PROCESS FOR THE PREPARATION OF OXIME DERIVATIVES, CERTAIN INTERMEDIATES AND THE USE OF THE OXIME DERIVATIVES AS FUNGICIDES

Abstract: A process for the preparation of a compound of formula (I), wherein Y is O, S(O)n (wherein n is 0, 1 or 2) or NR<5>; W is CH3O.CH=C.CO2CH3, CH3O.CH=C.CONR<6>R<7>, CH3O.N=C.CO2CH3 or CH3O.N=C.CONR<6>R<7>; R<1> is hydrogen, C1-4 alkyl, C1-4 haloalkyl or cyano; R<2>, R<3>, R<5>, R<6> and R<7> are independently hydrogen or C1-4 alkyl; p is 1; and R<4> is hydrogen, C1-10 alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substitued heteroarylalkyl; the process comprising reacting a compound of formula (II), wherein W, R<1>, R<2> and R<3> are as previously defined and L is a leaving group, with a compound of formula (III), wherein R<4> and Y are as previously defined.

Description: PROCESS FOR THE PREPARATION OF OXIME DERIVATIVES, CERTAIN INTERMEDIATES AND THE USE OF THE OXIME DERIVATIVES AS FUNGICIDES The present invention relates to chemical processes for the preparation of oximes, to certain intermediate oximes, to oxime derivatives useful as fungicides, to compositions containing said derivatives and to methods of using the oxime derivatives to combat fungi, especially fungal infections of plants. 2 3 Various compounds of formula (Ia) wherein R is hydrogen and R is hydrogen or methyl are disclosed in EP-A-0370629, W092/13830, W092/18487, EP-A-0463488, EP-A-0414153 , EP-A-0460575 and W092/18494 (which was published after the priority date of the present application) . The present invention provides a process for the preparation of a is hydrogen, C alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; the process comprising reacting a compound of 1 2 3 formula (II), wherein W, R , R and R are as previously defined and L is a leaving group, with a compound of formula (III), wherein R and Y are as previously defined; preferably at a temperature in the range 0-120°C, especially in the range 20-60°C, and in a polar solvent such as acetone, N,N-dimethylformamide or N-methylpyrrolidinone. In one particular aspect the present invention provides a process for 1 2 3 4 the preparation of a compound of formula (I), wherein R , R , R , R , , p and Y are as defined above, the process comprising the steps of: a) dehydroxylating a compound of formula (IV), wherein Y is oxygen and 1 2 3 R , R , R and W are as defined above, for example with methanesulphonyl chloride or p-toluenesulphonyl chloride, in the presence of a convenient base such as pyridine or triethylamine, in the presence of a solvent such as diethyl ether or tetrahydrofuran at a temperature in the range 0-60°C, to form a compound of formula (II), 1 2 3 wherein R , R , R , W and L are as defined above; and, b) reacting the product of (a) with a compound of formula (III), wherein 5 4 5 Y is 0, S(0) or NR and R , n and R are as defined above in a n solvent such as acetone, N,N-dimethylformamide or N-methylpyrrolidinone at a temperature in the range 0-120°C. In another aspect the present invention provides a process for the 5 preparation of a compound of formula (I), wherein Y is 0, S(0) or NR and R , R , R , R , V, p, n and R are as defined above, the process comprising the steps of: a) reacting a compound of formula (V), wherein W is as defined above, in a polar solvent such as water, methanol or ethanol at a temperature in the range 0-120°C, with a compound of formula (VI), wherein Y is 1 2 3 oxygen and R , R and R are as defined above, to form a compound of formula (IV) wherein Y is oxygen; b) dehydroxylating the compound of formula (IV), wherein Y is oxygen and 1 2 3 R , R , R and are as defined above, to form a compound of formula ι 2 3 (II), wherein R~, R , R , W and L are as defined above; and c) reacting the product of (b) with a compound of formula (III), wherein 5 4 5 Y is 0, S(0) or NR , and R , n and R are as defined above. n In another aspect the present invention provides a process for the 1 2 3 preparation of a compound of formula (II), wherein W, L, R , R and R are as defined above, the process comprising dehydroxylating a compound of 1 2 3 formula (IV), wherein Y is oxygen and R , R , R and are as defined above, preferably using methanesulphonyl chloride or p-toluenesulphonyl chloride as a dehydroxylating reagent with a suitable base such as pyridine or triethylamine in a convenient solvent such as diethyl ether or tetrahydrofuran and at a temperature in the range 0-120°C, especially in the range 20-60°C. In a further aspect the present invention provides a process for the 1 2 3 preparation of a compound of formula (II), wherein W, L, R , R and R are as defined above, the process comprising the steps of: a) reacting a compound of formula (V), wherein ¥ is as defined above, 1 2 with a compound of formula (VI), wherein Y is oxygen, and R , R and 3 R are as defined above, in a solvent such as water, methanol or ethanol and at a temperature in the range 0-120°C, to form a compound 1 2 3 of formula (IV), wherein Y is oxygen are R , R , R and W are as defined above; and, b) dehydroxylating the compound of formula (IV), wherein Y is oxygen, and 1 2 3 W, R , R and R are as defined above. In another aspect the present invention provides a process for the 1 2 3 preparation of a compound of formula (II), wherein R , R , R and W are as defined above and L is chlorine, the process comprising reacting a compound of formula (V), wherein W is as defined above, with a compound of formula 1 2 3 (VII), wherein R , R and R are as defined above, in a solvent such as water, methanol or ethanol at a temperature in the range 0-120°C. In another aspect the present invention provides a process for the preparation of a compound of formula (I), wherein Y is 0, S(0) or NR , and V, p, R , R , R , R , R and n are as defined above, the process comprising reacting a compound of formula (IV), wherein Y is 0, S(0) or NR , and W, R~, R , R , R , R and n are as defined above, with a compound of formula 4 4 R , wherein R is as defined above and L is a leaving group, preferably at a temperature in the range 0-120°C, especially in the range 20-60°C, and in a polar solvent such as acetone, N,N-dimethylformamide or N-methylpyrrolidinone. In a further aspect the present invention provides a process for the preparation of a compound of formula (I), wherein Y is 0, S(0) or NR and V, p, R , R , R , R , n and R are as defined above, the process comprising the steps of: a) reacting a compound of formula (V), wherein is as defined above, with a compound of formula (VI), wherein Y is 0, S(0) or NR , and R , 2 3 5 n R , R , n and R are as defined above; and, 4 4 (b) reacting the product of (a) with a compound of formula R L, wherein R is as defined above and L is a leaving group, in a solvent such as acetone, N,N-dimethylformamide or N-methylpyrrolidinone at a temperature in the range 0-120°C in the presence of a convenient organic base (such as pyridine or triethylamine) or an inorganic base (such as potassium carbonate or sodium hydride). In another aspect the present invention provides a process for the 1 2 3 preparation of a compound of formula (I), wherein p is 0 and W, R , R , R 4 and R are as defined above, the process comprising coupling a compound of 4 4 formula (II) with a compound of formula R X, wherein R is as defined above and X is either a leaving group or a metallated species. The