CA1064490A - Imidazole derivatives - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Novel imidazole compounds, pesticidal compositions and methods of using them, and their preparation are described The compounds have the formula

Description

.o6449 - ` This invention relates to new chemical compounds, pesticidal com~ositions containing the compounds as active ingred~:ent and the use of the compounds in controlling pests.
The compounds of the invention have the following general formula R4 ~ N~ R3 r X=C NE~lR2 in which X is oxygen or sulphur, R3 is an alkylthio group containing 1-4 carbon atom~, an alkenylthio group con~aining

2-4 carbon a~oms, a benzyl-thio group optionally substituted with one or two halogen, nitro, methoxy, trihalomethyl or methyl substituents, alko,yalkyl containing 2-4 car~on atoms or alkylthioaL~yl containing 2-4 carbon atoms, R4 is alkyl ~ ~ ~ ~ 15 containing up to 10 carbon atoms or cycloalkyl contain~ng up to 10 carbon atoms, and Rl and R2 are each alkyl conta~ning 1 ~ ~ to 4 carbon atoms, alkenyl containing 2 to 4 carbon atoms, y~; ~ alkoxyalkyl containing 2 to 4 carbon atom~ or chloroal~yl containing 1 to 4 carbon atoms, or Rl and R , together with ~ 20 the nitrogen atoms to which the~ are attached, form a i ; ~ heterocyclic ri~g, optionally containing 1 to 4 methyl - ~ sùbstituents attached to carbon atoms of the heterocyclic ring, -~
r(~ ; selected from morpholino, l-pyrrolidinyl and l-piperidino;
. J
and acid~addition salts formed with an inorganic or organic acid. -~
The radicals Rl and R2 can be the same or different and when they are alkyl they contain 1 to 4 carbon atoms.
; Examples o~ alkyl groups include methyl, ethyl, propyl, j~ isopropyl and n-butyl, the most preferred group being methyl.
When Rl or ~2 is alkenyl it contains 2 to 4 carbon atoms an~ c~n ~è,~-io~ ë~ampie, allyl or 2-methylallyl~ When 2 - ~--- . `

R or R is an alkoxyalkyl radical it preferably contains 2 to ~- :
4 carbon atoms and can be, for example 2~methoxyethyl and 2-ethoxyethyl. Values of Rl or R2 when it is a chloroalkyl ` radical contain 1 to 4 carbon atoms and it is suitably :-substituted with a single . ~, .
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~064490 chlorine atom; examples include chloromethyl and 2-chloroethyl.
When the group NRlR2 is substituted heterocyclic it can be substituted by for example 1 to 4 alkyl, especially methyl, substituents attached to carbon atoms of the heterocyclic ring. Such alkyl-substituted heterocyclic groups include for example 2,6-dimethylmorpholino, 4-methyl-1 piperidino, 2-methyl-1-piperidino, 2,6-dimethyl-1-piperidino and 2-ethyl-1-piperidino. The heterocyclic radical NRlR2 is preferably chosen from l-pyrrolidinyl, l-piperidino and, most suitably, morpholino.
Preferred groups of compounds are those in which (a) both Rl and R2 are methyl, (b) Rl is methyl and R2 is methyl, ethyl or propyl, and (c) Rl and R2, together with the ~1 nitrogen atom to which they are attached, form a morpholino group. It is also preferred that X is oxygen.
The radical R3 is optionally substituted alkylthio, alkenylthio, aralkylthio, alkoxyalkyl or alkylthioalkyl. When ;l it is optionally substituted alkylthio the radical can be {~ branched or unbranched and examples include methylthio, ~ 20 ethylthio, propylthio, isopropylthio, butylthio, sec.
`i butylthio, pentylthio and hexylthio. The alkylthio group ~;;
contains 1 to 4 carbon atoms and especially preferred radicals ;
are methylthio and ethylthio. The alkylthio group can be substituted with one or more substituent such as one or more ", halo atoms, an alkoxy group, an alkoxycarbonyl group, an ;- alkylthio group, an alkenyloxy group or a dialkylamino group.

