AU596794B2 - Pesticidal compounds - Google Patents

Description

4 4ji~~t~c~ For59679m Form PATENTS ACT 1952 COMPLETE SPECIFICATION

(ORIGINAL)

FOR OFFICE USE Short Title: Int. Cl: Application Number: 5 This (ocun n Lodged: dments made unidhe I tion 49 and e s de r Prniting. or Complete Specification-Lodged: Accepted: Lapsed: Published: Priority: Related Art: o a 0a o a O 0 SName of Applicant: Address of Applicant: 0 00 a00 ctual Inventor: 0 00 Address for Service: ooo 0 a 0 TO BE COMPLETED BY APPLICANT THE WELLCOME FOUNDATION LIMITED 183-193 Euston Road, LONDON N.W.1 Malcolm Henry Black John Bernard Patrick Larkin Robert John Blade Robinson GRIFFITH HASSEL FRAZER 71 YORK STREET SYDNEY, N.S.W. 2000, AUSTRALIA 2BP, ENGLAND Weston John and John Edward Complete Specification for the invention entitled: PESTICIDAL COMPOUNDS The following statement is a full description of this invention, including the best method of performing it known to me:-* SNote: The description is to be typed in double spacing, pica type face, in an area not exceeding 250 mm in depth and 160 mm in width, on tough white paper of good quality and it is to be inserted inside this form.

14599/78- L Printed by C. J. THOMPSON, Commonwealth Government Printer, Canberra -IoF- Pesticidal Compounds This invention relates to pesticidal compounds.

European patent publication No 111 105 discloses a class o0 w-phenyl unsaturated amide compounds as insecticides, all o* these compounds having an unsaturated bond conjugated to the phenyl ring. The same document also discloses a larger class of related compounds, stated to have any 5- or 6membered aromatic ring in the w-position and without being limited to compounds having an unsaturated bond conjugated to the aromatic ring.

However, these compounds are disclosed only as acaricides. We have now Sound that insecticidal activity is lound in compounds without conjugation to the aromatic group, and also that pesticidal activity is 'ound in compounds having aromatic or partially aromatic groups with more than 5 or 6 members.

Meisters and Wailes (Aust. J. Chem. (1966), 19, 1215) disclose N-isobuty! (2E,4E)-7-phenylhepta-2,4-dienamide but assert that it had no insecticidal activity against Musca domestica at up to 100% concentration. Vig et al (J.

Indian Chem. Soc. 1974, 51(9), 817) disclose piperovatine (N-isobutyl 6-(4methoxyphenyl)-hexa-2,4-dienamide) but do not mention any insecticidal activity.

Japanese patent application No. 57/212, 150 discloses certain w-phenyl deca-, undeca- and dodecadienamides as insecticides.

European patent publication No. 142 593, having an earliest priority date o' 21st November 1983 and a publication date of 6th June 1985, discloses unsaturated amide pesticides having an w-aromatic group which is polynuclear.

All o' the compounds which are specifically disclosed have polynuclear systems which are entirely aromatic.

The invention provides compounds of Formula 3 0 Ar (CH (CK =CR NRR (I) wherein: Ar is phenyl, naphthyl, thienyl, ^luorenyl, phenanthrenyl, dibenzofuranyl or a polynuclear group (^)CH2L 0 0 0 00 '0 0.

0 0U RSB/OLM/29th January 1986 2 2 in which a is 0, 1 or 2; B is (D)b(CH 2 where each of D and E is oxygen or sulphur, b and e are independently 0 or 1 but not both 1, and c is 0, 1, 2 or 3, the sum of a, b, c and e being at least 2, and the ring containing B is wholly or partially saturated; and G is hydrogen or a benzene ring fused to the benzene ring of group any of the groups Ar may be substituted by one or more of

C

1 4 alkyl, halo-(C 4) alkyl, halo, C14 alkoxy (except 3, 4-methylenedioxy) and halo-(C -alkoxy); n is 0 to 8, except that n is 1 to 3 when Ar is phenyl or S substituted phenyl; 2 3 each of R and R is in each case independently hydrogen, C1-4 alkyl or halo-(C 4 )alkyl; and R and R are each selected from hydrogen, alkyl, C 3

-C

6 cycloalkyl, alkenyl or alkoxy (any of which may be substituted by halo, alkenyl, alkyl, cycloalkyl, alkoxy, 20 alkynyl or cyano containing 1-6 carbon atoms (or 2-6 for alkenyl and alkynyl), except that the following compounds are excluded o S0. N-isobutyl 7-phenyl hepta-(2,4)-dienamide N-isobutyl 6-phenyl hexa-(2,4)-dienamide N-isobutyl 6-(4-methoxyphenyl)hexa-(2,4)-dienamide N-isobutyl 6-(2-thienyl)hexa-(2,4)-dienamide N-isobutyl 8-phenylocta-(2,4)-dienamide N-isobutyl 6-(l-naphthyl)hexa-(2,4)-dienamide -3- A second aspect of the invention provides compounds of Formula (IA): 0 (IA) Ar-(CH )n (CR 2 =CR )2 CNRR' 1 2 3 wherein Ar, n, R, R R 2 and Rare as defined above except that, WI when n is 1 and R is H and Ar is 2-fluorenyl, 2-phenanthrenyl, 2-dibenzofuranyl, 9,10dihydro-2-phenanthrenyl, 6- or 7 -halo- 2-n aph thyl, 5,8-dibromo-2-naphthyl or 3-(9-bromo)-phenanthrenyl then R 1is not isobutyt, 2,2-dimethylpropyl,2,2dimethyl-13-butenyl, 2-methylbutyl, 1,2,2-trimethyipropyl or 1,2-dimethyipropyl, and (ii) when n is 1 an'd R is H and Ar is 2-fiaphthyl then R Iis. not 2,2dimethyipropyl, 2,2-dimethyl-3-butenyl, 2-methylbutyl or 1,2,2-.trimethylpropyl.

oo. A third aspect provides Compounds of Formula (IB): 0 (IB) /Ar-(CH (CR 2=CR3 1n 2 3;4R wherein Ar, n, R, R I, R 2, and R 3are as defined above, except that, when n is 1 and R is H and Ar is either a polycyclic wholly 00aromatic ring system joined at the 2-position or 3-phenanthrenyl, then R is not *,isobutyl, 2,2-dimethyipropyl, 2,2-dimethyl-3-butenyl, 2-methylbutyl, 1,2,2- -7 trimethyipropyl or 1,2-dimethyipropyl, with the proviso that N-isobutyl 8-(2- .naphthyl)-octa-2E,4E-dienamide and N-(1,2-dimethylpropyl)8-(2-nzaphthyl)acta-2F,4E-dienamide are not excluded.

In Formulae (IA) and the following features and any and all combinations thereof are preferred: Preferably, n is odd. Suitably, n is 1, 3 or 5, most preferably 1 or 3. The configuration of both double bonds in the diene group is preferably F.

Preferred groups for Ar include phenl, furyl, thienyl, naphthyl (especially 2naphthyl) benzofuranyl, benzopyranyl, chromanyl, indanyl, tetrahydronaphthyl, or any of the followinq qroups: w on" so o r o any of which may be substituted as above.

Any substitution of a single phenyl ring is preferably at the 3-position and is preferably halo (eg 'luoro), haloalkyl (eg trifluoromethyl) or alkoxy (eg methoxy). 3,4-Dihalophenyl is also a preferred value 'or Ar. When Ar is naphthyl or benzofuranyl, the said (CH2) n link is preferably attached at the 1position.

o 0t oU o 8 900 8s 080.00 Trifluoromethyl is particularly preferred.

trifluoromethylphenyl, particularly when n is 1.

