Insecticidal N-(Heteroarylalkyl)Alkanediamine Derivatives

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 N-(heteroarylalkyl)alkanediamine derivatives and 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 structures. Although there are many orders of insects that can cause significant crop damage, insects, for example, of the suborder “Homoptera” are of major importance. The suborder Homoptera includes, for example, aphids, leafhoppers, cicadas, whiteflies, and mealybugs, to name a few. Homopterans have piercing/sucking mouthparts, enabling them to feed by withdrawing sap from vascular plants. Insect damage from homopterans 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 homopterans 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. Homopterans 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 alkanediamine compounds that are reported to be insecticidally active. For example, U.S. Pat. No. 4,806,553 discloses certain insecticidal alkylenediamine compounds of the general formula I:

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where

W¹is a five- or six-membered heterocyclic group, which may be substituted, containing at least one heteroatom selected from —O—, —S—, and —N—;

R¹, R², and R³are hydrogen or alkyl;

R⁴is hydrogen, alkyl, aryl, aralkyl, alkoxy, dialkylamino, alkoxyalkyl, alkylthioalkyl, or —CH₂—W²— in which W²═W¹;

X is —S—, —NR⁵—, or a single bond, in which R⁵is hydrogen or alkyl, and in the case where X is —NR⁵—, the group —NR⁴R⁵—, in the formula I may have the same meaning as the group

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in formula I;

Y is —N—, or ═CR⁶—, in which R⁶is hydrogen, alkyl, aryl, acyl, alkoxycarbonyl, or cyano;

Z is cyano or nitro; and,

A is ethylene or trimethylene, which may be substituted with alkyl.

Published Japanese Patent Application 08269035A discloses certain tetrahydrofuran-3-ylmethyl derivatives of the general formula I:

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where

R₁and R₂are hydrogen, or optionally substituted C₁-C₅alkyl; R₃-R₅are hydrogen, optionally substituted C₁-C₅alkyl, optionally substituted C₂-C₅alkenyl, or optionally substituted C₂-C₅alkynyl; n is 2-5; R₆is hydrogen or C₁-C₃alkyl; X is CH or N; Y is NO₂or C≡N; and R₃and R₄together may form a ring.

U.S. Pat. No. 5,075,301 claims, inter alia, certain furan derivatives of the following general formula that are useful for the treatment of gastro-intestinal disorders:

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where

X is, among others, R¹CH₂— where R¹is R²R³N—, where R²and R³are the same or different and each is hydrogen or lower alkyl;

Y is —CH₂— or —C(═O)—;

l is an integer of 1 through 3;

R_Ais hydrogen, lower alkyl, lower alkanoyl, or substituted or un-substituted aroyl;

Z is, among others,

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where

Q is oxygen or sulfur, R⁵is hydrogen, lower alkyl, or substituted or un-substituted aryl,

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where

R⁶and R⁷may be the same or different and each is hydrogen, cyano, lower alkoxycarbonyl, lower alkylsulfonyl, substituted or un-substituted arylsulfonyl, or nitro; provided that R⁶and R⁷cannot concurrently be hydrogen; R^2aand R^3ahave the same meaning as R²and R³described above,

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where

R⁶and R⁷are as described above, R⁸is hydrogen or lower alkyl, and n is 1 or 2. European Patent EP 0547451 B1 claims compounds of the following general formula that are useful as insecticides:

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where

X represents 2-chloro-5-pyridyl or 2-chloro-5-thiazolyl;

R¹represents hydrogen or (C₁-C₄)alkyl;

R²is hydrogen, (C₁-C₄)alkyl, (C₃-C₄)alkynyl, (C₃-C₄)alkenyl and 2-chloro-5-pyridyl;

R³and R⁴are selected from hydrogen, halogen, (C₁-C₄)alkyl, (C₃-C₄)alkynyl, (C₃-C₄)alkenyl and benzyl which may be substituted, or a group represented by X—C(R¹)H— wherein X and R¹are the same meaning as above;

N is an integer of 2 or 3, and

Y is —NO₂or —CN.

U.S. Pat. No. 5,852,012 claims compositions of compounds and salts thereof of the following general formula that are useful as insecticides:

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where

A is 2-chloropyrid-5-yl, 2-methylpyrid-5-yl, 1-oxido-3-pyridinio, 2-chloro-1-oxido-5-pyrinio, or 2-chlorothiazol-5-yl;

R is hydrogen; (C₁-C₆)alkyl, phenyl(C₁-C₄)alkyl, (C₃-C₆)cycloalkyl, (C₂-C₆)alkenyl or (C₂-C₆)alkynyl;

And
X is N—NO₂or N—CN.

US patent discloses compounds of the following general formula that are useful as insecticides:

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where

n is 0 or 1;

R¹, R², R⁵and R⁶independently represent hydrogen or alkyl; R³and R⁴independently represent hydrogen, hydroxy or alkyl; where n is 1, then R²may form a single bond with R⁵;

X represents —S—, —O—, ═N—R⁷or ═CH—R⁸wherein R⁷is, inter alia, hydrogen, halogen, alkyl, hydroxy, benzyl, benzyloxy, alkenylcarbonyl, benzyloxycarbonyl, mono- and dialkylaminocarbonyl, phenylaminocarbonyl, phenylsulfonylaminocarbonyl, alkylsulfonyl, and phenacyl; R⁸is hydrogen, alkyl, aryl and benzyl;

Y represents —N— or ═C(−)-R⁹wherein R⁹is, inter alia, hydrogen, halogen, hydroxy, alkyl, alkoxy, alkylthiocarbonyl, phenoxycarbonyl, phenylthiocarbonyl, benzoylaminocarbonyl, phenylsulfonylamino, alkylthio, alkylsulfonyl and phenylthio, phenylsulfonyl;

R represents hydrogen and alkyl;

and,

U represents a 5- or 6-membered heterocyclis group containing at least one hetero atom selected from —O—, —S— and —N—; which may be substituted

There is no disclosure or suggestion in any of the above-referenced patents or patent application of the structures and 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 novel N-(heteroarylalkyl)alkanediamine 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 compounds of formula I are represented by the following general formula:

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wherein

—Ar is selected from

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where

R¹, R², R³, and R⁴are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;

and,

s is an integer selected from 0 or 1;

-a and r are integers independently selected from 0 or 1;

—R is selected from hydroxy, haloalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, cycloalkylalkyl, cyanoalkyl, formyl, alkylcarbonyl, alkoxycarbonyl, alkylsulfonyl, dialkylphosphonato, oxolan-3-ylmethyl, 2H-3,4,5,6-tetrahydropyran-2-ylmethyl, cyclohex-1-en-3-yl, thien-3-ylmethyl, furan-2-ylmethyl, furan-3-ylmethyl, benzo[b]furan-2-ylmethyl, 2-R⁸-1,3-thiazol-4-ylmethyl, 5-R⁸-1,2,4-oxadiazol-3-ylmethyl,

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where

R⁸is selected from halogen, alkyl, aryl, and heteroaryl, wherein aryl and heteroaryl are optionally substituted with at least one of halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy;

m is an integer selected from 1 or 2;

and,

R⁹, R¹⁰, R¹¹, R¹², and R¹³are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyiminoalkyl, cyano, nitro, 2-alkyl-2H-tetrazol-5-yl, aryl, and aryloxy;

R¹⁴, R¹⁵and R¹⁶are independently selected from hydrogen, halogen, alkyl and aryl;

R¹⁷is selected from hydrogen, alkyl,

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where

n is an integer selected from 1 or 2; and,

R²³, R²⁴, R²⁵, R²⁶, and R²⁷are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy;

-d and e are integers independently selected from 0 and 1;

and,

when d and e are 1;

—U and V are —CH₂—;

—R⁶is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, alkenyl, haloalkenyl, and

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R³³, R³⁴, R³⁵and R³⁶are independently selected from hydrogen and alkyl; provided that when

i) Ar is oxolan-3-yl (M); ii) a, b and c are 1, and R^athrough R^g, inclusively, are hydrogen; iii) d, e and r are 0; iv) R is —(CH₂)_mCR¹⁴═CR¹⁵R¹⁶or —(CH₂)_mC≡CR¹⁷; v) R⁵is hydrogen or alkyl; vi) R⁶is hydrogen, alkyl, alkenyl or haloalkenyl and vii) W is —CR³³— where R³³is hydrogen; viii) then X is other than —S—;

when d and e are 0,

—R⁵and X may be taken together with —CH₂(CH₂)_q— or —CH₂YCH₂— to form a ring,

where

q is an integer selected from 1 or 2;

Y is selected from O, S and NR³⁷, where R³⁷is hydrogen or alkyl;

—X is elected from —CH—, —O—, —S—, and —N—;

where

when X is —CH— or —N—,

R⁶is selected from hydrogen, alkyl and that set forth above for R;

when b and c are 0,

—R and R⁵may be taken together with —CH₂CH₂— to form a piperazine ring;

and

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 of a second 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 certain new and useful compounds, namely novel N-(heteroarylalkyl)alkanediamine derivatives (hereinafter termed “compounds of formula I”) as depicted in formula I:

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where

—Ar is selected from

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—U and V are —CH₂—;

—R⁶is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, alkenyl, haloalkenyl, and

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where

p is an integer selected from 1 and 2;

and,

R²⁸, R²⁹, R³⁰, R³¹and R³²are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy;

—R⁷is selected from —C≡N and —NO₂;

—W is selected from —CR³³— and —N—;

—X is elected from —CR³⁴R³⁵—, —O—, —S—, and —NR³⁶;

where

R³³, R³⁴, R³⁵and R³⁶are independently selected from hydrogen and alkyl;

provided that when

i) Ar is oxolan-3-yl (M); ii) a, b and c are 1, and R^athrough R^g, inclusively, are hydrogen; iii) d, e and r are 0; iv) R is —(CH₂)_mCR¹⁴═CR¹⁵R¹⁶or —(CH₂)_mC≡CR¹⁷; v) R⁵is hydrogen or alkyl; vi) R⁶is hydrogen, alkyl, alkenyl or haloalkenyl and vii) W is —CR³³— where R³³is hydrogen; viii) then X is other than —S—;

when d and e are 0,

—R⁵and X may be taken together with —CH₂(CH₂)_q— or —CH₂YCH₂— to form a ring,

where

q is an integer selected from 1 or 2;

Y is selected from O, S and NR³⁷, where R³⁷is hydrogen or alkyl;

—X is elected from —CH—, —O—, —S—, and —N—;

where

when X is —CH— or —N—,

R⁶is selected from hydrogen, alkyl and that set forth above for R;

when b and c are 0,

—R and R⁵may be taken together with —CH₂CH₂— to form a piperazine ring;

and

agriculturally acceptable salts thereof.

Preferred species are those compounds of formula I where a is 1; b, c, d and e are each 0; R^a, R^b, R^cand R^dare each hydrogen; R⁵is selected from hydrogen and alkyl; W is selected from —CR³³— and —N—, where R³³is hydrogen; X is selected from —O—, —S—, and —NR³⁶—;

and

R⁵and X may be taken together with —CH₂(CH₂)_q— or —CH₂YCH₂— to form a ring,

where

Y is selected from —O— and —NR³⁷—, where R³⁷is hydrogen or alkyl; X is —N— and R⁶is selected from hydrogen and alkyl.

More preferred species are those compounds of formula I where Ar is selected from

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where

s is 0; R¹, R²and R⁴are each hydrogen and R³is halogen.

More specifically, in one aspect of the present invention certain new and useful N-(heteroarylalkyl)alkanediamine derivatives as depicted in formula I are providing unexpected control of insects and acarids:

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where

—Ar is selected from

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—U and V are —CH₂—;

—R⁶is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, alkenyl, haloalkenyl, and

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Preferred species in this aspect of the present invention are those compounds of formula I where a is 1; b, c, d and e are each 0; R^a, R^b, R^cand R^dare each hydrogen; R⁵is selected from hydrogen and alkyl; W is selected from —CR³³— and —N—, where R³³is hydrogen and X is selected from —O—, —S—, and —NR³⁶—. More preferred species in this aspect of the present invention are those compounds of formula I where Ar is selected from

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where

s is 0; R¹, R²and R⁴are each hydrogen and R³is halogen.

More specifically, in another aspect of the present invention certain new and useful N-(heteroarylalkyl)alkanediamine derivatives as depicted in formula I are providing unexpected control of insects and acarids:

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where

—Ar is selected from

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where

R¹, R², R³, and R⁴are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, and haloalkoxy;

and,

s is an integer selected from 0 or 1;

-a and r are integers independently selected from 0 or 1;

—R is selected from hydrogen, hydroxy, alkyl, haloalkyl, alkoxyalkyl, alkoxyalkoxyalkyl, cycloalkylalkyl, cyanoalkyl, formyl, alkylcarbonyl, alkoxycarbonyl, alkylsulfonyl, dialkylphosphonato, oxolan-3-ylmethyl, 2H-3,4,5,6-tetrahydropyran-2-ylmethyl, cyclohex-1-en-3-yl, thien-3-ylmethyl, furan-2-ylmethyl, furan-3-ylmethyl, benzo[b]furan-2-ylmethyl, 2-R⁸-1,3-thiazol-4-ylmethyl, 5-R⁸-1,2,4-oxadiazol-3-ylmethyl,

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where

R¹⁸, R¹⁹, R²⁰, R²¹, and R²²are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy;

—R^a, R^b, R^cand R^dare independently selected from hydrogen and alkyl;

-b and c are integers independently selected from 0 or 1;

and

when b and c are 1,

—R^e, R^f, R^gand R^hare independently selected from hydrogen and alkyl;

-d and e are 0;

—R⁵and X are taken together with —CH₂(CH₂)_q— or —CH₂YCH₂— to form a ring,

where

q is an integer selected from 1 or 2;

Y is selected from —O—, —S— and —NR³⁷—, where R³⁷is hydrogen or alkyl;

—X is elected from —CH—, —O—, —S—, and —N—;

where

when X is —CH— or —N—,

—R⁶is selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, alkenyl, haloalkenyl, and

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where

p is an integer selected from 1 and 2;

and,

R²⁸, R²⁹, R³⁰, R³¹and R³²are independently selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, and haloalkoxy;

—R⁷is selected from —C≡N and —NO₂;

—W is selected from CR³³— and —N—, where R³³is selected from hydrogen and alkyl;

and

agriculturally acceptable salts thereof.

Preferred species in this aspect of the present invention are those compounds of formula I where a is 1; b, c, d and e are each 0; R^a, R^b, R^cand R^dare each hydrogen; W is selected from —CR³³— and —N—, where R³³is hydrogen; Y is selected from —O— and NR³⁷; X is —N— and R⁶is selected from hydrogen and alkyl.

More preferred species in this aspect of the present invention are those compounds of formula I where Ar is selected from

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where

s is 0; R¹, R²and R⁴are each hydrogen and R³is halogen.

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 second 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 “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 or naphthyl. 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. The term “GC analysis” refers to gas chromatographic analysis of, for example, a chemical reaction mixture. The term “DMF” refers to N,N-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° C. to 30° C. The term “insecticidal” or “acaricidal”, “insecticide” or “acaricide” refers to a compound of the present invention, either alone or in admixture with at least one of a second compound, or with at least one compatible carrier, which causes the destruction or the inhibition of action of insects or acarids.

The novel compounds of formula I can be synthesized by methods that are individually known to one skilled in the art from intermediate compounds readily available in commerce.

