IL116562A - 1,2,3,4-substituted naphthalene compounds for use as pesticides, their preparation and use - Google Patents

Description

116562/2 υ ιη>υτ ΐ 3,2,1 im»j>a η βί »η .mron* 1,2,3,4-Substituted naphthalene compounds for use as pesticides, their preparation and use British Technology Group Ltd C.100403 116562 3 FESTICH AL COMPOUNDS The present invention relates to certain 1,2,3, ^substituted naphthalene compounds useful as pesticides against hitefly and/or lepidoptera pests; to methods for preparation of these compounds; to compositions containing them and id use of the compounds and compositions for the control of whitefly and fungal pests.

US 2,572,946 discloses a composition for the control of mites and aphids in which the active ingredient is a compound of the general formula (PI) where R is a radical, containing from 6 to 15 carbon atoms, selected from alkyi, cyciohexyl and cyclohexylalkyl groups; n-alkyl, iso-alkyl, alkylcycloalkyl and aralkyi groups being exemplified. No specific miticidal or aphicidal data is given for these compounds and thus no indication is given as to which of the many compounds is best or, indeed, whether these are useful for control of pests other than mites and aphids.

EP 000222$ genetically discloses compounds of Hie general formula (P8) in which R is a substituted or unsubstituted C3-12 cycloalkyl group. The compounds are said to be active against Tkeileria in cattle and sheep, though only the compound in which R1 is cycloheptyi is shown to have such activity.

DE 2641343 Al generically discloses compounds of the general formula (P2) in which is a straight, branched or cyclic Cg.14 alkyl group, R2 is a straight or branched Ci„i7 alkyl, ¾.χ7 alkenyl, C3^ cycloalkyl, alkoxy, -C¾0CH3» -CH20CH2CH3 or -CH=CH-COOK group, and X and Y represent a hydrogen, fluorine, chlorine or bromine atom or a methyl or methoxy group. These compounds are said to exhibit acaricidai and aphicidal activity but only compounds where j is a linear Cg or C\ 1 4 alkyl group are shown to have such activity.

US 4,1 10,473 concerns a method for protecting plants from mites (acarids) which comprises treating the plant with a compound of the general formula (P3) where Y is hydrogen, fluorine, chlorine or bromine; Rj is branched, cyclic or straight chain Cg.14 alkyl; R2 is branched or straight chain C _\2 saturated alkyl or C3.J2 unsaturated alkyl optionally substituted by one or two chlorine, bromine, methoxy or ethoxy substituents, or C3. cycloalkyl.

GB 1553424 discloses compound of general formula (P3) wherein R^ is H and R^ is optionally substituted cyclohexyl, for use as an active agent for treatment of infection of cattle with theilerosis, while EP 0123238 and EP 0123230 relate to similar such compounds for use as antiprotozoal! and anti-coccodiosis agents.

DE 3801743 Al generically discloses compounds of the general formula (P4) 0 in which n is 0 to 12, R1 represents hydrogen or an optionally substituted alkyl, aralkyl, alkylcarbonyl, (hetero)arylcarbonyl, alkoxycarbonyl, alkylsulphonyl or arylsulphonyl group, and R^ represents a haloalkyl, optionally substituted (hetero)aryl or substituted cycloalkyl group. These compounds are said to exhibit acaricidal and fungicidal activity. Ten compounds are specifically disclosed of formula (P4) in which n is 0, R^ is a hydrogen atom and R2 is a 4-(t-butyl)cyclohexyl, 4-(trimethylsilyl)cyclohexyl, 4-(cyclohexyl)-cyclohexyl, 2-trifluoromethylcyclohexyl or 3,5-di(trifluoromethyl)-cyclohexyl group or n is 0, Rl is an ethanoyl group and R2 is a 4-(t-butyl)cyclohexyl, 4-(cyclohexyl)cyclohexyl, 2- or 3-trifluoromethylcyclohexyl or 3,5-di(trifluoromethyl)-cyclohexyl group. Of these, acaricidal activity is demonstrated for two compounds of formula (P4) in which n is 0, p is a hydrogen atom and is a 4-(i-butyl)cyciohexyi or 4-(trimethylsilyl)-cyciohexyl group.

EP 0077550 (corresponding to IL 68,999) discloses compounds of general formula (PS) in which R is an alkyl group of from 1 to 10 carbon atoms and describes their use in veterinary formulations, particularly for prophylaxis against protozoan infection.

International application No. WO 95/32176- Al relates to naturally occurring compounds of the general formula ( 6) in which R represents a hydrogen atom or a hydroxyl or an ethanoyloxy group, and relates to their use as pesticides, especially fungicides, insecticides and/or acaricides. These compounds were previously disclosed as plant metabolites by Chamy et al, (1993) Bol. Soc. Chil. Quim. 38 187-190.

Numerous 2-hydroxy or 2 alkoxy- 3 -substituted naphthalene- 1,4-dione compounds have been disclosed by Fieser et al and other workers for use in treatment of malaria (see eg. US 2553647, US 3578685 and JACS (1948) Vol 70 pp3151, 3156-3165) or as antitumour agents (see FR 2085660). These include a number of 3-isoalkyl substituted compounds.

The present inventors have determined that many of the prior art naphthoquinones do not have high activity against whitefly, and particularly that most of the aphicidal and acaricidal compounds specifically disclosed in the prior art have dissapointing efficacy when tested against whitefly of resistant and susceptible types.

The present inventors have now detemiined that certain synthetic naphthoquinones and related 1,4 derivatized compounds have advantageous pesticidal properties over those disclosed for such use in the prior art, particularly as applied to treatment of whitefly. Preferred synthetic compounds of the invention have excellent pesticidal activity against, inter alia, whitefly and or fungi, with most preferred compounds also showing good activity against mites and/or aphids. The compounds identified by the present inventors have particular use against strains of whitefly and fungi that have become resistant to currently commercially available pesticides.

