CA2098704A1 - Heterocyclic pesticidal compounds - Google Patents
Heterocyclic pesticidal compoundsInfo
- Publication number
- CA2098704A1 CA2098704A1 CA002098704A CA2098704A CA2098704A1 CA 2098704 A1 CA2098704 A1 CA 2098704A1 CA 002098704 A CA002098704 A CA 002098704A CA 2098704 A CA2098704 A CA 2098704A CA 2098704 A1 CA2098704 A1 CA 2098704A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- formula
- compound
- group
- optionally substituted
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/24—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms
- A01N43/32—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with two or more hetero atoms six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D327/00—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms
- C07D327/02—Heterocyclic compounds containing rings having oxygen and sulfur atoms as the only ring hetero atoms one oxygen atom and one sulfur atom
- C07D327/06—Six-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/08—Six-membered rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyridine Compounds (AREA)
Abstract
The present invention describes a method for controlling pests which comprises contacting the pest with a pesticidally effective amount of a compound of formula (I) which contains between 8 and 30 carbon atoms, and wherein Y is oxygen or a group S(O)m and m and n are independently selected from 0, 1 and 2; R2a and R2b are the same or different and each is selected from cyano, nitro, methyl optionally substituted by halo, a group S(O)qR7 where q is 0, 1, or 2 and R7 is methyl or ethyl, or a group COR8 where R8 is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkyl optionally substituted by fluoro or a group NR9R10 wherein R9 and R10 are independently selected from hydrogen, methyl or ethyl;
R4a and R4b, R6a and R6b are independently selected from hydrogen, methyl, cyano or trifluoromethyl, R5a is a primary, secondary or tertiary C2-5 alkyl group optionally substituted by halo or C1-4 alkoxy, or a C3-4 cycloalkyl group, or R5a is a C3-4 cycloalkyl group and R5b is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkanoyloxy, or C1-4 alkyl optionally substituted by alkoxy; or R5a and R5b form a gem di-methyl group or are linked together with the ring carbon to which they are attached to form a 3 to 5-membered ring that optionally contains a hetero atom or an olefinic bond and is optionally substituted by a C1-4 alkyl group optionally substituted by halo. A method for preparing the compounds of formula (I) and pesticidal formulations containing the compounds are also described.
R4a and R4b, R6a and R6b are independently selected from hydrogen, methyl, cyano or trifluoromethyl, R5a is a primary, secondary or tertiary C2-5 alkyl group optionally substituted by halo or C1-4 alkoxy, or a C3-4 cycloalkyl group, or R5a is a C3-4 cycloalkyl group and R5b is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkanoyloxy, or C1-4 alkyl optionally substituted by alkoxy; or R5a and R5b form a gem di-methyl group or are linked together with the ring carbon to which they are attached to form a 3 to 5-membered ring that optionally contains a hetero atom or an olefinic bond and is optionally substituted by a C1-4 alkyl group optionally substituted by halo. A method for preparing the compounds of formula (I) and pesticidal formulations containing the compounds are also described.
Description
:
~92/112~4 PCT/GB91/02268 ,, - - 1 -2 ~ 9 ~
. .
. HETEROCYCLIC PESTICIDAL COMPOUNDS --.`
The present invention is concerned wieh a ~ethod of controlling pests such as arthropods, e.g. insects and acarine pests, helminths, e . g.
nematodes, and molluscs e.g. slugs by contacting the pests with novel -~.
.. , pesticides. The invention is also concerned with the novel pes~icides ~, used for controlling the pests and processes for making such ::~ pesticides.
. ~ .
European Paten. Applications 294228 and 29422~ disclose inter alia :
~hat 5-substituted dithianes with a suostituted phenyl moiety or a C2 16 hydrocaroyl group at the 2-position nave pesticidal activity.
European Patent Application 102062 discloses inter alia ~at S-disubstituted amino dithianes having a hydrocarbon or heterocyclic -group at the 2-position have pesticidal activity.
., .
It has been discovered that a class of novel 2,2,5-trisubstituted .' dithianes has pesticidal activity.
''' " .
Accordingly, the present invention provides a ~ethod for controlling pests which comprises contacting the pesc with a pesticidally l efective amount of a compound o ~he ormula (I):
.~ R4b ~ 4a ~ ~S~YX2~ (1) ` ~5 ( ) n , a R6b which contains between 8 and 30 carbon atoms, and wherein Y is o~ygen or a group S(O)m and ~ and n are independently selected from 0 l and 2; R2 and R2 are the sa~e or different and each is selectéd from cyano, nitro, ~ethyl optionally substituted by halo,a group S(O)qR
.~ :
-, W O 92/11254 ~ ~7 ~ ~ 2 - PCT/GB91/02 where q is 0, 1 or 2 and R is methyl or ethyl, or a ~roup COR where R is hvdrogen, hydroxy, Cl 4 alkoxy, Cl 4 alkyl o~tionall;
substituted bv fluoro or a group NR R wherein R and R are independently selected from hydrogen, methyl or ethyl; R4a and R4b, R and R are independently selected fro~ hydrogen, ~ethyl, cvano or trifluoromethyl, R is a primary, secondary or tertiary C2 5 alkyl ~roup optionally substituted bv halo or Cl 4 alko~y, or a C
cycloalkyl group, or R is a C3 4 cycloalkyl group and R is hydro~en, hydroxy, C1 4 alkoxy, Cl 4 alkanoyloxy, or C1 ~ alkyl optionally s~bstitutzd 3V alkoxy; or R and R form a gem di-methyl group or are linked together with the rin~ carbon to which they are attached to form a 3 to 5-membered ring that optionally contains a hetero atom or an olefinic bond and is optionally substituted by a Cl 4 alkyl group optionally substituted by halo.
By the term "halo" is meant fluoro, chloro, bromo or iodo.
By the term "hetero atom" is meant oxygen, sulphur (optionally present Ln an oxidised form) or nitrogen substituted by hydrogen or Cl 4 alkyl.
Preferably Y is oxygen or sulphur.
Suitably R2a and R2 are che sama o~ difi'erent and e~ch is selected ~rom methyl, ethyl, cyano or ~rifluorome~hyl.
.
Preferably R2a is methyl.
2b Preferably R is methyl or cyano.
` Suitably R4a, R b, R a and R6 are each selec~ed from hydrogen, or methyl, and preferably thev are all hydrogen.
:
~ .
0 ~2/11254 PCT/GB91/02268 2~g7b~
~- Suitably R is a secondary or tertiary C2 5 alkyl ~roup optionallysubstituted by fluoro or a cyclopropyl group~ Preferably R is ~ tertiary butyl or 2,2,2-trifluoro-1-methylethyl.
;~J
~ Suitably R is hydrogen, methyl or ~thyl, preferably R is hydrogen.
. .
In accordance with another embodiment of the present invention tner~
~ is provided a compound of the formula (I) wherein R2a, R , R , R b, -I R , R , m and n are as hereinbefore defined and R2b is cyano, nitro~
a group S(O)q R , a group COR wherein q, R' and R are as . hereinbefore defined, or a Cl 3 alkyl group substituted by halo.
,.~
The compounds o. the formula (I) may exis. in a number oî
- stereoisomeric forms. The presen~ invention encompasses both individual conformational and stereoisomers and mixtures thereof~ The ; present invention also encompasses compounds of the formula (I~
. containing radioisotopes particularly those in which or one to three ,3 hydrogen atoms are replaced by tritium or one or more carbon atoms are replaced by 14C.
.,~ .
~ Preferred compounds of the invention include:
,.
':' ,~ S(e)-t-Butyl-2(e)-methyl-1,3-diehiane-2(a)-carbonitrile ~ S(e)-t-Butyl-2(a)-methyl-1,3-dithiane-2(e)-carbonlcrile `i S(e) S Butyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile-l(e)-oxide ~ S(e)-~-Butyl-2(e)-methyl-1,3-dithiane-2(a)~carbonierile~ dioxide ;,~ 2(e)-Methyl-S(e)-(l-methyl-2,2,2-trifluoroethyl)-1,3-dithiane-2(a)-!, carbonitrile ;~ 5(e)-Cyclopropyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3(a)-oxide 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3(e)-oxide 5(e)-t-Butyl-2(e)-~ethyl-1,3-oxathiane-2(a)-carbonitrile-3,3-dioxide , ; :
W O 92/11254 4 PCT/GB91/02~.
~, ~ 9 ~ ~ ~
. ~ - . The present invention also provides for the preparation of the compounds of the formula (I) by methods àerived from those known in the art for the preparation of analogous compounds. Thus, the .~ compounds may be prepared :, ' , (i) by the reaction of a compound of the formula (II): -R R6a '.: \ ,~
R~ X
,~ ~< yl -.':
R ~'/ R4a (II) ~:
IR4b :.:
wherein X is SH and yl is SH or OH with a suitable alde~yde or ketone of the formula R a :' \R2b or a reactive derivative thereof, wherein the R substituents at the 2, 4, 5 and 6 posi~ions are as hereinbefore deEined and, if required.
, chereafter oxidizing one or ewo rins sulphur acoms.
! The reaction is suitably carried ou~ in che presance of a Gatalys~ or of a dehydrating agent in a non-polar solvent at a non-extreme eempqra~ure. Suitable caealyses include a dimethyl formamide~dimethyl :.
sulphate catalyst and catalysts such as sulphonic acids or : -perfluorinated resins thereof or Lewis acids such as boron trifluoride etherate, or stannic chloride or concentrated formic acid which also serves as the reac~ion medium~ Suitable solvents include hydrocarbons such as benzene, toluene or xylene or chlorina~ed hydrocarbons such as l dichloromethane. The reaction is normally performed between O and 200 and conveniently between 20 and 120 .
;'', . ~
, ~ 92/11254 PCT/GB91/Ot268 2~9~7~
,' Suitable reactive derivatives of aldehydes and ketones include acetals ;,' and ketals.
`' .
The compounds of the formula (II) may be prepared from .he corresponding diols wherein X and Y are hydroxy. Thus the dithiols may be prepared via the sulphonate derivatives (i.e., compounàs of ehe formula (II) wherein X and yl are groups OSo2Rll wherein Rll is C.
alkyl or para-tolyl) and the hydroxythiols may be prepared ~ia precursors of the formula (II) in which X is halo, particularly bromo, and Y is a protected hydroxy group, for example an acetoxy group.
, ~
This precursor is then reacted with an appropriate reager.~ for replacing t~e halo atom with sulphur, for exa~ple po~assi~T.
thiocyanate or thioacetate, followed by alkaline hydrolysis. The . preparation or the diols and their conversion to the corresponding dithiols can be carried oue by methods known in the art.
'''1 ;1 The aldehydes and keeones reacted with the compounds of the formula ~ (II) are either known in ehe literaeure or are prepared by literature ,;, methods.
,, .
(ii) when it is desired eo prepare a co~pound of ~he formula (T) when one of R2a and R2b is cyano and the other is an alkyl group optionally ;7 substitu~ed by halo, . ~
;1 a) by the reactlon of a compound of the formula (III):
R4b R4a R \ )~ y CN , ~, /\ /'\~
'! R~b k;()n ~H (III) ~6a l~6b . . .
.
WO 92/11254 PCr/GB91/022 ::
?.99~
' ~:
with an alkvlating agent.
Suitable al~ylatin~ agents include alkyl halides, for example meth~l iodide. The reaction is suitably carried out in the presence of a strong base such as butyllithium in an inert solvent, for example an ether such as tetrahydrofuran, at a non-extreme temperature conveniently between -100 and 50C and suitably between -70 and 30C.
, . .
The compounds of the formula (III) are suitably prepared by conYersion of the corresponding compound containing an aldehyde function instead of a nitrile group. This conversion may be carried out by the reaction of the aldehvde with a sui.able reagent such as 0, ~'-bis (trifluoro-acetyl)-hydroxylamine. This aldehyde is prepared in turn from ehe .
2-unsubstituted dithiane or oxathiane by reaction with a formylating .
agent, such as dimethylformamide, in the presence of a strong base, ..
for example butyllithium.
; .
. b) by the reaction of a compound of the ~ormula (IV) :
,', . . .
.
P; /~ oill3 (Iv) R5 )~ 5 X~l ~
~ R 6a 6b . . .
,j . , wherein Rll is Cl 4 alkyl and R12 is methyl optionally substituted b halo, with a trialkylsilylcyanide in ~he presence of an acid catalys~
'`~ '.
,~,..
'~ 92/l1254 2~'J()~ `
Suitably the alkyl groups in the trialkylsilylcyanide reagent contain 1 to 4 carbon atoms and are preferably methyl groups. Suitably the acid catalyst is a Lewis acid such as boron trifluoride etherate. The reaction is carried out in an inert solvent, such as a halovenated hydrocarbon, e.g. dichloromethane, at a non extreme temperature, for example between -50 and 80C, and conveniently between 0 and 30 C.
The compounds of ~he formula (IV) may be prepared by the reaction of a compound of the formula (II) with the appropriate orthoester of the formula (V):
?'3~
\ 12 ~ R (v) R130 ~ l3 OR
..
wherein R12 and Rl3 are as hereinbefore defined. This reaction is conveniently carried out in the presence of an acid catalyst such as para toluene sulphonic acid, at an elevated eemperature, i.e. between jo and 180C.
(iii) The compounds of the formula (I) wherein one or ~ore of m and n is other chan 0 may be prepared by oxidacion of the corresponding compound of a lower oxidacion state. The reaccion is usually carried out in an inert solvenc such as aceconitrile or a halogenated hydrocarbon such as chloroform at a non-extreme temperature, for example between 0 and 100 C and preferably between 20 and 30 C.
Suitable oxidising agents include peracids such as metachloro-perbenzoic acid. The oxidation is conveniently carried out in the presence of a buffer such as anhydrous sodium acetate. Compounds where m is 2 and n is O may be prepared from compounds of the formula (~) where m is O or 1, using potassium permanganate in a ketone, for W O 92/11254 9 ~ ~ o;i~ - 8 - PCT/GB91/02~
example, acetone, at a non-extreme temperature for example -30c ~o 100 C and conveniently between -10 and 30 C.