Examples of these substituents include chloro, bromo, . .~:~ .
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10644~0 fluoro, methoxy, ethoxy, methoxycarbonyl, ethoxycarbonyl, methylthio, ethylthio, vinyloxy, dimethylamino and diethylamino.
Particularly preferred instances of R3 when it is a substituted alkylthio group are methoxymethylthio, ethoxycarbonylme-S thylthio, methylthiomethylthio, vinyloxyethylthio anddimethylaminoethylthio.
When R is an optionally substituted alkenylthio group it can be branched or unbranched and can be, for example, optionally substituted allylthio, 2-methylallylthio, - 10 prop-2-enylthio or but-2-enylthio, and contains 2 to 4 carbon atoms. When the radical is substituted preferred substituents are one or two halogen atoms such as for example, bromo, fluoro and especially chloro.
. ,~ .
~1~ When R3 is benzylthio, it may be substituted with , . ~ .
one or more substituents such as hologen, nitro, alkoxy, , trihalomethyl or alkyl especially methyl. There are most i~ suitably one or two substituents on the phenyl ring. Examples of such groups are benzylthio, 4-chlorobenzylthio, 2,4-~ dichlorobenzylthio, 2-methyl-4-chlorobenzylthio, 2-methyl-i~ 20 benzylthio, 2,4-dimethylbenzylthio, 3-nitrobenzylthio, 2-methoxybenzylthio, 4-methoxybenzylthio and 3-trifluoromethyl-benzylthio.
When R is optionally substituted alkoxyalkyl or alklthioalkyl it contains 2 to 4 carbon atoms and preferred values are methoxymethyl and methylthiomethyl, especially methoxymethyl.
The radical R4 is alkyl or cycloalkyl and preferably contains up to 10 carbon atoms. Thus when R4 is alkyl it can be straight or branched chain and can be for example ~ .. ,; .
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, ~, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. butyl, l-methylbutyl, l-ethylprapyl, pentyl, tert.
pentyl, hexyl, 1,1,2-trimethylpropyl, heptyl, l~l~et~ylpn~
2,3,3-trimethylbut-2-yl, octyl, 2-ethylhexyl, nonyl or decyl. Preferably R4 contains 3 to 5 carbon atoms and especially pre~erred valuas of R4 when it is an alkyl group are isopropyl, tert. butyl, sec. butyl, l-ethylpropyl and tert. pentyl. When R4 is cycloalkyl it can oontain, for example, up to 8, and more especially from 3 to 7, carbon atoms in the cyclo ring. m e cycloaL~yl group can optionally -contain one or more substituents on the ring, for example, one or more lower alkyl, especially methyl, substituents.
.;
A lower alkyl substituent is preferably in the l-position attached to the cycloalkyl carbon atom joined to the imidazole ring and when there is more than one substituent on the cycloalkyl group they can be the same or differënt. Thus, ~, for example, values of R4 include cyclopropyl, cyclobutyl, ~; l-methylcyclobutyl, cyclopentyl, l-methylcyclopentyl, cyclohexyl, l-methylcyclohexyl, l-methylcyclohexyl l~ 20 containing 1,2 or 3 further meth 1 substituents such as for example 1,3-dimethylcyclohexyl, 1,4-dimethylcyclohexyl, cycloheptyl or cyclooctyl. Preferably, when R4 is cycloalkyl, it contains five or six carbon atoms in the cyclo ring and ` is cyclopentyl optionally containing 1 to 3 methyl substituents - 25 or cyclohexyl optionally containing 1 to 3 methyl substituents.
", A particular group of compounds o~ formula I is one in which X is oxygen or sulphur, R3 is alkylthio, alkenylthio; aral~ylthio or alkoxyalkyl, R4 is alkyl or cycloalkyl, and Rl and R2 are each alkyl, alkenyl, ~l 30 . _ . . . . .

` 1064490 alkoxyal~yl or haloalkyl, or Rl and R2, together with the nitroge~ atom to which they are attached, form a heterocyclic ring optionally containing 1 to 4 alkyl ; substituents attached to carbon atoms of the heterocyclic ring, selected from morpholino, thiamorpholino, pyrrolidi~yl and l-piperidino.
` An especi~lly preferred compound of formula I is one ;~ in which X is oxygen, R3 is alkylthio, R4 is alkyl, and - and R2 are bo~ methyl or Rl and R2, together with the ~; 10 nitrogen atom ~o which they are attached, form an optionally substitute~ morpholino group. Compounds of formula I in which the ~- 1 2 ; group NR ~ is ~orpholino have the added advantage of low mammalian toxicity.
,~ In utilising their pesticidal properties the compounds ~;1,` 15 of the invention are preferably used as the free base but may also be e~ployed as an acid addition salt which can be ,1 formed with an inorganic or organic acid, for example hydrochloric, hydrobrom:c, hydroiodic, hydrofluoric, sulphuric, nitric, phosphoric, perchloric, sulphamic, formic, acetic, trichloroacetic, oxalic ,fpf cric, benzenesulphonic, dodecylbenzenesulphonic, p-toluenesulphonic, stearic, flavianic, embo~ic or tetraiodophthailic acids. Such salts are pesticidally active by virtue of the imidazole cation ~ .
content of the s lt. --2~ We have fo~d that the compounds of the present ~ invention have pesticidal activity and can, for instance, `!~ be used to combat insects. They are especially~use~ul in -~ controlli~ig aphids such as, for exaimple, Aphis ~abae, I
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~ ~ i064490 ~ Me~oura viciae, Mvzus persicae, Phorodon _umNli, Eriosoma .~ . . . .
s~ laniFerum, Brevicorvne brassicae and Acrythosi~hon Pisum.
Other insect species which can be controlled include for example the larvae of the diamond back moth (Plutella maculipennis) the larvae of the codling moth (Cydia '.,?j ` ~ 5 omonella). caterpillars such as for exiample those of the ~; ; cabbage which butterfly (Pieris brassicae) and plant hoppers such as for example the green rice leafhopper (Ne~hotettix cinctice~s). In addition the compounds are active against sheep blow fly (Lucilia sericata) and~aoarids for example adults of the two spotted mite (Tetranvchus urticae). ;~; AccordLngly the inventLon also includes a pesticidal, preferably an insecticidal, composition which comprises as an active ingredient a compound of the invention together with a diluent. The diluent can be a solid or a liquid, optionally in associatLon with a surface-active agent, for example. a dispersing agent, emulsifying agent or wetting -gent. ~ ~~~~
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More than~one compound o$~the invention can be 20 ~ included ln the~compos1t10n. If desired the composition `can also oontain-one~or more additional pesticides, such as compounds known to possess fungicidal, acaricidal or insecticidal ; activity.~Exa~ples oi insecticldal compounds include an organochlorine compound such as for example DDT, benzene hexachloride or dicofol; an organophosphorus compound such as f~or exn~ple fenitrothion azinphos-methyl, demeton or dimethoate; or a~ca~rbamate such as for example carbaryl.
8xamp1es~of fungicidal compounds that can be used, include binapacryl, beno~yl, captan and maneb.

