GB2325932A - Isonicotinic Acid Hydrazide Derivatives - Google Patents
Isonicotinic Acid Hydrazide Derivatives Download PDFInfo
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- GB2325932A GB2325932A GB9811957A GB9811957A GB2325932A GB 2325932 A GB2325932 A GB 2325932A GB 9811957 A GB9811957 A GB 9811957A GB 9811957 A GB9811957 A GB 9811957A GB 2325932 A GB2325932 A GB 2325932A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/86—Hydrazides; Thio or imino analogues thereof
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
Abstract
Novel isonicotinic acid hydrazide derivatives of the formula in which R<SP>1</SP> is hydrogen, alkyl or alkenyl, R<SP>2</SP> is hydrogen, alkyl, haloalkyl or cyanoalkyl, R<SP>3</SP> is optionally substituted phenyl, or is an optionally substituted 5- or 6-membered heterocyclic radical, or is an optionally substituted benzo-fused heterocyclic radical comprising a 5- or 6-membered heterocycle and R<SP>4</SP> and R<SP>5</SP> independently of each other are hydrogen, halogen, hydroxy or alkoxy, processes for the preparation of the new compounds and their use as microbicides, particularly fungicides for use in agriculture and horticulture.
Description
2325932 Isonicotinic Acid Hydrazide Derivatives The present invention
relates to novel isonicotinic acid hydrazide derivatives, to processes for their preparation and to their use as microbicides.
It has already been known that certain acylhydrazines can be used as anthelmintics (see P-A Hei 3-500 769). Fungicidal properties of said compounds, however, have not been disclosed.
Further, it has already been described that certain hydrazide derivatives can be em- ployed for combating undesired microorganisms (see P-C 2 575 046). The activity of these substances, however, is not always satisfactory when they are applied at low dosages.
There have now been found novel isonicotinic acid hydrazide derivatives of the for- mula R 4 to N1 N N::== R R 1 in which R1 is hydro-(-,,en, alkyl or alkenyl, R2 is hydro,=,,en, alkyl, haloalkyl or cyanoalkyl, R 2 R 2 is opt o I uted phenvi, or 'I I I R3 I nally subst t s an optionally substituted 5- or 6-mem- bered heterocyclic radical, or is an optionally substituted benzo-fused hetero cyclic radical comprisin,-, a 5- or 6-membered heterocvc1e. and Nit 347- ForeiQn Countries -2 R4 and R5 independently of each other are hydrogen, halogen, hydroxy or alkoxy.
It has furthermore been found that isonicotinic acid hydrazide derivatives of the for- mula (1) can be prepared by a) reacting isonicotinic acid derivatives of the formula R 4 0 k N (II) - cl R 5 in which R4 and R5 have the above-mentioned meanings, with hydrazine derivatives of the formula H R 2 N-N---/ R in which RI, R2 and R3 have the abovementioned meanings, =1 if appropriate in the presence of an acid-binding, agent and if appropriate in the presence of a diluent, or "' 5 b) reactin-gy isonicotinte acid hydrazldes of the formuia Nit 347- ForeiQn Countries 1 R 4 0 NX (IV) R 5 / N-NH 2 R 1 in which RI, R4 and R5 have the above-mentioned meanings, with carbonyl compounds of the formula R 2 O=C \ (V) R 3 in which R2 and R3 have the above-mentioned meanings, 1 if appropriate in the presence of an acid catalyst and if appropriate in the pres- ence of a diluent.
1 Finally, it has been found that the isonicotinic acid hydrazide derivatives of the for mula (I) are outstandingly active as microbicides, which can be used in agriculture and horticulture. They can either be used for directly combating undesired microorga nisms, such as phytopathogenic fungi and bacteriae, or for inducing in the plant bodies n themselves resistance to phytopathogenic fungi and bacteriae.
ty SurprIsingly, the compounds according to the invention have a much better microbicidal activity, particularly fungicidal activity than the already known compounds. which are structurally most similar and have the same type of action.