: . - .
he compounds of formula (I) may be used to control pests such as arthropods, e.g. insect and acarine pests, helminths, e.g. nematodes and molluscs, e.g. slugs. Thus, the present invention provides a method for the control of arthropods, helminths and/or molluscs which comprises ad~inistering ~o the arthroood, helminth and/or mollusc or to their environmeno an effective amoun~ of a compound of the formula (I). The present invention also provides a method for the control of arthropod, hel~_nth and/or mollusc infestations of animals (including humans) and/or of plancs ~including trees) and/or stored products which comprises ad~inistering an effectiv~ amount of a compound of the .
formula (I). The present invention further provides for the compounds of the formula (I) for use in human and veterinary medicine, in public health control and in agriculture for the control of arthropod helminth and/or mollusc pests.
-:
~y the term "control" is meant the amelioration of present or future deleterious effects of pests and includes killing adults, larvae and eggs, ehe inhibition of reproduction, the repellency and/or knockdowT.
of pests, and any other influence on behaviour.
:. .
Compounds of for~ula (I) are of particular value in the pro~ection of field, forage, plantatLon, glasshouse, orchard and vineyard crops, of ornamencals and of plantation and forest trees, for exa~ple, cereals (such as maize, wheat, rice, mill~e, oa~s, barley, sorghum), cotton, tobacco, vegeeables and salads (such as beans, cole crops, cucurbits lettuce, onions, tomatoes and peppers), field crops (such as potato, sugar beet, ground nuts, soyabean, oil seed rape), sugar cane, grassland and forage crops (such as lucerne), plantations (such as of cea, coffee, cocoa, banana, oil palm, coconut, rubber, spices), orchards and groves (such as of stone and pip fruit, cierus fruits kiwifruit, avocado, mango, olives and walnuts), vineyards, ornamenta1 plancs, flowers and shrubs under glass and in gardens and parks, .' . ~
., .
~ .
'~ 92/11254 9 2 ~ ~ 3 ~
forest trees (both deciduous and evergreen~ in forests, plantations and nurseries and plants grown for industrial or pharmaceutical purposes (such as the evening primrose).
They are also valuable in the protection of timber (standing, felled, converted, stored or structural) from attack by sawflies (a.g.
~rocerus) or beetles (e.g. scolytids, platypodids, lyctids, bosLrychids, cerambycids, anobiids).
They have applications in the protection of stored products suc~. as ~rains, fruits, nuts, spices and tobacco, whether whole, ~illed or co~pounded into products, .rom moth, beetle and mite attack. .~iso protected are stored animal products sucn as skins, hair, woo anc feathers in natural or converted form (e.g. as carpets or te~iles~
from moth and beetle attack; also stored meat and fish from beetle, mite and fly attack.
Compounds of formula tI) are of value in the control of public health pests, for example cockroaches and ants.
Compounds of formula I are also of value in the control of arthropods, helminths or molluscs which are injurious to, or spread or ac~ as vectors of diseases in man and domescic animals, for ~xample those hereinbefore men~ioned, and more especially in the control of ticks, mites, lice, fleas, midges bi~ing, nuisance and myiasis flies, mosquicos, hemip~rean bugs and snails, The compounds of Formula (I) may be used for such purposes by application of the compounds themselves or in diluted form in known fashion as a dip, spray, fog, lacquer, foam, dust, powder, aqueous suspension, paste, gel, cream, shampoo, grease, combustible solid, vapourising mat, combustible coil, bait, dietary supplement, wettable powder, granule, aerosol, emulsifiable concentrate, oil suspension, oil solution, pressure-pack, impregna.ed article, microcapsule, pour on formulation or other standard for~ulations well known to those , W O 92/11254 ~ lO - PCT/GB91/022 ski~led in ~he art Sprays may be applied by hand or by means of spray race or arch or by vehicle or aircraft mounted apparatus. The animal, soil, plant or other surface being treated may be saturated wi~h the spray bv means of high volum2 application or superficiall~
coated with the spray by means of lig~t or ultra low volume application. Dip concentrates are not applied ~er se, but diluted with water and the animals immersed in a dipping bath containing the dip wash. Aqueous suspe~sions may be applied in the same manner 25 sprays or dips. Dusts may be distributed b~ means of a powder applicator or, ir. the case o, animals, incorporated in perforated bags attached to trees or rubbing bars. Pastes, snamDoos and greases may be applied manually or dist~i~u~2d over th~ surrace or an iner~
material, suc;- as ,ha~ agains, ~ ic;~ animals ruD and transfer the material to their skins. Pour-on for~ulations are dispensed as a unit of liquid of small volume on to the backs of animals such that all or most of the liquid is recained on the animals.
Compounds of Formula (I) may be prepared either as formulations ready for use on the animals, plants or surface or as formulations requiring dilution prior to application, but both types of formulation comprise a campound of Formula ~I) in intimate admixture with one or more carriers or diluents. The carriers may be liquid, solid or gaseous or comprise mixtures of such subs~ances, and the compound of ~ormula (I) may be presenc in a concen~ration of from 0.025 eo 99~ w/~
dependlng upon whecher the formulation requires furcher dilu~ion.
DUsts, powders and ~ranules and ocher solid formulations comprise ehe compound of formula (I) in ineimate admi~ture with a powdered solid inert carrior for example suitable clays, kaolin, bentonite, attapulgite, adsorbent carbon black, talc, mica, silica, chalk, gypsum, tricalcium phosphate, powdered cork, magnesium silicate, vegetable carriers, starch and diatomaceous earths. Such solid formulations are generally prepared by impregnating the solid diluPn~s with solutions of the compound of formula (I) in volatile solvents evaporating the solvents and, if desired, grinding the products so as PCT/GB91/0' 68 `'O 92/11254 2~s~ail to obtain powders and, if desired, granulating, compacting or encapsulating the products.
Sprays of a compound or Formula (I) may comprise a solution in an organic solvent (e.g. those listed below) or an emulsion in water (dip wash or spray wash) prepared in the field from an emulsifiable concentrate (otherwise known as a water miscible oil) which may also be used for dipping purposes. The concentrate preferably comprises 2 mixture of the active ingredient, with or without an organic solven and one or ~ore e~ulsifiers. Solvents may be present withi-. ~ide limits but prererably in an amount o- from O eo qY.5~ wf~i o- e~e composition and ~av be selected from kerosen2 ketones, alc^hols xylene, aromacic naphtha, water, mineral oil, aromatic and ali?ha~ic esters, and other solvents known in the formulating art. The concentration of emulsifiers may be varied within wide limits bu~ is preferably in the range of 5 to 25~ w/v and the emulsifiers are conveniently non-ionic surface active agents including polyoxyalkylene esters of alkyl phenols and polyoxyethylene derivatives of hexitol anhydrides and anionic surface active agents including Na lauryl sulphate, fatty alcohol ether sulphates, Na and Ca salts of alkyl aryl sulphonates and alkyl sulphosuccinates, soaps, lecithins, hydrolysed glues, eec.
W~ctable powders comprise an inert solid carrier, one or more surface ac~ive agents, and optionally seabilisers and/or anti-oxidants.
Emulsifiable concentrates comprise emulsifying agents, and often an organic solvent, such as kerosene, ketones, alcohols, xylenes, aromatic naphtha, and other solvenes known in the art.
Wettable powders and emulsifiable concentrates will normally contain from 0.5 to 99.5~ by weight of the active ingredient, and are diluted, for example with water, before use.
~ S 1 - 12 - PCT/GB91/022~
Lacquers comprise a solution of the active ingredient in an organic solvent, together with a resin, and optionally a plasticiser.
3ip washes may be prepared not only from emulsifiable concentrates but also from wettable powders, soap based dips and aqueous suspensions comprising a compound of Formula (I) i~ intima~e admix,ure with a dispersing agent and one or more surface active agents.
Aqueous suspensions of a comoound of ~or~ula (I) may comprise a suspension in water together wlth suspending, stabili~in~ o- othar agents. The suspensions or sol~tions ma~ be applied ~er sa o- in a diluted form in known fashion.
Creases (or ointments) may be prepared from vegetable oils, synthetic esters of fatty acids or wool fat together with an inert base such as soft paraffin. A compound of Formula (I) is preferably distributed uniformly through the mixture in solution or suspension. Greases may also be made from emulsifiable concentrates by diluting them with an ointment base.
Pastes and shampoos are also semi-solid preparations in which a compound of Formula (I) may be present as an uniform dispersion in a suitable base such as soft or liquid paraffin or made on a non-greasy basis with glycerin, mucilage or a suitable soap. As greases, shampoos and pastes are usually applied wichout further dilution they should contain ehe appropriate percentage of ~ho compound of Formul~
(I) requlred for treacment, ' :'', Aerosol sprays may be prepared as a simple solution of the active ingredient in the aerosol propellant and co-solvent such as halogenated alkanes, propane, butane, dimethyl ether and the solvents referred to above, respectively. Pour-on formulations may be made as a solution or suspension of a compound of Formula (I) in a liquid medium. An avian or mammal hos~ may also be protected against infestation of acarine ectoparasites by means of carrying a ~ o 92/11254 - 13 - PCT/GB91/02268~
2Q~7Q;l ``
suitably-moulded, shaped plastics article impregnated with a compound of Formula (I). Such areicles include impregnated collars, ~ags, bands, sheets and strips suitablY attached to appropriate parts of the body. Suitably the plasticS material is a polyvinyl chloride (PVC) The concentration of the compound of formula (I) to be applied to an animal, premises, other substrates or outdoor areas will vary according to the compound chosen, the interval between treatmen~s~ the nature of the formulation and the likely infestation, but in generai O.OOl to 20.0~ w/v and preferably O.Ol to lO~ of the compound should be presenc in the applied formulation. The amount of the compound deposi~ed will vary according to the compound chosen~ the method of applicaoion, area of applica;ion, concentra~ion of the compound in ~ne applied for~ulation, faccor by which the formulation is dilu~ed and the nature of the formulation.
Undiluted formulations such as pour-on formulations in general will be applied at a concentration in the range from O.l to 20.0~ w/w and preferably O.l to lO~. The amount of compound to be applied to stored products in general will lie in the range of from O.l to 20ppm. Space sprays may be applied to give an average initial concentration of O.OOl to l mg of compound of formula (I) per cubic metre of ~rea~ad space.
Co~pounds of formula (I) are of use in the protection and treatment of plant species, in which case an effective insecticidal, acaricidal, nematacidal or molluscicidal amount of the active ingredient is applied. The application ra~e will vary accord~ng to the compound chosèn, the nature of the formulation, the mode of application, the plant species, the planting density and likely infestation and other like factors but in general, a suitable use rate for agricultural crops is in the range O.OOl to 3kg/Ha and preferably between O.Ol and lkg/Ha. Typical formulations for agricultural use contain between O.OOOl~ and 50~ of a compound of formula (I) and conveniently be~ween 0,l and 15~ by weight of a compound of the formula (I).
~54 PCr/GB91/0~2~P
~OI~J~ O ;~ ~
Dusts, greases. pastes and aerosol formulations are usually applied in a random fashion as described above and concen~rationS of O.OOl to 20~
~/v of a compound of Formula (I) in the applied for~ulation mav `~-used.
Ihe compounds of formula (I) have been round to have activity against the common housefly (Musca domesCica). In addition, certain compounds of formula (I) have activity against other arthropod pests including ~y~y~ persicae, Tetranvchus urticae. Plutella xvlostell2, Culex SDp Tribolium cas.aneum, sitO3hiluS _ranarius, Peri~Dlane~a àmericana and 31a~tella ~ermanica. Th2 compounds of formula (I) are thus useful in .he control or ar.hropods e-g. insects and acarines ~. anY environment where these constitute pests, e.g. in agricult~_re, in anima husbandry, in public health control and in domestic situations.
Insect pesCs include members of the orders Coleoptera (e g Anobium,Ceutorhv ~ ,Rhvnchophorus, Cosmopolites, Lissorhoptru~_ Meli~e~hes, Hy~3h_nemus, H ~ nus, Acaly~ma, Lema, Psy~liodes, Lepti~oearsa, Gonocee~lum, Ag~Q_es, Dermolepida, Heteronychus Phaedon, Triboliu , Sitophilus, Diabrotica, Anthonomus or Anthrenus spp.), Lepidoptera (e.g, Ephestia, Mam~stra, Earias, ~ , Ostrinia, TrichoPlusia, Pieris, LaDhy~ma~ AEroels, A~3~h~, Wiseana TrvPorYza, Diatraea, Spor~anoth~s, Cvdia, ~rchips, Plutella, Chilo, Heliothis, Spo~Eter~ or Tineola spp.), Diptera (e.g. ~S_, ~edes Anopheles, Culex, Glossi~l~, Si~Ll~, ~ , Haem ~ , Tabanus, Hvdrotaea, Lucil~, Chr~somia~., Ct ~ , ~ togi~ Gascero~hilus Hypod~mL, Hvlemy~3, AeheriRona, Chlorsps. Phvtomvza, Ceratitis LirlQmy~ and Melophagus spp.), Phthiraptera (MaloDha&~ e.g Dama~ina spp. and Anoplura e.g. Linognathus and Haema o~inus spp.) Hemipcera (e.g. Aphis, Bemisia,Phorodon, Aeneolamia, Em_oasca Parkinsiella, Pyrilla, Aonidiella, Coccus, Pseudococcus Helopeltis, Lvgus, Dvsdercus, Ox~carenus, Nezar , Aleurodes, Tria~om_, Rhodnius, Psvlla, Myzus, Me~oura, Phvlloxera, Adelves, Niloparvata, NeDhrotettlx or Cimex spp . ), Orthoptera (e.g. Locusta, Gryllus, Schistocerca o~
Achet~a spp.~, Dictyoptera (e.g. Blatte11a, Per~i~laneca or j `'O 92/11254 - 15 -2~9Q7~
spp.), Hymenoptera (e.g. Athalia, Cephus, Atta Lasius, SolenoPsis or Monomorium spp.), Isoptera (e.g. Odontotermes and Reticulitermes spp.), Siphonaptera (e.g. Ctenocephalides or Pulex spp.), Thysanura (e.g. Le~isma spp.), Der~aptera (e.g. Forficula spp.), Psocoptera (e.g. Perlpsocus spp.) and Thysanoptera (e.g. Thrips tabaci),.