coupling 4 reaction can be carried out by treating the metallated species R X with a compound of formula (II) in the presence of a palladium catalyst such as tetrakis (triphenylphosphine)palladium(O) . In another aspect the present invention provides a process for the 1 2 3 preparations of a compound of formula (I), wherein p is 0 and W, R , R , R 4 and R are as defined above, the process comprising metallating a compound of formula (II) and coupling this metallated species with a compound of 4 4 rormula R X, wherein R is as defined above and X is a leaving group. For example the compound of formula (II) is metallated with n-butyllithium in a convenient solvent such as diethyl ether or tetrahydrofuran at a 4 temperature of -70-20°C and reacted with R X in a convenient solvent such as diethyl ether or tetrahydrofuran at a temperature of 0-60°C. When X is a leaving group it can be a halogen atom (including fluorine, chlorine, bromine and iodine) or CH SO or CH SO 0. When X is a metallated species it can be a magnesium halide (chloride, bromide or iodide), a zinc halide (chloride, bromide or iodide) or a lithium species. Examples of the L group are halogen (including fluorine, bromine and iodine but preferably chlorine), CH SO and CH SO 0. Compounds of formula (I) wherein p is 1 can be prepared by reacting a compound of formula (II) with a compound of formula (III) optionally in the presence of a base (such as potassium carbonate or sodium hydride), optionally in a convenient solvent (such as acetone or N,N dimethylformamide) at a temperature of 20-110°C. Compounds of formula (II) can be prepared by reacting compounds of formula (VI), wherein Y is oxygen, with an agent such as phosphorus trichloride, phosphorus pentachloride, phosphorus tribromide, phosphorus pentabromide, phosphorus oxychloride, phosphorus oxybromide, methanesulphonyl chloride or para-toluenesulphonyl chloride optionally in the presence of a base (such as triethylamine or pyridine), in a convenient solvent (such as chloroform or methylene chloride) at a temperature of 20-110°C. Alternatively compounds of formula (I), wherein p is 1 can be prepared by reacting compounds of formula (IV) with compounds of formula R L, optionally in the presence of a base (such as sodium hydride, potassium carbonate or triethylamine), in a convenient solvent (such as toluene or N,N-dimethylformamide) at a temperature of 20-110°C. Compounds of formula (IV) can be prepared by reacting a compound of formula (VI) with a compound of formula (V), optionally in the presence of a base (such as triethylamine or pyridine), in a convenient solvent (such as methanol, ethanol or water) at a temperature of 20-110°C. In another aspect the present invention provides a compound of formula (II), wherein W is CH O.CH=C.CO CH , CH 0.CH=C.CONR 6 R 7 , CH 0.N=C.C0 CH or 6 7 1 ? CH 0.N=C.CONR R ; R is hydrogen, C alkyl, C haloalkoxy or cyano; R , 3 fi 7 — 4 R , R and R are independently hydrogen or C alkyl; and L is a leaving group; provided that when L is chlorine, W is CH 0.CH=C.C0 CH , and R and 3 1 3 2 3 R are both hydrogen then R is not methyl. In another aspect the present invention provides the compounds of formula (IV), wherein Y is 0, S(0) (wherein n is 0, 1 or 2) or NR n 6 7 (preferably oxygen); W is CH 3 0.CH=C.C0 CH 3 , CH 3 0.CH=C.C0NR R , CH_,0.N=C.C0 CH, or CH.,0.N=C.C0NR 6 R 7 ; R is hydrogen, C. . alkyl, C. . J 2 3 2 3 6 7 haloalkoxy or cyano; and R , R , R and R are independently hydrogen or C χ _ 4 alkyl. In one aspect the present invention provides compounds of formula (Ia) is are substituted aryl (but not C.H,.), optionally substituted arylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl; wherein the foregoing aryl and heteroaryl moieties are substituted by one or more of halogen, hydroxy, mercapto, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroaryalkenyl, optionally substituted arylalkoxy, optionally substituted heteroarylalkoxy, optionally substituted aryloxyalkyl, optionally substituted heteroaryloxyalkyl, acyloxy, cyano, thiocyanato, nitro, -NR'R", -NHCOR', -NHCONR'R", -CONR'R", -C00R' , -OSO R' , -SO R', -COR', -CR'=NR" or -N=CR'R" in which R' and R" are independently hydrogen, alkyl, alkoxy, alkylthio, cycloalkyl, cycloalkylalkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C alkyl or C alkoxy; when R' and R" are in CONR'R" they can together form a 5- or 6-membered heterocyclic ring (for example a pyrrole, imidazole, pyrrolidine, piperidine or morpholine ring); or two substituents, when they are in adjacent positions on the aryl or heteroaryl ring can join to form a fused alphatic ring (especially to form a fused 6-membered carbon aliphatic ring); provided that when W is CH..CH=C.C0 CH , 1 2 3 4 R is methyl and R and R are both hydrogen then when Y is S, R is 4 neither benzyl nor CH -fur-2-yl, when Y is 0, R is neither 2-chlorophenyl 4 nor 2,4-dichloroρhenyl, and when Y is NCH , R is not benzyl. The double bonds of the W group (the propenoate, oximinoacetamide, oxyiminoacetate or propenamide group) and the oxime side chain are unsymetrically substituted and both can, independently, be in the form of an (E)- or (Z_)-isomer. Mixtures of isomer pairs can be separated and this invention embraces all such isomer pairs and mixtures in all proportions of isomer pairs. The (E)-isomers of the W group of the compounds of formula (I) are more fungicidally active and form a preferred embodiment of the invention. The (E)-isomers of the oxime side chain of the compounds of formula (I) are more fungicidally active and form a preferred embodiment of the invention. Aryl includes naphthyl but is preferably phenyl. 4 Arylalkyl and heteroarylalkyl as a values of R include aryl(C )alkyl and heteroaryKC )alkyl and are, for example, benzyl, phenylethyl, phenyl-n-propyl, pyrid-2-ylmethyl, pyrimidin-2-ylmethyl or pyrimidin-4-ylmethyl. 4 It is preferred that when R is an optionally substituted heteroaryl or optionally substituted heteroarylalkyl group then the heteroaryl moiety is a pyridine or pyrimidine ring, especially a 2-linked pyridine or pyrimidine ring. Heteroaryl includes 5- and 6-membered aromatic rings containing one, two, three or four heteroatoms selected from the list comprising oxygen, sulphur and nitrogen and can be fused to benzenoid ring systems. Examples of heteroaryl are pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl (1,2,3-, 1,2,4- and 1,3,5-), furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (1,2,3- and 1,2,4-), tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl, indolinyl, isoindolinyl, benzofuranyl, benzothienyl, benzi idazolyl, benzoxazole, benzthiazole, oxadiazole and thiadiazole. Substitutents which may be present in optionally substituted aryl, the aryl part of optionally substituted arylalkyl, optionally substituted heteroaryl and the heteroaryl part of optionally substituted heteroarylalkyl moieties include one or more of the following: halogen, 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 )alkoxy (especially trifluoromethoxy) , C alkylthio (especially methylthio) , halo(C )alkylthio, hydroxy(C )alkyl, C alkoxy(C alkyl, C cycloalkyl, C 3 cycloalkyl(C 1 _ 4 )alkyl, optionally substituted methylenedioxy (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 heterocyclyl (especially optionally substituted pyrrolidine) , 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 