WO2006089038A2 - Insecticidal tetrahydroindenopyridine derivatives - Google Patents

Abstract

Certain tetrahydroindenylpyridine derivatives provide unexpected insecticidal and acaricidal activity. These compounds are represented by formula (I); wherein R, R1, R2, and R3 are fully described herein. In addition, compositions comprising an insecticidally effective amount of at least one compound of formula (I), and optionally, an effective amount of an additional compound, and an insecticidally compatible carrier are also disclosed; along with methods of controlling insects comprising applying said compositions to a locus where insects are present or are expected to be present.

Description

INSECTICIDAL TETRAHYDROINDENOPYRIDINE DERIVATIVES

This application claims the benefit of U.S. Provisional Application No. 60/653703 filed February 17, 2005.

FIELD OF THE INVENTION

The present invention generally relates to pesticidal compounds and their use in controlling insects and acarids. In particular, it pertains to compositions of pesticidal tetrahydroindenopyridine derivatives, agriculturally acceptable salts thereof, and methods for their use in controlling insects and acarids.

BACKGROUND OF THE INVENTION

It is well known that insects in general can cause significant damage, not only to crops grown in agriculture, but also, for example, to structures and turf where the damage is caused by soil-borne insects, such as termites and white grubs. Such damage may result in the loss of millions of dollars of value associated with a given crop, turf or structure. Although there are many orders of insects that can cause significant crop damage, insects, for example, of the order "Homoptera" are of major importance. The order Homoptera includes, for example, aphids, leafhoppers, cicadas, whiteflies, and mealy bugs. Homoptera have piercing/sucking mouthparts, enabling them to feed by withdrawing sap from vascular plants. Insect damage from Homoptera is manifested in several different ways, other than damage caused by direct feeding. For example, many species excrete honeydew, a sticky waste product that adheres to plants upon which the insect feeds and lives. Honeydew alone causes cosmetic injury to crop plants. Sooty molds will often grow on honeydew, making food products or ornamental plants look unappealing, thereby reducing their cosmetic and economic value. Some Homoptera have toxic saliva that is injected into plants while they are feeding. The saliva can cause plant damage through disfigurement and in some instances plant death. Homoptera can also vector disease-causing pathogens. Unlike direct damage, it does not take a large number of disease-vectoring insects to cause considerable damage to crop plants.

Thus, there is a continuing demand for new insecticides, and for new acaricides that are safer, more effective, and less costly. Insecticides and acaricides are useful for controlling insects and acarids which may otherwise cause significant damage both above and below the soil level to crops such as wheat, corn, soybeans, potatoes, and cotton to name a few. For crop protection, insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and which have no deleterious effects to mammals and other living organisms. A number of patents disclose some tetrahydroindenopyridine compounds that are reported to have pharmaceutical activity. For example, US Patent 3,928,360 discloses pharmaceutically acceptable acid addition salts of the general formula I:

I wherein

R₁ is lower alkyl of one to four carbon atoms, cycloalkyl of five or six carbon atoms, phenyl or phenyl monosubstituted by chlorine, bromine, fluorine, methoxy, methylthio or lower alkyl of one to four carbon atoms, and A is a straight or branched alkylene of one to four carbon atoms.

German Offenlegungsschrift DE 2002499 discloses certain 2,5-dialkyl- 1,3,4,9a- tetrahydro-2H-indeno[1.2-c]pyridines having salidiuretic, analgesic and antiphlogistic activity.

German Offenlegungsschrift DE 2300617 discloses certain 5-alkyl- 1,3 ,4,9a- tetrahydro-2H-indeno[ 1.2-c]pyridines having pharmaceutical activity.

Switzerland CH 555336 claims l,3,4,9b-tetrahydro-2H-indeno[l,2-c]pyridine derivatives useful as analgesics. US Patent 3,737,544 claims 2,5-dimethyl-l,3,4,9b-tetrahydro-2H-indeno[1.2- c]pyridine salts useful as psychotropics, sedatives, and analgesics.

Netherland NL 6500312 discloses l,3,4,9b-tetrahydro-2H-indeno[1.2- c]pyridines and their salts as^' having sedative neuroleptic and adrenolytic properties. US Patent 3,678,057 discloses the preparation of several l,3,4,9b-tetrahydro-

2H-indenol[l,2-c]pyridine compounds as intermediates.

US Patent 3,497,517 describes l,3,4,9b-tetrahydro-2H-indeno[l,2-c]pyridine compounds which exhibit analgesic and blood pressure lowering activity.

As set forth in J. Med. Chem., 1995, 38,753-763, the preparation of certain 2,7- dialkyl-l,3,4,9b-tetrahydro-lH-indeno[l,2-c]pyridines is described as intermediates to 2,7-dialkyl-l,3,4,4a,5,9b-hexahydro-lH-indeno[l,2-c]ρyridines.

There is no disclosure or suggestion in any of the above-referenced patents or articles of the insecticidal and acaricidal activity of the compounds of the present invention. SUMMARY OF THE INVENTION

In accordance with the present invention, it has now been found that certain tetrahydroindenopyridine derivatives are surprisingly active in the control of insects and acarids when used in the insecticidal and acaricidal compositions and methods of this invention. The insecticidal and acaricidal compositions of the present invention are comprised of at least one of an insecticidally effective amount of a compound of formula I and at least one insecticidally compatible carrier therefor, wherein the compound of formula I is:

I wherein

R and R¹ are independently selected from hydrogen and alkyl; R² is selected from hydrogen, alkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, hydroxycarbonyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; provided that when R is hydrogen and R¹ and R³ are each methyl, then R² is other than 3-trifluoromethylphenyl; or

R and R¹ are taken together with =CR⁴-CR⁵=CR⁶-CR⁷= to form a benzo-fused ring; wherein R⁴, R⁵, R⁶, and R⁷ are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, formyl, hydroxycarbonyl, alkoxycarbonyl, and mono- or dialkylaminocarbonyl;

R² is selected from hydrogen, alkyl aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; the N-oxides thereof; and the agriculturally acceptable salts thereof. The present invention is also directed to compositions containing an insecticidally effective amount of at least one of a compound of formula I, and optionally, an effective amount of at least one additional compound, with at least one insecticidally compatible carrier.

The present invention is also directed to methods of controlling insects, where control is desired, which comprise applying an insecticidally effective amount of the above composition to the locus of crops, or other areas where insects are present or are expected to be present.

DETAILED DESCRIPTION OF THE INVENTION

The present invention generally relates to insecticidal and acaricidal compositions of tetrahydroindenopyridine derivatives and to certain new and useful compounds, namely certain tetrahydroindenopyridine derivatives that are surprisingly active in the control of insects and acarids when used in the insecticidal and acaricidal compositions and methods of this invention. The insecticidal and acaricidal compositions of the present invention are comprised of at least one of an insecticidally effective amount of a compound of formula I and at least one insecticidally compatible carrier therefor, wherein the compound of formula I is:

I wherein

R and R¹ are independently selected from hydrogen and alkyl;

R² is selected from hydrogen, alkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, hydroxycarbonyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; provided that when R is hydrogen and R and R are each methyl, then R is other than 3 -trifluoromethylphenyl; or R and R¹ are taken together with =CR⁴-CR⁵=CR⁶-CR⁷= to form a benzo-fused ring; wherein R⁴, R⁵, R⁶, and R⁷ are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, formyl, hydroxycarbonyl, alkoxycarbonyl, and mono- or dialkylaminocarbonyl; R² is selected from hydrogen, alkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; the N-oxides thereof; and the agriculturally acceptable salts thereof.