Acarine pests include ticks, e.~. members of the genera BooPhilus,Ornithodorus, Rhipicephalus~ AmblYomma, Hvalomma, Ixodes, Haemaphvsalis, Dermacentor and Anocen~or, and mites and manges such as Acarus, Te~ranvchus, Psoro~tes, Notoednes, Sarco~tes, Psorer~ates, ChorioDtes, Eu~rombicula, Demode~ Panonvchus, BrYobia and Erio~hves spp .
~ematodes ~hich a~sack plants and trees of importance to agriculture, fores~ry, horticul~ure, either directly or by spreading bacterial, viral, mycoplasma or fungal diseases of the plants, include root-knot nematodes such as Meloido~Yne spp. (e.g. M. incognita); cyst nematodes such as Globodera spp. (e.g. G. rostochiensis) Heterodera spp. (e.g.
H. avenae): Radopholus spp. (e.g. ~. similis); lesion nematodes such as Pratvlenchus spp. (e.g. P. Pratensis); Belonolaimus spp. (e.g. B.
~racilis); Tvlenchulus spp. (e.g. T. se~ipenetrans); Rotvlenchulus spp. (e.g.R. reniformis); Rotylenchus spp, (e,g, ~, robustus);
HelicoCYlenchus spp. (e.g. H, mulcicinc~us); HemicYclioPhora spp.
(e,g, ~. racilis); Criconemoides spp. (e.g. C. ~ ); Trichodorus spp. ~e,g, T p~imitivus)- dag8er nematodes such as XiPhinemA spp.
(e.g. _, diversicaudatum), Longidorus spp (e.g. ~. eloneatus);
Hoplolaimus spp, (e,g, ~, coronatus); APhelenchoides spp. (e.g. A.
ritzema-bosi, _. besseYi~; stem and bulb eelworms such as Ditvlenchus spp. (e.g. D. dipsaci).
Mollusc pests which attack plants and trees of importance to j agriculture, foresty and horticulture include slugs such as Deroceras spp. (e.g. D. reticulatum - the grey field slug); the Arion group;
Milax spp; land snails such as Helix spp. and aquatic snails such as Planorbis spp. Mollusc pests which act as vectors of diseases in man WO 92/11254 PCT/GB91/0~2 ~ 16 -and domestic animals include Bulinus spp., Phvsopsis spp., Planorbi spp. and Oricomelania spp.
.
Compounds of the invention may be combined with one or more other pesticidally active ingredients (for example pyrethroids, carbamates lipid amides and organophosphates) and/or with attractants;
repellents, bacteriocides, fungicides, anthelmintics and the like.
Furthermore, the activity of compounds of the invention may be enhanced by the addition of a synergist or potentiator, for example:
one of the oxidase inhibitor class o~ synergists, such as piperonYl butoxide, propyl 2-propynylphenyl- phosphonate; a second co~pound of the invention; or a pyrethroid pesticidal comDound~ ~en an oxidase inhibitor synergist is present in a formulation of the inventior., the ratio of synergist to compound of Formula (I) will be in the range 500:1-1:25 eg about 100:1 to 10:1.
Stabilisers for preventing any chemical degradation which may occur with the compounds of the invention include, for example, antioxidants (such as tocopherols, butylhydroxyanisole and butylhydroxytoluene) and scavengers (such as epichlorhydrin) and organic or inorganic bases e.g. trialkylamines such as triethylamine which can act as basic stabilisers and as scavengers.
The following examples serve eo illustraee ehe preparation and properties of compounds of the present invencion, Example 1, 5(e)-e~Butvl-2(e)-methvl.1.3-dithiane-2(a)-carbonitrile i) A solution of _-butyllithium in hexane (1.6M; 17.75mls) was added to a stirred solution of 5-t-butyl-1,3-dithiane (5g) (E.L. Eliel et al. J.Amer.Chem.Soc 1976, 98(12),3583) in tetrahydrofuran (50mls) ac -30 under a nitrogen atmosphere. After 1 hour of additional stirring, the mixture was transferred by syringe and PCI /GB91/0~268 ~,0 92/11254 - 17 -2~3~7~
added, dropwise, to neat dimethylformamide (lOmls) cooled o -10 . The mix~ure was stirred for 1 hour at -10 and then stored overnight a~ 0C. The reaction mixture was then poured into ice-wa~er (lOOmls) and extracted with hexane. The aqueous layer was neutralised with dilute hydrochloric acid and then re-extracted with diethyl ether, The ethereal extracts were dried over anhydrous magnesium sulphate and the evaporated in vacuo ~o leave a white solid residue (3.1g). 5-t-sutyl-2-formyl-1,3-di.hiane, thus obcained, is present to a large e~tent as a dimer.
ii) 5-~-But~i-2-Lormyl-1,3-dithiane (lg) was heated to melting, under 2 nitrogen atmosphere, and then allowed to cool. ~he viscous oil thus obtained was taken up in dry benzene (lOOmls) containing pyridine (0.78g). O,N-Bis-(trifluoroacetyl)-hydroxylamine (l.lg) (J.H. Pomeroyn et al, J.Amer.Chem,Soc. 1959, 81 6340) was added and the resulting mixture was heated to reflux for two hours.
After cooling, ether and water were added and the organic layer separated, The aqueous layer was further extracted with fresh ether and the combined organic extracts were dried over anhydrous magnesium sulphate and then evaporated ~n vacuo to leave a yellow solid, which was purified bY column chromatography on silic~.
Gradien~ elu~ion with hexane/dichloromethane mixtures gave 5-t-butyl-1-cyano-1,3-dithiane as a white solid (0~38g).
~, iii) A solu~ion of 5-t-butyl-~-cyano-1,3-dithiane ~0,2g) in , eecrahydrofuran (lOml) was cooled to -40 under a nitrogen I atmosphere. A solution of n-butyllithium in hexane (1.6M,0.7mls) was added and che resulting mixture maintained at -40 for 1.5 l~ hours when methyl iodide (0.2~1) was added. The reaction mixture j was allowed to warm to room ~emperature overnight. After this time, diethyl ether and water ~ere added. The organic phase was separated and the aqueous layer extracted with fresh ether. The combined organic extracts wera dried over anhydrous magnesium sulphate and evaporated i vacuo, The residue was purified by . .. .
, :
' , . ~.
, ~
: !/11254 ~ 18 - PCT/GB91/022~
, column chromatograph on alumina, eluting with hexane/ether (1:9), to give 5(e)-t-butyl-2(e)-methyl-l~3-dithiane-2~a)carboni~- le as a white solid (lOOmg) after recrystallisation from hexane.
E~amvle 2.
:.
s(e~-e-gutvl-2(a)-methy~ 3-dithia-ne-2te)-carbonitrile i) Boron crifluoride etherata (2.15mls) was added to a stirred solution of 2-t-bu~ylpropane-1,3-dithiol (4.4g) ~European patenC
application 294228) and acetaldehyde (1.5mls) in dry chloroform under nitrogen. The resulting mixture was stirred at room cemperature overnight. After this time, the mixture was washed with water, saturated sodium bicarbonate and brine before drying over anhydrous magneSium sulphate and evaporation in vacuo, 5-t-Butyl-2-methyl-ll3-di~hiane (4.7g) was obtained as a pale yellow oil which solidified on cooling.
A ii) Using the methods described in Example 1 stages (i) and ~ii) 5-t-butyl-2-methyl-1,3-dithiane was. converted to 5(e)-t-butyl 2(a)-methyl-1,3-dithiane-2(e)-carbonitrile~
.
Example ~, S(e)-t-Butyl~2 2-dimethyl-1,3-dithiane i Usin~ ~he me~hod deacribed in Example 2 sta~e (i), 5(e)-t-butyl-2,2 . dimethyl~l,3-dithiane was prepared from acetone and 2-e-butylpropane-i 1,3-dithiol. The crude product was purified by chromatograpny on silica, eluting with hexane/dichloromethane ~9:1) followed by recrystallisation from chloroform/methanol. ..
}
~ trans-5(e)-t-Butyl-2-methyl-2-trifluoromethyl-1,3-dithiane was ., prepared in an analo~ous manner starting from l,1,1-trifluoroacetone ' and 2-t-butylpropane-1,3-dithiol.
.' '~ ' .
',' 'I ~ : , .
`1~ 92/11254 PCT/GB91/02268 2 Q ~ ~ r~
Exam~le .
2(e)-Methvl-5(e)-(2 2.2-trifluoro-1-methylethvl)-1 3-dithiane-2(a)-carbonitrile i) A mi~ture of 2-(2,2,2-trifluoro-1-methylethyl)-propan,1,3-dithiol (4.8g) (European patent 0372816A) and dimethoxymethane (2.lml) in dry chloroform (15ml) was added to a refluxing solution of boron trifluoride etherate (2.9ml) and glacial acetic acid (lOml) in chloroform (50ml) under a nitrogen atmospnere. ~he addition took place over one hour and the resulting mixture was then refluxed ror e rurther ~wo hours and then stirred at room .emperature overnignt. .~fter this ~ime the reaction mixture ~as washed with ~ater, saturated sodium bicarbonate and brine before drying over anhydrous magnesium sulphate and evaporation in vacuo. 5-(2,2,2-trifluoro-l-methylethyl)-1,3-dithiane (3.6g), thus obtained, was used without further purification.
ii) Using ~he methods described in Example 1, 5-(2,2,2-trifluoro-1-methylethyl)-1,3-dithiane was converted to 2~e)-Methyl-5(e)-(2,2,2-trifluoro-1-methylethyl)-1,3-dithiane-2(a).carbonitrile.
~92/112~4 PCT/GB91/02268 ,, - - 1 -2 ~ 9 ~
. .
. HETEROCYCLIC PESTICIDAL COMPOUNDS --.`
The present invention is concerned wieh a ~ethod of controlling pests such as arthropods, e.g. insects and acarine pests, helminths, e . g.
nematodes, and molluscs e.g. slugs by contacting the pests with novel -~.
.. , pesticides. The invention is also concerned with the novel pes~icides ~, used for controlling the pests and processes for making such ::~ pesticides.
. ~ .
European Paten. Applications 294228 and 29422~ disclose inter alia :
~hat 5-substituted dithianes with a suostituted phenyl moiety or a C2 16 hydrocaroyl group at the 2-position nave pesticidal activity.
European Patent Application 102062 discloses inter alia ~at S-disubstituted amino dithianes having a hydrocarbon or heterocyclic -group at the 2-position have pesticidal activity.
., .
It has been discovered that a class of novel 2,2,5-trisubstituted .' dithianes has pesticidal activity.
''' " .
Accordingly, the present invention provides a ~ethod for controlling pests which comprises contacting the pesc with a pesticidally l efective amount of a compound o ~he ormula (I):
.~ R4b ~ 4a ~ ~S~YX2~ (1) ` ~5 ( ) n , a R6b which contains between 8 and 30 carbon atoms, and wherein Y is o~ygen or a group S(O)m and ~ and n are independently selected from 0 l and 2; R2 and R2 are the sa~e or different and each is selectéd from cyano, nitro, ~ethyl optionally substituted by halo,a group S(O)qR
.~ :
-, W O 92/11254 ~ ~7 ~ ~ 2 - PCT/GB91/02 where q is 0, 1 or 2 and R is methyl or ethyl, or a ~roup COR where R is hvdrogen, hydroxy, Cl 4 alkoxy, Cl 4 alkyl o~tionall;
substituted bv fluoro or a group NR R wherein R and R are independently selected from hydrogen, methyl or ethyl; R4a and R4b, R and R are independently selected fro~ hydrogen, ~ethyl, cvano or trifluoromethyl, R is a primary, secondary or tertiary C2 5 alkyl ~roup optionally substituted bv halo or Cl 4 alko~y, or a C
cycloalkyl group, or R is a C3 4 cycloalkyl group and R is hydro~en, hydroxy, C1 4 alkoxy, Cl 4 alkanoyloxy, or C1 ~ alkyl optionally s~bstitutzd 3V alkoxy; or R and R form a gem di-methyl group or are linked together with the rin~ carbon to which they are attached to form a 3 to 5-membered ring that optionally contains a hetero atom or an olefinic bond and is optionally substituted by a Cl 4 alkyl group optionally substituted by halo.
By the term "halo" is meant fluoro, chloro, bromo or iodo.
By the term "hetero atom" is meant oxygen, sulphur (optionally present Ln an oxidised form) or nitrogen substituted by hydrogen or Cl 4 alkyl.
Preferably Y is oxygen or sulphur.
Suitably R2a and R2 are che sama o~ difi'erent and e~ch is selected ~rom methyl, ethyl, cyano or ~rifluorome~hyl.
.
Preferably R2a is methyl.
2b Preferably R is methyl or cyano.
` Suitably R4a, R b, R a and R6 are each selec~ed from hydrogen, or methyl, and preferably thev are all hydrogen.
:
~ .
0 ~2/11254 PCT/GB91/02268 2~g7b~
~- Suitably R is a secondary or tertiary C2 5 alkyl ~roup optionallysubstituted by fluoro or a cyclopropyl group~ Preferably R is ~ tertiary butyl or 2,2,2-trifluoro-1-methylethyl.
;~J
~ Suitably R is hydrogen, methyl or ~thyl, preferably R is hydrogen.
. .
In accordance with another embodiment of the present invention tner~
~ is provided a compound of the formula (I) wherein R2a, R , R , R b, -I R , R , m and n are as hereinbefore defined and R2b is cyano, nitro~
a group S(O)q R , a group COR wherein q, R' and R are as . hereinbefore defined, or a Cl 3 alkyl group substituted by halo.