heteroaryl- (C )alkyl (especially optionally substituted pyridyl- or pyrimidinyl- (C ,)alkyl), optionally substituted aryl(C )alkenyl (especially optionally substituted phenylethenyl) , optionally substituted heteroaryl- (C )alkenyl (especially optionally substituted pyridylethenyl or pyrimidinylethenyl) , optionally substituted aryl(C )alkoxy (especially optionally substituted benzyloxy) , optionally substituted heteroaryKC - alkoxy (especially optionally substituted pyridyl- or pyrimidinyl(C - alkoxy), optionally substituted aryloxy(C )alkyl (especially phenoxy- methyl) , optionally substituted heteroaryloxy(C ,)alkyl (especially optionally substituted pyridyloxy- or pyrimidinyloxy(C )alkyl), acyloxy (including C alkanoyloxy (especially acetyloxy) and benzoyloxy), cyano, thiocyanato, nitro, -NR'R", -NHCOR*. -NHCONR'R", -CONR'R", -C00R' , -0S0 R', -SO R', -COR', -CR'=NR" or -N=CR*R" in which R' and R" are independently hydrogen, C alkyl, C. . alkoxy, C. alkylthio, C, cycloalkyl, C, , 1-4 1-4 1-4 J—D O-D cycloalkyl(C )alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C alkyl or C alkoxy; when R' and R" are in CONR'R" they can together form a 5- or 6-membered heterocyclic ring (for example a pyrrole, imidazole, pyrrolidine, piperidine or morpholine ring); or two substituents, when they are in adjacent positions on the aryl or heteroaryl ring can join to form a fused alphatic ring (especially to form a fused 6-membered carbon aliphatic ring) . 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 alkylthio, hydroxy(C )alkyl, C alkoxy(^ )alkyl, C cycloalkyl, C cycloalkyl(C )alkyl, alkanoyloxy, benzoyloxy, cyano, thiocyanato, nitro, -NR'R", -NHC0R' , -NHCONR'R", -CONR'R", -C00R' , -SO R', -0S0 R', -COR', -CR'=NR" or -N=CR'R" in which R' and R" have the meanings given above. All alkyl moieties, including the alkyl moiety of, for example, alkoxy and haloalkylthio, preferably contain, unless otherwise stated, from 1 to 6, more preferably from 1 to 4, carbon atoms. They can be in the form of straight or branched chains, for example methyl, ethyl, n- or iso- propyl, or n-, sec-, iso- or tert-butyl. Alkenyl and alkynyl moieties preferably contain from 2 to 6, more preferably from 2 to 4, carbon atoms. They can be in the form of straight or branched chains, and 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 a further aspect the present invention provides a compound of formula (Ia), wherein W is CH O.CH=C.CO CH . It is preferred that Y is oxygen, sulphur or NCH, . In another aspect the present invention provides a compound of formula (Ia) wherein Y is sulphur. It is preferred that R 1 is methyl. It is also preferred that R2 and 3 R are both hydrogen. It is preferred that R is hydrogen and that R is methyl. In another aspect the present invention provides a compound of formula 4 (Ia) wherein R is phenyl, naphthyl, phenyl(C )alkyl, naphthyl(C )alkyl, pyridyl, pyrimidinyl, pyridyl(C )alkyl or pyrimidinyl(C )alkyl; wherein the aromatic moiety is substituted by C alkyl, halo(C )alkyl, C alkoxy, halo(C )alkoxy or halogen. It is especially preferred that R is phenyl substituted by C alkyl (such as methyl, ethyl, n-propyl or iso-propyl) or C alkoxy (such as methoxy, ethoxy, n-propoxy or iso-propoxy) . In yet another aspect the present invention provides a compound of formula (Ia) wherein W is CH 3 0.CH=C.CO CH , CH O.CH=C.CONHCH , CH 3 0.N=C.C0 2 CH 3 or CH 3 O.N=C.CONHCH 3 ; Y is 0, S or NR 5 ; R 1 , R , R 3 and R 5 are independently hydrogen or methyl; and R is phenyl, naphthyl, phenyl(C )alkyl, naphthyl(C )alkyl, heteroaryl (especially pyridyl, pyrimidinyl, benzothiazolyl, benzimidazolyl, tetrazolyl, benzoxazolyl, 1,2, -triazolyl, imidazc yl or thienyl) or heteroaryl(C )alkyl (especially pyridylmethy.: or pyrimidinylmethyl) , all of which, other than phenyl which must be subst tuted, are optionally substituted with halogen, C alkyl, C alkoxy, hai.o(C )alkyi, halo(C )alkoxy, cyano, phenyl, phenoxy or nitro; provided that when W is CH .CH=C.C0 CH , R is methyl and R 2 and R3 are both hydrogen then when Y is S R4 is neither benzyl nor 4 CH -fur-2-yl, when Y is 0, R is neither 2-chlorophenyl nor 4 2,4-dichlorophenyl, and when Y is NCH , R is not benzyl. In a further aspect the present invention provides a compound of alkyl (such as methyl, ethyl, n-propyl or iso-propyl) or C alkoxy (such as methoxy, ethoxy, n-propoxy or iso-propoxy) . In a further aspect the present invention provides a compound of 1 2 3 formula (Ia) wherein W is CH O.CH=C.CO CH ; R is methyl; R and R are 4 both hydrogen; Y is sulphur; and R is optionally substituted pyrimidinyl . (for example substituted by halogen, C alkyl (especially methyl), halo(C, ,)alkyl,, C, , alkoxy or halo(C, ,)alkoxy). 1-4 1-4 1-4 In another aspect the present invention provides a compound of formula (Ia) wherein W is CH O.CH=C.CO CH ; Y is oxygen or sulphur; R is methyl; 2 3 4 R and R are both hydrogen; and R is phenyl [optionally substituted with C alkyl (especially methyl), cyano or C alkoxy (especially ethoxy)], thienyl, pyrimidinyl [optionally substituted with hydroxy, phenyl or C alkyl (especially methyl, ethyl or n-propyl)], pyridinyl, pyridinyl-N-oxide, benzothiazolyl, benzimidazolyl, tetrazolyl [optionally substituted with C alkyl (especially methyl)], benzoxazolyl or 1,2, -triazolyl [optionally substituted with C alkyl (especially methyl) ] . The compounds listed in Tables Ia to Ii can be made using the process of the present invention. According to the present invention there are provided certain individual compounds listed in these Tables. The group W of all the compounds in Tables Ia to Ii is the (E)-geometric isomer, so E/E ^ and E/Z mixtures refer to isomers about the oxime bond in the side chain. TABLE Ia Compounds in this Table are of formula (VIII) and have the values of Y 4 and R given below. _ R Isomer Mixture H E E E/£ thien-2-yl E/E thien-2-yl £/E:E/_Z pyrimidin-2-yl E/E:E/Z_ 4-CH 3„-C6„H4, E/E:E/—Z pyrimidin-2-yl E/ :E/Z. pyridin-2-yl £/E:E/Z_ 4-hydroxypyrimidin-2-yl E/E:E/Z_ pyridin-4-yl E/E:E/Z_ benzthiazol-2-yl E/E : _E/_?_ 2-CH 3_,0-C £ 6H4. E/E:E/—Z 4-methylpyrimidin-2-yl E/E : E/Z_ 2-CN-C 8 H 4 E/E:E/Z_ benzimidazol-2-yl E/E:E/E l-methyltetrazol-5-yl E/E:E/Z. pyridin-2-yl-N-oxide _.I_. : .I_. benzoxazol-2-yl E/E:E/Z_ 3-methyl-l,2,4-triazol-5-yl E/'E:E/Z_ 2-CH 3 -C 5 H 4 E/EsE/Z. 4-n-propyl-6-ethoxypyrimidin-2-yl E/E:E./Z_ 4-phenyl-pyrimidin-2-yl E/E:E/Z_ 3-CH J-CH _0-C O.H4. —E/—E: — E/—Z 3-CH 3,-C c 6H4. —E/—E:—E/—Z 4-C H 0-pyrimidin-2-yl E/E:E/Z_ 4-CH,-C £ H, E/E:E/Z j b 4 — — — — 3,4-di-CH,0-C_H, E/E:E/Z 3 b j — — — — 5-CF 3 -pyridin-2- E/E:E/Z_ l-CH 3 -imidazol-2-yl I/E:E/Z_ 3-CH 3_,0-C6„H4, —E/—E:—E/—Z TABLE Ia (continued) Compound Isomer Mixture No E/E:E/Z_ E/E:E/^ E/E:E/Z_ E/E E/Z_ E/E:E/Z_ E/E:E/ _.!_. E/E E/E E/Z. E/E E/2. E/E E/Z. E/E.