BENZOXAZOLE AND BENZOTHIAZOLE DERIVATIVES

The present invention relates to novel benzoxazole and benzthiazole derivatives having nematicidal, insecticidal, acaricidal and fungicidal activity, to processes for their preparation, to compositions containing them, to methods for killing or controlling nematode, insect and acarid pests using them, and to methods of combating fungi using them.

UK Patent No 1413519 generically discloses 2-substituted benzoxazoles and benzthiazoles carrying the very specific isothiocyano substituent on the benzo-fused ring. No specific 2-haloalkylthio examples are disclosed and the compounds are not mentioned in the context of agrochemical nematicidal activity. US Patent No 4328219 discloses 2-substituted benzoxazoles and benzthiazoles as synergists for various conventional insecticides. No specific 2-fluoroalkylthio examples are disclosed and there is no disclosure of nematicidal activity. The present invention relates to novel 2- (2-fluoroethylthio)-substituted benzoxazoles and benzthiazoles and oxidised derivatives thereof which exhibit significantly improved levels of nematicidal activity across a wide spectrum of nematode pests, as well as insecticidal activity (including systemic activity) and fungicidal activity.

According to the present invention there is provided a compound of formula (I) wherein

X is oxygen or sulphur;

n is 0, 1 or 2;

1 2 3 4 R , R , R , and R are independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted aryloxy, optionally substituted arylalkoxy, alkoxy, alkenyloxy, alkynyloxy, hydroxyalkyl, alkoxyalkyl, alkylthio, alkenylthio, alkynylthio, haloalkyl, haloalkenyl, haloalkynyl, haloalkoxy, haloalkenyloxy, haloalkynyloxy, haloalkylthio, haloalkenylthio, haloalkynylthio, halogen, hydroxy, cyano,

fused 5- or 6-membered carbocyclic or heterocyclic ring;

5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

„21 _D 22 _23 _24 „25 _26 _27 _28 _D 29 _30 , _31 . , , _, R , R , R , R , R , R , R , R , R , R and R are independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, optionally substituted aryl and optionally substituted arylalkyl; and

Z is halogen.

1 31 When any one of R to R is an alkyl group it may be straight or branched chain and is preferably C alkyl, and in particular C , alkyl, for example methyl, ethyl, propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl or t-butyl.

1 31 When any one of R to R is an alkenyl or alkynyl group it may be straight or branched chain and is preferably C alkenyl or C alkynyl, for example vinyl, allyl, but-3-enyl, 3-methyl-but-3-enyl, ethynyl or propargyl.

1 4 When any one of R to R is a cycloalkyl or alkylcycloalkyl group, it is preferably C cycloalkyl or C alkylcycloalkyl, for example, cyclopropyl, cyclopentyl, cyclohexyl or methylcyclopropyl.

1 31 When any one of R to R is an optionally substituted aryl or an optionally substituted arylalkyl group, it is preferably an optionally substituted phenyl group or an optionally substituted phenyl-C -alkyl group, wherein the preferred optional substitution is one or more substituents selected from halogen such as chlorine, fluorine or bromine,

C alkyl such as methyl or ethyl, C alkoxy such as methoxy or ethoxy,

C haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or

2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or

2,2,2-trifluoroethoxy, hydroxy, cyano and nitro, for example phenyl, benzyl, 4-methylphenyl, 4-chlorophenyl, 4-fluorophenyl, 4-nitrophenyl,

3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 4-chlorobenzyl,

4-fluorobenzyl, 3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl,

4-nitrobenzyl or 4-methylbenzyl.

1 4 When any one of R to R is an optionally substituted aryloxy or an optionally substituted arylalkoxy group, it is preferably optionally substituted phenoxy or optionally substituted phenyl-C -alkoxy, group, wherein the preferred optional substitution is one or more substituents selected from halogen such as chlorine, fluorine or bromine, C alkyl

such as methyl or ethyl, C , alkoxy such as methoxy or ethoxy, C haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or 2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or 2,2,2-trifluoroethoxy, hydroxy, cyano and nitro, for example phenoxy, benzoxy, 4-methylphenoxy, 4-chlorophenoxy, 4-fluorophenoxy, 4-nitrophenoxy, 3-trifluoromethylphenoxy, 4-trifluoromethylphenoxy 4-chlorobenzoxy, 4-fluorobenzoxy, 3-trifluoromethylbenzoxy, 4-trifluoromethylbenzoxy,

4-nitrobenzoxy or 4-methylbenzoxy.

1 31 When any one of R to R is a haloalkyl, haloalkenyl or haloalkynyl group, it may contain one or more halogen atoms selected from chlorine, fluorine or bromine, and the alkyl, alkenyl or alkynyl moiety may be straight or branched chain and is preferably C alkyl, especially C alkyl, C„ - alkenyl or C„ „ alkynyl, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl,

2,2-difluoroethenyl, 3,3-dichloroprop-2-enyl, 2-chloroprop-2-enyl,

3 , 4, -trifluorobut-3-enyl, 4-fluorobut-3-enyl, 4, 4-difluorobut-3-enyl or

3-methy1-4,4-difluorobut-3-enyl.

1 4 When any one of R to R is an alkoxy, alkenyloxy, alkynyloxy, hydroxyalkyl or alkoxyalkyl group it may be straight or branched chain and is preferably C. , alkoxy, for example methoxy, ethoxy, n-propoxy, l-o iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy or t-butoxy, C alkenyloxy, for example vinyloxy, allyloxy, but-3-enyloxy or 3-methylbut-3-enyloxy, C alkynyloxy, for example propargyloxy, hydroxy-C -alkyl, for example hydroxymethyl, 2-hydroxyethyl or 3-hydroxypropyl, C alkoxyalkyl, for example methoxymethyl, methoxyethyl or ethoxymethyl, or C dialkoxyalkyl, for example dimethoxymethy1 or diethoxymethyl.

1 4 When any one of R to R is a haloalkoxy group, a haloalkenyloxy group or a haloalkynyloxy group, it may contain one or more halogen atoms selected from chlorine, fluorine or bromine, and the alkoxy, alkenyloxy or alkynyloxy moiety may be straight or branched chain and is preferably C.

1-6 alkoxy, C„ alkenyloxy or C„ alkynyloxy, for example, trichloromethoxy, -o 2-0 fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy,

2,2,2-trifluoroethoxy, pentafluoroethoxy, 1,1,2,2-tetrafluoroethoxy,

2,2-difluoroethenyloxy, 3,4, 4-trifluorobut-3-enyloxy,

4-fluorobut-3-enyloxy, 4,4-difluorobut-3-enyloxy,

3-methyl-4,4-difluorobut-3-enyloxy, 2-chloroprop-2-enyloxy or

3 , 3-dichloroprop-2-enyloxy.

When any one of R1 to R4 is an alkylthio group, an alkenylthio group or an alkynylthio group, the alkyl, alkenyl or alkynyl moiety is preferably

C alkyl, especially C alkyl, C alkenyl or C alkynyl, for example methylthio, ethylthio, n-propylthio, iso-propylthio, n-butylthio, iso-butylthio, sec-butylthio, t-butylthio, allylthio, but-3-enylthio,

3-methylbut-3-enylthio or propargylthio. When any one of R 1 to R4 is a haloalkylthio group, a haloalkenylthio group or a haloalkynylthio group, it may contain one or more halogen atoms selected from chlorine, fluorine or bromine, and the alkyl, alkenyl or alkynyl moiety is preferably C alkyl, especially C , alkyl, C , alkenyl or C alkynyl, for example fluoromethylthio, difluoromethylthio, trifluoromethylthio, trichloromethylthio, 2-fluoroethylthio,

2,2,2-trifluoroethylthio, 3-fluoro-n-propylthio, pentafluoroethylthio,

2-chloroprop-2-enylthio, 3,3-dichloroprop-2-enylthio,

3,4,4-trifluorobut-3-enylthio, 4-fluorobut-3-enylthio,

4,4-difluorobut-3-enylthio or 3-methyl-4,4-difluorobut-3-enylthio. When any one of R 1 to R4 is halogen, it is preferably fluorine, chlorine, bromine or iodine.

1 4 When any one of R to R is the group -N R, it is preferably -NH„, a

C alkylamino group, for example methylamino or ethylamino, or a di-(C _{1 g} alkyl)-amino group, for example dimethylamino or diethyla ino.

When any one of R to R is the group -NR COR it is preferably,

-NHCHO, a C„ acylamino group or an optionally substituted benzamido group, for example -NHCOCH , -NHCOC-H , benzamido or benzamido optionally substituted with one or more substituents selected from halogen such as chlorine, fluorine or bromine, C alkyl such as methyl or ethyl, C alkoxy such as methoxy or ethoxy, C , haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or 2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or 2,2,2-trifluoroethoxy, hydroxy, cyano and nitro.

1 4 9 10

When any one of R to R is the group -NR SO R it is preferably a

C. alkanesulphonamido group, for example -NHS0„CH, or -NHS0_C„H _c .

1 4 II 12

When any one of R to R is the group -N(S0„R ) (SO R ) it is preferably a di-(C alkanesulphonyl)amino group, for example -N(S0 CH )„ or -N(S0 C H ) .

1 4 13

When any one of R to R is the group -COR , it is preferably formyl, a C acyl group or an optionally substituted benzoyl group, for example acetyl, propionyl, n-butanoyl, benzoyl or benzoyl optionally substituted with one or more substituents selected from halogen such as chlorine,

fluorine or bromine, C alkyl such as methyl or ethyl, C alkoxy such as methoxy or ethoxy, C haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or 2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or 2, 2,2-trifluoroethoxy, hydroxy, cyano and nitro, for example 4-chlorobenzoyl, 4-fluorobenzoyl, 4-bromobenzoyl, 4-methylbenzoyl or 4-trifluoromethylbenzoyl.

1 4 14 15

When any one of R to R is the group -C0NR R , it is preferably

-C0NH , an N-(C alkyl)-carboxamido group, for example -C0NHCH ,

-C0NHC ₂ H ₅ or -C0NHCH ₂ CH ₂ CH ₃ , or an N,N-di-(C _{1 g} alkyl)-carboxamido group, for example -C0N(CH ) , -C0N(CH ) (C H ) or -C0N(C H ) .

When any one of R to R is the group -C00R , it is preferably -C00H, a C alkoxycarbonyl group, for example methoxycarbonyl or ethoxycarbonyl, a C haloalkoxycarbonyl group, for example 2-fluoroethoxycarbonyl, or a

C haloalkenyloxycarbonyl group, for example 3, , 4-trifluorobut-

3-enyloxycarbonyl, 4-fluorobut-3-enyloxycarbonyl, 4, 4-difluorobut-

3-enyloxycarbonyl or 3-methyl-4,4-difluorobut-3-enyloxycarbonyl,

1 4 17

When any one of R to R is the group -0C0R , it is preferably a C acyloxy group or an optionally substituted benzoyloxy, for example -OCOCH ,

-0C0C H ₅ , benzoyloxy or benzoyloxy optionally substituted with one or more substituents selected from halogen such as chlorine, fluorine or bromine,

C alkyl such as methyl or ethyl, C alkoxy such as methoxy or ethoxy,

C haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or

2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or

2,2,2-trifluoroethoxy, hydroxy, cyano and nitro.

