STEVENSON THOMAS MARTIN (US)
CHIANG GEORGE CHIHSHU (US)
STEVENSON THOMAS MARTIN (US)
| WO1995004726A1 | 1995-02-16 |
| US4977171A | 1990-12-11 | |||
| EP0432661A2 | 1991-06-19 |
| 1. | A compound selected from Formula I, Noxides and agriculturallysuitable salts thereof, I wherein A is selected from the group a direct bond, C 1C4 alkylene, C2C alkenylene, C2C4 alkynylene, O and ΝR10; each E is independently selected from the group C1C4 alkyl and CjC4 haloalkyl; Y is selected from the group 2 () alkenylene, C2C£ haloalkenylene, C2C6 alkynylene and C3Cg haloalkynylene; Z is selected from the group O and S; R1 is selected from the group 1. |
| 2. | halogen, C Cg alkyl, CjC6 haloalkyl, CjC6 alkoxy, CιC6 haloalkoxy, S O^R1 * , cyano and nitro; R2 is selected from the group H, 12 halogen, C]Cg alkyl, CjC^ haloalkyl, CjCg alkoxy, CjCg haloalkoxy, S(O)tR1 1, cyano and nitro; R3 is selected from the group Si(R6)(R7)(R8); Ge(R6)(R7)(R8); 2,8,9trioxa5azalsilabicyclo[3.3.3]undecan 1yl optionally substituted with 16 CrC3 alkyl; CrC3 alkylthio; CrC3 haloalkylthio; CrC3 alkylsulfinyl; CrC3 haloalkylsulfinyl; CrC3 alkylsulfonyl; CrC3 haloalkylsulfonyl; phenyl substituted with CjC3 haloalkylthio, CrC3 haloalkylsulfinyl, CjC3 haloalkylsulfonyl or ^Cj haloalkylsulfonyloxy and optionally substituted with 12 W; hydroxymethyl substituted on the carbon atom with 12 J; and CjCg alkyl substituted with 13 members independently selected from the group cyano, hydroxy, CrC4 alkoxy, CrC4 haloalkoxy, C1C4 alkylthio, C1C4 alkylsulfinyl, CrC4 alkylsulfonyl, CrC4 haloalkylthio, CrC haloalkylsulfinyl, CjC4 haloalkylsulfonyl, formyl, C2C4 alkoxycarbonyl, C2C alkylcarbonyloxy, C C4 alkoxycarbonyloxy, phenoxy optionally substituted with 13 W, phenylthio optionally substituted with 13 W, phenylsulfinyl optionally substituted with 13 W, and phenylsulfonyl optionally substituted with 1. |
| 3. | W, or, when two members are attached to the same carbon atom, said members can be taken together as OCH2CH2O, OCH2CH2CH2O, SCH2CH2S, or SCH2CH2CH2S, each CH2 of said taken together members optionally substituted with 1 2 CrC3 alkyl; R4 and R5 are independently selected from the group H, halogen, CjCjg alkyl, CrC16 haloalkyl, C2C16 alkenyl, C2C16 haloalkenyl, C2C16 alkynyl, C2C16 haloalkynyl, C2C16 alkoxyalkyl, C2C16 alkylthioalkyl, C2Cl6 cyanoalkyl, C3C6 cycloalkyl, C3C6 halocycloalkyl, cyano, nitro, SfO^R1 J, OR9, formyl, C(O)R21, C(O)OR2l, C(O)NR1 R13, S(O)2NR14Rl5, NR16R17, Si(R6)(R7)(R8), SF5 and MJ; each M is independently selected from the group direct bond, S, O, C(O) and C1C. |
| 4. | alkylene; each J is independently selected from the group phenyl, naphthalenyl and pyridinyl, each optionally substituted with 1. |
| 5. | R19; each R6 and R7 is independently selected from the group CjC12 alkyl and CrCι2 alkoxy; each R8 is independently selected from the group CjC12 alkyl; CjC^ alkoxy; and phenyl optionally substituted with 13 W; each R9 is independently selected from the group H, C1C4 alkyl, C]C haloalkyl, C2C4 alkenyl, C2C haloalkenyl, C C4 alkynyl, C2C4 haloalkynyl, C(O)R18, C(O)OR18, C(O)NR12R13, S(O)2NR14R15 and S(O)2R ; R10 is CjCg alkyl, C2Cg alkylcarbonyl and C2Cg alkoxycarbonyl; each R1 *, R12, R14, R16 and R18 is independently selected from the group C rC6 alkyl, C j C6 haloalkyl, C2C6 alkenyl, C2C6 haloalkenyl, C2C6 alkynyl, C2C6 haloalkynyl, C2C6 alkoxyalkyl, C2C6 alkylthioalkyl, C3C6 cycloalkyl, C3Cg halocycloalkyl, C4C7 cycloalkylalkyl, phenyl optionally substituted with 13 W and benzyl optionally substituted with 13 W; each R13, R15 and R17 is independently selected from the group H and C1C4 alkyl; or each pair of R12 and R13, R14 and R15, and R16 and R17, when attached to the same atom, can independently be taken together as (CH2)4, (CH2)5 or CH2CH2OCH2CH2, each group optionally substituted with 13 CH3; each R19 is independently selected from the group halogen, cyano, nitro, C]Cg alkyl, CrC6 haloalkyl, OR20, C(O)R18, C(O)OR18 and Si(R6)(R7)(R8); each R20 is independently selected from the group H, CjC4 alkyl, C1C4 haloalkyl, C C4 alkenyl, C2C haloalkenyl, C C alkynyl, C2C haloalkynyl, C(O)R18, C(O)OR18, C(O)NR12R13, S(O)2NR14R15, S(O) R' *, phenyl optionally substituted with 13 W and benzyl optionally substituted with 13 W; each R21 is independently selected from the group C Cg alkyl, CjCg haloalkyl, C2C6 alkenyl, C2C6 haloalkenyl, C2C6 alkynyl, C2C6 haloalkynyl, C2C6 alkoxyalkyl, C2C6 alkylthioalkyl, C3Cg cycloalkyl, C3C6 halocycloalkyl and C4C7 cycloalkylalkyl; each W is independently selected from the group halogen, cyano, nitro, CjC2 alkyl, CrC2 haloalkyl, CrC2 alkoxy, CrC2 haloalkoxy, CrC2 alkylthio, CrC2 haloalkylthio, CrC2 alkylsulfinyl, CrC2 haloalkylsulfinyl, CrC2 alkylsulfonyl and CιC2 haloalkylsulfonyl; q is 0, 1 or 2; and each t is independently 0, 1 or 2. |
| 6. | 2 A compound of Claim 1 wherein: R3 is selected from the group Si(R6)(R7)(R8); Ge(R6)(R7)(R8); 2,8,9trioxa5azalsilabicyclo[3.3.3]undecanlyI optionally substituted with 1. |
| 7. | CrC3 alkyl; CrC3 alkylthio; CrC3 haloalkylthio; CrC3 alkylsulfinyl; CrC3 haloalkylsulfinyl; CrC3 alkylsulfonyl; CrC3 haloalkylsulfonyl; phenyl substituted with CjC3 haloalkylthio, CrC3 haloalkylsulfinyl or CjC3 haloalkylsulfonyl and optionally substituted with 12 W; and CjCg alkyl substituted with 13 members independently selected from the group cyano, hydroxy, CjC4 alkoxy, CjC4 haloalkoxy, C1C4 alkylthio, C 1 C4 alkylsulfinyl, C j C4 alkylsulfonyl, C l C4 haloalkylthio, C]C haloalkylsulfinyl, CJC4 haloalkylsulfonyl, formyl, C2C4 alkoxycarbonyl, C C4 alkylcarbonyloxy, C2C4 alkoxycarbonyloxy, phenoxy optionally substituted with 13 W, phenylthio optionally substituted with 13 W, pnenylsulfinyl optionally substituted with 13 W, and phenylsulfonyl optionally substituted with 13 W, or, when two members are attached to the same carbon atom, said members can be taken together as OCH2CH2O, OCH2CH2CH2O, SCH2CH2S, or SCH2CH2CH2S, each CH2 of said taken together members optionally substituted with 12 CjC3 alkyl. |
| 8. | 3 A compound of Claim 2 wherein: A is selected from the group a direct bond, 1,2ethenediyl and 1,2ethynediyl; Y is selected from the group C2Cg alkenylene and C2Cg alkynylene; R1 is halogen; R2 is selected from the group H and halogen; R3 is selected from the group Si(R6)(R7)(R8); and CrC2 alkyl substituted with 12 independently selected C1C4 alkoxy; R4 and R5 are independently selected from the group H, halogen, CrC16 alkyl, cyano, S(O)tRπ and OR9; each R6 and R7 is independently selected from the group CrC alkyl and CrC4 alkoxy; each R8 is independently selected from the group C]C4 alkyl; CrC4 alkoxy; and phenyl optionally substituted with 13 W; each R9 is independently selected from the group C]C4 alkyl and CrC4 haloalkyl; each R11 is independently selected from the group CrC4 alkyl and CrC4 haloalkyl; and q is O. 4. A compound of Claim 3 wherein: A is a direct bond; Z is O; R1 is selected from the group F and Cl in the 2position; and R2 is selected from the group H, F and Cl in the 6position. 5. A compound of Claim 4 wherein: Y is 1,2ethynediyl. |
| 9. | 6 The compound of Claim 4 which is selected from the group: 2(2,6difluorophenyl)4,5dihydro4[4[(trimethylsilyl)ethynyl]phenyl]oxazole; 2(2,6difluorophenyl)4[2ethoxy4[(trimethylsilyl)ethynyl]phenyl]4,5 dihydrooxazole; 2(2,6difluorophenyl)4,5dihydro4[4[3(trimethylsilyl)l propyny l]phenyl]oxazole ; 4[4(3,3diethoxy 1 propynyl)phenyl]2(2,6difluorophenyl)4,5 dihydrooxazole; and 4[4(3,3diethoxylpropynyl)2ethoxyphenyl]2(2,6difluorophenyl)4,5 dihydrooxazole. |
| 10. | A compound of Claim 1 wherein: R3 is selected from the group phenyl substituted with CrC3 haloalkylsulfonyloxy and optionally substituted with 12 W; and hydroxymethyl substituted on the carbon atom with 12 J. |
| 11. | The compound of Claim 7 which is selected from the group: [4[[4[2(2,6difluorophenyl)4,5dihydro4oxazolyl]phenyl]ethynyl]phenyl] trifluoromethanesulfonate; and α[[4[2(2,6difluorophenyl)4,5dihydro4oxazolyl]phenyl]ethynyl]α phenylbenzenemethanol. |
| 12. | An arthropodicidal composition comprising an arthropodicidally effective amount of a compound of Claim 1 and at least one of a surfactant, a solid diluent or a liquid diluent. |
| 13. | A method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of a compound of Claim 1. |
The control of arthropod pests is extremely important in achieving high crop efficiency. Arthropod damage to growing and stored agronomic crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of arthropod pests in forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health is also important. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer or have different modes of action. U.S. 5,141,948 discloses insecticidal oxa- and thia-zolines of Formula i:
wherein
R j and R 2 are independently H, halogen, lower alkyl, lower alkoxy, nitro, lower haloalkyl or lower haloalkoxy, provided that R ] and R 2 are not simultaneously H; R 3 is H, halogen, lower alkyl or lower alkoxy;
R 4 is alkyl having 7 or more carbon atoms, alkoxy having 7 or more carbon atoms, alkylthio, lower alkoxy-lower alkyl, lower alkoxy-lower alkoxy, alkenyloxy having 3 or more carbon atoms, lower alkynyloxy, tri(lower alkyl)silyl, cycloalkyl which may be substituted by a lower alkyl, or
B is a direct bond, O, lower a y ene, lower alkyleneoxy, lower alkylenedioxy or a di(lower alkyl)silyl; Q is CH or N;
n is 0-5; each R5 is independently halogen, alkyl, alkoxy, lower haloalkyl, lower haloalkoxy or tri(lower alkyl)silyl; A is a direct bond or lower alkylene; and Z is O or S.
U.S. 4,977,171 discloses insecticidal and acaricidal oxa- or thia-zoline derivatives of Formula ii:
wherein X 1 and X 2 are independently H, lower alkyl, lower alkoxy, halogen, trifluoromethyl or trifluoromethoxy; Y 1 and Y 2 are independently H, lower alkyl, lower alkoxy, lower alkylthio, cyano, nitro, halogen or trifluoromethyl; Z is O or S; and n is O or l.
