SUBSTITUTED PYRIMIDINIUM COMPOUNDS FOR COMBATING ANIMAL PESTS

Abstract

Substituted pyrimidinium compounds of the general formula (I):

##STR00001##

wherein the compounds are useful for controlling invertebrate pests.

Claims

1. A substituted pyrimidinium compound of formula (I), ##STR00122## wherein X, Y are each independently O or S; Z is a direct bond, O, S(O).sub.m, NR.sup.b, C(R.sup.aaR.sup.aa)O, C(═X.sup.1), C(═X.sup.1)Y.sup.1 or Y.sup.1C(═X.sup.1); X.sup.1 is O, S or NR.sup.b; Y.sup.1 is O, S or NR.sup.c; A is CH or N, or, if part of a double bond, C, wherein the nitrogen of the pyrimidinium ring taken together with the contiguous linking carbon atom B and A as depicted in formula (I), form a four- to eight-membered ring, wherein each remaining ring member is selected from carbon atoms and up to 3 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 3N(R.sup.c).sub.p, wherein up to 2 carbon atom ring members are independently selected from C(═O) and C(═S), and the sulfur atom ring members are independently selected from S(═O).sub.m, wherein each ring may be substituted with up to 3 R.sup.a; B is CR′R″, NR.sup.b, S(O).sub.m, O or, if part of a double bond, CR′ or N; R′, R″ is each independently H, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl, CN, OR.sup.c, NR.sup.bR.sup.c, NO.sub.2, C(═O)(O).sub.pR.sup.c, OC(═O)(O).sub.pR.sup.e, C(═O)NR.sup.bR.sup.c, OC(═O)NR.sup.bR.sup.e, NR.sup.bC(═O)(O).sub.pR.sup.e, NR.sup.bC(═O)NR.sup.bR.sup.c, C(═S)NR.sup.bR.sup.c, S(O).sub.mR.sup.b, SO.sub.2NR.sup.bR.sup.c, OSO.sub.2R.sup.c, OSO.sub.2NR.sup.bR.sup.c, NR.sup.bSO.sub.2R.sup.c, NR.sup.bSO.sub.2NR.sup.bR.sup.c, N═S(═O).sub.pR.sup.cR.sup.c, S(═O).sub.o(═NR.sup.b).sub.qR.sup.c, SF.sub.5, OCN, SCN, Si(R.sup.d).sub.3 or a three- to six-membered saturated, or partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N—(R.sup.c).sub.p, O, and S which may be oxidized, and wherein the aforementioned groups and the carbo- or heterocyclic ring may be partially or fully substituted by R′″, R′″ is each independently halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy or C.sub.1-C.sub.6-haloalkoxy; or R′ and R″ together form a group selected from ═O, ═S, ═CR.sup.bR.sup.c, ═NR.sup.c, ═NOR.sup.c and ═NNR.sup.cR.sup.c, or, together with the carbon atom to which they are attached, form a three- to six-membered saturated or partially unsaturated carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N—(R.sup.c).sub.p, O, and S which may be oxidized, and wherein the afore-mentioned groups and the carbo- or heterocyclic ring may be partially or fully substituted by R′″; Het is a three- to ten-membered heterocyclic ring or a seven- to eleven-membered heterocyclic ring system, each ring or ring system member selected from carbon atoms and up to 4 heteroatoms independently selected from up to 2 O, up to 2 S, and up to 4N(R.sup.c).sub.p, wherein up to 3 carbon atom ring members are independently selected from C(═O) and C(═S) and the sulfur atom ring members are independently selected from S(═O).sub.o(═NR.sup.b).sub.q, each ring or ring system optionally substituted with up to 5 R.sup.a; o, q are each independently 0, 1 or 2, provided that the sum (o+q) is 0, 1 or 2 for each ring; R.sup.1 is hydrogen, C.sub.1-C.sub.8-alkyl, C.sub.2-C.sub.8-alkenyl, C.sub.2-C.sub.8-alkynyl, C.sub.3-C.sub.10-cycloalkyl, C.sub.4-C.sub.10-cycloalkenyl, C.sub.5-C.sub.14-cycloalkylcycloalkyl or R.sup.1 may form a three- to eleven-membered saturated, partially unsaturated or aromatic carbo- or heterocyclic ring or ring system, which may contain 1 to 4 heteroatoms selected from N(R.sup.c).sub.p, O, and S, wherein S may be oxidized, and wherein the aforementioned groups and the carbo- or heterocyclic ring system may be unsubstituted, partially or fully substituted by R.sup.a; or R.sup.1 is C(═O)R.sup.b, C(═O)OR.sup.e, NR.sup.bR.sup.c, C(═O)NR.sup.bR.sup.c, C(═S)NR.sup.bR.sup.c, SO.sub.2NR.sup.bR.sup.c, OC(═O)R.sup.c, OC(═O)OR.sup.e, OC(═O)NR.sup.bR.sup.e, N(R.sup.c)C(═O)R.sup.c, N(R.sup.c)C(═O)OR.sup.e, N(R.sup.c)C(═O)NR.sup.bR.sup.c, NR.sup.cSO.sub.2R.sup.b, NR.sup.cSO.sub.2NR.sup.bR.sup.c, Si(R.sup.d).sub.3, C(═NR)R.sup.c, C(═NOR.sup.c)R.sup.c, C(═NNR.sup.bR.sup.c)R.sup.c, C(═NN(C(═O)R.sup.b)R.sup.c)R.sup.c)R.sup.c, C(═NN(C═O)OR.sup.c)(R.sup.c).sub.2, S(═O).sub.o(═NR.sup.b).sub.qR.sup.c