ring, optionally substituted by halogen, or a C 1-4 aliphatic or alkoxy group; AX containing between 3 and 20 carbon atoms, wherein A is a C ₂ _ ₁₂ non-aromatic hydrocarbon (hydrocarbyl) means group, optionally containing one to six hetero atoms which are the same or different and each is selected from oxygen, sulfur, nitrogen, Fluorine or chlorine and optionally substituted by one or two hydroxy groups or A represents a CH ₂ O or CH ₂ S (O) _n group, wherein η is 0.1 or 2; X represents hydrogen, halogen, a group Si R ^s , R ⁸ , R ⁷ or Sn R ^B , R ⁸ , R ⁷ , wherein R ^B , R ^e and R ^{7 are the} same or different and each is a hydrocarbyl (hydrocarbyl) group represents, containing up to 8 carbon atoms, optionally substituted by one to three halogens, C ₁ ^ ₆ alkoxy, C ^ alkylthio, C ^ alkylsulphinyl, C ^ alkylsulphonyl, cyano, C ^ acyloxy or C ₁ ^ - carbalkoxy Or when one or more of R ₅ to R _{7 is} an alkynyl, this is optionally substituted by a SiIyI substituted by three C 1-4 alkyl groups or X represents a group CR ¹⁰ wherein R ⁸ and R ^{9 are the} same or different and each is independently selected Hydrogen, halogen, cyano, C ₁ -C 6 -carbalkoxy, C ₁ -C 4 -alkyl, optionally substituted by one to three halogen atoms, cyano, C 1 -C 4 -carboxy, C ₁ -C 4 -alkoxy or a group S (O) _m R ¹¹ wherein "is 0,1 or 2 and R ¹¹ are C ^ alkyl; C ₁ ^ alkoxy or S (O) _m" R ¹² wherein rn '"m bedoutet 0,1 or 2 and R ¹² is C ^ alkyl. optionally substituted by one to three fluorine atoms, or R ⁸ and R ⁹ and the carbon atoms to which they are attached form a C 1-4 cycloalkyl ring and R ¹⁰ is hydrogen, halogen, hydroxy, cyano, C 1-4 alkoxy, C 1-4 acyloxy, C 1-4 -Carbalkoxy or a C 1-5 hydrocarbon (hydrocarbyl) group optionally substituted by hydroxy, cyano, C 1, alkoxy, C 1-4 acyloxy, C 1-4 carbalkoxy, one to three halogeno atoms, or a group S (O) _n , -> R ¹³ in which m "" 0, 1 or 2 andR ^ C ^ -alkyl, or R ^ represents a Cr ··, ..., 3 (O) ₁₁ , R ¹⁴ , wherein m "'' is 0, 1 or ² , and R ¹⁴ a C 4 -alkyl group optionally substituted by one to three fluorine atoms. Y and Y ¹ are the same or different and each is selected from oxygen and S (O) _n , where _n 'is 0, 1 or 2 and Z is CH ₂ CH ₂ , CH ₂ O or CH ₂ S (O) _n , where n "0 , 1or2, provided that R ⁸ that A contains no C = C fragment, X represents a group C-R ¹⁰ , wherein R ⁸ , R ⁹ and R ^{10 are} the R ⁹ have the abovementioned meaning, with the exception that R ⁸ and R ^{9 are} not hydrogen, characterized in that the process comprises: For the preparation of compounds wherein Y and Y ^{1 are} oxygen and Z is CH ₂ O: the cyclization of a compound of formula (II): -A-X wherein R to R ² , A and X have the abovementioned meaning, in the presence of an acid catalyst or; for the preparation of compounds wherein A contains a terminal C = C fragment: The reaction of a compound HCsC-X with a compound of formula (V): (V) Wherein R to R ^{2 have} the meaning given above, A ¹ CsC forms a group A and L ¹ denotes an exit group, or when X denotes hydrogen: the reaction of a strong base with a compound of the formula (VII): Wherein R to R ^{2 have} the abovementioned meaning and Q denotes a group which is capable of conversion into an ethynyl group or: When AX contains a CH = CH-CsC-X linkage: the reaction of a compound HC = C-X with a compound of the formula (IX): A -CH = CH-hal (IX). wherein R to R ² and X have the abovementioned meaning and A ³ -CH = CH-C = CX is a group AX as defined above, or: For the preparation of compounds in which Aeine-CONH group contains, the reaction of a compound NH ₂ CH ₂ A ³ X with a compound of formula (X): A CO ₂ AIk (X) wherein R to R ² and X have the abovementioned meaning and Alk a C ₁ - ^ ₄ alkyl group and A ² CONHCH ₂ A ³ X a group AX as defined above, or denoted; For the preparation of compounds in which A contains a -COO- group, the reaction