Oxa- and Thiadlazole Derivatives used as Insecticides and Fungicides

The present invention relates to novel thiaαiazole and oxadiazo e derivatives, to processes for preDaπng them, to fungicidal and insecticidal compositions containing them and to methods of using tnem to comDat fungi, especially fungai infections of plants, and insect pests.

Certain derivatives of 5-memDered heterocycles, including 1,3,4-thιadιazole, are described in EP-A-0256667 together with tneir use as fungicides ana insecticides. In these derivatives, tne heterocycle is linked to a methyl 2-phenyl-3-metnoxyacrylate grou .

According to the present invention there is provided a compounα having the general formula (I), or a stereoisomer thereof, wnerem A is CH or N; B is OCH, or NHCH ; one of L and M is N and the other is S or 0, X is an optionally substituted carbocyclic or heterocyclic group; and n is 0 or 1.

Because the double bond of the group, B0C.C=A.0CH. , is unsymmetricaily substituted, the compounds of the invention may be obtained in the form of mixtures of (E)- and (Z_)-geometric isomers. However, these mixtures can be separated into individual isomers, and this invention emDraces such isomers and mixtures thereof in all proportions including those which consist substantially of the (Z _^ )-isomer and those whicn consist substantially of the (E)-isomer. The (E)-isomer, in which the groups -COB and -OCH are on opposite sides of the olefmic bond, is generally the more fungicidally active and forms a preferred embodiment of the invention. Of particular interest is the grouD, CH 0 C.C=CH.0CH , and especially its (E_)-isomer.

The 5-membered ring in which one of L and M is N and the other is S or 0, is a 1,3, -thιadιazole or, preferably, a 1,2,4-thιadιazole ring, or a 1,2,<-oxadιazole or, preferably, a 1,3,4-oxadιazole ring.

X is an optionally substituted carbocyclic or heterocyclic group, wnich may be an optionally suDStituted aryl or optionally substituted heteroaryl grouD or an optionally substituted alicyclic or an optionally substituted non-aromatic heterocyclic group.

Aryl includes phenyl and naυnthyl. Heteroaryl includes 5- and 6- memoered aromatic rings containing one or more oxygen, sulphur or nitrogen atoms and such rings fused to a benzene ring. Examples of heteroaryl are pyπdinyl, pyri idinyl, pyridazmyl, pyrazmyl, triazmyl, furyl, thienyl,

:rclv__, pvrazolvl, __r.ιαazolyl, πazo yl, oxazolyl, soxazolyl, thiazolvl, isothiazolyi, quinolmyl, lsoqumolmyl, cmnolm l,

quinazoiinyi, qumoxaiinyl, indolinyi, isoindolinyi, benzofuranyl, benzothiophenyl. benzimidazolinyl, benzoxazolyl and benzthiazolyl. Of particular interest are 6-membered heteroaromatic rings containing one, two or three nitrogen atoms, ie pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl and triazmyl rings.

Alicyclic groups include cyciopropyi, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyciooctyl, norbornanyl, adamantyl, cyclopentenyl, cycloheptenyl, cyclooctenyl, cyclohexenyl and norbornenyl groups. Non-aromatic heterocyclic groups include oxiranyl, aziridinyl, azetidinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidinyl, tetrahydropyranyl, tetrahydrothiopyranyi, morpholinyi and morpholino groups .

Substituents which may be present in the optionally substituted carbocyclic or heterocyclic group include one or more of the following: halo, hydroxy, mercapto, C alkyl (especially methyl and ethyl), C alkenyl (especially allyl), C alkynyl (especially propargyl), C alkoxy (especially methoxy), C alkenyloxy (especially allyloxy) , C alkynyloxy (especially propargyloxy) , halo(C )alkyl (especially trifluoromethyl) , halo(C ₁ ,)alkoxy (especially trifluoromethoxy) , C alkylthio (especially methylthio), hydroxy(C )alkyl, C- alkoxy(C _Λ )alkyl, C cycloalkyl, C cycloalkyl(C )alkyl, optionally substituted methylenedioxy or ethylenedioxy (especially optionally substituted with fluorine or C alkyl), optionally substituted aryl (especially optionally substituted phenyl), optionally substituted heteroaryl (especially optionally substituted pyridyl or pyrimidinyl), optionally substituted aryloxy (especially optionally substituted phenoxy) , optionally substituted heteroaryloxy (especially optionally substituted pyridyloxy or pyrimidinyloxy) , optionally substituted aryl(C )alkyl (especially optionally substituted benzyl, optionally substituted phenethyl and optionally substituted phenyl n-propyl) in which the alkyl moiety is optionally substituted with hydroxy, optionally substituted heteroaryKC )alkyl (especially optionally substituted pyridyl- or pyrimidinyl(C )alkyl), optionally substituted aryl(C _ώ )alkenyl (especially optionally substituted phenylethenyl) , optionally substituted heteroaryKC )alkenyl (especially optionally substituted pyridylethenyl or pyrimidinylethenyl) , optionally substituted aryl(C )alkoxy (especially zi-tionally substituted benzyloxv), optionally substituted heteroaryl(C_.-4. ),- alkoxy (especially optionally substituted pyridyl-, or pyrimidinyl(C -

alkoxy), optionally suDstituted aryloxy(C )alkyl (especially onenoxvmethyl) , optionally substituted heteroaryloxy(C )alkyl (especially optionally substituted pyπdyloxy- or pyrimidmyloxy(C )alkyl), acyloxy (including C. aικanoyloxy (especially acetyloxy) and benzoyloxy) , cyano, thiocyanato, nitro. -NR'R', -NHCOR' , -NHCONR'R , -CONR'R , -COOR , -0S0 _? R' ,

-S0 _? R , -COR , -CR =NR or -N=CR R in wnich R and R are independently hydrogen, C, alkyl, C alkoxy, C alkylthio, C cycloalkyl, C cycloalkyKC )alkyl, pnenyl or benzyl, the phenyl and benzyl groups being optionally substituted with haiogen, C alkyl or C alkoxy.

Substituents which may be present in the aryl or heteroaryl rings of any of the foregoing substituents include one or more of the following: halo, hydroxy, mercapto, C alkyl, C_ , alkenyl, C alkynyl, C alkoxy, C alkenyloxy, C alkynyloxy, halo(C ,)alkyl, halo(C - alkoxy, C _u alkylthio, hydroxy(C )alkyl, C alkoxy(C )alkyl, C cycloalkyl, C cycloalkyKC )alkyl, alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, -NR R ' , -NHCOR', -NHCONR R ' , -CONR R", -COOR', -SO R',

-0S0 R , -COR , -CR =NR or -N=CR R in wnich R and R have the meanings given above.

Substituted alicyclic and non-aromatic heterocyclic groups include, in particular, those groups substituted by alkyl, haloalkyl, cycloalkylalkyl, alkenyl and haloalkenyl. Alicyclic groups are typically substituted by methyl.

All alkyl moieties and the alkyl moiety of alkoxy suitably contain from 1 to 6, for example from 1 to 4, carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and iso- propyl, and n-, sec-, iso- and tert- butyl.

Alkenyl and alkynyl moieties suitably contain from 2 to 6, for example from 2 to 4, caroon atoms in the form of straight or branched chains. The alkenyl moieties, where appropriate, may have either the (E)- or (Z_)-configuration. Examples are vinyl, allyl and propargyl.