WO 95/04726 discloses insecticidal and acaricidal oxa- or thia-zoline derivatives of Formula iii:
111 wherein, inter alia, A is selected from the group a direct bond and C1-C3 straight or branched chain alkylene; R 3 is selected from the group C3-C7 halocycloalkyl; C2-C10 haloalkenyl optionally substituted with at least one member independently selected from the group CN and C2-C6 alkoxycarbonyl; Cj-Cio alkyl substituted with at least one member independently selected from the group Si(R 6 )(R 7 )R 8 , CN, C 2 -C 6 alkylcarbonyl, C 2 -C 6 haloalkylcarbonyl, C 2 -Cό haloalkoxycarbonyl, and
C 2 -Cg alkoxycarbonyl; C 2 -C 6 alkylcarbonyl; C 2 -C 10 alkenyl optionally substituted with at least one member independently selected from R 9 ; C 2 -CJ Q alkynyl optionally substituted with at least one member independently selected from R 9 ; C 2 -C^ haloalkylcarbonyl; C 2 -C£ alkoxycarbonyl; C 2 -C 6 haloalkoxycarbonyl; C(O)R 9 ; C(O)OR 9 ; C(O)N(R 10 )R 1 1 ; OR 12 ; tetrahydropyranyl; phenyl substituted with at least one member independently selected from W 1 ; and an 8- to 12-membered fused bicyclic ring system containing 0-4 heteroatoms independently selected from 0-4 nitrogen, 0-2 oxygen and 0-2 sulfur, the ring system optionally substituted with at least one member independently selected from W;
R 9 is selected from the group phenyl and pyridyl, each optionally substituted with at least one member independently selected from W; and W is selected from the group halogen, CN, CHO, NO 2 , SF 5 , C r C 3 alkyl, C r C 3 haloalkyl, C r C 3 alkylthio, C r C 3 alkoxy, C r C 3 haloalkoxy, C 2 -C 4 alkylcarbonyl and C 2 -C4 alkoxycarbonyl.
SUMMARY OF THE INVENTION This invention is directed to compounds of Formula I including all geometric and stereoisomers, N-oxides, and agriculturally suitable salts thereof, agricultural compositions containing them and their use as arthropodicides:
I wherein
A is selected from the group a direct bond, C C 4 alkylene, C 2 -C 4 alkenylene, C 2 -C 4 alkynylene, O and ΝR 10 ; each E is independently selected from the group C j -C alkyl and C j -C 4 haloalkyl;
Y is selected from the group C 2 -Cg alkenylene, Cp Cg haloalkenylene, -C^ alkynylene and yC^ haloalkynylene; Z is selected from the group O and S;
R 1 is selected from the group 1-2 halogen, C r C 6 alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, Ci -C 6 haloalkoxy, SCO^R 1 ] , cyano and nitro;
R 2 is selected from the group H, 1-2 halogen, Ci-Cg alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C1-C6 haloalkoxy, SCO^R 11 , cyano and nitro; R 3 is selected from the group Si(R 6 )(R 7 )(R 8 ); Ge(R 6 )(R 7 )(R 8 );
2,8,9-trioxa-5-aza-l-silabicyclo[3.3.3]undecan-l-yl optionally substituted with 1-6 C r C 3 alkyl; C r C 3 alkylthio; C r C 3 haloalkylthio; C r C 3 alkylsulfinyl; C r C 3 haloalkylsulfinyl; C r C 3 alkylsulfonyl; C r C 3 haloalkylsulfonyl; phenyl substituted with Cι-C 3 haloalkylthio, C j -C 3 haloalkylsulfinyl, Cj-C 3 haloalkylsulfonyl or Cj-C 3 haloalkylsulfonyloxy and optionally substituted with 1-2 W; hydroxymethyl substituted on the carbon atom with 1-2 J; and C j -Cg alkyl substituted with 1-3 members independently selected from the group cyano, hydroxy, C ] -C 4 alkoxy, C j -C 4 haloalkoxy, C C 4 alkylthio, C r C 4 alkylsulfinyl, C r C alkylsulfonyl, C r C haloalkylthio, C r C 4 haloalkylsulfinyl, Cj-C 4 haloalkylsulfonyl, formyl, C 2 -C 4 alkoxycarbonyl, C -C 4 alkylcarbonyloxy, C 2 -C 4 alkoxycarbonyloxy, phenoxy optionally substituted with 1-3 W, phenylthio optionally substituted with 1-3 W, phenylsulfinyl optionally substituted with 1-3 W, and phenylsulfonyl optionally substituted with 1-3 W, or, when two members are attached to the same carbon atom, said members can be taken together as -OCH 2 CH 2 O-, -OCH 2 CH 2 CH 2 O-, -SCH 2 CH 2 S-, or -SCH 2 CH 2 CH 2 S-, each CH 2 of said taken together members optionally substituted with 1-2
C r C 3 alkyl; R 4 and R 5 are independently selected from the group H, halogen, C j -Cig alkyl, C j -Cj 6 haloalkyl, C 2 -C j 6 alkenyl, C 2 -C]6 haloalkenyl, C 2 -Cj6 alkynyl, C 2 -Cι 6 haloalkynyl, C 2 -C 16 alkoxyalkyl, C 2 -C 16 alkylthioalkyl, C 2 -C ] 6 cyanoalkyl, C β -Cg cycloalkyl, C 3 -C 6 halocycloalkyl, cyano, nitro, SCO^R 1 * ,
OR 9 , formyl, C(O)R 21 , C(O)OR 21 , C(O)NR 1 R 13 , S(O) 2 NR 14 R 1 5, NR 16 R 17 , Si(R6)(R 7 )(R8), SF 5 and M-J; each M is independently selected from the group direct bond, S, O, C(O) and Cι-C 4 alkylene; each J is independently selected from the group phenyl, naphthalenyl and pyridinyl, each optionally substituted with 1-4 R 19 ; each R 6 and R 7 is independently selected from the group C j -C 12 alkyl and C j -Cι 2 alkoxy; each R 8 is independently selected from the group Cι-C 12 alkyl; C j -Cι 2 alkoxy; and phenyl optionally substituted with 1-3 W;
each R 9 is independently selected from the group H, C]-C 4 alkyl, Cι-C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkynyl, C(O)R 18 , C(O)OR 18 , C(O)NRl 2 R 13 , S(O) 2 NR 14 R 15 and S(O) 2 R n ; R 10 is C j -C 6 alkyl, C 2 -Cg alkylcarbonyl and 2 - 6 alkoxycarbonyl; each R 1 1 , R 12 , R 14 , R 16 and R 18 is independently selected from the group C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 2 -C 6 alkoxyalkyl, C 2 -C 6 alkylthioalkyl, C 3 -C 6 cycloalkyl, C 3 -Cg halocycloalkyl, C4-C7 cycloalkylalkyl, phenyl optionally substituted with 1-3 W and benzyl optionally substituted with 1-3 W; each R 13 , R 15 and R 17 is independently selected from the group H and C,;-C 4 alkyl; or each pair of R 12 and R 13 , R 14 and R 15 , and R 16 and R 17 , when attached to the same atom, can independently be taken together as (CH 2 ) , (CH 2 ) 5 or CH 2 CH 2 OCH 2 CH 2 , each group optionally substituted with 1-3 CH 3 ; each R 19 is independently selected from the group halogen, cyano, nitro, C j -Cg alkyl, C r C 6 haloalkyl, OR 20 , C(O)R 18 , C(O)OR 18 and Si(R 6 )(R 7 )(R 8 ); each R 20 is independently selected from the group H, C j -C alkyl, C C haloalkyl, C -C 4 alkenyl, C 2 -C haloalkenyl, C 2 -C alkynyl, C 2 -C haloalkynyl, C(O)R 18 , C(O)OR 18 , C(O)NR 12 R 13 , S(O) 2 NR 14 R 15 , S(O) 2 R ! phenyl optionally substituted with 1-3 W and benzyl optionally substituted with 1-3 W; each R 21 is independently selected from the group C j -Cg alkyl, C j -Cg haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, C 2 -C 6 haloalkynyl, C 2 -C 6 alkoxyalkyl, C 2 -Cg alkylthioalkyl, C 3 -C6 cycloalkyl, C 3 -C 6 halocycloalkyl and C4-C7 cycloalkylalkyl; each W is independently selected from the group halogen, cyano, nitro, Cι-C 2 alkyl, C r C 2 haloalkyl, C r C 2 alkoxy, C r C 2 haloalkoxy, C r C 2 alkylthio, C r C 2 haloalkylthio, C r C 2 alkylsulfinyl, C r C 2 haloalkylsulfinyl, C r C 2 alkylsulfonyl and C ] -C 2 haloalkylsulfonyl; q is 0, 1 or 2; and each t is independently 0, 1 or 2.
DETAILS OF THE INVENTION In the above recitations, the term "alkyl", used either alone or in compound words such as "alkylthio" or "haloalkyl" includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers. The term "1-6 alkyl" indicates that one to six of the available positions for that substituent
may be alkyl which are independently selected. "Alkenyl" includes straight-chain or branched alkenes such as vinyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl and hexenyl isomers. "Alkenyl" also includes polyenes such as 1 ,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes such as ethynyl, 1-propynyl, 2-propynyl and the different butynyl, pentynyl and hexynyl isomers. "Alkynyl" can also include moieties comprised of multiple triple bonds such as 2,5-hexadiynyl. "Alkylene" denotes a straight-chain or branched alkanediyl. Examples of "alkylene" include CH 2 , CH 2 CH 2 , CH(CH 3 ), CH 2 CH 2 CH 2 , CH 2 CH(CH 3 ) and the different butylene isomers. "Alkenylene" denotes a straight-chain or branched alkenediyl containing one olefinic bond. Examples of "alkenylene" include CH=CH, CH 2 CH=CH, CH=C(CH 3 ) and the different butenylene isomers. "Alkynylene" denotes a straight-chain or branched alkynediyl containing one triple bond. Examples of "alkynylene" include C≡C, CH 2 C≡C, G_CCH 2 and the different butynylene isomers. "Alkoxy" includes, for example, methoxy, ethoxy, n-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. "Alkoxyalkyl" denotes alkoxy substitution on alkyl. Examples of "alkoxyalkyl" include CH 3 OCH 2 , CH 3 OCH 2 CH 2 , CH 3 CH 2 OCH 2 , CH 3 CH 2 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 . "Alkylthio" includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio and butylthio isomers. "Alkylthioalkyl" denotes alkylthio substitution on alkyl. Examples of "alkylthioalkyl" include CH 3 SCH 2 , CH 3 SCH 2 CH 2 , CH 3 CH 2 SCH 2 , CH 3 CH 2 CH 2 CH 2 SCH 2 and CH 3 CH 2 SCH 2 CH 2 . "Alkylsulfinyl" includes both enantiomers of an alkylsulfinyl group. Examples of "alkylsulfinyl" include CH 3 S(O), CH 3 CH 2 S(O), CH 3 CH 2 CH 2 S(O), (CH 3 ) 2 CHS(O) and the different butylsulfinyl isomers. Examples of "alkylsulfonyl" include CH 3 S(O) 2 , CH 3 CH 2 S(O) 2 , CH 3 CH 2 CH 2 S(O) 2 , (CH 3 ) 2 CHS(O) 2 and the different butylsulfonyl isomers.
"Cyanoalkyl" denotes an alkyl group substituted with one cyano group. Examples of "cyanoalkyl" include NCCH 2 , NCCH 2 CH 2 and CH 3 CH(CN)CH 2 . "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moieties bonded to straight-chain or branched alkyl groups. One skilled in the art will appreciate that not all nitrogen containing heterocycles can form N-oxides since the nitrogen requires an available lone pair for oxidation to the oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides. One skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for the preparation of N-oxides of heterocycles and tertiary amines are very well known by one skilled in the art including the oxidation of heterocycles and tertiary
amines with peroxy acids such as peracetic and m-chloroperbenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethydioxirane. These methods for the preparation of N-oxides have been extensively described and reviewed in the literature, see for example: T. L. Gilchrist in Comprehensive Organic Synthesis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press; M. Tisler and B. Stanovnik in Comprehensive Heterocyclic Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds., Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol. 43, pp 149-161, A. R. Katritzky, Ed., Academic Press; M. Tisler and B. Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp 285-291 ,
A. R. Katritzky and A. J. Boulton, Eds., Academic Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in Advances in Heterocyclic Chemistry, vol. 22, pp 390-392, A. R. Katritzky and A. J. Boulton, Eds., Academic Press.
The term "halogen", either alone or in compound words such as "haloalkyl", includes fluorine, chlorine, bromine or iodine. The term "1-2 halogen" indicates that one or two of the available positions for that substituent may be halogen which are independently selected. Further, when used in compound words such as "haloalkyl", said alkyl may be partially or fully substituted with halogen atoms which may be the same or different. Examples of "haloalkyl" include F 3 C, C1CH 2 , CF 3 CH 2 and CF 3 CC1 2 . The terms "haloalkenyl", "haloalkynyl", "haloalkoxy", and the like, are defined analogously to the term "haloalkyl". Examples of "haloalkenyl" include (C1) 2 C=CHCH 2 and CF 3 CH 2 CH=CHCH 2 . Examples of "haloalkynyl" include HOCCHC1, CF 3 C≡C, CCl 3 OC and FCH 2 C≡CCH 2 . Examples of "haloalkoxy" include CF 3 O, CCl 3 CH 2 O, HCF 2 CH 2 CH 2 O and CF 3 CH 2 O. Examples of "haloalkylthio" include CC1 3 S, CF 3 S, CC1 3 CH 2 S and C1CH 2 CH 2 CH 2 S. Examples of "haloalkylsulfonyl" include CF 3 S(O) 2 , CCl 3 S(O) 2 , CF 3 CH 2 S(O) 2 and CF 3 CF 2 S(O) 2 . Examples of "haloalkylsulfonyloxy" include CF 3 S(O) 2 O, CCl 3 S(O) 2 O, CF 3 CH 2 S(O) 2 O and CF 3 CF 2 S(O) 2 O.
