N-Substituted Azacycles

FIELD OF THE INVENTION

The present invention generally relates to novel compounds, processes and intermediates useful in preparing such compounds, compositions containing such compounds and the use of such compounds in controlling insects. In particular, it pertains to N-substituted azacycle derivatives, N-oxides, and agriculturally acceptable salts thereof, compositions of these insecticides, and methods for their use in controlling insects.

BACKGROUND OF THE INVENTION

A longstanding worldwide demand exists for new, effective, less costly, and safe means to control pests in agricultural crops, greenhouse crops, nursery crops, ornamentals, turfs, forestry, stored food and fiber products, structures, livestock, households, and public and animal health. Agricultural crop costs incurred by pests exceed billions of dollars annually in decreased crop yields, reduced crop quality and increased harvesting costs. Agricultural crops include wheat, corn, soybeans, potatoes, and cotton to name a few. Soil-bourne insects, such as termites and white grubs, cause millions of dollars of damage to structures, turfs and ornamentals. Household pests, such as flies, ants and cockroaches, carry disease and are undesirable in peoples' homes. In addition to these pests, many blood-feeding insects are vectors for pathogenic microorganisms that threaten human and animal health, or are annoying at the least. Insecticides are desired which can control these pests without damaging crops, turfs, ornamentals or structures, and which have no deleterious effects to mammals and other living organisms.

A number of patents disclose a variety of insecticidally active azacycle derivatives. For example, as set forth in U.S. Pat. No. 5,569,664, compounds of the following structure are reported to be insecticidally active:

where U is selected from —(CH₂)_n— and ethylidine, where n is 1, 2, or 3; Q is selected from hydrogen, hydroxy, sulfhydryl, and fluorine; V is selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsilyloxy, dialkylamino, cyano, nitro, hydroxy, and phenyl; W is selected from hydrogen, halogen, alkyl, haloalkyl, alkoxy, nitro, amino, phenoxy, and phenylalkoxy; X is selected from hydrogen, hydroxy, halogen, alkyl, alkoxyalkyl, alkoxy, cycloalkylalkoxy, haloalkoxy, alkenyloxy, alkynyloxy, alkylsilyloxy, alkylthio, haloalkylthio, cyano, cyanoalkoxy, nitro, amino, monoalkylamino, dialkylamino, alkylaminoalkoxy, alkylcarbonylamino, alkoxycarbonylamino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, aminocarbonyloxy, phenyl, phenylalkoxy, ohenoxy, and phenoxyalkyl; Y and Z are independently selected from hydrogen and alkoxy; R¹and R²are independently selected from phenyl substituted with halogen, alkyl, haloalkyl, haloalkoxy, alkoxyalkyl, hydroxy, arylthio, alkoxy, dialkylamino, dialkylaminosulfonyl, hydroxyalkylaminocarbonyl, alkylsulfonyloxy, and haloalkylsulfonyloxy; and the corresponding N-oxides and agriculturally acceptable salts.

As set forth in U.S. Pat. No. 5,639,763 compounds of the following structure are reported to be insecticidally active:

As set forth in U.S. Pat. No. 5,795,901 compounds of the following structure are reported to be insecticidally active:

where V, W, Y, and Z are hydrogen; X is alkoxy, cycloalkoxy, alkoxycarbonyl, alkoxycarbonylamino, or a five- or six-membered heteroaryl or heteroaryloxy, each heteroaryl optionally substituted with halogen, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl, or haloalkoxyalkyl; R¹and R²are independently selected from haloalkyl, phenyl substituted with halogen, halothio, haloalkyl, or haloalkoxy; or a five- or six-membered heteroaryl substituted with halogen or alkyl; R³is alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, dialkylaminoalkyl, alkylaminocarbonyloxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, alkylcarbonyloxyalkyl, alkoxycarbonylalkyl, carboxyalkyl, carboxyarylalkyl, arylcarbonyl, sulfonato, or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt, and a separate anion is chloride, bromide, iodide, or a phenyl, or alkyl sulfate or sulfonate.

As set forth in U.S. Pat. No. 5,939,438 compounds of the following structure are reported to be insecticidally active:

where R is hydrogen, halogen, alkyl, alkoxy, or dialkylamino; R¹is hydrogen, alkyl, haloalkyl, alkoxyalkyl, alkylcarbonyl, or alkylaminocarbonyl; Q is fluoro or hydroxy; X is oxygen or NR²; Z is halogen, haloalkyl, haloalkoxy, pentahalothio, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl, or —OCF₂O— attached to two adjacent carbon atoms of the phenyl ring; n is 0 or 1; and, when X is NR², R²is hydrogen, alkyl, alkylcarbonyl, alkoxycarbonyl, or R¹and R²taken together may be —C_mH_2m—, or —C₂H₄OC₂H₄—, where m is 3-9; and their agriculturally acceptable salts.

As set forth in U.S. Pat. No. 6,017,931 compounds of the following structure are reported to be insecticidally active:

where V, W, and Z are hydrogen; X is selected from alkoxy, haloalkoxy, alkoxyalkyl, cycloalkylalkoxyl, halocycloalkylalkoxy, alkoxycarbonyl, haloalkoxycarbonyl, cycloalkylalkoxylcarbonyl, halocycloalkylalkoxylcarbonyl, alkoxyalkoxycarbonyl, alkoxycarbonylamino, haloalkoxycarbonylamino, cycloalkylalkoxycarbonylamino, halocycloalkylalkoxycarbonylamino, alkylaminocarbonyl, haloalkylaminocarbonyl, cyanoalkoxycarbonylamino, phenylcarbonylamino, and phenoxycarbonyl, each cycloalkyl moiety or phenyl ring optionally substituted with halogen; Y is selected from hydrogen or halogen; R¹and R²are independently selected from phenyl or pyridyl, each substituted with haloalkyl, haloalkoxy, or alkylthio, and the corresponding N-oxides and agriculturally acceptable salts.

As set forth in U.S. Pat. No. 6,030,987 compounds of the following structure are reported to be insecticidally active:

where V, W, Y and Z are hydrogen; X is a five- or six-membered heterocycle optionally substituted with halogen, alkyl, alkoxy, alkoxyalkyl, cyano, aminocarbonyl, haloalkyl, haloalkoxy, or haloalkoxyalkyl; and the heterocycle is optionally connected to the phenyl ring through a —O—, —S—, —(CH₂)_p—, —C(O)—, or —O(CR³R⁴)_q— linkage; R¹and R²are independently selected from phenyl or pyridyl, each substituted with haloalkyl, or haloalkoxy; R³and R⁴are independently selected from hydrogen and methyl; n and p are independently 1, 2, or 3; and q is 1 or 2, and the corresponding N-oxides and agriculturally acceptable salts.

As set forth in U.S. Pat. No. 6,184,234 compounds of the following structure are reported to be insecticidally active:

where V, W, Y and Z are hydrogen; X is a five- or six-membered heterocycle optionally substituted with bromine, chlorine, fluorine, alkyl, alkoxy, alkoxyalkyl, cyano, aminocarbonyl, haloalkyl, haloalkoxy, or haloalkoxyalkyl; and the heterocycle is optionally connected to the phenyl ring through a —O—, —S—, —(CH₂)_p—, —C(O)—, or —O(CR³R⁴)_q— linkage; R¹and R²are independently selected from i) phenyl or pyridyl, each substituted with pentahalothio, haloalkylthio, haloalkylsulfinyl, or haloalkylsulfonyl; ii) phenyl substituted with —OC(M)₂O—, where M is bromine, chlorine, or fluorine to provide a dihalobenzodioxolyl fused ring; or iii) pyridyl substituted with —OC(M)₂O—, to provide a dihalodioxoleneopyridyl fused ring; R³and R⁴are independently selected from hydrogen and methyl; n and p are independently 1, 2, or 3; and q is 1 or 2, and the corresponding N-oxides and agriculturally acceptable salts.

As set forth in United States Statutory Invention Registration H1,838 compounds of the following structure are reported to be insecticidally active:

where m is 2 or 3; n is 0 or 1; W is hydrogen or alkoxy; X is hydrogen, alkoxy, cycloalkylalkoxy, haloalkoxyimino, or a five- or six-membered heteroaryl or heteroaryloxy in which one or more hetero atoms may be optionally substituted with alkyl; R¹and R²are independently selected from hydrogen, haloalkyl, halothio, or haloalkoxy; and when n is 1, Y represents (a) an N-oxide of the ring nitrogen; or (b) an agriculturally acceptable anionic salt of the ring nitrogen; or (c) forms an OR³linkage in which R³is selected from hydrogen, alkyl, alkoxycarbonylalkyl, hydroxycarbonylethyl in association with an agriculturally acceptable anion resulting in an ionic salt, or R³is an oxycarbonylalkyl group bearing a negative charge resulting in an inner salt.

As set forth in United States Statutory Invention Registration H1,996 photostable, agriculturally acceptable acid salts of an organic or inorganic acid of the following structure are reported to be insecticidally active:

where R is alkoxycarbonyl, alkoxycarbonylamino, cycloalkylalkoxy, 2-alkyl-2H-tetrazol-5-yl, or 2-haloalkyl-2H-tetrazol-5-yl; R¹is trihaloalkyl, or trihaloalkoxy; n is 0, or 1; and said salt is at least 2.5 times more photostable than its non-ionic parent and is derived from hydrochloric acid, hydrobromic acid, boric acid, phosphoric acid, maleic acid, fumaric acid, phthalic acid, D-glucuronic acid; the sulfonic acid R²SO₃H where R²is alkyl, haloalkyl, hydroxyalkyl, D-10-camphoryl, or phenyl optionally substituted with alkyl or halogen; the carboxylic acid R³CO₂H where R³is hydrogen, alkyl, trihaloalkyl, carboxyl, phenyl optionally substituted with alkyl or halogen, or pyridyl; the boronic acid R⁴B(OH)₂where R⁴is alkyl or phenyl optionally substituted with alkyl or halogen; the phosphonic acid R⁵PO₃H₂where R⁵is alkyl, haloalkenyl, or phenyl optionally substituted with alkyl or halogen; the sulfuric acid R⁶OSO₃H where R⁶is hydrogen or alkyl; or the alkanoic acid X—(CH₂)_qCO₂H where q is 0 to 11, X is halogen, trihaloalkyl, haloalkenyl, cyano, aminocarbonyl, or CO₂R⁷where R⁷is hydrogen or alkyl.

As set forth in United States Statutory Invention Registration H2,007 compounds of the following structures are reported to be insecticidally active:

where A and B are independently selected from lower alkyl; U is selected from lower alkylidene, lower alkenylidene, and CH-Z, where Z is selected from hydrogen, lower alkyl, lower cycloalkyl, or phenyl; R is —CHR³R⁴where R³and R⁴are independently selected from phenyl, optionally substituted with halogen, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, lower alkenyl, or phenyl; R¹is phenyl, naphthyl, tetrazolylphenyl, phenylcyclopropyl, phenoxyphenyl, benzyloxyphenyl, pyridylphenyl, pyridyloxyphenyl, or thiadiazolyloxyphenyl, each optionally substituted with halogen, cyano, hydroxy, lower alkyl, lower haloalkyl, lower alkoxy, amino, lower dialkylamino, nitro, lower haloalkylsulfonyloxy, lower alkylcarbonyloxy, lower alkylcarbonylamino, lower alkoxycarbonyl, lower alkoxyalkoxycarbonyl, lower cycloalkylalkoxycarbonyl, lower alkoxyalkylalkoxycarbonyl, lower alkoxycarbonylamino, alkoxythiocarbonylamino, lower alkyldithiocarbonylamino, lower dialkyldioxolylalkoxycarbonylamino, or halophenylamino; or lower alkyl substituted with any one of the foregoing cyclic R¹groups; m is 2 or 3; and n is 1, 2, or 3.

As set forth in unexamined Japanese Patent Application 2002-220372 compounds of the following structures are reported to be insecticidally active:

where R¹and R²are independently selected from hydrogen, halogen, lower alkyl, lower haloalkyl, lower alkoxy, lower haloalkoxy, or lower alkylsulfonyloxy; R²is selected from hydrogen, lower alkyl, lower alkenyl, lower alkoxyalkyl, or lower alkylcarbonyl; X and Y are independently oxygen or sulfur; R³is selected from lower alkenyl, or lower alkynyl, which are optionally substituted with hydroxy, halogen, lower alkoxy, lower haloalkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, lower cycloalkyl, lower alkoxyalkoxy, amino, lower alkylamino, lower dialkylamino, lower alkoxycarbonyl, nitro, cyano, trimethylsilyl, phenyl, or lower cycloalkenyl; and the corresponding N-oxides and salts.

As set forth in PCT Publication WO 02/068392A1 compounds of the following structures are reported to be insecticidally active:

where R¹and R²are independently selected from halogen, C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, —S(═O)_p—R⁹, or SF₅; R³is hydrogen, hydroxy, C₁-C₆alkoxy, or —OC(═O)—C₁-C₆alkyl; R⁴is hydrogen, halogen, C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy, or —S(═O)_p—R⁹, or —SCN; R⁵and R⁶are independently selected from C₁-C₁₂alkyl, haloC₁-C_1-2alkyl, C₂-C₁₂alkenyl, haloC₂-C₁₂alkenyl, C₂-C₁₂alkynyl, haloC₂-C₁₂alkynyl, C₃-C₈cycloalkyl, —C(═O)—OR⁷, —C(═S)—OR⁸, —C(═Y)-ZR⁸, —S(═O)_p—R⁹, aryl, arylC₁-C₆alkyl, heterocycle, heterocycleC₁-C₆alkyl, each substituted in the ring from one to five times independently of one another by halogen, hydroxy, cyano, nitro, C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, haloC₁-C₆alkoxy; or in common together with the nitrogen atom to which they are attached to form a heterocyclic ring which is substituted or unsubstituted; Y is oxygen or sulfur; X is a bond, —NR¹⁰—, or sulfur; R⁷is C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkylthio-C₁-C₆alkyl, C₁-C₆alkylamino-C₁-C₆alkyl, C₃-C₆alkynyl, C₁-C₆alkyl-S(═O)_p—C₁-C₆alkyl, C₃-C₈cycloalkyl, aryl, aryl-C₁-C₆alkyl, heterocyclyl, or heterocyclyl-C₁-C₆alkyl each substituted in the ring from one to five times independently of one another by halogen, cyano, nitro, C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, or haloC₁-C₆alkoxy; R⁸is C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy-C₁-C₆alkyl, C₁-C₆alkylthio-C₁-C₆alkyl, C₂-C₆alkenyl, C₃-C₆alkynyl, C₁-C₆alkyl-S(═O)_p—C₁-C₆alkyl, C₃-C₈cycloalkyl, aryl, aryl-C₁-C₆alkyl, heterocyclyl, or heterocyclyl-C₁-C₆alkyl, or is C₃-C₈cycloalkyl, aryl, aryl-C₁-C₆alkyl, heterocyclyl, or heterocyclyl-C₁-C₆alkyl each substituted in the ring from one to five times independently of one another by halogen, cyano, nitro, C₁-C₆alkyl, haloC₁-C₆alkyl, C₁-C₆alkoxy, or haloC₁-C₆alkoxy; R⁹is C₁-C₆alkyl, C₃-C₈cycloalkyl, haloC₁-C₆alkyl, or benzyl; R¹⁰is hydrogen, C₁-C₆alkyl, C₃-C₈cycloalkyl, haloC₁-C₆alkyl, or benzyl; p is 0, 1, or 2; q is 0 or 1; and, where appropriate, E/Z isomers, E/Z isomer mixtures and/or toutomers, each in free form or in salt form.

As set forth in PCT Publication WO 200020409A1 compounds of the following structures are reported to be insecticidally active:

where R¹is halo, C₁-C₄alkyl, C₁-C₄alkoxy, C₁-C₄haloalkyl, C₁-C₄haloalkoxy; R²is hydrogen, hydroxyl, halo, C₁-C₄alkyl, C₁-C₄alkoxy, C₁-C₄alkoxycarbonyl, C₁-C₄alkylthio, C₁-C₄alkylsulfonyl, optionally substituted phenyl or carbamoyl; Z is O or S(O)_p, p is 0 or 2; and m and n are 0 or 1.

As set forth in PCT Publication WO 03/022808A1 compounds of the following structures are reported to be insecticidally active:

where R¹is an aryl or heteroaryl that is optionally identically or differently substituted once or several times; R²and R³are independently selected from aryl or heteroaryl that is optionally identically or differently substituted once or several times, whereby both groups can also be bridged by a common substitutent; M is optionally substituted (CH₂)_I, where I is 1, 2 or 3, CO or —HNC(O); X is H, OH, halogen, OR⁴or CN; Y is (O), H, OH, OR⁴, R⁴; (in the last four groups, in which nitrogen has a positive charge, in combination with a corresponding anion); R⁴is identical or different and represents C₁-C₄alkyl, C₁-C₄alkanoyl, C₁-C₄haloalkyl; m is 0, 1, 2, 3 or 4; and n is 0 or 1.

There is no disclosure or suggestion in any of the citations set forth above of the azacycle derivatives of the present invention.