Halogen is typically fluorine, chlorine or bromine.

In one aspect, the invention provides a compound of the general formula (I) wnerem A is CH or N; B is OCH.. ; one of L and M is N and the other is S or 0; X is pnenyl optionally substituted with halo (especially fluoro, chloro or bromo), C alkyl (especially methyl or ethyl), halo(C, )alkyl (especially trifluoromethvl) , C , alkoxy (especially etnoxv or etnoxy , na o(C ,aικoxy 'especially trifluoromethoxy) , C_ alkoxy(C _η )alkyl (especially methoxymethyl) , methylenedioxy,

ethylenedioxy, cyano, nitro, -NR'R", -NHCOR', -NHCONR'R", -CONR'R", -COOR' , -COR', -S0..R' cr -0S0„R' in which R' and R" are independently hydrogen or

2 Δ.

Cj..— α alkyl; and n is 0 or 1. Particular compounds of this type include those where A is CH; L is S; M is N: and n is 0, and where A is CH; L is N; M is 0; and n is 0.

In another aspect, the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH ; one of L and M is N and the other is S or 0; X is 2-, 3- or 4-pyridinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 2- or 4-pyridazinyi or 2-1,3,5-triazinyl, any one of which is optionally substituted with halo (especially fluoro or chloro), C alkyl (especially methyl), halo(C alkyl (especially trifluoro ethyl) , C, alkoxy (especially methoxy or ethoxy) or halo(C )alkoxy (especially trifluoromethoxy or trifluoroethoxy) ; and n is 0 or 1. Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.

In yet another aspect, the invention provides a compound of the general formula (I) wherein A is CH or N; B is OCH ; one of L and M is N and the other is S or 0; X is C cycloalkyl optionally substituted with C alkenyl or halo(C ) lkenyl; and n is 0 or 1. Particular compounds of this type include those where A is CH; L is S; M is N; and n is 0, and where A is CH; L is N; M is 0; and n is 0.

The present invention is illustrated by compounds of the general formula (I) listed in Tables 1 to 16 and in Tables 1* to 16' which follow. Throughout these Tables the group B0C.C=A.0CH has the (E)-configuration.

TABLE 1 Table 1 comprises 370 compounds of the general formula (I), wherein A s CH, B is OCH,, L is S, M is N, n is 0 and X has the value listed.

Compound No

Compound No

324 2-Cl-ό-CN-CH, o 3

325 3-C1-2-CN-CH,

5 3

326 3-C1-4-CN-CH, o 3

327 3-C1-5-CN-CH,

6 3

328 3-C1-6-CN-CH, b 3

329 4-C1-2-CN-CH,

6 3

330 4-C1-3-CN-CH.

6 J

331 2-C1-3-F-CH, b 3

332 2-C1-4-F-CH, b 3

333 2-C1-5-F-C.H, o 3

334 2-C1-6-F-C.H, o 3

335 3-C1-2-F-C.b.H3,

336 3-C1-4-F-C.H, b 3

337 3-C1-5-F-Cb.H3,

338 3-C1-6-F-CoH3,

339 4-C1-2-F-CH, b 3

340 4-C1-3-F-CH, b 3

341 2,3-(N0 ₂ ) ₉ -C ₈ H ₃

342 2,4-(N0 ₂ ) ₂ -C ₆ H ₃

343 2,5-(N0„)-,-C,H,

Δ I b 3

344 2,6-(N0 ₂ ) ₂ -C ₆ H ₃

345 3,4-(N0 ₉ ) ₂ -C ₈ H ₃

346 3,5-(N0 ₂ ) ₂ -C ₅ H ₃

347 2,3-(CF _,:} Δ _Λ -C,6H3,

TABLE 2 Table 2 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH,, L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 3 Table 3 comprises 370 compounds of the general formula (I), wherein A is CH. Ξ is NHCH, , __ is £, M is N, n is 0 and X has the vaiue listed for the correspondingly numbered compound in Table 1.

TABLE 4 Table 4 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH , L is S, M is N, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 5 Table 5 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 6 Table 6 comprises 370 compounds of the general formula (I) , wherein A is N, B is OCH , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 7 Table 7 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 8 Table 8 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH , L is N, M is S, n is 0 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 9 Table 9 comprises 370 compounds of the general formula (I), wherein A is CH, B is OCH , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1. _,

TABLE 10 Table 10 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 11 Table 11 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH , L is S, M is N, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 12 Table 12 comprises 370 compounds of rΛe general formula (I), wherein A is N, B is NHCH,, L is S, M is N. n is 1 a;_-_ X has the value listed for the correspondingly numbered compounc in Table 1.

TABLE 13 Table 13 comprises 370 compounds of the general formula (I), wherein A

is CH, B is OCH , L is N, M is S, n is 1 ano X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 14 Table 14 comprises 370 compounds of the general formula (I), wherein A is N, B is OCH,, L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 15 Table 15 comprises 370 compounds of the general formula (I), wherein A is CH, B is NHCH., L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLE 16 Table 16 comprises 370 compounds of the general formula (I), wherein A is N, B is NHCH , L is N, M is S, n is 1 and X has the value listed for the correspondingly numbered compound in Table 1.

TABLES 1' TO 16'

Sixteen tables numbered Tables 1' to 16' correspond to Tables 1 to 16, respectively, except that in Tables 1' to 4' and 9' to 12' L, in the general formula (I), is 0 instead of S and in Tables 5' to 8' and Tables 13' to 16' M, in the general formula (I), is 0 instead of S. Thus the 370 compounds in each of Tables 1* to 16' are the same as those in each of the corresponding Tables 1 to 16 except that the compounds in Tables 1' to 16' contain an oxathiazole ring instead of the thiadiazole ring contained by the compounds m Tables 1 to 16.

TABLE 17

Table 17 shows melting point or selected proton NMR data obtained at 270 MHz for certain compounds described in Tables 1 to 16. Chemical shifts are measured at 20°C unless otherwise stated and in ppm from tetramethyl silane. Deuterochloroform was used as solvent unless otherwise stated. The following abbreviations are used: s = singlet α = doublet t = triplet tt = tπpie triplet q = quartet = multiplet

Compound No

Melting Point (°C)/NMR (ppm) (Table No)

1(1) 3.2(m,2H); 7.59(s,lH) 7.2-7.5(m,7H) ; 3.75(s,3H); 3.6(s,3H) . ! ^• ; 73-80.

^: ° ^{mp0Und N} ° Melting Point (°C)/NMR (ppm)

(Table No)

1(5) 7.80-7.86(m,2H) ; 7.58(s,lH); .3-7.48 ( .7H) ; 3.79(s,3H); 3.65(s,3H) . 1(5') 3.64(s,3H); 3.80(s,3H); 7.28-7.38(m,2H) ; 7.40-7.54(m, 4H) ; 7.56-7.60(d,lH) ; 7.60(s,lH); 7.94-7.99(m,2H) . 1(13') 3.56(s,3H), 3.65(s,3H), 4.09(s,2H), 7.26-7. 1(m, 8H) , 7.48-7.52(m,2H) . 2(1) 3.60(s,3H); 3.85(s,3H); 7.1-7.5(m, 7H) ; 7.55(s,lH); 8.1(m,lH) 2(1') 90-92. 2(5') 90-92. 3(1) ^■ 3.61(s,3H); 3.75(s,3H); 7.12(m,lH); 7.35-7.46(m,5H) ;

7.55(s,lH); 7.88(d,lH); 7.98(d,lH). 3(2) 3.79(s,3H); 3.95(s,3H); 7.12(m,lH); 7.4(m,3H); 7.55(m,2H);

7.85(d,lH); 7.96(d,lH). 3(4) 130-132. 3(5') 91-94. 4(1) 3.6(s,3H); 3.75(s,3H); 7.1(t,2H); 7.37-7.46(m, H) ; 7.57(s.lH); 8.18(m,2H). 4(5') 95-97.

