WO2004026030A2 - Insecticidal tricyclic derivatives - Google Patents

Insecticidal tricyclic derivatives Download PDF

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Publication number
WO2004026030A2
WO2004026030A2 PCT/US2003/028791 US0328791W WO2004026030A2 WO 2004026030 A2 WO2004026030 A2 WO 2004026030A2 US 0328791 W US0328791 W US 0328791W WO 2004026030 A2 WO2004026030 A2 WO 2004026030A2
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Prior art keywords
aryl
hydrogen
alkyl
halogen
alkoxy
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PCT/US2003/028791
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French (fr)
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WO2004026030A3 (en
Inventor
Joseph A. Argentine
Franz Schuler
John A. Dixson
Scott D. Crawford
Daniel H. Cohen
Elizabeth G. Rowley
Saroj Sehgel
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Fmc Corporation
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Priority to MXPA05002884A priority Critical patent/MXPA05002884A/en
Priority to AU2003272362A priority patent/AU2003272362A1/en
Priority to EP03754541A priority patent/EP1538906A2/en
Priority to JP2004537792A priority patent/JP2005539076A/en
Priority to BRPI0314108-0A priority patent/BR0314108A/en
Priority to US10/528,740 priority patent/US20060111342A1/en
Publication of WO2004026030A2 publication Critical patent/WO2004026030A2/en
Publication of WO2004026030A3 publication Critical patent/WO2004026030A3/en
Priority to ZA2005/01774A priority patent/ZA200501774B/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
    • A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
    • A01N43/18—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with sulfur as the ring hetero atom
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
    • A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
    • A01N43/22—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom rings with more than six members
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/62—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms three- or four-membered rings or rings with more than six members

Definitions

  • the present invention generally relates to insecticidal compounds and their use in controlling insects.
  • it pertains to insecticidal tricyclic derivatives and agriculturally acceptable salts thereof, compositions of these insecticides, and methods for their use in controlling insects.
  • insects can cause significant damage to crops grown in agriculture, resulting in loss of millions of dollars of value associated with a given crop. Although there are many orders of insects that can cause significant crop damage, insects of the suborder "Homoptera" are of major importance.
  • the suborder Homoptera includes, for example, aphids, leafhoppers, cicadas, whiteflies, and mealybugs, to name a few.
  • Homopterans have piercing/sucking mouthparts, enabling them to feed by withdrawing sap from vascular plants. Insect damage from homopterans is manifested in several different ways, other than damage caused by direct feeding.
  • honeydew a sticky waste product that adheres to plants upon which the insect feeds and lives.
  • Honeydew alone causes cosmetic injury to crop plants. Sooty molds will often grow on honeydew, making food products or ornamental plants look unappealing, thereby reducing their cosmetic and economic value.
  • Some homopterans have toxic saliva that is injected into plants while they are feeding. The saliva can cause plant damage through disfigurement and in some instances plant death. Homopterans can also vector disease-causing pathogens. Unlike direct damage, it does not take a large number of disease-vectoring insects to cause considerable damage to crop plants.
  • insecticides for control of, for example, Homoptera and other orders of insects; as well as new acaricides, that are safer, more effective, and less costly for use on crops such as wheat, corn, soybeans, potatoes, and cotton to name a few.
  • acaricides for crop protection, insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and have no deleterious effects to mammals and other living organisms.
  • WO93/00811 and US Patent 5,366,975 disclose a method of controlling an invertebrate pest, comprising contacting the pest with a pest- controlling amount of an agent having substantial inhibitory activity toward a phenylethanolamine reuptake transporter as determined by a radioactive octopamine reuptake inhibition assay.
  • compositions capable of inhibiting the octopamine transporter set forth in WO93/00811 and US Patent 5,366,975 include tricyclic antidepressants, wherein the tricyclic antidepressants exemplified are desipramine, amitriptyline, imipramine, amoxapine, nortriptyline, protriptyline, maprotiline, and doxepin, and pharmaceutically acceptable salts thereof. Desipramine and amitriptyline are specifically shown to have anti-feeding activity against tobacco hornworm.
  • the tricyclic antipruritic cyproheptadine is also disclosed as having anti-feeding activity against tobacco hornworm.
  • R is selected from the group which consists of hydrogen and - alkyl.
  • the dibenzocyclohepten-5-ylidene thiazolidinones are reported to have larvicidal activity against horse strongyles, anthelminthic activity against Syphacia obvelata and are useful for the treatment of pinworm infestations in mammals, and also possess antibacterial activity against certain gram-positive and gram-negative organisms.
  • R through R are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkenyl, alkynyl, trialkylsilylalkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl, dialkylaminosulfonyl, nitro, cyano, amino, formyl, or alkylcarbonyl;
  • R 9 and R 10 are independently selected from hydrogen, alkyl, or (piperidin-4- yl)alkyl; or
  • R 39 , R 40 and R 41 are independently selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 40 and R may be taken together with -C 2 H 4 N(CH 3 )C 2 H 4 - to form a piperazine ring; u is 0 or 1, and when u is 1, an N-oxide is formed; n is 0, and R a is hydrogen; or n is 1 to 8, and R a is selected from one or more of alkyl, alkoxyalkyl, alkoxycarbonyl, and aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R 11 is selected from hydrogen, alkyl, alkylaminoalkoxy, dialkylaminoalkoxy,
  • v is 0 or 1
  • A is a bridging group selected from -O-, -S-, -NH-, and -CH 2 -; u is as described above;
  • R 42 through R 45 are independently selected from hydrogen; alkyl alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 43 and R 44 may be taken together with -C 5 H 10 - to form a piperidine ring; m, p, and q are 0, and R b , R c and R d are hydrogen; or m is 1 to 8, p is 1 to 7, and q is 1 to 10, and R b , R c , and R d , respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 11 and R 12 may be taken together with where R a , n, u, and R 39 are as described above;
  • R 12 when not taken together with R u , and R 13 , R 14 , and R 16 , are independently selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, or dialkylaminosulfonyl;
  • R 15 is selected from
  • R 17 is hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy,
  • R 46 is selected from selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R 47 and R 48 are independently selected from hydrogen and alkyl; or R 47 and R 48 may be taken together with -C 5 H 10 - to form a piperidine ring, or with -C 2 H 4 N(CH 3 )C 2 H 4 -, or -C 2 H 4 N(C 2 H 4 OH)C 2 H 4
  • R 18 and R 19 are independently selected from hydrogen, alkyl, amino, alkylaminoalkyl, and dialkylaminoalkyl;
  • R is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocai'bonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl;
  • R 21 is selected from hydrogen, alkyl,
  • R 49 through R 52 are independently selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 50 and R 51 may be taken together with -C 5 H1 0 - to form a piperidine ring; r, s, and t are 0, and R e , R f , and R ⁇ are hydrogen, or
  • R e , R f , and R ⁇ are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl;
  • R " through R , inclusively, are independently selected from hydrogen, and alkyl;
  • R is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl;
  • R 31 and R 32 are independently selected from hydrogen, and alkyl,
  • R 33 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl
  • the present invention is also directed to compositions containing an insecticidally effective amount of at least one of a compound of formula I, and optionally, an effective amount of at least one of a second compound, with at least one insecticidally compatible carrier.
  • the present invention is also directed to methods of controlling insects, where control is desired, which comprise applying an insecticidally effective amount of the above composition to the locus of crops, or other areas where insects are present or are expected to be present.
  • compositions comprising at least one of an insecticidally effective amount of a compound of formula I and at least one insecticidally compatible carrier therefor, wherein the compound of formula I is:
  • R through R are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkenyl, alkynyl, trialkylsilylalkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl, dialkylaminosulfonyl, nitro, cyano, amino, formyl, or alkylcarbonyl;
  • R 9 and R 10 are independently selected from hydrogen, alkyl, or (piperidin-4- yDalkyl; or
  • R 9 and R 10 may be taken together with , where
  • R 39 , R 40 and R 41 are independently selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or R 40 and R 41 may be taken together with -C 2 H 4 N(CH 3 )C 2 H 4 - to form a piperazine ring; u is O or l, and when u is 1, an N-oxide is formed; n is 0, and R a is hydrogen; or n is 1 to 8, and R a is selected from one or more of alkyl, alkoxyalkyl, alkoxycarbonyl, and aryl, wherein aryl is optionally substitute
  • v is 0 or 1
  • A is a bridging group selected from -O-, -S-, -NH-, and -CH 2 -; u is as described above;
  • R 42 through R 5 are independently selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 43 and R 44 may be taken together with -C 5 H 10 - to form a piperidine ring; m, p, and q are 0, and R b , R c and R d are hydrogen; or m is 1 to 8, p is 1 to 7, and q is 1 to 10, and R b , R c , and R d , respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 11 and R 12 may be taken together with where R a , n, u, and R 39 are as described above;
  • R 12 when not taken together with R 11 , and R 13 , R 14 , and R 16 , are independently selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, or dialkylaminosulfonyl;
  • R 15 is selected from
  • R is hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy,
  • R 46 is selected from selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R 47 and R 48 are independently selected from hydrogen and alkyl; or R 47 and R 48 may be taken together with -C 5 H 10 - to form a piperidine ring, or with
  • R 18 and R 19 are independently selected from hydrogen, alkyl, amino, alkylaminoalkyl, and dialkylaminoalkyl
  • R 20 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl
  • R 21 is selected from hydrogen, alkyl,
  • R 49 through R 52 are independently selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
  • R 50 and R 51 may be taken together with -C 5 H 10 - to form a piperidine ring; r, s, and t are 0, and R e , R f , and R s are hydrogen, or r is 1 to 8, s is 1 to 7, t is 1 to 10, and R e , R f , and R g , respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R 22 through R 29 , inclusively, are independently selected from hydrogen, and alkyl; R 30 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl
  • Preferred insecticidal compositions of the present invention are comprised of compounds of formula I, wherein X is -CR 9 R 10 - and Y is selected from -O-, -S-,
  • R 39 is selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; and, R 22 , R 23 , R 34 and R 35 are independently selected from hydrogen and alkyl.
  • compositions of the present invention are comprised of compounds of formula I, wherein X is -CR 1 'R ⁇ CR ⁇ R 14 - and Y is selected from -O-, -S- and -CR 22 R 23 -; where R 11 is selected from
  • R 42 and R 45 are independently selected from hydrogen; alkyl; alkenyl; alkynyl hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R 12 is selected from selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbon
  • R 22 and R 23 are independently selected from hydrogen and alkyl.
  • Yet other preferred insecticidal compositions of the present invention are comprised of compounds of formula I, wherein X is -CR 18 R 1 NR 20 - and Y is selected from -O-, -S- and -CR 22 R 23 -; where
  • R is selected from hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, dialkylaminoalkyl, alkylaminocarbonyl, and dialkylaminocarbonyl; and, R 22 and R 3 are independently selected from hydrogen and alkyl.
  • R 49 is selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; and, R 22 and R 23 are independently selected from hydrogen and alkyl.
  • Certain compounds within the scope of formula I which find utility in the novel insecticidal compositions of the present invention, may be new and novel compositions of matter.
  • 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.
  • Agriculturally acceptable salts and metal complexes include, without limitation, for example, ammonium salts, the salts of organic and inorganic acids, such as hydrochloric acid, sulfonic acid, ethanesulfonic acid, trifluoroacetic acid, methylbenzenesulfonic acid, phosphoric acid, gluconic acid, pamoic acid, and other acid salts, and the alkali metal and alkaline earth metal complexes with, for example, sodium, potassium, lithium, magnesium, calcium, and other metals.
  • the methods of the present invention are predicated on causing an insecticidally effective amount of a compound of formula I to be present within insects in order to kill or control the insects.
  • Preferred insecticidally effective amounts are those that are sufficient to kill the insect. It is within the scope of the present invention to cause a compound of formula I to be present within insects by contacting the insects with a derivative of that compound, which derivative is converted within the insect to a compound of formula I. This invention includes the use of such compounds, which can be referred to as pro-insecticides.
  • Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present.
  • the present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents and compositions thereof.
  • alkyl As used in this specification and unless otherwise indicated the substituent terms "alkyl”, “alkenyl”, “alkynyl”, “alkoxy”, “alkenyl”, and “alkynyl” 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.
  • aryl refers to an aromatic ring structure, including fused rings, having four to ten carbon atoms, for example, phenyl and naphthyl.
  • 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.
  • THF refers to tetrahydrofuran.
  • DMF refers to N,N-dimethylformamide.