According to a first aspect of the present invention there is provided a compound of general formula (I) or a salt thereof for use as a pesticide against whitefly and/or lepidcptera pests, in which n rePresents 211 integer from 0 to 4: m repres_ents an integer 0 or 1 ; "each R independently represents a halogen atom or a nitro, cyano, hydroxyl, alkyl, alkenyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, haloalkenoxy, amino, alkylamino, dialkylamino, alkcxycarbonyl, carboxyl, alkanoyl, alkylthio, alkyisulphinyi, alkylsulphonyl,- carbamoyl, alkylamido, cycloalkyl, aryl or aralkyl group; R* and R^ each independently represent an optionally substituted alkoxy group or together represent a group =0, =S or =N-OR^, where R^ represents a hydrogen atom or an optionally substituted alkyl group; RJ represents a hydroxyl group, or a group -OL where L is a leaving group, or a group which in vivo is transformed into a group -OL^ where is a leaving group; R^ and R^ independently represent an optionally substituted alkoxy group or together represent a group =0, =S or =N-OR^, where R^ is as previously defined; and wherein R4 and R5 independently represent a hydrogen or halogen atom or an optionally substituted alkyl or alkenyl group, or together with the interjacent carbon atom represent an optionally substituted; -cycloalkyl or cycloalkenyi group; and A represents a straight or branc ed chain alkyl or alkenyl group, which may be optionally substituted, preferably with -4- halogen, an acyclic carbon chain of which links the 3 position of the naphthalene ring shown and the moiety -CHR^R^ and wherein A does not include a quaternary carbon atom in that chain; and wherein the total number of carbon atoms in the longest carbon chain running from the 3-position of the naphthalene ring shown is no more than 8.

Preferably the total number of carbon atoms in the longest chain running from the 3-position is from 3 to 8, more preferably from 3 to 5. Where the number of carbon atom is restricted to 1 or 2, whitefly activity is lost but antifungal activity remains high.

The present use particularly provides compounds for use against whitefly and/or fungi, eg. R. solani, P. oryzae and A. niger, that have developed resistance to one or more commercially available non-naphthoquinone based pesticides, and most preferably against whitefly species Bemisia tabaci such as Ned 1/2, Ned 7, and PAC; these having been determined by the present inventors to be particularly susceptible to the pesticidal actions of the presently identified compounds as compared to those of, for example, those compounds specifically tested in US 2572946, US 41 10473 and DE 2641343. Although DE 3801743 lists some of the present used compounds per se and describes them as useful against many different species of insect and fungus, no indication is given as to the significantly advantageous application of such compounds to combating whitefly.

When the compounds of formula I contain a group defined as an alkyl, alkenyl or alkynyl substituent group otherwise undefined, this may be linear or branched and may contain up to 12, preferably up to 6 and especially up to 4, carbon atoms. A cycloalkyl or cycloalkenyl group may contain from 3 to 10, but most preferably contains 5 to 8 carbon atoms. An aryl group may be any aromatic hydrocarbon group, especially a phenyl or naphthyl group. An aralkyl group may be any alkyl group as defined above which is substituted by an aryl group as defined above, especially a beri2yl group, or may be an aryl group substituted by an alkyl group.

When any of the foregoing substituents are designated as being optionally substituted, the substituent groups which are optionally present may be any one or more of those customarily employed in the development of pesticidal compounds and/or the modification of such compounds to influence their activity, persistence, penetration or other •5- property. Specific examples of such substituents include, for example, halogen atoms, nitro, cyano, hydroxyl, alkyl, alkenyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, amino, alkylamino, dialkylamino, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido, cycloalkyl, phenyl and benzyl groups. Typically, 0-3 substituents may be present. When any of the foregoing substituents represents or contains an alkyl substituent group, this may be linear or branched and may contain up to 12, preferably up to 6, and most preferably up to 4, carbon atoms. When any of the foregoing substituents represents or contains an aryl or cycloalkyl moiety, the aryl or cycloalkyl moiety may itself be substituted by one or more halogen atoms, nitro, cyano, alkyl, alkenyl, haloalkyl, haloalkenyl, alkoxy or haloalkoxy groups. Preferably, the aryl moiety is a phenyl moiety and the cycloalkyl moiety contains from 3 to 8, preferably 4 to 7, carbon atoms.

It is preferred that R, if present, represents a halogen atom or a nitro, cyano, hydroxyl, Cj.4 alkyl, Cj_4 haloalkyl, C2-4 alkenyl, C2.4 haloalkenyl, Cj_4 alkoxy, Cj.4 haloalkoxy, Cj_4 alkylamino, di-Cj_4 alkylamino, C1.4 alkoxycarbonyl, Cj_4 alkylthio, Cj_4 alkylsulphinyl or C 1.4 alkylsulphonyl group.

More preferably, R, if present, represents a halogen atom or a Cj_ alkyl, Cj_4 haloalkyl, C2.4 alkenyl, C2.4 haloalkenyl, Cj_4 alkoxy or C 1.4 haloalkoxy group. Preferably, n is 0, 1 or 2 and it is especially preferred that n is 0.

It is also preferred that R^ and R2 each independently represent a Cj_4 alkoxy group, especially a methoxy group, or together represent a group =0 or =N- OR9 , where R9 represents a hydrogen atom or a C 1.4 alkyl, especially a methyl, group. It is especially preferred that R^ and R^ are both methoxy or together represent a group =0.

When R^ is a group -OL where L is a leaving group, or a group which in vivo is transformed into a group -OL^where is a leaving group, the leaving group may be any group customarily employed as a leaving group. It is preferred that the leaving group is such that the pKa value of the acid LOH or L^OH in water is from 1 to 7, more preferably from 1 to 6 and especially from 1 to 5.

When R^ represents a group which in vivo is transformed into a group -OL^ where L is a leaving group, it is preferred that the transformation is carried out in a plant to be protected or a pest to be combated, preferably by action of enzymes within the plant or pest.

For instance, if R3 represents a β-acid group, such as -O-CH2CH2CO-OH where -CH2CH2CO-OH is not a leaving group, it may be subjected to enzymatic oxidation in vivo to form a group -0-CO-CH2-CO-OH, e.g. by a β-oxidase, where -CO-CH2-CO-OH is a leaving group.