Scheme 1 below illustrates a general procedure for synthesizing N-(heteroarylalkyl)alkanediamine derivatives of formula I, inter alia, where, for example Ar is pyrid-3-yl (A, where s is 0) substituted with R¹through R⁴, inclusively, a is 1; R^athrough R^d, inclusively, are hydrogen; b through e, inclusively, and r are 0; W is CR³³where R³³is hydrogen; and R⁷is —NO₂:

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As depicted in Scheme 1, an appropriate diamine, for example the commercially available ethylenediamine, was treated with di-tert-butyl dicarbonate as a means of protecting one of the amino groups from unwanted reactions, yielding the corresponding (tert.-butoxy)carboxamide, which is a known compound. The (tert-butoxy)carboxamide was in turn reacted with 1) either an appropriate aryl halide such as the known compound (6-chloropyrid-3-yl)methyl chloride or 2) an appropriate (aryl)formaldehyde such as the known compound (6-chloro-3-pyridyl)formaldehyde. The former reaction 1) was conducted under basic conditions in an appropriate solvent and resulted in the formation of a mixture of products, for example a di-alkylated material, namely, i) N-(2-[bis[6-chloro(3-pyridyl)methyl]amino]ethyl)(tert-butoxy)carboxamide, and a mono-alkylated material, namely, ii) (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl]amino}ethyl)carboxamide. The so-formed mixture of i) and ii) was easily separated into its individual components with column chromatography, thereby providing two useful intermediates finding utility in preparing compounds of formula I. In the more preferred latter reaction 2), the formaldehyde was condensed under basic conditions with the (tert-butoxy)carboxamide in the presence of a drying agent, providing the corresponding imine, which was not isolated. The so-formed imine was in turn reduced with, for example, sodium borohydride, yielding the corresponding intermediate ii) set forth above. Intermediate (b-ii), where R is hydrogen, was then reacted under basic conditions with an appropriate halogen derivative, such as (4-methoxyphenyl)methyl chloride, or propargyl bromide, yielding the corresponding intermediates (c), wherein the moiety R is now, for example, (4-methoxyphenyl)methyl or propargyl. Intermediate (c) was then treated with an acid, such as trifluoroacetic acid, to remove the amine-protecting (tert-butoxy)carboxamide group, affording intermediate (d), for example, (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine and (2-aminoethyl)[(6-chloro(3-pyridyl)methyl]prop-2-ynylamine. The free amine, intermediate (d) was converted to compounds of formula I by the reaction of it, in the presence of a catalyst, with an appropriate alkylthio derivative, for example, the commercially available 1,1-bis(methylthio)-2-nitroethylene, thereby introducing the moiety —C(XR⁶)═WR⁷into the molecule wherein X is S, R⁶is —CH₃, W is —CR³³— where R³³is hydrogen, and R⁷is —NO₂.

Compounds of formula I may be converted to other compounds of formula I. For example, compounds wherein X is S and R⁶is CH₃may be treated with sodium methylate in methanol, affording those compounds of formula I where X is O and R⁶is —CH₃. Examples 1 and 2 set forth below provide in detail certain methods by which compounds of formula I depicted in Scheme 1 were prepared.

Scheme 2 below illustrates a general procedure for synthesizing N-(heteroarylalkyl)alkanediamine derivatives of formula I, inter alia, where, for example Ar is pyrid-3-yl (A, where s is 0) substituted with R¹through R⁴, inclusively; a is 1; R^athrough R^d, inclusively, are hydrogen; b through e, inclusively, and r are 0; R⁵, and X are taken together with —CH₂(CH₂)_q— to form a ring wherein X and W are N, R⁶is hydrogen, and R⁷is —NO₂

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As depicted in Scheme 2, an appropriate (aryl)formaldehyde such as the known compound (6-chloro-3-pyridyl)formaldehyde, was condensed with an aminoalkanol, such as 2-aminoethan-1-ol, then reduced with a reducing agent, such as sodium borohydride as set forth above, providing the corresponding alcohol intermediate (e), for example, 2-{[(6-chloro-3-pyridyl)methyl]amino}ethan-1-ol. Intermediate (e), where R is hydrogen, was then reacted under basic conditions with an appropriate halogen derivative, such as 1-iodopropane, yielding the corresponding intermediate (f), wherein the moiety R is now, for example, n-propyl. Intermediate (f) was in turn treated with, for example thionyl chloride, thereby converting intermediate (f) to the corresponding halogen intermediate (g), for example, [(6-chloro(3-pyridyl))methyl](2-chloroethyl)propyl amine. The so-prepared intermediate (g) was converted to compounds of formula I by the reaction of it with, for example, the sodium salt of the commercially available 2-(nitromethylene)imidazolidine, thereby introducing a ring into the molecule wherein R⁵and X are taken together with —CH₂(CH₂)_q—, X and W are N, R⁶is hydrogen, and R⁷is —NO₂. Example 3 set forth below provides in detail one method by which compounds of formula I depicted in Scheme 2 are prepared.

Intermediate (g) was converted to additional compounds of formula I by the reaction of it with, for example, 4-(azanitromethylene)-3-methyl-1,3,5-oxadiazaperhydroine (prepared by the method of P. Maienfisch et al; Pest Management Science 165-176 (2001), under basic conditions, thereby introducing a different ring into the molecule wherein R⁵and X are taken together with —CH₂YCH₂—, where Y is, for example, 0, X and W are N, R⁶is —CH₃, and R⁷is —NO₂. Example 4 set forth below provides in detail another method by which compounds of formula I depicted in Scheme 2 were prepared.

Scheme 3 below illustrates another general procedure for synthesizing N-(heteroarylalkyl)alkanediamine derivatives of formula I, inter alia, where, for example Ar is pyrid-3-yl (A, where s is 0) substituted with R¹through R⁴, inclusively; a is 1; R^athrough R^d, inclusively, are hydrogen; b through e, inclusively, and r are 0; R⁵and X are taken together with —CH₂(CH₂)_q— to form a ring wherein X is N, W is CR³³where R³³is hydrogen, R⁶is hydrogen, and R⁷is —NO₂:

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As depicted in Scheme 3, an appropriately protected diamine, for example the commercially available N-{2-[(2-aminoethyl)amino]ethyl}(tert-butoxy)carboxamide was cyclized under basic conditions with a known or commercially available (dialkylthio)ethene compound, for example 1,1-di(methylthio)-2-nitroethene, yielding the corresponding cyclic derivative (h), such as (tert-butoxy)-N-{2-[2-(nitromethylene)imidazolidinyl]ethyl}carboxamide. Intermediate (h) was in turn deprotected under acidic conditions, affording the free amine (i), as a salt, for example 2-[2-(nitromethylene)imidazolidinyl]ethylamine, acetic acid salt. The moiety Ar was then introduced into the molecule by reacting the salt (i) with, for example (6-chloro-3-pyridyl)formaldehyde, providing the corresponding substituted amine intermediate (j), such as [(6-chloro(3-pyridyl))methyl]{2-[2-(nitromethylene)imidazolidinyl]ethyl]amine. Intermediate (j) was then converted to a compound of formula I, by the reaction of (j) with, for example 2-chlorobenzaldehyde, under basic conditions that introduced moiety R into the molecule. Example 5 set forth below provides in detail the method by which compounds of formula I depicted in Scheme 3 were prepared.

Scheme 4 below illustrates another general procedure for synthesizing N-(heteroarylalkyl)alkanediamine derivatives of formula I, inter alia, where, for example Ar is pyrid-3-yl (A, where s is 0) substituted with R¹through R⁴, inclusively; a is 1; R^athrough R^d, inclusively, are hydrogen; b, c and r are 0:

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As depicted in Scheme 4, intermediate (d), for example, the free amine (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine, prepared as set forth above in Scheme 1 and Example 1, was reacted with the known compound (2Z)-2-aza-3-ethoxybut-2-enenitrile, thereby introducing the moiety —C(XR⁶)═WR⁷into compounds of formula I, wherein —XR⁶is —CH₃, W is —N—, R⁷is —NO₂and d and e are 0. Example 6 set forth below provides in detail the method by which these compounds of formula I depicted in Scheme 4 were prepared.

In a similar manner, intermediate (d) was reacted under basic conditions with, for example (2Z)-2-aza-3-(diethylamino)-4-chlorobut-2-enenitrile, thereby introducing the moiety —U_dC(XR⁶)═WR⁷into compounds of formula I, wherein d is 1, U is —CH₂—, —X— is NR³⁶where R³⁶and R⁶are —C₂H₅, W is —N— and R⁷is CN. Example 7 set forth below provides in detail the method by which these compounds of formula I depicted in Scheme 4 were prepared.

In still a similar manner, intermediate (d) was reacted with, for example the known compound (2Z)-2-aza-4-chloro-3-methoxybut-2-enenitrile, thereby introducing the moiety —C(V_eCl)═WR⁷into the molecule and depicted as intermediate (k), wherein e is 1, V is —CH₂—, W is —N— and R⁷is CN. Intermediate (k) was in turn reacted with, for example diethylamine, thereby introducing the moiety XR⁶into compounds of formula I, wherein —X— is NR³⁶where R³⁶and R⁶are —C₂H₅. Example 8 set forth below provides in detail the method by which these compounds of formula I depicted in Scheme 4 were prepared.

Scheme 5 below illustrates another general procedure for synthesizing N-(heteroarylalkyl)alkanediamine derivatives of formula I, inter alia, where, for example Ar is 1,3-thiazol-5-yl or oxolan-3-yl (B or M, respectively, where s is 0), a is 1; R^athrough R^d, inclusively, are hydrogen; b through e, inclusively, and r are 0; W is N and R⁷is —NO₂:

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As depicted in Scheme 5, which is a variation of the route set forth in Scheme 1, intermediate (a), for example, N-(2-aminoethyl)(tert-butoxy)carboxamide was reacted with an appropriate (aryl)formaldehyde, such as 4-methoxybenzaldehyde, yielding, for example (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl]amino}ethyl)carboxamide (m), wherein moiety R is now (4-methoxyphenyl)methyl. Intermediate (m) was in turn reacted in the same manner with an appropriate second (aryl)formaldehyde, such as (2-chloro-1,3-thiazol-5-yl)formaldehyde or (oxolan-3-yl)formaldehyde, thereby introducing the moiety Ar to the molecule, providing intermediate (n), for example (tert-butoxy)-N-(2-{[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)carboxamide or (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amino}ethyl)carboxamide. Intermediate (n) was then treated with an acid, such as trifluoroacetic acid, to remove the amine-protecting (tert-butoxy)carboxamide group, affording intermediate (o), for example (2-aminoethyl)[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amine or (2-aminoethyl)[4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amine. The free amine, intermediate (o), was converted to compounds of formula (I) by the reaction of it with an appropriate alkylthio derivative, for example, the known compound dimethyl N-nitroimidodithiocarbonate, thereby introducing the moiety —C(XR⁶)═WR⁷into the molecule wherein X is S, W is N, R⁶is —CH₃and R⁷is —NO₂. Examples 9 and 10 set forth below provide in detail the method by which these compounds of formula I depicted in Scheme 5 were prepared.

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 for to facilitate dispersion on the foliage of the plant.

Other useful formulations for insecticidal applications are emulsifiable 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, isphorone, or other non-volatile organic solvents. For insecticidal application these concentrates are dispersed in 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, emulsifiable 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 second 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.

Second compounds include, without limitation, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals. In 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 of second compounds, e.g., with other pesticides such as herbicides, the herbicides include, without limitation, for example: N-(phosphonomethyl)glycine (“glyphosate”); aryloxyalkanoic acids such as (2,4-dichlorophenoxy)acetic acid (“2,4-D”), (4-chloro-2-methylphenoxy)acetic acid (“MCPA”), (+/−)-2-(4chloro-2-methylphenoxy)propanoic acid (“MCPP”); ureas such as N,N-dimethyl-N′-[4-(1-methylethyl)phenyl]urea (“isoproturon”); imidazolinones such as 2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-pyridinecarboxylic acid (“imazapyr”), a reaction product comprising (+/−)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-4-methylbenzoic acid and (+/−)2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-methylbenzoic acid (“imazamethabenz”), (+/−)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-ethyl-3-pyridinecarboxylic acid (“imazethapyr”), and (+/−)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-3-quinolinecarboxylic acid (“imazaquin”); diphenyl ethers such as 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid (“acifluorfen”), methyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate (“bifenox”), and 5-[2-chloro-4-(trifluoromethyl)phenoxy]-N-(methylsulfonyl)-2-nitrobenzamide (“fomasafen”); hydroxybenzonitriles such as 4-hydroxy-3,5-diiodobenzonitrile (“ioxynil”) and 3,5-dibromo-4-hydroxybenzonitrile (“bromoxynil”); sulfonylureas such as 2-[[[[(4chloro-6-methoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]benzoic acid (“chlorimuron”), 2-chloro-N-[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]benzenesulfonamide (achlorsulfuron”), 2-[[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]methyl]benzoic acid (“bensulfuron”), 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]amino]sulfonyl]-1-methyl-1H-pyrazol-4-carboxylic acid (“pyrazosulfuron”), 3-[[[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]amino]sulfonyl]-2-thiophenecarboxylic acid (“thifensulfuron”), and 2-(2-chloroethoxy)-N[[(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino]carbonyl]benzenesulfonamide (“triasulfuron”); 2-(4-aryloxy-phenoxy)alkanoic acids such as (+/−)-2[4-[(6-chloro-2-benzoxazolyl)oxy]phenoxy]-propanoic acid (fenoxaprop”), (+/−)-2-[4[[5-(trifluoromethyl)-2-pyridinyl]oxy]-phenoxy]propanoic acid (“fluazifop”), (+/−)-2-[4-(6chloro-2-quinoxalinyl)oxy]-phenoxy]propanoic acid (“quizalofop”), and (+/−)-2-[(2,4-dichlorophenoxy)phenoxy]propanoic acid (“diclofop”); benzothiadiazinones such as 3-(1-methylethyl)-1H-1,2,3-benzothiadiazin-4(3H)-one-2,2-dioxide (“bentazone”); 2-chloroacetanilides such as N-(butoxymethyl)-2-chloro-N-(2,6-diethylphenyl)acetamide (“butachlor”), 2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)acetamide (“metolachlor”), 2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)acetamide (“acetochlor”), and (RS)-2-chloro-N-(2,4-dimethyl-3-thienyl)-N-(2-methoxy-1-methylethyl)acetamide (“dimethenamide”); arenecarboxylic acids such as 3,6-dichloro-2-methoxybenzoic acid (“dicamba”); pyridyloxyacetic acids such as [(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]acetic acid (“fluoroxypyr”), and other herbicides.

When the active insecticidal compounds of the present invention are used in combination with one or more of second 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, alpha-cypermethrin, bifenthrin, cypermethrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomethrin, 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 of second 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 of second compounds, e.g., with other pesticides such as nematicides, the nematicides include, for example: carbofuran, carbosulfan, turbufos, 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 of second 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 {2-[((1Z)-1-methylthio-2-nitrovinyl)amino]ethyl}[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine (Compound 138).

Step A—Synthesis of a mixture of i) N-(2-[bis[6-chloro(3-pyridyl)methyl]amino]ethyl)(tert-butoxy)carboxamide and ii) (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl]amino}ethyl)carboxamide as intermediates

A solution of 14.5 grams (0.09 mole) N-(2-aminoethyl)(tert.-butoxy)carboxamide (known compound) and 25 mL (excess) of triethylamine in 200 mL of acetonitrile was stirred and a solution of 29.3 grams (0.18 mole) of (6-chloropyrid-3-yl)methyl chloride (known compound) in 100 mL of acetonitrile was added dropwise. Upon completion of addition, the reaction mixture was stirred at ambient temperature during a 24 hour period. After this time the reaction mixture was filtered to collect a solid. The solid was washed with acetonotrile, and the combined wash and filtrate was concentrated under reduced pressure to one half volume. The concentrate was taken up in an aqueous solution saturated with sodium chloride, and the mixture was extracted several times with ethyl acetate. The combined extracts were dried with sodium sulfate, filtered, and concentrated under reduced pressure to a residue. The gelatinous residue was slurried in methylene chloride and filtered to remove a solid material. The solid was then taken up in an aqueous solution saturated with potassium carbonate and extracted with methylene chloride. The extract was concentrated under reduced pressure to a residual oil. The filtrate set forth above was dissolved in methylene chloride and washed with an aqueous solution saturated with potassium carbonate. The organic layer was concentrated under reduced pressure to a second residual oil. The two residual oils were combined and purified with column chromatography on silica gel. Elution was accomplished using methylene chloride and mixtures of up to 4% methanol in methylene chloride. Appropriate fractions were combined and concentrated under reduced pressure, giving a mixture of predominantly i) and ii) as a residue. The residue containing i) and ii) was further purified with column chromatography on silica gel. Elution was accomplished using 2% methanol in methylene chloride. Appropriate fractions were combined and concentrated under reduced pressure, yielding 12.8 grams each of i) and ii). The NMR spectra were consistent with the proposed structures.