,.~
The compounds o. the formula (I) may exis. in a number oî
- stereoisomeric forms. The presen~ invention encompasses both individual conformational and stereoisomers and mixtures thereof~ The ; present invention also encompasses compounds of the formula (I~
. containing radioisotopes particularly those in which or one to three ,3 hydrogen atoms are replaced by tritium or one or more carbon atoms are replaced by 14C.
.,~ .
~ Preferred compounds of the invention include:
,.
':' ,~ S(e)-t-Butyl-2(e)-methyl-1,3-diehiane-2(a)-carbonitrile ~ S(e)-t-Butyl-2(a)-methyl-1,3-dithiane-2(e)-carbonlcrile `i S(e) S Butyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile-l(e)-oxide ~ S(e)-~-Butyl-2(e)-methyl-1,3-dithiane-2(a)~carbonierile~ dioxide ;,~ 2(e)-Methyl-S(e)-(l-methyl-2,2,2-trifluoroethyl)-1,3-dithiane-2(a)-!, carbonitrile ;~ 5(e)-Cyclopropyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3(a)-oxide 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3(e)-oxide 5(e)-t-Butyl-2(e)-~ethyl-1,3-oxathiane-2(a)-carbonitrile-3,3-dioxide , ; :
W O 92/11254 4 PCT/GB91/02~.
~, ~ 9 ~ ~ ~
. ~ - . The present invention also provides for the preparation of the compounds of the formula (I) by methods àerived from those known in the art for the preparation of analogous compounds. Thus, the .~ compounds may be prepared :, ' , (i) by the reaction of a compound of the formula (II): -R R6a '.: \ ,~
R~ X
,~ ~< yl -.':
R ~'/ R4a (II) ~:
IR4b :.:
wherein X is SH and yl is SH or OH with a suitable alde~yde or ketone of the formula R a :' \R2b or a reactive derivative thereof, wherein the R substituents at the 2, 4, 5 and 6 posi~ions are as hereinbefore deEined and, if required.
, chereafter oxidizing one or ewo rins sulphur acoms.
! The reaction is suitably carried ou~ in che presance of a Gatalys~ or of a dehydrating agent in a non-polar solvent at a non-extreme eempqra~ure. Suitable caealyses include a dimethyl formamide~dimethyl :.
sulphate catalyst and catalysts such as sulphonic acids or : -perfluorinated resins thereof or Lewis acids such as boron trifluoride etherate, or stannic chloride or concentrated formic acid which also serves as the reac~ion medium~ Suitable solvents include hydrocarbons such as benzene, toluene or xylene or chlorina~ed hydrocarbons such as l dichloromethane. The reaction is normally performed between O and 200 and conveniently between 20 and 120 .
;'', . ~
, ~ 92/11254 PCT/GB91/Ot268 2~9~7~
,' Suitable reactive derivatives of aldehydes and ketones include acetals ;,' and ketals.
`' .
The compounds of the formula (II) may be prepared from .he corresponding diols wherein X and Y are hydroxy. Thus the dithiols may be prepared via the sulphonate derivatives (i.e., compounàs of ehe formula (II) wherein X and yl are groups OSo2Rll wherein Rll is C.
alkyl or para-tolyl) and the hydroxythiols may be prepared ~ia precursors of the formula (II) in which X is halo, particularly bromo, and Y is a protected hydroxy group, for example an acetoxy group.
, ~
This precursor is then reacted with an appropriate reager.~ for replacing t~e halo atom with sulphur, for exa~ple po~assi~T.
thiocyanate or thioacetate, followed by alkaline hydrolysis. The . preparation or the diols and their conversion to the corresponding dithiols can be carried oue by methods known in the art.
'''1 ;1 The aldehydes and keeones reacted with the compounds of the formula ~ (II) are either known in ehe literaeure or are prepared by literature ,;, methods.
,, .
(ii) when it is desired eo prepare a co~pound of ~he formula (T) when one of R2a and R2b is cyano and the other is an alkyl group optionally ;7 substitu~ed by halo, . ~
;1 a) by the reactlon of a compound of the formula (III):
R4b R4a R \ )~ y CN , ~, /\ /'\~
'! R~b k;()n ~H (III) ~6a l~6b . . .
.
WO 92/11254 PCr/GB91/022 ::
?.99~
' ~:
with an alkvlating agent.
Suitable al~ylatin~ agents include alkyl halides, for example meth~l iodide. The reaction is suitably carried out in the presence of a strong base such as butyllithium in an inert solvent, for example an ether such as tetrahydrofuran, at a non-extreme temperature conveniently between -100 and 50C and suitably between -70 and 30C.
, . .
The compounds of the formula (III) are suitably prepared by conYersion of the corresponding compound containing an aldehyde function instead of a nitrile group. This conversion may be carried out by the reaction of the aldehvde with a sui.able reagent such as 0, ~'-bis (trifluoro-acetyl)-hydroxylamine. This aldehyde is prepared in turn from ehe .
2-unsubstituted dithiane or oxathiane by reaction with a formylating .
agent, such as dimethylformamide, in the presence of a strong base, ..
for example butyllithium.
; .
. b) by the reaction of a compound of the ~ormula (IV) :
,', . . .
.
P; /~ oill3 (Iv) R5 )~ 5 X~l ~
~ R 6a 6b . . .
,j . , wherein Rll is Cl 4 alkyl and R12 is methyl optionally substituted b halo, with a trialkylsilylcyanide in ~he presence of an acid catalys~
'`~ '.
,~,..
'~ 92/l1254 2~'J()~ `
Suitably the alkyl groups in the trialkylsilylcyanide reagent contain 1 to 4 carbon atoms and are preferably methyl groups. Suitably the acid catalyst is a Lewis acid such as boron trifluoride etherate. The reaction is carried out in an inert solvent, such as a halovenated hydrocarbon, e.g. dichloromethane, at a non extreme temperature, for example between -50 and 80C, and conveniently between 0 and 30 C.
The compounds of ~he formula (IV) may be prepared by the reaction of a compound of the formula (II) with the appropriate orthoester of the formula (V):
?'3~
\ 12 ~ R (v) R130 ~ l3 OR
..
wherein R12 and Rl3 are as hereinbefore defined. This reaction is conveniently carried out in the presence of an acid catalyst such as para toluene sulphonic acid, at an elevated eemperature, i.e. between jo and 180C.
(iii) The compounds of the formula (I) wherein one or ~ore of m and n is other chan 0 may be prepared by oxidacion of the corresponding compound of a lower oxidacion state. The reaccion is usually carried out in an inert solvenc such as aceconitrile or a halogenated hydrocarbon such as chloroform at a non-extreme temperature, for example between 0 and 100 C and preferably between 20 and 30 C.
Suitable oxidising agents include peracids such as metachloro-perbenzoic acid. The oxidation is conveniently carried out in the presence of a buffer such as anhydrous sodium acetate. Compounds where m is 2 and n is O may be prepared from compounds of the formula (~) where m is O or 1, using potassium permanganate in a ketone, for W O 92/11254 9 ~ ~ o;i~ - 8 - PCT/GB91/02~
example, acetone, at a non-extreme temperature for example -30c ~o 100 C and conveniently between -10 and 30 C.
: . - .
he compounds of formula (I) may be used to control pests such as arthropods, e.g. insect and acarine pests, helminths, e.g. nematodes and molluscs, e.g. slugs. Thus, the present invention provides a method for the control of arthropods, helminths and/or molluscs which comprises ad~inistering ~o the arthroood, helminth and/or mollusc or to their environmeno an effective amoun~ of a compound of the formula (I). The present invention also provides a method for the control of arthropod, hel~_nth and/or mollusc infestations of animals (including humans) and/or of plancs ~including trees) and/or stored products which comprises ad~inistering an effectiv~ amount of a compound of the .
formula (I). The present invention further provides for the compounds of the formula (I) for use in human and veterinary medicine, in public health control and in agriculture for the control of arthropod helminth and/or mollusc pests.
-:
~y the term "control" is meant the amelioration of present or future deleterious effects of pests and includes killing adults, larvae and eggs, ehe inhibition of reproduction, the repellency and/or knockdowT.
of pests, and any other influence on behaviour.
:. .
Compounds of for~ula (I) are of particular value in the pro~ection of field, forage, plantatLon, glasshouse, orchard and vineyard crops, of ornamencals and of plantation and forest trees, for exa~ple, cereals (such as maize, wheat, rice, mill~e, oa~s, barley, sorghum), cotton, tobacco, vegeeables and salads (such as beans, cole crops, cucurbits lettuce, onions, tomatoes and peppers), field crops (such as potato, sugar beet, ground nuts, soyabean, oil seed rape), sugar cane, grassland and forage crops (such as lucerne), plantations (such as of cea, coffee, cocoa, banana, oil palm, coconut, rubber, spices), orchards and groves (such as of stone and pip fruit, cierus fruits kiwifruit, avocado, mango, olives and walnuts), vineyards, ornamenta1 plancs, flowers and shrubs under glass and in gardens and parks, .' . ~
., .
~ .
'~ 92/11254 9 2 ~ ~ 3 ~
forest trees (both deciduous and evergreen~ in forests, plantations and nurseries and plants grown for industrial or pharmaceutical purposes (such as the evening primrose).
They are also valuable in the protection of timber (standing, felled, converted, stored or structural) from attack by sawflies (a.g.
~rocerus) or beetles (e.g. scolytids, platypodids, lyctids, bosLrychids, cerambycids, anobiids).
They have applications in the protection of stored products suc~. as ~rains, fruits, nuts, spices and tobacco, whether whole, ~illed or co~pounded into products, .rom moth, beetle and mite attack. .~iso protected are stored animal products sucn as skins, hair, woo anc feathers in natural or converted form (e.g. as carpets or te~iles~
from moth and beetle attack; also stored meat and fish from beetle, mite and fly attack.
Compounds of formula tI) are of value in the control of public health pests, for example cockroaches and ants.
Compounds of formula I are also of value in the control of arthropods, helminths or molluscs which are injurious to, or spread or ac~ as vectors of diseases in man and domescic animals, for ~xample those hereinbefore men~ioned, and more especially in the control of ticks, mites, lice, fleas, midges bi~ing, nuisance and myiasis flies, mosquicos, hemip~rean bugs and snails, The compounds of Formula (I) may be used for such purposes by application of the compounds themselves or in diluted form in known fashion as a dip, spray, fog, lacquer, foam, dust, powder, aqueous suspension, paste, gel, cream, shampoo, grease, combustible solid, vapourising mat, combustible coil, bait, dietary supplement, wettable powder, granule, aerosol, emulsifiable concentrate, oil suspension, oil solution, pressure-pack, impregna.ed article, microcapsule, pour on formulation or other standard for~ulations well known to those , W O 92/11254 ~ lO - PCT/GB91/022 ski~led in ~he art Sprays may be applied by hand or by means of spray race or arch or by vehicle or aircraft mounted apparatus. The animal, soil, plant or other surface being treated may be saturated wi~h the spray bv means of high volum2 application or superficiall~
coated with the spray by means of lig~t or ultra low volume application. Dip concentrates are not applied ~er se, but diluted with water and the animals immersed in a dipping bath containing the dip wash. Aqueous suspe~sions may be applied in the same manner 25 sprays or dips. Dusts may be distributed b~ means of a powder applicator or, ir. the case o, animals, incorporated in perforated bags attached to trees or rubbing bars. Pastes, snamDoos and greases may be applied manually or dist~i~u~2d over th~ surrace or an iner~
material, suc;- as ,ha~ agains, ~ ic;~ animals ruD and transfer the material to their skins. Pour-on for~ulations are dispensed as a unit of liquid of small volume on to the backs of animals such that all or most of the liquid is recained on the animals.
Compounds of Formula (I) may be prepared either as formulations ready for use on the animals, plants or surface or as formulations requiring dilution prior to application, but both types of formulation comprise a campound of Formula ~I) in intimate admixture with one or more carriers or diluents. The carriers may be liquid, solid or gaseous or comprise mixtures of such subs~ances, and the compound of ~ormula (I) may be presenc in a concen~ration of from 0.025 eo 99~ w/~
dependlng upon whecher the formulation requires furcher dilu~ion.
DUsts, powders and ~ranules and ocher solid formulations comprise ehe compound of formula (I) in ineimate admi~ture with a powdered solid inert carrior for example suitable clays, kaolin, bentonite, attapulgite, adsorbent carbon black, talc, mica, silica, chalk, gypsum, tricalcium phosphate, powdered cork, magnesium silicate, vegetable carriers, starch and diatomaceous earths. Such solid formulations are generally prepared by impregnating the solid diluPn~s with solutions of the compound of formula (I) in volatile solvents evaporating the solvents and, if desired, grinding the products so as PCT/GB91/0' 68 `'O 92/11254 2~s~ail to obtain powders and, if desired, granulating, compacting or encapsulating the products.
Sprays of a compound or Formula (I) may comprise a solution in an organic solvent (e.g. those listed below) or an emulsion in water (dip wash or spray wash) prepared in the field from an emulsifiable concentrate (otherwise known as a water miscible oil) which may also be used for dipping purposes. The concentrate preferably comprises 2 mixture of the active ingredient, with or without an organic solven and one or ~ore e~ulsifiers. Solvents may be present withi-. ~ide limits but prererably in an amount o- from O eo qY.5~ wf~i o- e~e composition and ~av be selected from kerosen2 ketones, alc^hols xylene, aromacic naphtha, water, mineral oil, aromatic and ali?ha~ic esters, and other solvents known in the formulating art. The concentration of emulsifiers may be varied within wide limits bu~ is preferably in the range of 5 to 25~ w/v and the emulsifiers are conveniently non-ionic surface active agents including polyoxyalkylene esters of alkyl phenols and polyoxyethylene derivatives of hexitol anhydrides and anionic surface active agents including Na lauryl sulphate, fatty alcohol ether sulphates, Na and Ca salts of alkyl aryl sulphonates and alkyl sulphosuccinates, soaps, lecithins, hydrolysed glues, eec.