  • halogen or “halo” refers to fluorine, bromine, iodine, or chlorine.
  • 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.
  • insecticidal composition refers to a composition containing an insecticide capable of killing an insect pest.
  • insecticidally effective amount refers a composition containing an insecticide that is applied at a rate of application of insecticide sufficient to kill an insect pest.
  • tricyclic derivatives of formula I can be synthesized by methods that are individually known to one skilled in the art from intermediate compounds readily available in commerce.
  • Scheme 1 illustrates a general procedure for synthesizing tricyclic derivatives of formula I, where, for example, X is -CR 9 R 10 -, and Y is -O- or -S-, where R 9 and R 10 are taken together with
  • R 39 is, for example ' -CH .
  • TiCl 4 / Zn / THF / 60 °C b) C1C0 2 CH 2 CC1 3 / CH 3 CN / CHC1 3 / Reflux; c) NaOH / H 2 0 / CH 3 OH / Reflux; d) LiAlH 4 / THF / RT
  • Y is, for example, -S- or -O- and R is 1-methylethyl
  • Intermediate Ha was in turn cyclized with aluminum chloride in an appropriate high-boiling solvent such as chlorobenzene, yielding the corresponding cyclized ketone derivative lib, for example 2-(methylethyl)-10-dibenzo[b,f]-l,4- thiazaperhydroepin-11-one.
  • Intermediate lib was then chlorinated with, for example, phosphorous oxychloride in the presence of a base catalyst, providing the corresponding chloride derivative lie.
  • the so-prepared chloride derivative lie, for example, H-chloiO-2-(methylethyl)dibenzo[b,fJl,4-thiazepine, was then converted to compounds of formula I by reacting it with an appropriate amine, for example 1- methylpiperazine, providing the compound 2-(methylethyl)-l l-(4- methylpiperazinyl)dibenzo[b,f] 1,4-thiazepine I.
  • an appropriate amine for example 1- methylpiperazine
  • Scheme 3 illustrates a general procedure for synthesizing tricyclic derivatives of formula I, where, for example, X is CR ⁇ R 12 CR 13 R 14 and Y is -O- or -S-, and R 11 and R 12 represent a number of moieties.
  • Y is, for example, -S- or -0-; and R 2 is -OCF.
  • R 42 is, for example -CH 3 m and u are 0
  • those compounds of formula I for example, where X is -CR ⁇ R 12 CR 13 R 14 - and Y is -O- or -S-, were again prepared in multi-step syntheses.
  • an appropriately substituted acetic acid derivative such as 2- ⁇ 2-[4- (trifluoromethoxy)phenylthio]phenyl ⁇ acetic acid, was cyclized with Eaton's Reagent affording the corresponding ketone derivative Ilia, for example, 8- (trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-one.
  • the ketone intermediate Ilia may be reacted directly with an appropriate base to provide additional compounds of formula I.
  • 8- (trifluoromethoxy)-HH-dibenzo[b,fJthiepan-10-one Ilia may be reacted under basic conditions with halogen-containing compound, such as 4- bromopyridine, in an appropriate solvent, providing a compound of formula I, for example, 10-(4-pyridyl)-8-(trifluoromethoxy)-l lH-dibenzo[b,f]thiepan-10-ol.
  • Any compound of formula I containing an alcohol moiety may be further reacted to prepare yet other compounds of formula I.
  • 10-(4-pyridyl)- 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol was alkylated with an alkyl halide, such as methyl iodide, then reduced with a reducing agent in an appropriate solvent, yielding the corresponding alkyl derivative, a compound of formula I, for example, 10-(1 -methyl (4- 1,2,5, 6-tetrahydropyridyl))- 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol I.
  • a compound of formula I containing an alcohol moiety such as 10-(4-pyridyl)-8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10- ol, as set forth above, may be reacted with, for example, (diethylamino) sulfur trifluoride in an appropriate solvent, affording yet other compounds of formula I, for example, 10-fluoro-10-(4-pyridyl)-8-(trifluoromethoxy)-l lH- dibenzo[b,f]thiepane.
  • the present insecticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water-soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about" were placed in front of the amounts specified.
  • 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.
  • 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.
  • ECs emulsifiable concentrates
  • ECs emulsifiable concentrates
  • ECs emulsifiable concentrates
  • 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.
  • 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.
  • compositions 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.
  • 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.
  • 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.
  • higher application rates e.g., four times the rates mentioned above may be employed.
  • the herbicides include, without limitation, for example: N- (phosphonomethyl)glycine ("glyphosate”); aryloxyalkanoic acids such as (2,4- dichlorophenoxy)acetic acid (“2,4-D"), (4-chloro-2-methylphenoxy)acetic acid (“MCPA”), (+/-)-2-(4chloro-2-methylphenoxy)propanoic acid (“MCPP”); ureas such as N,N-dimethyl-N'-[4-(l-methylethyl)phenyl]urea (“isoproturon”); imidazolinones such as 2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH- imidazol-2-yl]-3-pyridinecarboxylic acid (“imazapyr”),
  • 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- cypermefhrin, biphenthrin, resolved cyhalothrin, etofenprox, esfenvalerate, tralomehtrin, tefluthrin, cycloprothrin, betacyfluthrin, and acrinathrin; carbamate insecticides, such as aldecarb, carbaryl, carbofuran, and
  • 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 fosetyl, iprobenfos, pyrazophos, edifenphos, and tolclofos-
  • 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.
  • 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.
  • 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.
  • 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.
  • nitrogen fertilizers such as ammonium sulfate, ammonium nitrate, and bone meal
  • phosphate fertilizers such as superphosphate, triple superphosphate, ammonium sulfate, and diammonium sulfate
  • potassium fertilizers such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers.
  • reaction mixture was stirred for ten minutes, then it was heated to 60 °C where it stirred for about 20 hours. After this time, the reaction mixture was cooled and poured into 50 mL of an aqueous 10% solution of potassium carbonate. The mixture was stirred for about 20 minutes, then 50 mL of ethyl acetate was added and the mixture was stirred for an additional 20 minutes. The mixture was then filtered through a pad of diatomaceous earth, and the diatomaceous earth pad was washed with 50 mL of ethyl acetate.
  • Example 1 by the reaction of 0.78 gram (0.004 mole) of xanthone, 0.95 gram
  • Step C Synthesis of 9-(l-methoxycarbonyl-4-piperidylidene)xanthene as an intermediate
  • the mixture was extracted with two 20 mL portions of ethyl acetate and the combined extracts were dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to an oil residue. The residue was purified with column chromatography on silica using 5: 1 heptane:ethyl acetate as eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.28 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
  • Step B Synthesis of 2-(methylethyl)-10-dibenzo[b,f]-l,4- thiazaperhydroepin-11-one as an intermediate Under a nitrogen atmosphere a stirred mixture of 1.0 gram (0.0075 mole) of aluminum chloride in five mL of chlorobenzene was warmed to 80 °C, and a solution of 1.4 grams (0.0052 mole) of 2- [4-
  • the aqueous extracts were combined and washed with 20 mL of diethyl ether, made basic with aqueous 10% potassium carbonate; then extracted with three 20 mL portions of diethyl ether.
  • the ether extracts were combined, dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue.
  • the residue was purified with column chromatography on silica using methylene chloride, 1% methanol in methylene chloride, and 3% methanol in methylene chloride as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.21 gram of Compound 193.
  • the NMR spectrum was consistent with the proposed structure.
  • EXAMPLE 4 This example illustrates one protocol for the preparation of 11 -(4- methylpiperazinyl)-2-(trifluoromethoxy)- 10H, 1 lH-dibenzo[b,f]thiopane (Compound 106 in table below)
  • Step A Synthesis of 2- ⁇ 2-[4-(trifluoromethoxy)phenylthio]phenyl ⁇ acetic acid as an intermediate
  • the reaction mixture was warmed to reflux where it stirred for about 18 hours. After this time the reaction mixture was cooled to ambient temperature and filtered.
  • Step C Synthesis of l l-chloro-2-(trifluoiOmethoxy)-10H,HH- dibenzo[b,f]fhiepane as an intermediate
  • reaction mixture was poured into 100 mL of aqueous 10% hydrochloric acid, to which was then added 300 mL of an aqueous solution saturated with sodium chloride.
  • the mixture was extracted with three 100 mL portions of ethyl acetate.
  • the combined extracts were dried with sodium sulfate, filtered and the filtrate concentrated under reduced pressure to a residue.
  • it was dissolved in 50 mL of methylene chloride and the mixture was concentrated under reduced pressure to a residue.
  • the drying process was repeated two additional times, yielding a dried residue.
  • the residue was again dissolved in 50 mL of methylene chloride and 3 mL of thionyl chloride was added.
  • the reaction mixture was stirred at ambient temperature during a 2.5 hour period. After this time the reaction mixture was concentrated under reduced pressure, yielding 2.0 grams of the subject compound.
  • Step D Synthesis of Compound 106 A solution of 1.0 gram (0.0030 mole) of l l-chloro-2-(trifluoromefhoxy)-
  • This example illustrates one protocol for the preparation of 10-(4-pyridyl)- 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol (Compound 61 in table below)
  • An aliquot of 1.0 gram (0.0051 mole) of 4-bromopyridine hydrochloride was stirred for 20 minutes with 20 mL of an aqueous solution saturated with sodium bicarbonate. The mixture was then extracted with two 20 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure, providing 0.5 gram of the free pyridine.
  • reaction mixture Upon completion of addition the reaction mixture was allowed to warm to ambient temperature as it stirred during a 1.5 hour period. After this time the reaction mixture was poured into 50 mL of water and the organic layer was separated. The aqueous layer was extracted with two 30 mL portions of diethyl ether. The extracts and the organic layer were combined and washed with an aqueous solution saturated with sodium chloride. The combination was then dried with sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica using 3:1 heptane:ethyl acetate, then 1:1 heptane:ethyl acetate as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.6 gram of Compound 61. The NMR spectrum was consistent with the proposed structure. This reaction was repeated several times.
  • EXAMPLE 6 This example illustrates one protocol for the preparation of 10-(l -methyl (4- l,2,5,6-tetrahydropyridyl))-8-(trifluoromethoxy)-l lH-dibenzo[b,f]thiepan-10-ol (Compound 215 in table below)
  • EXAMPLE 7 This example illustrates one protocol for the preparation of 10-fluoro-lO-
  • Example 5 in 10 mL of methylene chloride was stirred and 0.12 gram (0.0008 mole) of (diethylamino) sulfur trifluoride was added by syringe. Upon completion of addition the reaction mixture was stirred for a 20 minute period, then it was poured into 30 mL of an aqueous dilute solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with 25 mL of methylene chloride. The extract and the organic layer were combined and washed with an aqueous solution saturated with sodium chloride. The combination was then dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue.
  • 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.
  • X is -CR 9 R 10 -; Y is -CR 34 R 35 O-, and R 1 , R 3 , R 4 , R 5 , R 7 , R 8 , R 34 , R 35 are hydrogen; n is 0, and R a is hydrogen:
  • H Cl HC 2 H 4 NR 40 R 41 CH 3 CH 3
  • H OCH 3 CHC 2 H 4 NR 40 R 41 CH 3 CH 3
  • H SCH 3 CHC 2 H 4 NR 40 R 41 CH 3 CH 3
  • H SCH 3 CHC 2 H 4 NR 40 R 41 -C 2 H 4 N(CH 3 )C 2 H 4 - where u is 0
  • X is -CR 9 R 10 -; Y is -CR 36 R 37 S-, and R 1 through R 5 , inclusively, R 7 , R 8 , R : and R >37 are hydrogen; n is 0 and R is hydrogen:
  • X is -CR 9 R 10 -, and Y is -CR 31 R 32 NR 33 -, where R 1 through R 8 , inclusively, and R 31 and R 32 are hydrogen; and n is 0 and R a is hydrogen:
  • R 11 is:
  • R 11 is:
  • Y is -S-, where R 1 , R 3 through R 8 , inclusively, and
  • R 12 through R 14 inclusively, are hyd Irogen ;
  • R 11 is:
  • R 11 is:
  • X is -NR 17 - and Y is -CR 24 R 25 CR 26 R 27 -; where R 1 , R 3 through R 7 , inclusively, and R 24 through R 25 , inclusively, are hydrogen; v is 0; and u is 0:
  • the compounds of formula I useful in the present invention were tested for insecticidal activity by observing mortality in a population of cotton aphid (Aphis gossypii) on treated cotton plants caused by a test compound, when compared to like populations of cotton aphid on untreated plants. These tests were conducted in the following manner:
  • test compound For each rate of application of test compound, two seven-to-ten days old cotton seedlings (Gossypium hirsutium) grown in 7.6 cm diameter pots were selected for the test. Each test plant was infested with about 120 adult cotton aphids by placing onto each test plant cuttings of leaves from cotton plants grown in a cotton aphid colony. Once infested, the test plants were maintained for up to about 12 hours to allow complete translocation of the aphids onto the test plant. A solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 milligrams of the test compound in 1 mL of acetone.
  • ppm part per million
  • each solution was then diluted with 9 mL of a solution of 0.03 mL of polyoxyethylene(l ⁇ ) isooctylphenyl ether in 100 mL of water. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (5 mL total for each test compound). If needed, the solution of 1000 ppm of test compound was serially diluted with a solution of 10% acetone and 300 ppm of polyoxyethylene(l ⁇ ) isooctylphenyl ether in water to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm.
  • test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants.
  • a solution of a standard such as amitraz or demethylchlordimeform (DCDM), prepared in a manner analogous to that set forth above, as well as a solution of 10% acetone and 300 ppm of polyoxyethylene(l ⁇ ) isooctylphenyl ether in water containing no test compound were also sprayed onto test plants.
  • DCDM demethylchlordimeform
  • test compound was designated as possessing insecticidal activity (SA) if there was 20% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 20% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
  • SA insecticidal activity
  • Insecticidal activity data at selected rates of application from this test are provided in Table 2.
  • the test compounds of formula I are identified by numbers that correspond to those in Table 1.
  • Table 2 Insecticidal Activity of Certain Tricyclic Derivatives