When any one of R to R is the group -0S0 R , it is preferably a

C alkanesulphonyloxy group or an optionally substituted benzenesulphonyloxy group, for example methanesulphonyloxy, ethanesulphonyloxy, benzenesulphonyloxy or benzenesulphonyloxy optionally substituted with one or more substituents selected from halogen such as chlorine, fluorine or bromine, C alkyl such as methyl or ethyl, C alkoxy such as methoxy or ethoxy, C haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or 2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or 2,2,2-trifluoroethoxy, hydroxy, cyano and nitro, for example 4-methylbenzenesulphonyloxy.

1 4 19 20

When any one of R to R is the group -SO NR R , it is preferably

-SO NH , a C alkylaminosulphonyl group, for example -SO NHCH or

-S0„NHC H , or a di-(C alkyl)-aminosulphonyl group, for example

-S0 ₉ N(CH ₃ ) ₂ or -S0 ₂ N(C ₂ H ₅ ) ₂ .

^ι 21

When any one of R to R is the group -SO R , it is preferably a C alkanesulphonyl group, a C haloalkanesulphonyl group or an optionally substituted benzenesulphonyl group, for example methanesulphonyl, ethanesulphonyl, trifluoromethanesulphonyl, benzenesulphonyl or benzenesulphonyl optionally substituted with one or more substituents selected from halogen such as chlorine, fluorine or bromine, C alkyl such as methyl or ethyl, C alkoxy such as methoxy or ethoxy, C haloalkyl such as chloromethyl, fluoromethyl, trifluoromethyl or

2,2,2-trifluoroethyl, C haloalkoxy such as trifluoromethoxy or

2,2,2-trifluoroethoxy, hydroxy, cyano and nitro, for example

4-methylbenzenesulphonyl.

1 4 22

When any one of R to R is the group -SOR , it is preferably a C alkanesulphinyl group, for example methanesulphinyl or ethanesulphinyl, or a C. haloalkanesulphinyl group, for example trifluoromethanesulphinyl.

^1_ 1 4 23 24

When any one of R to R is the group -CSNR R it is preferably

-CSNH , -CSNHCH or -CSN(CH ) .

1 L ~ ~ ?fi 77

When any one of R to R is the group -SiR R R , it is preferably a tri-(C alkyl)silyl group, for example, trimethylsilyl or triethylsilyl.

When any one of R to R is the group -0CH CO R , it is preferably a C _g alkoxycarbonylmethoxy group, for example methoxycarbonylmethoxy or ethoxycarbonylmethoxy.

1 4 29

When any one of R to R is the group -0CH _? CH„C0 R , it is preferably a C alkoxycarbonylethoxy group, for example methoxycarbonylethoxy or ethoxycarbonylethoxy.

When any one of R to R is the group -CONR SO R , it is preferably an N-(C alkanesulphonyl)carboxamido group or an N-(C alkyl)-N-(C. alkanesulphonyl)carboxamido group, for example N-(methanesulphonyl)- carboxamido or N-methyl-N-(methanesulphonyl)carboxamido.

1 4 When any one of R to R is the group -SO Z, it is preferably -S0„F,

-SO Cl or -SO Br.

1 2 3 4 When an adjacent pair of R , R , R and R taken together form a fused

5- or 6-membered carbocyclic or heterocyclic ring, the pair of substituents taken together is preferably -(CH ) -, -(CH _£ ) ₄ -, -CH=CH-CH=CH-, -0-CH -0- optionally substituted with one or two halogen atoms, for example -0-CHF-O- or -0-CF -0-, -0-CH(CH )-0-, -0-C(CH ) -0- or -0-(CH^-O-, and the fused ring formed thereby is preferably a 5- or 6-membered heterocyclic ring containing two oxygen atoms and optionally substituted with one or more halogen or methyl groups, or a 5- or 6-membered carbocyclic ring.

Accordingly, the invention provides, in a further aspect, a compound of formula (I) wherein

X is oxygen or sulphur;

n is 0, 1 or 2;

1 2 3 4 R , R , R , and R are independently selected from hydrogen, C alkyl,

C_ - alkenyl, C_ _c alkynyl, C- , cycloalkyl, C. alkylcycloalkyl, phenyl

Z-0 Z-0 j-O h - l optionally substituted by halogen, C , alkyl, C alkoxy, C haloalkyl,

C haloalkoxy, hydroxy, cyano or nitro, phenyl-C „-alkyl optionally substituted by halogen, C alkyl, C , alkoxy, C , haloalkyl, C. , haloalkoxy, hydroxy, cyano or nitro, phenoxy optionally substituted by halogen, C alkyl, C alkoxy, C haloalkyl, C , haloalkoxy, hydroxy, cyano or nitro, phenyl-C -alkoxy optionally substituted by halogen, C alkyl, C alkoxy, C , haloalkyl, C. , haloalkoxy, hydroxy, cyano or nitro, C. alkoxy, C alkenyloxy, C alkynyloxy, hydroxy-C -alkyl,

C„ _c alkoxyalkyl, C3-6 dialkoxyalkyl, C. - alkylthio, C„ alkenylthio, Z-o l-o Δ- Ό

C„ , alkynylthio, C- - haloalkyl, C„ , haloalkenyl, C„ , haloalkynyl,

Z-O 1-0 Z-0 Z-0

C haloalkoxy, C haloalkenyloxy, C haloalkynyloxy, C haloalkylthio, C„ haloalkenylthio, C haloalkynylthio, halogen, ,

taken together form a fused 5- or 6-membered heterocyclic ring containing two oxygen atoms and optionally substituted with one or more halogen or methyl groups, or a 5- or 6-membered carbocyclic ring;

5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 _n 21 „22 „23 _n 24 _n 25 _π 26 _n 27 ,,28 _π 29 „30 , _31 . , ,

R , R , R , R , R , R , R , R , R , R and R are independently selected from hydrogen, C alkyl, C _fi alkenyl, C alkynyl, C _fi haloalkyl, C haloalkenyl, C„ haloalkynyl, phenyl optionally substituted by halogen, C alkyl, C , alkoxy, C , haloalkyl, C , haloalkoxy, hydroxy, cyano or nitro, and benzyl optionally substituted by halogen, C alkyl, C alkoxy, C haloalkyl, C haloalkoxy, hydroxy, cyano or nitro; and

Z is fluoro, chloro or bromo.

A further group of compounds according to the invention which are of particular interest are those of Formula (I) wherein:

X is oxygen or sulphur;

n is 0, 1 or 2;

1 2 3 4 R , R , R , and R are independently selected from hydrogen, C alkyl such as methyl or ethyl, C _fi alkenyl such as allyl, but-3-enyl or

3-methylbut-3-enyl, C„ , alkynyl such as ethynyl or propargyl, C

Z-o J-O cycloalkyl such as cyclopropyl, C alkylcycloalkyl such as

1-methylcyclopropyl, phenyl optionally substituted by chloro, fluoro, methyl, ethyl, methoxy, trifluoromethoxy, trifluoromethyl or nitro, such as phenyl, 4-chlorophenyl, 4-fluorophenyl, 3-trifluoromethylphenyl,

4-trifluoromethylphenyl, 4-methylphenyl or 4-nitrophenyl, benzyl optionally substituted by chloro, fluoro, methyl, ethyl, methoxy, trifluoromethoxy, trifluoromethyl or nitro, such as benzyl, 4-chlorobenzyl, 4-fluorobenzyl,

3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 4-methylbenzyl or

4-nitrobenzyl, phenoxy optionally substituted by chloro, fluoro, methyl, trifluoromethyl or nitro, such as phenoxy, 4-chlorophenoxy,

4-fluorophenoxy, 3-trifluoromethylphenoxy, 4-trifluoromethylphenoxy,

4-methylphenoxy or 4-nitrophenoxy, benzoxy optionally substituted by chloro, fluoro, methyl, trifluoromethyl or nitro, such as benzoxy,

4-chlorobenzoxy, 4-fluorobenzoxy, 3-trifluoromethylbenzoxy,

4-trifluoromethylbenzoxy, 4-methylbenzoxy or 4-nitrobenzoxy, C alkoxy such as methoxy, ethoxy, iso-propoxy, n-propoxy or sec-butoxy, C alkenyloxy such as allyloxy, but-3-enyloxy or 3-methylbut-3-enyloxy, C„ alkynyloxy such as propargyloxy, hydroxy-C , -alkyl such as hydroxymethyl,

2-hydroxyethyl or 3-hydroxypropyl, C alkoxyalkyl such as methoxymethyl, ethoxymethyl, methoxyethyl, C _fi dialkoxyalkyl such as dimethoxymethy1,

C alkylthio such as methylthio or ethylthio, C„ alkenylthio such as allylthio, but-3-enylthio or 3-methylbut-3-enylthio, C , alkynylthio such as propargylthio, C fluoroalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl or 2-fluoroethyl, C chloroalkyl such as chloromethyl, dichloromethyl or trichloromethyl, C fluoroalkenyl such as

2,2-difluoroethenyl, 3 , 4, 4-trifluorobut-3-enyl, 4, 4-difluorobut-3-enyl or

4, -difluoro-3-methylbut-3-enyl, C chloroalkenyl such as

3,3-dichloroprop-2-enyl or 2-chloroprop-2-enyl, C fluoroalkoxy such as fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethoxy or

1,1,2,2-tetrafluoroethoxy, C chloroalkoxy such as trichloromethoxy, C fluoroalkenyloxy such as 3, 4, 4-trifluorobut-3-enyloxy,

4, 4-difluorobut-3-enyloxy or 4, 4-difluoro-3-methylbut-3-enyloxy, Z chloroalkenyloxy such as 2-chloroprop-2-enyloxy or

3 ,3-dichloroprop-2-enyloxy, C fluoroalkylthio such as fluoromethylthio, difluoromethylthio, trifluoromethylthio or 2-fluoroethylthio, C chloroalkylthio such as trichloromethylthio, C„ fluoroalkenylthio such as

3 , 4, 4-trifluorobut-3-enylthio, 4, 4-difluorobut-3-enylthio or

4, 4-difluoro-3-methylbut-3-enylthio, C chloroalkenylthio such as

2-chloroprop-2-enylthio or 3,3-dichloroprop-2-enylthio, chloro, fluoro,

^• bromo, iodo, hydroxy, cyano, nitro, amino, -NHR where R is C alkyl, such as methylamino or ethylamino, -NR R where R and R are C alkyl

7 8 7 ³ .- ^h such as dimethylamino or diethylamino, -NR COR where R is hydrogen and R is hydrogen or C alkyl, such as formamido, acetamido, propionamido or benz meth and N,N- such hydrogen or C alkyl, such as carboxamido, N-methylcarboxamido,

N-ethylcarboxamido, N,N-dimethylcarboxamido, N-methyl-N-ethylcarboxamido,

N,N-diethylcarboxamido or N-(n-propyl)carboxamido, -C00R where R is hydrogen, C alkyl, C haloalkyl or C - fluoroalkenyl, such as -C00H, methoxycarbonyl, ethoxycarbonyl, 2-fluoroethoxycarbonyl,

3,4, -trifluorobut-3-enyloxycarbonyl, 3-methyl-4,4-difluorobut-3-

17 17 enyloxycarbonyl or 4, -difluorobut-3-enyloxycarbonyl, -0C0R where R is

is C alkyl or C , haloalkyl such as methanesulphonyl, ethanesulphonyl

22 22 or trifluoromethanesulphonyl, -SOR where R is C , alkyl or C haloalkyl such as methanesulphinyl, ethanesulphinyl or

23 24 23 24 trifluoromethanesulphinyl, -CSNR R where R and R are hydrogen or

C _η , alkyl such as -CSNH„, -CSNH(CH,) or -CSN(CH„)„, -SiR ²⁵ R ²⁶ R ²⁷ where 1-4 Z J J 2

-0-CH -0- optionally substituted with one or two halogen atoms, for example

-0-CHF-O- or -0-CF -0-, -0-CH(CH )-0-, -0-C(CH ₃ ) _£ -0- or -0- (CH^-O- .