-E/Z. E/E:E/Z_ E/E:E/Z_ E/E:E/Z_ E/E:E/Z_ E/E E/Z. E/E:E/Z_ E/E VL E/E This Table consists of 88 compounds of formula (Ia) wherein W is CH 3 0.CH=C.C0 2 CH 3 , R 1 , R 2 and R 3 are all hydrogen and Y and R 4 have the values given in Table Ia. TABLE Ic This Table consists of 88 compounds of formula (Ia) wherein W is CH O.CH=C.CO CH , R 1 and R 2 are both methyl, R 3 is hydrogen and Y and R 4 have the values given in Table Ia. TABLE Id This Table consists of 88 compounds of formula (Ia) wherein W is 1 2 3 ώ CH O.N=C.CO CH , R is methyl, R and R are both hydrogen and Y and R have the values given in Table Ia. TABLE le This Table consists of 88 compounds of formula (Ia) wherein W is CH O.N=C.CO CH , R 1 , R 2 and R 3 are all hydrogen and Y and R 4 have the values given in Table Ia. TABLE If This Table consists of 88 compounds of formula (Ia) wherein W is 2 CH 3 0.,NN==CC..CC00 22 CCHH 33 ,, R 1 aanndd RR 2 aarree bbootth methyl, R3 is hydrogen and Y and R4 have the values given in Table Ia. TABLE Ig This Table consists of 88 compounds of formula (Ia) wherein W is CH_,0.N=C.C0NHCH 3 , R 1 is methyl, R 2 and R 3 are both hydrogen and Y and R 4 have the values given in Table Ia. TABLE Ih This Table consists of 88 compounds of formula (Ia) wherein W is CH 3 O.,NN==CC..CC0ONNHHCCHH 33 ,, RR 11 ,, RR 22 and R 3 are all hydrogen and Y and R 4 have the values given in Table Ia TABLE Ii This Table consists of 88 compound of formula (Ia) wherein W is CH 3 O.N=C.CONHCH 3 , R 1 and R 2 are both methyl, R 3 is hydrogen and Y and R 4 have the values given in Table Ia. TABLE II Table II shows selected proton NMR data for certain compounds in Table Ia to Ii. Chemical shifts are measured in parts per million (ppm) from tetramethylsilane and deuterochloroform was used as solvent throughout. The following abbreviations are used: s = singlet d = doublet t = triplet m = multiplet brs = broad singlet q = quartet dd = doublet of doublets Compound Proton NMR DATA (δ) No. (Table No) l(Ia) Major isomer: 1.83(3H,s); 2.62(lH,t); 3.70(3H,s); 3.82(3H,s); 4.13(2H,d); 5.02(2H,s); 7.11-7.17(lH.m) ; 7.25-7.35 (2H,m) ; 7.40-7.46(lH,m) ; 7.58(lH,s) ppm. Minor isomer: 1.94(3H,s); 2.53(lH,t); 3.70(3H,s); 3.82(3H,s); 4.29(2H,d); 4.98(lH,s); 7.11-7.17(lH.m) ; 7.25-7.35(2H,m) ; 7.40-7.46(lH,m) ; 7.58(lH,s) ppm. 2(Ia) Major isomer: 1.99(3H,s); 3.44(2H,s); 3.68(3H,s); 3.80(3H,s); 4.90(2H,s); 6.92-6.96 (lH,m) ; 7.08-7.16 (2H,m) ; 7.25-7.37(4H,m) ; 7.55(lH,s) ppm. 3(Ia) Minor isomer: 1.93(3H,s); 3.64(2H,s); 3.69(3H,s); 3.81(3H,s); 4.87(2H,s); 6.92-6.97(lH,m) ; 7.08-7.17(2H,m) ; 7.25-7.37(4H,m) ; 7.56(lH,s) ppm. 4(Ia) Major isomer: . 2.01(3H, s) ; 3.69(3H,s); 3.81(3H,s); 4.89(2H,s); 5.06(2H,s); 6.97(lH,t); 7.13-7.18(lH,m) ; 7.29-7.36(2H,m) ; 7.43-7.48(lH,m) ; 7.58(lH,s); 8.54(2H,d); ppm. Minor isomer: 1.97(3H,s); 3.70(3H,s); 3.82(3H,s); 5.04(2H,s); 5.25(2H,s); 6.98(lH,t); 7.13-7.18(lH.m) ; 7.29-7.36(2H,m) ; 7.43-7.52(lH,m) ; 7.59(lH,s); 8.55(2H,d) ppm. (Ia) Isomer mixture: 1.91(3H,s); 1.95(3H,s); 2.31(3H,s); 2.32(3H,s); 3.56(2H,s); 3.67(3H,s); 3.68(3H,s); 3.76(2H,s); 3.78(3H,s); 3.80(3H,s); 4.92(2x2H, s) ; 7.05 (2x2H,d) ; 7.11-7.18(2xlH,m) ; 7.22-7.38(2x5H,m) ; 7.55(lH,s); 7.58(lH,s) ppm. (Ia) Major isomer: 2.04(3H,s); 3.77(3H,s); 3.90(3H,s); 4.11(2H,s); 5.11(2H,s); 7.07(lH,t); 7.20-7.26(IH.m) ; 7.34-7.42(2H,m) ; 7.49-7.55(lH,s) ; 7.67(lH,s); 8.60(2H,d) ppm. Minor isomer: 2.07(3H,s); 3.78(3H,s); 3.91(3H,s); 4.20(2H,s); 5.12(2H,s); 7.07(lH,t); 7.20-7.26(lH,m) ; 7.34-7. 2(2H,m) ; 7.59-7.64(lH,m) ; 7.68(lH,s); 8.60(2H,d) ppm. (Ia) Major isomer: 1.95(3H,s); 3.68(3H,s); 3.79(3H,s); 3.97(2H,s); 5.00(2H,s); 6.95-7.01(lH.m) ; 7.01-7.85(5H,m) ; 7.57(lH,s); 8.40(lH,d) ppm. Compound Proton NMR DATA (δ) No. Minor isomer: 2.18(3H,s); 3.69(3H,s); 3.80(3H,s); 3.97(2H,s); 5.04(2H,s); 6.95-7.01(lH,m) ; 7.01-7.85 (5H,m) ; 7.58(lH,s); 8.40(lH,d) ppm. 8(Ia) Major isomer: 1.95(3H,s); 3.69(3H,s); 3.82(3H,s); 3.96(2H,s); 5.04(2H,s); 6.22(lH,d); 7.11-7.18(lH,m) ; 7.25-7.34(2H,m) ; 7.38-7.49(lH,m) ; 7.58(lH,s); 7.83(lH,d) ppm. Minor isomer: 1.98(3H,s); 3.70(3H,s); 3.80(3H,s); 4.05(2H,s); 5.05(2H,s); 6.08(lH,d); 7.11-7.18(lH.m) ; 7.25-7.34(2H,m) ; 7.38-7.49(lH,m) ; 7.59(lH,s); 7.70(lH,s) ppm. 9(Ia) Isomer mixture: 1.95(6H,s); 3.64(3H,s); 3.67(3H,s); 3.67(2H,s); 3.79(3H,s); 3.81(3H,s); 3.86(2H,s); 5.00(2H,s); 5.08(2H,s); 7.08(lH,d); 7.11-7.40(7H,m) ; 7.14(lH,d); 7.45-7.51(lH,m) ; 7.57(lH,s); 7.60(lH,s); 8.23-8.29(4H,m) ppm. 10(Ia) Major isomer: 2.00(3H,s); 3.68(3H,s); 3.80(3H,s); 4.14(2H,s); 5.02(2H,s); 7.11-7.18(lH,m) ; 7.23-7.61(5H,m) ; 7.56(lH,s); 7.71-7.78(lH,m); 7.81-7.89(lH,m) ppm. Minor isomer: 2.04(3H,s); 3.70(3H,s); 3.82(3H,s); 4.27(2H,s); 5.05(2H,s); 7.11-7.18 (lH.m) ; 7.23-7.61(5H,m) ; 7.59(lH,s); 7.71-7.78(lH,m) ; 7.81-7.89(lH.m) ppm. ll(Ia) Isomer mixture: 1.95(3H,s); 1.98(3H,s); 3.67(6H,s); 3.79(3H,s); 3.80(3H,s); 3.87(3H,s); 3.88(3H,s); 4.61(2H,s); 4.94(2H,s); 5.03(2H,s); 5.04(2H,s); 6.74-6.97(8H,m) ; 7.12-7.19(2H,m) ; 7.27-7.37(4H,m) ; 7.41-7.49(2H,m) ; 7.57(lH,s); 7.58(lH,s) ppm. 12(Ia) Major isomer: 1.96(3H,s); 2.45(3H,s); 3.69(3H,s); 3.80(3H,s); 4.04(2H,s); 5.02(2H,s); 6.84(lH,d); 7.11-7.18(lH,m) ; 7.26-7.35(2H,m) ; 7. 1-7.47(lH,m) ; 7.58(lH,s); 8.36(lH,d) ppm. Minor isomer: 1.99(3H,s); 2.45(3H,s); 3.70(3H,s); 3.81(3H,s); 4.13(2H,s); 5.03(2H,s); 6.84(lH,d); 7.11-7.18(1H,m) ; 7.26-7.35(2H,m) ; 7.51-7.58(lH,m) ; 7.59(lH,s); 8.36(lH,d) ppm. 3(Ia) 2.03(3H,s); 3.77(3H,s); 3.81(3H,s); 4.94(2H,s); 5.05(2H,s); 6.89(lH,d); 7.03(lH,t); 7.15-7.21(lH.m) ; 7.31-7.38 (2H,m) ; 7.42-7.59(3H,m) ; 7.59(lH,s) ppm. Compound Proton NMR DATA (δ) No. 14(Ia) 1.99(3H,s); 3.77(3H,s); 3.80(3H,s); 4.64(2H,s); 5.05(2H,s); 6.95-7.03(2H,m) ; 7.12-7.19(lH.m) ; 7.28-7.35(2H,m) ; 7.38-7.47(2H,m) ; 7.54-7.58 (lH.m) ; 7.58(lH,s) ppm. 15(Ia) Major isomer: 2.05(3H,s); 3.68(3H,s); 3.67(3H,s); 3.88(2H,s); 5.07(2H,s); 6.90-7.61(8H,m) ; 7.58(lH,s); 10.10(1H,brs) ppm. Minor isomer: 2.02(3H,s); 3.66(3H,s); 3.67(3H,s); 3.88(2H,s); 5.13(2H,s); 6.59-6.65(1H,d) ; 6.90-7.61(7H,m) ; 7.58(lH,s); lO.lO(lH.brs) ppm. 6(Ia) Isomer mixture: 1.97(3H,s); 2.03(3H,s); 3.79(3H,s); 3.80(3H,s); 3.82(2x3H,s); 3.89(3H,s); 3.91(3H,s); 4.09(2H,s); 4.11(2H,s); 4.99(2H,s); 5.01(2H,s); 7.12-7.18(2H,m) ; 7.28-7.46(6H,m) ; 7.57(lH,s) ; 7.58(lH,s) ppm. 7(Ia) Isomer mixture: 1.97(3H,s); 1.98(3H,s); 3.60(2H,s); 3.75(2x3H,s) ; 3.79(2x3H, s) ; 3.81(2H,S); 5.00(2H,s); 5.08(2H,s); 6.73-7.38(13H,m) ; 7.47-7.53 (lH,m) ; 7.57(lH,s); 7.59(lH,s); 8.20(2xlH,s) ppm. 8(Ia) Isomer mixture: 1.99(3H,s); 2.07(3H,s); 3.69(3H,s); 3.70(3H,s); 3.81(3H,s); 3.82(3H,s); 4.12(2H,s); 4.18(2H,s); 5.02(2H,s); 5.05(2H,s); 7.10-7.18(2H,m) ; 7.20-7.41(12H,m) ; 7.58(lH,s); 7.58-7.62(2H,m) ; 7.60(lH,m) ppm. 9(Ia) Major isomer: 1.79(lH,bs); 1.97(3H,s); 2.39(3H,s); 3.70(3H,s); 3.71(2H,s); 3.82(3H,s); 4.96(2H,s); 7.11-7.18(lH.m) ; 7.26-7.37(3H,m) ; 7.60(lH,s) ppm. Minor isomer: 1.79(lH,bs); 1.98(3H,s); 2.29(3H,s); 3.71(3H,s); 3.81(2H,s); 3.82(3H,s); 4.96(2H,s); 7.11-7.18(lH,m) ; 7.26-7.37(2H,m) ; 7.40-7.45(lH,m) ; 7.59(lH,s) ppm. 0(Ia) Major isomer: 1.98(3H,s); 2.22(3H,s); 3.68(3H,s); 3.80(3H,s); 4.52(2H,s); 5.04(2H,s); 6.82(lH,d); 6.98(lH,d); 7.08-7.18(3H,m) ; 7.28-7.35(2H,m) ; 7.41-7.48(lH,m) ; 7.58(lH,s) ppm. Minor isomer: 1.99(3H,s); 2.23(3H,s); 3.68(3H,s); 3.80(3H,s); 4.85(2H,s); 5.03(2H,s); 6.74(lH,d); 7.04-7.18(4H,m) ; 7.28-7.35(2H,m) ; 7.41-7.48(lH,m) ; 7.58(lH,s) ppm. Compound Proton NMR DATA (δ) No. 21(Ia) Major isomer: 0.93(3H,t); 1.33(3H,t); 1.70(2H,q); 1.97(3H,s); 2.56(2H,q); 3.68(3H,s); 3.82(3H,s); 4.10(2H,s); 4.36(2H,q); 5.02(2H,s); 6.21(lH,s); 7.1-7.5 (4H,m) ; 7.58(lH,s) ppm. Minor isomer: 0.93(3H,t); 1.33(3H,t); 1.70(2H,q); 1.95(3H,s); 2.56(2H,q); 3.68(3H,s); 3.82(3H,s); 4.00(2H,s); 4.37(2H,q); 5.01(2H,s); 6.22(lH,s); 7.1-7.5(4H,m) ; 7.56(lH,s) ppm. 2(Ia) Major isomer: 1.98(3H,s); 3.65(3H,s); 3.79(3H,s); 4.12(2H,s); 5.03(2H,s); 7.1-7.5(7H,m) ; 7.40(lH,d); 7.56(lH,s); 8.1(2H,m); 8.54(lH,d) ppm. Minor isomer: 