Preferably, R3 represents a group -OR^ where R}® represents a hydrogen atom, an optionally substituted alkyl, alkenyl, aryl or aralkyl group or a group -CO-R^ 1 , -CO-O-R1 1, -SOR1 1, -SO2-R1 1, -P(X)(OR12)(OR13), -P(X)(R12)(OR1 3), -P(ORI 2)(OR13) or -P(R^2)(OR^3) where R^ ^ represents a hydrogen atom, an optionally substituted alkyl, alkenyl, aryl or aralkyl group or a group -NR^R^3; R'2 and R^3 independently representing a hydrogen atom or an optionally substituted alkyl group and X represents an oxygen or sulphur atom. Where R^ or R^ ^ represents an optionally substituted aryl or aralkyl group, it is preferred that the aryl group or moiety is a phenyl group or moiety and that the optional substituents are selected from halogen atoms, nitro and Cj_4 alkyl groups. Substitution at the 4-position of the phenyl ring is particularly preferred. For the purposes of R3, the term optionally substituted includes, e.g.. substitution with silicon containing groups, e.g.. trialkylsilyl groups such as trimethylsilyl, as a substituent on R^, R^ ^ or R^2.

Preferably R3 represents a hydroxyl group or a group -0-CO-Rn or -0-CO-ORn where R^ represents a hydrogen atom or a \_\2 alkyl, Cj_j2 haloalkyl, Cj_i2 hydroxyalkyl, Cj_j2 carboxylalkyl, phenyl or benzyl group.

It is particularly preferred that R3 represents a group -OH or -O-CO-R^, where R11 represents a hydrogen atom or a C \. alkyl, C\.^ haloalkyl, phenyl or benzyl group. Most preferred for R^ is a methyl, ethyl, propyl or butyl group.

Preferably, R^ and R^ independently represent a Cj_4 alkoxy group or together represent a group =0 or =N- OR9 where R9 represents a hydrogen atom or a C 1.4 alkyl group, but it is especially preferred that R? and R^ are both methoxy or together represent a group =0.

It will be realised by those skilled in the art that compounds wherein R^ and R2, and R^ and R8 are each alkoxy, or in pairs =S or a group NOR9, will be potential biological precursors for the corresponding naphthoquinones; the naphthoquinones being the preferred compounds of the invention.

Preferably, R^ and R^ represent a hydrogen, C\. alkyl or haloalkyl, C2.7 alkenyl -7- or haloalkenyl group or, together with the interjacent carbon atom, represent a cycloalkyl or cycloalkenyl group which is optionally substituted with a halogen, methyl, ethyl, ethenyl or halomethyl, haloethyl or haloethenyl group.

The compounds of formula I may form salts, e.g. when R3 represents a hydroxyl group. Suitable bases for forming such salts include inorganic bases, such as sodium hydroxide, potassium hydroxide or sodium carbonate, and organic bases, for example tertiary amines such as triethylamine and cyclic amines such as pyrrolidine.

It will be appreciated by those skilled in the art that many of the compounds for the use of the present invention will exist as different geometric isomers and diastereomers. The invention thus includes both the individual isomers and mixtures of these.

In a first preferred distinct group of compounds for the use of the first aspect of the invention the moiety -CHR^R^ is provided immediately adjacent the naphthalene ring wherein R^ and R-> independently represent a hydrogen, halogen or an optionally halo-substituted alkyl or alkenyl group.

In this first preferred group compounds of general formula (II) or a salt thereof are used in which R, R1, R2, R3, R7 and R8 and n are as defined for formula I and R^ and R^ independently represent a hydrogen or halogen or an alkyl or alkenyl group that is optionally substituted while remaining within the limits for carbon chain length set out for formula I.

More preferred compounds of the general formula (II) are those where n is 0, R1 with R2, and B? with R^ are both =0; wherein one of R^ and R^ represents hydrogen, C _ alkyl or haloalkyl or a C . alkenyl or haloalkenyl group and the other is independently selected from C\_-j alkyl or haloalkyl or a C2.7 alkenyl or haloalkenyl group. R3 is preferably -OH, -O-CO-R1 1 or -O-CO-O-R1 1 where R1 1 is C]_3 alkyl, most preferably -OH It is found by the inventors that compounds of this first preferred group generally have good activity against whitefly and, when the longest 3 position chain is 7 carbons or less, fungi, eg. R. solani, P. Oryzae and A. niger, while retaining activity against mites.

In a second preferred distinct group of compounds provided for the use of the first aspect of the invention the moiety -CHR^RS is provided as part of a cycloalkyl or cycloalkenyl ring and thus this second group of preferred compounds of formula (I) are of preferred formula (III) wherein n, A, R, R1 , R2, R3, R7 and R8 are as defined for general formula (I); m represents an integer 0 to 1 ; and R^ and R^ together with the interjacent carbon atom represent an optionally substituted C5.7 cycloalkyl or cycloalkenyl group.

More preferably the compounds of this group are of formula (III) wherein R^ with R2, and R7 with R8 are both =0; n and m are 0; and R^ and R^ together with the interjacent carbon atom represent a fully saturated cycloalkyl ring which is optionally substituted.

Still more preferably R4 and R5 together with the interjacent carbon atom represent a C5.7 saturated cycloalkyl ring substituted with halogen, most preferably chlorine or fluorine, or with C]_4 alkyl or haloalkyl or C2.4 alkenyl or haloalkenyl group R2^. Most preferably R^ and R^ together with the interjacent carbon atom represent a cyclopentyl or cyclohexyl ring substituted in one or more of the 2, 3 or 4 positions with a group Preferred compounds of this second preferred group of the invention are exceptionally effective against whitefly, especially species of B. tabaci. as well as certain fungi when the longest 3 position chain is 7 carbons or less.

In a third distinct group of compounds of the first aspect of the invention the moiety -CHR4R jogs not represent a cycloalkyl or cycloalkenyl group and is provided spaced by between 2 and 6 carbon atoms length away from the naphthalene ring, and most preferably 116562/2 between 2 and 4 carbon atoms length away from the naphthalene ring.

Thus in this distinct group of compounds for the use of the invention the compounds of formula (I) are of preferred formula (IV) wherein n, A, R, R1, R2, R3, R? and R^ are as defined for general formula (I); and R4 and R^ each independently represent a halogen or optionally substituted alkyl or alkenyi group.