SUMMARY OF THE INVENTION

In accordance with the present invention, it has now been found that N-substituted azacycle derivatives of Formula I and salts thereof having a substituent X as indicated in the Formula have improved insecticidal activity. The compounds of formula I are represented by the following general formula I:

wherein;

m, q, r, t and u are independently selected from 0 or 1; and p is 0, 1, 2, or 3;

X is selected from halogen, hydroxyl, hydroxyalkyl, alkyl, alkoxy, haloalkyl, haloalkoxy, thio, alkylthio, acetoxyalkyl, azidoalkyl, aminoalkyl, acetylaminoalkyl, alkylsulfonyl, alkylsulfoxy, pentahalothio, cyano, nitro, acetyloxy, alkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, aryl, or aryloxy;

Y is selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, thio, alkylthio, pentahalothio, cyano, nitro, alkylsulfonyl, alkylsulfoxy, alkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, aryl, or aryloxy; or

X and Y taken together with —OCR¹²R¹³O—, form a 1,3-dioxolane ring; where

R¹²and R¹³are independently selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkylthio, cyano, nitro, alkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, aryl, or aryloxy; or

R¹²and R¹³taken together with (═O), form 1,3-dioxol-2-one ring;

R¹, R², R³, R⁴, and R⁵are independently selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, pentahalothio, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, dialkoxyalkylcarbonyl, alkoxycarbonylamino, alkylaminoxyalkyl, alkoxyiminoalkyl, alkenyloxyiminoalkyl, aryl, aryloxy, dioxanyl, dioxolanyl or either of R¹and R², or R²and R³, or R³and R⁴, or R⁴and R⁵taken together with —OC(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)₂—, —OC(R¹⁹)═N—, or —SC(R¹⁹)═N—, forming a benzo-fused ring, where R¹⁹is hydrogen, halogen, alkyl or haloalkyl; and, wherein at least one of R¹, R², R³, R⁴, and R⁵is other than hydrogen;

R⁷, R⁸, R⁹, R¹⁰, and R¹¹are independently selected from hydrogen, halogen, alkyl, hydroxy, hydroxyalkyl, hydroxyalkoxy, alkoxy, alkoxyalkyl, alkoxyiminoalkyl, haloalkoxyiminoalkyl, cyanoalkoxyiminoalkyl, cyanoiminothioalkylamino, alkenyloxyiminoalkyl, alkynyloxyiminoalkyl, cycloalkoxy, cycloalkylalkoxy, phenoxy, alkoxycarbonylphenoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkylthio, alkylsulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, cycloalkylaminosulfonyl, alkenyloxy, alkynyloxy, haloalkenyloxy, alkylsulfonyloxy, optionally substituted arylalkoxy, cyano, nitro, amino, alkylamino, alkylcarbonylamino, alkoxycarbonylamino, cycloalkylalkoxycarbonylamino, alkenyloxycarbonylamino, alkynyloxycarbonylamino, haloalkylcarbonylamino, alkoxyalkoxycarbonylamino, alkoxycarbonylamino, alkoxycarbonyloxy, alkenylaminocarbonyloxy, alkynylaminocarbonyloxy, (alkyl)(alkoxycarbonyl)amino, alkylsulfonylamino, optionally substituted (heteroaryl)(alkoxycarbonyl)amino, optionally substituted arylcarbonylamino, alkoxycarbonyl, alkylaminocarbonyloxy, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkylamino(thiocarbonyl)amino, dialkylphosphoroureidyl, acetoxyalkoxy, sulfonyloxyalkoxy, dialkoxyalkoxy, trialkoxyalkoxy, dialkoxyalkylacetal, trialkoxymethylorthoester, cyclic acetal, optionally substituted cyclic acetal, optionally substituted thienyl, optionally substituted 1,3-thiazolylalkoxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted aryloxyalkyl, optionally substituted arylaminocarbonyloxy, optionally substituted arylalkoxycarbonylamino, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted pyrrolyl, optionally substituted pyrazolyl, optionally substituted pyrazinyloxy, optionally substituted cycloalkylcarbonylamino, optionally substituted 1,3-oxazolinyl, optionally substituted 1,3-oxazolinyloxy, optionally substituted 1,3-oxazolinylamino, optionally substituted 1,2,4-triazolyl, optionally substituted 1,2,3-thiadiazolyl, optionally substituted 1,2,5-thiadiazolyl, optionally substituted 1,2,5-thiadiazolyloxy, optionally substituted 2H-tetrazolyl, optionally substituted pyridyl, optionally substituted pyridyloxy, optionally substituted pyridylamino, optionally substituted pyrimidinyl, optionally substituted pyrimidinyloxy, optionally substituted 3,4,5,6-tetrahydropyrimidinyloxy, optionally substituted pyridazinyloxy, or optionally substituted 1,2,3,4-tetrahydronaphthalenyl, wherein the optional substituent is selected from one or more of halogen, alkyl, haloalkyl, alkoxy, cyano, nitro, amino, alkylcarbonyl, alkoxycarbonyl, alkoxyiminoalkyl, dialkylacetal, alkylthiol, alkylsulfoxide, or alkoxycarbonylamino; and, wherein at least one of R⁷, R⁸, R⁹, R¹⁰, and R¹¹is other than hydrogen;

R is alkyl, cycloalkyl, alkenyl, alkoxycarbonyl, optionally substituted pyrid-2-yl wherein the optional substituent is selected from hydrogen, halogen, haloalkoxy or haloalkyl, or

substituted phenyl have the following structure,

where

R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸are independently selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, pentahalothio, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, dialkoxyalkylcarbonyl, alkoxycarbonylamino, alkylaminoxyalkyl, alkoxyiminoalkyl, alkenyloxyiminoalkyl, aryl, aryloxy, dioxanyl, dioxolanyl or either of R¹⁴and R¹⁵, or R¹⁵and R¹⁶, or R¹⁶and R¹⁷, or R¹⁷and R¹⁸taken together with —OC(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)₂—, —OC(R¹⁹)═N—, or —SC(R¹⁹)═N—, forming a benzo-fused ring, where R¹⁹is hydrogen, halogen, alkyl or haloalkyl; and, wherein at least one of R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸is other than hydrogen;

A is selected from —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂—, —OCH₂CH₂—, —OCH₂CH₂CH₂—, —OCH₂CH₂CH₂CH₂—, —OCH₂CH(OH)CH₂—, —NHCH₂CH₂—, —N(CH₃)CH₂CH₂—, —N[C(═O)CH₃]CH₂CH₂—, or —N[C(═O)OCH₃]CH₂CH₂—;

B is selected from —O—, —S—, —CH₂O—, —OCH₂—, —OC(═O)NH—, —OC(═O)O—, or —NHSO₂—;

when p is 1, 2, or 3;

D is —CH₂—;

R⁶is selected from alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, dialkylaminoalkyl, alkylaminocarbonyloxyalkyl, alkylthioalkyl, alkylsulfonylalkyl, alkylcarbonyloxyalkyl, alkoxycarbonylalkyl, carboxyalkyl, arylalkyl, arylcarbonyl, sulfonato, or sulfonatoalkyl, and may bear a negative charge resulting in an inner salt; and a separate ion is chloride, bromide, iodide, or an alkyl or phenyl sulfate or sulfonate; 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 agriculturally acceptable extender or adjuvant.

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. Other aspects of the present invention will become apparent.

DETAILED DESCRIPTION OF THE INVENTION

One aspect of the present invention relates to certain new and useful compounds, namely certain novel N-substituted azacycle derivatives as depicted in general formula I:

where

R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸are independently selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, pentahalothio, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, dialkoxyalkylcarbonyl, alkoxycarbonylamino, alkylaminoxyalkyl, alkoxyiminoalkyl, alkenyloxyiminoalkyl, aryl, aryloxy, dioxanyl, dioxolanyl or either of R¹⁴and R¹⁵, or R¹⁵and R¹⁶, or R¹⁶and R¹⁷, or R¹⁷and R¹⁸taken together with —OC(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)_2-0—, —OC(R¹⁹)₂(R¹⁹)₂—, —OC(R¹⁹)═N—, or —SC(R¹⁹)═N—, forming a benzo-fused ring, where R¹⁹is hydrogen, halogen, alkyl or haloalkyl; and, wherein at least one of R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸is other than hydrogen;

A is selected from —CH₂—, —CH₂CH₂—, —CH₂CH₂CH₂—, —OCH₂CH₂—, —OCH₂CH₂CH₂—, —OCH₂CH₂CH₂CH₂—, —OCH₂CH(OH)CH₂—, —NHCH₂CH₂—, —N(CH₃)CH₂CH₂—, —N[C(═O)CH₃]CH₂CH₂—, or —N[C(═O)OCH₃]CH₂CH₂—;

B is selected from —O—, —S—, —CH₂O—, —OCH₂—, —OC(═O)NH—, —OC(═O)O—, or —NHSO₂—;

when p is 1, 2, or 3;

D is —CH₂—;

Within the scope set forth above, preferred compounds of the present invention are those of formula I wherein m, q and p are 0; t and u are 1; A is —CH₂—; X is selected from halogen, hydroxyl or alkoxycarbonyl; Y is selected from hydrogen, halogen or hydroxyl; R¹, R², R³and R⁴are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy, —CH₂(OH)CH₃, —CH═NOC₂H₅, 1,3-dioxolan-2-yl, or R²and R³taken together with —OCF₂O—; R⁵is hydrogen; R⁷, R¹⁰and R¹¹are hydrogen; R⁵is selected from hydrogen, halogen, alkyl or alkoxy; R⁹is selected from alkoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, cyclopropylmethoxy, 2-halophenoxy, 3-halophenoxy, 4-halophenoxy, pyrimidin-2-yl, pyrid-2-yl, 3-halo-pyrid-2-yl, 3-alkyl-pyrid-2-yloxy, 4-alkyl-pyrid-2-yloxy, 5-alkyl-pyrid-2-yloxy, 6-alkyl-pyrid-2-yloxy, 3-halo-pyrid-2-yloxy, 3-trihaloalkyl-pryid-2-yloxy, 3-cyano-pyrid-2-yloxy, 5-cyano-pyrid-2-yloxy, 6-dialkoxyalkyl-pyrid-2-yloxy, pyrid-2-yloxy, CO₂CH(CH₃)₂, —CH═NOCH₃, —CH═NOC₂H₅, —CH═NOCH₂CF₃, —CH═NOCH₂CH═CH₂, —CH═NOCH₂CN, —CH═NOCH(CH₃)₂, —CH═NOCH₂C≡CH, —CH═NOCH₂CH₂F, —CH═NOCH₂CH₂OCH₃, —CH═NOCH₂OC₂H₅, —CH═NOCH₂CH₂OCH₂CH₂OCH₃, —NHCO₂CH₃, —NHCO₂C₂H₅, —NHCO₂CH(CH₃)₂, —NHCO₂CH₂-c-C₃H₅, —CH(OH)C₆H₅-p-Cl, —OC(═O)NHCH₃, —OC(═O)NHC₂H₅, —OC(═O)NHCH(CH₃)₂, —NHC(SCH₃)═NCN, pyrimidin-2-yloxy, 6-halo-pyridazin-3yloxy, 6-alkoxy-pyridazin-3yloxy, 6-alkyl-pyridazin-3yloxy, 2-alkyl-2H-tetrazol-5-yl, 1,3-dioxan-2-yl or 5,5-dialkyl-1,3-dioxan-2-yl; and R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸,

where

R¹⁴, R¹⁵, R¹⁶and R¹⁷are independently selected from halogen, haloalkyl, haloalkoxy or R¹⁵and R¹⁶taken together with —OCF₂O—; and R¹⁸is hydrogen.

Within the scope set forth above, more preferred compounds of the present invention are those of formula I wherein X is selected from halogen, —CO₂C₂H₅or hydroxyl; and R⁹is selected from —OC₂H₅, —OC₃H₇, —OCH(CH₃)₂, —OCH₂CH₂OCH₃, —OCH₂CH₂CH₂OCH₃, cyclopropylmethoxy, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, pyrimidin-2-yl, pyrid-2-yl, 3-chloro-pyrid-2-yl, 3-methyl-pyrid-2-yloxy, 4-methyl-pyrid-2-yloxy, 5-methyl-pyrid-2-yloxy, 6-methyl-pyrid-2-yloxy, 3-chloro-pyrid-2-yloxy, 3-trifluoromethyl-pryid-2-yloxy, 3-cyano-pyrid-2-yloxy, 5-cyano-pyrid-2-yloxy, 6-dimethoxymethyl-pyrid-2-yloxy, pyrid-2-yloxy, —CO₂CH(CH₃)₂, —CH═NOCH₃, —CH═NOC₂H₅, —CH═NOCH₂CF₃, —CH═NOCH₂CH═CH₂, —CH═NOCH₂CN, —CH═NOCH(CH₃)₂, —CH═NOCH₂C≡CH, —CH═NOCH₂CH₂F, —CH═NOCH₂CH₂OCH₃, —CH═NOCH₂OC₂H₅, —CH═NOCH₂CH₂OCH₂CH₂OCH₃, —NHCO₂CH₃, —NHCO₂C₂H₅, —NHCO₂CH(CH₃)₂, —NHCO₂CH₂-c-C₃H₅, —CH(OH)C₆H₅-p-Cl, —OC(═O)NHCH₃, —OC(═O)NHC₂H₅, —OC(═O)NHCH(CH₃)₂, —NHC(SCH₃)═NCN, pyrimidin-2-yloxy, 6-chloro-pyridazin-3yloxy, 6-methoxy-pyridazin-3yloxy, 6-methyl-pyridazin-3yloxy, 2-methyl-2H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 1,3-dioxan-2-yl or 5,5-dimethyl-1,3-dioxan-2-yl.

Within the scope set forth above, even more preferred compounds of the present invention are those of formula I wherein X is selected from fluorine, —CO₂C₂H₅or hydroxyl; Y is selected from hydrogen, fluorine, chlorine or hydroxyl; R¹, R², R³and R⁴are independently selected from hydrogen, halogen, alkyl, tert-butyl, methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, —OCF₂CHFCF₃, —CH₂(OH)CH₃, —CH═NOC₂H₅, 1,3-dioxolan-2-yl, or R²and R³taken together with —OCF₂O—; R⁵is hydrogen; R⁹is selected from —OCH₂CH₂OCH₃, —CH═NOCH₃, —CH═NOC₂H₅, —CH═NOCH₂CN, —CH═NOCH₂CH₂OCH₃, —NHCO₂CH(CH₃)₂, —OC(═O)NHCH(CH₃)₂, pyrimidin-2-yl, pyrid-2-yl, 3-chloro-pyrid-2-yl, 3-methyl-pyrid-2-yloxy, 4-methyl-pyrid-2-yloxy, 5-methyl-pyrid-2-yloxy, 6-methyl-pyrid-2-yloxy, 3-chloro-pyrid-2-yloxy, 3-trifluoromethyl-pryid-2-yloxy, 3-cyano-pyrid-2-yloxy, 5-cyano-pyrid-2-yloxy, 6-dimethoxymethyl-pyrid-2-yloxy, pyrid-2-yloxy, pyrimidin-2-yloxy, 6-chloro-pyridazin-3yloxy, 6-methoxy-pyridazin-3yloxy or 6-methyl-pyridazin-3yloxy; and R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸,

where

R¹⁴, R¹⁵, R¹⁶and R¹⁷are independently selected from fluorine, chlorine, trifluoromethyl, difluoromethoxy, trifluoromethoxy, —OCF₂CHFCF₃or R¹⁵and R¹⁶taken together with —OCF₂O—.

Within the scope set forth above, most preferred compounds of the present invention are those of formula I wherein X is hydroxyl; Y is hydrogen; R³is haloalkoxy; R⁹is selected —OCH₂CH₂OCH₃, —CH═NOCH₃, —CH═NOC₂H₅, —CH═NOCH₂CN, —CH═NOCH₂CH₂OCH₃, —NHCO₂CH(CH₃)₂, OC(═O)NHCH(CH₃)₂, pyrid-2-yloxy, pyrid-2-yl, 3-cyano-pyrid-2-yloxy, 5-methyl-pyrid-2-yloxy, pyrimidin-2-yloxy, pyrimidin-2-yl, 6-chloro-pyridazin-3-yloxy or 6-methoxy-pyridazin-3-yloxy; and R¹⁶is haloalkoxy.

An embodiment of the present invention is a compound of formula I:

wherein;

m, q and r are independently selected from 0 or 1; t and u are 1; and p is 0;

X is selected from halogen, hydroxyl, hydroxyalkyl, alkyl, alkoxy, haloalkyl, haloalkoxy, thio, alkylthio, acetoxyalkyl, azidoalkyl, aminoalkyl, acetylaminoalkyl, alkylsulfonyl, alkylsulfoxy, pentahalothio, cyano, nitro, acetyloxy, alkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, aryl, or aryloxy;

Y is selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, thio, alkylthio, pentahalothio, cyano, nitro, alkylsulfonyl, alkylsulfoxy, alkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, aryl, or aryloxy; or

X and Y taken together with —OCR¹²R¹³O—, form a 1,3-dioxolane ring; where

R¹²and R¹³are independently selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkylthio, cyano, nitro, alkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, aryl, or aryloxy; or

R¹²and R¹³taken together with (═O), form 1,3-dioxol-2-one ring;

R¹, R², R³, R⁴, and R⁵are independently selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyl, hydroxyalkyl, alkoxy, haloalkoxy, thio, alkylthio, haloalkylthio, pentahalothio, cyano, nitro, alkylsulfonyl, haloalkylsulfonyl, alkylsulfinyl, haloalkylsulfinyl, alkylsulfonyloxy, haloalkylsulfonyloxy, alkylcarbonyl, alkoxycarbonyl, dialkoxyalkylcarbonyl, alkoxycarbonylamino, alkylaminoxyalkyl, alkoxyiminoalkyl, alkenyloxyiminoalkyl, aryl, aryloxy, dioxanyl, dioxolanyl or either of R¹and R², or R²and R³, or R³and R⁴, or R⁴and R⁵taken together with —OC(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)₂O—, —OC(R¹⁹)₂(R¹⁹)₂—, —OC(R¹⁹)═N—, or —SC(R¹⁹)═N—, forming a benzo-fused ring, where R¹⁹is hydrogen, halogen, alkyl or haloalkyl; and, wherein at least one of R¹, R², R³, R⁴, and R⁵is other than hydrogen;