Preferably Ar is 3- Preferably, R is hydrogen. Suitably, Rlis alkyl, C 1 6 being preferred and isobutyl, 1-methylpropyl, 2,2-dimethylpropyl, 1,2,2-trimethylpropyl and 1,2dimethylpropyl being particularly preferable. It has been found that acaricidal activity is enhanced if there is an alkyl group a to the nitrogen.

R

2 and R 3 are preferably in each case hydrogen.

RSB/OLM/29th January 1986 r P2 Compounds of Formula (IA) and (IB) may be prepared in any o' the Following ways:by amidation of the corresponding acid or acid derivative, ie. by reaction of a compound of Formula (II) with a compound o f Formula (III): (II) Ar (CH 2 )n (CR2=CR) 2 COZ' (III) HNRR 1

O

wherein Z 1 is hydroxyl, halo or a phosphoroimidate ester group (0 Aryl) NH aryi) and the other variables are as delined above; by reaction o' a compound of Formula (IV) with a compound o" Formula or (VI): 0 2 3 (IV) Ar (CH 2 )n(CR =CR CH 3 P=CH(CR =CHR 3

C()NRR

1 (VI) 2 F =CH(CR 2

=CR

3 )qC(O)NRR 1

O

wherein Z" is alkyl, alkoxy (pre'erably ethoxy) or aryl (pre'erably phenyl), and p+q=l. The locations of the aldehyde and the phosphorus containing groups, 3 P and 2 may be swapped to give an exactly analogous reaction; by 5-elimination 'rom a compound o' Formula (VII) or (VIII): (VII) Ar(CH2)n (CR 2

=CR

3 6R'RC(O)NRR X 2

Y

3 2 3 1 (VIII) Ar(CH2)nR 6 R (CR =CR )C(0)NRR wherein one of X and Y is hydrogen and the other is a group Q(O-)0 Q is sulphur or selenium and L is a suitable group such as lower alkyl (pre'erably methyl) or aryl; by reaction o' a compound of Formula (IX) with a compound of Formula (IX) Ar(CH2)nCH2-Hal 0( I r a e 0 0 0 0 00 00 a a 0 0 RSB/OLM/29th January 1986

R

2

C=CR

3 (CR2=CR 3

)C(O)NR

1 where Hal is a halogen atom, followed by reduction o' the triple bond; or by reacting a compound of Formula (XI) with a compound of Formula

(XII):

(XI) Ar (CH 2 n CRCR3-M 0 (XII) Hal-(CR 2 CR )C NRR wherein Hal is halide eg. bromide or iodide and M is a metal atom or metal group, for example com-rising zirconium, aluminium or zinc, e.g. a bis- (cyclopentadienyl) zirconium chloride group. Compounds of Formula (XI) may be made with, for example, vinyl-bis-(cyclopentadienyl)zirconium chloride in THF in the presence of a palladium catalyst.

Process is normally carried out in an aprotic solvent, such as ether, dichloromethane or benzene, optionally in the presence of a tertiary amine, such as triethylamine, but in the absence of water. If the compound of Formula is an acid halide, for example acid chloride, then it may be 'ormed from the corresponding acid by reaction with a suitable reaoent such as oxalyl chloride or thionyl chloride. When Z' is a phosphoroimidate group then this is suitably formed "rom (PhO)P(-O)NHPh Cl. The acid, or the acid 'unction in the compound of Formula may be prepared by hydrolysis of an ester, the ester being prepared by a conventional Wittig or Wadsworth-Emmons reaction, using r 0 0.

0 0 for example an aldehyde and ethoxycarbonylmethylene triphenvlphosphorane or the anion from triethylphosphonocrotonate. This latter reaction may result in an isomeric mixture, 'or example a (2,4)-hexadienoate and such a mixture may be reacted as above, and the resulting mixture of amides o separated by chromatography or other convenient techniques. When n is 1, hydrolysis of the ester is preferably acidic, *or example using aqueous Sa hydrochloric acid and dioxan.

00 0 000 OsmLse Alternatively, the ester referred to above may be derived by rearranoement and elimination on a compound of Formula (XIII): (XIII) Ar(CH) .n2CR 2

=C

l R 4

COOR

RSB/OLM/29th Januarv 1986 ;i ~a31~ wherein R 5 is any suitable group, such as phenyl, and R 4 is alkyl.

The compound of Formula (XIII) may be obtained by reaction of a compound of Formula (XIV) wita compound of Formula (XV): (XIV) Ar(CH 2 )n+ 2

CH

(XV) Ph CHz2OR 4 A further route is for the ester referred to above to be prepared by elimination on a compound of Formula (XVI): (XVI) Ar(CH 2

)-A

1

-A

2

-A

3

-COOR

wheren R is 3 as de'inrd gbove, one of A 1

A

2 nd A is (CR 2

CR

3 another oa A A and A is -CR R the third of A A and A is -CR (OR R 6 being 3_ 2 grups 6 H or acyl such as acetyl, and the said -CR R and -CR 2

(OR

6 groups are adjacent one another. The reaction is preferably carried out in an aromatic solvent, conveniently in the presence of a molybdenum catalyst and a base, such as bis-trimethylsilylacetamide Intermediates of Formula (XVI) may be obtained by reaction o' a suitable sn aldehyde with a suitable sulphinyl compound, 'ollowed by acylation.

The reaction is carried out in a suitable solvent such as acetonitrile with a base such as piperidine.

0 0 o o 0 0 Process is carried out in a dry solvent, 'or example tetrahydro'uran, optionally in the presence of a base, and preferably in the absence of oxygen, e.g. under a nitrogen atmosphere, at a low temperature. The Wittiq-type reagent may be obtained with lithium diisopropylamide.

9 9 Process is normally carried out by heating in an aprotic solvent such as benzene or toluene, preferably in the presence of an acid catalyst, such as paratoluene-sulphonic acid. Process proceeds by reaction of the compound of Formula with a base (such as lithium diisopropylamide) and the compound of Formula (IX)inanaproticsolventsuchasTHF. Process(e)ispreerablycarriedoutin an aprotic solvent such as THF, under an inert atmosphere (such as argon) and in the presence of a palladium catalyst, such as bis-(triphenylphosphine) palladium.

RSB/OLM/29th January 1986 The intermediates o- Formulae (III) (XIV) may be prepared by standard methods. For example, the compounds of Formulae and (VI) may be prepared by the reaction of an appropriate phosphine, phosphonate or hosphite with an w-halo amide. Compounds of Formula (IV) may be prepared by hydrolysis of a ketal ring or oxidation of an alcohol.

The carbonyl-containing compounds of Formula (IV) may be prepared by oxidation of the corresponding alcohol, for example using pyridinium chlorochromate or o-alyl chloride/DMSO.

The compounds of Formula may be used to control arthropods such as insect and acarine pests.

The compounds of formula may be used 'or such purposes by application o0 the compounds themselves or in diluted form in known fashion as a dip, spray, lacquer, foam, dust, powder, aqueous suspension, paste, gel, shampoo, grease, combustible solid, vapourising mat, wettable powder, granule, aerosol, emulsifiable concentrate, oil suspensions, oil solutions, pressure-pack, "o impreanated article (such as an ear tag or collar) or pour on ormulation. Dip S concentrates are not applied per se, but diluted with water and the animals immersed in a dipping bath containing the dip wash. Sprays may be applied by hand or by means of a spray race or arch. The animal may be saturated with 0t .#o S the spray by means of high volume application or superficially coated with the :oi2 spray by means of light or ultra low volume application. Aqueous suspensions may be applied to the animal in the same manner as sprays or dips. Dusts may be distributed over the animals by means of a powder applicator or incoroorated o ,e in perforated bags attached to trees or rubbing bars. Pastes, shampoos and greases may be applied manually or distributed over the surface of an inert material against which animals rub and transfer the material to their skins.