5(1) 127-129. 5(5') 95-97. 6(1) 3.62(s,3H); 3.75(s,3H); 7.32-7. 7(m, 6H) ; 7.55(s,lH); 8.05(d,lH); 8.19(s,lH). 6(5') 124-126.

7(1) 8.1(d,2H); 7.55(s,lH); 7.4(m,6H); 3.75(s,3H); 3.6(s,3H). 7(1') 88-90. 7(2) 84-86. 7(4) 148-150. 7(5') 109-111. 8(1) 3.60(s,3H); 3.75(s,3H); 7.2-8.85(m.8H) ; 7.55(s,lH). 9(1) 3.6(s,3H); 3.7(s,3H); 7.2-7.6(m, 6H) ; 7.57(s,lH); 8.1(m,lH); 8.35(m,lH) . 9(5') 128-131. ιc;5'; 109.

Compound No

Melting Point (°C)/NMR (ppm)

(Table No)

17(1) 3.62(s,3H) ; 3.74(s,3H) ; 7.4(m,4H) ; 7.58(s,lH) .

25(1) 109.

25(5* ) 89-91.

26(1) 2.4(s,3H) ; 3.6(s,3H) ; 3.75(s,3H) ; 7.2-7.5 (m, 6H) ; 7.57(s,lH) ;

8.0(m,2H) . 26(5') 112-115.

26(9) 2.32(s,3H) ; 3.58(s,3H) ; 3.65(s,3H) ; 4.1(s,2H) ; 7.5(s.lH) ;

7.0-7.45(m,8H) . 27(1) 2.49(s,3H) ; 3.60(s,3H) ; 3.73(s,3H) ; 7.25(d,2H) ; 7.4(m,4H) ;

7.56(s,lH) ; 8.1(d,2H) . 27(5') 96-98.

31(1) 3.61(s,3H) ; 3.74(s,3H) ; 7.3-7.65 (m, 6H) ; 7.55(s,lH) ;

7.8(m,2H) . 32(1) 3.6(S,3H); 3.85(s,3H); 7.58(s,lH); 7.35-7.75 (m, 6H) ;

8.35-8.50(m,2H) . 32(1') 3.64(s,3H) ; 3.77(s,3H) ; 7.34-7.61 (m, 6H) ; 7.72-7.76 (d, IH) ;

8.16-8.20(d,lH) , 8.24(s,lH) . 32(2) 64-65.

32(5) 8.0-8. l(m, 2H) ; 7.69-7.73 (m, IH) ; 7.58(s,lH) ; 7.55-7.61 (m, IH) ;

7.3-7.44(m,4H) ; 3.81(s,3H) ; 3.66(s,3H) . 32(5') 120-122.

33(1) 85-87.

33(5') 97-99.

35(1) 3.6(s,3H) ; 3.75(s,3H) ; 3.9(s,2H) ; 7.0(m,lH) ; 7.3-7.5 (m, 5H) ;

7.55(s,lH) ; 7.7-7.85 (m, 2H) . 35(5') 123-126.

36(1) 104-106.

36(5' ) 107-110.

38(1) 3.61(s,3H) ; 3.75(s,3H) ; 7.27(m,lH); 7.37-7.50 (m, 5H) ;

7.57(s,lH) ; 8.05(s,lH) ; 8.13(d,lH) . 38(2) 64-66.

38(4) 122-124.

Compound No

Melting Point (°C)/NMR (ppm) (Table No)

41(1) 3.4(s,3H); 3.6(s,3H); 3.75(s,3H); 4.5(s,2H); 7.3-7. (m, 6H) ;

7.57(s,lH); 8.1-8.2 (m,2H) .

44(1) 3.6(s,3H); 3.77(s.3H); 7.4-7.75 (m, 6H) ; 7.65(s.lH); 8.4(m,2H)

44(5') 147-149.

45(1) 3.60(s,3H); 3.77(s,3H); 7.4(m,4H); 7.56(s,lH); 7.72(d,2H);

8.3(d,2H) .

45(5) 7.93-7.97(d,2H) ; 7.72-7.76 (d, 2H) ; 7.57(s,lH);

7.33-7.43(m,4H) ; 3.80(s,3H); 3.65(s,3H).

45(5') 146-148. 46(5') 3.68(s,3H); 3.82(s,3H); 7.28-7.47(m, 3H) ; 7.53-7.57(d.lH) ; .

7.62(s,lH); 7.70-7.81(m,2H) ; 7.91-7.95( .lH) ;

8.04-8.08(m.lH) .

47(1) 3.62(s, ^' 3H); 3.76(s,3H); 7.3-7.5(m, 4H) ; 7.58(s,lH);

7.62(t,lH); 8.3(m,lH); 8.5(m,lH); 9.05(s.lH).

47(5') 149-149.

48(1) 150.

48(5') 117-119.

176(5') 3.64(s,3H); 3.80(s,3H); 6.05(s,2H); 6.87-6.91(d, IH) ;

7.28-7.60(m,7H) - including 7.59(s,lH).

178(1) 1.25-2.0(m,10H) ; 2.8(m,lH); 3.6(s,3H); 3.72(s,3H);

7.30-7.40(m,4H) ; 7.55(s,lH).

180(1) 3.62(s,3H); 3.77(s,3H); 7.1(m,lH); 7.4(m,5H); 7.57(s,lH);

7.8(m,lH) .

180(5' ) 93-95. 181(1) 3.6(s,3H); 3.75(s,3H); 6.5(m,lH); 7.1(d,lH); 7.4(m,4H);

7.55(s,2H) .

181(5' ) 3.66(s,3H); 3.80(s,3H); 6.56-6.60(m, IH) ; 7.04- .08(d,IH) ;

7.28-7.37(m,2H) ; 7.38-7. 6(m,IH) ; 7.53-7.61(m,3H) .

183(1) 3.65(s,3H) 3.77(s,3H); 7.35-7.50(m,5H) ; 7.57(s,lH); 7.84(m,lH) 8.23(d,lH); 8.79(d,lH).

184(5) 3.67(s,3H) 3.81(s,3H); 7.33-7.44(m.5H) ; 7.59(s,lH);

8.18-8.24(m,lH) ; 8.68-8.72(m,IH) ; 8.98-9.00(m,IH)

Compound No

Melting Point (°C)/NMR (ppm) (Table No)

191(1) 3.65(s,3H); 3.8(s,3H); 7.4(m,4H); 7.57(s,lH); 8.7(m,2H);

9.45(s,lH) .

193(5') 3.68(s,3H); 3.80(s,3H); 7.33-7.38 (m,2H) ; 7.42-7.56(m,3H) ;

7.57-7.62(m,2H) ; 7.67-7.71(m,IH) ; 7.86-7.91(m,IH) .

