GB2361474A - Novel azole/azine compounds having fungicidal/pesticidal properties - Google Patents

Novel azole/azine compounds having fungicidal/pesticidal properties Download PDF

Info

Publication number
GB2361474A
GB2361474A GB0106313A GB0106313A GB2361474A GB 2361474 A GB2361474 A GB 2361474A GB 0106313 A GB0106313 A GB 0106313A GB 0106313 A GB0106313 A GB 0106313A GB 2361474 A GB2361474 A GB 2361474A
Authority
GB
United Kingdom
Prior art keywords
optionally substituted
alkyl
optionally
formula
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
GB0106313A
Other versions
GB0106313D0 (en
Inventor
Patrick Jelf Crowley
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Syngenta Ltd
Original Assignee
Syngenta Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Syngenta Ltd filed Critical Syngenta Ltd
Publication of GB0106313D0 publication Critical patent/GB0106313D0/en
Publication of GB2361474A publication Critical patent/GB2361474A/en
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

A compound of formula (I): <EMI ID=1.1 HE=27 WI=102 LX=599 LY=752 TI=CF> <PC>wherein<BR> A is optionally substituted C<SB>1-6</SB> alkylene, optionally containing double or triple bonds or S, N or O atoms;<BR> J and L are independently CR<SP>3</SP> or N;<BR> M is N(R<SP>51</SP>)C(=Y), N=C(OR<SP>52</SP>), N=C(SR<SP>53</SP>) or N=C(NR<SP>54</SP>R<SP>55</SP>) where O or N is the atom of attachment to the isothiazole ring;<BR> Y is O, S or NR<SP>13</SP>; and<BR> R<SP>1</SP>,R<SP>3</SP>,R<SP>13</SP>,R<SP>51</SP>,R<SP>52</SP>,R<SP>53</SP>,R<SP>54</SP> and R<SP>55</SP> are specified organic groups; the compounds have fungicidal, insecticidal, acaricidal, nematicidal and molluscicidal activity.