More preferred compounds of this group are of formula (IV) wherein R^ with R2, and R7 with R° are both =0; A is a C2-6 ^kyl, haloalkyl, alkenyi or haloalkenyl chain, which may be substituted by a halogen or a branch chain which may be halogenated. Preferably R4 and R^ are C2.6 alkyl or haloalkyl or C2-6 alkenyi or haloalkenyl. R^ is preferably -0-CO-R1 1 or -0-CO-O-R1 1 where R1 1 is alkyl, most preferably OH.

Preferred compounds of this group are those where A is a group -(CH2)A- where a is an integer of 1-6 or where a and b are integers which add up to 0 to 4, and analogues of these wherein one or more of the carbon atoms in the these groups are substituted by alkyl, haloalkyl, alkenyi, haloalkenyl or halogen.

Particularly effective compounds of formula (III) for the use of the invention are those wherein one or more of A, R4 and R5 includes a haloalkyl or haloalkenyl group, particularly a trifluoromethyl group. Preferred compounds include those where -A-CHR4R5 is an isofluoroalkyl group, eg. such as 2-trifluoromethylpropyl or 2,2-di-trifluoromethylethyl. Both unsubstituted and halogenated compounds have good activity against the aforesaid fungi when the longest chain at the 3 position is up to 7 carbons.

A second aspect of the present invention provides novel compounds of formula (I), wherein R4 and R54 independently represent a C1-7 alkyl or haloalkyl group or C2-7 alkenyi or haloalkenyl group, in which at least one of R4 and R5 is a haloalkyl group. - 10 - 116562/2 Preferred 2-substituted cycloalkyl compounds, such as 2-hydroxy-3(-2-methyl-cyclohexyl)-naphihalene-l,4-dione, are not only novel, but have surprisingly high activity against whitefly as compared to the 3- and 4- substituted cycloalkyl compounds.

Preferred isohaloalkyl compounds, such as 2-hydroxy-3-(2-trifluoromethylpropyl)-naphthalene-l,4-dione, are not only novel, but have high activity against mites as well as whitefly and fungi.

A third aspect of the present invention provides a method of combating the aforesaid insect and/or fungal pests at a locus which comprises treating the locus with a compound of the general, formula (I), preferably of general formula (II), (III) or (IV).

Preferably, the locus comprises the pests, i.e. insects, acarids and/or fungi, per se or environments subject to or subjected to attack by pests. More preferably, the locus comprises the pests per se, stored food material, plants or animals subject to or subjected to attack by pests, seeds of such plants or the medium in which such plants are growing or are to be grown. Specifically, compounds of formula I may be used in a domestic environment for spraying rooms to combat infestation by houseflies or other insects, acarids or fungi, in a horticultural or agricultural environment for treatment of stored crops, especially cereals, or to spray growing crops such as cotton or rice to combat infestation by pests, particularly whitefly and related species, and in a medical or veterinary environment, for instance, as a cattle spray to prevent or treat infestation by insects or acarids.

In a fourth aspect the present invention also provides processes for the preparation of compounds of formula (I) and particularly of formula (II), (III) and (IV) as defined above.

In a preferred process for preparing compounds of formula (I), (II), (III) and (IV), a compound of the general formula (V) in which n, R and R-* are as defined above, is reacted with a carboxylic acid CHR4R5-(A)m-COOH where R4 and R5 are as defined above, in the presence of a free radical initiator, such as ammonium peroxysulphate and silver nitrate in a suitable solvent, such as aqueous acetonitrile, to form a compound of the general formula (I), (II), (III) or (IV).

In a still further process for preparation of the compounds of the present invention the compound of formula (V) is reacted with a compound of formula X-(A)m-CHR4R5 wherein R4, R5, A and m are as defined for formula I and X is a leaving group that will leave the compound to give a charged radical +(A)m-CHR4R^; eg. X may be a halogen atom or tosyl group. This reaction is carried out in the presence of an acid, eg. a Lewis acid such as aluminium chloride, using conditions broadly as described by Fieser and Gates (J. Am. Chem. Soc. (1941) 63, 2943-2953.

Compounds of formula (I) obtained by these processes may then be further reacted using the derivatisation processes described above or combinations thereof to obtain further 7compounds of formula (I), as desired.

For use in this alternative method, in the case where R4 and R^ together with their interjacent carbon atom form a cycloalkyl or cycloalkenyl ring of from 3 to 10 carbons, many of the cycloalkyl and cycloalkylenecarboxylic acids are commercially available and the carboxylic acid groups thereon may be extended by known techniques to give access to longer carbon chain lengths, and then substituted if required using techniques well known to those skilled in the art. For example the Arnst-Elstert reaction may be used to give a -CH2" extension (see e.g.. Meier and Zeller (1975) Angew. Chem. Int. Ed. Ewgl. 14. 32). Alternatively compounds where m is 1 may be accessed by the reaction of the corresponding cycloalkanone with ethyl cyanoacetate and subsequent reaction with a Grignard reagent, followed by hydrolysis to yield the cycloalkyl acetic acid (see e.g. Amsterdamsky et al (1975) Bull. Soc. Chim. Fr. (3-4 Part 2), p635-643 and Muhs M. A. PhD Thesis, University of Washington, Diss Abst. 14, 765 ( 954) to increase the carbon chain length in increments of 1.

For preparation of compounds containing R4 R5 rings having higher numbers of carbons, the corresponding monobromo-substituted cycloalkyl or cycloalkenyl compounds -12- may be converted to the carboxylates by formation of the Grignard compound using magnesium and then treating this with CO2, e.g.. in the form of dry ice. The carboxylic acid so formed may be converted to the alkyl carboxylate by alkylation using, e.g. a compound R^-I, e.g. methyl iodide, in the presence of butyl-lithium, where is a group as defined above that is stable under these conditions.

Substitutions, e.g. alkylation, of the cycloalkyl/cycloalkylene ring at positions other than the 1 -position to the carboxylate may be accomplished by methods known to those skilled in the art. Starting from the ring mono-unsaturated cycloalkylene carboxylic alkyl esters, alkylation may be directed at the desired position as previously described and then, using light as initiator, reaction with e.g. CF3X allows introduction of CF3- groups with reduction using palladium carbon catalysis conditions allowing saturation of the unsaturated bond. Many other manipulations will occur to those skilled in the art for the purposes of accessing other compounds of the general formula (I).