Step B—Synthesis of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)carboxamide as an intermediate

A stirred solution of 1.5 grams (0.0052 mole) of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl]amino}ethyl)carboxamide and 2.3 mL (0.013 mole) of diisopropylethyl amine in about 15 mL of methylene chloride was cooled to 0° C., and 0.7 mL (0.0052 mole) of (4-methoxyphenyl)methyl chloride in about 3 mL of methylene chloride was added dropwise. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature, where it stirred during an 18 hour period. After this time, analysis of the reaction mixture by thin layer chromatography (TLC) indicated that no reaction had taken place. The reaction mixture was then heated at reflux for two hours, after which TLC analysis indicated that no reaction had taken place. The methylene chloride solvent was removed under reduced pressure from the reaction mixture, which was replaced with chloroform. The reaction mixture was heated at reflux during one hour, and then it was allowed to cool to ambient temperature, where it stirred during an 18 hour period. After this time TLC analysis indicated the presence of some reaction product. The reaction mixture was then heated at reflux for about a nine hour period and then it was allowed to cool to ambient temperature as it stirred during an additional 18 hour period. After this time the chloroform solvent was removed under reduced pressure from the reaction mixture, which was replaced with acetonitrile. The reaction mixture was then stirred at ambient temperature during a four hour period, warmed to 60° C. where it stirred for a ten hour period, and finally stirred at ambient temperature during a 60 hour period. The reaction mixture was concentrated under reduced pressure to a residue, and the residue was purified with column chromatography on silica gel. Elution was accomplished using 30% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under reduced pressure, yielding 1.6 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C—Synthesis of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine as an intermediate

A stirred aliquot of 1.4 grams (0.0035 mole) of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)carboxamide was cooled to 0° C., and 10 mL of trifluoroacetic acid (excess) was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for one hour. After this time TLC analysis of the reaction mixture indicated that the reaction had gone to completion. The reaction mixture was concentrated under reduced pressure to a residue. The residue was dissolved in methylene chloride and made basic with aqueous 15% sodium hydroxide. The mixture was extracted several times with methylene chloride, and the combined extracts were dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure, yielding about 1.0 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step D—Synthesis of Compound 138

A stirred solution of 0.5 gram (0.0016 mole) of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine, 0.24 gram (0.0016 mole) of 1,1-bis(methylthio)-2-nitroethylene, and a catalytic amount of 4-dimethylaminopyridine in 15 mL of acetonitrile was heated at reflux for 20 hours. After this time the reaction mixture was allowed to cool to ambient temperature as it stirred for an additional 60 hours. The reaction mixture was then concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using 25% to 40% mixtures of ethyl acetate in hexane. Appropriate fractions were combined and concentrated under reduced pressure, yielding about 0.5 gram of Compound 138. The NMR spectrum Was consistent with the proposed structure.

EXAMPLE 2

This example illustrates one protocol for the preparation of {2-[((1Z)-1-methoxy-2-nitrovinyl)amino]ethyl}[(6-chloro(3-pyridyl)methyl]prop-2-ynylamine (Compound 244).

Step A—Synthesis of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl]amino}-ethyl)carboxamide as an intermediate (designated ii in Step A of Example 1), an alternate method

A solution of 28.0 grams (0.198 mole) of (6-chloro-3-pyridyl)formaldehyde (known compound), 38.1 grams (0.238 mole) of N-(2-aminoethyl)(tert.-butoxy)carboxamide (known compound), 80.0 grams (0.790 mole) of triethylamine, and 35.7 grams (0.297 mole) of magnesium sulfate in about 1000 mL of methanol was stirred at ambient temperature during an 18 hour period. After this time the reaction mixture was cooled in an ice-water bath, and 44.8 grams (1.188 moles) of sodium borohydride was added portion-wise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature as it stirred during an 18 hour period. After this time about 500 mL of water was added to the reaction mixture, which was then concentrated under reduced pressure to remove some of the methanol. The mixture was then extracted with multiple portions of ethyl acetate. The combined extracts were washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using hexane, ethyl acetate, and a mixture of 1:9 methanol in ethyl acetate. Appropriate fractions were combined and concentrated under reduced pressure, yielding about 35.9 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl)methyl]prop-2-ynylamino}ethyl)carboxamide as an intermediate

A stirred solution of 3.0 grams (0.011 mole) of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl))methyl]amino}ethyl)carboxamide, 2.3 grams (0.016 mole) of propargyl bromide, and 2.0 grams (0.016 mole) of diethanolamine in 100 mL of acetonitrile was heated to reflux where it was maintained during an 18 hour period. After this time the reaction mixture was cooled and the solvent was removed under reduced pressure to a residue. The residue was dissolved in methylene chloride and washed with three 50 mL portions of water, and then with one 50 mL portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using a mixture of 3:1 hexane:ethyl acetate. Appropriate fractions were combined and concentrated under reduced pressure, yielding 2.1 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C—Synthesis of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl]prop-2-ynylamine as an intermediate

This compound was made in a manner analogous to that set forth in Step C of Example 1, using 2.1 grams (0.0064 mole) of (tert-butoxy)-N-(2-{[(6-chloro(3-pyridyl)methyl]prop-2-ynylamino}ethyl)carboxamide and 20 mL (excess) of trifluoroacetic acid in 20 mL of methylene chloride. The yield of the subject compound was 1.3 grams. The NMR spectrum was consistent with the proposed structure.

Step D—Synthesis of {2-[((1Z)-1-methylthio-2-nitrovinyl)amino]ethyl}[(6-chloro(3-pyridyl)methyl]prop-2-ynylamine (Compound 248) as an intermediate

This compound was made in a manner analogous to that set forth in Step D of Example 1, using 1.3 grams (0.0056 mole) of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl]prop-2-ynylamine and 1.0 gram (0.0068 mole) of 1,1-bis(methylthio)-2-nitroethylene in 75 mL of acetonitrile. The reaction product was purified with column chromatography on silica gel. Elution was accomplished using a mixture of 1:1 hexanes:ethyl acetate. Appropriate fractions were combined and concentrated under reduced pressure, yielding 1.1 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step E—Synthesis of Compound 244

A solution of 0.5 gram (0.0015 mole) of Compound 183 and about 0.1 gram (0.0015 mole) of sodium methylate in 20 mL of methanol was stirred at ambient temperature during an 18 hour period. After this time the reaction mixture was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using a mixture of 7:3 ethyl acetate:hexanes. Appropriate fractions were combined and concentrated under reduced pressure, yielding about 0.4 gram of Compound 244, mp 114-115° C. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 3

This example illustrates one protocol for the preparation of {2-[azanitromethylene)imidazolidinyl]ethyl}[(6-chloro(3-pyridyl))methyl]propylamine (Compound 488).

Step A—Synthesis of 2-{[(6-chloro-3-pyridyl)methyl]amino}ethan-1-ol as an intermediate

This compound was made in a manner analogous to that set forth in Step A of Example 2, using 8.5 grams (0.060 mole) of (6-chloro-3-pyridyl)formaldehyde (known compound), 4.4 grams (0.072 mole) of 2-aminoethan-1-ol, 4.9 grams (0.048 mole) of triethylamine, 14.4 grams (0.119 mole) of magnesium sulfate, and 13.6 grams (0.360 mole) of sodium borohydride in 150 mL of methanol. The yield of the subject compound was about 11.3 grams, which included an impurity of about 10% by weight. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of 2{[(6-chloro(3-pyridyl))methyl]propylamino}ethan-1-ol as an intermediate

This compound was made in a manner analogous to that set forth in Step B of Example 2, using 11.3 grams (about 0.055 mole) of 2-{[(6-chloro-3-pyridyl)methyl]amino}ethan-1-ol, 25.4 grams (0.150 mole) of 1-iodopropane, and 14.5 grams (0.143 mole) of triethylamine in 50 mL of acetonitrile. The yield of the subject compound was about 2.2 grams.

Step C—Synthesis of [(6-chloro(3-pyridyl))methyl](2-chloroethyl)propylamine as an intermediate

A stirred solution of 1.0 gram (0.0044 mole) of 2 {[(6-chloro(3-pyridyl))methyl]propylamino}ethan-1-ol in two mL of chloroform was cooled to 0° C., and 2 mL (excess) of thionyl chloride was added dropwise. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature, and then it was heated to reflux where it was stirred for one hour. After this time the reaction mixture was concentrated and made basic with aqueous 10% sodium hydroxide. The mixture was then extracted multiple times with ethyl acetate. The combined extracts were then dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding about 1.0 gram of the subject compound.

Step D—Synthesis of Compound 488

A stirred solution of 0.90 gram (0.004 mole) of [(6-chloro(3-pyridyl))methyl](2-chloroethyl)propylamine and 0.47 gram (0.004 mole) of 2-(nitromethylene)imidazolidine in 20 mL of DMF was cooled to 0° C., and 0.19 gram (0.005 mole) of 60% sodium hydride (in mineral oil) was added. Upon completion of addition the reaction mixture was stirred at 0° C. for four hours, then it was allowed to warm to ambient temperature as it stirred during an 18 hour period. After this time the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was dried with magnesium sulfate, filtered and concentrated under reduced pressure to a residue. The NMR spectrum indicated that complete reaction had not taken place. The residue was dissolved in DMF and a fresh quantity of 60% sodium hydride in the amount set forth above was added to the reaction mixture. Upon completion of addition the reaction mixture was warmed to 60 to 70° C. where it stirred for two hours. After this time the reaction mixture was worked up as set forth above, yielding 0.63 gram of Compound 488. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 4

This example illustrates one protocol for the preparation of {2-[4-(azanitromethylene)-5-methyl(1,3,5-oxadiazahydroin-3-yl)]ethyl}bis[6-chloro(3-pyridyl)methyl]amine (Compound 548).

Step A—Synthesis of bis[(6-chloro(3-pyridyl)methyl](2-bromoethyl)amine as an intermediate

This compound was prepared in a manner analogous to that set forth in Steps A-C of Example 3. The yield of subject compound was 3.3 grams. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of Compound 548

A stirred solution of 0.62 gram (0.0016 mole) of bis[(6-chloro(3-pyridyl)methyl](2-bromoethyl)amine, 0.25 gram (0.0015 mole) of 4-(azanitromethylene)-3-methyl-1,3,5-oxadiazaperhydroine (prepared by the method of P. Maienfisch et al; Pest Management Science 165-176 (2001); is Compound 17c in this paper) and 0.32 gram (0.0023 mole) of potassium carbonate in 20 mL of DMF was heated to 70° C. where it was maintained for three hours. After this time the reaction mixture was allowed to cool to ambient temperature where it stood for 40 hours. The reaction mixture was then filtered and concentrated under reduced pressure to a residue. The residue was dissolved in ethyl acetate and washed with water. The organic layer was dried with sodium sulfate and filtered. The filtrate was purified with column chromatography on silica gel. Elution was accomplished using ethyl acetate and 10% methanol in methylene chloride as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.45 gram of Compound 548. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 5

This example illustrates one protocol for the preparation of [(6-chloro(3-pyridyl)))methyl][(2-chlorophenyl)methyl]{2-(nitromethyleneimidazolidinyl]ethyl}-amine (Compound 501).

Step A—Synthesis of (tert-butoxy)-N-{2-[2-(nitromethylene)imidazolidinyl]ethyl}-carboxamide as an intermediate

A stirred mixture of 2.03 gram (0.010 mole) of N-{2-[(2-aminoethyl)amino]ethyl}(tert-butoxy)carboxamide (commercially available), 1.18 gram (0.010 mole) of 1,1-di(methylthio)-2-nitroethene and 2 mL (excess) of triethylamine in 40 mL of acetonitrile was warmed to reflux where it was maintained for four hours. After this time the reaction mixture was concentrated under reduced pressure to a solid residue. The residue was washed with diethyl ether and dried, yielding 1.76 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of 2-[2-(nitromethylene)imidazolidinyl]ethylamine, acetic acid salt as an intermediate

With stirring and cooling in an ice-water bath (0° C.), 0.40 gram (0.0015 mole) of (tert-butoxy)-N-{2-[2-(nitromethylene)imidazolidinyl]ethyl}carboxamide and 2 mL of trifluoroacetic acid (excess) in 10 mL of methylene chloride were combined. Upon completion of addition, the ice-water bath was removed, and the reaction mixture was allowed to warm to ambient temperature as it stirred during an 18 hour period. After this time the reaction mixture was concentrated under reduced pressure to a residue. The residue was stirred with 10 mL of acetonitrile and 50 mL of diethyl ether, to precipitate a solid. The solid was collected by filtration and dried, yielding 0.4 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C—Synthesis of [(6-chloro(3-pyridyl))methyl]{2-[2-(nitromethylene)-imidazolidinyl]ethyl]amine as an intermediate

With stirring and cooling in an ice-water-salt bath (−5° C.), 0.14 gram (0.0005 mole) of 2-[2-(nitromethylene)imidazolidinyl]ethylamine, acetic acid salt, 0.09 gram (0.0006 mole) of (6-chloro-3-pyridyl)formaldehyde, 0.05 gram (0.0008 mole) of sodium cyanoborohydride and 0.5 mL of acetic acid in 10 mL of methanol were combined. Upon completion of addition, the cooling bath was removed and the reaction mixture was allowed to warm to ambient temperature as it stirred during an 18 hour period. After this time the reaction mixture was neutralized to a pH of 8 using aqueous 10% ammonium hydroxide. The mixture was then extracted with two 50 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using mixtures of methanol and methylene chloride as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.05 gram of the subject compound. The NMR spectrum was consistent with the proposed structure. Steps A-C were repeated to obtain additional intermediate with which to continue.

Step D—Synthesis of Compound 501

With stirring and cooling in an ice-water bath (0° C.) 0.12 grams (0.0004 mole) of [(6-chloro(3-pyridyl))methyl]{2-[2-(nitromethylene)imidazolidinyl]ethyl]amine, 0.06 gram (0.0004 mole) of 2-chlorobenzaldehyde, 0.13 gram (0.0006 mole) of sodium triacetoxyborohydride and 0.10 gram (0.0008 mole) of magnesium sulfate in about 20 mL of 1,2-dichloroethane were combined. Upon completion of addition, the cooling bath was removed and the reaction mixture was allowed to warm to ambient temperature as it stirred during an 18 hour period. After this time the reaction was quenched by the addition of five mL of water, then the reaction mixture was neutralized to pH of 8-9. The reaction mixture was then extracted with two 50 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure, yielding 0.07 gram of Compound 501. The

NMR spectrum was consistent with the proposed structure.

EXAMPLE 6

This example illustrates one protocol for the preparation of (2E)-2-aza-3-[(2-{[(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)amino]but-2-enenitrile (Compound 178).

A stirred solution of 0.2 gram (0.0007 mole) of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine (prepared in Steps A-C of Example 1) and 0.11 gram (0.0010 mole) of (2Z)-2-aza-3-ethoxybut-2-enenitrile (known compound) in 10 mL of acetonitrile was warmed to reflux where it was maintained during a two hour period. After this time the cooled reaction mixture was purified with column chromatography on silica gel. Elution was accomplished using 85% ethyl acetate in hexane as an eluant. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.14 gram of the Compound 178. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 7

This example illustrates one protocol for the preparation of (2Z)-2-aza-3-(diethylamino)-4-[(2-{([(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)amino]but-2-enenitrile (Compound 181).

