Compositions and methods for controlling nematode pests

Abstract

Compositions and processes for controlling nematodes are described herein, e.g., nematodes that infest plants or animals. The compounds include certain 2,5-substituted tetrazoles.

Claims

1. A compound of Formula I or a salt thereof, ##STR00042## wherein, A is an optionally substituted aryl, wherein said substituents are selected from the group consisting of CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and C is a heteroaryl selected from the group consisting of 3-thienyl and 3-furanyl, each of which can be optionally independently substituted with one or more substituents selected from the group consisting of F, Cl, Br, CH.sub.3, and OCF.sub.3, or C is selected from the group consisting of 1-pyrrolidinyl and pyrrolyl, each of which can be optionally independently substituted with one or more substituents selected from the group consisting of CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, hydroxyalkyl, and halogen.

2. The compound of claim 1 of Formula Ia or a salt thereof, ##STR00043## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, and halogen.

3. The compound of claim 1 of Formula Ic or a salt thereof, ##STR00044## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.6, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl Br, CH.sub.3, and OCF.sub.3; and E is O or S.

4. The compound of claim 1 of Formula Id or a salt thereof, ##STR00045## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.6 through R.sub.13 are independently selected from the group consisting of hydrogen, CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, and halogen.

5. A compound of Formula II or a salt thereof, ##STR00046## wherein, A is an optionally substituted aryl, wherein said substituents are selected from the group consisting of CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and C is a heteroaryl selected from the group consisting of thienyl and furanyl, each of which can be optionally independently substituted with one or more substituents selected from the group consisting of F, Cl, Br, CH.sub.3 and OCF.sub.3, or C is selected from the group consisting of pyrrolidinyl and pyrrolyl, each of which can be optionally independently substituted with one or more substituents selected from the group consisting of CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, hydroxyalkyl and halogen.

6. The compound of claim 5 of Formula IIa or a salt thereof, ##STR00047## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, and halogen.

7. The compound of claim 5 of Formula IIb or a salt thereof, ##STR00048## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl, Br, CH.sub.3, and OCF.sub.3; and E is O or S.

8. The compound of claim 5 of Formula IIc or a salt thereof, ##STR00049## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.6, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl, Br, CH.sub.3, and OCF.sub.3; and E is O or S.

9. The compound of claim 5 of Formula IId or a salt thereof, ##STR00050## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and R.sub.6 through R.sub.13 are independently selected from the group consisting of hydrogen, CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, and halogen.

10. A nematicidal composition comprising a compound of claim 1 at a concentration sufficient to reduce the viability of a parasitic nematode.

11. The nematicidal composition of claim 10 wherein the composition comprises one or more of a surfactant, a co-solvent, a fungicide, an herbicide, or another pesticide.

12. A nematicidal composition comprising a compound of claim 5 at a concentration sufficient to reduce the viability of a parasitic nematode.

13. The nematicidal composition of claim 12 wherein the composition comprises one or more of a surfactant, a co-solvent, a fungicide, an herbicide, or another pesticide.

14. A treated seed comprising a nematicidal composition comprising a compound of Formula I or Formula II, or a salt thereof, ##STR00051## wherein, A is selected from the group consisting of aryl, arylalkyl, aryloxo, arylthio, heteroaryl, heteroarylalkyl, heteroaryloxo, and heteroarylthio, each of which may be optionally substituted with one or more substituents selected from the group consisting of halo, C.sub.1-C.sub.6 haloalkyl, C.sub.6-C.sub.10 aryl, C.sub.4-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.2-C.sub.6 alkynyl, C.sub.6-C.sub.10 aryl(C.sub.1-C.sub.6)alkyl, C.sub.6-C.sub.10 aryl(C.sub.2-C.sub.6)alkenyl, C.sub.6-C.sub.10 aryl(C.sub.2-C.sub.6) alkynyl, C.sub.1-C.sub.6 hydroxyalkyl, amino, ureido, cyano, C.sub.1-C.sub.6 acylamino, hydroxy, thiol, C.sub.1-C.sub.6 acyloxy, azido, C.sub.1-C.sub.6 alkoxy and carboxy, and C(H)O; and C is a heteroaryl selected from the group consisting of thienyl, furanyl, oxazolyl, or isoxazolyl, each of which can be optionally independently substituted with one or more substituents selected from the group consisting of F, Cl, Br, CH.sub.3, and OCF.sub.3, or C is selected from the group consisting of pyrrolidinyl, piperidinyl, pyrrolyl, pyrrolyloxo, pyrrolythio, and pyrrolylalkyl, each of which can be optionally independently substituted with one or more substituents selected from the group consisting of, alkyl, cycloalkyl, heterocycle, hydroxyalkyl, and halogen.