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The co~position o~ the invention can take any of the forms known in the art for the formulation o~ pesticidal compounds ~or ex2mples solutions, aqueous dispersions, aqueous emulsi~ns, dusting powders, dispersible powders, -5 fumigants, emulsifiable concentrates and granules. Such compositions i~clude not only a ¢omposition in a suitable .. ..
~orm for application but also a concentrated primary composition ~nich requires dilution with a suitable quantity or water or o~her diluent before application. Dispersible powders and e3ulsifiable concentrates are typical examples of such primary compositions.
As a disp_rsion, the composition comprises a compound of the inventio~ dispersed in an aqueous medium. It is :i, often convenien~ to supply the consumer with a primary ',r, ~ ' 15 composition which can be diluted with waterto form a ; dispersion of t~e desired concentration. The primary composition can be provided in any one of the following forms. It ca~ ~e a dispersible solution which comprises a compound of the invention dissolved in a water-miscible - 20 ; solvent with t~e addition of a ~ispersin~g agent. Alternatively it can be a dispersible powder which comprises a compound of the in~en~ion and a dispersing agent. A further alternative comprises a co~ound of the invention in the form of a finely ground p~wder in association with a dispersing agent and intimately mixed with water to give a paste or cream ~ . ~
which can if desired be added to an emulsion of oil in water to give a dispersion of active ingredient in an aqueous oil emulsion.
An emulsion comprises a compound of the inventio~
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dissolved in a water-immiscible solvent which is formed into an emulsion with water in the presence ol an emulsi~ying agent. An emulsion of the desired concentration can be formed from a primary composition of the following -types. A concentrated stock emulsion can be supplied comprising a compound of the invention in combination with an emulsifying agent, water and a water-immiscible solvent.
Alternatively an emulsifiable concentrate can be supplied to the user comprising a solution of a compound of the - 10 invention in a water-immlscible solvent containing an emulsifying agent.
A dusting powder comprises a compound o~ the invention `; intimately mixed and ground with a solid pulverulent ., diluent, for example kaolin.
~ . .
A granular solid comprises a compound of the invention associated with similar diluents to those which can be employed in dusting powders, the mixture being granulated by known methods. Alternatively it comprises the active ingredient absorbed or adsorbed on a pre-for~ed granul~r diluent for example fuller's earth, attapulgite or lime~tone grit.
The concentration of the active ingredient in a composition intended for direct application to the pests is ~ i generally within the range 0.001 to 10 per ce~t by weight, ~`
especially 0.005 to 5 per cent by weight. In a primary composition the amount of active ingredient can vary widely .~ .
and can be, for example, from 5 to 95 per cent by weight of the compo~ition.

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Also included in the invention is a method for `-i combating pests which comprises applying a compound of ; the present invention to the locus of the pests, i.e. the pests or their habitat. A particular embodiment of this method is a method for protecting plants from insects in ~ particular aphids, which comprisesapplying a compound o~
i the present invention to plants or their surroundings.
In controlling pests the active compound can be applied on its own or preferably as one of the compositions described above. Direct treatment is oiten the preferred method by for example spraying, dusting or fumigation of plants infested with insects. Alternatively the active compound can be applied to the soil in which plants are ` grown as granules or as a root drench. In such instances the active compound is absorbed by the roots of the plant and confers protection from the insects. A preferred `(~ applicaticn rate of the active ingredient is within the range 0.005 to 10 lb./acre, more particularly 0.01 to - 5 lb./acre. m e compounds of the present--invention can be ` 20 used to protect a variety of pla~ts from aphids, for example, ornamental plants such as roses, and crop plants such as fruit trees, leguminous crops, potatoes, hops, . ,~,. .
~ sugar beet, cotton, maize, rice and tobacco.
~ ....... . - .
m e compounds of the present invention can be prepared ... . .
by a process which comprises reacting an imidazole of the general formula . . ~
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' ' ` ' . ' , ` ` ` ' ; , ~': . ~'' ', ; " . ' ` ' , ' ' ." ~ ~ ' ~ r~~\ 1064490 N
H
in which R3 and R4 are as defined above, with a carbamoyl ; 5 halide or thiocarbamoyl halide of the general formula Z-CXNRlR2 ~III) in which Rl, R2 and ~ are as defined above and Z is halogen, for example, chlorine or bromine, preferably chlorine. The reaction is most suitably effected ln the presence of an inert organic li~uid as the reaction medium which is preferably a solvent for the reactants.
Advantageously the reaction is effected in the presence ;~ of a suitable base,for example, a tertiary amine such as triethylamine, pyridine or alkali métal carbonate, in order to take up the hydrogen halide produced in the reaction.
Alternatively the imidazole can be reacted with an alkali metal hydride, such as sodium hydride, to form an N-alkali metal derivative, before reaction with a halide of formula III. In preparing the compounds by this route the reactants are preferably reacted together ~t a temperature of from 0 to 120C. for example from 50 to 95C. The salts of the invention can readily be prepared by treatment o~ the product thus prepared with acid by wellknown methods.
The imidazole compounds of formula II in which R3 is ;~; optionally substituted alkylthio, alkenylthio, aralkylthio, alkoxyalkyl or alkylthioalkyl and R4 is cycloalkyl or alkyl containing more than one carbon atom are novel compounds.
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~ `` 1064490 Compo~nds of formula II in which R3 is optionally ;.
, substituted all~ylthio, alkenylthio or aralkylthio can be .~: prepared by, for example,-reacting an alkali metal ; thiocyanate wiih an appropriate aminomethyl ketone of the general formula `~. R4CoCH2NH2 - ' ~ to give a ~hiol of the following formula :............................. 4 R I _ N
~ IV
;~ 10 ~ N - SH
H
; which in its turn, can be alkylated, alkenylated or aralkyl-ated according to well known methods to give compound~ of formula II. Alternatively, compounds of formula II in t~ 15 which R3 $s optionally substituted alkylthio, alkenylthio or aralXylthio can be prepared by reacting, in the presènce of alkali, an a-hialo~etone of the general formula R4CoCH2Z in , "
which Z is a halogen atom with an S-alkylisothiouronium salt of the followi~g formula ~ ~3 ~ ~
. H2N-C=NH2 A~ :

