NZ619234B2 - Microbiocidal heterocycles - Google Patents

Abstract

Disclosed are {[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidine and piperazine tetralin derivatives and analogues as represented by the general formula I, wherein A is x-C(R10R11)-C(=O)-, x-C(R12R13)-C(=S)-, x-O-C(=O)-, x-O-C(=S)-, x-N(R14)-C(=O)-, x-N(R15)-C(=S)-, x-C(R16R17)-SO2-, or x-N=C(R30)-, in each case x indicates the bond that is connected to R1; T is CR18 or N; Y1, Y2, Y3, and Y4 are independently CR19 or N; Q is O or S; n is 1 or 2; p is 1 or 2, providing that when n is 2, p is 1; R1 is 3,5-bis(difluoromethyl)-1H-pyrazol-1-yl; R2, R3, R4, R5, R6, R7, R10, R11, R12, R13, R16, R17, R18,R19 and R30 each independently are hydrogen, halogen, cyano, alkyl, or haloalkyl; R8, R14 and R15 each independently are hydrogen or alkyl; and R9 is phenyl, benzyl or tetralin-1-yl, each optionally substituted with 1 to 3 substituents independently selected from alkyl, haloalkyl, halogen, cyano, hydroxy and amino; or a salt or a N-oxide thereof. Of particular importance are the three compounds 4-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyridine-2-carboxamide, 4-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyridine-2-carboxamide and 3-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)benzamide. Also disclosed is a fungicidal composition comprising at least one compound as defined above and an agriculturally acceptable carrier, optionally comprising an adjuvant, and optionally comprising at least one additional fungicidally active compound. =C(R30)-, in each case x indicates the bond that is connected to R1; T is CR18 or N; Y1, Y2, Y3, and Y4 are independently CR19 or N; Q is O or S; n is 1 or 2; p is 1 or 2, providing that when n is 2, p is 1; R1 is 3,5-bis(difluoromethyl)-1H-pyrazol-1-yl; R2, R3, R4, R5, R6, R7, R10, R11, R12, R13, R16, R17, R18,R19 and R30 each independently are hydrogen, halogen, cyano, alkyl, or haloalkyl; R8, R14 and R15 each independently are hydrogen or alkyl; and R9 is phenyl, benzyl or tetralin-1-yl, each optionally substituted with 1 to 3 substituents independently selected from alkyl, haloalkyl, halogen, cyano, hydroxy and amino; or a salt or a N-oxide thereof. Of particular importance are the three compounds 4-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyridine-2-carboxamide, 4-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyridine-2-carboxamide and 3-(4-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperazin-1-yl)-N-(1,2,3,4-tetrahydronaphthalen-1-yl)benzamide. Also disclosed is a fungicidal composition comprising at least one compound as defined above and an agriculturally acceptable carrier, optionally comprising an adjuvant, and optionally comprising at least one additional fungicidally active compound.

Description

Microbiocidal Heterocycles The present invention relates to heterocycles, eg. as active ingredients, which have microbiocidal activity, in particularfungicidal activity. The invention also relates to preparation of these heterocycles, to cyclic derivatives used as intermediates in the preparation of these heterocycles, to preparation of these intermediates, to agrochemical compositions which comprise at least one of the heterocycles, to preparation of these compositions and to use of the heterocycles or compositions in agriculture or horticulture for controlling or preventing infestation of plants, harvested food crops, seeds or non-living materials by phytopathogenic microorganisms, preferably fungi. e the ecological and economical requirements of modern crop protection agents are steadily changing, there is a continuing need for the discvovery and development of novel fungicides with advanced properties compared to the known products. Surprisingly, it has now been found that the described bis(difluoromethyl)pyrazol derivatives have, for cal purposes, a very advantageous level of biological activity for protecting plants against diseases that are caused by fungi.

The present invention es compounds of a l: 3 4 R R R%R5 Q R‘\ /N T Y1 /R9 (I) A W\ N R6 R7 Y“ Y2 R8 \Y3// wherein A is x—C(R1°R“)-C(=O)—, x—C(R‘2R13)-C(=S)—, x-O—C(=O)-, x-O—C(=S)~, x-N(R14)—C(=O)-, x- N(R15)~C(=S)-, x-C(R16R17) or x-N=C(R3°)- in each case x indicates the bond that is ted to R1; T is CR18 or N; Y1, Y2, Y3, and Y4 are independently CR19 or N; Q is O or S; n is 1 or 2; p is 1 or 2, providing that when n is 2, p is 1.

R1 is R2, R3, R4, R5, R6, R7, R10, R“, R12, R13, R16, R17, R18, R19 and R30 each independently are hydrogen, n, cyano, C1-C4alkyl, or C1-C4haloalkyl; R8, R14 and R15 each independently are hydrogen or lkyi; and R9 is phenyl, benzyl or group (a): wherein the phenyl, benzyl and group (a) are each optionally tuted with 1 to 3 substituents independently selected from C1—C4 alkyl, C1—C4 haloalkyl, halogen, cyano, hydroxy and amino; or a salt or a N-oxide thereof.

Where substituents are indicated as being optionally substituted, this means that they may or may not carry one or more identical or different substituents. Normally not more than three such optional substituents are present at the same time.

The term en" stands for ne, ne, bromine or iodine.

The term "amino" stands for -NH2.

Alkyl, alkenyl or alkynyl substituents may be straight-chained or ed. Alkyl on its own or as part of another substituent is, depending upon the number of carbon atoms mentioned, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n—hexyl and the isomers thereof, for example, iso—propyl, iso-butyl, sec-butyl, tert—butyl, iso—amyl or pivaioyi.

A haloalkyl group may contain one or more cal or different halogen atoms and, for example, may stand for CHgCI, CHCIZ, CCI3, CHZF, CHFZ, CF3, , CHsch, CF30F2 or CClgcclz.

The presence of one or more possible tric carbon atoms in a compound of formula I means that the compounds may occur in optically isomeric froms, i.e. enantiomeric or diastereomeric forms. As a result of the presence of a possible aliphatic C=C double bond, geometric isomerism may occur, i.e. cis—trans or (E)-(Z) isomerism. Also atropisomers may occur as a result of restricted rotation about a single bond. Formula | is intended to include all those possible isomeric forms and mixtures thereof. The present invention includes all those possible isomeric forms and mixtures thereof for a compound of formula I. Likewise, formula I is intended to include all possible tautomers. The present invention includes all possible tautomeric forms for a compound of formula I.

In each case, the compounds of formula l according to the invention are in free form, in oxidized form as a N-oxide or in salt form, e.g. an agronomically usable salt form.

N—oxides are ed forms of teriary amines or oxidized forms of en containing heteroaromatic compounds. They are described for instance in the book “Heterocyclic N- oxides” by A. Albini and S. Pietra, CRC Press, Boca Raton 1991.

Suitable salts of the compounds of formula I include those resulting after addition of 1O acid such as those with an inorganic mineral acid e.g. hydrochloric, hydrobromic, ric, nitric or phosphoric acid, or an organic carboxylic acid e.g. oxalic, tartaric, lactic, butyric, toluic, hexanoic or phthalic acid, or a sulfonic acid e.g. methane, benzene or toluene ic acid.

Preferably the compound of formula l is a compound wherein: A is x—C(R10R“)-C(=O)-, x—C(R12R‘3)-C(=S)-, x—O-C(=O)—, =S)—, x-N(R14)-C(=O)—, x— N(R15)-C(=S)-or 5R17)-SOZ-, in each case x indicates the bond that is connected to T is CR18 or N; Y1, Y2, Y3, and Y4 are independently CR19 or N; Q is O or S; n is 1 or 2; p is 1 or 2, ing that when n is 2, p is 1.

R2, R3, R4, R5, R5, R7, R10, R“, R12, R13, R16, R17, R18 and R19 each independently are hydrogen, halogen, cyano, Ci-C4alkyl, or aloalkyl; R8, R14 and R15 each independently are en or C1—C4alkyl; and R9 is phenyl, benzyl or group (a): wherein the phenyl, benzyl and group (a) are each ally substituted with 1 to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, halogen, cyano, hydroxy and amino; or a salt or a N-oxide thereof.