SPour-on formulations 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 retained on the animals.

o The compounds of formula may be formulated either as formulations ready 0o" f or use on the animals or as formulations requiring dilution prior to application, but both types of formulation comprise a compound of formula in intimate admixture with one or more carriers or diluents. The carriers may be liquid, solid or gaseous or comprise mixtures of such substances, and the compound of formula may be present in a concentration of 'rom 0.025 to 99% w/v depending upon whether the Lormulation requires further dilution.

RSB/OLM/29th January 1986 r~i llp__ l_ Dusts, powder and granules comprise the compound of 'ormula in intimate admixture with a powdered solid inert carrier for example suitable clays, kaolin, talc, mica, chalk, gypsum, vegetable carriers, starch and diatomaceous earths.

Sprays of a compound of formula may comprise a solution in an organic solvent 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 a mixture of the active ingredient, with or without an organic solvent and one or more emulsifiers. Solvents may be present within wide limits but preferably in an amount of from 0 to 90% w/v of the composition and may be selected from kerosene, ketones, alcohols, xylene, aromatic naphtha, and other solvents known in the Formulating art. The concentration of emulsifiers may be varied within wide limits but 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 o' hexitol anhydrides and anionic sur'ace active agents including Na lauryl sulphate, fatty alcohol ether sulphates, Na and Ca salts of alkyl aryl sulphonates and alkyl sulphosuccinates.

Wettable powders comprise an inert solid carrier, one or more surface active agents, and optionally stabilisers and/or anti-oxidants.

a

I

006 6 Emulsifiable concentrates comprise emulsifying agents, and often an organic o solvent, such as kerosene, ketones, alcohols, xylenes, aromatic naphtha, and other solvents known in the art.

o u Wettable powders and emulsifiable concentrates will normally contain from 5 to o: 95% by weight of the active ingredient, and are diluted, for example with water, before use.

.9 Lacquers comprise a solution of the active ingredient in an organic solvent, together with a resin, and optionally a plasticiser.

Dip 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 in intimate admixture with a dispersing agent and one or more surface active agents.

RSB/OLM/29th January 1986 i P2 Aqueous suspensions of a compound of formula may comprise a suspension in water together with suspending, stabilizing or other aoents. Aqueous solutions may also be formed from acid addition salts of a compound of the formula The suspensions or solutions may be applied per se or in a diluted form in known fashion.

Greases (or ointments) may be prepared from vegetable oils, synthetic esters of fatty acids or wool 'at together with an inert base such as soft paraffin. A compound of formula is preferably distributed uniformly through the mixture in solution or suspension. Greases may also be made from emulsifiable concentrates by diluting then with an ointment base.

Pastes and shampoos are also semi-solid preparations in which a compound of 'ormula 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 without further dilution they should contain the appropriate percentage o' the compound of formula required 'or treatment.

0 1 0 os Aerosol sprays may be prepared as a simple solution of the active ingredient in g the aerosol propellant and co-solvent such as halogenated alkanes and the solvents referred to above, respectively. Pour-on ormulatiaons may be made as o° a solution or suspension oa a compound of formula in a liquid medium which 0 also contains a viscous oil to minimise spreading of the formulation on the surface of the animals. An avian or mammal host may also be protected against infestation of Acarine ectoparasites by means of carrying a suitably-moulded, shaped plastics article impregnated with a compound o' rormula Such articles include impregnated collars, tags, bands, sheets and strips suitably attached to appropriate parts of the body.

The concentration of the compound of formula to be applied to an animal will vary according to the compound chosen, the interval between treatments, the nature of the formulation and the likely infestation, but in general 0.001 to 20.0% w/v and preferably 0.01 to 10% of the compound should be present in the applied formulation. The amount of the compound deposited on an animal will vary according to the method of application, size of the animal, concentration of the compound in the applied formulation, factor by which the formulation is diluted' and the nature of the formulation but in general will lie in the range o a from 0.0001% to 0.5% e-cept for undiluted formulations such as pour-on RSB/OI-M/29th January 1986 -11- P2 ormulations which in general will be deposited at a concentration in the range from 0.1 to 20.0% and preferably 0.1 to Dusts, greases, pastes and aerosol formulations are usually applied in a random fashion as described above and concentrations of 0.001 to 209o w/v of a com-ound of formula in the applied formulation may be used.

Insect pests include members of the orders Coleoptera Anobium, Tribolium, Sitophilus, Diabrotica, Anthonomus or Anthrenus spp.), Lepidoptera Ephestia, Plutella, Chilo, Heliothis, Spodoptera or Tineola spp.), Diptera Musca, Aedes, Culex, Glossina, Stomoxys, Haematobia, Tabanus, drtaea, Lucilia, Chrysomia, Callitroqa, Dermatobia, Hypoderma, Liriomyza, and Melophaqus spp.), Phthiraptera (Malophaa e.g. Damalina spp. and Anoolura e.g. LinoQnathus and Haematopinus spp.), Hemiptera Aphis, Bemisia, Aleurodes, Nilopavata, Nephrotetix or Cimex spp.), Orthoptera (e.g.

Schistocerca or Acheta spp.), Dictyoptera Blattella, Periplanet or Blatta spp.), Hymenoptera Solenoosis or Monomorium spp.), Isoptera (e.g.

Reticulitermes spp.), Siphonaptera Ctenocephalides or Pulex spp.), Thysanura Lepisma spp.), Dermaptera Forficula spp.) and Pscoptera Peripsocus spp.).

Acarine pests include ticks, e.g. members of the genera Boophilus, Rhipicephalus, Amblyomma, Hyalomma, Ixodes, Hae.maphysalis, Dermocentor and Anocentor, and mites and manges such as Tetranychus, Psoroptes, Psoreraates, Chorioptes and Demodex spp.

The compounds exhibit killing and/or knockdown activity against arthropod pests, and can be used to control larval pests as well as adult pests.

Compounds of the invention may be combined with one or more other active ingredients (for example pyrethroids, carbamates and organophosphates) and/or with attractants and the like. Furthermore, it has been found that the activity 00 of the compounds of the invention may be enhanced by the addition of a synergist or potentiator, for example: one of the oxidase inhibitor class of synergists, such as piperonyl butoxide or NIA 16388; a second compound of the invention; or a pyrethroid pesticidal compound. When an oxidase inhibitor synergist is present in a formula of the invention, the ratio of synergist to compound of formula will be in the range 25:1-1:25 eg about 10:1.

RSB/OLM/29th January 1986 -t -12- 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).

It will be understood that what we will claim may comprise: compounds of Formula processes for the preparation of compounds of Formula insecticidal and acaricidal compositions comprising a compound of Formula in admixture with a carrier: processes for the preparation of such pesticidal compositions; methods for the control of insect or acarine pests comprising the application to the pest or its environment of a compound of Formula synergised pesticidal compositions comprising a compound of Formula potentiating or non-potentiating mixtures of a compound of Formula (I) and another pesticidal compound; and novel intermediates of the preparation o' compounds o Formula especially compounds of Formula (II).

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

o t b Examole 1: (2E),(4E)-N-Isobutyl 6-ohenyl-2,4-hexadienamide Triethylphosphonocrotonate (20.85g, 83 mmol) in tetrahydrofuran (THF) was added at -70 0 C to lithium diisopropylamide (83 mmol) in THF (50ml). The oo :temperature of the mixture was allowed to reach -200C and recooled to -400C.

Phenylacetaldehyde (10g, 83 mmol) in THF (30ml) was added. The mixture was left overnight at room temperature and worked up in the standard manner. The crude material was purified by column chromatography (silica; 9:1 hexane: ether) to give a yellow oil (10g, 56%) consisting substantially of (2F,4F) ethyl 6- S. phenyl-2,4-hexadienoate and the The mixture of esters (10g), water (40ml), cone. HCI (60ml) ind dioxan (200ml) was heated under reflux for 16h. The product was extracted into ether, washed with NaHCO 3 and brine, and dried. Solvents were removed to give a crude product, (2E),(4F)-6-phenyl-2,4-hexadienoic acid and (3E,5F)-6-phenyl-3,5hexadienoic acid which was carried on to the next stage.