. .; ~ , in which:R3:is as defined immediately above and A representJ
a suitable anion, for example,sulphate or halide.
Those compounds of formula II in which R3 is optionally substltuted aIkoxyalkyl or alkylthioalkyl can be made by, : : for example, condensing an aldehyde of the general formula :: i ::
R3CHo in which ~ is optionally substituted alkoxyalkyl or alkylthioalkyl with an acyloxylated ketone of the general formula R4C ~ ~ in which B is acyloxy, in the presence of ` ammonia.
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` - 1064490 Carbamo~-l nalides or thiocarbamoyl halides of the ~enerai formula III can be prepared by reacting a secondary amine of the general formula RlR2NH with a carbonyl halide or thiocarbonyl halide of the general formula CXZ2 in which Z is halogen, preferably chlorine, in accordance with known methods.
The compounds of the present invention can also be prepared by a process which comprises reacting a carbamoyl halide or thiocarbamoyl halide of the general formula ~ 10 " ~ R4~1_R3 CXZ
in which R3, R4 and X are as defined above, Z being halogen ~l 15 preferably chlorine, with a secondary amine of the ; general formula RlR2NH, Rl and R2 being as defined above. m e ;, compound of formula V can be prepared by reaction of an~hl ~ imidazole of formula II with a carbamoyl or thiocarbamoyl . . . ,, _ . . .
halide CXZ2 in which Z is halogen.
., ., ~ .
; 20 In a further method of preparing the compounds of the ~ invention a carbonylbisimidazole or thiocarbonylbisimidazole sl~ of the general formula .~ X
R ~ ~ 3 ~ ~ VI

, , , in which R3, R4 ard X are as defined above, can be reacted with a secondarg amine of the general formula RlR2NH, Rl and ., ;~ R' being as defined above. The compound of formula VI can be prepared by reacting an imidazole of formula II with about `` ~064490 0.5 molecular proportions of a carbamoyl or thiocarbamoyl halide CXZ2 ~ n which Z is halogen.
It will be appreciated that the reactions described above for the preparation of compounds of formula I may give either or both of two isomeric products, depending on which nitrogen atom in the imidazole ring is substituted (the free hydrogen of the imidazole molecule of formula II
can be associa ed with either-of the ring nitrogen atoms).
m e products of t~e present invention may conveniently be ~ 10 designated as l-(N,N-disubstituted-carbamoyl or -thiocarbamoyl)--l 2-R~-4(5)-R4-i~idazoles and this designation corresponds to- --formula I which e~compasses both of the isomeric forms. The current state of our knowledge indlcates that the solid products of the reactions described above, after purification ,. 41, 15 by conventiomal techniques such as crystallization, are obtained in ~a~y instances as substantially pure ~ 4-substituted compounds. Our knowledge also indicates; that the liquid products of t~e reactions described above, after isolation ~y conventional techniques such as ~ 20 distillatio~ i~ vacuo, are obtai~ed in many instances -, predominantly i~ the 4-substituted isomeric form. Such 4-substituted isomers may be designated as l-tN,N-~ disubstituted-carbamoyl or-thiocarbamoyl)-2-R3--4-R4-imidazoles.
; m e iollowing examples illistrate the invention.
.. . . .
Where the physical properties of compounds are tabulated, a solid is characterised by the melting point and a li~uid .
~ by its boiling ~oint.
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, -- ``1064490 This example illustrates the preparation of compounds according to the invention. -5.1 ml. DLmethylcarbamoyl chloride in 20 ml. dry -dioxan was added to a mixture of g.2 g. 2-ethylthio-4-tert. butylimidazole and 8.4 ml. triethylamine in 30 ml.
dry dioxan. A~ter heating the mi~xture on a steam bath for 24 hours, the triethylamine hydrochloride was removed and the product, l-dimethylcarbamoyl-2-ethylthio-4(5)-tert.
butylimidazole, distilled. It had a boiling point of 108-111C. at 0.10-0.12 mm. Hg. pressure and on cooling ; crystallised to a solid with a melting point of 45C.
The Z-ethylthio-4-tert. butylimidazole employed in the above reaction was prepared in the following w~y.
i 104 g. Po~assium phthalimide was suspended in a solution of 100 g. bromopinacolone in 300 ml. dry toluene.
is reaction mixture was stirred on a steam bath for 18 ~' `,~ hours and the solid precipitate filtered off and washed with toluene. The washings were added to the filtrate which was I ~ 20 heated on a steam bath to concentTated. The product, 3,3-; ~ dimethyl-l-phthal~midobutan-2-one, crystallised out on cooling.
It wa~ washed with light petroleum (b.p. 80-100C) and its ... . . .
,, meltlng point was 97-101.5C. 82.6 g. 3,3-Dimethyl-l-phthalimidobutan-2-one was refluxed for 10 hours with a -mixture o~ 465 ml. concentrated hydrochloric acid, 400 ml.
water and 324 ml. acetic acid. The mixture was evaporated, 360 ml. water were added and the solution ", ~ ' ' .