A further group of compounds according to the invention which are of particular interest are those of Formula (I) wherein:

X is oxygen or sulphur;

n is 0, 1 or 2;

1 2 3 4 R , R , R , and R are independently selected from hydrogen, C alkyl such as methyl or ethyl, C , alkoxy such as methoxy, ethoxy, iso-propoxy or sec-butoxy, C alkylthio such as methylthio or ethylthio, C fluoroalkyl such as fluoromethyl, difluoromethyl or trifluoromethyl, C fluoroalkoxy such as fluoromethoxy, difluoromethoxy, trifluoromethoxy,

2-fluoroethoxy or 1,1,2,2-tetrafluoroethoxy, C„ - fluoroalkenyloxy such as

Z-o

3,4, -trifluorobut-3-enyloxy, 4,4-difluorobut-3-enyloxy or

4,4-difluoro-3-methylbut-3-enyloxy, C fluoroalkylthio such as trifluoromethylthio, C Z„-6, fluoroalkenylthio such as

3,4,4-trifluorobut-3-enylthio, 4,4-difluorobut-3-enylthio or

4,4-difluoro-3-methylbut-3-enylthio, chloro, fluoro, bromo, iodo, hydroxy, cyano, nitro, -C00R is hydrogen, C alkyl, C haloalkyl or C fluoroalkenyl such as -C00H, methoxycarbonyl, ethoxycarbonyl, 2-fluoroethoxycarbonyl, 3,4,4-trifluorobut-3-enyloxycarbonyl,

3-methyl-4, 4-difluorobut-3-enyloxycarbonyl or 4,4-difluorobut-3-enyloxycarbonyl, -SO R 21 where R21 is C alkyl or C haloalkyl such as methanesulphonyl or trifluoromethanesulphonyl, -SOR

22 where R is C alkyl or C. , haloalkyl such as methanesulphinyl trifluoromethanesulphinyl and -CSNH ; or where R and R taken together are

-0-(CH ₂ ) ₂ -0-.

A further group of compounds according to the invention which are of

1 2 3 4 particular interest are those of Formula (I) wherein R , R , R , R , Z, X and n have any of the meanings given in claim 1, with the proviso that at

1 2 3 4 least two of the groups R , R , R , and R are hydrogen.

A further group of compounds according to the invention which are of particular interest are those of Formula (I) wherein X and n have any of

1 2 3 4 the meanings given in claim 1 and each of the groups R , R , R and R is hydrogen.

Compounds according to the invention which are of particular interest

1 4 are those of Formula (I) wherein X, R -R and Z have any of the meanings given above and n is 0.

Those compounds of Formula (I) in which n is 1 exhibit stereoisomerism at the oxidised sulphur atom. The scope of the invention is to be understood to include all individual isomers of any compound according to the invention, and all isomer mixtures, including racemic mixtures.

Examples of compounds of formula (I) according to the invention are set out in Table I.

TABLE I

H H H

H H H

F H H

H F H

H H H

H H H

H H H

F F H

H H H

H H H

H H H

H H H

H H H

H H H

H H H

H H CH„

H CH. H

H CH CH=CH H

H ^C C ₃ H ₅ H

H

H

CH ₃

CH ₂ CH=CH,

^C C ₃ H ₅

Cl

^C 6 ^H 5 CH ₃

Cl

Cl

H

H

OCH ₃

H

TABLE I (continued)

R

OH

OH

H

0CH ₂ CF ₃

0CH ₂ CF ₃

0CH ₂ CH ₃

H

H

H

TABLE I (continued)

TABLE I (continued)

NO. X

99 H

100 H

101 H

102 H

103 H

104 0CH ₂ CC1=CH

105 OCH ₂ CH=CCl

106 0CH ₂ C0 ₂ C ₂ H ₅

107 CN

108 CONH

109 CON(CH ₃ )C ₂ H ₅

110 0CH ₂ CH ₂ F

111 OCH ₂ CH ₂ CH ₃

112 OCH(CH ₃ )C ₂ H ₅

113 H

114 H

115 H

116 H

117 H

118 H

119 H

120 S0 ₂ NH _£

121 H

122 H

123 H

124 H

125 H

126 H

127 H

128 --0--CH --0-

129 S0 ₂ F

130 H

131 OCH„

TABLE I (continued)

TABLE I (continued)

NO. R X n

164 -CH=CH-CH=CH-

165 1-CH ₃ - C ₃ H ₅ H

166 Br H

167 Br H

168 C≡CH H

170 C _C H _C H o o

171 ^C C ₃ H ₅ H

172 ^C C ₃ H ₅ H

173 CF ₂ H ₂ H

174 CF ₂ H ₂ H

175 CF ₃ H

176 CF ₃ H

177 CH ₂ CH=CH ₂ H

178 CH ₂ CH=CH ₂ H

179 CH CH F H

180 CH ₂ CH ₂ F H

181 CH ₂ CH ₃ H

182 CH CH H

183 CH OH H

184 CH OH H

185 CH CH,

186 CH H

187 CH ₃ H

188 CH ₃ H

189 CH H

190 Cl Cl

191 Cl H

192 Cl H

193 CN H

194 CO CH CH ₂ CH=CF ₂ H

195 C0 ₂ CH ₂ CH ₂ CH=CF ₂ H

196 CO CH CH ₂ CH=CF ₂ H

TABLE I (continued)

NO. R

TABLE I (continued)

NO. R

TABLE I (continued)

TABLE I (continued)

R ² R ³ R ⁴ X n

TABLE I ( continued )

NO.

328 H

329 H

330 H

331 H

332 H

333 H

334 H

335 H

336 H

337 H

338 H

339 H

340 H

341 H

342 H

343 H

344 H

345 H

346 H

347 H

348 H

349 H

350 H

351 H

352 H

353 H

354 H

355 H

356 H 357' H

358 H

359 H

360 H

TABLE I (continued)

NO.

361 H

362 H

363 H

364 H

365 H

366 H

367 H

368 H

369 H

370 H

371 H

372 H

373 H

374 H

375 H

376 H

377 H

378 H

379 H

380 H

381 H

382 H

383 H

384 H

385 H

386 H

387 H

388 H

389 H

390 -H

391 H

392 H

393 H

TABLE I (continued)

_ _ _

R R R X n

TABLE I (continued)

2 3 4 .

The compounds of formula (I) where R1, R2, R.3, R4 and Z have any of the meanings given above and n is 0 may be prepared by reacting a correspondingly substituted benzoxazole or benzthiazole of formula (II) with the commercially available l-bromo-2-fluoroethane under reaction conditions well known for such substitution reactions, for example in the presence of a base such as an alkali metal carbonate, for example potassium carbonate or sodium carbonate, in a suitable inert solvent, typically within a temperature range of 20°C - 100°C, and most suitably at the reflux temperature of a suitable solvent having a boiling point within this range, for example, acetone.

Thus, according to a further aspect of the present invention there is provided a process for the preparation of compounds of formula (I) wherein

1 2 3 4 R , R , R , R and Z have the any of meanings defined above and n is 0,

' which comprises reacting a correspondingly substituted compound of formula

(II) with l-bromo-2-fluoroethane in the presence of a base.

Many compounds of Formula (I) as described herein may also be prepared from other compounds of Formula (I) by transformation of the appropriate

1 2 3 4 R , R , R and R substituents using standard chemical procedures.

It will be appreciated by those skilled in the art that compounds of Formula (II) exist in tautomeric equilibrium between the equivalent 2-mercapto and 2-thione forms. For the sake of convenience, the compounds are referred to herein in their 2-mercapto form unless otherwise stated.

Compounds of Formula (II) are commercially available or may be prepared from commercially available precursors by standard procedures well known in the art. Typical procedures suitable for the preparation of many of the relevant compounds of Formula (II) and their precursors may be found in the following standard references: Comprehensive Heterocyclic Chemistry (Published by Pergamon, Edited by Katritzky and Rees), 1984, e.g. pages 177-331; Journal of Organic Chemistry, 1£, 758-766 (1954); Heterocyclic Compounds (Published by Wiley, Edited by Elderfield) , Volume 5; Organic Compounds of Sulphur, Selenium and Tellurium (Published by The Chemical Society, Specialist Reports), Volumes 3, 4 and 5; Warburton et al, Chemical Reviews, 5_7, 1011-1020 (1957). By way of example, many of the compounds of formula (II) where X is oxygen may be prepared by reacting a correspondingly substituted 2-aminophenol or a salt thereof, with thiophosgene or carbon disulphide, in an inert solvent such as diethyl ether or chloroform, and optionally in the presence of a base, such as potassium carbonate or triethylamine, and/or water. Also by way of

example, many of the compounds of formula (II) where X is sulphur may be prepared by the Herz Reaction (Warburton et al, Chemical Reviews, 57,

1011-1020 (1957)) in which appropriately substituted anilines are reacted sequentially with disulphur dichloride and aqueous sodium hydroxide to produce the corresponding 2-mercapto aniline derivative, which is then reacted with carbon disulphide to produce the 2-mercaptobenzthiazole of formula (II). Benzthiazoles of formula (II) may also be prepared from appropriately substituted N-phenylthioureas by oxidation (for example in the presence of molecular bromine) and replacement of the amino group of the resulting 2-aminobenzthiazole with a 2-mercapto group by reaction with a base and carbon disulphide or by diazotisation, reaction with a halide and displacement of the 2-halo group using NaSH or thiourea.