Nit 347- ForeiQn Countries In the present context,,haloL-en" in the terms,halocen" and,haloaikvi" represents fluorine, chlorine, bromine or iodine, preferably fluonne, chlorine or bromine.
The term,alkyP' represents straight chain or branched alk-yl, and includes, for exampie, methyl, ethyl, propyi, isopropyl and n-, iso-, secor tert-butyl.
The term,alkoxy" represents straight chain or branched alkoxy, and includes, for example, methoxy, ethoxy, propoxy, isopropoxy and n-, iso-, sec or tert-butoxy.
The term,haloalkyP' represents straight chain or branched haloalkyl, and includes, for example, trifluoromethyl and 2,2,2-tnfluoroethyl.
The term,alkvlthio" represents straight chain or branched alkvlthio, and includes. for example. methylthio. ethylthio. propylthio and isopropylthio, The term,alkenyl" represents straight chain or branched alkenyl. and includes, for example, allyl and 2-methyi-2-propenyl.
The term _5- or 6-membered heterocyclic radical" includes, for example, pyndyl.
- thienyl, thiazoivi, furyi, pyrrolyl. pyrazolyl, pyrazinvi and pyri idinyl. These hetero- cvchc radicals mav be substituted bv cvano. nitro. haloizen (such as fluorine. chlorine and bromine), alkyl (such as methv]. ethyl, propyl, isopropyl and n-, sec-, iso- or tertbutyl), alkoxy (such as methoxv, ethoxy, propox-y, and isopropoxv), alkvithio (such as methvithio, ethylthio. propylthio and isopropylthio), amino. alkVlamino (such as methviamino), dialkvlamino (such as dimethylamino) or phenvl. When a plurality of substituents are present, they may be identical or different, The term,benzo-fused lieteroc-,.,clic radical comprising a 5- or omenibered beterocvcle- represents. for example, a benzo-fused heterocyclic radical selected from pyridyl, thienvi, thiazolvl, furvi, pyrrolyl, pyrazolvi, pyrazinyl and pyrimidinyl. and the exampies thereof include monovalent radicals selected from benzo[blthien,1. quinolinvi. isoquinolinyl and the like. Nit 347- Foreiqn Countries These benzo-fiised heterocyclic radicals may be substituted by cyano, nitro, halogen (such as fluorine, chlorine and bromine), alkyl (such as methyl, ethyl, propyl, isopro pyl and n-, sec-, iso- or tert-butyl), alkoxy (such as methoxy, ethoxy, propoxy and isopropoxy), alkylthio (such as methylthio, ethylthio, propylthio and isopropylthio), amino, alkylamino (such as methylarnino) or dialkylamino (such as dimethylamino).
When a plurality of substituents are present, they may be identical or different.
Formula (1) provides a general definition of the isonicotinic acid hydrazide derivatives according to the invention.
Preferred compounds of the formula (1) are those. in which RI is hydrogen, C 1-4 alkyl or C2-4 alkenyl, is p,2 is hydrogen, C 1-4 alky], C 1-4 haloalkyl or C 1-4 cyanoalkyl, R3 is phenyl, or is pyridyl, thienyl, pyrrolyl, thiazolyl, furyi, pyrazolyl, pyrazinyl, pynmidinyl, benzo[b]thienyl, quinolyl or isoquinoiyl, each of which may be substituted by up to 3) substituents selected from halogen, cyano. nitro, C1-4 alkyl, C 1-4 alkoxy, C 1 -4 alkylthio, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino and phenyl, and R4 and R5 independently of each other represent hydrogen, chlorine, hydroxy or methoxy.