or N═CR.sup.bR.sup.c; R.sup.a is each independently halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl, CN, OR.sup.c, NR.sup.bR.sup.c, NO.sub.2, C(═O)(O).sub.pR.sup.c, OC(═O)(O).sub.pR.sup.e, C(═O)NR.sup.bR.sup.c, OC(═O)NR.sup.bR.sup.e, NR.sup.bC(═O)(O).sub.pR.sup.e, NR.sup.bC(═O)NR.sup.bR.sup.c, C(═S)NR.sup.bR.sup.c, S(O).sub.mR.sup.b, SO.sub.2NR.sup.bR.sup.c, OSO.sub.2R.sup.c, OSO.sub.2NR.sup.bR.sup.c, NR.sup.bSO.sub.2R.sup.c, NR.sup.bSO.sub.2NR.sup.bR.sup.c, N═S(═O).sub.pR.sup.cR.sup.c, S(═O).sub.o(═NR.sup.b).sub.qR.sup.c, SF.sub.5, OCN, SCN, Si(R.sup.d).sub.3 or a three- to six-membered saturated, or partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N—(R.sup.c).sub.p, O, and S which may be oxidized, and wherein the aforementioned groups and the carbo- or heterocyclic ring may be partially or fully substituted by R.sup.aa, or two geminally bound groups R.sup.a together may form a group selected from ═O, ═S, ═CR.sup.bR.sup.c, ═NR.sup.c, ═NOR.sup.c, and ═NNR.sup.cR.sup.c; R.sup.aa is each independently hydrogen, halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy or C.sub.1-C.sub.6-haloalkoxy; R.sup.b is each independently hydrogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy or a three- to six-membered saturated, or partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N(R.sup.c).sub.p, O, and S, wherein S may be oxidized and which carbo- or heterocyclic ring may be partially or fully substituted by R.sup.aa; R.sup.c is each independently hydrogen, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.6 cycloalkyl, or a three- to six-membered saturated, partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N(R.sup.aa).sub.p, O and S, wherein S may be oxidized and wherein the carbo- or heterocyclic ring may be partially or fully substituted by R.sup.aa; wherein two geminally bound groups R.sup.bR.sup.b, R.sup.cR.sup.b or R.sup.cR.sup.c together with the atom to which they are bound, may form a 3-, 4-, 5-, 6- or 7-membered saturated, partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 or 2 heteroatoms or heteroatoms groups selected from N, O, S, NO, SO and SO.sub.2 and wherein the carbo- or heterocyclic ring may be partially or fully substituted by R.sup.bb; R.sup.bb is each independently halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl, CN, OR.sup.c, NR.sup.bR.sup.c, NO.sub.2, C(═O)(O).sub.pR.sup.c, OC(═O)(O).sub.pR.sup.e, C(═O)NR.sup.bR.sup.c, OC(═O)NR.sup.bR.sup.e, NR.sup.bC(═O)(O).sub.pR.sup.e, NR.sup.bC(═O)NR.sup.bR.sup.c, C(═S)NR.sup.bR.sup.c, S(O).sub.mR.sup.b, SO.sub.2NR.sup.bR.sup.c, OSO.sub.2R.sup.c, OSO.sub.2NR.sup.bR.sup.c, NR.sup.bSO.sub.2R.sup.c, NR.sup.bSO.sub.2NR.sup.bR.sup.c, SF.sub.5, OCN, SCN, Si(R.sup.d).sub.3, C(═N(O).sub.pR.sup.b)R.sup.b, C(═NNR.sup.bR.sup.c)R.sup.b, C(═NN(C(═O)O.sub.pR.sup.c)R.sup.b)R.sup.b, ON═CR.sup.bR.sup.c, ONR.sup.bR.sup.c, S(═O).sub.o(═NR.sup.b).sub.qR.sup.c, SO.sub.2NR.sup.b(═O)NR.sup.bR.sup.c, P(═X.sup.2)R.sup.bR.sup.c, OP(═X.sup.2)(O.sub.pR.sup.c)R.sup.b, OP(═X.sup.2)(OR).sub.2, N═CR.sup.bR.sup.c, NR.sup.bN═CR.sup.bR.sup.c, NR.sup.bNR.sup.bR.sup.c, NR.sup.bC(═S)NR.sup.bR.sup.c, NR.sup.bC(═NR.sup.b)NR.sup.bR.sup.c, NR.sup.bNR.sup.bC(═X.sup.2)NR.sup.bR.sup.c, NR.sup.bNR.sup.bSO.sub.2NR.sup.bR.sup.c, or N═S(═O).sub.pR.sup.cR.sup.c or two geminally bound groups R.sup.bb together may form a group selected from ═O, ═S, ═CR.sup.bR.sup.c, ═NR.sup.c, ═NOR.sup.c, and ═NNR.sup.cR.sup.c; R.sup.d is each independently hydrogen, phenyl, C.sub.1-C.sub.6-alkyl, C.sub.2-C.sub.6-alkenyl, C.sub.2-C.sub.6-alkynyl, C.sub.3-C.sub.8-cycloalkyl, or C.sub.1-C.sub.6-alkoxyalkyl, wherein the above mentioned groups may be substituted by one or more halogen; R.sup.e is each independently, C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkylcarbonyl, C.sub.1-C.sub.6 cycloalkyl, or a three- to six-membered saturated, partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N(R.sup.aa).sub.p, O