Description

2361474 CHEMICAL COMPOUNDS The present invention relates to azole and
azine derivatives, to processes for preparing them, to ftmgicidal, insecticidal, acaricidal, molluscicidal and nernaticidal compositions comprising them, to methods of using them to combat fungal diseases (especially ftmgal diseases of plants) and to methods of using them to combat and control insect, acarine, mollusc and nematode pests.
Azole and azine derivatives are disclosed in W095/31448, W097/18198, W098/02424 and W098/05670.
The present invention provides a compound of formula (I):
(R)M --'- R 3)n L N' S M-A' N wherein A is optionally substituted C1, allcylene, optionally substitutedC2, alkenylene, optionally substituted C2, alkynylene, optionally substituted C,6 alkylenoxy, optionally substituted oxy(CI-6)alkylene, optionally substituted CI-6 alkylenethio, optionally substituted thio (CI-6)alkylene, optionally substituted CI-6 alkylenamino, optionally substituted amino (C,-6)alkylene, optionally substituted [C,-6 alkyleneoxy(C,-6)alkylene], optionally substituted ICI-6 alkylenethio(CI-6)alkylene], optionally substituted [CI-6 alkylenesulfinyl(CI-6)alkylene], optionally substituted [CI-6 alkylenesulfonyl(CI-6)alkylene] or optionally substituted [C,-6 alkyleneamino(C,-6)alkylenel; J and L are independently CR' or N; M is N(R")C(=Y), N=C(OW2), N=C(SR") or N=C(NR4W') where N is the atom of attaclunent to the isothiazole ring; Y is 0, S or NR 13; each R' group is independently halogen, optionally substituted C,-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted CI-6 alkoxy, optionally substituted C1, alkylthio, optionally substituted C, cycloalkyl, cyano, nitro or SF5; W'is hydrogen, optionally substituted CI-10 alkyl, optionally substituted [C2-6 alkenyl(C,-6)alkyl], optionally substitutedIC2-6alkynyl(C,-6)alkyl], optionally substituted C, cycloalkyl, optionally substituted CI-10 alkylcarbonyl, optionally substituted CI-10 alkoxycarbonyl, formyl, optionally substituted CI-10 alkylaminocarbonyl, optionally substituted di(C 1-1 O)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted C,-6alkylthio, optionally substituted C,-6 alkylsulfinyl, optionally substituted CI-6 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, or R"R2'NS; optionally substitutedICI-12alkoxy (C,-2)alkyl], optionally substituted [aryloxy(Cl-2)alkyl], optionally substituted [aryl (CI-3)alkoxy (C,-2)dkyl], optionally substituted [aryl (CI-3)alkyl]; W2 is optionally substituted CI-10 alkyl, optionally substituted IC2-6 alkenyl(CI-6)alkyl], optionally substitutedIC2-6alkynyl(C,-6)alkyl], optionally substituted C31 CYCloalkyl, optionally substituted CI-10 alkylcarbonyl, optionally substituted CI-10 alkoxycarbonyl, formyl, optionally substituted C,-,,, alkylaminocarbonyl, optionally substituted di(Cj-,,)aHcylaminocarbonyl, optionally substituted phenoxycarbonyl, tri(C,4)alkylsilyl, aryldi(CI-4)alkylsilyl, (C14)alkyldiarylsilyl or triarylsilyl, optionally substituted[Cl-,2alkoxy (C,-,)alkyl], optionally substituted [aryloxy (CI-2)alkyl], optionally substituted [aryl (CI-3)alkoXY (CI-2)alkYl1I optionally substituted [aryl (C,-3)alkyl]; R 13 is optionally substituted CI-1. alkyl, optionally substituted [C2-6 alkenyl(C,-6)akl], optionally substituted IC2-6 alkynyl(CI-6)alkyl], optionally substituted C3-7 cycloalkyl, optionally substituted C,-,o alkylcarbonyl, optionally substituted C1.10 alkoxycarbonyl, optionally substituted C1,, alkylaminocarbonyl, optionally substituted di(C,-,,)alkylaminocarbonyl or optionally substituted phenoxycarbonyl), optionally substituted [C,-,, alkoXY (CI-2)alkYl1I optionally substituted [aryloxy (CI-2)alkyl], optionally substituted [aryl (CI-3)alkoxy (CI-2)alkyl], optionally substituted [aryl (C,-3)alkyll; W' and R" are, independently optionally substituted CI-10 alkyl, optionally substituted C,-, alkoxy, optionally substituted [C2-6 alkenyI(C,-6)alkyl], optionally substituted IC2-6 aknYl(CI-6)alkYl]I optionally substituted C3-7 cycloalkyl, optionally substituted CI-10 alkylcarbonyl, optionally substituted C,-,, alkoxycarbonyl, formyl, optionally substituted CI-10 alkylaminocarbonyl, optionally substituted di(Cl-lo)alkylaminocarbonyl, hydroxy, amino, optionally substituted C,-6 alkylamino, optionally substituted di(CI-6)alkylamino, or optionally substituted phenoxycarbonyl, optionally substituted [aryl (C,,)alkyl]; each W group is independently halogen, cyano, optionally substituted CI-20 alkyl, optionally substituted C2-20 alkenyl, optionally substituted C2-20 alkynyl, optionally substituted C3-7 cycloalkyl, optionally substituted C,-6 cycloalkenyl, formyl, optionally substituted CI-20 alkoxycarbonyl, optionally substituted CI-20 alkylcarbonyl, aminocarbonyl, optionally substituted C1-2 alkylaminocarbonyl, optionally substituted di(CI-20)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted ary1carbonyl, optionally substituted arylarninocarbonyl, optionally substituted N-alkyl-N-arylaminocarbonyl, optionally substituted diarylarninocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, io optionally substituted alkylheteroarylaminocarbonyl, optionally substituted dihetero arylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, W'O, HS, optionally substituted CI-20 alkylthio, optionally substituted CI-20 alkylsulfinyl, optionally substituted CI-20 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, W8R29N or W'ON=C(W'), or where (R). can fonn a fused benzene ring, itself optionally substituted by halogen, cyano, optionally substituted CI-20 alkyl, optionally substituted CI-20 alkoxy, optionally substituted C2-20 alkenyl, optionally substituted C2-2. alkynyl, optionally substituted C, cycloalkyl, optionally substituted C5-6 cycloalkenyl, optionally substituted Cl-20 alkoxycarbonyl, optionally substituted CI-20 alkylearbonyl; R 13 is hydrogen, OH, NH2, cyano, nitro, optionally substituted C1-6 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted (C2-6)alkenyl(CI-6)alkyl, optionally substituted (C2-6)alkynyl(Cl-6)alkyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted C1-6 alkylcarbonyl, optionally substituted C,-6 alkoxycarbonyl, optionally substituted CI-6 alkylaniino, optionally substituted di(CI-6)alkyl amino, optionally substituted C, alkylearbonylamino, optionally substituted CI-6 alkoxycarbonylamino, optionally substituted CI-6 alkoxy, optionally substituted C,-6 alkylthio, optionally substituted CI-6 alkylsulfinyl, optionally substituted CI-6 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl or C -6 acyloxy; WO and W' are, independently, optionally substituted C,-6 alkyl or W'and W' together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C,.6 alkyl groups; W' is hydrogen, optionally substituted C,,, alkyl, optionally substitutedIC2-20 alkenyl(C,-6) alkyl], optionally substitutedIC2-20 alkynyl(C,-6)alkyl], optionally subsfitutedC3.7cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted [heterocyclyl(CI-6)alkylCH=N] or di(C,-6)alkylC=N; R2' and R2' are, independently, hydrogen, optionally substituted CI-20 alkyl, optionally substitutedC3-7cycloalkyl, optionally substitutedIC2-20 alkenyl(CI-6)alkyl], optionally substitutedIC2-20 alkynyl(CI-6)alkyl], optionally substituted CI-20 alkoxycarbonyl, optionally io substituted phenoxycarbonyl, formyl, optionally substituted CI-20 alkylcarbonyl, optionally substituted CI-20 alkylsulfonyl or optionally substituted phenylsulfonyl; or W' and e together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C,-, alkyl groups; R2' and W' are independently hydrogen, optionally substituted phenyl or optionally substituted CI-6alkyl; and R" is hydrogen, optionally substituted phenyl (C,-2)alkyl or optionally substituted Cl a1kYl; m is an integer from 0 to 2; and n is an integer from 0 to 4 provided that the compound is other than N-(4-chloro-3 methyl-5-isothiazolyl)-6-(2,2,2-trifluoroethoxy)-3-pyridineacetamide.
The compounds of formula (1) may exist in different geometric or optical isomers or tautomeric forms. This invention covers all such isomers and tautomers and mixtures thereof in all proportions.
When present, optional substituents on alkylene, alkenylene or alkynylene moieties include, subject to valency constraints, one or more of halogen, C,-6alkyl,C,-6haloakl,C,-6 cyanoalkyl, C,-6alkoxy(C,,) alkyl, C,, alkoxy, cyano, =0, =NW' and =CWR3', wherein R" is C,, alkyl, CI, haloalkyl, OW6 or W'WN; where W4 and WI are, independently, hydrogen, CI-6alkyl, Cl.6alkoxy,CI-6haloalkyl, cyano,CI-6alkoxycarbonyl, CI-6 alkylcarbonyl or WIWON; R36 is C,-6alkyl, C,-6haloalkyl or phenyl(CI-2)akl; W 7 and WI are, independently, hydrogen, CI-8 alkyl,C3-,cycloalkyl,C2-6alkenyl(CI-6)alkyl, C2-6 a'kYnY'(CI-6)a'kY'l C2-6 haloalkyl, CI-6alkoxy(CI-6)alkyl, CI-6alkoxycarbonyl(Cl-6)alkyl, carboxy(CI-6)alkyl or phenyl(C,-2)alkyl or R" and R38 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C1_6alkyl groups; R" and W' are, independently, hydrogen,C1-8alkyl, C3-7 cycloalkyl, C2-6alkenyl(CI-6)alkyl,C2-6aUcynyl(CI-6)a&y'I C2-6haloalkyl, CI-6alkoxy(C, jalkyl, Cj_6alkoxycarbonyl(C,_6)a1kyl, carboxy(C,-6)alkyl or phenyl(C.-2)alkyl; or W9 and R 40 together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S io and which may be optionally substituted by one or two C,-6alkyl groups.
Each alkyl moiety is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. When present, the optional substituents on alkyl include one or more of halogen, nitro, cyano, H02C, C1_6alkoxy (itself optionally substituted by C1_6alkoxy), aryl(C14) alkoxy, CI-6alkylthio, C,-6alkylcarbonyl, CI-6alkoxycarbonyl, CI-6alkylaminocarbonyl, di(C,-6alkyl)aminocarbonyl, optionally substituted phenyl, heteroaryl, aryloxy, arylcarbonyloxy, heteroaryloxy, heterocyclyl, heterocyclyloxy, C3-1 CYCloalky" C3-7 cycloalkyloxy,C5-7cycloalkenyl, CI-6alkylsulfonyl, CI-6alkylsulfinyl, tri(C,4)alkylsilyl, aryldi(C,4)alkylsilyl, (C14)alkyldiarylsilyl and triarylsilyl.
Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (LE)- or (z)-configuration.
Examples are vinyl, allyl and propargyl. When present, the optional substituents on alkenyl or alkynyl include one or more of halogen, aryl and C3-7 CYC'Oalkyl, In the context of this specification acyl is optionally substituted C,-6alkylcarbonyl (for example acetyl), optionally substituted C2-6alkenylcarbonyl, optionally substitutedC2-6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroary1carbonyl.
Halogen is fluorine, chlorine, bromine or iodine.
Haloalkyl groups are alkyl groups which are optionally substituted with one or more of the same or different halogen atoms and are, for example, CF3,CF2C'ICF3CH2 or CHF2CH2' Aryl includes naphthyl, anthracyl, fluorenyl and indenyl but is preferably phenyl.
The term heteroaryl refers to an aromatic ring containing up to 10 atoms including one or more heteroatoms (preferably one or two heteroatoms) selected from 0, S and N. Examples of such rings include pyridine, pyrimidine, furan, quinoline, quinazoline, pyrazole, 5 thiophene, thiazole, oxazole and isoxazole.
The terms heterocycle and heterocyclyl refer to a non-aromatic ring containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from 0, S and N. Examples of such rings include 1,3-dioxolane, tetrahydrofuran and morpholine. It is preferred that heterocyclyl is optionally substituted by C,-6alkyl.
Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl. The optional substituents for cycloalkyl include halogen, cyano and CI-3alkyl.
Cycloalkenyl includes cyclopentenyl and cyclohexenyl. The optional substituents for cycloalkenyl includeCI-3alyl, halogen and cyano.
Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups.
For substituted phenyl moieties, heterocyclyl and heteroaryl groups it is preferred that one or more substituents are independently selected from halogen,C,-6alkyl, C1_6 haloalkyl, C,-6alkoxy(C,.,6)alkyl, C, alkoxy, C,-6haloalkoxy, CI-6alkylthio, CI-6haloalkylthio, C,_6 alkylsulfinyl, C,-6haloalkylsulfinyl,CI-6akisulfonyl, C1, haloalkylsulfonyl,C2-6alkenyl, C2-6haloalkenyl,C2-6alkynyl,C3-7cycloalkyl, nitro, cyano, C02H, C,-6 alkylcarbonyl,C,-6 alkoxycarbonyl, R"R2N or eeNC(O) wherein W', R42, W, and R44are, independently, hydrogen orC,-6akl.
It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or sevenmembered heterocyclic ring which may contain one or two ftirther hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C,, alkyl groups. When heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two (C,.6)alkyl groups.
Preferably A is CH2,CH(CH3), -C(O) or CH20, even more preferably CH2.
Preferably J and L are independently CR.
M is preferably N(R")C(=Y), where N is the atom of attachment to the isothiazole ring.
Each R' group is preferably independently chosen from halogen,C,-6alkyl,C2.6 alkenYl, C2-6 alkynyl, C,-6cyanoalkyl, C,-6haloalkyl, C,-6alkoxy, CI-6haloalkoxy, CI-6 alkylthio, CI-6haloalkylthio,C3.6cycloalkyl,C3-7cycloalkyl(CI4)alkyl, CI-6alkoxy(C,-6)alkyl, cyano, nitro or SF,; m is an integer from 0 to 2; Preferably each Wis C,-, alkyl, CI-8haloalkyl,CI-8cyanoalkyl,C3-7cycloalkyl,C 1-3 alkyl(C3-7)cycloalkyl,CI-6alkoxy (CI-6) alkyl, heterocyclic (optionally substituted by halo, nitro, cyano, Cl-, alkyl, CI-6haloalkyl, CI-6alkoxy or CI-6haloalkoxy) or R2'R2N where W' and W' are independently C,., alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C,-6alkyl groups.
n is preferably 1-3.
R" is preferably hydrogen, CI-10 alkyl, benzyloxymethyl, benzoyloxymethyl, C,-6alkoxy (CI-6)a'kY" C2-6alkenyl(C,,)alkyl (especially allyl),C2_6aIkynyl(Cj_6)aIkyI (especially propargyl), CI-10 alky1carbonyl or CI-10 alkoxycarbonyl; Y is preferably 0 or S.
It is more preferred that M is NR"C(=O), most preferably NHC(=O).
One preferred group of compounds is a compound of formula (IA):