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Abstract

It has now been found that certain tricyclic derivatives have provided unexpected insecticidal activity. These compounds are represented by formula I: wherein R1 through R8, inclusively, and X and Y are fully described. Compositions comprising an insecticidally effective amount of at least one compound of formula I, and optionally, an effective amount of at least one of a second compound, with at least one insecticidally compatible carrier are also disclosed; along with methods of controlling insects comprising applying said compositions to the locus where insects are present or are expected to be present.

Description

INSECTICIDAL TRICYCLIC DERIVATIVES
FIELD OF THE INVENTION
The present invention generally relates to insecticidal compounds and their use in controlling insects. In particular, it pertains to insecticidal tricyclic derivatives and agriculturally acceptable salts thereof, compositions of these insecticides, and methods for their use in controlling insects.
BACKGROUND OF THE INVENTION
It is well known that insects can cause significant damage to crops grown in agriculture, resulting in loss of millions of dollars of value associated with a given crop. Although there are many orders of insects that can cause significant crop damage, insects of the suborder "Homoptera" are of major importance. The suborder Homoptera includes, for example, aphids, leafhoppers, cicadas, whiteflies, and mealybugs, to name a few. Homopterans have piercing/sucking mouthparts, enabling them to feed by withdrawing sap from vascular plants. Insect damage from homopterans is manifested in several different ways, other than damage caused by direct feeding. For example, many species excrete honeydew, a sticky waste product that adheres to plants upon which the insect feeds and lives. Honeydew alone causes cosmetic injury to crop plants. Sooty molds will often grow on honeydew, making food products or ornamental plants look unappealing, thereby reducing their cosmetic and economic value. Some homopterans have toxic saliva that is injected into plants while they are feeding. The saliva can cause plant damage through disfigurement and in some instances plant death. Homopterans can also vector disease-causing pathogens. Unlike direct damage, it does not take a large number of disease-vectoring insects to cause considerable damage to crop plants.
Accordingly, there is a continuing demand for new insecticides for control of, for example, Homoptera and other orders of insects; as well as new acaricides, that are safer, more effective, and less costly for use on crops such as wheat, corn, soybeans, potatoes, and cotton to name a few. For crop protection, insecticides and acaricides are desired which can control the insects and acarids without damaging the crops, and have no deleterious effects to mammals and other living organisms. Its equivalent WO93/00811 and US Patent 5,366,975 disclose a method of controlling an invertebrate pest, comprising contacting the pest with a pest- controlling amount of an agent having substantial inhibitory activity toward a phenylethanolamine reuptake transporter as determined by a radioactive octopamine reuptake inhibition assay. Compounds in compositions capable of inhibiting the octopamine transporter set forth in WO93/00811 and US Patent 5,366,975 include tricyclic antidepressants, wherein the tricyclic antidepressants exemplified are desipramine, amitriptyline, imipramine, amoxapine, nortriptyline, protriptyline, maprotiline, and doxepin, and pharmaceutically acceptable salts thereof. Desipramine and amitriptyline are specifically shown to have anti-feeding activity against tobacco hornworm. The tricyclic antipruritic cyproheptadine is also disclosed as having anti-feeding activity against tobacco hornworm.
The disclosure of invertebrate pesticidal activity of certain tricyclic antidepressants and antipruritics in WO93/00811 and US Patent 5,366,975, based on the limited data presented therein, does not suggest insecticidal activity, or the degree of that insecticidal activity, of other tricyclic derivatives whose antidepressant or antipruritic activity is unknown.
US Patent 3,436,397 claims a class of dibenzocyclohepten-5-ylidene thiazolidinones of the formula:
Figure imgf000003_0001
wherein R is selected from the group which consists of hydrogen and - alkyl. The dibenzocyclohepten-5-ylidene thiazolidinones are reported to have larvicidal activity against horse strongyles, anthelminthic activity against Syphacia obvelata and are useful for the treatment of pinworm infestations in mammals, and also possess antibacterial activity against certain gram-positive and gram-negative organisms.
There is no disclosure or suggestion in US Patent 3,436,397 that any of the compounds disclosed therein have insecticidal activity.
SUMMARY OF THE INVENTION
In accordance with the present invention, it has now been found that certain tricyclic derivatives (hereinafter termed "compounds of formula I") and agriculturally acceptable salts thereof are suiprisingly active when used in the insecticidal compositions and methods of this invention. The compounds of formula I are represented by the following general formula I:
Figure imgf000004_0001
wherein
R through R , inclusively, are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkenyl, alkynyl, trialkylsilylalkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl, dialkylaminosulfonyl, nitro, cyano, amino, formyl, or alkylcarbonyl;
X is selected from -CR9R10-, -CRπR12CR13R14-, -CR15=CR16-, -NR17-,
-CR 1 1185τR, 1ι9yNτιR_ 2z0υ-,
Figure imgf000004_0002
and Y is selected from -CR22R23-, -CR24R25CR26R27-, -CR28=CR29-, -NR30-,
Figure imgf000004_0003
-O-, -S-, -S(O)-, -S(O)2-, -CR 3J44rR>3J5O, -, -CR ι3J6DτR_ 3"7Sc -, or
-CR38=N- where R9 and R10 are independently selected from hydrogen, alkyl, or (piperidin-4- yl)alkyl; or
R9 and R10 may be taken together with
Figure imgf000005_0001
, or with =CHC2H4NR40R41, where
R39, R40 and R41 are independently selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R40 and R [ may be taken together with -C2H4N(CH3)C2H4- to form a piperazine ring; u is 0 or 1, and when u is 1, an N-oxide is formed; n is 0, and Ra is hydrogen; or n is 1 to 8, and Ra is selected from one or more of alkyl, alkoxyalkyl, alkoxycarbonyl, and aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R11 is selected from hydrogen, alkyl, alkylaminoalkoxy, dialkylaminoalkoxy,
N(alkyl)(alkylaminoalkyl) , N(alkyl) (dialkylaminoalkyl) , alkylaminoalkylalkynyl, dialkylaminoalkylalkynyl, morpholinyl, imidazolinyl, alkylpyrrolidinyloxy,
Figure imgf000006_0001
where v is 0 or 1, and when v is 1, A is a bridging group selected from -O-, -S-, -NH-, and -CH2-; u is as described above;
R42 through R45, inclusively, are independently selected from hydrogen; alkyl alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R43 and R44 may be taken together with -C5H10- to form a piperidine ring; m, p, and q are 0, and Rb, Rc and Rd are hydrogen; or m is 1 to 8, p is 1 to 7, and q is 1 to 10, and Rb, Rc, and Rd, respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
Figure imgf000007_0001
R11 and R12 may be taken together with where Ra, n, u, and R39 are as described above;
R12, when not taken together with Ru, and R13, R14, and R16, are independently selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, or dialkylaminosulfonyl;
R15 is selected from
Figure imgf000007_0002
where m, u, v, A, Rb and R42 are as described above;
R17 is hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy,
Figure imgf000007_0003
where
A, v, and u are as described above;
R46 is selected from selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R47 and R48are independently selected from hydrogen and alkyl; or R47 and R48 may be taken together with -C5H10- to form a piperidine ring, or with -C2H4N(CH3)C2H4-, or -C2H4N(C2H4OH)C2H4- to form a piperazine ring;
R18 and R19 are independently selected from hydrogen, alkyl, amino, alkylaminoalkyl, and dialkylaminoalkyl;
00
R is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocai'bonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R21 is selected from hydrogen, alkyl,
Figure imgf000008_0001
where
A, v, and u are as described above;
R49 through R52, inclusively, are independently selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R50 and R51 may be taken together with -C5H10- to form a piperidine ring; r, s, and t are 0, and Re, Rf, and Rε are hydrogen, or
\r is 1 to 8, s is 1 to 7, t is 1 to 10, and Re, Rf, and Rε, respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl;
00 90
R " through R , inclusively, are independently selected from hydrogen, and alkyl; R is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R31 and R32 are independently selected from hydrogen, and alkyl, R33 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R34 through R38, inclusively, are independently selected from hydrogen, and alkyl; and, agriculturally acceptable salts thereof.
The present invention is also directed to compositions containing an insecticidally effective amount of at least one of a compound of formula I, and optionally, an effective amount of at least one of a second compound, with at least one insecticidally compatible carrier.
The present invention is also directed to methods of controlling insects, where control is desired, which comprise applying an insecticidally effective amount of the above composition to the locus of crops, or other areas where insects are present or are expected to be present.
DETAILED DESCRIPTION OF THE INVENTION
One aspect of the present invention is insecticidal compositions comprising at least one of an insecticidally effective amount of a compound of formula I and at least one insecticidally compatible carrier therefor, wherein the compound of formula I is:
Figure imgf000009_0001
wherein R through R , inclusively, are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkenyl, alkynyl, trialkylsilylalkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl, dialkylaminosulfonyl, nitro, cyano, amino, formyl, or alkylcarbonyl;
X is selected from -CR9R10-, -CRπR1 CR13R14-, -CR15=CR16-, -NR17-,
-CR18R19NR20-, or -CR21=N-; and
Y is selected from -CR22R23-, -CR24R25CR26R27-, -CR28=CR29-, -NR30-, -CR31R32NR33-, -O-, -S-, -S(O)-, -S(O)2-, -CR34R35O-, -CR36R37S-, or
-CR38=N-; where
R9 and R10 are independently selected from hydrogen, alkyl, or (piperidin-4- yDalkyl; or
R9 and R10 may be taken together with
Figure imgf000010_0001
, where
R39, R40 and R41 are independently selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or R40 and R41 may be taken together with -C2H4N(CH3)C2H4- to form a piperazine ring; u is O or l, and when u is 1, an N-oxide is formed; n is 0, and Ra is hydrogen; or n is 1 to 8, and Ra is selected from one or more of alkyl, alkoxyalkyl, alkoxycarbonyl, and aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R11 is selected from hydrogen, alkyl, alkylaminoalkoxy, dialkylaminoalkoxy, N(alkyl)(alkylaminoalkyl), N(alkyl) (dialkylaminoalkyl), alkylaminoalkylalkynyl, dialkylaminoalkylalkynyl, morpholinyl, imidazolinyl, alkylpyrrolidinyloxy,
where v is 0 or 1, and when v is 1, A is a bridging group selected from -O-, -S-, -NH-, and -CH2-; u is as described above;
R42 through R 5, inclusively, are independently selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R43 and R44 may be taken together with -C5H10- to form a piperidine ring; m, p, and q are 0, and Rb, Rc and Rd are hydrogen; or m is 1 to 8, p is 1 to 7, and q is 1 to 10, and Rb, Rc, and Rd, respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R11 and R12 may be taken together with
Figure imgf000012_0001
where Ra, n, u, and R39 are as described above; R12, when not taken together with R11, and R13, R14, and R16, are independently selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, or dialkylaminosulfonyl;
R15 is selected from
Figure imgf000012_0002
where m, u, v, A, Rb and R42 are as described above;
17
R is hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy,
haloalkyl, or aryl;
Figure imgf000012_0003
. ; o Λ„r
Figure imgf000012_0004
where
A, v, and u are as described above;
R46 is selected from selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R47 and R48are independently selected from hydrogen and alkyl; or R47 and R48 may be taken together with -C5H10- to form a piperidine ring, or with
-C2H4N(CH3)C2H4-, or -C2H4N(C2H4OH)C2H - to form a piperazine ring; R18 and R19 are independently selected from hydrogen, alkyl, amino, alkylaminoalkyl, and dialkylaminoalkyl; R20 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R21 is selected from hydrogen, alkyl,
Figure imgf000013_0001
where A, v, and u are as described above;
R49 through R52, inclusively, are independently selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R50 and R51 may be taken together with -C5H10- to form a piperidine ring; r, s, and t are 0, and Re, Rf, and Rs are hydrogen, or r is 1 to 8, s is 1 to 7, t is 1 to 10, and Re, Rf, and Rg, respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R22 through R29, inclusively, are independently selected from hydrogen, and alkyl; R30 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R31 and R32 are independently selected from hydrogen, and alkyl, R33 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R34 through R38, inclusively, are independently selected from hydrogen, and alkyl; and, agriculturally acceptable salts thereof.
Preferred insecticidal compositions of the present invention are comprised of compounds of formula I, wherein X is -CR9R10- and Y is selected from -O-, -S-,
-CR22R23-, and _CR34R350_. where R9 and R10 are taken together with
Figure imgf000014_0001
where
R39 is selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; and, R22, R23, R34 and R35 are independently selected from hydrogen and alkyl. Other preferred insecticidal compositions of the present invention are comprised of compounds of formula I, wherein X is -CR1 'R^CR^R14- and Y is selected from -O-, -S- and -CR22R23-; where R11 is selected from
