Fungicides

Abstract

This invention relates to novel derivatives of pyridopyrazines and pyridopyridazines, to processes for preparing them, to intermediate chemicals used in their manufacture, to compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants. The fungicidal compounds have the general formula (1) wherein R, R 1 , R 2 , W, X Y and Z are defined in the specification

1 . The compound of the general formula (1): 
     
       
         
         
             
             
         
       
       wherein 
       W and X, X and Y or Y and Z are N and the other two are CR 8 ; 
       R 8  is H, halo, C 1-4  alkyl, C 1-4  alkoxy or halo(C 1-4 )alkyl; 
       R is halo; 
       R 1  is halo, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, C 1-8  alkoxy, C 1-8  alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C 1-4 )alkyl, aryl(C 1-4 )alkoxy, heteroaryl(C 1-4 )alkyl, heteroaryl(C 1-4 )alkoxy, aryl(C 1-4 )alkylthio, heteroaryl(C 1-4 )alkylthio, morpholino, piperidino or pyrrolidino; 
       R 2  is NR 3 R 4 ; 
       R 3  and R 4  are independently H, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, aryl(C 1-8 )alkyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, heteroaryl, heteroaryl(C 1-8 )alkyl, NR 5 R 6 , provided that not both R 3  and R 4  are H or NR 5 R 6 , or 
       R 3  and R 4  together form a C 3-7  alkylene or C 3-7  alkenylene chain optionally substituted with one or more C 1-4  alkyl or C 1-4  alkoxy groups, or, 
       together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C 1-4 )alkyl ring; and 
       R 5  and R 6  are independently H, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, aryl(C 1-8 )alkyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl (C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-8 )alkyl; 
       any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R 8 ) being optionally substituted with halogen, cyano, C 1-6  alkoxy, C 1-6  alkylcarbonyl, C 1-6  alkoxycarbonyl, C 1-6  haloalkoxy, C 1-6  alkylthio, tri(C 1-4 )alkylsilyl, C 1-6  alkylamino or C 1-6  dialkylamino, 
       any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C 1-4  alkyl, and 
       any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 2-6  alkenyloxy, C 2-6  alkynyloxy, halo(C 1-6 )alkyl, halo(C 1-6 )alkoxy, C 1-6  alkylthio, halo(C 1-6 )alkylthio, hydroxy(C 1-6 )alkyl, C 1-4  alkoxy(C 1-6 )alkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO 2 R′″, —OSO 2 R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy, halo(C 1-4 )alkoxy, C 1-4  alkylthio, 
       C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C 1-4  alkyl or C 1-4  alkoxy. 
     
   
   
       2 . A compound according to  claim 1  wherein
 R 3  is C 1-8  alkyl, halo(C 1-8 )alkyl, hydroxy(C 1-8 )alkyl, C 1-4  alkoxy(C 1-8 )alkyl, C 1-4  alkoxyhalo-(C 1-8 )alkyl, tri(C 1-4 )alkylsilyl(C 1-6 )alkyl, C 1-4  alkylcarbonyl(C 1-8 )alkyl, C 1-4  alkylcarbonyl-halo(C 1-8 )alkyl, phenyl(1-4)alkyl, C 2-8  alkenyl, halo(C 2-8 )alkenyl, C 2-8  alkynyl, C 3-8  cycloalkyl optionally substituted with chloro, fluoro or methyl, C 3-8  cycloalkyl(C 1-4 )alkyl, phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy and halo(C 1-4 )alkoxy; and   R 4  is H, C 1-4  alkyl, halo(C 1-4 )alkyl or amino, or   R 3  and R 4  together form a C 3-7  alkylene or alkenylene chain optionally substituted with methyl, or,   together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C 1-4 )alkyl ring, in which the morpholine or piperazine rings are optionally substituted with methyl.   
   
   
       3 . A compound according to  claim 1  wherein
 R 1  is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy or halo(C 1-4 )alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy or halo(C 1-4 )alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl,   C 1-4  alkoxy or halo(C 1-4 )alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups.   
   
   
       4 . A compound according to  claim 4  wherein R 1  is 2,6-difluorophenyl, 2-fluoro-6-chlorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl or pentafluorophenyl. 
   