W~ctable powders comprise an inert solid carrier, one or more surface ac~ive agents, and optionally seabilisers and/or anti-oxidants.
Emulsifiable concentrates comprise emulsifying agents, and often an organic solvent, such as kerosene, ketones, alcohols, xylenes, aromatic naphtha, and other solvenes known in the art.
Wettable powders and emulsifiable concentrates will normally contain from 0.5 to 99.5~ by weight of the active ingredient, and are diluted, for example with water, before use.
~ S 1 - 12 - PCT/GB91/022~
Lacquers comprise a solution of the active ingredient in an organic solvent, together with a resin, and optionally a plasticiser.
3ip washes may be prepared not only from emulsifiable concentrates but also from wettable powders, soap based dips and aqueous suspensions comprising a compound of Formula (I) i~ intima~e admix,ure with a dispersing agent and one or more surface active agents.
Aqueous suspensions of a comoound of ~or~ula (I) may comprise a suspension in water together wlth suspending, stabili~in~ o- othar agents. The suspensions or sol~tions ma~ be applied ~er sa o- in a diluted form in known fashion.
Creases (or ointments) may be prepared from vegetable oils, synthetic esters of fatty acids or wool fat together with an inert base such as soft paraffin. A compound of Formula (I) is preferably distributed uniformly through the mixture in solution or suspension. Greases may also be made from emulsifiable concentrates by diluting them with an ointment base.
Pastes and shampoos are also semi-solid preparations in which a compound of Formula (I) may be present as an uniform dispersion in a suitable base such as soft or liquid paraffin or made on a non-greasy basis with glycerin, mucilage or a suitable soap. As greases, shampoos and pastes are usually applied wichout further dilution they should contain ehe appropriate percentage of ~ho compound of Formul~
(I) requlred for treacment, ' :'', Aerosol sprays may be prepared as a simple solution of the active ingredient in the aerosol propellant and co-solvent such as halogenated alkanes, propane, butane, dimethyl ether and the solvents referred to above, respectively. Pour-on formulations may be made as a solution or suspension of a compound of Formula (I) in a liquid medium. An avian or mammal hos~ may also be protected against infestation of acarine ectoparasites by means of carrying a ~ o 92/11254 - 13 - PCT/GB91/02268~
2Q~7Q;l ``
suitably-moulded, shaped plastics article impregnated with a compound of Formula (I). Such areicles include impregnated collars, ~ags, bands, sheets and strips suitablY attached to appropriate parts of the body. Suitably the plasticS material is a polyvinyl chloride (PVC) The concentration of the compound of formula (I) to be applied to an animal, premises, other substrates or outdoor areas will vary according to the compound chosen, the interval between treatmen~s~ the nature of the formulation and the likely infestation, but in generai O.OOl to 20.0~ w/v and preferably O.Ol to lO~ of the compound should be presenc in the applied formulation. The amount of the compound deposi~ed will vary according to the compound chosen~ the method of applicaoion, area of applica;ion, concentra~ion of the compound in ~ne applied for~ulation, faccor by which the formulation is dilu~ed and the nature of the formulation.
Undiluted formulations such as pour-on formulations in general will be applied at a concentration in the range from O.l to 20.0~ w/w and preferably O.l to lO~. The amount of compound to be applied to stored products in general will lie in the range of from O.l to 20ppm. Space sprays may be applied to give an average initial concentration of O.OOl to l mg of compound of formula (I) per cubic metre of ~rea~ad space.
Co~pounds of formula (I) are of use in the protection and treatment of plant species, in which case an effective insecticidal, acaricidal, nematacidal or molluscicidal amount of the active ingredient is applied. The application ra~e will vary accord~ng to the compound chosèn, the nature of the formulation, the mode of application, the plant species, the planting density and likely infestation and other like factors but in general, a suitable use rate for agricultural crops is in the range O.OOl to 3kg/Ha and preferably between O.Ol and lkg/Ha. Typical formulations for agricultural use contain between O.OOOl~ and 50~ of a compound of formula (I) and conveniently be~ween 0,l and 15~ by weight of a compound of the formula (I).
~54 PCr/GB91/0~2~P
~OI~J~ O ;~ ~
Dusts, greases. pastes and aerosol formulations are usually applied in a random fashion as described above and concen~rationS of O.OOl to 20~
~/v of a compound of Formula (I) in the applied for~ulation mav `~-used.
Ihe compounds of formula (I) have been round to have activity against the common housefly (Musca domesCica). In addition, certain compounds of formula (I) have activity against other arthropod pests including ~y~y~ persicae, Tetranvchus urticae. Plutella xvlostell2, Culex SDp Tribolium cas.aneum, sitO3hiluS _ranarius, Peri~Dlane~a àmericana and 31a~tella ~ermanica. Th2 compounds of formula (I) are thus useful in .he control or ar.hropods e-g. insects and acarines ~. anY environment where these constitute pests, e.g. in agricult~_re, in anima husbandry, in public health control and in domestic situations.
Insect pesCs include members of the orders Coleoptera (e g Anobium,Ceutorhv ~ ,Rhvnchophorus, Cosmopolites, Lissorhoptru~_ Meli~e~hes, Hy~3h_nemus, H ~ nus, Acaly~ma, Lema, Psy~liodes, Lepti~oearsa, Gonocee~lum, Ag~Q_es, Dermolepida, Heteronychus Phaedon, Triboliu , Sitophilus, Diabrotica, Anthonomus or Anthrenus spp.), Lepidoptera (e.g, Ephestia, Mam~stra, Earias, ~ , Ostrinia, TrichoPlusia, Pieris, LaDhy~ma~ AEroels, A~3~h~, Wiseana TrvPorYza, Diatraea, Spor~anoth~s, Cvdia, ~rchips, Plutella, Chilo, Heliothis, Spo~Eter~ or Tineola spp.), Diptera (e.g. ~S_, ~edes Anopheles, Culex, Glossi~l~, Si~Ll~, ~ , Haem ~ , Tabanus, Hvdrotaea, Lucil~, Chr~somia~., Ct ~ , ~ togi~ Gascero~hilus Hypod~mL, Hvlemy~3, AeheriRona, Chlorsps. Phvtomvza, Ceratitis LirlQmy~ and Melophagus spp.), Phthiraptera (MaloDha&~ e.g Dama~ina spp. and Anoplura e.g. Linognathus and Haema o~inus spp.) Hemipcera (e.g. Aphis, Bemisia,Phorodon, Aeneolamia, Em_oasca Parkinsiella, Pyrilla, Aonidiella, Coccus, Pseudococcus Helopeltis, Lvgus, Dvsdercus, Ox~carenus, Nezar , Aleurodes, Tria~om_, Rhodnius, Psvlla, Myzus, Me~oura, Phvlloxera, Adelves, Niloparvata, NeDhrotettlx or Cimex spp . ), Orthoptera (e.g. Locusta, Gryllus, Schistocerca o~
Achet~a spp.~, Dictyoptera (e.g. Blatte11a, Per~i~laneca or j `'O 92/11254 - 15 -2~9Q7~
spp.), Hymenoptera (e.g. Athalia, Cephus, Atta Lasius, SolenoPsis or Monomorium spp.), Isoptera (e.g. Odontotermes and Reticulitermes spp.), Siphonaptera (e.g. Ctenocephalides or Pulex spp.), Thysanura (e.g. Le~isma spp.), Der~aptera (e.g. Forficula spp.), Psocoptera (e.g. Perlpsocus spp.) and Thysanoptera (e.g. Thrips tabaci),.
Acarine pests include ticks, e.~. members of the genera BooPhilus,Ornithodorus, Rhipicephalus~ AmblYomma, Hvalomma, Ixodes, Haemaphvsalis, Dermacentor and Anocen~or, and mites and manges such as Acarus, Te~ranvchus, Psoro~tes, Notoednes, Sarco~tes, Psorer~ates, ChorioDtes, Eu~rombicula, Demode~ Panonvchus, BrYobia and Erio~hves spp .
~ematodes ~hich a~sack plants and trees of importance to agriculture, fores~ry, horticul~ure, either directly or by spreading bacterial, viral, mycoplasma or fungal diseases of the plants, include root-knot nematodes such as Meloido~Yne spp. (e.g. M. incognita); cyst nematodes such as Globodera spp. (e.g. G. rostochiensis) Heterodera spp. (e.g.
H. avenae): Radopholus spp. (e.g. ~. similis); lesion nematodes such as Pratvlenchus spp. (e.g. P. Pratensis); Belonolaimus spp. (e.g. B.
~racilis); Tvlenchulus spp. (e.g. T. se~ipenetrans); Rotvlenchulus spp. (e.g.R. reniformis); Rotylenchus spp, (e,g, ~, robustus);
HelicoCYlenchus spp. (e.g. H, mulcicinc~us); HemicYclioPhora spp.
(e,g, ~. racilis); Criconemoides spp. (e.g. C. ~ ); Trichodorus spp. ~e,g, T p~imitivus)- dag8er nematodes such as XiPhinemA spp.
(e.g. _, diversicaudatum), Longidorus spp (e.g. ~. eloneatus);
Hoplolaimus spp, (e,g, ~, coronatus); APhelenchoides spp. (e.g. A.
ritzema-bosi, _. besseYi~; stem and bulb eelworms such as Ditvlenchus spp. (e.g. D. dipsaci).
Mollusc pests which attack plants and trees of importance to j agriculture, foresty and horticulture include slugs such as Deroceras spp. (e.g. D. reticulatum - the grey field slug); the Arion group;
Milax spp; land snails such as Helix spp. and aquatic snails such as Planorbis spp. Mollusc pests which act as vectors of diseases in man WO 92/11254 PCT/GB91/0~2 ~ 16 -and domestic animals include Bulinus spp., Phvsopsis spp., Planorbi spp. and Oricomelania spp.
.
Compounds of the invention may be combined with one or more other pesticidally active ingredients (for example pyrethroids, carbamates lipid amides and organophosphates) and/or with attractants;
repellents, bacteriocides, fungicides, anthelmintics and the like.
Furthermore, the activity of compounds of the invention may be enhanced by the addition of a synergist or potentiator, for example:
one of the oxidase inhibitor class o~ synergists, such as piperonYl butoxide, propyl 2-propynylphenyl- phosphonate; a second co~pound of the invention; or a pyrethroid pesticidal comDound~ ~en an oxidase inhibitor synergist is present in a formulation of the inventior., the ratio of synergist to compound of Formula (I) will be in the range 500:1-1:25 eg about 100:1 to 10:1.
Stabilisers for preventing any chemical degradation which may occur with the compounds of the invention include, for example, antioxidants (such as tocopherols, butylhydroxyanisole and butylhydroxytoluene) and scavengers (such as epichlorhydrin) and organic or inorganic bases e.g. trialkylamines such as triethylamine which can act as basic stabilisers and as scavengers.
The following examples serve eo illustraee ehe preparation and properties of compounds of the present invencion, Example 1, 5(e)-e~Butvl-2(e)-methvl.1.3-dithiane-2(a)-carbonitrile i) A solution of _-butyllithium in hexane (1.6M; 17.75mls) was added to a stirred solution of 5-t-butyl-1,3-dithiane (5g) (E.L. Eliel et al. J.Amer.Chem.Soc 1976, 98(12),3583) in tetrahydrofuran (50mls) ac -30 under a nitrogen atmosphere. After 1 hour of additional stirring, the mixture was transferred by syringe and PCI /GB91/0~268 ~,0 92/11254 - 17 -2~3~7~
added, dropwise, to neat dimethylformamide (lOmls) cooled o -10 . The mix~ure was stirred for 1 hour at -10 and then stored overnight a~ 0C. The reaction mixture was then poured into ice-wa~er (lOOmls) and extracted with hexane. The aqueous layer was neutralised with dilute hydrochloric acid and then re-extracted with diethyl ether, The ethereal extracts were dried over anhydrous magnesium sulphate and the evaporated in vacuo ~o leave a white solid residue (3.1g). 5-t-sutyl-2-formyl-1,3-di.hiane, thus obcained, is present to a large e~tent as a dimer.
ii) 5-~-But~i-2-Lormyl-1,3-dithiane (lg) was heated to melting, under 2 nitrogen atmosphere, and then allowed to cool. ~he viscous oil thus obtained was taken up in dry benzene (lOOmls) containing pyridine (0.78g). O,N-Bis-(trifluoroacetyl)-hydroxylamine (l.lg) (J.H. Pomeroyn et al, J.Amer.Chem,Soc. 1959, 81 6340) was added and the resulting mixture was heated to reflux for two hours.
After cooling, ether and water were added and the organic layer separated, The aqueous layer was further extracted with fresh ether and the combined organic extracts were dried over anhydrous magnesium sulphate and then evaporated ~n vacuo to leave a yellow solid, which was purified bY column chromatography on silic~.
Gradien~ elu~ion with hexane/dichloromethane mixtures gave 5-t-butyl-1-cyano-1,3-dithiane as a white solid (0~38g).
~, iii) A solu~ion of 5-t-butyl-~-cyano-1,3-dithiane ~0,2g) in , eecrahydrofuran (lOml) was cooled to -40 under a nitrogen I atmosphere. A solution of n-butyllithium in hexane (1.6M,0.7mls) was added and che resulting mixture maintained at -40 for 1.5 l~ hours when methyl iodide (0.2~1) was added. The reaction mixture j was allowed to warm to room ~emperature overnight. After this time, diethyl ether and water ~ere added. The organic phase was separated and the aqueous layer extracted with fresh ether. The combined organic extracts wera dried over anhydrous magnesium sulphate and evaporated i vacuo, The residue was purified by . .. .
, :
' , . ~.
, ~
: !/11254 ~ 18 - PCT/GB91/022~
, column chromatograph on alumina, eluting with hexane/ether (1:9), to give 5(e)-t-butyl-2(e)-methyl-l~3-dithiane-2~a)carboni~- le as a white solid (lOOmg) after recrystallisation from hexane.
E~amvle 2.