WO 00943 Preferably the compound of a I is a compound n: A is x—C(R1°R")-C(=O)-, X-C(R12R13)—C(=S)—, x-O—C(=O)-, x—O-C(=S)-, or x-C(R16R17)—SOZ-, in each case X indicates the bond that is connected to R‘; T is CR18 or N; Y1, Y2, Y3, and Y4 are independently CR19 or N providing that at least 2 of Y1, Y2, Y3, and Y4 are CR“); Q is O or S; n is 1 or 2; p is 1; 1O R2, R3, R4, R5, R6, R7, R10, R11, R12, R13, R16, R17, R18, and R19 each independently are hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl; R8 is hydrogen or C1-C4alkyl; and R9 is phenyl, benzyl or group (a): (8) wherein the phenyl, benzyl and group (a) are each optionally substituted with 1 to 3 substituents independently selected from C1—C4 alkyl, C1—C4 haloalkyl, halogen, cyano, hydroxy and amino.

Preferably the compound of formula l is a compound wherein: A is x-CR10R11—C(=O)-, x—O—C(=O)-, or R17-802—, in each case x indicates the bond that is connected to R1; T is CR”; Y1, Y2, Y3, and Y4 are independently CR19 or N providing that at least 2 of Y1, Y2, Y3, and Y4 are CR19 and providing that there are no N—N bonds in the ring containing Y1, Y2, Y3, and Y4; Q is O or S; n is 1 or 2; p is 1; R2, R3, R4, R5, R6, R7, R10, R“, R15, R17, R18, and R19 each independently are hydrogen, , or methyl; R8 is hydrogen or methyl; and R9 is phenyl, benzyl or group (a) wherein the , benzyl and group (a) are each ally substituted with 1 to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, hydroxy and halogen.

Preferably the compound of formula I is a compound n: A is x—CHz-C(=O)-, X—O—C(=O)— or X—CH2-SOz-, in each case x indicates the bond that is connected to R1; T is CH; Y1, Y2, Y3, and Y4 are independently CH or N providing that at least 2 of Y1, Y2, Y3, and Y4 1O are CH and providing that there are no N-N bonds in the ring containing Y1, Y2, Y3, and Y4; Q is O; n is 1 or 2; p is 1; R2, R3, R4, R5, R6 and R7 are each en; R8 is hydrogen or methyl; and R9 is phenyl, benzyl or group (a) wherein the phenyl, benzyl and group (a) are each optionally substituted with 1 to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, hydroxy and halogen.

Preferably the compound of formula l is a compound n: A is x—CHz—C(=O)-, wherein x indicates the bond that is connected to R1; T is CH; Y1, Y2, Y3, and Y4 are independently CH; Q is O; n is 2; p is 1; R2, R3, R4, R5, R5, and R7 are each hydrogen; R8 is hydrogen or methyl; and R9 is phenyl, benzyl or group (a) wherein the phenyl, benzyl and group (a) are each optionally substituted with 1 to 3 substituents independently selected from , halomethyl, and halogen.

The invention also relates to compounds of formula I wherein A is x—CHz-C(=O)-, X-CHZC(=S)-, X-OC(=O)—, X-CH2302-, in each case x being the bond to T is CH or N; Y1, Y2, Y3, and Y4 are independently CH or N, providing that at least 2 of Y1, Y2, Y3, and Y4 are CH and providing that there are no N—N bonds in the ring containing Y1, Y2, Y3; Q is O or S; n is ’l or 2; p is 1 or 2, ing that when n is 2, p is 1; R2, R3, R4, R5, R6 and R7 are each hydrogen; R8 is hydrogen or ; R9 is group (i), (j), or (k): (i) (i) (k) The following list provides tions, including preferred definitions, for substituents A, T, Y1, Y2, Y3, Y4, Q, n, p, R1: R2: R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R22, R23, R24, R25 and R30 with reference to compounds of formula I. For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below. The invention includes compounds of a having all possible combinations of substituent definitions given below or elsewhere in this document. Generally, in this document any substituent definition may be combined with any other substituent definition.

A is x-C(R‘°R“)-C(=O)-, x-C(R12R13)-C(=S)-, x-O-C(=O)-, x-O-C(=S)—, 4)- C(=O)-, x-N(R15)-C(=S)-or x-C(R15R17)—SOZ-, in each case x tes the bond that is connected to R1. Preferably, A is x-C(R1°R11)-C(=O)-, x-C(R12R13)—C(=S)—, X—O-C(=O)-, x—O- , or X'C(R16R17)‘SOZ‘, in each case X indicates the bond that is connected to R1.

More preferably, A is x—CR10R11-C(=O)—, x—O—C(=O)-, or x—CR‘6R17-SOZ—, in each case x indicates the bond that is connected to R1. Even more preferably, A is X—CH2-C(=O)-, x- S)-, X-OC(=O)—, x-CH2802—, in each case x indicates the bond that is connected to R1. Yet more preferably, A is X-CHz-C(=O)-, x-O-C(=O)- or x—CH2, in each case x indicates the bond that is connected to R1. Most preferably, A is x—CHz-C(=O)-, wherein x indicates the bond that is connected to R1.

T is CR‘8 or N. Preferably, T is CH or N. Most preferably, T is CH. n is 1 or 2. ably, n is 2. p is 1 or 2, providing that when n is 2, p is 1. Preferably, p is 1.

Y1, Y2, Y3, and Y4 are independently CR19 or N, e.g. Y1, Y2, Y3, and Y4 may be independently CH or N. More preferably, Y1, Y2, Y3, and Y4 are ndently CR19 or N providing that at least 2 of Y1, Y2, Y3, and Y4 are CR‘Q. Even more preferably, Y1, Y2, Y3, and Y4 are independently CR19 or N providing that at least 2 of Y1, Y2, Y3, and Y4 are CR19 and providing that there are no N-N bonds in the ring containing Y1, Y2, Y3, and Y4. Yet more preferably, Y1, Y2, Y3, and Y4 are independently CH or N providing that at least 2 of Y1, Y2, Y3, and Y4 are CH and providing that there are no N—N bonds in the ring containing Y1, Y2, Y3, and Y4.

Q is O or S. Preferably, Q is 0.

R2, R3, R4, R5, R5, R7, R10, R“, R12, R13, R15, R", R18 and R19 each independently are hydrogen, halogen, cyano, Cr-C4alkyl, or C1-C4haloalkyl. More preferably, R2, R3, R4, R5, R6, R7, R10, R“, R12, R13, R15, R17, R18, and R19 each independently are hydrogen, halogen, C1—C4alkyl, Cr—C4haloalkyl. Even more preferably, R2, R3, R4, R5, R6, R7, R10, R“, R16, R", R”, and R19 each independently are hydrogen, fluoro, or methyl. Yet more ably, R2, R3, R4, R5, R6, R7, R10, R11, R16, R17, R18, and R19 each are hydrogen.

R8, R14 and R15 each independently are hydrogen or C1-C4alkyl. Preferably, R8, R14 and R15 each independently are hydrogen or methyl. Preferably, R8, R14 and R15 each are hydrogen.

R9 is phenyl, benzyl or group (a): wherein the , benzyl and group (a) are each optionally substituted with 1 to 3 substituents ndently selected from C1-C4 alkyl, C1-C4 kyl, halogen, cyano, hydroxy and amino. Preferably, R9 is phenyl, benzyl or group (a): wherein the phenyl, benzyl and group (a) are each optionally substituted with 1 to 3 substituents ndently selected from C1-C4 alkyl, C1-C4 kyl, hydroxy and halogen.

More preferably, R9 is phenyl, benzyl or group (a): wherein the phenyl, benzyI and group (a) are each ally substituted with 1 to 3 substituents independently selected from methyl, halomethyl, and halogen.

In one group of compounds R9 is (i), (j), or (k): (i) (i) (k) R30 is en, halogen, cyano, C1—C4aikyl, or C1-C4haloalkyi. Preferably, R30 is hydrogen, halogen, C1-C4alkyl, or C1—C4haloalkyl. Preferably, R30 is hydrogen, fluoro, or methyl. More preferably, R30 is hydrogen.