The total number of carbon atoms in a substituent group is indicated by the "C j -Cj" prefix where i and j are numbers from 1 to 16. For example, C C 3 alkylsulfonyl designates methylsulfonyl through propylsulfonyl; C 2 alkoxyalkyl designates CH 3 OCH ; C 3 alkoxyalkyl designates, for example, CH 3 CH(OCH 3 ), CH 3 OCH 2 CH 2 or CH 3 CH 2 OCH 2 ; and C 4 alkoxyalkyl designates the various isomers of an alkyl group substituted with an alkoxy group containing a total of four carbon atoms, examples including CH 3 CH 2 CH 2 OCH 2 and CH 3 CH 2 OCH 2 CH 2 . Examples of "alkylcarbonyl" include C(O)CH 3 , C(O)CH 2 CH 2 CH 3 and C(O)CH(CH 3 ) 2 . Examples of
"alkoxycarbonyl" include CH 3 OC(=O), CH 3 CH 2 OC(=O), CH 3 CH 2 CH 2 OC(=O),
(CH 3 ) 2 CHOC(=O) and the different butoxy- or pentoxycarbonyl isomers. In the above recitations, when a compound of Formula I is comprised of one or more heterocyclic rings, all substituents are attached to these rings through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen. The term "2,8,9-trioxa-5-aza-l-silabicyclo[3.3.3]undecan-l-yl" designates the silyl radical:
When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1 , said substituents (when they exceed 1) are independently selected from the group of defined substituents.
When a group contains a substituent which can be hydrogen, for example R 2 or R 5 , then, when this substituent is taken as hydrogen, it is recognized that this is equivalent to said group being unsubstituted.
Compounds of this invention can exist as one or more stereoisomers. The various stereoisomers include enantiomers, diastereomers, atropisomers and geometric isomers. One skilled in the art will appreciate that one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively prepare said stereoisomers. Accordingly, the present invention comprises compounds selected from Formula I, N-oxides and agriculturally suitable salts thereof. The compounds of the invention may be present as a mixture of stereoisomers, individual stereoisomers, or as an optically active form. The salts of the compounds of the invention include acid-addition salts with inorganic or organic acids such as hydrobromic, hydrochloric, nitric, phosphoric, sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, salicylic, tartaric, 4-toluenesulfonic or valeric acids. The salts of the compounds of the invention also include those formed with organic bases (e.g., pyridine, ammonia, or triethylamine) or inorganic bases (e.g., hydrides, hydroxides, or carbonates of sodium, potassium, lithium, calcium, magnesium or barium) when the compound contains an acidic group such as a phenol.
Preferred compounds for reasons of better activity and/or ease of synthesis are: Preferred 1. Compounds of Formula I above, and N-oxides and agriculturally-suitable salts thereof, wherein:
R 3 is selected from the group Si(R 6 )(R 7 )(R 8 ); Ge(R 6 )(R 7 )(R 8 ); 2,8,9-trioxa-5-aza- 1 -silabicyclo[3.3.3]undecan- 1 -yl optionally substituted with 1-6 C r C 3 alkyl; C r C 3 alkylthio; C r C 3 haloalkylthio; C r C 3 alkylsulfinyl; C r C 3 haloalkylsulfinyl; C r C 3 alkylsulfonyl; C1-C3 haloalkylsulfonyl; phenyl substituted with C r C 3 haloalkylthio, C r C 3 haloalkylsulfinyl or C r C 3 haloalkylsulfonyl and optionally substituted with 1-2 W; and C j -C^ alkyl substituted with 1-3 members independently selected from the group cyano, hydroxy, C j -C 4 alkoxy, C j -C 4 haloalkoxy, C j -C 4 alkylthio, Cj-C 4 alkylsulfinyl, Cj-C alkylsulfonyl, C r C 4 haloalkylthio, C j -C 4 haloalkylsulfinyl, Cι-C 4 haloalkylsulfonyl, formyl, C 2 -C 4 alkoxycarbonyl, C 2 -C 4 alkylcarbonyloxy, C 2 -C 4 alkoxycarbonyloxy, phenoxy optionally substituted with 1-3 W, phenylthio optionally substituted with 1-3 W, phenylsulfinyl optionally substituted with 1-3 W, and phenylsulfonyl optionally substituted with 1-3 W, or, when two members are attached to the same carbon atom, said members can be taken together as
-OCH 2 CH 2 O-, -OCH 2 CH 2 CH 2 O-, -SCH 2 CH 2 S-, or -SCH 2 CH CH 2 S-, each CH of said taken together members optionally substituted with 1-2 C j -C 3 alkyl. Preferred 2. Compounds of Preferred 1 wherein: A is selected from the group a direct bond, 1,2-ethenediyl and
1,2-ethynediyl; Y is selected from the group C 2 -Cg alkenylene and C 2 -C6 alkynylene; R 1 is halogen;
R 2 is selected from the group H and halogen; R 3 is selected from the group Si(R 6 )(R 7 )(R 8 ); and C r C 2 alkyl substituted with 1-2 independently selected C j -C 4 alkoxy; R 4 and R 5 are independently selected from the group H, halogen, C j -C j g alkyl, cyano, S(O) t R π and OR 9 ; each R 6 and R 7 is independently selected from the group Cι-C 4 alkyl and C j -C 4 alkoxy;
each R 8 is independently selected from the group C r C 4 alkyl; C r C 4 alkoxy; and phenyl optionally substituted with 1-3 W; each R 9 is independently selected from the group C r C 4 alkyl and C r C haloalkyl; each R 11 is independently selected from the group C r C alkyl and C j -C haloalkyl; and q is O. Preferred 3. Compounds of Preferred 2 wherein: A is a direct bond; Z is O;
R 1 is selected from the group F and Cl in the 2-position; and R 2 is selected from the group H, F and Cl in the 6-ρosition. Preferred 4. Compounds of Preferred 3 wherein: Y is 1,2-ethynediyl. Preferred 5. Compounds of Formula I above, and N-oxides and agriculturally-suitable salts thereof, wherein:
R 3 is selected from the group phenyl substituted with C j -C 3 haloalkylsulfonyloxy and optionally substituted with 1-2 W; and hydroxymethyl substituted on the carbon atom with 1-2 J. Most preferred are compounds of Formula I selected from the group:
2-(2,6-difluorophenyl)-4,5-dihydro-4-[4-[(trimethylsilyl) ethynyl]phenyl]oxazole; 2-(2,6-difluorophenyl)-4-[2-ethoxy-4-[(trimethylsilyl)ethyny l]phenyl]-4,5- dihydrooxazole;
2-(2,6-difluorophenyl)-4,5-dihydro-4-[4-[3-(trimethylsily l)-l- propynyl]phenyl]oxazole;
4-[4-(3,3-diethoxy-l-propynyl)phenyl]-2-(2,6-difluorophen yl)-4,5- dihydrooxazole;
4-[4-(3,3-diethoxy-l-propynyl)-2-ethoxyphenyl]-2-(2,6-dif luorophenyl)-4,5- dihydrooxazole; [4-[[4-[2-(2,6-difluorophenyl)-4,5-dihydro-4-oxazolyl]phenyl ]ethynyl]phenyl] trifluoromethanesulfonate; and α-[[4-[2-(2,6-difluorophenyl)-4,5-dihydro-4-oxazolyl]phenyl ]ethynyl]-α- pheny lbenzenemethanol . This invention also relates to arthropodicidal compositions comprising arthropodicidally effective amounts of the compounds of the invention and at least one
of a surfactant, a solid diluent or a liquid diluent. The preferred compositions of the present invention are those which comprise the above preferred compounds.
This invention also relates to a method for controlling arthropods comprising contacting the arthropods or their environment with an arthropodicidally effective amount of the compounds of the invention (e.g., as a composition described herein). The preferred methods of use are those involving the above preferred compounds.
It is noted that the compound 2-(2,6-difluorophenyl)-4,5-dihydro-4-[4- [(trimethylsilyl)ethynyl]phenyl]oxazole can be desilylated with base and thus used as an intermediate for the preparation of other arthropodicides (see WO 95/04726). In accordance with the present invention, the compound 2-(2,6-difluorophenyl)-4,5- dihydro-4-[4-[(trimethylsilyl)ethynyl]phenyl]oxazole itself is of particular note for its arthropodicidal activity. The present invention also includes compounds of Formula I other than 2-(2,6-difluorophenyl)-4,5-dihydro-4-[4- [(trimethylsilyl)ethynyl]phenyl]oxazole. Of note are embodiments where Y is selected from the group C 2 -Cg alkenylene, C 2 -Cg haloalkenylene, C 3 -Cg alkynylene and C 3 -C 6 haloalkynylene.
Also of note are embodiments where R 1 is selected from the group halogen, C j -C alkyl, C r C 6 haloalkyl, C r C 6 alkoxy, C r C 6 haloalkoxy, SCO^R 1 ! , CN and NO 2 ; embodiments where R 2 is selected from the group H, halogen, alkyl, Ci-Cg haloalkyl, C r C 6 alkoxy, C r C 6 haloalkoxy, S(O) t R ! l , CN and NO 2 ; embodiments where R 3 is selected from the group Si(R 6 )(R 7 )(R 8 ), Ge(R 6 )(R 7 )(R 8 ), and 2,8,9-trioxa-5-aza-l-silabicyclo[3.3.3]undecan-l-yl optionally substituted with 1-6 C ] -C 3 alkyl; embodiments where R 3 is other than C r C 3 alkylthio, C j -C 3 haloalkylthio, C r C 3 alkylsulfinyl, C r C 3 haloalkylsulfinyl, C r C 3 alkylsulfonyl, C C 3 haloalkylsulfonyl, and phenyl substituted with C j -C 3 haloalkylthio, C j -C 3 haloalkylsulfinyl or Cι-C 3 haloalkylsulfonyl and optionally substituted with 1-2 W; embodiments where each W is other than C j -C 2 alkylsulfinyl and C j -^ haloalkylsulfinyl; embodiments where R 3 is other than phenyl substituted with C j -C 3 haloalkylsulfonyloxy and optionally substituted with 1-2 W, and hydroxymethyl substituted on the carbon atom with 1-2 J; and embodiments where R 3 is other than Si(R 6 )(R 7 )(R 8 ), Ge(R 6 )(R 7 )(R 8 ), and
2,8,9-trioxa-5-aza-l-silabicyclo[3.3.3]undecan-l-yl optionally substituted with 1-6 C r C 3 alkyl.
The compounds of Formula I can be prepared by one or more of the following methods and variations as described in Schemes 1-9. The definitions of A, E, Y, Z,
R!-R 21 , M, J, W, q and t in the compounds of Formulae El-XIV below are as defined above in the Summary of the Invention.
Compounds of Formula I can be made from compounds of Formula II and silicon-containing alkynes or alkenes of Formula III. This sequence is known as the Heck reaction which has been discussed in great detail by Heck in Palladium Reagents in Organic Synthesis, Academic Press, London, (1985). Other more recent modifications of this reaction are summarized in Larock and Baker, Tetrahedron Lett. (1988) 29, 905-908 and in Cabri et al., J. Org. Chem. (1992) 57, 3558-3563. Typically, the compound of Formula II and palladium acetate (1-5 mol ) and triphenylphosphine (2-10 mol%) are heated with the silicon-containing alkene (R 3 -YH, Y = alkenylene) (1 to 3 equivalents) in dimethylformamide or other aprotic solvents at 60-120 °C. The presence of a base such as triethylamine, sodium acetate, sodium carbonate or potassium carbonate is required. When an alkyne (R 3 -YH, Y = alkynylene) is used, the presence of a catalytic amount of copper (I) iodide (1-5 mol ) greatly accelerates the reaction. In this case, it is often preferable to carryout the reaction using an organic base (e.g., triethylamine) as the solvent or a mixed solvent of an organic base (e.g., acetonitrile and triethylamine). Under these conditions, the reaction with alkynes (R 3 -YH, Y = alkynylene) often proceeds without external heating. Alkynes of Formula HI with R 3 equal to Cj-C 2 alkyl substituted with two alkoxy groups can be synthesized from either acrolein (Le Coq and Gorgues, Org. Synth., Coll. Vol. VI ( 1988) p 954) or alkyl vinyl ethers (Skattelbol, J. Org. Chem. (1966), 31, 1554).
Scheme 1
B = halogen, C j -C 4 alkyls ulfonyloxy , C]-C 4 haloalkylsulfonyloxy Y= alkene, alkyne
Compounds of Formula II can be made from amino alcohols (or thiols) of
Formula IV and benzoic acid derivatives as shown in Scheme 2.
IV Catalyst
This transformation generally consists of two steps. First, the compound of Formula IV is condensed with the benzoic acid derivative to form an amide of Formula V. A generally useful way to do this is to treat the compound of Formula IV with an aroyl chloride in the presence of an acid acceptor (usually a tertiary amine base such as triethylamine) at room temperature or below. This reaction can be carried out in an inert solvent such as dichloromethane, tetrahydrofuran, toluene and other solvents which will not react with acid chlorides or bases. There are other useful ways to form amides, many examples of which are found in Larock, Comprehensive Organic Transformations, VCH New York, pp 972-981. The second step carried out is the ring closure. This can be accomplished by treating the intermediate amide of Formula V with a dehydrating agent. Some useful reagent systems for this transformation include but are not limited to triphenylphosphine/carbon tetrachloride, diethyl azodicarboxylate/triphenylphosphine and thionyl chloride. An especially useful method for ring closure involves treatment of the amide with thionyl chloride in benzene or another inert solvent at reflux until the starting material is consumed (usually 30 min to 3 h). The residue of this reaction is treated with an inorganic base such as sodium or potassium hydroxide in an alcoholic or aqueous medium (usually heating to reflux for 30 min to 2 h is required). Many methods for ring closure to oxazolines have been compiled by Frump (Chem. Rev. (1971) 71, 483-505).