and S, wherein S may be oxidized and wherein the carbo- or heterocyclic ring may be partially or fully substituted by R.sup.aa; M is 0, 1, or 2; p is 0 or 1; R.sup.2 is H, halogen, CN, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.4-C.sub.10 alkylcycloalkyl, C.sub.4-C.sub.10 cycloalkylalkyl, C.sub.6-C.sub.14 cycloalkylcycloalkyl, C.sub.5-C.sub.10 alkylcycloalkylalkyl, or C.sub.3-C.sub.6 cycloalkenyl, wherein the aforementioned groups may be unsubstituted, partially, or fully substituted with R.sup.2a, or R.sup.2 may form a carbo- or heterocyclic three- to ten-membered ring or a seven- to eleven-membered ring system, which ring or ring system may be saturated, partially unsaturated, or aromatic, and which ring or ring system may contain 1 to 4 heteroatoms selected from N(R.sup.c).sub.p, O and S, wherein S may be oxidized, and wherein the carbo- or heterocyclic ring or ring system may be unsubstituted, partially or fully substituted by R.sup.2a; with the proviso that if R.sup.2 is halogen or CN, then Z is a direct bond; R.sup.2a is each independently halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl, CN, OR, NR.sup.bR.sup.c, NO.sub.2, C(═O)(O).sub.pR.sup.c, OC(═O)(O).sub.pR.sup.e, C(═O)NR.sup.bR.sup.c, OC(═O)NR.sup.bR.sup.e, NR.sup.bC(═O)(O).sub.pR.sup.e, NR.sup.bC(═O)NR.sup.bR.sup.c, C(═S)NR.sup.bR.sup.c, S(O).sub.mR.sup.b, SO.sub.2NR.sup.bR.sup.c, OSO.sub.2R.sup.c, OSO.sub.2NR.sup.bR.sup.c, NR.sup.bSO.sub.2R.sup.c, NR.sup.bSO.sub.2NR.sup.bR.sup.c, SF.sub.5, OCN, SCN, Si(R.sup.d).sub.3, C(═N(O).sub.pR.sup.b) R.sup.b, C(═NNR.sup.bR.sup.c)R.sup.b, C(═NN(C(═O)O.sub.pR.sup.c)R.sup.c)R.sup.b, ON═CR.sup.bR.sup.c, ONR.sup.bR.sup.c, S(═O).sub.o(═NR.sup.b).sub.qR.sup.c, SO.sub.2NR.sup.b(═O)NR.sup.bR.sup.c, P(═X.sup.2)R.sup.bR.sup.c, OP(═X.sup.2)(O.sub.pR.sup.c)R.sup.b, OP(═X.sup.2)(OR).sub.2, N═CR.sup.bR.sup.c, NR.sup.bN═CR.sup.bR.sup.c, NR.sup.bNR.sup.bR.sup.c, NR.sup.bC(═S)NR.sup.bR.sup.c, NR.sup.bC(═NR.sup.b)NR.sup.bR.sup.c, NR.sup.bNR.sup.bC(═X.sup.2)NR.sup.bR.sup.c, NR.sup.bNR.sup.bSO.sub.2NR.sup.bR.sup.c, N═S(═O).sub.pR.sup.cR.sup.c, or a three- to six-membered saturated, or partially unsaturated or aromatic carbo- or heterocyclic ring, which may contain 1 to 3 heteroatoms selected from N—(R.sup.c).sub.p, O and S, wherein S may be oxidized, and wherein the aforementioned groups and the carbo- or heterocyclic ring may be partially or fully substituted by R.sup.2aa or two geminally bound groups R.sup.2a together may form a group selected from ═O, ═S, ═CR.sup.bR.sup.c, ═NR.sup.c, ═NOR.sup.c and ═NNR.sup.cR.sup.c; R.sup.2aa is each independently halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-alkoxy, C.sub.1-C.sub.6-haloalkoxy, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.3-C.sub.6-cycloalkyl, CN, OR.sup.c, NR.sup.bR.sup.c, NO.sub.2, C(═O)(O).sub.pR.sup.c, OC(═O)(O).sub.pR.sup.e, C(═O)NR.sup.bR.sup.c, OC(═O)NR.sup.bR.sup.e, NR.sup.bC(═O)(O).sub.pR.sup.e, NR.sup.bC(═O)NR.sup.bR.sup.c, C(═S)NR.sup.bR.sup.c, S(O).sub.mR.sup.b, SO.sub.2NR.sup.bR.sup.c, OSO.sub.2R.sup.c, OSO.sub.2NR.sup.bR.sup.c, NR.sup.bSO.sub.2R.sup.c, NR.sup.bSO.sub.2NR.sup.bR.sup.c, SF.sub.5, OCN, SCN, Si(R.sup.d).sub.3, C(═N(O).sub.pR.sup.b)R.sup.b, C(═NNR.sup.bR.sup.c)R.sup.b, C(═NN(C(═O)O.sub.pR.sup.c)R.sup.b)R.sup.b, ON═CR.sup.bR.sup.c, ONR.sup.bR.sup.c, S(═O).sub.o(═NR.sup.b).sub.qR.sup.c, SO.sub.2NR.sup.b(═O)NR.sup.bR.sup.c, P(═X.sup.2)R.sup.bR.sup.c, OP(═X.sup.2)(O.sub.pR.sup.c)R.sup.b, OP(═X.sup.2)(OR).sub.2, N═CR.sup.bR.sup.c, NR.sup.bN═CR.sup.bR.sup.c, NR.sup.bNR.sup.bR.sup.c, NR.sup.bC(═S)NR.sup.bR.sup.c, NR.sup.bC(═NR.sup.b)NR.sup.bR.sup.c, NR.sup.bNR.sup.bC(═X.sup.2)NR.sup.bR.sup.c, NR.sup.bNR.sup.bSO.sub.2NR.sup.bR.sup.c, or N═S(═O).sub.pR.sup.cR.sup.c; or two geminally bound groups R.sup.2aa together may form a group selected from ═O, ═S, ═CR.sup.bR.sup.c, ═NR.sup.c, ═NOR.sup.c and ═NNR.sup.cR.sup.c; X.sup.2 is independently O or S; or an agriculturally or veterinary acceptable salt or tautomer or N-oxide thereof, excluding the compound ##STR00123## agriculturally and veterinary acceptable salts and tautomers and N-oxides thereof.