15. The treated seed of claim 14 wherein the compound is of Formula Ia or a salt thereof, ##STR00052## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, and halogen.

16. The treated seed of claim 14 wherein the compound is of Formula Ib or a salt thereof, ##STR00053## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3: R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl, Br, CH.sub.3, and OCF.sub.3; and E is O or S.

17. The treated seed of claim 14 wherein the compound is of Formula Ic or a salt thereof, ##STR00054## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.6, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl, Br, CH.sub.3, and OCF.sub.3; and E is O or S.

18. The treated seed of claim 14 wherein the compound is of Formula Id or a salt thereof, ##STR00055## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.6 through R.sub.13 are independently selected from the group consisting of hydrogen, CH.sub.3, C.sub.2-C.sub.4 alkyl, cycloalkyl, heterocycle, and halogen.

19. The treated seed of claim 14 wherein the compound is of Formula IIa or a salt thereof, ##STR00056## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, CH.sub.3, alkyl, cycloalkyl, heterocycle, and halogen.

20. The treated seed of claim 14 wherein the compound is of Formula IIb or a salt thereof, ##STR00057## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.7, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl, Br, CH.sub.3, and OCF.sub.3; and E is O or S.

21. The treated seed of claim 14 wherein the compound is of Formula IIc or a salt thereof, ##STR00058## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3, and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; R.sub.6, R.sub.8 and R.sub.9 are independently selected from the group consisting of hydrogen, F, Cl, Br, CH.sub.3, and OCF.sub.3; and E is O or S.

22. The treated seed of claim 14 wherein the compound is of Formula IId or a salt thereof, ##STR00059## wherein, R.sub.1 and R.sub.5 are independently selected from the group consisting of hydrogen, CH.sub.3, F, Cl, Br, CF.sub.3 and OCF.sub.3; R.sub.2 and R.sub.4 are independently selected from the group consisting of hydrogen, F, Cl, Br, and CF.sub.3; R.sub.3 is selected from the group consisting of hydrogen, CH.sub.3, CF.sub.3, F, Cl, Br, OCF.sub.3, OCH.sub.3, CN, and C(H)O; and R.sub.6 through R.sub.13 are independently selected from the group consisting of hydrogen, CH.sub.3, alkyl, cycloalkyl, heterocycle, and halogen.

23. The treated seed of claim 14 wherein the compound is selected from the group consisting of: 2-phenyl-5-(thiophen-2-yl)-2H-tetrazole, 5-(furan-2-yl)-2-phenyl-2H-tetrazole, 2-(4-chlorophenyl)-5-(thiophen-2-yl)-2H-tetrazole, 2-(4-chlorophenyl)-5-(furan-2-yl)-2H-tetrazole, 2-(4-chloro-2-methylphenyl)-5-(thiophen-2-yl)-2H-tetrazole, 2-(4-chloro-2-methylphenyl)-5-(furan-2-yl)-2H-tetrazole, 5-phenyl-2-(thiophen-2-yl)-2H-tetrazole, 2-(furan-2-yl)-5-phenyl-2H-tetrazole, 5-(4-chlorophenyl)-2-(thiophen-2-yl)-2H-tetrazole, 5-(4-chlorophenyl)-2-(furan-2-yl)-2H-tetrazole, 5-(4-chloro-2-methylphenyl)-2-(thiophen-2-yl)-2H-tetrazole, 5-(4-chloro-2-methylphenyl)-2-(furan-2-yl)-2H-tetrazole, and salts thereof.

24. The treated seed of claim 14 wherein the composition comprises one or more of a fungicide, an herbicide, or another pesticide.

Description

DETAILED DESCRIPTION

(1) Described herein are certain tetrazole compounds with potent broad spectrum nematicidal activity.