(R 1)m '_ N' 0 (R 3)n S N (IA) H N wherein, each R' group is independently halogen, C,, alkyl, C,-6alkenyl,C2, alkynyl, CI-6cyanoalkyl, C,-6haloalkyl, CI-6alkoxy, CI-6haloalkoxy, C,-6alkylffiio, CI-6haloalkylthio, C3-6cycloalkyl,C3-7cycloalkyl(CI4)alkyl, CI-6alkoxy(CI-6)alkyl, cyano, nitro or SF5; m is an integer from 0 to 2; Each W group is independently selected from C,-, alkyl, C1-8 haloalkyl, CI-8 eYanoalkyl, CM cycloalkyl, C,-3 alkyl (C3-7) cycloalkyl, C,-6 alkoxy (C,-6) alkyl, heterocyclyl (optionally substituted by halo, nitro, cyano, CI-6 alkyl, CI-6 haloalkyl, CI-6 alkoxy or CI-6 haloalkoxy) or W'W9N where W'andR" are independently C, alkyl or together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C,_6 alkyl groups. n is preferably 1-3.
The compounds in the following Tables illustrate compounds of the invention. Table 1 provides compounds of formula (IA) wherein the point of attachment is to the 2- position of the pyridine ring and (R). and are as defined in the Table.
3 n (R'),,, N' 0 S NiJN' H TABLE 1
Compound R. Wn No.
1 3-Me, 4-CI 6-CI 2 3-Me, 4-Cl 6-Et 3 3-Me, 4-CI 6-OMe 4 3-Me, 4-CI 6-(4-fluorophenoxy) 3-Me, 4-CI 6-(2',2'-dimethylpropoxy) 7 3-Me, 4-CI 5-OMe 8 3 -Me, 4-Cl 4-CI 9 3-Me, 4-CI 4-OMe 3-Me, 4-CI 4-phenoxy Table 2 provides compounds of formula GA) wherein the point of attachment is to the 3position of the pyridine ring and (R'). and R' are as defined in the Table.
3 (R)m N N H TABLE2
Compound Win No.
11 3-Me, 4-Cl OMe 12 3-Me, 4-Cl O-nPr 13 3-Me, 4-Cl Phenoxy 14 3 -Me, 4-Cl 2',2'-Dimethylpropoxy 3-Me, 4-Cl 2'-Methoxyethoxy Table 3 provides compounds of formula (IA) wherein the point of attachment is to the 4position of the pyridine ring and (R'). and W are as defined in the Table.
TABLE3 (R)m 0 N N, Z1111111 R 3 H Compound R'm No.
16 3-Me, 4-Cl OMe 17 3-Me, 4-Cl F 18 3-Me, 4-Cl O-iPr -lo- Compound Rlm No.
19 3-Me, 4-Cl 2',2'-dimethylpropoxy 3-Me, 4-Cl phenoxy 21 3-Me, 4-CI 2'-methoxyethoxy 22 3-Me, 4-Cl 2'-methylallyloxy Table 4 provides 5-pyrimidinyl compounds of formula (1) wherein J is CH, L is N, M is NH-C(O), A is CH2and (R'),,, and (R3),, are as defined in the Table.
(R)m 0 N) N' N S N H TABLE4
Compound Rlm R3n No.
23 3-Me, 4-CI 2-tBu 24 3-Me, 4-Cl 2-phenyl 3 -Me, 4-Cl 2-OMe 26 3-Me, 4-Cl 2-phenoxy Other Examples of compounds of formula (I) are Compound 27 C1 0 NY'N H Compound 28 C1 0 0 U S\ N 'IN' H Compound 29 ci 0 S 1 N 7N' C I H Compound 30 C1 0 N t( 'a' S N H The compounds of the invention may be made in a variety of ways. For example the compounds of formula (1) where M is N(R")C(=Y), where W1 is H and Y is 0, A is CH21 and J=L=CR, where W is as defmed above, may be made by reacting a compound of formula (II) with a compound of formula (III) preferably in the presence of a known coupling agent such as 1,3-dicyclohexylcarbodiimide (DCQ or 1-(3-dimethylaniinopropyl)-3ethylcarbodiimide. Alternatively compound of formula (111) may be first converted to an acid chloride, anhydride or activated acid derivative suitable for reaction with an amine to forrn an amide. Such procedures are well known and are described, for example in J. March, Advanced Organic Chemistry, Third Edition, John Wiley and Sons, New York, 1985, pps 370-376 and references therein. The reaction may be carried out in a solvent such as dichloromethane or toluene at a temperature of -20'C to 150 C, optionally in the presence of a catalyst such as 4-dimethylaminopyridine (DMAP) for 1 to 24 hours.
Alternatively compounds of formula (1) where M is N(R")C(=Y), where R" is H and Y is 0, A is CH., and J=L=CR, where R' is as defined above, can be made by direct reaction of compounds of formula (IV) with compounds of formula (11) in the presence of a alkali metal alkoxide such as sodium methoxide in a suitable solvent such as THE (R 3)" 0 L (R 3 HOj 0 n j N,' L S N H2 N N S N H N Carbodflmide/ DMAP (1) NaOCH (R 0 (R')n J L 3 m THF/RT N, N!JN5r'j N,S'NI-12 S H (11) alkylO'O J'Z' L (1) N (IV) Compounds of formula (IV) may be prepared from compounds of formula (V) by reaction with a strong base such lithium diisopropylamide at a low temperature such as -78'C in a suitable solvent such THF, followed by addition of a dialkylcarbonate such as dimethyl lo carbonate, and then warming the reaction mixture to room temperature.
Compounds of formula (IV) where alkyl is for example methyl or ethyl, can also be prepared from compounds of formula (VI), where hal is chlorine, bromine or iodine, by reaction with dialkyhnalonates of formula (VII) in the presence of a base such potassium tbutoxide, and a palladium catalyst such palladium acetate, and a phosphine ligand such as trit-butylphosphine, under an inert atmosphere, and in a suitable dry solvent such as tetrahydrofuran. Heating compounds of formula (VIII) in dimethylsulphoxide at reflux in the presence of a small amount of water, or an alkali metal salt such as lithium chloride, then gives compounds of formula (IV). Alternatively compounds of formula (IV) can be produced directly by reacting alkyl, trialkylsilyl malonate of formula (IX) with compounds of formula (VI) in the presence of a base such as potassium butoxide and a palladium catalyst such as palladuirn acetate and a phosphine ligand such as n-t-butylphosphine under an inert atmosphere and in a suitable dry solvent such as tetrahydrofuran, followed by work-up with a weak aqueous acid such as dilute hydrochloric acid.
3 (R 3 (R)n JZ, 0 n j L LIDAff HF/ (alkylo)2CO L CH'.- 'j alkylO 3 N' -.' M (IV) 0 Oalkyl (2)H+/H20 0 Otrialkylsilyl DMSO/H 0 (IX) 2 Base/Pd(OAc)2/ reflux trialkylphosphine 0 (R 3)" Oalkyl (R)n L (VI 1) L Hal: 0 Oalkyl alkylO N -- --31. N-) Base/Pd(OAC)2/. ? (VI) trialkylphosphine alkylO 0 (Vill) Compounds of formula (V) and (VI) are available commercially or can be made by standard methods well known in the literature.
Compounds of formula (XVII) are particular examples of compounds of formula (I), where M = N(R")C(=Y), where R" is H and Y is 0, A= CH21 J= CR, and L N.
alkylO 0 OalkyL--- Na/PhMeM IN 0 OH Oalkyl 11- HCOOalkyl aIkYIO i---- (X) 0 cat. alkylOH 0 (XI) 56 HN Y R 56 NC (X11) H 2./ Na/alkylCOH N R 56 N R 56 0 r POC13 NH alkylO i-- PhMe alky[O (XIII) 0 CI (XIV) H2/Pd/C Et3N/PhMe 0 N Y R 56 NaOH/H20IEtOH am- 0 NY R 56 N alky[O" HO" (XV) (XVI) (R56),,_/, DCC/CH2C'2/ N'K DMAP S, NH 2 (11) (R 56)111 NyR56 S 1 N H (XVII) Compounds of formula (XVII) can be prepared from compounds of formula (XVI) by reaction with compounds of formula (II), with a condensing agent such as DCC and in the presence of DMAP in a suitable solvent such as dichloromethane. Compounds of formula (XVI) are made by hydrolysing compounds of formula (XV) with aqueous alkali such as sodium hydroxide with a co-solvent such as ethanol. Compounds of formula (XV) are made by hydrogenolysis of compounds of formula (XIV) with hydrogen gas over a suitable catalyst such as palladium on carbon, in the presence of a base such as triethylamine, in a solvent such as toluene. Compounds of formula (XIV) can be made from compounds of formula (XIII) by reaction with a reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene. Compounds of formula (Mll) are made by condensation of an amidine of general formula (XII) with a compound of general formula (M) in the presence of a base, such as a sodium alkoxide made by reaction of sodium metal with an alcohol. Compounds of general formula (XI) can be prepared by reaction of a succinate diester of general formula (X-) with an alkyl formate, in the presence of a base such as sodium, in a suitable solvent such as toluene with a catalytic amount of an alcohol, such as ethanol or io methanol.
Compounds of formula (XXII) are particular examples of compounds of formula (I), where M = N(W')C(=Y), where R" is H and Y is 0, A= CH2, J= CR, and L = N.
0 0 0 R 56 R 56 alkyK)-Oalkyl (XVI 11) POC'3/PhMe 0 N INI NH 0 N)'NH I R 5'r-'KNH2 Na/EtOH alkyIOIAO alkyjo CI (XII) (XIX) (XX) HPd/C Et3N/PhMe R 56 R 56 NaOCHJHF/RT -:k 0 N N N al 0 N N alkylO.-k S N)t"I H (XXI) NS ' NH2 (XXII) Compounds of formula (=I) can be prepared from compounds of formula (M) by reacting them with compounds of formula (II), in the presence of an alkali metal alkoxide such as sodium methoxide in a suitable solvent such as THE Compounds of formula (=) can be made by hydrogenolysis of compounds of formula (,NX) with hydrogen gas over a suitable catalyst such as palladium on carbon, in the presence of a base such as triethylamine, in a solvent such as toluene. Compounds of formula (XX) can be made from compounds of formula (XIX) by reaction with a reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene. Compounds of formula (XIX) are made by condensation of a compound of general formula (XII) with a compound of general formula (XVIII) in the presence of a base, such as a sodium alkoxide made by reaction of sodium metal with an 5 alcohol. Compounds of general formula (XVIII) are available commercially.
The compounds of formula (1) can be used to combat and control infestations of insect pests such as Lepidoptera, Diptera, Herniptera, Thysanoptera, Orthoptera, Dictyoptera, Coleoptera, Siphonaptera, Hymenoptera and Isoptera and also other invertebrate pests, for example, acarine, nematode and mollusc pests. Insects, acarmies, nematodes and molluscs io are hereinafter collectively referred to as pests. The pests which may be combated and controlled by the use of the invention compounds include those pests associated with agriculture (which term includes the growing of crops for food and fibre products), horticulture and animal husbandry, companion animals, forestry and the storage of products of vegetable origin (such as fi-uit, grain and timber); those pests associated with the damage of man-made structures and the transmission of diseases of man and animals; and also nuisance pests (such as flies).
Examples of pest species which may be controlled by the compounds of formula (1) include: Myzus persicae (aphid), Aphis gossypii (aphid), Aphisfabae (aphid), Lygus spp. (capsids), Dysdercus spp. (capsids), Nilaparvata lugens (planthopper), Nephotettixc incticeps (leafhopper), Nezara spp. (stinkbugs), Euschistus spp. (stinkbugs), Leptocorisa spp. (stinkbugs), Frankliniella occidentalis (thrip), Thrips spp. (thrips), Leptinotarsa decemlineata (Colorado potato beetle), Anthonomus grandis (boll weevil), Aonidiella spp. (scale insects), Trialeurodes spp. (white flies), Bemisia tabaci (white fly), Ostrinia nubilalis (European corn borer), Spodoptera littoralis (cotton leafWorm), Heliothis virescens (tobacco 25 budworm), Helicoverpa armigera (cotton bollworm), Helicoverpa zea (cotton bollworm), Sylepta derogata (cotton leaf roller), Pieris brassicae (white butterfly), Plutella xylostella (diamond back moth), Agrotis spp. (cutworms), Chilo suppressalis (rice stem borer), Locusta_ migratoria (locust), Chortiocetes terminifera (locust), Diabrotica spp. (rootworms), Panonychus u1mi (European red mite), Panonychus citri (citrus red mite), Tetranychus 30 urticae (two-spotted spider mite), Tetranychus cinnabarinus (carmine spider mite), Phyllocoptruta oleivora (citrus rust mite), Polyphagotarsonemus latus (broad mite), Brevipalpus spp. (flat mites), Boophilus microplus (cattle tick), Dermacentor variabilis (American dog tick), Ctenocephalidesfelis (cat flea), Liriomyza spp. (leafminer), Musca domestica (housefly), Aedes aegypti (mosquito), Anopheles spp. (mosquitoes), Culex spp. (mosquitoes), Lucillia spp. (blowflies), Blattella germanica (cockroach), Periplaneta americana (cockroach), Blatta orientalis (cockroach), termites of the Mastotennitidae (for example Mastotermes spp.), the Kalotermitidae (for example Neotermes spp.), the Rhinotermitidae (for example Coptotermesformosanus, Reficulitermesflavipes, R. speratu, R. virginicus, R. hesperus, and R. santonensis) and the Termitidae (for example Globitermes sulphureus), Solenopsis geminata (fire ant), Monomorium pharaonis (pharaoh's ant), Io Damalinia spp. and Linognathus spp. (biting and sucking lice), Meloidogyne spp. (root knot nematodes), Globodera spp. and Heterodera spp. (cyst nematodes), Pratylenchus spp. (lesion nematodes), Rhodopholus spp. (banana burrowing nematodes), Tylenchulus spp.(citrus nematodes), Haemonchus contortus (barber pole worm), Caenorhabditis elegans_ (vinegar eelworm), Trichostrongylus spp. (gastrointestinal nematodes) and Deroceras is reticulatum (slug).
The compounds of formula (I) are also active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae (Magnaporthe grisea) on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striffiormis and other rusts on wheat, Puccinia hordei, Puccinia striffibrinis and other rusts on barley, and rusts on other hosts (for example turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants); Erysiphe cichoracearum on cucurbits (for example melon); Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts, such as Sphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerothecafuliginea) on cucurbits (for example cucumber), Leveillula taurica on tomatoes, aubergine and green pepper, Podosphaera leucotricha on apples and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Mycosphaerella graminicola (Septoria tritici) and Phaeosphaeria nodorum (Stagonospora nodorum or Septoria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (for example wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora spp. 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 (for example carrots), oil-seed rape, apples, tomatoes, potatoes, cereals (for example wheat) and other hosts; Venturia spp. (including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (for example wheat) and tomatoes; Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat, cucurbits 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; Stemphylium spp. (Pleospora spp.) on apples, pears, onions and other hosts; summer diseases (for example bitter rot (Glomerella cingulata), black rot or frogeye leaf spot (Botryosphaeria obtusa), Brooks fruit spot (Mycosphaerellapomi), Cedar apple rust (Gymnosporangiumjuniperi-virginianae), sooty blotch (Gloeodespomigena), flyspeck (Schizothyrium pomi) and white rot (Botryosphaeria dothidea)) on apples and pears; 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. (including Pythium ultimum) 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 spp. on various hosts such as wheat and barley, peanuts, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, potatoes, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Gibberellafujikuroi on rice; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laefisariafuciformis on turf; Mycosphaerella spp. on bananas, peanuts, citrus, pecans, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pears, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Verticillium spp. on a range of hosts including hops, potatoes and tomatoes; 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., Urocystis spp., Tilletia spp. and Clavicepspurpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet, barley and other hosts; post-harvest diseases particularly of fruit (for example Penicillium digitatum, Penicillium 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, Pseudopeziza tracheiphila and Stereum hirsutum; other pathogens on trees (for example Lophodermium seditiosum) or lumber, notably Cephaloascusfragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and Rmgal vectors of viral diseases (for example Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV) and Polymyxa betae on sugar beet as the vector of rhizomania).