Alternatively, compounds of Formula V (where A is a direct bond) can be prepared in two steps as shown in Scheme 3. First, compounds of Formula VI are amidoalkylated with a compound of Formula VII to form Formula VIII compounds. A typical reaction involves the combination of compounds of Formula VI and VII in an acid such as
sulfuric acid, methanesulfonic acid, trifluoroacetic acid, polyphosphoric acid or perchloric acid. The reaction can be run in a cosolvent such as acetic acid. The reaction temperature can range from -10° to 200 °C with 0°-100 °C being preferred. Alternatively, the reaction can be carried out in an inert solvent such as chloroform, methylene chloride, benzene, toluene or ether in the presence of a Lewis acid such as aluminum chloride or boron trifluoride. The acid, temperature, and time of the reaction vary according to the relative reactivity of Formula VI compound towards electrophilic substitution reactions. Amidoalkylation reactions have been extensively reviewed in the literature (see Zaugg, Synthesis (1984), 85-1 10). The second step is the reduction of a Formula VHI compound to form a Formula V compound. Reductions of this type are well-known in the art (see Hudlicky, Reductions in Organic Chemistry ( 1984), 136-163). Typical reducing agents include the alkali metal borohydrides and diborane. When U is a lower alkyl group, the use of lithium borohydride as reducing agent, tetrahydrofuran as solvent and performance of the reactions at 65°C for 1-6 h, is preferred. An alternate strategy is illustrated in Example 6 where the amidoalkylation is performed using a compound with a halomethyl group in place of the CO 2 U group in compounds of Formula VII and the product is directly cyclized under basic conditions to give oxazolines of Formula II (Z = O and A = direct bond).
Scheme 3
reduction
A = direct bond
The preparation of Formula VII compounds can be accomplished by refluxing glyoxylic acid derivatives (Formula IX) and commercially available benzamides (Formula X) in an inert solvent such as acetone, benzene and chloroform (Scheme 4). This procedure is known in the art (see Ben-Ishai, Tetrahedron (1975), 31, 863-866 and Tetrahedron (1977), 33, 881-883).
Scheme 4
IX
U = H, C!-C 4 alkyl
As shown in Scheme 5, amino alcohols of Formula IV can be produced by the treatment of an amino acid derivative of Formula XI with a reducing agent. In the reducing process, amino esters are preferred, but amino acids themselves can also be used. There are many reagents known to reduce acids and esters to alcohols (see Larock, Comprehensive Organic Transformations, VCH, New York, pp 548-553). Particularly useful are alkali metal hydrides and boranes. For example, treatment of a compound of Formula XI with lithium aluminum hydride at 0-50 °C in ether solvents
such as tetrahydrofuran, diethyl ether, or dimethoxyethane gives an alcohol of Formula IV.
Scheme 5
U = H,C 1 -C 4 alkyl
As shown in Scheme 6, amino alcohols of Formula IV can be produced by the direct reaction of oximino acids and esters of Formula XII with boranes or alkali metal hydrides. The reaction conditions with lithium aluminum hydride are as described for Scheme 5.
Scheme 6
xπ
U = H, C 1 -C 4 alkyl
Aryl-substituted amino acids and esters of Formula XI are known in the art as are methods for their preparation. Useful compendia of methods for their synthesis are contained in Kukolja, J. Med. Chem. ( 1958), 28, 1886- 1896, Bohme J. Med. Chem. (1980), 23, 405-412 and O'Donnell Tetrahedron Lett. (1989), 30, 3909-3912 and references cited therein.
Oxime esters of Formula XII are especially suitable intermediates for the synthesis of compounds of Formula II. They can be made from aryl acetic esters of Formula XIII by reaction, in the presence of base, with nitrosating agents such as inorganic and organic
nitrites as shown in Scheme 7. Typically, the compound of Formula XIII is treated with an alkyl nitrite such as butyl nitrite in an alcoholic solvent such as ethanol in the presence of a strong base such as a sodium ethoxide at the reflux temperature of the solvent.
Scheme 7
Alternatively, as shown in Scheme 8, compounds of Formula XII can be produced from aryl glyoxalates of Formula XTV by treatment with hydroxylamine.
Scheme 8
U = H q-C 4 alkyl
A method for the synthesis of compounds of Formula XIV using the Friedel -Crafts reaction is shown in Scheme 9. Monoesters of oxalyl chloride react with electron-rich aromatics in the presence of Lewis acids to give compounds of Formula XIV. See Olah Ed., Friedel-Crafts and Related Reactions, Vol. 3, Part 1, pp 1-6. Treatment of optionally substituted benzenes with aluminum chloride and ethyl or methyl oxalyl chloride in an inert solvent such as dichloromethane, nitrobenzene, carbon disulfide, or dichloroethane will produce compounds of Formula XIV. Aryl glyoxalates can also be made by the reaction of an organometallic species with a derivative of oxalic acid. For instance, diethyl oxalate can be treated with an aryl Grignard or lithium reagent at low
temperature in ether/tetrahydrofuran mixtures (Rambaud, et al., Synthesis (1988), 564-567. The Grignard or lithium reagent can be generated from an optionally substituted haloaromatic compound by conventional methods.
Scheme 9
XTV where A is a direct bond
XTV where U = ethyl
It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula I may not be compatible with certain functionalities present in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group intercon versions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform additional routine synthetic steps not described in detail to complete the synthesis of compounds of Formula I. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to prepare the compounds of Formula I.
One skilled in the art will also recognize that compounds of Formula I and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and reduction reactions to add substituents or modify existing substituents. Without further elaboration, it is believed that one skilled in the art using the preceding description can utilize the present invention to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the
disclosure in any way whatsoever. Percentages are by weight except for chromatographic solvent mixtures or where otherwise indicated. Parts and percentages for chromatographic solvent mixtures are by volume unless otherwise indicated. ] H NMR spectra are reported in ppm downfield from tetramethylsilane; s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br s = broad singlet.
EXAMPLE 1 Step A: Methyl f(2.6-chfluorobenzoyl)aπύno]hydroxyacetate
A solution of glyoxylic acid monohydrate (37.2 g) was stirred in methanol (125 mL) and after 72 h the solvent was evaporated. The residue was dissolved in benzene (150 mL) and heated to reflux with 2,6-difluorobenzamide (44 g). After 16 h the cooled reaction mixture was diluted with benzene (100 mL) and filtered. Air drying left 64 g of the title compound of Step A which was used without further purification. l NMR (CDC1 3 , 200 MHz): δ 9.7 (IH), 7.5 (IH), 7.2 (2H), 6.9 (IH), 3.7 (3H). Step B: 2-(2.6-Difluorophenyl)-4.5-dihydro-4-(4-iodophenyl)oxazole The title compound of Step A (31.0 g, 0.13 mol) and iodobenzene (40.2 g,
0.19 mol) were suspended in sulfuric acid (100 mL) and stirred for 3 days at 23 °C. The mixture was poured onto ice and extracted with dichloromethane (200 mL). The dichloromethane layer was dried over magnesium sulfate and evaporated under reduced pressure. Methanol (200 mL) and thionyl chloride (6 mL) were added to the mixture and heated at reflux for 30 min. The methanol was removed under reduced pressure and the residue was dissolved in tetrahydrofuran (200 mL). Lithium borohydride (55 mL, 2N in tetrahydrofuran, 0.11 mol) was added slowly and, after completion of the addition, the mixture was heated at reflux for 1 h. The mixture was cooled and quenched by slow addition of aqueous hydrochloric acid (200 mL, IN). The mixture was extracted with dichloromethane (200 mL), dried over magnesium sulfate and evaporated under reduced pressure. The residue was then treated with toluene (100 mL) and thionyl chloride (23 mL, 0.3 mol). The mixture was heated to reflux for 45 min and then evaporated under reduced pressure. The residue was dissolved in methanol (200 mL) and treated with aqueous sodium hydroxide (30 mL, 50% solution). The mixture was heated to reflux for 30 min and then evaporated under reduced pressure. The residue was partitioned between water (100 mL) and dichloromethane (200 mL). The dichloromethane solution was dried over magnesium sulfate and evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel using hexanes/ethyl acetate (10:1) as eluent to give the title compound of Step B (23. l g) as a white solid melting at 105-106 °C. l H NMR (CDC1 3 , 200 MHz): δ 7.7 (m,2H), 7.5 (m,lH), 7.1 (m,lH), 7.0 (m,2H), 5.4 (m,lH), 4.8 (m,lH), 4.3 (m,lH).
Step C: 2-(2.6-Difluorophenyl)-4.5-dihydro-4-f4-r(trimethylsilyDethv nyll- phenylloxazole The title compound of Step B (10 g, 25.9 mmol), (trimethylsilyl )acety lene (5.1 g, 52 mmol), bis(triphenylphosphine)palladium dichloride (910 mg, 1.29 mmol), and copper(I) iodide (250 mg, 1.31 mmol) were mixed together in a mixed solvent of triethylamine (60 mL) and acetonitrile (60 mL). The reactants were stirred at 23 °C for 18 h and the solvent evaporated. The residue was partitioned between water (400 mL) and ethyl ether (400 mL). The ether ethyl was dried over anhydrous magnesium sulfate and evaporated. The residue was chromatographed on silica gel with hexane-ethyl acetate (4:1) as eluent to give 7.8 g of the title compound of Step C, a compound of the invention, as an oil. *H NMR (CDC1 3 , 300 MHz): δ 0.24 (s,9H), 4.24 (m,lH), 4.81 (m,lH), 5.44 (m,lH), 6.99 (m,2H), 7.26 (m,2H), 7.46 (m,3H).
EXAMPLE 2 2-(2.6-Difluorophenyl)-4.5-dihydro-4-[4-[(triethylsilyl)ethy nynphenylloxazole The title compound of Step B in Example 1 (2 g, 5.2 mmol), (triethylsilyl)acetylene
(1.45 g, 10.3 mmol), bis(triphenylphosphine)palladiurn dichloride (180 mg, 0.25 mmol), and copper(I) iodide (50 mg, 0.26 mmol) were mixed together in a mixed solvent of triethylamine (15 mL) and acetonitrile (15 mL). The reactants were stirred at 23 °C for 18 h and the solvent evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ethyl ether layer was dried over anhydrous magnesium sulfate and evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4:1) as eluent to give 1.2 g of the title compound of Example 2, a compound of the invention, as an oil. ! H NMR (CDC1 3 , 300 MHz): δ 0.68 (q,6H), 1.04 (t,9H), 4.24 (m,lH), 4.82 (m,lH), 5.44 (m,lH), 7.00 (m,2H), 7.26 (m,2H), 7.49 (m,3H).
EXAMPLE 3 2-('2.6-Difluorophenyl'>-4.5-dihydro-4-f4-rrtris(l-methyl ethyl silyl1- ethynyl]phenyl]oxazole The title compound of Step B in Example 1 (2 g, 5.2 mmol), (triisopropylsilyl)acetylene ( 1.89 g, 1.03 mmol), bis(triphenylphosphine)palladium dichloride (180 mg, 0.25 mmol), and copper (I) iodide (50 mg, 0.26 mmol) were mixed together in a mixed solvent of triethylamine (15 mL) and acetonitrile (15 mL). The reactants were stirred at 23 °C for 18 h and the solvent was evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ethyl ether layer was dried over anhydrous magnesium sulfate and evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4:1) as eluent to give 1.26 g of
the title compound of Example 3, a compound of the invention, as an oil. Η NMR (CDC1 3 , 300 MHz): δ 1.05 (s,3H), 1.12 (s,18H), 4.24 (m,lH), 4.82 (m,lH), 5.46 (m,lH), 7.00 (m,2H), 7.26 (m,2H), 7.47 (m,3H).
EXAMPLE 4 2-(2.6-Difluorophenyl1-4-r4-rf dimethylf 1.1 -dimethylethynsilyllethynyllphenyll-4.5- dihydrooxazole The title compound of Step B in Example 1 (2.29 g, 5.9 mmol), (dimethyl-tert- butylsilyl)acetylene (1 g, 7.01 mmol), bis(triphenylphosphine)palladium dichloride (180 mg, 0.25 mmol), and copper(I) iodide (50 mg, 0.26 mmol) were mixed together in a mixed solvent of triethylamine (15 mL) and acetonitrile (15 mL). The reactants were stirred at 23 °C for 18 h and the solvent was evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ethyl ether layer was dried over anhydrous magnesium sulfate and was evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4: 1) as eluent to give 1.45 g of the title compound of Example 4, a compound of the invention, as an oil. l H NMR (CDC1 3 , 300 MHz): δ θ.18 (s,6H), 0.99 (s,9H), 4.24 (m,lH), 4.82 (m,lH), 5.42 (m.lH), 7.00 (m,2H), 7.28 (m,2H), 7.49 (m,3H).