N-phenylthioureas are available by reaction of the corresponding anilines with ammonium thiocyanate. Compounds of Formula (II) may also be prepared by reaction of the correspondingly substituted 2-halonitrobenzene by reaction with sodium sulphide, sulphur (S ), and carbon disulphide, or by

8 reaction of the correspondingly substituted phenyl isothiocyanate with sulphur (S ) to produce the corresponding benzthiazole. All of these reactions are well documented in the chemical literature. The choice of the appropriate procedure will depend upon the particular nuclear substitution pattern required and is within the normal skill of the art.

Examples of these and many other procedures for the preparation of the compounds of Formula (II) are provided in the experimental examples. For any given compound of Formula (I) as herein described the appropriate starting materials may be prepared by these or directly analogous procedures. Suitable procedures are also described in the experimental examples for the preparation of other starting materials and intermediates for the various processes described herein, to provide access directly or by analogy to any such starting material or intermediate which is not readily available commercially.

1 2 3 4 The compounds of formula (I) where R , R , R , R and X have the meanings defined above and n is 1 or 2, are prepared by oxidising the correspondingly substituted compound of formula (I) when n is 0, using conventional methods, for example by treatment with a suitable oxidising agent in an inert organic solvent. In general, oxidation of a compound of

Formula (I) with one equivalent of a suitable oxidising agent provides the corresponding compound wherein n is 1, and oxidation using two equivalents of the oxidising agent provides the corresponding compound wherein n is 2.

Suitable oxidising agents include organic and inorganic peroxides such as hydrogen peroxide, peroxy carboxylic acids or their salts, for example, meta-chloroperbenzoic acid, perbenzoic acid, magnesium monoperoxy-phthalic acid, potassium peroxymono-sulphate or sodium periodate.

Thus, according to a further aspect of the present invention there is provided a process for the preparation of compounds of formula (I) where n is 1 or 2 and R 1, R2, R3, R4, X and Z have the meanings defined above, which comprises oxidation of the correspondingly substituted compound of formula (I) when n is 0.

The compounds of formula (I) are nematicidal and can be used to control nematodes in crop plants. Therefore, in a further aspect of the invention, there is provided a method for killing or controlling nematodes which comprises applying to the locus of the pests or to a plant susceptible to attack by the pest an effective amount of a compound of formula (I) as defined herein.

The term "controlling" extends to non-lethal effects which result in the prevention of damage to the host plant and the limitation of nematode population increase. These effects may be the result of chemical induced disorientation, immobilisation, or hatch prevention or induction. The chemical treatment may also have deleterious effects on nematode development or reproduction.

The compounds of the invention can be used against both plant- parasitic nematodes and nematodes living freely in the soil. Examples of plant-parasitic nematodes are: ectoparasites, for example Xiphinema spp. , Longidorus spp. and Trichodorous spp. ; semi-endoparasites, for example, Tylenchulus spp.; migratory endoparasites, for example, Pratylenchus spp., Radopholus spp. and Scutellonema spp. ; sedentary endoparasites, for example, Heterodera spp. , Globodera spp. and Meloidogyne spp. ; and stem and leaf endoparasites, for example, Ditylenchus spp., Aphelenchoides spp. and Hirshmaniella spp..

The compounds of formula (I) display nematicidal activity against different types of nematodes including the cyst nematode.

The compounds of formula (I) may also be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Homoptera and Coleoptera (including Diabrotica i.e. corn rootworms) and also other invertebrate pests, for example, acarine pests. The insect and acarine pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term

includes the growing of crops for food and fibre products), horticulture and animal husbandry, forestry, the storage of products of vegetable origin, such as fruit, grain and timber, and also those pests associated with the transmission of diseases of man and animals. Examples of insect and acarine pest species which may be controlled by the compounds of Formula (I) include:

Myzus persicae (aphid)

Aphis gossypii (aphid)

Aphis fabae (aphid)

Megoura viceae (aphid)

Aedes aegypti (mosquito)

Anopheles spp. (mosquitos)

Culex spp. (mosquitos)

Dysdercus fasciatus (capsid)

Musca domestica (housefly)

Pieris brassicae (white butterfly)

Plutella maculipennis (diamond back moth)

Phaedon cochleariae (mustard beetle)

Aonidiella spp. (scale insects)

Trialeuroides spp. (white flies)

Bemisia tabaci (white fly)

Blattella germanica (cockroach)

Periplaneta americana (cockroach)

Blatta orientalis (cockroach)

Spodoptera littoralis (cotton leafworm)

Heliothis virescens (tobacco budworm)

Chortiocetes terminifera (locust)

Diabrotica spp. (rootworms)

Agrotis spp. (cutworms)

Chilo partellus (maize stem borer)

Nilaparvata lugens (planthopper)

Nephotettix cincticeps (leafhopper)

Panonychus ulmi (European red mite)

Panonychus citri (citrus red mite)

Tetranychus urticae (two-spotted spider mite)

Tetranychus cinnabarinus (carmine spider mite)

Phvllcoptruta oleivora (citrus rust mite)

Polyphagotarsonemus latus (broad mite) Brevipalpus spp. (mites)

In order to apply the compound to the locus of the nematode, insect or acarid pest, or to a plant susceptible to attack by the nematode, insect or acarid pest, the compound is usually formulated into a composition which includes in addition to the compound of formula (I) suitable inert diluent or carrier materials, and/or surface active agents. Thus in two further aspects of the invention there is provided a nematicidal, insecticidal or acaricidal composition compriεing an effective amount of a compound of formula (I) as defined herein and an inert diluent or carrier material and optionally a surface active agent.

The amount of composition generally applied for the control of nematode pests gives a rate of active ingredient from 0.01 to 10 kg per hectare, preferably from 0.1 to 6 kg per hectare.

The compositions can be applied to the soil, plant or seed, to the locus of the pests, or to the habitat of the pests, in the form of dusting powders, wettable powders, granules (slow or fast release), emulsion or suspension concentrates, liquid solutions, emulsions, seed dressings, fogging/smoke formulations or controlled release compositions, such as microencapsulated granules or suspensions.

Dusting powders are formulated by mixing the active ingredient with one or more finely divided solid carriers and/or diluents, for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers.

Granules are formed either by absorbing the active ingredient in a porous granular material for example pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths, ground corn cobs, and the like, or on to hard core materials such as sands, silicates, mineral carbonates, sulphates, phosphates, or the like. Agents which are commonly used to aid in impregnation, binding or coating the solid carriers include aliphatic and aromatic petroleum solvents, alcohols, polyvinyl acetates, polyvinyl alcohols, ethers, ketones, esters, dextrins, sugars and vegetable oils, with the active ingredient. Other additives may also be included, such as emulsifying agents, wetting agents or dispersing agents.

Microencapsulated formulations (microcapsuie suspensions CS) or other controlled release formulations may also be used, particularly for slow release over a period of time, and for seed treatment.

Alternatively the compositions may be in the form of liquid preparations to be used as dips, irrigation additives or sprays, which are generally aqueous dispersions or emulsions of the active ingredient in the presence of one or more known wetting agents, dispersing agents or emulsifying agents (surface active agents). The compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of an emulsifiable concentrate (EC) or a suspension concentrate (SC) containing a high proportion of the active ingredient or ingredients. An EC is a homogeneous liquid composition, usually containing the active ingredient dissolved in a substantially non-volatile organic solvent. An SC is a fine particle size dispersion of solid active ingredient in water. To apply the concentrates they are diluted in water and are usually applied by means of a spray to the area to be treated. For agricultural or horticultural purposes, an aqueous preparation containing between 0.00012 and 0 . 1Z by weight of the active ingredient (approximately equivalent to from 5-2000g/ha) is particularly useful.

Suitable liquid solvents for ECs include methyl ketone, methyl isobutyl ketone, cyclohexanone, xylenes, toluene, chlorobenzene, paraffins, kerosene, white oil, alcohols, (for example, butanol), methylnaphthalene, trimethylbenzene, trichloroethylene, N-methyl-2-pyrrolidone and tetrahydrofurfuryl alcohol (THFA).

Wetting agents, dispersing agents and emulsifying agents may be of the cationic, anionic or non-ionic type. Suitable agents of the cationic type include, for example, quaternary ammonium compounds, for example cetyltrimethyl ammonium bromide. Suitable agents of the anionic type include, for example, soaps, salts of aliphatic monoesters of sulphuric acid, for example sodium lauryl sulphate, salts of sulphonated aromatic compounds, for example sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, or butylnaphthalene sulphonate, and a mixture of the sodium salts of diisopropyl- and triisopropylnaphthalene sulphonates. Suitable agents of the non-ionic type include, for example, the condensation products of ethylene oxide with fatty alcohols such as oleyl alcohol or cetyl alcohol, or with alkyl phenols such as octyl phenol, nonyl phenol and octyl cresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the

condensation products of the said partial esters with ethylene oxide, and the lecithins.

These concentrates are often required to withstand storage for prolonged periods and after such storage, to be capable of dilution with water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may contain 1-85Z by weight of the active ingredient or ingredients. When diluted to form aqueous preparations such preparations may contain varying amounts of the active ingredient depending upon the purpose for which they are to be used.

The compounds of formula (I) may also be formulated as powders (dry seed treatment DS or water disperible powder WS) or liquids (flowable concentrate FS, liquid seed treatment LS), or microcapsule suspensions CS for use in seed treatments. The formulations can be applied to the seed by standard techniques and through conventional seed treaters. In use the compositions are applied to the nematodes, to the locus of the nematodes, to the habitat of the nematodes, or to growing plants liable to infestation by the nematodes, by any of the known means of applying pesticidal compositions, for example, by dusting, spraying, or incorporation of granules.

The compounds of the invention may be the sole active ingredient of the composition or they may be admixed with one or more additional active ingredients such as nematicides or agents which modify the behaviour of nematodes such as hatching factors, insecticides, synergists, herbicides, fungicides or plant growth regulators where appropriate.

Suitable additional active ingredients for inclusion in admixture with the compounds of the invention may be compounds which will broaden the spectrum of activity of the compounds of the invention or increase their persistence in the location of the pest. They may synergise the activity of the compound of the invention or complement the activity for example by increasing the speed of effect or overcoming repellency. Additionally multi-component mixtures of this type may help to overcome or prevent the development of resistance to individual components.