2.00(3H,s); 3.68(3H,s); 3.80(3H,s); 4.22(2H,s); 5.16(2H,s); 7.1-7.5(7H,m) ; 7.40(lH,d); 7.59(lH,s); 8.1(2H,m); 8.54(lH,d) ppm. 3(Ia) Major isomer: 1.40(3H,t); 1.97(3H,s); 3.68(3H,s); 3.80(3H,s); • 3.99(2H,q); 4.50(2H,s); 5.05(2H,s); 6.38-6.52(3H,m) ; 7.10-7.18(2H,m) ; 7.26-7.36(2H,m) ; 7.40-7.48(lH.m) ; 7.57(1H, s)ppm. Minor isomer: 1.40(3H,t); 1.98(3H,s); 3.68(3H,s); 3.80 (3H,s); 3.99(2H,q); 4.83(2H,s); 5.02(2H,s); 6.38-6.52(3H,m) ; 7.10-7.18(2H,m) ; 7.26-7.36(2H,m) ; 7.40-7.48(lH,m) ; 7.58(lH,s)ppm. 4(Ia) Major isomer: 1.97(3H,s); 2.30(3H,s); 3.68(3H,s); 3.80(3H,s); 4.50(2H,s); 5.05(2H,s); 6.69-6.79(3H, s) ; 7.10-7.18(2H,m) ; 7.27-7.35(2H,m) ; 7.40-7.48(lH,m) ; 7.58(1H, s)ppm. Minor isomer: 1.97(3H,s); 2.30(3H,s); 3.69(3H,s); 3.81(3H,s); 4.06(2H,s); 5.04(2H,s); 6.69-6.79(3H,m) ; 7.10-7.18(2H,m) ; 7.27-7.35(2H,m) ; 7.40-7.48(lH,m) ; 7.58(1H, s)ppm. 5(Ia) Major isomer: 1.38(3H,t); 1.97(3H,s); 3.69(3H,s); 3.82(3H,s); 4.40(2H,q); 4.50(2H,s); 5.01(2H,s); 6.38(lH,d); 7.11-7.17(lH,m) ; 7.26-7.34(2H,m) ; 7.40-7.46(lH. ) ; 7.57(lH,s); 8.20(1H, d)ppm. Minor isomer: 1.38(3H,t); 1.99(3H,s); 3.69(3H,s); 3.82(3H,s); 4.10(2H,s); 4.40(2H,q); 5.02(2H,s); 6.38(lH,d); 7.11-7.17(lH,m) ; 7.26-7.34(2H,m) ; 7.40-7.46(lH.m) ; 7.58(lH,s); 8.20(1H, d)ppm. Compound Proton NMR DATA (δ) No. (Table No) 26(Ia) Major isomer: 1.95(3H,s); 2.28(3H,s); 3.67(3H,s); 3.79(3H,s); 4.49(2H,s); 5.04(2H,s); 6.80(2H,d); 7.05(2H,d); 7.12-7.18(lH.m) ; 7.26-7.35(2H,m) ; 7.40-7.47(lH,m) ; 7.57(IH, s)ppm. Minor isomer: 1.94(3H,s); 2.28(3H,s); 3.67(3H,s); 3.79(3H,s); 4.81(2H,s); 5.02(2H,s); 6.75(2H,d); 7.05(2H,d); 7.12-7.18(lH,m) ; 7.26-7.35(2H,m) ; .7.40-7.47(lH,m) ; 7.58(IH, s)ppm. 7(Ia) Major isomer: 1.96(3H,s); 3.68(3H,s); 3.80(3H,s); 4.56(2H,s); 5.05(2H,s); 6.95-7.23 (4H,m) ; 7.29-7.39(3H,m) ; 7.39-7.48(lH,m) ; 7.57(lH,s)ppm. Minor isomer: 1.96(3H,s); 3.68(3H,s); 3.80(3H,s); 4.87(2H,s); 5.05(2H,s); 6.95-7.23 (4H,m) ; 7.29-7.39(3H,m) ; 7.39-7.48(lH,m) ; 7.58(lH,s)ppm. 8(Ia) Major isomer: 1.97(3H,s); 3.67(3H,s); 3.80(6H,s); 3.83(3H,s); 4.49(2H,s); 5.05(2H,s); 6.30-6.55 (2H,m) ; 6.74(lH,d); 7.12-7.19(lH,m) ; 7.28-7.36(2H,m) ; 7. 0-7.47(lH.m) ; 7.57(lH,s)ppm. Minor isomer: 1.96(3H,s); 3.67(3H,s); 3.80(3H,s); 3.83(6H,s); 4.80(2H,s); 5.03(2H,s); 6.30-6.55(2H,m) ; 6.71(lH,d); 7.12-7.19(lH,m) ; 7.28- .36(2H,m) ; 7.40-7. 7(lH.m) ; 7.58(lH,s)ppm. 9(Ia) Major isomer: 1.95(3H,s); 3.78(3H,s); 3.80(3H,s); 3.98(2H,s); 5.01(2H,s); 7.12-7.19(lH,m) ; 7.23-7.34(3H,m) ; 7.36-7.42(lH.m) ; 7.53-7.60(lH,m) ; 7.57(lH,s); 8.63 (lH.brs)ppm. Minor isomer: 1.96(3H,s); 3.79(3H,s); 3.81(3H,s); 4.14(2H,s); 5.05(2H,s); 7.12-7.19(lH,m) ; 7.23-7.60(6H,m) ; 8.63 (IH,brs)ppm. 0(Ia) 1.95(3H,s); 3.57(3H,s); 3.69(3H,s); 3.70(2H,s); 3.80(3H,s); 4.93(2H,s); 6.91(lH,s); 7.07(lH,s); 7.11-7.17(lH,m) ; 7.26-7.42(3H,m); 7.56(IH, s)ppm. 1(Ia) 1.98(3H,s); 3.76(3H,s); 3.78(3H,s); 3.80(3H,s); 4.51(2H,s); 5.05(2H,s); 6. 0-6.55(3H,m) ; 7.10-7.19(2H,m) ; 7.29-7.35(2H,m) ; 7.41-7.48(lH,m) ; 7.58 (IH, s)ppm. Compound Proton NMR DATA (δ) No. (Table No) 32(Ia) 1.90(3H,s); 3.69(3H,s); 3.81(3H,s); 3.82(2H,d); 5.05(2H,s); 6.74-6.79(lH,m) ; 6.85(IH,brs) ; 6.91-6.96(lH,m) ; .13-7.36(5H,m) ; 7.43-7.48(lH,m) ; 7.59(IH, s)ppm. 33(Ia) Isomer mixture: 1.97(6H,s); 3.67(3H,s); 3.68(3H,s); 4.61(2H,s); 4.91(2H,s); 5.07(4H,s); 7.15-7.50(13H,m) ; 7.58(lH,s); 7.60(lH,s); 7.80-7.88 (3H,m)ppm. 4(Ia) 1.90(3H,s); 3.69(3H,s); 3.82(3H,s); 3.83(2H,d); 4.87(lH,t); 5.05(2H,s); 6.91(lH,dd); 7.12-7.18(lH,m) ; 7.27-7.35(3H,m) ; 7.41-7.47(2H,m) ; 7.53(lH,dd); 7.59(1H, s)ppm. 5(Ia) 1.95(3H,s); 3.07(2H,s); 3.52(2H,s); 3.69(3H,s); 3.81(3H,s); 5.03(2H,s); 7.12-7.35(8H,m) ; 7.43-7.49(lH,m) ; 7.58(IH, s)ppm. 6(Ia) 1.95(3H,s); 3.34(2H,s); 3.66(3H,s); 3.67(2H,s); 3.78(3H,s); 5.00(2H,s); 7.12-7.33 (8H,m) ; 7.40-7. 5(lH.m) ; 7.57(IH, s)ppm. 7(Ia) Major isomer: 1.91(3H,s); 3.67(3H,s); 3.78(3H,s); 4.07(2H,s); 4.90(2H,s); 5.05(2H,s); 7.10-7.18(lH,m) ; 7.25-7.36(2H,m) ; 7.36-7.55(5H,m); 7.56(lH,s); 7.76-7.89(2H,m) ; 8.05-8.11(lH,m)ppm. Minor isomer: 1.95(3H,s); 3.64(3H,s); 3.74(3H,s); 4.05(2H,s); 4.41(2H,s); 4.60(2H,s); 7.10-7.18(lH.m) ; 7.25-7.36(2H,m) ; 7.36-7.55(6H,m) ; 7.56(lH,s); 7.76-7.89(2H,m) ; 8.05-8.11(lH,m)ppm. 8(Ia) Major isomer: 1.95(3H,s); 3.67(3H,s); 3.80(3H,s); 4.33(2H,s); 4.49(2H,s); 4.96(2H,s); 6.76-6.90(2H,m) ; 7.10-7.18(lH,m) ; 7.28-7.48(4H,m) ; 7.58(IH, s)ppm. Minor isomer: 1.91(3H,s); 3.67(3H,s); 3.80(3H,s); 4.02(2H,s); 4.45(2H,s); 5.03(2H,s); 6.76-6.90(2H,m) ; 7.10-7.18(lH.m) ; 7.28-7.48(4H,m) ; 7.59(IH, s)ppm. 9(Ia) Isomer mixture: 1.94(3H,s); 1.98(3H,s); 2.36(6H,s); 3.67(3H,s); 3.68(3H,s); 3.79(3H,s); 3.81(3H,s); 4.02(2H,s); 4.35(2H,s); 4.42(2H,s); 4.47(2H,s); 4.97(2H,s); 5.04(2H,s); 7.06-7.19 (8H,m) ; 7.20-7.37(6H,m) ; 7.39-7.49 (2H,m) ; 7.57(lH,s); 7.58(IH, s)ppm. Compound Proton NMR DATA (δ) No. (Table No) 40(Ia) 1.95(3H,s); 2.31(3H,s); 3.07(2H,s); 3.50(2H,s); 3.68(3H,s); 3.80(3H,s); 5.03(2H,s); 6.98-7.08(3H,m) ; 7.10-7.19(2H,m) ; 7.23-7.35(2H,m) ; 7.43-7.49(lH.m) ; 7.58 (IH, s)ppm. 41(Ia) 1.94(3H,s); 2.28(3H,s); 3.34(2H,s); 3.62(2H,s); 3.63(3H,s); 3.78(3H,s); 4.99(2H,s); 6.99-7.17(5H,m) ; 7.23-7.32(2H,m) ; 7.38-7.44(lH,m) ; 7.56(IH, s)ppm. 42(Ia) 1.95(3H,s); 3.00(2H,s); 3.43(2H,s); 3.69(3H,s); 3.81(3H,s); 5.02(2H,s); 7.07(2H,q); 7.12-7.38(5H,m) ; 7. 2-7.49(lH,m) ; 7.59(lH,s)ppm. 43(Ia) 1.95(3H,s); 3.30(2H,s); 3.59(2H,S); 3.64(3H,s); 3.78(3H,s); 4.98(2H,s); 7.10-7.19(5H,m) ; 7.27-7.35 (2H,m) ; 7.37-7.42(lH.m) ; 7.57(lH,s)ppm. 44(Ia) 1.95(3H,s); 2.58-2.65(2H,m) ; 2.78-2.85(2H,m) ; 3.19(2H,s); 3.67(3H,s); 3.77(3H,s); 5.01(2H,s); 7.10-7.30(8H,m) ; 7.40-7.47(lH,m) ; 7.55 (IH, s)ppm. 45(Ia) 1.97(3H,s); 2.68-2.75(2H,m) ; 2.80-2.88(2H,m) ; 3.40(2H,s); 3.66(3H,s); 3.77(3H,s); 4.99(2H,s); 7.09-7.31(8H,m) ; 7.38-7.44(lH,m) ; 7.55(IH, s)ppm. 79(Ia) 1.95(3H,s); 3.69(3H,s); 3.81(3H,s); 4.49(2H,s); 5.05(2H,s); 6.55-6.70(3H,m) ; 6.98-7.08(2H,m) ; 7.09-7.22(3H,m) ; 7.27-7.38(4H,m) ; 7.41-7.47(lH,m) ; 7.58(IH, s)ppm. 80(Ia) Isomer mixture: 2.0(3H,s); 2.05(3H,s); 3.65(6H,s); 3.80(6H,s); 4.90(2H,s); 5.11(4H,d); 5.21(2H,s); 7.10-7.21(4H,m) ; 7.30-7.52(12H,m) ; 7.59(2H,s); 8.11(lH,s); 8.13(lH,s); 8.91(lH,s); 8.94(IH, s)ppm. 81(Ia) 1.95(3H,s); 2.35(3H,s); 3.67(3H,s); 3.70(3H,s); 4.03(2H,s); 4.44(2H,s); 5.04(2H,s); 7.11-7.22(4H,m) ; 7.26-7.30(3H,m) ; 7.31-7.39(lH,m) ; 7 .57(IH, s)ppm. 82(Ia) 1.92(3H,s); 3.69(3H,s); 3.81(3H,s); 4.02(2H,s); 4.38(2H,s); 5.06(2H,s); 7.02-7.18(2H,m) ; 7.22-7.37(3H,m) ; 7.42-7.48(lH,m) ; 7.57(lH,s); 7.59-7.70 (2H,m)ppm. Compound Proton NMR DATA ( δ ) No . ( Table No ) 83(Ia) 1.90(3H,s); 2.33(3H,s); 3.64(3H,s); 3.80(3H,s); 3.98(2H,s); 4.39(2H,s); 5.03(2H,s); 7.09-7.19(4H,m) ; 7.22-7.33 (3H,m) ; 7.40-7.47(lH,m) ; 7.55 (IH, s)ppm. 89(Ia) 1.81(3H,s); 2.90(3H,s); 3.68(3H,s); 3.80(3H,s); 3.94(2H,s); 5.04(2H,s); 6.70-6.81(3H,m) ; 7.11-7.38(5H,m) ; 7.41-7.48(lH.m) ; 7.58(lH,s) ppm. 12(Ig) Major isomer: 1.90(3H,s); 2.45(3H,s), 2.90(3H,d); 3.96(3H,s); 3.99(2H,s); 4.98(2H,s); 6.73(lH,q); 6.84(lH,d); 7.16-7.21(lH,m) ; 7.31-7.46(3H,m) ; 8.33(lH,d) ppm. Minor isomer: 1.95(3H,s); 2.45(3H,s); 2.92(3H,d); 3.96(3H,s); 4.08(2H,s); 5.00(2H,s); 6.73(lH,q); 6.84(lH,d); 7.16-7.21(lH.m) ; 7.31-7.46(2H,m) ; 7.48-7.53 (lH,m) ; 8.34(lH,d) ppm. 36(Ig) 1.90(3H,s); 2.84(3H,d); 3.29(2H,s); 3.65(2H,s); 3.94(3H,s); 4.94(2H,s); 6.68(lH,q); 7.15-7.45(9H,m) ppm. 84(Ib) 3.68(3H,s); 3.81(3H,s); 4.81(2H,d); 5.09(2H,s); 6.88(2H,d); 6.95-7.00(2H,m) ; 7.15-7.19(lH,m) ; 7.26-7.35(4H,m) ; 7.41-7.47(lH,m) ; 