Step A—Synthesis of (2Z)-2-aza-3-(diethylamino)-4-chlorobut-2-enenitrile as an intermediate

A solution of 0.5 gram (0.0038 mole) of (2Z)-2-aza-4-chloro-3-methoxybut-2-enenitrile (known compound) in 10 mL of acetonitrile was stirred, and 0.3 gram (0.0042 mole) of diethylamine was added. Upon completion of addition, the reaction mixture was stirred for an additional 30 minutes, then it was absorbed in silica gel. The mixture was then purified by column chromatography. Elution was accomplished using methylene chloride as an eluant. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.32 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of Compound 181

A solution of 0.25 gram (0.0008 mole) of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine (prepared in Steps A-C of Example 1), 0.14 gram (0.0008 mole) of (2Z)-2-aza-3-(diethylamino)-4-chlorobut-2-enenitrile and 0.13 gram (0.0010 mole) of N,N-diisopropylethylamine in 10 mL of acetonitrile was stirred at ambient temperature during a 48 hour period. After this time a solid was collected by filtration. The solid was washed with diethyl ether and dried, yielding 0.25 gram of Compound 181; mp 68-72° C. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 8

This example illustrates one protocol for the preparation of (2E)-2-aza-4-(diethylamino)-3-[(2-{[(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)amino]but-2-enenitrile (Compound 183).

Step A—Synthesis of (2E)-2-aza-4-chloro-3-[(2-{[(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)amino]but-2-enenitrile as an intermediate

A solution of 0.50 gram (0.0016 mole) of (2-aminoethyl)[(6-chloro(3-pyridyl)methyl][(4-methoxyphenyl)methyl]amine (prepared in Steps A-C of Example 1) and 0.32 gram (0.0024 mole) of (2Z)-2-aza-4-chloro-3-methoxybut-2-enenitrile (known compound) in 10 mL of acetonitrile was stirred at ambient temperature during a 30 minute period. After this time the reaction mixture was absorbed in silica gel, and purified by column chromatography. Elution was accomplished using methylene chloride, then ethyl acetate as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.47 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of Compound 183

A solution of 0.3 gram (0.0007 mole) of (2E)-2-aza-4-chloro-3-[(2-{[(6-chloro(3-pyridyl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)amino]but-2-enenitrile and 0.11 gram (0.0015 mole) of diethylamine in about 10 mL of acetonitrile was stirred at ambient temperature during a 48 hour period. After this time the reaction mixture was dissolved in 100 mL of methylene chloride and washed with 50 mL of aqueous 5% sodium carbonate. The organic layer was dried with magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel. Elution was accomplished using 75% diethyl ether in hexane and 100% diethyl ether as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.30 gram of Compound 183. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 9

This example illustrates one protocol for the preparation of {2-[((1Z)-2-aza-1-methylthio-2-nitrovinyl)amino]ethyl}[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amine (Compound 300).

Step A—Synthesis of (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl]amino}-ethyl)carboxamide as an intermediate

This compound was made in a manner analogous to that set forth in Step D of Example 5, using 3.0 grams (0.022 mole) of 4-methoxybenzaldehyde, 3.6 grams (0.022 mole) of N-(2-aminoethyl)(tert-butoxy)carboxamide (known compound), 7.0 grams (0.033 mole) of sodium triacetoxyborohydride and 5.3 grams (0.044 mole) of magnesium sulfate in 30 mL of 1,2-dichloroethane. The reaction product was purified with column chromatography on silica gel. Elution was accomplished using mixtures of 2% to 5% methanol in methylene chloride as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.72 gram of the subject compound. The NMR spectrum was consistent with the proposed structure. The reaction was repeated to obtain additional material.

Step B—Synthesis of (tert-butoxy)-N-(2-{[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)carboxamide as an intermediate

This compound was also made in a manner analogous to that set forth in Step D of Example 5, and Step A above, using 0.25 gram (0.0017 mole) of (2-chloro-1,3-thiazol-5-yl)formaldehyde, 0.47 gram (0.0017 mole) of (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl]amino}ethyl)carboxamide, 0.54 gram (0.0025 mole) of sodium triacetoxyborohydride and 0.40 gram (0.0034 mole) of magnesium sulfate in about 10 mL of 1,2-dichloroethane. The reaction product was purified with column chromatography on silica gel. In a first chromatography, elution was accomplished using mixtures of 2% to 5% methanol in methylene chloride as eluants. In a second chromatography, elution was accomplished using a mixture of 1.5% methanol in methylene chloride as an eluant. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.48 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C—Synthesis of (2-aminoethyl)[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amine as an intermediate

This compound was made in a manner analogous to that set forth in Step C of Example 1, using 0.3 gram (0.0007 mole) of (tert-butoxy)-N-(2-{[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amino}ethyl)carboxamide and 3 mL (excess) of trifluoroacetic acid in 20 mL of methylene chloride. The yield of subject compound was 0.20 gram. The NMR spectrum was consistent with the proposed structure.

Step D—Synthesis of Compound 300

This compound was made in a manner analogous to that set forth in Step D of Example 1, using 0.20 gram (0.0006 mole) of (2-aminoethyl)[(2-chloro(1,3-thiazol-5-yl))methyl][(4-methoxyphenyl)methyl]amine and 0.18 gram (0.0011 mole) of dimethyl N-nitroimidodithiocarbonate in 40 mL of acetonitrile. The reaction product was purified with column chromatography on silica gel. Elution was accomplished using mixtures of 15% and 50% ethyl acetate in hexane as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.23 gram of Compound 300. The NMR spectrum was consistent with the proposed structure.

EXAMPLE 10

This example illustrates one protocol for the preparation of {2-[((1Z)-2-aza-1-methylthio-2-nitrovinyl)amino]ethyl}[(4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amine (Compound 486).

Step A—Synthesis of (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amino}ethyl)carboxamide as an intermediate

This compound was made in a manner analogous to that set forth in Step D of Example 5, using 0.2 gram (0.0020 mole) of (oxolan-3-yl)formaldehyde, 0.56 gram (0.0020 mole) of (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl]amino}-ethyl)carboxamide (prepared in Step A of Example 9), 0.64 gram (0.0030 mole) of sodium triacetoxyborohydride and 2.5 grams (0.021 mole) of magnesium sulfate in 50 mL of 1,2-dichloroethane. The reaction product was purified with column chromatography on silica gel. Elution was accomplished using a mixture of 1% methanol in methylene chloride as an eluant. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.59 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B—Synthesis of (2-aminoethyl)[4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amine as an intermediate

This compound was made in a manner analogous to that set forth in Step C of Example 1, using 0.3 gram (0.00082 mole) of (tert-butoxy)-N-(2-{[(4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amino}ethyl)carboxamide and 3 mL (excess) of trifluoroacetic acid in 20 mL of methylene chloride. The yield of subject compound was 0.22 gram. The NMR spectrum was consistent with the proposed structure.

Step C—Synthesis of Compound 486

This compound was made in a manner analogous to that set forth in Step D of Example 1, using 0.22 gram (0.0008 mole) of (2-aminoethyl)[4-methoxyphenyl)methyl](oxolan-3-ylmethyl)amine and 0.21 gram (0.0012 mole) of dimethyl N-nitroimidodithiocarbonate in 35 mL of acetonitrile. The reaction product was purified with column chromatography on silica gel. Elution was accomplished using mixtures of 15% and 50% ethyl acetate in hexane as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 0.23 gram of Compound 486. 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 N-(Heteroarylalkyl)alkanediamine Derivatives

I

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where Ar is selected from:

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A
A1
A2
B
C

pyrid-3-yl
pyrid-2-yl
pyrid-4-yl
1,3-thiazol-5-yl
1-methyl-

imidazol-4-

yl

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D
E
F
G
H

1,3-oxazol-5-
1,2,3-thia-
1,3,4-oxa-
pyridazin-4-
pyrimidin-5-yl

yl
diazol-5-yl
diazol-2-yl
yl

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J
K
L
M

pyridazin-3-yl
pyrazin-5-yl
3-methyl-
oxolan-3-yl

isoxazol-5-yl

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R³is chloro; W is CR³³where R³³is hydrogen; and R⁷is NO₂:

I

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Cmpd

No
R
X
R⁶
R³⁴
R³⁵
R³⁶

1
C₂H₄CH₂F
O
CH₃
—
—
—

2
C₂H₄CH₂F
S
CH₃
—
—
—

3
C₂H₄CF₃
S
CH₃
—
—
—

4
C₂H₄OCH₃
S
CH₃
—
—
—

5
C₂H₄OC₂H₅
S
CH₃
—
—
—

6
C₂H₄OC₂H₄OCH₃
O
CH₃
—
—
—

7
C₂H₄OC₂H₄OCH₃
S
CH₃
—
—
—

8
C₂H₄OC₂H₄OCH₃
O
C₂H₄OCH₃
—
—
—

9
OH
S
CH₃
—
—
—

10
CH₂C≡N
S
CH₃
—
—
—

11
C(═O)CH₃
S
CH₃
—
—
—

12
SO₂CH₃
S
CH₃
—
—
—

13
P(O)(OC₂H₅)₂
S
CH₃
—
—
—

14
oxolan-3-ylmethyl
S
CH₃
—
—
—

15
2H-3,4,5,6-tetrahydropyran-2-ylmethyl
S
CH₃
—
—
—

16
cyclohex-1-en-3-yl
S
CH₃
—
—
—

17
thien-3-ylmethyl
S
CH₃
—
—
—

18
furan-2-ylmethyl
S
CH₃
—
—
—

19
furan-3-ylmethyl
S
CH₃
—
—
—

20
benzo[b]furan-2-ylmethyl
S
CH₃
—
—
—

21
C₂H₄CH₂F
CR³⁴R³⁵
H
H
H
—

22
C₂H₄CF₃
CR³⁴R³⁵
H
H
H
—

23
C₂H₄OCH₃
CR³⁴R³⁵
H
H
H
—

24
C₂H₄OC₂H₅
CR³⁴R³⁵
H
H
H
—

25
C₂H₄OC₂H₄OCH₃
CR³⁴R³⁵
H
H
H
—

26
OH
CR³⁴R³⁵
H
H
H
—

27
CH₂C≡N
CR³⁴R³⁵
H
H
H
—

28
C(═O)CH₃
CR³⁴R³⁵
H
H
H
—

29
SO₂CH₃
CR³⁴R³⁵
H
H
H
—

30
P(O)(OC₂H₅)₂
CR³⁴R³⁵
H
H
H
—

31
oxolan-3-ylmethyl
CR³⁴R³⁵
H
H
H
—

32
2H-3,4,5,6-tetrahydropyran-2-ylmethyl
CR³⁴R³⁵
H
H
H
—

33
cyclohex-1-en-3-yl
CR³⁴R³⁵
H
H
H
—

34
thien-3-ylmethyl
CR³⁴R³⁵
H
H
H
—

35
furan-2-ylmethyl
CR³⁴R³⁵
H
H
H
—

36
furan-3-ylmethyl
CR³⁴R³⁵
H
H
H
—

37
benzo[b]furan-2-ylmethyl
CR³⁴R³⁵
H
H
H
—

38
CHO
S
CH₃
—
—
—

39
CO₂C(CH₃)₃
S
CH₃
—
—
—

¹40
—(CH₂)_mCR¹⁴≡CR¹⁵R¹⁶
O
CH₃
—
—
—

41
C₂H₅
O
CH₃
—
—
—

42
C₂H₅
NR³⁶
CH₃
—
—
H

43
CH₂C≡N
NR³⁶
CH₃
—
—
H

44
H
NR³⁶
CH₃
—
—
CH₃

¹where m is 1 and R¹⁴, R¹⁵and R¹⁶are hydrogen

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R³is chloro; W is N; and R⁷is NO₂:

Cmpd.

No.
R
X
R⁶
R³⁶

45
C₂H₄CH₂F
O
CH₃
—

46
C₂H₄CH₂F
S
CH₃
—

47
C₂H₄CF₃
S
CH₃
—

48
C₂H₄OCH₃
S
CH₃
—

49
C₂H₄OC₂H₅
S
CH₃
—

50
C₂H₄OC₂H₄OCH₃
O
CH₃
—

51
C₂H₄OC₂H₄OCH₃
S
CH₃
—

52
C₂H₄OC₂H₄OCH₃
O
C₂H₄OCH₃
—

53
OH
S
CH₃
—

54
CH₂C≡N
S
CH₃
—

55
C(═O)CH₃
S
CH₃
—

56
SO₂CH₃
S
CH₃
—

57
P(O)(OC₂H₅)₂
S
CH₃
—

58
oxolan-3-ylmethyl
S
CH₃
—

59
2H-3,4,5,6-tetrahydropyran-2-ylmethyl
S
CH₃
—

60
cyclohex-1-en-3-yl
S
CH₃
—

61
thien-3-ylmethyl
S
CH₃
—

62
furan-2-ylmethyl
S
CH₃
—

63
furan-3-ylmethyl
S
CH₃
—

64
benzo[b]furan-2-ylmethyl
S
CH₃
—

65
CH₂CH₃
S
CH₃
—

66
CH(CH₃)₂
S
CH₃
—

67
CH₂CH(CH₃)₂
S
CH₃
—

68
CH₂-cyclopropyl
S
CH₃
—

69
CH₂-cyclobutyl
S
CH₃
—

70
CH₂-cyclohexyl
S
CH₃
—

71
CH₂CH₂F
S
CH₃
—

72
CHO
S
CH₃
—

73
CO₂C(CH₃)₃
S
CH₃
—

74
H
NR³⁶
CH₃
H

75
CO₂C(CH₃)₃
NR³⁶
CH₃
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R³is chloro; W is N; and R⁷is C≡N:

Cmpd

No.
R
X
R⁶
R³⁶

76
C₂H₄CH₂F
O
CH₃
—

77
C₂H₄CH₂F
S
CH₃
—

78
C₂H₄CF₃
S
CH₃
—

79
C₂H₄OCH₃
S
CH₃
—

80
C₂H₄OC₂H₅
S
CH₃
—

81
C₂H₄OC₂H₄OCH₃
O
CH₃
—

82
C₂H₄OC₂H₄OCH₃
S
CH₃
—

83
C₂H₄OC₂H₄OCH₃
O
C₂H₄OCH₃
—

84
OH
S
CH₃
—

85
CH₂C≡N
S
CH₃
—

86
C(═O)CH₃
S
CH₃
—

87
SO₂CH₃
S
CH₃
—

88
P(O)(OC₂H₅)₂
S
CH₃
—

89
oxolan-3-ylmethyl
S
CH₃
—

90
2H-3,4,5,6-tetrahydropyran-2-ylmethyl
S
CH₃
—

91
cyclohex-1-en-3-yl
S
CH₃
—

92
thien-3-ylmethyl
S
CH₃
—

93
furan-2-ylmethyl
S
CH₃
—

94
furan-3-ylmethyl
S
CH₃
—

95
benzo[b]furan-2-ylmethyl
S
CH₃
—

96
CH(CH₃)₂
S
CH₃
—

97
C(═O)H
S
CH₃
—

98
C(═O)Ot-Bu
S
CH₃
—

99
C(═O)Ot-Bu
NR³⁶
CH₃
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R³is chloro; W is CR³³where R³³is hydrogen; X is S; R⁶is CH₃; and R⁷is NO₂:

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Cmpd.

No.
R
R⁸

100
2-R⁸-1,3-thiazol-4-ylmethyl
Cl

101
2-R⁸-1,3-thiazol-4-ylmethyl
CH₃

102
2-R⁸-1,3-thiazol-4-ylmethyl
4-Cl-Ph

103
5-R⁸-1,2,4-oxadiazol-3-ylmethyl
2-OCH₃-Ph

104
5-R⁸-1,2,4-oxadiazol-3-ylmethyl
3-OCH₃-Ph

105
5-R⁸-1,2,4-oxadiazol-3-ylmethyl
4-OCH₃-Ph

106
5-R⁸-1,2,4-oxadiazol-3-ylmethyl
4-CF₃-Ph

107
5-R⁸-1,2,4-oxadiazol-3-ylmethyl
3,5-di(CH₃)-isoxazol-4-yl

where Ar is A; a is 1, unless otherwise noted; b, c, d and e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴andR⁵are hydrogen; R is —(CH₂)_m-phenyl, wherein phenyl is substituted with R⁹through R¹³, inclusively; X is S, unless otherwise noted; and R⁷is NO₂:

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Cmpd

No.
m
R³
R⁶
R⁹
R¹⁰
R¹¹
R¹²
R¹³
W
R³³

108
1
Cl
CH₃
H
H
H
H
H
CR³³
H

109
3
Cl
CH₃
H
H
H
H
H
CR³³
H

110
1
Cl
CH₃
Cl
H
H
H
H
CR³³
H

111
1
Cl
CH₃
H
Cl
H
H
H
CR³³
H

112
1
Cl
CH₃
H
H
Cl
H
H
CR³³
H

113
1
Br
CH₃
H
H
Cl
H
H
CR³³
H

114
1
F
CH₃
H
H
Cl
H
H
CR³³
H

115
3
Cl
CH₃
H
H
Cl
H
H
CR³³
H

116
1
Cl
CH₃
F
F
F
F
F
CR³³
H

117
1
Cl
CH₃
H
H
C≡N
H
H
CR³³
H

118
1
Cl
CH₃
H
H
NO₂
H
H
CR³³
H

119
1
Cl
CH₃
CH₃
H
H
H
H
CR³³
H

120
1
Cl
CH₃
H
CH₃
H
H
H
CR³³
H

121
1
Cl
CH₃
H
H
CH₃
H
H
CR³³
H

122
1
Br
CH₃
H
H
CH₃
H
H
N
—

123
1
Br
CH₃
H
H
OCH₃
H
H
CR³³
H

124
1
F
CH₃
H
H
OCH₃
H
H
CR³³
H

125
1
Cl
CH₃
H
H
C(CH₃)₃
H
H
CR³³
H

126
1
Cl
CH₃
CH₃
CH₃
H
H
H
CR³³
H

127
1
Cl
CH₃
CH₃
H
CH₃
H
H
CR³³
H

128
1
Cl
CH₃
CH₃
H
H
CH₃
H
CR³³
H

129
1
Cl
CH₃
CH₃
H
H
H
CH₃
CR³³
H

130
1
Cl
CH₃
H
CH₃
CH₃
H
H
CR³³
H

131
1
Cl
CH₃
H
CH₃
H
CH₃
H
CR³³
H

132
1
Cl
CH₃
CH₃
H
CH₃
H
CH₃
CR³³
H

133
1
Cl
CH₃
H
H
CF₃
H
H
CR³³
H

134
1
Cl
CH₃
H
H
Ph
H
H
CR³³
H

135
1
Cl
CH₃
CH₃
Ph
H
H
H
CR³³
H

136
1
Cl
CH₃
OCH₃
H
H
H
H
CR³³
H

137
1
Cl
CH₃
H
OCH₃
H
H
H
CR³³
H

138
1
Cl
CH₃
H
H
OCH₃
H
H
CR³³
H

¹139
1
Cl
CH₃
H
H
OCH₃
H
H
N
—

140
1
Cl
CH₃
H
H
OCH₃
H
H
N
—

141
1
Cl
CH₃
H
OPh
H
H
H
CR³³
H

142
1
Cl
CH₃
H
H
CH═NOC₂H₅
H
H
CR³³
H

143
1
Cl
CH₃
H
H
2-ethyl-2H-
H
H
CR³³
H

tetrazol-5-yl

144
1
Cl
CH₂-c-hexyl
H
H
H
H
H
CR³³
H

145
1
Cl
CH₃
H
H
H
H
H
N
—

146
1
Cl
CH₃
H
H
CF₃
H
H
N
—

147
1
Cl
CH₃
H
H
F
H
H
N
—

148
1
Cl
CH₃
H
OCH₃
H
H
H
N
—

149
1
Cl
CH₃
H
H
OCF₃
H
H
N
—

150
1
Cl
CH₃
H
H
CN
H
H
N
—

151
1
Cl
CH₃
H
Cl
H
Cl
H
N
—

152
1
Cl
CH₃
H
H
F
H
H
CR³³
H

153
1
Cl
CH₃
H
H
OCF₃
H
H
CR³³
H

154
1
Cl
CH₃
H
H
Cl
H
H
N
—

155
1
Cl
CH₃
H
Cl
H
H
H
N
—

156
1
Cl
CH₃
OCH₃
H
H
H
H
N
—

157
1
Cl
CH₃
H
H
CH₃
H
H
N
—

158
1
Cl
CH(CH₃)₂
H
H
OCH₃
H
H
N
—

159
1
H
CH₃
H
H
OCH₃
H
H
N
—

160
1
OCH₃
CH₃
H
H
OCH₃
H
H
N
—

161
1
CF₃
CH₃
H
H
OCH₃
H
H
N
—

²162
1
Cl
CH₃
H
H
OCH₃
H
H
CR³³
H

163
1
Cl
CH₃
OCH₃
H
H
OCH₃
H
N
—

³164
1
Cl
C₂H₅
H
H
OCH₃
H
H
N
—

⁴165
1
Cl
C₂H₅
H
H
OCH₃
H
H
N
—

166
1
Cl
C₂H₅
H
H
OCH₃
H
H
N
—

167
1
CH₃
CH₃
H
H
OCH₃
H
H
N
—

168
1
F
CH₃
H
H
OCH₃
H
H
N
—

169
1
Cl
C₂H₄OCH₃
H
H
OCH₃
H
H
N
—

170
1
Br
CH₃
H
H
OCH₃
H
H
N
—

171
1
OCH₂CF₃
CH₃
H
H
OCH₃
H
H
N
—

172
1
OCH₂CF₃
CH₃
H
H
OCH₃
H
H
CR³³
H

173
1
Cl

⁵CH₃
H
H
Cl
H
H
CR³³
H

174
1
Cl

⁵CH₃
H
H
OCH₃
H
H
CR³³
H

175
1
Cl
CH₃
H
H
OCH₃
H
H
CR³³

⁶note

¹a is 0;

²X is NR³⁶where R³⁶is CH₃;

³X is NR³⁶where R³⁶is hydrogen;

⁴X is NR³⁶where R³⁶is C₂H₅;

⁵X is oxygen;

⁶R³³is 4-(OCH₃)PhSCH₂—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R³is chloro; R is —(CH₂)m-phenyl, wherein m is 1, phenyl is substituted with R⁹through R¹³, inclusively; where R⁹, R¹⁰, R¹²and R¹³are hydrogen; and R⁷is C≡N:

Cmpd.

No.
W
X
R⁶
R¹¹
R³⁴
R³⁵

176
N
S
CH₃
Cl
—
—

177
N
S
CH₃
OCH₃
—
—

178
N
CR³⁴R³⁵
H
OCH₃
H
H

179
N
CR³⁴R³⁵
Cl
OCH₃
H
H

180
N
O
C₂H₅
OCH₃
—
—

where Ar is A; a is 1; b, c, e, r and s are 0; d is 1; R^a, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R³is chloro; R is —(CH₂)_m-phenyl, wherein m is 1, phenyl is substituted with R⁹through R¹³, inclusively; where R⁹, R¹⁰, R¹²and R¹³are hydrogen; and R⁷is C≡N:

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Cmpd.

No.
U
W
X
R⁵
R⁶
R¹¹
R³⁶

181
CH₂
N
NR³⁶
H
C₂H₅
OCH₃
C₂H₅

182
CH₂
N
NR³⁶
CH₃
C₂H₅
OCH₃
C₂H₅

where Ar is A; a is 1; b, c, d, r and s are 0; e is 1; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R³is chloro; R is —(CH₂)m-phenyl, wherein m is 1, phenyl is substituted with R⁹through R¹³, inclusively; where R⁹, R¹⁰, R¹²and R¹³are hydrogen; and R⁷is C≡N:

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Cmpd.

No.
V
W
X
R⁶
R¹¹
R³⁶

183
CH₂
N
NR³⁶
C₂H₅
OCH₃
C₂H₅

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m-pyrid-2-yl, wherein pyrid-2-yl is substituted with R¹⁰through R¹³, inclusively; where R¹⁰, R¹¹, R¹², and R¹³are hydrogen; m is 1; and R⁷is NO₂:

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Cmpd.

No.
R³
X
R⁶
W
R³³
R³⁴
R³⁵

184
Cl
S
CH₃
CR³³
H
—
—

185
Cl
S
CH₃
N
—
—
—

186
Cl
CR³⁴R³⁵
H
N
—
H
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R is —(CH₂)_m-pyrid-3-yl, wherein pyrid-3-yl is is substituted with R⁹and R¹¹through R¹³, inclusively; where R⁹, R¹², and R¹³are hydrogen; and m is 1:

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Cmpd.

No.
R³
R⁵
X
R⁶
R⁷
R¹¹
W

187
Cl
H
O
CH₃
NO₂
Cl

²CR³³

188
Cl
H
O
C₂H₅
NO₂
Cl

²CR³³

189
Cl
H
O
CH₂CH(CH₃)₂
NO₂
Cl

²CR³³

190
Cl
H
O
CH₂-c-hexyl
NO₂
Cl

²CR³³

191
H
H
S
CH₃
NO₂
H

²CR³³

192
Cl
H
S
CH₃
NO₂
H

²CR³³

193
Br
H
S
CH₃
NO₂
H

²CR³³

194
F
H
S
CH₃
NO₂
H

²CR³³

195
CH₃
H
S
CH₃
NO₂
H

²CR³³

196
CF₃
H
S
CH₃
NO₂
H

²CR³³

197
F
H
S
CH₃
NO₂
H

²CR³³

198
Cl
H
S
CH₃
NO₂
Cl

²CR³³

199
Cl
H
S
CH₃
NO₂
Cl

²CR³³

200
Cl
C₂H₄CH(CH₃)₂
S
CH₃
NO₂
Cl

²CR³³

201
Cl
H
S
C₂H₅
NO₂
Cl

²CR³³

202
Cl
H
S
CH₂CH(CH₃)₂
NO₂
Cl

²CR³³

203
Cl
H
S
CH₂-c-hexyl
NO₂
Cl

²CR³³

204
Cl
H
S
C₂H₄CH(F)═CF₂
NO₂
Cl

²CR³³

¹205
Cl
H
S
CH₃
NO₂
H

²CR³³

206
Cl
H

⁴NR³⁶
CH₃
NO₂
Cl

²CR³³

207
Cl
H

⁴NR³⁶
C₂H₅
NO₂
Cl

²CR³³

208
Cl
H

⁴NR³⁶
C(CH₃)₃
NO₂
Cl

²CR³³

209
Cl
H

⁴NR³⁶
OCH₃
NO₂
Cl

²CR³³

210
Cl
H

⁴NR³⁶
cyclopentyl
NO₂
Cl

²CR³³

211
Cl
H

⁵NR³⁶
CH₃
NO₂
Cl

²CR³³

212
Cl
H

⁶NR³⁶
C₂H₅
NO₂
Cl

²CR³³

213
Cl
H
S
CH₃
C≡N
Cl
N

214
Cl
H

⁷CR³⁴R³⁵
H
C≡N
Cl
N

215
Cl
H

⁷CR³⁴R³⁵
H
NO₂
Cl
N

216
Cl
H
S
CH₃
NO₂
Cl
N

¹methyl iodide salt;

²R³³is hydrogen;

³R³³is CH₃;

⁴R³⁶is hydrogen;

⁵R³⁶is CH₃;

⁶R³⁶is C₂H₅;

⁷R³⁴and R³⁵are hydrogen.

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m-pyrid-4-yl, wherein pyrid-4-yl is substituted with R⁹, R¹⁰, R¹²and R¹³; where R⁹, R¹⁰, R¹², and R¹³are hydrogen; m is 1; and R⁷is NO₂:

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Cmpd

No.
R³
X
R⁶
W
R³³

217
Cl
S
CH₃
CR³³
H

218
Cl
S
CH₃
N
—

219
Cl
CH₂
H
N
—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen;

R is —(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶; and R⁷is NO₂, unless otherwise noted:

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Cmpd.

No.
R³
W
X
R⁶
m
R¹⁴
R¹⁵
R¹⁶

220
Cl

¹CR³³
S
CH₃
1
H
H
H

221
Cl

¹CR³³
S
CH₂-c-hexyl
1
H
H
H

222
Cl

¹CR³³
S
CH₃
2
H
H
H

223
Cl

¹CR³³
S
CH₃
1
H
H
CH₃

224
Cl

¹CR³³
S
CH₃
1
H
H
Cl

225
Cl

¹CR³³
S
CH₃
1
Cl
H
H

226
Cl

¹CR³³
S
CH₃
1
Cl
H
cis-Cl

227
Cl

¹CR³³
S
CH₃
1
Cl
H
trans-Cl

228
Cl

¹CR³³
S
CH₃
1
H
Cl
Cl

229
Cl

¹CR³³
S
CH₃
2
F
F
F

230
Cl

¹CR³³
S
CH₃
1
H
H
Ph

231
Cl
N
S
CH₃
1
H
H
H

232
Cl
N
S
CH₂-c-hexyl
1
H
H
H

233
Cl
N
S
CH₃
2
H
H
H

234
Cl
N
S
CH₃
1
H
H
CH₃

235
Cl
N
S
CH₃
1
H
H
Cl

236
Cl
N
S
CH₃
1
Cl
H
H

237
Cl
N
S
CH₃
1
Cl
H
cis-Cl

238
Cl
N
S
CH₃
1
Cl
H
trans-Cl

239
Cl
N
S
CH₃
1
H
Cl
Cl

240
Cl
N
S
CH₃
2
F
F
F

241
Cl
N
S
CH₃
1
H
H
Ph

242
Cl

¹CR³³
O
CH₃
1
H
H
H

243
Cl

²N
S
CH₃
I
H
H
H

¹R³³is hydrogen;

²R⁷is C≡N

where Ar is A; a is 1; b, c, d, e, r and s are 0; R⁹, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R is —(CH₂)_m—C≡CR¹⁷; and R⁷is NO₂unless otherwise noted:

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Cmpd.

No.
R³
W
X
R⁵
R⁶
m
R¹⁷

244
Cl

¹CR³³
O
H
CH₃
1
H

245
Cl

¹CR³³
O
H
C₂H₅
1
H

246
Cl

¹CR³³
O
H
C₂H₄OCH₃
1
H

247
Cl

¹CR³³
O
H
C₂H₄OC₂H₄OCH₃
1
H

248
Cl

¹CR³³
S
H
CH₃
1
H

249
I

¹CR³³
S
H
CH₃
1
H

250
CH₃

¹CR³³
S
H
CH₃
1
H

251
CF₃

¹CR³³
S
H
CH₃
1
H

252
Cl

¹CR³³
S
H
CH₃
2
H

253
Cl

¹CR³³
S
H
CH₃
1
CH₃

254
Cl

¹CR³³
S
H
CH₃
2
CH₃

255
Cl

¹CR³³
S
H
CH₃
1
C₅H₁₁

256
Cl

¹CR³³
O
H
CH₂-c-hexyl
1
H

257
Cl

¹CR³³
S
H
CH₂-c-hexyl
1
H

258
Cl

¹CR³³
S
H
CH₂-c-hexyl
2
H

259
Cl

¹CR³³
S
CH₃
CH₃
1
H

260
Cl

¹CR³³
S
CH₂H₄CH(CH₃)₂
CH₃
1
H

261
Cl

¹CR³³

²NR³⁶
CH₃
CH₃
1
H

262
Cl

¹CR³³

³NR³⁶
CH₃
CH₃
1
H

263
Cl

¹CR³³

⁴CR³⁴R³⁵
H
H
1
H

264
Cl

¹CR³³

⁴CR³⁴R³⁵
H
H
2
H

265
I

¹CR³³

⁴CR³⁴R³⁵
H
H
1
H

266
CH₃

¹CR³³

⁴CR³⁴R³⁵
H
H
1
H

267
CF₃

¹CR³³

⁴CR³⁴R³⁵
H
H
1
H

268
Cl

¹CR³³

⁴CR³⁴R³⁵
H
H
1
CH₃

269
Cl

¹CR³³

⁴CR³⁴R³⁵
H
H
2
CH₃

270
Cl

¹CR³³

⁴CR³⁴R³⁵
H
H
1
C₅H₁₁

271
Cl

¹CR³³

⁴CR³⁴R³⁵
H
H
1
H

272
Cl

¹CR³³

⁴CR³⁴R³⁵
CH₃
H
1
H

273
Cl

¹CR³³

⁴CR³⁴R³⁵
C₂H₄CH(CH₃)₂
H
1
H

274
Cl
N
O
H
CH₃
1
H

275
F
N
O
H
CH₃
1
H

276
Cl
N
O
H
C₂H₅
1
H

277
Cl
N
O
H
C₂H₄OCH₃
1
H

278
Cl
N
O
H
C₂H₄OC₂H₄OCH₃
1
H

279
Cl
N
S
H
CH₃
1
H

280
I
N
S
H
CH₃
1
H

281
CH₃
N
S
H
CH₃
1
H

282
CF₃
N
S
H
CH₃
1
H

283
Cl
N
S
H
CH₃
2
H

284
Br
N
S
H
CH(CH₃)₂
1
H

285
Cl
N
S
H
CH₃
1
CH₃

286
Cl
N
S
H
CH₃
2
CH₃

287
Cl
N
S
H
CH₃
1
C₅H₁₁

288
Cl
N
O
H
CH₂-cyclohexyl
1
H

289
Cl
N
S
H
CH₂-cyclohexyl
1
H

290
Cl
N
S
H
CH₂-cyclohexyl
2
H

291
Cl
N
S
CH₃
CH₃
1
H

292
Cl
N
S
C₂H₄CH(CH₃)₂
CH₃
1
H

293
F
N

²NR³⁶
H
CH₃
1
H

294
Cl
N

²NR³⁶
CH₃
CH₃
1
H

295
Cl
N

³NR³⁶
CH₃
CH₃
1
H

296
CH₃
N
S
H
CH₃
1
H

297
Cl

¹CR³³

²NR³⁶
H
CH₃
1
H

298
Cl

⁵N
S
H
CH₃
1
H

299
Cl

⁵N

²NR³⁶
H
CH₃
1
H

¹R³³is hydrogen;

²R³⁶is hydrogen;

³R³⁶is CH₃;

⁴R³⁴and R³⁵are hydrogen;

⁵R⁷is C≡N

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m—C≡CR¹⁷, wherein R¹⁷is phenyl substituted with R¹⁸through R²², inclusively; where R¹⁸, R¹⁹, R²¹, and R²²are hydrogen; and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R³
m
W
X
R⁶
R²⁰
R³³

300
Cl
1
CR³³
S
CH₃
H
H

301
Cl
2
CR³³
S
CH₃
Cl
H

302
Cl
1
CR³³
S
CH₃
F
H

303
Cl
1
CR³³
S
CH₃
CH₃
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m—C≡CR¹⁷, wherein R¹⁷is pyrimidin-5-yl substituted with R¹⁸, R²⁰, and R²²where R¹⁸, R¹⁹, R²⁰, and R²²are hydrogen; and R⁷is NO₂:

I

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Cmpd.

No.
R³
m
W
X
R⁶
R³³

304
Cl
1
CR³³
S
CH₃
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R is —(CH₂)_m—C≡CR¹⁷; R⁵is —(CH₂)_n-phenyl where phenyl is substituted with R²³through R²⁷, inclusively, where R¹⁷, R²³, R²⁴, R²⁶, and R²⁷are hydrogen; m and n are 1; and R⁷is NO₂:

I

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Cmpd.

No.
R³
W
X
R⁶
R²⁵
R³³

305
Cl
CR³³
S
CH₃
F
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b,R^c, R^d, R¹, R²and R⁴are hydrogen; R is —(CH₂)_m-pyrid-3-yl, wherein pyrid-3-yl is substituted with R⁹, and R¹¹through R¹³, inclusively; R⁵is phenyl, wherein phenyl is substituted with R²³through R²⁷, inclusively; where R⁹, R¹², R¹³, R²³, R²⁴, R²⁶and R²⁷are hydrogen;m and n are 1; and R⁷is NO₂:

I

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Cmpd.

No.
R³
W
X
R⁶
R¹¹
R²⁵
R³³

306
Cl
CR³³
S
CH₃
Cl
F
H

where Ar is A; a is 1; b, c, d, e, r and s are O; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m-phenyl, wherein phenyl is substituted with R⁹through R¹³, inclusively; R⁶is —(CH₂)_p-phenyl, wherein phenyl is substituted with R²⁸through R³², inclusively, R⁹, R¹⁰, R¹², R¹³, R²⁸, R²⁹, R³¹andR³²are hydrogen; m is 1; and R⁷is NO₂:

I

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Cmpd.

No.
R³
X
W
R¹¹
p
R³⁰
R³³

307
Cl
S
CR³³
H
1
CF₃
H

308
Cl
S
N
OCH₃
0
OCH₃
—

309
4-(OCH₃)PhS
S
N
OCH₃
0
OCH₃
—

310
Cl
S
N
OCH₃
1
H
—

311
Cl
S
N
OCH₃
1
Cl
—

312
Cl
S
N
OCH₃
1
OCH₃
—

313
Cl
S
CR³³
OCH₃
0
OCH₃
4-(OCH₃)PhSCH₂—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m-pyrid-3-yl, wherein pyrid-3-yl is substituted with R⁹, and R¹¹through R¹³, inclusively; R⁶is —(CH₂)_p-phenyl, wherein phenyl is substituted with R²⁸through R³², inclusively, R⁹, R¹², and R¹³are hydrogen; R³and R¹¹are chloro; m and p are 1; X is S; W is CR³³where R³³is hydrogen; and R⁷is NO₂;

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Cmpd.

No.
R²⁸
R²⁹
R³⁰
R³¹
R³²

314
Cl
H
H
H
H

315
H
Cl
H
H
H

316
H
H
Cl
H
H

317
H
H
F
H
H

318
F
F
F
F
F

319
CH₃
H
H
H
H

320
H
CH₃
H
H
H

321
H
H
CH₃
H
H

322
CF₃
H
H
H
H

323
H
CF₃
H
H
H

324
H
H
CF₃
H
H

325
OCH₃
H
H
H
H

326
H
OCH₃
H
H
H

327
H
H
OCH₃
H
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m—CR¹⁴≡CR¹⁵R¹⁶; R⁶is —(CH₂)_p-phenyl, wherein phenyl is substituted with R²⁸through R³², inclusively; where R¹⁴, R¹⁵, R¹⁶, R²⁸, R²⁹, R³¹, and R³²are hydrogen; m and p are 1; andR⁷is NO₂:

I

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Cmpd.

No.
R³
W
X
R³⁰
R³³

328
Cl
CR³³
S
CF₃
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴and R⁵are hydrogen; R is —(CH₂)_m—C≡CR¹⁷; R⁶is —(CH₂)_p-phenyl, wherein phenyl is substituted with R²⁸through R³², inclusively; where R¹⁷, R²⁸, R²⁹, R³¹, and R³²are hydrogen; m and p are 1; and R⁷is NO₂:

I

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Cmpd.

No.
R³
W
X
m
R³⁰
R³³

329
Cl
CR³³
S
1
CF₃
H

330
Cl
CR³³
S
2
CF₃
H

where a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R⁵, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶, R¹⁷, R²⁸, R²⁹, R³⁰, R³¹and R³²are hydrogen; m and p are 1; X is —S—; and when W is CR³³, R³³is hydrogen:

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Cmpd.

No.
Ar
R
R¹¹
W
R⁶
R⁷

331

¹B
(CH₂)_m-Phenyl where
Cl
CR³³
CH₃
NO₂

phenyl is substituted

with R⁹—R¹³as shown

above

332
B
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

333
B
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

334
B
(CH₂)_m-3-pyridyl
H
CR³³
CH₃
NO₂

where pyridyl is

substituted with R⁹and

R¹¹—R¹³as shown

above

335
B
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

336
B
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

337
B
Same as Cmpd 331
Cl
N
CH₃
NO₂

338
B
Same as Cmpd 331
CH₃
N
CH₃
NO₂

339
B
Same as Cmpd 331
OCH₃
N
CH₃
NO₂

340
B
Same as Cmpd 334
H
N
CH₃
NO₂

341
B
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
CH₃
NO₂

342
B
—(CH₂)_m—C≡CR¹⁷
—
N
CH₃
NO₂

343
B
Same as Cmpd 331
Cl
N
CH₃
C≡N

344
B
Same as Cmpd 331
CH₃
N
CH₃
C≡N

345
B
Same as Cmpd 331
OCH₃
N
CH₃
C≡N

346
B
Same as Cmpd 334
H
N
CH₃
C≡N

347
B
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
CH₃
C≡N

348
B
—(CH₂)_m—C≡CR¹⁷
—
N
CH₃
C≡N

349
B
Same as Cmpd 331
Cl
N
CH(CH₃)₂
NO₂

350
B
Same as Cmpd 331
CH₃
N
CH(CH₃)₂
NO₂

351
B
Same as Cmpd 331
OCH₃
N
CH(CH₃)₂
NO₂

352
B
Same as Cmpd 334
H
N
CH(CH₃)₂
NO₂

353
B
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
CH(CH₃)₂
NO₂

354
B
—(CH₂)_m—C≡CR¹⁷
—
N
CH(CH₃)₂
NO₂

355
B
Same as Cmpd 331
Cl
N
CH₂CH═CH₂
NO₂

356
B
Same as Cmpd 331
CH₃
N
CH₂CH═CH₂
NO₂

357
B
Same as Cmpd 331
OCH₃
N
CH₂CH═CH₂
NO₂

358
B
Same as Cmpd 334
H
N
CH₂CH═CH₂
NO₂

359
B
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
CH₂CH═CH₂
NO₂

360
B
—(CH₂)_m—C≡CR¹⁷
—
N
CH₂CH═CH₂
NO₂

361
B
Same as Cmpd 331
Cl
N
(CH₂)_p-Phenyl where
NO₂

phenyl is substituted

with R²⁸—R³²as shown

above

362
B
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

363
B
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

364
B
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

365
B
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

366
B
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

367
C
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

368
C
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

369
C
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

370
C
Same as Cmpd 334
H
CR³³
CH₃
NO₂

371
C
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

372
C
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

373
C
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

374
C
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

375
C
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

376
C
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

377
C
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

378
C
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

379
D
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

380
D
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

381
D
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

382
D
Same as Cmpd 334
H
CR³³
CH₃
NO₂

383
D
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

384
D
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

385
D
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

386
D
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

387
D
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

388
D
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

389
D
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

390
D
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

391
E
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

392
E
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

393
E
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

394
E
Same as Cmpd 334
H
CR³³
CH₃
NO₂

395
E
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

396
E
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

397
E
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

398
E
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

399
E
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

400
E
Same as Cmpd 334
H
CR³³
CH₃
NO₂

401
E
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

402
E
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

403
E
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

404
E
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

405
E
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

406
E
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

407
E
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

408
E
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

409
F
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

410
F
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

411
F
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

412
F
Same as Cmpd 334
H
CR³³
CH₃
NO₂

413
F
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

414
F
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

415
F
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

416
F
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

417
F
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

418
F
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

419
F
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

420
F
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

421
G
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

422
G
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

423
G
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

424
G
Same as Cmpd 334
H
CR³³
CH₃
NO₂

425
G
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

426
G
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

427
G
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

428
G
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

429
G
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

430
G
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

431
G
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

432
G
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

433
H
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

434
H
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

435
H
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

436
H
Same as Cmpd 334
H
CR³³
CH₃
NO₂

437
H
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

438
H
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

439
H
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

440
H
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

441
H
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

442
H
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

443
H
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

444
H
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

445
J
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

446
J
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

447
J
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

448
J
Same as Cmpd 334
H
CR³³
CH₃
NO₂

449
J
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

450
J
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

451
J
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

452
J
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

453
J
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

454
J
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

455
J
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

456
J
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

457
K
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

458
K
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

459
K
Same as Cmpd 334
H
CR³³
CH₃
NO₂

460
K
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

461
K
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

462
K
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

463
K
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

464
K
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

465
K
Same as Cmpd 334
H
N
Same as Cmpd 361
NO₂

466
K
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
N
Same as Cmpd 361
NO₂

467
K
—(CH₂)_m—C≡CR¹⁷
—
N
Same as Cmpd 361
NO₂

468
L
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

469
L
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

470
L
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

471
L
Same as Cmpd 334
H
CR³³
CH₃
NO₂

472
L
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

473
L
—(CH₂)_m—C≡CR¹⁷
—
CH
CH₃
NO₂

474
L
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

475
L
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

476
L
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

477
M
Same as Cmpd 331
Cl
CR³³
CH₃
NO₂

478
M
Same as Cmpd 331
CH₃
CR³³
CH₃
NO₂

479
M
Same as Cmpd 331
OCH₃
CR³³
CH₃
NO₂

480
M
Same as Cmpd 334
H
CR³³
CH₃
NO₂

481
M
—(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶
—
CR³³
CH₃
NO₂

482
M
—(CH₂)_m—C≡CR¹⁷
—
CR³³
CH₃
NO₂

483
M
Same as Cmpd 331
Cl
N
Same as Cmpd 361
NO₂

484
M
Same as Cmpd 331
CH₃
N
Same as Cmpd 361
NO₂

485
M
Same as Cmpd 331
OCH₃
N
Same as Cmpd 361
NO₂

486
M
Same as Cmpd 331
OCH₃
N
CH₃
NO₂

¹when Ar is B, R³is chloro

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R³is chloro; and R⁵and X are taken together with —CH₂(CH₂)_q— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R
q
W
X
R⁶
R³³
R³⁴

487
C₂H₄OCH₃
1
CR³³
CR³⁴
CH₃
H
H

488
n-C₃H₇
1
N
N
H
—
—

489
C₂H₄OCH₃
1
N
N
CH(CH₃)₂
—
—

490
C₂H₄OCH₃
2
CR³³
S
—
H
—

491
cyclohex-1-en-3-yl
2
CR³³
S
—
H
—

492
H
1
CR³³
N
H
H
—

493
CH₂CN
1
CR³³
N
H
H
—

494
H
1
N
N
H
—
—

495
CH₂CN
1
N
N
H
—
—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², R⁴are hydrogen; R is —(CH₂)_m-phenyl, wherein phenyl is substituted with R⁹through R¹³, inclusively; where R¹³is hydrogen; R³is chloro; m is 1; R⁵and X are taken together with —CH₂(CH₂)_q— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd

No.
W
X
q
R⁶
R⁹
R¹⁰
R¹¹
R¹²
R³³

496
CR³³
N
1
H
H
H
OCH₃
H
H

497
N
N
1
H
H
H
Cl
H
—

498
N
N
1
H
H
H
OCH₃
H
—

499
CR³³
N
1
H
H
H
Cl
H
H

500
CR³³
S
2
—
H
H
Cl
H
H

501
CR³³
N
1
H
Cl
H
H
H
H

502
CR³³
S
2
—
H
H
CH₃
H
H

503
CR³³
S
2
—
H
H
OCH₃
H
H

504
CR³³
N
1
H
H
OCH₃
H
OCH₃
H

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R is —(CH₂)_m-pyrid-3-yl, wherein pyrid-3-yl is substituted with R⁹, and R¹¹through R¹³, inclusively; where R⁹, R¹¹, R¹²and R¹³are hydrogen; m is 1; R⁵and X are taken together with —CH₂(CH₂)_q— to form a ring:

I

embedded image

Cmpd

No.
W
R³
X
q
R⁶
R⁷
R³³
R³⁴

505
CR³³
Cl
CR³⁴
1
CH₃
NO₂
H
H

506
N
Cl
CR³⁴
1
CH₃
NO₂
—
H

507
N
Cl
CR³⁴
1
CH(CH₃)₂
C≡N
—
H

508
N
F
CR³⁴
1
CH(CH₃)₂
NO₂
—
H

509
CR³³
Cl
N
1
CH(CH₃)₂
NO₂
H
—

510
CR³³
Cl
S
2
—
NO₂
H
—

511
N
Cl
S
2
—
NO₂
—
—

512
N
Cl
S
2
—
C≡N
—
—

513
N
Cl
O
2
—
NO₂
—
—

514
N
Cl
S
3
—
NO₂
—
—

515
N
Cl
O
3
—
NO₂
—
—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R is —(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶, where R¹⁴, R¹⁵, and R¹⁶are hydrogen; m is 1; R⁵and X are taken together with —CH₂(CH₂)_q— to form a ring; and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R³
q
W
X
R⁶
R³³
R³⁴

516
Cl
1
CR³³
CR³⁴
H
H
H

517
Cl
1
CR³³
N
CH(CH₃)₂
H
—

518
Cl
2
CR³³
CR³⁴
H
H
H

519
Cl
1
CR³³
N
H
H
—

520
Cl
1
N
N
H
—
—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R³is chlorine; R is —(CH₂)_m—C≡CR¹⁷; m is 1; and R⁵and X are taken together with —CH₂(CH₂)_q— to form a ring:

I

embedded image

Cmpd.