A compound of formula (I) may move acropetally, basipetally or locally in plant tissue to be active against one or more ftmgi. Moreover, a compound of formula (I) may be volatile enough to be active in the vapour phase against one or more fungi on the plant.
The invention therefore provides a method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (I), to a pest, a locus of pest, or to a plant susceptible to attack by a pest, and a method of combating and controlling fungi which comprises applying a fimgicidally effective amount of a compound of formula (I), or a composition containing a compound of formula (1), to a plant, to a seed of a plant, to the locus of the plant or seed, to soil or to any other growth medium (for example a nutrient solution). The compounds of formula (1) are preferably used against insects, acarines, nematodes or:ftmgi.
The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes protectant, curative, systemic, eradicant and antisporulant treatments.
As fungicides, the compounds of formula (1) are preferably used for agricultural, horticultural and turfgrass purposes in the form of a composition.
In order to apply a compound of formula (I) as an insecticide, acaricide, nematicide or molluscicide to a pest, a locus of pest, or to a plant susceptible to attack by a pest, or, as a fungicide to a plant, to a seed of a plant, to the locus of the plant or seed, to soil or to any other growth medium, a compound of formula (1) is usually formulated into a composition which includes, in addition to the compound of formula 0), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals which are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably I to 85%, for example 5 to 60%, of a compound of formula (1). The composition is generally io used for the control of pests or ftingi such that a compound of formula (1) is applied at a rate of from 0. 1 g to I Okg per hectare, preferably from I g to 6kg per hectare, more preferably from I g to I kg per hectare.
When used in a seed dressing, a compound of formula (1) is used at a rate of 0. 000 1 g to lOg (for example 0.001g or 0.05g), preferably 0.005g to 10g, more preferably 0.005g to 4g, per kilogram of seed.
In another aspect the present invention provides an insecticidal, acaricidal, nernaticidal, molluscicidal or fungicidal composition comprising an insecticidally, acaricidally, nematicidally, molluscicidally orfangicidally effective amount of a compound of formula (1) and a suitable carrier or diluent therefor. The composition is preferably an insecticidal, acaricidal, nematicidal or fungicidal composition.
In a still ftu-ther aspect the invention provides a method of combating and controlling pests or fungi at a locus which comprises treating the pests or fungi or the locus of the pests or:ftmgi with an insecticidally, acaricidally, nematicidally, molluscicidally or fungicidally effective amount of a composition comprising a compound of formula (1). The compounds of formula (1) are preferably used against insects, acarines, nematodes or fungi.
The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EQ, dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (Nffi), suspension concentrates (SQ, aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula M.
Dustable powders (DP) may be prepared by mixing a compound of formula (1) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
Soluble powders (SP) may be prepared by mixing a compound of formula (1) with one or mbre water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
Wettable powders (VVT) may be prepared by mixing a compound of formula (1) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or from pre-formed blank granules by absorbing a compound of formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatornaceous earths or ground com cobs) or by adsorbing a compound of formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (1) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
Emulsifiable concentrates (EQ or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable io organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfiiryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl. amides of fatty acids (such as Cs-CIO fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (1) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70'C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (I) is present initially in either the water or the solvent/SFA blend. Suitable solvents for use in MEs include those hereiribefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-water emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I). SCs may be prepared by ball or bead milling the solid compound of formula (1) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of formula (1) may be dry milled and added to water, containing agents hereinbefore described, Io to produce the desired end product.
Aerosol formulations comprise a compound of formula (1) and a suitable propellant (for example n-butane). A compound of formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
A compound of formula (1) may be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula Q) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula Q) and they may be used for seed treatment. A compound of formula (1) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.
A composition may include one or more additives to improve the biological performance of the composition (for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of formula (1)). Such additives include surface active agents, spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (1)).
A compound of formula (1) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP, VVT, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed i o (for example a mineral oil or a filin-fonning barrier).
Wetting agents, dispersing agents and emulsifying agents may be surface SFAs of the cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butyinaphthalene sulphonate and mixtures of sodium diisopropyl- and tri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octyleresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).
A compound of formula (I) may be applied by any of the known means of applying pesticidal or fungicidal compounds. For example, it may be applied, formulated or unformulated, to the pests or to a locus of the pests (such as a habitat of the pests, or a growing plant liable to infestation by the pests) or to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
A compound of formula (1) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (1) (for example 0.000 1 to 10%, by weight) depending upon the purpose for which they are to be used.
A compound of formula (1) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types include granules of fertiliser. The mixtures suitably contain up to 25% by weight of the compound of formula (1).
The invention therefore also provides a fertiliser composition comprising a fertiliser and a compound of formula (I).
The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal, insecticidal, nernaticidal or acaricidal activity.
By including another fungicide, the resulting composition may have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (1) alone. Further the other fungicide may have a synergistic effect on the fungicidal activity of the compound of formula 0).
The compound of formula (1) may be the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (I); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition. Examples of suitable pesticides include the following:
a) Pyrethroids, such as permethrin, cypermethrin, fenvalerate, esfenvalerate, deltamethrin, cyhalothrin (in particular lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish safe pyrethroids (for example ethofenprox), natural pyrethrin, tetramethrin, 2:5 s-bioallethrin, fenfluthrin, prallethrin or 5-benzyl-3-furylmethyl-(]E)-(IIZ,3S)-2,2-dimethyl3-(2-oxothiolan-3-ylidenemethyl)cyclopropane carboxylate; b) Organophosphates, such as, profenofos, sulprofos, acephate, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiometon, fenamiphos, monocrotophos, profenofos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phosalone, terbufos, fensulfothion, fonofas, phorate, phoxim, pirimiphos-methyl, pirimiphos-ethyl, fenitrothion, fosthiazate or diazinon; c) Carbamates (including aryl carbarnates), such as pirimicarb, triazamate, cloethocarb, carbofuran, furathiocarb, ethiofencarb, aldicarb, thiofurox, carbosulfan, bendiocarb, fenobucarb, propoxur, methomyl or oxamyl; d) Benzoyl ureas, such as diflubenzuron, triflumuron, hexaflumuron, flufenoxuron or 5 chlorfluazuron; e) Organic tin compounds, such as cyhexatin, fenbutatin oxide or azocyclotin; f) Pyrazoles, such as tebufenpyrad and fenpyroximate; g) Macrolides, such as averniectins, or milbernycins, for example abamectin, emamectin benzoate, ivermectin, milbernycin, spinosad or azadirachtin; h) Hormones or pheromones; i) Organochlorine compounds such as endosulfan, benzene hexachloride, DDT, chlordane or dieldrin; j) Amidines, such as chlordiniefonn. or amitraz; k) Fumigant agents, such as chloropicrin, dichloropropane, methyl bromide or metarn; 1) Chloronicotinyl compounds such as imidacloprid, thiacloprid, acetamiprid, niteripyram or thiamethoxam; m) Diacylhydrazines, such as tebufenozide, chrornafenozide or methoxyfenozide; n) Diphenyl ethers, such as diofenolan or pyriproxifen; o) Indoxacarb; p) Chlorfenapyr; or q) Pymetrozme.
In addition to the major chemical classes of pesticide listed above, other pesticides having particular targets may be employed in the composition, if appropriate for the intended utility of the composition. For instance, selective insecticides for particular crops, for example sternborer specific insecticides (such as cartap) or hopper specific insecticides (such as buprofezin) for use in rice may be employed. Alternatively insecticides or acaricides specific for particular insect species/stages may also be included in the compositions (for example acaricidal ovo-larvicides, such as clofentezine, flubenzimine, hexythiazox or tetradifon; acaricidal motilicides, such as dicofol or propargite; acaricides, such as bromopropylate or chlorobenzilate; or growth regulators, such as hydramethy1non, cyromazine, methoprene, chlorfluazuron or diflubenzuron).
Examples of ftmgicidal compounds which may be included in the composition of the invention are (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxyiminoacetamide (SSF-129),4-bromo-2-eyano-NV-dimethyl-6-trifluoromethylbenzimidazole- I -sulphonamide, (x-[N-(3-chloro-2,6-xylyl)-2-methoxyacetaniido]-y-butyrolactone, 4-chloro 2-cyano-NN-dimethyl-5-p-tolylimidazole-1-sulfonamide (IKF-916, cyamidazosulfamid), 3-5-dichloro-N-(3-chloro- I -ethyl- I -methyl-2-oxopropyl)-4-methylbenzamide (RH-7281, zoxamide), N-allyl-4,5,-dimethyl-2-trimethylsilylthiophene-3-carboxamide (MON65500), N (1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy)propionamide (AC382042), N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, acibenzolar (CGA245704), alanycarb, io aldimorph, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, biloxazol, bitertanol, blasticidin S, bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim.
chlorhydrate, carboxin, carpropamid, carvone, CGA41396, CGA41397, chinomethionate, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate and Bordeaux mixture, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide 1,1'-dioxide, dichlofluanid, diclomezine, dicloran, diethofencarb, difenoconazole, difenzoquat, diflumetorim, 0,0-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole, dinocap, dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, ethirimol, ethyl(Z)-N-benzyl-N([methyl(methyl-thioethylidenewninooxycarbonyI)amino]th io)- fenfuram, fenhexamid (KBR2738), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin. hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos, iprodione, iprovalicarb (SZX0722), isopropanyl butyl carbarnate, isoprothiolane, kasugamycin, kresoxim-methyl, LYI 86054, LY211795, LY248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil, metalaxyl, metconazole, metiram, metirain-zinc, metominostrobin, myclobutanil, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, picoxystrobin (ZAl 963), polyoxin D, polyram, probenazole, prochloraz, procyrnidone, propamocarb, propiconazole, propineb, propionic acid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate, 5 quinoxyfen, quintozene, sipconazole (F- 15 5), sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamid, 2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram, timibenconazole, toiclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin (CGA279202), triforine, triflurnizole, io triticonazole, validamycin A, vapam, vinclozolin, zineb and ziram.