Particularly preferred compounds of the formula (1) are those, wherein p is hydrogen, C 1-4 alkA or C2-4 alkenvi, R2 is hydrogen, C 1-4 alkvl, C t -4 haloalkyl or C 1-4 cyanoalkyl, Nit 347- ForeiQn Countries R3 is pyridyl, thienyl, pyrrolyl, thiazolyi, furyl, pyrazolyl, pyrazinyl, pyrimidinyl, benzo[b]thienyl, quinolyl or isoquinolyl, each of which may be substituted by up to 3 substituents selected from fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, sec-butyl, methoxy, ethoxy, methylthio, ethylthio, amino, dimethylamino and phenyl, and R4 and R5 independently of each other represent hydrogen, chlorine, hydroxy or methoxy.
Specific examples of the compounds of the formula (I) according to the invention, which may be mentioned, are the compounds shown in Table 1 below.
In Table 1 as well as in Table 2, which follows later, 15,Me" represents a methyl radical,,,Et" represents an ethyl radical,,,n- Pr" represents a normal propyl radical,,j-Pr" represents an isopropyl radical,,,t-Bu" represents a tertiary butyl radical, 20 -1-Bu" represents an isobutyl radical.,,Allyl" represents an allyl radical,,,Ph" represents a phenyl radical,,,MeO" represents a methoxy radical,,,EtO" represents an ethoxy radical,,,MeS" represents a methylthio radical, and --- IEtS"represents an ethylthio radical.
Nit 347- ForeiQn Countries Table 1
R 4 0 1 N 7 -3-l R'(I) 1 - N N = 3 R R 1 RI p 2 - R4 -1 R Me Me v \ cl 1 \ N3 H Me 7 \ cl 1 \ N3 H Me 1 c Cl 1 c- S H Me cl cl 11 me S Me b"\- 1 Allyl Me cl 1 cl W i-Pr Me -Q cl cl H Me OZ-\_ cl cl 1 S 1 1 H Me cl 7' B r H Me MC cl 113 S H Me cl S W -- in, X - H Me J3 cl N m - H Me \ 11 cl N e H Me W N cl JI S- "A--me - - RS cl cl cl 1 cl cl cl cl cl cl Nit 347Foreign Countries Table 1 (continued) -S- RI R2 R3 1 m P's H Me N cl s- H - cl S7 C1)sQ \l Me cl Me cl i m0 m H Me er cl S er H Me 1 cl S - 1 H Me cl Nb S - Ph H H cl S H Me m cl N '--c -l-S ' H Me me cl 1 --- - 1 WS SN H Me 1 cl H Me p02 C, 1 H Me Br cl 3 m H Me C,,,e cl 2 H Me Cl ES u cl cl cl cl cl cl 1 cl cl cl cl cl cl cl Nit 347- Foreim Countries Table 1 (continued) R' R2 R3 R4 RS H CHW cl cl H Et cl cl H CF3 fl cl cl S H H Br cl cl _nl ar S H t-Bu 3 cl cl --JCI S- 1 H 1 i-pr cl cl H i-Bu 3 cl cl -ú1 S 1 H CF3 Ph cl cl H i-pr 3 cl cl N 46 H i-pr k_3 cl cl N Zb H Me N cl Ome H Me cl OH N b H Me 3 cl H __CS 1 H Me -J-SF cl cl H Me F cl cl --- ls H Me Cl cl - 1 - -il S cl Nit 347- Foreim Countries Table 1 (continued) RI 1 R2 R R4 RS H Me er cl cl -s F H Me -- hs \ cl cl H me - Me --/ s cl cl W H Me 1 bis \ cl cl m H H cl cl H Me S Me cl cl H Me S E 1 cl cl Ppr H Me 1 bts k cl cl E3f H H -- ns k cl cl 13, H Me cl cl H Me cl cl er H Me ni, cl cl S CN H Me cl cl S m H Me s cl - cl Nit 347- Foreiqn Countries Table 1 (continued) R' R 2 M RS H Me W- 4 hils, \ cl cl H Me NCS cl cl H Me lsSW cl cl H H s\ cl cl H H cl cl S H H NC cl cl S H M e cl cl k H Me s cl cl --/ S Me 0 H H -l s-- cl cl me H IM e B, cl cl H M e cl cl S A H IM e -lleY-Br cl cl S H H W cl cl Br H & Br Me s\ cl cl Nit 347- ForeiQn Countries Table 1 (continued) R1 R2 R3 M RS t-Bu H Me cl cl we H Me cl cl cl H Me ú1s-Cl cl cl WS H Me cl cl -ls\ -ST C14 H Me S ar cl cl H Me Mes cl cl k OW me H Me cl cl me H H Cl cl cl cl H Me cl cl H Me er-ls\13r cl cl H S cl cl H Me n-Pr S me cl cl 1 Me -bk ' cl - H Ets S Et cl m H Me l S- cl cl me - - - Nit 347- Foreign Countries Table 1 (continued) - 1 " R' R2 1 R3 R' 1 RS cl H Me me k CI cl "/ S C, H H m-ls\ cl cl H Me bi^ \ ' cl cl W S Cl H Me WO- blls\ _sw cl cl H H 1 \ cl cl OEt H IN 1 e cl cl S Er cl 1 H Me cl cl S Cl H Me 1 Cl cl 1 mo-- CS H Me St CI cl lsker om H 1 Me V ls \ cl 1 Cl S H H o"O cl cl 1 Ma H Me 1 X cl cl 1 kts,x ' E H Me ow cl cl X mes-) xcl H Me OW cl cl l- H H 1 l \ -- cl cl W.' 1 \ 01,49 sl - Nit 347- Foreic in Countries Table 1 (continued) R' R2 R3 R 4 RS H Me -C,N\ cl cl H H - Q-N cl cl H Me N cl cl H H N cl cl H H N cl cl he H 'P Me cl cl H H H 'I3 cl cl N H H Me hie cl cl wytr4\ H Me 1 \ ?'0 cl cl 1 N H -ú3 N Me cl cl W,N, ve H 1 X Me kN)--W Cl Cl e H H WC cl W N cl e H MC Me N cl cl 1 m Nit 347- ForeiQn Countries Table 1 (continued) R' R2 1 R3 m 1 P's H Me N.N cl cl Nic H T H m 'WN cl cl zt H Me l cl cl C H " H c cl cl , 1 4,N e H Me j cl cl 7 N N P., H Me x cl cl 1 W'.N m H H 1 cl cl N N h m H H ciN cl cl MO H we Me 1 cl cl H c 1 M M e N cl c 1 - 4 H M e N c 1 - -C -- 14 Nit 347- Forelqn úCountries Table 1 (continued) RI R2 R3 R4 RS H Me ( Nl cl cl H Me CY cl cl N N H Me N 1 J' cl cl H H ()N cl cl H H r, "- 1 _ cl cl N H H c 1 c 1 H K_ 1 - cl cl Me V, N H H ' cl c 1 ..4 Me N cl cl N H H N cl cl "CN Nit 347- Foreign Countries If 2,6-dichloroisonicotinoyl chloride and 3-acetyl-5-cyano-4-methyi-2- methylthiothiophene hydrazone are used as starting materials, the course of process (a) according to the invention can be illustrated by the following formula scheme.
cl 7 0 N - cl cl CH3 H2 N-N CH 3 H3CS- S CN cl 0 N CH3 NH-N CH, H3C: S CN - HCl Base cl If 2,6-dichloroisonicotinic acid hydrazide and 3) -acetyl-2,5 -d i methyl -t hi o phene are used as starting materials, the course of process (b) according to the invention can be illustrated by the following formula scheme.
cl CH 3 N + -CH N-NH, H3C S 3 cl H - H,0 0 - N CH Acid cl / N-N- H: C H 3 S 3 cl H Nit 347- ForeiQn Countries If 2,6-dichloroisonicotinic acid hydrazide and 3,5-dibromo-thlophene-2- carbaidehyde are used as starting materials, the course of process (b) according to the invention can be illustrated by the following formula scheme.
