Field of the Invention

This invention relates to novel N-(5- isothiazolyl)amide compounds useful as nematicides, insecticides, miticides, and plant fungicides. The present invention also provides nematicidal, insecticidal, miticidal, and fungicidal methods.

There is an acute need for new nematicides, insecticides, miticides, and plant fungicides. Available nematicides typically have high mammalian toxicity and must be used at high rates. A nematicide that can be applied at lower rates and that has lower mammalian toxicity would represent a significant advance.

Mites and insects are developing resistance to the miticides and insecticides in current use. Resistance to insecticides in anthropods is widespread, with at least 400 species resistant to one or more insecticides. The development of resistance to some of the older insecticides, such as DDT, the carbamates, and the organophosphates is well known. But resistance has even developed to some of the newer pyrethroid insecticides and miticides. Similarly, target pathogens are rapidly developing resistance to currently used fungicides. At least 50 species of fungi have developed resistance to the benzimidazole fungicides. Even recently introduced fungicides, like the acylalanines, which initially exhibited excellent control of potato late blight and grape downy mildew in the field, have become less effective because of resistance. Therefore a need exists for new insecticides, miticides, and fungicides, and

particularly for compounds that have new or atypical modes of action.

Summary of the Invention

This invention provides compounds represented by Formula (1), (2), and (3), below:

wherein:

R and R! are each independently independently H, (C1-C4) alkyl, (C1-C4) alkyl optionally substituted with CH2CH(OCH3)2, halo, (C1-C4) alkoxy, or

H ₂ C-<I

^{( H} 2)n, wherein B is O or NR ¹ and n is an integer

1-4; halo(Cι-C4)alkyl; deuterio (C1-C4) alkyl; (C1-C4) acyl; (C1-C4) alkyl-C02-E. wherein E is H, (C1-C4) alkyl, or a cation, such as, for example, sodium, potassium, or ammonium; trifluoroacetyl; alkoxymethyl; hydroxymethyl; formyl; (R ² )2NS(0) _X ; benzyl; or benzyl optionally substituted with (C1-C4) alkyl, (C1-C4) alkoxy, halo, halo (C1-C4) alkyl;

Each R- is independently lower alkyl, aryl, or together form with nitrogen a saturated (C3-C7) ring such as morpholino, piperidinyl, pyrrolidinyl;

x is an integer from 0 to 2;

R- and R ⁴ are each independently H, (C1-C4) alkyl, halogen, I, (C1-C4) alkoxy, halo (C1-C4) alkoxy, (C1-C4

carboalkoxy, halo (C1-C4) alkyl, or together form a saturated or unsaturated six membered carbon ring;

Y-Z together form a (C2-C11) saturated or unsaturated hydrocarbon chain, straight chain or branched, optionally including a hetero atom selected from 0, NR ⁵ , S, SO, SO2, or SiR ⁶ R ⁷ , and optionally substituted with one or more groups independently selected from (C1-C4) alkyl, (C2-C4) alkenyl, (C2-C4) alkynyl, branched (C3-C7) alkyl, (C3-C7) cycloalkyl, (C3-C7) cycloalkenyl, halo, halo (C1-C4) alkyl, halo (C1-C4) alkoxy, hydroxy, or (C1-C4) acyl;

R- is H, (C1-C4) alkyl, or (C1-C4) acyl;

R ⁶ and R ⁷ are independently (C1-C4) alkyl, (C3-C4) branched alkyl, phenyl, or substituted phenyl; or

Y is a bond, CHD, CD2, C=0, or a bivalent hydrocarbon radical one to five carbon atoms long, optionally substituted with (C1-C4) alkyl, (C2-C4) alkenyl, (C2-C4) alkynyl, branched (C3-C7) alkyl, (C3- C7) cycloalkyl, (C3-C7) cycloalkenyl, halo, halo (Ci- C4) alkyl, halo (C1-C4) alkoxy, hydroxy, CN, (C1-C4) acyl, (C1-C4) alkoxycarbonyl, aryloxycarbonyl, hydroxy (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, methylene, methylene optionally substituted with one or more groups independently selected from hydrogen; (C1-C4) alkyl; (C1-C4) alkoxy; SH; S-lower alkyl; H2; NH-lower alkyl or N,N-di-lower alkyl, optionally substituted with carboxy, carboalkoxy, or carboaryloxy; NHOH; NH0- lower alkyl; N-lower alkyl-OH; N-lower alkyl-lower alkl; 0-lower alkyl; OH; morpholino; piperidinyl; pyrrolidinyl; thiomorpholino; or methylene forming part of a (C5-C6) saturated or unsaturated ring optionally

including 1 or 2 hetero atoms selected from 0, S, or NR ⁵ ;

Z is

(a) aryl or

(b) (C3-C8) cycloalkyl or cycloalkenyl, optionally substituted with one or more groups independently selected from (C1-C4) alkyl, (C1-C4) alkoxy, halo (Ci- C4) alkyl, halo (C1-C4) alkoxy, halo, hydroxy, or (Ci- C4) acyl; where

aryl is

(a) a phenyl group optionally substituted with one or more groups independently selected from: halo,

I, (C ₃ -C ₈ ) cycloalkyl,

(C ₃ -C8) cycloalkenyl, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, phenyl, substituted phenyl,

N0 ₂ ,

0 —C "-R8°, where R ⁸ is (C ₁ -C ₇ ) alkyl, halo (Ci- C ₇ ) alkyl, (C ₃ -C ₇ ) branched alkyl, halo (C ₃ -C ₇ ) branched alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (C ₁ -C ₇ ) alkoxy, hydroxy, phenyl, substituted phenyl, phenoxy, or substituted phenoxy,

0 II

—o-c-R ⁸ , wherein R° cannot be hydroxy,

OH,

CN,

SiR ⁹ R ¹⁰ R ⁿ or OSiR ⁹ R ¹⁰ R ⁿ , where R ⁹ ,R ^l ° and R ¹¹ are independently (C ₁ -C ₄ ) alkyl, (C ₃ -C ₄ ) branched alkyl,

phenyl, or substituted phenyl,

NR ¹ R ¹³ , where R ¹² and R ¹³ are independently H, (C ₁ -C ₄ ) alkyl, or (C ₁ -C ₄ ) acyl,

S(0)R ¹⁴ , S0 ₂ R ¹⁴ , or OSO2R ¹⁴ , where R ¹⁴ is

(C ₁ -C ₁₀ ) alkyl, phenyl, or substituted phenyl;

a (C ₁ -C ₁₂ )saturated or unsaturated hydrocarbon chain, straight chain or branched optionally including a hetero atom selected from O, S, SO, S0 ₂ , NR ⁵ , or SiR ⁶ R ⁷ , where R ⁵ , R ⁶ and R ⁷ are as defined above, and optionally substituted with halo, halo (C ₁ -C ₄ ) alkoxy, hydroxy, (C ₃ -C ₈ ) cycloalkyl or cycloalkenyl, (C ₁ -C ₄ ) acyl, phenoxy, substituted phenoxy, phenyl, substituted phenyl, phenylthio, substituted phenylthio, or cyano;