Compounds of formula (I) in which represents a leaving group as defined above may be prepared by reacting a compound of formula (I) in which represents a hydroxyl group with a compound X-L, where X represents a halogen atom, in the presence of an organic base, preferably a tertiary amine such as triethylamine, or an inorganic base such as sodium carbonate. For instance compounds of formula I in which R^ represents a group -O-CO-R^ 1, where R^ is as defined above, may be prepared by acylation of the hydroxy group in a suitable compound of formula I, for instance, by using an acyl chloride R^ 1-CO-Cl in a suitable solvent, such as dichloromethane, in the presence of a base, such as triethylamine. Alternatively compounds of formula I in which R^ represents a hydroxyl group may be reacted with a compound HO-L where L is as defined above and includes the acid C=0, in the presence of a dehydrating agent such as dicyclohexylcarbodiimide. A further route to such compounds is provided by reacting a metal salt of a compound of formula (I) in which R^ represents a hydroxyl group, that is, R^ represents a group -OM where M is a metal ion, with a compound X-L as defined above.

Compounds of formula (I) in which R^ with R2 and/or R7 with R8 each independently represent an optionally substituted alkoxy group may be prepared by ketalisation of one or both carbonyl groups in a suitable compound of formula (VI), for instance, by using a suitable alcohol in basic or acidic conditions, such as by use of a -13- solution of potassium hydroxide in methanol.

Compounds of formula (I) in which R1 and R2 together and/or R7 and R8 together represent a thiocarbonyl group =S may be prepared by treating a suitable compound of formula (I), wherein R'and R2 and R7 and R8 are both =0, with a thiating agent, such as Lawesson's Reagent (2,4-bis(4-methoxyphenyl)-l ,3-dithia-2,4-diphosphetane-2,4-disulphide), using protecting groups where required.

Compounds of formula (I) in which R* and R2 together and/or R7 and R8 together represent an oxime group =N- OR9, where R9 is as defined above, may be prepared by treating a suitable compound of formula (I), wherein R^and R2 and R7 and R8 are both =0, with a hydroxylamine or alkoxylamine of formula R^O-NP^, where R9 is as defined above, in the presence of a base, such as pyridine.

Combinations of the above derivatisation processes may be performed to achieve the desired compound of formula (I).

In a fifth aspect of the present invention an insecticidal and/or fungicidal composition is provided which comprises a compound of formula (I) and preferably of formula (II), (III) or (IV), as defined above, in association with at least one carrier. Such a composition may contain a single compound or a mixture of several compounds of the present invention. It is also envisaged that different isomers or mixtures of isomers may have different levels or spectra of activity and thus compositions may comprise individual isomers or mixture of isomers.

The compositions of the invention typically contain from 0.001 to 95% by weight of the active ingredient of formula I. Preferably the compositions contain from 0.001 to 25% by weight of the active ingredient when they are in ready-to-use form. However, higher concentrations, for instance, up to 95%, may be present in compositions to be sold as concentrates for dilution before use.

The compositions of the invention may be mixed with a variety of appropriate inert carriers such as solvents, diluents and/or surface-active agents to form dusts, granular solids, wettable powders, mosquito coils or other solid preparations or emulsions, emulsifiable concentrates, sprays, aerosols or other liquid preparations. Suitable solvents and diluents include water, aliphatic and aromatic hydrocarbons such as xylene or other petroleum fractions and alcohols such as ethanol. Surface-active agents may be of an -14- anionic, cationic or non-ionic type. Anti-oxidants or other stabilisers may also be includedas well as perfumes and colourings. These inert carriers may be of the type and in proportions such as are conventionally used in pesticidal compositions.

In addition to these inert carriers, the compositions of the invention may also contain one or more further active ingredients. These further active ingredients may be other compounds which exhibit pesticidal activity and these other compounds may exhibit a synergistic effect with the compounds of the present invention.

The present invention will now be described further by way of illustration only by reference to the following non-limiting Examples and Comparative Examples. Further embodiments of the invention will occur to those skilled in the art in the light of these.

EXAMPLES Example 1 : Preparation of 2-cyclohexyl-3-hydroxynaphthalene- 1.4-dione To a stirred solution of 2-hydroxynaphthalene-l , 4-dione (1.00 g, 5.74 mmol), cyclohexane carboxylic acid (1.10 g, 8.61 mmol) and silver nitrate (520mg) in acetonitrile (15ml) and water (20ml) heated at 65-70°C was added an aqueous solution of ammonium persulphate (1.77g, 7.77mmol) in water (10ml). After heating for 1 hour the mixture was cooled, diluted with water (50ml) and extracted with ether (3 x 40ml). The combined ether fractions were washed with water (3x25ml), saturated sodium chloride solution (25ml) and dried over magnesium sulphate. Filtration and evaporation of solvents under reduced pressure and silica gel chromatography yielded the title compound (364 mg, m.p. 133 °C). This compound is listed as compound 12 in the Tables below.

Example 2: Preparation of 2-hydroxy-3-(4-methylcyclohexyDnaphthalene- 1.4-dione.

The method of Example 1 was followed using lawsone(2-hydroxynaphthalene-l ,4-dione (1.00 g) and 4-methylcyclohexanecarboxylic acid (1.23 g), and yielded the title compound (100 mg, m.p. 101 °C).

This compound is listed as compound 19 in the Tables below. -15- Example 3: Preparation of 2-hydroxy-3-f 1 -methy lbuty 1 Vnaphthalene- 1.4-dione.

The method of Example 1 was followed using 2-acetyloxynaphthalene-l , 4-dione (1.24 g, 5.74 mmol) and 2-methylpentanoic acid (1.00 g) yielded the title compound (608 mg) after hydrolysis in. 30 ml THF using potassium hydroxide (5 x exess) in water (8ml) (mp 82-83°C).

This compound is listed as compound 3 in the Tables below.