   
       5 . A compound according to  claim 1  wherein
 R 8  is H, halo, C 1-4  alkyl, C 1-4  alkoxy or halo(C 1-4 )alkyl;   R is halo;   R 1  is halo, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, C 1-8  alkoxy, C 1-8  alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C 1-4 )alkyl, aryl(C 1-4 )alkoxy, heteroaryl(C 1-4 )alkyl, heteroaryl(C 1-4 )alkoxy, aryl(C 1-4 )-alkylthio, heteroaryl(C 1-4 )alkylthio, morpholino, piperidino or pyrrolidino;   R 2  is NR 3 R 4 ;   R 3  and R 4  are independently H, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, aryl(C 1-8 )alkyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, heteroaryl, heteroaryl(C 1-8 )alkyl, NR 5 R 6 , provided that not both R 3  and R 4  are H or NR 5 R 6 , or   R 3  and R 4  together form a C 3-7  alkylene or C 3-7  alkenylene chain optionally substituted with one or more C 1-4  alkyl or C 1-4  alkoxy groups, or,   together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C 1-14 )alkyl ring; and   R 5  and R 6  are independently H, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, aryl(C 1-8 )alkyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-8 )alkyl;   any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R 8 ) being optionally substituted with halogen, cyano, C 1-6  alkoxy, C 1-6  alkylcarbonyl, C 1-6  alkoxycarbonyl, C 1-6  haloalkoxy, C 1-6  alkylthio, tri(C 1-4 )alkylsilyl, C 1-6  alkylamino or C 1-6  dialkylamino,   any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C 1-4  alkyl, and   any of the aryl, heteroaryl, aryloxy or heteroaryl groups being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C 1-6  alkyl, C 2-6  alkenyl,   C 2-6  alkynyl, C 1-6  alkoxy, C 2-6  alkenyloxy, C 2-6  alkynyloxy, halo(C 1-6 )alkyl, halo(C 1-6 )alkoxy, C 1-6  alkylthio, halo(C 1-6 )alkylthio, hydroxy(C 1-6 )alkyl, C 1-4  alkoxy(C 1-6 )alkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO 2 R′″, —OSO 2 R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy, halo(C 1-4 )alkoxy, C 1-4  alkylthio,   C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C 1-4  alkyl or C 1-4  alkoxy.   
   
   
       6 . A compound according to  claim 1  wherein
 R 8  is H, halo, C 1-4  alkyl, C 1-4  alkoxy or halo(C 1-4 )alkyl;   R is halo;   R 1  is halo, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, C 1-8  alkoxy, C 1-8  alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C 1-4 )alkyl, aryl(C 1-4 )alkoxy, heteroaryl(C 1-4 )alkyl, heteroaryl(C 1-4 )alkoxy, aryl(C 1-4 )alkylthio, heteroaryl(C 1-4 )alkylthio, morpholino, piperidino or pyrrolidino;   R 2  is NR 34 ;   R 3  is C 1-4  alkyl, halo(C 1-4 )alkyl, C 2-4  alkenyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy and halo(C 1-4 )alkoxy; and   R 4  is H, C 1-4  alkyl or amino, or   R 3  and R 4  together form a C 4-6  alkylene chain optionally substituted with C 1-4  alkyl or C 1-4  alkoxy, or,   together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C 1-4 )alkyl ring;   any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R 8 ) being optionally substituted with halogen, cyano, C 1-6  alkoxy, C 1-6  alkylcarbonyl,   C 1-6  alkoxycarbonyl, C 1-6  haloalkoxy, C 1-6  alkylthio, tri(C 1-4 )alkylsilyl, C 1-6  alkylamino or   C 1-6  dialkylamino,   any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C 1-4  alkyl, and   any of the aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl,   C 1-6  alkoxy, C 2-6  alkenyloxy, C 2-6  alkynyloxy, halo(C 1-6 )alkyl, halo(C 1-6 )alkoxy,   C 1-6  alkylthio, halo(C 1-6 )alkylthio, hydroxy(C 1-6 )alkyl, C 1-4  alkoxy(C 1-6 )alkyl, C 3-6  cycloalkyl,   C 3-6  cycloalkyl(C 1-4 )alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO 2 R′″, —OSO 2 R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy, halo(C 1-4 )alkoxy, C 1-4  alkylthio,   C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C 1-4  alkyl or C 1-4  alkoxy.   
   