EXAMPLE 5 2-(2,6-Difluorophenyl)-4.5-dihydro-4-r4-f3-(trimethylsilyl)- l-propynyllphenylloxazole The title compound of Step B in Example 1 (2.86 g, 7.4 mmol),
(trimethylsilylmethyl)acetylene (1 g, 8.9 mmol), bis(triphenylphosphine)palladium dichloride (50 mg, 0.07 mmol), and copper(I) iodide (25 mg, 0.13 mmol) were mixed together in a mixed solvent of triethylamine (15 mL) and acetonitrile (15 mL). The reactants were stirred at 23 °C for 18 h and the solvent was evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ether ethyl layer was dried over anhydrous magnesium sulfate and was evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4:1) as eluent to give 1.65 g of the title compound of Example 5, a compound of the invention, as an oil. *H NMR (CDC1 3 , 300 MHz): δ θ.16 (s,9H), 1.69 (s,2H), 4.25 (m,lH), 4.82 (m,lH), 5.46 (m,lH), 6.99 (m,2H), 7.22 (m,2H), 7.38 (m,3H).
EXAMPLE 6 Step A: N-(2-Chloro- 1 -methoxyethyl)-2.6-difluorobenzamide
2,6-Difluorobenzamide (100 g, 0.63 mol) and 2-chloroacetaldehyde dimethylacetal (240 g, 1.93 mol) were mixed with concentrated sulfuric acid (60 mL) at 0 °C and then stirred at 23 °C for 3 days. The mixture was poured onto ice (1 L) and extracted with chloroform (1 L). The chloroform was dried over magnesium sulfate and
evaporated under reduced pressure and the residue was treated with 1-chlorobutane and filtered to give 55.8 g of the title compound of Step A as a solid. *H NMR (CDC1 3 , 300 MHz): δ 3.51 (s,3H), 3.75 (m,2H), 5.60 (m,lH), 6.50 (br s,lH), 6.96 (m,2H), 7.42 (m,lH). Step B: 2-(2.6-Difluorophenyl)-4-(2-ethoxy-4-iodophenyl)-4.5-dihydro oxazole
The title compound of Step A (5.1 g, 20 mmol) and 3-ethoxyiodobenzene (5.08 g, 20 mmol) were mixed with aluminum chloride (5.45 g, 40 mmol) in dichloromethane (40 mL) and refluxed for 4 h. After cooling to 23°C, the mixture was poured onto ice (500 g) and extracted with dichloromethane (300 mL). The dichloromethane was dried over magnesium sulfate, evaporated under reduced pressure and then treated with ethanol (50 mL) and potassium hydroxide (1.79 g, 30 mmol) at 23 °C for 3 days. The reaction mixture was concentrated under reduced pressure and then partitioned between water (100 mL) and dichloromethane (100 mL). The dichloromethane was dried over magnesium sulfate and evaporated under reduced pressure to a crude oil which was chromatographed on silica gel using diethyl ether and hexane ( 1 :4) as the eluent to produce 2.0 g of the title compound of Step B as a solid melting at 74-77°C. H NMR (CDC1 3 , 300 MHz): δ 1.42 (t,3H), 4.1 1 (m,3H), 4.82 (m,lH), 5.60 (m,lH), 7.00 (m,2H), 7.16 (m,2H), 7.42 (m,lH). Step C: 2-(2.6-Difluorophenyl)-4-r2-ethoxy-4-.(trimethylsilyl)ethyny llphenyll- 4.5-dihydrooxazole
The title compound of Step B (1 g, 2.3 mmol), (trimethylsilyl)acetylene (457 mg, 4.6 mmol), bis(triphenylphosphine)palladium dichloride (75 mg, 0.1 mmol) and copper(I) iodide (75 mg, 0.39 mmol) were mixed together in a mixed solvent of triethylamine (15 mL) and acetonitrile (15 mL). The reactants were stirred at 23 °C for 18 h and the solvent was evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ethyl ether layer was dried over anhydrous magnesium sulfate and was evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4: 1 ) as eluent to give 0.15 g of the title compound of Step C, a compound of the invention, as an oil. ! H NMR (CDC1 3 , 300 MHz): δ 0.25 (s,9H), 1.42 (t,3H), 4.08 (q,2H), 4.14 (m,lH), 4.90 (m,lH), 5.65 (m,lH), 7.00 (m,3H), 7.10 (m,lH), 7.40 (m,2H).
EXAMPLE 7 4-f4-(3.3-Diethoxy-l-propynyl)phenyll-2-(2.6-difluorophenyl) -4.5-dihydrooxazole The title compound of Step B in Example 1 (2.0 g, 5.2 mmol), 3,3-diethoxy-l- propyne (1.0 g, 8.3 mmol), bis(triphenylphosphine)palladium dichloride (75 mg,
0.10 mmol), and copper (I) iodide (75 mg, 0.39 mmol) were mixed together in a mixed
solvent of triethylamine (20 mL) and acetonitrile (20 mL). The reactants were stirred at 23 °C for 18 h and the solvent was evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ethyl ether layer was dried over anhydrous magnesium sulfate and was evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4: 1) as eluent to give 1.58 g of the title compound of Example 7, a compound of the invention, as an oil. l K NMR (CDC1 3 , 300 MHz): δ 1.27 (t,6H), 3.66 (m,2H), 3.82 (m,2H), 4.25 (m,lH), 4.82 (m,lH), 5.40 (m,lH), 5.50 (s,lH), 7.00 (m,2H), 7.30 (m,2H), 7.40-7.50 (m,3H).
EXAMPLE 8 4-f4-(3.3-Diethoxy-l-propynyl)-2-ethoxyphenyll-2-(2.6-difluo rophenyI)-4.5- dihydrooxazole The title compound of Step B in Example 6 (0.50 g, 1.16 mmol), 3,3-diethoxy-l- propyne (0.20 g, 1.56 mmol), bis(rriphenylphosphine)palladium dichloride (50 mg, 0.08 mmol) and copper (I) iodide (20 mg, 0.10 mmol) were mixed together in a mixed solvent of triethylamine (15 mL) and acetonitrile (15 mL). The reactants were stirred at 23 °C for 18 h and the solvent was evaporated. The residue was partitioned between water (100 mL) and ethyl ether (100 mL). The ethyl ether layer was dried over anhydrous magnesium sulfate and was evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (4:1) to give 300 mg of the title compound, a compound of the invention, as an oil. J H NMR (CDC1 3 , 300 MHz): δ 1.28 (m,6H), 1.41 (t,3H), 3.64 (m,2H), 3.82 (m,2H), 4.05 (m,2H), 4.14 (m,lH), 4.88 (m,lH), 5.50 (s,lH), 5.66 (m,lH), 6.99 (m,3H), 7.10 (m,lH), 7.40 (m,2H).
EXAMPLE 9 α-ff4-r2-(2.6-Difluorophenyl)-4.5-dihydro-4-oxazolyl1phenyl lethynyl1-α- phenylbenzenemethanol
The title compound of Step B in Example 1 (1.0 g, 2.6 mmol), l,l-diphenyl-2- propyn-1-ol (0.54 g, 2.6 mmol), bis(triphenylphosphine)palladium dichloride (50 mg, 0.07 mmol), and copper(I) iodide (50 mg, 0.26 mmol) were mixed together in a mixed solvent of triethylamine (20 mL) and acetonitrile (20 mL). The reactants were stirred at 23 °C for 18 h and then the solvent was evaporated. The residue was partitioned between ethyl ether (100 mL) and water (100 mL) containing 1% EDTA (ethylenediaminetetraacetic acid). The ethyl ether layer was dried over anhydrous magnesium sulfate and was then evaporated. The residue was chromatographed on silica gel with hexane/ethyl acetate (2: 1) as eluent to give 0.65 g of the title compound of Example 9, a compound of the invention, as a solid melting at 156- 158 °C. H NMR
(CDC1 3 , 300 MHz): δ 3.78(br s,lH), 4.20 (m,lH), 4.74 (m,lH), 5.34 (m,lH), 6.94 (m,2H), 7.20-7.44 (m,HH), 7.63 (m,4H).
EXAMPLE 10 Step A: 2-(2.6-Difluorophenyl)-4-(4-ethynylphenyl)-4.5-dihydrooxazol e The title compound of Step B in Example 1 (25 g, 64 mmol),
(trimethylsilyl)acetylene (16 mL, 110 mmol), bis(triphenylphosphine)palladium dichloride (0.5 g, 0.7 mmol), and copper(I) iodide (0.22 g, 1.1 mmol) were mixed together in triethylamine (200 mL). The reaction mixture slowly exothermed to 65 °C over 30 min and then slowly cooled to room temperature. After 2 h the mixture was evaporated and partitioned between dichloromethane (200 mL) and water (400 mL). The dichloromethane was washed with water (200 mL) and dried over magnesium sulfate. The residue after evaporation of solvent was dissolved in methanol (200 mL) and treated with sodium hydroxide (10 mL, 50% in water). The reaction mixture was stirred at room temperature for 30 min. The methanol was evaporated and the residue was partitioned between water (500 mL) and dichloromethane (300 mL). The dichloromethane layer was dried over magnesium sulfate and evaporated. The residue was subjected to chromatography on silica gel in hexanes/ethyl acetate (5: 1 to 3: 1) to afford the title compound of Step A as an oil (7.2 g). ! H NMR (CDC1 3 , 300 MHz) δ 7.5-7.0 (m,7H), 5.45 (m,lH), 4.8 (m,lH), 4.3 (m,lH), 3.1 (m,lH). Step B: f4-rr4-r2-(2.6-Difluorophenvn-4.5-dihvdro-4- oxazolyllphenyllethynyllphenyll trifluoromethanesulfonate The title compound of Step A (0.43 g, 2.1 mmol), 4-iodophenyl trifluoromethanesulfonate (0.60 g, 1.7 mmol), bis(triphenylphosphine)palladium dichloride (30 mg, 0.04 mmol), and copper(I) iodide (30 mg, 0.15 mmol) were mixed together in a mixture of triethylamine (15 mL) and acetonitrile (15 mL) under nitrogen at 23 °C for 18 h. The reaction mixture was evaporated to dryness under vacuum and partitioned between ethyl ether (100 mL) and water (100 mL). The ether was washed with saturated aqueous NaCl and dried over magnesium sulfate. The residue after evaporation was chromatographed on silica gel using hexanes/ethyl acetate (4:1) to give the title compound of Step B, a compound of the invention, as a solid melting at
90-92 °C. J H NMR (CDC1 3 , 300 MHz): δ 4.28 (m,lH), 4.82 (m,lH), 5.48 (m,lH), 7.01 (m,2H), 7.25 (m,2H), 7.33 (m,2H), 7.42 (m,lH), 7.56 (m,4H).
By the procedures described herein together with methods known in the art, the following compounds of Tables 1 to 4 can be prepared. The following abbreviations are used in the Tables which follow: t = tertiary, n = normal, i = iso, Me = methyl,
Et = ethyl, Pr = propyl, /-Pr = isopropyl, Bu = butyl, Ph = phenyl, OMe = methoxy,
OEt = ethoxy, SMe = methylthio, and CN = cyano.