The particular additional active ingredient included will depend upon the intended utility of the mixture and the type of complementary action required. Examples of suitable insecticides include the following: a) Pyrethroids such as permethrin, esfenvalerate, deltamethrin, cyhalothrin in particular lambda-cyhalothrin, biphenthrin, fenpropathrin,

cyfluthrin, tefluthrin, fish safe pyrethroids for example ethofenprox, natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin and 5-benzyl-3-furylmethyl-(E)-(1R,3S)-2,2-dimethyl- 3- (2-oxothiolan-3-ylidenemethyl) cyclopropane carboxylate; b) Organophosphates such as profenofos, sulprofos, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenophos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chloropyrifos, phosalone, terbufos, fensulphothion, fonofos, phorate, phoxi , pyrimiphos-methyl, pyrimiphos-ethyl, fenitrothion or diazinon; c) Carbamates (including aryl carbamates) such as pirimicarb, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulphan, bendiocarb, fenobucarb, propoxur or oxamyl; d) Benzoyl ureas such as triflumuron, or chlorofluazuron; e) Organic tin compounds such as cyhexatin, fenbutatin oxide, azocyclotin; f) Macrolides such as avermectins or milbemycins, for example such as abamectin, avermectin, and milbemycin; g) Hormones and pheromones; h) Organochlorine compounds such as benzene hexachloride, DDT, endosulphan, chlordane or dieldrin; i) Amidines, such as chlordimeform or amitraz; j) Fumigant agents; k) nitromethylenes such as imidacloprid.

In addition to the major chemical classes of insecticide listed above, other insecticides having particular targets may be employed in the mixture if appropriate for the intended utility of the mixture. For instance selective insecticides for particular crops, for example stemborer specific insecticides for use in rice such as cartap or buprofezin can be employed. Alternatively insecticides specific for particular insect species/stages for example ovo-larvicides such as chlofentezine, flubenzimine, hexythiazox and tetradifon, motilicides such as dicofol or propargite, acaricides such as bromopropylate, chlorobenzilate, or growth regulators such as hydramethylon, cyromazin, methoprene, chlorfluazuron and diflubenzuron may also be included in the compositions.

Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamax, safroxan and dodecyl imidazole.

Suitable herbicides, fungicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.

An example of a rice selective herbicides which can be included is propanil, an example of a plant growth regulator for use in cotton is "Pix", and examples of fungicides for use in rice include blasticides such as blasticidin-S. The ratio of the compound of the invention to the other active ingredient in the composition will depend upon a number of factors including type of target, effect required from the mixture etc. However in general, the additional active ingredient of the composition will be applied at about the rate as it is usually employed, or at a slightly lower rate if synergism occurs.

Compounds of Formula (I) according to the invention also show fungicidal activity and may be used to control one or more of a variety of plant pathogens. In a further aspect the invention therefore includes a method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a compound as herein defined or a composition containing the same. The invention further includes a fungicidal composition comprising a fungicidally effective amount of a compound as herein defined and a fungicidally acceptable carrier or diluent therefor.

Examples of plant pathogens which the compounds or fungicidal compositions of the invention may control, methods by which fungi may be combatted and the form of suitable compositions, including acceptable carriers ad diluents, adjuvants such as wetting, dispersing, emulsifying and suspending agents, and other ingredients, such as fertilisers and other biologically active materials, are described, for instance, in International application No WO 93/08180, the content of which is incorporated herein by reference.

The invention is illustrated by the following Examples in which percentages are by weight and the following abbreviations are used: gc = gas chromatography; nmr = nuclear magnetic resonance; s = singlet; d = doublet; t = triplet; q = quartet; = multiplet; dd = double doublet; ddt = double doublet of triplets, dtd = double triplet of doublets; b or br = broad; g = grammes; mg = milligrammes; CDC1 = deuterochloroform; DMSO = d -dimethyl sulphoxide; Chemical shifts (δ) are measured in parts per million from tetramethylene silane. CDC1 was used as solvent unless

+ otherwise stated. M = molecular ion as determined by mass spectrometry;

ir = infra red spectrometry; tic = thin layer chro atography; (dec) = decomposed on melting.

EXAMPLE IA A general procedure for the preparation of 2-mercaptobenzthiazoles (from the corresponding 2-halonitrobenzene) is illustrated by the following preparation of 2-mercaptobenzthiazol-5-yl methyl sulphone (Ref. J.Am.Chem.

Soc. (1944) 66_, 835).

3 A solution of sodium sulphide nonahydrate (17.8g) in water (16cm ) containing sulphur (4.8g) was stirred at 75-80 °C for 0.5 hour under an atmosphere of nitrogen to give a yellow solution. To the solution was added in portions 4-fluoro-3-nitrobenzene methyl sulphone (Fairfield

Chemical Co ,5.6g). The temperature of the mixture gradually rose to 100°C, and the mixture was cooled to 60°C to complete the addition. Carbon

3 disulphide (5cm ) was added to the reaction mixture at 60°C through the condenser and the mixture was heated to reflux for 2 hours after which time the initially orange mixture gave a yellow precipitate. The reaction

3 mixture was cooled, diluted with water (400cm ), the insoluble material was filtered from the solution, and the filtrate was acidified with acetic acid. The precipitated solid was filtered, washed with water and dried by

3 suction. The solid was extracted with ethyl acetate (600cm ), the solution washed with water, dried (magnesium sulphate) and- evaporated under reduced pressure to give the title product as a yellow solid, mp 242-244°C; ir:

3246,1328,1158. cm ^"1

The following compounds were prepared using the method of Example IA.

(i) 2-Mercapto-5-methoxybenzthiazole: yellow solid mp 198-200°C (from 4-methoxy-2-nitrochlorobenzene)

(ii) 2-Mercapto-5-fluorobenzthiazole: yellow solid mp 125°C (dec) (from 1,4-difluoro-2-nitrobenzene)

(iii) 2-Mercapto-7-chlorobenzthiazole: fawn solid mp 250-251°C (dec) (from l,2-dichloro-3 nitrobenzene)

(iv) 5-Bromo-2-mercaptobenzthiazole: yellow solid mp 186°C; M =245 (from 1,4-dibromo-2-nitrobenzene)

(v) 2-Mercapto-5-trifluoromethoxybenzthiazole: colourless solid mp 144°C; M =251 (from 2-nitro-4-trifluoromethoxyfluorobenzene)

(vi) 2-Mercapto-5-trifluoromethylthiobenzthiazole: colourless solid mp 138-140°C; M =267 (see Example 5(i) for preparation of starting material)

(vii) 2-Mercapto-5-trifluoromethylsulphinylbenzthiazole (M =283) and 2-Mercapto-5-trifluoromethylsulphonylbenzthiazole (M 299) from 2-nitro-4-

trifluoromethylsulphinylbro obenzene and 2-nitro-4- trifluoromethylsulphonylbromobenzene; (see Example 5(iii) for preparation of starting materials)

(viii) 2-mercapto-5-methylbenzthiazole: yellow crystals mp 173-175°C (from 4-chloro-3-nitrotoluene)

(ix) 2-mercapto-5-(N,N-dimethylsulphonamido)benzthiazole: mp 220°C (see Example 5(ii) for preparation of starting material).

EXAMPLE IB

A general procedure for the preparation of 2-mercaptobenzthiazoles (from the corresponding 2-aminobenzthiazoles) is illustrated by the following preparation of 6-fluoro-2-mercaptobenzthiazole (Ref. J.Het. Chem.

(1980) 17_ 1325) .

3 A solution of 2-amino-6-fluorobenzthiazole (10.Og) in water (100cm ) containing sodium hydroxide (50.Og) was stirred and heated to reflux for 18 hours, cooled to the ambient temperature and filtered. Carbon disulphide

3 (17.5cm ) was added to the filtrate and the mixture was heated to reflux for 4 hours, cooled to the ambient temperature, diluted with water and neutralised with acetic acid. The fawn solid which precipitated was filtered from solution, washed with water and dried by suction to give the title product, mp above 260°C, M =185.

The following compounds were prepared using the method of Example IB.

(i) 2-Mercapto-4-methylbenzthiazole: mp above 260°C; M =181; yellow solid , ^' ii) 2-Mercapto-6-methylbenzthiazole: mp 248°C; M =181; yellow solid

EXAMPLE 1C A general procedure (the 'Herz process') for the preparation of 2-mercaptobenzthiazoles from the corresponding 2-mercaptoaniline (and a procedure for preparing the 2-mercaptoaniline from the corresponding aniline) is illustrated by the following preparation of 6-chloro-2-mercaptobenzthiazole.

To a stirred solution of 4-chloroaniline (2.55 g) in acetic acid (5

3 3 cm ) was added sulphur monochloride (10 cm ) causing formation of a thick red slurry. The reaction was heated at 60°C for 4 hours giving a mixture of green solid and a green solution. The mixture was diluted with hexane and the green solid waε filtered off. The solid was taken into water and

2M NaOH was added and the mixture heated for 4 hours at 100°C and then filtered through celite to give a pale pink filtrate. Carbon disulphide (2

3 cm ) was added to the filtrate and the reaction was heated at reflux for 15

hours. The mixture was cooled and acidfied to pH 1 causing formation of a thick yellow precipitate. Filtration and recrystallisation from ethanol/acetone/water gave 6-chloro-2-mercaptobenzthiazole as a white solid. ¹ H NMR (DMSO): d 7.97 (IH, d) , 7.58 ( IH, dd) , 7.41 (IH, d) . Mp 251 -253°C (dec) .

The following compounds were prepared using the method of Example IC from the corresponding starting materials.

(i) 2-mercapto-6-methoxybenzthiazole. tan solid; H nmr (DMSO) d: 13.10 (IH, bs), 7.21 (IH, d) , 6.95 (IH, bs), 6.88 (IH, dd) , 3.89 (3H, s). Mp 199-200°C

(ii) 2-mercapto-5-trifluoromethylbenzthiazole. yellow solid; H nmr (CDC1 , drop of DMSO) d: 13.50 (IH, bs), 7.40-7.60 (3H, m, overlapping aromatic signals). Mp 218-219°C (dec), M =235.

EXAMPLE ID

This Example illustrates miscellaneous preparative methods for 2-mercaρtobenzthiazoles.

(i) 2-mercaptobenzthiazole-5-carboxylic acid.

To a stirred suspension of 4-chloro-3-nitrobenzoic acid (20 g) in DMF

3 3

(1 cm ) and dichloromethane (100 cm ) was added oxalyl chloride (13 g) in

3 dichloromethane (50 cm ) over 1 hour. The reaction was stirred at 30°C for

5 hours, after which reaction became homogeneous, and stirred at the ambient temperature for 18 hours. Evaporation under reduced pressure gave a white solid that was triturated with hexane and dried to give 4-chloro-3- nitrobenzoyl chloride as a white solid (21.82 g) . H nmr (CDC1 ) d: 8.61

(IH, d), 8.26 (IH, dd) , 7.78 (IH, d) . Mpt 49-51°C.