   
       7 . A compound according to  claim 1  wherein
 R 8  is H, halo, C 1-4  alkyl, C 1-4  alkoxy or halo(C 1-4 )alkyl;   R is halo;   R 1  is optionally substituted phenyl;   R 2  is NR 3 R 4 ;   R 3  and R 4  are independently H, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, aryl(C 1-8 )alkyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, heteroaryl, heteroaryl(C 1-8 )alkyl, NR 5 R 6 , provided that not both R 3  and R 4  are H or NR 5 R 6 , or   R 3  and R 4  together form a C 3-7  alkylene or C 3-7  alkenylene chain optionally substituted with one or more C 1-4  alkyl or C 1-4  alkoxy groups, or,   together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C 1-4 )alkyl ring; and   R 5  and R 6  are independently H, C 1-8  alkyl, C 2-8  alkenyl, C 2-8  alkynyl, aryl, aryl(C 1-8 )alkyl, C 3-8  cycloalkyl, C 3-8  cycloalkyl(C 1-6 )alkyl, heteroaryl or heteroaryl(C 1-8 )alkyl;   any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R 8 ) being optionally substituted with halogen, cyano, C 1-6  alkoxy, C 1-6  alkylcarbonyl, C 1-6  alkoxycarbonyl, C 1-6  haloalkoxy, C 1-6  alkylthio, tri(C 1-4 )alkylsilyl, C 1-6  alkylamino or C 1-6  dialkylamino,   any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C 1-4  alkyl, and   any of the aryl or heteroaryl groups or moieties, including the phenyl group of R 1 , being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 2-6  alkenyloxy, C 2-6  alkynyloxy, halo(C 1-6 )alkyl, halo(C 1-6 )alkoxy, C 1-6  alkylthio, halo(C 1-6 )alkylthio, hydroxy(C 1-6 )alkyl, C 1-4  alkoxy(C 1-6 )alkyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-14 )alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO 2 R′″, —OSO 2 R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independently hydrogen, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy, halo(C 1-4 )alkoxy, C 1-4  alkylthio, C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C 1-4  alkyl or   C 1-4  alkoxy.   
   
   
       8 . A compound according to  claim 1  wherein
 R 8  is H, halo, C 1-4  alkyl, C 1-4  alkoxy or halo(C 1-4 )alkyl;   R is halo;   R 1  is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy or halo(C 1-4 )alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy or halo(C 1-4 )alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy or halo(C 1-4 )alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups;   R 2  is NR 3 R 4 ;   R 3  is C 1-8  alkyl, halo(C 1-8 )alkyl, hydroxy(C 1-8 )alkyl, C 1-4  alkoxy(C 1-8 )alkyl, C 1-4  alkoxyhalo-(C 1-8 )alkyl, tri(C 1-4 )alkylsilyl(C 1-6 )alkyl, C 1-4  alkylcarbonyl(C 1-8 )alkyl, C 1-4  alkylcarbonyl-halo(C 1-8 )alkyl, phenyl( 1-4 )alkyl, C 2-8  alkenyl, halo(C 2-8 )alkenyl, C 2-8  alkynyl, C 3-8  cycloalkyl optionally substituted with chloro, fluoro or methyl, C 3-8  cycloalkyl(C 1-4 )alkyl, phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy and halo(C 1-4 )alkoxy; and   R 4  is H, C 1-4  alkyl, halo(C 1-4 )alkyl or amino, or   R 3  and K 4  together form a C 3-7  alkylene or C 3-7  alkenylene chain optionally substituted with methyl, or,   together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N—(C 1-4 )alkyl ring, in which the morpholine or piperazine rings are optionally substituted with methyl.   
   
   
       9 . A compound according to  claim 1  wherein
 R 8  is H, halo, C 1-4  alkyl, C 1-4  alkoxy or halo(C 1-4 )alkyl;   R is halo;   R 1  is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy or   halo(C 1-4 )alkoxy;   R 2  is NR 3 R 4 ;   R 3  is C 1-4  alkyl, halo(C 1-4 )alkyl, C 2-4  alkenyl, C 3-6  cycloalkyl, C 3-6  cycloalkyl(C 1-4 )alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two or three substituents selected from halo, C 1-4  alkyl, halo(C 1-4 )alkyl, C 1-4  alkoxy and halo(C 1-4 )alkoxy; and   R 4  is H, C 1-4  alkyl or amino, or R 3  and R 4  together form a C 4-6  alkylene chain optionally substituted with methyl, or, together with the nitrogen atom to which they are attached, R 3  and R 4  form a morpholine ring.   
   
   
       10 . A process for preparing a compound of the general formula (1) according to  claim 1  wherein R is chloro or fluoro and R 2  is NR 3 R 4  and W, X, Y, Z, R 1 , R 3  and R 4  are as defined in  claim 1 , which comprises reacting an amine of the general formula NR 3 R 4  with a compound of the general formula (6) or (13) 
     
       
         
         
             
             
         
       
     
   
   
       11 . The intermediate chemicals having the general formulae (4), (5), (6) and (13): 
     
       
         
         
             
             
         
       
     
     wherein W, X, Y, Z and R 1  are as defined in  claim 1  and R 7  is C 1-4  alkyl, other than the compound of formula (6) wherein X and Y are N, W and Z are C—Cl and R 1  is Cl. 
   
   
       12 . A plant fungicidal composition comprising a fungicidally effective amount of a compound as defined in  claim 1  and a suitable carrier or diluent therefor. 
   
   
       13 . A method of combating or controlling phytopathogenic fungi which comprises applying to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or to any other plant growth medium, a fungicidally effective amount of a compound according to  claim 1  or a composition according to  claim 13 .