N-heterocycl1c nltro anilines as fungicides

This invention provides new anilino heterocyclic compounds that are useful as agricultural chemicals. More specifically, the invention provides new anilino heterocyclic compounds that are useful as plant fungicides, new plant fungicide compositions utilizing the new compounds, and new methods of combating plant pathogens utilizing the new compounds and compositions.

European Patent Application' 478,974A discoses insecticidal use of compounds of the formula

R Hetaryl—N ζ -R

R N0 ₂ R

where hetaryl is thienyl, thiazolyl, isothiazolyl, or thiadiazolyl. There is no disclosure of fungicidal activity for these compounds.

In one aspect, the present invention provides a method of inhibiting plant pathogens which comprises applying an effective amount of a compound of formula (1) :

Het-N-Ar

R ⁴ (1)

or a salt thereof, wherein:

Ar is a group of the formula

R ¹ and R ² are independently H, NO ₂ . halo, Ci-Cβ alkyl, C ₁ -C6 haloalkyl, C ₂ -C6 alkenyl, C2-C6 alkynyl, C3.-C ₄ alkylsulfonyl, phenylsulfonyl, substituted phenylsulfonyl, Sθ ₂ NR ⁵ R ⁶ , C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C ₄ alkyl hio, Ci- C ₄ haloalkylthio, COOR ⁵ , or CN, provided R ¹ is not CN, or

CONR ⁵ R ⁶ , where R ⁵ and R ⁶ are H, C ₁ -C ₄ alkyl, C ₃ -C ₇ alkenyl, C3- C ₇ cycloalkyl or cycloalkenyl, or R ⁵ and R ⁶ together with the nitrogen atom to which they are attached form a 5-7 member ring containing up to three additional heteroatoms selected from 0, N, and S; R ³ is H, halo, R ⁵ R ^e , C ₁ -C6 haloalkyl, Cι~ Cβ alkoxy, C ₁ -C ₆ haloalkoxy, C -Cζ alkylthio, Ci-Cg haloalkylthio, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, benzyloxy, substituted benzyloxy, benzylthio, or substituted benzylthio;

R4 is H, C00R ⁷ , C0NR ⁵ R ⁶ , CH0,'C0R ⁷ , or SO2R ⁷ , S02NR ⁵ R ⁶ , where R ⁵ and R ⁶ are as defined above and R ⁷ is C1-C8 alkyl, C ₃ -C ₈ alkenyl, C ₂ -C ₈ branched alkyl, C1-C4 haloalkyl, aralkyl, phenyl, or substituted phenyl;

Het is a group selected from:

where

Q is S or 0;

R ¹⁰ is H, halo, Ci-Cδ alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₈ branched alkyl or alkenyl, C ₃ -C7 cycloalkyl or cycloalkenyl, NO ₂ , CΝ, SCΝ, CO ₂ H, COΝR ⁵ R ⁶ where R ⁵ and R ⁶ are as defined above, CO ₂ R ⁷ where R ⁷ is as defined above, or S(0)mR^ where m is 0,1,or 2 and R ⁷ are as defined above.

.R ¹¹ is H, halo, C ₁ -C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₈ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, aralkyl, (C3-C7 cycloalkyl)methyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, S(0) _m R ⁷ , OR ⁷ ,

R ⁵ Q ^' R ⁵ R ⁵ I M i l

NHR ⁷ , NR ⁵ R ⁶ , NR ⁷ R ⁷ , NH2, R ⁵ R ⁶ N—N—, R ⁷ —C~N—N—,

R ⁵ R ⁵ 0 R ⁵ R ⁵ - c ' ' II I I _c , _n

R ⁵ R ⁶ N-C—N—N—, R ⁷ —s—N—N—; where m, Q, R ⁵ , R ⁶ , and R' are II II

Q 0 as defined above;

R ¹² is H, halo, CN, CO ₂ H, halo C ₁ -C3 alkyl, phenyl, substituted phenyl, CONR ⁵ R ⁶ , or CO2R ⁷ where R ⁵ , R ⁶ , and R ⁷ are as defined above;

R ¹³ is H, halo, CN, CO ₂ H, halo C ₁ -C3 alkyl, phenyl, substituted phenyl, CONR ⁵ R ⁶ , or CO ₂ R ⁷ where R ⁵ , R ⁶ , and R ⁷ are as defined above;

R ¹⁴ is Ci-Cβ alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 branched alkyl or alkenyl, Ci-Cβ haloalkyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, thienyl, substituted thienyl, furyl, substituted furyl, or aralkyl;

R ¹⁵ is H, halo, NO ₂ , CN, CO ₂ H, CONR ⁵ R ⁶ , or CO ₂ R ⁷ where R ⁵ , R ⁶ , and R ⁷ are as defined above;

R ¹⁶ is H, halo, Cχ-C8 alkyl, C2-C8 alkenyl, C2-C8 .alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C7 cycloalkyl or cycloalkenyl, Ci-Cβ haloalkyl, CN, NO ₂ , Ci-Cs alkoxy, Ci-Cβ haloalkoxy, Ci-Cs haloalkylthio, phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, pyridyl, substituted pyridyl, aralkyl, phenoxy, or substituted phenoxy;

R ¹⁷ is H, halo, Ci-Cβ alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cβ haloalkyl, CN, NO ₂ , Ci-Cβ alkoxy, Ci-Cs haloalkoxy, Ci-Cβ haloalkylthio, phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, ■pyridyl, substituted pyridyl, aralkyl, phenoxy, or substituted phenoxy;

R ¹⁸ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C7 cycloalkyl or

cycloalkenyl, Ci-Cs haloalkyl, CN, NO ₂ , Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs haloalkylthio, phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, pyridyl, substituted pyridyl, aralkyl, phenoxy, or substituted phenoxy, S(0) _n R', where n is 0-3, and R ¹ is H, Ci-Cs alkyl, C2-C8 alkenyl, C ₃ -C ₆ branched alkyl or alkenyl, phenyl, .substituted phenyl, aralkyl, CF3, or NR ⁵ R ⁶ where R ⁵ and R ⁶ are as defined above;

R ¹⁹ is Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, phenyl, substituted phenyl, or aralkyl;

R ²⁰ is H, halo, Ci-Cβ alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Cχ-C ₆ haloalkyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, phenyl, or substituted phenyl;

R ²¹ and R ²¹ ' are Ci-Cs alkyl, C2-C8 alkenyl, C3-C8 alkynyl, C ₃ -C _S branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, C ₁ -C ₆ haloalkyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, phenyl, or substituted phenyl, aralkyl, COR ⁷ , CR ⁷ 'R ⁷ 'COOR ⁷ , CR ⁷ 'R ⁷ 'CONR ⁵ R ⁶ , Or S(0) _m R ⁷ / where m and R ⁷ are as defined above and R ⁷ ' is H or C ₁ -C ₃ alkyl;

R ²² is H, Ci-Cβ alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3- C _δ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cβ haloalkyl, aralkyl, Ci-Cg alkoxy, Ci-Cβ haloalkoxy, Cχ-Cζ alkylthio, Ci-Cε haloalkylthio, (C ₅ -C ₇ -cycloalkyl)methyl, halo, CN, SCN, NO ₂ , NR ⁵ R ⁶ , phenyl, substituted phenyl, phenoxy, substituted phenoxy, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl; and

R ²³ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 .alkynyl, C ₃ -C ₈ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cβ haloalkyl, NO ₂ , CN, SCN, CO ₂ H, CONR ⁵ R ⁶ where R ⁵ and R ⁶ are as defined above, CO ₂ R ⁷ , S(0)mR ⁷ where m

and R ⁷ are as defined above, phenyl, substituted phenyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, or aralkyl.

The invention also provides novel compounds of the formula (1) :

Het-N-Ar

R ⁴ (1)

and salts thereof, wherein:

R ¹ and R ² are independently H, NO ₂ , halo, C ₁ -C6 alkyl,

Ci-Cδ haloalkyl, C ₂ -C ₆ alkenyl, C ₂ -C6 alkynyl, C ₁ -C ₄ alkylsulfonyl, phenylsulfonyl, substituted phenylsulfonyl, ^• Sθ ₂ -NR ⁵ R ^β , C ₁ -C ₄ alkoxy, C ₁ -C ₄ haloalkoxy, C ₁ -C4 alkylthio, Ci- C ₄ haloalkylthio, COOR ⁵ , or CN, provided R ¹ is not CN, or CONR ⁵ R ⁶ ;

R ³ is H, halo, 1SIR ⁵ R ⁶ , Ci-Cβ haloalkyl, Ci-Cβ alkoxy, Ci-Cε haloalkoxy, Ci-Cg alkylthio, C ₁ -C6 haloalkylthio, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, benzyloxy, substituted benzyloxy, benzylthio, or substituted benzylthio;

R ⁴ is H, COOR ⁷ , CONR ⁵ R ⁶ , CHO, COR ⁷ , SO2R ⁷ , or Sθ2NR ⁵ R ⁶ ;

R ⁵ and R ⁶ are H, C ₁ -C ₄ alkyl, C ₃ -C ₇ alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, or R ⁵ and R ⁶ together with the nitrogen atom to which they are attached form a 5-7 member ring containing up to three additional heteroatoms selected from 0, N, and S;

R ⁷ is C1-C8 alkyl, C3-C ₈ alkenyl, C3-C ₈ branched alkyl, C1-C4 haloalkyl, aralkyl, phenyl, or substituted phenyl;

Het is a group selected from:

where

Q is S or 0;

R ¹² is H, halo, CN, CO ₂ H, halo C ₁ -C ₃ alkyl, phenyl, substituted phenyl, CONR ⁵ R ⁶ , or CO ₂ R ⁷ where R ⁵ , R ⁶ , and R ⁷ are as defined above;

R ¹³ is H, halo, CN, CO ₂ H, halo C ₁ -C ₃ alkyl, phenyl, substituted phenyl, CONR ⁵ R ⁶ , or CO ₂ R ⁷ where R ⁵ , R ⁶ , and R ⁷ are as defined above;

R ¹⁴ is Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 branched alkyl or alkenyl, Ci-Cs haloalkyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, thienyl, substituted thienyl, furyl, substituted furyl, or aralkyl;

R ¹⁵ is H, halo, NO ₂ , CN, CO ₂ H, CONR ⁵ R ⁶ , or CO ₂ R ⁷ where R ⁵ , R ⁶ , and R ⁷ are as defined above;

R ¹⁶ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cs haloalkyl, CN, NO ₂ , Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs haloalkylthio, phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, pyridyl, substituted pyridyl, aralkyl, phenoxy, or substituted phenoxy;

R ¹⁷ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C7 cycloalkyl or cycloalkenyl, Cχ-Cs haloalkyl, CN, NO ₂ , Ci-Cs alkoxy, C -Cs

haloalkoxy, Ci-Cs haloalkylthio, phenyl, substituted phenyl, thienyl, substituted thienyl, furyl, substituted furyl, pyridyl, substituted pyridyl, aralkyl, phenoxy, or substituted phenoxy;

R ¹⁸ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cs haloalkyl, CN, NO2, Ci-Cs alkoxy, Ci-Cs haloalkoxy, Ci-Cs haloalkylthio, phenyl, substituted phenyl, thienyl, substituted thienyl,. furyl, substituted furyl, pyridyl, substituted pyridyl, aralkyl, phenoxy, or substituted phenoxy, S(0) _n R', where n is 0-3, and R' is H, Ci-Cs alkyl, C2-C8 alkenyl, C ₃ -C ₆ branched alkyl or alkenyl, phenyl, substituted phenyl, aralkyl, CF ₃ , or NR ⁵ R ⁶ where R ⁵ and R ⁶ are -as defined above;

R ¹⁹ is Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C6 branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, phenyl, substituted phenyl, or aralkyl;

R ²⁰ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cβ haloalkyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, phenyl, or substituted phenyl;

R ²¹ and R ²¹ ' are Ci-Cs alkyl, C2-C8 alkenyl, C3-C8 alkynyl, C ₃ -C ₆ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-C _δ haloalkyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, phenyl, substituted phenyl, aralkyl, COR ⁷ , CR ⁷ 'R ⁷ 'COOR ⁷ , CR ⁷ 'R ⁷ 'CONR ⁵ R ⁶ , or S(0) _m R ⁷ , where m, R ⁵ , R ⁶ , and R ⁷ are as defined above, and R ⁷ ' is H or C ₁ -C ₃ alkyl;

R ²² is H, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-

C8 branched alkyl or alkenyl, C3-C7 cycloalkyl or cycloalkenyl,- C±-Cβ haloalkyl, aralkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkylthio, C1-C6 haloalkylthio, (C5-C7 cycloalkyl)methyl, halo/ CN, SCN, N02, phenyl, substituted ^" phenyl, phenoxy, substituted phenoxy, pyridyl, substituted

pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, or NR ⁵ R ⁶ where R ⁵ and R ⁶ are as defined above; and

R ²³ is H, halo, Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C ₃ -C ₈ branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, Ci-Cβ haloalkyl, N0 ₂ , CN, SCN, C0 ₂ H, CONR ⁵ R ⁶ , CO ₂ R ⁷ , COR ⁷ , S(0) _m R ⁷ , phenyl, substituted phenyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl, or aralkyl, where m, R ⁵ , R ⁶ , and R ⁷ are as defined above;

provided that the following compounds are excluded:

-a) 2-methyl-5-(2,4-dinitrophenylamino) -1,3,4-oxadiazole;

b) N-methyl-5-trifluoromethyl-2- (2-chloro-4, 6- dinitroanilino) -1,3,4-thiadiazole;

c) Ν-methyl-5-t-butyl-2- (2-chloro-4, 6-dinitroanilino) -1,3,4- thiadiazole;

d) 3- (2,4-dinitroanilino) -4-nitro-5-phenylpyrazole; and

e) 3-(2,6-dinitro-p-toluidino) -4-nitro-5-phenylpyrazole.

Another aspect of the invention comprises compounds having the following general formula (10) :

wherein:

Q is S or 0;

R ¹ and R ² are independently H, NO ₂ , halo, Ci-Cβ alkyl, C1-C6 haloalkyl, C ₂ -C6 alkenyl, C ₂ -Cg alkynyl, C1-C4 alkyIsulfonyl, phenylsulfonyl, substituted phenylsulfonyl,

Sθ2NR ⁵ R ⁶ , C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, Cι~ C4 haloalkylthio, COOR ⁵ , CONR ⁵ R ⁶ ,or CN, provided R ¹ is not CN;

R ³ is H, halo, NR ⁵ R ⁶ , Ci-Cβ haloalkyl, Ci-Cβ alkoxy, Ci-Cβ haloalkoxy, Ci-Cβ alkylthio, Ci-C _δ haloalkylthio, phenoxy, substituted phenoxy, phenylthio, substituted phenylthio, benzyloxy, substituted benzyloxy, benzylthio, or substituted benzylthio;

R ⁵ and R ⁶ are H, C ₁ -C ₄ alkyl, C3-C7 alkenyl, C3-C7 cycloalkyl or cycloalkenyl, or R ⁵ and R ⁶ together with the. nitrogen atom to which they are attached form a 5-7 member ring containing up to three additional heteroatoms selected from 0, N, and S;

R ¹¹ ' is Ci-Cs alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 branched alkyl or alkenyl, C ₃ -C ₇ cycloalkyl or cycloalkenyl, aralkyl, (C ₃ -C ₇ cycloalkyl)methyl, halo Ci-Cs alkyl, phenyl, substituted phenyl, pyridyl, substituted pyridyl, furyl, substituted furyl, thienyl, substituted thienyl; and

R ²⁴ and R ² 'are independently Cl or Br.

The ^' invention also provides a method of inhibiting plant pathogens which comprises applying an effective amount of a compound of formula (10) to the locus of the pathogen.

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) or (10) 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) or (10) .

Detailed Description of the Invention

Throughout this document, all temperatures are given in degrees Celsius, and all percentages are weight percentages unless otherwise stated.

The term "halo" refers to a F, Cl, Br, or I atom.

The term "haloalkyl" refers to straight chain, branched chain, and cyclo groups.

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

The term "substituted phenyl" refers to phenyl substituted with Ci-Cg alkyl, C ₂ -C ₇ alkenyl, C ₂ -C ₇ alkynyl, C ₃ - C ₇ branched alkyl, C ₃ -C ₇ cycloalkyl, Cχ-Cg alkoxy, Ci-Cg alkylthio, halo, hydroxy, NO ₂ , Ci-Cg haloalkyl, Cι~Cg haloalkoxy, Ci-Cg haloalkylthio, CN, phenyl, substituted phenyl, phenoxy, substituted phenoxy, C ₁ -C ₄ alkanoyloxy, benzyloxy, or S(0) _m Alk, where m=0-2.

The terms "substituted benzyl", "substituted benzyloxy", and "substituted benzylthio" refer to such groups that are ring substituted with Ci-Cg alkyl, C ₂ -C ₇ alkenyl, C ₂ -C ₇ alkynyl, C ₃ -C ₇ branched alkyl, C3-C7 cycloalkyl, Ci-Cg alkoxy, Cχ-Cg alkylthio, halo, hydroxy, NO ₂ , Cχ-Cg haloalkyl, C ₁ -C ₆ haloalkoxy, Cχ-Cg haloalkylthio, CN, phenyl, substituted phenyl, phenoxy, substituted phenoxy, C ₁ -C ₄ alkanoyloxy, benzyloxy, or S(0)mAlk, where m-=0-2.

The terms "substituted phenoxy" and "substituted phenylthio", and "substituted phenylsulfonyl" refer to such groups that are substituted with Cχ-C ₆ alkyl, C ₂ -C ₇ alkenyl, C ₂ -C ₇ alkynyl, C ₃ -C ₇ branched alkyl, C ₃ -C ₇ cycloalkyl, Cχ-Cg alkoxy, Cχ-Cg alkylthio, halo, hydroxy, NO ₂ , Cχ-Cg haloalkyl, Cχ-Cg haloalkoxy, Cχ-Cg haloalkylthio, CN, phenyl, substituted phenyl, phenoxy, substituted phenoxy, C ₁ -C ₄ alkanoyloxy, benzyloxy, or S(0) _m Alk, where m=0-2.

The term "aralkyl" refers to such groups wherein the aryl portion is phenyl or substituted phenyl and the alkyl portion

CH,

I ³ is C ₁ -C ₃ straight chain or C ₂ -C ₃ branched chain, e. g. — CH— ,

I ³ I ^{2 5}

— c — , or — CH— .

CH ₃

Substituted pyridyl, substituted furyl, and substituted thienyl refer to such groups substituted with halo, halo C ₁ -C ₄

alkyl, CN, NO ₂ , C ₁ -C ₄ alkyl, C3-C ₄ branched alkyl, phenyl, (Cχ~ C ₄ ) alkoxy, or halo (Cχ-C ₄ ) alkoxy.

The invention includes salts of the compounds of formulas 1, 10 and 10A. Specifically contemplated are compounds of those formulas wherein R ⁴ is

(a) an alkali metal or alkaline earth metal ion such as sodium, potassium, calcium, magnesium, barium,

(b) an ammonium ion whose nitrogen can carry up to four C ₁ -C ₄ alkyl, hydroxy Cχ-C ₄ alkyl, phenyl, substituted phenyl, benzyl, or substituted benzyl substituents,

(c) a phosphonium ion,

(d) a sulfonium ion,

(e) an equivalent of a transition metal cation, especially manganese, iron, copper, and zinc.

As will be apparent to those skilled in the art, for compounds having pyridyl, furyl, or thienyl as an optional substituent, as in the case where R ¹⁸ , R ²⁰ , or R ²¹ is such a group, a variety of other heteroaryl groups are functionally equivalent to the named heteroaryl groups, and substitution of these equivalents is within the scope of the invention. A preferred heteroaryl group is 2-pyridyl.

Compounds of formula (1) wherein Het is a group of formula (2) are N-(substituted phenyl)-5-isothiazolamines.

Compounds of formula (1) wherein Het is a group of formula (3) and Q is S are N-(substituted phenyl)-4- isothiazolamines. Compounds of formula (1) wherein Het is a group of formula (3) and Q is 0 are N-(substituted phenyl) -4- isoxazolamines.

Compounds of formula (1) wherein Het is a group of formula (4) and Q is S are N-(substituted phenyl)-3- isothiazolamines. Compounds of formula (1) wherein Het is a

group of formula (4) and Q is 0 are N-(substituted phenyl)-3- isoxazolamines.

Compounds of formula (1) wherein Het is a group of formula (5) and Q is S are N-(substituted phenyl)-2- thiazolamines. Compounds of formula (1) wherein Het is a group of formula (5) and Q is O are N-(substituted phenyl) -2- oxazolamines.

Compounds of formula (1) wherein Het is a group of formula (6) and Q is S are N-(substituted phenyl)-1,3,4- thiadiazol-5-amines and N-(substituted phenyl)-1,3,4- thiadiazol-2-amines. Compounds of formula (1) wherein Het is a group of formula (6) and Q is 0 are N-(substituted phenyl)- 1,3,4-oxadiazol-5-amines and N-(substituted phenyl)-1,3,4- oxadiazol-2-amines.

Compounds of formula (1) wherein Het is a group of formula (7) and Q is S are N-(substituted phenyl)-1,2,5- thiadiazol-3-amines. Compounds of formula (1) wherein Het is a group of formula (7) and Q is 0 are N-(substituted phenyl)- 1,2,5-oxadiazol-3-amines.

Compounds of formula (1) wherein Het is a group of formula (8) and Q is S are N-(substituted phenyl)-1,2,4- thiadiazol-5-amines. Compounds of formula (1) wherein Het is a group of formula (8) and Q is 0 are N-(substituted phenyl)- 1,2,4-oxadiazol-5-amines.

Compounds of formula (1) wherein Het is a group of formula (9) are N-(substituted phenyl)-5-pyrazolamines.

Preferred Embodiments

The compounds of formulas (1) and (10) have demonstrated useful activity against plant pathogens, however certain classes of these compounds are preferred for reasons of greater efficacy. More specifically, -the following classes of compounds are preferred:

1) isothiazole derivatives of formula (1) wherein Het is a group of formula (2);

2) compounds of class 1 wherein R^-0 i _s halo;

3) compounds of class 2 wherein R^-0 is bromo;

4) compounds of class 1 wherein R^O is iodo;

5) compounds of any one of classes 1 to 4 wherein R^-l is C1-C4 alkyl, C3-C4 branched alkyl, C ₃ -C ₇ cycloalkyl, phenyl, or phenyl subsituted with- C1-C4 alkyl, halo, Cχ-Cg haloalkyl;

6) compounds of any one of classes 1 to 5 wherein Ar is a substituted phenyl group of the formula

wherein n is 1 or 2;

7) compounds of any one of classes 1 to 5 wherein Ar is DTI;

8) compounds of any one of classes 1 to 5 wherein Ar is o-DTI;

9) compounds of formula (10) wherein Ar is DTI;

10) compounds of formula (10) wherein R ²⁴ and R ²⁴ ' are Cl.

The following specific compounds are preferred for their exceptional activity:

3-methyl-N-(2,4-dinitro-6-(trifluoromethyl)phenyl)iso- thiazol-5-amine;

4-bromo-3-methyl-N-(2,4-dinitro-6-(trifluoromethyl)- phenyl)isothiazol-5-amine;

N- (4,4-dichloro-3-methyl-5(4H)-isothiazolylidene)-2,4- dinitro-6- (trifluoromethyl)benzenamine;

4-chloro-3-methyl-N-(2,4-dinitro-6-(trifluoromethyl)- phenyl)isothiazol-5-amine;

3-methyl-4-nitro-N- (2,4-dinitro-6-(trifluoromethyl)- phenyl)isothiazol-5-am.ine;

3-(3-methylpheny1)-N-(2, -dinitro-6-(trifluoromethyl)- phenyl)isothiazol-5-amine;

4-bromo-3-ethyl-N-(2,4-dinitro-6-(trifluoromethyl)- phenyl)isothiazol-5-amine;

4-bromo-3-(3-methylphenyl)-N-(2,4-dinitro-6- (trifluoromethyl) henyl)isothiazol-5-amine;

3-t-butyl-N-(2,6-dinitro-4-(trifluoromethyl)phenyl)- isothiazol-5-amine;

4-bromo-3-t-butyl-N-(2,4-dinitro-6-(trifluoromethyl)- phenyl)isothiazol-5-amine;

4-bromo-3-methyl-N-(2,6-dinitro-4-(trifluoromethyl)- phenyl)isothiazol-5-amine;

N-(4-bromo-4-dichloro-3-ethyl-5(4H)-isothiazolyl-idene) 2,4-dinitro-6-( rifluoromethyl)benzenamine;

N-(4, -dichloro-3-n-butyl-5(4H)-isothiazolylidene)-2,4- dinitro-6-(trifluoromethyl)benzenamine;

N-(4,4-dibromo-3-methyl-5(4H)-isothiazolylidene)-2,4- dinitro-6-(trifluoromethyl)benzenamine;

4-bromo-3-ethyl-N-(2,6-dinitro-4-(trifluoromethyl) - phenyl)isothiazol-5-amine;

4-chloro-3-methyl-N-(2,6-dinitro-4-(trifluoromethyl)- phenyl)isothiazol-5-amine;

N-(4,4-dichloro-3-t-butyl-5(4H)-isothiazolylidene)-2,6- dinitro-4-(trifluoromethyl)benzenamine;

4-chloro-3-t-butyl-N-(2,6-dinitro-4-(trifluoromethyl)- phenyl)isothiazol-5-amine;

3-methyl-4-iodo-N-(2,6-dinitro-4-(trifluoromethyl)- phenyl)isothiazol-5-amine;

3-t-butyl-4-bromo-N-(2,6-dinitro-4-(trifluoromethyl)- phenyl)isothiazol-5-amine;

4-bromo-3-cyano-N-(2,6-dinitro-4-(trifluoromethyl)- phenyl)isothiazo1-5-amine;

1-(3-trifluoro-methylphenyl)-4-cyano-N-(2,6-dinitro-4- (trifluoro-methyl)phenyl)pyrazol-5-amine;

N-(2,6-dinitro-4- (trifluoromethyl)phenyl)-2-phenyl- l,2,4-thiadiazol-5-amine;

N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-2-phenyl- 1,3,4-thiadiazol-5-amine;

N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-4-phenyl-- thiazol-2-amine;

N-(2,6-dinitro-4-(trifluoromethyl)phenyl)-3-phenyl- isoxazol-5-amine;

N- (2,6-dinitro-4-(trifluoromethyl)phenyl)-4-bromo-3- pheny1isoxazo1-5-amine;

3-t-butyl-4-bromo-N- (2,6-dinitro-4-cyanophenyi)- isothiazol-5-amine;

1-(3-nitrophenyl)-4-phenyl-N-(2,6-dinitro-4- (trifluoro¬ methyl)phenyl)pyrazol-5-amine.

The following tables identify representative compounds of formulas (1) and (10) , together with characterizing physical and biological activity. Abbreviations used in the table include the following: 0 refers to phenyl, Me refers to methyl, Et. refers to ethyl, n-Bu refers to n-butyl, t-Bu refers to t-butyl, Bz refers to benzyl. The term "DTI" refers to the group

The term "o-DTI" refers to the group

An explanation of the biological data reported in the table is given hereinafter in the section titled "Greenhouse Tests."

Tefrle l_\

R*

Compound RIO .11

.10 .11

Compound

I

.10 .11

Compound

I 00

_> 10 .11

Compound

•.a I

.10 .11 melting POWD RICE LEAF DOWN LEAF DOWN

Compound point MDEW BLAST RUST MDEW BLOT MDEW °c S U S G

Table IB

Compound RIO jll

I to

Compound RIO .11 melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW

I N-.

I

Table 2A

Compound »10 .11 Ar melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW

°C S UASH GRAPE

I t - I

Tc le 2P

Compound R 10 R" Ar LEAF DOWN BLOT MDEW GRAPE

I t -t->

Compound ιlθ R 11 Ar

Table 3

Compound ,13 R 12 Ar melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW °C S UASH GRAPE

Table 4A

Compound Q .14 .15 Ar R4 melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW

°C S UASH GRAPE

l to

I

Compound Q R 14 -15 Ar

I t

00 I

Table 5A

Compound R ⁱ⁶ .17 Ar

I to vO

I

Compound .16 RI ⁷ Ar 4 melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW °C S UASH GRAPE

Table 5B

Compound 1I6 »17 Ar

l co

Table 6A

Compound Q .18 Ar melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW °C S UASH GRAPE

I O t I

Table 7

Table 9ft

Compound R ² 1 _R 22 R23 Ar

CO

-o-

I

Table 9P

Compound R ² 1 _R 22 R23 Ar R« melting point

°C

Compound 21 R2 _J 23 Ar melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW

°C S UASH GRAPE

CO

Compound R21 ,22 R23 Ar melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW

°C S UASH GRAPE

Table 8C

t-'

Compound R ² 1' ,22 R 3 Ar melting POWD RICE LEAF DOWN LEAF DOWN point MDEW BLAST RUST MDEW BLOT MDEW

°C S UASH GRAPE

Table 9A

Compound R 4 R 4 ill' MP POWD RICE LEAF DOWN LEAF DOWN °C MDEW BLAST RUST MDEW BLOT MDEW S UASH GRAPE

I O vO I

Compound R24 R 4 ' Rll-

I o

I

Table 9B

Compound _R 24 _R 24' _R ll' R ² R ³ MP POWD RICE LEAF DOWN LEAF DOWN °C MDEW BLAST RUST MDEW BLOT MDEW S UASH GRAPE

l -is

Synthesis

Compounds of general formula (1) wherein R ¹ is H or halo can be prepared using the following general procedure:

Het-Z + Y-Ar ► Het-NH—Ar wherein one of Y and Z is H ₂ and the other is halo. The reaction is preferrably carried out in the presence of a base such as an alkali metal hydroxide, carbonate, hydride or alkaline earth metal hydroxide or carbonate. Preferred bases are sodium hydride, sodium hydroxide, sodium carbonate, potassium carbonate, potassium t-butoxide, sodium bicarbonate and potassium hydroxide. The reaction is carried out in a nonreactive organic solvent such as tetrahydrofuran, at a temperature in the range from -20 to 200°C. It is preferred for Y to be halo and Z to be NH ₂ -

Compounds of formula (1) wherein Het is

can be synthesized by the foregoing general procedure, using a 4-halo-5-isothiazolamine starting material. Alternatively, they can be prepared by halogenating a compound of formula (1) wherein Het is oil

Halogenation is typically carried out by reacting the compound of formula (1) with a small excess of elemental bromine, chlorine, or iodine in CH ₂ CI ₂ or CHCI ₃ . Bromination and ^■ chlorination usually proceed rapidly at room temperature. Iodination may require addition of potassium carbonate or sodium carbonate and brief heating to reflux. Other

halogenating agents, such as N-bromosucciriimide and N- chlorosuccinimide may also be used.

Compounds of formula (1) wherein Het is

can be made by nitrating a compound of formula (1) wherein Het is

Nitration is typically carried out by dissolving the compound of formula (1) in concentrated sulfuric acid and adding excess fuming nitric acid at room temperture. If no conversion has occurred within ten minutes, brief heating at 100°C may be used.

Compounds of formula (10) are prepared by halogenating a compound of formula (1) wherein Het is

wherein R ¹⁰ ' is H or halo.

Starting Materials

The starting materials used in preparing compounds of the invention are commercially available or they are readily prepared by known synthetic methods. The following table identifies some of the available sources for the starting materials.

For example, 5-aminoisothiazole starting materials can be prepared by the routes illustrated in the following Schemes 1A-1C:

Scheme IA

Scheme IB

Scheme 1C

5-Aminoisoxazole starting materials can be prepared, for example, by the procedure illustrated in Scheme 2.

2-Aminothiazole starting materials can be prepared, for example, by the procedure illustrated in Scheme 3.

Scheme 3

2-Amino-l,3,4-oxadiazole starting materials can be prepared, for example, by the procedure illustrated in Scheme 4.

Scheme 4

or

!--— Δ

2-Amino-l,3,4-thiadiazole starting materials can be prepared, for example, by the pro.cedure illustrated in Schemes 5A and 5B

Scheme 5A

Scheme 5B

- EtOH

R-CHO ⁺

H,NNH ANH, p-toluenesulfonic acid

5-Aminopyrazole starting materials can be prepared, for example, by the procedures illustrated in Scheme 6A-6D.

Scheme 6A

Scheme 6B

πnl -.ύ- M- ------- nτ?>- HOAC n ^H NaOAc

Scheme 6C

Scheme 6D

₊ RNHNH ₂

Scheme 6E

Scheme 6F

Scheme 6G

5-Amino-l, 2 , 4-thiadiazole starting materials can be prepared, for example, by the procedures illustrated in Schemes 7A and 7B.

Scheme 7 A

Scheme 7B

^R R V- λ— H ₂ + Br ₂ _-- ^► — NH + ^■ -KSCN +~ ff

HN ^base ^___ -NH.

Br Preparation 1

2-t-Butyl-4,6-dinitrochlorobenzene

To mechanically stirred concentrated nitric acid (750mL) , cooled to 0°C, was added 150.2 g (1 mole) of 2-t-butylphenol at such a rate that the reaction temperature never exceded 10°C. The mixture was stirred one-half hour after the addition of the phenol was completed. Then the mixture was poured upon ice in a 4L beaker and allowed to stand overnight at room temperature. After filtering the mixture, the precipitate was washed with water and recrystalized from 800 mL of ethanol and cooled in a refrigerator. 2-t-Butyl-4,6- dinitrophenol, in the form of yellow prisms, was collected by suction filtratrion and air dried. Yield 84.0 g. M.P. 125- 128°Q.

To a suspension of 60.01 g (0.25 mole) of 2-t-butyl-4,6- dinitrophenol in 125 mL of 1,2-dichloroethane was added 38.3 g (0.275 mole) of 2,4,6-trimethylpyridine. Mechanical stirring was started and 115 g (0.75 mole) of phosphorous oxychloride

was added in many small portions, keeping the temperature of the mixture below 50°C. The mixture was then stirred for 40 hours under reflux. The cooled mixture was then poured into hot water (55°C) a little at a time, ice was added whenever the reaction temperature exceeded 65°C. The mixture was extracted with IL of CHCI ₃ and again with 500 mL of CHCI ₃ . The combined extracts were washed twice with water and dried over anhydrous Na ₂ S0 ₄ and filtered. The filtrate was concentrated in a rotary evaporator to a black oil that crystallized on standing. The solid was dissolved in IL of benzene, treated with 100 g of fϊorisil and filtered. The filtrate was concentrated to a wine colored oil, which was dissolved in 200 mL of Skelly B and chilled. White platelets of the title product formed. Yield 59.2 g. M.P. 62-63°C.

Preparation 2

5-amino-4-bromo-3-ethylisothiazole

Sodium hydride (60%, 32.0 g, 0.8 mole) was suspended in dry THF (250 mL) and heated to reflux (70°C) with vigorous stirring. To this suspension was added a mixture of ethyl propionate (30.7 g, 0.3 mole) and acetonitrile (27.0 g, 0.6 mole) over a 2.0 hour period and further refluxed for 9.0 hours. After cooling to 25°C, ethanol (15.0 mL) followed by water (350 mL) was added to the reaction mixture. To the resulting yellowish-brown solution was added hexane (500 mL) and vigorously stirred. The aqueous layer obtained was washed with hexane/ethyl ether (2:1, 400 mL) , acidified with 5N HCl (about 130 mL) and then extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to give 28.0 g of 3-oxopentane nitrile (96%) .

Ammonia (about 3.5 g) was bubbled at a steady rate over a 5.0 min period through a solution of 3-oxopentane nitrile (7.09, 72.2 mmol ) in absolute ethanol (130 mL) in a heavy wall tube (Ace Glass Inc.) and immediately sealed with a teflon plug. The sealed tube was then placed in an oven and heated at 110°C for 16 hours. After cooling to 2°C, the

solvent was removed under vacuum to give 6.39 of 3- aminopentene nitrile (91%) as red oil.

H2S (7.2 g) was bubbled at a steady rate over a 4.5 min period through a solution of 3-aminopentene nitrile (11.1 g, 115.6 mmol) in THF (35 mL) and ethyl alcohol (25 mL) at 0°C in a heavy wall tube and immediately sealed with a teflon plug. After the reaction mixture was allowed to warm to 25°C, the sealed tube was placed in an oven and heated 90°C for 3 hours. The sealed tube was allowed to stand at 25°C for 48.0 hours and then removal of solvent under- vacuum gave 3-amino-2- pentene thioamide 14.5 g of lb (96% yield) as thick red oil.

Bromine (2.72g, 17.0 mmol) in dichloromethane (50.0 ml) was added dropwise to a solution of 3-amino-2-pentene thioamide (l.lg, 8.5 mmol), in dichloromethane (50.0 mL) at 5°C over a 30 min period. The resulting reddish-brown solution was stirred at ambient temperature for 2 hours. After the removal of dichloromethane in vacuo, the residue was titrated with ethyl acetate. The white solid obtained was • filtered to give and basified, pH between 9 to 10, with ammonium hydroxide and extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to give 5-amino-4-bromo-3- ethylisothiazole (1.30g, 74%) as a yellow oil.

Example 1 3-methyl-N-[2,6-dinitro-4-(trifluoromethyl)phenyl]isothiazol -

5-amine

To a solution of 1.14 g (.01 mole) of 3-methyliso- thiazol-5-amine and 2.78 g (.01 mole) of 4-chloro-3,5- dinitrobenzotrifluoride in about 50 mL of anhydrous THF was added 0.7 g of 50% NaH in oil. On the following day TLC showed some starting material remained. A few milliliters of ^■ ethyl alcohol were added and the mixture was evaporated to dryness under vaccum providing a black solid. This residue was boiled up in hexane. The resulting black red material was isolated by decanting the hexane and the residue was dissolved in water. When the aqueous mixture was acidified a dark

orange oil formed, which was extracted into methylene chloride. The extract was filtered and concentrated to dryness under vacuum. The resulting material was first purified by chromatography (Siθ ₂ /3:l Et ₂ θ/Pentane) then recrystallized in hexane, providing 1.1 g of yellow-orange crystalline powder. M.P. 118-120°C.

Example 2

4-bromo-3-methyl-N-[2, 6-dinitro-4-(trifluoromethyl)- phenyl]isothiazol-5-amine

To a solution of 0.9 g (.0025 ^' mole) of 3-methyl-N-[2,6- dinitro-4-(trifluoromethyl)phenyl]isothiazol-5-amine in about 50 mL of CHCI ₃ was added 0.46 g of Br ₂ with swirling. The solution became cloudy and then turned clear orange. The solution was washed with water, filtered, and evaporated to dryness under vacuum to provide 1.14 g of a bright yellow solid. The product was again washed with water, filtered, and dried, providing 0.98 g of. golden-yellow crystals. M.P. 171- 172°C.

Example 3 N-(4-bromo-3-methylisothiazol-5-yl)-N-[2,6-dinitro-4-

(trifluoromethyl)phenyl]acetamide

To a solution of 0.64 g of 4-bromo-3-methyl-N-[2,6- dinitro-4-(trifluoromethyl)phenyl]-5-isothiazolamine in about 15 mL of acetic anhydride was added about 1 g of granular K ₂ CO ₃ . The mixture was heated to near reflux temperature for about 1 minute. The solution was then filtered and the salts were washed with ethyl ether. The solution was concentrated to dryness under vacuum providing a dark oil, which was equilibrated between ethyl ether and dilute HCl. Hexane was added to the mixture, the aqueous layer was removed, and the organic layer was concentrated under vacuum to provide .72 g of orange oil. Crystallization from Et ₂ θ/hexane provided yellow-brown crystals. Recrystallization from CH ₂ Cl ₂ /hexane provided .55 g of the title product. MP 136-139°C.

Example 4

3-methyl-4-nitro-N-[2, 6-dinitro-4-(trifluoromethyl)- phenyl]isothiazol-5-amine

A solution of 0.5 g of 3-methyl-N-[2,6-dinitro-4- (trifluoromethyl)phenyl]isothiazol-5-amine in 10 mL of concentrated sulfuric acid was warmed to 50°C on a steam bath. To this solution was added 2 mL of fuming nitric acid. After swirling, the mixture was allowed to stand for 10 minutes. The mixture was first diluted with ice water, then flooded with 150 mL of water. The resulting yellow powder was isolated by filtration and air dried to provide 0.89 g of product, which was purified by recrystallization from CHCI3/hexane to provide 0.66 g of the title product. MP 175-178°C.

Example 5

3-ethy1-4-bromo-N-[2,6-dinitro-4-(trifluoromethyl)phenyl] - isothiazol-5-amine

To a solution of 0.45 g of 4-bromo-3-ethylisothiazol-5- amine and 0.6 g of 4-chloro-3,5-dinitro-benzotrifluoride in 75 .mL of anhydrous THF was added 0.25 g of 50% NaH in oil. On the following day, TLC showed some starting material remained. Two milliliters of ethyl alcohol were added and the mixture was concentrated to dryness under vaccum providing a black ' solid. This residue was dissolved in water. When the aqueous mixture was acidified with dilute HCl the solution turned a -bright yellow. An extraction using hexane/Et ₂ θ was followed by extractions using dilute sodium hydroxide until the organic layer showed only a single product when tested using TLC. The aqueous layer was separated, acidified, and extracted with hexane/Et ₂ θ to provide a material which was recrystallized from pentane to provide 0.5 g of the title product. MP 99- -103°C.

Example 6 N-(4-bromo-4-chloro-3-methyl-5 (4H)-isothiazolylidene)- 2,4-dinitro-6- (trifluoromethyl)benzenamine

Excess chlorine was bubbled into a solution of 0.56 g of 4-bromo-3-methyl-N-[2,6-dinitro-4-(trifluoromethyl) - phenyl]isothiazol-5-amine in 50 mL of chloroform. After ten minutes the solution was concentrated to dryness under vacuum to provide 0.52 g of the title product as a yellow solid. Rec ystallization from hexane gave pale yellow crystals. MP 133-137°C.

Example 7

N- (4,4-dichloro-3-n-butyl-5 (4H)-isothiazolylidene)-2,4- dinitro-6- (trifluoromethyl)benzenamine

A solution of 0.65 g of 3-n-butyl-N-[2,6-dinitro-4- (trifluoromethyl)phenyl]isothiazol-5-amine in 30 mL of chloroform was saturated with chlorine. After 3 to 4 minutes TLC indicated that the reaction had progressed to completion. •The mixture was concentrated under vacuum to provide 0.82 g of a clear yellow oil. The oil was dissolved in pentane and crystals slowly developed. After cooling the mixture in a freezer, 0.43 g of pale orange crystals were collected. MP 115-120°C.

Example 8 3,N-Dimethyl-N-[2,6-dinitro-4- (trifluoromethyl)phenyl]isothiazol-5-amine

To 3-methyl-N-[2,6-dinitro-4-(trifluoromethyl) - phenyl]isothiazol-5-amine (1.4 g, .004 mole) in 75 mL of methylethyl ketone was added 3 g of potassium carbonate and 2 -g of methyl iodide. The container was stoppered and stirred for 48 hours. The mixture was filtered, then the organic layer was concentrated using a rotary evaporator to give 1.3 g of a red solid, which was purified on a Siθ ₂ /CHCl ₃ column, then recrystallized from hexane. Yield .27g. M.P. 147-149°C.

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 .25 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 screen was used to evaluate the efficacy of the present compounds against a variety of different organisms that cause plant diseases.

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 ethanol. 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 in Host Tables 1-9

Erysiphe graminis tritici POWD wheat (powdery mildew) MDEW

Pyricularia oryzae RICE rice (rice blast) BLAST

Puccinia recόndita tritici LEAF wheat

(leaf rust) RUST

Septoria nodorum LEAF wheat

(glume blotch) BLOT

Plasmopara viticola DOWN grape (downy mildew) MDEW

The formulated technical compounds were sprayed on all foliar surfaces of the host plant (or cut' erry) 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.

Tables 1-9 report 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 An arabic numeral following this rating gives the control rating at 6.25 ppm on the following scale:

Phytotoxic effects, if any, observed when the compound was tested at 100 ppm are also reported in the line below the activity rating in Tables 1-9. This rating consists of an arabic numeral and a letter. The arabic numeral reports the degree of chemical injury as rated on the following scale: rating degree of in ur

The letter reports the type of symptomology observed, using the following code: letter symptom

Insecticide and Miticide Utility

The compounds of formulas (1) and (10) show activity against a number of insects and mites.

The compounds of formulas (1) and (10) 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 formulas (1) and (10) . 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 caμse 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.

In a preferred embodiment, the present invention is directed to a method for inhibiting a mite which comprises applying to a plant an effective mite-inactivating amount of a compound of formulas (1) and (10) in accordance with the present invention.

MITE/INSECT SCREEN

The compounds of the foregoing examples were tested for miticidal and insecticidal activity in the following mite/insect screen.

Each test compound was formulated as a 400 ppm solution, and this solution was then diluted with water to give the indicated 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 .8 mL of acetone/EtOH (9/1) .

Twospotted spider mites {Tetranychus urticae Koch) and melon aphids (Aphis gossypii Glover) are introduced on squash cotyledons and allowed to establish on both leaf surfaces. Other plants in the same treatment pot are left uninfested. The leaves are then 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 a compound is determined 48 hours after treatment. Activity is rated as a percent based on the mites/aphids present in plants sprayed with solvent alone. An uninfested plant is cut after the spraying and drying steps and placed into a Petri dish containing larval southern armyworm (Spodopetra eridania Cramer) . The larvae are checked after 72 to 96 hours for mortality and for antifeedent activity of the compound. The ratings are based on comparison to results on plants sprayed -with solvent alone.

Activity on Southern corn rootworm (Diabrotica undecimpuctata howardi Barber) is evaluated by adding one mL 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 are added to the individual cups. Mortality is measured at 3-4 days by emptying the cup onto a pan and inspecting the soil for live rootworms.

Results for are reported in the following table. The following abbreviations are used in the table: CRW refers to corn rootworm SAW refers to Southern armyworm SM refers to twospotted spider mites MA refers to melon aphids.

24.00 400 80 100 100

Nematicide Utility ^'

Some of the compounds of the present invention are also useful for reducing populations of nematodes. Accordingly, another aspect of the invention is a method of inhibiting a nematode population which comprises applying to a locus of a nematode an effective nematode inactivating amount of a compound of formula (Dor (10). The term "inhibiting a nematode" refers to a decrease in the numbers of living nematodes. The extent of reduction accomplished by a compound depends upon the application rate.of the compound, the particular compound used, and the target species. At least a nematode-inactivating amount should be used. The term "nematode-inactivating amount" is used to describe the amount, which is sufficient to cause a measurable reduction in the treated nematode population.

The method is practiced in accordance with standard techniques for the application of nematicides. In general, good nematicidal activity can be expected at rates of 1-10 lbs/acre. ^• The compound can be formulated as described below in the Compositions section. When formulated as dispersions, nematicides are typically applied as aqueous drenches around growing plants or applied incrementally via irrigation systems. When applied as granules, nematicides may be incorporated into the soil before planting, or applied in a band on top of a seed row, or broadcast and then incorporated into the soil, or used as a side dressing to an established crop.

Compositions

The compounds of formulas (1) and (10) are applied in the form of compositions which are important embodiments of the invention, and which comprise a compound of formula (1) or (10) 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 compounds. Such water-soluble, water-suspendable or emulsifiable formulations are either solids usually known as wettable powders, or liquids usually known as emulsifiable concentrates 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 montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of 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 10% 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 emulsifi¬ able 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 homogenizer.

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) and (10) 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 .suspen¬ sions 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.

The following formulations of compounds of the invention are typical of compositions useful .in the practice of the present invention.

A. Emulsifiable Concentrate

Compound of Formula (1) or (10) 9.38%

"TOXIMUL D" 2.50%

(nonionic/anionic surfactant blend) "TOXIMUL H" 2.50%

(nonionic/anionic surfactant blend)

"EXXON 200" 85.62%

(naphthalenic solvent)

B. Emulsifiable Concentrate

Compound of Formula (1) or (10) 18.50%

"TOXIMUL D" 2.50%

"TOXIMUL H" ' 2.50%

"EXXON 200" 76.50%

C. Emulsifiable Concentrate

Compound of Formula (1) or (10) 12.50%

N-methylpyrrolidone 25.00%

"TOXIMUL D" 2.50% "TOXIMUL H" 2.50%

"EXXON 200" 57.50%

D. Aσueous Suspension Compound of Formula (1) or (10) 12.00% "PLURONIC P-103" 1.50% (block copolymer of propylene oxide and ethylene oxide, surfactant)

"PROXEL GXL" .05%

(biocide/preservative)

"AF-IOO" .20%

(silicon based antifoam agent) "REAX 88B" 1.00%

(lignosulfonate dispersing agent) propylene glycol 10.00% veegum .75% xanthan .25% water 74.25%

E. Aαueous Suspension Compound of Formula (1) or (10) 12.50% "MAKON 10" (10 moles ethyleneoxide 1.00% nonylphenol surfactant)

"ZEOSYL 200" (silica) 1.00%

"AF-100" 0.20%

"AGRIWET FR" (surfactant) 3.00%

2% xanthan hydrate 10.00% water 72.30%

F. Aqueous Suspension Compound of Formula (1) or (10) 12.50% "MAKON 10" 1.50% "ZEOSYL 200" (silica) 1.00%

"AF-100" 0.20%

"POLYFON H" 0.20% (lignosulfonate dispersing agent)

2% xanthan hydrate 10.00% water 74.60%

G. Suspension Concentrate

Compound of Formula (1) or (10) 10.20%

"TERGITOL TMN-6" 3.40%

"ZEOSYL 200" 0.90%

2% "KELZAN" solution 8.60%

"AF-100" 0.20% water 76.70%

G. Wettable Powder Compound of Formula (1) or (10) 25.80%

"POLYFON H" 3.50%

"SELLOGEN HR" 5.00%

"STEPANOL ME DRY" 1.00% gum arabic 0.50% "HISIL 233" 2.50%

Barden clay 61.70%

H. Granules

Compound of Formula (1) or (10) 5.0% propylene glycol 5.0% Exxon 200 . 5.0%

Florex 30/60 granular clay 85.0%