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- -- ` 1064490 chilled in ice. Phthalic acid was filtered off and the solution again evaporated, the residual solid being dissolved in warm absolu~e alcohol. Ether was added to the cooled solution and l-amino-3,3-dimethylbutan-2-one hydrochloride precipitated as product, m.p. 199-200C.
35.2 g. 1-~mino-3,3-dimethylbutan-2-one hydrochloride and 30 g. po~assium thiocyanate in 50 ml. water were heated on the steam bath for two hours. After cooling, k1 the solid formed was collected washed with water, dried and recrystallised from industrial methylated spirit to give 4-tert. butyl~inidazole-2-thiol, m.p. 232-234C. A solution/
suspension of this material in industrial methylated spirit was added to a solution of 4.5 g. sodium hydroxide in 100 ml.
water. 17.6 g. Ethyl iodide was then added and the mixture was shaken for twenty minutes. The resulting product was neutralised by passing in carbon dioxide and the methylated spirit removed by evaporation. The solid was collected, -I washed with waier, dried, and on recrystallisation from toluene gave 2-e~hylthio-4-tert. butylimidazole, mp.ll6.5-120C
EXAMPLE 2 f .' ! .
` This example illustrates a method of preparing l-dimethyl-carbamoyl-2-methylthio-4(5)-tert. butylimidazole.
~. 1 1.2 g. Sodium hydride in mineral oil (50 per cent disper-; sion) was added to 3.4 g. 2-methylthio-4-tert. butylimidazole in dry tetrakydrofuran. When the evolution of hydrogen had ~ ..
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`` 1064490 ceased, 2.7 g. dimethylcarbamoyl chloride was carefully -- added. Hea~ was evolved and a precipitate formed. After aperiod of ~n hour the solid was removed and the product distilled. It was l-dimethylcarbamoyl-2-methylthio-4(5~-tert. butyli~'dazole, b.p. 107C. at 0.07 mm. Hg pressure.
The imidazole reactant used in the above preparation -~ was prepared in a similar way to that of 2-ethylthio-4-tert.
butylimidazole described in-Example 1.

This exa~ple illustrates a further method o~ preparing ~ compounds according to the invent~on.
;-1~ To a stirred solution of 11.3 g. 2-methox~methyl-4-tert.
_s : butylimid ole in 30 ml. tetrahydrofuran and 20 ml.
triethylamine was added 8 g. dimethylcarbamoyl chloride.
The result~g mixture was boiled under reflux for three hours i. .
'~ and then diluted with methylene chloride, washed with water :i - .
, and the methyle~e chloride solution then dried over magnesium su~phate. Evaporation of the solvent left a ~, residue which distilled under reduced pressure to give the ;
product, 1-dim~hylcarbamoyl-2-methoxymethyl-4(5)-tert.
butylimidazole, ~.p. 106-108C. at 0.1 mm. Hg pressure.
, ,~ .
`~ m e imidazole reactant used in the above preparation' t~ :
was prepared i~ the following way.
To a solution of 123 g. potassium acetate in 1200 ml.
methanol was added 143 g. bromopinacolone. This reaction . .
mixture was re~luxed for two hours, then cooled and filtered.
The filtrate was added with stirring to a solution of 320 g.

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I, ' .' ""',.'' .. "' ,'' . , ' .,.. ' " '. "' "'.; '. ~. '' .. ''." " ' ; ' ', ,' ', .--`` 1064490 cupric acetate moni~hydrate in 1600 ml. 25 per cent ammonia and 1400 ml. water, followed by addition of 100 g. 77 per cent aqueous solutions of methoxyacetaldehyde. The temperature of the reaction mixture was maintained at 30-40C. for an hour and the mixture then heated on a steam bath for a iurther four hours. After cooling overnight, the insoluble copper salt was collected, washed with water and suspended in 500 ml. of 4~-acetic acid. A solution oi 133 g. po~assium ferricy~n7de in 400 ml. water was added and the precipitated copper complex removed and washed with water. m e combined supernatant liquors were basified (pH. 9-10) with 5N-sodium hydroxide a~Zid extracted with ether. m e ethereal extracts were combined, washed with water and dried over magnesium sulphate. rne solvent was evaporated and the residue re-crystallised from petroleum ether (b.p. 60-80C.) to give , the product, 2-methoxymethyl-4- '~ert. butylimidazole, m.p.
- 65-66C.
The iollowLng compounds were prepared in an analogous manner.
1-dimethylcarbamoyl-2-metho~methyl-4(5)-sec.
butylimidazole, b.p. 108-110C./0.01 mm.
1-dimet~ylcarbonyl-2-methoxymethyl-4(5)-(1-methylcyclo-ii ; pentyl)imidazole, b.p. 132-134C/0.2 mm.
,1~ 1-morpholi~ZZcarbonyl-2-methoxymethyl-4(5)-(l-me~ylcyclopentyl)imidazole, m.p. 150-152C.
i; l-(N-meihyl-N-ethylcarbamoyl)-2-methoxymethyl-4(5)-tert.LZutylimidazole, b.p. 112-114C/0.2 mm.
: . `1 ~1 l-(N-met`Qyl-N-ethylcarbamoyl)-2-methoxymethyl-~!
~-1 4(5)-sec.butylimidazole, b.p. 116-118C/0.25 mm.
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, - , : ., , ,, . ~ ... . . . : ., ~ ' 1064490 l-dimethylcar~amoyl-2-methoxymethyl-4(5)-(1-ethylpropyl)-imidazole, b.p. 118-120C/0.1 mm.
dimethylcarbamoyl-2-methoxymethyl-4(5)-(1-me~hylcyclohexyl)imidazole b.p. 145-146C/0.1 mm.
i-dimetnylcarbamoyl-2-methoxymethyl-4(5)-tert.pentyl-imidazole, b.p. llSC/0.2 mm.
l-morpholinocarbonyl-2-methoxymethyl-4(5)-tert.
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~ .
~''r - pentylimidazole, b.p. 1~8-140 C/0.1 mm. -51' 1-morpholinocarbonyl-2-methoxymethyl-4(5)-tert.
butylim;dazole, m.p. 57-58C.
~, The following intermediates were isolated in the course -i~ of prepari g the above compound~.
.~
2-methoxym~thyl-4-sec.butylimidazole, b.p. 122-124C/0.6 mm.
2-methoxymethyl-4-(1-methylcyclopentyl)imidazole, b.p. 126-128C/0.~ mm.
2-methoxymethyl-4-(1-ethylpropyl)imidazole, b.p.
126-128C/0.2 mm.
2-methoxymethyl-4-(1-methylcyclohexyl)imidazole b.p.
142-144C/0.5 mm.
r 1 2-methoxymethyl-4-tert. pen~ylimidazole, b.p. 116-118/
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Intermediates of the formula IV were prepared in : a similar way to that described in Example 1. :~

. 4 Physical State R _and Constant sec. butyl solid, 109-112C.
. isopropyl solid, 147-150C
;~ 5 l-methylcyclohexyl solid, 205C.
.~ l-ethylpropyl solid, 171C. ~ -. cyclohexyl solid, 260-261C.
l-methylcyclopentyl solid, 182-183C.
tert. pentyl solid, 174C.