RSB/OLM/29th January 1986 -13- P2 Triethylamine (6.4ml, 46.3 mmol) was added to the acids (8.7g, 46.3 mmol) and phenyl N-phenylphosporamidochloridate (12.4g, 46.3 mmol) in dichloromethane (about 50ml) with cooling. The yellow solution was stirred under nitrogen Lor lhr at room temperature, and then triethylamine (6.4ml, 46.3 mmol) and isobutylamine (4.6ml, 46.3m) were added with cooling. A'ter 16hr at room temperature the reaction was worked up with ether. The crude title product was purified, first by column chromatography (silica hexane/ether) then by recrystallisation (6:4 hexane: ethyl acetate) to give colourless needles (1.7g), m.p. 119-20 0 C. Tic. Silica/ether, 1 spot Rf 0.46, GC (OV210 2000); retention time 1.3 min.

NMR: 7.16, m, aryl, H3; 6.20(3H), m, H4, H5, NH; 5.83 d, H2; 3.48(2H), d, H6; 3.16(2H), d of d, 1.8 m, 0.95 d, isobutyl.

EXAMPLE 2: (2E),(4E)-N-isobutyl 6-(3-trifluoromethylphenyl)-2,4-hexadienamide 3-Trifluoromethylbromobenzene (3g, 13.3 mmol), prop-2-yne-l-ol (13.3 mmol) bis-triphenylphosphine palladium chloride (0.2g) and cuprous iodide (80mg) in triethylamine (20ml) were reacted together at room temperature under dry nitrogen for 16hrs. The reaction was worked up and the crude product purified by column chromatography (silica/ether) (3.4g).

Compound 17mmol was subjected to catalytic hydrogenation in ethyl acetate solution in the presence o 5% palladium on charcoal. Hydrogen (820 ml) was taken up, the solution 'iltered and the solvent removed under reduced pressure to give 3-(3-trifluoromethylphenyl)-propan-l-ol which was used without further purification.

Redistilled oxalyl chloride (1.6ml, 18.33 mmol) in dry dichloromethane was cooled to -600C. Dimethyl sulphoxide (2.85g, 36.6 mmol) was added and, after 10 mins, the alcohol (3.4g, 16.7 mmol) was added. The temperature was held at -60 0 C for 1.5hrs, and then triethylamine (11.6ml, 84 mmol) was added. The mixture was allowed to reach room temperature and extracted into S dichloromethane with washing by aq. HCI, NaHCO 3 and brine. The solution was dried and the solvents removed to give 3-(3-trifluoromethylphen-l)-propan-1-ai which was used without further purification.

To methyl triphenvlphosphonium iodide (5g, 12.4 mmol)in dry THF (30ml) was added n-butyl lithium (7.8 mn at 1.6M, 12.4 mmol) at -20 0 C. After lhr, the RSB/O1-M/29th January 1986

I

i i -14- P2 aldehyde (2.5g, 12.4 mmol) in THF was added. After 18hrs at room temperature under nitrogen, the reaction mixture was worked-up in conventional fashion. The crude material was purified by column chromatography (Silica/hexane) to give, 4-(3'-trifluoromethylphenvl)-but-l-ene (2g, To N-isobutyl methylsulphinylacetamide (1.55g, 8.75 mmol) in tri'luoroacetic acid (12ml) under nitrogen at O°C, was added trifluoroacetic anhydride (1.23 ml, 8.75 mmol). After 10 mins the olefin (1.75g, 8.75 mmol) was added.

The reaction mixture was left overnight at room temperature and worked-up in conventional fashion. The crude material was purified by column chromatography (Silica, hexane/ether, 1:1) to give (E)-N-isobutyl trifluoromethylphenyl)-2-methylthio-4-hexenamide (1.06g, 32%).

Compound E (ig, 2.79 mmol) in methanol was treated with sodium periodate (0.57g, 2.65 mmol) in water (18ml) at 0oC. The mixture was left overnight and then filtered, and the filtrate was extracted with chloroform. The organic extracts were dried and the solvent removed. The crude sulphoxide was dissolved in dry toluene (20ml) and heated under reflux for 10hrs. After a standard work-up, flash-column chromatography (silica, 4:1 ether:hexane) gave the title product as a colourless solid (0.2g, m.p. 133-135 C. Tlc (silica/ether) 1 spot Rf 0.43. Glc OV210 2000) 1 peak. Retention time mins.

NMR spectrum: 7.40 m, aromatic H3; 6.08 m, H4, H5, NH; 5.83 d, H2; 3.55 m, H6; 3.18 d of d, 1.8 (1H)m, 0.95 d, isobutyl.

FXAMPLE 3 (2E).(4E)-N-isobutyl 6-(3'-fluorophenyl)-2,4-hexadienamide 4-(3-fluorophenyl)-but-3-yne-l-ol was prepared 'rom but-3-yne-l-ol and 3- 'luoro-iodobenzene using an analogous sequence to that of Example 2 and was then similarly reacted to give 4-(3-fluorophenyl)-butan-l-ol which in turn gave 4-(3-fluorophenyl)-butan-l-al as in Example 2.

Compound (0.8g, 4.8 mmol), methyl 2-phenylsulphinylacetate (0.61g, 3.2 mmol) and piperidine (0.027g, 0.32 mmol) were reacted in dry acetonitrile under nitrogen at O°C for 2 days. Working up gave a crude product which was purified by column chromatography (silica, ether/hexane) to give methyl 2-phenylsulphinyl-6-(3-fluorophenyl)-2-hexenoate oa 9,4* 4 4 O4 *4

P

4 4 4* *I 4 9 0* 9 ft own *0*000 0 RSB/OLM/29th January 1986 Potassium carbonate (anhydrous, 0.163g, 1..L8mmai) was added to a solution Of (0.34g, 0.98 mmcl) in dry xylene (3m1). After heating to reflux, the mixture was cooled and the solvent evaporated to give a crude product. Flash column chromatography (silica, ether/hexane) gave methyl -'uocrop heny1)-Z, 4 hexadienoate, (170mg).

This was treated by the method of Example 1 to give 6-(3-'1uorophenyl)-2,4hexadienoic acid which, also as in Example 1, yielded the title compound Off-white solid m.p. 108-11a; Tic (silica/ether), 1 spot, Rf 0.38; Gic 0v210 2200), Retention time 1.0 min.

NMR:7.22 m, H3; 6.90 m, aromatic; 6.15 m, HA, H5; 5.78 d, H2; 5.43 Ud, NH; 3.50, d, Ha; 3.16 d of; d, 1.8 0.92, (6H) d, isobutyl. M.P. 108 111 0

C

Examo le 4: (2F.(4E)-iN-tsobutvl 8-(3-trifluoromethvlcohenvi)-2.4-Octadienamide 3-Trifl'uoromethylbromooenzene (4g, 17.8 mmol) and but-3ye1o (12g1.

mmal) were reacted together in the presence of bis-triphenylphospohine 6 0 palladium dichloride-cuprous iodide, as in Example 2, to give 4-(3a trifIluoro me thyp henyl)-but-3 -yne-1-0 I which was subjected to a hydrogenation, as in Example 2, to give Compound was oxidised, as in Example 2, to give 4-3trifluoromethylphenyl)-butan-1-aI which (2.2g, 10.18 mmcl) was reacted with triethylp hasp honocro tonate lithium diisopropylamide, as in Example 1, to ogive ethyl 8-(3 -trif luoro methylp henyl)- 2,4-octadi eno ate

-C-

Compound (1.7g, 5.45 mmol) was hydrolysed with potassium hydroxide (1.67g, 19.07 mmnol) in aqueous ethanol at room temperature, under nitrogen.