2. The compound according to claim 1, wherein A, B and the nitrogen of the pyrimidinium ring together with the contiguous linking carbon atom as depicted in formula (I), and in particular (Ia), form a five or six-membered ring.

3. The compound of claim 1 which is selected from formulae (Iaa)-(Iag): ##STR00124## wherein M.sup.1, M.sup.2 are independently CR′R″, NR.sup.b, S(O).sub.m, O, or, if part of a double blond, CR′ or N.

4. The compound according to claim 1, wherein Het is selected from D-1 to D-56, ##STR00125## ##STR00126## ##STR00127## ##STR00128## ##STR00129## wherein n is 0, 1, 2, 3 or 4; R.sup.a has the meanings given in formula (I) and # denotes the bond to A in formula (I).

5. The compound according to claim 4, wherein Het is selected from structures D-2, D-9, D-22, D-25, D-28, D-29, D-54 and D-56, wherein R.sup.a is halogen, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-alkylthio or phenyl, n is 0, 1 or 2 and # denotes the bond to A in formula (I).

6. The compound according to claim 1, wherein X and Y are O.

7. The compound according to claim 1, wherein Z is a direct bond, and R.sup.2 is a six membered carbo- or heterocyclic ring, which ring may be unsubstituted, partially or fully substituted by R.sup.2a, and wherein R.sup.2a is halogen, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-haloalkoxy, OR.sup.c, C(═O)OR.sup.c, C(═O)NR.sup.bR.sup.c, phenyl, or pyridyl, which may be substituted by halogen, C.sub.1-C.sub.6-haloalkyl and/or C.sub.1-C.sub.6-haloalkoxy.

8. The compound according to claim 1, wherein R.sup.1 is C.sub.1-C.sub.4-alkyl, C.sub.3-C.sub.6-cycloalkyl, C.sub.2-C.sub.4-alkenyl, benzyl or phenyl, which groups may be partially or fully substituted by halogen or C.sub.1-C.sub.4-alkyl.

9. The compounds of formula (I) and/or stereoisomers or agriculturally or veterinary acceptable salts or tautomers or N-oxides thereof according to claim 3, wherein X, Y are each O; A is CH and the nitrogen of the pyrimidinium ring taken together with the contiguous linking carbon atom and A as depicted in formula (I), form a five or six membered ring, wherein each remaining ring member is selected from 2 and 3 carbon atoms; R.sup.1 is CH.sub.3, CH.sub.2CH.sub.3, isopropyl, cyclopropyl, CH.sub.2CF.sub.3, phenyl, allyl or benzyl; B is CH.sub.2, NH or, if part of a double bond, CH or N; R.sup.2 is phenyl which may be substituted by halogen, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-haloalkoxy or phenyl; Z is a direct bond and Het is D-2, D-9, D-25 or D-56 and R.sup.a is Cl, Br, F, SCH.sub.3, CF.sub.3, OCH.sub.3 or phenyl.

10. A compound according to claim 1 of the formula I-ex: ##STR00130## in which the substituents Het, Z—R.sup.2 and R.sup.1 are defined as follows: TABLE-US-00003 Compound No Het Z—R.sup.2 R.sup.1 1 CH.sub.3 2 CH.sub.3 3 CH.sub.3 4 CH.sub.3 5 CH.sub.3 6 CH.sub.3 7 CH.sub.3 8 CH.sub.3 9 CH.sub.3 10 CH.sub.3 11 CH.sub.3 12 CH.sub.2CH.sub.3 13 CH.sub.3 14 CH.sub.3 15 CH.sub.3 16 CH.sub.3 17 CH.sub.3 18 CH.sub.3 19 CH.sub.3 20 CH.sub.3

11. A mixture comprising at least one compound according to claim 1, and at least one further pesticide.

12. A composition comprising at least one compound according to claim 1, and at least one of an inert liquid carrier and a solid carrier.

13. A method for at least one of protecting crops, plants, plant propagation material and/er growing plants from attack or infestation by invertebrate pests comprising contacting the crops, plants, plant propagation material and growing plants, or soil, material, surface, space, area or water in which the crops, plants, plant propagation material is stored or the plant is growing, with a pesticidally effective amount of at least one compound according to claim 1.