More specifically, preferred species of this invention are insecticidal and acaricidal compositions containing certain tetrahydroindenopyridine derivatives that provide unexpected control of insects and acarids as depicted in formula Ia:

Ia wherein R and R¹ are independently selected from hydrogen and alkyl;

R² is selected from aryl and aryl optionally substituted with halogen; and R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonyl and arylalkyl.

Preferred species in this aspect of the present invention are those insecticidal and acaricidal compositions comprised of compounds of formula Ia where: i) R is hydrogen, R¹ is ethyl, R² is phenyl, and R³ is methyl; and ii) R is methyl, R¹ is hydrogen, R² is 4-fluorophenyl, and R³ is methyl. In another aspect of this invention, preferred species are those insecticidal and acaricidal compositions, comprised of compounds of formula Ib:

Ib wherein

R and R¹ are taken together with =CR⁴-CR⁵=CR⁶-CR⁷= to form a benzo-fused ring; wherein R⁴, R⁵, R⁶, and R⁷ are independently selected from hydrogen, halogen or alkoxy; R² is selected from alkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with halogen, alkyl, alkoxy or haloalkyl; and R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy.

Preferred species in this aspect of the present invention are those insecticidal and acaricidal compositions, comprised of compounds of formula Ib where: iii) R² and R³ are methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; iv) R² is methyl, R³ is ethyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; v) R² and R³ are methyl, and R⁴, R⁵ and R⁶ are hydrogen, and R⁷ is methoxy; vi) R² is phenyl, and R³, R⁴, R⁵, R⁶ and R⁷ are hydrogen; vii) R² is phenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; viii) R² is phenyl, R³ is 2,2,2-trifluoroethyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; ix) R² is 4-fluorophenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; or x) R² is 3-methoxyphenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen. Certain of the tetrahydroindenopyridine derivatives, useful in the compositions of the present invention, are novel compounds. These compounds are represented by formulae Ic and Id. The compounds of formula Ic are represented by the following general formula:

wherein

R and R¹ are independently selected from hydrogen and alkyl;

R² is selected from hydrogen, alkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, hydroxycarbonyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl, and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; provided that when R is hydrogen and R¹ and R³ are each methyl, then R² is other than

3 -trifluoromethylphenyl; the N-oxides thereof; and agriculturally acceptable salts thereof.

Preferred species of this aspect of the present invention are compounds in which;

R² is selected from aryl and aryl optionally substituted with halogen; and R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonyl and arylalkyl. Most preferred species in this aspect of the present invention are those insecticidal and acaricidal compositions comprised of compounds of formula Ic where: xi) R is hydrogen, R¹ is ethyl, R² is phenyl, and R³ is methyl; and xii) R is methyl, R¹ is hydrogen, R² is 4-fluorophenyl, and R³ is methyl. The compounds of formula Id are represented by the following general formula:

Id wherein

R⁴, R⁵, R⁶ and R⁷ are independently selected from hydrogen, halogen, alkyl and alkoxy; R² is selected from alkyl, aryl, heteroaryl and aryl optionally substituted with one or more halogen or alkoxy;

R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy or haloalkoxy; provided that

1) when (i) R² is alkyl and R³ is hydrogen, alkyl, cyanoalkyl, benzyl or alkoxycarbonylalkyl; and (ii) R³ is alkyl and R² is phenyl, 2-methylphenyl, 3- chlorophenyl, 4-chlorophenyl, 4-methoxyphenyl, 2-pyridyl or 2-thienyl, then one of R⁴, R⁵, R⁶ and R⁷ is other than hydrogen; and

2) when R³ is hydrogen or alkyl, R² is alkyl and R⁴ and R⁷ are both hydrogen then (i) R⁵ is other than hydrogen and alkyl or (ii) R⁶ is other than hydrogen, halogen and alkyl; and

3) when R³ is alkyl and R² is 3-methylphenyl or 4-methylphenyl then R⁶ is other than alkyl; and

4) when R² is phenyl then (i) R³ is other than hydrogen or alkyl, or (ii) one of R⁴, R⁵, R⁶ and R⁷ is other than hydrogen; the N-oxides thereof; and the agriculturally acceptable salts thereof. Preferred species in this aspect of the present invention are those compounds of formula Id where R² is selected from alkyl, phenyl and phenyl optionally substituted with halogen or alkoxy; R³ is selected from hydrogen, alkyl and haloalkyl; and

R⁴, R⁵, R⁶ and R⁷ are independently selected from hydrogen and alkoxy.

More preferred species in this aspect of the invention are those compounds of formula Id where: xiii) R² and R³ are methyl, R⁴, R⁵ and R⁶ are hydrogen, and R⁷ is methoxy; xiv) R² is phenyl, R³ is 2,2,2-trifluoroethyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; xv) R² is 4-fluorophenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; and xvi) R² is 3-methoxyphenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen.

In addition, in certain cases the compounds of the present invention may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers. The compounds may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties. The compounds of the present invention may also exist as tautomers, in which migration of a hydrogen atom within the molecule results in two or more structures, which are in equilibrium. The compounds of the present invention may also possess acidic or basic moieties, which may allow for the formation of agriculturally acceptable salts or agriculturally acceptable metal complexes.

This invention includes the use of such enantiomorphs, polymorphs, tautomers, salts and metal complexes. Agriculturally acceptable salts and metal complexes include, without limitation, for example, ammonium salts, the salts of organic and inorganic acids, such as hydrochloric acid, sulfonic acid, ethanesulfonic acid, trifluoroacetic acid, methylbenzenesulfonic acid, phosphoric acid, gluconic acid, pamoic acid, and other acid salts, and the alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and other metals. The methods of the present invention are predicated on causing an insecticidally effective amount of a compound of formula I to be present within insects in order to kill or control the insects. Preferred insecticidally effective amounts are those that are sufficient to kill the insect. It is within the scope of the present invention to cause a compound of formula I to be present within insects by contacting the insects with a derivative of that compound, which derivative is converted within the insect to a compound of formula I. This invention includes the use of such compounds, which can be referred to as pro-insecticides.

Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I with at least one insecticidally compatible carrier therefor.

Another aspect of the present invention relates to compositions containing an insecticidally effective amount of at least one compound of formula I, and an effective amount of at least one additional compound, with at least one insecticidally compatible carrier therefor.

Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present. The present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents and compositions thereof. In the field of veterinary medicine, the compounds of the present invention are expected to be effective against certain endo- and ecto-parasites, such as insects and worms, which prey on animals. Examples of such animal parasites include, without limitation, Gastrophilus spp., Stomoxys spp., Trichodectes spp., Rhodnius spp., Ctenocephalides canis, and other species.