Key Structure for Tables 1-4
Table 1 R 1 = 2-F. R 2 = 6-F. R 4 = H. R 5 = H. and R 3 -Y =
C≡C-SiMe 3 C≡C-CH 2 SiMe 2 (4-CN-Ph) CsC-SiMe 2 Ph
C≡C-SiMe 2 Cl C≡C-CH 2 SiMe 2 (4-CF 3 -Ph) C≡C-SiMe 2 (4-F-Ph)
C≡C-SiMeCl 2 C≡C-CH 2 SiMe 2 (4-CF 3 0-Ph) C_ -SiMe 2 (4-Cl-Ph)
C≡C-SiMe 2 Et G_C-CH 2 SiMe 2 (4-SMe-Ph) CsC-SiMe 2 (4-Br-Ph)
C≡C-SiMeEt 2 C≡C-CH 2 SiMe 2 (4-SCHF 2 -Ph) C≡C-SiMe 2 (4-CF 3 -Ph)
C≡C-SiEt 3 OC-CH 2 SiMe 2 (4-SCF 3 -Ph) C≡C-SiMe 2 (4-CF 3 0-Ph)
C≡C-Si(CH 2 CCl 3 ) 3 C≡C-CH 2 SiMe 2 (4-SF 5 -Ph) C≡C-SiMe 2 (4-SMe-Ph)
C≡C-Si(CH 2 CF 3 ) 3 CH=CH-SiMe 3 G_C-SiMe 2 (4-SCHF 2 -Ph)
C≡C-Si(«-Pr) 3 CH=CH-SiEt 3 C≡C-SiMe 2 (4-SCF 3 -Ph)
G_C-Si(ι-Pr) 3 CH=CH-SiMe 2 (r-Bu) C≡C-SiMe 2 (4-SF 5 -Ph)
C≡C-SiMe 2 (r-Bu) CH=CH-SiMe 2 (4-F-Ph) C≡C-SiMe 2 (4-CN-Ph)
OC-SiMe 2 (ι-Pr) CH=CH-SiMe 2 (4-CI-Ph) C≡C-SiMe 2 (2,4-diCl-Ph)
C≡C-CH 2 SiMe 3 CH=CH-SiMe 2 (4-Br-Ph) C≡C-SiMe 2 (2-Cl-4-F-Ph)
C=C-CH 2 SiEt 3 CH=CH-SiMe 2 (4-SMe-Ph) CsC-CH 2 SiMe 2 Cl
C≡C-CH 2 SiMe 2 (/-Bu) CH=CH-SiMe 2 (4-SCHF 2 -Ph) CsC-CH 2 SiMe 2 (2,4-diCl-Ph)
OC-CH 2 SiMe 2 (Ph) CH=CH-SiMe 2 (2,4-diF-Ph) C=C-CH 2 SiMe 2 (2-Cl-4-F-Ph)
OC-CH SiMe 2 (4-F-Ph) CH=CH-SiMe 2 (2,4-diC)-Ph) C=C-CH 2 SiMe 2 (3,5-diF-Ph)
OC-CH 2 SiMe 2 (4-Cl-Ph) CH=CH-CH 2 SiMe 3 CH=CH-CH 2 SiMe 2 (r-Bu)
G_C-CH 2 SiMe 2 (4-Br-Ph) CH=CH-CH 2 SiEt 3 C=C-CH(OMe) 2
C≡C-CH(OEt) 2 C≡C-CH(OMeXOEt) C≡C-CH(OEt)(0-«-Pr)
C≡C-CH(0-ι ' -Pr) 2 C_C-CH(OEt)(0-ι-Pr) C=C-CH(0-n-Pr) 2
C≡C-CH(0-«-Bu) 2 C≡C-CH(OEt)(0-n-Bu) C-C-CH(OEtχθ-i-Bu)
C≡C-CH(0-r-Bu) 2 C≡C-CH(0-/-Bu) 2 CsC-CH(OEt)(0-ι-Bu)
OC-CH(OMe)(0-n-Pr) C≡C-CH(0-/-Bu)(0-r-Bu) C≡C-CH(OMe)(0-t-Pr)
-C≡C-
Table 2 R 1 = 2-F. R 2 = 6-Cl. R 4 = H. R 5 = H. and R 3 -Y =
C≡C-SiMe 3 C≡C-CH 2 SiMe 2 (4-CN-Ph) C=C-SiMe 2 Ph
CsC-SiMe 2 Cl C≡C-CH 2 SiMe 2 (4-CF 3 -Ph) C≡C-SiMe 2 (4-F-Ph)
OC-SiMeCl 2 C≡C-CH 2 SiMe 2 (4-CF 3 0-Ph) C=C-SiMe 2 (4-Cl-Ph)
C≤C-SiMe 2 Et CsC-CH 2 SiMe 2 (4-SMe-Ph) C=C-SiMe 2 (4-Br-Ph)
CsC-SiMeEt C≡C-CH 2 SiMe 2 (4-SCHF 2 -Ph) C≡C-SiMe 2 (4-CF 3 -Ph)
OC-SiEt 3 C≡C-CH 2 SiMe 2 (4-SCF 3 -Ph) C≡C-SiMe 2 (4-CF 3 0-Ph)
C≡C-Si(CH 2 CCl 3 ) 3 C≡C-CH 2 SiMe 2 (4-SF 5 -Ph) G-C-SiMe 2 (4-SMe-Ph)
C=C-Si(CH 2 CF 3 ) 3 CH=CH-SiMe 3 C≡C-SiMe 2 (4-SCHF 2 -Ph)
C≡C-Si(«-Pr) 3 CH=CH-SiEt 3 C≡C-SiMe 2 (4-SCF 3 -Ph)
C- -Si(j-Pr) 3 CH=CH-SiMe 2 (r-Bu) C≡C-SiMe 2 (4-SF 5 -Ph)
C≡C-SiMe 2 (/-Bu) CH=CH-SiMe 2 (4-F-Ph) C≡C-SiMe 2 (4-CN-Ph)
C≡C-SiMe 2 ( -Pr) CH=CH-SiMe 2 (4-Cl-Ph) C≡C-SiMe 2 (2,4-diCl-Ph)
C≡C-CH 2 SiMe 3 CH=CH-SiMe 2 (4-Br-Ph) G≡C-SiMe 2 (2-Cl-4-F-Ph)
Table 3 R 1 = 2-F. R 2 = 6-F. R 4 = H. R 5 = 2-OEt. and R 3 -Y =
C≡C-SiMe 3 CsC-CH 2 SiMe 2 (4-CN-Ph) C≡C-SiMe 2 Ph
OC-SiMe 2 Cl CsC-CH 2 SiMe 2 (4-CF 3 -Ph) CsC-SiMe 2 (4-F-Ph)
C≡C-SiMeCl 2 C=C-CH 2 SiMe 2 (4-CF 3 0-Ph) C=C-SiMe 2 (4-Cl-Ph)
C≡C-SiMe 2 Et CsC-CH 2 SiMe 2 (4-SMe-Ph) C=C-SiMe 2 (4-Br-Ph)
CsC-SiMeEt 2 C≡C-CH 2 SiMe 2 (4-SCHF 2 -Ph) C=C-SiMe 2 (4-CF 3 -Ph)
C≡C-SiEt 3 C≡C-CH 2 SiMe 2 (4-SCF 3 -Ph) C≡C-SiMe 2 (4-CF 3 0-Ph)
C≡C-Si(CH 2 CCl 3 ) 3 CsC-CH 2 SiMe 2 (4-SF 5 -Ph) C=C-SiMe 2 (4-SMe-Ph)
C=C-Si(CH 2 CF 3 ) 3 CH=CH-SiMe 3 OC-SiMe 2 (4-SCHF 2 -Ph)
OC-Si(n-Pr) 3 CH=CH-SiEt 3 C≡C-SiMe 2 (4-SCF 3 -Ph)
OC-Si(«-Pr) 3 CH=CH-SiMe 2 (f-Bu) C≡C-SiMe 2 (4-SF 5 -Ph)
C≡C-SiMe 2 (f-Bu) CH=CH-SiMe 2 (4-F-Ph) C=C-SiMe 2 (4-CN-Ph)
C≡C-SiMe 2 (i-Pr) CH=CH-SiMe 2 (4-Cl-Ph) C≡C-SiMe 2 (2,4-diCl-Ph)
C≡C-CH 2 SiMe 3 CH=CH-SiMe 2 (4-Br-Ph) C=C-SiMe 2 (2-Cl-4-F-Ph)
C≡C-CH 2 SiEt 3 CH=CH-SiMe 2 (4-SMe-Ph) C≡C-CH 2 SiMe 2 Cl
G_C-CH 2 SiMe 2 (f-Bu) CH=CH-SiMe 2 (4-SCHF 2 -Ph) C=C-CH 2 SiMe 2 (2,4-diCl-Ph)
G_C-CH 2 SiMe 2 (Ph) CH=CH-SiMe 2 (2,4-diF-Ph) C=C-CH 2 SiMe 2 (2-Cl-4-F-Ph)
C≡C-CH 2 SiMe 2 (4-F-Ph) CH=CH-SiMe 2 (2,4-diCl-Ph) G=C-CH 2 SiMe 2 (3,5-diF-Ph)
C≡C-CH 2 SiMe 2 (4-Cl-Ph) CH=CH-CH 2 SiMe 3 CH=CH-CH 2 SiMe 2 (f-Bu)
C≡C-CH 2 SiMe 2 (4-Br-Ph) CH=CH-CH 2 SiEt 3 C=C-CH(OMe) 2
C≡C-CH(OEt) 2 CsC-CH(OMe)(OEt)
C≡C-CH(0-ι-Pr) 2 CsC-CH(OEtXO-i-Pr) C≡C-CH(0-«-Pr) 2
C≡C-CH(0-,ι-Bu) 2 G-C-CH(OEtXO-rt-Bu) C≡C-CH(OEt)(C ' -Bu)
C≡C-CH(0-/-Bu) 2 C_C-CH(0-ι-Bu) 2 G-C-CH(OEtχθ-ι-Bu)
CsC-CH(OMe)(0-n-Pr) CsC-CH(0-i-Bu)(0-?-Bu) C≡C-CH(OMeXO-ι-Pr)
OC-CH(OMe)(0-ι-Bu) CsC-CH(OMeXO-n-Bu) C≡C-CH(OMe)(0-t-Bu)
-C=C-
Table 4 R 1 = 2-Cl. R 2 = 6-Cl. R 4 = H. R 5 = H. and R 3 -Y =
C≡C-SiMe 3 C_iC-CH 2 SiMe 2 (4-CN-Ph) C≡C-SiMe 2 Ph
C=C-SiMe 2 Cl C≡C-CH 2 SiMe 2 (4-CF 3 -Ph) OC-SiMe 2 (4-F-Ph)
C≡C-SiMeCl 2 C≡C-CH 2 SiMe 2 (4-CF 3 0-Ph) C≡C-SiMe 2 (4-Cl-Ph)
C≡C-SiMe 2 Et C=C-CH 2 SiMe 2 (4-SMe-Ph) C≡C-SiMe 2 (4-Br-Ph)
C=C-SiMeEt 2 OC-CH 2 SiMe 2 (4-SCHF 2 -Ph) C≡C-SiMe 2 (4-CF 3 -Ph)
C≡C-SiEt 3 C≡C-CH 2 SiMe 2 (4-SCF 3 -Ph) C≡C-SiMe 2 (4-CF 3 0-Ph)
C=C-Si(CH 2 CCl 3 ) 3 C=C-CH 2 SiMe 2 (4-SF 5 -Ph) C≡C-SiMe 2 (4-SMe-Ph)
CsC-Si(CH 2 CF 3 ) 3 CH=CH-SiMe C-C-SiMe 2 (4-SCHF 2 -Ph)
C≡C-Si(π-Pr) 3 CH=CH-SiEt 3 C≡C-SiMe 2 (4-SCF 3 -Ph)
C≡C-Si(/-Pr) 3 CH=CH-SiMe 2 (f-Bu) C≡C-SiMe 2 (4-SF 5 -Ph)
C≡C-SiMe 2 (f-Bu) CH=CH-SiMe 2 (4-F-Ph) G-C-SiMe 2 (4-CN-Ph)
C≡C-SiMe 2 (i-Pr) CH=CH-SiMe 2 (4-Cl-Ph) D-C-SiMe 2 (2,4-diCl-Ph)
G-C-CH 2 SiMe 3 CH=CH-SiMe 2 (4-Br-Ph) D≡C-SiMe 2 (2-Cl-4-F-Ph)
CsC-CH 2 SiEt 3 CH=CH-SiMe 2 (4-SMe-Ph) G-C-CH 2 SiMe 2 Cl
C=C-CH 2 SiMe 2 (f-Bu) CH=CH-SiMe 2 (4-SCHF 2 -Ph) CsC-CH 2 SiMe 2 (2,4-diCl-Ph)
C≡C-CH 2 SiMe 2 (Ph) CH=CH-SiMe 2 (2,4-diF-Ph) CsC-CH 2 SiMe 2 (2-Cl-4-F-Ph)
-C=C-
Formulation/Utility
Compounds of this invention will generally be used as a formulation or composition with an agriculturally suitable carrier comprising at least one of a liquid diluent, a solid diluent or a surfactant. The formulation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of
application and environmental factors such as soil type, moisture and temperature. Useful formulations include liquids such as solutions (including emulsifiable concentrates), suspensions, emulsions (including microemulsions and/or suspoemulsions) and the like which optionally can be thickened into gels. Useful formulations further include solids such as dusts, powders, granules, pellets, tablets, films, and the like which can be water-dispersible ("wettable") or water-soluble. Active ingredient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternatively the entire formulation of active ingredient can be encapsulated (or "overcoated"). Encapsulation can control or delay release of the active ingredient. Sprayable formulations can be extended in suitable media and used at spray volumes from about one to several hundred liters per hectare. High-strength compositions are primarily used as intermediates for further formulation.
The formulations will typically contain effective amounts of active ingredient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.
Weight Percent
High Strength Compositions 90-99 0-10 0-2
Typical solid diluents are described in Watkins, et al., Handbook of Insecticide Dust Diluents and Carriers, 2nd Ed., Dorland Books, Caldwell, New Jersey. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed., Interscience, New York, 1950. McCutcheon 's Detergents and Emulsifiers Annual, Allured Publ. Corp., Ridgewood, New Jersey, as well as Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964, list surfactants and recommended uses. All formulations can contain minor amounts of additives to reduce foam, caking, corrosion, microbiological growth and the like, or thickeners to increase viscosity. Surfactants include, for example, polyethoxylated alcohols, polyethoxylated alkylphenols, polyethoxylated sorbitan fatty acid esters, dialkyl sulfosuccinates, alkyl sulfates, alkylbenzene sulfonates, organosilicones, NN-dialkyltaurates, lignin sulfonates,
naphthalene sulfonate formaldehyde condensates, polycarboxylates, and polyoxyethylene/polyoxypropylene block copolymers. Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, starch, sugar, silica, talc, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Liquid diluents include, for example, water, N,N-dimeώylfoπrιamide, dimethyl sulfoxide, N-alkylpyrrolidone, ethylene glycol, polypropylene glycol, paraffins, alkylbenzenes, alkylnaphthalenes, oils of olive, castor, linseed, tung, sesame, corn, peanut, cotton-seed, soybean, rape-seed and coconut, fatty acid esters, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- methyl-2-pentanone, and alcohols such as methanol, cyclohexanol, decanol and tetrahydrofurfuryl alcohol.