The usual work up afforded 8-('3-trifl'uoromerhylchenyl)-2,4,-octa-dienoic acid Compound was reacted with N-.phenylchoschor2midochloridate, triethylamine and isobutylamine as in Example 1, to give (2E),(4E)-N-iSo o~tyl 8- (3-t'ri-fluoromethylohenyl)-2,4-octadienamide as a pale yellow solid (230 mg). Tic (silica/ether), 1 spot Rf 0.44, CC (0V210,230 0 retention time 1.0 min.

NMIR: 7.39 m, aryl; 7.20 m, H3; 6.10 m, H4 ,HI5; 5.31 d, H2; 5.8 bd, NH; 2.75 t, H8; 1.95 m, H6, H7; 3.20 d of d, 0.95 d, isobutyl.

Fxamole s: (2E).(LL)-N-isobutv/l 6-.(2-.nar-hthvl)-.2.L,.-.exadienamide 2-Sromonaohthalene (0og, 48.3 mmol) and but-3-yne-1-ol (3.38g, 48.3 mmol) were reacted together-, analogously to Example 2, to give 4-(2Z-naphthyl)-but-3yne-1-ol which was hydrogenated, as in Example 2, to give 4-(2-napthyl)butan-1-ol, oxidised to 4-(2--napthyl)-.butan-1-al Com pound (1.691 8.08 mmol) in dry acetonitrile was added over 1.5h. to a solution of methyl chlorochenyl~sulphinyl acetate (1.78g, 7.68 mmol) and piperidine (0.69o, 8.08 mmol) in dry acetonitrile. After 16h at room temperature, under nitrogen, the reaction was worked up to give, a-fter column chromatograpchy (silica, 8:2 ether- :.hexane)t, methyl 4-hydroxy-6-f(2-nap thyl)-2-thexeno ate (1.3 2g)(D).

Comound (1.32go 4.39 mmol), aceti;c anhydride (1.05o, 10.27 mmol) and a e triethylamine (0.7&og, 7.31L mmol) were treated with L-N.N-dimethylaminopyridine (50mg) at 0 0 C After several hours at room temoeracure. the react~on mixture was wor-ked up and the Crude 2C-2t-te Was puri-ied on a Silica column to give methyl 4-acetoxy-Q'-(2-nap thyi)-Z-he xeno ate (1.2nj(F).

,~0 Compound*(E-) (1.2o, d..05 mmol) in dry toluene (10mI) was heated under re~lux, under dry nitrogen, with bis-trimethylsilylacetamide (0.82a L,..05mmoi) and molybdenum hexacarbonyl (0.84g, 3.2 mmoi) -or about 2h. The reaction was worked up and the product purified by flash column chrornatography to give m ethyi-6(2-.nap thyl)-2, 4-he,-adieno ate (0.35g) which was hydrolysed, as in 2isb ti 4? Example 1, to give the acid, in turn converted to (2F),(AE)Nsouy 6nap hthyl)-2,4-,-hexadienamide (120mg), m.p. 138-4L0; Tic, silica/ether, Rf 0.40.

NNIR: 7.6 (7H,m, aryl; 7.25 m, H3; 6.25 (21H), m, H4, H5; 5.77 d, HZ; 5.45 bd, NH; 3.66 d, H6; 3.18 d of d. 1.80 m, 0.93 d, isobutyl.

LU

11

I

I

-17- Examcle 6: N-Isobutvi 8-(2-benzofuranvi)-2.4-actadienamide 1-lodophenoal (6g, 27.4 mmol) and but-3-yne-l-ol (2.68g, 27.4 mmol) were reacted together over a prolonged period with bis-triphenyl--hosphine palladium dichloride cuprous iodide in diethylamine to yield 4-(2-benzofuranyl)-butrn-l- 01 This compound was taken through to the title compound using a sequence analogous to that in Fxample 5, yielding 0.43g. GC (OV210 at 2500), retention time 1.5 mins.

NMR:7.20, m, aryl, H3; 6.37 s, benzofuran H3; 6.18 m, H4, 5.78 d, H2; 5.6 bd, NH; 2.08 m, H6, H7,; 2.78 t, H8; 3.21 d of d, 0.95 (6H) d, isobutyl.

Examcles 7 to 87 By analogous methods, the compounds listed in Table 1 and Table 2 were made.

The configuration of. all double bonds conjugated to the amide carbonyl was E in all specific embodiments of the invention.

Table i Ar (CH 2 )n (CH=CH)m CONHR Example No. Ar n m R (Melting Preparation Point) as Fxample No.

7. Ph 1 2 1,2-dimethylpropyl (141-2) 1 oa gt it a 4 t 0a 6 a Ita 8 ne i a.n p 0 4 a 8* i( aI 0* 88 0 08*4* 1 2 2-methoxypropyl 1 2 2-methylprop-2-ene 3 2 isobutyl 3 2 sec-butyl Example No. Ar n m R (Melting Preparation Point) as Example No.

9 94 4 4 44, 1 44 9 4 4 1

II-

9* 4 99 99 o 9 99 9 99.9 9 99 9. 9 9 99 4 9 99 9 9 9 99* 9 99 9 999, Ph Ph 3-Trifluoromethyiphenyl 3-Trif1uoro methylphenyl 3-trifluoromethylphenyl 3,5-bis-trifluorornethyiphenyi 3,5-bis-tri'luoromethylphenyi 3-Fluoropheny.

3-Fluorophen-l 3-Fluoraphenvi 3,5-Dichlorophenyl 3,5-Dichiorophenyt 2-Naphthyi 3 2 1,2-dimethyipropyl (87) 3 2 l-cyano-2methyipropyl 3 2 cyclohexyl 2 2 isobutyl 3 2 1,2-dimethyi-propyl 3 2 2-methylpropyl 3 2 isobutyl 3 2 1,2 -dime thylprop yl isobu ty I isobutyl 1,2-dime thyip rop yl 1,2-dime thyip rop yi 4-methylpentyl isobu ty I (135-7) Example No. Ar n m R (Melting Preparation point) as Example No.

26.

2.7.

28.

29.

31.

0 09 9 t 99. 9 9 II o 9 *99W 9 9 9909 99 09 0 0 0 0 99 99 9 9099 0 9 99 09 09 9 9 9* 99.999 9999 9,~ o 9 99 00 9 99** 2 -Naphthyl 2-Thienyi 2-Thienyl 2-Benzo'urany.

2-Benzofuranyl 3,5-bis-trifluoro.; methylphenyi 4-.methoxyphenyt 4-methoxyphenyt phenyi 2-nap hthyl 2-naohthyl 3-methoxyphenyl 1, 2-dimethyipropyl (100-104) isobutyl 1,2-dimethylpropyi (78-80) 1,2-dimethylpropyl isobutyl isoburtyt (119.5) isobutyl (116-19) 2-methoxypropyl 2-merhyi-2-mechoxy p rap y 1,2-dim.echylpropyl (174) 2-methoxypro'yt isabutyi (91.5-92.0) Example No. Ar n m R (Melting Preparation Point) as Fxample No.