cl 0 N: + t - N-NH 2 cl H H 0 4 S Br 1 1 Br cl v 0 N -/1 H N-N- > /r S cl H / 1 1 Br Br -H 2 0 Formula (If) provides a general definition of the isonicotinic acid derivatives, which are required as starting materials for carrying out process (a) according to the inven- 1 1 tion. In this formula, R4 and R5 preferably have the meanings, which have already Z:1 been mentioned as being preferred for these radicals.
c Examples of the isonicotinic acid derivatives of the formula (If) include 2,6-dichloroisonicotinic acid chloride, 2-chloroisonicotinic acid chloride, 2-chloro-6-methylisonicotinic acid chloride, and the like.
The isonicotinic acid derivatives of the formula (If) are well known compounds in the field of organic chemistry.
Formula (III) provides a general definition of the hydrazine derivatives. which are required as reaction components in carrying out process (a) according to the invention. In this formula, R], R2 and R-' preferably have the rneanings, which have already been mentioned as being, preferred for these radicals.
Nit 347- Foreim Countries The following compounds may be mentioned as examples of hydrazine derivatives of 0 1 1 the formula (III):
3-acetyl-5-cyano-4-methyi-2-(methylthio)-thiophene hydrazone, 3 -acetyi- 1 -methylpyrrole hydrazone, 2-methyl- 1 -(2-thienyl)- 1 -propanone hydrazone, 2-acetylthiophene hydrazone, and the like.
The hydrazine derivatives of the formula (111) are known or can be prepared by known methods. Thus, they can be obtained by heating a carbonyl compound of the formula (V) (see below) and a hydrazine derivative under reflux in an alcohol solvent in the presence of an acid catalyst.
Formula (IV) provides a general definition of the isonicotinic acid hydrazides. which are required as starting materials for carrying out process (b) accordinta: to the inven tion. In this formula, R1, R4 and R5 preferably, have the meanings, which have al ready been mentioned as being preferred for these radicals.
Examples of isonicotinic acid hydrazides of the formula (IV) include 2.6dichlorolso nicotinic acid hydrazide, 2-chloroisonicotinic acid hydrazide, 2-chloro-6- methyliso nicotinic acid hydrazide, and the like.
The isonicotinic acid hydrazides of the formula (IV) are known or can be svnthesized by known methods. Thus, they can be obtained by reacting an isonicotinic acid deriva tive of the formula (II) with hydrazine hydrate under conditions corresponding to those of process (a) according to the invention.
Formula (V) provides a general definition of the carbonyl compounds, which are re quired as reaction components for carrying out process (b) according to the invention.
In this formula, R2 and R, preferably have the meanings, which have already been mentioned as being preferred for these radicals.
Nit 347- Foreiqn Countries Examples of carbonyl compounds of the formula (V) include 3-acetyi-2,5- dimethylthiophene, 3,5-dibromothiophene-2-carbaldehyde, 1-methylpyrrole-2- carbaidehyde, 1, 3,5 -trimethylpyrazole-4-carb aldehyde, and the like.
The carbonyl compounds of the formula (V) are known or can be prepared by known methods.
Suitable acid-binding agents for carrying out process (a) according to the invention are all customary inorganic and organic acid acceptors. The following can preferably be used: the hydrides, hydroxides, carbonates and bicarbonates of alkali metals or alkaline earth metals, such as sodium hydride, lithium hydride, sodium hydrogencar bonate, potassium hydrogencarbonate, sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide., and further alcoholates, tertiary amines, dialkylaminoanilines and pyridines, such as sodium methylate, triethylamine, 1, 1,4,4-tetramethylethylenediamine (TMEDA), N,N dimethylaniline, N,N-diethylaniline, pyridine, 4-dimethylaminopyridine (DMAP), 1,4 diazab icyclo [2,2,2]octane (DABCO) and 1,8-diazabicyclo[5,4,Olundec-7- ene (DBU).