198(1) 3.62(s,3H); 3.76(s,3H); .39-7.50( , H) ; 7.56(s,lH);

7.93-7.97(m,lH); 8.08(s,lH); 8.47-8.50(d,IH) .

213(1) 3.63(s,3H); 3.77(s.3H); 6.91-6.95(m,IH) ; 7.38-7.46(m, H) ;

7.56(s,lH); 8.61-8.71(q,IH) (94Z by glc; 61 Cl,F-pyridine unknown isomers) .

214(1) 3.64(s,3H); 3.75(s,3H); 7.38-7.50(m, 4H) ; 7.55(s,lH);

8.89(s,2H) .

229(1) 3.62(s,3H); 3.77(s,3H); 5.0(q,2H); 6.95(d,lH); 7.4(m,4H);

7.58(s,lH); 8.72(d,lH).

234(5' ) 125-127. 235(1) 0.95-l.ll(m,4H) ; 2.07-2.17(m,IH) ; 3.62(s,3H); 3.75(s,3H);

7.32-7.44(m,4H) ; 7.55(s,lH).

235(5* ) 1.06-l.ll(m,4H) ; 1.99-2.10(m,IH) ; 3.66(s,3H); 3.80(S,3H);

7.24-7.34(m,2H) ; 7.35-7.42(m,IH) ; 7.48-7.52(m,IH) ;

7.58(s,lH) .

236(1) 1.90-2.12(m,2H) ; 2.28-2.50(m, 4H) ; 3.60-3.72(m,IH) ;

3.62(s,3H); 3.74(s,3H); 7.33-7. 2(m, H) ; 7.56(s,lH). 236(5') 1.92-2.18(m,2H) ; 2.34-2.50(m, H) ; 3.56-3.69(m,IH) ;

3.64(s,3H); 3.80(s,3H); 7.24-7.43 (m,3H) ; 7.51-7.5 (d,IH) ;

7.58(s,lH) .

237(5* ) 1.66-1.96(m,6H) ; 2.00-2.13 (m,2H) ; 3.14-3.26(m,IH) ;

3.64(s,3H); 3.80(s,3H); 7.24-7.36(m, H) ; 7.36-7.42(m,IH) ;

7.51-7.54(d,lH) ; 7.57(s,lH).

237(13') 1.19-1.34(m,2H) 1.52-1.71(m,4H) 1.78-1.90(m,2H) ; 2.22-2.34(m,lH) 2.72-2.76(d,2H) 3.65(s,3H); 3.80(s,3H); 7.25-7.43(m,3H) 7.50-7.54(d,lH) 7.58(s,lH) .

244(5' ) 1.70-185(m,6H) ; 2.00-2.05(m, 6H) ; 2.05-2.12(m,3H) ; 3.64(s,3H); 3.80(s.3H); 7.52- .56(d,IH) ; 7.58(s,lH).

Compound No

Melting Point (°C)/NMR (ppm) (Table No)

246(13') 1.10-1.40(m,5H) ; 1.44-1.57 (m,3H) ; 1.86-1.96(m,IH) ;

2.08(s,lH); 2.24-2.29(m,lH) ; 2.50-2.7 (m,2H) ; 3.65(s,3H);

3.80(s,3H): 7.51-7.54(d, IH) ; 7.58(s,lH). 246(14') 1.10-1.23(m,4H) ; 1.32-1.40(m,IH) ; 1.48-1.58(m,3H) ;

1.83-1.98( (S,1H) ; 2.09(s,lH); 2.25-2.30(m,IH) ;

2.52-2.76(m,2H) ; 3.86(s,3H); 4.00(s,3H); 7.32-7.38(m.2H) ;

7.48-7.56(m,lH) ; 7.66-7.70(d,IH) . 246(16') 1.10-1.27(m,4H) ; 1.32-1. 0(m,IH) 1.45-1.57(m,3H) ;

1.87-1.98(m,lH) ; 2.06-2.10(m, IH) ; 2.24-2.30(m,IH) ;

2.51-2.75(m,2H); 2.92-2.9 (d,3H) ; 3.88(s,3H); 6.80(s,lH);

7.30-7.38(m,2H) ; 7.46-7.54(m,IH) ; 7.62-7.65(d,IH) .

95-97. 247(1) 60-62. 247(5') 0.86-0.90(m,2H) ; 1.19-1.25(m,2H) ; 1.50(s,3H); 3.64(s,3H);

3.80(s,3H); 7.22-7.42(m, 3H) ; 7.49-7.52(d,IH) , 7.58!'_,1H). 258(5') 1.2-2.l(m, 10H) ; 2.8(tt,lH); 3.63(s,3H); 3.8(s,3H);

7.2-7.55(m,4H) ; 7.57(s,lH). 277(1) 145-147. 270(1) 1.9-2.4(m,4H) ; 3.62(s,3H); 3.75(s,3H); 3.9-4.0(m,IH) ,

4.1-4.18(m,lH) ; 5.0(m,lH); 7.32-7.45(m, 4H) ; 7.57(s,lH). 270(5') 1.94-2.21(m,2H) ; 2.29-2.37 (q,2H) ; 3.64(s,3H); 3.78(s,3H);

5.00-5.05(t,lH) ; 7.24-7.43 (m,3H) ; 7.50-7.5 (d,IH) ;

7.58(s,lH) . 278(13') 3.59(s,3H); 3.70(s,3H); 4.13(s,2H); 7.04-7.06(d,IH) ;

7.19-7.21(m,lH) ; 7.24-7.42(m, 4H) ; 7.49-7.53 (d,IH) ;

7.53(s,lH) .

Compounds of the present invention can be prepared by reacting together a phenol of the general formula (II), wherein A and B have the meanings given before, with a thiadiazole or oxadiazole derivative of the general formula (III), wherein L, M, X and n have the meanings given before anu ϊ s a suitaDie leaving group sucn as methyisuipnonyl, tosyl or nalo, for example chloro, n a suitable solvent, such as N,N-dimethylformamide,

and in the presence of a suitable base, such as potassium camonate or sooium hydride. Conveniently, the pneno and thiadiazole or oxadiazole derivative are dissolved in the solvent at a temperature of about 5°C and tne base added. Alternatively, the Dase is stirred in a solution of the phenol in part of the solvent at a temperature of about 5°C and the tmadiazo e or oxadiazole added in the remaining solvent. The reaction mixture is then stirred at room temperature for several hours, before extraction of the desired product.

Phenols of the formula (II) can be prepared by methods described in, for example, EP-A-0242081, EP-A-0398692 and GB-A-2249092.

Thiadiazole and oxadiazole derivatives of the formula (III) can be prepared by adapting standard literature methods (see, for example, J.Goerdeler, H.Grochopp and U.So merlad, Chem. Ber., 1957, £, 182 for 1,2,4-thιadιazoles, S.Kubota, K.Toyooka, J.Ikeda, N.Yamamoto and M Shibuya, J. Chem. Soc. Perkm Trans. 1, 1983, 967 or EP-A-0486798 for 1,3, 4-thιadιazoles, C.Moussebois and F.Eloy, Helv. Chun. Acta, 47, 838 (1964), P C Unangst, G P Shrum, D T Connor, R D Dyer and D J Schπer, J. Med. Chem; 1992, 3_5. 3691 or EP-A-0446010 for 1,2,4-oxadιazoles and EP-A-0486798 for 1,3,4-oxadιazoles) .