As used in this specification and unless otherwise indicated the substituent terms "alkyl" and "alkoxy", used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. The term "cycloalkyl", used alone or as part of a larger moiety, includes cyclic rings of at least three carbon atoms and up to eight carbon atoms, more preferably three to six carbon atoms. The terms "haloalkyl" and "haloalkoxy" used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms, wherein one or more hydrogen atoms have been replaced with halogen atoms, for example, trifluoromethyl or 2,2,2-trifluoroethoxy. The term "alkenyl" and "alkynyl" used alone or as part of a larger moiety, includes straight or branched chains of at least two carbon atoms containing at least one carbon- carbon double bond or triple bond, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. The term "aryl" refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, phenyl, indanyl, indenyl, naphthyl or 5,6,7,8- tetrahydronaphthyl. The term "heteroaryl" refers to an aromatic ring structure, including fused rings, in which at least one of the atoms is other than carbon, for example, without limitation, sulfur, oxygen, or nitrogen. Heteroaryl rings include, without limitation, for example, pyrimidinyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolyl or thiadiazolyl. The term "GC analysis" refers to gas chromatographic analysis of, for example, a chemical reaction mixture. The term "DMF" refers to N₅N- dimethylformamide. The term "THF" refers to tetrahydrofuran. The term "halogen" or "halo" refers to fluorine, bromine, iodine, or chlorine. The term "ambient temperature" or "room temperature" often abbreviated as "RT", for example, in reference to a chemical reaction mixture temperature, refers to a temperature in the range of 20 ⁰C to 30 ⁰C. The terms "insecticidal" or "acaricidal", "insecticide" or "acaricide" refers to a compound of the present invention, either alone or in admixture with at least one of an additional compound, or with at least one compatible carrier, which causes the destruction or the inhibition of action of insects or acarids. The term "independently selected from" as set forth above and in the claims section of the present specification refers to the possibility that moieties, for example the R⁴ through R⁷ substituents may be the same or they may be different within the group that the selection is made. The compound name (1) substituted 3-aza-bicyclo[4.3.0]non-6-ene denotes those compounds of formula I which are comprised of a R and R¹ substituent that are not taken together and do not form a benzo-fused ring. Compound name (2) substituted l,3,4,9b-tetraydro-2H-indeno[l,2-c]pyridine denotes those compounds of formula I in which R and R¹ are taken together to form a benzo-fused ring. The general name "tetrahydroindenopyridine" refers to both (1) and (2).

The compounds of the present invention were prepared by methods generally known to those skilled in the art from intermediate compounds readily available in commerce. Compounds of formula I in which the R¹ substituent is other than hydrogen were prepared in the manner shown in Scheme 1.

Scheme 1

Base, Solvent

(SMl) (SM2) (a )

Where R² is phenyl, R¹ is C₂H₅

Lithium diisopropylamide, Solvent

(SM3) Where R³ is methyl

As depicted in Scheme 1, the reaction of an appropriately substituted butyrophenone (SMl) and tert-butyl chloroacetate (SM2) in an appropriate solvent, under basic conditions, yielded an appropriately substituted prop-2-en-l-one (a), for example, 2-ethyl-l-phenylprop-2-en-l-one. The reaction of prop-2-en-l-one (a) with a 1 -substituted piperidin-4-one (SM3) under strongly basic conditions, in an appropriate solvent yielded the corresponding 3-(substituted)-l-substituted-piperidin-4-one (b), for example 3-(2-ethyl-3-oxo-3-phenylpropyl)-l-methylpiperidin-4-one. Treatment of the substituted-piperidin-4-one (b) with zinc and titanium (IV) chloride in an appropriate solvent provided the appropriately substituted bicyclo[4.3.0]non-6-ene, for example 3- aza-8-ethyl-3-methyl-7-phenylbicyclo[4.3.0]non-6-ene, a compound of formula I, described in detail in Example 1 set forth below. Scheme 2 provides a general method for the preparation of compounds of formula I in which the R substituent is other than hydrogen.

Scheme 2

(SM3) Where R³ is methyl

As depicted in Scheme 2, in one reaction, an appropriately substituted acetophenone (SM4) was reacted with acetaldehyde (SM5) in an appropriate solvent under strongly basic conditions to yield a l-substituted-3-hydroxybutan-l-one (c), for example, l-(4-fluorophenyl)-3-hydroxybutan-l-one. Reduction of the hydroxybutan-1- one (c) with cesium (III) chloride in a solvent yielded the corresponding 1-substituted- but-2-en-l-one (d), for example, (2E)-l-(4-fluorophenyl)but-2-en-l-one. The reaction of but-2-en-l-one (d) with a 1 -substituted piperidin-4-one (SM3) under strongly basic conditions, in an appropriate solvent yielded the corresponding 1-substituted-piperidin- 4-one (e), for example 3-[3-(4-fiuorophenyl)-l-methyl-3-oxopropyl]-l-methylpiperidin- 4-one. Treatment of the l-substituted-piperidin-4-one (e) with zinc and titanium (IV) chloride in an appropriate solvent yielded the appropriately substituted bicyclo[4.3.0]non-6-ene, for example 3-aza-3,9-dimethyl-7-(4- fluorophenyl)bicyclo[4.3.0]non-6-ene, a compound of formula I, described in detail in Example 2 set forth below.

Scheme 3 provides a method for the preparation of compounds of formula I in which an R³ substituent was replaced.

Scheme 3

Solvent ^CH3

Where R is methyl, R¹ is H, R² is 4-fluorophenyl and R³ is (f) Benzyl

(g )

A compound of formula I where R³ is H Base, Solvent o

As depicted in Scheme 3, the reaction of a compound of formula I in which the

R³ substituent is benzyl with 1-chloroethyl chloroformate in an appropriate solvent yielded a 1-chloroethyl substituted bicyclo[4.3.0]non-6-ene carboxylate (f), for example, 1-chloroethyl 3-aza-7-(4-fluorophenyl)-9-methylbicyclo[4.3.0]non-6-ene-3- carboxylate. Heating bicyclo carboxylate (f) in an appropriate solvent removed the carboxylate group to yield a compound of formula I in which R³ is hydrogen (g), for example, 3-aza-7-(4-fluorophenyl)-9-methylbicyclo[4.3.0]non-6-ene. The compound of formula I in which R³ is hydrogen (g) was reacted with a haloalkyl sulfonate in the presence of a base in an appropriate solvent to yield a compound of formula I wherein R³ is haloalkyl, for example, 3-aza-7-(4-fluorophenyl)-9-methyl-3-(2,2,2- trifluoroethyl)bicyclo[4.3.0]non-6-ene, a compound of formula I, described in detail in Example 3 set forth below. Similar chemistry was used to prepare 5-phenyl-2-(2,2,2- trifluoroethyl)-l,3,4,9b-tetrahydro-2H-indeno[l,2-c]pyridine, another compound of formula I, which is described in detail in Example 3 set forth below.

Scheme 4 provides a method for the preparation of compounds of formula 1 in which an R" substituent, other than hydrogen, was added. Scheme 4

3-methoxyphenyl

As depicted in Scheme 4, the reaction of 2-methylindano[l,2-c]piperdin-5-one (SM6) (known compound, US Patent 3,462,443) with an appropriately substituted phenyl halide (SM7) with n-butyllithium in an appropriate solvent yielded a compound of formula I in which the R² substituent is a substituted phenyl, for example, 5-(3- methoxyphenyl)-2-methyl-l,3,4,9b-tetrahydro-2H-indeno[l,2-c]pyridine, a compound of formula I, described in detail in Example 4 set forth below.

One skilled in the art will, of course, recognize that the formulation and mode of application of a toxicant may affect the activity of the material in a given application. Thus, for agricultural use the present insecticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water- soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about" were placed in front of the amounts specified.

These insecticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which suppression of insects is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient.

Dusts are free flowing admixtures of the active ingredient with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns. A typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc.

Wettable powders, also useful formulations for insecticides, are in the form of finely divided particles that disperse readily in water or other dispersant. The wettable powder is ultimately applied to the locus where insect control is needed either as a dry dust or as an emulsion in water or other liquid. Typical carriers for wettable powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet inorganic diluents. Wettable powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion. For example, a useful wettable powder formulation contains 80.0 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Additional wetting agent and/or oil will frequently be added to a tank mix to facilitate dispersion on the foliage of the plant.

Other useful formulations for insecticidal applications are emulsifϊable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or other dispersant, and may consist entirely of the insecticidal compound and a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, or other non- volatile organic solvents. For insecticidal application these concentrates are dispersed m water or other liquid carrier and normally applied as a spray to the area to be treated. The percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the insecticidal composition.