R⁷, R⁸, R⁹, R¹⁰, and R¹¹are independently selected from hydrogen, halogen, alkyl, hydroxy, hydroxyalkyl, hydroxyalkoxy, alkoxy, alkoxyalkyl, alkoxyiminoalkyl, haloalkoxyiminoalkyl, cyanoalkoxyiminoalkyl, cyanoiminothioalkylamino, alkenyloxyiminoalkyl, alkynyloxyiminoalkyl, cycloalkoxy, cycloalkylalkoxy, phenoxy, alkoxycarbonylphenoxy, alkoxyalkoxy, alkoxyalkoxyalkoxy, alkylthio, alkylsulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, cycloalkylaminosulfonyl, alkenyloxy, alkynyloxy, haloalkenyloxy, alkylsulfonyloxy, optionally substituted arylalkoxy, cyano, nitro, amino, alkylamino, alkylcarbonylamino, alkoxycarbonylamino, cycloalkylalkoxycarbonylamino, alkenyloxycarbonylamino, alkynyloxycarbonylamino, haloalkylcarbonylamino, alkoxyalkoxycarbonylamino, alkoxycarbonylamino, alkoxycarbonyloxy, alkenylaminocarbonyloxy, alkynylaminocarbonyloxy, (alkyl)(alkoxycarbonyl)amino, alkylsulfonylamino, optionally substituted (heteroaryl)(alkoxycarbonyl)amino, optionally substituted arylcarbonylamino, alkoxycarbonyl, alkylaminocarbonyloxy, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkylamino(thiocarbonyl)amino, dialkylphosphoroureidyl, acetoxyalkoxy, sulfonyloxyalkoxy, dialkoxyalkoxy, trialkoxyalkoxy, dialkoxyalkylacetal, trialkoxymethylorthoester, cyclic acetal, optionally substituted cyclic acetal, optionally substituted thienyl, optionally substituted 1,3-thiazolylalkoxy, optionally substituted aryl, optionally substituted aryloxy, optionally substituted aryloxyalkyl, optionally substituted arylaminocarbonyloxy, optionally substituted arylalkoxycarbonylamino, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted pyrrolyl, optionally substituted pyrazolyl, optionally substituted pyrazinyloxy, optionally substituted cycloalkylcarbonylamino, optionally substituted 1,3-oxazolinyl, optionally substituted 1,3-oxazolinyloxy, optionally substituted 1,3-oxazolinylamino, optionally substituted 1,2,4-triazolyl, optionally substituted 1,2,3-thiadiazolyl, optionally substituted 1,2,5-thiadiazolyl, optionally substituted 1,2,5-thiadiazolyloxy, optionally substituted 2H-tetrazolyl, optionally substituted pyridyl, optionally substituted pyridyloxy, optionally substituted pyridylamino, optionally substituted pyrimidinyl, optionally substituted pyrimidinyloxy, optionally substituted 3,4,5,6-tetrahydropyrimidinyloxy, optionally substituted pyridazinyloxy, or optionally substituted 1,2,3,4-tetrahydronaphthalenyl, wherein the optional substituent is selected from one or more of halogen, alkyl, haloalkyl, alkoxy, cyano, nitro, amino, alkylcarbonyl, alkoxycarbonyl, alkoxyiminoalkyl, dialkylacetal, alkylthiol, alkylsulfoxide, or alkoxycarbonylamino; and, wherein at least one of R⁷, R⁸, R⁹, R¹⁰, and R¹¹is other than hydrogen;

R is alkyl, cycloalkyl, alkenyl, alkoxycarbonyl, optionally substituted pyrid-2-yl wherein the optional substituent is selected from hydrogen, halogen, haloalkoxy or haloalkyl, or

substituted phenyl have the following structure,

Another embodiment of the present invention is a compound of formula I:

wherein;

r is selected from 0 or 1; m, q and p are 0; t and u are 1;

A is —CH₂—;

X is selected from halogen or hydroxyl;

Y is selected from hydrogen or hydroxyl;

R¹, R², R³and R⁴are independently selected from hydrogen, halogen, alkyl, alkoxy, haloalkyl, haloalkoxy or —CH═NOC₂H₅;

R⁵is hydrogen;

R⁷, R⁸, R¹⁰and R¹¹are hydrogen;

R⁹is selected from —OC₂H₅, —OC₃H₇, —OCH(CH₃)₂, —OCH₂CH₂OCH₃, —OCH₂CH₂CH₂OCH₃, cyclopropylmethoxy, 2-chlorophenoxy, 3-chlorophenoxy, 4-chlorophenoxy, pyrimidin-2-yl, pyrid-2-yl, 3-chloro-pyrid-2-yl, 3-methyl-pyrid-2-yloxy, 4-methyl-pyrid-2-yloxy, 5-methyl-pyrid-2-yloxy, 6-methyl-pyrid-2-yloxy, 3-chloro-pyrid-2-yloxy, 3-trifluoromethyl-pryid-2-yloxy, 3-cyano-pyrid-2-yloxy, 5-cyano-pyrid-2-yloxy, 6-dimethoxymethyl-pyrid-2-yloxy, pyrid-2-yloxy, CO₂CH(CH₃)₂, —CH═NOCH₃, —CH═NOC₂H₅, —CH═NOCH₂CF₃, —CH═NOallyl, —CH═NOCH₂CH═CH₂, —CH═NOCH₂CN, —CH═NOCH(CH₃)₂, —CH═NOCH₂C≡CH, —CH═NOCH₂CH₂F, —CH═NOCH₂CH₂OCH₃, —CH═NOCH₂OC₂H₅, —CH═NOCH₂CH₂OCH₂CH₂OCH₃, —NHCO₂CH₃, —NHCO₂C₂H₅, —NHCO₂CH(CH₃)₂, —NHCO₂CH₂-c-C₃H₅, —CH(OH)C₆H₅-p-Cl, —OC(═O)NHCH₃, —OC(═O)NHC₂H₅, —OC(═O)NHCH(CH₃)₂, —NHC(SCH₃)═NCN, pyrimidin-2-yloxy, 6-chloro-pyridazin-3yloxy, 6-methoxy-pyridazin-3yloxy, 6-methyl-pyridazin-3yloxy, 2-methyl-2H-tetrazol-5-yl, 2-ethyl-2H-tetrazol-5-yl, 1,3-dioxan-2-yl or 5,5-dimethyl-1,3-dioxan-2-yl; and

R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, and R¹⁸,

where

R¹⁶is selected from haloalkyl or haloalkoxy, and R¹⁴, R¹⁵, R¹⁷and R¹⁸are hydrogen.

Another embodiment of the present invention is a compound of formula I-H or I-J:

wherein,

R³is haloalkyl or haloalkoxy;

R⁹is selected from —OCH₂CH₂OCH₃, pyrid-2-yloxy, pyrid-2-yl, 3-cyano-pyrid-2-yloxy, 5-methyl-pyrid-2-yloxy, pyrimidin-2-yloxy, pyrimidin-2-yl, 6-chloro-pyridazin-3-yloxy or 6-methoxy-pyridazin-3-yloxy; and R¹⁶is haloalkyl or haloalkoxy.

Yet another embodiment of the present invention is the compound:

namely, 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-hydroxy-1-[(4-(2-pyridyloxy)phenyl)methyl]piperidin-1-oxide, and agriculturally-acceptable salts thereof.

In certain cases the compounds within the scope of formula I may possess asymmetric centers, which can give rise to optical enantiomorphs and diastereomers. Compounds within the scope of formula I may exist in two or more forms, i.e., polymorphs, which are significantly different in physical and chemical properties. Compounds within the scope of formula I may also exist as tautomers, which are in equilibrium. Compounds within the scope of formula I 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, oleic acid, octanoic acid, 2-ethylhexanoic acid, alkyl 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, and, optionally, an effective amount of at least one second compound, with at least one agriculturally acceptable extender or adjuvant.

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, other areas where insects are present or are expected to be present, or adjacent to 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 insects in greenhouse crops, nursery crops, ornamentals, turfs, forestry, stored food and fiber products, structures, livestock, households, and public and animal health, for example, ants, flies, cockroaches, white grubs, dry wood termites and subterranean termites as well as other insects; and also for use in promotion of animal and human health as pharmaceutical agents and compositions thereof.

As used in this specification and unless otherwise indicated the substituent terms “alkyl”, “alkenyl”, “alkynyl”, “alkoxy”, “alkenyloxy”, and “alkynyloxy” used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms, wherein “alkenyl” has at least one carbon to carbon double bond, and “alkynyl” has at least one carbon to carbon triple bond. The term “aryl” refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, phenyl and naphthyl. The term “heteroaryl” refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, and in which one or more of the atoms in the ring is other than carbon, for example, sulfur, oxygen, or nitrogen. The term “THF” refers to tetrahydrofuran. The term “DMSO” refers to methyl sulfoxide. The term “DMF” refers to N,N-dimethylformamide. 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.

Scheme 1 below illustrates a general procedure for synthesizing compounds of formula I, where, for example, m, p, and q are 0; t and u are 1; r is 0 or 1, and if r is 1 an N-oxide is formed; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷and R¹⁸; X is OH or F; Y, R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are H; R³and R¹⁶are —OCF₃; and R⁹is pyrimidin-2-yloxy.

In a first step as depicted in Scheme 1, an appropriately substituted alcohol, for example, the known compound (4-pyrimidin-2-yloxyphenyl)methan-1-ol, is halogenated with, for example thionyl chloride, to afford the corresponding 2-[4-(chloromethyl)phenoxy]pyrimidine (A). Intermediate (A) is then reacted under basic conditions with an appropriately substituted cyclic amine derivative, for example, the known compound 4-piperidone hydrochloride monohydrate, to afford the corresponding 1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-one (B). A mixture of intermediate (B) and an appropriately substituted haloalkyl derivative, for example bis(trifluoromethoxyphenyl)bromomethane, is reacted in the presence of n-butyl lithium, to afford the corresponding 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-ol (I-A). Intermediate (I-A) is then oxidized, with for example hydrogen peroxide, in an appropriate solvent, to form an N-oxide, a compound of formula I-C. In a separate synthesis, intermediate (I-A) is reacted with a thiohalide, for example (dimethylamino)sulfur trifluoride, to provide halogen-derived compounds of formula I-D, wherein X is, for example fluorine. Examples 1 and 3, set forth below, provide detailed methods to how compounds of formula I (-A, -C and -D) shown in Scheme 1 were prepared.

Scheme 2 below illustrates a general procedure for synthesizing compounds of formula I similar to those set forth in Scheme 1, differing in that Y is OH; X is OH; r is 0; and R⁹is 2-methyl-2H-tetrazol-5-yl.

In a first step as depicted in Scheme 2, an appropriately substituted phenyl derivative, for example, the known compound 2-methyl-5-(4-methylphenyl)-1,2,3,4-tetrazole, is brominated with, for example N-bromosuccinimide and light, to afford the corresponding 5-[4-(bromomethyl)phenyl]-2-methyl-1,2,3,4-tetrazole (A1). Intermediate (A1) is then reacted under basic conditions with an appropriately substituted cyclic amine derivative, for example, the known compound 4-piperidone hydrochloride monohydrate, to afford the corresponding 1-{[4-(2-methyl-1,2,3,4-tetrazol-5-yl)phenyl]methyl}piperidin-4-one (B1). Intermediate (B1) is then reacted under acidic conditions with, for example sodium cyanide, to afford the corresponding nitrile compound, 4-hydroxy-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carbonitrile (C1). Intermediate (C1) is esterified under acidic conditions with, for example ethanol, to afford the corresponding ethyl 4-hydroxy-1-{[4-(2-methyl-(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carboxylate (D1). The Grignard of an appropriately substituted halophenyl derivative, for example 4-trifluoromethoxybromobenzene, is reacted with intermediate (D1) to provide compounds of formula I-B, wherein X and Y are, for example hydroxyl. Example 2, set forth below, provides detailed methods to how compounds of formula I (-B) shown in Scheme 2 were prepared.

Scheme 3 below illustrates a general procedure for synthesizing compounds of formula I similar to those set forth in Scheme 1, differing in that Y is Cl; X is —CO₂C₂H₅; r is 0; R³and R¹⁶are —CF₃; and R⁹is pyrid-2-yloxy.

In a first step as depicted in Scheme 3, an appropriately substituted piperidine, for example, the known compound ethyl 1-[(tert-butyl)oxycarbonyl]piperidine-4-carboxylate, is enolated, with for example lithium diisopropylamide, and then reacted under basic conditions with an appropriately substituted phenyl ketone, for example di-4-(trifluoromethyl)phenyl ketone, to afford the corresponding ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]hydroxymethyl}piperidine-4-carboxylate (A2). Intermediate (A2) is then chlorinated with, for example thionyl chloride, to afford the corresponding ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate (B2). The (tert-butyl)oxycarbonyl group is cleaved under acidic conditions from the piperidine ring of (B2), to afford the corresponding 4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate (C2). Intermediate (C2) is then reacted under basic conditions with an appropriately substituted haloalkylphenyl derivative, for example 2-[4-(chloromethyl)phenoxy]pyridine, to provide compounds of formula I-D, wherein X is, for example an alkoxycarbonyl and Y is, for example chlorine. Example 4, set forth below, provides detailed methods to how compounds of formula I (-D) shown in Scheme 3 were prepared.

Scheme 4 below illustrates a general procedure for synthesizing compounds of formula I, where, for example, m, p, and q are 0; t and u are 1; r is 0 or 1, and if r is 1 an N-oxide is formed; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷and R¹⁸; X is OH; Y, R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are H; R³and R¹⁶are —OCF₃; and R⁹is pyrid-2-yloxy.

In the first step as depicted in Scheme 4, two appropriately substituted aryl halides, for example, the known compound 4-bromo-1-(trifluoromethoxy)benzene (A3), were cross-coupled with a Grignard reagent and an alkyl formate, for example, ethyl formate to form bis[4-(trifluoromethoxy)phenyl]methan-1-ol (B3). Intermediate (B3) was then reacted under acidic conditions with hydrogen bromide, to afford the corresponding bis(trifluoromethoxyphenyl)bromomethane (C3). Intermediate (C3) was then lithiated, for example with butyl lithium, and then reacted with an appropriately N-substituted piperidin-4-one, formula (D3), for example 1-benzylpiperidin-4-one, at a temperature in the range of −85° C. to −60° C. to afford the corresponding 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-benzylpiperidin-4-ol (E3). Intermediate (E3) was then reacted with an acid, for example formic acid, in the presence of a catalyst, for example a palladium catalyst, to form the hydrogen chloride salt of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}piperidin-4-ol (F3). Next, an appropriately substituted phenol, for example, the known compound 4-hydroxybenzaldehyde, was cross-coupled with a halopyridine, for example 2-chloropyridine, in the presence of potassium carbonate and a catalytic amount of copper oxide at a temperature in the range of 145° C. to 170° C. to form 4-(2-pyridyloxy)benzaldehyde (G3). Intermediate (F3) was then cross-coupled with Intermediate (G3) in the presence of sodium triacetoxyborohydride to form 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-[(4-(2-pyridyloxy)phenyl)methyl]piperidin-4-ol (I-A). Intermediate (I-A) was then oxidized with hydrogen peroxide at a temperature in the range of 40° C. to 55° C. to form a compound of formula I-C.

Scheme 5 below illustrates a general procedure for synthesizing compounds of formula I, where, for example, m, p, and q are 0; t and u are 1; r is 0 or 1, and if r is 1 an N-oxide is formed; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷and R¹⁸; X is OH; Y, R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are H; R³and R¹⁶are —OCF₃; and R⁹is pyrid-2-yloxy.

In the first step of Scheme 5, an appropriately substituted phenol, for example, the known compound 4-methyl phenol, can be cross-coupled with a halopyridine, for example 2-chloropyridine, in the presence of potassium carbonate and a catalytic amount of copper oxide at a temperature in the range of 145° C. to 170° C. to form 2-(4-methylphenoxy)pyridine (A4). Intermediate (A4) can then be halogenated with, for example bromine, to form 2-[4-(bromomethyl)phenoxy]pyridine (B4). Intermediate (F3), made as in Scheme 4, can then be cross-coupled with Intermediate (B4) in the presence of potassium carbonate to form 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-[(4-(2-pyridyloxy)phenyl)methyl]piperidin-4-ol (I-A). Intermediate (I-A) can then be oxidized as in Scheme 4 to form a compound of formula I-C.

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 product 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 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-(4-chloro-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-[[[[(4-chloro-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-(6-chloro-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, biphenthrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomehtrin, tefluthrin, cycloprothrin, betacyfluthrin, and acrinathrin; carbamate insecticides, such as aldecarb, carbaryl, carbofuran, and methomyl; organochlorine insecticides, such as endosulfan, endrin, heptachlor, and lindane; benzoylurea insecticides, such as diflubenuron, triflumuron, teflubenzuron, chlorfluazuron, flucycloxuron, hexaflumuron, flufenoxuron, and lufenuron; and other insecticides, such as amitraz, clofentezine, fenpyroximate, hexythiazox, spinosad, and imidacloprid.

When the active insecticidal compounds of the present invention are used in combination with one or more 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 the preparation of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-hydroxy-1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-1-oxide (Compound 112 in table below)
Step A Synthesis of 2-[4-(chloromethyl)phenoxy]pyrimidine as an Intermediate

A stirred solution of 2.0 grams (0.0099 mole) of (4-pyrimidin-2-yloxyphenyl)methan-1-ol (known compound) and 7 drops of pyridine in 50 mL of methylene chloride was cooled in an ice-water bath, and 0.94 mL (0.013 mole) of thionyl chloride was added dropwise. Upon completion of the addition, the reaction mixture was stirred for 3 hours at 10° C. to 20° C. The reaction mixture was then poured into ice-water and basified using sodium bicarbonate. The aqueous layer was separated from the organic layer, and was extracted one time with 75 mL of methylene chloride. The methylene chloride extract and organic layer were combined and passed through silicone coated filter paper. The fitrate was then concentrated under reduced pressure, yielding 2.1 grams of the subject compound.

Step B Synthesis of 1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-one as an Intermediate

A solution of 1.47 grams (0.0096 mole) of 4-piperidone monohydrate hydrochloride, 2.1 grams (0.0096 mole) of 2-[4-(chloromethyl)phenoxy]pyrimidine, and 4.34 grams (0.0336 mole) of bis(methylethyl)ethylamine in 35 mL of dimethylsulfoxide (DMSO) was stirred at ambient temperature for about 24 hours. The reaction mixture was then diluted with 200 mL of water and was extracted two times with 200 mL of ethyl acetate. The extracts were then combined and washed two times with 75 mL of an aqueous mixture of 10% lithium chloride. The resultant organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica get using 1:2 ethyl acetate:petroleum ether as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 2.71 grams of the subject compound.

Step C Synthesis of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-ol as an Intermediate

A stirred solution of 0.8 gram (0.0019 mole) of bis(trifluoromethoxyphenyl)bromomethane and 2.2 grams (0.0078 mole) of 1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-one in 50 mL of THF was chilled to −78° C., and 1.5 mL of n-butyl lithium (2.5 M) was added dropwise during a 15-minute period while maintaining the temperature of the reaction mixture between −80° C. to −70° C. The reaction mixture was then allowed to warm to about 0° C. The reaction mixture was quenched with a saturated aqueous solution of ammonium chloride, and the mixture was extracted two times with 75 mL of ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 1:4 acetone:methylene chloride as an eluant. The appropriate fractions were combined and further purified by passing them through a Waters SEP-PAK® Vac 35 cc NH2 Cartridge (purchased from Waters, 34 Maple Street, Milford, Mass. 01757) using 1:4 ethyl acetate:petroleum ether as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.42 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step D Synthesis of Compound 112

A solution of 0.28 gram (0.00045 mole) of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-ol and 1.4 grams of 50% aqueous hydrogen peroxide in 40 mL of methanol was stirred at ambient temperature for about 4 days. The reaction mixture was then diluted with 200 mL of water and extracted twice with 200 mL each of ethyl acetate. The combined extracts were then washed twice with 75 mL each of aqueous mixture of 10% lithium chloride. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica get using 1:2 ethyl acetate:petroleum ether as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.29 gram of Compound 112.