(2) The nematicidal compounds may be supplied to plants exogenously, through sprays for example. These compounds may also be applied as a seed coat. The compounds can be applied to plants or the environment of plants needing nematode control, or to animals or the food of animals needing nematode parasite control. The compositions may be applied by, for example drench or drip techniques. With drip applications compounds can be applied directly to the base of the plants or the soil immediately adjacent to the plants. The composition may be applied through existing drip irrigation systems. This procedure is particularly applicable for cotton, strawberries, tomatoes, potatoes, vegetables and ornamental plants. Alternatively, a drench application can be used where a sufficient quantity of nematicidal composition is applied such that it drains to the root area of the plants. The drench technique can be used for a variety of crops and turf grasses. The drench technique can also be used for animals. Preferably, the nematicidal compositions would be administered orally to promote activity against internal parasitic nematodes. Nematicidal compositions may also be administered in some cases by injection of the host animal or by topical applications.

(3) The concentration of the nematicidal composition should be sufficient to control the parasite without causing significant phytotoxicity to the desired plant or undue toxicity to the animal host. The compounds disclosed in this invention have a good therapeutic window.

(4) We have surprisingly found that certain tetrazole analogs (e.g., 2-phenyl-5-(thiophen-2-yl)-2H-tetrazole, 5-(furan-2-yl)-2-phenyl-2H-tetrazole, 2-(4-chlorophenyl)-5-(thiophen-2-yl)-2H-tetrazole, 2-(4-chlorophenyl)-5-(furan-2-yl)-2H-tetrazole, 2-(4-chloro-2-methylphenyl)-5-(thiophen-2-yl)-2H-tetrazole, 2-(4-chloro-2-methylphenyl)-5-(furan-2-yl)-2H-tetrazole, 5-phenyl-2-(thiophen-2-yl)-2H-tetrazole, 2-(furan-2-yl)-5-phenyl-2H-tetrazole, 5-(4-chlorophenyl)-2-(thiophen-2-yl)-2H-tetrazole, 5-(4-chlorophenyl)-2-(furan-2-yl)-2H-tetrazole, 5-(4-chloro-2-methylphenyl)-2-(thiophen-2-yl)-2H-tetrazole, 5-(4-chloro-2-methylphenyl)-2-(furan-2-yl)-2H-tetrazole) have nematicidal potencies comparable with organophosphate and carbamate standards yet display excellent selectivity for nematodes over plants and animals. Thus, these analogs will provide useful compounds for nematode parasite control.

(5) The nematicidal agents described herein can be applied in conjunction with another pesticidal agents. The second agent may, for example, be applied simultaneously or sequentially. Such pesticidal agents can include for example, avermectins for animal applications.

(6) The aforementioned nematicidal compositions can be used to treat diseases or infestations caused by nematodes of the following non-limiting, exemplary genera: Anguina, Ditylenchus, Tylenchorhynchus, Pratylenchus, Radopholus, Hirschmanniella, Nacobbus, Hoplolaimus, Scutellonema, Rotylenchus, HelicoOenchus, Rotylenchulus, Belonolaimus, Heterodera, other cyst nematodes, Meloidogyne, Criconemoides, Hemicycliophora, Paratylenchus, Tylenchulus, Aphelenchoides, Bursaphelenchus, Rhadinaphelenchus, Longidorus, Xiphinema, Trichodorus, and Paratrichodorus, Dirofiliaria, Onchocerca, Brugia, Acanthocheilonema, Aelurostrongylus, Anchlostoma, Angiostrongylus, Ascaris, Bunostomum, Capillaria, Chabertia, Cooperia, Crenosoma, Dictyocaulus, Dioctophyme, Dipetalonema, Dracunculus, Enterobius, Filaroides, Haemonchus, Lagochilascaris, Loa, Manseonella, Muellerius, Necator, Nematodirus, Oesophagostomum, Ostertagia, Parafilaria, Parascaris, Physaloptera, Protostrongylus, Setaria, Spirocerca, Stephanogilaria, Strongyloides, Strongylus, Thelazia, Toxascaris, Toxocara, Trichinella, Trichostrongylus, Trichuris, Uncinaria, and Wuchereria. Particularly preferred are nematodes including Dirofilaria, Onchocerca, Brugia, Acanthocheilonema, Dipetalonema, Loa, Mansonella, Parafilaria, Setaria, Stephanofilaria, and Wucheria, Pratylenchus, Heterodera, Meloidogyne, Paratylenchus. Species that are particularly preferred are: Ancylostoma caninum, Haemonchus contortus, Trichinella spiralis, Trichurs muris, Dirofilaria immitis, Dirofilaria tenuis, Dirofilaria repens, Dirofilari ursi, Ascaris suum, Toxocara canis, Toxocara cati, Strongyloides ratti, Parastrongyloides trichosuri, Heterodera glycines, Heterodera schachtii, Globodera pallida, Globodera rostochiensis, Meloidogyne javanica, Meloidogyne incognita, and Meloidogyne arenaria, Radopholus similis, Longidorus elongatus, Meloidogyne hapla, Belonolaimus longicaudatus, Hoplolaimus galeatus, Pratylenchus scribberi, Pratylenchus brachyurus, Pratylenchus zeae and Pratylenchus penetrans.

(7) The following examples are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. All of the publications cited herein are hereby incorporated by reference in their entirety.

EXAMPLES

Example 1: M. Incognita Testing of Several Nematicidal Compounds in a Miniaturized Greenhouse Assay

(8) Overview:

(9) The test compound is dissolved in an acetone solution and added to water. A sprouted cucumber seedling is placed into a vial with dry sand and the water-chemical solution is added immediately. Twenty four hours later Meloidogyne incognita eggs are added to the vials and 10 to 12 days later the roots are evaluated for nematode galling.

(10) Procedure:

(11) Cucumber seeds are sprouted for 3 days in moist paper towels. Acceptable sprouts should be 3 to 4 cm long with several lateral roots just emerging. Stock solutions of chemistry are prepared in a mixture of acetone and Triton X100 (412 mg in 500 mL) to a final concentration of 5 mg/mL. The chemical stock solution is then added to 10 mL deionized water plus 0.015% Triton X100 and mixed thoroughly. This is enough to test each condition in triplicate. Ten mL dry sand is added to each vial. At this time the solubility of the chemistry is visually determined and recorded as either ppt (large precipitates) or cloudy (fine precipitates). Seedlings are planted by tilting the vial and laying the seedling in the correct orientation so that the cotyledons are just above the sand and then tilting back to cover the radicles with sand. 3.3 ml water/chemical mix is added to each vial and the vials placed in racks under fluorescent light banks. The vials are inoculated two days after planting by adding 500 vermiform M. incognita eggs to each vial in 50 uL of deionized or spring water. The vials are then kept under the fluorescent lamps at ambient room temperature and watered as needed with 1 mL deionized water, usually twice during duration of test. Harvest of the cucumber plants is done 10 to 12 days after inoculation by washing sand off the roots. A root gall rating and visual phytotoxicity rating is assigned using the following scales: Gall rating scale (Gall: % root mass galled): 0=0-5%; 1=6-20%; 2=21-50%; and 3=51-100%. The average of the triplicate gall rating is then calculated: green=0.00-0.33 (no galls); yellow=0.67-1.33 (mild galling); orange=1.67-2.33 (moderate galling); red=2.67-3.00 (severe galling). Visual phytotoxicity scale is also assigned (Vis. tox; visual reduction in root mass compared to the control): rs1=mild stunting; rs2=moderate stunting; rs3=severe stunting.

(12) TABLE-US-00001 TABLE 1A Potent nematicidal tetrazole analogs showing examples of substitution compatible with high activity 8/1 ppm Name Analog gall ratings 1 0.sup.a/0.67.sup.b 2 0 0.33.sup.a/0.67.sup.b 3 0.sup.c/1.33.sup.d 4 0.33/1.33 5 0.00/2.33 6 0.00/1.33 7 0.33/1.67 Oxamyl (1 ppm) 1.33.sup.a, 1.33.sup.b, 0.67.sup.c, 1.67.sup.d *Data with the same letters are taken from the same test.

(13) A variety of single or double substitutions on the six membered aromatic ring of the phenyl-2-furan and phenyl-2-thiophene tetrazoles are compatible with high nematicidal activity comparable to oxamyl (oxamyl is a highly toxic compounds classified as a toxicity Class I chemical by the US Environmental Protection Agency). Examples of preferred single substitutions include but are not limited to halogens, CH.sub.3, CF.sub.3, OCF.sub.3 and OCH.sub.3 especially in the para position (4-position) of the phenyl ring. The phenyl ring can also be multiply substituted in a way compatible with high nematicidal efficacy. Ring numbering system is shown below.

(14) ##STR00026##

Example 2: General Greenhouse Testing Protocols

(15) Soybean Planting and Growth:

(16) Soybeans seeds are planted in 100% sand in two inch square plastic pots.

(17) Chemical treatment is done when the soybeans show the first trifoliate beginning to emerge about 10 to 12 days after planting. At least four hours after chemical application the nematode soybean cyst nematode (SCN) eggs are applied and 28 days after the egg inoculation the test is harvested.

(18) Cucumber Planting and Growth

(19) Cucumber seeds are planted in a sandy soil mixture in two inch square plastic pots. When the cotyledons are fully opened and just as the first leaf begins to emerge, usually 7 days after planting, chemistry for the 7-day treatment is applied. One week later the chemistry for the 0 day treatment is applied. Separate plants are used for each application. The plants are generally in the 1-2 leaf stage now. At least four hours after the chemistry application the pots are inoculated with root knot nematode (RKN) eggs. Plants are rated for galling 14 days after the egg inoculation.

(20) Chemical Formulation and Application

(21) One milligram of chemistry per four pots is equal to one kilogram per hectare of chemical. A standard test uses four replications. For rates above 2 kg/ha, the desired amount of chemical is weighed into a 30 ml vial (example: 8 kg/ha rate=8 mg chemical in 30 ml vial). The chemical is dissolved in 2 ml of appropriate solvent, generally acetone. For rates below 2 kg/ha, 2 milligrams of chemistry is weighed into the vial and dissolved in 2 ml of the solvent. The appropriate amount of chemical concentrate is then pipetted into a separate 30 ml vial and solvent is added to bring the volume to 2 ml (example 0.5 kg/ha=0.5 ml of concentrate+1.5 ml solvent). Each dissolved concentrate is then brought to a total of 20 milliliters using 0.05% Triton X 100 surfactant solution.

(22) Chemical and Nematode Application

(23) Pots to be treated are moist but not saturated. To each of four pots, five milliliters of the appropriate chemical solution is pipetted to the media surface making sure to avoid contact with the base of the plant. Immediately following chemical application, using a mist nozzle, the pot surface is wetted sufficiently to saturate the pot watering in the chemistry. The chemical application is done in the morning.

(24) Nematode eggs, either SCN or RKN, are added to distilled water to create a concentration of 1000 vermiform eggs per liter of water. At least four hours after chemical treatment (0 day testing) or 1 week later (7 day longevity testing) the eggs are applied to the treated pots plus non-treated check plants. A small hole about 1 cm deep is punched into the pot surface. One milliliter of the nematode egg slurry is pipetted into the hole. Immediately afterwards the hole is gently covered. Watering of the test plants is then restricted to only water as needed to prevent wilt for a period of 24 hours. After the 24 hour restricted watering, normal sub-irrigation watering is done for the duration of the test.

(25) TABLE-US-00002 TABLE 2A RKN greenhouse soil assay on cucumber plants 7 day 0.25/ 0.1 kg/ Name Analog ha rate* 1 92%/89% 2 53%/47% Fenam- iphos 94%/80% *Data shows percent control (i.e., galling reduction) relative to the control blank treatment. Data with the same letters are taken from the same test.

(26) TABLE-US-00003 TABLE 2B SCN greenhouse soil assay on soybean plants 0 day 0.25 kg/ Name Analog ha rate* 1 24%.sup. 2 0 52%.sup. 3 44%.sup. Oxamyl 75%.sup. Fenamiphos 90%.sup.a *Data shows percent control (i.e., cyst reduction) relative to the control blank treatment. Data with the same letters are taken from the same test.

(27) Certain oxazoles, oxadiazoles and thiadiazoles are highly efficacious nematicides in bioactive soil with potencies comparable to fenamiphos and oxamyl.

Example 3: Belonolaimus Longicaudatus (Sting Nematode) Testing Protocols

(28) Populations of sting (Belonolaimus longicaudatus) nematodes are maintained on St. Augustine turf grass on soil in 15-cm pots. At test initiation the turf is removed from the pots and the soil containing nematode eggs, juveniles, and adults is subdivided into pots each containing a volume of 125 cm.sup.3 The compounds to be tested are dissolved in 3 ml of acetone using 3, 6, or 15 mg to achieve equivalent surface area application rates of 2, 4, or 10 kg/ha, respectively. The 3 ml acetone stock solution is added to 30 ml of water, and 5 ml of that solution is used to drench each of 6 replicate test pots prepared as described above. The treated pots containing nematodes are incubated in the laboratory at ambient temperature of approximately 25 C. After 3 days the soil from each pot is washed onto a modified Baermann apparatus comprised of a screen supporting a layer of filter paper on which the soil sample is placed and set in a dish of water. The samples are then incubated at 25 C. for 24 hours to allow the live nematodes to migrate through the paper and screen and into a water reservoir to be collected for counting with a light microscope. Nematodes that have been killed or immobilized by the test compounds are not able to migrate into the reservoir.