Flowable formulations are similar to ECs, except that the active ingredient is suspended in a liquid carrier, generally water. Flowables, like ECs, may include a small amount of a surfactant, and will typically contain active ingredients in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition. For application, flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated.

Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. Surface-active agents, when used, normally comprise 1 to 15% by weight of the composition.

Other useful formulations include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents. Still other useful formulations for insecticidal applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents. Granular formulations, wherein the toxicant is carried on relative coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy. Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low-boiling dispersant solvent carrier may also be used. Water-soluble or water-dispersible granules are free flowing, non-dusty, and readily water-soluble or water-miscible. In use by the farmer on the field, the granular formulations, emulsifϊable concentrates, flowable concentrates, aqueous emulsions, solutions, etc., may be diluted with water to give a concentration of active ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%.

The active insecticidal and acaricidal compounds of this invention may be formulated and/or applied with one or more additional compounds. Such combinations may provide certain advantages, such as, without limitation, exhibiting synergistic effects for greater control of insect pests, reducing rates of application of insecticide thereby minimizing any impact to the environment and to worker safety, controlling a broader spectrum of insect pests, safening of crop plants to phytotoxicity, and improving tolerance by non-pest species, such as mammals and fish. Additional compounds include, without limitation, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals, hi applying an active compound of this invention, whether formulated alone or with other agricultural chemicals, an effective amount and concentration of the active compound is of course employed; the amount may vary in the range of, e.g. about 0.001 to about 3 kg/ha, preferably about 0.03 to about 1 kg/ha. For field use, where there are losses of insecticide, higher application rates (e.g., four times the rates mentioned above) may be employed.

When the active insecticidal compounds of the present invention are used in combination with one or more additional compounds, e.g., with other pesticides such as herbicides, the herbicides include, without limitation, for example: N-

(phosphonomethyl)glycines such as glyphosate; aryloxyalkanoic acids such as 2,4-D, MCPA, and MCPP; ureas such as isoproturon; imidazolinones such as imazapyr, imazamethabenz, imazethapyr, and imazaquin; diphenyl ethers such as acifluorfen, bifenox, and fomasafen; hydroxybenzonitriles such as ioxynil and bromoxynil; sulfonylureas such as chlorimuron, achlorsulfuron, bensulfuron, pyrazosulfuron, thifensulfuron, and triasulfuron; 2-(4-aryloxyphenoxy)alkanoic acids such as fenoxaprop, fluazifop, quizalofop, and diclofop; benzothiadiazinones such as bentazone; 2-chloroacetanilides such as butachlor, metolachlor, acetochlor, and dimethenamide; arenecarboxylic acids such as dicamba; pyridyloxyacetic acids such as fluroxypyr, aryl triazolinones such as sulfentrazone and carfentrazone-ethyl; isoxazolidinones such as clomazone; and other herbicides.

When the active insecticidal compounds of the present invention are used in combination with one or more additional compounds, e.g., with other pesticides such as other insecticides, the other insecticides include, for example: organophosphate insecticides, such as chlorpyrifos, diazinon, dimethoate, malathion, parathion-methyl, and terbufos; pyrethroid insecticides, such as fenvalerate, deltamethrin, fenpropathrin, cyfluthrin, flucythrinate, α/p&α-cypermethrin, i»eto-cypermethrin, zetø-cypermethrin, bifenthrin, cypermethrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomehtrin, tefluthrin, cycloprothrin, betacyfluthrin, and acrinathrin; carbamate insecticides, such as aldecarb, carbaryl, carbofuran, and methomyl; organochlorine insecticides, such as endosulfan, endrin, heptachlor, and lindane; benzoylurea insecticides, such as diflubenuron, triflumuron, teflubenzuron, chlorfluazuron, flucycloxuron, hexaflumuron, flufenoxuron, and lufenuron; and other insecticides, such as amitraz, clofentezine, fenpyroximate, hexythiazox, spinosad, and imidacloprid.

When the active insecticidal compounds of the present invention are used in combination with one or more additional compounds, e.g., with other pesticides such as fungicides, the fungicides include, for example: benzimidazole fungicides, such as benomyl, carbendazim, thiabendazole, and thiophanate-methyl; 1,2,4-triazole fungicides, such as epoxyconazole, cyproconazole, flusilazole, flutriafol, propiconazole, tebuconazole, triadimefon, and triadimenol; substituted anilide fungicides, such as metalaxyl, oxadixyl, procymidone, and vinclozolin; organophosphorus fungicides, such as fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-methyl; morpholine fungicides, such as fenpropimorph, tridemorph, and dodemorph; other systemic fungicides, such as fenarimol, imazalil, prochloraz, tricyclazole, and triforine; dithiocarbamate fungicides, such as mancozeb, maneb, propineb, zineb, and ziram; non- systemic fungicides, such as chlorothalonil, dichlofluanid, dithianon, and iprodione, captan, dinocap, dodine, fluazinam, gluazatine, PCNB, pencycuron, quintozene, tricylamide, and validamycin; inorganic fungicides, such as copper and sulphur products, and other fungicides. When the active insecticidal compounds of the present invention are used in combination with one or more additional compounds, e.g., with other pesticides such as nematicides, the nematicides include, for example: carbofuran, carbosulfan, terbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides. When the active insecticidal compounds of the present invention are used in combination with one or more additional compounds, e.g., with other materials such as plant growth regulators, the plant growth regulators include, for example: maleic hydrazide, chlormequat, ethephon, gibberellin, mepiquat, thidiazon, inabenfide, triaphenthenol, paclobutrazol, unaconazol, DCPA, prohexadione, trinexapac-ethyl, and other plant growth regulators.

Soil conditioners are materials which, when added to the soil, promote a variety of benefits for the efficacious growth of plants. Soil conditioners are used to reduce soil compaction, promote and increase effectiveness of drainage, improve soil permeability, promote optimum plant nutrient content in the soil, and promote better pesticide and fertilizer incorporation. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as soil conditioners, the soil conditioners include organic matter, such as humus, which promotes retention of cation plant nutrients in the soil; mixtures of cation nutrients, such as calcium, magnesium, potash, sodium, and hydrogen complexes; or microorganism compositions which promote conditions in the soil favorable to plant growth. Such microorganism compositions include, for example, bacillus, pseudomonas, azotobacter, azospirillum, rhizobium, and soil-borne cyanobacteria.

Fertilizers are plant food supplements, which commonly contain nitrogen, phosphorus, and potassium. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as fertilizers, the fertilizers include nitrogen fertilizers, such as ammonium sulfate, ammonium nitrate, and bone meal; phosphate fertilizers, such as superphosphate, triple superphosphate, ammonium sulfate, and diammonium sulfate; and potassium fertilizers, such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.

The following examples further illustrate the present invention, but, of course, should not be construed as in any way limiting its scope. The examples are organized to present protocols for the synthesis of the compounds of formula I of the present invention, set forth a list of such synthesized species, and set forth certain biological data indicating the efficacy of such compounds.