Figure imgf000015_0001
where
R42 and R45 are independently selected from hydrogen; alkyl; alkenyl; alkynyl hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R12 is selected from selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, and dialkylaminosulfonyl; R13 and R14 are hydrogen; and,
R22 and R23are independently selected from hydrogen and alkyl. Yet other preferred insecticidal compositions of the present invention are comprised of compounds of formula I, wherein X is -CR18R1 NR20- and Y is selected from -O-, -S- and -CR22R23-; where
10
R is selected from hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, dialkylaminoalkyl, alkylaminocarbonyl, and dialkylaminocarbonyl; and, R22 and R 3are independently selected from hydrogen and alkyl.
Yet still other preferred insecticidal compositions of the present invention are comprised of compounds of formula I, wherein X is -CR21=N- and Y is selected from -S- and -CR22R23-; where R21 is
Figure imgf000016_0001
where
R49 is selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; and, R22 and R23are independently selected from hydrogen and alkyl.
One skilled in the art will, of course, recognize that certain combinations of X and Y as set forth above, for example, when X is -CR9R10- and Y is -NR30-, or when X is -NR17- and Y is -CR22R23-, may lead to duplicity of compounds of formula I. Such duplicity of compounds is outside the scope of the present invention.
Certain compounds within the scope of formula I, which find utility in the novel insecticidal compositions of the present invention, may be new and novel compositions of matter. In addition, 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, 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 insecticidally compatible carrier therefor.
Another aspect of the present invention relates to methods of controlling insects by applying an insecticidally effective amount of a composition set forth above to a locus of crops such as, without limitation, cereals, cotton, vegetables, and fruits, or other areas where insects are present or are expected to be present.
The present invention also includes the use of the compounds and compositions set forth herein for control of non-agricultural insect species, for example, dry wood termites and subterranean termites; as well as for use as pharmaceutical agents and compositions thereof.
As used in this specification and unless otherwise indicated the substituent terms "alkyl", "alkenyl", "alkynyl", "alkoxy", "alkenyl", and "alkynyl" 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 "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. The term "insecticidal composition" refers to a composition containing an insecticide capable of killing an insect pest. The term "insecticidally effective amount" refers a composition containing an insecticide that is applied at a rate of application of insecticide sufficient to kill an insect pest.
The tricyclic derivatives of formula I can be synthesized by methods that are individually known to one skilled in the art from intermediate compounds readily available in commerce. Scheme 1 below illustrates a general procedure for synthesizing tricyclic derivatives of formula I, where, for example, X is -CR9R10-, and Y is -O- or -S-, where R9 and R10 are taken together with
Figure imgf000018_0001
SCHEME 1:
Figure imgf000019_0001
la
I as depicted and prepared as above, where Ra is hydrogen; n is 0; and R39 is phenylmethyl
Figure imgf000019_0002
Figure imgf000020_0001
I where R39 is, for example ' -CH. a) TiCl4 / Zn / THF / 60 °C; b) C1C02CH2CC13 / CH3CN / CHC13 / Reflux; c) NaOH / H20 / CH3OH / Reflux; d) LiAlH4 / THF / RT
As depicted in Scheme 1, compounds of formula I, for example, where X is
-CR9R10-, and Y is -O- or -S-, and where R9 and R10 are taken together with
=<JN-R 39
were prepared in one-step syntheses by reacting, for example, thioxanthen-9-one (Y is -S-), l-methyl-4-piperidone, titanium(IV) chloride, and zinc in an appropriate solvent, affording the corresponding 10-(l-methyl-4- piperidylidene)benzo[b,e]thiane, a compound of formula I.
Other compounds of formula I were prepared in multi-step syntheses, for example, xanthone (Y is -O-), was reacted with l-phenylmethyl-4-piperidone, zinc, and titanium(IV) chloride in an appropriate solvent, as set forth above, yielding the corresponding 9-(l-phenylmethyl-4-piperidylidene)xanthene. The xanthene intermediate was, in turn, reacted with 2,2,2-trichloroethyl chloroformate in an appropriate solvent, affording the corresponding 9-[l-(2,2,2- trichloroethoxycarbonyl)-4-piperidylidene]xanthene (la). Intermediate (la) was then treated with a strong base for example, sodium hydroxide, and an appropriate alcohol, such as methanol, yielding the corresponding 9-(l-methoxycarbonyl-4- piperidylidene)xanthene (lb), which was, in turn, reduced with, for example, lithium aluminum hydride in an appropriate solvent, affording 9-(l-methyl-4- piperidylidene)xanthene, a compound of formula I. Scheme 2 below illustrates a general procedure for synthesizing tricyclic derivatives of formula I, where, for example, X is -CR21=N- and and Y is -O- or
-S-, where R 2Δ1l is
Figure imgf000021_0001
SCHEME 2
Figure imgf000021_0002
where Y is, for example, -S- or -O- and R is 1-methylethyl
Figure imgf000021_0003
lib where X will be, for example, -CR21=N-
Figure imgf000022_0001
a) C1C02C13 / EtOAc / Reflux b) A1C13 / C6H5C1 / 80-110 °C c) POCl3 / C6H5N(C2H5)2 / RT d) 1-methylpiperazine / xylenes / Rt
As depicted in Scheme 2, those compounds of formula I, for example, where X is -CR21=N- and Y is -O- or -S-, were also prepared in multi-step syntheses. For example, the known amine, 2-[4- (methylethyl)phenylthio]phenylamine (Y is S), was reacted with trichloromethyl chloroformate in an appropriate solvent, affording the corresponding isocyanate Ila. Intermediate Ha was in turn cyclized with aluminum chloride in an appropriate high-boiling solvent such as chlorobenzene, yielding the corresponding cyclized ketone derivative lib, for example 2-(methylethyl)-10-dibenzo[b,f]-l,4- thiazaperhydroepin-11-one. Intermediate lib was then chlorinated with, for example, phosphorous oxychloride in the presence of a base catalyst, providing the corresponding chloride derivative lie. The so-prepared chloride derivative lie, for example, H-chloiO-2-(methylethyl)dibenzo[b,fJl,4-thiazepine, was then converted to compounds of formula I by reacting it with an appropriate amine, for example 1- methylpiperazine, providing the compound 2-(methylethyl)-l l-(4- methylpiperazinyl)dibenzo[b,f] 1,4-thiazepine I.
Scheme 3 below illustrates a general procedure for synthesizing tricyclic derivatives of formula I, where, for example, X is CRπR12CR13R14 and Y is -O- or -S-, and R11 and R12 represent a number of moieties.
SCHEME 3
Figure imgf000023_0001
where Y is, for example, -S- or -0-; and R2 is -OCF.
Figure imgf000023_0002
Figure imgf000024_0001
where, for example, where R42 is, for example -CH3 m and u are 0
Figure imgf000024_0002
a) Eatons Reagent / RT b) NaBH4 / CH3OH / THF / RT c) SOCl2 / CH2C12 / DMF / RT d) 1-methylpiperazine / CHC13 / 80 °C e) C5H5NBr / n-BuLi / Et20 / -50 °C to RT f) CH3I / Acetone / NaBH4 / EtOH / RT g) SF3N(C2H5)2 / CH2C12 / RT
As depicted in Scheme 3, those compounds of formula I, for example, where X is -CRπR12CR13R14- and Y is -O- or -S-, were again prepared in multi-step syntheses. For example, an appropriately substituted acetic acid derivative, such as 2-{2-[4- (trifluoromethoxy)phenylthio]phenyl} acetic acid, was cyclized with Eaton's Reagent affording the corresponding ketone derivative Ilia, for example, 8- (trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-one. Intermediate Ilia was first reduced to the corresponding alcohol by treatment of Ilia with sodium borohydride in an appropriate solvent, then the alcohol was chlorinated with thionyl chloride, yielding the corresponding chloro derivative Illb. The so- prepared chloride derivative Illb, for example, 1 l-chloro-2-(trifluoromethoxy)- 10H,llH-dibenzo[b,f]thiepane, was then converted to compounds of formula I by reacting it with an appropriate amine, for example 1-methylpiperazine, providing the compound 1 l-(4-methylpiperazinyl)-2-(trifluoromethoxy)- 10H, 11H- dibenzo[b,f]thiopane I.
Alternatively, the ketone intermediate Ilia may be reacted directly with an appropriate base to provide additional compounds of formula I. For example, 8- (trifluoromethoxy)-HH-dibenzo[b,fJthiepan-10-one Ilia, as set forth above, may be reacted under basic conditions with halogen-containing compound, such as 4- bromopyridine, in an appropriate solvent, providing a compound of formula I, for example, 10-(4-pyridyl)-8-(trifluoromethoxy)-l lH-dibenzo[b,f]thiepan-10-ol.
Any compound of formula I containing an alcohol moiety may be further reacted to prepare yet other compounds of formula I. For example, 10-(4-pyridyl)- 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol, as set forth above, was alkylated with an alkyl halide, such as methyl iodide, then reduced with a reducing agent in an appropriate solvent, yielding the corresponding alkyl derivative, a compound of formula I, for example, 10-(1 -methyl (4- 1,2,5, 6-tetrahydropyridyl))- 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol I.
In yet another method, a compound of formula I containing an alcohol moiety, such as 10-(4-pyridyl)-8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10- ol, as set forth above, may be reacted with, for example, (diethylamino) sulfur trifluoride in an appropriate solvent, affording yet other compounds of formula I, for example, 10-fluoro-10-(4-pyridyl)-8-(trifluoromethoxy)-l lH- dibenzo[b,f]thiepane.
Examples 1 through 7, inclusively, set forth below, provide in detail the methods by which compounds of formula I were prepared.
One skilled in the art will, of course, recognize that the formulation and mode of application of a toxicant may affect the activity of the material in a given application. Thus, for agricultural use the present insecticidal compounds may be formulated as a granular of relatively large particle size (for example, 8/16 or 4/8 US Mesh), as water-soluble or water-dispersible granules, as powdery dusts, as wettable powders, as emulsifiable concentrates, as aqueous emulsions, as solutions, or as any of other known types of agriculturally-useful formulations, depending on the desired mode of application. It is to be understood that the amounts specified in this specification are intended to be approximate only, as if the word "about" were placed in front of the amounts specified.
These insecticidal compositions may be applied either as water-diluted sprays, or dusts, or granules to the areas in which suppression of insects is desired. These formulations may contain as little as 0.1%, 0.2% or 0.5% to as much as 95% or more by weight of active ingredient.
Dusts are free flowing admixtures of the active ingredient with finely divided solids such as talc, natural clays, kieselguhr, flours such as walnut shell and cottonseed flours, and other organic and inorganic solids which act as dispersants and carriers for the toxicant; these finely divided solids have an average particle size of less than about 50 microns. A typical dust formulation useful herein is one containing 1.0 part or less of the insecticidal compound and 99.0 parts of talc.
Wettable powders, also useful formulations for insecticides, are in the form of finely divided particles that disperse readily in water or other dispersant. The wettable powder is ultimately applied to the locus where insect control is needed either as a dry dust or as an emulsion in water or other liquid. Typical carriers for wettable powders include Fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet inorganic diluents. Wettable powders normally are prepared to contain about 5-80% of active ingredient, depending on the absorbency of the carrier, and usually also contain a small amount of a wetting, dispersing or emulsifying agent to facilitate dispersion. For example, a useful wettable powder formulation contains 80.0 parts of the insecticidal compound, 17.9 parts of Palmetto clay, and 1.0 part of sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as wetting agents. Additional wetting agent and/or oil will frequently be added to a tank mix for to facilitate dispersion on the foliage of the plant.
Other useful formulations for insecticidal applications are emulsifiable concentrates (ECs) which are homogeneous liquid compositions dispersible in water or other dispersant, and may consist entirely of the insecticidal compound and a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isphorone, or other non- volatile organic solvents. For insecticidal application these concentrates are dispersed in water or other liquid carrier and normally applied as a spray to the area to be treated. The percentage by weight of the essential active ingredient may vary according to the manner in which the composition is to be applied, but in general comprises 0.5 to 95% of active ingredient by weight of the insecticidal composition.
Flowable formulations are similar to ECs, except that the active ingredient is suspended in a liquid carrier, generally water. Flowables, like ECs, may include a small amount of a surfactant, and will typically contain active ingredients in the range of 0.5 to 95%, frequently from 10 to 50%, by weight of the composition. For application, flowables may be diluted in water or other liquid vehicle, and are normally applied as a spray to the area to be treated.
Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, but are not limited to, the alkyl and alkylaryl sulfonates and sulfates and their sodium salts; alkylaryl polyether alcohols; sulfated higher alcohols; polyethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addition products of such esters; and the addition product of long-chain mercaptans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. Surface-active agents, when used, normally comprise 1 to 15% by weight of the composition.