4 1 itt it i I 4411 44 9 4 9999 *4 14 I 0 99 4 994 0 9990 9 40 99 0 04 o a 0 00 99s 6e 9 499 o a 99 4 9 99 3-rnethoxyphenyl pentafluorophenyt phenyl phenyl pheny.

p henyl phenyl phenyl 3-methoxyphenyt 4-bromophen-I 4-bromophenyl 4-bromophenyl 1 2 1,2-dirnethylpropyl 3 2 isobutyl 3 2 dimethyicyclopropyl 3 2 1,2,2-trimethyl propyt 3 2 1-ethyl-propyl 3 2 3:1, 1,2-dimethyl propyl 3 2 1,2-dimethylpropyi 3 2 I-rnethoxy-2-methyl propyl 3 2 1,2-dimethyl propyl 3 2 1,2-dimethylpropyt 3 2 1,2-dimethyipropyl 3 2 1,2,2-trimethyl propyl (97.5) (103) (78-9) (72.5) (87) (87) 6 5* Li Example No. Ar n m R (Melting Preparation Point) as Example No.

4 I 4 1 44 44., 4.

4 4 .44, U, 44 o o a 4 44 0 4 444 4 4.444 44 44 4 4 44 44 4 44 4 .44444 4 4 4 4444-4 4 4 44 09 4 3,4-dichiorophenyl 3,4--dichiorophenyl 1-.Naphthyl 1-Naphthyl phenyl phenyl 3-tO(CH 2 OPhIPh 3-(O(CH 2 C2 Me]Ph 3-tO(CH 2 2OMe]Ph 3-tO(CH 2 2OMe]Ph 2-Be nzo furanfy i 2-Benzofuranyl 2- e nzo'u rany I 1 7 ,2-dimethytpropyl 3 2 1,2,2-trimethyt propyl 4 2 1,2-dimnethyipropyl 4 2 1,2,2-tr imethyl propyl 3 2 1-fluoromethyi-2methyipropyl 3 2 I-ethynyi-2-methyl prop yi 1. 2 isobutyl (134.7) 1 2 isobutyl 3 2 isobutyl (81.5) 3 2 1,2-dimethylpropyL 5 2 isobutyl 4 2 isobutyl 4 2 b2Z-dimethylpropyl Example No. Ar n m R (Melting Preparation Point) as Example No.

2-8enzo furanyl 2-Benzofuranyl 2-Senzofuranyt 2-Benzofuranyl Phenyl 2-Thianaphthenyl 2-Thianaphthenyl 4 2 2-rnethoxypropyl 5 2 1,2-dimethylpropyl 2 2 isobutyl 2 2 1,2-dimethylpropyl 3 2 1-mnethy-2-methoxypropyl 6 2 isobut~yl 6 2 1,2-di methy [propy I 3 2 (2-(1,3-dioxalano))-methyl 5 2 1, 2-dimethyip ropy[ 3 2 I-e thy i-2-methyl-propyl j4 0 044* 0 44 0 0 0 0 0 440 00 0 04 0 0 44 0 Phenyl 1-INaphthy[ Phenyl Phenyl 3 2 cyclopentylmethyl (76.9) *44.4444 0 044 440 0 0 4* 0 0 4444 0 *t'd4440 0 0 04.044044 0 0 444 0 0 0 4444-4 Exampole 7- (2E, 4E) IT- (2 -me thoxyprooyl) 6- (3-triffluoromethvlphenyl) -hexa-2, 4-dienamide.

F>xamole 74 (2F,4F) N-Isobutyl 6-(1,2,3,4-tecrahydronaphtha-2-yl)hexa- 2 4 dienamide Sodium (1.53g) was reacted with dlethylmnalonate (10.99g) in anhvdrous ethanol (150 ml) and 2-bromo-t-tetralone (15g) (prepared by standard literature methods) was added at room temperature. The reacrtion mixture was heated under reflux 'or 2 hours under nitrogen. The ethanol was removed, the residue diluted with water and the aqueous mixture partitioned with ether and worked up in standard 'ashion to give an oil.

-23- P2 The product from above was dissolved in glacial acetic acid (225 ml) and treated with cone. hydrochloric acid (225 ml) and water (90 ml). After heating under reflux for 10 hours and allowing to cool, the mixture was partitioned between water and ether and worked up in standard fashion to give crude product acid.

The above acid (13g) in toluene (100 ml) was treated with amalgamated zinc, prepared from zinc powder (100g) and mercurous chloride (10g). The mixture was heated to reflux and cone. hydrochloric acid (140 ml) added in 2 portions.

After heating under reflux for 7 hours, the mixture was worked up in standard fashion to give 1,2,3,4-tetrahydronaphtha-2-yl acetic acid.

Sodium borohydride (1.63 g) in dry tetrahydrofuran (70 ml) was added to the above acid (7.6g) in dry THF (20 ml). After 10 mins boron trifluoride etherate (8.52g) was added and the whole stirred for 18 hrs. at room temperature under nitrogen. The reaction mixture was poured onto ice-hydrochloric acid and worked up in the standard manner to give a crude product which was purified by column chromatography to give 1,2,3,4-tetrahydronaphtha-2-yl ethanol.

The previous alcohol (4.3g) was subjected to Swern oxidation as described previously using oxalyl chloride (2.35 ml), dimethylsulphoxide (3.8 ml) and triethylamine (16.95 ml) in dichloromethane to give 1,2,3,4-tetrahydronaphtha- 2-yl ethanal.

4C. 4 The aldehyde (4g) was treated with the anion derived from triethyl phosphonocrotonate (5.75g) and lithium diisopropylamide (22.99 mmol) in tetrahydrofuran as in previous examples. The crude product was purified by column chromatography (silica: ether-hexane) to give an ester (3.65g) which was hydrolysed by aqueous hydrochloric acid/dioxane to give 6-(1,2,3,4- S tetrahydronaphtha-2-yl) hexa-2,4-dienoic acid.

The above acid (0.4g) was reacted with phenyl N-phenylphosphoramido- Schloridate (0.44g), isobutylamine (0.165 mi) and triethylamine (2 x 0.23 ml) in dichloromethane as in previous examples. After purification, (2E,4E) N-isobutyl 6-(1,2,3,4-tetrahydronaphtha-2-yl) hexa-2,4-dienamide was obtained as a colourless solid. m.p. 1220; Tic: (Silica-ether), I spot, R,0.43; NMR 7.03 M, aryl, H3; 6.10 (2H),m,H4,5; 5.76 (1H),d,H2; 3.23 (2H),d of d; 0.94(6H),d,isobutyl;2.74(4H),m,benzylic; 2.17 allylic; 1.8(4H),m, ring protons, Bui; 5.6H(IH), NH. m.p. 122.5° RSB/OLM/29th January 1986 ~i -24- Examole 75 (2E,4E) N-Isobutyl 6-(indan-Z-yl) hexa-2,4-dienamide 3-Benzoylpropianic acid (35.6g) was added to potassium carbonate (27.6g) in water (100 ml). After solution, 37% aqueous formaldehyde (6g) was added and the mixture stirred 'or 4 days. Cone. hydrochloric acid (50 ml) was added and the whole heated at 100for 30 mins. After extraction into dichloromethane, washing with aqueous sodium carbonate and standard work-up, the crude product was purified by column chromatography (silica/ether) to -yield 4benzoyl-butyrolactone.

The above lactone (13g) was heated 'or 9 mins. at 1000with conc. sulphuric acid mi). The mixture was poured onto ice and the solid product collected, dried and extracted with hot benzene. Filtration, cooling and removal of solvent from the 'iltrate yielded indanone acetic acid.

The above acid (7.1g) in glacial acetic acid (90 ml) was hydrogenated in the presence of 10% palladium on carbon (1.4g) to give indan-2-yl acetic acid.

The above acetic acid was subject to the same sequence o a transformation as described in Example 69 to give ultimately (2E,4E) N-isobutyl 6-indan-2-yl) hexa-2,4-dienamide as a colourless solid.m.p. 149 Tic; 1 spot, R,0.48. NMR; 7.05 m, aryl, H3; 6.05 (2H)m,H4,5; 5.80 (1H),d,H2; 5.98 NH; 3.23 .to. (2H),d of d; 1.8(1H),m; 0.94(6H), d, isobutyl; 2.76(4H)m,benzylic; 2.36 .(3H),m,allylic, H2.