No.
q
W
X
R⁶
R⁷
R¹⁷
R³³
R³⁴

521
1
CR³³
CR³⁴
CH₃
NO₂
H
H
H

522
1
CR³³
N
CH(CH₃)₂
C≡N
H
H
—

523
2
CR³³
S
—
NO₂
H
H
—

524
1
N
N
H
NO₂
H
—
—

525
1
CR³³
N
H
NO₂
H
H
—

526
1
CR³³
N
N
NO₂
CH₃
H
—

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R⁵and X are taken together with —CH₂YCH₂— to form a ring; and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R
R³
W
X
Y
R⁶
R³⁷

527
CH₃
Cl
N
N
O
H
—

528
CH₃
Cl
N
N
O
CH₃
—

529
CH₃
Cl
N
N
S
H
—

530
CH₃
Cl
N
N
S
CH₃
—

531
CH₃
Cl
N
N
NR³⁷
H
CH₃

532
CH₃
Cl
N
N
NR³⁷
CH₃
CH₃

533
C₂H₄OCH₃
Cl
N
N
O
CH₃
—

534
CH₂C≡N
Cl
N
N
O
H
—

535
CH₂C≡N
Cl
N
N
O
CH₃
—

536
CH₂C≡N
Cl
N
N
S
H
—

537
CH₂C≡N
Cl
N
N
S
CH₃
—

538
CH₂C≡N
Cl
N
N
NR³⁷
H
CH₃

539
CH₂C≡N
Cl
N
N
NR³⁷
CH₃
CH₃

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R is —(CH₂)_m—phenyl, wherein phenyl is substituted with R⁹through R¹³, inclusively, where R⁹, R¹⁰, R¹²and R¹³are hydrogen; m is 1; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd

No
R³
W
X
Y
R⁶
R¹¹
R³⁷

540
Cl
N
N
O
CH₃
Cl
—

541
Cl
N
N
O
CH(CH₃)₂
Cl
—

542
Cl
N
N
O
H
CH₃
—

543
Cl
N
N
O
CH₃
CH₃
—

544
Cl
N
N
O
H
OCH₃
—

545
Cl
N
N
O
CH₃
OCH₃
—

546
Cl
N
N
NR³⁷
CH₃
OCH₃
CH₃

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R², and R⁴are hydrogen; R is —(CH₂)_m-pyrid-3-yl, wherein pyrid-3-yl is substituted with R⁹, and R¹¹through R¹³, inclusively; where R⁹, R¹²and R¹³are hydrogen; m is 1; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R³
W
X
Y
R⁶
R¹¹

547
Cl
N
N
O
H
Cl

548
Cl
N
N
O
CH₃
Cl

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R is —(CH₂)_m—CR¹⁴═CR¹⁵R¹⁶, where R¹⁴, R¹⁵, and R¹⁶are hydrogen; m is 1; R⁵and X are taken together with —CH₂YCH₂— to form a ring; and R⁷is NO₂:

I

embedded image

Cmpd

No.
R³
W
X
Y
R⁶

549
H
CH
S
O
—

550
Cl
CH
S
O
—

551
Br
CH
S
O
—

552
F
CH
S
O
—

553
CH₃
CH
S
O
—

554
OCH₃
CH
S
O
—

555
Cl
N
N
O
H

556
Cl
N
N
O
CH₃

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R is —(CH₂)_m—C≡CR¹⁷, where R¹⁷is hydrogen; m is 1; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R³
W
X
Y
R⁶
R³⁷

557
Cl
N
O
O
—
—

558
Cl
N
N
O
H
—

559
Cl
N
N
S
H
—

560
Cl
N
N
S
CH₃
—

561
Cl
N
N
NR³⁷
H
CH₃

562
Cl
N
N
NR³⁷
CH₃
CH₃

where Ar is B and R³is chloro; a is 1; b, c, d, e and r are 0; R^a, R^b, R^c, and R^dare hydrogen; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R
W
X
Y
R⁶

563
CH₃
N
N
O
H

564
CH₃
N
N
O
CH₃

565
CH₂C≡N
N
N
O
H

566
CH₂C≡N
N
N
O
CH₃

567
2-Cl-1,3-thiazol-5-ylmethyl
N
N
O
H

568
2-Cl-1,3-thiazol-5-ylmethyl
N
N
O
CH₃

where Ar is B and R³is chloro; a is 1; b, c, d, e and r are 0; R^a, R^b, R^c, and R^dare hydrogen; R is —(CH₂)_m—C≡CR¹⁷, where R¹⁷is hydrogen; m is 1; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd

No.
W
X
Y
R⁶

569
N
N
O
H

570
N
N
O
CH₃

where Ar is M; a is 1; b, c, d, e and r are 0; R^a, R^b, R^c, and R^dare hydrogen; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd.

No.
R
W
X
Y
R⁶

571
oxolan-3-ylmethyl
N
N
O
H

572
oxolan-3-ylmethyl
N
N
O
CH₃

where Ar is M; a is 1; b, c, d, e and r are 0; R^a, R^b, R^cand R^dare hydrogen; R is —(CH₂)_m-phenyl, wherein phenyl is substituted with R⁹through R¹³, inclusively, where R⁹, R¹⁰, R¹²and R¹³are hydrogen; m is 1; and R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷NO₂:

I

embedded image

Cmpd

No
W
X
Y
R⁶
R¹¹

573
N
N
O
H
OCH₃

574
N
N
O
CH₃
OCH₃

where Ar is M; a is 1; b, c, d, e and r are 0; R^a, R^b, R^cand R^dare hydrogen; R is —(CH₂)_m—C≡CR¹⁷, where R¹⁷is hydrogen; m is 1; R⁵and X are taken together with —CH₂YCH₂— to form a ring, and R⁷is NO₂:

I

embedded image

Cmpd.

No.
W
X
Y
R⁶

575
N
N
O
H

576
N
N
O
CH₃

where Ar is A; a is 1; b, c, d, e, r and s are 0; R^a, R^b, R^c, R^d, R¹, R²and R⁴are hydrogen; R³is chloro; and R and R⁵are taken with —CH₂CH₂— to form a piperazine ring:

I

embedded image

Cmpd.

No.
X
R⁶
W
R⁷
R³³

577
S
CH₃
N
C≡N
—

578
S
CH₃
N
NO₂
—

579
S
CH₃
CR³³
NO₂
H

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

TABLE 2

Insecticidal N-(Heteroarylalkyl)alkanediamine Derivatives

Compound Characterization

Melting Point

(° C.) of Solids

Molecular Formula
Or Physical State

1
C₁₄H₂₀ClFN₄O₃
64-65

2
C₁₄H₂₀ClFN₄O₂S
79-80

3
C₁₄H₁₈ClF₃N₄O₂S
SYRUP

4
C₁₄H₂₁ClN₄O₃S
OIL

5
C₁₅H₂₃ClN₄O₃S
OIL

6
C₁₆H₂₅ClN₄O₅
LIQUID

7
C₁₆H₂₅ClN₄O₄S
LIQUID

8
C₁₈H₂₉ClN₄O₆
LIQUID

9
C₁₁H₁₅ClN₄O₃S
SOLID

10
C₁₃H₁₆ClN₅O₂S
142

11
C₁₃H₁₇ClN₄O₃S
OIL

12
C₁₂H₁₇ClN₄O₄S₂
63-66

13
C₁₅H₂₄ClN₄O₅PS
OIL

14
C₁₆H₂₃ClN₄O₃S
SYRUP

15
C₁₇H₂₅ClN₄O₃S
OIL

16
C₁₇H₂₃ClN₄O₂S
OIL

17
C₁₆H₁₉ClN₄O₂S₂
SYRUP

18
C₁₆H₁₉ClN₄O₃S
102-104

19
C₁₆H₁₉ClN₄O₃S
SYRUP

20
C₂₀H₂₁ClN₄O₃S
OIL

38
C₁₂H₁₅ClN₄O₃S
85-90

39
C₁₆H₂₃ClN₄O₄S
SYRUP

40
C₁₄H₁₉ClN₄O₃
OIL

41
C₁₃H₁₉ClN₄O₃
OIL

42
C₁₃H₂₀ClN₅O₂
SOLID

43
C₁₃H₁₇ClN₆O₂
156-158

44
C₁₂H₁₈ClN₅O₂
SYRUP

46
C₁₃H₁₉ClFN₅O₂S
OIL

51
C₁₅H₂₄ClN₅O₄S
OIL

54
C₁₂H₁₅ClN₆O₂S
SOLID

65
C₁₂H₁₈ClN₅O₂S
—

66
C₁₃H₂₀ClN₅O₂S
OIL

67
C₁₄H₂₂ClN₅O₂S
OIL

68
C₁₄H₂₀ClN₅O₂S
OIL

69
C₁₅H₂₂ClN₅O₂S
OIL

70
C₁₇H₂₆ClN₅O₂S
OIL

71
C₁₂H₁₇ClFN₅O₂S
OIL

72
C₁₁H₁₄ClN₅O₃S
FOAM

73
C₁₅H₂₂ClN₅O₄S
SYRUP

74
C₁₀H₁₅ClN₆O₂
SYRUP

75
C₁₅H₂₃ClN₆O₄
46-49

96
C₁₄H₂₀ClN₅S
OIL

97
C₁₂H₁₄ClN₅OS
49-53

98
C₁₆H₂₂ClN₅O₂S
SYRUP

99
C₁₆H₂₃ClN₆O₂
55-69

100
C₁₅H₁₇Cl₂N₅O₂S₂
124

101
C₁₆H₂₀ClN₅O₂S₂
112-114

102
C₂₁H₂₁Cl₂N₅O₂S₂
50-55

103
C₂₁H₂₃ClN₆O₄S
110-112

104
C₂₁H₂₃ClN₆O₄S
SYRUP

105
C₂₁H₂₃ClN₆O₄S
SYRUP

106
C₂₁H₂₀ClF₃N₆O₃S
137-138

197
C₁₉H₂₂ClN₇O₄S
SYRUP

108
C₁₈H₂₁ClN₄O₂S
OIL

109
C₂₀H₂₅ClN₄O₂S
OIL

110
C₁₈H₂₀Cl₂N₄O₂S
OIL

111
C₁₈H₂₀Cl₂N₄O₂S
OIL

112
C₁₈H₂₀Cl₂N₄O₂S
128.5-131

115
C₂₀H₂₄Cl₂N₄O₂S
OIL

116
C₁₈H₁₆ClF₅N₄O₂S
OIL

117
C₁₉H₂₀ClN₅O₂S
OIL

118
C₁₈H₂₀ClN₅O₄S
OIL

119
C₁₉H₂₃ClN₄O₂S
OIL

120
C₁₉H₂₃ClN₄O₂S
OIL

121
C₁₉H₂₃ClN₄O₂S
106-108.5

125
C₂₂H₂₉ClN₄O₂S
107-108.5

126
C₂₀H₂₅ClN₄O₂S
OIL

127
C₂₀H₂₅ClN₄O₂S
OIL

128
C₂₀H₂₅ClN₄O₂S
OIL

129
C₂₀H₂₅ClN₄O₂S
OIL

130
C₂₀H₂₅ClN₄O₂S
OIL

131
C₂₀H₂₅ClN₄O₂S
OIL

132
C₂₁H₂₇ClN₄O₂S
OIL

133
C₁₉H₂₀ClF₃N₄O₂S
OIL

134
C₂₄H₂₅ClN₄O₂S
OIL

135
C₂₅H₂₇ClN₄O₂S
OIL

136
C₁₉H₂₃ClN₄O₃S
OIL

137
C₁₉H₂₃ClN₄O₃S
OIL

138
C₁₉H₂₃ClN₄O₃S
OIL

139
C₁₇H₂₀ClN₅O₂S
143-146

140
C₁₈H₂₂ClN₅O₃S
OIL

141
C₂₄H₂₅ClN₄O₃S
OIL

142
C₂₄H₃₁ClN₄O₂S
LIQUID

143
C₂₁H₂₅ClN₈O₂S
60-69

144
C₂₄H₃₁ClN₄O₂S
SEMI SOLID

145
C₁₇H₂₀ClN₅O₂S
OIL

146
C₁₈H₁₉ClF₃N₅O₂S
OIL

147
C₁₇H₁₉ClFN₅O₂S
OIL

148
C₁₈H₂₂ClN₅O₃S
OIL

149
C₁₈H₁₉ClF₃N₅O₃S
OIL

150
C₁₈H₁₉ClN₆O₂S
150-156

151
C₁₇H₁₈Cl₃N₅O₂S
OILY SOLID

152
C₁₈H₂₀ClFN₄O₂S
OIL

153
C₁₉H₂₀ClF₃N₄O₃S
OIL

154
C₁₇H₁₉Cl₂N₅O₂S
115-116

155
C₁₇H₁₉Cl₂N₅O₂S
OIL

156
C₁₈H₂₂ClN₅O₃S
OIL

157
C₁₈H₂₂ClN₅O₂S
OIL

158
C₂₀H₂₆ClN₅O₃S
OIL

159
C₁₈H₂₃N₅O₃S
OIL

160
C₁₉H₂₅N₅O₄S
OIL

161
C₁₉H₂₂F₃N₅O₃S
OIL

162
C₂₀H₂₆ClN₅O₃
93-95

163
C₁₉H₂₄ClN₅O₄S
OIL

164
C₁₉H₂₅ClN₆O₃
144-146

165
C₂₁H₂₉ClN₆O₃
OIL

166
C₁₉H₂₄ClN₅O₃S
OIL

167
C₁₉H₂₅N₅O₃S
OIL

168
C₁₈H₂₂FN₅O₃S
OIL

169
C₂₀H₂₆ClN₅O₄S
OIL

170
C₁₈H₂₂BrN₅O₃S
OIL

171
C₂₀H₂₄F₃N₅O₄S
OIL

172
C₂₁H₂₅F₃N₄O₄S
OIL

173
C₁₈H₂₀Cl₂N₄O₃
SOLID

174
C₁₉H₂₃ClN₄O₄
OIL

175
C₂₇H₃₁ClN₄O₄S₂
OIL

176
C₁₈H₁₉Cl₂N₅S
OIL

177
C₁₉H₂₂ClN₅OS
OIL

178
C₁₉H₂₂ClN₅O
OIL

179
C₁₉H₂₁Cl₂N₅O
FOAM

180
C₂₀H₂₄ClN₅O₂
OIL

181
C₂₃H₃₁ClN₆O
68-72

182
C₂₄H₃₃ClN₆O
OIL

183
C₂₃H₃₁ClN₆O
OIL

184
C₁₇H₂₀ClN₅O₂S
OIL

187
C₁₇H₁₉Cl₂N₅O₃
GUM

188
C₁₈H₂₁Cl₂N₅O3
GUM

189
C₂₀H₂₅Cl₂N₅O₃
GUM

190
C₂₃H₂₉Cl₂N₅O₃
GUM

192
C₁₇H₂₀ClN₅O₂S
OIL

198
C₁₇H₁₉Cl₂N₅O₂S
107-110

199
C₁₈H₂₁Cl₂N₅O₂S
117-118

200
C₂₂H₂₉Cl₂N₅O₂S
GUM

201
C₁₈H₂₁Cl₂N₅O₂S
93

202
C₂₀H₂₅Cl₂N₅O₂S
123

203
C₂₃H₂₉Cl₂N₅O₂S
101

204
C₂₀H₂₀Cl₂F₃N₅O₂S
GUM

205¹
C₁₈H₂₃ClN₅O₂SI
FOAM

206
C₁₇H₂₀Cl₂N₆O₂
137-138

207
C₁₈H₂₂Cl₂N₆O₂
149-150

208
C₂₀H₂₆Cl₂N₆O₂
72-75

209
C₁₇H₂₀Cl₂N₆O₃
SOLID

210
C₂₁H₂₆Cl₂N₆O₂
135-136

211
C₁₈H₂₂Cl₂N₆O₂
SOLID

212
C₂₀H₂₆Cl₂N₆O₂
OIL

213
C₁₇H₁₈Cl₂N₆S
140.5-142.5

214
C₁₇H₁₈Cl₂N₆
130.5-131.5

216
C₁₆H₁₈Cl₂N₆O₂S
110-112

217
C₁₇H₂₀ClN₅O₂S
OIL

220
C₁₄H₁₉ClN₄O₂S
OIL

221
C₂₀H₂₉ClN₄O₂S
OIL

222
C₁₅H₂₁ClN₄O₂S
OIL

223
C₁₅H₂₁ClN₄O₂S
OIL

224
C₁₄H₁₈Cl₂N₄O₂S
OIL

225
C₁₄H₁₈Cl₂N₄O₂S
OIL

226
C₁₄H₁₇Cl₃N₄O₂S
OIL

227
C₁₄H₁₇Cl₃N₄O₂S
SOLID

228
C₁₄H₁₇Cl₃N₄O₂S
OIL

229
C₁₅H₁₈ClF₃N₄O₂S
OIL

230
C₂₀H₂₃ClN₄O₂S
OIL

231
C₁₃H₁₈ClN₅O₂S
OIL

235
C₁₃H₁₇Cl₂N₅O₂S
OIL

242
C₁₄H₁₉ClN₄O₃
OIL

243
C₁₄H₁₈ClN₅S
OIL

244
C₁₄H₁₇ClN₄O₃
114-115

245
C₁₅H₁₉ClN₄O₃
107-110

246
C₁₆H₂₁ClN₄O₄
106-110

247
C₁₈H₂₅ClN₄O₅
84-87

248
C₁₄H₁₇ClN₄O₂S
SOLID

249
C₁₄H₁₇ClN₄O₂S
125-127

250
C₁₅H₂₀N₄O₂S
109-112

251
C₁₅H₁₇F₃N₄O₂S
108-110

252
C₁₅H₁₉ClN₄O₂S
OIL

253
C₁₅H₁₉ClN₄O₂S
123-124

254
C₁₆H₂₁ClN₄O₂S
OIL

255
C₁₉H₂₇ClN₄O₂S
OIL

256
C₂₀H₂₇ClN₄O₃
112-113

257
C₂₀H₂₇ClN₄O₂S
OIL

258
C₂₁H₂₉ClN₄O₂S
OIL

259
C₁₅H₁₉ClN₄O₂S
OIL

260
C₁₉H₂₇ClN₄O₂S
OIL

261
C₁₅H₂₀ClN₅O₂
OIL

262
C₁₆H₂₂ClN₅O₂
OIL

279
C₁₃H₁₆ClN₅O₂S
SOLID

285
C₁₄H₁₈ClN₅O₂S
SOLID

296
C₁₄H₁₉N₅O₂S
SOLID

297
C₁₄H₁₈ClN₅O₂
153-155

298
C₁₄H₁₆ClN₅S
SOLID

299
C₁₄H₁₇ClN₆
OIL

300
C₂₀H₂₁ClN₄O₂S
OIL

301
C₂₁H₂₂Cl₂N₄O₂S
OIL

302
C₂₀H₂₀ClFN₄O₂S
OIL

303
C₂₁H₂₃ClN₄O₂S
OIL

304
C₁₈H₁₉ClN₆O₂S
103-106

305
C₂₁H₂₂ClFN₄O₂S
OIL

306
C₂₄H₂₄Cl₂FN₅O₂S
113-120

307
C₂₅H₂₄ClF₃N₄O₂S
SEMI-SOLID

308
C₂₄H₂₆ClN₅O₄S
OIL

309
C₃₁H₃₃N₅O₅S₂
OIL

310
C₂₄H₂₆ClN₅O₃S
OIL

311
C₂₄H₂₅Cl₂N₅O₃S
OIL

312
C₂₅H₂₈ClN₅O₄S
OIL

313
C₃₃H₃₅ClN₄O₅S₂
OIL

314
C₂₃H₂₂Cl₃N₅O₂S
GLASS

315
C₂₃H₂₂Cl₃N₅O₂S
149

316
C₂₃H₂₂Cl₃N₅O₂S
131

317
C₂₃H₂₂Cl₃N₅O₂S
116

318
C₂₃H₁₈Cl₂F₅N₅O₂S
GUM

319
C₂₄H₂₅Cl₂N₅O₂S
GUM

320
C₂₄H₂₅Cl₂N₅O₂S
150

321
C₂₄H₂₅Cl₂N₅O₂S
GUM

322
C₂₄H₂₂Cl₂F₃N₅O₂S
GUM

323
C₂₄H₂₂Cl₂F₃N₅O₂S
GUM

324
C₂₄H₂₂Cl₂F₃N₅O₂S
GUM

325
C₂₄H₂₅Cl₂N₅O₃S
GLASS

326
C₂₄H₂₅Cl₂N₅O₃S
GLASS

327
C₂₄H₂₅Cl₂N₅O₃S
137

328
C₂₁H22ClF₃N₄O₂S
OIL

329
C₂₁H₂₀ClF₃N₄O₂S
124-125

330
C₂₂H₂₂ClF₃N₄O₂S
OIL

339
C₁₆H₂₀ClN₅O₃S₂
OIL

486
C₁₇H₂₆N₄O₄S
OIL

488
C₁₄H₂₁ClN₆O₂
OIL

492
C₁₂H₁₆ClN₅O₂
SOLID

493
C₁₄H₁₇ClN₆O₂
OIL

494
C₁₁H₁₅ClN₆O₂
OIL

495
C₁₃H₁₆ClN₇O₂
OIL

496
C₂₀H₂₄ClN₅O₃
OIL

497
C₁₈H₂₀Cl₂N₆O₂
SOLID

498
C₁₉H₂₃ClN₆O₃
SOLID

499
C₁₉H₂₁Cl₂N₅O₂
FOAM

501
C₁₉H₂₁Cl₂N₅O₂
OIL

504
C₂₁H₂₆ClN₅O₄
FOAM

519
C₁₅H₂₀ClN₅O₂
OIL

520
C₁₄H₁₉ClN₆O₂
OIL

524
C₁₄H₁₇ClN₆O₂
OIL

525
C₁₅H₁₈ClN₅O₂
OIL

526
C₁₆H₂₀ClN₅O₂
OIL

527
C₁₂H₁₇ClN₆O₃
OIL

528
C₁₃H₁₉ClN₆O₃
130-132

529
C₁₂H₁₇ClN₆O₂S
OIL

530
C₁₃H₁₉ClN₆O₂S
OIL

531
C₁₃H₂₀ClN₇O₂
OIL

532
C₁₄H₂₂ClN₇O₂
OIL

534
C₁₃H₁₆ClN₇O₃
OILY SOLID

535
C₁₄H₁₈ClN₇O₃
122-124

536
C₁₃H₁₆ClN₇O₂S
135-138

537
C₁₄H₁₈ClN₇O₂S
SOLID

538
C₁₄H₁₉ClN₈O₂
129-131

539
C₁₅H₂₁ClN₈O₂
122-125

540
C₁₉H₂₂Cl₂N₆O₃
SYRUP

542
C₁₉H₂₃ClN₆O₃
OIL

543
C₁₉H₂₃ClN₆O₃
OIL

544
C₁₉H₂₃ClN₆O₄
OIL

545
C₂₀H₂₅ClN₆O₄
115-120

546
C₂₁H₂₈ClN₇O₃
SYRUP

548
C₁₈H₂₁Cl₂N₇O₃
SYRUP

555
C₁₄H₁₉ClN₆O₃
OIL

556
C₁₅H₂₁ClN₆O₃
OIL

558
C₁₄H₁₇ClN₆O₃
OILY-SOLID

559
C₁₄H₁₇ClN₆O₂S
129-132

560
C₁₅H₁₉ClN₆O₂S
105-108

561
C₁₅H₂₀ClN₇O₂
114-117

562
C₁₆H₂₂ClN₇O₂
107-109

563
C₁₀H₁₅ClN₆O₃S
OIL

564
C₁₁H₁₇ClN₆O₃S
85-87

565
C₁₁H₁₄ClN₇O₃S
76-80

566
C₁₂H₁₆ClN₇O₃S
OIL

567
C₁₃H₁₅Cl₂N₇O₃S₂
OIL

568
C₁₄H₁₇Cl₂N₇O₃S₂
SOLID

569
C₁₂H₁₅ClN₆O₃S
159-162

570
C₁₃H₁₇ClN₆O₃S
160-161

571
C₁₅H₂₇N₅O₅
Oil

572
C₁₆H₂₉N₅O₅
Oil

573
C₁₈H₂₇N₅O₅
Oil

574
C₁₉H₂₉N₅O₅
Oil

575
C₁₃H₂₁N₃O₄
80-84

576
C₁₄H₂₃N₅O₄
110-114

577
C₁₃H₁₆ClN₅S
108-110

578
C₁₂H₁₆ClN₅O₂S
86-89

579
C₁₃H₁₇ClN₄O₂S
Syrup

Candidate insecticides were evaluated for activity against the tobacco budworm (Heliothis virescens [Fabricius]) in a surface-treated diet test.

In this test one mL of molten (65-70° C.) wheat germ-based artificial diet was pipetted into each well of a four by six (24 well) multi-well plate (ID# 430345-15.5 mm dia.×17.6 mm deep; Corning Costar Corp., One Alewife Center, Cambridge, Mass. 02140). The diet was allowed to cool to ambient temperature before treatment with candidate insecticide.

For a determination of insecticidal activity, solutions of the candidate insecticides were prepared for testing using a Packard 204DT Multiprobe® Robotic System (Packard Instrument Company, 800 Research Parkway, Meriden, Conn. 06450), in which the robot first diluted a standard 50 millimolar DMSO solution of candidate insecticide with a 1:1 water/acetone solution (V/V) in a ratio of 1:7 stock solution to water/acetone. The robot subsequently pipetted 40 microliters of the so-prepared solution onto the surface of the diet in each of three wells in the 24 multi-well plate. The process was repeated with solutions of seven other candidate insecticides. Once treated, the contents of the multi-well plate were allowed to dry, leaving 0.25 millimoles of candidate insecticide on the surface of the diet, or a concentration of 0.25 millimolar. Appropriate untreated controls containing only DMSO on the diet surface were also included in this test.

For evaluations of the insecticidal activity of a candidate insecticide at varying rates of application, the test was established as described above using sub-multiples of the standard 50 millimolar DMSO solution of candidate insecticide. For example, the standard 50 millimolar solution was diluted by the robot with DMSO to give 5, 0.5, 0.05, 0.005, 0.0005 millimolar, or more dilute solutions of the candidate insecticide. In these evaluations there were six replicates of each rate of application placed on the surface of the diet in the 24 multi-well plate, for a total of four rates of application of candidate insecticide in each plate.

In each well of the test plate was placed one second instar tobacco budworm larvea, each weighing approximately five milligrams. After the larvae were placed in each well, the plate was sealed with clear polyfilm adhesive tape. The tape over each well was perforated to ensure an adequate air supply. The plates were then held in a growth chamber at 25° C. and 60% relative humidity for five days (light 14 hours/day).

After the five-day exposure period insecticidal activity for each rate of application of candidate insecticide was assessed as percent inhibition of insect weight relative to the weight of insects from untreated controls, and percent mortality when compared to the total number of insects infested.

Insecticidal activity data at selected rates of application from this test are provided in Table 3. The test compounds of formula I are identified by numbers that correspond to those in Table 1.

TABLE 3

Insecticidal Activity of Certain N-(Heteroarylalkyl)alkanediamine

Derivatives When Applied to the Surface of the Diet of Tobacco Budworm

(Heliothis virescens [Fabricius])

Percent

Percent

Percent
Growth

Percent
Growth

Cmpd No.
Mortality
Inhibition
Cmpd No.
Mortality
Inhibition

1
83
100
2
100
100

3
50
96
4
100
100

5
100
100
6
67
95

7
67
99
8
50
100

9
50
91
10
17
90

14
50
100
15
17
85

17
67
99
18
33
100

19
100
100
40
83
100

41
83
100
44
83
100

46
0
78
54
0
67

65
67
100
66
0
73

71
33
100
100
50
99

101
83
100
102
100
100

103
100
100
104
100
100

105
100
100
106
67
100

107
100
100
108
67
50

109
83
100
110
0
50

111
17
87
115
100
100

116
100
100
119
67
87

120
17
93
125
100
100

126
50
85
127
33
78

129
50
85
132
50
92

134
100
100
135
100
100

136
0
50
141
100
100

142
50
93
143
67
93

144
100
100
151
33
83

154
33
75
173
0
76

174
17
86
184
17
82

187
0
50
189
100
100

190
100
100
192
83
92

198
33
50
202
100
100

203
100
100
217
17
81

220
100
100
221
100
100

222
100
100
223
83
98

224
100
100
225
17
89

226
100
100
227
17
92

228
83
100
229
100
96

230
33
88
231
67
100

242
83
96
244
83
100

245
50
100
246
100
100

247
100
100
248
100
100

249
83
99
252
100
100

253
83
100
254
100
100

255
50
88
256
100
100

257
100
100
258
100
100

279
83
100
301
100
100

302
50
97
304
0
61

307
100
100
310
50
100

311
50
100
314
100
100

315
83
98
317
100
100

318
100
100
319
100
10

320
100
96
321
100
100

322
100
100
323
10
100

324
100
100
325
100
100

326
100
100
327
83
100

328
83
98
558
33
85

Concentration of the candidate insecticide on the surface of the diet is 0.25 millimolar.

As set forth in Table 3, all of the tested compounds of the present invention provided insecticidal activity against the tobacco budworm, with many of the compounds providing 100% mortality and/or 100% growth inhibition.

Candidate insecticides were also 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(10) 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(10) 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, Calif.) 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(10) 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 20% 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 20% 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 Tables 4 and 4A. Again, the test compounds of formula I are identified by numbers that correspond to those in Table 1.

TABLE 4

The following Compounds of The Present Invention Reduced the Population of

Cotton Aphid by At Least 75% when Applied at an Application Rate of 1000 ppm or

Less

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

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

1
2
3
4

5¹
6
7
8
9
14

15
16
17
18
19
20
38
39
40
41

42
44
46
51
54
65
66
68
69
70

71
72
73
74
96
97
99
100
101
102

103
104
105
106
107
108
109
110
111
112

115
116
117
118
119
120
121
126
127
128

129
130
131
132
133
134
135
136
137
140

141
142
143
144
146
147
148
149
150
151

152
153
154
155
156
157
158
159
160
161

162
163
164
165
166
167
168
169
170
173

174
177
178
184
187
188
189
190
192
198

199
200
201
202
203
204
206
207
208
209

210
211
212
213
214
216
217
220
221
222

223
224
225
226
227
228
229
230
231
235

243
244
245
246
247
248
249
250
251
252

253
254
255
256
257
258
259
260
261
262

279
285
296
298
299
300
301
302
303
304

305
306
307
310
311
312
314
315
316
317

318
319
320
321
322
323
324
325
326
327

329
330
339
486
488
501
527
528
529
530

531
532
534
535
540
542
543
544
545
548

555
556
558

¹96 hr exposure period; all others 72 hr exposure period

TABLE 4A

The following Compounds of The Present Invention Reduced the Population of

Cotton Aphid Between 20% and 75% when Applied at an Application Rate of

1000 ppm or Less

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

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

75
98
180
181
183
205
297
504
525
526

538
539
546

72 hr exposure period

As set forth in Tables 4 and 4A, most of the tested compounds of the present invention reduced the aphid population by at least 75% at an application rate of 1000 ppm or less. A small number of tested compounds of the present invention reduced the aphid population by 20% to 75% at an application rate of 1000 ppm or less.

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.

	Number	Date	Country
	60526760	Dec 2003	US
	60609590	Sep 2004	US

Insecticidal N-(Heteroarylalkyl)Alkanediamine Derivatives

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