14. A method for combating or controlling invertebrate pest, which method comprises contacting said pest or its food supply, habitat or breeding grounds with a pesticidally effective amount of at least one compound as defined in claim 1.

15. A non-therapeutic method for at least one of treating animals infested or infected by parasites, preventing animals from getting infected or infested by parasites, and protecting animals against infestation or infection by parasites which comprises at least one of orally, topically and parenterally administering or applying to the animals a parasiticidally effective amount of at least one compound according to claim 1.

16. A seed comprising a compound according to claim 1 in an amount of from 0.1 g to 10 kg per 100 kg of seed.

Description

EXAMPLES

Example Compound C-1

[0513] ##STR00079##

[0514] Characterization (.sup.1H-NMR): CDCl.sub.3/ppm/400 MHz)

[0515] 7.76 (d, 2H), 7.54 (s, 1H), 7.37 (t, 2H), 7.21 (t, 1H), 5.26 (t, 1H), 4.96 (q, 1H), 4.53 (q, 1H), 3.49 (s, 3H)

Further Examples

[0516] Procedure of Synthesis for Example 11:

[0517] To a stirred solution of 2-chlorothiazole E-1 (80 g) in anhydrous THF (1000 mL) was added nBuLi (320 mL, 0.8 mol) drop wise at −78° C. for one hour. Ethyl formate (74 g) was added dropwise to the solution at −78° C., and stirred for one additional hour. Saturated NH.sub.4Cl was added to the reaction mixture and stirred for 30 min, then diluted with ethyl acetate. The aqueous phase was extracted with ethyl acetate. The organic phase was washed and dried, then concentrated to give the crude product, which was purified by re-crystallized with hexane/ethyl acetate to give 2-chlorothiazole-5-carbaldehyde E-2 (72 g yield: 73%); 1H NMR (400 MHz, CDCl.sub.3): δ ppm 9.96 (s., 1H), 8.21 (s, 1H).

[0518] To a stirred solution of 2-chlorothiazole-5-carbaldehyde E-2 (23.3 g) in acetonitrile (500 mL) was added nitromethane (38.6 g), followed by DBU (36.3 g) at 0° C. The solution was stirred for 3 hours at 0° C. To the reaction mixture, 1.5N HCl (50 ml) was added, then extracted with ethyl acetate. The organic phase was washed and dried, then concentrated to give the crude product, which was purified by column chromatography to afford pure 1-(2-chlorothiazol-5-yl)-2-nitro-ethanol E-3 (17.3 g, yield: 52.3%); 1H NMR (400 MHz, CDCl.sub.3): δ ppm 3.60 (br. S, 1H), 4.58-4.76 (m, 2H), 5.72 (dd, J=8.91, 3.14 Hz, 1H), 7.42-7.54 (m, 1H)

[0519] To a solution of 1-(2-chlorothiazol-5-yl)-2-nitro-ethanol E-3 (17.3 g) in ethanole (550 mL) and water (180 mL) was added NH.sub.4Cl (44.9 g, 832 mmol), followed by Fe powder (46.6 g) at 18° C. in portions over an hour. The solution was heated at 100° C. for 16 hours. The reaction mixture was cooled to room temperature and the dark solution was filtered through a pad of celite, and the filter cake was washed with EtOH. The filtrate was concentrated in vacuo, then dissolved in water (100 ml) and extracted with ethyl acetate, the aqueous layer was extracted with DCM: IPA (3:1). The organic layers were combined, dried, filtered and concentrated to give the crude product 2-amino-1-(2-chlorothiazol-5-yl)ethanol E-4 (6.3 g, yield: 42.6%), which was taken to next step without purification.

[0520] To a stirred solution of 2-amino-1-(2-chlorothiazol-5-yl)ethanol E-4 (6.3 g, 35.4 mmol) in anhydrous EtOH (300 mL) was added TEA (7.15 g, 70.8 mmol), followed by methyl isothiocyanate (5.45 g, 70.8 mmol) at 0° C. The reaction mixture was stirred at 18° C. for 16 hours. The reaction mixture was concentrated in vacuo and then dissolved in ethyl acetate and washed with water. The combined organic layer was washed, filtered and concentrated to give the crude product 1-[2-(2-chlorothiazol-5-yl)-2-hydroxy-ethyl]-3-methyl-thiourea E-5, which was purified by column to afford as yellow solid (5.5 g, yield: 61.9%). 1H NMR (400 MHz, MeOD): δ ppm 2.95 (d, J=9.29 Hz, 3H), 3.65-3.90 (m, 2H), 5.19 (s., 1H), 7.41-7.55 (m, 1H).

[0521] To a solution of 1-[2-(2-chlorothiazol-5-yl)-2-hydroxy-ethyl]-3-methyl-thiourea E-5 (5.5 g) in anhydrous THF (150 mL) was added CDI (5.3 g, 32.9 mmol) at 0° C. The reaction mixture solution was stirred at 15° C. for 16 hours. Water was added, and the reaction mixture was extracted with ethyl acetate. The organic phase was washed, filtered and concentrated to give the crude product. The crude product was purified by column to afford 5-(2-chlorothiazol-5-yl)-N-methyl-4,5-dihydrothiazol-2-amine E-6 (2 g, yield: 39.2%) as a white solid; 1H NMR (400 MHz, CDCl.sub.3): δ ppm 2.95-3.03 (m, 3H), 4.09 (dd, J=13.55, 4.77 Hz, 1H), 4.32 (dd, J=13.55, 7.03 Hz, 1H), 5.14 (dd, J=7.03, 4.77 Hz, 1H), 7.40 (s, 1H).