7.58(IH, s)ppm. 85(Ib) 3.68(3H,s); 3.86(3H,s); 4.61(2H,d); 5.04(2H,s); 6.90(2H,d); 6.98(lH,t); 7.14-7.19(lH,m) ; 7.24-7.36(4H,m) ; 7.42-7.47(lH.m) ; 7.57-7.61(lH,m) ; 7.58(IH, s)ppm. 86(Ic) 1.48(3H,d); 1.80(3H,s); 3.63(3H,s); 3.75(3H,s); 4.87(lH,q); 5.02(2H,s); 6.89-6.94(3H,m) ; 7.11-7.25(3H, s) ; 7.27-7.34(2H,m) ; 7.37-7.42(lH,m) ; 7.55(IH, s)ppm. 87(Ic) 1.58(3H,d); 1.96(3H,s); 3.78(3H,s); 3.80(3H,s); 4.70(lH,q); 5.02(2H,s); 6.95(lH,t); 7.10-7.16(lH,m) ; 7.25-7.31(2H,m) ; 7.39-7.45(lH,m) ; 7.55(lH,s); 8.49(2H,d)ppm. 88(Ic) 1.59(3H,d); 1.96(3H,s); 3.68(3H,s); 3.81(3H,s); 4.70(lH,q); 5.02(2H,s); 6.96(lH,t); 7.10-7.16(lH,m) ; 7.25-7.31(2H,m) ; 7.39-7.45(lH,m) ; 7.57(lH,s); 8.50(2H,d)ppm. 12(Id) Major isomer: 1.91(3H,s); 2.45(3H,s); 3.85(3H,s); 4.01(2H,s); 4.05(3H,s); 4.99(2H,s); 6.84(lH,d); 7.15-7.21(lH.m) ; 7.32-7.48(3H,m) ; 8.35(lH,d) ppm. Compound Proton NMR DATA (δ) No. (Table No) Minor isomer: 1.97(3H,s); 2.45(3H,s); 3.88(4H,s); 4.06(3H,s); 4.09(2H,S); 5.00(2H,s); 6.84(lH,d); 7.15-7.21(lH,m) ; 7.32-7.48(2H,m) ; 7.49-7.5 (lH.m) ; 8.35(lH,d) ppm. 35(Id) 1.90(3H,s); 3.01(2H,s); 3.49(2H,s); 3.86(3H,s); 4.05(3H,s); 5.00(2H,s); 7.15-7.50(9H,m) ppm. 36(Id) 1.93(3H,s); 3.30(2H,s); 3.64(2H,s); 3.81(3H,s); 4.03(3H,s); 4.96(2H,s); 7.12-7.31(6H,m) ; 7.31-7.48(3H,m) ppm. 12(Ig) Major isomer: 1.90(3H,s); 2.45(3H,s), 2.90(3H,d); 3.96(3H,s); 3.99(2H,s); 4.98(2H,s); 6.73(lH,q); 6.84(lH,d); 7.16-7.21(lH,m) ; 7.31-7.46(3H,m); 8.33(lH,d) ppm. Minor isomer: 1.95(3H,s); 2.45(3H,s); 2.92(3H,d); 3.96(3H,s); 4.08(2H,s); 5.00(2H,s); 6.73(lH,q); 6.84(lH,d); 7.16-7.21(lH,m) ' ; 7.31-7.46(2H,m) ; 7.48-7.53(lH.m) ; 8.34(lH,d) ppm. 36(Ig) 1.90(3H,s); 2.84(3H,d); 3.29(2H,s); 3.65(2H,s); 3.94(3H,s); 4.94(2H,s); 6.68(lH,q); 7.15-7.45(9H,m) ppm. Besides the methods previously outlined, the compounds of formula (Ia) can be made by adapting processes outlined in EP 0370629, WO 90/07493, PCT/GB92/00681, EP 0414153, EP 0403618, EP 0426460 and EP 0463488 and the processes outlined in these documents are hereby incorporated in this application. The compounds of formula (Ia) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants; Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Seotoria spp. (including Mycosphaerella graminicola and Leptosphaeria nodorum) , Pseudocercosporella herpotrichoides and Gaeumannomvces graminis on cereals (e.g. wheat, barley, 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; Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis 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 inaeoualis (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; Ascochyta 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 Phytophthora 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; Mycosphaerella spp. on banana, peanut, citrus, pecan, papaya and other hosts; Diaporthe 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., Typhula spp., Microdochium nivale, Ustilago spp., Urocvstis spp., Tilletia spp., and Claviceps 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. italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopezicula tracheiphila and Stereum hirsutum; other pathogens on lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostoma piceae, Penicilliu spp., Trichoderma pseudokoningii, Trichoderma viride Trichoder a harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and fungal vectors of viral diseases e.g. Polymvxa 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. Further, some of the compositions may be active as seed dressings against pathogens including Fusarium spp., Septoria spp., Tilletia spp., (e.g. bunt, a seed-borne disease of wheat), Ustilago spp. and Helminthosporiu spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice. The compounds of formula (Ia) 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 of formula (Ia) or a composition containing the same. The compounds of formula (Ia) 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 of formula (Ia) 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 257. or 25 to 60Z, of a compound as hereinbefore defined. When applied the foliage of plants, the compounds of formula (Ia) 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 formula (Ia) 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 of formula (Ia) can be applied in a number of ways. For example, they can be applied, formulated or unformulated, 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 hydroponic culture systems. The compounds of formula (Ia) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods. The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments. The compounds of formula (Ia) 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 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 such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth 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-dimethylformamide) . 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 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 polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank. Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or 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. 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 compounds of formula (Ia) 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 (Ia) 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 formula (Ia) or a salt or metal complex thereof. Water dispersible powders, emulsifiable 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 bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates) . 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, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite. 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 time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 952, suitably 1-851, 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 compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity. An additional fungicidal compound may be present in the composition of the invention. By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (Ia) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of formula (Ia) . Examples of fungicidal compounds which may be included in the composition of the invention are (RS)-1-aminopropyl- phosphonic acid, (RS.)-4-(4-chlorophenyl)-2-phenyl-2- (lH-1,2, 4-triazol-l-yl- methyl)butyronitrile, (Z.)-N-but-2-enyloxymethyl-2-chloro-2' ,6'-diethylacet- anilide, 1- (2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro- -1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethy1- -6-trifluoromethylbenzimidazole-1-sulphonamide, 5-ethyl-5,8-dihydro-8- -oxo(l,3)-dioxol-(4,5- )quinoline-7-carboxylic acid, α- [N-(3-chloro-2, 6- -xylyl)-2-methoxyacetamido]-γ-butyrolactone, N-(2-methoxy-5-pyridyl)-cyclo¬ propane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, BAS 490F, benalaxyl, 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, 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, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z.)