In one group of compounds at least two of Y1, Y2, Y3 and Y4 are CH and the others of Y1, Y2, Y3 and Y4 are CH or N.

In one group of compounds at least three of Y1, Y2, Y3 and Y4 are CH and the other of Y1, Y2, Y3 and Y4 is CH or N.

In one group of compounds Y1 and Y4 are CH, one of Y2 and Y3 is CH and the other of Y2 and Y3 is CH or N.

In one group of compounds Y1, Y2 and Y4 are CH, and Y3 is N.

In one group of compounds Y1, Y3 and Y4 are CH, and Y2 is N.

In one group of compounds Y1, Y2, Y3 and Y4 are CH.

In one group of compounds Y2 is N.

In one group of compounds Y3 is N.

In one group of compounds p is 1 and n is 2.

In one group of compounds R2, R3, R4, R5, R6 and R7 are H.

WO 00943 In one group of compounds Q is O.

In one group of compounds A is x-CHz-C(=O)—, in which x represents the bond that is connected to R‘.

In one group of nds R8 is hydrogen.

Forthe avoidance of doubt, when n is 1 and p is 1 compounds offormula I have the formula according to formula lA: R R9 \A/NR><5TYY / (lA) \ N f!6 R7 V’\Yévz R8 in which A, T, Y1, Y2, Y3, Y4, Q, R‘, R2, R3, R4, R5, R6, R7, R8, and R9 have the definitions as described for formula I.

When n is 2 and p is 1, compounds of formula l have the formula according to formula R3 R4 Rfi—ks” R1 N T Y1 \A/ R Y\ N/ ( lB ) R6 Y4| 2 '8 R7 R6 R7 \Y3//Y in which A, T, G, Y1, Y2, Y3, Y4, Q, R1, R2, R3, R4, R5, R6, R7, R8, and R9 have the ions as described for formula l.

When n is 1 and p is 2, compounds of formula l have the formula according to formula /R9 (IO) Y“\Y3//Y2 R8 in which A, T, G, Y1, Y2, Y3, Y4, Q, R‘, R2, R3, R4, R5, R6, R7, R8, and R9 have the definitions as described for formula I.

The invention also s to compounds of formula IA, formula IB, and formula lC as shown above.

The invention also relates to compounds of formula ID: R3 R4 R‘\ N Y1 R9 A/ N/ (“3) 6 7 4| R R 2 8 Y\ 3//Y R , Y wherein Y1, Y2, Y3, Y4, A, Q, R1, R2, R3, R4, R5, R6, R7, R8, and R9 have the definitions as described for formula l as d above. Preferred definitions of Y1, Y2, Y3, Y4, A, Q, R1, R2, R3, R4, R5, R6, R7, R8, and R9 are as defined above.

The invention also relates to compounds of formula lE: n Y1, Y2, Y3, Y4, A, Q, R‘, R2, R3, R4, R5, R5, R7, R8, and R9 have the definitions as described for formula I as defined above. Preferred definitions of Y1, Y2, Y3, Y4, A, Q, R1, R2, R3, R4, R5, R6, R7, R8, and R9 are as defined above.

The invention also s to a compound of formula IF: R1\JkN/fi K/TNN’R9 (lF) 3.Y2 H wherein T is N or CH; Y2 and Y3 are both CH, or one of Y3 and Y2 is N and the other is CH; and R1 and R9 are as described for a compound of formula I as d above. Preferred definitions of R1 and R9 are as as defined above The invention also relates to a compound of formula IG: WO 00943 FZHC ghK/UNN o FZHC K/T ,Rg \ N (IG) I 2 H v3"Y wherein T is N or CH; Y2 and Y3 are both CH, or one of Y3 and Y2 is N and the other is CH; and R9 is as described for a compound of formula I as defined above. Preferred definitions of R9 are as defined above.

The invention also relates to other intermediates useful in the preparation of compounds of formula i. Accordingly, the invention relates to a compound of formula ll: R3 R4 R2 R5 Q R1 N T v1 \A/ NnY\ 0H R6 R7 /Y2 wherein Y1, Y2, Y3, Y4, A, Q, T, n, p, R1, R2, R3, R4, R5, R6 and R7 have the definitions as described for formula I as defined above. Preferred definitions of Y1, Y2, Y3, Y4, A, Q, T, n, p, R1, R2, R3, R4, R5, R8 and R7 are as defined above.

The invention relates to a compound of formula W: 3 4 R R R5 O \A/ WY\N T v‘ R26 R6 R7 y4l 2 \ 3¢Y wherein Y1, Y2, Y3, Y4, A, Q, T, n, p, R1, R2, R3, R4, R5 R6 and R7, have the definitions as described for formula I as defined above, and preferred definitions of Y1, Y2, Y3, Y4, A, Q, T, n, p, R1, R2, R3, R4, R5 R6 and R7 are as defined above; and R26 is 01-06 alkyl or optionally tuted aryl. ably, R28 is 01-05 alkyl or phenyl optionally substituted with 1 to 3 substituents independently selected from C1-C4 alkyl, C1-C4 haloalkyl, hydroxyl, amino, cyano and halogen.

The invention relates to a compound of formula V: R\/N Y \ / (V) Y4\Y3//Y wherein Y1, Y2, Y3, Y4, A, o, n, p, R‘, R2, R3, R4, R6 and R7, have the definitions as described for formula I as defined above, and preferred definitions of Y1, Y2, Y3, Y4, A, Q, n, p, R‘, R2, R3, R4, R6 and R7 are as defined above; and R26 is C1—Ce alkyl or optionally substituted aryl. Preferably, R26 is Ci-Cs alkyl or phenyl optionally substituted with 1 to 3 substituents independently selected from C1—C4 alkyl, C1~C4 haloalkyl, hydroxyl, amino, cyano and halogen.

The invention relates to a compound of formula Xl: 3 4 R R R R5 Q 1 1 R\A/N T Y nY$Hai R6 R7 Y4 \yaéYZ wherein Y1, Y2, Y3, Y4, A, Q, n, p, R1, R2, R3, R4, R5, R6 and R7, have the definitions as described for formula I as defined above, and preferred tions of Y1, Y2, Y3, Y4, A, Q, n, p, R1, R2, R3, R4, R5, R6 and R7 are as defined bove; Hal stands for halogen. nds of formula (I) can be made in an analogous way to those described in W02011/018401 and as shown in the following schemes.

The nds of a i, wherein R1, R2, R3, R4, R5, R6, R7 , R8, R9, A, T, Y1, Y2, Y3, and Y4, n, p and Q are as defined for formula I, can be ed by transformation of a compound of formula ll, wherein R1, R2, R3, R4, R5, R5, R7, A, T, Y1, Y2, Y3, and Y4, n, p and Q are as defined for formula I, with a compound of formula III, wherein R8 and R9 are as defined for formula 1 ,and a e coupling reagent, such as BOP, PyBOP, HATU. This is shown in Scheme 1. coupling reagent R N T Y1 R9 \A/ MM YR.“ ") 6 R7 V1\ 3/,Y2 8 The nds of formula II, wherein R1, R2, R3, R4, R5, R6, R7, A, T, Y1, Y2, Y3, and Y4, n, p and Q are as defined for formula I can be obtained by saponification of a compound of formula iv, wherein R1, R2, R3, R4, R5, R5, R7, A, T, Y1, Y2, Y3, and Y“, n, p and Q are as defined for formula I and R26 is C1-Cealkyl or optionally substituted aryl, with a base, such as potassium hydroxide, sodium hydroxide, lithium hydroxide, ium ate, sodium carbonate, etc.. This is shown in Scheme 2.