##STR00080##

[0522] To a solution of 2-(3-fluorophenyl)acetic acid E-7 (1 g) in anhydrous CH.sub.2Cl.sub.2 (50 mL) was added phenol (0.66 g), DCC (1.6 g) and catalytic amount of DMAP. The reaction mixture was stirred at room temperature (20-25° C.) for 16 hours. The mixture was filtered and diluted with CH.sub.2Cl.sub.2, then washed with water. The organic layers were concentrated, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to afford the product phenyl 2-(3-fluorophenyl)acetate E-8 as oily liquid (0.850 g Yield: 57%); 1H NMR—(400 MHz, CDCl.sub.3): δ ppm 7.31 (m, 2H), 7.29-6.90 (m, 9H), 3.78 (s, 2H)

[0523] To a solution of phenyl 2-(3-fluorophenyl)acetate E-8 (1 g) in anhydrous THF (50 mL) was added lithium hexamethyldisilane (10.8 ml) at −78° C. After an hour, phenyl chloroformate (1.2 eq) was added, and the reaction mixture was stirred at the same temperature for an hour. Saturated NH.sub.4Cl solution was added, and the mixture was diluted and extracted with ethyl acetate. The organic layers were concentrated, and the resulting residue was purified by silica flash column chromatography (hexane/ethyl acetate) to afford the product diphenyl 2-(3-fluorophenyl)propanedioate E-9 as oily liquid (0.850 g Yield: 57%.)

[0524] 1H NMR—(400 MHz, CDCl.sub.3): δ ppm 7.32 (m, 4H), 7.29-6.90 (m, 14H), 5.72 (s, 1H)

[0525] To a solution of 5-(2-chlorothiazol-5-yl)-N-methyl-4,5-dihydrothiazol-2-amine E-6 (0.250 g) in anhydrous toluene (50 mL) was added diphenyl 2-(3-fluorophenyl)propanedioate E-9 (0.424 g), and the mixture was heated at 120° C., for 12 hours. The mixture was cooled to room temperature and triturated with MTBE. The solid was filtered through a sintered funnel to get the crude product as an off-white solid. The crude product was recrystallized with MTBE to afford the example compound 11 as pale yellow solid (0.210 g Yield: 50%.)

[0526] 1H NMR—(400 MHz, CDCl.sub.3): δ ppm 9.34 (s, 1H), 7.86 (m, 2H), 7.63 (m, 1H), 6.93 (m, 1H), 5.80 (t, 1H), 4.84 (m, 2H), 2H).

[0527] By analogous procedures to the procedure described above for example 11, the following examples of formula I-ex were prepared, wherein the substituents Het, Z—R.sup.2 and R.sup.1 are as depicted in the table and wherein “*” denotes the attachment site.

TABLE-US-00002 I-ex [00081] Example Physicochemical data: No Het Z—R.sup.2 R.sup.1 HPLC-Retention [min]  1 = C-1 [00082] [00083] CH.sub.3 t = 0.815 (MS [m/z]: 377.9) [A]  2 [00084] [00085] CH.sub.3 t = 1.058 (MS [m/z]: 441.9) [A]  3 [00086] [00087] CH.sub.3 t = 1.083 (MS [m/z]: 447.8) [A]  4 [00088] [00089] CH.sub.3 t = 0.824 (MS [m/z]: 407.9) [A]  5 [00090] [00091] CH.sub.3 t = 1.018 (MS [m/z]: 445.9) [A]  6 [00092] [00093] CH.sub.3 t = 0.797 (MS [m/z]: 371.9) [A]  7 [00094] [00095] CH.sub.3 t = 0.806 (MS [m/z]: 401.9) [A]  8 [00096] [00097] CH.sub.3 t = 0.998 (MS [m/z]: 439.9) [A]  9 [00098] [00099] CH.sub.3 t = 1.235 (MS [m/z]: 384.0) [B] 10 [00100] [00101] CH.sub.3 t = 2.127 (MS [m/z]: 384.0) [C] 11 [00102] [00103] CH.sub.3 t = 1.223 (MS [m/z]: 396.2) [B] 1H NMR see above 12 [00104] [00105] CH.sub.2CH.sub.3 t = 2.654 (MS [m/z]: 498.0) [C] 13 [00106] [00107] CH.sub.3 t = 2.468 (MS [m/z]: 484.0) [C] 14 [00108] [00109] CH.sub.3 t = 1.744 (MS [m/z]: 430.0) [C] 15 [00110] [00111] CH.sub.3 t = 2.662 (MS [m/z]: 498.0) [C] 16 [00112] [00113] CH.sub.3 t = 1.852 (MS [m/z]: 396.0) [C] 17 [00114] [00115] CH.sub.3 t = 2.188 (MS [m/z]: 422.0) [C] 18 [00116] [00117] CH.sub.3 t = 2.589 (MS [m/z]: 490.0) [C] 19 [00118] [00119] CH.sub.3 t = 1.849 (MS [m/z]: 452.0) [C] 20 [00120] [00121] CH.sub.3 t = 1.197 (MS [m/z]: 403.3) [B]