Example 2
This example illustrates the preparation of 4-{bis[4-(trifluoromethoxy)phenyl]hydroxymethyl}-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidin-4-ol (Compound 93 in the table below)
Step A Synthesis of 5-[4-(bromomethyl)phenyl]-2-methyl-1,2,3,4-tetrazole as an Intermediate

A stirred solution of 45 grams (0.258 mole) of 2-methyl-5-(4-methylphenyl)-1,2,3,4-tetrazole (known compound), 46 grams (1 equivalent) of N-bromosuccinimide, and a catalytic amount of benzoyl peroxide in 200 mL of carbon tetrachloride was irradiated with light during a 3.5 hour period. The mixture was then cooled in an ice bath and filtered to collect 35.1 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B Synthesis of 1-{[4-(2-methyl-1,2,3,4-tetrazol-5-yl)phenyl]methyl}piperidin-4-one as an Intermediate

A solution of 23 grams (0.091 mole) of 5-[4-(bromomethyl)phenyl]-2-methyl-1,2,3,4-tetrazole, 14 grams (0.091 mole) of 4-piperidone monohydrate hydrochloride, and 47 mL (3 equivalents) of N,N-diisopropylethylamine in 200 mL of dimethylsulfoxide (DMSO) was stirred for about 3 days. The reaction was quenched by pouring the reaction mixture onto 400 mL of dilute, cold sodium hydroxide. The resultant solution was extracted one time with 300 mL of ethyl acetate. An emulsion formed, which was broken up by warming it to about 35° C. The organic layer was separated and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 40:1 methylene chloride:methanol as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 9.12 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C Synthesis of 4-hydroxy-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carbonitrile as an Intermediate

A stirred solution of 8.62 grams (0.032 mole) of 1-{[4-(2-methyl-1,2,3,4-tetrazol-5-yl)phenyl]methyl}piperidin-4-one in 100 mL of ether and 150 mL of water was cooled to about 10° C. and 3.9 grams (2.5 equivalents) of sodium cyanide was added in one portion. To this was added 6.6 mL (2.5 equivalents) of hydrochloric acid (12 M) dropwise while maintaining the reaction mixture temperature at about 10° C. Upon completion of the addition, the reaction mixture was stirred for 1.5 hours while warming to ambient temperature. The reaction mixture was then poured into 200 mL of water, to which was then added 200 mL of ethyl acetate. The organic layer was separated and concentrated under reduced pressure to yield 9.6 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step D Synthesis of ethyl 4-hydroxy-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carboxylate as an Intermediate

A solution of 9.6 grams (0.032 mole) of 4-hydroxy-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carbonitrile in 200 mL of ethanol was saturated with gaseous hydrogen chloride, and then it was stirred at 55° C. for about 20 hours. The reaction mixture was allowed to cool and then it was poured onto 500 mL of ice. The resultant mixture was basified with 50% sodium hydroxide and extracted once with 300 mL of ethyl acetate. The extract was washed three times with 80 mL brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to a residue, yielding 5.14 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step E Synthesis of Compound 93

A solution of 1.6 grams (4.5 equivalents) of magnesium and 8.9 mL (4 equivalents) of 4-trifluoromethoxybromobenzene (known compound) in 75 mL of THF was stirred and 5.14 grams (0.0149 mole) of ethyl 4-hydroxy-1-{[4-(2-methyl(1,2,3,4-tetrazol-5-yl))phenyl]methyl}piperidine-4-carboxylate was added in one portion. After a mild exotherm, the reaction mixture was heated to 50° C. where it was stirred for 2 hours. The reaction mixture was allowed to cool to ambient temperature as it stirred for 72 hours; then it was poured into 200 mL of an aqueous solution saturated with ammonium chloride. The mixture was extracted one time with 200 mL of ethyl acetate, and the extract was washed two times with 80 mL of brine. The extract was dried with magnesium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using diethyl ether as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 9.29 grams of Compound 93.

Example 3
This example illustrates the preparation of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-fluoro-1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidine (Compound 192 in the table below)

A stirred solution of 0.11 gram (0.170 mmole) of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-[(4-pyrimidin-2-yloxyphenyl)methyl]piperidin-4-ol (prepared as in Example 1, Steps A through C) in 2.0 mL of methylene chloride was cooled to −40° C., and 18.2 μL (0.186 mmoles) of (dimethylamino)sulfur trifluoride was added. The reaction mixture was allowed to warm to ambient temperature where it stirred for 20 minutes. The reaction mixture was then poured onto 10 mL of an aqueous solution saturated with sodium bicarbonate, and the mixture was extracted with three 20 mL portions of ethyl acetate. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 1:1 ethyl acetate:hexane as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 85 milligrams of Compound 192. The NMR spectrum was consistent with the proposed structure.

Example 4
This example illustrates the preparation of ethyl 4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}-1-[(4-(2-pyridyloxy)phenyl)methyl]piperidine-4-carboxylate (Compound 195 in the table below)
Step A Synthesis of ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]hydroxymethyl}piperidine-4-carboxylate as an Intermediate

A stirred solution of 1 mL of diisopropyl amine in10 mL THF was cooled to about 0° C. and 2.55 mL of n-butyl lithium (2.5 M in hexane) was added slowly. The reaction mixture was stirred for 15 minutes, then it was cooled to −78° C. To this was then added a solution of 1.26 grams (4.9 mmole) of ethyl 1-[(tert-butyl)oxycarbonyl]piperidine-4-carboxylate (known compound) in 10 mL of THF. The reaction mixture continued to stir at −78° C. for 1 hour, then a solution of 1.56 grams (4.9 mmole) of di-4-(trifluoromethyl)phenyl ketone (known compound) in 5 mL of THF was added. Upon completion of the addition, the reaction mixture was warmed to ambient temperature during a 14 hour period. The reaction was then quenched by adding 125 mL of aqueous 5% hydrochloric acid to the reaction mixture. The mixture was then extracted with three 125 mL portions of ethyl acetate and the combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 1:5 ethyl acetate:hexane as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 2.2 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B Synthesis of ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate as an Intermediate

A solution of 290 milligrams (0.504 mmole) of ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]hydroxymethyl}piperidine-4-carboxylate, 110 μL (1.513 mmole) of thionyl chloride, and 408 μL (5.04 mmole) of pyridine in 5 mL of methylene chloride was stirred at ambient temperature for 1 hour. The reaction mixture was then poured into 25 mL of an aqueous solution saturated with sodium bicarbonate, and the mixture was extracted with three 50 mL portions of ethyl acetate. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 1:10 ethyl acetate:hexane as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 240 milligrams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C Synthesis of ethyl 4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate as an Intermediate

A solution of 190 milligrams (0.320 mmole) of ethyl 1-[(tert-butyl)oxycarbonyl]-4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate and 2 mL of trifluoro acetic acid (TFA) in 0.5 mL of methylene chloride was stirred at room temperature for 10 minutes. The reaction mixture was then diluted with toluene and concentrated under reduced pressure, yielding 158 milligrams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step D Synthesis of Compound 195

A solution of 158 milligrams (0.320 mmole) of ethyl 4-{bis[4-(trifluoromethyl)phenyl]chloromethyl}piperidine-4-carboxylate, 78 milligrams (0.352 mmole) of 2-[4-(chloromethyl)phenoxy]pyridine and 0.28 mL of diisopropylethylamine in 4 mL of DMF was stirred at room temperature for 48 hours. The reaction mixture was then poured into 20 mL of an aqueous solution saturated with sodium bicarbonate, and the mixture was extracted with three 40 mL portions of ethyl acetate. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 1:5 ethyl acetate:hexane as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 42 milligrams of Compound 195. The NMR spectrum was consistent with the proposed structure.

Example 5
This example illustrates the preparation of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-hydroxy-1-{[4-(2-methoxyethoxy)phenyl]methyl}piperidin-1-oxide (Compound 385 in table below)
Step A Synthesis of 4-(2-methoxyethoxy)benzaldehyde as an Intermediate

A solution of 5.0 grams (0.041 mole) of 4-hydroxybenzaldehyde, 9.5 grams (0.041 mole) of p-toluene sulfonic acid 2-methoxyethyl ester, and 6.3 grams (0.046 mole) of anhydrous potassium carbonate in 50 mL of dimethylsulfoxide (DMSO) was stirred at ambient temperature for about 72 hours. The reaction mixture was then partitioned between 300 mL of an aqueous mixture of 10% lithium chloride and 100 mL of ethyl acetate. The ethyl acetate portion was washed three times; first, with 100 mL of an aqueous mixture of 10% sodium hydroxide, second, with 100 mL of an aqueous mixture of 10% lithium chloride, and, third, with 100 mL of brine. The resultant organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using methylene chloride as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 7.3 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step B Synthesis of tert-butyl 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-hydroxypiperidine carboxylate as an Intermediate

A stirred solution of 8.9 grams (0.022 mole) of bis(trifluoromethoxyphenyl)bromomethane and 4.82 grams (0.024 mole) of tert-butyl 4-oxo-1-piperidine carboxylate in 150 mL of THF was chilled to −78° C., and 9.24 mL of n-butyl lithium (2.5 M) was added dropwise during a 15-minute period while maintaining the temperature of the reaction mixture between −85° C. to −75° C. The reaction mixture was then stirred for 30 minutes while maintaining the temperature of the reaction mixture between −80° C. to −70° C. The reaction mixture was quenched with an aqueous solution saturated with ammonium chloride keeping the internal temperature at less than −55° C., then the mixture was extracted two times with 100 mL of ethyl acetate. The extracts were combined and washed once with 75 mL of an aqueous mixture of 10% lithium chloride. The combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was triturated with petroleum ether and a trace of ether then filtered, yielding 3.43 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step C Synthesis of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}piperidin-4-ol as an Intermediate

A mixture of 3.0 grams (0.0057 mole) of tert-butyl 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-4-hydroxypiperidine carboxylate and 25 mL of methylene chloride was chilled in a wet ice bath. A solution of 2.63 mL trifluoro acetic acid and 5 mL methylene chloride was added dropwise to the reaction mixture during a 5-minute period. The wet ice bath was removed and the reaction mixture was allowed to warm to ambient temperature. The reaction mixture was then warmed to reflux, and allowed to cool to ambient temperature. The reaction mixture was concentrated under reduced pressure. The residue can then be dissolved in 100 mL methylene chloride and reacted with 200 mL of an aqueous solution saturated with sodium carbonate. The methylene chloride layer can then be separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield the subject compound.

Step D Synthesis of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-1-{[4-(2-methoxyethoxy)phenyl]methyl}piperidin-4-ol (Compound 308 in table below) as an Intermediate

A solution of 2.2 grams (0.0050 mole) of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}piperidin-4-ol, 1.1 grams (0.0061 mole) of 4-(2-methoxyethoxy)benzaldehyde and 1.35 grams (0.0064 mole) of sodium triacetoxyborohydride in 25 mL of methylene chloride was stirred at ambient temperature for 18 hours. The reaction mixture was then diluted with 200 mL of water and stirred at ambient temperature for 5 hours. The phases were separated. The organic phase was washed three times; first, with 100 mL of an aqueous mixture of 10% sodium hydroxide, second, with 100 mL of an aqueous mixture of 10% lithium chloride, and, third, with 100 mL of brine. The resultant organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using methylene chloride:1%-5% methanol as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 2.2 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Step E Synthesis of Compound 385

A solution of 1.9 grams (0.0032 mole) of 4-{bis[4-(trifluoromethoxy)phenyl]methyl}-{[4-(2-methoxyethoxy)phenyl]methyl}piperidin-4-ol and 2.0 mL of 50% aqueous hydrogen peroxide in 25 mL of methanol was stirred at ambient temperature for about 7 days. The reaction mixture was then partitioned between 300 mL of an aqueous mixture of 10% lithium chloride and 100 mL of ethyl acetate. The aqueous phase was extracted twice with 100 mL each of ethyl acetate. The organic phase and extracts were combined and washed twice; first, with 100 mL of aqueous mixture of 10% lithium chloride, second, with 100 mL of brine. The resultant organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to a residue, yielding 1.9 gram of Compound 385. 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.

TABLE 1

N-Substituted Azacycles

I

Where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; and R⁵, R⁷, R⁸, R¹⁰, R¹¹and Y are H:

I-A

Compd

No.
R¹
R²
R³
R⁴
R⁹
R¹⁴
R¹⁵
R¹⁶
R¹⁷
R¹⁸

1
Cl
H
H
H
pyrimidin-2-yloxy
H
H
H
H
Cl

2
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
OCF₃
H
H

3
H
Cl
H
Cl
pyrimidin-2-yloxy
H
H
CF₃
H
H

4
H
F
Cl
H
pyrimidin-2-yloxy
H
H
Cl
F
H

5
H
H
CF₃
H
pyrimidin-2-yloxy
H
OCH₃
H
OCH₃
H

6
H
Cl
Cl
H
pyrimidin-2-yloxy
H
Cl
Cl
H
H

7
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
Cl
H
H

8
H
F
H
H
pyrimidin-2-yloxy
H
H
H
F
H

9
H
Cl
Cl
H
pyrimidin-2-yloxy
H
H
CF₃
H
H

10
H
F
H
F
pyrimidin-2-yloxy
H
F
H
F
H

11
H
F
H
F
pyrimidin-2-yloxy
H
H
CF₃
H
H

12
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
H
F
H

13
H
H
CF₃
H
pyrimidin-2-yloxy
Cl
H
H
Cl
H

14
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
H
Cl
H

15
Cl
H
Cl
H
pyrimidin-2-yloxy
H
H
CF₃
H
H

16
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
CF₃
H
H

17
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
F
F
H

18
H
H
CF₃
H
pyrimidin-2-yloxy
H
H
H
H
Cl

19
H
H
OCF₃
H
pyrimidin-2-yloxy
H
H
OCF₃
H
H

20
H
H
OCF₃
H
pyrimidin-2-yl
H
H
OCF₃
H
H

21
H
H
OCF₃
H
pyrid-2-yloxy
H
H
OCF₃
H
H

22
H
H
CF₃
H
pyrid-2-yloxy
H
H
CF₃
H
H

23
H
H
Cl
H
2-ethyl-2H-tetrazol-5-yl
H
H
Cl
H
H

24
H
H
H
Cl
2-ethyl-2H-tetrazol-5-yl
H
H
H
Cl
H

25
H
H
OCF₃
H
2-ethyl-2H-tetrazol-5-yl
H
H
OCF₃
H
H

26
H
Cl
Cl
H
2-ethyl-2H-tetrazol-5-yl
H
H
Cl
Cl
H

27
H
H
CF₃
H
2-ethyl-2H-tetrazol-5-yl
H
H
CF₃
H
H

28
H
H
OCF₃
H
CH═NOC₂H₅
H
H
OCF₃
H
H

29
H
H
OCF₃
H
NHC(═O)OCH(CH₃)₂
H
H
OCF₃
H
H

30
H
H
OCF₃
H
3-(CF₃)pyrid-2-yloxy
H
H
OCF
H
H

31
H
H
CF₃
H
CH═NOCH₃
H
H
CF₃
H
H

32
H
H
CF₃
H
CH═NOC₃H₇
H
H
CF₃
H
H

33
H
H
CF₃
H
CH═NOCH(CH₃)₂
H
H
CF₃
H
H

34
H
H
CF₃
H
CH═NOCH₂CH═CH₂
H
H
CF₃
H
H

35
H
H
CF₃
H
CH═NOCH₂C≡CH
H
H
CF₃
H
H

36
H
H
CF₃
H
CH═NOC₂H₅
H
H
CF₃
H
H

37
H
H
OCF₃
H
CH═NOCH₃
H
H
OCF₃
H
H

38
H
H
OCF₃
H
CH═NOC₃H₇
H
H
OCF₃
H
H

39
H
H
OCF₃
H
CH═NOCH(CH₃)₂
H
H
OCF₃
H
H

40
H
H
OCF₃
H
CH═NOCH₂CH═CH₂
H
H
OCF₃
H
H

41
H
H
OCF₃
H
CH═NOCH₂C≡CH
H
H
OCF₃
H
H

42
H
H
OCF₃
H
CH═NOC₂H₅
H
H
OCF₃
H
H

43
H
H
CF₃
H
CH═NOC₂H₅
F
H
CF₃
H
H

44
H
H
CF₃
H
CH═NOC₂H₅
Cl
H
CF₃
H
H

45
H
H
OCF₃
H
phenoxy
H
H
OCF₃
H
H

46
H
H
OCF₃
H
4-(1-methylethyoxycarbonyl)phenoxy
H
H
OCF₃
H
H

47
H
H
OCF₃
H
4-(methoxycarbonyl)phenoxy
H
H
OCF₃
H
H

48
H
H
OCF₃
H
6-chloro-pyridazin-3yloxy
H
H
OCF₃
H
H

49
H
H
CF₃
H
6-chloro-pyridazin-3yloxy
H
H
CF₃
H
H

50
H
H
OCF₃
H
NHCO₂CH₃
H
H
OCF₃
H
H

51
H
H
OCF₃
H
NHCO₂C₂H₅
H
H
OCF₃
H
H

52
H
H
OCF₃
H
NHCO₂CH₂CH═CH₂
H
H
OCF₃
H
H

53
H
H
OCF₃
H
NHCO₂CH₂C≡CH
H
H
OCF₃
H
H

54
H
H
CF₃
H
NHCO₂CH(CH₃)₂
H
H
CF₃
H
H

55
H
H
CF₃
H
NHCO₂CH₃
H
H
CF₃
H
H

56
H
H
CF₃
H
NHCO₂CH₂CH═CH₂
H
H
CF₃
H
H

57
H
H
CF₃
H
OC(═O)NHCH₃
H
H
CF₃
H
H

58
H
H
CF₃
H
OC(═O)NHC₂H₅
H
H
CF₃
H
H

59
H
H
CF₃
H
OC(═O)NHCH(CH₃)₂
H
H
CF₃
H
H

60
H
H
CF₃
H
OC(═O)NHCH₂CH═CH₂
H
H
CF₃
H
H

61
H
H
OCF₃
H
OC(═O)NHCH₃
H
H
OCF₃
H
H

62
H
H
OCF₃
H
OC(═O)NHC₂H₅
H
H
OCF₃
H
H

63
H
H
OCF₃
H
OC(═O)NHCH(CH₃)₂
H
H
OCF₃
H
H

64
H
H
OCF₃
H
OC(═O)NHCH₂CH═CH₂
H
H
OCF₃
H
H

65
H
H
OCF₃
H
OC(═O)NHCH₂C≡CH
H
H
OCF₃
H
H

66
H
H
CF₃
H
OCH₃
H
H
CF₃
H
H

67
H
H
CF₃
H
OC₂H₅
H
H
CF₃
H
H

68
H
H
CF₃
H
OC₃H₇
H
H
CF₃
H
H

69
H
H
CF₃
H
cyclopentoxy
H
H
CF₃
H
H

70
H
H
OCF₃
H
OCH₃
H
H
OCF₃
H
H

71
H
H
OCF₃
H
OC₂H₅
H
H
OCF₃
H
H

72
H
H
OCF₃
H
OC₃H₇
H
H
OCF₃
H
H

73
H
H
OCF₃
H
OCH(CH₃)₂
H
H
OCF₃
H
H

74
H
H
OCF₃
H
cyclopentoxy
H
H
OCF₃
H
H

75
H
H
OCHF₂
H
pyrid-2-yloxy
H
H
OCHF₂
H
H

76
H
H
OCHF₂
H
pyrimidin-2-yloxy
H
H
OCHF₂
H
H

77
H
H
OCHF₂
H
CH═NOC₂H₅
H
H
OCHF₂
H
H

78
H
H
OCHF₂
H
OC(═O)NHCH(CH₃)₂
H
H
OCHF₂
H
H

79
H
H
OCHF₂
H
NHCO₂CH(CH₃)₂
H
H
OCHF₂
H
H

80
H
H
OCHF₂
H
OC₃H₇
H
H
OCHF₂
H
H

81
H
H
OCF₂CHF₂
H
pyrid-2-yloxy
H
H
OCF₂CHF₂
H
H

82
H
H
OCF₂CHF₂
H
pyrimidin-2-yloxy
H
H
OCF₂CHF₂
H
H

83
H
H
OCF₂CHF₂
H
6-chloro-pyridazin-3yloxy
H
H
OCF₂CHF₂
H
H

84
H
H
OCF₂CHF₂
H
OC₃H₇
H
H
OCF₂CHF₂
H
H

85
H
H
OCF₂CHF₂
H
OC(═O)NHCH(CH₃)₂
H
H
OCF₂CHF₂
H
H

86
H
H
OCF₂CHF₂
H
NHCO₂CH(CH₃)₂
H
H
OCF₂CHF₂
H
H

87
H
H
OCF₂CHF₂
H
OCO₂CH(CH₃)₂
H
H
OCF₂CHF₂
H
H

88
H
H
SF₅
H
pyrimidin-2-yloxy
H
H
SF₅
H
H

89
H
H
SF₅
H
pyrimidin-2-yloxy
H
H
CF₃
H
H

90
H
H
OCF₃
H
CO₂CH(CH₃)₂
H
H
OCF₃
H
H

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X and Y are OH; A is —CH₂—; and R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰, and

R¹¹are H:

I-B

Compd.

No.
R³
R⁹
R¹⁶

91
OCF₃
OC₃H₇
OCF₃

92
CF₃
OC₃H₇
CF₃

93
OCF₃
2-methyl-2H-tetrazol-5-yl
OCF₃

94
CF₃
pyrid-2-yloxy
CF₃

95
CF₃
pyrimidin-2-yloxy
CF₃

96
CF₃
6-chloro-pyridazin-3yloxy
CF₃

97
CF₃
6-methoxy-pyridazin-3yloxy
CF₃

98
CF₃
2-ethyl-2H-tetrazol-5-yl
CF₃

99
CF₃
CH═NOCH₃
CF₃

100
CF₃
CH═NOCH₂CH═CH₂
CF₃

101
CF₃
CH═NOCH₂C≡CH
CF₃

102
CF₃
4-(1-methylethoxycarbonyl)phenoxy
CF₃

103
OCF₃
CH═NOCH₂C≡CH
OCF₃

104
OCF₃
pyrid-2-yloxy
OCF₃

105
OCF₃
pyrimidin-2-yloxy
OCF₃

106
OCF₃
6-chloro-pyridazin-3yloxy
OCF₃

107
OCF₃
6-methoxy-pyridazin-3yloxy
OCF₃

108
OCF₃
CH═NOCH₃
OCF₃

109
OCF₃
CH═NOCH₂CH═CH₂
OCF₃

110
OCF₃
4-(1-methylethoxycarbonyl)phenoxy
OCF₃

where

m, p, and q are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; and R¹, R⁴, R⁵, R¹⁵, R¹⁸, R⁷, R⁸,

R¹⁰, and R¹¹are H:

I-C

Compd.

No.
R²
R³
R⁹
R¹⁴
R¹⁶
R¹⁷
Y

111
H
CF₃
pyrid-2-yloxy
H
CF₃
H
H

112
H
OCF₃
pyrimidin-2-yloxy
H
OCF₃
H
H

113
H
CF₃
2-ethyl-2H-tetrazol-5-yl
H
CF₃
H
H

114
H
OCF₃
2-ethyl-2H-tetrazol-5-yl
H
OCF₃
H
H

115
F
Cl
pyrimidin-2-yloxy
H
Cl
F
H

116
H
OCF₃
pyrimidin-2-yl
H
OCF₃
H
H

117
H
OCF₃
pyrid-2-yloxy
H
OCF₃
H
H

118
H
OCF₃
CH═NOC₂H₅
H
OCF₃
H
H

119
H
OCF₃
NHC(═O)OCH(CH₃)₂
H
OCF₃
H
H

120
H
CF₃
pyrimidin-2-yloxy
H
CF₃
H
H

121
H
CF₃
OC₃H₇
H
CF₃
H
OH

122
H
OCF₃
2-methyl-2H-tetrazol-5-yl
H
OCF₃
H
OH

123
H
OCF₃
OC₃H₇
H
OCF₃
H
OH

124
H
CF₃
CH═NOCH₃
H
CF₃
H
H

125
H
CF₃
CH═NOC₃H₇
H
CF₃
H
H

126
H
CF₃
CH═NOCH(CH₃)₂
H
CF₃
H
H

127
H
CF₃
CH═NOCH₂CH═CH₂
H
CF₃
H
H

128
H
CF₃
CH═NOCH₂C≡CH
H
CF₃
H
H

129
H
CF₃
CH═NOC₂H₅
H
CF₃
H
H

130
H
OCF₃
CH═NOCH₃
H
OCF₃
H
H

131
H
OCF₃
CH═NOC₃H₇
H
OCF₃
H
H

132
H
OCF₃
CH═NOCH(CH₃)₂
H
OCF₃
H
H

133
H
OCF₃
CH═NOCH₂CH═CH₂
H
OCF₃
H
H

134
H
OCF₃
CH═NOCH₂C≡CH
H
OCF₃
H
H

135
H
OCF₃
CH═NOC₂H₅
H
OCF₃
H
H

136
H
CF₃
CH═NOC₂H₅
H
CF₃
H
H

137
H
CF₃
CH═NOC₂H₅
H
CF₃
H
H

138
H
OCF₃
phenoxy
H
OCF₃
H
H

139
H
OCF₃
4-(1-methylethyoxycarbonyl)phenoxy
H
OCF₃
H
H

140
H
OCF₃
4-(methoxycarbonyl)phenoxy
H
OCF₃
H
H

141
H
OCF₃
6-chloro-pyridazin-3yloxy
H
OCF₃
H
H

142
H
CF₃
6-chloro-pyridazin-3yloxy
H
CF₃
H
H

143
H
OCF₃
NHCO₂CH₃
H
OCF₃
H
H

144
H
OCF₃
NHCO₂C₂H₅
H
OCF₃
H
H

145
H
OCF₃
NHCO₂CH₂CH═CH₂
H
OCF₃
H
H

146
H
OCF₃
NHCO₂CH₂C≡CH
H
OCF₃
H
H

147
H
CF₃
NHCO₂CH(CH₃)₂
H
CF₃
H
H

148
H
CF₃
NHCO₂CH₃
H
CF₃
H
H

149
H
CF₃
NHCO₂CH₂CH═CH₂
H
CF₃
H
H

150
H
CF₃
OC(═O)NHCH₃
H
CF₃
H
H

151
H
CF₃
OC(═O)NHC₂H₅
H
CF₃
H
H

152
H
CF₃
OC(═O)NHCH(CH₃)₂
H
CF₃
H
H

153
H
CF₃
OC(═O)NHCH₂CH═CH₂
H
CF₃
H
H

154
H
OCF₃
OC(═O)NHCH₃
H
OCF₃
H
H

155
H
OCF₃
OC(═O)NHC₂H₅
H
OCF₃
H
H

156
H
OCF₃
OC(═O)NHCH(CH₃)₂
H
OCF₃
H
H

157
H
OCF₃
OC(═O)NHCH₂CH═CH₂
H
OCF₃
H
H

158
H
OCF₃
OC(═O)NHCH₂C≡CH
H
OCF₃
H
H

159
H
CF₃
OCH₃
H
CF₃
H
H

160
H
CF₃
OC₂H₅
H
CF₃
H
H

161
H
CF₃
OC₃H₇
H
CF₃
H
H

162
H
CF₃
cyclopentoxy
H
CF₃
H
H

163
H
OCF₃
OCH₃
H
OCF₃
H
H

164
H
OCF₃
OC₂H₅
H
OCF₃
H
H

165
H
OCF₃
OC₃H₇
H
OCF₃
H
H

166
H
OCF₃
OCH(CH₃)₂
H
OCF₃
H
H

167
H
OCF₃
cyclopentoxy
H
OCF₃
H
H

168
H
OCHF₂
pyrid-2-yloxy
H
OCHF₂
H
H

169
H
OCHF₂
pyrimidin-2-yloxy
H
OCHF₂
H
H

170
H
OCHF₂
CH═NOC₂H₅
H
OCHF₂
H
H

171
H
OCHF₂
OC(═O)NHCH(CH₃)₂
H
OCHF₂
H
H

172
H
OCHF₂
NHCO₂CH(CH₃)₂
H
OCHF₂
H
H

173
H
OCHF₂
OC₃H₇
H
OCHF₂
H
H

174
H
OCF₂CHF₂
pyrid-2-yloxy
H
OCF₂CHF₂
H
H

175
H
OCF₂CHF₂
pyrimidin-2-yloxy
H
OCF₂CHF₂
H
H

176
H
OCF₂CHF₂
6-chloro-pyridazin-3yloxy
H
OCF₂CHF₂
H
H

177
H
OCF₂CHF₂
OC₃H₇
H
OCF₂CHF₂
H
H

178
H
OCF₂CHF₂
OC(═O)NHCH(CH₃)₂
H
OCF₂CHF₂
H
H

179
H
OCF₂CHF₂
NHCO₂CH(CH₃)₂
H
OCF₂CHF₂
H
H

180
H
OCF₂CHF₂
OCO₂CH(CH₃)₂
H
OCF₂CHF₂
H
H

181
H
SF₅
pyrid-2-yloxy
H
SF₅
H
H

182
H
OCF₃
pyrid-2-yloxy
Cl
OCF₃
H
H

183
H
CF₃
pyrid-2-yloxy
Cl
CF₃
H
H

184
H
OCF₃
pyrimidin-2-yloxy
Cl
OCF₃
H
H

185
H
OCF₃
CH═NOC₂H₅
Cl
OCF₃
H
H

186
H
OCF₃
6-chloro-pyridizin-3yloxy
Cl
OCF₃
H
H

187
H
OCF₃
pyrid-2-yloxy
Cl
Cl
H
H

188
H
OCF₃
pyrid-2-yloxy
F
OCF₃
H
H

189
H
OCF₃
pyrimidin-2-yloxy
F
OCF₃
H
H

190
H
OCF₃
CH═NOC₂H₅
F
OCF₃
H
H

191
H
OCF₃
CO₂CH(CH₃)₂
H
OCF₃
H
H

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴,R¹⁵, R¹⁶, R¹⁷, R¹⁸;

A is —CH₂—; and R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R⁷, R⁸, R¹⁰and R¹¹are H:

I-D

Compd.

No.
X
Y
R³
R⁹
R¹⁶

192
F
H
OCF₃
pyrimidin-2-yloxy
OCF₃

193
F
H
CF₃
pyrid-2-yloxy
CF₃

194
F
H
CF₃
pyrimidin-2-yloxy
CF₃

195
C(═O)OC₂H₅
Cl
CF₃
pyrid-2-yloxy
CF₃

196
C(═O)OC₂H₅
H
CF₃
pyrid-2-yloxy
CF₃

197
C(═O)OC₂H₅
F
CF₃
pyrid-2-yloxy
CF₃

198
C≡N
Cl
CF₃
pyrid-2-yloxy
CF₃

199
OH
CH₃
CF₃
pyrid-2-yloxy
CF₃

200
OH
CH(CH₃)₂
CF₃
pyrid-2-yloxy
CF₃

201
CH₂OH
H
CF₃
pyrid-2-yloxy
CF₃

202
OH
CH₃
CF₃
pyrimidin-2-yl
CF₃

203
OH
CH₃
CF₃
CH═NOCH₃
CF₃

204
OH
CH₃
OCF₃
pyrid-2-yl
OCF₃

205
OH
CH₃
OCF₃
pyrimidin-2-yl
OCF₃

206
OH
CH₃
OCF₃
CH═NOCH₃
OCF₃

207
C(═O)OCH₃
CH₃
OCF₃
pyrid-2-yl
OCF₃

208
OSO₂CH₃
CH₃
OCF₃
pyrid-2-yl
OCF₃

209
SH
H
OCF₃
pyrid-2-yl
OCF₃

210
C(═O)OH
H
OCF₃
pyrid-2-yl
OCF₃

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are H; A is —CH₂—; and X and Y

are taken together with —OCR¹²R¹³O—, forming a 1,3-dioxolane ring:

I-E

Compd.

No.
R³
R⁹
R¹²
R¹³
R¹⁶

211
CF₃
pyrid-2-yloxy
H
H
CF₃

212
CF₃
pyrimidin-2-yloxy
H
H
CF₃

213
CF₃
6-chloro-pyridazin-3yloxy
H
H
CF₃

214
CF₃
2-ethyl-2H-tetrazol-5-yl
H
H
CF₃

215
CF₃
OC₃H₇
H
H
CF₃

216
CF₃
CH═NOCH₃
H
H
CF₃

217
CF₃
CH═NOC₂H₅
H
H
CF₃

218
CF₃
pyrid-2-yloxy
CH₃
CH₃
CF₃

219
CF₃
pyrimidin-2-yloxy
CH₃
CH₃
CF₃

220
CF₃
6-chloro-pyridazin-3yloxy
CH₃
CH₃
CF₃

221
CF₃
2-ethyl-2H-tetrazol-5-yl
CH₃
CH₃
CF₃

222
CF₃
OC₃H₇
CH₃
CH₃
CF₃

223
CF₃
CH═NOCH₃
CH₃
CH₃
CF₃

224
CF₃
CH═NOC₂H₅
CH₃
CH₃
CF₃

225
CF₃
OC(═O)NHCH(CH₃)₂
CH₃
CH₃
CF₃

where

m, p, q and r are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸; R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are

H; A is —CH₂—; and X and Y are taken together with —OCR¹²R¹³O—, forming a 1,3-

dioxolane ring:

I-F

Compd.

No.
R³
R⁹
R¹²
R¹³
R¹⁶

226
CF₃
pyrid-2-yloxy
H
H
CF₃

227
CF₃
pyrimidin-2-yloxy
H
H
CF₃

228
CF₃
6-chloro-pyridizin-3yloxy
H
H
CF₃

229
CF₃
2-ethyl-2H-tetrazol-5-yl
H
H
CF₃

230
CF₃
OC₃H₇
H
H
CF₃

231
CF₃
CH═NOCH₃
H
H
CF₃

232
CF₃
CH═NOC₂H₅
H
H
CF₃

233
CF₃
pyrid-2-yloxy
CH₃
CH₃
CF₃

234
CF₃
pyrimidin-2-yloxy
CH₃
CH₃
CF₃

235
CF₃
6-chloro-pyridizin-3yloxy
CH₃
CH₃
CF₃

236
CF₃
2-ethyl-2H-tetrazol-5-yl
CH₃
CH₃
CF₃

237
CF₃
OC₃H₇
CH₃
CH₃
CF₃

238
CF₃
CH═NOCH₃
CH₃
CH₃
CF₃

239
CF₃
CH═NOC₂H₅
CH₃
CH₃
CF₃

240
CF₃
OC(═O)NHCH(CH₃)₂
CH₃
CH₃
CF₃

where

p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

A is —CH₂—; and R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are H:

I-G

Compd.

No.
R³
R⁹
X
Y
B
R¹⁶

241
CF₃
pyrid-2-yloxy
OH
H
O
CF₃

242
CF₃
pyrid-2-yloxy
OH
CH₃
O
CF₃

243
CF₃
pyrimidin-2-yloxy
OH
H
O
CF₃

244
CF₃
CH═NOCH₃
OH
H
O
CF₃

245
CF₃
pyrid-2-yloxy
OH
H
OC(═O)NH
CF₃

246
OCF₃
pyrid-2-yloxy
OH
H
O
OCF₃

247
OCF₃
pyrid-2-yloxy
OH
CH₃
O
OCF₃

248
OCF₃
pyrid-2-yloxy
F
H
O
OCF₃

249
OCF₃
pyrid-2-yloxy
F
CH₃
O
OCF₃

250
OCF₃
pyrid-2-yloxy
F
H
OC(═O)NH
OCF₃

251
OCF₃
CH═NOCH₃
F
H
O
OCF₃

252
OCF₃
pyrid-2-yloxy
OH
H
NHSO₂
OCF₃

253
OCF₃
pyrid-2-yloxy
OH
H
OCH₂
OCF₃

254
OCF₃
pyrid-2-yloxy
OH
H
CH₂O
OCF₃

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; and R¹, R², R⁴, R⁵, R⁷, R⁸, R¹⁰, R¹¹, R¹⁴,

R¹⁵, R¹⁷, R¹⁸and Y are H:

I-H

Compd

No.
R³
R⁹
R¹⁶

255
OCF₃
6-methyl-pyridazin-3-yloxy
OCF₃

256
CHO
pyrid-2-yloxy
OCF₃

257
C(CH₃)₃
pyrid-2-yloxy
OCF₃

258
OCF₃
CH═NOCH₂CH₂OCH₂CH₂OCH₃
OCF₃

259
OCF₃
CH═NOCH₂OCH₂CH₃
OCF₃

260
OCH₃
pyrid-2-yloxy
OCF₃

261
Br
pyrid-2-yloxy
OCF₃

262
CH₃
pyrid-2-yloxy
OCF₃

263
OCF₃
1,3-dioxolan-2-yl
OCF₃

264
CF₃
1,3-dioxolan-2-yl
CF₃

265
CF₃
pyrid-2-yloxy
OCF₃

266
OCF₃
CH═NOCH₂CH₂OCH₃
OCF₃

267
Cl
pyrid-2-yloxy
Cl

268
F
pyrid-2-yloxy
OCF₃

269
OCHF₂
pyrid-2-yloxy
OCF₃

270
CF₃
CH═NOH
CF₃

271
OCF₃
3-methyl-pyrid-2-yloxy
OCF₃

272
OCF₃
5-methyl-pyrid-2-yloxy
OCF₃

273
OCF₃
CH(OCH₂CH₃)₂
OCF₃

274
OCF₃
6-methoxy-pyridazin-3-yloxy
OCF₃

275
OCF₃
CH═NOCH₂C≡N
OCF₃

276
OCF₃
6-methyl-pyrid-2-yloxy
OCF₃

277
OCF₃
C(Cl)═NOCH₃
OCF₃

278
OCF₃
4-chlorophenylCH(OH)
OCF₃

279
OCF₃
OCH₂C(═O)OCH₂CH₃
OCF₃

280
OCF₃
5,5-dimethyl-1,3-dioxan-2-yl
OCF₃

281
OCF₃
3-cyano-pyrid-2-yloxy
OCF₃

282
OCF₃
pyrid-2-yl-CH(OH)
OCF₃

283
OCF₃
5-cyano-pyrid-2-yloxy
OCF₃

284
OCF₃
pyrid-2-yloxy
CH═NOCH₂CH═C(CH₃)CH₂—

CH₂CH═C(CH₃)₂

285
OCF₃
C(═O)NHOCH₃
OCF₃

286
OCF₃
3-chlorophenoxy
OCF₃

287
OCF₃
pyrid-2-yloxy
CH(OH)CH₃

288
H
pyrid-2-yloxy
OCF₃

289
OCF₃
4-chlorophenyl-CH(OC(═O)CH₃)
OCF₃

290
OCF₃
4-chlorophenoxy
OCF₃

291
CF₃
OCH₂C(═O)OCH₂CH₃
CF₃

292
OCF₃
1,3-dioxan-2-yl
OCF₃

293
OCF₃
OCH₂CH═C(Cl)₂
OCF₃

294
OCF₃
3-(dimethoxymethyl)-pyrid-2-yl
OCF₃

295
1,3-dioxolan-
pyrid-2-yloxy
OCF₃

2-yl

296
OCF₃
C(C≡N)═NOCH₃
OCF₃

297
OCF₃
2-chlorophenoxy
OCF₃

298
OCF₃
OC(═O)NH-cyclopropane
OCF₃

299
CF₃
cyclopropylmethoxy
CF₃

300
OCF₃
OC(═O)NHC₃H₇
OCF₃

301
OCF₃
CH═NOCH₂CF₃
OCF₃

302
CF₃
OH
CF₃

303
CF₃
OCH(CH₃)₂
CF₃

304
OCF₃
phenylmethoxy
OCF₃

305
OCF₃
CH═NHOCH₂CH═C(CH₃)CH₂CH₂—
OCF₃

CH═C(CH₃)₂

306
OCF₂CHFCF₃
pyrimidin-2-yloxy
OCF₂CHFCF₃

307
CF₃
6-chloro-pyridazin-3-yloxy
CF₃

308
OCF₃
OCH₂CH₂OCH₃
OCF₃

309
OCF₃
pyrid-2-yl
OCF₃

310
OCF₃
NHC(═O)OCH₂CH₂CH₃
OCF₃

311
OCF₃
OC(═O)NHC(CH₃)₃
OCF₃

312
OCF₃
CH═NOCH₂CH₂F
OCF₃

313
CF₃
NHC(═O)OCH₂CH₂CH₃
CF₃

314
Cl
pyrid-2-yloxy
OCF₃

315
OCF₃
cyclopropylmethoxy
OCF₃

316
CF₃
phenylmethoxy
CF₃

317
OCF₃
OC(═O)NHCH₂C(═O)OC₂H₅
OCF₃

318
CF₃
NHC(═O)OCH₂CH₃
CF₃

319
CF₃
NHC(═O)OCH₂-cyclopropane
CF₃

320
OCF₃
OC(═O)NH-cyclopentane
OCF₃

321
OCF₃
4-methyl-pyrid-2-yloxy
OCF₃

322
OCF₃
3-chloro-pyrid-2-yloxy
OCF₃

323
OCF₃
OC(═O)NHCH₂(3,4-
OCF₃

dichlorophenyl)

324
OCF₃
OC(═O)NH(4-chlorophenyl)
OCF₃

325
Cl
pyrimidin-2-yloxy
OCF₃

326
OCF₃
OC(═O)NHC₄H₉
OCF₃

327
OCF₃
NHC(═O)OCH₂-cyclopropane
OCF₃

328
Cl
CH═NOC₂H₅
OCF₃

329
OCF₃
OC(═O)NH-cyclohexane
OCF₃

330
CF₃
C(═O)OCH(CH₃)₂
CF₃

331
CF₃
OH
CF₃

332
OCF₃
NHC(═O)C(CH₂CH₂)C≡N
OCF₃

333
CF₃
NHC(═O)C(CH₂CH₂)C≡N
CF₃

where

m, p, and q are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸; X is OH, A is —CH₂—; and R¹, R², R⁴, R⁵, R⁷, R⁸, R¹⁰, R¹¹,

R¹⁴, R¹⁵, R¹⁷, R¹⁸and Y are H:

I-J

Compd

No.
R³
R⁹
R¹⁶

334
CHO
pyrid-2-yloxy
OCF₃

335
C(CH₃)₃
pyrid-2-yloxy
OCF₃

336
OCF₃
CH═NOCH₂CH₂OCH₂CH₂OCH₃
OCF₃

337
OCF₃
CH═NOCH₂OCH₂CH₃
OCF₃

338
OCH₃
pyrid-2-yloxy
OCF₃

339
Br
pyrid-2-yloxy
OCF₃

340
CH₃
pyrid-2-yloxy
OCF₃

341
OCF₃
1,3-dioxolan-2-yl
OCF₃

342
CF₃
1,3-dioxolan-2-yl
CF₃

343
CF₃
pyrid-2-yloxy
OCF₃

344
OCF₃
CH═NOCH₂CH₂OCH₃
OCF₃

345
Cl
pyrid-2-yloxy
Cl

346
F
pyrid-2-yloxy
OCF₃

347
OCHF₂
pyrid-2-yloxy
OCF₃

348
CF₃
CH═NOH
CF₃

349
OCF₃
3-methyl-pyrid-2-yloxy
OCF₃

350
OCF₃
5-methyl-pyrid-2-yloxy
OCF₃

351
OCF₃
CH(OCH₂CH₃)₂
OCF₃

352
OCF₃
6-methoxy-pyridazin-3-yloxy
OCF₃

353
OCF₃
CH═NOCH₂C≡N
OCF₃

354
OCF₃
6-methyl-pyrid-2-yloxy
OCF₃

355
OCF₃
C(Cl)═NOCH₃
OCF₃

356
OCF₃
4-chlorophenylCH(OH)
OCF₃

357
OCF₃
OCH₂C(═O)OCH₂CH₃
OCF₃

358
OCF₃
5,5-dimethyl-1,3-dioxan-2-yl
OCF₃

359
OCF₃
3-cyano-pyrid-2-yloxy
OCF₃

360
OCF₃
pyrid-2-yl-CH(OH)
OCF₃

361
OCF₃
5-cyano-pyrid-2-yloxy
OCF₃

362
OCF₃
pyrid-2-yloxy
CH═NOCH₂CH═C(CH₃)CH₂—

CH₂CH═C(CH₃)₂

363
OCF₃
C(═O)NHOCH₃
OCF₃

364
OCF₃
3-chlorophenoxy
OCF₃

365
OCF₃
pyrid-2-yloxy
CH(OH)CH₃

366
H
pyrid-2-yloxy
OCF₃

367
OCF₃
4-chlorophenyl-CH(OC(═O)CH₃)
OCF₃

368
OCF₃
4-chlorophenoxy
OCF₃

369
CF₃
OCH₂C(═O)OCH₂CH₃
CF₃

370
OCF₃
1,3-dioxan-2-yl
OCF₃

371
OCF₃
OCH₂CH═C(Cl)₂
OCF₃

372
OCF₃
3-(dimethoxymethyl)-pyrid-2-yl
OCF₃

373
1,3-dioxolan-
pyrid-2-yloxy
OCF₃

2-yl

374
OCF₃
C(C≡N)═NOCH₃
OCF₃

375
OCF₃
2-chlorophenoxy
OCF₃

376
OCF₃
OC(═O)NH-cyclopropane
OCF₃

377
OCF₃
OC(═O)NHC₃H₇
OCF₃

378
OCF₃
CH═NOCH₂CF₃
OCF₃

379
CF₃
OH
CF₃

380
CF₃
OCH(CH₃)₂
CF₃

381
OCF₃
phenylmethoxy
OCF₃

382
OCF₃
CH═NHOCH₂CH═C(CH₃)CH₂CH₂—
OCF₃

CH═C(CH₃)₂

383
CF₃
cyclopropylmethoxy
CF₃

384
CF₃
6-chloro-pyridazin-3-yloxy
CF₃

385
OCF₃
OCH₂CH₂OCH₃
OCF₃

386
OCF₃
pyrid-2-yl
OCF₃

387
OCF₃
NHC(═O)OCH₂CH₂CH₃
OCF₃

388
OCF₃
OC(═O)NHC(CH₃)₃
OCF₃

389
OCF₃
CH═NOCH₂CH₂F
OCF₃

390
CF₃
NHC(═O)OCH₂CH₂CH₃
CF₃

391
Cl
pyrid-2-yloxy
OCF₃

392
OCF₃
cyclopropylmethoxy
OCF₃

393
CF₃
phenylmethoxy
CF₃

394
OCF₃
OC(═O)NHCH₂C(═O)OC₂H₅
OCF₃

395
CF₃
NHC(═O)OCH₂CH₃
CF₃

396
CF₃
NHC(═O)OCH₂-cyclopropane
CF₃

397
OCF₃
OC(═O)NH-cyclopentane
OCF₃

398
OCF₃
4-methyl-pyrid-2-yloxy
OCF₃

399
OCF₃
3-chloro-pyrid-2-yloxy
OCF₃

400
OCF₃
OC(═O)NHCH₂(3,4-
OCF₃

dichlorophenyl)

401
OCF₃
OC(═O)NH(4-chlorophenyl)
OCF₃

402
Cl
pyrimidin-2-yloxy
OCF₃

403
OCF₃
OC(═O)NHC₄H₉
OCF₃

404
OCF₃
NHC(═O)OCH₂-cyclopropane
OCF₃

405
Cl
CH═NOC₂H₅
OCF₃

406
OCF₃
OC(═O)NH-cyclohexane
OCF₃

407
CF₃
C(═O)OCH(CH₃)₂
CF₃

408
CF₃
OH
CF₃

409
OCF₂CHFCF₃
pyrimidin-2-yloxy
OCF₂CHFCF₃

410
OCF₃
CH═NOCH₂C(═O)NH₂
OCF₃

411
OCF₃
3-chloro-pyrid-2-yl
OCF₃

412
OCF₃
6-chloro-pyridazin-3-yloxy
OCF₃

413
OCF₃
6-methyl-pyridazin-3-yloxy
OCF₃

414
OCF₃
NHC(═O)C(CH₂CH₂)C≡N
OCF₃

415
CF₃
NHC(═O)C(CH₂CH₂)C≡N
CF₃

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X and Y are OH; R³and R¹⁶are OCF₃; A is —CH₂—; and R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷,

R¹⁸, R⁷, R⁸, R¹⁰, and R¹¹are H:

I-K

Compd.

No.
R⁹

416
2-ethyl-2H-tetrazol-5-yl

417
CH═NOCH₂CH₃

418
CHO

419
NHC(═O)OCH(CH₃)₂

420
NHC(═O)C(CH₂CH₂)C≡N

where

m, p, and q are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸; A is —CH₂—; and R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸,

R¹⁰, and R¹¹are H:

I-L

Compd.

No.
R³
R⁹
R¹⁶
X
Y

421
OCF₃
pyrid-2-yloxy
OCF₃
OH
OH

422
OCF₃
pyrimidin-2-yloxy
OCF₃
OH
OH

423
OCF₃
NHC(═O)OCH(CH₃)₂
OCF₃
OH
OH

424
OCF₃
CH═NOCH₂CH₃
OCF₃
OH
OH

425
OCF₃
6-chloro-pyridazin-3-yloxy
OCF₃
OH
OH

426
OCF₃
2-ethyl-2H-tetrazol-5-yl
OCF₃
OH
OH

428
OCF₃
NHC(═O)C(CH₂CH₂)C≡N
OCF₃
OH
OH

429
CF₃
NHC(═O)C(CH₂CH₂)C≡N
CF₃
OH
OH

430
OCF₃
pyrid-2-yloxy
OCF₃
OH
F

431
OCF₃
pyrid-2-yloxy
OCF₃
X and Y taken

together with

bridging group

—O—

432
OCF₃
pyrimidin-2-yloxy
OCF₃
X and Y taken

together with

bridging group

—O—

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

A is —CH₂—; and R⁷, R⁸, R¹¹, R¹⁴and Y are H:

I-M

Compd

No.
R¹
R²
R³
R⁴
R⁵
R⁹
R¹⁰
R¹⁵
R¹⁶
R¹⁷
R¹⁸
X

433
Cl
H
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

434
F
H
H
H
H
pyrimidin-2-yloxy
H
H
H
H
F
OH

435
H
CH₃
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

436
CH₃
H
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

437
Cl
H
H
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

438
Cl
Cl
H
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

439
H
Cl
H
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

440
H
H
CH═NO—
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

C₂H₅

441
H
Cl
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

442
H
Cl
H
Cl
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

443
Cl
H
H
Cl
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

444
Cl
H
Cl
H
H
CH═NOC₂H₅
H
H
OCF₃
H
H
OH

445
F
H
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

446
H
H
R³and R⁴taken
H
pyrid-2-yloxy
H
H
R¹⁶and R¹⁷taken
H
OH

together with

together with

bridging group

bridging group

—OC(F₂)O—

—OC(F₂)O—

447
H
H
OCF₃
H
H
pyrid-2-yloxy
OCH₃
H
OCF₃
H
H
OH

448
H
H
CF₃
H
H
pyrimidin-2-yloxy
H
H
CF₃
H
H
CH₂OH

449
H
H
CF₃
H
H
OCH₂-
H
H
CF₃
H
H
CH₂N═N═N

cyclopropane

450
H
H
CF₃
H
H
OCH₂-
H
H
CF₃
H
H
CH₂NH₂

cyclopropane

451
H
H
CF₃
H
H
pyrimidin-2-yloxy
H
H
CF₃
H
H
CH₂NH—

C(═O)—CH₃

452
H
H
CF₃
H
H
pyrimidin-2-yloxy
H
H
CF₃
H
H
CH₂O—C(═O)—

CH₃

where

m, p, and q are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸; A is —CH₂—; and R⁷, R⁸, R¹¹, R¹⁴

and Y are H:

I-N

Compd

No.
R¹
R²
R³
R⁴
R⁵
R⁹
R¹⁰
R¹⁵
R¹⁶
R¹⁷
R¹⁸
X

453
Cl
H
Cl
H
H
CH═NOC₂H₅
H
H
OCF₃
H
H
OH

454
Cl
H
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

455
H
Cl
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

456
Cl
Cl
H
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

457
H
Cl
H
Cl
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

458
H
Cl
H
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

459
Cl
H
H
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

460
Cl
H
H
Cl
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

461
CH₃
H
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

462
H
CH₃
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

463
F
H
Cl
H
H
pyrid-2-yloxy
H
H
OCF₃
H
H
OH

464
H
R²and R³taken
H
H
pyrid-2-yloxy
H
R¹⁵and R¹⁶taken
H
H
OH

together with

together with

bridging

bridging

group

group

—OC(F₂)O—

—OC(F₂)O—

465
H
H
OCF₃
H
H
pyrid-2-yloxy
OCH₃
H
OCF₃
H
H
OH

466
H
H
CF₃
H
H
pyrimidin-2-yloxy
H
H
CF₃
H
H
CH₂NH—

C(═O)—CH₃

467
H
H
CF₃
H
H
OCH₂-cyclopropane
H
H
CF₃
H
H
CH₂N═N═N

468
H
H
CF₃
H
H
pyrimidin-2-yloxy
H
H
CF₃
H
H
CH₂O—C(═O)—

CH₃

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸; R³and R¹⁶are OCF₃; and R¹, R², R⁴, R⁵,

R¹⁴, R¹⁵, R¹⁷, R¹⁸, R¹⁰and R¹¹are H:

I-P

Compd.

No.
X
Y
A
R⁷
R⁸
R⁹

470
OH
H
OCH₂CH(OH)CH₂
H
H
Cl

471
OH
H
OCH₂CH(OH)CH₂
H
Cl
H

472
OH
H
OCH₂CH(OH)CH₂
Cl
H
H

473
OH
H
OCH₂CH₂CH₂
H
H
Cl

474
OH
H
CH₂CH₂
H
H
Cl

475
OH
H
OCH₂CH₂
H
H
Cl

476
OH
H
OCH₂CH₂CH₂CH₂
H
H
Cl

477
OH
H
OCH₂CH₂
H
H
Br

where

m, p, and q are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸; R³and R¹⁶are OCF₃; and R¹, R², R⁴, R⁵, R⁷, R⁸, R¹⁰,

R¹¹, R¹⁴, R¹⁵, R¹⁷, R¹⁸and Y are H:

I-Q

Compd.

No.
X
A
R⁹

478
OH
OCH₂CH₂
Cl

479
OH
CH₂CH₂
Cl

480
OH
OCH₂CH₂CH₂CH₂
Cl

481
OH
OCH₂CH₂CH₂
Cl

482
OH
OCH₂CH₂
Br

where

m, p, and q are 0; t and u are 1; r is 1, R is phenyl substituted with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; and R¹, R², R⁴, R⁵, R⁷, R⁸, R¹⁰,

R¹¹, R¹⁴, R¹⁵, R¹⁷, R¹⁸and Y are H:

I-R

Compd

No.
R³
R⁹
R¹⁶

⁻Salt

483
OCF₃
CH═NOC₂H₅
OCF₃
3-hydroxypropanesulfonic acid

484
OCF₃
CH═NOC₂H₅
OCF₃
2-ethoxypropanoic acid

485
OCF₃
6-chloro-pyridazin-3-yloxy
OCF₃
2-ethylhexanoic acid

486
OCF₃
CH═NOC₂H₅
OCF₃
2-ethylhexanoic acid

487
OCF₃
CH═NOC₂H₅
OCF₃
1,1,2,2,3,3,4,4,4-nonafluorobutanesulfonic acid

488
CF₃
6-chloro-pyridazin-3-yloxy
CF₃
2-hydroxypropane-1,2,3-tricarboxylic acid

489
OCF₃
CH═NOCH₂C(═O)NH₂
OCF₃
2-hydroxypropane-1,2,3-tricarboxylic acid

490
OCF₃
CH═NOC₂H₅
OCF₃
((4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptyl)methanesulfonic

acid

491
OCF₃
CH═NOC₂H₅
OCF₃
ethanesulfonic acid

492
OCF₃
6-chloro-pyridazin-3-yloxy
OCF₃
2-hydroxypropane-1,2,3-tricarboxylic acid

493
OCF₃
CH═NOC₂H₅
OCF₃
cyclohexanecarboxylic acid

494
OCF₃
CH═NOC₂H₅
OCF₃
2-hydroxypropane-1,2,3-tricarboxylic acid

495
OCF₃
CH═NOC₂H₅
OCF₃
1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctanesulfonic acid

496
OCF₃
pyrid-2-yloxy
OCF₃
1,1,2,2,3,3,4,4,5,5,6,6,7,7,8, 8,8-heptadecafluorooctanesulfonic acid

497
OCF₃
pyrid-2-yloxy
OCF₃
C1

498
OCF₃
pyrid-2-yloxy
OCF₃
((4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptyl)methanesulfonic

acid

499
OCF₃
pyrid-2-yloxy
OCF₃
2-ethylhexanoic acid

500
OCF₃
pyrid-2-yloxy
OCF₃
3-hydroxypropanesulfonic acid

501
OCF₃
CH(Cl)═NOCH₃
OCF₃
2-hydroxypropane-1,2,3-tricarboxylic acid

502
OCF₃
pyrid-2-yloxy
OCF₃
cyclohexanecarboxylic acid

503
OCF₃
pyrid-2-yloxy
OCF₃
2-ethoxypropanoic acid

504
OCF₃
pyrid-2-yloxy
OCF₃
2-hydroxypropane-1,2,3-tricarboxylic acid

505
OCF₃
pyrid-2-yloxy
OCF₃
((4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptyl)methanesulfonic

acid

506
OCF₃
pyrid-2-yloxy
OCF₃
ethanesulfonic acid

507
OCF₃
CH═NOC₂H₅
OCF₃
((4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptyl)methanesulfonic

acid

508
OCF₃
pyrid-2-yloxy
OCF₃
1,1,2,2,3,3,4,4,4-nonafluorobutanesulfonic acid

509
OCF₃
pyrid-2-yloxy
OCF₃
3,7-dimethyloct-6-enoic acid

510
OCF₃
pyrid-2-yloxy
OCF₃
2-hydroxyacetic acid

511
OCF₃
pyrid-2-yloxy
OCF₃
adamantanecarboxylic acid

512
OCF₃
pyrid-2-yloxy
OCF₃
pentanedioic acid

513
OCF₃
pyrid-2-yloxy
OCF₃
(9E)octadec-9-enoic acid

514
OCF₃
pyrid-2-yloxy
OCF₃
heptanedioic acid

515
OCF₃
pyrid-2-yloxy
OCF₃
4-dodecylbenzenesulfonic acid

516
OCF₃
pyrid-2-yloxy
OCF₃
hexanedioic acid

517
OCF₃
pyrid-2-yloxy
OCF₃
octanoic acid

518
CF₃
6-chloro-pyridazin-3-yloxy
CF₃
ethanesulfonic acid

519
CF₃
6-chloro-pyridazin-3-yloxy
CF₃
3-((1Z)-2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-

dimethylcyclopropanecarboxylic acid

520
CF₃
6-chloro-pyridazin-3-yloxy
CF₃
1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,9-nonadecafluorononanesulfonic

acid

where

m, p and r are 0; t and u are 1; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; R³and R¹⁶are OCF₃; and R¹, R², R⁴, R⁵, R⁷, R⁸, R¹⁰,

R¹¹, R¹⁴, R¹⁵, R¹⁷and R¹⁸are H:

I-S

Compd

No.
q
Y
R⁶
R⁹

⁻Salt

521
1
OH
(methylethoxy)-carboxamide-
NHC(═O)OCH(CH₃)₂

⁻Cl

phenyl-4-meth-yl

522
0
H
—
pyrid-2-yloxy
H•⁻Cl

where

m, p, and q are 0; t and u are 1; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

R¹, R², R⁴, R⁵, R¹⁴, R¹⁵, R¹⁷, R¹⁸, R⁷, R⁸, R¹⁰and R¹¹are H;

A is —CH₂—; and X and Y are taken together with —OC(═O)O—, forming a 1,3 dioxol-2-one ring:

I-T

note if r = 1, the n-oxide is formed:

Compd.

No.
r
R³
R⁹
R¹⁶

523
0
CF₃
pyrid-2-yloxy
CF₃

524
0
CF₃
pyrimidin-2-yloxy
CF₃

525
0
CF₃
6-chloro-pyridazin-3yloxy
CF₃

526
0
CF₃
2-ethyl-2H-tetrazol-5-yl
CF₃

527
0
CF₃
OC₃H₇
CF₃

528
0
CF₃
CH═NOCH₃
CF₃

529
0
CF₃
CH═NOC₂H₅
CF₃

530
0
CF₃
pyrid-2-yloxy
CF₃

531
0
CF₃
pyrimidin-2-yloxy
CF₃

532
0
CF₃
6-chloro-pyridazin-3yloxy
CF₃

533
0
CF₃
2-ethyl-2H-tetrazol-5-yl
CF₃

534
0
CF₃
OC₃H₇
CF₃

535
0
CF₃
CH═NOCH₃
CF₃

536
0
CF₃
CH═NOC₂H₅
CF₃

537
0
CF₃
OC(═O)NHCH(CH₃)₂
CF₃

538
1
CF₃
pyrid-2-yloxy
CF₃

539
1
CF₃
pyrimidin-2-yloxy
CF₃

540
1
CF₃
6-chloro-pyridazin-3yloxy
CF₃

541
1
CF₃
2-ethyl-2H-tetrazol-5-yl
CF₃

542
1
CF₃
OC₃H₇
CF₃

543
1
CF₃
CH═NOCH₃
CF₃

544
1
CF₃
CH═NOC₂H₅
CF₃

545
1
CF₃
pyrid-2-yloxy
CF₃

546
1
CF₃
pyrimidin-2-yloxy
CF₃

547
1
CF₃
6-chloro-pyridazin-3yloxy
CF₃

548
1
CF₃
2-ethyl-2H-tetrazol-5-yl
CF₃

549
1
CF₃
OC₃H₇
CF₃

550
1
CF₃
CH═NOCH₃
CF₃

551
1
CF₃
CH═NOC₂H₅
CF₃

552
1
CF₃
OC(═O)NHCH(CH₃)₂
CF₃

553
0
OCF₃
pyrid-2-yloxy
OCF₃

554
0
OCF₃
pyrimidin-2-yloxy
OCF₃

555
0
OCF₃
6-chloro-pyridazin-3yloxy
OCF₃

556
0
OCF₃
2-ethyl-2H-tetrazol-5-yl
OCF₃

557
0
OCF₃
OC₃H₇
OCF₃

558
0
OCF₃
CH═NOCH₃
OCF₃

559
0
OCF₃
CH═NOC₂H₅
OCF₃

560
0
OCF₃
pyrid-2-yloxy
OCF₃

561
0
OCF₃
pyrimidin-2-yloxy
OCF₃

562
0
OCF₃
6-chloro-pyridazin-3yloxy
OCF₃

563
0
OCF₃
2-ethyl-2H-tetrazol-5-yl
OCF₃

564
0
OCF₃
OC₃H₇
OCF₃

565
0
OCF₃
CH═NOCH₃
OCF₃

566
0
OCF₃
CH═NOC₂H₅
OCF₃

567
0
OCF₃
OC(═O)NHCH(CH₃)₂
OCF₃

568
1
OCF₃
pyrid-2-yloxy
OCF₃

569
1
OCF₃
pyrimidin-2-yloxy
OCF₃

570
1
OCF₃
6-chloro-pyridazin-3yloxy
OCF₃

571
1
OCF₃
2-ethyl-2H-tetrazol-5-yl
OCF₃

572
1
OCF₃
OC₃H₇
OCF₃

573
1
OCF₃
CH═NOCH₃
OCF₃

574
1
OCF₃
CH═NOC₂H₅
OCF₃

575
1
OCF₃
pyrid-2-yloxy
OCF₃

576
1
OCF₃
pyrimidin-2-yloxy
OCF₃

577
1
OCF₃
6-chloro-pyridazin-3yloxy
OCF₃

578
1
OCF₃
2-ethyl-2H-tetrazol-5-yl
OCF₃

579
1
OCF₃
OC₃H₇
OCF₃

580
1
OCF₃
CH═NOCH₃
OCF₃

581
1
OCF₃
CH═NOC₂H₅
OCF₃

582
1
OCF₃
OC(═O)NHCH(CH₃)₂
OCF₃

where

m, p, q and r are 0; t and u are 1; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; R³and R¹⁶are OCF₃; and R¹, R², R⁴, R⁵, R¹⁰, R¹¹, R¹⁴,

R¹⁵, R¹⁷, R¹⁸and Y are H:

I-U

Compd

No.
R⁷
R⁸
R⁹

583
H
H
OCH₂CH₂OCH₂CH₂OCH₃

584
H
H
OCH₂CH₂CH₂OCH₃

585
H
H
6-methoxy-pyrid-2-yloxy

586
H
methoxy
OCH₂CH₂OCH₃

587
H
Cl
OCH₂CH₂OCH₃

588
Cl
H
OCH₂CH₂OCH₃

where

m, p, and q are 0; t and u are 1; r is 1, forming an N-oxide; R is phenyl substituted

with R¹⁴, R¹⁵, R¹⁶, R¹⁷, R¹⁸;

X is OH; A is —CH₂—; R³and R¹⁶are OCF₃; and R¹, R²,

R⁴, R⁵, R¹⁰, R¹¹, R¹⁴, R¹⁵, R¹⁷, R¹⁸and Y are H:

I-V

Compd

No.
R⁷
R⁸
R⁹

589
H
H
OCH₂CH₂OCH₂CH₂OCH₃

590
H
H
OCH₂CH₂CH₂OCH3

591
H
H
6-methoxy-pyrid-2-yloxy

592
H
methoxy
OCH₂CH₂OCH₃

593
H
Cl
OCH₂CH₂OCH₃

594
Cl
H
OCH₂CH₂OCH₃

The following table sets forth physical characterizing data for compounds of formula I:

TABLE 2

Physical Characteristics

Cmpd

Physical State/Melting Point

No.
Emperical Formula
(° C.)

1
C₂₉H₂₇Cl₂N₃O₂
Solid Foam

2
C₃₁H₂₇F₆N₃O₃
Solid

3
C₃₀H₂₆Cl₂F₃N₃O₂
—

4
C₂₉H₂₅Cl₂F₂N₃O₂
Solid Foam

5
C₃₂H₃₂F₃N₃O₄
Solid

6
C₂₉H₂₅C₁₄N₃O₂
Solid Foam

7
C₃₀H₂₇ClF₃N₃O₂
Solid

8
C₂₉H₂₇F₂N₃O₂
—

9
C₃₀H₂₆Cl₂F₃N₃O₂
—

10
C₂₉H₂₅F₄N₃O₂
—

11
C₃₀H₂₆F₅N₃O₂
—

12
C₃₀H₂₇F₄N₃O₂
Solid

13
C₃₀H₂₆Cl₂F₃N₃O₂
Solid

14
C₃₀H₂₇ClF₃N₃O₂
Solid

15
C₃₀H₂₆Cl₂F₃N₃O₂
—

16
C₃₁H₂₇F₆N₃O₂
—

17
C₃₀H₂₆F₅N₃O₂
Oil

18
C₃₀H₂₇ClF₃N₃O₂
Solid

19
C₃₁H₂₇F₆N₃O₄
Solid, 68-79

20
C₃₁H₂₇F₆N₃O₃
Solid, 59-65

21
C₃₂H₂₈F₆N₂O₄
—

22
C₃₂H₂₈F₆N₂O₂
Solid

23
C₂₈H₂₉Cl₂N₅O
—

24
C₂₈H29Cl₂N5O
Solid

25
C₃₀H₂₉F₆N₅O₃
Solid/Solid Foam

26
C₂₈H₂₇Cl₄N₅O
Solid Foam

27
C₃₀H₂₉F₆N₅O
Solid Foam

28
C₃₀H₃₀F₆N₂O₄
Liquid

29
C₃₁H₃₂F₆N₂O₅
Solid, 82-85

30
C₃₃H₂₇F₉N₂O₄
—

91
C₃₀H₃₁F₆NO₅
Solid, 52-57

92
C₃₀H₃₁F₆NO₃
Solid, 65-70

93
C₂₉H₂₇F₆N₅O₄
Solid

111
C₃₂H₂₈F₆N₂O₃
Solid

112
C₃₁H₂₇F₆N₃O₅
Solid, 198-202

113
C₃₀H₂₉F₆N₅O₂
—

114
C₃₀H₂₉F₆N₅O₄
Solid

115
C₂₉H₂₅Cl₂F₂N₃O₃
Solid Foam

116
C₃₁H₂₇F₆N₃O₄
Solid, 213-215

117
C₃₂H₂₈F₆N₂O₅
Solid

118
C₃₀H₃₀F₆N₂O₅
Solid, 82-184

119
C₃₁H₃₂F₆N₂O₆
Solid, 149-162

120
C₃₁H₂₇F₆N₃O₃
Solid

121
C₃₀H₃₁F₆NO₄
Solid, 151-154

122
C₂₉H₂₇F₆N₅O₅
Solid, 208-211

123
C₃₀H₃₁F₆NO₆
Solid, 219-221

192
C₃₁H₂₆F₇N₃O₃
Solid

193
C₃₂H₂₇F₇N₂O
Solid

194
C₃₁H₂₆F₇N₃O
Solid

195
C₃₅H₃₁ClF₆N₂O₃
Solid

255
C₃₂H₂₉F₆N₃O₄
Solid

256
C₃₂H₂₉F₃N₂O₄
Solid Foam, 54-57

257
C₃₅H₃₇F₃N₂O₃
Solid Foam, 71-75

258
C₃₃H₃₆F₆N₂O₆
Liquid

259
C₃₁H₃₂F₆N₂O₅
Liquid

260
C₃₂H₃₁F₃N₂O₄
Solid Foam, 54-56

261
C₃₁H₂₈BrF₃N₂O₃
Solid Foam, 52-54

262
C₃₂H₃₁F₃N₂O₃
Semi-Solid, 54-57

263
C₃₀H₂₉F₆NO₅
Oil/Solid, 55-65

264
C₃₀H₂₉F₆NO₃
Yellow Amorphous Solid

265
C₃₂H₂₈F₆N₂O₃
Solid Foam, 55-58

266
C₃₁H₃₂F₆N₂O₅
Liquid

267
C₃₀H₂₈Cl₂N₂O₂
Solid Foam 68-71

268
C₃₁H₂₈F₄N₂O₃
Solid Foam, 60-63

269
C₃₂H₂₉F₅N₂O₄
Solid Foam, 54-56

270
C₂₈H₂₆F₆N₂O₂
Solid

271
C₃₃H₃₀F₆N₂O₄
Solid

272
C₃₃H₃₀F₆N₂O₄
Solid

273
C₃₂H₃₅F₆NO₅
Oil

274
C₃₂H₂₉F₆N₃O₅
Solid

275
C₃₀H₂₇F₆N₃O₄
Solid

276
C₃₃H₃₀F₆N₂O₄
Solid

277
C₂₉H₂₇ClF₆N₂O₄
Liquid

278
C₃₄H₃₀ClF₆NO₄
Solid Foam, 67-70

279
C₃₁H₃₁F₆NO₆
Solid

280
C₃₃H₃₅F₆NO₅
Solid, 63-68

281
C₃₃H₂₇F₆N₃O₄
Solid

282
C₃₃H₃₀F₆N₂O₄
Solid Foam, 53-56

283
C₃₃H₂₇F₆N₃O₄
Solid

284
C₄₂H₄₆F₃N₃O₄
Oil

285
C₂₉H₂₈F₆N₂O₅
Solid, 83-92

286
C₃₃H₂₈ClF₆NO₄
Syrup

287
C₃₃H₃₃F₃N₂O₄
Solid Foam, 50-53

288
C₃₁H₂₉F₃N₂O₃
Solid Foam, 49-53

289
C₃₆H₃₂ClF₆NO₅
Solid Foam, 58-64

290
C₃₃H₂₈ClF₆NO₄
Syrup

291
C₃₁H₃₁F₆NO₄
Solid

292
C₃₁H₃₁F₆NO₅
Solid, 68-75

293
C₃₀H₂₇Cl₂F₆NO₄
Oil

294
C₃₅H₃₄F₆N₂O₆
Glass

295
C₃₄H₃₃F₃N₂O₅
Solid Foam, 52-56

296
C₃₀H₂₇F₆N₃O₄
Liquid

297
C₃₃H₂₈ClF₆NO₄
Solid, 45-47

298
C₃₁H₃₀F₆N₂O₅
Semi Solid

299
C₃₁H₃₁F₆NO₂
Solid

300
C₃₁H₃₂F₆N₂O₅

301
C₃₀H₂₇F₉N₂O₄
Oil

302
C₂₇H₂₅F₆NO₂
Solid

303
C₃₀H₃₁F₆NO₂
Solid

304
C₃₄H₃₁F₆NO₄
Solid

305
C₃₈H₄₂F₆N₂O₄
Syrup

306
C₃₅H₂₉F₁₂N₃O₄
Solid

307
C₃₁H₂₆ClF₆N₃O₂
Solid

308
C₃₀H₃₁F₆NO₅
Glass

309
C₃₂H₂₈F₆N₂O₃
Solid

310
C₃₁H₃₂F₆N₂O₅
Oil

311
C₃₂H₃₄F₆N₂O₅

312
C₃₀H₂₉F₇N₂O₄
Oil

313
C₃₁H₃₂F₆N₂O₃
Solid

314
C₃₁H₂₈ClF₃N₂O₃
Solid, 61-85/Solid Foam,

65-95

315
C₃₁H₃₁F₆NO₄
Solid

316
C₃₄H₃₁F₆NO₂
Solid

317
C₃₂H₃₂F₆N₂O₇

318
C₃₀H₃₀F₆N₂O₃
Solid

319
C₃₂H₃₂F₆N₂O₃
Oil

320
C₃₃H₃₄F₆N₂O₅

321
C₃₃H₃₀F₆N₂O₄
Solid

322
C₃₂H₂₇ClF₆N₂O₄
Solid

323
C₃₅H₃₀Cl₂F₆N₂O₅

324
C₃₄H₂₉ClF₆N₂O₅

325
C₃₀H₂₇ClF₃N₃O₃
Solid, 75-81

326
C₃₂H₃₄F₆N₂O₅

327
C₃₂H₃₂F₆N₂O₅
Solid

328
C₂₉H₃₀ClF₃N₂O₃
Solid Foam, 54-57

329
C₃₄H₃₆F₆N₂O₅

330
C₃₁H₃₁F₆NO₃
Solid

331
C₂₇H₂₅F₆NO₄
Solid

335
C₃₅H₃₇F₃N₂O₄
Solid, 108-112

336
C₃₃H₃₆F₆N₂O₇
Solid, 137-142

337
C₃₁H₃₂F₆N₂O₆
Solid, 173-176

338
C₃₂H₃₁F₃N₂O₅
Solid, 98-104

339
C₃₁H₂₈BrF₃N₂O₄
Solid, 103-107

340
C₃₂H₃₁F₃N₂O₄
Solid, 85-90

341
C₃₀H₂₉F₆NO₆
Solid, 164-185

342
C₃₀H₂₉F₆NO₄
Yellow Solid

343
C₃₂H₂₈F₆N₂O₄
Solid, 118-121

344
C₃₁H₃₂F₆N₂O₆
Solid, 165-174

345
C₃₀H₂₈Cl₂N₂O₃
Solid, 95-101

346
C₃₁H₂₈F₄N₂O₄
Solid, 94-96

347
C₃₂H₂₉F₅N₂O₅
Solid, 98-118

349
C₃₃H₃₀F₆N₂O₅
Solid

350
C₃₃H₃₀F₆N₂O₅
Solid

351
C₃₂H₃₅F₆NO₆
Solid

353
C₃₀H₂₇F₆N₃O₅
Solid, 136-140

354
C₃₃H₃₀F₆N₂O₅
Solid

355
C₂₉H₂₇ClF₆N₂O₅
Solid, 181-184

357
C₃₁H₃₁F₆NO₇
Solid

358
C₃₃H₃₅F₆NO₆
Solid, 210-212

359
C₃₃H₂₇F₆N₃O₅
Solid

370
C₃₁H₃₁F₆NO₆
Solid, 212-214

371
C₃₀H₂₇Cl₂F₆NO₅
Oil

372
C₃₅H₃₄F₆N₂O₇
Solid

375
C₃₃H₂₈ClF₆NO₅
Solid Foam, 70-74

378
C₃₀H₂₇F₉N₂O₅
Solid, 192-194

380
C₃₀H₃₁F₆NO₃
Solid

381
C₃₄H₃₁F₆NO₅
Solid

383
C₃₁H₃₁F₆NO₃
Solid

384
C₃₁H₂₆ClF₆N₃O₃
Solid

385
C₃₀H₃₁F₆NO₆
Solid

387
C₃₁H₃₂F₆N₂O₆
Oil

389
C₃₀H₂₉F₇N₂O₅
Solid, 193-195

390
C₃₁H₃₂F₆N₂O₄
Solid

391
C₃₁H₂₈ClF₃N₂O₄
Solid, 62-66

392
C₃₁H₃₁F₆NO₅
Solid

393
C₃₄H₃₁F₆NO₃
Solid

395
C₃₀H₃₀F₆N₂O₄
Solid

396
C₃₂H₃₂F₆N₂O₄
Solid

399
C₃₂H₂₇ClF₆N₂O₅
Solid, 200-203

402
C₃₀H₂₇ClF₃N₃O₄
Solid, 84-88

404
C₃₂H₃₂F₆N₂O₆
Solid

405
C₂₉H₃₀ClF₃N₂O₄
Solid, 77-82

407
C₃₁H₃₁F₆NO₄
Solid

409
C₃₅H₂₉F₁₂N₃O₅
Solid

410
C₃₀H₂₉F₆N₃O₆
Solid, 210-213

411
C₃₂H₂₇ClF₆N₂O₄
Solid, 204-207

412
C₃₁H₂₆ClF₆N₃O₅
Solid, 210-212

413
C₃₂H₂₉F₆N₃O₅
Solid

416
C₃₀H₂₉F₆N₅O₄
Solid

417
C₃₀H₃₀F₆N₂O₅
Solid

418
C₂₈H₂₅F₆NO₅
Solid

419
C₃₁H₃₂F₆N₂O₆
Solid

421
C₃₂H₂₈F₆N₂O₆
Solid

422
C₃₁H₂₇F₆N₃O₆
Solid

423
C₃₁H₃₂F₆N₂O₇
Solid

424
C₃₀H₃₀F₆N₂O₆
Solid

425
C₃₁H₂₆ClF₆N₃O₆
Solid

426
C₃₀H₂₉F₆N₅O₅
Solid

430
C₃₂H₂₇F₇N₂O₅
Solid

431
C₃₂H₂₆F₆N₂O₅
Solid

432
C₃₁H₂₅F₆N₃O₃
Solid

433
C₃₁H₂₇Cl₂F₃N₂O₃
Solid Foam, 69-71

434
C₂₉H₂₇F₂N₃O₂
Solid Foam

435
C₃₂H₃₀ClF₃N₂O₃
Solid Foam, 60-64

436
C₃₂H₃₀ClF₃N₂O₃
Solid Foam, 59-62

437
C₃₁H₂₈ClF₃N₂O₃
Solid Foam, 59-62

438
C₃₁H₂₇Cl₂F₃N₂O₃
Solid Foam, 59-63

439
C₃₁H₂₈ClF₃N₂O₃
Solid Foam, 55-58

440
C₃₄H₃₄F₃N₃O₄
Solid Foam, 53-56

441
C₃₁H₂₇Cl₂F₃N₂O₃
Solid Foam, 60-64

442
C₃₁H₂₇Cl₂F₃N₂O₃
Solid Foam, 58-62

443
C₃₁H₂₇Cl₂F₃N₂O₃
Solid Foam, 55-59

444
C₂₉H₂₉Cl₂F₃N₂O₃
Solid Foam, 55-59

445
C₃₁H₂₇ClF₄N₂O₃
Solid Foam, 60-63

446
C₃₂H₂₆F₄N₂O₆
Oil/Solid Foam, 60-64

447
C₃₃H₃₀F₆N₂O₅
Solid

448
C₃₂H₂₉F₆N₃O₂
Solid

449
C₃₂H₃₄F₆N₄O
Solid

450
C₃₂H₃₄F₆N₂O
Solid

451
C₃₄H₃₂F₆N₄O₂
Solid

452
C₃₄H₃₁F₆N₃O₃
Solid

453
C₂₉H₂₉Cl₂F₃N₂O₄
Solid, 83-86

454
C₃₁H₂₇Cl₂F₃N₂O₄
Solid, 101-105

455
C₃₁H₂₇Cl₂F₃N₂O₄
Solid, 100-104

456
C₃₁H₂₇Cl₂F₃N₂O₄
Solid, 79-82

457
C₃₁H₂₇Cl₂F₃N₂O₄
Solid, 98-102

458
C₃₁H₂₈ClF₃N₂O₄
Solid, 85-89

459
C₃₁H₂₈ClF₃N₂O₄
Solid, 98-102

460
C₃₁H₂₇Cl₂F₃N₂O₄
Solid Foam, 76-80

461
C₃₂H₃₀ClF₃N₂O₄
Solid, 145-149

462
C₃₂H₃₀ClF₃N₂O₄
Solid, 89-92

463
C₃₁H₂₇ClF₄N₂O₄
Solid, 84-87

464
C₃₂H₂₆F₄N₂O₇
Solid Foam, 72-77

465
C₃₃H₃₀F₆N₂O₆
Solid

466
C₃₄H₃₂F₆N₄O₃
Solid

467
C₃₂H₃₂F₆N₄O₂
Solid

468
C₃₄H₃₁F₆N₃O₄
Solid

470
C₂₉H₂₈ClF₆NO₅
Solid Foam, 42-45

471
C₂₉H₂₈ClF₆NO₅
Solid Foam, 42-44

472
C₂₉H₂₈ClF₆NO₅
Solid Foam, 43-45

473
C₂₉H₂₈ClF₆NO₄
Syrup

474
C₂₈H₂₆ClF₆NO₃
Syrup

475
C₂₈H₂₆ClF₆NO₄
Syrup

476
C₃₀H₃₀ClF₆NO₄
Oil

477
C₂₈H₂₆BrF₆NO₄
Syrup

478
C₂₈H₂₆ClF₆NO₅
Solid, 54-58

479
C₂₈H₂₆ClF₆NO₄
Solid, 55-60

480
C₃₀H₃₀ClF₆NO₅
Semi-Solid

481
C₂₉H₂₈ClF₆NO₅
Solid, 57-61

482
C₂₈H₂₆BrF₆NO₅
Solid, 60-65

483
C₃₀H₃₁F₆N₂O₅•C₃H₇O₄S
Solid, 120-128

484
C₃₀H₃₁F₆N₂O₅•C₅H₉O₃
Solid, 74-80

485
C₃₁H₂₇ClF₆N₃O₅•C₈H₁₅O₂
Solid, 190-194

486
C₃₀H₃₁F₆N₂O₅•C₈H₁₅O₂
Solid, 53-65

487
C₃₀H₃₁F₆N₂O₅•C₄F₉O₃S
Solid, 85-94

488
C₃₁H₂₇ClF₆N₃O₃•C₆H₇O₇
Solid, 132-142

489
C₃₀H₃₀F₆N₃O₆•C₆H₇O₇
Solid, 113-123

490
C₃₀H₃₁F₆N₂O₅•C₁₀H₁₅O₄S
Solid, 123-131

491
C₃₀H₃₁F₆N₂O₅•C₂H₅O₃S
Solid, 188-192

492
C₃₁H₂₇ClF₆N₃O₅•C₆H₇O₇
Solid, 135-144

493
C₃₀H₃₁F₆N₂O₅•C₇H₁₁O₂
Solid, 78-88

494
C₃₀H₃₁F₆N₂O₅•C₆H₇O₇
Solid, 114-119

495
C₃₀H₃₁F₆N₂O₅•C₈F₁₇O₃S
Solid, 74-84

496
C₃₂H₂₉F₆N₂O₅•C₈F₁₇O₃S
Solid, 96-101

497
C₃₂H₂₉F₆N₂O₅•Cl
Solid, 140-143

498
C₃₂H₂₉F₆N₂O₅•C₁₀H₁₅O₄S
Solid, 122-136

499
C₃₂H₂₉F₆N₂O₅•C₈H₁₅O₂
Solid, 55-65

500
C₃₂H₂₉F₆N₂O₅•C₃H₇O₄S
Solid, 111-128

501
C₂₉H₂₉ClF₆N₂O₅•C₆H₇O₇
Solid, 96-115

502
C₃₂H₂₉F₆N₂O₅•C₇H₁₁O₂
Solid, 80-85

503
C₃₂H₂₉F₆N₂O₅•C₅H₉O₃
Solid, 75-81

504
C₃₂H₂₉F₆N₂O₅•C₆H₇O₇
Solid, 195-197

505
C₃₂H₂₉F₆N₂O₅•C₁₀H₁₅O₄S
Solid, 121-132

506
C₃₂H₂₉F₆N₂O₅•C₂H₅O₃S
Solid, 168-184

507
C₃₀H₃₁F₆N₂O₅•C₁₀H₁₅O₄S
Solid, 118-119

508
C₃₂H₂₉F₆N₂O₅•C₄F₉O₃S
Solid, 94-104

509
C₃₂H₂₉F₆N₂O₅•C₁₀H₁₇O₂
Solid, 43-58

510
C₃₂H₂₉F₆N₂O₅•C₂H₃O₃
Solid, 87-103

511
C₃₂H₂₉F₆N₂O₅•C₁₁H₁₅O₂
Solid, 100-125

512
C₃₂H₂₉F₆N₂O₅•C₅H₇O₄
Solid, 80-85

513
C₃₂H₂₉F₆N₂O₅•C₁₈H₃₃O₂
Liquid

514
C₃₂H₂₉F₆N₂O₅•C₇H₁₁O₄
Solid, 78-88

515
C₃₂H₂₉F₆N₂O₅•C₁₈H₂₉O₃S
Solid, 85-97

516
C₃₂H₂₉F₆N₂O₅•C₆H₉O₄
Solid, 78-90

517
C₃₂H₂₉F₆N₂O₅•C₈H₁₅O₂
Solid, 44-65

518
C₃₁H₂₇ClF₆N₃O₃•C₂H₅O₃S
Solid

519
C₃₁H₂₇ClF₆N₃O₃•C₉H₉ClF₃O₂
Solid, 112-117

520
C₃₁H₂₇ClF₆N₃O₃•C₈F₁₇O₃S
Solid

521
C₄₂H₄₆F₆N₃O₈•Cl
Solid,

522
C₃₂H₂₉F₆N₂O₄•ClH
Solid, 78-82

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 Test Compounds Applied to the

Surface of the Diet of Tobacco Budworm

Cmpd. No

1
2
3
4
5
6
7
8
9
10

Percent Mortality
0
100
100
100
0
83
100
0
100
0

Percent Growth
57
100
100
100
97
100
100
41
100
50

Inhibition

Cmpd. No

11
12
13
14
15
16
17
18
19
20

Percent Mortality
33
0
100
100
100
100
83
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

21
22
23
24
25
26
27
28
29
30

Percent Mortality
100
100
100
0
100
100
100
100
100
100

Percent Growth
100
100
100
98
100
100
100
100
100
100

Inhibition

Cmpd. No

91
92
93
111
112
113
114
115
116
117

Percent Mortality
100
100
100
100
100
100
100
50
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

118
119
120
121
122
123
192
193
194
195

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

255
256
257
258
259
260
261
262
263
264

Percent Mortality
100
17
100
100
100
100
100
100
100
33

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

265
266
267
268
269
270
271
272
273
274

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

275
276
277
278
279
280
281
282
283
284

Percent Mortality
100
100
100
100
83
100
100
100
100
17

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

285
286
287
288
289
290
291
292
293
294

Percent Mortality
100
100
100
100
100
100
17
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

295
297
298
299
300
301
302
303
304

Percent Mortality
100
100
100
100
100
100
17
100
100

Percent Growth
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

305
306
307
308
309
310
311
312
313
314

Percent Mortality
0
100
100
100
100
100
100
100
100
100

Percent Growth
31
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

315
316
317
319
320
321
322
323
324

Percent Mortality
100
67
100
100
100
100
100
33
33

Percent Growth
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

325
3256
327
328
329
330
331
335
336
337

Percent Mortality
100
100
100
100
67
100
50
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

338
339
340
341
342
343
344
345
346
347

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

349
350
351
353
354
355
357
358
359
370

Percent Mortality
100
100
100
100
100
100
0
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

371
372
375
378
380
381
383
384
385
387

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

389
390
391
392
393
396
399
402
404

Percent Mortality
100
100
100
100
100
67
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

405
407
409
410
411
412
413
416
417
418

Percent Mortality
100
100
100
100
100
100
100
100
100
0

Percent Growth
100
100
100
100
100
100
100
100
100
83

Inhibition

Cmpd. No

419
421
422
423
424
425
426
430
431

Percent Mortality
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

432
433
434
435
436
437
438
439
440
441

Percent Mortality
100
100
0
100
100
100
100
100
100
100

Percent Growth
100
100
56
100
100
100
100
100
100
100

Inhibition

Cmpd. No

442
443
444
445
446
447
448
449
450
451

Percent Mortality
100
100
100
100
100
100
0
0
50
0

Percent Growth
100
100
100
100
100
100
96
78
100
100

Inhibition

Cmpd. No

452
453
454
455
456
457
458
459
460
461

Percent Mortality
0
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

462
463
464
465
466
467
468
470
471

Percent Mortality
100
100
100
100
17
50
17
17
0

Percent Growth
100
100
100
100
100
100
100
89
82

Inhibition

Cmpd. No

472
473
474
475
476
477
478
479
480
481

Percent Mortality
17
100
83
100
67
100
100
100
100
100

Percent Growth
93
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

482
483
484
485
486
487
488
489
490
491

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

492
493
494
495
496
497
498
499
500
501

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

502
503
504
505
506
507
508
509
510
511

Percent Mortality
100
100
100
100
100
100
100
100
100
100

Percent Growth
100
100
100
100
100
100
100
100
100
100

Inhibition

Cmpd. No

512
513
514
515
516
517
518
519
520
521
522

Percent Mortality
100
100
100
100
100
100
100
100
100
50
100

Percent Growth
100
100
100
100
100
100
100
100
100
100
100

Inhibition

These tests were conducted with 0.25 millimoles of candidate insecticide on the surface of the diet

As set forth in the foregoing Table 3, most of the compounds therein provided 100% mortality and 100% growth inhibition of tobacco budworm.

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
	60510568	Oct 2003	US
	60609533	Sep 2004	US

N-Substituted Azacycles

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

Parent Case Info

PCT Information

Provisional Applications (2)