Other useful formulations include suspensions of the active ingredient in a relatively non-volatile solvent such as water, corn oil, kerosene, propylene glycol, or other suitable solvents.
Still other useful formulations for insecticidal applications include simple solutions of the active ingredient in a solvent in which it is completely soluble at the desired concentration, such as acetone, alkylated naphthalenes, xylene, or other organic solvents. Granular formulations, wherein the toxicant is carried on relative coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy. Pressurized sprays, typically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low- boiling dispersant solvent carrier may also be used. Water-soluble or water- dispersible granules are free flowing, non-dusty, and readily water-soluble or water-miscible. In use by the farmer on the field, the granular formulations, emulsifiable concentrates, flowable concentrates, aqueous emulsions, solutions, etc., may be diluted with water to give a concentration of active ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%. The active insecticidal compounds of this invention may be formulated and/or applied with one or more second compounds. Such combinations may provide certain advantages, such as, without limitation, exhibiting synergistic effects for greater control of insect pests, reducing rates of application of insecticide thereby minimizing any impact to the environment and to worker safety, controlling a broader spectrum of insect pests, safening of crop plants to phytotoxicity, and improving tolerance by non-pest species, such as mammals and fish.
Second compounds include, without limitation, other pesticides, plant growth regulators, fertilizers, soil conditioners, or other agricultural chemicals. In applying an active compound of this invention, whether formulated alone or with other agricultural chemicals, an effective amount and concentration of the active compound is of course employed; the amount may vary in the range of, e.g. about 0.001 to about 3 kg/ha, preferably about 0.03 to about 1 kg/ha. For field use, where there are losses of insecticide, higher application rates (e.g., four times the rates mentioned above) may be employed.
When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as herbicides, the herbicides include, without limitation, for example: N- (phosphonomethyl)glycine ("glyphosate"); aryloxyalkanoic acids such as (2,4- dichlorophenoxy)acetic acid ("2,4-D"), (4-chloro-2-methylphenoxy)acetic acid ("MCPA"), (+/-)-2-(4chloro-2-methylphenoxy)propanoic acid ("MCPP"); ureas such as N,N-dimethyl-N'-[4-(l-methylethyl)phenyl]urea ("isoproturon"); imidazolinones such as 2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH- imidazol-2-yl]-3-pyridinecarboxylic acid ("imazapyr"), a reaction product comprising (+/-)-2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH-imidazol-2- yl]-4-methylbenzoic acid and (+/-)2-[4,5-dihydro-4-methyl-4-(l-methylethyl)-5- oxo-lH-imidazol-2-yl]-5-methylbenzoic acid ("imazamethabenz"), (+/-)-2-[4,5- dihydro-4-methyl-4-(l-methylethyl)-5-oxo-lH-imidazol-2-yl]-5-ethyl-3- pyridinecarboxylic acid ("imaze hapyr"), and (+/-)-2-[4,5-dihydro-4-methyl-4-(l- methylethyl)-5 -oxo- 1 H-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-(methylsulf onyl)-2- nitrobenzamide ("fomasafen"); hydroxybenzonitriles such as 4-hydroxy-3,5- diiodobenzonitrile ("ioxynil") and 3,5-dibromo-4-hydroxybenzonitrile ("bromoxynil"); sulfonylureas such as 2-[[[[(4chloro-6-mefhoxy-2- pyrimidinyl) amino] carbonyl] amino] suϊfonyl]benzoic acid ("chlorimuron"), 2- chloro-N-[ [(4-methoxy-6-methyl-l,3,5-triazin-2- yl)amino]carbonyl]benzenesulfonamide (achlorsulfuron"), 2-[[[[[(4,6-dimethoxy- 2-pyrimidinyl)amino] carbonyl] amino] sufonyl] methyl]benzoic acid
("bensulfuron"), 2-[[[[(4,6-dimethoxy-2-pyrimidinyl)amino]carb- onyl]amino]sulfonyl]-l-methy-lH-pyrazol-4-carboxylic acid ("pyrazosulfuron"), 3-[[[[(4-methoxy-6-methyl-l,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-aryloxyphenoxy)alkanoic acids such as (+/-)-2[4-[(6-chloro- 2-benzoxazolyl)oxy]phenoxy]propanoic acid (fenoxaprop"), (+/-)-2-[4[[5- (trifluoiOmethyl)-2-pyridinyl]oxy]phenoxy]propanoic acid ("fluazifop"), (+/-)-2- [4-(6chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid ("quizalofop"), and (+ /-) -2-[(2,4-dichlorophenoxy)phenoxy]propanoic acid ("diclofop"); benzothiadiazinones such as 3-(l-methylethyl)-lH-l,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-l-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 ("fluroxypyr"), 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- cypermefhrin, 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 friforine; dithiocarbamate fungicides, such as mancozeb, maneb, propineb, zineb, and ziram; non-systemic fungicides, such as chlorothalonil, dichlofluanid, dithianon, and iprodione, captan, dinocap, dodine, fluazinam, gluazatine, PCNB, pencycuron, quintozene, tricylamide, and validamycin; inorganic fungicides, such as copper and sulphur products, and other fungicides. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other pesticides such as nematicides, the nematicides include, for example: carbofuran, carbosulfan, turbufos, aldecarb, ethoprop, fenamphos, oxamyl, isazofos, cadusafos, and other nematicides.
When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as plant growth regulators, the plant growth regulators include, for example: maleic hydrazide, chlormequat, ethephon, gibberellin, mepiquat, thidiazon, inabenfide, triaphenthenol, paclobutrazol, unaconazol, DCPA, prohexadione, trinexapac-ethyl, and other plant growth regulators.
Soil conditioners are materials which, when added to the soil, promote a variety of benefits for the efficacious growth of plants. Soil conditioners are used to reduce soil compaction, promote and increase effectiveness of drainage, improve soil permeability, promote optimum plant nutrient content in the soil, and promote better pesticide and fertilizer incorporation. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as soil conditioners, the soil conditioners include organic matter, such as humus, which promotes retention of cation plant nutrients in the soil; mixtures of cation nutrients, such as calcium, magnesium, potash, sodium, and hydrogen complexes; or microorganism compositions which promote conditions in the soil favorable to plant growth. Such microorganism compositions include, for example, bacillus, pseudomonas, azotobacter, azospirillum, rhizobium, and soil-borne cyanobacteria.
Fertilizers are plant food supplements, which commonly contain nitrogen, phosphorus, and potassium. When the active insecticidal compounds of the present invention are used in combination with one or more of second compounds, e.g., with other materials such as fertilizers, the fertilizers include nitrogen fertilizers, such as ammonium sulfate, ammonium nitrate, and bone meal; phosphate fertilizers, such as superphosphate, triple superphosphate, ammonium sulfate, and diammonium sulfate; and potassium fertilizers, such as muriate of potash, potassium sulfate, and potassium nitrate, and other fertilizers. The following examples further illustrate the present invention, but, of course, should not be construed as in any way limiting its scope. The examples are organized to present protocols for the synthesis of the compounds of formula I of the present invention, set forth a list of such synthesized species, and set forth certain biological data indicating the efficacy of such compounds.
EXAMPLE 1 This example illustrates one protocol for the preparation of 10-(l-methyl-4- piperidylidene)benzo[b,e]thiane (Compound 2 in table below)
Under a nitrogen atmosphere, 45 mL of stirred THF was cooled in an ice- water bath. To this was added 8 mL (0.008 mole) of titanium(IV) chloride (1.0M solution in toluene) via a syringe, then 1.0 gram (0.016 mole) of zinc was added in two portions during a five-minute period. After this time the reaction mixture was stirred during a ten-minute period, then a solution of 0.76 gram (0.0036 mole) of thioxanthen-9-one and 0.56 gram (0.005 mole) of l-methyl-4-piperidone in 20 mL of THF was added drop-wise during a ten-minute period. Upon completion of addition, the reaction mixture was stirred for ten minutes, then it was heated to 60 °C where it stirred for about 20 hours. After this time, the reaction mixture was cooled and poured into 50 mL of an aqueous 10% solution of potassium carbonate. The mixture was stirred for about 20 minutes, then 50 mL of ethyl acetate was added and the mixture was stirred for an additional 20 minutes. The mixture was then filtered through a pad of diatomaceous earth, and the diatomaceous earth pad was washed with 50 mL of ethyl acetate. The combined ethyl acetate from the wash and from the filtrate was separated, and the aqueous phase was extracted with 20 mL of ethyl acetate. The combined ethyl acetate fractions were then washed with an aqueous solution saturated with sodium bicarbonate and dried with sodium sulfate. The mixture was filtered and the filtrate concentrated under reduced pressure to a solid residue. The residue was purified with column chromatography on aluminum oxide (neutral activated HI) using mixtures of heptane and ethyl acetate as eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.25 gram of the Compound 2. The NMR spectrum was consistent with the proposed structure. EXAMPLE 2 This example illustrates one protocol for the preparation of 9-(l-methyl-4- piperidylidene)xanthene (Compound 8 in table below) Step A Synthesis of 9-(l-phenylmethyl-4-piperidylidene)xanthene as an intermediate This compound was prepared in a manner analogous to that set forth in
Example 1, by the reaction of 0.78 gram (0.004 mole) of xanthone, 0.95 gram
(0.005 mole) of l-phenylmethyl-4-piperidone, 1.6 grams (0.024 mole) of zinc, and 12 mL (0.012 mole) of titanium(IV) chloride (l.OM solution in toluene) in 70 mL of THF. The yield of the subject compound was 1.4 grams. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of 9-[l-(2,2,2-trichloroethoxycarbonyl)-4- piperidylidene]xanthene as an intermediate
Under a nitrogen atmosphere, a solution of 0.7 gram (0.002 mole) of 9-(l- phenylmethyl-4-piperidylidene)xanthene in 50 mL of 1:2 chloroform : acetonitrile was stirred, and 0.85 gram (0.004 mole) of 2,2,2-trichloroethyl chloroformate was added in one portion via a syringe. Upon completion of addition, the reaction mixture was warmed to reflux where it stirred for one hour, then the reaction mixture was cooled to ambient temperature where it stirred for about 18 hours. After this time the reaction mixture was poured into 50 mL of water and extracted with two 40 mL portions of ethyl acetate. The combined extracts were then washed with an aqueous solution saturated with sodium chloride and dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to a residual oil. The oil was dissolved in 20 mL of methanol, to which was added 5 mL of water. The mixture was cooled in an ice-water bath, and a solid precipitate formed. The solid was collected by filtration and dried under vacuum, yielding 0.73 gram of the subject compound, mp 132-134 °C. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of 9-(l-methoxycarbonyl-4-piperidylidene)xanthene as an intermediate A stirred solution of 0.6 gram (0.0013 mole) of 9-[l-(2,2,2- trichloroethoxycarbonyl)-4-piperidylidene]xanthene, 0.25 gram (0.0062 mole) of sodium hydroxide, and 2 mL of water in 20 mL of methanol was warmed to reflux where it stirred for six hours. After this time the reaction mixture was cooled to ambient temperature where it stirred for about 18 hours. The reaction mixture was then concentrated under reduced pressure to remove the majority of the methanol, and 30 mL of an aqueous solution saturated with sodium bicarbonate was added. The mixture was extracted with two 20 mL portions of ethyl acetate and the combined extracts were dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to an oil residue. The residue was purified with column chromatography on silica using 5: 1 heptane:ethyl acetate as eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.28 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
Note: The intended intermediate of Step C in the above preparative example was 9-(4-piperidylidene)xanthene.
Step D Synthesis of Compound 8
Under a nitrogen atmosphere a solution of 0.28 gram (0.0008 mole) of 9-
(l-methoxycarbonyl-4-piperidylidene)xanthene in 20 mL of THF was stirred, and
3 mL of lithium aluminum hydride (l.OM in THF) was added via a syringe during a ten minute period. After this time the reaction mixture was warmed to 40 °C where it stirred for two hours. The reaction mixture was then cooled and 20 mL of aqueous 0.5N sodium hydroxide was added in one portion. The mixture was extracted with two 40 mL portions of ethyl acetate, and the combined extracts were washed with 20 mL of an aqueous solution saturated with sodium bicarbonate. The extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure, yielding 0.2 gram of Compound 5. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 3 This example illustrates one protocol for the preparation of 2-
(methylethyl)-l l-(4-methylpiperazinyl)dibenzo[b,f] 1,4-thiazepine (Compound 193 in table below) Step A Synthesis of 2-[4-(methylethyl)phenylthio]benzenisocyanate as an intermediate Under a nitrogen atmosphere a solution of 1.2 grams (0.0049 mole) of 2- [4-
(methylethyl)phenylthio]phenylamine (known compound) in 60 mL of ethyl acetate was stirred, and 2.2 grams (0.011 mole) of trichloromethyl chlorooate was added by pipette in one portion. Upon completion of addition the reaction mixture was heated to reflux where it stirred for three hours. After this time the reaction mixture was cooled and concentrated under reduced pressure to a residue. The residue was further dried under vacuum, yielding 1.5 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step B Synthesis of 2-(methylethyl)-10-dibenzo[b,f]-l,4- thiazaperhydroepin-11-one as an intermediate Under a nitrogen atmosphere a stirred mixture of 1.0 gram (0.0075 mole) of aluminum chloride in five mL of chlorobenzene was warmed to 80 °C, and a solution of 1.4 grams (0.0052 mole) of 2- [4-