1,2, 4-Thιadιazoles of the formula (III), where L is tosyl (p-tolyl- sulphonyl) may be obtained by the thermolysis of 5-substituted 1,3, 4-oxathιazol-2-ones in excess p-tolylsulphonylnitπle conveniently in a hydrocarbon solvent, such as dodecane (see R K Howe and J E Franz, J.Ore.Chem. , 39, 962 (1974)). The 1,3, 4-oxathιazolones can be prepared by reaction of acid amides with chlorocarbonylsulphenyl chloride by known procedures (see, for example, GB-A-1079348) .

1,2, 4-Thιadιazoles of the formula (III), where L is methylsulphonyl mav be prepared by the reaction of methyl iodide followed by 3-chloroperoxybenzoιc acid with 3-substιtuted-5-mercapto-l,2, -thιazoles . The 5-mercapto-l,2,4-thιazoles can be prepared by the reaction of amidmes with camon disulphide and sulphur in the presence of sodium methoxide m methanol (see GB-A-1116198) .

1,2, 4-0xaoιazoles of the formula (III), where L is chloro, may be obtained bv reacting 3-substιtuteo 1,2,4-oxadιazol-5-ones with phosphoryl chloride. The 1,2, 4-oxadιazolones can be prepared by acylation of amidoximes and cyclization of the resulting intermediate (see EP-A-0446010 or P C Unangst, G P Shrum, D T Connor, R D Dyer ano D J Schrier,

.Med.Chem. , 35, 3591 (1992)). Amidoximes are obtained by known methods, for example by the action of hvdroxylamine on the appropriate nitπles.

Alternatively, the invention compounds of formula (I) may be prepared from a compound of the formula (IV), wnerem L, M, X and n have the meanings given before and W is a group which can be converted by standard procedures described in tne literature into the group B0C.C=A.0CH . For example, wnere W is the group CH CO C.C=CH.0H, CH CO C.C=N.0H or CH,NH0C.C=N.0H it may be converted to the appropriate group B0C.C=A.0CH by methylation with a compound CH L, wherein L is a leaving group such as halo or CH SO .0, in the presence of a convenient base (such as sodium hydride or potassium carbonate). Where W is the phenylglyoxylic acid derivative, CO.CO CH or C0.C0NHCH , it may be converted to the appropriate group B0C.C=A.0CH Dy treatment with the Wittig reagent Ph P=CH.0CH , wherein Ph s phenyl, or with methylhydroxylamme.

The compounds (IV) can be prepared by reacting a phenol of the general formula (Ha) with a thiadiazole or oxadiazole derivative of the general formula (III), as described above for the phenol (II). The phenol (Ha) can conveniently be prepared from appropriately substituted phenylacetic acid derivatives by methods known in the literature (see, for example, EP-A-0178826, EP-A-0254426, EP-A-0278595, EP-A-0299694 and EP-A-0398692) .

The compounds of formula (I), wherein A is CH or N and B is NHCH , can also be prepared from the corresponding compounds wherein A is CH or N and B is OH, by methods set out in the literature and in other ways described in EP-A-0398692.

In a further aspect the invention provides processes for preparing compounds of formula (I) .

The compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pyriculaπa oryzae on rice and wheat and other Pyr culaπa spp. on other hosts; Puccinia recond ta, Puccinia strnformis and other rusts on wneat, Puccinia hordei, Puccinia stπiformis and other rusts on barley, and rusts on other hosts e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants; Ervsipne gramin s (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis cn hops, Sohaerotheca fuligmea on cucurbits (e.g. cucumber), Podosphaera leucotr cna on apple and Uncmula necator on vines; Cochliobolus spp., ne mintnospor um spp., Drecnsiera spp. (Pyrenoonora spp.), Rhvnchosponum spp., Septoria spp. (including Mvcosphaerella graminicola and Leptosphaeria

nodorum) , Pseudocereosnore11a herpotrichoides and Gaeumannomyces graminis on cereals (e.g. wheat, bariey, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora species on other hosts, for example, sugar beet, bananas, soya beans and rice; Botrvtis cinerea (grey mouid) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrvtis spp. on other hosts; Alternaria spp. on vegetables (e.g. cucumber), oil-seed rape, apples, tomatoes, cereals (e.g. wheat) and other hosts; Venturia spp. (including Venturia inaeαualis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (e.g. wheat); Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochvta spp.* on peas, wheat, barley and other hosts; Plasmopara viticola on vines; other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. on turf and other hosts; Phytophthora infestans on potatoes and tomatoes and other Phvtophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia species on various hosts such as wheat and barley, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mvcosphaerella spp. on banana, peanut, citrus, pecan, papaya and other hosts; Dianorthe spp. on citrus, soybean, melon, pear, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium theobromae on cocoa causing vascular streak dieback; Fusarium spp., Tvphula spp., Microάochium nivale, Ustilago spp., Urocvstis spp., Tilletia spp., and Claviceos purpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet and other hosts; post-harvest diseases particularly of fruit (e.g. Pencillium digitatum and P. italicu and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musarum on bananas and Botrvtis cinerea on grapes); other pathogens on vines, notably Eutvpa iata, Guignardia biάwellii, Phellinus igniarus, Phomopsis viticola.

Pseudopezicula tracheiphila and Stereum hirsutum; other pathogens on lumber, notably Cephaloascus fragrans. Ceratocystis spp., Qphiostoma pjceae, Penicillium spp., Trichoderma pseudokonineii, Trichoderma viride Trichoderma harzianum, Aspergillus niger. Leptograohium lindbergi and Aureobasidium pullulans; and fungal vectors of viral diseases e.g. Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV) . Some of the compositions show a broad range of activities against fungi _in vitro.

The compounds may move acropetally/locally in plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.

The invention therefore provides 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 hereinbefore defined, or a composition containing the same.

The compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor. It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 952, more preferably 1 to 852, for example 1 to 252 or 25 to 602, of a compound as hereinbefore defined.

When applied the foliage of plants, the compounds of the invention; are applied at rates of O.lg to 10kg, preferably lg to 8kg, more preferably lOg to 4kg, of active ingredient (invention compound) per hectare.

When used as seed dressings, the compounds of the invention are used at rates of O.OOOlg (for example O.OOlg or 0.05g) to lOg, preferably 0.005g to 8g, more preferably 0.005g to 4g, of active ingredient (invention compound) per kilogram of seed.

The compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulate,: directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules .

Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to

hvdroponic culture systems. The invention compounds may also oe injected into plants or soraveo onto vegetation using electrodynamic spraying techniques or other low volume methods or applied by land or aerial irrigation systems.

The term "plant as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of tne invention includes preventative, protectant, propny actic, systemic and eradicant treatments.

The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.

The fungicidal compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers sucn as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous eartn and china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrol-idone, propylene glycol or N,N-dιmethylformamιde) . The compositions may also be in the form of water dispersible powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.

The fungicidal compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.

Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polvsaccharide, and a wetting or dispersing agent to improve water dispersioility/solubilit . The mixture may tnen be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may De prepared by dissolving tne active ingredient in polar solvents such as ketones, alcohols and glycoi etners. These solutions may contain surrace active agents to improve water dilution and prevent crystallisation in a spray tan .

Emuisifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting cr emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.

Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.