EXAMPLE 1 This example illustrates one protocol for the preparation of 3-aza-8-ethyl-3-methyl-7- phenylbicyclo[4.3.0]non-6-ene

(Compound 3) ₍

Step A Synthesis of 2-ethyl- 1 -phenylprop-2-en- 1 -one as an intermediate

Under a dry nitrogen atmosphere, a mixture of 0.72 gram (60% dispersion in mineral oil, 0.018 mole) of sodium hydride in 80 mL of THF was stirred and cooled to 5°C. Butyrophenone (1.9 mL, 0.014 mole) was added to this mixture drop-wise during a five-minute period. The reaction mixture was stirred for 40 minutes at which time 2.6 mL (0.018 mole) of tertiary-butyl chloroacetate was added. The reaction mixture was heated to reflux and was stirred for four hours. The reaction mixture was cooled, diluted with 50 mL of water, and extracted with two 50 mL portions of ethyl acetate. The extracts were combined, washed with an aqueous saturated sodium chloride solution, dried with sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure yielding 3.8 grams of a liquid residue. The residue was diluted with a mixture of 50 mL of 1,4-dioxane and 10 mL of DMF and the mixture stirred as 2.8 grams (0.02 mole) of potassium carbonate was added. Upon completion of addition, the reaction mixture was heated to reflux where it stirred for two hours. The reaction mixture was cooled, concentrated under reduced pressure, and diluted with 60 mL of water. The aqueous mixture was extracted with two 50 mL portions of diethyl ether. The extracts were combined, washed with a saturated aqueous sodium chloride solution, and dried with anhydrous magnesium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to yield 1.3 grams of the title compound as a liquid. The NMR spectrum was consistent with the proposed structure.

Step B Synthesis of 3-(2-ethyl-3-oxo-3-phenylpropyl)-l-methylpiperidin-4-one as an intermediate

Under a dry nitrogen atmosphere, a stirred solution of 0.68 gram (0.006 mole) of l-methyl-4-piperidone in 35 mL of THF was cooled to minus 78°C. Lithium diisopropylamide (3.4 mL of a 1.8 molar solution in heptane/THF/ethylbenzene, 0.0062 mole) was then added slowly to the cold solution. After completion of addition, the mixture was stirred for 30 minutes at which time 0.8 gram (0.005 mole) of 2-ethyl-l- phenylprop-2-en-l-one was added slowly. After completion of addition, the reaction mixture stirred at minus 78⁰C for 20 minutes then was allowed to warm to ambient temperature where it stirred for one hour. After this time, the reaction mixture was diluted with 20 mL of water and extracted with two 40 mL portions of diethyl ether. The extracts were combined, washed with a saturated aqueous sodium carbonate solution, and dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to a liquid residue. This residue was purified by column chromatography on neutral alumina (Activity III), eluting first with 200 mL of heptane followed by 500 mL of ethyl acetate in heptane (1:4) then 300 mL of ethyl acetate in heptane (1:2). The appropriate fractions were combined and concentrated under reduced pressure toyield 0.50 gram of the title compound as an oil. The NMR was consistent with the proposed structure.

Step C Synthesis of 3-aza-8-ethyl-3-methyl-7-phenylbicyclo[4.3.0]non-6-ene (Compound 3)

Under a dry nitrogen atmosphere, 1.1 grams (0.003 mole) of titanium (IV) chloride tetrahydrofuran complex (1:2) was added to a stirred mixture of 0.42 gram (0.0064 mole) of zinc in 35 mL of THF. The reaction mixture was stirred at ambient temperature for five minutes and was then heated to 60⁰C for 40 minutes. The reaction mixture was cooled to ambient temperature and a solution of 0.45 gram (0.0016 mole) of 3-(2-ethyl-3-oxo-3-phenylpropyl)-l-methylpiperidin-4-one in five mL of THF was added. The reaction mixture was heated at reflux for 2.5 hours at which time it was cooled to ambient temperature. The reaction mixture was poured into a mixture of 20 mL of aqueous IN potassium carbonate and 40 mL of ethyl acetate. The mixture was filtered through a pad of silicon dioxide filter agent, followed by rinsing the filter pad with 40 mL of ethyl acetate. The filtrate and rinse were combined and an organic phase was separated from the mixture. The organic phase was washed with a saturated aqueous sodium bicarbonate solution, dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, leaving an oil residue. The residue was purified by column chromatography on neutral alumina (Activity III), eluting first with 600 mL of ethyl acetate in heptane (1:5) followed by 200 mL of ethyl acetate in heptane (1:1). The appropriate fractions were combined and concentrated under reduced pressure to yield 0.07 gram of compound 3 as an oil. The NMR was consistent with the proposed structure

EXAMPLE 2

This example illustrates one protocol for the preparation of 3-aza-3,9-dimethyl-7-(4- fluorophenyl)-bicyclo[4.3.0]non-6-ene

(Compound 6) Step A Synthesis of l-(4-fluorophenyl)-3-hydroxybutan-l-one as an intermediate

Under a dry nitrogen atmosphere, a stirred solution of 2.0 grams (0.015 mole) of

4'-fluoroacetophonone in 80 mL of THF was cooled to minus 78⁰C. Lithium diisopropylamide (8.9 mL of a 1.8 molar solution in heptane/THF/ethylbenzene, 0.016 mole) was then added slowly to the cold solution. After completion of addition, the mixture was stirred for one hour at which time 1.0 mL (0.018 mole) of acetaldehyde was added slowly. After completion of addition, the reaction mixture stirred at minus

78°C for 40 minutes. After this time, the cold reaction mixture was diluted with 10 mL of an aqueous 5% ammonium chloride solution followed by 50 mL of water. The mixture was extracted with two 50 mL portions of ethyl acetate. The extracts were combined, washed with a saturated aqueous sodium chloride solution, and dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to an oil residue. This residue was combined with 0.63 gram of an oil residue prepared in a manner as described above from 0.5 gram (0.0036 mole) of 4'- fluoroacetophonone, 0.24 mL (0.0042 mole) of acetaldehyde, and 2.OmL (0.0036 mole) of lithium diisopropylamide (1.8 Molar solution in heptane/THF/ethylbenzene) in 25 mL of THF. The combined oil was purified by column chromatography on silica gel, eluting first with 500 mL of ethyl acetate in heptane (1:4), then 600 mL of ethyl acetate in heptane (1:2), followed by 80OmL of ethyl acetate in heptane (1:1). The appropriate fractions were combined and concentrated under reduced pressure to yield 1.75 gram of the title compound. The NMR was consistent with the proposed structure.

Step B Synthesis of (2E)- 1 -(4-fluorophenyl)but-2-en- 1 -one as an intermediate

A stirred mixture of 1.2 grams (0.0065 mole) of l-(4-fluorophenyl)-3- hydroxybutan-1-one and 2.5 grams (0.01 mole) of cerium (III) chloride in 50 mL of acetonitrile was heated at reflux for approximately 18 hours. The reaction mixture was cooled, diluted with 30 mL of IN hydrochloric acid, then was extracted with two 30 mL portions of ethyl acetate. The combined extracts were washed with an aqueous saturated sodium chloride solution, dried with sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, yielding 1.0 gram of the title compound as an oil. This process was repeated using 0.25 gram (0.0014mole) of l-(4-fluorophenyl)-3- hydroxybutan-1-one and 0.54 gram (0.0022 mole) of cerium (III) chloride in 25 mL of acetonitrile to yield 0.2 gram of the title compound as an oil. The NMR of the combined materials was consistent with the proposed structure.