HPLC Methods:

Method A:

[0528] Column: Phenomenex Kinetex 1.7 μm XB-C18 100A, 50×2.1 mm; MSD4/5 Shimadzu Nexera UHPLC+Shimadzu LCMS 20-20, ESI; Mobile Phase: A: water+0.1% TFA; B: acetonitrile: Temperature: 60° C.; Gradient: 5% B to 100% B in 1.50 min; 100% B 0.25 min; Flow: 0.8 ml/min to 1.0 ml/min in 1.51 min; MS method: ESI positive; Mass range (m/z): 100-700

Method B:

[0529] Column: YMC-PACK ODS-A, 50 mm*3.0 mm ID, 3 um 12 nm (BCIPL/COL/15/LC/019)
A=10 mM Amm. Formate (0.1% Formic Acid) B=Acetonitrile (0.1% Formic Acid)
Flow=1.2 ml/min. Column oven: 40 C

Method C:

[0530] Column: Agilent Eclipse Plus C18, 50 mm*4.6 mm ID, 5 um
A=10 mM Amm. Formate (0.1% Formic Acid) B=Acetonitrile (0.1% Formic Acid)
Flow=1.2 ml/min. Column oven: 30 C

[0531] The biological activity of the compounds of formula (I) of the present invention can be evaluated in biological tests as described in the following.

[0532] General conditions: If not otherwise specified, most test solutions are to be prepared as follows:

[0533] The active compound is dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water:acetone. The test solution is prepared at the day of use.

[0534] Test solutions are prepared in general at concentrations of 2500 ppm, 1000 ppm, 500 ppm, 300 ppm, 100 ppm and 30 ppm (wt/vol).

1.) Green Peach Aphid (Myzus persicae)

[0535] a) For evaluating control of green peach aphid (Myzus persicae) through systemic means the test unit consisted of 96-well-microtiter plates containing liquid artificial diet under an artificial membrane.

[0536] The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were pipetted into the aphid diet, using a custom built pipetter, at two replications.

[0537] After application, 5-8 adult aphids were placed on the artificial membrane inside the microtiter plate wells. The aphids were then allowed to suck on the treated aphid diet and incubated at about 23±1° C. and about 50±5% relative humidity for 3 days. Aphid mortality and fecundity was then visually assessed.

[0538] In this test, compound C-1 at 2500 ppm showed over 75% mortality in comparison with untreated controls.

[0539] b) The active compounds were formulated by a Tecan liquid handler in 100% cyclohexa-none as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solu-tions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 10 or 20 ml glass vials. A nonionic surfactant (Kinetic®) was included in the solution at a volume of 0.01% (v/v).

[0540] The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[0541] Bell pepper plants at the first true-leaf stage were infested prior to treatment by placing heavily infested leaves from the main colony on top of the treatment plants. Aphids were allowed to transfer overnight to accomplish an infestation of 30-50 aphids per plant and the host leaves were removed. The infested plants were then sprayed by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood, removed, and then maintained in a growth room under fluorescent lighting in a 24-hr photoperiod at about 25° C. and about 20-40% relative humidity. Aphid mortality on the treated plants, relative to mortality on untreated control plants, was determined after 5 days.

[0542] In this test, compounds 1, 2, 3, 4, 5, 6, 7 and 8 at 2500 ppm showed over 75% mortality in comparison with untreated controls.

2.) Orchid Thrips (Dichromothrips Corbetti)

[0543] Dichromothrips corbetti adults used for bioassay were obtained from a colony maintained continuously under laboratory conditions. For testing purposes, the test compound is diluted in a 1:1 mixture of acetone:water (vol:vol), plus 0.01% vol/vol Alkamuls® EL 620 surfactant.

[0544] Thrips potency of each compound was evaluated by using a floral-immersion technique. Plastic petri dishes were used as test arenas. All petals of individual, intact orchid flowers were dipped into treatment solution and allowed to dry. Treated flowers were placed into individual petri dishes along with about 20 adult thrips. The petri dishes were then covered with lids. All test arenas were held under continuous light and a temperature of about 28° C. for duration of the assay. After 3 days, the numbers of live thrips were counted on each flower, and along inner walls of each petri dish. The percent mortality was recorded 72 hours after treatment.

[0545] In this test, compounds C-1 and 8 at 500 ppm showed over 75% mortality in comparison with untreated controls.

3.) Rice Green Leafhopper (Nephotettix virescens)

[0546] Rice seedlings were cleaned and washed 24 hours before spraying. The active compounds were formulated in 50:50 acetone:water (vol:vol), and 0.1% vol/vol surfactant (EL 620) was added. Potted rice seedlings were sprayed with 5 ml test solution, air dried, placed in cages and inoculated with 10 adults. Treated rice plants were kept at about 28-29° C. and relative humidity of about 50-60%. Percent mortality was recorded after 72 hours.

[0547] In this test, compound C-1 at 500 ppm showed over 75% mortality in comparison with untreated controls.

4.) Rice Brown Plant Hopper (Nilaparvata lugens)

[0548] Rice seedlings were cleaned and washed 24 hours before spraying. The active compounds were formulated in 50:50 acetone:water (vol:vol) and 0.1% vol/vol surfactant (EL 620) was added. Potted rice seedlings were sprayed with 5 ml test solution, air dried, placed in cages and inoculated with 10 adults. Treated rice plants were kept at about 28-29° C. and relative humidity of about 50-60%. Percent mortality was recorded after 72 hours.