R3 R4 RZ-‘H-]—_I'R5 R3 R4 Q 2 5 Q R R R1\ N p\T Y1 R26 base 1 P / 1 / (IV) R N T Y R6 R7 Y4\ /Y2 6 7 Y3/ R R Y4\Y3’/Y2 The compounds of formula |V.1, wherein R1, R2, R3, R4, R5, R6, R7, A, Y1, Y2, Y3, and Y4, n, p and Q are as defined for formula l and R26 is lkyl or optionally substituted aryl, can be obtained by reduction of a nd of formula V, wherein R1, R2, R3, R4, R6, R7, A, Y1, Y2, Y3, and Y4 i and R26 is C1—Cealkyl or , n, p and Q are as defined for formula optionally substituted aryl, and hydrogen with a catalyst, such as palladium on charcoal, raney—nickel, etc, or with lithium aluminum hydride. This is shown in Scheme 3.

Scheme 3 The compounds of formula V, wherein R1, R2, R3, R4, R8, R7, A, Y1, Y2, Y3, and Y4, n, p and Q are as defined for formula I and R26 is C1-Cealkyl or optionally substituted aryl, can be obtained by transformation of a compound of formula Vl, n R2, R3, R5, R6, R7 n, p and A are as defined for formula I and R27 and R28 are each independently hydroxy or C1- Cealkyl or together with the interjacent boron atom form a five- or mbered saturated heterocyclic ring, with a compound of formula Vll, wherein Y1, Y2, Y3, and Y4 and Q are as defined for formula I, R26 is C1-C5alkyl or optionally substituted aryl and Hal is halogen, preferably iodo, bromo or chloro, and a catalyst. This is shown in Scheme 4.

Scheme 4 The compounds of formula VI, n R1, R2, R3, R4, R6, R7 n, p and A are as defined for formula I and R27 and R28 are each ndently hydroxy or C1-Cealkyl or together with the interjacent boron atom form a five- or mbered saturated heterocyclic ring, can be obtained by transformation of a compound of formula Vlll, wherein R1, R2, R3, R4, R5, R7, n and p are as defined for formula l and R27 and R28 are each independently hydroxy or C1-C5alkyl or together with the interjacent boron atom form a five- or six-membered saturated heterocyclic ring, with a nd of formula lX, wherein R1 and A are as defined for formula I and R29 is hydroxy or halogen, preferably, fluoro, chloro or bromo, and a peptide coupling reagent or a base, such as ne, triethylamine, ethyl diisopropylamine etc.. This is shown in Scheme 5.

Scheme 5 base atively, the compounds of formula V, wherein R1, R2, R3, R4, R6, R7, A, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula I and R28 is C1—Cealkyl or optionally substituted aryl, can be obtained by transformation of a compound of formula X, wherein R2, R3, R4, R6, R7 A, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula 1 and R26 is C1—Csalkyl or optionally substituted aryl, with a compound of formula IX, wherein R1 and A are as defined for formula I and R29 is hydroxy or halogen, preferably, , chloro or bromo, and a peptide coupling reagent or a base, such as pyridine, triethylamine, ethyl diisopropylamine etc.. This is shown in Scheme 6. n 0 (V) 7 4 2 Alternatively, the compounds of formula I, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, A, T, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula I can be obtained by transformation of a compound of formula XI, n R‘, R2, R3, R4, R5, R6, R7, A, T, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula I and Hal is n, preferably fluoro, chloro or bromo, with a compound of formula Ill, wherein R8 and R9 are as defined for formula I, with a base, such as pyridine, triethylamine, ethyl diisopropylamine etc.. This is shown in Scheme 7.

Scheme 7 R\ /N‘b<J/T Y + H A nY \ Hal (XI) | 8/N\ 9 III R R l ) base R1 R9 \A/ WW? \N T Y T/ ()I 6 7 R R Y4\Y3’/Y2 8 The compounds of formula Xl, wherein R‘, R2, R3, R4, R5, R6, R7, A, T, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula I and Hal is n, preferably fluoro, chloro or bromo, can be obtained by transformation of a compound of formula ll, wherein R1, R2, R3, WO 00943 R4, R5, R6, R7, A, T, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula I, with a phosphoryl halide, such as phosphoryl chloride or phosphoryl bromide, or a thionyl halide, such as thionyl de or thionyl bromide. This is shown in Scheme 8.

Scheme 8 R3 R" 3 R2 R5 Q F’O(Hal)3 or p 30(Hal)2 R2 R5 Q 1 1 p R\ /N T Y (ll) —> 1 1 A wa \ N T Y OH \A/ WpY \ Hal (XI) 6 7 R R v“ v2 \Y3// R6 R7 Y4\ 3¢Y2 The compounds of formula lV.2, wherein R1, R2, R3, R4, R5, R5, R7, A, Y1, Y2, Y3, Y4, n, p and Q are as defined for formula I and R26 is C1-Caalkyl or optionally substituted aryl, can be obtained by transformation of a compound of formula Xll, wherein R1, R2, R3, R4, R6, R7 n, p and A are as defined for formula l, with a compound of a Vll, wherein Y1, Y2, Y3, Y4 and Q are as defined for formula I, R26 is C1-Cgalkyl or optionally substituted aryl and Hal is halogen, preferably iodo, bromo or chloro. This is shown in Scheme 9.

Scheme 9 R3 R4 R2 R5 1 26 Hal Y R p + 1 \ 0/ (W) R N NH 0‘”) \A/ l n Y4\ 3&Y2 R6 R7 Y 1 st R3 R4 singly, it has now been found that the novel compounds of formula I have, for practical purposes, a very advantageous level of ical activity for protecting plants against diseases that are caused by fungi.

The compounds of formula I can be used in the agricultural sector and related fields of use e.g. as active ingredients for controlling plant pests or on non—living materials for control of spoilage microorganisms or organisms ially l to man. The novel compounds are guished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and may be used for protecting numerous cultivated plants. The compounds of formula I can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later eg. from phytopathogenic microorganisms.

It is also possible to use nds of a I as dressing agents for the treatment of plant propagation material, e.g., seed, such as fruits, tubers or grains, or plant cuttings (for example rice), for the protection against fungal infections as well as against athogenic fungi occurring in the soil. The propagation material can be treated with a composition comprising a compound of formula l before ng: seed, for example, can be dressed before being sown. The active ingredients ing to the invention can also be applied to grains (coating), either by impregnating the seeds in a liquid formulation or by coating them with a solid formulation. The composition can also be applied to the planting site when the propagation material is being planted, for example, to the seed furrow during sowing. The invention relates also to such methods of treating plant propagation material and to the plant propagation material so treated.

Furthermore the compounds according to present invention can be used for controlling fungi in related areas, for example in the protection of technical materials, including wood and wood d technical products, in food e, in e management.

In addition, the invention could be used to protect non—living materials from fungal attack, e.g. lumber, wall boards and paint.

The compounds of formula l are, for example, ive against the phytopathogenic fungi of the following classes: Fungi imperfecti (e.g. Alternaria spp.), Basidiomycetes (e.g.

Corticium spp., Ceratobasidium spp., Waitea spp., Thanatephorus spp., Rhizoctonia spp., Hemileia spp., Puccinia spp., Phakopsora spp., Usz‘i/ago spp., Tilletia spp.), Ascomycetes 3O (e.g. Venturia spp., Blumeria spp., Erysiphe spp., Podosphaera spp., Uncinula spp., Moni/inia spp., Sclerotinia spp., Colletotrichum spp., Glomerella spp., Fusarium spp., e/la spp., Monographs/la spp., Phaeosphaeria spp., Mycosphaere/Ia spp., Cercospora spp., phora spp., Rhynchosporium spp., Magnaporthe spp., Gaeumannomyces spp., Oculimacula spp., Ramuiaria spp., Botryotinia spp.) and Oomycetes (e.g. Phytophthora spp., m spp., para spp., Peronospora spp., Pseudoperonospora spp. Bremia spp). Outstanding activity is observed against downy mildew (e.g. Plasmopara viticola) and late blight (e.g. Phytophthora infestans).

Furthermore, the novel compounds of formula 1 are effective against phytopathogenic gram negative and gram positive bacteria (e.g. monas spp, Pseudomonas spp, Erwinia amylovora, Ralstonia spp.) and viruses (e.g. tobacco mosaic virus).

Within the scope of t invention, target crops and/0r useful plants to be protected lly comprise the following s of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, es, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers, coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucumbers, ); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as o, nuts, , eggplants, sugar cane, tea, , vines, hops, bananas and natural rubber plants, as well as turf and ornamentals.

The useful plants and / or target crops in accordance with the invention include conventional as well as genetically ed or engineered varieties such as, for example, insect resistant (e.g. Bt. and VIP varieties) as well as disease resistant, herbicide tolerant (e.g. glyphosate— and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®) and nematode tolerant varieties. By way of example, le genetically enhanced or ered crop varieties include the Stoneville 55998R cotton and Stoneville 48923R cotton varieties.

The term "useful plants" and/or “target crops” is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS tors, for e primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol-pyrovyl-shikimate—B- phosphate—synthase) inhibitors, GS (glutamine synthetase) inhibitors or PPO porphyrinogen—oxidase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to ides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate—resistant maize varieties commercially available under the trade names RoundupReady® l® and LibertyLink®.

, Herculex The term "useful plants" and/or “target crops” is to be understood as including also useful plants which have been so transformed by the use of inant DNA techniques that they are capable of synthesising one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria, especially those of the genus Bacillus.

The term "useful " and/or “target crops” is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesising antipathogenic substances having a selective action, such as, for e, the so—called "pathogenesis-related proteins" (PRPs, see e.g. EP-A—0 392 225). Examples of such antipathogenic nces and transgenic plants capable of synthesising such antipathogenic substances are known, for example, from EP-A-0 392 225, WO 95/33818, and EP-A—0 353 191. The s of ing such transgenic plants are generally known to the person skilled in the art and are described, for example, in the publications mentioned above.

The term “locus” of a plant as used herein is intended to embrace the place on which the plants are growing, where the plant propagation materials of the plants are sown or where the plant propagation materials of the plants will be placed into the soil. An example for such a locus is a field, on which crop plants are growing.

The term “plant propagation material” is understood to denote generative parts of the plant, such as seeds, which can be used for the multiplication of the latter, and vegetative material, such as gs or tubers, for example potatoes. There may be mentioned for e seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes and parts of . Germinated plants and young plants which are to be transplanted after germination or after emergence from the soil, may also be mentioned. These young plants may be protected before transplantation by a total or partial treatment by immersion. Preferably “plant propagation material” is understood to denote seeds.

The compounds of formula I may be used in unmodified form or, preferably, er with the adjuvants conventionally employed in the art of ation. To this end they may be conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions or suspensions, dilute emulsions, wettable powders, e powders, dusts, granulates, and also encapsulations e.g. in polymeric substances.

As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or g, are chosen in accordance with the intended objectives and the prevailing stances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.

Suitable carriers and adjuvants, eg. for agricultural use, can be solid or liquid and are substances useful in formulation technology, e.g. l or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or izers. Such carriers are for example described in WO 97/33890.

The compounds of formula I may be used in the form of compositions and can be applied to the crop area or plant to be d, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations, which nce the growth of . They can also be selective herbicides or non—selective herbicides as well as insecticides, ides, bactericides, 1O nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.

The compounds of formula I are normally used in the form of fungicidal compositions for controlling or protecting against phytopathogenic rganisms, comprising as active ient at least one compound of formula l or of at least one preferred individual compound as above-defined, in free form or in agrochemically usable salt form, and at least one of the above-mentioned adjuvants The invention es a fungicidal composition comprising at least one compound a l, an lturally able carrier and optionally an adjuvant. An agricultural acceptable carrier is for example a carrier that is suitable for agricultural use. Agricultural carriers are well known in the art. Preferably said fungicidal compositions may comprise an additional fungicidal active ingredient in addition to the compound of formula I.

The compound of formula (I) may be the sole active ient of a composition or it may be admixed with one or more additional active ingredients such as an insecticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may, in some cases, result in unexpected synergistic activities. Examples of suitable additional active ingredients include the following: Azoxystrobin 08), Dimoxystrobin (1499614), Enestrobin (238410-11—2), Fluoxastrobin (1937400), Kresoxim-methyl 00), Metominostrobin (133408—50—1 ), Orysastrobin (248593 0), strobin (117428—22-5), ostrobin (175013-18—0), Azaconazole (60207—31-0), Bromuconazole (116255-48—2), Cyproconazole (94361 5), Difenoconazole (119446 3), Diniconazole (83657-24—3), Diniconazole—M (83657-18—5), Epoxiconazole (13385-98—8), Fenbuconazole (114369—43—6), Fluquinconazole (136426—54-5), Flusilazole 9), Flutriafol (766740), Hexaconazole 4), lmazalil (585942), lmibenconazole (86598-92—7), lpconazole (125225-28—7), Metconazole (125116-23—6), Myclobutanil (88671- 89-0), Oxpoconazole (174212-12—5), Pefurazoate (58011—68—0), Penconazole (66246-88—6), Prochloraz 5), Propiconazole (60207-904), Prothioconazole (1789286), Simeconazole (1495087), Tebuconazole (1075343), Tetraconazole (1122813), Triadimefon (43121—43-3), Triadimenol (552193), Triflumizole (99387-89—0), Triticonazole 37), Diclobutrazol (767380), Etaconazole (60207~93-4), Fluconazole (86386—73—4), Fluconazole—cis (112839-32—4), Thiabendazole 9-8), Quinconazole (1039708), Fenpiclonil 3), Fludioxonil 1—86-1), Cyprodinil (1215522), Mepanipyrim 57), Pyrimethanil (53112-28—0), Aldimorph (91315-15—0), Dodemorph 77-7), Fenpropimorph (67564-91—4), Tridemorph (814123), Fenpropidin (673067), Spiroxamine (118134-30—8), 1O Isopyrazam (881685-584 ), Sedaxane (874967—67-6), Bixafen (5818093), Penthiopyrad —82—3), Fluxapyroxad (9072043), Boscalid (1884256), Penflufen (494793- 67—8), Fluopyram (658066—35—4), Mandipropamid (374726-62—2), Benthiavalicarb (413615— —7), Dimethomorph (1104885), Chlorothalonil (18976), Fluazinam (79622—59-6), Dithianon (33476), Metrafenone 96), Tricyclazole (418142), xam (70630—17—0), Metalaxyl (578371), Acibenzolar (1264487) (Acibenzolar—S—methyl (1264487)), Mancozeb (8018-01—7), Ametoctradine 84) Cyflufenamid (1804093), lpconazole (125225-28—7), brom (3486350), Ethaboxam (16650~ 77-3), Fluopicolide (2391107), Fluthianil 02), Isotianil 91), ProquinaZid (1892784), Valiphenal (2831590), 1-methyl-cyclopropene (31007), Trifloxystrobin (1415177), Sulfur (7704—34-9), Copper ammoniumcarbonate (CA8 331135); Copper oleate (CAS 11201); Folpet (133-07—3), Quinoxyfen (124495-18— 7), Captan (133—06-2), Fenhexamid (1268338), Glufosinate and its salts (512762, 35597—44-5 (S—isomer)), Glyphosate (10716 ) and its salts 6 onium), 344947 (Dimethylammonium), 38641—94—0 (lsopropylammonium), 40465-66—5 (Monoammonium), 709011 (Potassium), 70393-85—0 (Sesquisodium), 81591-81—3 (Trimesium)), 1-methyl-3—difluoromethyl—1H-pyrazolecarboxylic acid (2— dich|oromethylene-3—ethyl~1-methyl—indan-4—yl)—amide, 1-methyl-3—difluoromethyI—1 H- pyrazolecarboxylic acid (4'-methylsulfanyl—biphenyl-Z-yI)-amide, 1—methyI-3— difluoromethyl-4H-pyrazoIe—4-carboxylic acid [2-(2,4-dichloro-phenyl)—2-methoxy—1—methyl- ethyl]—amide, (5-Chloro-2,4-dimethyl-pyridin—3-yl)—(2,3,4-trimethoxymethyl-phenyl)— methanone, (5-Bromochloro-2—methoxy—pyridinyl)—(2,3,4-trimethoxy—6—methyl-phenyl)— one, (E)—3-(2,6-Dichloro-phenyl)—1-methyl-propen-(E)- ylideneaminooxymethyl]-phenyl}[(Z)-methoxyimino]-N-methyl-acetamide, 3-[5-(4-Chloro- phenyl)—2,3—dimethyI-isoxazolidin-S—yH—pyridine.