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"` ~064490 Inte~edia'es of the ~ormula IV were prepared in a similar way to ~-hat described in Example 1.

:.......... , ~ Physical State R and Constant . ~ .
ethyl solid, 163-165C.
propyl solid, 183-184C. : : -methylbutyl . solid, 88-90C.
.~ isobutyl solid, 185-186C. ~
, methyl solid, 246C. .
l-ethylpropyl solid, 171C. . :~
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~-` 1064490 EXA~
This exa~ple illustrates the preparation of compounds according LO ~e invention 1.8 ~. ~odium hydride in mineral oil (50 per cent dispersion) was added gradually to a solution of 5.4 g.

4-isopropyl-2-methylthioimidazole in 30 ml. dry tetrahydrofuran.
After a pe-iod of 30 minutes 5.05 g. morpholinocarbonyl --chloride was added. Heat was evolved and the mixture refluxed ~or an hour. The tetrahydrofuran was filtered and evaporated to give a residue which on crystallisation from , ~ ~ petroleum ether ~b.p. 100-120C.) gave the product, l-morpholinocarbonyl-2-methylthio-4(5)-isopropylimidazole m.p. 63-65C.
j~ The imidazole reactant used in the above preparation . ,~ . .
was prepared i~ the following way.
126 g. 3-~Iethylbutan-2-one in 600 ml. methanol was treated with 74 ml. bromine which wa~ added dropwise at o ~` ~ a temperature of about 10 C. The solution was quenched on ice and the bromoketone then separated and washed with water.
The aqueous liauors were extracted with three 50 ml. portions of petroleu~ ether and the combined bromoketone and petrol portions added ~o 216 g. potassium phthalimide in 500 ml.
dimethylfo~amide. The mixture waæ then heated with j ., ~ stirring on a steam bath for two hours then filtered to .~ .
remove i~soluble matter and poured into three litres of water with stirrinb~. The solid was collected, dried, and : I;
recrystallised from industrial methylated spirit, 3-methyl-1-i phthalimidoouuan-2-one, m.p. 98-99C.

~ ~ 30 - 29 -.. . . .
. , . , . . ~ .

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' ' ,: ' , , . : ' 176.3 g. Of the phthalimidoketone was refluxed for 20 ~ hours with a mi~ture of one litre of concentrated hydrochloric - acid, 1020 ml. water and 710 ml. acetic acid. The solution was evaporated and the residue taken up in 800 ml. water.
After separation o~ phthalic acid, the solution was -il evaporated to dryness. The solid was air-dried to free it ~~ from excess acid, l-amino-3-methylbutan-2-one hydrochloride, -~ m.p. 155-158C. -~
- An aqueous solution of 98.8 g. of the aminoketone and -i - 10 63.6 g. potassium thiocyanate was heated on a steam-bath for 2~ hours. The oil which deposited solidified to give 3i 4-isopropyli~dazole-2-thiol, m.p.147-150C.
, .
~ A solution of 6.16 g. potassium hydroxide in 50 ml.
. , .
; industrial met~ylated spirit was added to 14.2 g.
~ 15 4-isopropylim;dazole-2-thiol in 150 ml. industrial methylated .. ... .. .....
spirit, followed by 15.6 g. methyliodide. The solution was refluxed for 1~ hours and the solvent then evaporated. After treating the residue with water the remaining æolid was collected ~nd recrystallised from ethyl acetate. It was 2-methylthio 4-isopropylimidazole, m.p. 96-98C.
e following compounds of general formula I were :. ,. - .
~. 3; prepared in an analogouæ manner.

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: :t This exæmple describes the preparation of thiocarbamoylimidazole compounds of the invention.
17.0 g. 2-l~e~hylthio-4-tert. butylimidazole were dissolved in 200 ml. dry dioxan, after which 13.9 ml.
... .
triethyl~mi~e ?nd 12.3 g. dimethylthiocarbamoyl chloride were added. The mixture was refluxed for eight hours, then cooled and the precipitate of triethylamine hydrochloride filtered off. On distilling off the dioxan a brown oil rem~ined. Thi3 oil was extracted with two 50 ml. portions o~ petroleum ether (b.p. 60-80C.) and , . .
on cooling a solid was deposited which was collected and recryst~lised from petroleum ether (b.p. 80-100C.) with charcoal to give l-dimethylthiocarbamoyl-2-methylthio-4(5)-tert.butylimidaz31e, m.p. 94-96C.
~` The followlng compounds were prepared in an analogous ~ ,;j.
,~, manner.
~¦ l-dimethyl~hiocarbamoyl-2-ethylthio-4(5)-(1-methylcyclo-¦ ~ hexyl)imidazole, b.p. 180-190C/0.2 mm.
1-dimethylthiocarbamoyl-2-methylthio-4(5)-tert. pentyl-~; imidazole, b.p. 126-130C/O.l mm.
,4j:
~ EXAMPLE 8 ;1~ This example describes the preparation of l-(N-methyl-N-2-ethoxyethyl)carbamoyl-2-methylthio-4(5)-tert.
'~ 25 butylimidazole and related compounds.
A solution o~ 7 g. 2-methylthio-4-tert. butylimidazole in 45 ml. dry te~rahydrofuran was added to 2.4~ g. sodium hydride in mineral oil (60 per cent dispersion~ The resulting , ' ~ .