(methylethyl)phenylthio]benzenisocyanate in one mL of chlorobenzene was added dropwise during a one minute period. Upon completion of addition the reaction mixture was warmed to 110 °C where it stirred for two hours. After this time the reaction mixture was cooled and poured into water. The mixture was extracted with two 40 mL portions of ethyl acetate, and the extracts were combined. The combined extracts were then washed with an aqueous solution saturated with sodium chloride, dried with sodium sulfate, filtered; and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica using 5:1 and 3:1 mixtures of heptane:ethyl acetate as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.65 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of l l-chloro-2-(methylethyl)dibenzo[b,f]l,4-thiazepine as an intermediate Under a nitrogen atmosphere a solution of 0.62 gram (0.0023 mole) of 2-
(methylethyl)-10-dibenzo[b,f]-l,4-thiazaperhydroepin-ll-one in 10 mL of phosphorous oxychloride was stirred and 5 drops of diethylphenylamine was added. Upon completion of addition the reaction mixture was heated to reflux where it stirred for 3.5 hours. The reaction mixture was then concentrated under reduced pressure to remove the majority of the phosphorous oxychloride, and the residue was poured into 50 mL of ice-water. The mixture was then extracted three 30 mL portions of diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium chloride, dried with sodium sulfate, filtered; and the filtrate was concentrated under reduced pressure, yielding 0.55 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step D Synthesis of Compound 193
Under a nitrogen atmosphere a stirred solution of 0.24 gram (0.0008 mole) of ll-chloro-2-(methylethyl)dibenzo[b,f]l,4-thiazepine and 0.4 mL (0.0036 mole) of 1-methylpiperazine in 25 mL of xylenes was heated to reflux where it stirred for two hours. After this time the reaction mixture was cooled ambient temperature and poured into 25 mL of diethyl ether. The mixture was then extracted with three 20 mL portions of aqueous 3N hydrochloric acid. The aqueous extracts were combined and washed with 20 mL of diethyl ether, made basic with aqueous 10% potassium carbonate; then extracted with three 20 mL portions of diethyl ether. The ether extracts were combined, dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica using methylene chloride, 1% methanol in methylene chloride, and 3% methanol in methylene chloride as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.21 gram of Compound 193. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 4 This example illustrates one protocol for the preparation of 11 -(4- methylpiperazinyl)-2-(trifluoromethoxy)- 10H, 1 lH-dibenzo[b,f]thiopane (Compound 106 in table below)
Step A Synthesis of 2- {2-[4-(trifluoromethoxy)phenylthio]phenyl} acetic acid as an intermediate A mixture of 26.2 grams (0.47 mole) of potassium hydroxide and 1.1 grams (0.018 mole) of powdered copper (catalyst) in 200 mL of water was stirred, and 30.6 grams (0.117 mole) of 2-iodophenylacetic acid and 22.7 grams (0.117 mole) of 4-trifluoromethoxyphenol were added. Upon completion of addition the reaction mixture was warmed to reflux where it stirred for about 18 hours. After this time the reaction mixture was cooled to ambient temperature and filtered. The filtrate was poured into500 mL of aqueous 10% hydrochloric acid and the mixture was extracted with three 250 mL portions of ethyl acetate. The combined extracts washed with an aqueous solution saturated with sodium chloride, dried with sodium sulfate, filtered, and concentrated under reduced pressure, yielding 39.6 grams of the subject compound.
Step B Synthesis of 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-one as an intermediate A mixture of 10.0 grams (0.0304 mole) of 2-{2-[4-
(trifluoromethoxy)phenylthio]phenyl] acetic acid in 75 mL of Eatons Reagent was stirred for an 18 hour period during which time complete solution was obtained.
After this time the reaction mixture was poured into ice-water and extracted with four 150 mL portions of ethyl acetate. The combined extracts were then washed with one portion of a aqueous dilute solution of sodium bicarbonate and with one portion of an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate, filtered and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica using 1:2 ethyl acetate :hexane as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 4.0 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.
Step C Synthesis of l l-chloro-2-(trifluoiOmethoxy)-10H,HH- dibenzo[b,f]fhiepane as an intermediate A solution of 2.3 grams (0.0073 mole) of 8-(trifluoromethoxy)-l lH- dibenzo[b,f]thiepan-10-one in a mixture of 5 mL of THF and 30 mL of methanol was stirred and 0.4 gram of sodium borohydride was added. The reaction mixture was then stirred at ambient temperature during a two hour period. After this time the reaction mixture was poured into 100 mL of aqueous 10% hydrochloric acid, to which was then added 300 mL of an aqueous solution saturated with sodium chloride. The mixture was extracted with three 100 mL portions of ethyl acetate. The combined extracts were dried with sodium sulfate, filtered and the filtrate concentrated under reduced pressure to a residue. In an effort to further dry the residue, it was dissolved in 50 mL of methylene chloride and the mixture was concentrated under reduced pressure to a residue. The drying process was repeated two additional times, yielding a dried residue. The residue was again dissolved in 50 mL of methylene chloride and 3 mL of thionyl chloride was added. The reaction mixture was stirred at ambient temperature during a 2.5 hour period. After this time the reaction mixture was concentrated under reduced pressure, yielding 2.0 grams of the subject compound.
Step D Synthesis of Compound 106 A solution of 1.0 gram (0.0030 mole) of l l-chloro-2-(trifluoromefhoxy)-
10H,1 lH-dibenzo[b,f]thiepane was dissolved in 5 mL of chloroform and placed in a sealable tube, followed by 1.2 grams (0.0119 mole) of 1-methylpiperazine. The sealable tube was then sealed and the tube and contents were heated at 80 °C during an 18 hour period. The reaction mixture was taken from the tube and purified with column chromatography on silica using methylene chloride, then ethyl acetate as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.6 gram of Compound 106. The
NMR spectrum was consistent with the proposed structure.
EXAMPLE 5
This example illustrates one protocol for the preparation of 10-(4-pyridyl)- 8-(trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol (Compound 61 in table below) An aliquot of 1.0 gram (0.0051 mole) of 4-bromopyridine hydrochloride was stirred for 20 minutes with 20 mL of an aqueous solution saturated with sodium bicarbonate. The mixture was then extracted with two 20 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure, providing 0.5 gram of the free pyridine.
Under a nitrogen atmosphere, about 0.4 grams of the free pyridine was dissolved in 40 mL of diethyl ether and cooled to about -50 °C in a dry ice- acetonitrile bath. To this cold solution was added by syringe 1.0 mL (0.0025 mole) of 2.5 M n-butyllithium (in hexanes) while maintaining the reaction mixture temperature at -45 °C or below. Upon completion of addition the reaction mixture was stirred for 30 minutes at -50 °C, then 0.6 gram (0.0020 mole) of 8- (trifluoiOmethoxy)-HH-dibenzo[b,f]thiepan-10-one (prepared in Step B of Example 4) was added in one portion. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature as it stirred during a 1.5 hour period. After this time the reaction mixture was poured into 50 mL of water and the organic layer was separated. The aqueous layer was extracted with two 30 mL portions of diethyl ether. The extracts and the organic layer were combined and washed with an aqueous solution saturated with sodium chloride. The combination was then dried with sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica using 3:1 heptane:ethyl acetate, then 1:1 heptane:ethyl acetate as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.6 gram of Compound 61. The NMR spectrum was consistent with the proposed structure. This reaction was repeated several times.
EXAMPLE 6 This example illustrates one protocol for the preparation of 10-(l -methyl (4- l,2,5,6-tetrahydropyridyl))-8-(trifluoromethoxy)-l lH-dibenzo[b,f]thiepan-10-ol (Compound 215 in table below)
A solution of 0.55 gram (0.0014 mole) of 10-(4-pyridyl)-8- (trifluoromethoxy)-llH-dibenzo[b,f]thiepan-10-ol (prepared in Example 5) and
0.43 gram (0.0030 mole) of methyl iodide in 60 mL of acetone was stirred in a stoppered reaction vessel for about 18 hours. After this time the reaction mixture was analyzed by thin layer chromatography (TLC), which indicated some unreacted thiepan-10-ol. An additional 0.43 gram of methyl iodide was added to the reaction mixture, and stirring was continued for an additional 24 hours. After this time the reaction mixture was concentrated under reduced pressure to a residual solid, which was triturated with petroleum ether and dried. The solid was dissolved in 40 mL of ethanol and, with stirring, 0.45 gram (0.012 mole) of sodium borohydride was added. Upon completion of addition the reaction mixture was during a three hour period. After this time the reaction mixture was poured into 75 mL of aqueous 1% sodium bicarbonate. The mixture was then extracted with three 20 mL portions of ethyl acetate. The combined extracts were washed with an aqueous solution saturated with sodium chloride, then dried with sodium sulfate, filtered, and concentrated under reduced pressure, yielding 0.40 gram of Compound 215. The NMR spectrum was consistent with the proposed structure.
EXAMPLE 7 This example illustrates one protocol for the preparation of 10-fluoro-lO-
(4-pyridyl)-8-(trifluoromethoxy)-l lH-dibenzo[b,f]thiepane (Compound 216 in table below)
Under a nitrogen atmosphere a solution of 0.12 gram (0.0003 mole) of 10- (4-pyridyl)-8-(trifluoromethoxy)-l lH-dibenzo[b,f]thiepan-10-ol (prepared in
Example 5) in 10 mL of methylene chloride was stirred and 0.12 gram (0.0008 mole) of (diethylamino) sulfur trifluoride was added by syringe. Upon completion of addition the reaction mixture was stirred for a 20 minute period, then it was poured into 30 mL of an aqueous dilute solution of sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted with 25 mL of methylene chloride. The extract and the organic layer were combined and washed with an aqueous solution saturated with sodium chloride. The combination was then dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on alumina (Neutral, Activity IQ) using 5:1 heptane:ethyl acetate as an eluant. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.1 gram of Compound 216. The NMR spectrum was consistent with the proposed structure. It is well known to one of ordinary skill in the art that compounds like the compounds of formula I of the present invention can contain optically active and racemic forms. It is also well known in the art that compounds like the compounds of formula I may contain stereoisomeric forms, tautomeric forms and/or exhibit polymorphism. It is to be understood that the present invention encompasses any racemic, optically active, polymorphic, tautomeric, or stereoisomeric form, or mixtures thereof. It should be noted that it is well known in the art how to prepare optically active forms, for example by resolution of a racemic mixture, or by synthesis from optically active intermediates.
The following table sets forth some additional examples of compounds of formula I useful in the present invention:
Table 1
Insecticidal Phenothiazines, Phenoxazines, Dihydrophenazines,
Dibenzothiepins, Dibenzooxepins, Dibenzoazepines
Figure imgf000041_0001
Where X is -CR9R10-, R9 and R10 taken together is
Figure imgf000041_0002
, where u is 0, and R is hydrogen; R1 and R5 through R8, inclusively, are hydrogen:
Cmpd. 30
No. R- Rz RJ R4 R 39 R"
1 S H H H H H 0
2 s H H H CH3 H 0 3 s H H H CH(CH3)2 H 0 4 s Cl H H CH3 H 0 5 s CF3 H H CH3 H 0 6 s SCH3 H H CH3 H 0 Cmpd.
No. Y R30 R2 R3 R4 R39 Ra n
7 S H H H CH2C≡N H 0
8 0 — H H H CH3 H 0
9 0 — F H H CH3 H 0
10 0 — H F H CH3 H 0
11 0 — H H F CH3 H 0
12 0 — C2H5 H H CH3 H 0
13 0 — OC2H5 H H CH3 H 0
14 0 — C2H4OCH3 H H CH3 H 0
15 0 — CF3 H H CH3 H 0
16 0 — H OCF3 H CH3 H 0
17 Q — Cl H H CH2Ph H 0
18 0 — CF3 H H CH2Ph H 0
19 0 — SCH3 H H CHaPh H 0
20 0 — H H H C2H4C02C2H5 H 0
21 0 — H H H CH3 2-CH3 1
22 0 — H H H CH3 3-CH3 1
23 NR30 H H H H CH3 H 0
24 NR30 CH3 H H H CH3 H 0
25 NR30 CH3 CF3 H H CH3 H 0
where X is -CR9R10-; Y is -CR34R35O-, and R1, R3, R4, R5, R7, R8, R34, R35 are hydrogen; n is 0, and Ra is hydrogen:
Cmpd.
No. R R° Ry R 10 R 39 R 40 R4
Figure imgf000042_0001
292 Cl H =CHC2H4NR40R41 CH3 CH3
306 H Cl = HC2H4NR40R41 CH3 CH3
31 H Cl =CHC2H4NR40R41 H CH(CH3)2
322 OCH3 H =CHC2H4NR40R41 CH3 CH3
336 H OCH3 =CHC2H4NR40R41 CH3 CH3
34s H SCH3 =CHC2H4NR40R41 CH3 CH3
356 H S(0)2N(CH3)2 =CHC2H4NR40R41 CH3 CH3
367 H SCH3 =CHC2H4NR40R41 -C2H4N(CH3)C2H4- where u is 0
where X is -CR9R10-; Y is -CR36R37S-, and R1 through R5, inclusively, R7, R8, R: and R >37 are hydrogen; n is 0 and R is hydrogen:
Cmpd.
No. R" Ry R to R 39 R 40 R 41
Figure imgf000043_0001
39 H =CHC2H4NR40R41 CH3 CH3 where u is 0
where X is -CR9R10-, and Y is -CR31R32NR33-, where R1 through R8, inclusively, and R31 and R32 are hydrogen; and n is 0 and Ra is hydrogen:
Cmpd.
No. Ry R" R ' R 40 R4 R 33
Figure imgf000043_0002
42 -CHC2H4NR40R41 CH3 CH3 CH3 where u is 0 where X is -CR9R10-; Y is -CR38=N-, and R1, R3 through R8, inclusively, and R38 are hydrogen; n is 0 and Ra is hydrogen:
Cmpd. No. R2 R9 R10 R39 R40 R41
Figure imgf000044_0001
46 H =CHC2H4NR40R41 CH3 CH3
47 Cl =CHC2H4NR40R41 CH3 CH3
48 H =CHC2H4NR40R41 CH3 CH3
49 OCH3 =CHC2H4NR 0R41 CH3 CH3
50 SCH3 =CHC2H4NR40R41 — - CH3 CH3