Solutions, including emulsifiable concentrates, can be prepared by simply mixing the ingredients. Dusts and powders can be prepared by blending and, usually, grinding as in a hammer mill or fluid-energy mill. Suspensions are usually prepared by wet-milling; see, for example, U.S. 3,060,084. Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Browning, "Agglomeration", Chemical Engineering, December 4, 1967, pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and following, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U.S. 3,299,566.
For further information regarding the art of formulation, see U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John Wiley and Sons, Inc., New York, 1961, pp 81-96; and Hance et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989.
In the following Examples, all percentages are by weight and all formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-B.
Example A Wettable Powder
Compound 1 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%.
Example B Granule Compound 11 10.0% attapulgite granules (low volatile matter,
0.71/0.30 mm; U.S.S. No. 25-50 sieves) 90.0%.
Example C Extruded Pellet Compound 36 25.0% anhydrous sodium sulfate 10.0% crude calcium ligninsulfonate 5.0% sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0%. Example D
Emulsifiable Concentrate
Compound 40 20.0% blend of oil soluble sulfonates and polyoxyethylene ethers 10.0% isophorone 70.0%.
The compounds of this invention exhibit activity against a wide spectrum of foliar-feeding, fruit-feeding, stem or root feeding, seed-feeding, aquatic and soil-inhabiting arthropods (term "arthropods" includes insects, mites and nematodes) which are pests of growing and stored agronomic crops, forestry, greenhouse crops, ornamentals, nursery crops, stored food and fiber products, livestock, household, and public and animal health. Those skilled in the art will appreciate that not all compounds are equally effective against all growth stages of all pests. Nevertheless, all of the compounds of this invention display activity against pests that include: eggs, larvae and adults of the Order Lepidoptera; eggs, foliar-feeding, fruit-feeding, root-feeding, seed-feeding larvae and adults of the Order Coleoptera; eggs, immatures and adults of the Orders Hemiptera and Homoptera; eggs, larvae, nymphs and adults of the Order
Acari; eggs, immatures and adults of the Orders Thysanoptera, Orthoptera and Dermaptera; eggs, immatures and adults of the Order Diptera; and eggs, juveniles and adults of the Phylum Nematoda. The compounds of this invention are also active against pests of the Orders Hymenoptera, Isoptera, Siphonaptera, Blattaria, Thysanura and Psocoptera; pests belonging to the Class Arachnida and Phylum Platyhelminthes. Specifically, the compounds are active against southern corn rootworm (Diabrotica undecimpunctata howardi), aster leafhopper (Mascrosteles fascifrons), boll weevil (Anthonomus grandis), two-spotted spider mite (Tetranychus urticae), fall armyworm (Spodoptera frugiperda), black bean aphid (Aphis fabae), green peach aphid (Myzus persica), cotton aphid (Aphis gossypii), Russian wheat aphid (Diuraphis noxia), English grain aphid (Sitobion avenae), tobacco budworm (Heliothis virescens), rice water weevil (Lissorhoptrus oryzophilus), rice leaf beetle (Oulema oryzae), whitebacked planthopper (Sogatellafurcifera), green leafhopper (Nephotettix cincticeps), brown planthopper (Nilaparvata lugens), small brown planthopper (Laodelphax striatellus), rice stem borer (Chilo suppressalis), rice leafroller (Cnaphalocrocis medinalis), black rice stink bug (Scotinophara lurida), rice stink bug (Oebalus pugnax), rice bug (Leptocorisa chinensis), slender rice bug (Cletus puntiger), and southern green stink bug (Nezara viridula). The compounds are active on mites, demonstrating ovicidal, larvicidal and chemosterilant activity against such families as Tetranychidae including Tetranychus urticae, Tetranychus cinnabarinus, Tetranychus mcdanieli, Tetranychus pacificus, Tetranychus turkestani, Byrobia rubrioculus, Panonychus ulmi, Panonychus citri, Eotetranychus carpini borealis, Eotetranychus, hicoriae, Eotetranychus sexmaculatus, Eotetranychus yumensis, Eotetranychus banksi and Oligonychus pratensis; Tenuipalpidae including Brevipalpus lewisi, Brevipalpus phoenicis, Brevipalpus califomicus and Brevipalpus obovatus; Eriophyidae including Phyllocoptruta oleivora, Eriophyes sheldoni, Aculus cornutus, Epitrimerus pyri and Eriophyes mangiferae. See WO 90/10623 and WO 92/00673 for more detailed pest descriptions.
Compounds of this invention can also be mixed with one or more other insecticides, fungicides, nematocides, bactericides, acaricides, growth regulators, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants or other biologically active compounds to form a multi-component pesticide giving an even broader spectrum of agricultural protection. Examples of such agricultural protectants with which compounds of this invention can be formulated are: insecticides such as abamectin, acephate, azinphos-methyl, bifenthrin, buprofezin, carbofuran, chlorpyrifos, chlorpyrifos-methyl, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, deltamethrin, diafenthiuron, diazinon, diflubenzuron, dimethoate,
esfenvalerate, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flucythrinate, ' tau-fluvalinate, fonophos, imidacloprid, isofenphos, malathion, metaldehyde, methamidophos, methidathion, methomyl, methoprene, methoxychlor, methyl 7-chloro- 2,5-dihydro-2-[[N-(methoxycarbonyl)-N-[4- (trifluoromemoxy)phenyl]amino]carbonyl]indeno[ 1 ,2-e] [ 1 ,3 ,4]oxadiazine-4a(3H)- carboxylate (DPX-JW062), monocrotophos, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, rotenone, sulprofos, tebufenozide, tefluthrin, terbufos, tetrachlorvinphos, thiodicarb, tralomethrin, trichlorfon and triflumuron; fungicides such as azoxystrobin (ICIA5504), benomyl, blasticidin-S, Bordeaux mixture (tribasic copper sulfate), bromuconazole, captafol, captan, carbendazim, chloroneb, chlorothalonil, copper oxychloride, copper salts, cymoxanil, cyproconazole, cyprodinil (CGA 219417), diclomezine, dicloran, difenoconazole, dimethomorph, diniconazole, diniconazole-M, dodine, edifenphos, epoxiconazole (BAS 480F), fenarimol, fenbuconazole, fenpiclonil, fenpropidin, fenpropimoφh, fluazinam, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fosetyl-aluminum, furalaxyl, hexaconazole, ipconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, kresoxim-methyl (BAS 490F), mancozeb, maneb, mepronil, metalaxyl, metconazole, 5-methyl 7-benzothiazolecarbothioate (CGA 245704), 5-methyl-5-(4-phenoxyphenyl)-3-phenylamino-2,4-oxazolidinedi one (DPX-JE874), myclobutanil, neo-asozin (ferric methanearsonate), oxadixyl, penconazole, pencycuron, probenazole, prochloraz, propiconazole, pyrifenox, pyroquilon, sulfur, tebuconazole, tetraconazole, thiabendazole, thiophanate-methyl, thiram, triadimefon, triadimenol, tricyclazole, triticonazole, validamycin and vinclozolin; nematocides such as aldoxycarb and fenamiphos; bactericides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, fenazaquin, fenbutatin oxide, fenpropathrin, fenpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad; and biological agents such as Bacillus thuringiensis, Bacillus thuringiensis delta endotoxin, baculovirus, and entomopathogenic bacteria, virus and fungi.
In certain instances, combinations with other arthropodicides having a similar spectrum of control but a different mode of action will be particularly advantageous for resistance management.
Preferred for better control of pests (use rate or spectrum) or resistance management are mixtures of a compound of this invention with an arthropodicide selected from the group abamectin, fenpropathrin, fipronil, imidacloprid, methomyl, propargite, pyridaben, tebufenozide and tebufenpyrad. Specifically preferred mixtures (compound numbers refer to compounds in Index Tables A-B) are selected from the
group: compound 1 and abamectin; compound 1 and fenpropathrin; compound 1 and fipronil; compound 1 and imidacloprid; compound 1 and methomyl; compound 1 and propargite; compound 1 and pyridaben; compound 1 and tebufenozide; compound 1 and tebufenpyrad; compound 4 and abamectin; compound 4 and fenpropathrin; compound 4 and fipronil; compound 4 and imidacloprid; compound 4 and methomyl; compound 4 and propargite; compound 4 and pyridaben; compound 4 and tebufenozide; compound 4 and tebufenpyrad; compound 5 and abamectin; compound 5 and fenpropathrin; compound 5 and fipronil; compound 5 and imidacloprid; compound 5 and methomyl; compound 5 and propargite; compound 5 and pyridaben; compound 5 and tebufenozide; compound 5 and tebufenpyrad; compound 11 and abamectin; compound 11 and fenpropathrin; compound 11 and fipronil; compound 11 and imidacloprid; compound 11 and methomyl; compound 11 and propargite; compound 11 and pyridaben; compound 1 1 and tebufenozide; compound 11 and tebufenpyrad; compound 25 and abamectin; compound 25 and fenpropathrin; compound 25 and fipronil; compound 25 and imidacloprid; compound 25 and methomyl; compound 25 and propargite; compound 25 and pyridaben; compound 25 and tebufenozide; compound 25 and tebufenpyrad; compound 36 and abamectin; compound 36 and fenpropathrin; compound 36 and fipronil; compound 36 and imidacloprid; compound 36 and methomyl; compound 36 and propargite; compound 36 and pyridaben; compound 36 and tebufenozide; compound 36 and tebufenpyrad; compound 40 and abamectin; compound 40 and fenpropathrin; compound 40 and fipronil; compound 40 and imidacloprid; compound 40 and methomyl; compound 40 and propargite; compound 40 and pyridaben; compound 40 and tebufenozide; and compound 40 and tebufenpyrad.
Arthropod pests are controlled and protection of agronomic, horticultural and specialty crops, animal and human health is achieved by applying one or more of the compounds of this invention, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. Thus, the present invention further comprises a method for the control of foliar and soil inhabiting arthropods and nematode pests and protection of agronomic and/or nonagronomic crops, comprising applying one or more of the compounds of the invention, or compositions containing at least one such compound, in an effective amount, to the environment of the pests including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled. A preferred method of application is by spraying. Alternatively, granular formulations of these compounds can be applied to the plant foliage or the soil. Other methods of application include direct and residual sprays, aerial
sprays, seed coats, microencapsulations, systemic uptake, baits, eartags, boluses, foggers, fumigants, aerosols, dusts and many others. The compounds can be incoφorated into baits that are consumed by the arthropods or in devices such as traps and the like. The compounds of this invention can be applied in their pure state, but most often application will be of a formulation comprising one or more compounds with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. A preferred method of application involves spraying a water dispersion or refined oil solution of the compounds. Combinations with spray oils, spray oil concentrations, spreader stickers, adjuvants, other solvents, and synergists such as piperonyl butoxide often enhance compound efficacy.
The rate of application required for effective control will depend on such factors as the species of arthropod to be controlled, the pest's life cycle, life stage, its size, location, time of year, host crop or animal, feeding behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredient per hectare are sufficient to control pests in agronomic ecosystems, but as little as 0.001 kg/hectare may be sufficient or as much as 8 kg hectare may be required. For nonagronomic applications, effective use rates will range from about 1.0 to 50 mg/square meter but as little as 0.1 mg/square meter may be sufficient or as much as 150 mg/square meter may be required.
The following TESTS demonstrate the control efficacy of compounds of this invention on specific pests. "Control efficacy" represents inhibition of arthropod development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-B for compound descriptions. The following abbreviations are used in the Index Tables which follow: t = tertiary, n = normal, i = iso, Me = methyl, Et = ethyl, Pr = propyl, /-Pr = isopropyl, Bu = butyl, Ph = phenyl, MeO = methoxy, EtO and OEt = ethoxy, EtS = ethylthio, and TASBU = 2,8,9-trioxa-5-aza-l-silabicyclo[3.3.3]undecan-l-yl. The abbreviation "Ex." stands for "Example" and is followed by a number indicating in which example the compound is prepared.
INDEX TABLE A
*See Index Table B for ] H NMR data. a Trans isomer. b Cis isomer.
INDEX TABLE B
Cmpd No. *H NMR Data (CDC1 solution unless indicated otherwise) 2 δ θ.24 (s,9H), 4.24 (m,lH), 4.81 (m,lH), 5.44 (m, lH), 6.99 (m,2H), 7.26
(m,2H), 7.46 (m,3H).
60.68 (q,6H), 1.04 (t,9H), 4.24 (m,lH), 4.82 (m,lH), 5.44 (m,l H), 7.00
(m,2H), 7.26 (m,2H), 7.49 (m,3H). δ 1.05 (s,3H), 1.12 (s,18H), 4.24 (m,lH), 4.82 (m,lH), 5.46 (m,l H), 7.00
(m,2H), 7.26 (m,2H), 7.47 (m,3H). δ θ.25 (s,9H), 1.42 (t,3H), 4.08 (q,2H), 4.14 (m, lH), 4.90 (m, l H), 5.65
(m,lH), 7.00 (m,3H), 7.10 (m,lH), 7.40 (m,2H). δ θ.16 (s,9H), 1.69 (s,2H), 4.25 (m,lH), 4.82 (m, lH), 5.46 (m, l H), 6.99
(m,2H), 7.22 (m,2H), 7.38 (m,3H).
60.18 (s,6H), 0.99 (s,9H), 4.24 (m,lH), 4.82 (m.lH), 5.42 (m.lH), 7.00
(m,2H), 7.28 (m,2H), 7.49 (m,3H).
7 δ 0.25 (s,9H), 3.90 (s,3H), 4.22-4.30 (m, lH), 4.75-4.85 (m,lH), 5.35-5.45
(m,lH), 6.92-7.52 (m,6H). 9 δ 4.3 (m,lH), 4.8 (m,lH), 4.9 (s,2H), 5.45 (m.lH), 7.5-7.0 (m,12H).
11 δ 1.27 (t,6H), 3.66 (m,2H), 3.82 (m,2H), 4.25 (m,lH), 4.82 (m,lH), 5.40 (m,lH), 5.50 (s, lH), 7.00 (m,2H), 7.30 (m,2H), 7.40-7.50 (m,3H).
12 δ 3.45 (s,3H), 4.26 (m,lH), 4.32 (s,2H), 4.82 (m.lH), 5.46 (m,lH), 7.00 (m,2H), 7.28 (m,2H), 7.45 (m,3H).
13 δ 1.62 (m.lH), 1.96 (m,lH), 3.90 (m,2H), 4.26 (m,3H), 4.82 (m, lH), 5.46 (m,lH), 5.59 (s,lH), 7.00 (m,2H), 7.26 (m,2H), 7.49 (m,3H).
14 δ 1.30 (s,9H), 1.45 (d,3H), 4.25 (m. lH), 4.52 (m.lH), 4.82 (m, lH), 5.44 (m,lH), 7.00 (m,2H), 7.26 (m,2H), 7.40 (m,3H).
15 δ 1.33 (t,3H), 2.75 (q,2H), 3.51 (s,2H), 4.22 (m.lH), 4.80 (m,lH), 5.44 (m,lH), 7.00 (m,2H), 7.26 (m,2H), 7.42 (m,3H).
16 δ 1.24 (t,3H), 1.33 (s,9H), 3.78(m, 2H), 4.25 (m,lH), 4.82 (m,lH), 5.44 (m, lH), 5.69 (s,lH), 7.00 (m,2H), 7.26 (m,2H), 7.40-7.49 (m,3H).
17 δ 1.36 (s,18H), 4.25 (m.lH), 4.80 (m,lH), 5.42 (m.lH), 5.64 (s,lH), 7.00 (m,2H), 7.26 (m,2H), 7.34-7.46 (m,3H).
18 δ 0.93 (d,6H), 1.32 (s,9H), 7.46 (m,2H), 4.24 (m,lH), 4.80 (m, lH), 5.44 (m.lH), 5.70 (s.lH), 7.00 (m,2H), 7.26 (m,2H), 7.30-7.46 (m,3H).
19 δ 1.35 (d,3H), 4.3 (m.lH), 4.5 (m.lH), 4.8 (m,lH), 5.45 (m.lH), 6.3 (m,lH), 6.6 (d,lH), 7.0 (m,2H), 7.5-7.2 (m,5H).
21 δ 2.82 (t,6H), 3.81 (t,6H), 4.24 (m,lH), 4.76 (m,lH), 5.40 (m.lH), 6.28 (dd.lH), 6.95 (m,2H), 7.05 (dd.lH), 7.19 (m,2H), 7.39 (m,3H).
22 δ 1.22 (m,6H), 2.58 (m,2H), 3.56 (m,2H), 3.66 (m,2H), 4.28 (m,lH), 4.40 (m,lH), 4.82 (m.lH), 5.42 (m,lH), 6.22 (m,lH), 6.44 (dd.lH), 6.44 (m,2H), 7.26 (m,2H), 7.28-7.46 (m,3H).
23 δ 1.23 (br s,6H), 3.58 (m,2H), 3.70 (m,2H), 4.24 (m.lH), 4.80 (m, lH), 5.08 (br s, IH), 5.46 (m.lH), 6.20 (dd.lH), 6.70 (dd.lH), 7.00 (m,2H), 7.30 (m,3H), 7.43 (m,2H).
24 δ 1.26 (s,12H), 4.24 (m,lH), 4.80 (m,lH), 5.44 ( , IH), 5.54 (dd,lH), 6.16 (dd,lH), 6.72 (dd.lH), 7.00 (m,2H), 7.27 (m,2H), 7.40 (m,3H).
25 δ 1.28 (m,6H), 1.41 (t,3H), 3.64 (m,2H), 3.82 (m,2H), 4.05 (m, 2H), 4.14 (m,lH), 4.88 (m,lH), 5.50 (s.lH), 5.66 (m,lH), 6.99 (m,3H), 7.10 (m,lH), 7.40 (m,2H).
26 δ 0.94 (m,6H), 1.42 (m,4H), 1.62 (m,4H), 3.58 (m,2H), 3.76 ( , 2H), 4.24 (m.lH), 4.80 (m,lH), 5.44 (m,lH), 7.00 (m,2H), 7.28 (m,2H), 7.44 (m,lH), 7.50 (m,2H).
27 δ 3.44(s,6H), 4.25(m,lH), 4.82(m,lH), 5.38(s,lH), 5.44(m,lH), 7.00 (m,2H), 7.28 (m,2H), 7.42 (m.lH), 7.48 (m,2H).
28 δ 1.24 (m,12H), 4.18 (m,2H), 4.25 (m,lH), 4.80 (m,lH), 5.44 (m, lH), 5.55 (s.lH), 7.00 (m,2H), 7.28 (m,2H), 7.42 (m,lH), 7.49 (m,2H).
29 δ 0.97 (m,6H), 1.66 (m,4H), 3.56 (m,2H), 3.74 (m,2H), 4.24 (m.lH), 4.82 (m,lH), 5.42 (m,lH), 5.48 (s,lH), 7.00 (m,2H), 7.30 ( , 2H), 7.42 (m,lH), 7.48 (m,2H).
30 δ 0.49 (s,6H), 4.24 (m.lH), 4.82 (m,lH), 5.44 (m,lH), 7.00 (m,2H), 7.26 (m,3H), 7.39 (m,4H), 7.50 (m,2H), 7.68 (m.lH).
31 δ 1.27 (m,6H), 1.44 (s,9H), 3.67 (m,2H), 3.80 (m,2H), 4.24 (m,lH), 4.80 (m,lH), 5.42 (m.lH), 5.49 (s,lH), 7.00 (m,lH), 7.26 (m,2H), 7.34 (m,2H), 7.48 (m,2H).
32 δ 1.26 (s,6H), 1.28 (s,6H), 4.24 (m, IH), 4.80 (m,lH), 5.44 (m.l H), 5.84 (s.lH), 7.00 (m,2H), 7.27 (m,2H), 7.47 (m,3H).
41 δ 1.27 (t,6H), 3.69 (m,2H), 3.80 (m,2H), 4.28 (m,lH), 4.84 (m.lH), 5.50 (m,2H), 7.10 (m,2H), 7.26-7.42 (m,4H), 7.48(m,2H).
42 δ θ.00 (s,9H), 4.28 (m,lH), 4.87 (m,lH), 5.54 (m.lH), 7.04 (m,2H), 7.36 (m,4H), 7.48 (m,lH). a Η NMR data are in ppm downfield from tetramethylsilane. Couplings are designated by (s)-singlet, (d)-doublet, (t)-triplet, (q)-quartet, (m)-multiplet, (dd)-doublet of doublets, (br s)-broad singlet.
BIOLOGICAL EXAMPLES OF THE INVENTION TEST A
Fall Armyworm
Test units, each consisting of a H.I.S. (high impact styrene) tray with 16 cells were prepared. Wet filter paper and approximately 8 cm 2 of lima bean leaf was placed into twelve of the cells. A 0.5-cm layer of wheat germ diet was placed into the four remaining cells. Fifteen to twenty third-instar larvae of fall armyworm (Spodoptera frugiperda) were placed into a 230-mL (8-ounce) plastic cup. Solutions of each of the test compounds in 75:25 acetone-distilled water solvent were sprayed into the tray and cup. Spraying was accomplished by passing the tray and cup on a conveyer belt directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.138 kilograms of active ingredient per hectare (about 0.13 pounds per acre) at 207 kPa
(30 p.s.i.). The insects were transferred from the 230-mL cup to the H.I.S. tray (one insect per cell). The trays were covered and held at 27°C and 50% relative humidity for 48 hours, after which time readings were taken on the twelve cells with lima bean leaves. The four remaining cells were read at 6-8 days for delayed toxicity. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 1 , 4, 5, 6, 11, 14, 16, 18, 22, 26, 29, 30, 34, 35, 36, 38, 39, 40 and 42.
TEST B Tobacco Budworm
The test procedure of TEST A was repeated for determining efficacy against third-instar larvae of the tobacco budworm (Heliothis virescens) except that three 230-mL (8-ounce) plastic cups with wheat germ diet were used in place of the H.I.S. tray, with each cup pre-infested with five third-instar larvae. Of the compounds tested, the following gave mortality levels of 80% or higher: 1, 4, 5 and 33.
TEST C Southern Corn Rootworm
Test units, each consisting of a 230-mL (8-ounce) plastic cup containing a 6.5-cm 2 (1 -square-inch) plug of a wheatgerm diet, were prepared. The test units were sprayed as described in TEST A with individual solutions of the test compounds. After the spray on the cups had dried, five second-instar larvae of the southern corn rootworm (Diabrotica undecimpunctata howardi) were placed into each cup. The cups were held at 27°C and 507c relative humidity for 48 hours, after which time mortality readings were taken. The same units were read again at 6-8 days for delayed toxicity. Of the compounds tested, the following gave control efficacy levels of 80% or greater: 16 and 28.
TEST D Boll Weevil
Test units consisting of 260-mL (9-ounce) cups containing five adult boll weevils (Anthonomus grandis) were prepared. The test units were sprayed as described in TEST A with individual solutions of the test compounds. Each cup was covered with a vented lid and held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher: 14*. * Compound was sprayed at a concentration of 50 ppm (equivalent to 28 g ha).
TEST E Contact Test Against Black Bean Aphid Individual nasturtium leaves were infested with 10 to 15 aphids (all moφhs and growth stages of Aphis fabae) and sprayed with their undersides facing up as described
in TEST A. The leaves were then set in 0.94-cm (3/8-inch) diameter vials containing 4 mL of sugar solution (approximately 1.4 g per liter) and covered with a clear plastic 29-mL (1 -ounce) cup to prevent escape of the aphids that drop from the leaves. The test units were held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher: 7 and 17.
TEST F Two-Spotted Spider Mite
Pieces of kidney bean leaves, each approximately 6.5 cm 2 (1 square inch) in area, that had been infested on the undersides with 25 to 30 adult mites (Tetranychus urticae), were sprayed with their undersides facing up on a hydraulic sprayer with a solution of the test compound in 75:25 acetone-distilled water solvent. Spraying was accomplished by passing the leaves, on a conveyor belt, directly beneath a flat fan hydraulic nozzle which discharged the spray at a rate of 0.138 kilograms of active ingredient per hectare (about 0.13 pounds per acre) at 207 kPa (30 p.s.i.). The leaf squares were then placed underside-up on a square of wet cotton in a petri dish and the perimeter of the leaf square was tamped down onto the cotton with forceps so that the mites could not escape onto the untreated leaf surface. The test units were held at 27°C and 50% relative humidity for 48 hours, after which time mortality readings were taken. Of the compounds tested, the following gave mortality levels of 80% or higher:
The same units were held an additional 5 days and read for larvicide/ovicide mortality and/or developmental effects. Of the compounds tested, the following gave activity levels of 80% or higher: 1, 4, 5, 6, 7, 12, 14, 15, 16, 17, 18, 20, 23, 26, 27, 28, 29, 30, 31, 34, 35, 36, 38, 39, 40 and 42. TEST G
Larval two-Spotted Spider Mites (Tetranychus urticae)
Solutions of the test compounds were prepared by dissolving in a minimum of acetone and then adding water containing a wetting agent until the concentration of the compound was 50 ppm. Two-week old red kidney bean plants infested with two-spotted spider mites eggs were sprayed to run-off (equivalent to 28 g/ha) with the test solution using a turntable sprayer. Plants were held in a chamber at 25°C and 50% relative humidity. Of the compounds tested, the following gave larvicide/ovicide activity of 80% or higher seven days after spraying: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12*, 13*, 14*, 15*, 16*, 17*, 18*, 19, 22*, 23*, 24*, 25*, 26*, 27*, 28*, 29*, 30*, 32*, 33*, 34*, 35*, 36*, 37*, 38*, 39*, 40* and 42*.
* Compound was sprayed at a concentration of 5 ppm (equivalent to 2.8 g/ha).
TEST H Fall Armyworm Whole Plant Test
Solutions of the test compounds were prepared by dissolving in a minimum of acetone and adding water containing a wetting agent until the concentration of the compounds was 10 ppm. Test compounds were then sprayed to run-off (equivalent to 5.5 g/ha) onto soybean plants utilizing a rotating platform and an atomizing sprayer. Treated plants were dried, and fall armyworm (Spodoptera frugiperda) larvae were exposed to excised, treated leaves. Test units were held at 27°C and 50% relative humidity, and evaluated for larval mortality 120 h post-infestation. Of the compounds tested, the following gave mortality levels of 80% or higher: 1, 2, 4*, 5, 6, 11, 16, 18, 24, 25, 26, 29, 30, 32, 33, 34, 35, 36, 38, 39, 40 and 42. * Compound was sprayed at a concentration of 3 ppm (equivalent to 1.6 g/ha).