Another aspect of invention is related to the use of a compound of formula l or of a preferred individual compound as above-defined, of a composition comprising at least one compound of formula I or at least one preferred individual compound as above-defined, or of a fungicidal mixture comprising at least one compound of formula I or at least one preferred individual compound as defined, in admixture with other fungicides, as described above, for controlling or preventing ation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or non—living materials by phytopathogenic microorganisms, preferably fungal organisms.

A r aspect of invention is d to a method of controlling or preventing an infestation of plants, e.g. useful plants such as crop plants, propagation material thereof, e.g. seeds, harvested crops, e.g. harvested food crops, or of ving materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, especially fungal organisms, which comprises the application of a compound of formula I or of a red dual compound as above—defined as active ingredient to the plants, to parts of the plants or to the locus thereof, to the propagation material thereof, or to any part of the ving materials.

Controlling or preventing means reducing infestation by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man, ally fungal organisms, to such a level that an improvement is demonstrated.

A preferred method of controlling or ting an infestation of crop plants by phytopathogenic microorganisms, especially fungal organisms, which comprises the application of a nd of formula I, or an emical composition which ns at least one of said compounds, is foliar application. The frequency of application and the rate of application will depend on the risk of infestation by the corresponding pathogen.

However, the compounds of formula I can also penetrate the plant through the roots via the soil (systemic action) by drenching the locus of the plant with a liquid formulation, or by applying the compounds in solid form to the soil, e.g. in granular form (soil application). in crops of water rice such granulates can be applied to the flooded rice field. The compounds of formula I may also be applied to seeds (coating) by impregnating the seeds or tubers either with a liquid formulation of the fungicide or coating them with a solid formulation.

Aformulation, e.g. a composition containing the compound of formula I, and, if desired, a solid or liquid adjuvant or monomers for encapsulating the compound of formula I, may be prepared in a known manner, typically by intimately mixing and/or grinding the compound with extenders, for example ts, solid rs and, optionally, surface active compounds (surfactants).

The agrochemical formulations and/or compositions will usually contain from 0.1 to 99% by weight, ably from 0.1 to 95% by , of the compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and from O to % by weight, ably from 0.1 to 25% by weight, of a surfactant. ageous rates of application are ly from 59 to 2kg of active ingredient (a.i.) per hectare (ha), preferably from 10g to 1kg a.i.lha, most preferably from 209 to 6009 a. When used as seed drenching agent, convenient dosages are from 10mg to 19 of active substance per kg of seeds.

Whereas it is preferred to formulate commercial products as concentrates, the end user will normally use dilute formulations.

The following non—limiting example illustrates the above—described invention in more 1O detail.

Example 1: This example illustrates the preparation of 3—{4—[2—(3,5-bis-difluoromethyl-pyr azolyl)-acetyl]-piperaziny|}-N-(R)—1,2,3,4-tetrahydro—naphthalenyl—benzamide (Compound No. 1) a) Preparation of 4-{3-[(R)-(1 ,2,3,4-tetrahydro-naphthaleny|)carbamoyl]—phenyl}-piper azinecarboxylic acid tert—butyl ester HATU (6.6 g, 14.4 mmol) and ethyldiisopropylamine (4.1 g, 26 mmol) were added consecutively to a suspension of 4—(3—carboxy-phenyl)-piperazine-1~carboxylic acid tert- butyl ester (4.0 g, 13 mmol) in 30 ml of methylformamide. This mixture was stirred for 10 min at room temperature, then a solution of 1,2,3,4—tetrahydro—1-naphthylamine (1.9 g, 13 mmol) in 20 ml of N,N-dimethylformamide was added. The reaction mixture was stirred for 4 h at room temperature. Subsequently the solvent was removed in vacuo, the remaining oil dissolved in ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution, 0.5 N hydrochloric acid and brine. The organic layer was dried over sodium sulfate and evaporated, the e was purified by column chromatography on silica gel (ethylacetate/cyclohexane 3:7) to give 4-{3-[(R)—(1,2,3,4-tetrahydro—naphthalen~1- bamoyl]—phenyl}—piperazine—1-carboxylic acid tert—butyl ester. 1H-NMR (400 MHz, CDCls): 8 = 1.51 (s, 9H), 1.86 — 1.95 (m, 2H), 2.02 -— 2.16 (m, 2H), 2.82 — 2.91 (m, 2H), 3.20 (t, 4H), 3.61 (t, 4H), 5.37 (t, 1H). 7.12 — 7.19 (m, 4H), 7.26 (q, 1H), 7.37 (t, 2H), 7.48 (d, 1H), 8.69 (bs, 1H). MS: m/z = 436 (M+1). b) Preparation of 3-piperazinyl-N-(R)-1,2,3,4-tetrahydro-naphthalenyl-benzamide To a solution of 4-{3—[(R)—(1,2,3,4—tetrahydro-naphthalen-1—yl)carbamoyl]—phenyl}- piperazine—1-carboxylic acid tert-butyl ester (5.7 g, 13 mmol) in 150 ml of dioxane was added 33 ml of 4 N hydrochloric acid. The reaction mixture was stirred for 16 h at room WO 00943 temperature. Subsequently the solvent was removed in vacuo, the residue dissolved in ethyl acetate and washed with a saturated aqueous sodium onate solution. The organic layer was dried over potassium carbonate and evaporated, delivering 3-piperazin yl-N-(R)—1,2,3,4-tetrahydro-naphthalenyl-benzamide, which was pure enough to be transformed in the next step without further purification. 1H—NMR (400 MHz, MeOD): 6 = 1.83 — 1.92 (m, 2H), 2.02 (q, 1H), 2.13 (q, 1H), 2.83 — 2.89 (m, 2H), 3.00 (t, 4H), 3.21 (t, 4H), 5.34 (t, 1H), 7.11 — 7.19 (m, 4H), 7.27 (q, 1H), 7.34 (d, 2H), 7.48 (d, 1H). MS: m/z = 336 (M+1). 1O 0) ation of 3—{4—[2-(3,5-bis—difluoromethyl-pyrazol-1~yl)—acetyl]—piperazin-1 -yl}- N—(R)—1,2,3,4—tetrahydro—naphthalen-1—yl-benzamide (Compound No. |.z.001) To solution of 2-[3,5-bis(difluoromethyl)pyrazo—1-yl]acetic acid (0.1 g, 0.5 mmol) in 5 ml of dichloromethane was added at room temperature one drop of methylformamide, then oxalyl chloride (0.07 g, 0.6 mmol). This mixture was stirred for 15 min at room temperature and then ated. The residue was redissolved in 5 ml of romethane and slowly added at 0 0C to a solution of 3—piperazinyl—N—(R)—‘l ,2,3,4-tetrahydro-naphthalenyl- benzamide (0.2 g, 0.5 mmol) and triethylamine (0.3 g, 2.7 mmol) in 5 ml of dichloromethane. The reaction mixture was d for 2 h at room temperature, then d with water and dichloromethane. The organic layer was washed with water 1 N hydrochloric acid and brine, dried over sodium sulfate and evaporated. The remainder was purified by column chromatography on silica gel (ethylacetate/cyclohexane 3:7) to give 3-{4—[2-(3,5-bis- difluoromethyl-pyrazolyl)-acetyl}-piperazinyl}-N—(R)—1,2,3,4-tetrahydro—naphthalen—1-yl— benzamide (Compound No. |.z.001). 1H—NMR (400 MHz, CDCIs): 6 = 1.62 (t, 1H), 1.79 — 1.90 (m, 2H), 2.07 (q. 1H), 2.75 (q, 2H), 3.19 (s, 2H), 3.24 (s, 2H), 3.60 (s, 2H), 3.72 (s, 2H), 5.08 (s, 2H), 5.31 (q, 1H), 6.26 (d, 1H), 6.69 (d, 1H), 6.97 (q, 1H), 7.04 — 7.13 (m, 3H), 7.22 (t, 2H), 7.40 (s, 1H). MS: m/z = 544 (M+1).

Table 1 below illustrates examples of individual compounds of formula l according to the invention.

Table 1: individual com ounds of formula l accordin to the invention Compound R1 A WO 00943 -CH2C(=O)— -CHgC(=O)- —CHzC(=O)~ -CHgC(=O)- —CH2C(=O)— ~CH20(=O)' WO 20131000943 -CH2C(=O)- =O)- -CHzC(=O)- —CH2C(=O)— —CHZC(=S)— “CH2C(=S)" -CH20(=S)- —CH2C(=S)- =S)- ~CHgC(=S)— ~CHgC(=S)- —CHZC(=S)- —CH2C(=S)~ WO 00943 —CH20(=S)- -CH20(=S)— -CH20(=S)— WO 00943 - CHZSOZ- - CH2802- -CH2 802- - CH2802- —CH2 802- — CHQSOZ‘ — CH2802- ~ CstOQ- — CH2802- - CHZSOZ- where a) 48 compounds of formula (La): R1‘A’N ,R9 N (La, wherein A, Q, R1 and R9 are as defined in Table 1.

WO 00943 b) 48 compounds of formula (Lb): R1\A/N N/R (Lb) wherein A, o, R1 and R9 are as defined in Table 1. c) 48 compounds of formula (Lc): R‘\A’N N ,R9 \ N (Lei wherein A, Q, R1 and R9 are as defined in Table 1. ’10 d) 48 compounds of formula (Ld): R,\A wherein A, Q, R1 and R9 are as defined in Table 1. e) 48 nds of formula (Le): R1\A’N \ N’R (Le) | H wherein A, Q, R1 and R9 are as defined in Table 1. f) 48 compounds of formula (Lf): Rim/N [\ N/R (Lf) N / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. g) 48 compounds of formula (Lg): RP‘A/NWEIR9 (lg) N/ wherein A, Q, R1 and R9 are as defined in Table 1. h) 48 compounds of a (l.h): R1\AINWI\IJIR9 (Lh) N/ CH3 wherein A, Q, R1 and R9 are as defined in Table 1. i) 48 nds of formula (l.i): Rim/N \ (H) l NR 1O wherein A, Q, R1 and R9 are as defined in Table 1. j) 48 compounds of formula (l.j): Row“ \ I iii/R (U) /N CH3 wherein A, Q, R1 and R9 are as defined in Table 1. k) 48 compounds of formula (|.k): Rim/”OWN 9 N/R (l.k) wherein A, Q, R1 and R9 are as defined in Table 1. m) 48 compounds of formula (l.m): R1‘A’N©\WN\ 9 [Ti/R (l.m) N / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. n) 48 compounds of formula (l.n): R1/A\ :Z0 LO I2 3 wherein A, Q, R1 and R9 are as defined in Table 1. o) 48 compounds of formula (Lo): R1’A‘N o ”(R (Lo) wherein A, Q, R1 and R9 are as defined in Table 1. p) 48 compounds of formula (|.p): 1/A\ R N Q n A, Q, R1 and R9 are as defined in Table 1. q) 48 compounds of formula (I.q): 1/A\ R N Q IN\ 'll/R (l.q) / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. r) 48 nds of formula (l.r): RVA‘N Q wherein A, Q, R1 and R9 are as defined in Table 1. s) 48 compounds of formula (Ls): PCT/EPZO12/062428 RVA‘N Q I [F’R (Ls) N / CH3 wherein A, Q, R1 and R9 are as d in Table 1. t) 48 compounds of a (Lt): RVA‘N Q \ N’R (Lt) l H wherein A, Q, R1 and R9 are as defined in Table 1. u) 48 compounds of formula (Lu): RVA‘N 'f’R (l.u) wherein A, Q, R1 and R9 are as defined in Table 1. v) 48 compounds of formula (l.v): Ri’A‘N Q \ N’R (l.v) l H wherein A, Q, R1 and R9 are as defined in Table 1. w) 48 compounds of formula (l.w): RVA‘N Q \ N’R (l.w) l l /N CH3 wherein A, Q, R‘ and R9 are as defined in Table 1. x) 48 compounds of formula (l.x): R1’A‘N Q l iii/R (|.x) wherein A, Q, R1 and R9 are as defined in Table 1. y) 48 compounds of formula (Ly): RVA‘N Q i N’R (l.y) N / CH3 n A, Q, R1 and R9 are as defined in Table 1. z) 48 compounds of formula (l.z): RvA‘N/fi Q n A, Q, R1 and R9 are as defined in Table 1. aa) 48 compounds of formula (Iaa): R1’A‘N/fi Q K/N N’R9 (Laa) c5143 wherein A, Q, R1 and R9 are as defined in Table 1. ab) 48 compounds of formula (Lab): RVA‘N/fi Q K/N 9 |N\ ”’R (Lab) wherein A, o, R1 and R9 are as defined in Table 1. ac) 48 compounds of formula (Lac): R1/AxN/\| Q K/N 9 |N\ [fl/R (Lac) / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. ad) 48 compounds of a (Lad): RVA‘N/fi Q K/N 1R9 \ E: (Lad) wherein A, Q, R1 and R9 are as d in Table 1. ae) 48 compounds of formula (Lae): R” N Q K/N \ M’R9 (Lae) wherein A, Q, R1 and R9 are as defined in Table 1. af) 48 compoundsof formula (Laf): Rl’A‘N/fi Q K/N 1R9 | IZ (|.af) wherein A, Q, R1 and R9 are as defined in Table 1. ag) 48 compounds of formula (Lag): R1 / N Q K/N ~ng (Lag) wherein A, Q, R1 and R9 are as defined in Table 1. ah) 48 compounds of formula (Lah): Rl’A‘N Q K/N 9 \ (Lah) l N wherein A, Q, R1 and R9 are as defined in Table 1. ai) 48 compounds of formula (Lai): R1 ’A‘N’fi Q wherein A, Q, R1 and R9 are as defined in Table 1. aj) 48 compounds of formula (|.aj): /fi Q K/NTflem’R9 (Laj) wherein A, Q, R1 and R9 are as defined in Table i. ak) 48 compounds of a (lak): R1 /A\N Q K/NYN\ [YRS (Lak) N / CH3 1O wherein A, Q, R1 and R9 are as defined in Table 1. am) 48 compounds of formula (Lam): R\A’N 9 Ell/R (lam) wherein A, Q, R1 and R9 are as defined in Table 1. an) 48 compounds of formula (Lan): R\A’N ”(R (Lan) wherein A, Q, R1 and R9 are as defined in Table 1. a0) 48 compounds of formula (Lao): wherein A, Q, R1 and R9 are as defined in Table 1. ap) 48 compounds of formula (Lap): RK ,N N R9 A \ I if (I .ap) / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. aq) 48 compounds of formula (Laq): 1 9 R\A’N \ N’R (lati) l H wherein A, Q, R1 and R9 are as defined in Table 1. ar) 48 compounds of formula (Lar): 1 9 R\A’N \ N’R (Lar) | l N / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. as) 48 compounds of formula (Las): 1 9 | H wherein A, Q, R1 and R9 are as defined in Table 1. at) 48 nds of formula (Lat): 1 9 R\A’N \ N’R (Lat) l i N/ CH3 wherein A, Q, R1 and R9 are as defined in Table 1. au) 48 compounds of formula (Lau): R\A’N 9 \ N’R (Lau) I H n A, Q, R1 and R9 are as defined in Table 1. av) 48 compounds of formula (Lav): R1\AN, wherein A, Q, R1 and R9 are as defined in Table 1. aw) 48 compounds of a (Law): RK N N R9 wherein A, Q, R1 and R9 are as defined in Table 1. ax) 48 compounds of formula (Lax): RK N N R9 N / CH3 wherein A, Q, R1 and R9 are as defined in Table 1. ay) 48 compounds of formula (Lay): R”A,N Q \ N (Lay) i H wherein A, Q, R1 and R9 are as defined in Table 1.

Throughout this description, temperatures are given in degrees Celsius and “m.p.” means melting point. LC/MS means Liquid Chromatography Mass Spectroscopy and the description of the tus and the method is: (ACQUlTY UPLC from Waters, Phenomenex Gemini C18, 3 pm particle size, 110 Angstrom, 30 x 3 mm column, 1.7mL/min., 60 °C, H20 + 0.05% HCOOH (95%) / eOH 4:1 + 0.04% HCOOH (5%) — 2 min. — CchN/MGOH 4:1 + 0.04% HCOOH (5%) — 0.8 min., ACQUITY SQD Mass Spectrometer from Waters, tion method: electrospray (ESl), ty: positive ions, Capillary (W) 3.00, Cone (V) 20.00, Extractor (V) 3.00, Source Temperature (°C) 150, Desolvation Temperature (°C) 400, Cone Gas Flow (L/Hr) 60, Desolvation Gas Flow (L/Hr) 700)).

Table 2: Melting point and LC/MS data for compounds of Table 1 Compound No. Melting point (°C) LCIMS l.v.001 — 0 min; MS: m/z=544 (M+1) l.z.001 — Rt=1.88 min; MS: m/z=544 (M+1) l.ah.001 — Rt=1.25 min; MS: m/z=545 (M+1) Biological examples thtophthora infestans/ tomato / leaf disc reventative tomato late bli ht Tomato leaf disks are placed on water agar in multiwell plates ll format) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after ation. The ated leaf disks are incubated at 16°C and 75% rh under a light regime of 24 h darkness followed by 12 h light/ 12 h darkness in a climate cabinet and the activity of a compound is assessed as percent disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (5 — 7 days after application).

Compound 1, |.z.001 and |.ah.001 at 200 ppm give at least 80% disease control in this test when compared to untreated l leaf discs under the same conditions, which show extensive disease development.

Phflophz‘hora infestans / potato / preventative (potato late blight) 2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 2 days after application. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (5 — 7 days after application).

Compound |.v.001, |.z.001 and l.ah.001 at 200 ppm give at least 80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development.

Ph 0 hthora infestans/ otato / lon lastin reventative otato late bli ht 1O 2-week old potato plants cv. Bintje are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying them with a sporangia suspension 6 days after application. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by e is assessed when an riate level of disease appears on untreated check plants (9 — 11 days after application).

Compound l.v.001, |.z.001 and l.ah.001 at 200 ppm give at least 80% e control in this test when ed to untreated control plants under the same conditions, which show ive disease development.

Ph 0 hthora ans/ otato / curative otato late bli ht 2-week old potato plants cv. Bintje are inoculated by spraying them with a sporangia suspension one day before application. The ated plants are sprayed in a spray chamber with the formulated test nd diluted in water. The inoculated test plants are incubated at 18° C with 14 h light/day and 100 % rh in a growth chamber and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (3 — 4 days after application).

Compound |.v.001, 1 and l.ah.001 at 200 ppm give at least 80% e control in this test when compared to untreated control plants under the same conditions, which show extensive disease development.

Plasmogara vitico/a/ ra e/ leaf disc reventative ra e down mildew Grape vine leaf disks are placed on water agar in multiwell plates (24—well ) and sprayed with the formulated test compound diluted in water. The leaf disks are inoculated with a spore suspension of the fungus 1 day after application. The inoculated leaf disks are ted at 19°C and 80% rh under a light regime of 12 h light/ 12 h darkness in a climate cabinet and the activity of a compound is assessed as t disease control compared to untreated when an appropriate level of disease damage appears in untreated check leaf disks (6 — 8 days after ation).

Compound l.v.001, |.z.001 and l.ah.001 at 200 ppm give at least 80% disease control in this test when compared to ted control leaf discs under the same conditions, which show extensive disease development.

Plasma ara vitico/a/ ra e / reventative ra e down mildew -week old grape ngs cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants plants are inoculated by spraying a sporangia suspension on their lower leaf surface one day after application.

The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (6 — 8 days after ation).

Compound l.v.001, l.z.001 and l.ah.001 at 200 ppm give at least 80% disease control in this test when compared to untreated control plants under the same ions, which show extensive disease development.

P/asmo ara viticola/ ra e / Ion lastin reventative ra e down mildew -week old grape seedlings cv. Gutedel are sprayed in a spray chamber with the formulated test compound diluted in water. The test plants are inoculated by spraying a sporangia suspension on their lower leaf surface 6 days after application. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the percentage leaf area covered by disease is assessed when an appropriate level of disease appears on untreated check plants (11 — 13 days after application).

Compound l.v.001, l.z.001 and l.ah.001 at 200 ppm give at least 80% disease control in this test when compared to untreated control plants under the same ions, which show extensive disease development.

Plasmogara vitfcola / grape / curative (grape downy ) 5—week—0ld grape seedlings cv. l are inoculated by spraying a gia suspension on their lower leaf surface one day before application. The inoculated grape plants are sprayed in a spray chamber with the ated test compound diluted in water. The inoculated test plants are incubated at 22° C and 100% rh in a greenhouse and the tage leaf area covered by disease is assessed when an riate level of disease appears on untreated check plants (4 — 6 days after application).

Compound l.v.001, |.z.001 and l.ah.001 at 200 ppm give at least 80% disease control in this test when compared to untreated control plants under the same conditions, which show extensive disease development. wo 2013/000943

Claims (3)

What is claimed

1. A compound of formula I: wherein A is x-C(R1°R“)-C(=O)-, x-C(R12R13)—C(=S)-, x-O~C(=O)-, x—O—C(=S)—, x-N(R14)-C(=O)-, x—N(R15)-C(=S)-or X-C(R16R17)-SOg-, x-N=C(R30)~, in each case x indicates the bond 10 that is connected to R1; T is CR18 or N; Y1, Y2, Y3, and Y4 are independently CR19 or N; Q is O or S; n is 1 or 2; 15 p is 1 or 2, providing that when n is 2, p is 1. R1is F / \ \ N“; R2, R3, R4, R5, R6, R7, R10, R“, R12, R13, R16, R17, R18,R19 and R30 each independently are hydrogen, halogen, cyano, C1-C4alkyl, or aloalkyl; 20 R8, R14 and R15 each independently are hydrogen or lkyl; and R9 is phenyl, benzyl or group (a): wherein the phenyl, benzyl and group (a) are each optionally substituted with 1 to 3 substituents independently selected from C1-C4 alkyl, C1-C4 kyl, halogen, cyano, hydroxy and amino; or a salt or a N-oxide thereof.

2. The compound according to claim 1, wherein A is x—C(R1°R")-C(=O)-, x-C(R‘2R‘3)-C(=S)-, x—O-C(=O)-, x—O-C(=S)—, or x-C(R‘5R‘7)- 802-, in each case x indicates the bond that is connected to R1; T is CR18 or N; 1O Y1, Y2, Y3, and Y4 are independently CR19 or N providing that at least 2 of Y1, Y2, Y3, and Y4 are CR”; Q is O or S; n is 1 or 2; p is 1; 15 R2, R3, R4, R5, R6, R7, R10, R“, R12, R13, R16, R17, R18, and R19 each independently are hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl; R8 is hydrogen or C1-C4alkyl; and R9 is phenyl, benzyl or group (a): 20 (8) wherein the , benzyl and group (a) are each optionally substituted with 1 to 3 substituents independently selected from C1—C4 alkyl, C1—C4 haloalkyl, halogen, cyano, hydroxy and amino. 25

3. The compound according to claim 1, wherein A is R11-C(=O)-, =O)~, or x~CR15R17-802—, in each case x indicates the bond that is connected to R1; T is CR18; Y1, Y2, Y3, and Y4 are independently CR19 or N ing that at least 2 of Y1, Y2, Y3, 30 and Y4 are CR19 and providing that there are no N-N bonds in the ring containing Y‘, Y2, Y3, and Y4; Q is O or S; n is 1 or 2; pis1;