The compounds of formula (1) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-bome or foliar fungal diseases.
Examples of suitable synergists for use in the compositions include piperonyl butoxide, sesamex, safroxan and dodecyl imidazole.
Suitable herbicides and plant-growth regulators for inclusion in the compositions will depend upon the intended target and the effect required.
An example of a rice selective herbicide which may be included is propanil. An example of a plant growth regulator for use in cotton isPIXTM.
Some mixtures may comprise active ingredients which have signiflcantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional fonnulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoernulsion (SE) formulation.
The invention is illustrated by the following Examples, EXAMPLE I
This example illustrates the preparation of compound 4 in Table 1 Step I Diisopropylarnine (I. 09g, 10. 8 x I O'mol) was dissolved in dry THF (10 ml) and cooled to O'C with an ice/salt bath, under nitrogen. N-butyl lithium ( 2. OM in pentanes, 5.42ml, 10. 8 x I 0-'mol) was then added dropwise and the reaction mixture stirred for a further 3 0 minutes at OOC. 2-Methyl-6-(4-fluorophenoxy)pyridine.(2. 00g, 9.8 x 1 0-'mol) was dissolved in dry THF (25 ml) and cooled to -78'C. To this was added the above solution dropwise ensuring the temperature did not exceed -65'C. The reaction mixture was stiffed at -78'C for 30 io minutes before adding the dimethylcarbonate and allowing to warm to O'C. Aqueous ammonium chloride was added and the reaction mixture extracted into ethyl acetate(O).
The ethyl acetate layer was washed with brine, dried over magnesium sulphate, filtered and the solvent removed in vacuo to give 2.23g: of a yellow gum. Purification by flash column chromatography on sorbsil 40-60, eluting with 1:6 ethyl acetate:hexane gave methyl (6-(4 fluorophenoxy)pyrid-2-yl)acetate (0.270g) as a yellow oil.
1H NNM (CDC13) 8 ppm: 3.68(s,3H); 3.73 (s,2H); 6.71 (d, I H); 7.00(d, I H); 7.08(m,4H); 7.64(t, I H). MS MW 262 amu Step 2 The product from Step I ( 0.270g, 1.03 x I 0-3mol) was dissolved in methanol (5ml). Sodium hydroxide (0.042g, 1.03xlO'mol) was added and the reaction mixture stirred at room temp for 3 hours, then left to stand overnight. Water was added and the reaction mixture washed with ethyl acetate (0). Toluene was added to the aqueous layer and this was concentrated in vacuo to give (6-(4-fluorophenoxy(pyrid-2-yl)acetic acid (0.225g) as a pale yellow solid.
111 NMR (D20) 5 ppm: 4.70(s,2H); 6.97(d,lH); 7.23(m,4H); 7.35(d,IH); 8.10(t,IH).
Step 3 5-Amino-4-chloro-3-methylisothiazole(O. I 18g, 7.9xI O'mol), the product from Step 2 (0.225g,9.IxIO-'mol) and 4-dimethylaminopyridine(O.195g,1.6xlO-'mol) were dissolved in 5ml dichloromethane and stirred at room temperature. 1,3-dicyclohexylcarbodiimide (0. 164g,7.9x I 04MOI) was then added in one portion. The reaction mixture was stirred at room temperature for 3 hours, then left to stand overnight. A solid precipitate was filtered off before diluting the filtrate with dichloromethane. The filtrate was then washed with aqueous ammonium chloride, followed by aqueous sodium carbonate, and then brine to give a yellow oil (0.240g). Purification by flash column chromatography on sorbsil 40-60 eluting with 1:3 ethyl acetate:hexane gave the title compound (0.085g) as a yellow gum.
H NMR (CDC13) 8 ppm: 2.39(s,31-1); 3.92(s,2H); 6.80(d,lH); 7.08(m,5H); 7.72(t,IH).
MS MH378 ainu EXAMPLE 2 This example illustrates the preparation of compound 16 in Table 3 Step 1 Diisopropylamine (1.85g, 18 x I 0-'mol) was dissolved in dry THF (30 ml) and cooled to O'C with an ice/salt bath, under nitrogen. N-butyl lithium ( 2.OM in pentanes, 9.2ml, 18 x I O'mol) was then added dropwise and the reaction mixture stirred for a fin-ther 30 minutes at OOC before cooling to -78'C. 2-methoxy-4-methylpyridine(2.05g, 16 x I 0-'mol) was dissolved in (I Oml) dry THF and added to the above solution dropwise ensuring the temperature did not i o exceed -65'C. The reaction mixture was then stirred at -78'C for 30 minutes before adding the dimethy1carbonate (I ml) and stirring for a further 30 minutes before allowing to warin to O'C. Aqueous ammonium chloride was added and the reaction mixture extracted into ethyl acetate(x3). The ethyl acetate layer was washed with brine, dried over magnesium sulphate, filtered and the solvent removed in vacuo to give a brown gum (2.53g). Purification by flash column chromatography on sorbsil 40-60 eluting with 1:4 ethyl acetate:hexane gave methyl (2-methoxypyrid-4-yl)acetate (0.714 g) as a yellow oil.
1H NN4R (CDC13) 8 ppm: 3.59(s,2H); 3.72(s,3H); 3.93(s,3m; 6.68(s,IH); 6.81(d,lH); 8.12(d,IH).
MS N4H+ 182 amu Step 2 The product from Step I ( 0. 714g, 3.94 x I O'mol) was dissolved in methanol (20ml). Sodium hydroxide (0. 15 8g, 3.95x I 0-3mol) was added and the reaction mixture stirred at room temp for 4 hours, then left to stand overnight. The reaction mixture was concentrated in vacuo before dissolving in aqueous ammonium chloride. This was washed with dichloromethane (0). The aqueous layer was concentrated in vacuo and the solid stirred in ethyl acetate for 24 hours. The solid was filtered and the filtrate concentrated in vacuo to give (2-methoxypyrid-4-yl)acetic acid (0.209g) as a white solid.
H NMR (CDC13) 5 ppm: 3.62(s,2H); 3.94(s,3H); 6.69(s,IH); 6.83(dd,4H); 8.13(d,lH) MS ME' 168amu; M-H 166amu Step 3 5-Amino-4-chloro-3-methylisothiazole (0. 1 85g,1.25xlO-'mol), the product from step 2 (0.209g,1.25 xlO-'mol) and 4-dimethylaminopyridine(O.153g,1.25 xlO-'mol) were dissolved in dichloromethane (I Oml) and stirred at room temperature. 1,3-dicyclohexylearbodiimide (0.258g,1.25xlO'mol) was then added in one portion. The reaction mixture was stiffed at room temperature for 4 hours, then left to stand overnight. The precipitate was filtered, before diluting the filtrate with dichloromethane. The filtrate was then washed with aqueous ammonium chloride followed by brine, and then dried over magnesium sulphate, filtered and the solvent removed in vacuo to give a yellow solid (0.269g). Purification by flash column chromatography on sorbsil 40-60 eluting with 1:2 ethyl acetate:hexane gave the title compound (0.130g) as a yellow solid, m.p. 111-114'C.
'HNMR(CDCL3) 8ppm: 2.40(s,3H);3.83(s,2H);3.96(s,3H); 6.72(d,lH);6.87(d,lH); 8.21(d,IH); 8.28(bs,IH).
EXAMPLE 3
This example illustrates the preparation of compound 5 in Table 1.
6-(2,2'-Dimethylpropyloxy)-2-bromopyridine (0.717g, 2.95 xlO-'mol) was dissolved in dry toluene (10ml). Palladium acetate (0.33g, 0.15 xlO-'mol) was then added, followed by ethyl trimethylsilyl malonate (0.722g, 3.45 X10-3niol), then potassium t-butoxide (0.348g, 3.11 xl 0-'mol). Nitrogen gas was then bubbled through the solution for 30 minutes before adding 25 the tri-t-butyl phosphine (0.030g, 0.15 xlO-3mol). The reaction mixture was then heated at 90'C for 3 hours. The reaction mixture was then allowed to cool to room temperature. Aqueous ammonium chloride was added and this was extracted with ethyl acetate (0). The combined ethyl acetate layers were then washed with brine, dried over magnesium sulphate, filtered and the solvent removed in vacuo to give a yellow gum (0.90g). Purification by flash 30 column chromatography on sorbsil 40-60 gave ethyl [6-(2',2'-dimethylpropyloxy)pyrid-2yflacetate (0.072g) as a pale yellow solid.
H NMR (CDC13) 8ppm: 0.94(s,9H); 1.20(t,3H); 3.65(s,2H); 3.88(s,2H); 4.12(q,2H); 6.55(d,IH); 6.74(d,lH); 7.44(t,IH). 5 MS: MH' 252 amu.
EXAMPLE 4
This example illustrates the preparation of compound I I in Table 2.
Stepl 2-Methoxy-5-bromopyridine(O.37g, 1.96 xlO-'mol) was dissolved in dry toluene (6ml). Palladium acetate (0.033g, 0.15 xlO-'mol) was then added, followed by ethyl trimethylsilyl malonate (0.55ml, 2.7 X 1 0-3MOI), followed by potassium t-butoxide (0.265, 2.37 xlO'mol). Nitrogen gas was then bubbled through the solution for 10 minutes before adding the tri-tert15 butylphosphine(O.028g,0.113xlO'mol). The reaction mixture was then heated at 900C for 2hours. The reaction mixture was then allowed to cool to room temperature. Aqueous ammonium chloride was added and this was extracted with diethyl ether. The combined diethyl ether layers were then washed with brine, dried over magnesium sulphate, filtered and the solvent removed in vacuo to give a yellow oil (0.450g). Purification by flash column 20 chromatography on sorbsil 40-60, eluting with diethyl ether: hexane (1: 1) gave ethyl (2methoxy)pyrid-5-yl acetate (0.25g) as an oil. 'H NMR (CDC13) 8ppm: 1.25(t,3H); 3.5(s,2H); 3.95(s,3H); 4.15(q,2H); 6.7(d, 1 H); 7.55(dd,lH); 8.05(fd,IH).
Step2 A solution of the product from step 1 (0. 17g, 0.88 x 1 O'mol) in dry THF (5ml) was added dropwise to a mixture of potassium t-butoxide (0. 12g, 1. 1 x I O'mol) and 5-Amino-4-chloro3-methylisothiazole (0.12g, 0.88 XIO-3MOI) in dry THF (5ml), and the reaction stirred for 1 hour. The mixture was poured into water, extracted with diethyl ether, and the ethereal layer washed with aqueous ammonium chloride and dried over magnesium sulphate. The ether was evaporated to give an oil (0. 16g), which was purified by flash chromatography on sorbsil 40-60 to give the title compound as a solid (0. 12g), m.p. I I O'C.
H NMR (CDC13) 8ppm: 2.4 (s,3H), 3.8 (s,2H), 3.95 (s,3H), 6.80 (d,2H), 7.60 (dd, IH), 8.10 (d,M), 8.25 (bs, 1H).
EXAMPLE 5
This example illustrates the preparation of ethyl 2-phenoxypyrimidin-5-yl acetate Ethyl 2-phenoxy-5-bromopyrimidine (0.25g, 1 XI 0-3MOI) and palladium acetate (0.0 11 g, 0.05 io x I O'mol) were dissolved in dry toluene (3 ml) under nitrogen. Nitrogen gas was bubbled through the solution for 30 to 45 minutes before adding ethyl trimethylsilyl malonate (0.244g, 1.2 x 1 0-'mol) followed by potassium tert-butoxide (0. 1 17g, 1.05 x1 0-'mol) and tri tert-butyl phosphine (12.3 gl' 0.05 X10-3MOI). The mixture was degassed once more for 30 minutes and was then heated at 11 O'C until disappearance of the starting material. The reaction mixture was quenched by addition of water, extracted with diethyl ether (x2). The organic layer was washed with brine then dried over magnesium sulphate, filtered and the solvent removed in vacuo to give an orange oil (0.325g). This was purified by flash column chromatography on sorbsil (40-60) eluting with a mixture of ethyl acetate/hexane as a gradient from 1:4 to 1: 1, to give ethyl 2-phenoxypyrimidin-5-yl acetate (0. 173g) as a pale yellow solid.
1H NMR (CDC13): 8 ppm: 8.47 (s, 2H), 7.17-7.46 (m, 511), 4.15 (q, 2H, CH21), 3.56 (s, 2H), 1.26 (t, 3H) MS: MH: 259 amu EXAMPLE6
This example illustrates the preparation of compound 24 in Table 4.
Step 1 Sodium metal (0.6g, 26 xlO'mol) was dissolved in ethanol (90ml) at room temperature and stiffed at room temperature for 15 minutes. Benzamidine (4.0g, 26 xlO'mol) was added followed by a solution of ethyl 2-fonnylsuccinate (4.02g, 20 x I 0-'mol) dissolved in ethanol (I Oml). The suspension was heated at reflux. for 3 hours and then allowed to cool to room temperature. The reaction mixture was poured into water (1 50ml), precipitating a white solid, which was collected, washed with diethyl ether and dried by air suction to yield 2 phenyl-5-(ethoxycarbonylmethyl)-pyrimidin-4-one (2.2g), m.p. 164-1670C.
H NMR (CDC13) 5ppm: 1.25(t,3H); 3.55(s,2H); 4.2(q,2H); 7.55(m,3H); 8.1(s,IH); 8.2(m,2H).
Step 2 The product from step I (2.2g, 8.5 x I O-'mol) was suspended in toluene (50ml). Phosphorus oxychloride (1.5g 10 x I O'mol) was added dropwise to the stirring suspension, the reaction mixture heated at reflux for 2 hours, and allowed to cool to room temperature. The liquid was 15 decanted ftorn the reaction vessel and evaporated to yield a red oil. The crude oil was extracted with ethyl acetate and washed with saturated sodium carbonate solution and water, dried over magnesium sulphate and filtered. The solvent was removed in vacuo to give 1.6g of a red oil, which was purified by flash colurnn chromatography on sorbsil 40-60, eluting with diethyl ether to give ethyl 2-phenyl-4-chloropyrimidin-5-yl acetate as an oil (1.4g) 20 which crystallised m.p. 60-620C.
H NMR (CDC13) 8ppm: 1.25(t,3H); 3.8(s,2H); 4.3(q,2H); 7.5(m,3H); 8.4(s,IH); 8.65(m,2H).
Step 3 The product ftom. step 2 (1.2g, 4.34 x10-3mol) and triethylamine (1.2g, I I xlO'mol) were dissolved in toluene (12ml) and 5% palladium on carbon (0.5g, Johnson Matthey type 87L) added. The vessel was pressurised to 7.5 bar with hydrogen and the vessel left for 15 minutes. Stirring was started and the reaction heated slowly to 25'C. A slow uptake of hydrogen commenced immediately, and 65ml was used in the first 30 minutes. The reaction was left to run overnight. The reaction mixture was filtered, and the solvent removed in vacuo to give an oil. This was purified by flash column chromatography on sorbsil 40-60, eluting with diethyl ether:hexane (1: 1) to give ethyl 2-phenylpyrimidin-5-yl acetate as an oil (1.0g).
H NNM (CDC13) 8ppm: 1.25(t,3H); 3.65(s,2H); 4.2(q,2H); 7.5(m,3H); 8.4(m,2H); 8.75(s,2H).
Step 4 A solution of sodium hydroxide (0.2g, 5 XIO-3MOI) in water (3ml), was added to a stirring solution of the product from step 3 (1.0g, 4.1 x10-3mol) in ethanol (I 5ml) and stirred at room Io temperature for 2 hours. The solvent removed. in vacuo to give a white solid, which was treated with aqueous 2M hydrochloric acid. A white solid precipitated, which was extracted with ethyl acetate and washed with water. After drying over magnesium sulphate, the solution was filtered, evaporated in vacuo to give 2-phenylpyfimidin-5-yl acetic acid as a white solid (0.65g) m.p. I 88T.