Step C Synthesis of 3-[3-(4-fluorophenyl)-l-methyl-3-oxopropyl]-l- methylpiperidin-4-one as an intermediate

Under a dry nitrogen atmosphere, a stirred solution of 1.0 gram (0.006 mole) of l-methyl-4-piperidone in 45 mL of THF was cooled to -78°C. Lithium diisopropylamide (5.0 mL of a 1.8 molar solution in heptane/THF/ethylbenzene, 0.009 mole) was then added slowly to the cold solution. After completion of addition, the mixture was stirred for 30 minutes at which time 1.2 grams (0.0073 mole) of (2E)-I -(4- fluorophenyl)but-2-en-l-one was added slowly. After completion of addition, the reaction mixture stirred at minus 78⁰C for 20 minutes then was allowed to warm to ambient temperature where it stirred for one hour. After this time, the reaction mixture was diluted with 20 mL of an aqueous IN hydrochloric acid solution, and then was washed with two 10 mL portions of diethyl ether. The combined organic wash was extracted with two 10 mL portions of an aqueous IN hydrochloric acid solution. The acidic aqueous extracts were combined with the acidic aqueous solution from above and the mixture was made basic by adding solid potassium carbonate. The basic solution was extracted with two 40 mL portions of diethyl ether. The extracts were combined and dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to yield 1.1 grams of a yellow oil. This oil was purified by column chromatography on neutral alumina (Activity III), eluting first with 500 mL of ethyl acetate in heptane (1 :4) followed by 500 mL of ethyl acetate in heptane (1:1). The appropriate fractions were combined and concentrated under reduced pressure to yield 0.32 gram of the title compound as an oil.

Step D Synthesis of 3-aza-3,9-dimethyl-7-(4-fluorophenyl)-bicyclo[4.3.0]non-6- ene (Compound 6)

This compound was prepared in the manner of Step C of Example 1, using 0.3 gram (0.0011 mole) of l-(4-fluorophenyl)-3-(l-methyl(4-piperidyl))butan-l-one, 0.26 gram (0.004 mole) of zinc, and 0.67 gram (0.002 mole) of titanium (IV) chloride tetrahydrofuran complex (1:2) in 25 mL of THF. The title compound was purified by column chromatography on silica gel, eluting with a 1 : 1 mixture of ethyl acetate and heptane containing triethyl amine (1% by volume). The appropriate fractions were combined and concentrated under reduced pressure to yield 0.068 gram of an oil. The NMR spectrum was consistent with the proposed structure. EXAMPLE 3

This example illustrates one protocol for the preparation of 3-aza-7-(4-fluorophenyl)-9- methylbicyclo[4.3.0]non-6-ene (Compound 9) and 3-aza-7-(4-fluorophenyl)-9~methyl-

3-(2,2,2-trifluoroethyl)bicyclo[4.3.0]non-6-ene (Compound 11)

Step A Synthesis of 1-chloroethyl 3-aza-7-(4-fluorophenyl)-9- methylbicyclo[4.3.0]non-6-ene-3-carboxylate as an intermediate

Under a dry nitrogen atmosphere, a mixture of 2.1 grams (0.0065 mole) of 3- aza-3-benzyl-7-(4-fluorophenyl)-9-methylbicyclo[4.3.0]non-6-ene, prepared in the manner of Example 2, using l-benzyl-4-piperidone in Step C of the process, and 2.8 grams (0.02 mole) of 1-chloroethyl chloroformate in 45 mL of acetonitrile was heated to reflux where it stirred for two hours. The reaction mixture was cooled, concentrated under reduced pressure, then slurried in a mixture of 50 mL of water and 40 mL of methylene chloride. An organic phase was separated and was washed with 25 mL of an aqueous 1% sodium bicarbonate solution. The organic phase was dried with sodium sulfate, filtered, and the filtrate concentrated under reduced pressure to a liquid residue

(2.4 grams). NMR analysis of the residue indicated a 1:1 mixture of the title compound and benzyl chloride.

Step B Synthesis of 3-aza-7-(4-fluorophenyl)-9-methylbicyclo[4.3.0]non-6-ene

(Compound 9)

A solution of 2.1 grams of the mixture produced in Step A in 50 mL of methanol was heated to reflux where it stirred for one hour. The reaction mixture was cooled, concentrated under reduced pressure to a residue and the residue dissolved in 50 mL of 0.5 N hydrochloric acid. The aqueous solution was washed with 30 mL of diethyl ether then was made basic by adding an aqueous 10% potassium carbonate solution. The basic mixture was extracted with three 40 mL portions of ethyl acetate. The extracts were combined, dried with sodium carbonate and filtered. The filtrate was condensed under reduced pressure to an oil. The oil was purified by column chromatography on neutral alumina (Activity III), eluted first with 500 mL of heptane in ethyl acetate (1:1), followed by 600 mL of heptane in ethyl acetate (1:2), 800 mL of ethyl acetate, and 2 liters of methanol in ethyl acetate (5:95). The appropriate fractions were combined and concentrated under reduced pressure to yield 0.55 gram of the title compound as an oil. The NMR spectrum was consistent with the proposed structure.

Step C Synthesis of 3-aza-7-(4-fluorophenyl)-9-methyl-3-(2,2,2- trifluoroethyl)bicyclo[4.3.0]non-6-ene (Compound 11)

A mixture of 0.2 gram (0.0086 mole) of 3-aza-7-(4-fiuorophenyl)-9- methylbicyclo[4.3.0]non-6-ene, 0.31 gram (0.0031 mole) of 3,3,3-trifluoropropyl- (trifluoromethyl)sulfonate, and 0.19 gram (0.0015 mole) of N,N-diisopropylethylamine in 15 ml of acetonitrile was stirred in a sealed vessel for about 18 hours. The reaction mixture was concentrated under reduced pressure to a residue. The residue was purified by column chromatography on silica gel, eluted with heptane, to yield 0.19 gram of Compound 12 as a yellow liquid. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 4

This example illustrates one protocol for the preparation of 5-(3-methoxyphenyl)-2- methyl- 1 ,3,4,9b-tetrahydro-2H-indeno[ 1 ,2-c]pyridine

(Compound 30) Under a dry nitrogen atmosphere, a solution of 0.056 gram (0.003 mole) of 3- bromoanisole in 10 mL of THF was cooled to -78°C and stirred as 1.8 mL (0.0024 mole) of a 1.6 molar solution of n-butyl lithium in hexanes was slowly added during a five minute period. After completion of addition the reaction mixture was stirred for 40 minutes at which time a solution of 0.2 gram (0.002 mole) of 2-methylindano[l,2- c]piperidin-5-one in 5 mL of THF was added slowly during a five minute period. The reaction mixture was allowed to warm to ambient temperature where it stirred for about 20 hours. A solution of hydrogen chloride (6 mL of a 2.0 M solution in diethyl ether, 0.012 mole) was added portion wise during a 10 minute period. After completion of addition, the reaction mixture stirred for one hour. The reaction mixture was concentrated under reduced pressure to an oil residue. This residue was purified by column chromatography on silica gel, eluting first with 400 niL of ethyl acetate in heptane (1 :3, with 1% triethylamine by volume), followed by 750 mL of ethyl acetate in heptane (2:3, with 1% triethylamine by volume). The appropriate fractions were concentrated to yield 0.08 gram of compound 32 as an oil. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 5

This example illustrates one protocol for the preparation of 5-phenyl-2-(2,2,2- trifluoroethyl)- 1 ,3 ,4,9b-tetrahydro-2H-indeno[ 1 ,2-c]pyridine

(Compound 41)

This compound was prepared in the manner of Step C of Example 3, using 0.08 gram (0.00034 mole) of 5-ρhenyl-l,3,4,9b-tetrahydro-2H-indeno[l,2-c]ρyridine hydrochloride (known compound, NL 6500312), 0.1 gram (0.0008 mole) of N₅N- diisopropylethylamine, and 0.1 gram (0.00043 mole) of 3,3,3-trifluoropropyl-

(trifluoromethyl)sulfonate in 10 mL of methylene chloride to yield 0.03 gram of compound 55 as an oil. The NMR spectrum was consistent with the proposed structure.