To a stirred solution of 4-chloro-3-nitrobenzoyl chloride (20.5 g) in

3 ethyl acetate (80 cm ) was added a solution of triethylamme (10.1 g) and

3 i-propylalcohol (6 g) in ethylacetate (40 cm ) over 15 mins causing a slight exotherm. The reaction was stirred at the ambient temperature for a further 3.5 hours and then poured into water. The layers were separated and the aqueous layer was extracted with ethyl acetate and the combined ethyl acetate layers were washed with 102 HCl, brine and dried with sodium sulphate. Filtration and evaporation gave iso-propyl 4-chloro-3- nitrobenzoate as a yellow solid (22.5 g) . IH nmr (CDC13) d: 8.49 (IH, d), 8.17 (IH, dd), 7.64 (IH, d), 5.29 (IH, septet), 1.40 (6H, d) . Mpt 61-

62°C

A mixture of iso-propyl 4-chloro-3-nitrobenzoate (15.84 g) and sodium

- sulphide nonahydrate (47 g) in water (110 cm ^" ) was heated at reflux for 17

hours giving a homogeneous red solution. Carbon disulphide (6 cm ) was added and the reaction was heated under reflux for 4 hours. After cooling the mixture was acidified to pHl with concentrated HCl causing formation of a tan precipitate. The solid was filtred off and recrystallised from ethanol/acetone/water to give the title product as a tan solid (8.85 g) . ¹ H nmr d: 7.54 (IH, d) , 7.40 (IH, d) , 7.21 (IH, dd) . Mpt >300°C.

(ii) 3 Step preparation of 2-mercapto-5, 6-methylenedioxybenzthiazole.

Step 1: 2-Amino-5,6-methylenedioxybenzthiazole.

3, 4-Methylenedioxyphenylthiourea (1.96g; Lancaster Chemical Co) in 3 chloroform (6cm ) was stirred at ambient temperature and a solution of

3 3 bromine (0.37cm ) in chloroform (3cm ) was added in portions. The mixture was cooled using a water bath and after lhr. was stored for 64hr., diluted

3 with water (100cm ), basified with aqueous 2M sodium hydroxide and

3 extracted with ethyl acetate (2x150cm ) . The combined organic phases were washed with water and dried (magnesium sulphate). The solution was evaporated under reduced pressure to give the required product as a pale pink solid; mp 200°C; ^λ E NMR (CDC1 ) : δ 7.06(lH,s); 7.02(lH,s); 5.98(2H,s);

5.0(broad signal, 2H) .

Step 2: 2-Chloro-5,6-methylenedioxybenzthiazole.

The product from Step 1 (1.7g) was partially dissolved in dry 3 acetonitrile (50cm ) and added in portions to a stirred suspension of

3 copper(II) chloride (1.41g) and tert-butyl nitrite (1.56cm ) in dry

3 acetonitrile (15cm ) at 60°C. The mixture was heated for lhr., cooled to ambient temperature, poured into water/diethyl ether and acidified with aqueous 2M hydrochloric acid. The aqueous fraction was separated and

3 extracted with diethylether (3x100cm ) and the combined organic fractions

3 washed with water (3x50cm ) and dried (magnesium sulphate). The solution was evaporated under reduced pressure to give a brown solid. The solid was fractionated by absorbing it onto silica and eluting with hexane/ethyl acetate (50:1 by volume) to give the required product as a colourless solid, M ⁺ =213; ¹ H NMR (CDC1 ₃ ): δ 7.36(lH,s): 7.14(lH,s); 6.08(2H,s); mp

131-2°C.

Step 3: 2-Mercapto-5,6-methylenedioxybenzthiazole.

The product from Step 2 (0.67g) and thiourea (0.26g) were mixed in

3 ethanol (20cm ) and stirred and heated to reflux under an atmosphere of nitrogen for 18hr. The pale yellow solid which precipitated was filtered from the solution at ambient temperature, washed with ethanol and sucked to

dryness to give the required product. H NMR (DMSO): δ 7.26(lH,s); 6.80(lH,ε); 6.02(2H,s); mp 265°C (dec); M ⁺ =211.

EXAMPLE 2A A general procedure for the preparation of 2-mercaptobenzoxazoles (from the corresponding 2-aminophenol) is illustrated by the following preparation of 2-mercapto-5-methylbenzoxazole.

3 To a brown solution of 2-amino-5-methylphenol (5g) in 2M NaOH (80cm ) stirring at the ambient temperature was added carbon disulphide and the reaction mixture was stirred for 5 days. The solution was acidified to pH

4 by the addition of concentrated hydrochloric acid, causing formation of a beige precipitate. The precipitate was filtered and dried by suction to give the title product as a free flowing beige powder (4.06g). H NMR

(DMSO): δ 13.9 (lH.br s); 7.5(lH,d); 7.18(lH,d); 7.15(lH,s); 2.49(3H,s) ppm.

The following compounds were prepared using the method of Example 2A

( ;ii)) 22--mmeerrccaappttoo--44--mmeetthhyylbenzoxazole - beige powder. H NMR (DMSO): δ 7.27(lH,d); 6.98-7.18(2H,m) ( (iiii)) 44--hhyyddrrooxxyy--22--mmeerrccaaptobenzoxazole - beige powder. H NMR (DMSO): I 7.00(lH,t); 6.9(lH,d); 6.7(lH,d). ( (iiiiii)) 44--aammiinnoo--22--mmeerrccaappttoobbeennzzoxazole - ginger solid. H NMR (DMSO): δ IH NMR 12.45(2H, br s); 10.00 (lH,br s); 7.0(lH,t); 6.6-6.75(2H,2xd) ( (iivv)) 22--mmeerrccaappttoobbeennzzooxxaazzoollee--44--ccaarrboxyli c acid - beige solid. H NMR (DMSO): δ 7.65-7.85(2H,2xd) ; 7.30(lH,t) ( (vv)) 55 cchhlloorroo--22--mmeerrccaappto benzoxazole - grey solid. H NMR (DMSO): δ 7.60(lH,d); 7.30-7.40(2H,m) .

(vi) 2-mercaptobenzoxazole-5-carboxylic acid - beige solid. H NMR (DMSO): δ 7.95(lH,d); 7.78(lH,d); 7.65(lH,d).

(vii)4,5-benzo-2-mercaptobenzoxazole. H NMR (DMSO): δ 8.35(lH,d); 8.20(lH,d); 8.00(lH,d); 7.88(lH,d); 7.81(lH,t); 7.71(lH,t).

EXAMPLE 2B

This Example gives a general process for the preparation of 2- mercaptobenzoxazoles from the corresponding 2-aminophenol or a salt thereof, as illustrated by the procedure for preparing 2-mercapto-7- nitrobenzoxazole.

3 Carbon disulphide (0.6cm ) was added to a solution of potassium

3 3 hydroxide (0.652g) in methanol (16.5cm ) and water (3cm ). The resulting solution containing potassium methyl xanthate was added to 2-amino-6- nitrophenol (1.4g) and the mixture heated and stirred under reflux for 18

hours. The resulting solution was cooled, acidified to pH 3 with concentrated hydrochloric acid, and the dark orange solid which precipitated was recoved by filtration and dried by suction. This gave 2- mercapto-7-nitrobenzoxazole (1.25g). M ⁺ =196; H NMR (DMSO): δ 7.6(lH,t); 7.75(lH,d); 8.1(lH,d).

The following intermediates were prepared using the method of Example 2B.

(i) 2-mercapto-6-nitrobenzoxazole - yellow/orange solid. M =196; H

NMR (DMSO): δ 7.55(lH,d); 8.35(lH,dd); 8.55(lH,d).

( (iiii)) 22--mmeerrccaappttoo--66--mmeetthhyyllbbeennzzoxazole - cream solid. H NMR (CDC1 ) 2.45(3H,s); 7.1(2H,s); 7.2(lH,s).

(iii) methyl 2-mercaptobenzoxazol-6-carboxylate - orange solid. H NMR (CDC1 ): δ 3.9(3H,s); 7.2(lH,d); 7.9-8.05(2H,m) .

(iv) 5-(ethanesulphonyl)-2-mercaptobenzoxazole - grey/brown solid.

M ⁺ =243 3;; ^{1 ~} H NMR (DMSO): δ 1.15(3H,t); 3.35-3.45(2H,q) ; 7.7(lH,s); 7.8- 7.9(2H,m) ( (vv)) 5-cyano-2-mercaptobenzoxazole. M =176; H NMR (CDC1 ) : δ 6.9(lH,br ε); 7.2-7.5(2H,m) . ( (vvii)) 55--aammiinnoo--22--mmeerrccaappttoobenzoxazole - grey solid. M =166; H NMR (DMSO): δ 5.2-5.5(lH,br s); 6.5-6.6(2H,m) ; 7.25(lH,d). ( (vviiii)) 22--mmeerrccaappttoo--77--mmeetthhyyllbbeennzzoxazole - brown solid. M =165; H NMR (DMSO): δ 2.45(3H,s); 7.1-7.35(3H,m) .

(viii) 6-hydroxy-2-mercaptobenzoxazole - brown solid. H NMR (DMSO) 13.7-13.8(lH,bs) ; 9.75-10.0(IH,bs) ; 7.15-7.20(IH,d) ; 7.0-7.05(IH,d) ; 6.8-6.9(lH,dd) .

EXAMPLE 2C

A general procedure for the preparation of 2-mercaptobenzoxazoles (from the corresponding 2-aminophenol) is illustrated by the following preparation of 2-mercapto-4-nitrobenzoxazole.

3 Sodium hydroxide (1.2 g) was added to water (3 cm ) and allowed to

3 disεolve before addition of dioxane (45 cm ) and 2-amino-3-nitrophenol

(4.5g). The dark red solution was cooled to 0°C and thiophosgene (4.5 g in

3 dioxane (15 cm )) waε added and the reaction εtirred for 18 hours at the ambient temperature. Water was added to the mixture causing precipitation of an olive green solid which was filtered and dried under vacuum to give the title product (1.15 g) . ^λ E nmr (CDC1 ₃ ) : d 8.0 (IH, d) , 7.88 (IH, d), 7.4 (IH, t).

The following compound was also made by the method described in

Example 2C from 2-amino-4-nitrophenol.

( (ii)) 22--mmeerrccaappttoo--55--nniittrrcobenzoxazole H nmr (CDC1 ) : d 8.32 (IH, dd) , 8.08 (IH, bs), 7.85 (IH, d) .

EXAMPLE 3A

A general procedure for thepreparation of

2-(2-fluoroethylthio)-substituted benzoxazoles and benzthiazoles by reaction of the corresponding 2-mercaptobenzoxazole or

2-mercaptobenzthiazole with l-bromo-2-fluoroethane is illustrated by the following preparation of 2-(2-fluoroethylthio)benzthiazole (Compound No 1).

To a stirred suεpenεion of 2-mercaptobenzothiazole (1.05 g) and

3 potassium carbonate (862 mg) in acetone (15 cm ) at the ambient temperature was added l-bromo-2-fluoroethane (785 mg) and the reaction was then heated under reflux for 2 hours. The mixture was poured into water and the layers separated. The aqueous layer was extracted twice with ethyl acetate and the combined organic layers were washed with water, brine, and dried with magnesium sulphate. Filtration and evaporation gave 2-(2- fluoroethyl)benzthiazole as a brown oil (1.17 g) . H NMR (CDC1 ) : δ 7.85

(IH, d), 7.44 (IH, t), 7.30 (IH, t), 4.79 (2H, dt), 3.70 (2H, dt) .