1H NMR (CDC13) 8ppm: 3.65(s,2H); 7.5(m,3H); 8.4(m,2H); 8.75(s,2H).
Step 5 3-Methyl-4-chloro-5-aminoisothiazole (0.148g, I xlO'mol) and dicyclohexylcarbodiimide (0.206g 1 x I 0-3mol) was added to a stirring mixture of 4-dimethylaminopyridine (0. 122g, I xlO'mol) and the product from stage 4 (0.213g,l XIO-3MOI) in dichloromethane, and the reaction stirred for 2 hours at room temperature. The white solid that precipitated was filtered, washed with diethyl ether and discarded. The organic filtrates were combined and 25 evaporated to yield a solid. Purification by flash column chromatography on sorbsil 40-60, eluting with diethyl. ether gave the title compound (0. 1 56g). 'H NMR (CDC13) Sppm: 2.4 (s,2H); 3.9(s,2H); 7.5(m,3H); 8.45(m,2H); 8.8(s,2H); 9.0 (bs 1H). 30 EXAMPLE 7 This example illustrates the preparation of compound 27 Step 1 Sodium metal (2.4g, I 10 x I 0-'mol) was dissolved in ethanol (I 80ml) at room temperature and stirred at room temperature for 15 minutes. Benzamidine (12.0g, 100 xlO'mol) was added, followed by a solution of diethyl acetonedicarboxylate (17.0g, 100 xlO-'mol) in ethanol (20ml), and the suspension heated at reflux for 3 hours. The reaction mixture was allowed to cool to room temperature and then poured into water (I 50ml), precipitating a white solid, which was extracted into diethyl ether. The ethereal solution washed with water, dried over magnesium sulphate, filtered and evaporated in vacuo to give 2-phenyl-4 (ethoxycarbonyhnethyl)-pyrimidin-6-one (1 4.0g) as a buff solid m.p. 143 -145T.
H NNM (CDC13) 8ppm: 1.3(t,311); 3.65(s,2H); 4.25(q,2H); 6.4(s,H); 7.5(m,3H); 8.2(m,2H).
Step 2 The product from step I (5.0g, 19.4 X I 0-3MOI) was suspended in toluene (50ml) and 20 phosphorus oxychloride (5 ml) added dropwise to the stirring suspension. The reaction mixture was refluxed for 2 hours, and the reaction mixture allowed to cool to room temperature. The liquid was decanted and evaporated to yield a red oil, which was extracted with ethyl acetate, washed with saturated sodium carbonate solution and water, and dried over magnesium sulphate. The solution was filtered and evaporated in vacuo to give a red 25 oil (3.5g), which was purified by flash column chromatography on sorbsil 40-60, eluting with diethyl ether, to give ethyl 2-phenyl-4-chloropyri-tnidin-6-yI acetate (1.4g) as an oil. '11 NMR (CDC13) 8ppm: 13(t,311); 3.85(s,2H); 4.25(q,2H); 7.25 (s,H), 7.5(m,3H); 8.4(m,2H).
Step 3 The product from step 2 (3.5g, 11 XIO-3MOI) and triethylamine (2.2g, 22 x I 0-'mol) were dissolved in toluene (12 ml) and 5% palladium on carbon (0.5g, Johnson Matthey type 87L) added. The vessel was pressurised to 7.5 bar with hydrogen, left for 15 minutes and stirring started. The reaction was heated slowly to 25'C, and a slow uptake of hydrogen commenced immediately with 65 ml used in the first 30 minutes. The reaction was left to run overnight, the reaction mixture filtered and the solvent removed in vacuo to give an oil. This was purified by Rash column chromatography on sorbsil 40-60, eluting with diethyl ether:hexane (1: 1) to give ethyl 2-phenylpyrimidin4-yl acetate as an oil (2.2g).
1H NMR (CDC13) 8ppm: 1.3(t,3H); 3.9(s,2H); 4.25(q,2H); 7.25 (d,H), 7.5(m,3H); 8.45(m,2H); 8.75 (d,H).
Step 4 3-Methyl-4-chloro-5-aminoisothiazole (0.74g, 0.5 xIO-3mol) was dissolved in dry TBF (3ml) under nitrogen, sodium methoxide (0.68g, 1.26 xlO'mol) added and the reaction mixture stirred at room temperature for 15 minutes. The product from step 3 (0.121g, 0.53 ml) was then added. The reaction mixture was stirred for 5 hours, stood overnight, and then quenched with aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulphate, filtered, and evaporated in vacuo to give a yellow/orange oil. This was purified by flash column chromatography on sorbsil 40-60 eluting with diethyl ether, to give the title compound (0. 03 1 g) as a pale yellow solid, m.p. 1 17-119'C - H NMR (CDC13) 8ppm: 2.4(s,3H); 4.1(s,2H); 7.25 (d,H), 7.55(m,3H); 8.5(m,2H); 8.85 (d,H); 1 1.0(bs,H) amu M+ 345 The other compounds in Tables 1-4 were made by analogous methods and had the NMR characterising data as shown in Table 5 TABLE5
Compound 'H NMR (CDC13) 8 ppm: No.
1 2.41(s,3H); 4.00(s,2H); 7.24(d,IH); 7.35(d,IH); 7.72(t,lH); 11.20(s,IH). 2 1.38(t,3H); 2.42(s,3H); 2.97(q,2H); 3.99(s,2H); 7.09(d,lH); 7.18(d,lH); 7.65(t,IH); 12.44(s,lH). 3 2.41(s,3H); 3.92(s,2H); 4.10(s,3H); 6.75(d,IH); 6.87(d,lH); 7.60(dd,IH); 10.40(s,IH). 4 2.39(s,3H); 3.92(s,2H); 6.80(d,IH); 7.08(m,5H); 7.72(t,lH); 10.40(s,lH). 1.08(s,9H); 2.40(s,3H); 3.92(s,2H); 4.09(s,2H); 6.75(d,IH); 6.84(d,IH); 7.60(t,lH); 10.58(s,IH). 2.41(s,3H); 3.90(s,3H); 3.95(s,2H); 7.23(m,2H); 8.34(d,lH); 11.95(s,lH). 2.42(s,3H); 4.01(s,2H); 7.35(m,2H); 8.57(m,IH); 11.90(s,lH). 9 2.43(s,3H); 3.89(s,3H); 3.96(s,2H); 6.81(m,2H); 8.48(d,lH); 12.40(s,lH). 10 2.43(s,3H); 3.91(s,2H); 6.79(d,IM; 6.84(dd,IH); 7.11 (d,2H); 7.32(d, I H); 7.46(t,2H); 8.49(d, I H); 12.22(s,lH). 11 2.4(s,3H); 3.8(s,2H); 3.95(s,3H); 6.8(d,IH); 7.6(dd,lH); 8.1(d,IH); 8.25(bs,lH) 12 1.05(t,3H); 1.8(m,2H); 2.4(s,3H); 3.8(s,2H); 4.25(t,2H); 6.8(d,lH); 7.6(dd,lH); 8.1(d,lH); 8.25(bs,lH) 13 8.12(d, 1 H); 7.7 1 (dd, I H); 7.41 (m, 2H); 7.12-7.27(m, 3H); 6.95(d, IH); 3.82(s, 2H); 2.40(s, 3H). 14 1.0(s,9H); 2.4(s,3H); 3.8(s,2H); 4.0(s,2H); 6.8(d,lH); 7.6(dd,IH);8.1(d,IH); 8.15(bs,IH) 15 8.06(d,lH); 7.56(dd,IH); 6.84(d,IH); 4.47(m,2H); 3.78(s, 2H); 3.74(m, 2H); 3.44(s, 3H); 2.38(s, 3H). 16 2.40(s,3H); 3.83(s,2H); 3.96(s,3H); 6.72(d,lH); 6.87(d,lH); 8.20(d,lH); 8.28(s,lH). 17 2.42(s,3H); 3.94(s,2H); 6.97(s, 1 H); 7.20(d, 1 H); 8.26(d,lH); 8.34(s,lH). 1.35(d,6H); 2.40(s,3H); 3.80(s,2H); 5.32(m,IH); 6.67(s,IH); 6.82(dd,IH); 8.18(d,IH); 8.28(s,IH). 19 1.03(s,9H); 2.41(s,3H); 3.82(s,2H); 3.99(s,2H); 6.76(s,IH); 6.85(dd,lH); 8.17(m,2H). 20 2.40(s,3H); 3.85(s,2H); 6.88(s,IH); 6.98(d,lH); 7.20(m,3H); 7.40(t,2H); 8.20(d,IH); 8.55(s,lH). 21 2.38(s,3H); 3.44(s,3H); 3.75(m,2H); 3.80(s,2H); 4.48(m,2H); 6.72(s,IH); 6.85(dd,lH); 8.13(d,IH); 8.55(s,lH). 22 1.85(s,3H); 2.40(s,3H); 3.82(s,2H); 4.78(s,2H); 4.96(s,IH); 5.07(s,IH); 6.78(s,lH); 6.87(dd,lH); 8.13(s,lH); 8.20(d,lH). 23 1.4(s,9H); 2.4(s,3H); 3.85(s,2H); 8.5(bs,IH);8.7(s,2H) 24 2.4(s,3H); 3.85(s,2H); 7.5 (m,311), 8.45(m,2H); 8.8(s,2H); 9.0(bs,IH) 25 2.4(s,3H); 3.85(s,2H); 4.0(s,3H); 8.5(s,2H);8.85(bs,lH) 26 8.52(s,2H); 7.43(m,2H); 7.13-7.30(m,3H); 3.85(s,lH); 2.39(s,3H). 27 2.4(s,3H); 4.1(s,2H); 7.2 (d,3H); 7.55(M,3H); 8.5(m,2H); 8.85(s,2H); I 1.0(bs, I H) 28 13.0(s, 1 H); 8.11 (d,211); 7.45(dd, I H); 7.29(d, 1 H); 7.11(d,IH); 4.17(s,2H); 3.96 (s,311); 2.44(s,3H).
This Example illustrates the pesticidal properties of compounds of formula (1). The activities of individual compounds of formula (1) were determined using a variety of pests. With the exception of nematodes, the pests were treated with a liquid composition containing 500 parts per million (ppm) by weight of a compound unless otherwise stated. Each composition was made by dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water containing 0.05% by volume of a wetting agent, SYNPERONIC NP8, until the liquid composition contained the required concentration of the compound.
The test procedure adopted with regard to each pest, except nematodes, was essentially the same and comprised supporting a number of the pests on a medium which was usually a substrate, a host plant or a foodstuff on which the pests feed, and treating either or both the medium and the pests with a composition. Pest mortality was assessed usually between two and five days after treatment. Knockdown of housefly (Musca domestica) was assessed 15 minutes after treatment.
The test procedure for nematodes involved dissolving the compound in an acetone and ethanol (50:50 by volume) mixture and diluting the solution with water to obtain a final concentration of the compound of 12.5ppm. J2 infective juveniles of Meloidogyne inct?gnita were suspended in the solution in a glass vial and mortality assessed after a period of three days.
The results of the tests against peach aphid (Myzus persicae) are presented below. In this test Chinese cabbage leaves were infested with aphids, the infested leaves were sprayed with the test composition, and the mortality assessed after three days. The results indicate a grading of mortality (score) designated as 9, 5 or 0 wherein 9 indicates 80- 100% mortality, 5 indicates 40-79% mortality and 0 indicates less than 40% mortality.
Compound Nos. 7, 12, 13, 14, 15 and 18 each gave a mortality score of 9 whilst Compound Nos. 2, 3, 5, 8, 11, 17, 22, 24, 26, 27 and 28 gave a score of 5.
In addition, in a similar test against two-spotted spider mites (Tetranychus urticae) Compound Nos. 14, 15 and 23 each gave a mortality score of 9 whilst Compound Nos. 7, 12 5 and 17 gave a score of 5.
This Example illustrates the:ftmgicidal properties of compounds of formula (I). The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows.
Plants were grown in John Innes Potting Compost (No. 1 or 2) in 4cm diameter, 3.5cm io depth minipots. The test compounds were individually formulated as a solution either in acetone or acetone/ethanol (1: 1 by volume) which was diluted in deionised water to a concentration of I 00ppm (that is, I mg of compound in a final volume of I Oml) immediately before use. When foliar sprays were applied to monocotyledonous crops, TWEEN 20 (0.1 % by volume) was added. TWEEN is a registered trade mark.
Individual compounds of formula Q) were applied as a foliar (Folr) application (where the chemical solution was applied to the foliage of the test plants by spraying the plant to maximum droplet retention); as a systemic (Syst) application (where the chemical solution, I Oml, was applied as a root drench treatment) or as a stem (Stem) application (where the chemical solution was applied to the stems of the test plants by spraying the plants to run off) - These tests were carried out against Plasmopara viticola (PLASVI) and Uncinula necator (UNCINE), on vines; Phytophthora infestans lycopersici (PHYTIN) and Botrytis cinerea (BOTRCI), on tomatoes; Venturia inaequalis (VENTTN), on apples; Erysiphe graminisfsp. tritici (ERYSGT), Septoria nodorum (LEPTNO) and Puccinia recondita (PUCCRT), on wheat; and Pyricularia oryzae (PYRIOR) and Rhizoctonia solani (RHIZSO), on rice. Each treatment was applied to two or more replicate plants for Plasmopara viticola, Phytophthora infestans lycopersici, Botrytis cinerea, Uncinula necator and Venturia inaequalis. In tests on Erysiphe graminisf sp. tritici, Septoria nodorum, Puccinia recondita, Rhizoctonia solani and Pyricularia oryzae two replicate pots each containing 6 to 10 plants were used for each treatment. The plants were inoculated with a calibrated fimgal spore suspension one or two days before (Erad) or 6hours, one day or two days after (Prot) chemical application.
After chemical application and inoculation, the plants were incubated under high humidity conditions and then put into an appropriate environment to allow infection to proceed, until the disease was ready for assessment. The Erysiphe graminisfsp. tritici plants were inoculated using a 'shake' inoculation technique. The Uncinula necator plants were inoculated using a 'blowing' inoculation technique. For Plasmopara viticola, the plants were reincubated under high humidity conditions for 24hours prior to assessment. The time period between chemical application and assessment varied from five to fourteen days according to io the disease and environment. However, each individual disease was assessed after the same time period for all compounds.
Assessments were performed on a single leaf of each of the two replicate plants for Plasmopara viticola and Venturia inaequalis and on each of two leaves on each of the replicate plants for Phytophthora infiestans lycopersid and Botrytis cinerea. Assessments were performed on a single leaf of each of the three replicate plants for Uncinula necator.
For Erysiphe graminisfsp. tritici, Septoria nodorum, Puccinia recondita and Pyricularia recondita assessments were carried out collectively on the plants in each replicate pot. For Rhizoctonia solani, the number of infected plants in each of two replicate pots were assessed.
The disease level present (that is, the percentage leaf area covered by actively sporulating disease) or percentage of infected plants per pot wasassessed visually. For each treatment, the assessed values for all its replicates were meaned to provide mean disease values. Untreated control plants were assessed in the same manner. The data were then processed by either of two alternative methods, described hereinafter, each providing its own PRCO (Percentage Reduction from Control) value.
The method uses unbanded assessment values (that is, the mean disease values are used in the PRCO calculation without a banding step).
An example of a typical unbanded calculation is as follows:
Mean disease level for treatment A = 25% Mean disease level on untreated controls = 85% PRCO = 100 - t Mean disease level for treatment A I x 100 (Mean disease level on untreated controls} = 100 - (L5 x 100) = 70.6 85 The PRCO is then rounded to the nearest whole number; therefore, in this particular example, the PRCO result is 71. It is possible for negative PRCO values to be obtained. PRCO results are shown below.
TABLE 6
COMPOUND ERYSGT PHYTIN PUCCRT PYIOR UNCINE NO.
3 84 87 99 83 7 97 99 98 96 100 9 85 12 98 94 99 13 99 100 14 100 88 98 100 90 100 17 100 88 100 90 91 22 99 95 91 23 94 93 ERYSGT = Erysiphe graminis tritici PHYTIN = Phytophthora infestans lycopersici PUCCRT = Puccinia recondita PYRIOR = Pyricularia oryzae UNCINE = Uncinula necator