6 Examoles 78 to 89 The compounds of Examples 78 and 79, and the following compounds prepared using procedures analogous to those of Examples 78 and 79, are described in Table 2 below: C CH Z CcO^ E. xample No. X Y a rn R 1 (Melting Ppd as in Point) example 0 0* 74. H (CH 2 2 1 1 isobutyl (122) H CH 2 1 1 isobutyl (149) r il 76.

77.

78.

79.

81.

82.

83.

84.

85.

H

H

H

7-Cl 5,6-a 5,6-a

H

H

H

(CH 2 )2 (OH.)z

CH

2

(O

2 2 (CH 2 (CH 2 2 1 (CH 2 2 (CH 2 3 (OH 2 3 -OCH 2 1,2-dimethylpropyl 2-methyl-prop -2-enyt l,2-dimethylpropyl 1,2-dimethyipropyL iso buty I isobutyl 1,2-dimethylpropyL isobutyl 1,2-,dim ethy 1 p rap yL isobutyL (123 (106) (149-50) (139) (105) (164) (177) (158) (177) 44 4 4 444 4 44 44 4~ I~ 4 44 4 4 4 044* 44 44 44 4 O 44 44 4 444 4 4404 4 4 44 4 o 44 4 4 4 4 44 4 4 4 447* t44 4 4 4 4* 44 4 *4*4 The -'allowing two compounds were also made by methods ana~logous to those described above: N,N-di(f2-(1,3-dioxalano)]-methyl)) 6.-phenyi-hexa-(2F,4E)dienamide (Example 90) and N-methyl N-(1,2-dimethylpropyt) 6-phenyihexa- (2E,4E)-dienamide (Example 91).

Further nmr data Example 8: mp. 136.5-137.5 NMR :7.22 m, aryl, H3; 6.18 m, 5.78 H2; 5.60 NH; 3.44 (2H),d,H6; 3.96 (IH), m, 1.64 1.12(3H), d, 0.92 (6H),d,i,2-dimethylpropyl Example 14: NMR: 7.18 (6H),m,aryt, H3; 6.12 m,H4,5; 5.82 (1H),d,H2; 5.90 NH; 2.59 t, HB; 2.16 (2H),m,H6; 1.85(3H), m, H7,1,2-dimethylpropyl; 3.98 (1H),m,1.12 (3H),d,0.92 (6H) 1,2-.dimethyipropyl -4' -26- Examole 76 m.c. 123.5; NMF. 7.02 (5H),m,aryl,H3; 6.11 (2H),m,H4,5; 5.78(lH),d,H2; 5.64 (IH),NH; 2.75 benzylc; 2.20 m,HL16; 1.8 m, ring hydrogiens; 3.96 (1)mL3(1H), 1.14(31H), d, 0.94 1,2dimethyipropyl BIOLOGICAL EXA NPLE A. Topical acolication to housefly (Mlusca do mesti:ca) The compounds were administered topically to 'emale Mlusca dom estica in cellosolve solution, either alone or in conjunction with a synergist (611g piperonyl butoxide). The flies were kept with sucar 'Nater and the mortality Was assessed after 24 hours. The results are given in TableA (9:Irst- two colum ns): B. Activity acainst orain cests The compounds were applied (1:5 compound:piperonyt butoxide) in acetone to grain. When dry, the grain was in-asted with -'-itoohilus oranarius or Trioolium rastaneum. The insect mortality was assessed a:tEr 7 days to0 give an LC C 5 4gure in ppm. (Table A, cciumns 3 and 4).

C. Knockdown aCtivty aoa2inst insect6 4 04 Solutions o the compounds were Mace us- in CPD (odourless petroleum d-istiilat-e)/dichloromethane and sprayed intoc a Kearns and MN/arch chamber, -or N1. domestica, or directly onto Ela-tteila oermanic2 or into a ,/Ind tunnel in which Cule- ouinaoue-;asc-;atus-- were released. The time or knoc'-down o' 509/ of the insects Was measured, and the concentration (KC 5 0 required 'or 50%/ knockdown in L~ minutes was calculated. The compound was used alone against S.oermanica, but 1:5 compound: piperonyl. butoxide against K.domesticg and C.quinouefasciatus. The results are given in columns 5, 6 and 7 of Table A.

-27- Table A Example No. MI domestica Pipette on LC 5 0 (ppm) KC 50 (4 mins) alone +6pig PB S.gran T.cast Musca Blattella Culex <0.6 <2 <0.6 0.75 3 <0.2 e<1 <0.6 <2 6 e,6 -50 c200 0.3 <0.3 <1 <0.3 <50 c200 <0O.1 <0O.1 <,0.3 e,200 <1 <20 <200 <0.5 0.3 <200 c200 <0.3 0.3 e.0.3 <0.3 <0.3 <0.3 <0.3 0.3 <50 200 <50 <0.3 <0.3 1 1 <0.3 '3 43'' 44 .4 44 4 4 '3 4 44 44 4'34 4 '-4 44 '3 33 '-4 44 0 4 44 44 4 4 4 0 4 44 4 g44 4 4 <0.3 <0.3 0.1 <0.3 <50 <200 <0.3 40.3 <200 200 <0.3 RSB/01-M/29th January 1986 -28- 33 34 36 37 38 39 41 42 43 44 46 47 48 49 51 52 53 54 56 57 58 59 60 61 62 63 64 65 66 67 68 69 71 <3 -c2 >6 <(3 >3 <3 <3 c3 1 >3 <3 c3 3 <(3 c 3 c 3 <6 (3 <3 >3 3 c 6 >6 >6 >3 >6 c 6 >1 >5 6 <200 c200 <0.3 0.3 <0.1 200 <0.1 <0.1 0.3 <200 c200 <200 e<200 0$ o a 000 6 O 00 a a a 1,004 0 ('6 0 00 0,6 8 0 a 8 o *a o 4~0 OpaO,6,6 0 0 <200 200 <200 c200 RSB/Ci1-M/29th .January 1986 -29- <6 6 >3 I1 <3 <3 <0.6 <0.

1 1 ,<1 <,0.3 e<0.3 <0.1 <200 3 <0.2 3 ft ft 48 00 it 4 48 00 ci 0 4 o 44 0 ci 0 4 48 4* 0 o 0 0 ci 00 D. Acaricidal activity The compounds were tested by injecting l1vig in cellosolve into 'emale Boophilus micro~lus adults and assessing the percentage inhibition o' reproduction (MIR) over 2 weeks. The results are given in Table B: Table B Compound of Example No.

1R Compound o' Ex. No.

IR

44 o 'SO 0*0000 ci ci 100 100 RSB/OLM/29th January 1986 I I ft ~ft.

ft C~ ft ft. ft ftt ft*ft* ft ft q ft ft ft ft ft ft ft ft ft.

#0 ft *ft ft 6*ft ft*ft CC ft ft ft The compounds preferred.

of Examples 8, 14, 78 and 80 are particularly Formulations 1. Emulsifiable Concentrate Compound o' Example 1 Ethylan KEC Xylene Butylated Hydroxyanisole 10.00 20.00 67.50 2.50 100.00 -31- P2 2. Wettable Powder Compound of Example 1 25.0 Attapulgite 69.50 Sodium isopropylbenzene sulphonate 0.50 Sodium salt of condensed naphthalene suiphonic acid 2.50 Butylated hydroxytoluene 2.50 100.00 3. Dust Compound of Example 1 0.50 Butylated Hydroxyanisole 0.10 Talc 99.40 100.00 tki Bait 4Compound of Example 1 40.25 pp*Icing Sugar 99.65 Butylated hydroxy toluene 0.10 O 100.00 0 5. Lacquer Compound of Example 1 0Resin 00 0Butylated Hydroxy anisole High aromatic white spirit 92.0 100.00 RSB3/OLM/29th January 1986 6. Aerosol Compound o' Example 1 0.30 Butylated Hydroxy anisole 0.10 1,1,1-Trichloroethane 4.00 Odourless Kerosene 15.60 Arcton 11/12. 50:50 mix 80.00 100.00 7. Soray Compound o' Example 1 0.1 Butylated Hydroxy anisole 0.1 Xylene 10.0 Odourless Kerosene 89.8 100.00 8. Potentiated Soray 04 0ICompound a' Example 1 0.1 Permethrin 0.1 Butylated Hydroxyanisole 0.1 Xylene 10.1 Odourless Kerosene 89.8 440 4100.0 RSB/O0fvI/29th January 1986

Claims (7)

1. A compound of Formula Ar n 2= 3 Ar(CH (CR =CR 2 \NRR (I) wherein: Ar is phenyl, naphthyl, thienyl, fluorenyl, phenanthrenyl, dibenzofuranyl or a polynuclear group in which a is 0, 1 or 2; B is (D)b(CH 2 )c(E)e where each of D and E is oxygen or sulphur, b and e are independently 0 or 1 but not both 1, and c is 0, 1, 2 or S 3, the sum of a, b, c and e being at least 2, and the ring 15 containing B is wholly or partially saturated; and G is hydrogen or a benzene ring fused to the benzene ring of group any of the groups Ar may be substituted by one or more of C1-4 alkyl, halo-(C14)alkyl, halo, C 4 alkoxy (except 3, 4-methylenedioxy) or C1- 4 halo- -alkoxy; n is 0 to 8, except that n is 1 to 3 when Ar is phenyl or substituted phenyl; each of R and R is in each case independently hydrogen, C1-4 alkyl or halo-(C14)alkyl; and R and S R are each selected from hydrogen, alkyl, C -C 6 B 3 6 cycloalkyl, alkenyl or alkoxy (any of which may be substituted by halo, alkenyl, alkyl, cycloalkyl, alkoxy, alkynyl or cyano) containing 1-6 carbon atoms (or 2-6 for alkenyl and alkynyl), except for the following compounds N-isobutyl 7-phenyl hepta-(2,4)-dienamide N-isobutyl 6-phenyl hexa-(2,4)-dienamide N-isobutyl 6-(4-methoxyphenyl)hexa-(2,4)-dienamide N-isobutyl 6-(2-thienyl)hexa-(2,4)-dienamide N-isobutyl 8-phenylocta-(2 ,4)-dienamide N-isobutyl 6-(l-naphthyl)hexa-(2,4)-dienamide

2. A compound according to claim 1 wherein n is odd. /AL 4 3. A compound according to claim 1 wherein the configuration of both double bonds in the diene group is E. 7 S/sy P2C -34-

4. A compound according to any one of claims 1 to 3 wherein Ar is phenyl, furyl, thienyl, naphthyl, benzofuranyl, benzo- pyranyl, chromanyl, indanyl, tetrahydronaphthyl, or any of the following groups 00a any of which may be substituted as in claims 1 to 3. A compound according to claim 4 wherein Ar is phenyl or phenyl substituted at the 3-position by halo, haloalkyl or alkoxy or Ar is 3,4- dihalophenyl.

6. A compound according to any one of claims 1 to 5 wherein R is hydrogen and R is isobutyl, 1-methylpropyl, 2,2-dimethylpropyl, 1,2,2- trimethylpropyl or 1,2-dimethylpropyl. 1 2 3

7. A compound according to any one o' claims 1 to 6 wherein-R and R are a, in each case hydrogen. 4 a a

8. A process for preparing a compound according to any one of claims 1 to 7 by a S by reaction of a compound of Formula (II) with a compound o' Formula (II): (II) Ar (CH2 n (CR 2 =CR32 COZ' (III) HNRR 1 O wherein Zl is bydroxyl, halo or a phosphoroimidate ester group (0 Aryl) NH aryl) and the other variables are as de'ined in claim 1; RSB/OLM/31st January 1986 2 b) reaction of a compound Formula (IV) with a compound Formula MV or (VI): 0 2 3 1 Mv (z"9 3 P=CH(CR 2=CHR 3 )q C(0)NRR1 NOI 2 P =CH(CR 2 -CR 3 )q C(0)NRR 1 wherein Z" is alkyl, alkoxy (preferably ethoxy) or aryl (preferably phenyl), and p+q=1. The locations of the aldehyde and the phosphorus containing groups, (Zl) 3 P and 2 may be swapped to give an exactly analogous reaction; 5-elimination from a compound o' Formula (VII) or (V11I): (VII) Ar(CH 2 )n(CR 2 CR 3) 6R R C(0)NRR 1 X 2Y 3 2 31 (VIII) Ar(CH 2 6R R (CR -CR )C(C)NRR wherein one of X and Y is hydrogen and the other is a group where Q is sulphur or selenium and L is a suitable group; reaction of a compound o" Formula (IX) with a compound of Formula (IX) Ar(CH9)CH -Hai 2 3 1 R 2C_=CR 3(CR 2 -CR 3 )C(O)NR' where Hal is a halogen atom, followed by reduction of the triple bond; or by reacting a compound of Formula (XI) 'with a compound of Formula (XII): 2 C 3 (XI) Ar (CH 2 )n R= (XII) Hai-(CR 2=CR 3)9NRR 1 wherein Hal is halide and M is a metal atx'm or metal group, RSB/OLM/3lst January 1986 -36

9. A pesticidal composition comprising a compound Ar (CH 2 n (CR 2 CR 3 2 NRR 1 wherein: Ar is phenyl, naphthyl, thienyl, fluorenyl, phenanthrenyl, dibenzofuranyl or a polynuclear group in which a is 0, 1 or 2; B is (D)b(CH 2 )c(E)e where each of D and E is oxygen or sulphur, b and e are independently 0 or 1 but not both 1, Sand c is 1, 2 or 3, the sum of a, b, c and e being at least 2, and the ring containing B is wholly or partially saturated; and G is hydrogen or a benzene ring fused to the benzene ring of group any of the groups Ar may be substituted by one or more of C14 alkyl, halo-(C 4 alkyl, halo, C14 alkoxy (except 3,4-methylenedioxy) or C 4 halo- -alkoxy; n is 0 to 8, except that n is 1 to 3 when Ar is phenyl or o 25 substituted phenyl; 0 00 e2 3 Seach of R and R is in each case independently hydrogen, C 1 4 alkyl or halo- (C 1 4 alkyl; and R and 1 R are each selected from hydrogen, alkyl, C3-C 30 cycloalkyl, alkenyl or alkoxy (any of which may be substituted by halo, alkenyl, alkyl, cycloalkyl, alkoxy, alkynyl or cyano) except for the following compounds N-isobutyl 7-phenyl hepta-(2,4)-dienamide N-isobutyl 6-phenyl hexa-(2,4)-dienamide N-isobutyl 6-(4-methoxyphenyl)hexa-(2,4)-dienamide N-isobutyl 6-(2-thienyl)hexa-(2,4)-dienamide N-isobutyl 8-phenylocta-(2,4)-dienamide r N-isobutyl 6-(1-naphthyl)hexa-(2,4)-dienamide together with one or more pesticidally acceptable carriers. S/sy I I 36A A method of combatting pests by applying to a locus a compound according to any one of claims 1 to 8 or a composition according to claim 9. DATED 14th day of February 1990 THE WELLCOME FOUNDATION LIMITED By their Patent Attorney GRIFFITH HACK CO t $11 ~S3 4 5* *D 4 *p *1*44 4*44