Fungicidal compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a propellant, ^■ e.g. fluorotrichloromethane or dichlorodifluoromethane.

The invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.

Alternatively, the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.

By including suitable additives, for example additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.

The invention compounds can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, a compound of formula (I) are preferred. Such granules suitably contain up to 252 by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or etai complex thereof.

O 94/10159 - 2.4. - PCT/GB93/02097

ater dispersible powoers, emuisifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.

Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium Dromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of suiphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium dusopropyl- and tπisopropylnapnthalene sulpnonates) .

Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide. Suitable suspending agents are hydrophilic colloids (for example, polyvmylpyrrolidone and sodium carboxymethylcellulose) , and swelling clays such as bentomte or attapulgite.

Fungicidal compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use. These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient timε to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 952, suitably 1-852, for example 1-252 or 25-602, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 102. for example 0.005 to 102, by weight of active ingredient may be used.

The fungicidal compositions of this invention may contain other compounds navmg biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, ierc.c_.cai or -nsecticiαai activity

3y including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds which may be included in the composition of the invention are (RS)-1-aminopropyi- phosphonic acid, (RS_)-4-(4-chlorophenyi)-2-phenyl-2- (1H-1,2, -triazoi-l-yl- methyl)butyronitrile, (Z_)-N-but-2-enyioxymethyl-2-chloro-2' , 6'-diethylacet- aniiide, 1- (2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difiuoro- -1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl- -6-trifluoromethylbenzimidazole-l-sulphonamide, 5-ethyl-5,8-dihydro-8- -oxo(l,3)-dioxol-(4,5-£)quinoline-7-carboxylie acid, α- [N-(3-chloro-2, 6- -xylyl)-2-methoxyacetamido]-7-butyrolactone, N-(2-methoxy-5-pyridyl)-cyclo¬ propane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benaiaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprodinyl, cyprofuram, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole, 0,0-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditali fos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z_)-N-benzyl-N- ( [methyl(methylthioethylideneamino-oxy- carbonyl)amino]thio)-β-alaninate, etridiazole, fena inosulph, fenapanil, fenarimoi, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroi ide, fluquinconazole, flusilazole, flutolanii, flutriafol, foipet, fuberidazole, furametpyr, furalaxyl, furconazoie-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, ICIA5504, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, .~epar.ιpyr _., mepronii, metaiaxyl, metconazoie, methfuroxam, metiram. metiram-zinc, etsuifovax, mvclobutanil, NTN0301, neoasozin, nickel

dimethyidithiocarbamate, nitrothal-isopropyl, nuarimoi, ofurace, organomercury compounds, oxadixyl, oxoiinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, poiyoxin D, poiyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinconazole, quinomethionate, quintozene, rabenazole, sodium pentachloro- phenate, streptomycin, sulphur, tebuconazole, techlofthala , tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, 2-(thiocyanomethyl- thio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, tolclofos- -methyl, tolylfluanid, triacetate salt of 1,1'-iminodi(octamethylene)- diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vanam, vinclozolin, XRD-563, zineb and ziram. The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.

The compounds of formula (I) may also be used to combat and control infestations of insect pests 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.

In order to apply the compounds to the locus of the pests they are usually formulated into compositions which include in addition to the insecticidally active ingredient or ingredients of formula I suitable inert diluent or carrier materials, and/or surface active agents. The insecticidal compositions may also comprise another pesticidal material, for example another insecticide or acaricide, or a fungicide, or may also comprise an insecticide synergist, such as for example dodecyl imidazole, safroxan, or piperonyi butoxide.

The insecticidal compositions may be in the form of dusting powders wnerem the active ingredient is mixed with a solid diluent or carrier, for example kaolin, bentonite, kieselguhr, or talc, or they may be in the form

of granules, wherein tne active ingredient is absorped in a porous granular material for example pumice.

Alternatively the insecticidal compositions may be in the form of baits wnerem the active ingredient is mixed with a nutrient carrier for example sucrose, yeast, malt extract, cereal or cereal products and optionally an attractant such as a pheromone or pheromone analogue.

Alternatively the insecticidal compositions may be in the form of liquid preparations to be used as dips 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) of the type described above for the fungicidal compositions.

The insecticidal compositions may be prepared by dissolving the active ingredient in a suitable solvent, for example, a ketonic solvent such as diacetone alcohol, or an aromatic solvent such as trimethyIbenzene and adding the mixture so obtained to water which may contain one or more known wetting, dispersing or emulsifying agents.

Other suitable organic solvents are dimethyl foπnamide, ethylene dichloπde, isopropyl alcohol, propylene glycol and other glycols, diacetone alcohol, toluene, kerosene, white oil, methylnaphthalene, xylenes and trichloroethylene, N-methyl-2- pyrrolidone and tetrahydrofurfuryl alcohol (THFA).

The insecticidal compositions which are to be used in the form of aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient or ingredients, the said concentrate to be diluted with water before use. 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 10-852 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. For agricultural or horticultural purposes, an aqueous preparation containing between 0.00012 and 0.12 by weight of the active ingredient (approximately equivalent to from 5-2000g/na) is particularly useful.

In use the insecticidal compositions are applied to the pests, to the locus of the pests, to the habitat of the pests, to growing plants liable to infestation by the pests, or, where there is systemic uptake by plants, to the soil surrounding plants liable to infestation, by any of the known means of applying pesticidal compositions, for example, by dusting or spraying.

The compounds of the invention may be the sole active ingredient of the insecticidal composition or they may be admixed with one or more additional active ingredients such as insecticides, insecticide 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, improving knockdown 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 insecticide, herbicide or fungicide included in the mixture will depend upon its intended utility 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, cypermethrin, alpha cypermethrin, bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids for example ethofenprox, natural pyrethrin, tetramethrin, s-bioallethrin, fenfluthrin, prallethrin, or 5-benzyl-3-furylmethyl-(E)-(lR,3S)-2,2-dimethyl-3-(2-oxothio lan- -3-ylidenemethyl) cyclopropane carboxylate; b) Organophosphates such as profenofos, sulprofos, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chloropyrifos , phosalone, fensulfothion, fonofos, phorate, phoxim. pirimiphos-methyl, fenitrothion or diazinon; c) Carbamates (including aryl carbamates) such as pirimicarb, cloethocarb, carbofuran, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur or oxamyl; d) 3enzoyi ureas such as trifiumuron, or chlorfluazuron; e) Organic tin compounds such as cyhexatin, fenbutatin oxide, or

azocyciot ; f) Macrolides such as avermectins or milbemycins , for example such as abamectin, ivermectin, and milbemycin; g) Hormones such as pheromones: h) Organochlorine compounds such as benzene hexachloride, DDT, chlordane or dieldrin. i) Amidines, such as chlordimeform or amitraz.

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 clofentezine, flubenzimine, hexythiazox ' and tetradifon, acaricides such as dicofol, propargite, bromopropylate, chlorobenzilate, or growth regulators such as hydramethylnon, cyromazine, methoprene, hydroprene, chlorfluazuron and diflubenzuron may also be included in the compositions.

Examples of suitable insecticide synergists for use in the compositions include piperonyl butoxide, sesamex, and dodecyl i idazole.

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 herbicide 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.