Claims (4)

1. A compound of formula (I):
(R 1)m --- (R'),, J L NS ' M-A' N wherein A is optionally substitutedC]-6alkylene, optionally substitutedC2-6alkenylene, optionally substitutedC2-6alkynylene, optionally substitutedC,-6alkylenoxy, optionally substituted oxy(C,,)alkylene, optionally substituted C1-6 alkylenethio, optionally substituted thio(CI-6)alk-ylene, optionally substituted C1-6 alkylenamino, optionally substituted amino(Cl-6)alkylene, optionally substituted [Cl-6 alkyleneoxy (CI-6)-alkylene], optionally substituted [C,-6 alkylenethio(CI-6)alkylene], optionally substituted [CI-6 alkylenesulfinyl(C,,)alkylene], optionally substituted [C,-6 alkylene sulfonyl(C,-6)alkylene] or optionally substituted ICI-6 alkyleneamino(C,,)-alkylene]; J and L are independently CR' or N; M is N(R11)C(=y)' N=C(OR12), N=C(SR") or N=C(NW'R") where N is the atom of attachment to the isothiazole ring; Y is 0, S or NR 13; each R' group is independently halogen, optionally substituted C,-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2, akny', optionally substituted C,-6 alkoxy, optionally substituted C1-6 alkylthio, optionally substituted C3-1 CYcloalkyl, cyano, nitro or SF,; W1 is hydrogen, optionally substituted CI-10 alkyl, optionally substituted IC2-6 alkenyl(C,-6)alkyl], optionally substituted IC2-6 alkynYKI-Jalkyl], optionally substituted C3-, cycloalkyl, optionally substituted CI-10 alkylcarbonyl, optionally substituted CI-10 alkoxycarbonyl, formyl, optionally substituted CI-10 alkylaminocarbonyl, optionally substituted di(Cl-lo)alkylaminocarbonyl, optionally substituted phenoxycarbonyl, optionally substituted C,-6 alkylthio, optionally substituted C,6 alkylsulfinyl, optionally substituted C1, alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfinyl, optionally substituted arylsulfonyl, or WOR2'NS; optionally substituted[C,-,2alkoxy (CI-2)alkyl], optionally substituted [aryloxy (C,-2)alkyl], optionally substituted [aryl (CI-3)alkoxy(CI-2)alkyl], optionally substituted [aryl (CI-3)alkyl]; W2 is optionally substituted CI-10 alkyl, optionally substitutedIC2-6alkenyl(CI-6) alkyl], optionally substitutedIC2-6alkynyl(CI-6)alkyl], optionally substtUtedC3-7 cycloalkyl, optionally substituted CI-10 alky1carbonyl, optionally substituted CI-10 alkoxycarbonyl, formyl, optionally substituted CI-10 alkylarninocarbonyl, optionally substituted di(CI-10) alkylaminocarbonyl, optionally substituted phenoxycarbonyl, tfi(C -4)alkylsilyl, aryldi(C,4)alkylsilyl, (C,-4)alkyldiarylsilyl or triarylsilyl, optionally Substituted ICI-12 alkoXY (CI-2)alkyl], optionally substituted [aryloxy (CI-2)alkyl], optionally substituted [aryl(C,-3)alkoxy (C,-2)alkyl], optionally substituted [aryl(C,-3 )alkyl]; R' is optionally substituted CI-10 alkyl, optionally substituted [C2-6alkenyl(C,-6) alkyl], optionally substituted [C2, alkynyl(C,-6)alkyl], optionally substitUtedC3-7 cycloalkyl, optionally substituted CI-1,, alkylcarbonyl, optionally substituted Cj-'O alkoxycarbonyl, optionally substituted CI-10 alkylaminocarbonyl, optionally substituted di(CI-1.)alkylaminocarbonyl. or optionally substituted phenoxycarbonyl), optionally substitated[C,-,2alkoxy (C,-2)alkyl], optionally substituted [aryloxy (C,-2)alkyl], optionally substituted [aryl (CI-3)alkoxy (C,-2)alkyl], optionally substituted [aryl (C,-3)alkyl]; W4 and W' are, independently optionally substituted C,-,, alkyl, optionally substituted C,-6alkoxy, optionally subsfitutedIC2-6alkenyl(C,-6)alkyl], optionally substituted [C2.6 alkynyl(CI-6)alkyll, optionally substitutedC3-7cycloalkyl, optionally substituted C,-,, alk-ylcarbonyl, optionally substituted CI-1. alkoxycarbonyl, formyl, optionally substituted C,-,,alkylaminocarbonyl, optionally substituted di(C,-,O)alkylamino carbonyl, hydroxy, amino, optionally substituted CI-6alkylamino, optionally substituted di(CI-6)alkylamino, or optionally substituted phenoxycarbonyl, optionally substituted [aryl (Cl-3)alkyl]; each W group is independently halogen, cyano, optionally substitutedCI-20 alkyl, optionally substitutedC2-2, alkenyl, optionally substitutedC2-20 alkynyl, optionally substitutedC3-7cycloalkyl, optionally substitutedC5-6cycloalkenyl, formyl, optionally substituted C,-,, alkoxycarbonyl, optionally substituted CI-20 alkylcarbonyl, aminocarbonyl, optionally substituted CI-20 alkylaminocarbonyl, optionally substituted di(CI-20)alkylaminocarbonyl, optionally substituted aryloxycarbonyl, optionally substituted arylcarbonyl, optionally substituted arylaminocarbonyl, optionally substituted N-alkyl-N-arylaminocarbonyl, optionally substituted diarylaminocarbonyl, optionally substituted heteroaryloxycarbonyl, optionally substituted heteroarylcarbonyl, optionally substituted heteroarylaminocarbonyl, optionally substituted alkylheteroarylaminocarbonyl, optionally substituted diheteroarylaminocarbonyl, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted heterocyclyl, W'O, HS, optionally substituted CI-20 alkylthio, optionally substituted C1,0 alkylsulfinyl, optionally substituted CI-20 alkylsulfonyl, optionally substituted arylthio, optionally substituted ary1sulftyl, optionally substituted arylsulfonyl, W'R"N or RI I ON=C(W 7), or where (W),, can form a fused benzene ring, itself optionally substituted by halogen, cyano, optionally substituted CI-20 alkyl, optionally substituted CI-20 alkoxy, optionally substituted C2-20 alkenyl, optionally substituted C2-20 alkynyl, optionally substituted C31 cycloalkyl, optionally substituted C5-6 cycloalkenyl, optionally substituted CI-20 alkoxycarbonyl, optionally substituted CI-20 alkylcarbonyl; R 13 is hydrogen, OH, NH2, cyano, nitro, optionally substituted CI-6 alkyl, optionally substituted C3-7 cycloalkyl, optionally substituted (C2-6)alkenyl(CI-6)alkyl, optionally substituted (C2-6)alkynyl(C,-6)alkyl, optionally substituted phenyl., optionally substituted heteroaryl, optionally substituted C,-6 alkylcarbonyl, optionally substituted C,-6 alkoxycarbonyl, optionally substituted C,-6 alkylamino, optionally substituted di(C,-6)alkylamino, optionally substituted CI-6 alkylcarbonylamino, optionally substituted CI-6 alkoxycarbonylamino, optionally substituted CI-6 alkoxy, optionally substituted CI-6 alkylthio, optionally substituted C1, alkylsulfmyl, optionally substituted C,-6 alkylsulfonyl, optionally substituted arylthio, optionally substituted arylsulfmyl, optionally substituted arylsulfonyl or C1, acyloxy; W' and R2' are, independently, optionally substituted CI-6 alkyl or W' and W' together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two CI-6alkyl groups; W' is hydrogen, optionally substituted CI-20 alkyl, optionally substitutedIC2-20 alkenyl(C,-6)alkyl], optionally substitutedIC2-20 aknyl(CI-6)alkyl], optionally substitutedC3-7cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted [heterocyclyl(C,-6)alkylCH=Nl or di(C,-6) alkylC=N; W' and W' are, independently, hydrogen, optionally substituted CI-20 alkyl, optionally substitutedC31cycloalkyl, optionally substitutedIC2-20&kenyl(CI-6)alkyl], optionally substitutedIC2-20 aknyl(CI-6)alkyl], optionally substituted C,,, alkoxycarbonyl, optionally substituted phenoxycarbonyl, formyl, optionally substituted C,-2,, alkylearbonyl, optionally substituted CI-20 alkylsulfonyl or optionally substituted phenylsulfonyl; or W' and R2' together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two is further hetero atoms selected from 0, N or S and which may be optionally substituted by one or two C,, alkyl groups; k' and R3' are independently hydrogen, optionally substituted phenyl or optionally substituted C,-6 alkyl; and W' is hydrogen, optionally substituted phenyl (C,-2)aUcyl or optionally substituted CI-20 alkyl; m is an integer from 0 to 2; and n is an integer from 0 to 4 provided that the compound is other than N-(4-chloro-3 methyl-5-isothiazolyl)-6-(2,2,2-trifluoroethoxy)-3-pyridineacetamide.
2. A fungicidal, insecticidal, acaricidal, molluscicidal or nernaticidal composition comprising a fungicidally, insecticidally, acaricidally, molluscicidally or nernaticidally effective amount of a compound of formula (1) as claimed in claim 1 and a carrier or diluent therefor.
3. A method of combating and controlling fungi comprising applying to a plant, to a seed of a plant, to the locus of the plant or seed or to the soil a fungicidally effective amount of a compound of formula (1) as claimed in claim 1.
4. A method of combating and controlling insects, acarines, nematodes or molluscs which comprises applying to a pest, to a locus of a pest, or to a plant susceptible 5 to attack by a pest an insecticidally, acaricidally, nematicidally or molluscicidally effective amount of a compound of formula (1) as claimed in claim 1.
GB0106313A 2000-03-24 2001-03-14 Novel azole/azine compounds having fungicidal/pesticidal properties Withdrawn GB2361474A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB0007245A GB0007245D0 (en) 2000-03-24 2000-03-24 Chemical compounds