It is well known to one of ordinary skill in the art that compounds like the compounds of formula I of the present invention can contain optically active and racemic forms. It is also well known in the art that compounds like the compounds of formula I may contain stereoisomeric forms, tautomeric forms and/or exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically active, polymorphic, tautomeric, or stereoisomeric form, or mixtures thereof. It should be noted that it is well known in the art how to prepare optically active forms, for example by resolution of a racemic mixture, or by synthesis from optically active intermediates. The following table sets forth some additional examples of compounds of formula I, useful in the present invention:

Table 1 Insecticidal Tetrahydroindenopyridine Derivatives

CmpdNo R R¹ R 2 * R³

2 H H Ph CH₃

3 H C₂H₅ Ph CH₃

N-

7 H CH(CH₃)₂ Ph CH₃

8 CH₃ H 9 is "S", 1 is "R" - -F CH₃

12 H C₂H₅ C₂H₅ CH₃ Cmpd No R R¹ R² * R³

* Ph is unsubstituted phenyl

Formula I where R and R¹ are taken together with =CR⁴-CR⁵=CR⁶-CR⁷= forming compounds of formula Id

Cmpd No R² R³ R⁴ - R⁷

15 CH₃ CH₃ H

16 CH₃ CH₃ H Hydrochloride salt 17 CH₃ C₂H₅ H

18 CH₃ C₂H₅ H Hydrochloride salt 19 Ph CH₃ H

Cmpd No R² R³ R⁴ -R⁷

Bis

39 CH(CH₃)₂ CH₃ H

40 Ph COCH₃ H

41 Ph CH₂CF₃ H

42 Ph PO(OCH₃)₂ H

43 Ph CH₃ H methoxy methyl iodide salt

44 Ph CH₂CH₂F H

45 C₂H₅ CH₂CF₃ H

46 Ph CH₃ R⁷-OCH₃

47 Ph CH₃ R⁷-

C(O)N(CH₃)₂ * Ph is unsubstituted phenyl

The following table sets forth physical characterizing data for certain compounds of formula I of the present invention:

Table 2

Insecticidal Tetrahydroindenopyridine Derivatives Compound Characterization

Melting Point (^CC) of Sohds

Molecular Formula Or Physical State

1 C₂₁H₂₃N OIL

2 C₁₅H₁₉N OIL

3 C₁₇H₂₃N OIL

4 C₁₆H₂₀FN OIL

5 C₁₆H₂₀FNO 180-182

6 C₁₆H₂₀FN OIL

7 C₁₈H₂₅N OIL

8 C₁₆H₂₀FN OIL

9 C₁₅H₁₈FN OIL

10 C₁₈H₂₂FNO₂ OIL

11 C₁₇H₁₉F₄N LIQUID

15 C₁₄H₁₇N OIL

16 C₁₄H₁₈N-Cl 200-203

17 C₁₅H₁₉N OIL

18 C₁₅H₂₀N-Cl 240-245

19 C₁₉H₁₉N 106-108

20 C₂₀H₂₂N-Cl 220-224

21 C₁₉H₁₈FN 90-93

22 2 C₁₉H₁₉FN-C₂O₄ 50-60

23 C₁₇H₂₃N OIL

24 C₁₅H₁₉NO 76-80

25 C₁₄H₁₆ClN

26 C₁₅H₁₉NO OIL

27 C₁₉H₁₇F₂N 108-109

28 C₁₇H₂₃N OIL

29 C₂₀H₂₁NO 112-114

30 C₂₀H₂₁NO OIL

31 C₂₀H₂₁NO 39-41

32 C₁₈H₁₇N OIL

33 C₂₂H₂₃NO₂ OIL

34 C₂₀H₁₈N₂ 184-186

35 C₁₉H₁₈N₂O 195-197

36 C₁₉H₁₇NO OIL Melting Point (⁰C) of Solids Molecular Formula Or Physical State

38 C₁₇H₁₇N₃ 191-196

39 C₁₆H₂₁N OIL

40 C₂₀H₁₉NO OIL

41 C_2OH_1SF₃N OIL

42 C₂₀H₂₂NO₃P OIL

43 C₂₁H₂₄NO-I OEL

44 C₂₀H₂₀FN OIL

45 C₁₆H₁₈F₃N OIL

Candidate insecticides were evaluated for insecticidal activity by observing mortality in a population of cotton aphid (Aphis gossypii) on treated cotton plants when compared to like populations of cotton aphid on untreated plants. These tests were conducted in the following manner:

For each rate of application of test compound, two seven-to-ten days old cotton seedlings (Gossypium hirsutium) grown in 7.6 cm diameter pots were selected for the test. Each test plant was infested with about 120 adult cotton aphids by placing onto each test plant cuttings of leaves from cotton plants grown in a cotton aphid colony. Once infested, the test plants were maintained for up to about 12 hours to allow complete translocation of the aphids onto the test plant. A solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 milligrams of the test compound in 1 mL of acetone. Each solution was then diluted with 9 mL of a solution of 0.03 mL of polyoxyethylene(lθ) isooctylphenyl ether in 100 mL of water. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (5 mL total for each test compound). If needed, the solution of 1000 ppm of test compound was serially diluted with a solution of 10% acetone and 300 ppm of polyoxyethylene(lθ) isooctylphenyl ether in water to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm. Each replicate of test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants. For comparison purposes, a solution of a standard, such as amitraz or demethylchlordimeform (DCDM), prepared in a manner analogous to that set forth above, as well as a solution of 10% acetone and 300 ppm of polyoxyethylene(lθ) isooctylphenyl ether in water containing no test compound were also sprayed onto test plants. Upon completion of spraying the solutions of test compound, the solution of standard, and the solution containing no test compound, the plants were allowed to dry. Upon completion of drying, the test plants were placed in a tray containing about 2.5 centimeters of water, where they were maintained in a growth chamber for 24 hours. After this time, each plant was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plants prior to treatment with test compound. A test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 40% mortality or less of the cotton aphid, the test compound was termed as inactive (I).

An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 3. The test compounds of formula I are identified by numbers that correspond to those in Table 1.

Table 3

The Following Compounds Of The Present Invention Reduced The Population Of Cotton Aphid by 40% to 100% When Applied At An Application Rate Of 3 OOppm Or

Less Unless Otherwise Noted

Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. No. No. No. No. No. No. No. No. No. No.

2 3 4 6 7 8 9 10 11 15*

16* 17* 18* 19* 20* 21* 22* 23* 24* 25*

26* 27 28 30 31 32 33 34 36 37

38 41 42 43 44 ^! Application rate of lOOOppm

Candidate insecticides were also evaluated for cotton aphid insecticidal activity by observing mortality in a population of cotton aphid (Aphis gossypii) on treated cotton plant leaf discs when compared to like populations of cotton aphid on untreated plant leaf discs. These tests were conducted in the following manner:

Three week to one month-old cotton plants (Gossypium hirsutium) were prepared for infesting by cutting off the cotyledons and new true leaf growth, leaving the oldest two true leaves. To infest, two seven-to-ten day old cotton plants, grown in a cotton aphid colony were uprooted and lodged in the apex of the stem where the stems of the two true leaves meet with the main stem. Once infested, the test plants were maintained for up to about 12 hours to allow complete translocation of the aphids onto the leaves of the test plant. The wells of clear 128-well trays (CD-International, Pittman, New Jersey) were filled with 1 mL of a warm, aqueous 3% agar solution and allowed to cool to ambient temperature. The aphid infested cotton leaves were removed from the plants and placed bottom side up on a cutting platform. Circular discs were cut from the infested leaves and placed bottom side up onto the cooled agar gel, one disc per well. Each leaf disc was visually inspected to assure that a minimum of 10 live aphids were present. A 50 mM stock solution of the test compound was prepared by dissolving the appropriate amount of the test compound in DMSO. A solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 μl of the stock solution in 140 μl of an aqueous 0.003% Kinetic® (a nonionic wetter/spreader/penetrant adjuvant) solution. If needed, the solution of 1000 ppm of test compound was serially diluted with a solution of 66mL of DMSO and 30 μl of Kinetic® in 934 mL of water (diluting solution) to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm. Each replicate test plant disc was sprayed with 10 μl of the test solution at about 8 psi for 1 second. For comparison purposes, an aqueous solution of 0.003% Kinetic® containing no test compound and the diluting solution containing no test compound were also sprayed onto test plant discs. Upon completion of spraying the solutions of test compound and the solutions containing no test compound, the plant discs were allowed to dry. Upon completion of drying, the test trays were covered with a plastic film. Three slits were made in the film over each well to allow air into each well. The test trays were placed in a biochamber (25°C, 16 hours light, 8 hours of dark and 35-40% relative humidity) for three days. After this time, each plant disc was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plant discs containing no test compound. A test compound was designated as possessing insecticidal activity (SA) if there was 40% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was less than 40% mortality of the cotton aphid, the test compound was termed as inactive (I).

An assessment of the insecticidal activity at selected rates of application from this test is provided in Table 3 A. The test compounds of formula I are identified by numbers that correspond to those in Table 1.

Table 3A

The Following Compounds of The Present Invention Reduced the Population of Cotton Aphid on Treated Leaf Disks by 40% to 100% When Applied at an Application Rate of

300ppm or Less

Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd. Cmpd.

No. No. No. No. No. No. No.

1 5 29 35 39 40 45

While this invention has been described with an emphasis upon preferred embodiments, it will be understood by those of ordinary skill in the art that variations of the preferred embodiments may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the following claims.

Claims

WHAT IS CLAIMED IS:

Claim 1. An insecticidal composition comprising a compound of formula Ia:

wherein:

R and R¹ are independently selected from hydrogen and alkyl;

R² is selected from hydrogen, alkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, hydroxycarbonyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; provided that when R is hydrogen and R¹ and R³ are each methyl, then R² is other than

3 -trifluoromethylphenyl;

Claim 2. An insecticidal composition comprising a compound of formula Ib:

Ib wherein R⁴, R⁵, R⁶ and R⁷ are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, formyl, hydroxycarbonyl, alkoxycarbonyl and mono- or dialkylaminocarbonyl;

R² is selected from hydrogen, alkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; the N-oxides thereof; and the agriculturally acceptable salts thereof.

Claim 3. An insecticidal composition as claimed in claim 1, wherein R and R are independently selected from hydrogen and alkyl; R² is selected from aryl and aryl substituted with halogen; and R³ is alkyl.

Claim 4. An insecticidal composition as claimed in claim 3, wherein the compound is selected from:

R is hydrogen, R is ethyl, R is phenyl and R is methyl; and

R is methyl, R¹ is hydrogen, R² is 4-fluorophenyl and R³ is methyl.

Claim 5. An insecticidal composition as claimed in claim 2, wherein R⁴, R⁵, R⁶ and R⁷ are independently selected from hydrogen, halogen and alkoxy;

R² is selected from alkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with halogen, alkyl, alkoxy or haloalkyl; and R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy or haloalkoxy;

Claim 6. An insecticidal composition as claimed in claim 5, wherein the compound is selected from:

R² and R³ are methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; R² is methyl, R³ is ethyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; R² and R³ are methyl, R⁴, R⁵ and R⁶ are hydrogen, and R⁷ is methoxy; R² is phenyl, and R³, R⁴, R⁵, R⁶ and R⁷ are hydrogen; R² is phenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen;

R² is phenyl, R³ is 2,2,2-trifluoroethyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; R² is 4-fluorophenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; and R² is 3-methoxyphenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen.

Claim 7. A compound of formula Ic:

wherein R and R¹ are independently selected from hydrogen and alkyl;

R² is selected from hydrogen, alkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy;

R³ is selected from hydrogen, hydroxy, alkyl, haloalkyl, hydroxycarbonyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, alkylcarbonyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; provided that when R is hydrogen and R and R are each methyl, then R is other than

3 -trifluoromethylphenyl; the N-oxides thereof; and agriculturally acceptable salts thereof.

Claim 8. A compound of Claim 7, wherein

R² is selected from aryl and aryl optionally substituted with halogen; and

R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonyl and arylalkyl.

Claim 9. A compound of Claim 8, wherein the compound is selected from: R is hydrogen, R¹ is ethyl, R² is phenyl, and R³ is methyl; and R is methyl, R¹ is hydrogen, R² is 4-fluorophenyl, and R³ is methyl.

Claim 10. A compound of formula Id:

Id wherein

R⁴, R⁵, R⁶ and R⁷ are independently selected from hydrogen, halogen, alkyl and alkoxy; R² is selected from alkyl, aryl, heteroaryl and aryl optionally substituted with one or more halogen or alkoxy; R³ is selected from hydrogen, alkyl, haloalkyl, alkoxycarbonylalkyl, dialkylphosphonyl, cyanoalkyl, formyl, aminocarbonyl, arylalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl moieties are optionally substituted with one or more halogen, alkyl, haloalkyl, alkoxy, or haloalkoxy; provided that

1) when (i) R² is alkyl and R³ is hydrogen, alkyl, cyanoalkyl, benzyl or alkoxycarbonylalkyl; and (ii) R³ is alkyl and R² is phenyl, 2-methylphenyl, 3- chlorophenyl, 4-chlorophenyl, 4-methoxyphenyl, 2-pyridyl or 2-thienyl, then one of R⁴, R⁵, R⁶, and R⁷ is other than hydrogen; and

2) when R³ is hydrogen or alkyl, R² is alkyl and R⁴ and R⁷ are both hydrogen then (i) R⁵ is other than hydrogen and alkyl or (ii) R⁶ is other than hydrogen, halogen and alkyl; and i 3) when R³ is alkyl and R² is 3-methylphenyl or 4-methylphenyl then R⁶ is other than alkyl; and

4) when R² is phenyl then (i) R³ is other than hydrogen or alkyl, or (ii) one of R⁴, R⁵, R⁶ and R⁷ is other than hydrogen; the N-oxides thereof; and ' the agriculturally acceptable salts thereof.

Claim 11. A compound of claim 10, wherein

R² is selected from alkyl, phenyl and phenyl substituted with halogen and alkoxy;

R³ is selected from hydrogen, alkyl and haloalkyl; and

R⁴, R⁵, R⁶ and R⁷ are independently selected from hydrogen and alkoxy.

Claim 12. A compound of claim 11, wherein the compound is selected from:

R² and R³ are methyl, R⁴, R⁵, and R⁶ are hydrogen, and R⁷ is methoxy;

R² is phenyl, R³ is 2,2,2-trifluoroethyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen;

R² is 4-fluorophenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen; and R² is 3-methoxyphenyl, R³ is methyl, and R⁴, R⁵, R⁶ and R⁷ are hydrogen.

Claim 13. An insecticidal composition comprising a compound of claim 7.

Claim 14. An insecticidal composition as claimed in claim 1, further comprising one or more additional compounds selected from the group consisting of pesticides, plant growth regulators, fertilizers and soil conditioners.

Claim 15. A method of controlling insects, comprising applying a composition of claim 1 to a locus where insects are present or are expected to be present.

Claim 16. An insecticidal composition comprising a compound of claim 10.