The following compounds were prepared from the corresponding 2- mercaptobenzoxazole or 2-mercaptobenzothiazole using the method of Example 3A.

(i) 6-fluoro-2-(2-fluoroethylthio)benzoxazole (Compound No. 47). H NMR (CDC1 ₃ ): δ 7.50 (IH, m) , 7.15 (IH, m) , 7.01 (IH, m) , 4.60-4.90 (2H, m) , 3.44-3.70 (2H, m) ; solid; mp 42.7-44.5°C

(ii) 6-ethoxy-2-(2-fluoroethylthio)benzothiazole (Compound No. 56). ^λ U NMR (CDC1 ): δ 7.74 (IH, d) , 7.20 (IH, d) , 7.00 (IH, dd) , 4.75 (2H, dt), 4.05 (2H, q), 3.65 (2H, dt) , 1.44 (3H, t) ; solid; mp 69-73°C.

(iii) 5-chloro-2-(2-fluoroethylthio)benzoxazole (Compound No. 89). H NMR (CDC1 ₃ ): δ 7.82 (IH, d) , 7.62 (IH, d) , 7.25 (IH, dd) , 4.75 (2H, dt), 3.65 (2H, dt); oil.

(iv) 5-chloro-2-(2-fluoroethylthio)benzothiazole (Compound No. 63). ^X H NMR (CDC1 ₃ ): δ 7.55 (IH, d) , 7.33 (IH, d) , 7.20 (IH, dd) , 4.77 (2H, dt) , 3.58 (2H, dt); oil.

(v) 2-(2-fluoroethylthio)benzoxazole (Compound No. 2). H NMR (CDC1 ): δ 7.60 (IH, dd) , 7.45 (IH, dd) , 7.25 (IH, m) , 4.79 (2H, dt), 3.60 (2H, dt); oil.

(vi) 2-(2-fluoroethylthio)-6-methoxybenzoxazole (Compound No. 57). H NMR (CDC1 ): δ 7.47 (IH, d) , 7.00 (IH, d) , 6.89 (IH, dd) , 4.70 (2H, dt), 3.82-3.87 (5H, m) ; oil.

(vii) 2- (2-fluoroethylthio)-6-methoxybenzothiazole (Compound No. 58). ¹ H NMR (CDC1 ): δ 7.75 (IH, d) , 7.23 (IH, d) , 7.00 (IH, dd) , 4.71 (2H, dt) , 3.86 (3H, s), 3.64 (2H, dt); oil.

(viii) 2- (2-fluoroethylthio)-5-trifluoromethylbenzothiazole (Compound No. 62). ¹ H NMR (CDC1 ) : δ 8.11 (IH, s), 7.86 (IH, d) , 7.55 (IH, d), 4.80 (2H, dt) , 3.70 (2H, dt) ; oil.

(ix) 2-(2-fluoroethylthio)-5-methylbenzothiazole (Compound No. 22). ^λ E NMR (CDC1 ): δ 7.67 (IH, s), 7.10-7.18 (2H, m) , 4.77 (2H, dt), 3.73 (2H, dt), 2.48 (3H, s); oil.

(x) 2-(2-fluoroethylthio)-6-nitrobenzothiazole (Compound No. 52). H NMR (CDC1 ): δ 8.70 (IH, d) , 8.33 (IH, dd) , 7.92 (IH, d) , 4.81 (2H, dt), 3.76 (2H, dt); solid ; mp 140-145°C

(xi) 6-hydroxy-2-(2-fluoroethylthio)benzoxazole (Compound No 54). M ⁺ =213; -"-H NMR (CDC1 ) : δ 3.45-3.65(2H,m) ; 4.70-4.90(2H,m) ; 5.85(lH,s); 6.80(lH,dd); 7.0(lH,d); 7.45(lH,d); oil.

(xii) 2-(2-fluoroethylthio)-6-nitrobenzoxazole (Compound No. 5). M ⁺ =242; ^λ E NMR (CDC1 ) : δ 3.6-3.75(2H,m) ; 4.7-4.95(2H,m) ; 7.65(lH,d); 8.3(lH,dd); 8.4(lH,d); solid; mp 58.2-59.4°C.

EXAMPLE 3B An alternative procedure suitable for the preparation of 2-(2-fluoroethylthio)-substituted benzoxazolecarboxylic acids and benzthiazolecarboxylic acids is illustrated by the following preparation of 2-(2-fluoroethylthio)benzthiazole-5-carboxylic acid (Compound No 68).

To a suspension of 2-mercaptobenzothiazole-5-carboxylic acid (389 mg)

3 in tetrahydrofuran (10 cm ) was added triethylamine (371 mg) causing formation of a brown solution, l-bromo-2-fluoropropane (467 mg) was added and the reaction was heated at the reflux temperature for 6.5 hours. The reaction was cooled and diluted with ethyl acetate and the solution washed with 20Z HCl and brine. Ecaporation gave a white solid which was recrystallised from ethanol/water to give the product as a white solid (235 mg). ¹ H nmr (CDC1 and one drop of DMSO) : δ 8.52 (IH, d) , 8.02 (IH, dd) ,

7.80 (IH, d), 4.89 (IH, t), 4.75 (IH, t) , 3.78 (IH, t), 3.69 (IH, t); mp

173-175°C.

EXAMPLE 4

The following example illustrateε procedures suitable for the

preparation of compounds according to the invention in which the sulphur atom of the 2-substituent on the benzoxazole or benzthiazole ring of the corresponding unoxidised compound (prepared according to the procedures of

Example 3A and 3B) is oxidised to sulphoxide (sulphinyl) or εulphone

(sulphonyl). In general, the use of one equivalent of oxidising agent leads predominantly to the formation of the corresponding sulphoxide product and two equivalents lead to the formation of the sulphone.

Mixtures of the oxidised products are frequently obtained however, and these may be readily separated by standard techniques such as column chromatography.

Preparation of 2-(2-fluoroethylsulphonyl)benzothiazole (Compound No

14).

To a solution of 2-(2-fluoroethylthio)benzothiazole (Compound No 1,

3 Example 3A, 213 mg) in acetic acid (2 cm ) was added hydrogen peroxide (0.5

3 cm ) and the reaction was stirred at the ambient temperature for 2 hours and at 80°C for 3 hours. The reaction mixture was cooled and poured into water and the layers separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, saturated sodium bicarbonate, and dried with magnesium sulphate.

Filtration and evaporation gave the product as a pale yellow solid (167 mg). -" ^" H nmr (CDC1 ₃ ) : δ 8.24 (IH, dd) , 8.05 (IH, dd) , 7.65 (2H, m) , 4.95

(2H, dt), 3.96 (2H, dt) ; mp 89-93°C.

EXAMPLE 5

This Example illustrates the preparation of miscellaneous starting materials of use in the preparation of compounds according to the invention and intermediates therefor.

(i) 4-Step preparation of 4-trifluoromethylthio-2-nitrochlorobenzene (starting material for Example lA(vi) .

Step 1: 4-trifluoromethylthioacetanilide.

3 Acetic anhydride (5.9cm ) was added dropwise to 4-aminophenyl

3 trifluoromethyl sulphide (10.Og) in acetic acid (18cm ) to give a solid suspension. The mixture was poured into ice/water and the solid was filtered, waεhed with water dichloromethane, then dried by suction to give the required product; mp 188°C; M ⁺ =235; ¹ H NMR (CDC1 ) : δ 2.15(s 3H) ;

7.55(d 2H); 7.70(d 2H) ; 9.50(broad signal IH) .

Step 2: 2-nitro-4-trifluoromethylthioacetanilide.

4-Trifluoromethylthioacetanilide (12.2g) was stirred in 3 dichloromethane (200cm ) and treated dropwise with fuming nitric acid

3 (10.5cm ). The solution was stirred for 2hr., stored for 18hr. at ambient temperature, poured into ice/water and neutralised using aqueous sodium hydrogen carbonate. The organic phase was separated, washed with water, dried (magnesium sulphate) and evaporated under reduced pressure to give the required product aε a yellow solid; mp 106°C; M =280; H NMR (CDCl ) : δ

2.35(s 3H); 7.90(dd IH) ; 8.55(d IH) ; 8.95(d IH) .

Step 3: 2-nitro-4-trifluoromethylthioaniline.

3 2-Nitro-4-trifluoromethylthioacetanilide (10.5g) in ethanol (200cm ) containing potassium hydroxide (2.2g) was heated to reflux with εtirring for 0.25hr., cooled to ambient temperature and poured into water. The solid which precipitated was filtered from solution, washed with water and sucked to drynesε to give the required product, mp 86°C; M =238; H NMR (CDCl ) : δ

6.45(broad εignal 2H) ; 6.90(d IH); 7.60(dd IH) ; 8.50(d IH) .

Step 4: Preparation of 4-trifluoromethylthio-2-nitrochlorobenzene.

3 2-Nitro-4-trifluoromethylthioaniline (0.5g) in dry acetonitrile (3cm ) waε added over 0.5hr. with εtirring to copper (II) chloride (0.34g) and

3 tert-butyl nitrite (0.32g) in dry acetonitrile (5cm ) at 60°C. After lhr. the reaction was cooled to ambient temperature, poured into water, acidified with hydrochloric acid and extracted with ethyl acetate. The

3 organic phase was washed with water (3x50cm ) dried (magnesium sulphate) and evaporated under reduced pressure to give the required product as an oil; M ⁺ =257; ^λ E NMR (CDC1 ₃ ): δ 7.65(d IH) ; 7.80(dd IH) ; 8.20(d IH) .

(ii) Preparation of N,N-Dimethyl 4-chloro-3-nitrobenzenesulphonamide

(starting material for Example lA(ix).

3 4-Chloro-3-nitrobenzenesulphonyl chloride (3.0g) in toluene (20cm )

3 was treated with dimethylamine (l.lg) in water (10cm ) and stirred for

2hr. The reaction was stored for 18hr., poured into water, extracted with

3 ethyl acetate (3x20cm ), and the combined organic phase washed with brine

3 (3x20cm ), dried (magnesium sulphate) and evaporated under reduced pressure to give the title product as a yellow solid, mp 88°C; M =274; H NMR

(CDCl ): δ 2.90(s 6H) ; 7.90(d IH) ; 8.10(dd IH) ; 8.40(d IH) .

(iii) Two step preparation of 2-nitro-4- trifluoromethylsulphinylbromobenzene (a) and 2-nitro-4- trifluoromethylsulphonylbromobenzene (b) (starting materials for example la(vii)) .

Step 1: 4-Bromotrifluoromethylsulphinylbenzene and 4- bromotrifluoromethylsulphonylbenzene.

3 4-Bromotrifluoromethylthiobenzene (5.0g) in dichloromethane (50cm ) was stirred at 0°C and treated portionwise with eta-chloroperbenzoic acid

(6.7g of 502 reagent) and allowed to attain ambient temperature over 18hr.