Publications (2)

Publication Number Publication Date
GB0106313D0 GB0106313D0 (en) 2001-05-02
GB2361474A true GB2361474A (en) 2001-10-24

Family

ID=9888399

Family Applications (2)

Application Number Title Priority Date Filing Date
GB0007245A Ceased GB0007245D0 (en) 2000-03-24 2000-03-24 Chemical compounds
GB0106313A Withdrawn GB2361474A (en) 2000-03-24 2001-03-14 Novel azole/azine compounds having fungicidal/pesticidal properties

Family Applications Before (1)

Application Number Title Priority Date Filing Date
GB0007245A Ceased GB0007245D0 (en) 2000-03-24 2000-03-24 Chemical compounds

Country Status (1)

Country Link
GB (2) GB0007245D0 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7968536B2 (en) 2007-06-29 2011-06-28 Millennium Pharmaceuticals, Inc. Heterocyclic compounds useful as RAF kinase inhibitors
US8293752B2 (en) 2007-06-29 2012-10-23 Millennium Pharmaceuticals, Inc. Compounds useful as Raf kinase inhibitors
CN103288771A (en) * 2012-02-29 2013-09-11 中国中化股份有限公司 Isothiazole compound and use thereof as fungicide

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1281361A (en) * 1968-10-17 1972-07-12 Ciba Geigy 6-AMINO-4-OXO-4,5-DIHYDRO-ISOTHIAZOLO[5,4-d]-PYRIMIDINES AND PROCESS FOR THEIR MANUFACTURE
WO1995031448A1 (en) * 1994-05-17 1995-11-23 Dowelanco N-(5-isothiazolyl)amide pesticides

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1281361A (en) * 1968-10-17 1972-07-12 Ciba Geigy 6-AMINO-4-OXO-4,5-DIHYDRO-ISOTHIAZOLO[5,4-d]-PYRIMIDINES AND PROCESS FOR THEIR MANUFACTURE
WO1995031448A1 (en) * 1994-05-17 1995-11-23 Dowelanco N-(5-isothiazolyl)amide pesticides

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7968536B2 (en) 2007-06-29 2011-06-28 Millennium Pharmaceuticals, Inc. Heterocyclic compounds useful as RAF kinase inhibitors
US8293752B2 (en) 2007-06-29 2012-10-23 Millennium Pharmaceuticals, Inc. Compounds useful as Raf kinase inhibitors
US8802657B2 (en) 2007-06-29 2014-08-12 Millennium Pharmaceuticals, Inc. Compounds useful as Raf kinase inhibitors
US9556177B2 (en) 2007-06-29 2017-01-31 Millennium Pharmaceuticals, Inc. Substituted 1,3-thiazoles as synthetic intermediates for preparation of Raf kinase inhibitors
US9920048B2 (en) 2007-06-29 2018-03-20 Millennium Pharmaceuticals, Inc. Substituted pyrimidines for inhibiting Raf kinase activity
CN103288771A (en) * 2012-02-29 2013-09-11 中国中化股份有限公司 Isothiazole compound and use thereof as fungicide
CN103288771B (en) * 2012-02-29 2014-12-03 中国中化股份有限公司 Isothiazole compound and use thereof as fungicide

Also Published As

Publication number Publication date
GB0106313D0 (en) 2001-05-02
GB0007245D0 (en) 2000-05-17

Similar Documents

Publication Publication Date Title
WO2001055140A1 (en) Isothiazole derivatives and their use as pesticides
US9282742B2 (en) Insecticidal compounds
US8618173B2 (en) Insecticidal compounds
EP2044006B1 (en) Insecticidal compounds
EP2411384B1 (en) Insecticidal compounds
US20040209776A1 (en) Azole derivatives useful as insecticide
EP1171437B1 (en) Pesticidal indazole or benzotriazole derivatives
EP2167503B1 (en) Tropane derivatives useful as pesticides
WO2001055139A1 (en) Isothiazole derivatives and their use as pesticides
US6703347B2 (en) Isothiazole derivatives and their use as pesticides
WO2001055143A1 (en) Benzoxazole derivatives and their use as pesticides
US8586593B2 (en) Insecticidal compounds
GB2361474A (en) Novel azole/azine compounds having fungicidal/pesticidal properties
WO2001055141A1 (en) Azine derivatives as pesticides
WO2001055145A1 (en) Azine derivatives as pesticides
WO2001055136A1 (en) Benzoxazole derivatives and their use as pesticides
WO2001055137A1 (en) Azine derivatives as pesticides
WO2001055138A1 (en) Azole derivatives, their preparation and use
WO2001055142A1 (en) Isothiazole derivatives and their use as pesticides
WO2001090105A1 (en) Isothiazoles as pesticides
AU2002355672A1 (en) Azole derivatives useful as insecticide

Legal Events

Date Code Title Description
WAP Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1)