The compounds of formula I and insecticidal compositions comprising them have shown themselves active against a variety of insect and other invertebrate pests. They are particularly useful in controlling sucking pests sucn as aphids and mites. Compounds of the present invention are aiso generally cnaracteπseα DV a relatively proad spectrum of activity

wnich may include Leoidoptera and Coleoptera in audition to public health pests sucn as flies and cockroaches.

They may also De active against organophosphate, pyrethroid or cyclodiene (for example lmαane or dieidπn) resistant strains of puolic and animal health pests. They may De effective in combating both susceptiDie and resistant strains or the pests in their adult and immature stages of growth, and may be applied to the infested host animal by topical, oral or parenteral administration.

The following Examples illustrate the invention. Throughout the Examples, the term 'ether' refers to dietnyl ether, magnesium sulphate was used to dry solutions except where otherwise indicated, and solutions were concentrated under reduced pressure. All reactions were performed under an atmosphere of nitrogen and solvents were dried before use, where appropriate. Unless otherwise stated, chromatography was performed on a column of silica gel as the stationary phase. Where shown, infrared and NMR data are selective; no attempt is made to list every absorption in all cases. H NMR spectra were recorded using CDCl,-solutions unless otherwise stated. The following abbreviations are used throughtout: NMR = nuclear magnetic resonance ppm = parts per million m = multiplet s = singlet mp = melting point DMF = N,N-dιmethylformamide

EXAMPLE 1

This Example illustrates the preparation of (Ξ)-methyl 2-(2- [3- (3-trι- fluoromethylphenyl)-l,2,4-thiadιazol-5-yloxy]phenyl)-3-meth oxyacrylate (Compound 32 of Table 1).

(E)-Methyl 2- (2-hydroxyphenyl)-3-methoxyacrylate (1.26g; prepared as described in Example 3 of EP-A-0242081) and 5-chloro-3 [3-trifluoromethyl¬ phenyl]-1,2, 4-thιadιazole (0.8g) were dissolved in DMF (10ml) at 5°C. Fotassium carDonate (0.836g) was then added and the reaction mixture stirred at room temperature for 48 hours. Water and ether were added and the organic layer separated. Any residual product n the aqueous layer was extracted (twice) with ether and the combined ether layers washed with brine before drying (anhydrous sodium sulphate) and concentrating to give an oil. Column cnromatography (twice; firstly with 802 dichloromethane in hexane and then with 1:1 ether/hexane) gave the title product as an orange gum tO.cόg, 56;.); ^" H NMR (CDCl,, 270MKz): o 3.6(s,3H), 3.85(s,3H), 7.58(s,lH), 7.35-7.75(m.6H) , 8.35-8.50(m,2H) ppm.

EXAMPLE 2 This Example illustrates the preparation of (E)-methyl 2-(2-[3- - (3-methylbenzyl)-1,2, 4-thiadiazol-5-yloxy]phenyl)-3-methoxyacrylate (Compound 26 of Table 9).

(E)-Methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.48g; prepared as described in Example 3 of EP-A-0242081) and 5-chloro-3-(3-methylbenzyl)- -1,2,4-thiadiazole (0.8g) were dissolved in DMF (10ml) and cooled to 5°C. Potassium carbonate (0.98g) was then added and the reaction mixture stirred for 96 hours at room temperature. Further potassium carbonate (0.5g) was added and the reaction mixture stirred for a further 24 hours. Water and ether were added and the layers separated. Any residual product was extracted from the aqueous layer with ether (twice) and the combined organic layers washed with brine. After drying (anhydrous sodium sulphate) the solvent was removed under reduced pressure to give an oil. Column chromatography (twice; firstly wiih 102 ether/902 dichloromethane and then with 602 ether/402 hexane) gave the title product as a gum (117mg, 82); H NMR (CDCl , 270MHz): δ 2.32(s,3H), 3.58(s,3H), ,.65(s,3H), 4.1(s,2H), 7.5(s,lH), 7.0-7.45(m,8H) ppm.

EXAMPLE 3 This Example illustrates the preparation of (E_)-methyl 2-(2- [5-phenyl- -1,3, 4-thiadiazol-2-yloxy]phenyl)-3-methoxyacrylate (Compound 1 Table 5).

2-Methylsulphonyl-5-phenyl-l,3,4-thiadiazole (l.llg) and potassium carbonate (0.95g) were stirred in DMF (20ml) and cooled to 5°C. A solution of (E_)-methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.43g; prepared as described in Example 3 of EP-A-0242081) in DMF (10ml) was added over 2 minutes and the reaction mixture stirred for hour at 0°C in a cooling bath. The cooling bath was removed and the reaction stirred for 4% days. The reaction mixture was poured into water and the product extracted with ether (three times). The ether layers were washed twice with aqueous sodium hydroxide solution then 3 times with water before drying and concentrating to give a yellow solid. Column chromatography (twice, using 2:1 ether/hexane as eluent) gave the title product as a yellow gum (0.24g, 142); **H NMR (CDCl., 270 MHz): δ 7.80-7.86(m,2H) , 7.58(s,lH), 7.3-7.48(m.7H) , 3.79(s,3H), 3.65(s,3H) ppm.

EXAMPLE 4 This Example illustrates the preparation of (E)-methyl 2- (2- [3- (2- -pyrazmyi)-1,2, -thιadιazoi-5-yioxy]phenyi)-3-methoxyacr late (Compound 191 of Table 1) .

(E)-Methyl 2-(2-hydroxyphenyi)-3-methoxyacrylate (1.28g; prepared as described in Example 3 of EP-A-0242081) and 5-chloro-3-(2-pyrazinyl)-1,2, 4- -thiadiazole (0.61g) were dissolved in DMF (10ml) at room temperature. Potassium carbonate (0.85g) was added and the reaction mixture stirred for 25 hours. Water was added and the product extracted with ether (4 times). The combined organic phases were washed with brine, dried and concentrated to give an oil.

Column chromatography (602 ethyi acetate/402 dichloromethane) on silica gel gave the title product as a yellow gum (0.816g, 752); ^~ H NMR (CDCl,, 270MHz): δ 3.65(s,3H), 3.8(s,3H), 7.4(m,4H), 7.57(s,lH), 8.7(m,2H), 9.45(S,1H) ppm.

EXAMPLE 5 This Example illustrates the preparation of (E)-methyl 2-(2-[3-(2- -thienyl)-l,2, 4-thiadiazol-5-yloxy]phenyl)-3-methoxy acrylate (compound 180 of Table 1) .

5-Chloro-3-(2-thienyl)-l,2,4-thiadiazole (0.6g) was dissolved in DMF (10ml) and (E)-methyl 2-(2-hydroxyphenyl)-3-methoxyacrylate (1.23g; prepared as described in Example 3 of EP-A-0242081) was added followed by potassium carbonate (0.818g). The reaction mixture was stirred at room temperature for 48 hours and then diluted with water. Extraction three times with ether, drying and concentration gave an oil.

Column chromatography (firstly with 50/50 ether/hexane, then repeated with dichloromethane) gave the title product as a colourless gum (0.369g, 332); ¹ H NMR (CDC1 _3> 270 MHz): δ 3.62(s,3H), 3.77(s,3H), 7.1(m.lH), 7.4(m,5H), 7.57(s,lH), 7.8(m,lH) ppm.

EXAMPLE 6 This Example illustrates the preparation of (E)-methyl 2- (2- [5- (4- -chlorophenyl)-1,3, 4-oxadiazol-2-yioxy]phenyl)-3-methoxyacrylate (Compound No. 7 of Table 5') .

Potassium carbonate (0.76g) was added in one portion to a solution of (E)-methyl 2- (2-hydroxyphenyl)-3-methoxyacrylate (1.14g; prepared as described in Example 3 of EP-A-0242081) in DMF (20ml) kept at 5°C in a cooling bath. A solution of 2-methylsulphonyl-5-(4-chlorophenyl)-1,3,4- -oxadiazole in DMF (15ml) was added dropwise during 15 minutes. The cooling bath was removed and the reaction mixture stirred for 2 hours before leaving to stand overnight.

The solution was poured into water and the organic material extracted with ether three times.

The ether layer was dried before concentrating to a yellow solid. Tπturation with ether gave the title product as a pure white solid (1.36g, 702) ; m.p 109-111°C.

EXAMPLE 7 This Example illustrates the preparation of (E)-methyl 2-(2-[3-(2- -chlorophenvl)-1,2, 4-thιadιazol-5-v oxyjpnenyl)-3-methoxyacryiate (compound 5 of Table 1) .

5-(4-Methylphenylsulphonyl)-3- (2-chlorophenyl)-1,2, 4-thiadiazole 1.1. 3g) was dissolved in DMF (25ml) and (E)-methyl 2- (2-hyoroxpnenyi)-3- -methoxyacrylate (1.69g) was added. The solution was cooled to 5°C before potassium carbonate (1.12g) was added and the reaction stirred for 45 minutes at 5°C. After stirring at room temperature for 22 hours the reaction mixture was poured into water and extracted with ether. The solvent was dried and concentrated to give a tacky yellow solid. Column cnromatography (elutmg with dichloromethane) gave a yellow solid whicn, upon tπturation with hexane, gave the pure product (0.86g, 522); mp 127-129°C.

EXAMPLE 8 This Example illustrates the preparation of (E)-methyl 2-(2- [3-(2- -fluorophenyl)-1,2, 4-oxadiazol-5-yloxy]phenyl)-3-methoxyacrylate (compound 2 of Table 1') .

(E)-Methyl 2- (2-hydroxyphenyl)-3-methoxyacrylate (1.45g) was dissolved in DMF (10ml) and cooled to 5°C. Potassium carbonate (0.97g) was added followed by 5-chloro-3-(2-fluorophenyl)-1,2, 4-oxadιazole (1.32g) in DMF (15ml). The resulting mixture was stirred at room temperature for 4 hours and then poured into water. The product was extracted into ether and the solution dried and concentrated to give a yellow gum. Tπturation with ether and filtration gave the product as an off-white solid (1.82g, 742); p 90-92°C.

EXAMPLE 9 The compounds were tested against a variety of foliar fungal diseases of plants. The technique employee was as follows.

The plants were grown in Jonn Innes Potting Compost (No 1 or 2) in 4 cm diameter m ipots. The test compounds were formulated either by Dead milling with aqueous Dispersol T or as a solution m acetone or acetone/ethanol which was diluted to the required concentration immediately Derorε use. Tne formulations (100 ppm active ingredient) were sprayed on to tne foliage or applied to the roots of the plants in the so l. The

sprays were applied to maximum retention and the root drencnes to a final concentration equivalent to approximately 40 ppm a.i. in dry soil. Tween 20 was added to give a final concentration of 0.052 wnen the sprays were applied to cereals.

For most of tne tests the compounds were applied to the soil (roots) or to tne foliage (oy spraying) one or two oays before tne plant was inoculated with tne disease. An exception was the test on Erysiphe graminis in which tne plants were inoculated 24 hours before treatment. Foliar pathogens were applied by spray as zoosporangial suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.

The disease level present (i.e. leaf area covered by actively sporulatmg disease) on each of the treated plants was recorded using the following assessment scale:

0 = 02 disease present 20 = 10.1-202 disease present

1 = 0.1-12 disease present 30 = 20.1-302 disease present 3 = 1.1-32 disease present 60 = 30.1-602 disease present 5 = 3.1-52 disease present 90 = 60.1-1002 disease present

10 = 5.1-102 disease present

Each assessment was then expressed as a percentage of the level of disease present on the untreated control plants. This calculated value is referred to as a P0C0 (Percentage of Control) value. An example of a typical calculation s as follows:

Disease level cn untreated control = 90 Disese level on treated plant = 30

?0C0 = disease level on treated plant x 100 = 30 x 100 = 33.3 disease level on untreated control 90

This calculated POCO value is then rounded to the nearest of the values m tne 9-poιnt assessment scale snown aDove . In tnis particular example, the POCO value would be rounded to 30. If the calculated POCO

falls exactly mid-way between two of the points, it is rounded to the lower of the two values.

The results are shown in Table 18.

TABLE 18

TABLE 18 (Continued)

TABLE 18 (Continued)

Unless stated otherwise, data represent activity following application a combined foliar spray and root drench treatment at 100 ppm.

a 10 ppm foliar application only b 25 ppm foliar application only

- No result

Key to Diseases

Pr Puccinia recondita Tc Thanetophorus cucumeris Egt Ervsiphe graminis tritici Vi Venturia inaeoualis Sn Septoria nodorum Pv Plasmonara viticola

Po Pyricularia oryzae Pil Phytophthora infestans lycopersici

EXAMPLE 10 The activity of the compounds of formula (I) was determined using a variety of pests. The pests were treated with a liquid compo.sition containing 250 parts per million (ppm) by weight of the compound except in the case of Meloidogyne incognita, which was treated with a liquid composition containing 6.25 ppm by weight of the compound in an in vitro test. The compositions were made by dissolving the compound in acetone and ethanol (50:50) mixture and diluting the solutions with water containing 0.12 by weight of a wetting agent sold under the trade name "SYNPERONIC" NP8 (further diluting to 6.25ppm in the case of Meloidogyne incognita) 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 substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with the compositions. The mortality of the pests was then assessed at periods usually varying from two to five days after the treatment with the exception of Musca domestica. for which an additional initial knockdown assessment was made.

The results of the tests are presented in Table 19 for each of the compounds. The results indicate a grading of mortality (or knockdown in the case of Musca domestica) , designated as A, B or C wherein A indicates 80-1002 mortality, B indicates 40-792 mortality and C indicates 0-392 mortality. The pest species is designated by a letter code.

Information regarding the pest species, the support medium or food, and the type and duration of the test is given in Table 20.

TABLE 19 (Continued)

TABLE 19 (Continued)

TABLE 20

CODE LETTERS SUPPORT TYPE OF DURATION

TEST SPECIES (TABLE 18) MEDIUM/FOOD TEST (DAYS)

Tu Tetranvchus urticae French bean Contact (spider mite) leaf

Mp Myzus persicae Chinese Contact (aphid) Cabbage leaf

Md Musca domestica Cotton wool/ Contact ' 2

(housefly - adult) sugar Knockdown 15 min

Hv Heliothis virescens Soya leaf Residual (tobacco budworm)

Se Spodoptera exigua Cotton leaf Residual

(lesser armyworm - larva)

Db Diabrotica balteata Filter paper/ Residual

(cucumber beetle - larva) maize seed

Mi Meloidogyne incognita in vitro Contact (rootknot nematode - larva)

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

CHEMICAL FORMULAE (IN DESCRIPTION)

BOC ^' ^ A .OCH*,

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