The mixture was washed with aqueous sodium hydrogen carbonate, water, dried

(magnesium εulphate) and evaporated under reduced pressure to give a mixture of the sulphoxide and sulphone (ratio 3:1) which was used in the next stage:

Step 2: The mixture from Step 1 (5.4g) was dissolved in concentrated

3 sulphuric acid (20cm ) at ambient temperature and the stirred solution treated portionwise with potassium nitrate (2.02g). The reaction was stirred for 3hr., poured into ice/water, extracted with ethyl acetate and the organic phase washed with water, dried (magnesium sulphate) and evaporated under reduced pressure. The residual product was eluted through a column of silica using hexane/ethyl acetate (9:1 by volume) to give a mixture of the required products. M (A) (M-N0)=287; (B) (M-NO) 305.

An alternative synthesis of (B) is given in J. Org. Chem. (1960) 2J5 60.

EXAMPLE 6

The insecticidal and acaricidal activity of the compounds of formula (I) was determined using a variety of pests. The pests were treated with a liquid composition containing 500 parts per million (ppm) by weight of the compound unless otherwise stated. The compositions were made by dissolving the compound in acetone and diluting the solutions with water containing 0.012 by weight of a wetting agent sold under the trade name "SYNPERONIC" NX until the liquid composition contained the required concentration of the compound. "SYNPERONIC" is a Registered Trade Mark.

The test procedure adopted with regard to each pest was basically the same and comprised supporting a number of the pests on a medium which was usually a host plant or a foodstuff on which the pestε feed, and treating either or both the medium and the peεtε with the compositions. The mortality of the pestε was then assessed at periods usually varying from one to three days after the treatment.

The results of the testε are presented in Table II for each of the compounds at the rate in parts per million given in the second column. The results indicate a grading of mortality designated as A, B or C wherein A indicates lesε than 502 mortality, B indicates 50-792 mortality and C indicates 80-1002 mortality (figures indicate knockdown control for test MDb) ; - indicates that either the compound was not tested or no meaningful result was obtained.

Information regarding the pest species, the support medium or food, and the type and duration of the test is given in Table II. The pest specieε iε designated by a letter code.

TABLE III

CODE TEST SPECIES SUPPORT ^' TYPE OF DURATION LETTERS MEDIUM/FOOD TEST (days)

TU Tetranychuε urticae French bean leaf Contact (εpider mite)

MP Myzus persicae Chinese Contact

(green peach aphid) Cabbage leaf

MD Musca domestica Cotton wool/ Contact

(houseflies - adults) sugar

SE Spodoptera exigua Cotton leaf Residual

(lesser a myworm - larva)

DB Diabrotica balteata Filter paper/ Residual

(banded cucumber beetle maize seed - larva)

"Contact" test indicates that both pests and medium were treated, "Residual" indicates that the medium was treated before infestation with the pestε and "in vitro" indicateε that the pest was suspended in an aqueous medium containing the treatment.

EXAMPLE 7

This Example illustrates the nematicidal properties of the compounds of Formula (I) according to the invention.

In vitro activity against the root knot nematode, Meloidogyne incognita was evaluated by treatment of a suspension of freshly-hatched (0- 24 hours old) juveniles of M.incognita with a liquid composition containing the test chemical at test rates of 1.65-0.02 ppm. To prepare the compositions, the test chemicals were diluted to double the rate required

3 in 12 ethanol and acetone (1:1) and 992 deionised water. 0.5 cm of

3 chemical solution was added to 0.5 cm of nematode suspension (δ 200

3 nematodes/cm ) in a glass vial. Each treatment was replicated twice. The vials were capped and left for 72 hours in a Constant Temperature room at

23°C in the dark. The numbers of dead and alive nematodes were then counted under a stereomicroscope and the number of dead nematodes is expresεed in

Table IV as a percentage of the total nematode count (2 Dead).

TABLE IV

COMPOUND ZDead

NO 1.65ppm

1 82.5

2 85.4

5 58.8

15 59.9

22 91.6

52 75.8

57 77.4

58 89.6

62 75.2

EXAMPLE 8

This Example further illustrates the nematicidal activity of the compounds of the invention.

Methodology

Test A : Tomato plants (6-8 weeks old, variety 'Moneymaker' ) were planted out into soil infested with second stage juveniles of the root knot nematode Meloidogyne incognita. The soil was drenched with a composition of a compound of formula (I) (obtained by diluting 1 part of a solution of the compound in a 1:1 mixture of acetone and ethanol with 99 parts of water containing 0.052 of a wetting agent) at a rate of 2.5 or 1.25 ppm in a drench volume of 200 ml/kg of soil. The roots of the plants were examined after 3 weeks to determine the percentage reduction in the number of root

knots compared with a control treatment omitting the compound. There were 3 replicates per treatment.

Test B : Tomato plants (6-8 weeks old, variety 'Moneymaker') were transplanted into soil infested with potato cyst nematode (Globodera rostochienεiε) . The εoil was drenched with a composition of a compound of formula (I) (obtained by diluting 1 part of a solution of the compound in a 1:1 mixture of acetone and ethanol with 99 parts of water containing 0.052 of a wetting agent) at a rate of 10 or 20 ppm in a drench volume of 266 ml/kg of soil. The cysts were extracted from the soil after 8 weeks by flotation and percentage reduction in the number of cysts compared with a control treatment omitting the compound was determined. There were 5 replicateε per treatment.

Test C : Cucumber plants (9 days old, variety 'Telegraph') were soil drenched with a composition of a compound of formula (I) (obtained by diluting 1 part of a solution of the compound in a 1:1 mixture of acetone and ethanol with 99 parts of water containing 0.052 of a wetting agent) at a rate of 40ppm in a drench volume of 10ml/45g of soil. The plants were infested with second stage juveniles of the root knot nematode Meloidogyne incognita after the εolution of the compound had been absorbed by the soil. Nematodes were applied to the roots in a solution of water. The roots of the plants were examined after 9 days to determine the percentage reduction in the number of root knots compated with a control treatment omitting the compound. There were 3 replicates per treatment.

The results are given in Table V. In the table a blank indicates less than 252 reduction, a hyphen indicates no test carried out at that rate.

TABLE V

EXAMPLE 9

The spectrum of nematicidal activity of compounds of Formula (I) according to the invention was investigated in contact assays. Greatest activity was seen against endoparasitic species such as the root-knot nematode Meloidogyne incognita, the potato cyst nematode Globodera rostochiensis, the sugarbeet cyst nematode Heterodera schachtii and the reniform nematode Rotylenchulus reniformiε. Activity was evident, but to a lesser extent, against migratory species such as Aphelenchoides spp and Ditylenchus spp. This indicates that compounds according to the invention have the potential for broad spectrum control of nematode species representative of different habitats and feeding habits.

The following examples demonstrate formulations εuitable for applying the compounds of the present invention. The amount of ingredient is expressed in parts by weight or grams per litre as indicated. * indicates a trademark.

EXAMPLE 10 This example demonstrates granules suitable for soil application. The granules can be made be standard techniques such as impregnation, coating, extrusion or agglomeration.

Zw/w

Impregnated granule Active ingredient 5

Wood Rosin 2.5

Gypsum granules 92.5

(20-40 mesh)

Coated granule Active ingredient 0.5

'Solvesso' 200 0.4

Calcium carbonate granules 99.1

(30-60 mesh)

Slow release granule Active ingredient 10

Polyvinylacetate/vinyl 5 chloride copolymer latex

Attapulgus granuleε 85

EXAMPLE 11 This example demonstrates formulations for use as a spray. The compounds can be formulated as wettable powders, water dispersible granules, suspension concentrates, emulsifiable concentrates, emulsionε or microcapsule suεpensions for application diluted in water. g/1 Emulεifiable concentrate: Active ingredient 250

Calcium dodecyl- 50 benzene εulphonate

Nonyl phenol ethoxylate 50

Alkylbenzene εolvent to 1 litre

2w/w

Wettable powder : Liquid active ingredient 40 lignosulphonate dispersant 5 silica 25 sodium lauryl sulphate 3 china clay (kaolin) 27

Microcapsule suspension : Liquid active ingredient 250 toluene diisocyanate 10 polymethylene polyphenyi

isocyanate _ 20 nonyl phenol ethoxylate 6 lignosulphonate dispersant 15 xanthan gum 1 bentonite 10

* biocide 'Proxel' 0.1 sodium carbonate 5 water to 1 litre

The microcapsule suspensions can be used as a spray, soil drench or as an intermediate to prepare εlow release granules for application to the soil. ill

Suspension concentrate : Solid active ingredient 400 lignosulphonate dispersant 50 sodium lauryl sulphate 30 xanthan gum 1

* biocide 'Proxel* 0.1 bentonite 10 water to 1 litre

EXAMPLE 12

This example demonstrates formulations suitable for use as seed treatments in conventional application machinery.

2w/w

Dry seed treatment : Active ingredient 20 dodecyl benzene 3

Rubine Toner (dyestuff) 2.7

Talc 53.3

Silica to 1002

The εuspension concentrate and microcapsule suspenεion of Example 5 can be used as flowable concentrates for seed treatment.

EXAMPLE 13 This example demonstrates the formulation of the compounds for electrostatic spraying.

Active ingredient 200

N-methylpyrollidone 50

Soyabean oil 120

'Solvesso' 200 to 1 litre

EXAMPLE 14

This Example illustrates the fungicidal properties of the compounds of

Formula (I) according to the invention.

The test compounds were formulated either by bead milling with aqueous

Dispersol T or as a solution in acetone or acetone/ethanol. They were then

3 diluted to lOOppm in water, and 2.5cm aliquots were placed in Petri disheε. These were further diluted to 25ppm (active ingredient) with

Potato Dextrose Agar.

The diεhes were inoculated with the fungal pathogens shown in Table

VI, using either spore suεpenεionε or mycelial plugs. These were then incubated at an appropriate temperature (19- 25°C) and growth asεeεεmentε made after 2 dayε as a percentage of the level of diseaεe preεent on the untreated control medium. The results are expressed in Table VII as a POCO

(Percentage of Control) value calculated according to the formula given below and rounded to the nearest figure on the following standard scale:

0, 1, 3, 5, 10, 15, 20, 30, 60, 90.

POCO = disease level on treated medium disease level on untreated control

TABLE VI Test Organisms

Abbreviations Latin Name

Ch Pseudocercosporella herpotrichoides

Gg Gaeumannomyces graminis tritici

Sn Septoria nodorum

Be Botrytis cinerea

Pc Phytophthora cinnamomi

Po Pyricularia oryzae

Tc Thanatephorus cucumeris

Au Aureobaεidium pullulanε

Gr Gliocladium roεeum

Pe Penicillium pinophilum

TABLE VII

Compound Ch Gg Sn Be Pc Po Tc Au Gr Pe No

1

22 62 58

CHEMICAL FORMULAE (IN DESCRIPTION)

II)