; , ,, .
' ' ' . ' , .

~ ~ 1064g90 : `
mixture was cooled to a temperature of between O and 5C. and then 10 g. 1-(N-methyl-N-2-ethoxyethyl)carb ~oyl chloride added whilst the reaction mixture was maintained below 5C. After ~iltering to remove solid precipitate the filtrate was refluxed on a steam bath for two hours.
On distillation the product, l-(N-methyl-N-2-ethoxyethyl) carbamoyl-2-methylthio-4(5)-tert.butylimidazole, was collected, b.p. 130-134C./O.l mm. Hg pressure.
The following compounds were also prepared by a similar ` 1~ method; 1-(N-methyl-N-2-ethoxyethyl)carbamoyl-2-methylthio-4(5)-isopropylimidazole, b.p. 132-134C.jO.l mm. -l-(N-methyl-N-2-ethoxyethyl)carbamoyl-2-methylthio-4~5)-(l-methylcyclohexyl)imidazole, b.p. 165-168C/0.2 mm.
~: EXAMPLE 9 Thls example illustrates an alternative method of preparing the intermediate 2-methylthio-4-tert. butylimidazole ;l of formula II by a route which comprises reacting an a-haloketone with an S-alkylisothiouronium salt.
A mixture of 17.9 g. a-bromopinacolonej--16.7 g.
S-methyl-iso-thiouronium sulphate~and 32 g. sodium carbonate in 100 ml. water and 100 ml. ethanol was stirred under reflux for a period of 1 hour. m e ethanol w~s distilled off and after the addition of a further quantity of 100 ml.
. ~ . ' ! ' ., water, 150 ml. toluene was added. The mixture was stirred ~t~ ~ ~ 25 vigorously for ten minutes and the hot toluene separated ~` and washed with 1OO ml. hot water. 70 ml. of the toluene and traces of water were distilled off and the remaining toluene solution stirred at 0C. for 30 minutes when crystalline 2-methylthio-4-tert. butylimidazole separated.
- 30 The product w~s ~iltered off, washed with cold toluene and . ~
~ _ 34 _ . .. . .
,. . .

~`~ 1064490 j . ~
- dried, m.p. 149-150C.
EXAMPLE 10 '' m is example describes the preparation of salts . ~
of the invention.
A concentrated solution of 1.2. g. l-dimethylcarbamoyl-2-methylthio-4(5)-tert. butylimidazole in 50 ml. ether ~' was added to a concentrated solution of 1.5 g. flavianic acid in 4 1. ether. The flavianate crystallised on standing and was filtered off, m.p. 205-206C with decomposition. On recrystallisation from industrial methylated spiri*s a pure sample was obtained, m.p. 206C.
with decomposition.
, In a similar manner the followLng acid addition salts were prepared salt meltin~ point C
i~ bromide 18~C. with decomposition !': picrate 169-171C.
nitrate 152C. with decompo~ition , .
f This example illustrates the preparation of emulsifiable concentrates according to the invention.
Emulsifiable concentrates suitable for d1lution with ~., , water to form an a~ueous emulsion were prepared from the following ingredients: %W/v Active compound 25.0 Calcium dodecylbenzenesulphonate 3.0 - Nonylphenoxypolyethoxyethanol* 3.0 ~ Xylene 100.0% vol, ',.'',~ ~
0 _ 35 _ .

- ~ , . . ..

. . , .: :

lg6449~ ' *nonylphenol-ethylene oxide condensate containing ' an average of 14 mols. ethylene oxide per mol. nonylphenol.
; Emulsifiable concentrates containing the following compounds were prepared:
~- 5 1-dimethylcarbamoyl-2-methylthio-4(5)-~ert. butylimidazole l-dimethylcarbamoyl-2-ethylthio-4(5)-tert. butylimidazole l-dimethylcarbamoyl-2-methoxymethyl-4(5)-tert.butylimidazole l-morpholinocarbonyl-2-methylthio-4(5)-tert. butylimidazole ; 10 EXAMPLE 12 This example illustrates the preparation of granules according to the invention.
Granules containing 5% W/w o~ the compounds referred to in Example 11 were prepared by impregnating granules f fuller's earth (mesh size 20/40 British Standard Sieve) with a solution of the carbamoylimidazole compound in ' methylene chloride and then evaporating the methylenë
,,'''~! chloride from the impregnated granules.
`~ EXAMPLE 13 This example illustrates the preparatio~ of dispersible powders according to the inventiQn.
Dispersible powders were prepared from the following ingredients: YoW/w Active compound 25.0 2~ - Silicic acid 25.0 Calcium lignosulphonate10.0 Sodium dioctylsulphosuccinate 0.5 Kaolin to 100.0 . ,. ~ , , ., , ~,.' ,'~; ~ '. `
: ,~ , .. . ......... . . .

` ; 1064490 ,. ,, -- .
Dispersible powders containing the compounds referred to in Example 11, were prepared.

This example illustrates the aphicidal properties of the compounds of the invention.
Briad bean plants 3-5 cm~ high were infested with ` ~ aphids (Me~oura viciae) and then sprayed with an aqueous dispersion containing 250 parts per million W/v of the , .
i~ carbamoylimidazole compounds of Examples 1 to 8 and 10.
;, . .
; ~ 10 Each plant was kept under a lamp glass for 24 hours and then 4i~ ~' examined. It was iound that at least 50 per cent of the aphids were killed. m e aphid population of control `~
'I :
~ plants that had been treated with an aqueous spray not .; ~, ~ , .
containing any test compound were not affected.

This example further illustrates the aphicidal properties oi compounds of the invention.
Broad bean plants 3-5 cm. high were infested with balckbean aphids (~b~ fabae) and then sprayed with an aqueous dispersion containing 10~ parts per million W/v of each active compound listed below. The plants were Xept under a lamp glass for 24 houræ and then examined.
In all cases at least 50 per cent of the aphids were Xilled. The aphid populations of control plants that had been treated with an aqueous spray not containing any : ~ } ~
test compound were not affected.

,., . :
. i . ~ . .
., ~' : . ' . . . ' ' 1 , ' ' : ' ", ' ~ "
. . ~ :
~ .
: ~ . ' , '

5~ 1-dimethylcarbamoyl-2-methylthio-4(5)-tert. butylimidazole ' l-morpholinocarbonyl-2-methylthio-4(5)-tert. butylimidazole < l-morpholinocarbonyl-2-methylthio-4(5)-sec. butylimidazole ` l-morpholinocarbonyl-2-methylthio-4(5)-isopropylimidazole 5 1-morpholinocarbonyl-2-methylthio-4(5)-1-ethylpropylimidazole :~ l-dimethylcarbamoyl-2-methylthio-4(5)-isobutylimidazole This example illustrates the systemic activity of compounds of the invention against the aphid Me~oura ~. ~
' ~r1~ viciae.
The compounds to be tested were applied as soil . . .
drenches. 25 ml. of an aqueous test solution was watered ; into tne soil in an 8 cm. diameter plant pot containing ~,~...................................................................... .
~'3 a single broad bean plant. A cardb~ard shield was placed around the plant so that only a part of it protruded.
' m is was infested with aphids. After three days the aphicidal effect was assessed by counting the numbe~3of live and dead aphids.
m e following compounds were found to-have an LD5 of less than 100 p.p.m. ~ ~-~
, p l-dimethylcarbamoyl-2-methylthio-4(5)-tert. butylimidazole ; . .
l-dimethylthiocarbamoyl-2-methylthio-4(5)-tert. butylimidazole l-morpholinocarbonyl-2-methylthio-4(5)-tert. butylimidazole l-dimethylcarbamoyl-2-allylthio-4(5)-sec butylimidazole ~.-", 25 1-dimethylcarbamoyl-2-ethylthio-4(5)-(1-methylcyclopentyl) imidazole dimethylcarbamoyl-2-but-2-enylthio-4(5)-tert. pentylimidazole -~ .
.

-- 1064~90 ~XAMPLE 17 m is example illustrates the activity of 1-dimethylcarbamoyl-2-methylthio-4(5)-tert. bu~ylimidazole against larvae of the cabbage white butterfly (Pieris l~ 5 brassicae).
- Ten larvae were placed in a tube together with a square of cabbage leaf which had been dipped Ln the test solution and allowed to dry. After twenty-four hours untreated cabbage was added as food and after a further twenty-four hours an assessment was made o~ ihe mortality of the larvae by counting the numbers of live and dead insects.
Two replicates were carried out employing a test solution o~ 200 p.p. m. At this level of corcentration the active compound gave greater than 50 per cent control of the larvae .` .i . ' ; , ~
: - . .

- . , ,.~, .

. "1 ' .
~ 25 '"' ~

~ ':',1 ' ~ 30 _ ~9 _ . , .

Claims (11)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A compound useful as a pesticide, said compound having the general formula:

in which X is oxygen or sulphur, R3 is an alkylthio group containing 1 to 4 carbon atoms, an alkenylthio group containing 2 to 4 carbon atoms, a benzylthio group optionally substituted with one or two halogen, nitro, methoxy, trihalomethyl or methyl substituents, alkoxyalkyl containing 2 to 4 carbon atoms or alkylthioalkyl containing 2 to 4 carbon atoms, R4 is alkyl containing up to 10 carbon atoms or cycloalkyl containing up to 10 carbon atoms, and R1 and R2 are each alkyl containing 1 to 4 carbon atoms alkenyl containing 2 to 4 carbon atoms, alkoxyalkyl containing 2 to 4 carbon atoms or chloroalkyl containing 1 to 4 carbon atoms, or R1 and R2, together with the nitrogen atom to which they are attached, form a heterocyclic ring, optionally containing 1 to 4 methyl substituents attached to carbon atoms of the heterocyclic ring, selected from morpholino, 1-pyrrolidinyl and 1-piperidino; and acid addition salts formed with an inor-ganic or organic acid.

2. A compound according to claim 1 in which X is oxygen or sulphur, R3 is alkylthio, alkenylthio, aralkylthio or alkoxyalkyl, R4 is alkyl or cycloalkyl, and R1 and R2 are each alkyl, alkenyl, alkoxyalkyl or haloalkyl, or R1 and R2, together with the nitrogen atom to which they are attached, form a heterocyclic ring optionally containing 1 to 4 methyl substituents attached to carbon atoms of the heterocyclic ring, selected from morpholino, 1-pyrrolidinyl and 1-piperidino.

3. A compound according to claim 2 in which X is oxygen.

4. A compound according to claim 2 in which X is oxygen and R3 is alkylthio.

5. A compound according to claim 4 in which R4 is alkyl containing 3 to 5 carbon atoms.

6. A compound according to claim 2 in which x is oxygen, R3 is methylthio or ethylthio, and both R1 and R2 are methyl.

7. A compound according to claim 2 in which X is oxygen, R3 is methylthio or ethylthio, and R1 and R2, together with the nitrogen atom to which they are attached, form a morpholino group.

8. A method for combating insects which comprises applying a compound as defined in claim 1 to the insects or their habitat.

9. A method for combating insects which comprises applying a compound as defined in claim 6 to the insects or their habitat.

10. A method for combating insects which comprises applying a compound as defined in claim 7 to the insects or their habitat.

11. A process for preparing a compound as defined in claim 1 which comprises reacting an imidazole of the general formula:

in which R3 and R4 are as defined in claim 1, with a carbamoyl halide or thiocarbamoyl halide of the general formula Z-CXNR1R2 in which R1, R2 and X are as defined in claim 1 and Z is halogen.