Example 4: Preparation of 2-hvdroxy-3-f2-trifluoromethylpropyl)-1.4-naphthoquinone 2-acetyloxynaphthalene-l , 4-dione (1.24 g) and 3-trifluoromethylbutanoic acid (1.08 g) were reacted using the method as descibed in Example 3 yielding the title compound (353 mg) (mp 168°C). This compound is listed as compound 1 1 in the Tables below.

Other compounds set out in the tables below were produced using these general methods. Example 20 is Example 1 of Table 1 of DE 3801743 Al which is 2-hydroxy-3-(4-i-butylcyclohexyl)naphthalene-l, 4-dione (Formula I: n = 0; m=0, R1 + R2 together and R ' + R8 together both represent =0; R3 = -OH; -CHR4R5- = 4-t-butylcyclohexyl), -16- TABLE 1 the following examples n=0 and R and together represent a g nD signifies refractive index for the sodium D lines; ' - ' indicates absence of a group A -17- TABLE 2 In all the following examples n = 0, R1 + R2 together and R7 + R8 together both represent =0 and R3 = OH; m=0.

Pesticidal Activity Pesticidal activity was assessed against houseflies, mustard beetles, mites and whitefly using the following methods.

Houseflies (MP) (Musca domestica) Female flies were treated on the thorax with a one microlitre drop of test compound dissolved in acetone. Two replicates of 15 flies were used at each dose rate and 6 dose rates were used per compound under test. After treatment, the flies were maintained at a temperature of 20° ± 1 °C and kill was assessed 24 and 48 hours after treatment. LD50 values were calculated in micrograms of test compound per fly (see Sawicki et ai, Bulletin of the World Health Organisation, 35, 893 (1966) and Sawicki et αί, Entomologia and Exp. Appli 10, 253, (1967).

Mustard beetles (PC) (Phaedon cochleariae Fab) A one microlitre drop of an acetone solution of the test compound was applied -18- ventrally to adult mustard beetles using a micro drop applicator. The treated insects were maintained for 48 hours after which time kill was assessed. Two replicates each of 20 to 25 mustard beetles were used at each dose level and 5 dose levels were treated comparably. LD50 values were calculated as for houseflies.

Mites (TU) (Tetranvchus urticae) 25 adult female mites were immersed in 35 μΐ of a solution of the test compound in a 1 :4 acetone-water mixture for 30 seconds. The treated insects were maintained at 210 ± 2°C and kill was assessed 72 hours after treatment. Mites exhibiting repetitive (non-reflex) movement of more than one locomotory appendage after this period were recorded as alive. Three replicates of 25 mites each were used at each dose rate and 5 or 6 dose rates were used per compound under test. LC50 values were calculated in ppm of the solution of the test compound per insect. The test was carried out using a susceptible strain of mites (GSS) supplied by Schering, AG, Berlin.

Whiteflv (¾n (Bemisia tabaci) Acetone solutions (0.100 ml) of the test compounds were placed in 10 ml glass vials and evaporated with rotation to deposit a film of the compound. Thirty adult whiteflies were placed inside the vial, then after 60 minutes, the treated insects were transferred onto untreated cotton leaf discs which were kept moist on a bed of agar gel. The temperature was maintained at 25 °C and mortality assessed after 48 hours. Three replicates were used at each of 5 to 7 dose levels per compound. LC50 values were calculated by using a computer software package ("Polo-PC available from LeOra Software, Berkeley, California). (See M.R. Cahill and B. Hackett in Proceedings Brighton Crop Protection Conference, 1992). The test was carried out using a susceptible strain of whitefly (SUD-S) which was collected in Sudan in 1978 from cotton.

The results of these tests are set out in Table 2 below. The values given are LD50 g/insect) or LC50 (ppm solution of test ompound) unless otherwise specified. -19- TABLE 3 Example 1 , page 5 of DE 2641343 Al which is 2-n-dodecyl-3-ethanoyloxynaphthalene- 1 ,4-dione (Formula I : n = 0; R1 + R2 together and R7 + R8 together are both = 0; R3 = -O-CO-CH3; -CR4R5- = -CH2s R6 = -nC1 1H23) -20- TABLE 4 Activity against resistant whitefly fBT) (Bemisia tabaci) The whitefly test on (BT (SUD-S)) was repeated using a resistant strain of whitefly (Ned 1/2). The Ned 1/2 strain is a composite collection which was collected in the Netherlands in 1992 from Gerbera and Bouvardia by ICI Netherlands and exhibits high resistance to pyrethroid insecticides, such as cypermethrin, organophosphate and carbamate insecticides and the insect growth regulator buprofezin. The result of this test is set out in Table 5 below. The value given ise LC50 (ppm solution of test compound).

TABLE 5 In addition to acticity against whitefly, the presently investigated compounds were also found to have activity against Diabrotica (Western Corn Root worm), and Spodoptera eg. S. Httoralis. For example compound 4 has LC50 ppm topical of the order of 5 for the -21- former and 15 for the latter, while compound 13 has LC50 values of approximately 20 and 12. Antifeedant activity is also evident in the species specified.

Fungicidal Activity Fungitoxicity of coded compounds to isolates of Aspergillus niger, Pyricularia oryzae (=Magnaporthe grisea) and Rhizoctonia solani was tested in vitro.

Each compound was incorporated into potato dextrose agar in solvent (50/50 ethanol/acetone) at 0.5 ml solvent per 250 ml agar while the autoclaved agar was still molten and cooled to 50°C. Each compound was tested at a single concentration (100 mg Γ1).

Each test, usually of two compounds, included three control treatments: a standard fungicide (carbendazim at 1 or 5 mg 1 or prochloraz at 1 mg l 1); ethanol/acetone only; no additions. The fungicides used as standards may be considered as representative of active, commercially available compounds.

Each fungus was tested on agar in four Petri dishes per treatment, with three replicate fungal colonies per plate (one colony for R. solani). A. niger and R. solani were incubated for 4 days at 20-25°C , and P. oryzae for 7 days. Increase in colony diameter was then measured and used to determine activity: The results of these tests are set out in Table 6 below. The values given are % inhibition of growth in colony diameter in agar plates at a given concentration of agent. Compound numbers are as above with the addition of compound number 21 :- 2-methy 1-3 -hydroxy naphthalene- 1 ,4-dione, and compound number 22:- 2-ethyl-3-hydroxynaphthalene-l,4-dione. Inhibition by standard agents is given for comparison. -22- TABLE 6 In addition, tests have shown that the compounds of formula I exhibit good fungicidal activity against a broad spectrum of fungi which cause diseases in both cereal and broad leaved crops. Particularly, good activity has been observed against fungi of the genera Erysiphe, especially Erysiphe graminis, and Botrytis, especially Botrytis fabae and Botrytis cinerea, as well as the genera Rhizoctonia, Pyricularia and Aspergillus as illustrated above. -23- TABLE 6 insecticidal and acaricidal activity of comparative examples and Examples 21 and 22(*); R m =0 -24- Example 5 Preparation of 2-hvdroxy-naphthalene-1.4-dione starting materials for compounds where n=l or more.

Diels-Alder type reactions using corresponding quinone compounds yield suitable starting material 2-hydroxy-naphthalene-l ,4-diones for preparation of compounds where n=l or more. Examples are as follows. (a) Preparation of 6-methyl-naphthalene-1.4-dione.

A solution of 1 ,4-benzoquinone (13.9 g, 128 mmol) and isoprene (13.1 ml, 131 mmol) was stirred in glacial acetic acid (44 ml) for 68 hours at room temperature. The mixture was diluted with water (44 ml) and refluxed for 1 ½ hours. The mixture was cooled to room temperature and acetic acid (84 ml) and chromic acid [chromium trioxide (29.4 g)] in water (30 ml)] was added sequentially, before refluxing for a further 1 ½ hours. After cooling, the mixture was diluted with water (200 ml) and extracted with ether (3 x 50 ml). The combined ether fractions were washed with dilute sodium hydroxide solution (2M; 2 x 50 ml), water (2 x 50 ml), saturated sodium chloride solution (50 ml) and dried over magnesium sulphate. Filtration and evaporation of solvent under reduced pressure, and repeated recrystallisation from petroleum ether yielded the title compound (7 g). (b) 2-Amino-6 and 7-methyl-1.4-naphthalene-1.4-diones.

To a stirred solution of 6-methyl naphthalene- 1,4-dione (2.1 g, 12 mmol) in glacial acetic acid (60 ml) at room temperature was added a solution of sodium azide (1.58 g) in water (5 ml). The mixture was stirred for 2 days before diluting with water (200 ml) and, after stirring for a further 15 minutes, was filtered. The filtrate was neutralised with sodium bicarbonate and extracted with chloroform (3 x 25 ml). The combined chloroform extracts were washed with saturated sodium bicarbonate solution, brine and dried (CaSC^). Filtration and evaporation of solvent under reduced pressure and silica gel chromatography yielded the title compound (100 mg) as a 3:2 mixture of isomers. (c) 2-Hydroxy-6- and -7-methylnaphthalene-1.4-diones.

The aminomethyl naphthalene- 1,4-dione mixture from (b)(200 mg) was refluxed in water (20 ml) and concentrated sulphuric acid (10 ml) for 20 minutes. The cooled -25- mixture was poured into ice/water (50 g) and extracted with ether (3 x 25 ml). The combined ether extracts were washed with water, saturated NaHCC^, water, saturated NaCl solution and dried (MgSC>4). Filtration and evaporation of solvent and purification by silica gel column chromatography yielded the title compound (68 mg). -26-

Claims (42)

1 1 6562/4 We claim:

1. A method of combating white fly or Lepidoptera pests at a locus, which comprises treating the locus with a compound of formula (I) or a salt thereof, in which n represents an integer from 0 to 4; m represents an integer 0 or I; each R independently represents a halogen atom or a nitro, cyano, hydroxy 1, alkyl, alkenyl, haloalkyl, haloalkenyl, alkoxy, haloalkoxy, haloalkenoxy, amino, alkylamino, dialkylamino, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, alkylamido, cycloalkyl, aryl or aralkyl group; R and R each independently represent an optionally substituted alkoxy group or together represent a group =O, =S or =N~OR9, where R9 a hydrogen atom or an optionally substituted alkyl group; R3 represents a hydroxyl group, or a group --OL where L is a leaving group, or a group which in vivo is transformed into a group --OL1 is a leaving group; R and R independently represent an optionally substituted alkoxy group or together represent a group =O, =S or =N— OR9, where R9 is as previously defined; wherein R4 and R5 independently represent a hydrogen or halogen atom or an optionally substituted alkyl or alkenyl group, or together with the interjacent carbon atom represent an optionally substituted C4.g cycloalkyl or cycloalkenyl ring; and A represents a straight or branched chain alkyl or alkenyl group, which may be optionally substituted, an acyclic carbon chain of which links the 3 position of the naphthalene ring shown and the moiety 27 1 16562/2 CHR4 R5 and wherein A does not include a quaternary carbon atom in that chain; and wherein the total number of carbon atoms in the longest carbon chain running from the 3-position of the naphthalene ring shown is no more than 8.

2. A method as claimed in claim 1, wherein the pest is Bemisia whitefly.

3. A method as claimed in claim 2, wherein the pest is Bemisia tabaci.

4. A method as claimed in claim 1, wherein the pest is Spodoptera.

5. A method as claimed in claim 1, wherein the locus comprises the pest per se or environments subject to or subjected to attack by the pests.

6. A method as claimed in claim 1, wherein R1 with R2, and R7 with R8 each independently represent a Cw alkoxy group or R with R and/or R with R together represent a group =O.

7. A method as claimed in claim 1, wherein R3 is a group ~OL where L is a leaving group, or a group which in vivo is transformed into a group —OL.sup.l, wherein the pKa value of the acid LOH or L'OH in water is from 1 to 7.

8. A method as claimed in claim 6, wherein R3 is a group which in vivo is transformed into a group — OL1 where L1 is a leaving group and the transformation is carried out in a pest to be combated.

9. A method as claimed in claim 1, wherein the compound of formula (I) is a naphthalene- 1,4-dione.

10. A method as claimed in claim 1, wherein R4 and R5 independently represent a alkyl or haloalkyl group or a C2-4 alkenyl or haloalkenyl group, or together with the interjacent carbon atom, represents a C4-g cycloalkyl or cycloalkenyl ring which is optionally substituted with one or more substituents independently selected from halogen atoms and C]_4 alkyl, C1-4 haloalkyl, C2.4 alkenyl and C2-4 haloalkenyl groups. 28 1 16562/5

11. 1 1. A method as claimed in claim 1 wherein the compound is of formula (II) or a salt thereof in which R, R.sup.1, R2, R3, R7, and R8 and n are as defined in formula I and R4 and R5 each independently represent a halogen or an optionally substituted alkyl or alkenyl group.

12. A method as claimed in claim 1 1, wherein n is 0; R1 with R2, and R7 with R8 are both =O; R4 and R5 each independently represent a CM alkyl, C].4 haloalkyl, C2_4 alkenyl or C2-4 haloalkyl group.

13. A method as claimed in claim 11, wherein --CHR4 R5 represents a methyl or ethyl group.

14. A method as claimed in claim 1, wherein the compound is of formula (III) (HI) wherein n, m, A, R, R1, R2, R3, R7 and R8 are as defined for formula (I); ,· and R4 and R5 together with the interjacent carbon atom represent an optionally substituted C4.8 cycloalkyl or cycloalkenyl ring.

15. A method as claimed in claim 14, wherein R1 with R2, and R7 with R8 are both =0; n 29 1 16562/4 and m are 0; and R4 and R5 together with the interjacent carbon atom represents saturated C4.8 cycloalkyl ring which is optionally substituted.

16. A method as claimed in claim 1 1, wherein the compound is of formula (IV) or a salt thereof wherein n, A, R, R1, R2, R3, R7, and R8 are as defined for formula (I); and R4 and R5 each independently represent a halogen or optionally substituted alkyl or alkenyl group.

17. A method as claimed in claim 16, wherein Rl with R2, and R7 with R8 are both =0; m is 1 and A is a C)_6 alkyl or C2-6 alkenyl chain, which may be substituted by halogen or a branch alkyl or alkenyl chain which may be halogenated.

18. A method as claimed in claim 16, wherein R4 and R5 are independently selected from the group consisting of Ci_6 alkyl, Ci.6 haloalkyl, C2.6 alkenyl and C2.6 haloalkenyl.

19. A method as claimed in claim 16, wherein A is group ~(CH2)a — wherein a is an integer from 1 to 6 or ~(CH2)a -CH=CH--(CH )b — where a and b are integers which add up to 0 to 4, or an analogue of these wherein one or more of the carbon atoms in these groups are substituted by alkyl, haloalkyl, alkenyl, haloalkenyl or halogen. I'

20. A method as claimed in claim 19, wherein a is an integer from 1 to 4 or a and b are integers which add up to 0 to 2.

21. A compound of formula (VI) 30 116562/6 (VI) wherein m, n, A, R and R3 are as defined for formula (I) in claim 1 and R20 is selected from me group consisting of CM alky 1, C2-4 alkenyl and C2-4 haloalkenyl.

22. A compound of formula (VTI) wherein m, A and R3, are as defined for formula (I) in claim 1, and R4 and R5 independently represent a Cj.7 alkyl or haloalkyl group or C2.7 alkenyl or haloalkenyl group, in which at least one of R4 and R5 is a haloalkyl group.

23. A compound as claimed in claim 22, wherein A is a C alkylene group and one or both of R4 and R5 is trifluoromethyl.

24. A process for the preparation of a compound of formula (I) comprising reacting an aldehyde corresponding to the group --A--CHR4 R5, where —A— has an aldehyde group at its free end, directly with a compound of formula (V) wherein 31 1 16562/4 wherein R, RJ and n are as defined in formula I, in a polar organic solvent under alkaline conditions, and heating the product under acidic conditions in a non-polar solvent to effect elimination of water.

25. A process for the preparation of the compound of formula (I) comprising reacting a compound of the formula (V) (V) in which R, R3 and n are defined above, with a carboxylic acid CHR4 R5 ~(A)m — COOH where R4, R5, m and A are as defined above, in the presence of a free radical initiator.

26. A process for the preparation of a compound of formula (I) comprising reacting a compound of formula (V) with a compound of formula X~(A)m CHR4 R5 wherein X is a leaving group that will leave the compound to give a charged radical .sup.+ (A).sub.m —CHR4 R5 in the presence of an acid.

27. A compound of formula (VIII) ( m) Π 6562/5 wherein R, n and RJ are as defined for formula (I) in claim 1 and R 20 is selected from the group consisting of Ci_4 alkyl, C2-4 alkenyl and C2-4 haloalkenyl.

28. A compound according to claim 27 wherein R is methyl.

29. A compound according to claim 27, wherein R20 is t-butyl.

30. 2-hydroxy-3-(2-methylcyclohexyl)-naphthalene-l,4-dione.

31. 2-hydroxy-3-(3-methylcyclohexyl)-naphthalene-l,4-dione.

32. 2-hydroxy-3-(4-methylcyclohexyl)-naphthalene- 1 ,4-dione.

33. 2-hydroxy-3-(4-t-butylcyclohexyl)-naphthalene-l,4-dione.

34. A method of combating fungal pests at a locus, which comprises treating the locus with a compound of formula (VIII) as defined in claim 27.

35. A method of combating fungal pests at a locus, which comprises treating the locus with a compound of formula (VI) as defined in claim 21.

36. A method of combating fungal pests at a locus, which comprises treating the locus with a compound of formula (VII) as defined in claim 22.

37. A method as claimed in claim 34 wherein the use is against fungi of Rhizoctonia, Pyricularia and/or Aspergillus.

38. A method as claimed in claim 34 wherein the use is against R. solani, P. oryzae or A. niger. 33 1 16562/2

39. A method as claimed in claim 35 wherein the use is against fungi of Rhizoctonia, Pyricularia and/or Aspergillus.

40. A method as claimed in claim 35 wherein the use is against R. solani, P. oryzae or A. niger.

41. A method as claimed in claim 36 wherein the use is against fungi of Rhizoctonia, Pyricularia and/or Aspergillus.

42. A method as claimed in claim 36 wherein the use is against R. solani, P. oryzae or A. niger. RS f 34