[0549] In this test, compound C-1 at 500 ppm showed over 75% mortality in comparison with untreated controls.

5.) Boll Weevil (Anthonomus grandis)

[0550] For evaluating control of boll weevil (Anthonomus grandis) the test unit consisted of 96-well-microtiter plates containing an insect diet and 5-10 A. grandis eggs.

[0551] The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the insect diet at 5 μl, using a custom built micro atomizer, at two replications.

[0552] After application, microtiter plates were incubated at about 25+1° C. and about 75+5% relative humidity for 5 days. Egg and larval mortality was then visually assessed.

[0553] In this test, compounds 2, 3, 5, 8 at 2500 ppm showed over 75% mortality in comparison with untreated controls.

6.) Cowpea Aphid (Aphis craccivora)

[0554] The active compound is dissolved at the desired concentration in a mixture of 1:1 (vol:vol) distilled water: acetone. Surfactant (Kinetic® HV) is added at a rate of 0.01% (vol/vol). The test solution is prepared at the day of use.

[0555] Potted cowpea plants were colonized with approximately 30-50 aphids of various stages by manually transferring a leaf tissue cut from infested plant 24 hours before application. Plants were sprayed with the test solutions using a DeVilbiss® hand atom-izer at 20-30 psi (=1.38 to 2.07 bar) after the pest population has been checked. Treat-ed plants are maintained on light carts at about 25-26° C. Percent mortality was as-sessed after 72 hours.

[0556] In this test, compounds 1, 4, 5, 7, 8 at 500 ppm showed over 75% mortality in comparison with untreated controls.

7.) Cotton Aphid (Aphis gossypii) I

[0557] The active compounds were formulated by a Tecan liquid handler in 100% cyclohexa-none as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solu-tions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 10 or 20 ml glass vials. A nonionic surfactant (Kinetic®) was included in the solution at a volume of 0.01% (v/v).

[0558] The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[0559] Cotton plants at the cotyledon stage were infested with aphids prior to treatment by placing a heavily infested leaf from the main aphid colony on top of each cotyledon. Aphids were allowed to transfer overnight to accomplish an infestation of 80-100 aphids per plant and the host leaf was removed. The infested plants were then sprayed by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood, removed from the sprayer, and then main-tained in a growth room under fluorescent lighting in a 24-hr photoperiod at 25° C. and 20-40% relative humidity. Aphid mortality on the treated plants, relative to mortality on untreated control plants, was determined after 5 days.

[0560] In this test, compound 1 at 300 ppm showed over 75% mortality in comparison with untreated controls.

8.) Silverleaf Whitefly (Bemisia argentifolii)

[0561] The active compounds were formulated by a Tecan liquid handler in 100% cyclohexa-none as a 10,000 ppm solution supplied in tubes. The 10,000 ppm solution was serially diluted in 100% cyclohexanone to make interim solutions. These served as stock solu-tions for which final dilutions were made by the Tecan in 50% acetone:50% water (v/v) into 5 or 10 ml glass vials. A nonionic surfactant (Kinetic®) was included in the solution at a volume of 0.01% (v/v).

[0562] The vials were then inserted into an automated electrostatic sprayer equipped with an atomizing nozzle for application to plants/insects.

[0563] Cotton plants at the cotyledon stage (one plant per pot) were sprayed by an automated electrostatic plant sprayer equipped with an atomizing spray nozzle. The plants were dried in the sprayer fume hood and then removed from the sprayer. Each pot was pla-ced into a plastic cup and about 10 to 12 whitefly adults (approximately 3-5 days old) were introduced. The insects were collected using an aspirator and a nontoxic Tygon® tubing connected to a barrier pipette tip. The tip, containing the collected insects, was then gently inserted into the soil containing the treated plant, allowing insects to crawl out of the tip to reach the foliage for feeding.

[0564] Cups were covered with a reusable screened lid. Test plants were maintained in a growth room at about 25° C. and about 20-40% relative humidity for 3 days, avoiding direct exposure to fluorescent light (24 hour photoperiod) to prevent trapping of heat inside the cup. Mortality was assessed 3 days after treatment, compared to untreated control plants.

[0565] In this test, compounds 4 and 6 at 300 ppm showed over 75% mortality in comparison with untreated controls.

9.) Vetch Aphid (Megoura viciae)

[0566] For evaluating control of vetch aphid (Megoura viciae) through contact or systemic means the test unit consisted of 24-well-microtiter plates containing broad bean leaf disks.

[0567] The compounds were formulated using a solution containing 75% v/v water and 25% v/v DMSO. Different concentrations of formulated compounds were sprayed onto the leaf disks at 2.5 μl, using a custom built micro atomizer, at two replications.

[0568] After application, the leaf disks were air-dried and 5-8 adult aphids placed on the leaf disks inside the microtiter plate wells. The aphids were then allowed to suck on the treated leaf disks and incubated at about 23+1° C. and about 50+5% relative humidity for 5 days. Aphid mortality and fecundity was then visually assessed.

[0569] In this test, compounds 1, 2, 3, 4, 5, 6, 7 and 8 at 2500 ppm showed over 75% mortality in comparison with untreated controls.