Example 4: C. Elegans and H. contortus Testing Protocols

(29) C. elegans: Various compounds were tested for nematicidal activity against C. elegans using contact assays in wells. The assays were performed as described below. The test compounds were solubilized in DMSO at 10 mg/ml to create 100 stock solutions. A dilution series was created by diluting the stock solution with DMSO. For each well assay 4 ul of the appropriate dilution is added to a well of a test plate. A 400 ul aliquot of bacterial stock (in M9 buffer with ampicillin) is added to each well of the test plate. Worms are added and the test plate placed on a rotary shaker incubated at 20 C. Worms are examined and scored at 24 hrs, 48 hrs and 72 hours. L1 worms used in the assay are prepared by plating eggs on a plate without a bacterial feeding layer. The eggs hatch and arrest at the L1 stage. This L1 stage population is then used to create a stock for the experiments. A 25 ul aliquot of worms is added to each well in the assay.

(30) H. contortus:

(31) The assay was performed essentially as described in: Hubert J, Kerboeuf D. A new method for culture of larvae used in diagnosis of ruminant gastrointestinal strongylosis: comparison with fecal cultures. Can J Comp Med. 1984 48(1):63-71. H. contortus eggs were obtained from Myers Parasitology (Magnolia, Ky.). The test compounds were solubilized in DMSO to create 100 stock solutions. 2 ul of compound at various concentrations followed by 200 ul of molten agar were mixed into the wells. Approximately 50 eggs were placed in the well and incubated for 24 hours. After this time, >50% of the eggs were hatched in DMSO controls. After 24 hr, 100 ul of growth medium (Earle's salt solution, 1% yeast extract, 0.9% saline, and sodium bicarbonate to pH 7) containing compound was added to allow larval feeding. After 48 hr in growth medium (total of 72 hours) the wells were evaluated for hatching and larval movement.

(32) TABLE-US-00004 TABLE 4A C. elegans well test EC50 ppm Name Analog 1/2/3 days 1 0.8/0.8/0.9 2 >50/0.8/0.8 3 0.8/0.8/0.8

(33) TABLE-US-00005 TABLE 4B H. contortus larval development assay EC50 in ppm Name Analog at 72 hours 1 <6.3 2 6.3-25 3 <6.3

(34) These data indicate that the claimed nematicidal tetrazoles have excellent nematode spectrum showing efficacy against Glade V nematodes like C. elegans and H. contortus in addition to clade IVb tylenchid nematodes like M. incognita (root knot nematode) and H. glycines (soybean cyst nematode).

Example 5: Advanced Greenhouse Testing Protocols

(35) Pre-Plant Incorporated Test (PPI)

(36) The PPI test examines the effect of pre-incorporation of compounds in soil and longer aging to simulate in furrow methods of nematicide application in the field. The PPI test exposes compounds to a higher volume of soil and drying which can result in more severe soil binding. Compounds are also aged for longer periods which can lead to more extensive biotic and abiotic degradation further limiting activity.

(37) The chemically treated soil (sandy soil mix) for all treatment days (e.g., 7 days, 14 days, 21 days) treatments is potted into their appropriate pots. On the same day the 7 day treatment pots are seeded. One week later eggs are applied and 14 days after egg application the test is harvested. The 14 day treatments are planted 7 days after the first planting. The 14 day planting and 7 day inoculation happen on the same day. One week later the 14 day treatments are inoculated with eggs. These are harvested 14 days after the inoculation. The 21 day treatments are planted 14 days after the first planting. The 14 day inoculation and 21 day planting are done on the same day. One week later the 21 day plants are inoculated with eggs. The 7 day treatment is harvested the same day as the 21 day inoculation. Fourteen days after inoculation the 21 day plants are harvested.

(38) TABLE-US-00006 Treatment Planting Inoculation Harvest 7 day day 0 day 7 day 21 14 day day 7 day 14 day 28 21 day day 14 day 21 day 35

(39) For each compound a stock is prepared using 4 mg material in 4 ml of acetone. The soil is mixed by placing 80 ml of field soil and 320 ml of sand in a plastic bag and mixing well. The formulation for treatment is done by adding 2.13 ml (8 kg/ha rate), 1.06 ml (4 kg/ha rate) or 0.53 ml (2 kg/ha rate) to a vial and raising it with 10 ml in 0.05% X100. Soil is then treated by adding the entire 10 ml to the 400 ml of mix in the bag. The treated soil is immediately mixed well in the sealed bag to distribute the compound evenly. Approximately 95 ml is used to fill each 2-inch square pot up to the top with some soil compression and flattening. For each compound and for the control treatments 4 pots are filled. All pots are watered until moist but with no run-out through the bottom.

(40) The PPI test simulates 8, 4 and 2 kg/ha rates incorporated 15 cm deep in the field and is equivalent to the 2, 1 and 0.5 kg/ha drench application rates in the standard 2-inch pot cucumber greenhouse assay.

Example 6: Seed Treatment Test of Root Knot Nematode on Cucumber Plants and Soybean Cyst Nematode on Soybean Plants

(41) For a given concentration the chemical is dissolved in 500 ul of acetone and one gram of cucumber seed (RKN test) or soybean seed (SCN test) is added (e.g., 20 mg active ingredient in 500 ul acetone plus 1 gram of seed). The seed solutions are agitated until all seeds were thoroughly covered with the chemical solution. The acetone is then allowed to evaporate by air drying the seeds. The seeds are planted in 3-inch (RKN) or 4-inch (SCN) pots containing sandy soil and then the pots are inoculated with 1000 Meloidogyne incognita (RKN) or 1000 Heterodera glycines (SCN) eggs per pot three days after planting. Plants are rated for galling 14 days after egg inoculation for RKN or 28 days after egg inoculation for SCN.

Example 7: Description of Synthesis of the Compounds of the Formulas I to IId

(42) The compounds of this invention of the Formulas I to IId may be prepared using methods known to those skilled in the art. Specifically, the compounds of this invention with Formula Ia can be prepared as illustrated by the exemplary reaction in Scheme 1.

(43) The compounds of this invention of the Formulas I to IId may be prepared using methods known to those skilled in the art. Specifically, the compounds of this invention with Formula Ib can be prepared as illustrated by the exemplary reaction in Scheme 1.

(44) ##STR00038##

(45) The p-methylbenzenesulfonyl hydrazine 11 is reacted with an appropriate aldehyde 1.2 in ethanol to form a corresponding p-methylbenzenesulfonyl hydrazone 1.3. Then, a solution of diazinium salt 1.5 prepared from an appropriate aryl amine 4 is added to the hydrazone 3 in pyridine at 10-15 C. to form a desired 2,5-disubstituted tetrazole of the Formula Ia.

(46) Specifically, the compounds of this invention with Formulae Ic can be prepared as illustrated by the exemplary reaction in Scheme 2. The p-methylbenzenesulfonyl hydrazine 2.1 is reacted with an appropriate aldehyde 2.2 in ethanol to form corresponding p-methylbenzenesulfonyl hydrazone 2.3. Then, the diazinium salt 2.5 solution prepared from appropriate aryl amine 2.4 is added to hydrazone 2.3 in pyridine at 10-15 C. to form a desired 2,5-disubstituted tetrazole of the Formula Ic.

(47) ##STR00039##

(48) Specifically, the compounds of this invention with Formulae IIb can be prepared as illustrated by the exemplary reaction in Scheme 3. The p-methylbenzenesulfonyl hydrazine 3.1 is reacted with an appropriate aryl aldehyde 3.2 in ethanol to form corresponding p-methylbenzenesulfonyl hydrazone 3.3. Then, a solution of diazinium salt 3.5 prepared from appropriate heteroaryl amine 3.4 is added to hydrazone 2.3 in pyridine at 10-15 C. to form a desired 2,5-disubstituted tetrazole of the Formula IIb.

(49) ##STR00040##

(50) Specifically, the compounds of this invention with Formulae Id can be prepared as illustrated by the exemplary reaction in Scheme 4. The appropriate nitrile 4.1 was heated with sodium azide in the presence of ammonium chloride under microwave condition to form the corresponding 5-substituted tetarzole 4.2. An N-arylation of tetrazole 4.2 led to formation of two isomers that could be separated by normal phase chromatography and the desired 2,5-disubstituted tetrazole of the Formula Id could be isolated.

(51) ##STR00041##