-N-benzyl-N-( [methyl(methyl-thioethylideneamino-oxycarbonyl)amino]thio)- -β-alaninate, etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, ICIA5504, imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, myclobutanil, NTN0301, neoasozin, nickel dimethyldithio- carbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, polyoxin D, polyram, 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 pentachlorophenate, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, 2- (thiocyanomethylthio)benzothiazole, thiophanate- methyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of 1,1'-iminodi(octamethylene)diguanidine, triadi efon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram. The compounds of general formula (Ia) 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 following Examples illustrate the invention. EXAMPLE 1 This Example illustrates the preparation of (E)-methyl 2-[2-(hydroxy- methyl-acetoximinomethyl)phenyl]-3-methoxypropenoate (Compound No. 1 of Table Ia) . (E)-Methyl 2- [phthalimidooxymethylphenyl]-3-methoxypropenoate (1.97g) (prepared as described in Example 4 of EP 0463488) was suspended in methanol (20ml) at room temperature, hydrazine hydrate (0.27g) was added and the resulting solution stirred for 3 hours. The white precipitate which formed was filtered off and the solvent removed to give a white semi-solid. This was diluted with diethyl ether, the white solid filtered off and the filtrate evaporated to give (E)-methyl 2- [2-aminooxymethyl- phenyl]-3-methoxy-propenoate (1.18g, 932) as a yellow oil which was used immediately in the next stage without further purification. A mixture of (E)-methyl 2- [2-aminooxymethylphenyl]-3-methoxypropenoate (1.18g), acetol (0.4g) and pyridine (0.2ml) in methanol (10ml) and water (2ml) was stirred at room temperature for 24 hours. The solution was evaporated to dryness to give a yellow gum which was purified by flash column chromatography, eluted with diethyl ether:n-hexane 2:1, to give the title compound (0.71g, 452) as a yellow gum. H NMR, see Table II, showed this to be a mixture of isomers. vkm EXAMPLE 2 This Example illustrates the preparaton of (E) , (E)-methyl 2- [2-(2- -cyanophenoxymethyl-acetoximinomethyl)phenyl]-3-methoxypropenoate (Compound No. 13 of Table Ia) . A solution of (E)-methyl-2- [2-(hydroxymethyl-acetoximinomethyl)- phenyl]-3-methoxyρropenoate (0.51g) (prepared as described in Example 1), p-toluenesulphonyl chloride (1.65g) and triethylamine (1.2ml) in dry tetrahydrofuran (20ml) was stirred at room temperature for 12 hours. The solvent was removed under reduced pressure to leave a yellow-orange oil which was purified by flash column chromethography, eluted with n-hexane:diethyl ether 4:1, to give (E_)-methyl 2- [2-(chloromethyl- -acetoximinomethyl)phenyl]-3-methoxypropenoate (0.15g, 282) as a mixture of isomers. " NMR (270 MHz): major isomer - δ 1.97(3H,s), 3.69(3H,s), 3.82(3H,s), 4.06(2H,s), 5.03(2H,s), 7.12-7.19(lH,m) , 7.28-7.37(2H,m) , 7.40-7.47(lH,m) , 7.57(lH,s) ppm; minor isomer - δ 2.00(3H,s), 3.69(3H,s), 3.82(3H,s), 4.24(2H,s), 5.02(2H,s), 7.12-7.19(lH.m) , 7.28-7.37(2H,m) , 7.40-7.47(lH,m) , 7.57(lH,s) ppm. A mixture of (E_)-methyl 2- [2-(chloromethyl-acetoximinomethyl)phenyl]- -3-methoxypropenoate (0.27g), 2-cyanophenol (0.51g) and potassium carbonate (0.60g) in acetone (7ml) and water (1ml) was heated at 60°C for 5 hours. After cooling to room temperature, the solvent was removed under reduced pressure and the residue dissolved in diethyl ether (200ml). The ethereal extract was washed with 2N NaOH, water and dried. Removal of the solvent gave a brown gum which was purified by flash column chromatography, eluted with n-hexane:diethyl ether 1:1, to give the title compound (0.029g, 92) as a cryssttaalllliinnee ssoolliidd mpp 110022°°CC;; HH NNMMRR sseeee TTaabbllee IIII.. A fraction (0.062g, 182) was also obtained whiicchh wwaass aa mπixture (1:15) of thlee ttii'tle compound and the corresponding (Z.) , (E) isomer; H NMR see Table II. EXAMPLE 3 This Example illustrates the preparation of (E)-methyl 2- [2- -(benzoxazol-2-yl(thio)methy1-acetoximinometh 1)phenyl]-3-methoxypropenoate (Compound No. 18 of Table Ia) . A mixture of (E)- -:thyl-2- [2-(chloromethyl-acetoximinomethyl)phenyl]- -3-methoxypropenoate (0.21g) (prepared as described in Example 2), 2- -mercaptobenzoxazole (0.5g) and potassium carbonate (0.46g) in acetone (7ml) and water (1ml) was heated at 60°C for 5 hours. After cooling to room temperature the solvent was removed under reduced presure. The residue was purified by flash column chromatography, eluted with n-hexane:diethyl ether 1:1, to give the title compound (0.18g, 642) as a gum; H NMR see Table II. EXAMPLE 4 This Example illustrates the preparation (E) , (E)-methyl 2- [2-(3-nitroanilinomethyl-acetoximinomethyl)phenyl]-3-methoxypropenoate (Compound No. 34 of Table Ia) . A mixture of (E)-methyl-2- [2-(chloromethyl-acetoximinomethyl)phenyl]- -3-methoxypropenoate (0.188g, prepared as described in Example 2), 3-nitroaniline (0.416g) and potassium carbonate (0.416g) in acetone (18ml) and water (8ml) was heated at 60°C for 24 hours. After cooling to room temperature the solvent was removed under reduced pressure. The residue was purified by flash column chromatography, silica eluted with dichloromethane:n-hexane:tetrahydrofuran 20:10:1, to give the title compound (0.022g, 102) as a yellow gum; H NMR see Table II. EXAMPLE 5 This Example illustrates the preparation of (E) , (E) and (E) , (Z.)-methyl 2- [2-(4-chlorobenzyl(thio)methyl-acetoximinomethyl)phenyl]-3-methoxy- propenoate (Compound Nos. 42 and 43 in Table Ia) . A solution of (E)-methyl-2-[2- (chloromethyl-acetoximinomethyl)phenyl]- -3-methoxypropenoate (0.223g, prepared as described in Example 2) in DMF (6ml) was added dropwise to the sodium salt of 4-chlorobenzylmercaptan (prepared from 4-chlorobenzyl mercaptan (0.113g) and sodium hydride (0.029g)] in DMF (6ml) at 20°C. After complete addition the mixture was stirred for 30 minutes, poured into water and extracted with diethyl ether. The ethereal extracts were washed, dried and the solvent removed to give a crude gum which was purified by flash column chromatography, silica gel eluted with n-hexane: diethyl ether 3:1, to give the title compounds (0.211g, 682) as separate isomers; H NMR see Table II. EXAMPLE 6 This Example illustrates an alternative preparation of (E.)-methyl-2- - [2-(chloromethyl-acetoximinomethyl)phenyl]-3-methoxypropenoate (for use in Examples 2, 3, 4 and 5). A mixture of (E_)-methyl 2-(2-aminoxymethylphenyl)-3-methoxypropenoate (3.2g, prepared as described the first stage of Example 1), chloroacetone (0.83g), and pyridine (0.6ml) in ethanol (30ml) and water (4ml) was stirred at room temperature for 24 hours. The solution was evaporated to dryness to give a yellow gum which was purified by flash column chromatography, silica gel eluted with diethyl ether : n-hexane 4:1, to give the title compound (2.69g, 642) as a 1:1 mixture of isomers. 