51 S(0)2N(CH3)2 =CHC2H4NR40R41 CH3 CH3
*where u is 0
where X is -CRUR12CR13R14-; where R1, R3 through R8, inclusively, R13, and R14 are hydrogen, n and m are 0 and Ra and Rb are hydrogen, and when it is noted that v is 1, then A is -O-:
Cmpd.
No. R2 Rn R12 Y R39 R42
52 OCF3 OC2H4N(C2H5)2 H S
53 SCH3 NHC3H6OC2H5 H S — — -
54 SCH3 N(CH3)C2H4N(CH3)2 H s —
Figure imgf000044_0002
Cmpd.
No. Rz R1 R1 Y R- 39 R 42
Figure imgf000045_0001
58 Cl imidazolin-2-yl H O 59 OCF3 l-methylpyrrolidin-3-yloxy H S 60 OCF3 C≡CHCH2N(CH3)2 OH s
Figure imgf000045_0002
*where u is 0 **where v is 1
where X is -CRUR12CR13R14-; where R12, R13, and R14 are hydrogen; and
R11 is:
Figure imgf000045_0003
where v is 0; m is 0 and Rb is hydrogen; R42 is -CH3; and unless otherwise noted u is O:
Cmpd.
No. R1 R2 R3 R4 R5 R6 R7 R8 Y R- 22 Ώ R2"3 R 3- 0
63 H H H H H H H H O
64 H Cl H H H H H H O
65 H Br H H H H H H O
66 H F H H H H H H O
67 H I H H H H H H O
68 H CH3 H H H H H H O
69 H CF3 H H H H H H O Cmpd.
NO. R1 R2 R3 R4 R5 R6 R7 R8 γ R22 R23 R30
70 H SCH3 H H H H H H O
71 H OCF3 H H H H H H O — — — 72a H OCF3 H H H H H H O — -
73 H H OCF3 H H H H H O — — — -
74a H H OCF3 H H H H H O — — —
75 H SCF3 H H H H H H O — — —
76 H S(0)CF3 H H H H H H O — —
77 H S(0)2CF3 H H H H H H O
78 H -CH=CH2 H H H H H H O — -
79 H -C≡CH H H H H H H O — -
80 H -C≡CSI(CH3)3 H H H H H H O - —
81 H N02 H H H H H H O
82 H Cl Cl H H H H H O — —
83 H Cl H Cl H H H H O — —
84 H Cl F H H H H H O - —
85 H Cl H F H H H H O —
86 H F Cl H H H H H O - -
87 H F H C1 H H H H O - —
88 H Br H F H H H H O -
89 H Br H CH3 H H H H O — —
902 H H H H H H H H S
912 H H Cl H H H H H S
92 H H Cl H H Cl H H S
93 F H H H H H H H S — -
94 H H H F H H H H S -
95 H Cl F H H H H H S -
968 H Cl H F H H H H S — —
97 F H H F H H H H S — —
989 H C2H5 H H H H H H S - —
99 H C(CH3)3 H H H H H H S -
100 H OCH3 H H H H H H S — —
101 H H OCH3 H H H H H S — —
102 H H H OCH3 H H H H S - -
1032 H SCH3 H H H H H H S — — —
104s H SC2H5 H H H H H H S - —
105 H CF3 H H H H H H S — —
106 H OCF3 H H H H H H S -
107a H OCF3 H H H H H H S — — —
108 H OCF3 H H H H F H S — —
109 H OCF2CHF2 H H ' H H H H S — —
HO2 H H Cl Cl H H H H S - —
111 H CH3 F H H H H H S
112 c-C3H5 H H H H H H H S — — —
113 H c-C3H9 H H H H H H S — —
114 H NH2 H H H H H H S — —
115 H C(=0)CH3 H H H H H H S — -
116 H H H H F H H H S — - -
11710 H H H H F H H H S - —
118 H H H H H F H H S — — —
119 H H H H H H F H S — -
120 H H H H H H H F S — —
121 H Cl H H H F H H S — — —
122 H SCH3 H H H F H H S — — —
123 H SCH3 H H H H F H S — — — Cmpd.
No. R1 R2 R3 R4 R5 R6 R7 R8 Y R22 R23 R30
124 H SC2H5 H H H H F H S
1254 H CF3 H H H H F H S
126 H OCF3 H H H H F H S
127 H CH(CH3)2 H H H H F H S
1282 H CH(CH3)2 H H H H F H S — - — -
129 H CH(CH3)2 H H H H F H S(O) — -
130 H H H H H H H H CR22R23 H H
131 H OCF3 H H H H H H CR22R23 H H
132 H H H H H H H H NR30 — — H
133 H F H H H H H H NR30 — — H
134 H CF3 H H H H H H NR30 — — H
135 H SCH3 H H H H H H NR30 — — H
136 H OCF3 H H H H H H NR30 — — H
137 H H H H H H H H NR30 CH3 a u is 1, forming an N-oxide
where X is 13
Figure imgf000047_0001
where R 1i2, τ R. 1J, and R . 114 are hydrogen; and
R11 is:
Figure imgf000047_0002
where v is 0; m is 0 and R is hydrogen; R , R , and R are hydrogen; and unless otherwise noted u is 0;
Cmpd.
No. R1 R2 R5 R6 R7 Y R42
no
Figure imgf000047_0003
150 H CF3 H H F s C2H40H
151 H S(0)CH3 H H F s c2a,0H
152 H OCH3 H H H s C3H60H
1534 H SCH3 H H F s C3H60H Cmpd.
No. R1 R2 R5 R6 R7 Y R42
1542 H Cl H H H S C2H4OC2H5
155 H SCH3 H H H s CH2CH(OH)C2H5
156 H OCF3 H H H s C2H4OCH3
157 H OCF3 H H H s C2H4OC H5
158 H SCH3 H H H s C2H4Ophenyl
1592 H H H Cl H s C2H40phenyl
160 H Cl H ' H H s C H4SCH3
1614 H CH(CH3)2 H H F s 2-(4-fluorophenoxy)ethyl
162 H OCF3 H H H s C(=0)CH3
1639 H SCH3 H H H s C(=0)CH3
164 H OCF3 H H H s CO.CH3
165 H OCF3 H H H s CH2C02C2H5
166 H OCF3 H H H s C3H|5C02C2H5
1674 H OCH3 H H H s C3H6C02C4H9
168 H CH(CH3)2 H H F s 3-(4-fluorophenylcarbonyl)propyl
1694 H CH(CH3)2 H H F s 3-(4-fluorophenylcarbonyl)propyl
170 H SCH3 H H H s phenylmethyl
1712 H Cl H H F s 4-fluorophenylmethyl
172 H SCH3 H H H s pyrid-4-yl
173 H SCH3 H H H s pyrid-4-ylmethyl
where X is -CR UR12CR13R14.
■; Y is -S-, where R1, R3 through R8, inclusively, and
R12 through R14, inclusively, are hyd Irogen ; and
R11 is:
Figure imgf000048_0001
where v is 0; p is 0 and Rc is hydrogen:
Cmpd. 3
No R2 R 4 R4'
Figure imgf000048_0002
where X is l
Figure imgf000049_0001
w ...here τ R_ l1, RΛ through Rδ, inclusively, and R 12 through R , 14 , inclusively, are hydrogen; and
R11 is:
Figure imgf000049_0002
where v is 0; q is 0 and R is hydrogen; and u is 0:
Cmpd.
No R R 45
180 S H H 181 S H CH3 182 S H C2H5 183 S SCH3 CH3 184 S CF3 CH3 185 S OCF3 CH3 186 o OCF3 CH3
where X is -CR18R19NR20-, where R19 and R20 are hydrogen;
Cmpd.
R Through R , Inclusively RJi
No.
187 H CH2NHCH3
where X is -CR21=N-; Cmpd.
R1 R R3 Through Rs, R1
No. Inclusively
188 H Cl H l-methylpyrrolidin-3-yloxy
where X is -CR21=N-; where R4 through R8, inclusively, R12, R13, and R14 are hydrogen; and R21 is:
Figure imgf000050_0001
where v is 0; r is 0 and Re is hydrogen; and u is 0:
Cmpd.
Rλ Rό Y R4
No.
189 Cl H S CH3
190 Cl H S(O) CH3
191 Cl H s CH2CH=CH2
192 H Cl s CH3
193 CH(CH3)2 H s CH3
194 OCF3 H s CH3
where X is -NR17- and Y is -CR24R25CR26R27-; where R1, R3 through R7, inclusively, and R24 through R25, inclusively, are hydrogen; v is 0; and u is 0:
Cmpd.
Rz R_ R 17 R 46
No.
195 H Cl C3H6N(CH3)2
Figure imgf000050_0002
199
SCH3 H 46
(A)-N N '--R] ' CH3
\" (01 Cmpd.
Rz R8 R1 R 46
No.
Figure imgf000051_0001
where X is ■ -NR17; and R1, and R3 through R 8, inclusively, are hydrogen:
Cmpd.
Y R30 R2 R17 R47 R48
No.
202 s H C3H6NR47R48 H CH3
2032 s Cl C3H6NR47R48 H CH(CH3)CH2Ph
2046 s Cl C3H6NR47R48 CH3 CH3
2054 s OCH3 C3H6NR47R48 CH3 CH3
2062 s C(0)CH3 C3H6NR47R48 CH3 CH3
2077 s CF3 C3H6NR47R48 -c2a tN(CH3)C2H4-
2087 s CF3 C3H6NR47R48 -C2H4N(C2H4OH)C2H4-
209 0 H C3H6NR47R48 H CH3
210 0 H C3H6NR47R48 H C3H7
211 0 Cl C3H6NR47R48 H CH3
212 0 H C3H6NR47R48 CH3 CH3
213 NR30 CH3 H C3H6NR47R48 CH3 CH3
214 NR30 C2H5 H C3H6NR47R48 -C5H10-
where X is -CRnR12CR13R14-; where R1, R3 through R8, inclusively, R13, and R14 are hydrogen, v is 0; m is 0 and Rb is hydrogen; and u is 0:
Cmpd.
No. R2 R11 R12 R 42
Figure imgf000052_0001
^ethanesulfonate salt; 2maleate salt; 3dimethanesulfonate salt; 4dimaleate salt; 5oxalate salt; nydrochloride salt; 7dihydrochloride salt; 8 disulfite salt; 9sulfate salt; 10 oxalate salt-bis complex
The compounds of formula I useful in the present invention were tested for insecticidal activity by observing mortality in a population of cotton aphid (Aphis gossypii) on treated cotton plants caused by a test compound, when compared to like populations of cotton aphid on untreated plants. These tests were conducted in the following manner:
For each rate of application of test compound, two seven-to-ten days old cotton seedlings (Gossypium hirsutium) grown in 7.6 cm diameter pots were selected for the test. Each test plant was infested with about 120 adult cotton aphids by placing onto each test plant cuttings of leaves from cotton plants grown in a cotton aphid colony. Once infested, the test plants were maintained for up to about 12 hours to allow complete translocation of the aphids onto the test plant. A solution comprising 1000 part per million (ppm) of each test compound was prepared by dissolving 10 milligrams of the test compound in 1 mL of acetone. Each solution was then diluted with 9 mL of a solution of 0.03 mL of polyoxyethylene(lθ) isooctylphenyl ether in 100 mL of water. About 2.5 mL of solution of each test compound was needed to spray each replicate of test plant (5 mL total for each test compound). If needed, the solution of 1000 ppm of test compound was serially diluted with a solution of 10% acetone and 300 ppm of polyoxyethylene(lθ) isooctylphenyl ether in water to provide solutions of each test compound for lower rates of application, for example, 300 ppm, 100 ppm, 30 ppm, or 10 ppm. Each replicate of test plant was sprayed with the solutions of test compound until run-off on both the upper and lower surfaces of the leaves. All the test plants were sprayed using a DeVilbus Atomizer Model 152 (Sunrise Medical, Carlsbad, CA) at a pressure of about 0.63-0.74 kilogram per square centimeter from a distance of about 30.5 centimeters from the test plants. For comparison purposes, a solution of a standard, such as amitraz or demethylchlordimeform (DCDM), prepared in a manner analogous to that set forth above, as well as a solution of 10% acetone and 300 ppm of polyoxyethylene(lθ) isooctylphenyl ether in water containing no test compound were also sprayed onto test plants. Upon completion of spraying the solutions of test compound, the solution of standard, and the solution containing no test compound, the plants were allowed to dry. Upon completion of drying, the test plants were placed in a tray containing about 2.5 centimeters of water, where they were maintained in a growth chamber for 24 hours. After this time, each plant was assessed for percent mortality caused by the test compound when compared to the population of aphids that was infested onto the test plants prior to treatment with test compound. A test compound was designated as possessing insecticidal activity (SA) if there was 20% to 75% mortality of cotton aphid on plants sprayed with that compound. If there was 75% mortality or greater of the cotton aphid, a test compound was designated as being more insecticidally active (A). If there was 20% mortality or less of the cotton aphid, the test compound was termed as inactive (I).
Insecticidal activity data at selected rates of application from this test are provided in Table 2. The test compounds of formula I are identified by numbers that correspond to those in Table 1. Table 2 Insecticidal Activity of Certain Tricyclic Derivatives
Mortality of Cotton Aphid On Cotton Plants
Compound No. 20% to 75% Mortality More Than 75% Mortality (SA) (A)
1 X 2 X 3 X 7 8** X
9 X 11 X 12 X 13 X 14 X 15 X 16 X 20 X 24 X 26 X 36 X 52 X 53 X 54 X 55 X 56 57 X 59 X 60 X 61 X 62 X 63 X 64** X
65** X
66* X
67** X
68 X
69* X
70* X
71 X 72** X
73** X
74** X
75** X
76 X
77** X
78* X 79** X
80** X 8i** X
82** X 3** X Mortality of Cotton Aphid On Cotton Plants
Compound No. 20% to 75% Mortality More Than 75% Mortality
(SA) (A)
84** X
85** X
86 X
87 X
88** X
89** X
90 X
91 X
92 X
94** X
95 X
96** X
97** X
98** X
99** X
100** X
101** X
102** X
103** X
104** X
105** X
106** X
107** X
108** X
109** X
110** X
111** X
112** X
113** X
114 X
115** X
116 X
117 X
118** X
119** X
120 X
121 X
122** X
123** X
124** X
125** X
126** X
127** X
128** X
129 X
131
138** X
139** X
140** X
141 X
142 X Mortality of Cotton Aphid On Cotton Plants
Compound No. 20% to 75%; Mortality More Than 75% Mortality
(SA) (A)
143 X
144** X
145** X
146** X
147 X
148 X
149** X
150** X
151 X
152** X
153** X
154** X
155** X
156 X
157** X
158** X
159 X
160** X
16i** X
162 X
163** X
164 X
165 X
166** X
167** X
168** X
169** X
170 X
171** X
172 X
173** X
178 X
183** X
185** X
186** X
187** X
188 X
189 X
190 X
191 X
192 X
193 X
194 X
203** X
204** X
205** X
206**2 X
207** X
208** X
217 X Rate of application 1000 ppm * Rate of application 300 ppm ** Rate of application 100 ppm
As set forth in Table 2, most all the compounds of formula I tested provided 75% mortality or more of cotton aphid.
In a test conducted in the same manner as set forth above, certain compounds of formula I were tested to determine a more definitive percent mortality of cotton aphid. Insecticidal activity data at selected rates of application and insect exposure times from this test are provided in Table 3.
Table 3 Insecticidal Activity of Certain Tricyclic Derivatives
Rate of Percent Mortality of
Compound Application Cotton Aphid on Cotton Aphid Exposure to Test
No. (ppm) Plants Compound (Hours)
2 100 ppm 80 % 96 hours
3 100 80 96
8 100 88 96
9 100 26 72
11 100 42 96
12 100 26 72
15 100 28 96
20 100 37 72
26 100 84 72
52 300 100 72
64 100 74 168
65 100 100 168
66 100 61 168
67 100 75 168
69 100 69 168
70 100 57 168
71 100 100 168
72 100 100 168
73 100 35 168
75 100 86 168
76 100 32 168
77 100 37 168
78 100 53 168
79 100 35 168
80 1000 83 168
82 100 98 168
83 100 41 168
85 1000 92 168
87 1000 97 168
88 100 35 168
89 100 55 168 Rate of Percent Mortality of
Compound Application Cotton Aphid on Cotton Aphid Exposure to Test
No. (Ppm) Plants Compound (Hours)
90 1000 74 168
92 100 48 72
94 1000 100 72
95 1000 82 72
96 300 100 168
97 100 65 72
98 100 90 168
99 1000 100 168
100 1000 82 96
101 100 60 72
102 100 33 72
103 1000 90 72
104 100 75 168
105 1000 85 96
106 1000 100 96
107 100 82 168
108 1000 100 168
109 1000 100 168
110 300 65 168
111 100 94 72
112 100 92 72
113 100 78 72
115 100 93 72
118 100 85 72
119 100 85 72
121 1000 65 72
122 100 88 72
123 100 96 72
124 100 95 72
125 100 90 72
126 100 100 168
127 1000 100 168
128 100 95 72
131 100 90 168
138 1000 100 168
139 100 96 168
140 1000 73 168
144 100 100 168
145 100 98 144
146 300 88 72
149 100 68 168
150 100 93 72
151 300 72 72
152 300 74 168
153 300 93 168
154 100 83 72
155 100 73 72
156 100 55 168
157 100 64 144
158 300 82 72
159 100 28 72 Rate of Percent Mortality of
Compound Application Cotton Aphid on Cotton Aphid Exposure to Test
No. (ppm) Plants Compound (Hours)
160 100 71 72
161 100 73 72
162 300 31 168
163 1000 96 168
166 100 78 144
167 300 66 168
168 100 77 72
169 100 71 72
171 100 85 72
173 1000 82 96
183 1000 100 168
185 1000 100 168
186 100 100 168
187 100 94 168
189 1000 55 168
194 100 51 168
205 500 40 72
207 1000 25 72
208 , 500 43 72
As set forth in Table 3, compounds of formula I tested in this test, 60% of the compounds provided 75% or greater mortality of cotton aphid, while the remaining compounds of formula I, provided 26% to 74% control of cotton aphid.
While this invention has been described with an emphasis upon preferred embodiments, it will be understood by those of ordinary skill in the art that variations of the preferred embodiments may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the following claims.