:.
s(e~-e-gutvl-2(a)-methy~ 3-dithia-ne-2te)-carbonitrile i) Boron crifluoride etherata (2.15mls) was added to a stirred solution of 2-t-bu~ylpropane-1,3-dithiol (4.4g) ~European patenC
application 294228) and acetaldehyde (1.5mls) in dry chloroform under nitrogen. The resulting mixture was stirred at room cemperature overnight. After this time, the mixture was washed with water, saturated sodium bicarbonate and brine before drying over anhydrous magneSium sulphate and evaporation in vacuo, 5-t-Butyl-2-methyl-ll3-di~hiane (4.7g) was obtained as a pale yellow oil which solidified on cooling.
A ii) Using the methods described in Example 1 stages (i) and ~ii) 5-t-butyl-2-methyl-1,3-dithiane was. converted to 5(e)-t-butyl 2(a)-methyl-1,3-dithiane-2(e)-carbonitrile~
.
Example ~, S(e)-t-Butyl~2 2-dimethyl-1,3-dithiane i Usin~ ~he me~hod deacribed in Example 2 sta~e (i), 5(e)-t-butyl-2,2 . dimethyl~l,3-dithiane was prepared from acetone and 2-e-butylpropane-i 1,3-dithiol. The crude product was purified by chromatograpny on silica, eluting with hexane/dichloromethane ~9:1) followed by recrystallisation from chloroform/methanol. ..
}
~ trans-5(e)-t-Butyl-2-methyl-2-trifluoromethyl-1,3-dithiane was ., prepared in an analo~ous manner starting from l,1,1-trifluoroacetone ' and 2-t-butylpropane-1,3-dithiol.
.' '~ ' .
',' 'I ~ : , .
`1~ 92/11254 PCT/GB91/02268 2 Q ~ ~ r~
Exam~le .
2(e)-Methvl-5(e)-(2 2.2-trifluoro-1-methylethvl)-1 3-dithiane-2(a)-carbonitrile i) A mi~ture of 2-(2,2,2-trifluoro-1-methylethyl)-propan,1,3-dithiol (4.8g) (European patent 0372816A) and dimethoxymethane (2.lml) in dry chloroform (15ml) was added to a refluxing solution of boron trifluoride etherate (2.9ml) and glacial acetic acid (lOml) in chloroform (50ml) under a nitrogen atmospnere. ~he addition took place over one hour and the resulting mixture was then refluxed ror e rurther ~wo hours and then stirred at room .emperature overnignt. .~fter this ~ime the reaction mixture ~as washed with ~ater, saturated sodium bicarbonate and brine before drying over anhydrous magnesium sulphate and evaporation in vacuo. 5-(2,2,2-trifluoro-l-methylethyl)-1,3-dithiane (3.6g), thus obtained, was used without further purification.
ii) Using ~he methods described in Example 1, 5-(2,2,2-trifluoro-1-methylethyl)-1,3-dithiane was converted to 2~e)-Methyl-5(e)-(2,2,2-trifluoro-1-methylethyl)-1,3-dithiane-2(a).carbonitrile.
3 In a similar manner and starting from 2-(1,1-dimethyl~2,2,2-tri-~; fluoroethyl)-propan-1,3-dithiol (EP 0372816A) was prepared 1 S~e)-(l,l-dime~hyl-2,2,2-tri~luoroethyl)-2~e)-methyl-1,3-dithiane-', 2-(a)-carbonitrile. In a similar manner and starting from 2-cyclopropyl-propan-1,3-dithiol (EP 0372816A) was prepared :
5(e)-cyclopropyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile. :~
ExamPle 5. ";
. 5(e)-t-Butvl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile .',~
.:
:1 1 .....
~92/112~4 PCT/~B91/022~
: .
i) A mixi~ure of 2-t-butylpropane-1,3-diOl (ll.Og.) (E.L. Eliel et a' J Amer Che~ Soc. 1968, 90, 3444) in dry toluene (200ml), ~25 stirr~d at 20C- Sodium hydride (2.4g., 80% dispersion in oil) :
previously washed with hexane, was added carefully to the seirred mixture. The mixture was stirred at 120C for 30 minutes and cooled. Benzyl bromide (9.5ml) was added dropwise and the m1xture heated at 130, wi~h stirring for 6 hours. The ~ixtur~
was cooled, water was added and the mixture extracted wit~
diethyl echer. The ethereal extracts were washed with water.
dried over anhydrous magnesium sulphate and evaporated in The residue was purified by chroma.ography on silica, elutin~
wlth 1:4 diethyl ether: hexane. 2-BenzvloxymethYl-3,3-dimethYl bu~an-l-ol (8.0g) was obtained as a colourless oil.
ii) 2-Benzyloxymethyl-3,3-dimethylbutan-1-ol (5.8g) in dry pyridine (20ml) was stirred at 0C. Then methanesulphonyl chloride (3 5g) was added dropwise and the miXtUre Was stirred at 0C for 3 hours and at 20C for 5 hours. Water Was added and the aqueous mixture was extracted with diethyl ether. The ethereal eXtracts were evaporatqd in = dried over anhydrous magnesium sulphate and 2-Benzyloxymeehyl-3,3-dimethylbut-l~yl methanesulphonaee was obtained as a yellow oil (7.3g) and was uscd wiehout further purification.
:
Lii) Benzyl mercaptan (3.lml) was stirred in dry dimethylformamide ~lOOml), at 0, under a current oi nitrogen. Sodium hydride (0.75g., 80% dispersion in oil), previously washed with hexane was added carefully and the mixeure was stirred ae 0C for 30 minutes. 2-8enzyloxymeehyl-3,3-dime~hylbut-1-yl meehanesulpho-nate ,(7.3g), in dry dimethylformamide (20ml) was added and the mlxture was stirred at 100 for 3 hours. The mixture was cooled and water was added. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, , , ~, i~ ,`' ' ,.
PCT/~B91/0226 `~ O 92/11254 - 21 - '~
2~ 7a~ ' dried ~ver anhydrous magnesium sulphatP and evaporated in vacuo.
The residue was purified by chromatography on silica, eluting with 1:4 diethyl ether: hexane. 2-Ben~ylthiomethyl-3~3-dimeth butyl benzyl ether was obtained as a colourless oil (7.0g).
iv) Anhydrous liquid ammonia (400ml) was stirred at -70, under a current of nitrogen. 2-Benzylthiomethyl-3,3-dimethylbutyl benzyl ether (7.0g) in dry diethyl ether (lOOml) was added and this was followed by sodium (4.0g) in small pieces. The resulting mixture was s,irred a. -70 for 3 hours and then allowed to warm up to 20C. A~ onium chloride (20g) was added followed by drv methanol (70ml). Wnen all the sodium had dissolved, water was added and ~ne ~ix.ure was e~rac~ed with die~hyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulpha~e and evaporated in vacuo. 3,3-Dimethyl-2-mercaptomethyl-butan-l-ol was obtained as a pale yellow oil t2.8g) and was used without further purification.
, v) A mixture of 3,3-dimethyl-2-mercaptomethylbutan-1-ol (1.66g), ; triethyl orthoacetate (1.82g) and p-toluenes.ulphonic acid ¦ (catalytic quantity) was heated under a stream of nitrogen until ¦ no fur~her ethanol was evolved, The resultan~ brown oil was purified by chromatography on alumina, elueing wi~h 4~ dichloro-methane (saturated with ammonLa) in hexane. 5-S~Butyl-2-(a)-eth-, oxy-2(e)-methyl-1,3-oxathiane (1.0g) was obtained as a pale ¦ yellow oil.
vi) Trimethylsilyl cyanide (0.37g) was added to a solution of 5-S-butyl-2(a)-ethoxy-2(e)-methyl-1,3-oxathiane (0.78g) in dichloromethane (lOml) at 0C under nitrogen, followed by boron erifluOride etherate (0.02;g), in a dropwise manner, and the solution allowed to warm to room temperature overnight, The yellow solution was diluted with ether, washed with sodium bicarbonate solution, brine, dried over sodium sulphate and evaporated in vacuo. The residue was purified by chromatography ....
~ ]1254 - 22 - PCTtGB91/022f' ,., ~ ...
.', , .
on alumina eluting with 2% ether: hexane. S(e)-t-Butyl-2(e)-~ethy~ 3-oxathiane-2(a) carbonitrile (0.51g) was obtained as a ~3 palP y~llow oil.
. Exam~le 6.
5 ~ tvl-2~e)-meehyl 1.3-dithiane-2(a2-carbonitrile-1( ~ de 'J i j m-Chloroperoxybenzoic acid (85%, O.l9g) was added to a stirred solu~ion or 5(e)-;-butyl-2(e)-methyl-1,3-dithiane-2ta)-carbonit-rile (0.2g) in dry acetonitrile (30ml) containing sodium acetate (o~g). The resulting mixture was stirred for two hours at room cempera.ure. After this time, insoluble material was removed b~
filtration and washed with ethyl acetate. The resulting fIltrate was dried over magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica. Grad-ent elùtion with hexane/ethyl acetate mixtures gave 5(e)-t-bu-y (e~; e~hyl;l,3-dlchiane 2-(a~ carb In a similar manner, and starting from 5(e)-t-butyl-2(e)-methyl-3 1,3-oxachiane-2(a)-carbonierile, was prepared 5(e)-t-butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 3(a)-oxide and 5(e)-t-bu-cyl-2(e)-~ethyl-1,3-oxathiane-2(a)-carbonitrile 3(e)-oxide.
Example 7.
,.
5(e)-~ ~ Methyl-l.3-dithLa~e-2~a).carbo~itrile_1~1-dioxide Potassium permanganate (0.36g) was added to a stirred mixture of ~ 5(e)-t-bueyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile l(e)-ox-J (0.35g) and magnesium sulphate (lg) in acetone (15ml). The resultlng mlxture was maintained at room temperature fo~ 4 hours and then flltered throueh CeliCe. The colo~rless filtra~e VAS e~apora~ed ,' ~ .' '' - '~ 92/112~4 PCT/GB91/0226g - 23 ~
~ 3 8 7 ~ ~
in vacuo to leave 5(e)-t-butyl-2(e)-meehyl-1,3-dithiane-2(a)-carbonit-rile l,1-dioxide as a white solid (0.33g), E~ample 8.
5!e)-t-Butvl-2(e?-methvl-1~3-oxathiane-2Ca~-carbonitrile 3,3-dioxide A mix~ure of ~(e)-t-butyl-2(e)-methyl-1,3-oxathiane-2-(a)-carbonitrile (lOOm~), and ~agnesiw~ monoperoxyphthala~e (0.28g) in ethanol: water (20:10ml) ~ere heaoed at reflux for 2 hours. Ethanol was removed under reduced pressure, ehe produc~ ex~rac~ed wi~h ether, washed with brine, dried over magnesium sulpha~e and ehe solvent removed in vacuo, . The residue was purified by column chroma~ography on silica, elu~in~
with ether hexane (1:4). 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 3,3-dioxide (37mg) was obtained as a white solid.
Formulations ~, 1. Emulsifiable Co~centrate Compound of formula (I) 10.00 Alkyl phenol ethoxylaee* 7,50 ~ :
Alkyl aryl sulphonate* 2.50 ,13 aromatic solvent 80,00 100 . 00 .
2. Emulsi~ab~e Conce~c~a~
Compound of formula (I) 10.00 .~:
Alkyl phenol ethoxylate* 2.50 .
I~ Alkyl aryl sulphonate* 2.50 :
" Ketonic solvent 64.00 C8 13 aromatic solvent 18.00 Antioxidant 3.00 100 . 00 W 0 92/i1254 l ~ 4 - 24 - PCT/GB91/022 - 3. Wettable Powder Compound of formula (I) 5.00 C8 13 aro~atic solvent 7 0O
Cl8 aromatic solvent 28.00 China clay lO.00 Alkyl aryl sulphonate* l.00 Napthalene sulphonic acid* 3 00 Diatomaceous earth 46.00 _. Dust ' Compound of formula (I) 0.50 Talc 99.50 100.00 5. Bait Compound of formula (I) . 0.50 Su~ar 79.50 ! Paraffin wax 0.00 100.00 6. Emulsion Concentra~e Compound of formula (I) 5.00 ! C8 l3 aromatic solvent 32.00 Cetyl alcohol 3.00 Polyoxyethylene glycerol monooleate* 0.75 .
, ~ Polyoxyethylene sorbitan esters* 0.25 I Silicone solution O.lO
~ Water 58.90 `` ' `' ~
, .'.
1O 92/112~4 ~9~701 7. Suspension Concentrate Compound of formula (I)lO.00 Alkyl aryl ethoxylate* 3,00 Silicone solution O.lO
Alkane diol 5.00 Fumed silica 0.50 ,I Xanthan gum 0.20 '~ Water 80.00 Buffering agent 1.20 100.00 8. M.icroemulsion ~ Compound of formula (I) 10.00 3 Polyoxyethylene ~lycerol monooleate* 10.00 Alkane diol 4.00 Water 76.00 100,00 ~ 9 Water Dispersible Granules , ~ Compound of formula (I) 70.00 ! Polyvlnyl pyrrolidine 2.50 Alkyl aryl echoxyla~e 1. 25 Alkyl aryl sulphonace 1.25 China clay 25.00 . ::
100.00 ~, .
; ' ' .,~ , ,.