1 E NMR (270 MHz): δ 1.97(3H,s); 2.0(3H,s); 3.68(6H,s); 3.82(6H,s); 4.06(2H,s); 4.24(2H,s); 5.02(2H,s); 5.03(2H,s); 7.12-7.19(2H,m) ; 7.28-7.37(4H,m) ; 7.40-7.47(2H,m) ; 7.57(2H,s) ppm. EXAMPLE 7 The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows. The plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cm diameter minipots. The test compounds were formulated either by bead milling with aqueous DISPERSOL T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. The formulations (100 ppm active ingredient) were sprayed on to the foliage or applied to the roots of the plants in the soil. The sprays were applied to maximum retention and the root drenches 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 when the sprays were applied to cereals. For most of the tests the compounds were applied to the soil (roots) or to the foliage (by spraying) one or two days before the plant was inoculated with the disease. Exceptions were the test on Erysiphe graminis in which the plants were inoculated 24 hours before treatment and the test on Puccinia recondita in which the plants were inoculated 48 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 sporulating disease) on each of the treated plants was recorded using the following assessment scale: 0 = 02 disease present 20 and 24 = 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 and 94 = 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 POCO (Percentage of Control) value. An example of a typical calculation is as follows: Disease level on untreated control = 90 Disese level on treated plant = 30 POCO = disease level on treated plant x 100 = 3£ x 100 = 33.3 disease level on untreated control 90 This calculated POCO value is then rounded to the nearest of the values in the 9-point assessment scale shown above. In this 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 III. TABLE III TABLE III (continued) TABLE III ( continued) Compound Pr Egt Sn Po Tc Vi Pv Pil No (Table No. ) 42(Ia) 90a 30a 0a 43(Ia) 90 60 44(Ia) 60a 90a 0a 45(Ia) 60 90 a = lOppm foliar application only. b = combined foliar spray and root drench application at 125ppm. CHEMICAL FORMULAE (in description) (III) w R"

Claims: CLAIMS A process for the preparation of a compound of formula (I] optionally substituted heteroaryl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; the process comprising reacting a compound of formula (II): 1 2 3 wherein W, R , R and R are as previously defined and L is a leaving group , with a compound of formula ( III ) : HID wherein R and Y are as previously defined. 2. A process for the preparation of a compound of formula (II) wherein W, L, R1, R2 and R3 are as defined in claim 1, the process comprising dehydroxylating a compound of formula (IV) : 1 2 3 wherein Y is oxygen and R , R , R and W are as defined in claim 1. 3. A process for the preparation of a compound of formula (II) 1 2 3 wherein R , R , R and W are as defined in claim 1 and L is chlorine, the process comprising reacting a compound of formula (V): wherein W is as defined above, with a compound of formula (VII) R J I Cl .c- / (VII: * 2/ 1 2 3 wherein R , R and R are as defined in claim 1. 4. A process for the preparation of a compound of formula (I) 5 1 2 3 4 5 wherein Y is 0, S(0) or NR , and W, p, R , R , R , R , R and n are as defined in claim 1, the process comprising reacting a compound of formula (IV): wherein Y is 0, S(0) or NR , and W, R , R , R , R , R and n are as n 4 defined in claim 1, with a compound of formula R L, wherein R is as defined in claim 1 and L is a leaving group. 5. A compound of formula (II): wherein W is CH 0.CH=C.C0 CH , CH O.CH=C.CONR 6 R 7 , CH 3 0.N=C.C0 CH or CH O.N=C.CONR R ; R is hydrogen, C alkyl, C haloalkoxy or 2 3 6 7 1-4 _-Α cyano; R , R , R and R are independently hydrogen or C , alkyl; and L is a leaving group; provided that when L is chlorine, W is 2 3 1 CH O.CH=C.CO CH , and R and R are both hydrogen then R is not methyl. A compound of formula (IV) : (IV) 7. A compound of formula (la): is optionally substituted aryl (but not C H,), optionally substituted arylalkyl, optionally substituted heteroaryl or optionally substituted heteroarylalkyl; wherein the foregoing aryl and heteroaryl moieties are substituted by one or more of halogen, hydroxy, mercapto, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, alkynyloxy, haloalkyl, haloalkoxy, alkylthio, haloalkylthio, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted arylalkenyl, optionally substituted heteroaryalkenyl, optionally substituted arylalkoxy, optionally substituted heteroarylalkoxy, optionally substituted aryloxyalkyl, optionally substituted heteroaryloxyalkyl, acyloxy, cyano, thiocyanato, nitro, -NR'R", -NHC0R' , -NHCONR'R", -CONR'R", -C00R', -0S0 2 R\ -S0 2 R*. -COR', -CR'=NR" or -N=CR*R" in which R' and R" are independently hydrogen, alkyl, alkoxy, alkylthio, cycloalkyl, cycloalkylalkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C alkyl or C alkoxy; when R' and R" are in CONR'R" they can together form a 5- or 6-membered heterocyclic ring (for example a pyrrole, imidazole, pyrrolidine, piperidine or morpholine ring); or two substituents, when they are in adjacent positions on the aryl or heteroaryl ring can join to form a fused alphatic ring (especially to form a fused 6-membered carbon aliphatic ring); provided that when W is CH .CH=C.CO CH , R is methyl and R 2 and R3 are both hydrogen then when Y is S, R4 is neither benzyl 4 nor CH -fur-2-yl, when Y is 0, R is neither 2-chlorophenyl nor 4 2, 4-dichlorophenyl, and when Y is NCH,, R is not benzyl. 8. A compound of formula (Ia) as claimed in claim 7 wherein W is CH O.CH=C.CO CH , CH 3 0.CH=C.C0NHCH 3 , CH 3 O.N=C.C0 2 CH 3 or CH 0.N=C.C0NHCH ; Y is 0, S or NR 5 ; R 1 , R 2 , R 3 and R 5 are 4 independently hydrogen or methyl; and R is phenyl, naphthyl, phenyl(C )alkyl, naphthyl(C )alkyl, heteroaryl (especially pyridyl, pyrimidinyl, benzothiazolyl, benzimidazolyl, tetrazolyl, benzoxazolyl, 1,2,4-triazolyl, imidazolyl or thienyl) or heteroaryl(C )alkyl (especially pyridylmethyl or pyrimidinylmethyl) , all of which, other than phenyl which must be substituted, are optionally substituted with halogen, C , alkyl, C , alkoxy, halo(C )alkyl, halo(C 4 )alkoxy, cyano, phenyl, phenoxy or nitro; 1 2 3 provided that when W is CH .CH=C.C0_CH , R is methyl and R and R 3 4 are both hydrogen then when Y is S R is neither benzyl nor 4 CH -fur-2-yl, when Y is 0, R is neither 2-chlorophenyl nor 4 2,4-dichlorophenyl, and when Y is NCH , R is not benzyl. 9. A compound of formula (Ia) as claimed in claim 7 wherein W is are both hydrogen; Y is pyrimidinyl (for example substituted by halogen, C alkyl (especially methyl), halo(C )alkyl,, C , alkoxy or halo(C )alkoxy). 10. A fungicidal composition comprising, as an active ingredient, a compound as claimed in claim 7 and a fungicidally acceptable carrier or diluent therefor. 11. A method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of a seed or plant, a fungicidally effective amount of a compound as claimed in claim 7 or a composition according to claim 10. 12. A process for the preparation of a compound of formula (I), wherein p is 0 and W, R 1, R2, R3 and R4 are as defined in claim 1, the process comprising coupling a compound of formula (II) with a compound of formula R 4X, wherein R4 is as defined above and X is either a leaving group or a metallated species. 13. A process for the preparation of a compound of formula (I), wherein p is 0, W, R 1, R2, R3 and R4 are as defined in claim 1, the process comprising metallating a compound of formula (II) and coupling this metallated species with a compound of formula R 4X, wherein R4 is as previously defined and X is a leaving group.

Inventors: ASPINALL IAN HENRY, WORTHINGTON PAUL ANTHONY, ASPINALL, IAN, HENRY, WORTHINGTON, PAUL, ANTHONY
Applicants: ASPINALL IAN HENRY, WORTHINGTON PAUL ANTHONY, ZENECA LTD, ZENECA LIMITED
Application year: 1993
Main classification: C07C249
IPC codes: A01N37, A01N39, A01N43, C07C249, C07C251, C07C255, C07D213, C07D215, C07D233, C07D235, C07D239, C07D249, C07D257, C07D263, C07D277, C07D333