Claims

What is claimed is;
Claim 1. An insecticidal composition comprising at least one of an insecticidally effective amount of a compound of formula I and at least one insecticidally compatible carrier therefor, wherein the compound of formula I is:
Figure imgf000060_0001
wherein
R1 tlirough R8, inclusively, are independently selected from hydrogen, halogen, alkyl, cycloalkyl, alkenyl, alkynyl, trialkylsilylalkynyl, alkoxy, haloalkyl, haloalkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, haloalkylthio, haloalkylsulfinyl, haloalkylsulfonyl, dialkylaminosulfonyl, nitro, cyano, amino, formyl, or alkylcarbonyl;
X is selected from -CR >9yrR> 1ι0υ-,
Figure imgf000060_0002
-NR .17
-CR18R19NR20-, or -CR21=N-; and
Y is selected from -CR 22DR23J-, 9
Figure imgf000060_0003
y-, -NR 30
-CR ,3J11rR)3J2ZNτRτ.3J3% -O-, -S-, -S(O)-, -S(O)2-, -CR 3J44Ro3J5O. -, -CR ,3J6DRr.3J7/Sc -, or
-CR38=N-; where R9 and R10 are independently selected from hydrogen, alkyl, or (piperidin-4- yl)alkyl; or R9 and R10 may be taken together with
Figure imgf000061_0001
, or with =CHC2H4NR40R41, where
R39, R40 and R41 are independently selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R40 and R41 may be taken together with -C2H N(CH3)C2H - to form a piperazine ring; u is O or 1, and when u is 1, an N-oxide is formed; n is 0, and Ra is hydrogen; or n is 1 to 8, and Ra is selected from one or more of alkyl, alkoxyalkyl, alkoxycarbonyl, and aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R11 is selected from hydrogen, alkyl, alkylaminoalkoxy, dialkylaminoalkoxy,
N(alkyl) (alkylaminoalkyl) , N(alkyl) (dialkylaminoalkyl) , alkylaminoalkylalkynyl, dialkylaminoalkylalkynyl, morpholinyl, imidazolinyl, alkylpyrrolidinyloxy,
Figure imgf000061_0002
where v is 0 or 1, and when v is 1, A is a bridging group selected from -O-, -S-, -NH-, and -CH -; u is as described above;
R42 through R45, inclusively, are independently selected from hydrogen; alkyl alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R43 and R44 may be taken together with -C5H10- to form a piperidine ring; m, p, and q are 0, and Rb, Rc and Rd are hydrogen; or m is 1 to 8, p is 1 to 7, and q is 1 to 10, and Rb, Rc, and Rd, respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
K (0)»
=(!}-R 3-9
R11 and R12 may be taken together with where Ra, n, u, and R39 are as described above; R12, when not taken together with R11, and R13, R14, and R16, are independently selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, or dialkylaminosulfonyl; R15 is selected from
Figure imgf000063_0001
where m, u, v, A, R and R are as described above;
R17 is hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl,
or aryl;
Figure imgf000063_0002
; or -C3H6NR47R48 where
A, v, and u are as described above;
R46 is selected from selected from hydrogen; alkyl; alkenyl; alkynyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl; heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R47 and R48are independently selected from hydrogen and alkyl; or R47 and R48 may be taken together with -CsHio- to form a piperidine ring, or with
-C2H4N(CH3)C2H4-, or -C2H4N(C2H4OH)C2H4- to form a piperazine ring; R1 and R1 are independently selected from hydrogen, alkyl, amino, alkylaminoalkyl, and dialkylaminoalkyl; R20 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R21 is selected from hydrogen, alkyl,
Figure imgf000064_0001
where
A, v, and u are as described above;
R through R , inclusively, are independently selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; or
R50 and R51 may be taken together with -C5H10- to form a piperidine ring; r, s, and t are 0, and Re, Rf, and Rg are hydrogen, or r is 1 to 8, s is 1 to 7, t is 1 to 10, and Re, Rf, and Rs, respectively, are independently selected from one or more of alkyl, alkoxyalkyl, alkylamino, dialkylamino, alkoxycarbonyl, or aryl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R22 through R29, inclusively, are independently selected from hydrogen, and alkyl; R is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R31 and R32 are independently selected from hydrogen, and alkyl, R33 is selected from hydrogen; alkyl; alkoxyalkyl; alkoxycarbonyl; dialkylaminoalkyl; alkylaminocarbonyl; dialkylaminocarbonyl; alkylsulfonyl; aryl, and arylalkyl wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; R34 through R38, inclusively, are independently selected from hydrogen, and alkyl; and, agriculturally acceptable salts thereof.
Claim 2. An insecticidal composition of claim 1, wherein X is -CR9R10- and
Y is selected from -O-, -S-, -CR22R23-, and -CR34R35O-; where
R9 and R10 are taken together with
Figure imgf000065_0001
where
R39 is selected from hydrogen; alkyl; hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, wherein aryl is optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; and, R22, R23, R34 and R35 are independently selected from hydrogen and alkyl.
Claim 3. An insecticidal composition of claim 1, wherein X is
-CRnR12CR13R14- and Y is selected from -O-, -S- and -CR2 R23-; where
R11 is selected from
Figure imgf000065_0002
where
R and R are independently selected from hydrogen; alkyl; alkenyl; alkynyl hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl arylcarbonylalkyl; arylcarbonyloxyalkyl; heteroaryl; heteroarylalkyl heteroarylalkylamino; wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl;
R12 is selected from selected from hydrogen, hydroxy, halogen, alkyl, alkoxy, alkylcarbonyl, alkylcarbonyloxy, alkoxycarbonyl, alkoxycarbonyloxy, alkylaminocarbonyl, dialkylaminocarbonyl, alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminosulfonyl, and dialkylaminosulfonyl;
R13 and R14 are hydrogen; and,
R22 and R23are independently selected from hydrogen and alkyl.
Claim 4. An insecticidal composition of claim 1, wherein X is
-CR18R19NR20- and Y is selected from -O-, -S- and -CR22R23-; where
R20 is selected from hydrogen, alkyl, alkoxyalkyl, alkoxycarbonyl, dialkylaminoalkyl, alkylaminocarbonyl, and dialkylaminocarbonyl; and, R22 and R23are independently selected from hydrogen and alkyl.
Claim 5. An insecticidal composition of claim 1, wherein X is -CR21=N- and
Y is selected from -S- and -CR22R23-; where R21 is
Figure imgf000066_0001
where
R49 is selected from hydrogen; alkyl; alkenyl, alkynyl, hydroxylalkyl; alkoxyalkyl; alkylthioalkyl; alkylcarbonyl, alkoxycarbonylalkyl; haloalkoxycarbonyl; arylalkyl; aryloxyalkyl; arylcarbonylalkyl; arylcarbonyloxyalkyl, heteroaryl, heteroarylalkyl, heteroarylalkylamino, wherein aryl and heteroaryl are optionally substituted with one or more halogen, alkoxy, haloalkyl, or aryl; and, R22 and R23are independently selected from hydrogen and alkyl.
Claim 6. The insecticidal composition of claim 1, further comprising one or more second compounds.
Claim 7. The insecticidal composition of claim 2, further comprising one or more second compounds.
Claim 8. The insecticidal composition of claim 3, further comprising one or more second compounds.
Claim 9. The insecticidal composition of claim 4, further comprising one or more second compounds.
Claim 10. The insecticidal composition of claim 5, further comprising one or more second compounds.
Claim 11. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 1 to a locus where insects are present or are expected to be present.
Claim 12. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 2 to a locus where insects are present or are expected to be present.
Claim 13. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 3 to a locus where insects are present or are expected to be present.
Claim 14. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 4 to a locus where insects are present or are expected to be present.
Claim 15. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 5 to a locus where insects are present or are expected to be present.
Claim 16. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 6 to a locus where insects are present or are expected to be present.
Claim 17. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 7 to a locus where insects are present or are expected to be present.
Claim 18. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 8 to a locus where insects are present or are expected to be present.
Claim 19. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 9 to a locus where insects are present or are expected to be present.
Claim 20. A method of controlling insects, comprising applying an insecticidally effective amount of a composition of claim 10 to a locus where insects are present or are expected to be present.
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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006138528A3 (en) * 2005-06-16 2007-03-15 Janssen Pharmaceutica Nv Tricyclic opioid modulators
US7432257B2 (en) 2005-01-06 2008-10-07 Janssen Pharmaceutica N.V. Piperdinyl-phenoxazine and phenothiazine derivatives as δ-opioid modulators
US7439239B2 (en) 2004-12-22 2008-10-21 Janssen Pharmaceutica N.V. Tricyclic δ- opioid modulators
WO2009071631A2 (en) * 2007-12-05 2009-06-11 Janssen Pharmaceutica Nv Dibenzoazepine and dibenzooxazepine trpa1 agonists
US7553850B2 (en) 2004-08-05 2009-06-30 Janssen Pharmaceutica Nv Tricyclic-bridged piperidinylidene derivatives as δ-opioid modulators
US7589104B2 (en) 2004-12-22 2009-09-15 Janssen Pharmaceutica Nv Tricyclic-bridged piperidinyline derivatives as §-opioid modulators
US7589103B2 (en) 2003-06-27 2009-09-15 Janssen Pharmaceutica N.V. Tricyclic-bridged piperidinylidene derivatives as 8-opioid modulators
US8158618B2 (en) 2008-06-20 2012-04-17 Astrazeneca Ab Dibenzothiazepine derivatives and uses thereof—424
WO2016127924A1 (en) * 2015-02-13 2016-08-18 Sunshine Lake Pharma Co., Ltd. Tricyclic compounds and uses thereof in medicine
CN107001383A (en) * 2014-08-19 2017-08-01 日本农药株式会社 Oxygen azatropylidene compound and contain the compound as the insecticide for agricultural or horticultural use of active ingredient and its application method
CN109897027A (en) * 2019-04-28 2019-06-18 梯尔希（南京）药物研发有限公司 A kind of synthetic method of 3- hydroxyl Desloratadine metabolin
US11046651B2 (en) 2019-10-21 2021-06-29 Alairion, Inc. Piperazine substituted azapine derivatives and uses thereof

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003039255A1 (en) * 2001-11-05 2003-05-15 Basf Aktiengesellschaft Use of substituted dibenzothiepine derivatives as insecticidal, acaricidal and nematicidal agents
MXPA05007784A (en) * 2003-01-23 2005-09-30 Acadia Pharm Inc Use of n-desmethylclozapine to treat human neuropsychiatric disease.
US20050085463A1 (en) * 2003-01-23 2005-04-21 Weiner David M. Use of N-desmethylclozapine to treat human neuropsychiatric disease
US20050250767A1 (en) * 2003-01-23 2005-11-10 Weiner David M Use of N-desmethylclozapine to treat human neuropsychiatric disease
CN101962369A (en) * 2003-12-22 2011-02-02 阿卡蒂亚药品公司 Amino diaryl [a, d] the suberene analogue that replaces is as the purposes of muscarinic agonist and the methods of treatment of neuropsychiatric disease
CN1950346A (en) * 2004-04-01 2007-04-18 阿卡蒂亚药品公司 N-desmethylclozapine crystalline forms
US20070105836A1 (en) * 2005-10-31 2007-05-10 Lars Pettersson Prodrugs of muscarinic agonists and methods of treatment of neuropsychiatric disorders
CN110128432B (en) * 2018-02-02 2021-03-02 广东东阳光药业有限公司 Nitrogenous tricyclic compound and application thereof in medicine
BR112022024650A2 (en) * 2020-06-03 2023-03-07 Sound Agriculture Company COMPOUNDS AND METHODS TO STIMULATE PLANTS

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3351599A (en) * 1964-09-17 1967-11-07 Spofa Vereinigte Pharma Werke 10, 11-dihydro dibenzo [b, f] thiepins
US3357998A (en) * 1964-11-06 1967-12-12 Searle & Co Complex amides of dihydrodibenzo [b, f] [1, 4] oxazepine-10-carboxylic acids
US4308207A (en) * 1976-11-10 1981-12-29 Sandoz Ltd. Morphanthridine derivatives
US4777177A (en) * 1984-10-19 1988-10-11 Ciba-Geigy Corporation Pesticidal thioxanthen-9-ylidenepiperidines
US5436333A (en) * 1994-08-08 1995-07-25 American Cyanamid Company Process for the preparation of tricyclic-heterocycles
US5538965A (en) * 1993-12-23 1996-07-23 Allelix Biopharmaceuticals Inc. Dopamine receptor ligands
US5602124A (en) * 1994-12-12 1997-02-11 Allelix Biopharmaceuticals, Inc. 5-HT2 receptor ligands
WO2003039255A1 (en) * 2001-11-05 2003-05-15 Basf Aktiengesellschaft Use of substituted dibenzothiepine derivatives as insecticidal, acaricidal and nematicidal agents

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3436397A (en) * 1966-05-23 1969-04-01 American Home Prod Dibenzocyclohepten-5-ylidene thiazolidinones
JPS61106573A (en) * 1984-10-19 1986-05-24 チバ‐ガイギー　アクチエンゲゼルシヤフト Thioxanthene-9-ylidene-piperidine, manufacture and pesticide
WO1993000811A1 (en) * 1991-07-01 1993-01-21 The General Hospital Corporation Invertebrate phenylethanolamine transporter and the use thereof

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3351599A (en) * 1964-09-17 1967-11-07 Spofa Vereinigte Pharma Werke 10, 11-dihydro dibenzo [b, f] thiepins
US3357998A (en) * 1964-11-06 1967-12-12 Searle & Co Complex amides of dihydrodibenzo [b, f] [1, 4] oxazepine-10-carboxylic acids
US4308207A (en) * 1976-11-10 1981-12-29 Sandoz Ltd. Morphanthridine derivatives
US4777177A (en) * 1984-10-19 1988-10-11 Ciba-Geigy Corporation Pesticidal thioxanthen-9-ylidenepiperidines
US5538965A (en) * 1993-12-23 1996-07-23 Allelix Biopharmaceuticals Inc. Dopamine receptor ligands
US5436333A (en) * 1994-08-08 1995-07-25 American Cyanamid Company Process for the preparation of tricyclic-heterocycles
US5602124A (en) * 1994-12-12 1997-02-11 Allelix Biopharmaceuticals, Inc. 5-HT2 receptor ligands
WO2003039255A1 (en) * 2001-11-05 2003-05-15 Basf Aktiengesellschaft Use of substituted dibenzothiepine derivatives as insecticidal, acaricidal and nematicidal agents

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE CAPLUS [Online] WANDER A.G.: '5H-DibenzoÄb,e] [1,4Üdiazepines and 5H-dibenzoÄb,f] [1,4Üthiazepines', XP002975716 Retrieved from STN Database accession no. 1964:447951 & FR 51 F 04 May 1964 *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7589103B2 (en) 2003-06-27 2009-09-15 Janssen Pharmaceutica N.V. Tricyclic-bridged piperidinylidene derivatives as 8-opioid modulators
US8350041B2 (en) 2003-06-27 2013-01-08 Janssen Pharmaceutica, Nv Tricyclic δ-opioid modulators
US8106207B2 (en) 2003-06-27 2012-01-31 Janssen Pharmaceutica, Nv Tricyclic δ-opioid modulators
US7982042B2 (en) 2003-06-27 2011-07-19 Janseen Pharmacautica NV Thiozanthene derivatives as delta-opioid modulators
US7553850B2 (en) 2004-08-05 2009-06-30 Janssen Pharmaceutica Nv Tricyclic-bridged piperidinylidene derivatives as δ-opioid modulators
US7652005B2 (en) 2004-12-22 2010-01-26 Janssen Pharmaceutica N.V. Tricyclic δ-opioid modulators
US7589104B2 (en) 2004-12-22 2009-09-15 Janssen Pharmaceutica Nv Tricyclic-bridged piperidinyline derivatives as §-opioid modulators
US7439239B2 (en) 2004-12-22 2008-10-21 Janssen Pharmaceutica N.V. Tricyclic δ- opioid modulators
US7432257B2 (en) 2005-01-06 2008-10-07 Janssen Pharmaceutica N.V. Piperdinyl-phenoxazine and phenothiazine derivatives as δ-opioid modulators
US7582650B2 (en) 2005-06-16 2009-09-01 Janssen Pharmaceutica N.V. Tricyclic opioid modulators
WO2006138528A3 (en) * 2005-06-16 2007-03-15 Janssen Pharmaceutica Nv Tricyclic opioid modulators
WO2009071631A3 (en) * 2007-12-05 2009-11-12 Janssen Pharmaceutica Nv Dibenzoazepine and dibenzooxazepine trpa1 agonists
US8461145B2 (en) 2007-12-05 2013-06-11 Janssen Pharmaceutica Nv Dibenzoazepine and dibenzooxazepine TRPA1 agonists
WO2009071631A2 (en) * 2007-12-05 2009-06-11 Janssen Pharmaceutica Nv Dibenzoazepine and dibenzooxazepine trpa1 agonists
US8158618B2 (en) 2008-06-20 2012-04-17 Astrazeneca Ab Dibenzothiazepine derivatives and uses thereof—424
US8653257B2 (en) 2008-06-20 2014-02-18 Astrazeneca Ab Dibenzothiazepine derivatives and uses thereof—424
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EP3184528A4 (en) * 2014-08-19 2018-01-10 Nihon Nohyaku Co., Ltd. Oxazepine compound, pesticide for agricultural and horticultural use which contains said compound as active ingredient, and method for using said pesticide for agricultural and horticultural use
US10100061B2 (en) 2014-08-19 2018-10-16 Nihon Nohyaku Co., Ltd. Oxazepine compound and agricultural/horticultural insecticide containing said compound as active ingredient, and method for using the same
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US10183917B2 (en) 2015-02-13 2019-01-22 Sunshine Lake Pharma Co., Ltd. Tricyclic compounds and uses thereof in medicine
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