. `` ~',"
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.`, .' ~
W O 92/112~4 PCT/GB91/022 `
?~9~ ~
10. Granules Compound of formula (I) 2.00 Alkvl phenol ethoxylate* 5.00 Alkyl aryl sulphonate* 3.00 C8 13 aromatic solvent 20.00 Kieselguhr granules 70.00 100.00 ll. Aerosol (pressure ~ack~
Compound of formula (I) 0.30 Piperonyl butoxide l.iO
8-13 saturated hydrocarbon solvent 58.20 Butane 40 00 100.00 12. Ae~osol (pressure pack~
Compound of formula (I) 0.30 C8 13 saturated hydrocarbon solvent lO.00 Sorbi~a~ monooleate* l.00 WaCer 40.00 i Butane 48,ZQ
0.00 13. Aerosol (pressure pack~
Compound of formula (I) l.00 2 3.00 Polyoxyethylene glycerol monooleate* 1.40 Propanone 38.00 Water 56.60 100. 00 ~: ' :
92~11254 - 27 -2~87~ ~
i 14. Lacauer Compound of formula (I) 2.50 ~ Resin 5 oo ¦ Antioxidant 0.50 3 High aromatic wnite spirit 92,00 :
100.00 ,, ls. S~rav ~readv .o use) ' ' ' . ' Compound or .ormula (I) 0.l0 Ancioxidane 0.l0 Odourless kerosene 99.80 100, 00 16. Potentiated S~rav (ready to use) ', COMPOUnd of formula (I) 0.l0 Piperonyl butoxide 0.50 Antioxidant . 0.l0 . Odourless kerosene 99.3G
100,00 , 17. MicroencaDsulated ; Compound of formula (I) l0.00 C8,l3 aro~atic solvent l0.00 , Aroma~ic di-isocyanate~ 4.50 ~ Alkyl phenol ethoxylace* 6.00 ; Alkyl diamine# l.00 I Diethylene triamine l.00 Concentrated hydrochloric acid 2.20 I Xanthan gum 0.20 ; Fumed silica 0.50 Water 64.60 ` 100 . 00 ,~ , ': ' . '.'',' :~ ~
W O 92/11254 ~ PCT/GB91/02L
~Q~ - 28 -^ ~ Surfactant = i~ react to form the polyurea walls of the microcapsule .~ntioxidant could be any of the followin~ individually or combined 3utylated hydroxytoluene Butylated hydroxyanisole Vitamin C (ascrobic acid) The following examples illustrate in a non-limiting manner ~ne oes~icidal activitv of compounds of formula I. :
Sorav Tests The activity o~ the compounds of the invention was demonstrated bv dlssolving the compounds in acetone (5%) and then diluting in water "Synperonic" (94.5%: 0.5~) to give an aqueous emulsion. This was used to treat the followin~ insects.
Musca domestica 20 Female Musca were contained ln a cardboard cylinder with gauze over either end. Solution oP the compound was sprayed onto ~he insects so enclosed and mortality assessed afeer 48 hours at 25C.
The Pollowin~ compounds were active at less than lOOOp.p.m.:-t 6, 12, 13.
Plutella_xyostella 't 10 Plutella larvae were put onto leaf discs and sprayed with the; solution of the compound. Mortality was assessed after 2 days a~
o 92/11254 - 29 -20 9 8~
The following compounds were active at less than lOOOp.p.m.:-1, 2, 3, 5.
Mvzus Persicae 10 Adults were placed on a leaf disc of chinese cabbage. 24 Hours .
later the disc was sprayed with the solution of compound. Mortality was assessed after 2 days at 25C.
The following compounds were active ae less than lOOOp.p.m.:-11, '2, 13.
.:
The following compounds were active at less than 200p.p.m.:-3, 7, 10.
Diabrotica undecim~unctata Filter paper and food were sprayed with a solution of the compound.
Subsequently, the filter paper was infested wich 10 second instar larvae. ~ortality was assessed atter 48 hours.
The following compounds were active at less than lOOOp.p.m.:-The following compounds were ac~ive at less than 200p.p.m.:-1, ~, 3, 5, 11, 6, 7, 9, 8, 10, 12, 13.
: .:
' .
.,." . . ... .....
5(e)-cyclopropyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile. :~
ExamPle 5. ";
. 5(e)-t-Butvl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile .',~
.:
:1 1 .....
~92/112~4 PCT/~B91/022~
: .
i) A mixi~ure of 2-t-butylpropane-1,3-diOl (ll.Og.) (E.L. Eliel et a' J Amer Che~ Soc. 1968, 90, 3444) in dry toluene (200ml), ~25 stirr~d at 20C- Sodium hydride (2.4g., 80% dispersion in oil) :
previously washed with hexane, was added carefully to the seirred mixture. The mixture was stirred at 120C for 30 minutes and cooled. Benzyl bromide (9.5ml) was added dropwise and the m1xture heated at 130, wi~h stirring for 6 hours. The ~ixtur~
was cooled, water was added and the mixture extracted wit~
diethyl echer. The ethereal extracts were washed with water.
dried over anhydrous magnesium sulphate and evaporated in The residue was purified by chroma.ography on silica, elutin~
wlth 1:4 diethyl ether: hexane. 2-BenzvloxymethYl-3,3-dimethYl bu~an-l-ol (8.0g) was obtained as a colourless oil.
ii) 2-Benzyloxymethyl-3,3-dimethylbutan-1-ol (5.8g) in dry pyridine (20ml) was stirred at 0C. Then methanesulphonyl chloride (3 5g) was added dropwise and the miXtUre Was stirred at 0C for 3 hours and at 20C for 5 hours. Water Was added and the aqueous mixture was extracted with diethyl ether. The ethereal eXtracts were evaporatqd in = dried over anhydrous magnesium sulphate and 2-Benzyloxymeehyl-3,3-dimethylbut-l~yl methanesulphonaee was obtained as a yellow oil (7.3g) and was uscd wiehout further purification.
:
Lii) Benzyl mercaptan (3.lml) was stirred in dry dimethylformamide ~lOOml), at 0, under a current oi nitrogen. Sodium hydride (0.75g., 80% dispersion in oil), previously washed with hexane was added carefully and the mixeure was stirred ae 0C for 30 minutes. 2-8enzyloxymeehyl-3,3-dime~hylbut-1-yl meehanesulpho-nate ,(7.3g), in dry dimethylformamide (20ml) was added and the mlxture was stirred at 100 for 3 hours. The mixture was cooled and water was added. The aqueous mixture was extracted with diethyl ether. The ethereal extracts were washed with water, , , ~, i~ ,`' ' ,.
PCT/~B91/0226 `~ O 92/11254 - 21 - '~
2~ 7a~ ' dried ~ver anhydrous magnesium sulphatP and evaporated in vacuo.
The residue was purified by chromatography on silica, eluting with 1:4 diethyl ether: hexane. 2-Ben~ylthiomethyl-3~3-dimeth butyl benzyl ether was obtained as a colourless oil (7.0g).
iv) Anhydrous liquid ammonia (400ml) was stirred at -70, under a current of nitrogen. 2-Benzylthiomethyl-3,3-dimethylbutyl benzyl ether (7.0g) in dry diethyl ether (lOOml) was added and this was followed by sodium (4.0g) in small pieces. The resulting mixture was s,irred a. -70 for 3 hours and then allowed to warm up to 20C. A~ onium chloride (20g) was added followed by drv methanol (70ml). Wnen all the sodium had dissolved, water was added and ~ne ~ix.ure was e~rac~ed with die~hyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulpha~e and evaporated in vacuo. 3,3-Dimethyl-2-mercaptomethyl-butan-l-ol was obtained as a pale yellow oil t2.8g) and was used without further purification.
, v) A mixture of 3,3-dimethyl-2-mercaptomethylbutan-1-ol (1.66g), ; triethyl orthoacetate (1.82g) and p-toluenes.ulphonic acid ¦ (catalytic quantity) was heated under a stream of nitrogen until ¦ no fur~her ethanol was evolved, The resultan~ brown oil was purified by chromatography on alumina, elueing wi~h 4~ dichloro-methane (saturated with ammonLa) in hexane. 5-S~Butyl-2-(a)-eth-, oxy-2(e)-methyl-1,3-oxathiane (1.0g) was obtained as a pale ¦ yellow oil.
vi) Trimethylsilyl cyanide (0.37g) was added to a solution of 5-S-butyl-2(a)-ethoxy-2(e)-methyl-1,3-oxathiane (0.78g) in dichloromethane (lOml) at 0C under nitrogen, followed by boron erifluOride etherate (0.02;g), in a dropwise manner, and the solution allowed to warm to room temperature overnight, The yellow solution was diluted with ether, washed with sodium bicarbonate solution, brine, dried over sodium sulphate and evaporated in vacuo. The residue was purified by chromatography ....
~ ]1254 - 22 - PCTtGB91/022f' ,., ~ ...
.', , .
on alumina eluting with 2% ether: hexane. S(e)-t-Butyl-2(e)-~ethy~ 3-oxathiane-2(a) carbonitrile (0.51g) was obtained as a ~3 palP y~llow oil.
. Exam~le 6.
5 ~ tvl-2~e)-meehyl 1.3-dithiane-2(a2-carbonitrile-1( ~ de 'J i j m-Chloroperoxybenzoic acid (85%, O.l9g) was added to a stirred solu~ion or 5(e)-;-butyl-2(e)-methyl-1,3-dithiane-2ta)-carbonit-rile (0.2g) in dry acetonitrile (30ml) containing sodium acetate (o~g). The resulting mixture was stirred for two hours at room cempera.ure. After this time, insoluble material was removed b~
filtration and washed with ethyl acetate. The resulting fIltrate was dried over magnesium sulphate and evaporated in vacuo. The residue was purified by column chromatography on silica. Grad-ent elùtion with hexane/ethyl acetate mixtures gave 5(e)-t-bu-y (e~; e~hyl;l,3-dlchiane 2-(a~ carb In a similar manner, and starting from 5(e)-t-butyl-2(e)-methyl-3 1,3-oxachiane-2(a)-carbonierile, was prepared 5(e)-t-butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 3(a)-oxide and 5(e)-t-bu-cyl-2(e)-~ethyl-1,3-oxathiane-2(a)-carbonitrile 3(e)-oxide.
Example 7.
,.
5(e)-~ ~ Methyl-l.3-dithLa~e-2~a).carbo~itrile_1~1-dioxide Potassium permanganate (0.36g) was added to a stirred mixture of ~ 5(e)-t-bueyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile l(e)-ox-J (0.35g) and magnesium sulphate (lg) in acetone (15ml). The resultlng mlxture was maintained at room temperature fo~ 4 hours and then flltered throueh CeliCe. The colo~rless filtra~e VAS e~apora~ed ,' ~ .' '' - '~ 92/112~4 PCT/GB91/0226g - 23 ~
~ 3 8 7 ~ ~
in vacuo to leave 5(e)-t-butyl-2(e)-meehyl-1,3-dithiane-2(a)-carbonit-rile l,1-dioxide as a white solid (0.33g), E~ample 8.
5!e)-t-Butvl-2(e?-methvl-1~3-oxathiane-2Ca~-carbonitrile 3,3-dioxide A mix~ure of ~(e)-t-butyl-2(e)-methyl-1,3-oxathiane-2-(a)-carbonitrile (lOOm~), and ~agnesiw~ monoperoxyphthala~e (0.28g) in ethanol: water (20:10ml) ~ere heaoed at reflux for 2 hours. Ethanol was removed under reduced pressure, ehe produc~ ex~rac~ed wi~h ether, washed with brine, dried over magnesium sulpha~e and ehe solvent removed in vacuo, . The residue was purified by column chroma~ography on silica, elu~in~
with ether hexane (1:4). 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 3,3-dioxide (37mg) was obtained as a white solid.
Formulations ~, 1. Emulsifiable Co~centrate Compound of formula (I) 10.00 Alkyl phenol ethoxylaee* 7,50 ~ :
Alkyl aryl sulphonate* 2.50 ,13 aromatic solvent 80,00 100 . 00 .
2. Emulsi~ab~e Conce~c~a~
Compound of formula (I) 10.00 .~:
Alkyl phenol ethoxylate* 2.50 .
I~ Alkyl aryl sulphonate* 2.50 :
" Ketonic solvent 64.00 C8 13 aromatic solvent 18.00 Antioxidant 3.00 100 . 00 W 0 92/i1254 l ~ 4 - 24 - PCT/GB91/022 - 3. Wettable Powder Compound of formula (I) 5.00 C8 13 aro~atic solvent 7 0O
Cl8 aromatic solvent 28.00 China clay lO.00 Alkyl aryl sulphonate* l.00 Napthalene sulphonic acid* 3 00 Diatomaceous earth 46.00 _. Dust ' Compound of formula (I) 0.50 Talc 99.50 100.00 5. Bait Compound of formula (I) . 0.50 Su~ar 79.50 ! Paraffin wax 0.00 100.00 6. Emulsion Concentra~e Compound of formula (I) 5.00 ! C8 l3 aromatic solvent 32.00 Cetyl alcohol 3.00 Polyoxyethylene glycerol monooleate* 0.75 .
, ~ Polyoxyethylene sorbitan esters* 0.25 I Silicone solution O.lO
~ Water 58.90 `` ' `' ~
, .'.
1O 92/112~4 ~9~701 7. Suspension Concentrate Compound of formula (I)lO.00 Alkyl aryl ethoxylate* 3,00 Silicone solution O.lO
Alkane diol 5.00 Fumed silica 0.50 ,I Xanthan gum 0.20 '~ Water 80.00 Buffering agent 1.20 100.00 8. M.icroemulsion ~ Compound of formula (I) 10.00 3 Polyoxyethylene ~lycerol monooleate* 10.00 Alkane diol 4.00 Water 76.00 100,00 ~ 9 Water Dispersible Granules , ~ Compound of formula (I) 70.00 ! Polyvlnyl pyrrolidine 2.50 Alkyl aryl echoxyla~e 1. 25 Alkyl aryl sulphonace 1.25 China clay 25.00 . ::
100.00 ~, .
; ' ' .,~ , ,.
. `` ~',"
.! .