of a compound XA ³ CH ₂ Hal with a compound of the formula (XI):, 1 (XI) or an alkali metal salt thereof, wherein R to R ² and X have the abovementioned meaning, Hal is a halogen and A ² CO ₂ CH ₂ A ³ X is a group AX, as defined above, or; for the preparation of compounds in which A is a -CH-NO-group, the reaction of a compound XC = CCH ₂ Hal with a compound of formula (XII): ,1 A ² CH = NOH (XII) wherein R to R ² , X and Hai have the abovementioned meaning and A ² C-NOCH ₂ A ³ X is a group AX as defined above, or; for the preparation of compounds wherein A contains a group -OCO-, the reaction of a compound XA ³ CO ₂ H with a compound of the formula (XIII): A ² CH ₂ OH (XIII) wherein R to R ² and X have the abovementioned meaning and A ² CH ₂ OCOA ³ X is a group AX as defined above, or; ii) for the preparation of compounds in which n'O, Y ¹ 0 or S, ZCH ₂ S or CH ₂ O, the reaction of a compound (Alko) ₃ CsCAX with a compound of formula (XIV): (XIV) ₍ YH wherein R to R ² , A, X, Y, Y ¹ and Z have the abovementioned meaning and Alk is a d ^ alkyl group or; iii) for the preparation of compounds in which Z is CH ₂ S or CH ₂ O and Y and Y ^{1 are} sulfur, the reaction of a compound L ² AX with a compound of the formula (XV): (XV) wherein R to R ² , A and X have the above-mentioned interpretation and L ^{2 is} a leaving group, or; iv) for the preparation of compounds wherein Y, Y ¹ are O and Z is CH ₂ CH ₂ , the reaction of a compound of formula (XVI) with acid: ~ NMe ₂ (XVI) wherein R, A and X have the abovementioned meaning or; v) the conversion of a compound of the formula (I) into another compound of the formula (I). 2. A process for the preparation of a compound of formula (I) according to claim 1, characterized in that Π n-propyl, η-butyl, i-butyl, t-butyl or phenyl. 3. A process for the preparation of a compound according to formula (I), according to claim 1 or 2, characterized in that R ¹ and R ^{2 are} independently selected from hydrogen, methyl, cyano or trifluoromethyl. 4. A process for preparing a compound according to formula (I) according to any one of claims 1 to 3, characterized in that A is a- (CH ₂ UC = C group, a Csi group, a -CH = CH (CH ₂ J ₂ C ^ C group, a CH ₂ O (CH ₂ ) ₂ C = C group, a - -O (CH ₂ ) ₃ CH (CH ₃ ) C = C group, a - (CH ₂ J ₂ CH (CH ₃ ) CH ₂ CsC group, a -CH ₂ CH (CH ₃ ) (CH ₂ ) ₂ CsC- Group, a - (CH ₂ ) ₂ CH = CHCsC group or a - (CH ₂ ) ₃ CsC group, wherein X is hydrogen or d-4-alkyl, optionally substituted by a hydroxy, Ci-4-alkoxy - or C ₁ ^ - acyloxy group or one to three halogen atoms. 5. A process for preparing a compound according to formula (I) according to claim 1 to 3, characterized in that A is a -CH ₂ CH / -, -CH = CH- or a -CsC group and X is a Group -CR ¹⁰ , wherein R ⁸ , R ⁹ and R ^{10 are} each selected from chlorine, bromine, methoxy or methyl, R ⁹
optionally substituted by methoxy or fluorine. 6. A pesticidal composition, characterized by a compound according to formula (I), defined according to one of the preceding claims in admixture with one or more carriers or connecting agents. 7. pesticide composition g according to claim 6, characterized in that it additionally contains a synergist or an amplifier. 8. Composition according to claim 6 and 7, characterized in that it additionally contains one or more components with pesticidal activity, attractants, repellents, bacteriocides, fungicides and / or anthelmintic agents. 9. A method for pest control, namely for combating arthropod or helminther pests or pesticidal infestations of animals and / or plants and / or stored products and / or an environment, characterized in that an effective ivienge a compound according to formula (I) prepared according to one of the preceding claims, the animal and / or the plant and / or the stored product and / or an environment which is sensitive to pest infestation.