(C ₁ -C ₇ ) alkoxy optionally substituted with halo, phenyl, substituted phenyl, (C3-C ₈ ) cycloalkyl or cycloalkenyl, phenoxy, or substituted phenoxy; or

(C ₁ -C ₇ ) alkylthio optionally substituted with halo, phenyl, substituted phenyl, (C ₃ -C ₈ ) cycloalkyl or cycloalkenyl, phenoxy or substituted phenoxy;

(b) a furyl group of formula (3)

where R ¹⁵ is H, halo, halomethyl, CN, N0 ₂ , (C ₁ -C ₄ ) alkyl, (C ₃ -C ₄ ) branched alkyl, phenyl, (C ₁ -C ₄ ) alkoxy;

(c) a thienyl group of the formula (4)

where R ¹⁶ is H, halo, halomethyl, CN, N0 ₂ , (C ₁ -C ₄ ) alkyl, (C ₃ -C ₄ ) branched alkyl, phenyl, (C ₁ -C ₄ ) alkoxy, or thienyl;

(d) a group of formula (5) or (6)

where R ¹⁵ is as defined in paragraph (b), J is N or CH, and G is 0, NR ¹⁷ , or S, provided that if J is not N then G is NR, where R ¹⁷ is H, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) acyl, phenylsulfonyl, or substituted phenylsulfonyl;

(e) a group selected from

optionally substituted naphthyl, dihydronaphthyl, tetrahydronaphthyl, and decahydronaphthyl;

optionally substituted indolyl;

1,3-benzodioxolyl;

2,6-dimethyl-4-morpholinyl; and

1-adamantyl;

( f ) a group of the formula

wherein m is 4; R-® are independently H, halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, NO2, CN, lower alkyl carbonyl, phenoxy, or substituted phenoxy, provided that at least two of R-® are selected from H and F; and Het is pyridinyl, pyrazinyl, pyrimidinyl, or pyridazinyl, optionally substituted with one or more groups selected from halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, NO2, CN, and lower alkyl carbonyl;

(g) a group of the formula

wherein one of X ² and χ3 is N and the other is CR23.

R ²¹ is -T-R ²² , phenyl, substituted phenyl, (Ci- C10) alkyl, halo, or halo (Ci-Cβ) alkyl, where

T is 0 or S, and

R22 is (C1-C4) alkyl, (C3-C7) branched alkyl, halo (C1-C7) alkyl, halo (C3-C7) branched alkyl, (C1-C4) alkoxy (C1-C4) alkyl, or naphthyl or phenyl, either of which may be optionally substituted with up to three groups selected from halo, (Cχ-Cιo) alkyl, branched (C3-C7) alkyl, halo (C1-C7) alkyl, hydroxy (C1-C7) alkyl, (C1-C4) alkoxy, halo (C1-C4) alkoxy, phenoxy, substituted phenoxy, phenyl, substituted phenyl, CN, NO2, OH, (C1-C4) alkanoyloxy, or benzyloxy;

R ²³ is: H, halo,

I, (C ₃ -C ₈ ) cycloalkyl,

(C ₃ -C ₈ ) cycloalkenyl, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, phenyl, substituted phenyl,

N0 ₂ ,

0 -C ¹¹ -Ra ^a , where R ⁸ is (C ₁ -C ₇ ) alkyl, halo (C C ₇ ) alkyl, (C ₃ -C ₇ ) branched alkyl, halo (C ₃ -C ₇ ) branched alkyl, (C ₃ -C ₇ ) cycloalkyl, halo (C ₃ -C ₇ ) cycloalkyl, (Cι-C ₇ ) alkoxy, phenyl, substituted phenyl, or hydroxy,

acetoxy,

OH,

CN,

SiR ⁹ R ¹⁰ R ⁿ or OSiR ⁹ R ¹⁰ R ⁿ , where R ⁹ ,R ¹⁰ and R ¹¹ are independently (C ₁ -C ₄ ) alkyl, (C ₃ -C ₄ ) branched alkyl,

phenyl, or substituted phenyl,

NR ¹² R ¹³ , where R ¹² and R ¹³ are independently H, (C ₁ -C ₄ ) alkyl, or (C ₁ -C ₄ ) acyl,

S(0)R ¹⁴ , or S0 ₂ R ¹⁴ , where R ¹⁴ is (C ₁ -C ₁₀ ) alkyl, phenyl, or substituted phenyl;

a (C ₁ -C ₁₂ ) saturated or unsaturated hydrocarbon chain, straight chain or branched optionally including a hetero atom selected from 0, S, SO, S0 ₂ , NR ⁵ , or SiR ⁶ R ⁷ , where R ⁵ , R ⁶ and R ⁷ are as defined above, and optionally substituted with halo, halo (C ₁ -C ₄ ) alkoxy, hydroxy, (C ₃ -C ₈ ) cycloalkyl or cycloalkenyl, (C ₁ -C ₄ ) acyl, phenoxy, substituted phenoxy, phenyl, substituted phenyl, phenylthio, substituted phenylthio, or cyano;

(C ₁ -C ₇ ) alkoxy optionally substituted with halo, phenyl, substituted phenyl, (C ₃ -C ₈ ) cycloalkyl or cycloalkenyl, phenoxy, or substituted phenoxy; or

(C ₁ -C ₇ ) alkylthio optionally substituted with halo, phenyl, substituted phenyl, (C ₃ -C ₈ ) cycloalkyl or cycloalkenyl, phenoxy or substituted phenoxy.

W is 0, S(0)y, wherein y is an integer from 0 to 2, or NR ²⁴ ;

G is (C1-C4) alkyl, aryl, (C1-C4) acyl, NR ²⁵ R ²⁶ , deuterio (C1-C4) alkyl, halo (C1-C4) alkyl, benzyl, or benzyl optionally substituted with (C1-C4) alkyl, (Ci- C4) alkoxy, halo, halo (C1-C4) alkyl; or

W-G together are halo, SH, or NR ²⁵ R ²⁶ ;

R ²⁴ is H, OH, (C1-C4) alkyl, (C1-C4) alkoxy, aryl,

(C1-C4) acyl, NR ²⁵ R ²⁶ , benzyl, or benzyl optionally substituted with (C1-C4) alkyl, (C1-C4) alkoxy, halo, halo (C1-C4) alkyl; and

R ²⁵ and R ²⁶ are independently H, (C1-C4) alkyl, aryl, acyl, or together form with nitrogen a saturated

(C3-C7) ring such as morpholino, piperidinyl, pyrrolidinyl.

The invention also provides a method of inhibiting a nematode population which comprises applying to the locus of a nematode, a nematode inactivating amount of a compound of the Formula (1), (2) , or (3) as defined above.

The invention also provides a method of inhibiting an insect or mite population which comprises applying to the locus of the insect or arachnid an effective insect or mite inactivating amount of a compound of Formula (1), (2), or (3) .

The invention also provides a method of inhibiting plant pathogens which comprises applying an effective amount of a compound of Formula (1), (2), or (3) to a locus of the pathogen.

Detailed Description of the Invention

Unless otherwise indicated, the terms below are defined as follows:

The term "halo" or "halogen" refers to a F, CI, or Br atom.

The terms "alkyl", "alkoxy", "acyl", "haloalkyl", "haloalkoxy", "alkylsulfinyl", and "alkylsulfonyl" refer to straight chain and branched chain groups.

The terms "aryl", "Ar", "substituted phenyl", "substituted phenoxy", "substituted phenylthio", and "substituted phenylsulfonyl" refer to such groups wherein the phenyl ring is substituted with up to three groups independently selected from halo, I, (C ₁ -C ₁₀ ) alkyl, branched (C ₃ -C ₆ ) alkyl, halo (C ₁ -C ₇ ) alkyl, hydroxy (C ₁ -C ₇ ) alkyl, (C ₁ -C ₇ ) alkoxy, halo (C ₁ -C ₇ ) alkoxy, phenoxy, substituted phenoxy, phenyl, substituted phenyl, N0 ₂ , OH, CN, (C ₁ -C ₄ ) alkanoyl, benzoyl, (C ₁ -C ₄ ) alkanoyloxy, or benzoyloxy.

The terms "substituted naphthyl" and "substituted indolyl" refer to these ring systems substituted with one or more groups independently selected from halo, halo (C ₁ -C ₄ ) alkyl, CN, N0 ₂ , (C ₁ -C ₄ ) alkyl, (C ₃ -C ₄ ) branched alkyl, phenyl, (C ₁ -C ₄ ) alkoxy, or halo (C ₁ -C ₄ ) alkoxy.

The term "carbocyclic ring" refers to a saturated or unsaturated carbocyclic ring containing five or six carbon atoms.

The term "unsaturated hydrocarbon chain" refers to a hydrocarbon chain containing one or more sites of unsaturation.

The term "HPLC" refers to a high pressure liquid chromatography.

The term "T C" refers to thin layer chromatography.

The term "bivalent hydrocarbon radical" refers to bivalent radicals derived from normal alkanes by removal of hydrogen atoms from each of the two terminal carbon atoms of the chain, e.g. methylene, ethylene, trimethylene, tetramethylene, etc.

The term "substituted amino" refers to an amino group that is substituted with one or two (C ₁ -C ₄ ) alkyl groups or one (C ₁ -C ₄ ) alkanoyl group.

The term "lower alkyl" refers to (C1-C6) straight hydrocarbon chains and (C3-C6) branched and cyclic hydrocarbon groups.

The terms "lower alkenyl" and "lower alkynyl" refer to (C2-C6) straight hydrocarbon chains and (C3- Cβ) branched hydrocarbon groups containing at least one unsaturated bond.

The terms "lower alkoxy" and "lower alkylthio" refer to O-lower alkyl and S-lower alkyl groups.

The term "haloalkyl" refers to lower alkyl groups substituted with one or more halo atoms.

The term "deuterioalkyl" refers to lower alkyl groups substituted with one or more deuterium atoms.

The term "methylene" refers to =CH2-

Unless otherwise indicated, when it is stated that a group may be substituted with one or more

substituents selected from an identified class, it is intended that the substituents may be independently selected from the class. Throughout this document, all temperatures are given in degrees Celcius, and all percentages are weight percentages unless otherwise stated.

Preferred Embodiments

Preferred compounds of Formula (1), (2), or (3) include the following classes:

(a) compounds of Formula (1), (2), or (3) wherein Y is CH2;

(b) compounds of Formula (1), (2), or (3) wherein Z is a substituted phenyl group as defined in paragraph (a) of the foregoing definition of aryl;

(c) compounds of Formula (1), (2), or (3) wherein Z is a phenyl group substituted with a (C ₂ -C ₄ ) alkoxy group;

(d) compounds of Formula (1), (2), or (3) wherein Z is a phenyl group subsituted with a (C ₃ -C ₇ ) branched alkoxy group;

(e) compounds of Formula (1), (2), or (3) wherein Z is a phenyl group substituted with a halo (C ₂ -C ₄ ) alkoxy group;

(f) compounds of Formula (1), (2), or (3) wherein Z is a phenyl group substituted with a halo

(C ₃ -C ₇ ) branched alkoxy group;

(g) compounds of Formula (1), (2), (3) wherein Z is a phenyl group substituted with a phenoxy or substituted phenoxy group;

(h) compounds of any of the foregoing groups (c) to (g) wherein the phenyl group is monosubstituted in the 4-position;

(i) compounds of Formula (1) , (2) , or (3) wherein R ³ is (C ₁ -C ₄ ) alkyl and R ⁴ is H or halo, or more preferred are compounds of Formula (1), (2), (3) wherein R ³ is methyl or ethyl and R ⁴ is bromo or chloro;

(j) compounds of Formula (1) or (3) wherein R or Rl is ethyl, methoxymethyl, or ethoxyethyl; and

(k) compounds of Formula (1) or (3) wherein Y is methylene, optionally substituted with NH2, NH- lower alkyl, or N,N-di-lower alkyl, optionally substituted with carboxy, carboalkoxy, or carboaryloxy.

Synthesis

The compounds of this invention are made using well known chemical procedures. The required starting materials are commercially available, or they are readily synthesized using standard procedures.

For example, compounds of Formula (1) can be prepared using the process illustrated in Scheme 1:

Scheme 1

Z — y

In this procedure, the acid derivative (6) is mixed with an excess molar amount of thionyl chloride and the resulting mixture is heated at reflux for approximately one to three hours to yield the acid 5 chloride derivative (5) . The amine derivative (4) is dissolved in a sufficient quantity of an organic solvent, such as, for example xylene or toluene, with heating. The acid chloride (5) is added with continued heating for one to twelve hours, then the resulting JO mixture is allowed to cool. Separation utilizing standard techniques yields the desired compounds of Formula (1).

Compounds of Formula (1) and (3) can be prepared using the process illustrated below:

solvent solvent

The above compounds of Formula (1) and (3) are obtained by treatment of the carbonyl derviative (A) in the presence of a phase transfer reagent, such as, for example, benzyl triethylammonium bromide, a base, such

as, for example, sodium hydroxide, in amthylene chloride/water mixture.

The above compounds of formula (1) and (3) can also be obtained by heating the amide A with a dialkyl sulfate in the presence of potassium carbonate in a inert solvent such as, for example, benzene.

The above compounds of Formula (1) and (3) can also be obtained under non-aqueous conditions using sodium or potassium hydride and alkyl halide in an aprotic solvent such as, for example, ethyl ether or tetrahydrofuran.

Compounds of Formula (1) where Y is substituted with methylene or substituted methylene,

can be prepared by using the processes illustrated in Scheme 2:

Scheme 2

Methylene derivatives (3) wherein the methylene is substituted with N(CH3)2 may be prepared by treating the N-(5-isothiazolyl)amide (10) with the appropriate N ,N-dialkyIcarboxamide di-alkylacetal in the presence of toluene with heating. The N, -dialky1 derivatives (11) can be converted to their NHR ²⁴ derivatives by treating with the appropriate amine to give (12). The N-(5-isothiazolyl)amides (10) can also be converted to S,S-ketene acetals (14) and optionally, to cyclic systems (15).

Compounds of Formula (2) where W = 0, S, or NR ²⁴ can be prepared using the process illustrated in Scheme 3:

Scheme 3

The carbonyl derivative (1) is treated with Lawesson's reagent to give the thione (9) which can be converted to amidines where W-G = NR ²⁵ R ²⁶ or NHR ²⁵ with primary and secondary amines. The thione can also be S-alkylated using a dialkyl sulfate or alkyl iodide in the presence of potassium carbonate to give compounds (2) where W=S and G is alkyl, which in turn, can be reacted with nucleophiles such as, for example, OR", NH2R ²⁴ , NHR ² R ²⁵ , or NR ² R ²⁵ R ²⁶ to give other compounds of (2).

EXAMPLES

The following Tables I, II, and III identify compounds of Formula (1), (2), and (3), respectively, that were prepared by the processes illustrated in the foregoing schemes.

823392

823503

824752

826232

826321

826073

826326

504594

504595

- 34 -

SUBST/πiTESHEET(R _U 26)

Examples illustrating preparation of exemplary compounds follow below.

EXAMPLE 1 H ₃ c ^.

The starting acid (28.2 g, 0.187 mole) was added to H2O (200 ml). The insolubles were filtered and the filtrate's pH was adjusted to 10.0 with the addition of 2N NaOH (94 ml). The mixture was stirred for five minutes, then extracted with ethyl ether (1 x 230 ml). The organic layer was separated and the aqueous layer was saturated with NaCl, then extracted with ethyl ether (2 x 230 ml). The extracts were combined and given a brine wash, dried over MgSθ4, then concentrated under vacuum to give the product as a yellow oil (18.9 g).

EXAMPLE 2

Na ^CH 3CH ₂ . CH ₃

CH ₃ CH ₂ CN - / \

H ₂ N CN

Sodium (11.5 g, 0.5 g-atoms) and propionitrile (66g, 1.2 moles) were stirred in toluene (250 ml). There was a slight exotherm and a solid began separating. After one hour, gradual heating was applied until reflux was attained after about three hours. Reflux was maintained for one hour and the mixture was then allowed to cool, resulting in an extremely thick mass. The mixture was then washed with ethyl ether (300 ml) and placed in a large crystallizing dish and began smoking as the ethyl ether evaporated. Water (500 ml) was added and the product

was extracted into ethyl ether (2 x 500 ml). The two extracts were combined and dried over MgSθ4 and the ethyl ether was removed under vacuum, leaving a brown oil, which solidified. Product was then recrystallized from heptane-ethyl acetate (10:1) yielding about 22 g (m.p. 38-40°).

EXAMPLE 3

The starting nitrile (7.0 g, 0.063 mole), ethanol (35 ml), tetrahydrofuran (THF) (35 ml), and triethylamine (2.0 g, 0.02 mole) were placed in a Carius tube, cooled, and hydrogen sulfide (2.8 g, 0.082 mole) was bubbled in. The resulting mixture was placed in an oven at 115-120° for five hours. The solvent was removed under vacuum and the resulting mixture was dissolved in CH2CI2 (250 ml) and washed with water (50 ml). Thin layer chromatography indicated mostly starting material, so the mixture was dissolved in ethanol (50 ml). To this solution was added 30% H2O2 (20 ml),and water (100 ml), then most of the ethanol was removed under vacuum. The product was extracted with CH2CI2 (500 ml) and this extract was further extracted twice with IN NCI (2 x 100 ml). The acidic extracts were combined and washed with CH2CI2 (150 ml) and then made basic with ION NaOH. The resulting solution was then extracted with two portions of CH2CI2 (2 x 100 ml) and combined and dried over MgSθ4.The solvent was removed under vacuum to leave a semi-solid. T-60 NMR indicated mostly desired product which was then recrystallized from hexane to yield about 100 mg (m.p. 84-88°).

EXAMPLE 4

The starting nitrile (6.0 g) was dissolved in pyridine (20 ml) in a Carius tube. Hydrogen sulfide (2.8 g) was bubbled in. and the resulting mixture was placed in an oven at 120° for five hours. The solvent was removed under vacuum and the resulting mixture was dissolved in CH2CI2 (250 ml) and washed with water ( ml). Thin layer chromatography showed more extensive reaction and more impurities than material of Example 3. The solvent was removed under vacuum. To the product was added ethanol (100 ml) and 30% H2O2 (20 ml) . The resulting mixture became very hot. Water (200 ml) was then added and the mixture was extracted with two portions of CH2CI2 (2 x 150 ml). The extracts were combined and extracted with IN HC1 (2 x 100 ml). These extracts were combined and washed with CH2CI2 (150 ml) and before making basic with 30% NaOH. The product was then extracted twice with CH2CI2 (2 x 150 ml) and the combined extracts were dried over MgS04. Thin layer chromatography indicated product identical to that of Example 3, except for an additional spot which may be pyridine. This sample was combined with the product of Example 3 and chromatographed on silica gel, starting with CH2CI2 and eluting the product with 5% ethyl acetate. Product was recrystallized from hexane to give 240 mg of white crystals (m.p. 99-100°).

EXAMPLE 5

The starting amine (18.9 g, 0.166 mole) was slurried in CCI4 (600 ml) under an atmosphere of N2. N-chlorosuccinimide (NCS) (22.1 g, 0.166 mole) was added to the slurry over a five minute period at 30-44° and stirred at room temperature overnight. Analysis by TLC silica gel 1:1 heptane/ethyl acetate showed product and no starting material present. The mixture was then diluted with ethyl ether (100 ml) and the solids were filtered. The filtrate was concentrated under vacuum to a red oil which was dissolved in ethyl acetate (200 ml) and washed with H2O (2 x 200 ml). The organic layer was separated, given a brine wash, dried over MgSθ4, then concentrated under vacuum to a brown oil which crystallized to a brown solid (22.0 g).

EXAMPLE 6

O O

II ₊ J . I

CH ₃ CH ₂ COCH ₂ CH ₃ CH ₃ CN CH ₃ CH ₂ CCH ₂ CN

60% sodium hydride (40 g, 1 mole) in mineral oil was tirred under reflux in dry tetrahydrofuran (500 ml) as a solution of ethyl propionate (51 g, 0.5 mole) and acetonitrile (41 g, 1 mole) was added dropwise to the mixture. This mixture was maintained at reflux overnight. The mixture was then cooled and isopropanol (60 ml) was added dropwise. The solvent was removed under vacuum and after adding water (400 ml), the product was extracted with hexane (400 ml) and 1:1 hexane:ethyl ether (400 ml). Concentrated HC1 was added to the combined extracts to lower the pH to 6, and the solution was then extracted with two portions of ethyl ether (2 x 300 ml). The combined extracts were washed with water and the resulting solution was dried over MgS04. The ethyl ether was removed under vacuum to leave product as an oil (30 g).

EXAMPLE 7

To the product of Example 6 was added dry THF (270 ml) and ethanol (200 ml). Of this solution, 70 ml was put in each of two Carius tubes. The tubes were cooled and NH3 (2.1 g) was added followed by H2S (3.0 g) . The tubes were sealed and warmed in hot water to check for leaks, then placed in an oven at 110° for four hours, after which the mixture was cooled and the solvent removed under vacuum. To this product was added CH2CI2 (300 ml) and the mixture was washed with two portions of water (2 x 100 ml). The mixture was then dried over MgS04 and the solvent was removed under vacuum. Ethanol (100 ml) and 30% H2O2 (15 ml) was then added. Starch-iodide paper showed no excess H2O2. Another portion of H2O2 (30 ml) was added before an excess was obvious. Water (50 ml) was then added to the mixture and the ethanol was removed under vacuum. The aqueous layer was made slightly basic and product was extracted into CH2CI2. This product was then extracted with two portions of IN HC1 (2 x 100 ml), leaving black CH2CI2 solution. The combined aqueous extracts were extracted with CH2CI2 (100 ml) before making basic with NaOH and extracting product into CH2CI2. The product was dried over MgSθ4 and solvent was removed under vacuum to leave 3-7 g of dark oil.

EXAMPLE 8

The starting amine (3.7 g, 0.0289 mole) was dissolved in chloroform (100 ml) at room temperature under an atmosphere of N2, and the chlorine (2.25 g. 0.0317 mole) was dissolved in chloroform (120 ml). The amine solution was chilled to 15° and the chlorine solution was added dropwise over a 15 minute period at 15°, and a dark precipitate formed. The cooling bath was removed and the solution was heated to 50° for one hour. Heat was removed and saturated sodium bicarbonate solution (100 ml) was carefully added.

After shaking, the organic layer was separated, given a brine wash, dried over MgS04, then concentrated under vacuum to yield a dark oil (3.7 g). Chromatography using a Michel-Miller low pressure silica gel column and eluting with heptane/ethyl acetate, combining like fractions, and concentrating under vacuum yields a dark brown oil (2.8 g) .

EXAMPLE 9

The amine (3.73 g, 0.0327 mole) was slurried in

CCI4 (100 ml) at room temperature under an atmosphere of N2. The N-bromosuccinimide (1 equivalent) was added portionwise to the amine slurry over a 10 minute period at 24-30°, and the mixture was stirred for 1.5 hours. Analysis by TLC silica gel (1:1 heptane/ethyl acetate) showed product and some remaining starting amine. Heating at 70° was applied for 1.5 hours. Analysis by TLC showed mainly product. The mixture was cooled to room temperature and ethyl ether (about 100 ml) was added. The resulting mixture was chilled to 5° and filtered to yield solid material (2.6 g) which was

discarded. The solution was concentrated under vacuum to yield a red solid (6.5 g) . This material was dissolved in ethyl acetate (80 ml) and washed with H2O (2x80 ml). The organic layer was separated and given a brine wash, then dried over MgS04, and concentrated under vacuum to yield a tan solid (5.24 g).

EXAMPLE 10

The amine (4.0 g, 0.0312 mole) was slurried in CCI4 (130 ml) at room temperature under an atmosphere of N2- The N-chlorosuccinimide (4.25 g, 0.0312 mole) was added portionwise over a 5 minute period at 25-37°, and the mixture was stirred at room temperature for 1.5 hours. Analysis by TLC silica gel (1:1 heptane/ethyl acetate) showed no starting material remaining. The mixture was then diluted with ethyl ether (250 ml) and filtered. The filtrate was washed twice with water. The organic layer was separated and given a brine wash, then dried over MgSθ4, and concentrated under vacuum to yield a brown oil (4.65 g) .

EXAMPLE 11

(a,a,a-Trifluoro-p-tolyl) acetic acid (1.20 g, 0.0059 mole) was dissolved in thionyl chloride (25 ml) and heated at reflux for one hour, then concentrated under vacuum to a pale yellow oil. Analysis by NMR

showed starting material remaining and the mixture was then retreated with additional thionyl chloride (25 ml) and concentrated under vacuum to give the acid chloride as a pale yellow oil (1.26 g). The amine ( 0.73 g, 0.0049 mole) was dissolved in warm xylenes (40 ml) and heating was continued in an oil bath wherein the acid chloride (1.26 g, 0.0057 mole), dissolved in xylenes (10 ml), was added to the amine solution dropwise over a five minute period under an atmosphere of N2 at 80- 100°. A precipitate immediately formed. The slurry was then heated at 140° for one hour and all the precipitate dissolved. The resulting mixture was stirred overnight at room temperature. Analysis by TLC 9:1 CH2Cl2/et yl acetate silica gel showed a faint spot remaining for the starting amine. The mixture was then concentrated under vacuum to a tan solid (1.6 g). Chromatography using a Michel-Miller low pressure silica gel column and eluting with 1% ethyl acetate/CH2Cl2, pooling like fractions, then concentrating under vacuum yielded a light tan solid (1.2 g) recrystallized from ethyl ether.

EXAMPLE 12

The starting acid (1.20 g, 0.0051 mole) was slurried in dichloromethane (20 ml) under an atmosphere of N2- Thionyl chloride (1 ml, 0.0137 mole) was added and the resulting mixture was heated at reflux temperature for 1.5 hours, then concentrated under vacuum to give the acid chloride as a yellow oil. The amine (0.65 g, 0.0034 mole) was slurried at room temperature in CH2CI2 (100 ml) under an atmosphere of

_M 2, an _d TE _{A (} t iethy1amine) (0.52 g, 0-0051 raoie) was _d issolve _d in _t o _t his mixture. The above acid chloride, _d issolve _d in _C H2CI2 (10 ml) was added dropwise to the amine mix _t ure over a ten minute period at 23-27°, and " _t he resulting mixture was stirred at room temperature for one hour. Analysis by TLC silica gel 1:1 heptane/ethyl acetate showed starting amine remaining, so the mix _t ure was heating at reflux temperature overnight and analysis by TLC silica gel 3:1 in hep _t ane/ethyl acetate showed a very faint spot for the s _t ar _t ing amine. _A fter standing, the reaction mixture was poure _d in _t o a separation funnel with H2O (40 ml) where _t he mixture was shaken and the organic layer was separa _t e _d ana wasnea wito. toe following: 40 oil 2N HCl, ;- 40 mi H2O, 40 mi saturated NaHC03, and 20 mi brine. The organic layer was separated and dried over MgSθ4, then concentrated under vacuum to give a dark oil (about 1.2 g ₎ . Chromatography using a Michel-Miller low pressure silica gel column and eluting with 5% in ethyl acetate/CH2Cl2, combining like fractions, then concentrating under vacuum yielded a tan glass, which was crystallized from ethyl acetate/heptane then filtered to yield a light tan solid (0.29 g).

EXAMPLE 13

-D

The starting acid (1.25 g, 0.0048 mole) was dissolved in thionyl chloride (25 ml) and heated at reflux temperature for two hours, then concentrated under vacuum to give the acid chloride as a yellow oil

(1.34 g). The amine (0.80 g, 0.0041 mole) was dissolved in toluene (80 ml) and TEA (0.50 g) was added under an atmosphere of N2. The above acid chloride, dissolved in toluene (10 ml) was added to the amine mixture over a ten minute period at 30-35°, then the resulting mixture was heated overnight at 85°. Analysis by TLC silica gel 2:1 ethyl acetate/heptane showed a very faint spot remaining for the starting amine. The mixture was then concentrated under vacuum to an oil (1.8 g) . Chromatography using a Michel- Miller low pressure silica gel column and eluting with 2% ethyl acetate/CH2Cl2, combining like fractions and concentrating under vacuum yielded a solid product (0.84 g).

EXAMPLE 14

Anthranilonitrile (29.5 g, 0.25 mole) and triethylamine (25.3 g, 0.25 moles) were stirred in pyridine (160 ml), as H2S was bubbled in for one hour. TLC 1:1 CH2CI2:ethyl acetate showed starting material remaining. The addition of H2S was continued for an additional 30 minutes and the mixture was stirred for one hour, then poured onto ice-H2θ (700 ml). The solid was collected and washed with H2O (31 g) (m.p. 119- 121°).

EXAMPLE 15

The s _t ar _t ing aminobenzene-thioamide (19.3 g) was stirre _d in ethanol (200 ml), heating enough for the nitrile _t o _d issolve. To this solution was added 30% H2 _O 2 dropwise, while the reaction was monitored by silica gel TLC in ethyl acetate. When starting material was gone, H2O (200 ml) was added. The product was collected by filtration and recrystallized from ethanol-water to give a solid (12.5 g) (m.p. 165-166°). A second crop was also collected (3.6 g) (m.p. 163- 165 ° ) .

EXAMPLE 16

A mixture of the amide (1.0 g, 0.00234 mole), potassium carbonate (1.15 g, 0.00829 mole), water (5 ml), dichloromethane (10 ml), triethylbenzylammonium bromide (TEBA, 0.68 g, 0.0025 mole), methyl iodide (3 ml), and 10% sodium hydroxide (3 ml) was stirred vigorously a _t room temperature overnight. The contents were dilute _d with dichloromethane, the layers passed through phase-separating paper, and were stripped. The residue was triturated under ether and the mixture was filtered. The filtrate was washed once with brine and was dried with MgS04. Concentration gave 960 mg of material which was chromatographed on dry pack silica. Using heptane-ethyl acetate mixtures, compound (A) was obtained as a solid (370 mg, m.p. 84-86.5°), and compound ₍ B ₎ was also obtained as a solid (280 mg, m.p. 145-147°).

EXAMPLE 17

A solution of the amide (0.30 g, 0.703 mole) and dimethylformamide dimethylacetal (DMFDMA) (0.17 g, 1.41 mole) in toluene (5 ml) was heated at reflux for about seven hours, was cooled, and was stripped to dryness. The residue was then triturated under a few mis of ether to afford 200 mg of product (m.p. 194-200°).

EXAMPLE 18

It)

A solution of the ketoamide (250 mg, 0.567 mmol)and methoxyamine hydrochloride (250 mg) was heated for 4 hours at approximately 60° and was then allowed to cool. The solution was concentrated to a residue 75 which was taken up in cold water and ether. The ethereal was then washed once with brine and was dried. Concentration gave 230 mg of product.

EXAMPLE 19

_cl 0 CHiCONHNHi _cl

H ₃ C _N ,Y _s κ 1,-s:H ₂ - - _° θ w ^cr 3 ^~ ^ _CΛ r _αH ~ ^H3C _H _ _{s N i} - ^c -c _SOT 'O _COCBJ ^o -0- ^CT3

20 A solution of the ketoamide (250 mg, 0.567 mmol), acetic hydrazide (100 mg, 1.35 mmol), and a 0.41 M solution of dry hydrogen chloride (3.28 ml, 1.35 mmol) in ethanol all in 10 ml of ethanol was heated for about three hours at 60°-70° and was allowed to cool. The

ethanol was removed in vacuo and the residue was partitioned between ethyl acetate/ether/brine. The layers were separated and the organic phase was washed once with brine and was dried. Concentration gave 280 l mg of a yellow solid. This material was recrystallized from ethyl acetate to afford 70 mg of dimeric product (m.p. 233°-240°). The filtrate was concentrated and the residue was chromatographed on silica gel (230-400 mesh) to afford 140 mg of monomer hydrozone product. 0 M.P. 161-174 (dec). (Also obtained 10 mg of higher Rf material) .

EXAMPLE 20

A solution of the ketoamide (250 mg, 0.567 mmol), 5 1,2-ethanedithiol (0.062 ml, 69 mg, 0.74 mmol), and a 1.46 M solution of hydrogen chloride (0.39 ml, 0.57 mmol) in ethanol, all in 3 to 5 ml ethanol was heated at reflux overnight. The dithiol (0.062 ml) was then added and the contents were refluxerd for 7 hours. The 0 solution was diluted with ether and was washed twice with 0.1 N NaOH and once with brine and was dried. Concentration gave 300 mg which was chromatographed on silica (230-400 mesh) using heptane/dichloromethane eluants to afford 100 mg of compound.

15 EXAMPLE 21

aqueous N-c g •'

CH3OH CHNHCH ₂ C0 ₂ H

To a solution of the benzyl ester (1.3 g, 2.16 mmol) in 15 ml of ethanol was added potassium carbonate (0.30 g, 2.17 mmol) followed by 2-4 ml of water. After several hours, the mixture (precipitate present) was poured onto ice water which was then adjusted to pH 3 with dilute hydrochloric acid. The contents were extracted twice with ethyl acetate, the combined organics were washed once with brine and were dried. Concentration gave 1.0 g of product which was triturated with heptane/ethyl acetate to afford 680 mg of material. M.P. 177-183 (dec). This material was dissolved at reflux in approximately 50:50 heptane:ethyl acetate (10 ml). Upon cooling, the solution was stirred and was treated with about 4 ml heptane. Precipitation eventually occurred. The solid was collected to afford 270 mg of compound. M.P. 195- 196 (dec).

EXAMPLE 22

To a mixture of the acid (0.185 mg, 0.361 mmol) in about 5 ml of methanol was added 2N sodium hydroxide (0.18 ml, 0.36 mmol). The mixture immediately became a solution (yellow) but within 1 to 2 minutes began to show a white precipitate which accumulated over time. Collection and drying in vacuo at 50°-60° for one hour gave 100 mg compound.

EXAMPLE 23

C ₂ H ₅ TΓ '.NHCOCF ₃ CH ₂ C1 ₂ N-S

A solution of the isothiazoleamine (2.0 g, 15.6 mmol) was added to dichloromethane (25 ml). The mixture was cooled in ice and trifluoroacetic anhydride (3.4 ml, 5.06 g, 24.1 mmol) was added dropwise. The solution was allowed to warm to room temperature and then stirred overnight. Concentration gave 3.0 g of compound.

EXAMPLE 24

To a solution at 50°-65° of the amide (3.0 g, 13.4 mmol) in about 60 ml of sulfuric acid was added dropwise about 12 ml of fuming nitric acid. An exotherm was noted during the addition of the first 3 to 4 ml. The solution was heated for an additional 3 hours at 70°-75° and was then cooled. The solution was added to 500 ml ice water and the precipitate was

collected and air-dried to give 2 .45 g of compound (m.p. 115°-118°) .

EXAMPLE 25

H ₂

A mixture of the amide (2.35 g, 8.73 mmol) and potassium carbonate (2.65 g, 19.2 mmol) in 40 ml of water and 10 ml of methanol was stirred at room temperature overnight. The mixture was adjusted to pH 6-7 with 1.0 N HC1 and was then extracted three times with ether., The combined organics were then dried (MgS04). Concentration gave 1.47 of comound. M.P. 131°-132.5°.

EXAMPLE 26

A solution of thionyl chloride (1.96 g, 16.5 mmol) and phenylacetic acide (2.45 g, 8.27 mmol) in 20 ml of dichloromethane was heated at reflux for three hours and was then stripped to dryness. The liquid was then taken up in 5-10 ml of dry toluene, was added dropwise to a mixture of the amine (1.43 g, 8.26 mmol) in 20 ml of toluene. The contents were then heated at reflux overnight for 36 hours. The solution was stripped to dryness and was chromatographed on silica gel (230-400 mesh) to afford 1.22 g ofcompound (m.p. 135°-138°) .

Insecticide, Miticide and Nematicide Utility

The compounds of Formula (1), (2), or (3) show activity against a number of insects and mites. More specifically, the compounds show activity against melon aphid, which is a member of the insect order Homoptera . Other members of the Homoptera include leafhoppers, planthoppers, pear pyslla, apple sucker, scale insects, whiteflies, spittle bugs as well as numerous other host specific aphid species. Activity has also been observed against greenhouse thrips, which are members of the order Thysanoptera. The compounds also show activity against Southern armyworm, which is a member of the insect order Lepidoptera. Other typical members of this order are codling moth, cutworm, clothes moth, Indianmeal moth, leaf rollers, corn earworm, European corn borer, cabbage worm, cabbage looper, cotton bollworm, bagworm, eastern tent caterpillar, sod webworm, and fall armyworm.

The compounds of Formula (1), (2), or (3) are useful for reducing populations of insects and mites, and are used in a method of inhibiting an insect or mite population which comprises applying to a locus of the insect or mite an effective insect- or mite-inactivating amount of a compound of Formula (1) , (2), or (3). The "locus" of insects or mites is a term used herein to refer to the environment in which the insects or mites live or where their eggs are present, including the air surrounding them, the food they eat, or objects which they contact. For example, plant-ingesting insects or mites can be controlled by applying the active compound to plant parts, which the insects or mites eat, particularly the foliage. It is

contemplated that the compounds might also be useful to protect textiles, paper, stored grain, or seeds by applying an active compound to such substance. The term "inhibiting an insect or mite" refers to a decrease in the numbers of living insects or mites; or a decrease in the number of viable insect or mite eggs. The extent of reduction accomplished by a compound depends, of course, upon the application rate of the compound, the particular compound used, and the target insect or mite species. At least an insect-inactivating or mite-inactivating amount should be used. The terms "insect-inactivating amount" and "mite-inactivating amount" are used to describe the amount, which is sufficient to cause a measurable reduction in the treated insect or mite population. Generally an amount in the range from about 1 to about 1000 ppm active compound is used.

Compounds were tested for insecticidal, miticidal and nematicidal activity against eight species. Results are reported in the following table, wherein the following abbreviations are used:

ALH refers to aster leafhopper

BAW refers to beet armyworm

CA refers to cotton aphid

NEM refers to peanut root knot nematode

SCR refers to southern corn root worm

TB refers to tobacco budworm

TSSM refers to two spotted spider mite

GECR refers to German cockroach

In conducting evaluations of insecticidal activity, each test compound was formulated as a 400 ppm solution, and this solution was then diluted with water to give lesser concentrations. The 400 ppm solution was prepared by combining 19.2 mL of .05% solution of Tween 20 (polyoxyethylene (20) sorbitan monolaurate) in water with a solution of 8 mg of the compound in 0.8 mL of acetone/EtOH (9/1).

Activity against aster leafhopper (Macrosteles fascifrons ) was tested as follows. The test was run using concentrations of 400 ppm and 50 ppm. One ounce plastic cups containing a cotton wick was sprayed with 0.4 mL of formulated material using a flat-fan nozzle. The excess moisture was allowed to evaporate. Then five to ten carbon dioxide anesthetized adult leafhoppers were added to each cup. The cups were capped and held at room temperature for 24 hours. Percent mortality was then determined.

Activity against beet armyworm ( Spodoptera exiqua) was evaluated as follows. The test is run using concentrations of 400 ppm and 50 ppm. A general purpose lepidoptera artificial diet was diluted to half strength with a 5% non nutritive agar. 8 mL of this diet material was dispensed into one ounce diet cups. One hour prior to treatment, 35 to 40 eggs were dispensed onto the diet surface. The cups were then sprayed with formulated material through a flat-fan nozzle. Treated cups were air dried prior to sealing with plastic caps. The cups were held for 6 days at room temperature. Activity was then rated based on the

total number of live and dead larvae, and on the size of live larvae.

Activity against cotton aphid (Aphis gossypii ) and two spotted spider mite ( Tetranychus urticae) was evaluated as follows. Golden crookneck squash plants were grown to the expanded cotyledon stage (about 6 to 8 days) . The plants were infested with cotton aphids and two spotted spider mites 16 to 24 hours before application of the test material by transfer of infested foliage cut from a stock colony. Immediately prior to spray application of the test material the transfer foliage is removed from the squash plants. The test is run using concentrations of 400 ppm and 50 ppm. The plants are sprayed with test solution using an atomizing sprayer at 17 psi. Both surfaces of the leaves are covered until runoff, and then allowed to dry. Activity of each compound was determined three days after treatment. Activity was rated as a percent based on the mites/aphids present in plants sprayed with solvent alone.

Activity against peanut root knot nematode (Meloidogyne arenaria) was evaluated as follows. Five untreated cucumber seeds are placed into the bottom of a clear one ounce cup, 20 g of clean white sand is added, and the cups were sprayed while rotating on a pedestal allowing 1.0 mL of a 400 ppm solution to be deposited on the sand. To each cup was dispensed 2.5 to 3.0 mL of deionized water containing 300 to 500 nematodes. The cups were held for 10 to 12 days in an environmental growth chamber at a temperature of 76 to 85 °F and ambient humidity of 50 to 60%. After 10 to 12 days the cups were evaluated by inverting the cup and observing nematode mortality and feeding damage to the cucumber plants.

Activity on Southern corn rootworm ( Diabrotica undecimpuctata howardi Barber) was evaluated by adding one L of test solution containing a predetermined concentration of test compound to a cup containing a kernel of corn in 16 g of sterile soil. This produces a soil concentration of 24 ppm. After 1.5 to 2 hours of drying, five 4th instar corn rootworm larvae were added to the individual cups. Mortality was measured at 3-4 days by emptying the cup onto a pan and inspecting the soil for live rootworms.

Activity against tobacco budworm ( Heliothis virescens ) was evaluated as follows. A general purpose lepidoptera artificial diet was diluted to half strength with a 5% non nutritive agar. 8 mL of this diet material was dispensed into each one ounce diet cup. One hour prior to treatment 18 to 20 eggs were dispensed onto the diet surface. The cups were then sprayed with formulated material through a flat-fan nozzle. The test was run using concentrations of 400 ppm and 50 ppm. Treated cups were air dried prior to sealing with plastic caps. The cups were held for 6 days at room temperature. Activity was then rated based on the total number of live and dead larvae, and on the size of live larvae.

Activity against German cockroach ( Blattella germanicus ) was evaluated as follows. 8 mL of alfalfa based green insect diet material was dispensed into a one ounce diet cup. The cups were then sprayed with formulated material through a flat-fan nozzle. The test was run using concentrations of 400 ppm and 50 ppm. Treated cups were air dried for 24 hours and infested with five late third or early fourth instar German cockroaches. The cups were capped and held for seven days in an environmental growth chamber at a

temperature of 76-85°C. Activity was then rated based on the total number of live and dead insects.

The following results are expressed as percent of or anisms controlled.

Page blank upon filing

* indicates testing at 200 ppm.

Fungicide Utility

The compounds of the present invention have been found to control fungi, particularly plant pathogens. When employed in the treatment of plant fungal diseases, the compounds are applied to the plants in a disease inhibiting and phytologically acceptable amount. The term "disease inhibiting and phytologically acceptable amount", as used herein, refers to an amount of a compound of the invention which kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 1 to 1000 ppm, with 10 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type formulation employed, the method of application, the particular plant species, climate conditions and the like. A suitable application rate is typically in the range from 0.10 to 4 lb/A. The compounds of the invention may also be used to protect stored grain and other non-plant loci from fungal infestation.

Greenhouse Tests

The following experiments were performed in the laboratory to determine the fungicidal efficacy of the compounds of the invention.

The test compounds were formulated for application by dissolving 50 mg of the compound into 1.25 ml of solvent. The solvent was prepared by mixing 50 ml of "Tween 20" (polyoxyethylene (20) sorbitan monolaurate emulsifier) with 475 ml of acetone and 475 ml of etha-

nol. The solvent/compound solution was diluted to 125 ml with deionized water. The resulting formulation contains 400 ppm test chemical. Lower concentrations were obtained by serial dilution with the solvent-surfactant mixture.

The formulated test compounds were applied by foliar spray. The following plant pathogens and their corresponding plants were employed.

Pathogen Designation Host in following

Table

Erysiphe graminis tritici ERYSGT wheat

(powdery mildew)

Pyricularia oryzae (rice PYRIOR rice blast)

Puccinia recondite PUCCRT wheat tritici (leaf rust)

Leptosphaeria nodor m LEPTNO wheat

(glume blotch)

Plasmopara viticola PLASVI grape

(downy mildew)

The formulated technical compounds were sprayed on all foliar surfaces of the host plants ( or cut berry) to past run-off . single pots of each host plant were placed on raised, revolving pedestals in a fume hood. Test solutions were sprayed on all foliar surfaces . All treatments were allowed to dry and the plants were inoculated with the appropriate pathogens within 2-4 hours .

The following table presents the activity of typical compounds of the present invention when evaluated in this experiment . The effectiveness of

test compounds in controlling disease was rated using the following scale.

0 = not tested against specific organism

0-19% control at 400 ppm + = 20-89% control at 400 ppm ++ = 90-100% control at 400 ppm +++ = 90-100% control at 100 ppm

Compositions

The compounds of Formula (1) , (2) , or (3) may be applied in the form of compositions which are important embodiments of the invention, and which comprise a compound of Formula (1), (2), or (3) and a phytologically-acceptable inert carrier. The compositions are either concentrated formulations which are dispersed in water for application, or are dust or granular formulations which are applied without further treatment. The compositions are prepared according to procedures and formulae which are conventional in the agricultural chemical art, but which are novel and important because of the presence therein of the compounds of this invention. Some description of the formulation of the compositions will be given, however, to assure that agricultural chemists can readily prepare any desired composition.

The dispersions in which the compounds are applied are most often aqueous suspensions or emulsions prepared from concentrated formulations of the com¬ pounds. Such water-soluble, water-suspendable or emulsifiable formulations are either solids usually known as wettable powders, or liquids usually known as TΠΠIsif-iaHi^ ronrentrates or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the active compound, an inert carrier and surfactants. The concentration of the active compound is usually from about 10% to about 90% by weight. The inert carrier is usually chosen from among the attapulgite clays, the ontmorillonite clays, the diatomaceous

Mrl- s . nr +he* nnrϊ f i pH Ri' l i rsf-ps . Kff active s r a a.ri i-R . roτnr>τrs i n from ahfMit ft - % ^• »-<-> shnnt- 1 0% r»f

the wettable powder, are found among the sulfonated lignins, the condensed naphthalenesulfonates, the naphthalenesulfonates, the alkylbenzenesulfonates, the alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of the compounds comprise a convenient concentration of a compound, such as from about 50 to about 500 grams per liter of liquid, equivalent to about 5% to about 50%, dissolved in an inert carrier which is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially the xylenes, and the petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are chosen from conventional nonionic surfactants, such as those discussed above.

Aqueous suspensions comprise suspensions of water-insoluble compounds of this invention, dispersed in an aqueous vehicle at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the compound, and vigorously mixing it into a vehicle comprised of water and

surfactants chosen from the same types discussed above. Inert ingredients, such as inorganic salts and synthetic or natural gums, may also be added, to increase the density and viscosity of the aqueous

vehicle. It is often most effective to grind and mix the compound at the same time by preparing the aqueous mixture, and homogenizing it in an implement such as a sand mill, ball mill, or piston-type ho ogenizer.

The compounds may also be applied as granular compositions, which are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the compound, dispersed in an inert carrier which consists entirely or in large part of clay or a similar inexpensive substance. Such compositions are usually prepared by dissolving the compound in a suitable solvent, and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound, and crushing and drying to obtain the desired granular particle size.

Dusts containing the compounds are prepared simply by intimately mixing the compound in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock and the like. Dusts can suitably contain from about 1% to about 10% of the compound.

It is equally practical, when desirable for any reason, to apply the compound in the form of a solution in an appropriate organic solvent, usually a bland petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.

Insecticides and miticides are generally applied in the form of a dispersion of the active ingredient in a liquid carrier. It is conventional to refer to

application rates in terms of the concentration of active ingredient in the carrier. The most widely used carrier is water.

The compounds of Formula (1), (2), or (3) can also be applied in the form of an aerosol composition. In such compositions the active compound is dissolved or dispersed in an inert carrier, which is a pressure-generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve. Propellant mixtures comprise either low-boiling halocarbons, which may be mixed with organic solvents, or aqueous suspensions pressurized with inert gases or gaseous hydrocarbons.

The actual amount of compound to be applied to loci of insects and mites is not critical and can readily be determined by those skilled in the art in view of the examples above. In general, concentrations of from 10 ppm to 5000 ppm of compound are expected to provide good control. With many of the compounds, concentrations of from 100 to 1500 ppm will suffice. For field crops, such as soybeans and cotton, a suitable application rate for the compounds is about 0.5 to 1.5 lb/A, typically applied in 50 gal/A of spray formulation containing 1200 to 3600 ppm of compound. For citrus crops, a suitable application rate is from about 100 to 1500 gal/A spray formulation, which is a rate of 100 to 1000 ppm.

The locus to which a compound is applied can be any locus inhabited by an insect or arachnid, for example, vegetable crops, fruit and nut trees, grape vines, and ornamental plants. Inasmuch as many mite species are specific to a particular host, the

foregoing list of mite species provides exemplification of the wide range of settings in which the present compounds can be used.

Because of the unique ability of mite eggs to resist toxicant action, repeated applications may be desirable to control newly emerged larvae, as is true of other known acaricides.