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W O 92/112~4 PCT/GB91/022 `
?~9~ ~
10. Granules Compound of formula (I) 2.00 Alkvl phenol ethoxylate* 5.00 Alkyl aryl sulphonate* 3.00 C8 13 aromatic solvent 20.00 Kieselguhr granules 70.00 100.00 ll. Aerosol (pressure ~ack~
Compound of formula (I) 0.30 Piperonyl butoxide l.iO
8-13 saturated hydrocarbon solvent 58.20 Butane 40 00 100.00 12. Ae~osol (pressure pack~
Compound of formula (I) 0.30 C8 13 saturated hydrocarbon solvent lO.00 Sorbi~a~ monooleate* l.00 WaCer 40.00 i Butane 48,ZQ
0.00 13. Aerosol (pressure pack~
Compound of formula (I) l.00 2 3.00 Polyoxyethylene glycerol monooleate* 1.40 Propanone 38.00 Water 56.60 100. 00 ~: ' :
92~11254 - 27 -2~87~ ~
i 14. Lacauer Compound of formula (I) 2.50 ~ Resin 5 oo ¦ Antioxidant 0.50 3 High aromatic wnite spirit 92,00 :
100.00 ,, ls. S~rav ~readv .o use) ' ' ' . ' Compound or .ormula (I) 0.l0 Ancioxidane 0.l0 Odourless kerosene 99.80 100, 00 16. Potentiated S~rav (ready to use) ', COMPOUnd of formula (I) 0.l0 Piperonyl butoxide 0.50 Antioxidant . 0.l0 . Odourless kerosene 99.3G
100,00 , 17. MicroencaDsulated ; Compound of formula (I) l0.00 C8,l3 aro~atic solvent l0.00 , Aroma~ic di-isocyanate~ 4.50 ~ Alkyl phenol ethoxylace* 6.00 ; Alkyl diamine# l.00 I Diethylene triamine l.00 Concentrated hydrochloric acid 2.20 I Xanthan gum 0.20 ; Fumed silica 0.50 Water 64.60 ` 100 . 00 ,~ , ': ' . '.'',' :~ ~
W O 92/11254 ~ PCT/GB91/02L
~Q~ - 28 -^ ~ Surfactant = i~ react to form the polyurea walls of the microcapsule .~ntioxidant could be any of the followin~ individually or combined 3utylated hydroxytoluene Butylated hydroxyanisole Vitamin C (ascrobic acid) The following examples illustrate in a non-limiting manner ~ne oes~icidal activitv of compounds of formula I. :
Sorav Tests The activity o~ the compounds of the invention was demonstrated bv dlssolving the compounds in acetone (5%) and then diluting in water "Synperonic" (94.5%: 0.5~) to give an aqueous emulsion. This was used to treat the followin~ insects.
Musca domestica 20 Female Musca were contained ln a cardboard cylinder with gauze over either end. Solution oP the compound was sprayed onto ~he insects so enclosed and mortality assessed afeer 48 hours at 25C.
The Pollowin~ compounds were active at less than lOOOp.p.m.:-t 6, 12, 13.
Plutella_xyostella 't 10 Plutella larvae were put onto leaf discs and sprayed with the; solution of the compound. Mortality was assessed after 2 days a~
o 92/11254 - 29 -20 9 8~
The following compounds were active at less than lOOOp.p.m.:-1, 2, 3, 5.
Mvzus Persicae 10 Adults were placed on a leaf disc of chinese cabbage. 24 Hours .
later the disc was sprayed with the solution of compound. Mortality was assessed after 2 days at 25C.
The following compounds were active ae less than lOOOp.p.m.:-11, '2, 13.
.:
The following compounds were active at less than 200p.p.m.:-3, 7, 10.
Diabrotica undecim~unctata Filter paper and food were sprayed with a solution of the compound.
Subsequently, the filter paper was infested wich 10 second instar larvae. ~ortality was assessed atter 48 hours.
The following compounds were active at less than lOOOp.p.m.:-The following compounds were ac~ive at less than 200p.p.m.:-1, ~, 3, 5, 11, 6, 7, 9, 8, 10, 12, 13.
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Claims (16)
1. A method for controlling pests which comprises contacting the pest with a pesticidally effective amount of a compound of the formula (I):
(I) which contains between 8 and 30 carbon atoms, and wherein Y is oxygen or a group S(O)m and m and n are independently selected from 0, 1 and 2; R2a and R2 are the same or different and each is selected from cyano, nitro, methyl optionally substituted by halo, a group S(O)qR7 where q is 0, 1 or 2 and R7 is methyl or ethyl, or a group COR8 where R8 is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkyl optionally substituted by fluoro or a group NR9R10 wherein R9 and R10 are independently selected from hydrogen, methyl or ethyl; R4a and R4b, R6a and R6b are independently selected from hydrogen, methyl, cyano or trifluoromethyl, R5a is a primary, secondary or tertiary C2-5 alkyl group optionally substituted by halo or C1-4 alkoxy, or a C3-4 cycloalkyl group, or R5a is a C3-4 cycloalkyl group and R5b is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkanoyloxy, or C1-4 alkyl optionally substituted by alkoxy; or R5a and R5b form a gem di-methyl group or are linked together with the ring carbon to which they are attached to form a 3- to 5-membered ring that optionally contains a hetro atom or an olefinic bond and is optionally substituted by a C1-4 alkyl group optionally substituted by halo.
WO 92/11254 PCT/GB91/0226?
(I) which contains between 8 and 30 carbon atoms, and wherein Y is oxygen or a group S(O)m and m and n are independently selected from 0, 1 and 2; R2a and R2 are the same or different and each is selected from cyano, nitro, methyl optionally substituted by halo, a group S(O)qR7 where q is 0, 1 or 2 and R7 is methyl or ethyl, or a group COR8 where R8 is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkyl optionally substituted by fluoro or a group NR9R10 wherein R9 and R10 are independently selected from hydrogen, methyl or ethyl; R4a and R4b, R6a and R6b are independently selected from hydrogen, methyl, cyano or trifluoromethyl, R5a is a primary, secondary or tertiary C2-5 alkyl group optionally substituted by halo or C1-4 alkoxy, or a C3-4 cycloalkyl group, or R5a is a C3-4 cycloalkyl group and R5b is hydrogen, hydroxy, C1-4 alkoxy, C1-4 alkanoyloxy, or C1-4 alkyl optionally substituted by alkoxy; or R5a and R5b form a gem di-methyl group or are linked together with the ring carbon to which they are attached to form a 3- to 5-membered ring that optionally contains a hetro atom or an olefinic bond and is optionally substituted by a C1-4 alkyl group optionally substituted by halo.
WO 92/11254 PCT/GB91/0226?
2. A method according to claim 1 wherein Y is oxygen or sulphur.
3. A method according to claim 1 or 2 wherein R2a and R2b are the same or different and each is selected from methyl, ethyl, cyano or trifluoromethyl.
4. A method according to claim 3 wherein R2a is methyl.
5. A method according to claim 3 wherein R2b is methyl or cyano.
6. A method according to any of claims 1 to 5 wherein R4a, R4b, R6a and R6b are each selected from hydrogen, or methyl.
7. A method according to any of claims 1 to 6 wherein R5a is a secondary or tertiary C2-5 alkyl group optionally substituted by fluoro or a cyclopropyl group.
8. A method according to any of claims 1 to 7 wherein R5b is hydrogen, methyl or ethyl.
9. A compound of the formula (I) (I) wherein Y, R2a, R4a, R4b, R5b, R6b, m and n are as defined in claim 1 and R2b is cyano, nitro, a group S(O)qR7, a group COR8 wherein a R7 and R8 are as defined in claim 1, or a C1-3 alkyl group substituted by halo.
?O 92/11254 PCT/GB91/0226?
?O 92/11254 PCT/GB91/0226?
10. A compound selected from:-5(e)-t-Butyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile 5(e)-t-Butyl-2(a)-methyl-1,3-dithiane-2(e)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-l,3-dithiane-2(a)-carbonitrile-1(e) oxide 5(e)-t-Butyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile-1,1-dioxide 2(e)-Methyl-5(e)-(1-methyl-2,2,2-trifluoroethyl)-1,3-dithiane-2(a)-carbonitrile 5(e)-Cyclopropyl-2(e)-methyl-1,3-dithiane-2(a)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3(a)-oxide 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3(e)-oxide 5(e)-t-Butyl-2(e)-methyl-1,3-oxathiane-2(a)-carbonitrile-3,3-dioxide
11. A process for the preparation of a compound of the formula (I) (I) which process comprises:
WO 92/11254 PCT/GB91/0226?
(i) the reaction of a compound of the formula (II):
(II) wherein X is SH and Y1 is SH or OH with a suitable aldehyde or ketone of the formula or a reactive derivative thereof, wherein the R substituents at the 2,4,5 and 6 positions are as defined in claim 1 or
WO 92/11254 PCT/GB91/0226?
(i) the reaction of a compound of the formula (II):
(II) wherein X is SH and Y1 is SH or OH with a suitable aldehyde or ketone of the formula or a reactive derivative thereof, wherein the R substituents at the 2,4,5 and 6 positions are as defined in claim 1 or
claim 12 and, optionally, thereafter oxidising one or two ring sulphur atoms, or (ii) when one of R2a and R2b is cyano and the other is an alkyl group optionally substituted by halo a) the reaction of a compound of the formula (III):
(III) O 92/11254 PCT/GB91/022??
with an alkylating agent, or b) the reaction of a compound of the formula (IV):
(IV) wherein R11 is C1-4 alkyl and R12 is methyl optionally substituted by halo with a triakylsilylcyanide in the presence of an acid catalyst.
12. A method for the control of pest infestation of plants and/or stored products and/or an environment which comprises administering an effective amount of a compound of the formula (I) as defined according to any one of claims 1 to 9 to the plant and/or stored product and/or environment susceptible to pest infestation.
(III) O 92/11254 PCT/GB91/022??
with an alkylating agent, or b) the reaction of a compound of the formula (IV):
(IV) wherein R11 is C1-4 alkyl and R12 is methyl optionally substituted by halo with a triakylsilylcyanide in the presence of an acid catalyst.
12. A method for the control of pest infestation of plants and/or stored products and/or an environment which comprises administering an effective amount of a compound of the formula (I) as defined according to any one of claims 1 to 9 to the plant and/or stored product and/or environment susceptible to pest infestation.
13. A method for the control of pest infestations on animals which comprises administering to the animal an effective amount of a compound of the formula (I) as defined according to any one of claims 1 to 9.
14. A pesticidal formulation comprising a compound of the formula (I) as defined in any one claims 1 to 9 in admixture with one or more carriers or diluents.
?? 92/11254 PCT/GB91/022??
?? 92/11254 PCT/GB91/022??
15. A pesticidal formulation according to claim 14 which additionally contains a synergist or potentiator.
16. A pesticidal formulation according to either claim 14 or claim 15 which additionally contains one or more pesticidally active ingredients, attractants, repellents, bacteriocides, fungicides and/or anthelmintics.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9027571.0 | 1990-12-19 | ||
| GB909027571A GB9027571D0 (en) | 1990-12-19 | 1990-12-19 | Novel heterocyclic pesticidal compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2098704A1 true CA2098704A1 (en) | 1992-06-20 |
Family
ID=10687271
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002098704A Abandoned CA2098704A1 (en) | 1990-12-19 | 1991-12-18 | Heterocyclic pesticidal compounds |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0565550A1 (en) |
| JP (1) | JPH06503825A (en) |
| KR (1) | KR930703289A (en) |
| AU (1) | AU648626B2 (en) |
| BR (1) | BR9107171A (en) |
| CA (1) | CA2098704A1 (en) |
| CZ (1) | CZ114393A3 (en) |
| FI (1) | FI932846A0 (en) |
| GB (1) | GB9027571D0 (en) |
| HU (1) | HUT65130A (en) |
| NO (1) | NO932258L (en) |
| WO (1) | WO1992011254A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0103761D0 (en) | 2001-02-15 | 2001-04-04 | Syngenta Ltd | Agrochemical formulation |
| RU2536205C2 (en) * | 2012-09-27 | 2014-12-20 | Федеральное Государственное Бюджетное Учреждение Науки Институт Нефтехимии И Катализа Ран | Method of obtaining 5-methoxycarbonyl-1,3-dithiane, possessing fungicidal activity |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1491269A (en) * | 1974-08-02 | 1977-11-09 | Firmenich & Cie | Oxathiolane and oxathiane derivatives and perfuming and flavouring agents |
| EG19064A (en) * | 1987-06-05 | 1994-07-30 | Wellcome Found | Novel heterocyclic pesticidal compounds |
-
1990
- 1990-12-19 GB GB909027571A patent/GB9027571D0/en active Pending
-
1991
- 1991-12-18 CZ CS931143A patent/CZ114393A3/en unknown
- 1991-12-18 CA CA002098704A patent/CA2098704A1/en not_active Abandoned
- 1991-12-18 AU AU91041/91A patent/AU648626B2/en not_active Ceased
- 1991-12-18 HU HU9301793A patent/HUT65130A/en unknown
- 1991-12-18 JP JP4501455A patent/JPH06503825A/en active Pending
- 1991-12-18 WO PCT/GB1991/002268 patent/WO1992011254A1/en not_active Application Discontinuation
- 1991-12-18 BR BR919107171A patent/BR9107171A/en not_active Application Discontinuation
- 1991-12-18 KR KR1019930701861A patent/KR930703289A/en not_active Application Discontinuation
- 1991-12-18 EP EP92901389A patent/EP0565550A1/en not_active Withdrawn
-
1993
- 1993-06-18 FI FI932846A patent/FI932846A0/en not_active Application Discontinuation
- 1993-06-18 NO NO93932258A patent/NO932258L/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB9027571D0 (en) | 1991-02-06 |
| HU9301793D0 (en) | 1993-09-28 |
| WO1992011254A1 (en) | 1992-07-09 |
| AU648626B2 (en) | 1994-04-28 |
| FI932846A (en) | 1993-06-18 |
| AU9104191A (en) | 1992-07-22 |
| JPH06503825A (en) | 1994-04-28 |
| NO932258D0 (en) | 1993-06-18 |
| CZ114393A3 (en) | 1994-01-19 |
| NO932258L (en) | 1993-06-18 |
| EP0565550A1 (en) | 1993-10-20 |
| BR9107171A (en) | 1994-03-22 |
| KR930703289A (en) | 1993-11-29 |
| FI932846A0 (en) | 1993-06-18 |
| HUT65130A (en) | 1994-04-28 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |