CZ198A3 - Naphthoquinone derivatives and their use as pesticides - Google Patents

Abstract

This invention relates to certain naphthoquinone derivatives of general formula (1) or a salt thereof, in which m, n, R, R<1>, R<2>, R<3>, R<4>, R<5>, R<6>, R<7>, R<8> are as defined in the description; processes for their preparation; compositions containing such compounds and their use as a pesticide, such as a fungicide and, especially, an insecticide or an acaricide.

Description

Field of technology

The invention relates to certain naphthoquinone derivatives, * the method of their preparation, compositions which contain such compounds and which are used as pesticides, such as fungicides and especially insecticides and/or acaricides.

Current state of the art

DE Document No. 38 017 743 AI describes compounds of general formula A

0R ¹ (CH ₂ ) _n - r ² (A)

in which n means 0 to 12-, R ¹ means a hydrogen atom, an optionally substituted alkyl, aralkyl, alkylcarbonyl (hetero)arylcarbonyl, alkoxycarbonyl, alkylsulfonyl or arylsulfonyl group and R means a haloalkyl, optionally substituted (hetero)aryl or substituted cycloalkyl group. These compounds are reported to exhibit acaricidal and fungicidal activity. When R is phenyl or cyclohexyl, the list of preferred substituents includes tri(C 1-4 alkyl)silyl groups, of which trimethylsilyl is particularly preferred. Of the many compounds reported to fall within the general formula I as defined above, only one compound which contains such.

• ♦ substituent is described, i.e. the compound from Example 5, where n means 0, R means a hydrogen atom and R is

4-(trimethylsilyl)cyclohexyl group. Moreover, although the data indicating that the compound of Example 1 exhibits acaricidal and fungicidal activity, it is clear that this compound is not the most pesticidally active of the compounds ► listed in DE 38 01 743 AI.

The essence of the invention • +·

It has now been found that certain naphthoquinone derivatives which bear a group attached to the naphthoquinone ring and which contains at least one silicon atom as an integral part of the group rather than as part of an optional substituent exhibit excellent pesticidal, for example fungicidal and/or especially insecticidal and/or acaricidal effects, as a result of which many of these compounds are active against resistant strains of insects and/or mites, especially resistant strains of aphids and flies, as well as sensitive strains.

The present invention includes a compound of general formula I

h l

or a salt thereof, where m is 0 or 1, n is a number from 0 to 4, each R independently represents a halogen atom or a nitro group, cyano group, hydroxy group, alkyl, haloalkyl, alkoxy, haloalkyl, amino, alkylamino, dialkylamino, alkoxycarbonyl, carboxyl, alkanoyl ^{. ​} hydrogen or an optionally substituted alkyl group,

R ⁸ means an optionally substituted alkyl group, a hydroxyl group or a -OL group, where L means a leaving group or a group that is converted in vivo to a -OL ¹ group, where L ¹ means a leaving group,

R ⁴ and r 5 , if present, each independently represent a hydrogen atom or a halogen atom or an optionally substituted alkyl group or, together with an intermediate carbon atom, an optionally substituted cycloalkyl or cycloalkenyl group, optionally containing at least one silicon atom in the ring.

R ⁶ means an optionally substituted group containing at least one silicon atom, or in the case where m is 1' and the part -CR ⁴ R ⁸ contains at least one silicon atom, R ⁸ can further mean a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl , cycloalkenyl, aryl, alkoxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy or aryloxy and R ⁷ and R ⁸ independently represent an optionally substituted alkoxy group or together represent the group =0, =S or =N-0R®, where R® has the meaning listed above.

If any of the above groups R ⁴ , R ⁸ and R ⁸ contains at least one silicon atom, each such silicon atom forms an integral part of the group, i.e. each silicon atom is in a ring or in a chain and is not a substituent on the group. In particular, a silicon atom is not a substituent on a carbocyclic ring, but can be directly bonded to such a ring only if it is part of a chain that includes a carbon atom in the 1' position of the carbocyclic ring.

If the compound of general formula I contains a group defined as alkyl, alkenyl or alkynyl, then this group can be linear or branched and can contain up to 12, preferably up to 6, especially up to 4 carbon atoms. A cycloalkyl or cycloalkenyl group may contain 3 to 8, preferably 4 to 7, carbon atoms. The aryl group can be any aromatic group, especially a phenyl or naphthyl group. An aralkyl group can be any alkyl group defined above, I which is substituted with an aryl group as defined

Even from above, especially the benzyl group. , * If any of the above substituents is stated to be optionally substituted, then the substituents that are optionally present may be one or more commonly used substituents in the development of pesticide compounds and/or the modification of these compounds to affect their efficacy, persistence, penetration or other Properties. Specific examples of such substituents include, for example, halogen, nitro, cyano, hydroxy, alkyl, haloalkyl, alkoxy, halogeno, amine, alkylamino, dialkylamino, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamoyl, alkylamido, cycloalkyl, phenyl, and benzyl. group. Typically 0 to 3 substituents are present. If any of the above-mentioned substituents means an alkyl substituent, then this substituent may be linear or branched and may contain up to 12, preferably up to 6, most preferably up to 4 carbon atoms. If any of the above-mentioned substituents ¹ contains an aryl or cycloalkyl part, the aryl or cycloalkyl part may be substituted by one or more halogen atoms, a nitro group, a cyano group, an alkyl, haloalkyl, alkyloxy group or a haloalkyl group. Preferably, the aryl part is a phenyl part and the cycloalkyl part contains 3 to 8, preferably 4 to 7 carbon atoms.

Compounds of the general formula I, where R ³ means a hydroxyl group and the atom in the a- and S-position, especially the S-position of the group is a silicon atom, are synthetically less available than other compounds of the general formula I. It is therefore advantageous that when R ³ means a hydroxyl group that the atom in the α- and/or β-position of group 6 is not a silicon atom.

It is also preferred that R, when present, is halogen, nitro, cyano, hydroxy, C _{1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, chalco-alkyl, C 4-4 alkylamino , di-} C _{1_4 alkylamino} , C-]__ _{4 alkoxycarbonyl} , O _1-4 alkylthio, C _{1_4} alkylsulfinyl or C-[__ ₄ alkylsulfonyl group.

More preferably _, R, when present, is a halogen atom or _a C _1-4 alkyl, C _4-4 alkoxy or C _4-4 halo-alkyl group.

Preferably, n is 0, 1 or 2, particularly preferably 0.

It is also preferred when each R and R is independently _a C _4-4 alkoxy group, such as a methoxy group, or when , , . , aq , together mean the group =O or =N-OR, where R means a hydrogen atom or a C₁- _₄ alkyl group, especially a methyl group. It is particularly preferred when R ^X and R ² together represent the group =O.

If R ³ represents a group -OL in which L represents a leaving group or a group that is converted in vivo to a group -OL ^x , where L ^x is a leaving group, the leaving groups L and L ¹ can be any leaving group. It is preferred when the leaving groups L ¹ and L ² are such that the pK value _of the LOH acid and ιΛοη in water is less than 7, more preferably less than 6, especially less than 5.

If R ³ represents a group that is converted in vivo to the group -OL ^x , where L ¹ is a leaving group, it is preferred that this conversion is carried out in the plant to be protected or in the insect to be destroyed, preferably by the action of enzymes in a plant or insect. For example, if R is an S-acid group such as -O-CH2CH2COOH, where -CH2CH2COOH is not a leaving group, then it can be subjected to enzymatic oxidation in vivo by β-oxidase, for example to form a group.

-O-CO-CH ₂ -COOH, where -CO-CH ₂ -COOH is the leaving group. '

It is preferred when R ³ means an optionally substituted alkyl group or a group -OR ¹ ^, where it means a hydrogen atom, an optionally substituted alkyl, aryl or f aralkyl group or a group -COR ¹¹ , -SOR ¹¹ , -SC^R ¹¹ , -P(X)(OR ¹² )(OR ¹³ ), -P(X)(R ¹² )(OR ¹³ ), -P(OR ¹² )(OR ¹³ ) or

P(R ⁴ -' ^fi ) (OR ) , where R is a hydrogen atom, or a substituted alkyl, aryl or aralkyl group or a group -NR ¹² R ¹³ , where R ¹² and R ¹³ independently mean a hydrogen atom or an optionally substituted alkyl group and X represents an oxygen atom or a sulfur atom. If R ¹ ® and R ¹¹ represent an optionally substituted aryl group or aralkyl group, it is preferred when the aryl group or part thereof is a phenyl group or part thereof and when the optional substituents are selected from the group that includes halogen atoms, nitro groups and C _1-4 alkyl groups. Substitution of the phenyl ring in position 4 is preferred.

Preferably R ³ means a C 1-6 alkyl group or more preferably a hydroxyl group or a group -OCOR ¹¹ , where R ¹¹ means a hydrogen atom or a C 1-12 alkyl, C 1-12 haloalkyl, ^C 1-12 hydroxyalkyl, C _1-12 carboxyalkyl, phenyl or benzyl group.

It is particularly preferred when R ³ denotes a hydroxyl group or the group -O-COR ¹¹ , where R ¹¹ denotes a hydrogen atom or a C 1-6 alkyl, C 1-6 haloalkyl, phenyl or benzyl group.

In one preferred embodiment, R ⁴ and R ³ independently represent a hydrogen atom or a C- _1-4 alkyl group, especially a methyl group, or a C-1-4 haloalkyl group, especially a trifluoromethyl group. Especially preferably R ⁴ and both represent a hydrogen atom.

Alternatively, R ⁴ and R ⁵ together with an intermediate carbon atom may represent a C 8 -C 8 cycloalkyl group, optionally substituted by one or more substituents selected from halogen atoms, C _1-4 alkyl and C _1-4 haloalkyl groups.

·« ·

- 7 More preferably, R ⁴ and R ⁵ together with an intermediate carbon atom mean a C 8 -g cycloalkyl group, optionally substituted by one or more halogen atoms, especially chlorine or bromine atoms. In particular, preferably R ⁴ and R ⁵ together with the intermediate carbon atom represent an unsubstituted 5-7 cycloalkyl group.

If R ⁴ and R ⁵ have any of the meanings given in the previous two paragraphs, they must represent a group. containing at least one silicon atom. It is therefore preferred when * R ⁶ denotes an optionally substituted alkyl, alkenyl, or alkynyl, cycloalkyl, cycloalkenyl, aryl, alkoxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy or aryloxy group, each group containing at least one silicon atom and up to 20, in particular up to 15 and preferably 2 to 12 carbon atoms.

More preferably, R ⁶ means an alkyl, haloalkyl, alkoxyalkyl, alkoxyl, haloalkyloxy, alkyloxy, alkenyl, haloalkenyl or alkoxyalkenyl group, where each group contains one or two silicon atoms and up to 20, especially up to 15 and preferably 2 to 12 carbon atoms.

It is further preferred when R 1 denotes an alkyl or alkenyl group containing one silicon atom and up to 20, especially up to 15 and preferably 2 to 12 carbon atoms.

Preferred R® groups are groups of the general formula -(A) _m ~Si(R ¹⁴ )3, where m has the meaning as given for the general formula I, each R ¹⁴ independently represents a C _1-4 alkyl group or with an intermediate silicon atom forms two such groups a silacarbocyclic ring and A represents a C _{1_2} q' alkyl or alkenyl group which may be substituted by halogen and which may be straight or branched cut _or is or comprises a carbocyclic ring. Further preferred R₂ groups include silicon as a ring atom in another carbocyclic ring, where the silicon may be in any position of the ring, including the attachment of other groups, in £ such as alkyl or alkenyl chains in R₂.

• 1 ·· · In W • * « 9 9 9 * 9 9 • · • 9 9 « 9 • ♦ · • • ··♦ 9 • • 9 999 9 9 9 * • · • » • « 99 • 9 9 9· 9

More preferably, R ⁶ denotes the group -(CH ₂ )p-Si(R ¹⁴ ), where p denotes an integer from 1 to 15, preferably 1 to 10, especially 1 to 6, and] each R ¹⁴ independently denotes an alkyl group, especially methyl group. Alternatively, two R ¹⁴ groups may form i

V together with an intermediate silicon atom a 3- to 8-membered silacarbocyclic ring, for example a silacycloalkyl ring.

In another preferred embodiment, R ⁴ and R ⁵ together with an intermediate carbon atom can mean a silacycloalkyl group containing 3 to 8, preferably 5 to 7 atoms in the ring, optionally substituted by one or more substituents selected from the group that includes halogen atoms, C ₁ _ ₄ alkyl and C _1-4 haloalkyl groups. More preferably, R and R together with an intermediate carbon atom mean a silacycloalkyl group containing 3 to 8, preferably 5 to 7 ring atoms, optionally substituted by one or more halogen atoms, especially chlorine or bromine atoms. It is particularly preferred when R ⁴ and together with the intermediate carbon atom represent an unsubstituted silacycloalkyl group containing 5 to 7 atoms in the ring. Preferably, the silacycloalkyl group contains one or two silicon atoms, more preferably only one silicon atom.

If R ⁴ and R'' have any of the meanings given in the previous paragraph, it is preferred that R® represents a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, alkoxy, alkenyloxy, alkynyloxy, cycloalkyl, cycloalkenyloxy or aryloxy group, each group possibly containing at least one silicon atom and up to 20, especially up to 15 and preferably 2 to 12 carbon atoms.

Particularly preferably, R 1 denotes a hydrogen atom or an alkyl, haloalkyl, alkoxyalkyl, alkoxy, *halogenoxy, alkyloxy, alkenyl atom. a haloalkenyl or alkoxyalkenyl group, each group optionally containing one or two silicon atoms and up to 20, especially up to 15 and preferably 2 to 12 carbon atoms.

It is further preferred when R® represents alkyl or

- 9 alkenyl group, optionally containing up to 20, especially up to 15 and preferably 2 to 12 carbon atoms.

Preferably, R ⁷ and R ® independently mean a C _1-4 alkyl group, especially a methoxy group, or together they mean a group =O or =N-OR ⁹ , where R ⁹ means a hydrogen atom or an alkyl group, especially a methyl group.

It is particularly preferred when R ⁷ ' and R ® together represent the group =O.

A particularly preferred subgroup of compounds of the general formula is that where m is 1, n is 0, R ^x and R ³ are both methoxy or together =O, R ³ is hydroxyl, alkynoxy (for example, ethanoyloxy) or aryloxy (for example, benzoyloxy) ^{. ​ ​ ​}

If R ³ represents a hydroxyl group, the compounds of general formula I can form salts. Suitable bases for forming such salts include inorganic bases such as sodium hydroxide, potassium hydroxide and sodium carbonate and organic bases such as tertiary amines such as triethylamine and pyrrolidine.

It should also be appreciated that some compounds of formula I are capable of existing as different geometric isomers and diastereomers. The invention thus includes both * individual isomers and mixtures of such isomers.

The invention also relates to a process for the preparation of a compound of general formula I or a salt thereof as defined above, which comprises the reaction of a compound of general formula II

(Π) where n, R and R® are as defined above with the carboxylic acid HOOC-(CR ⁴ R ⁵ ) _m -R® where R ⁴ , R ⁵ and R ⁶ are as defined above with the proviso that when m 0, the atom in the α-position of the group R® is not a silicon atom, in the presence of a free radical initiator such as ammonium peroxysulfate and silver nitrate in a suitable solvent such as aqueous acetonitrile to give the compound of general formula III

R3 (CRi r5^r6 (III) where m, n, Ř®, ř ⁴ , r ⁵ á R ⁶ have the meaning defined above, with the fact that when m means 0, the atom in the cx position of the group R® is not a silicon atom.

Compounds of general formula III correspond to compounds of general formula I, where R ¹ and together and R 1 and R ® together mean the group =O and can then react using various known derivatizing agents or their combinations to form other compounds of general formula I, if the desirable.

For example, compounds of general formula II, where R® denotes the group -O-CO-CgH^ are suitable starting substances and can react as described above to form the corresponding compound of general formula III. Compounds of general formula I, where R® denotes a hydroxyl group, can be prepared ·· 9·9·

- 11 9 9 * · · ·· • · · «»·· • 9 9 · 9 · 9 · 9 • 9 9 9 · ·· *9 99 99·· by the reaction of the compound of general formula III, where R ³ denotes the group - O-CO-CgH ₅ with a suitable base, for example an inorganic base such as sodium hydroxide or potassium hydroxide in the presence of a suitable solvent such as tetrahydrofuran. Compounds of general formula I, where R ³ represents the group -OL, where L has the meaning defined above, can be prepared by reacting a compound of general formula I, where R ³ represents a hydroxyl group, with a compound of general formula YL, where Y represents a halogen atom, in the presence of organic .a base, preferably a tertiary amine such as triethylamine or an inorganic base such as sodium carbonate. For example, compounds of the general formula I, where R ³ is a group of the general formula -O-CO-R ¹¹ , where R ¹¹ has the meaning defined above, can be prepared by acylating the hydroxyl group in a suitable compound of the general formula I, for example, using an acyl chloride of the general formula R ¹¹ -CO-C1 in a suitable solvent such as dichloromethane in the presence of a base such as triethylamine or an acid anhydride in the presence of a base such as pyridine. Alternatively, compounds of formula I wherein R ³ is hydroxyl may be reacted with a compound of formula HO-L wherein L is as defined above in the presence of a dehydrating agent such as dicyclohexylcarbodiimide. Compounds of the general formula I, where R ³ means the group -OL, where L has the meaning defined above, can be prepared by reacting the metal salt of the compound of the general formula I, where R means a hydroxyl group, i.e. R means the group -OM, where M is a metal ion , with a compound of formula YL as defined above.

Compounds of general formula I, where R ¹ and R ² and/or R ⁷ and R ⁸ are independently optionally substituted alkoxy groups can be prepared by ketalization of one or both carbonyl groups in a suitable compound of general formula III, for example using a suitable alcohol under basic or acidic conditions, such as potassium hydroxide in methanol. ' Compounds of general formula I, where R ¹ ' and R ² together and/or R ⁷ and R ⁸ together represent a thiocarbonyl group =S can be prepared by processing a suitable compound of the general ·· ««·«

of formula III with a thiating agent such as Lawesson's reagent (2,4-bis(4-methoxyphenyl)-1,3-dithia-diphosphetane-2,4-disulfide) using protecting groups if desired.

Compounds of general formula I, where R ¹ and R ² together and/or R ⁷ and R ⁸ together mean an oxime group =N-OR ⁹ where R ⁹ has the meaning defined above, can be prepared by treating a suitable compound of general formula III with hydroxylamine or alkylamine of the general formula R ⁹ O-NH 4 , where R ⁹ is as defined above, in the presence of a base such as pyridine.

In an alternative method of preparing compounds of general formula I, especially where m means 0 and the atom in the α-position of group R ⁸ is a silicon atom, the compound of general formula IV reacts

where each Hal independently means a halogen, preferably a chlorine or bromine atom, and R have the meaning given above, with a compound of the general formula ZR ⁸ , where Z means a halogen, preferably a chlorine or bromine atom, and R ⁸ has the meaning given above, in particular with the fact that atom in the α-position of the group R ⁸ is a silicon atom, in the presence of an organometallic reagent such as butyllithium in a solvent such as diethyl ether or tetrahydrofuran at a low temperature, preferably at a temperature of -70°C to -120°C, to form the compound of the general formula V

(V) «· ····

- 13 where n, R, R ⁶ and Hal have the meaning defined above, especially with the fact that the atom in the α-position of the group R ⁶ is a silicon atom.

The compound of general formula V can then be reacted with a suitable base, for example an inorganic base such as sodium hydroxide or potassium hydroxide, to form the corresponding compound of general formula I, where is a hydroxyl group. .

By combining the derivatization procedures described above, other compounds of general formula I can be obtained, if desired.

The compounds of general formulas II and IV are known compounds or can be obtained from known compounds by procedures analogous to known procedures.

As mentioned above, the compounds of general formula I are characterized by pesticidal, for example fungicidal and/or especially insecticidal and/or acaricidal activity. The invention also further relates to a pesticide composition which contains a carrier and, as an active ingredient, a compound of general formula I or a salt thereof, as defined above. A method of preparing such a composition is also included and consists in converting the compound of general formula I as defined above into a mixture with at least one carrier. Such a composition may contain one compound or a mixture of several compounds according to the invention. It is believed that different isomers or mixtures of isomers may have different levels of spectrum of activity and compositions may contain individual isomers or mixtures of isomers.

The preparations according to the invention usually contain 0.001 to 25% by mass of the active ingredients of general formula I. Preferably, the preparations contain, if they are prepared for direct use, 0.001 to 25% by mass of the active ingredients. However, even higher concentrations, for example up to 95%, may be present in compositions that are sold as concentrates for dilution before use.

-—-The compositions according to the invention can be mixed with a number of suitable inert carriers, such as solvents, diluents and/or surfactants to form powders, granules, wettable powders, fly traps 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. Surfactants can be of anionic, cationic or nonionic type. They may also contain antioxidants or stabilizers as well as perfumes or dyes. These inert carriers are used in quantities as usual in pesticide preparations.

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

The compounds of general formula I as defined above can be used to control pest infestations in the domestic environment, in horticulture, agriculture, medicine and veterinary medicine. Thus, according to another aspect, the invention relates to the use of a compound of general formula I or a salt thereof as defined above or:

an agent as defined above, such as a pesticide, for example;

fungicide and/or especially insecticide and/or acaricide.

The invention also relates to a method of destroying pests such as fungi and/or in particular insects and/or mites at a site, which comprises treating the site with a compound of general formula I or a salt thereof as defined above or a composition as defined above. Preferably, the site includes the pests themselves or the environment infested by them. Most often, the location includes the pests themselves, stored food, plants or animals that are infested with pests, the seeds of such plants, or the media in which the plants are grown. Generally, the compounds of general formula I and the compositions as defined above can be used in households to spray rooms at

- suppressing the occurrence of houseflies or other insects, in horticulture or agriculture for the treatment of crop stocks, especially grain or for spraying growing crops such as cotton and rice to suppress infestation by fungi, insects and other pests, or in medicine or veterinary medicine for example as a preventive spray against infestation by insects or other pests in livestock.

The invention is further described by examples, which are only illustrative in nature and in no way limit the scope of the invention. The compounds are confirmed by determined ¹³ nmr shifts (in ppm), listed in the order: bicyclic system,; CH ₂ groups; (and =CH if present); groups Si(alk) ₃ ; other groups.

Examples of the embodiment of the invention

Example 1

Preparation of 2-benzoyloxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone (Formula I: m = 1; n = 0; R ¹ and R ² together and R ⁷ and R® together both mean =0; R ³ = -O-CO-CgH5; R ⁴ = R ⁵ = H; R ⁶ = -CH 2 Si(CH ₃ )' ₃ )

2-Benzoyloxy-1,4-naphthoquinone (1.39 g, 5 mmol), trimethylsilylpropionic acid (1.09 g, 7.5 mmol) and silver nitrate (523 mg, 3 mmol) were suspended in 40 mL of aqueous acetonitrile (1:1) and then heated to 65 °C. Ammonium persulfate (1.71 g, 7.5 mmol) in 20 mL of water is then slowly added dropwise to the mixture over 30 minutes. The reaction mixture was stirred at this temperature for another hour, then cooled, diluted with diethyl ether and the aqueous phase was removed. The organic extract was washed with saturated sodium bicarbonate solution, then with brine and dried over anhydrous magnesium sulfate. After concentration in vacuo, the crude material is chromatographed using a mixture of petroleum ether and ethyl acetate as eluant to give 2-benzoyloxy-3-(2 ¹ =trimethyls±iylethyl)

1,4-Naphtoquinone (879 mg) which recrystallises from methanol, mp 92-95°C.

♦· ····

99

99

9 99

9 99

9999 • ··* • · ·» •· ·· β · 4 ·9 ♦ ·* «·♦·

184.4, 178.2, 150.3, 142.6, 134.0, 133.8,

126.6, 126.6; 18.8, 16.2; -2.0; 163.8, 128.0, 134.2 (PhCO).

NMR peaks at: 132.1, 130.9,

128.7, 130.4,

Example 2

Preparation of 2-hydroxy-3-(2'-trimethylsilylethyl)-1,4naphthoquinone (Formula I: m = 1; n = 0; R ¹ and R ³ together and R ⁷ and R ³ together both mean =0; R ³ = -OH; R ⁴ = R ⁵ = H; R ⁶ = -CH ₂ Si(CH ₃ ) ₃ )

2-Benzyloxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone (270 mg, 0.71 mmol) obtained in Example 1 in tetrahydrofuran (10 mL) was treated with 2N sodium hydroxide (0.73 mL, 1, 42 mmol) and the mixture is stirred overnight at room temperature. The reaction mixture was concentrated in vacuo and the residue was taken up in diethyl ether and acidified to pH 2 with 1N hydrochloric acid. The organic phase is washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude material was chromatographed using a mixture of petroleum ether and ethyl acetate as eluant to give 2-hydroxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone (163 mg) which recrystallized from hexane, mp 98-100 °C.

NMR peaks at: 184.6, 181.6, 152.2, 134.7, 132.9, 13'2.8,

129.4, 127.3, 126.6, 126.0; 17.6, 15.7; -1.9.

Example 3

Preparation of 2-hydroxy-3-(5'-trimethylsilylpentyl)-1,4naphthoquinone (Formula I: m = 1; n = 0; R ¹ and R ³ together and R ⁷ and R ³ together both mean =0; R ³ = -OH; R ⁴ = R ⁵ = H; R ⁶ = -(CH ₂ ) ₄ Si(CH ₃ ) ₃ )

2-Hydroxy-3-(6'-trimethylsilylhexyl)-1,4-naphthoquinone

to to · « to · « « toto «· to (337 mg, 1.02 mmol), prepared from

of 2-benzyloxy-1,4-naphthoquinone and trimethylsilylheptanoic acid according to the method of Example 1 and then according to the method of Example 2 was dissolved under nitrogen in dioxane (2.5 ml). Sodium carbonate (120 mg) in water (2.5 mL) and an excess of 30% (w/v) hydrogen peroxide (200 μΐ) were then added. The mixture was heated at 70 °C for 40 min, with red the reaction mixture becomes colorless. The reaction mixture is allowed to cool and a 20% (w/v) solution of copper sulfate (100 μΐ) is added and the solution is stirred until bubbles form. A 25% (w/v) sodium hydroxide solution (2 mL) and a 20% (w/v) copper sulfate solution (5 mL) were then added and the reaction mixture was heated at 70 °C for 30 min. . The mixture is allowed to cool and acidified to pH 2 with 1N hydrochloric acid. The product was extracted into diethyl ether and the ether extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude material was chromatographed using 5% diethyl ether in hexane as eluent to give 2-hydroxy-3-(5'-trimethylsilylpentyl)-1,4-naphthoquinone (202 mg) which was recrystallized from hexane, mp 73-75° C.

NMR peaks at: 184.6, 181.4, 153.0, 134.8, 132.9, 132.7,

129.4, 126.7, 126.0, 124.8; 33.6, 27.9, 33.7, 23.2, 16.5; -1.7.

Example 4

Preparation of 2-Ethanyloxy-3-(2'-trimethylsilylethyl)-1,4naphthoquinone (Formula I: m = 1; n = 0; and R ³ together and R ⁷ and R 2 together both mean =0; R ³ · = - O-CO-CH^; R ⁴ = R ⁵ = H; R ⁶ = -CH ₂ Si(CH ₃ ) ₃ )

2-Benzyloxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone (346 mg, 0.92 mmol) obtained according to the method given in Example *· · ·

- 18 1 above is hydrolyzed as indicated in Example 2 above and the hydrolyzed substance is acetylated directly by adding pyridine (6;

ml) and acetic anhydride (3 ml). The mixture is allowed to stand] overnight and the volatiles are removed in vacuo. The crude product is chromatographed using a mixture of ethyl acetate and petroleum ether as eluent and is obtained

2-Ethanoyloxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone (265 mg) which recrystallizes from hexane, mp 85-87°C. NMR peaks at: 184.3, 178.2, 149.8, 142.2, 134.0, 133.7, 132.0, 130.8, 126.5, 126.4; 18.6, 16.1; -2.1; 167.9, 20.2 (COCH ₃ ) .

Example 5

Preparation of 1-dimethylacetal 2-hydroxy-3-(2'-trimethylsilylethyl)-j

1,4-naphthoquinone (Formula I: m = 1; n = 0; R ¹ = R ² = -OCH ₃ ; R ³ = -OH; R ⁴ = R ⁵ =

H; R 1 = -CH 2 S 1 (CH ₃ ) ₃ ); R ² and R® together mean =0 ? j 2-Ethanoyloxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone (3 '

g) obtained according to the method described in example 4 is dissolved in methanol (100 ml), water (5 ml) and potassium carbonate (1.5 g).

The reaction mixture was stirred at room temperature for 2 h and then diluted with water (about 400 mL). The mixture was extracted with diethyl ether, dried over anhydrous sodium sulfate, and the solvent was evaporated to give 2-hydroxy-3-(2'-trimethylsilylethyl)-1,4-naphthoquinone 1-dimethylacetal as a pale yellow solid, mp 102-104 °C.

NMR peaks at: 183.6, 158.4, 135.2, 133.4, 132.7, 130.0, 126.2, 125.6, 125.2, 97.3; 16.8, 16.3; -2.1; 51.9 (2 X OMe).

Example 6 to 13

Procedures similar to Examples 1 to 5 above

4 * « · • · • · « · » 4 * • » 4 « « « * • · 19 - * • · « * « ♦ « · • 4 • • • · · · • • · • · · • 4 ·· ♦ 4

t.

prepares other compounds of formula I as detailed;

shown in Table 1 below. In this table, compounds .'5 are identified by reference to the compound of general formula I.

1'

Table 1 i

Ϊ i Ί (In the following examples m = 1; n = 0; R ¹ and R ² together and

R ⁷ and R ® together represent the group =O; R ⁴ = R ⁵ = H)

Example number R3 R6 t.L (°C) ⁿ D 6 -OH -Si(CH ₃ ) ₃ 76-78 7 -OH -(CH ₂ ) ₂ -Si(CH ₃ ) ₃ 70-71 8 -OH -(CH ₂ ) ₃ -Si(CH ₃ ) ₃ 74 - 76 9 -OH -ÍCH ₂ ) ₅ -Si(CH ₃ ) ₃ 43-45 10 -OH -<CH ₂ ALL(CH ₃ ) _? 38-42 11 -OH -(CH ₂ ) ₇ -Si(CH ₃ ) ₃ 37-40 12 -OH -(CH ₂ ) _g -Si(CH ₃ ) ₃ 36 13 -OH -(CH ₂ ) ₉ -Si(CH ₃ ) ₃ 1.5356

Note:

n _D denotes the refractive index for the D line of sodium

NMR peaks were identified as follows:

Example 6

NMR peaks at: 184.7, 180.8, 151.3, 134.4, 132.9, 132.9,

129.7, 126.7, 126.0, 125.5; 15.0; -0.8.

* · « · ·«

Example 7: 184.7, 181.5, 154.0, 134.8, 132.9, 132.8, 129, 5, 127.6, 126.0, 125.6; 27, 1, 22.9, 17.0; -1.7. 1 Example 8: 184.6, 181.4, 152.9, 134.7, 132.9, 132.8, 129, 4 ' .1 126.7, 126.0, 124.8; 32, 1, 24,2, 23.1, 16.4; -1.7. and Example 9: 184.6, 181.4, 153.0, 134.7, 132.8, 132.6, 129, 4, 126.7, 126.0, 124.8; 33, 4, 29.5, 28.2, 23.8, 23.3, 16.5; -1.7.

Example 10: 184.7, 181.5, 153.0,

126.8, 126.0, 124.9, 33.5, 29.7, 16.6; -1.6.

134.8, 132.9, 132.8, 129.4;

29.2, 28.3, 23.9, 23.4,

Example 14

Preparation of 2-hydroxy-3-(8-(dimethylsilylethyl)octyl)-1,4naphthoquinone

Formula I: m = 1; n = 0; R ¹ and R ² together and R ⁷ and R ⁸ together both mean =0; R ³ = -OH; R ⁴ = R ⁵ = H; R ⁶ =

-(CH ₂ ) ₇ Si(CH ₃ ) ₂ ch ₂ ch ₃

A solution of 1,8-dibromoacetate is added dropwise to magnesium chips (1.98 g, 81.5 mmol) at room temperature toto toto toto • ·to • to« • * • to «·

this this « this · « · ·· this this · this · this this (11.1 g, 40.8 mmol) in dry THF (50 mL). When effervescence ceases, the mixture is refluxed for 2 hours to prepare octyl dimagnesium dibromide. After cooling to room temperature, a solution of chlorodimethylethylsilane (5.0 g, 40.8 mmol) in THF (5 mL) was slowly added. After the addition is complete, the reaction mixture is heated under ^reflux for another hour. Carbon dioxide gas was passed through the cold reaction mixture for 30 minutes before the mixture was diluted with ether (50 mL) and acidified with dilute hydrochloric acid. The aqueous layer was separated and extracted with ether (3 x 25 mL). The combined ether layers were washed with water (2 x 25 mL), saturated sodium chloride solution (50 mL) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure afforded a white waxy solid which was extracted with hexane (3 x 50 mL). The combined hexane extracts were evaporated under reduced pressure to give a colorless liquid (5.94 g). This liquid is reacted with 2-benzoyloxy-1,4-naphthoquinone according to the method described in Example 1 and then according to the method described in Example 2 to give 2-hydroxy-3-(8-(dimethylsilyl)octyl)-1,4-naphthoquinone (753 mg) which recrystallizes from hexane, mp 39-41°C.

NMR peaks at: 184.7, 181.5, 152.9, 134.8, 132.9, 129.4,

126.8, 126.0, 124.8; 33.7, 29.8, 29.4, 29.3, 28.3, 23.9,

23.4, 14.8; 7.4, 6.9 -3.9.

Examples 15 to 17

By a procedure identical to the procedure described in Example 13, other compounds of general formula I are prepared, as detailed in the table below. In this table, the compounds are identified by reference to the compound of formula I.

Table 2 (In the following examples m = 1; n = 0; R ¹ and R ² together and R ⁷ and r 8 together mean the group =0; R ⁴ = = h)

in 4 »9 ·>· *« • • · « · • ♦ · · • · · « ♦ • • · • • · · · · φ ··· · • • ··· * · · « ♦ ··· «· ·« • · ·· • • ·

Example number R ^{3 R6} m.p. (°C) 15 -OH -(CH,) _r SiEi ₃ 51-53 16 -OH -(CH ₂ ) ₇ -SiPr ₅ 48-50 17 -OH -(CH ₂ ) ₇ -SÎMe ₂ Pr 45-47

NMR peaks were identified as follows:

Example 15

NMR peaks at: 184.7, 181.5, 153.0, 134.8, 132.9, 132.9,

129.4, 126.8, 126.1, 124.8; 33.9, 29.8, 29.4, 29.3, 28.3,

23.8, 23.4, 11.3; 7.5, 3.3.

Example 16

NMR peaks at: 184.7, 181.5, 153.0, 134.8, 132.9, 132.8,

129.5, 126.8, 126.0, 124.9; 34.0, 29.9, 29.5, 29.3,

28.3, 23.9, 23.4, 12.6; 18.7, 17.5, 15.6.

Example 17

NMR peaks at: 184.7, 181.5, 153.1, 134.8, 133.0, 132.8,

129.5, 126.8, 126.0, 124.9; 33.7, 29.9, 29.4, 29.3, 28.3,

23.9, 23.4, 18.0; 18.4, 17.4, 15.3, -3.3.

Example 18

Preparation of 2-hydroxy-3-(8-(1-methyl-(tetramethylenesilyl)octyl)-

of 1,4-naphthoquinone

Formula I: m = 1; n = 0; R ³ · and R ³ together and R 3 and R ® together both mean =0; R ³ = -OH; R ⁴ = R ⁵ = H; R ⁶ =

-(CH ₂ ) ₇ SiCH ₃ (CH ₂ ) ₄

A solution of dibromobutane (20.0 g, 92.6 mmol) in dry THF »4 ···« • « · 9 · • · « ♦ * « • · ·

(100 mL) was slowly added to magnesium shavings (4.5 g, 185 mmol). After the addition was complete, the mixture was heated under reflux for 1 hour and then cooled to room temperature. A solution of trimethylsilyl chloride (13.8 g, 92.6 mmol) in THF (10 mL) was added dropwise and heating under reflux continued for 30 min. The cooled solution is added dropwise to the prepared octyl dimagnesium dibromide solution as described in Example 14. The mixture is heated under reflux for 1 hour before cooling to room temperature and then carbon dioxide gas is bubbled through the solution for 30 minutes. The residue was acidified with dilute hydrochloric acid and extracted with ether (4 x 50 mL). The combined ether layers were washed with water (2 x 50 mL), saturated sodium chloride solution (50 mL) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure gave an off-white waxy solid which was extracted with hexane (3 x 50 ml). The combined hexane extracts were evaporated under reduced pressure to give a pale yellow oil. This liquid is reacted with 2-benzoyloxy-1,4-naphthoquinone according to the method described in Example 1 followed by the method described in Example 2 to give 2-hydroxy-3-(8-(1-methyl-(tetramethylenesilyl)octyl)-1 ,4-naphthoquinone (161 mg), mp 42 to 44

NMR peaks at: 184.7, 181.5, 153.0, 134.8, 132.9, 132.8,

129.4, 126.8, 126.1, 124.8; 33.5, 29.8, 29.4, 29.3, 28.3,

24.3, 23.4; 27.4, 15.1, 11.8, -3.2.

Example 19

Preparation of 2-hydroxy-3-(8-(1-methyl(pentamethylenesilyl)octyl)-

of 1,4-naphthoquinone

Formula I: m = 1; n = 0; R ¹ and together and R ⁷ and R ® together both mean =0; = -OH; R ⁴ = = H; R ⁶ =

-(ch ₂ ) ₇ stitches ₃ (ch ₂ ) ₅

A AA A · A

A A A· *· ♦·♦·

««« ··· AA ·· /

The same procedure as described in Example 17, but replacing dibromobutane with dibromopentane, gives 2-hydroxy-3(8-(1-methyl(pentamethylenesilyl))octyl)-1,4-naphthoquinone (10 g), melting point 38 to 40 ° C.

NMR peaks at: 184.7, 181.5, 153.0, 134.8, 133.0, 132.9,

129.5, 126.8, 126.1, 124.9; 33.6, 29.8, 29.4, 29.3, 28.3, 23.7, 23.4, 14.1; 30.2, 24.5, 12.9, -4.8.

Example 20

Preparation of 2-hydroxy-3-(3-trimethylsilyl-1-propenyl)-

of 1,4-naphthoquinone

Formula I: m = 0; n = 0; R ¹ and R ² together and R ⁷ and R ⁸ together both mean =0; R ³ = -OH; R ⁴ = R ⁵ = H; R ⁶ =

-CH=CH-CH ₂ Si(ch ₃ ) ₃

To a stirred solution of 3-trimethylsilylpropanol (5.0 g, 37.8 mmol) in dichloromethane (120 mL) was added pyridinium chlorochromate (16.3 g, 75.6 mmol) at room temperature. The mixture was stirred for 2 h and then filtered through silica gel using ether as eluent. The filtrate was evaporated under reduced pressure to give a colorless liquid (3.96 g). 2-hydroxy-1,4*f naphthoquinone (1.11 g, 6.40 mmol) and pyrrolidine (598 mg, 8.00 mmol). The reaction mixture was stirred for 15 h and p-toluenesulfonic acid (3.04 g, 16.0 mmol) was added and stirring was continued at room temperature for an additional 24 h and then refluxed for 3 h. The mixture was cooled and the solvent was removed under reduced pressure. The residue is dissolved in ether (50 ml) and washed with water (2 x 25 ml), diluted with hydrochloric acid (25 ml), water, saturated sodium chloride solution (2.5 ml) and dried over sodium sulfate. Filtration and evaporation of the solvent under reduced pressure and chromatography using a mixture of hexane and ether as an eluent gives _ 9 ς _ ς * ♦ · · · ··· “ ··* ··♦ ♦ · ·· ·· ··

2-hydroxy-3-(3-trimethylsilyl-1-propenyl)-1,4-naphthoquinone (123 mg), mp 72-74°C.

NMR peaks at: 184.6, ca 182, 150.5, 134.7, 133.0, 132.8, ca

129, 126.9, 125.8, about 120 ^; 142.5, 117.0, 27.4' -1.8.

Example 21

4« ···»

Preparation of 2-ethanoyloxy-3-(9-trimethylsilylnonyl)-1,4naphthoquinone (Formula I; m = 1; n = 0; R ¹ and R ² together and R ⁷ and R ⁸ together both mean =0; R ³ = - O-CO-CH^; R ⁴ = R ⁵ = H; R ⁶ = -(CH ₂ ) ₈ Si(CH ₃ ) ₃ )

In the same manner as in Example 4 for 2-hydroxy-3-(9-trimethylsilynonyl)-1,4-naphthoquinone. Example 12 gives 2-ethanoyloxy-3-(9-trimethylsilynonyl)-1,4-naphthoquinone, mp 4.5 to 47°C.

NMR peaks at: 184.5, 178.1, 151.1, 139.9, 134.0, 133.8, 132.1, 130.9, 126.7, 126.6; 33.6, 29.7, 29.4, 29.3, 28.5,

24.3, 24.0, 16.7; -1.6; 168.0, 20.4, (COCH ₃ ).

Example 22

Preparation of 2-propanoyloxy-3-(9-trimethylsilylnonyl)-1,4naphthoquinone (Formula I: m = 1; n = 0, R ¹ and R ² together and R ⁷ and R ⁸ together both mean =0; R ³ = -O-CO-CH2CH3; R ⁴ = R ⁵ = H; R ⁶ = -(CH 2 ) ₈ Si(CH ₃ ) ₃ )

To a stirred solution of 2-hydroxy-3-(9-trimethylsilylnonyl)-

1,4-naphthoquinone, Example 12 (100 mg, 0.27 mmol) in dry dichloromethane (10 mL) was added at room temperature with pyridine (0.5 mL) and after 3 minutes propanoyl chloride (62 mg, 0.67 mmol) . The reaction mixture is stirred for 2 hours and diluted with dichloromethane (50 ·· ♦· • · · · · · · * • « · · « A « · · · · · ·♦♦ * * « · · « · ·*· ··· ·· ·« ·» ··

- 26 ·« · ··· ml), washed with water (2 x 30 ml), dilute hydrochloric acid (30 ml), saturated sodium chloride solution (30 ml) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure and chromatography using a mixture of hexane and ether as the eluent afforded 2-propanoyloxy-3-(9-trimethylsilylnonyl)-1,4-naphthoquinone (112 mg} ' temperature tan1^41 ¹ to'* '43°C.

NMR peaks at: 184.6, 178.2, 151.2, 139.8, 134.0, 133.7, 132.1, 130.9, 126.7, 126.5, 33.6, 29, 7, 29.4, 29.3, 29.3,

28.5, 24.3, 23.9, 16.7, -1.6; 171.6, 27.3, 9.1 (COCH ₂ CH ₃ ).

Example 23

Preparation of 2-vinylcarbonate-3-(9-trimethylsilylnonyl)-1,4naphthoquinone (Formula I: m = 1; n = 0; R ¹ and R ² together and R ⁷ and R ⁸ together both mean =0; R ³ - - O-CO-O-CH=CH2; R ⁴ = R ⁵ = H,- R ⁶ = -(ch 2 ) ₈ si(ch ₃ ) ₃ )

AND

To a stirred solution of 2-hydroxy-3-(9-trimethylsilylnonyl)-

1,4-naphthoquinone, Example 12 (100 mg, 0.27 mmol) in dry dichloromethane (10 mL) at room temperature is added pyridine (0.5 mL) and after 3 minutes vinyl chloroformate (43 mg, 0.40 mmol) . The reaction mixture was stirred for 2 hours and diluted with dichloromethane (50 mL), washed with water (2 x 30 mL), dilute hydrochloric acid (30 mL), saturated sodium chloride solution (30 mL), and dried over magnesium sulfate. and evaporation of the solvent under reduced pressure and chromatography using a mixture of hexane and ether as eluent gave 2-vinylcarbonato~3-(9-trimethylsilylnonyl)-1,4-naphthoquinone (79 mg), n _D 1.5123.

NMR peaks at: 184.6, 178.0, 149.9, 139.9, 134.6, 134.3,

132.3, 130.9, 127.1, .126.8, 33.9, 30.6, 30.0, 29.7, 29.6,

29.6, 29.5, 28.8, 24.5, 24.2, 16.9, -1.3; 149.8, 142.8, 99.8. (-O-CO-O-CH=CH ₂ ).

J , *· ···· »* *· .: · . · ···· • · · · · · ·· • · · · ·♦ ·· · · ♦ . .:. ’..··» ····»’

Example 24

Preparation of 2-ethoxymethoxy-3-(9-trimethylsilylnonyl)-1,4naphthoquinone (Formula I: m = 1; n = 0; R ¹ and together and R ⁷ and R® together .......: cha 7Π ampn a-jT-=QP ³ . - . - Q- GP-O - (TT„ - P ⁴ _ R® ₌ R ;*R®*= ..............

-(CH ₂ ) ₈ Si(CH ₃ ) ₃ )

To a stirred solution of 2-hydroxy-3-(9-trimethylsilylnonyl)-

To 1,4-naphthoquinone, Example 12 (500 mg, 2.06 mmol) in dry dichloromethane (20 mL) was added diisopropylethylamine (1.33, 10.3 mmol) at room temperature and after 3 minutes ethoxymethyl chloride (831 mg, 10 .3 mmol) in dichloromethane (5 mL). The reaction mixture is stirred for 1 hour and diluted with dichloromethane (30 mL), washed with water (2 x 20 mL), dilute hydrochloric acid (20 mL), saturated sodium chloride solution (20 mL) and dried over magnesium sulfate, Filtration and evaporation of the solvent under reduced pressure and chromatography using a mixture of hexane and ether as eluent gave 2-ethoxymethoxy-3-(9-trimethylsilylnonyl)-1,4-naphthoquinone (567 mg), n _D 1.5182.

NMR peaks at: 185.3, 181.6, 155.5, 137.1, 133.8, 133.2, 132.0, 131.4, 126.3, 12.6.,2,. 33.6, .30.1, 29.5, 29.4, 29.3, 28.9, 24.1, 23.9, 16.7, -1.6; 96.9, 65.8, 15.0 (o-ch ₂ -o-ch ₂ ch ₃ ).

Example 25

Preparation of 2-hydroxy-3-(2-(1',4 ¹ ,4'-dimethyl-4-silacyclohexyl)propyl)-1,4-naphthoquinone (Formula-Ι, as Example 24 with R® = -(CH ₂ ) ₃ -(C ₅ H _g Si)(CH ₃ ) ₂

To a stirred solution of 4,4-dimethyl-4-silacyclohexanone (prepared as described in Sonerquist and Negron: J. Org. Chem.) (900 mg, 6.32 mmol), ethyl cyanoacetate (716 mg, 6.32

- 28 • 99 • •9 •9 ·9··

9

mmol) and piperidine (215 mg) in benzene (30 mL) was added at room temperature with acetic acid (760 mg) and the mixture was heated under reflux under azeotropic conditions for 2.5 h. The reaction mixture was cooled to room temperature, diluted with ether (30 mL) and washed with water (2 x 25 mL). saturated sodium chloride solution (25 ml) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure and chromatography using a mixture of hexane and ether as eluent gave a colorless liquid (0.52 9).

This liquid was dissolved in ether (5 mL) and added dropwise with stirring at 0 °C under nitrogen to a solution of methylmagnesium bromide (30 mg, 1.8 mmol) in ether (20 mL). The mixture was stirred for an additional 2 hours and diluted with ether (25 mL), water (10 mL) and acidified with dilute hydrochloric acid. The aqueous layer was separated and further extracted with ether (2 x 25 mL) and the combined ether extracts were washed with water (2 x 20 mL), brine (20 mL) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure gave a colorless oil, which was treated with potassium hydroxide (550 mg) in ethylene glycol and refluxed for 16 h. The reaction mixture was cooled to room temperature, diluted with water (40 mL) and washed with ether (2 x 25 mL). The aqueous layer was acidified with dilute hydrochloric acid and extracted with ethyl acetate (4 x 25 mL). The combined extracts were washed with water (2 x 20 mL), brine (20 mL) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure gave an almost colorless liquid (300 mg).

The liquid was worked up ^by a procedure similar to that described in Example 1 above to give 2-hydroxy-3-(2-(1',41,4dimethyl-4-silacyclohexyl)propyl)-1,4-naphthoquinone.

»9 ·<♦

- 29 Example 26

Pesticidal efficacy

Pesticidal efficacy against houseflies, beetles, moths, mites and flies was determined using the following methods. ' ^{Ύ rr} ' ^r '··'··· ^nr ·····

House fly (Musea domestica)

A 1 μΐ drop of the solution of the tested compound was dripped onto the thorax of female houseflies. Two replicates with 15 flies were used for each dose of the substances examined (a total of 6 different doses for each substance). After application, the flies were kept at a temperature of 20 + - 1 °C and dead bodies were determined after 24 and 48 hours. LD _5Q values were calculated in micrograms of the test substance on the fly (see Sawicki et al., Bulletin of the World Health Organization, 35, 893 (1966) and Sawicki et al., Entomologie and Exp. Appli 10, 253, (1967) )

Beetle (PC) (Phaedon cochlearia Fab)

One microliter of an acetone solution of the test substance was applied ventrally (on the underside) to adult beetles using a microapplicator. The investigated insects were left for 48 hours, after which mortality was determined. Two replicate determinations with 20 to 25 beetles were used for each of the five different doses of the test substance. LD ₅₀ values were determined similarly to house flies.

Mite (TU) (Tetranychus urticae) adult females were immersed for 30 seconds in 35 μΐ of a solution of the test substance in a 1:4 mixture of acetone and water. Insects were kept at a temperature of 21 +/- 2 °C and death was determined after 72 •Φ ··· • 9

- 30 Φ φφ • Φ v · «· ♦· φφ ο Φ and ΦΦ • Φφ

ΦΦ ΦΦ hours. Mites showing repetitive (not reflex) movements of more than one of the locomotor projections were scored as alive. Three replicate measurements of groups of 25 mites each were used for each of 5 or 6 different doses of each test compound. LC ₅ q were calculated in ppm solution of the tested substance on one pest. The test was performed using a strain of mites**(GSŠj supplied by ScheringT ^r ÁG,' ^ΙΓΓ * Berlin.

Fly (BT) (Bemisia drag)

An acetone solution (0.100 ml) of the test substance was placed in a 10 ml vial and evaporated with rotation to form a deposit in the form of a film of the compound. Thirty adult flies were placed in a vial and after 60 minutes the test insects were transferred to pieces of cotton discs kept moist on a layer of agar gel. The temperature was maintained at 25°C and mortality recorded after 48 hours. Three replicate measurements were used for each of 5 to 7 different doses of the test compound. LC^q values were calculated using a computer program package (Polo-PC by LeOra Software, Berkley, California) (see M.R. Cahill and B. Hackett, Proceedings Brighton Crop Protection Conference, 1992). The test was performed using a strain of flies (SUD-S) collected in Sudan in 1978 on cotton.

The results of these tests are summarized in Table 3 below. Unless otherwise stated, values given are LD ₅₀ (pg/insect) or LC ₅₀ (ppm solution of test compound).

·♦ ··>·

4« ··

• • • 5 9 • 9 994 Ch

4 * * 9 «

0 9 • ♦ · ♦ *9 ·· » ·· « · ·9 • · ·· * 999 94 • 9· ··-»9

Table 3

Example number MD (LD50) pc (LD50) TU (GSS) (LC50) BT(SUD-S) (LC50) “-i— >20>-m. Wn >20 »·. -.....110 “ ”·*· - -·Μ- 9· 2 0.69 0.45 38 2.6 J 1.3 c.1.0 2.8 6.8 4 c.20 c.2.0 45 2.9 5 . >20 c.20 41 6 - c.20 - 1.7 7 4(4 c.8 6.4 c.9 8 1.8 c.l 9.2 duty 9 1.8 CD 4.5 100% 10 1-7 c.0.2 0.31 8.2 ¹¹ 2.3 c.l 0.51 14.6 12 '2.8 0.13 0.9 8.6 13 9.9 c.0.6 2.2 - 14 - c2 c2 15 15 - c2 5.2 22 16 - >20 - 79%* 17 - c.l 8.4 13 18 - c.2 3.6 - 19 c.l - 13%· 20 - >20 21 30 21 c2 c2 2.0 <100 22 - c2 c20 C100 23 - c2 c50 32%· 24 - c20 - 19%·

• · · · « · ·· • · · · · * = mortality at 100 ppm, - = not done

Example 27

Efficacy on ^aphids Efficacy on resistant (R) and susceptible (S) aphid strains (Myzus persicae) was evaluated using the following method.

Local application

Groups of 10 to 15 adult aphids were selected from stock farms and placed on 35 mm diameter Chinese cabbage slices and placed on a bed of agar in disposable plastic dishes. Using a Buckhard microdispenser, each aphid received a droplet of the chemical diluted to the desired concentration in acetone. Control insects received only acetone. Mortality and other effects were recorded at 24 hour intervals for a total duration of 72 hours inclusive. The results refer to the end time of the experiment.

Soaking aphids

Trap bands were painted inside 4 cm long glass tubes (1.5 cm in diameter) and squares of insect-proof gauze were applied to both ends of the tube. 15 wingless adults were transferred to tubes using a sable brush and the tube was sealed with a square of gauze.

Tubes containing aphids were immersed in the insecticide solutions for 10 seconds, dried on a blowtorch, and then inverted and sealed so that the affected aphids fell out of the non-immersed end of each tube. Mortality following this procedure (usually 0 or very little) was recorded after 1 hour when aphids were transferred to Chinese cabbage leaves (35 mm diameter) on an agar mat (25 mm deep) in a plastic container • « (30 mm high) and were pressed with a Teflon ring. The trays were placed upright without a lid in an incubator maintained at 25°C with constant lighting. Mortality was determined after 24, 48 and 72 hours. Two samples of 15 aphids were used for each dose and 5 or 6 doses were used for each test compound.

^,m '·....... ^1,1 .....The test'*was*carried out'using'sensitive' ^l km'ehe* ^r aphids*' (UŠIL) collected in a field in East Anglia and of an extremely resistant aphid strain (794Jz) (R3 esterase, sensitive to AChE) collected from a UK greenhouse

The results of this test are shown in Table 5 below. Values are given as % mortality with correction to the control sample. The control includes the tested solution without the active ingredient.

·· ···

Table 4: Results on aphids when applied topically

All results are reported as percent mortality unless otherwise noted.

...... ...Example MP number HE HAD 794JZ 2 45 3 100 7 45 8 90 100 9 100 10 100 11 100 95 12 89 13 90 14 74 15 58 16 24 17 88 18 59 21 66 < ² ' 89 22 37 23 63 24 16

W 1000 ppm ^l_í 125 ppm • a

Table 5

Aphid dipping results

All results are given as % mortality at 100 ppm

Example number MP A. G. - „ -794JZ , 81-171B _w -> 77 54 63 3 100 100 4 19 19 7 90 57 8 90 100 9 100 71 10 100 100 if 100 100 12 100 61 93 13 90 83 21 66

MP ~ Myzus AP = Aphis

Example 28

Fungicidal efficacy

The fungitoxicity of the compounds according to the invention to Aspergillus niger, Pyricularia orazae (= Magnaporthe grisea) and Rhizoctonia solani was tested in vitro.

Each compound was loaded onto potato dextrose agar in solvent (50/50 ethanol/acetone) in 0.5 ml solvent per 250 ml agar, with the autoclaved agar still melted and cooled to 50 °C. Each compound was tested at one concentration (100 mg I ^- · ⁵ ·).

Each test, usually of two compounds, included three control samples: (i) standard fungicide (carbendazim at 1 or 5 mg l ¹ or prochloraz at 1 mg 1 ^_1 ), (ii) only

- 36 ethanol/acetone,· and (iii) without additives. Fungicides used as standards can be considered representative of active, commercially available compounds.

Each fungus was tested on agar in 4 Petri dishes per experiment with three replicate fungal colonies per dish (one colony for R. solani). A. niger and R. solani were incubated for 4 days at 20 to 25°C with Z^Z^oryzae for 7 days. The increase in colony diameter was measured and used to determine efficacy.

The results of these tests are shown in Table 6 below. Values are given as % inhibition of colony diameter growth in agar plates.

· ····

- 37 Table

| Activity what P 1 ·»«* - - oo oč O\ - ⁴ *'*r O· h- ΠΊ «*ί >u O. — lips what 00 ’Τ _7Í •F" O oh > O what Act VI what O O Q what rΌ Vk Γ*Ί lips 4— ¹ > * >1 and 1—< at XI d »£? C with X l— C t) N > s TO C IN" O -w< IN) < rsZ < "•in* Π5 those >0 H N £ a lips with N Q> O lip ¹ >U r CM 04 04 r" <J Ό d AND! at ΰ ΰ O Ή O rH L_ what Λ ΰ ϋ

• ·

Tests have shown that the compounds of general formula I show a good fungicidal effect against a wide range of fungi that cause diseases in both grain and broadleaf crops. A particularly good activity was observed against fungi of the genus Erysiphe, especially Erysiphe graminis, and Botrytis, especially Botrytis fabae and Botrytis cinerea, also of the genus Rhizoctonia, Pyricularia and Èspergillus as indicated by Hora'.

Table 7 further shows the pesticidal efficacy of comparative prior art naphthoquinone compounds to better illustrate the relative efficacy of the compounds of the invention. The efficiencies reported were obtained using the methods described in Examples 27 and 28 above.

Considering the prior art naphthoquinones disclosed in DE 3801743 and EP 0300218, their list of activity against Tetranychus is less than the corresponding tert-butyl compound (see Table A for EP 0300218). This tert-butyl compound was tested by the present inventors of the invention and was found to have LC ₅₀ values of 44 ppm/insect against Tezranycus and 18 ppm against Bemisia; LD ₅ q 16 jzg/insect against Musea and 0.53 ^g/insect against Phaedon and gives 19% mortality against Myzus in the above tests.

* • 4

- 39 -*0· « “•‘pancake

O νι O

E a. &_;

ZZZ ⁰⁰ “ ~ — O

Λ

O

II

WHAT

Honor

About II

II what

Honor >

that (0

CN honors

H honor >4 n 05 i—I 4th •M . > P . and

Ή

U >

'Honor

O w rtd

4th rd P Λ

H

un Cl 0 vn XO 0 0 vS < Τ' O — r·“ 0 0 0 —* Ό —· in Ό at

o o rH •rl >μ

Ό c.

E ft

C

C4 CJ

ca

- <

OF

< < < Γ Γ* 00 Γ 0T < < of of of at at at at 0 —2 0 at of of

Γ*Ί

Ref

<r» rn jp γ-ϊ γ*ί mm JZ ¹ r*šT —

X UUUUOO^

CN rn Ťy <ΖΊ Γ· of ⁴ 3 D ¹ 3 3 3/ /?**CM ΐ - ý y. ΰΰ » ⁴ I * ) i**—* o

··'

In order to demonstrate the preparation of naphthoquinone rings bearing substituents in positions 5, 6, 7 or. 8 shows the following examples 29 to 31 falling outside the scope of the invention.

Example 29 "Preparation"2 *( tert -butyl )3-hydroxy-6-methyl-naphthalen-1·? 4-***..............

dione and 2-(tert.butyl)-3-hydroxy-7-methylnaphthalene-1,4-dione

a) Preparation of 6-methylnaphthalene-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 h at room temperature. The mixture was diluted with water (44 mL) and heated under reflux for 1.5 h. The mixture was cooled to room temperature and acetic acid (84 mL) and chromic acid [chromite oxide (29.4 g in water (30 mL)) were added sequentially and heating under reflux was continued for an additional 1.5 h. 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 sulfate. Filtration and evaporation of the solvent under reduced pressure and repeated recrystallization from petroleum ether gave the title compound (7 g).

b) 2-Amino-6 and 7-methyl-1,4-naphthalene-1,4-diones

To a stirred solution of 6-methylnaphthalene-1,4-dione (2.1 g, 12 mmol) in glacial acetic acid (60 mL) was added a solution of sodium azide (1.58 g) in water (5 mL) at room temperature. The mixture is stirred for 2 days and diluted with water (200 ml) and filtered after another IS minute stirring. The filtrate was neutralized 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 over calcium sulfate. Filtration and evaporation of the solvent under reduced pressure and chromatography on silica gel give ···

♦ · · · ·· ··* · ·

4*4 title compound (100 mg) as a 3:2 mixture of isomers.

c) 2-Hydroxy-6- and 7-methylnaphthalene-1,4-diones

The aminomethylnaphthalene-1,4-dione mixture of Example (b) (200 mg) was heated under reflux in water (20 mL) and concentrated sulfuric acid (10 mL) for 20 minutes. The cooled mixture was poured into a mixture of ice and water (50 g) and extracted with ether (3 x 25 mL). The combined ether extracts are washed with water, saturated sodium bicarbonate, water, saturated NaCl and dried over magnesium sulfate. Filtration and evaporation of the solvent and purification by column chromatography gave the title compound (68 mg).

d) Preparation of 2-(tert.butyl)-3-hydroxy-6 and 7-methyl-3-hydroxynaphthalene-1,4-diones

Standard radical addition of peroxysulfate and silver nitrate to aminomethyl compound (64 mg, 0.34 mmol), trimethylacetic acid (52 mg, 0.51 mmol) gave the title compound as a 3:2 mixture of isomers (12 mg).

r

Example 30

Preparation of 2-(tert.butyl)-6 and 7-dimethyl-3-hydroxy-naphthalene-1,4-diones

Steps (a) to (d) above are repeated, replacing isoprene

2.3-dimethyl-1,3-butadiene.

Example 31

Preparation of 2-(tert.butyl)-3-hydroxy-5 and 8-methyl-1,4-naphthalene-

1.4- diones

Steps (a) to (d) above are repeated, replacing isoprene with piperylene.

a) Preparation of 6-methyl-1,4-naphthalene-1,4-dione

A solution of 1,4-benzoquinone (13.9 g, 128 mmol) and isoprene

AI ····

AND

- 42 ♦·*

A* •A •A

A A A • A

And A

AND

A • A • A ··

AA AA

A A· A·

A A♦ tt ·· (13.1 mL, 131 mmol) was stirred in ice-cold acetic acid (44 mL) for 68 h at room temperature. The mixture was diluted with water (44 mL) and heated under reflux for 1.5 h. The mixture was cooled to room temperature and acetic acid (84 mL) and chromic acid [chromic oxide (29.4 g in water (30 mL)] were added sequentially and reflux continued for an additional 1.5 h. 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 chloride solution of sodium (50 ml) and dried over magnesium sulfate. Filtration and evaporation of the solvent under reduced pressure and repeated recrystallization from petroleum ether gave the title compound (7 g).

Claims (20)

PATENT CLAIMS R ³ ICR ^ RS} __ _R 6 A naphthoquinone compound of formula (I) or a salt thereof, wherein m is 0 or 1, n is a number from 0 to 4, each R independently represents a halogen or nitro, cyano, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, amino, alkylamino, a dialkylamino, alkoxycarbonyl, carboxyl, alkanoyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carbamoyl, alkylamide, cycloalkyl, aryl or aralkyl group, R ¹ and R ² each independently represent an optionally substituted alkoxy group or together represent = O; = S.,. = N-OR ⁹ where R ⁹ represents a hydrogen atom or an optionally substituted alkyl group, R ³ is an optionally substituted alkyl, hydroxyl or -OL group wherein L is a leaving group or a group that is converted in vivo to -L ¹ where L ¹ is a leaving group, R ⁴ and R ⁵ when each independently present are hydrogen or halogen or optionally substituted alkyl or together with an intermediate carbon atom are optionally substituted cycloalkyl or cycloalkenyl optionally containing at least one ring silicon atom, - 44 ^ ⁷ R ⁶ represents an optionally substituted group containing at least one silicon atom, or when m is 1 and the moiety -CR ⁴ R ⁵ contains at least one silicon atom, R 6 may further be a hydrogen atom or an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, alkoxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy or aryloxy group, and ^R7 and R® independently represent an optionally substituted alkoxy group or together gj represent a group = 0, = S or = N-oR, wherein R has the meaning above. '* The naphthoquinone compound of claim 1, wherein R 1 is I present, is halogen, nitro, cyano, hydroxy, 0 _1-4 alkyl, C -] __ ₄ haloalkyl, C j__ ₄ alkoxy, C ₄ _ ₄ haloalkoxy, C ₄ _ ₄ alkylamino, di-C _ _{L 4} alkylamino, C ₁ _ ₄ alkoxycarbonyl, _C1-4 alkylthio 0, C _1-4 alkylsulphinyl or C ₄ _ ₄ alkylsulfonyl. The naphthoquinone compound of claim 1, wherein n is 0. The naphthoquinone compound of any one of the preceding claims, wherein each R ¹ and R ^{2 is} independently a C 1-4 alkoxy group, or together is = O or = N-OR ⁹ wherein R ® is hydrogen or C _1-4 alkyl. A naphthoquinone compound according to any one of the preceding claims, wherein R ³ represents an optionally substituted alkyl group or -OR ¹ ®, wherein R ¹ ® represents a hydrogen atom, an optionally substituted alkyl, aryl or aralkyl group, or a -COR ¹¹ group, -SOR ¹¹ , -SO2R ¹¹ , -P (X) (OR ¹² ) (OR ¹³ ), -P (X) (R ¹² ) (OR ¹³ ), -P (OR ¹² ) (OR ¹³ ), or P (R ¹² ) (OR ¹³ ), where R ¹¹ represents a hydrogen atom, an optionally substituted alkyl, aryl or aralkyl group or a group -NR ¹² R ¹³ where R ¹² and R ¹³ independently represent an atom - 45 y 4. in hydrogen or an optionally substituted alkyl group and X represents an oxygen atom or a sulfur atom. A naphthoquinone compound according to any one of the preceding claims, wherein R ³ represents an alkyl group, a hydroxyl group or a group -OCOR ¹¹ , wherein R ¹¹ represents a hydrogen atom. · - ^ 1.11 ^ - 11--11) 111 ^ 1111.11-1.1111) .1-1 IIH I) U-) _'F <ι · · .ιίιι Τ J * />. -I lill · —UIHT-'Τ- -II < or alkyl, C ₁ _ ₁ 2 haloalkyl, C ₁ _ ₁₂ hydroxyalkyl, C ₁ _ 2 ₁ carboxylalkyl, phenyl or I, benzyl. ť * A naphthoquinone compound according to any one of the preceding claims wherein R ⁴ and R ³ are independently hydrogen or C _1-4 alkyl. A naphthoquinone compound according to any one of claims 1 to 10 6, wherein R ⁴ and R ³ together with the intermediate carbon atom represent a ^C 3-8 cycloalkyl group optionally substituted by one or more substituents selected from halogen atoms, alkyl and C _1-4 haloalkyl groups. A naphthoquinone compound according to any one of the preceding claims, wherein R ® represents an alkyl, haloalkyl, alkoxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, alkenyl, haloalkenyl or alkoxyalkenyl group, each group containing one or two silicon atoms and up to 20 carbon atoms. % A naphthoquinone compound according to any one of claims 1 to 6, wherein R ⁴ and R ³ together with the intermediate carbon atom represent a silacycloalkyl group containing from 3 to 8 atoms optionally substituted by one or more substituents selected from the group consisting of halogen atoms, Calkyl group or C _1-4 haloalkyl. A naphthoquinone compound according to claim 10, wherein R ⁶ represents a hydrogen atom or an alkyl, haloalkyl, alkoxyalkyl, alkoxy, haloalkoxy, alkoxyalkoxy, alkenyl, haloalkenyl or alkoxyalkenyl group, each optionally containing one or two silicon atoms and up to 12 atoms carbon. A naphthoquinone compound according to any one of UK »í» !IMIWI IIIWII They Mean III »«! —Μ ·· ΙίΙ> «. ..M ~ - Mlι »Ml I, ΜΜΜ» Q. - J - α .-, Γ. .. «|| _γ | _{Γ .Π} preceding claims wherein R 'and R ^{independently} represent a C 1-4 alkoxy group or together represent a group = 0 or = N · 0R ⁹ wherein R ⁹ is hydrogen or alkyl C4_ _4' group. > · A naphthoquinone compound according to any one of claims 1 to 12, wherein R 1 represents a group of the general formula - (A) _m -Si (R ¹⁴ ) 3, wherein m is as defined for formula (I), each R ¹⁴ independently represents a C 1-4 alkyl group or with an intermediate silicon atom forms two such groups a silacarbocyclic ring and A represents C an alkyl or alkenyl group which may be halogen-substituted and which may be a straight or branched chain or is or includes a carbocyclic ring. A naphthoquinone compound-according to any one of claims 1 to 12, wherein R 4 comprises a silicon atom as a ring atom in another carbocyclic ring A naphthoquinone compound according to any one of claims 1 9 to 12, wherein R 1 is - (CH ₂ ) p -Si (R ¹⁴ ), wherein p is an integer of 1 to 15, preferably 1 to 10, especially 1 to 6, and each * R ¹⁴ is independently C- [ __ ₄ alkyl or the two groups R ¹⁴ together with the intermediate silicon atom forms a 3 to 8-membered silacarbocyclic ring. 16. A pesticidal composition comprising a carrier and, as an active ingredient, a naphthoquinone compound of formula (I) or a salt thereof according to any one of claims 1 to 15. The composition of claim 16 substantially as described above. 18. A method of controlling pests at the locus of infestation, _V: -y * z '* N * C''* U * I C j Í ^^ - t ^ i-m · infestation that rnísto * * ** is a · A naphthoquinone compound of formula I or a salt thereof according to any one of claims 1 to 15 or i) a composition according to claim 16 or claim 17. Use of a naphthoquinone compound of formula I or a salt thereof according to any one of claims 1 to 15 or a composition according to claim 16 or 17 as a pesticide. 20. A naphthoquinone compound of formula I substantially as described above and with reference to any of Examples 1 to 26.