Diluents which are suitable for carrying out process (a) accordino to the invention are all customary inert organic solvents as well as water. The following can preferably be used: water, aliphatic, alicyclic or aromatic hydrocarbons (which may optionally be chlorinated), such as pentane, hexane, cyclohexane, petroleum ether, ligroin, benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, chlorobenzene and dichlorobenzene, ethers, such as diethyl ether, methyl ethyl ether, dilsopropyl ether, dibutyl ether, dioxane, dimethoxyethane (DMF-), tetrahydrofuran (THF) and di ethylene glycol dimethyl ether (DGM); nitriles, such as acetonitrile, propionitrile and acrylonitrile, alcohols, such as methanol, ethanol, isopropanol, butanol and ethylene U - - acid amides. such as dimethyl- glycol, esters, such as ethyl acetate and amyl acetate, I I I formamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, 1,3- dimethyl-2 imidazolidinone and hexamethylphosphoric triamide (HIMPA)l sulfones and sulf oxides, such as dimethyl sulfoxide (DMSO) and sulfolan-, and bases, such as pyridine.
Nit 347- Foreign Countries When carrying out process (a) according to the invention, the reaction t emperatures can be varied within a substantially wide range. The reaction is generally carried out at a temperature between about -73 C and about + 1 SO'C, preferably between about O'C and about + 1 OWC.
Process (a) according to the invention is generally carried out under atmospheric pressure but, if desired, can also be carried out under elevated or reduced pressure.
When carrying out process (a) according to the invention, in general 1 mole of an iso- nicotinic acid derivative of the formula (II) is reacted with 0. 1 to 10 moles of a hydra- zine derivative of the formula (M) in the presence of a diluent. such as toluene, and in the presence of an acid-binding agent. such as sodium hydroxide. Working up is carried out by customary methods.
1 Process (b) according to the invention can be carried out in the presence of an acid catalyst. Suitable acid catalysts preferably are mineral acids, such as livdrochloric acid, sulfuric acid, nitric acid, hydrobromic acid and sodium hydrogensulfite-, organic acids, such as formic acid, acetic acid. trifluoroacetic acid, propionic acid, methanesuffonic id. benzenesulfonic acid, p-toluenesulfonic acid, and organic amine hydrochloric aci I I acid salts, such as pyridine-hydrochloric acid salt and triethviaminehvdrochloric acid salt. amine sulfonic acid salts such as pyridine-p-toluenesuffonic acid salt and triethylamino-sulfonic acid salt.
Process (b) according to the invention can also be carried out in the presence of a diluent. Suitable diluents are all customai-v inert organic solvents as well as water. The following can preferably be used water; aliphatic. alicyclic or aromatic hydrocarbons (which rnav optionaliv be chlorinated). such as pentane. llexane, cyclohexane. petroleum ether. kgroin. benzene, toluene. xyiene. dichloromethane. chlorofiorm, carbon tetrachloride. l.'--dichloroethane. chlorobenzene and dichlorobenzene. ethers. such as -1)o diethyl ether. methyl ethyl ether, diisopropyl ether, dibutyl ether. dioxane. dimethoxy- ethane (DME), tetrahvdrofuran (THF) and diethyiene glycol dimethyl ether (DGIM). nitriles. such as acctonitrile. propionitrile and acrylonitrile. alcohols. such as methanol. Nit 347- ForeiQn Countries ethanol, isopropanol, butanol and ethylene glycol; esters, such as ethyl acetate and amyl acetate; acid amides, such as dimethylformamide (DMF), dimethylacetamide (DMA), N-methylpyrrolidone, 1,3-dimethyl-2- imidazolidinone and hexamethylphosphoric triamide (HNIPA); and sulfones and sulfoxides, such as dimethyl suffoxide (DMSO) and sulfolan.
When carrying out process (b) according to the invention, the reaction temperatures can be varied within a substantially wide range. The reaction is generally carried out at a temperature between about -7PC and about +150'C, preferably between about +20'C and about + 1 20'C.
Process (b) according to the invention is generally carried out under atmospheric pressure but, if desired, can also be carried out under elevated or reduced pressure.
When carrying out process (b) according to the invention, in general 1, mole of an iso- nicotinic acid hydrazlde of the formula (IV) is reacted with 0. 1 to 10 moles of a carbonyl compound of the formula (V) in the presence of a diluent, such as toluene, and in the presence of an acid catalyst, such as p-toluenesulphonic acid. Working up is carried out by customary methods.
The compounds according to the present invention exhibit a stronc microbicidal activity without causing phytotoxicity to cultivated plants. They can be used for combating undesired microorganisms, such as phytopathogenic fungi and bacteriae, in agriculture and horticulture. The compounds are suitable for the direct control Of undesired microorganisms as well as for generating resistance in plants against attack by undesirable microorganisms.
Resistance-inducing substances in the present context are to be understood as those substances which are capable of stimulating the defence system of plants such that the treated plants, when subsequently inoculated with undesirable microorganisms, dis play substantial resistance to these microorganisms.
Nit 347- ForeiQn Countries Undesirable microorganisms in the present case are to be understood as phytopathogenic fungi and bacteriae. The substances according, to the invention can thus be employed to generate resistance in plants against attack by the harmful organisms mentioned within a certain period of time after the treatment. The period of time within which resistance is brought about in general extends from I to 10 days, preferably I to 7 days, after treatment of the plants with the active compounds, -10 Generally, the compounds according to the invention can be used as fungicides for combating phytopathogenic fungi, such as Plasmodiophoromycetes, Oomycetes, Chytridiomycetes. Zygomycetes. Ascomycetes, Basidiomycetes and Deuteromycetes, and can also be used as bactericides for combatinu, bacteriae, such as Pseudomonoadaceae, Rhizobiaceae. Enterobacteriaceae. Cor,nebacteriaccae and Streptomycetaceae.
Some causative organisms of fungal and bacteri 1 1 ial diseases included under the abovemetioned main headings are mentioned below as non-limiting examples.. Xanthomonas species, such as, for example, Xanthomonas campestris pv.oryzae, Pseudomonas species, such as, for example, Pseudomonas syringae pv.1achrymans, Erwinia species, such as, for example, Erwinia arnylovora. Pythium species, such as, for example. Pythium ultimum. Phytophthora species. such as. for example. Phytophthora infestans.. Pseudoperonospora species. such as, for example. Pseudo pero nospora cubensis. Plasmopara species. such as, for example. Plasmopara,. ltlcola. Peronospora species. such as, for example. Peronospora pislor p,, , brassicae. ErvsIphe species. such as. for example, Erysiphe gramims; Sphaerotheca species, such as, for example, Sphaerotheca fullginea. Podosphaera species. such as. for example. Podosphaera leucotricha. Venturia species. such as, for example. Venturia inaequalls. Pyrenophora species. such as. for example. Pyrenophora teresor P graminea. (Conidial form. Dreclislera, Synonym. liciniinthosporiuni). Cochhobolus species. such as. for example, Cochliobolus satl,,.us. (Contd!al fornv DrechsIera, Synonvin: Ilelminthosportum). Uromyces species. such as. for example, Uromyces appendicuiatus. Puccinia species. such as. for example. Puccinia recondita,. Tilletia species. such as. for example. Tilletia caries. Ustilago species- such a.,,. ffir example. Ustilago nudaor.
Nit 347- Foreicin Countries Ustilago avenae; Pelliculana species, such as, for example, Pellicularia sasakii, Pyricularia species, such as, for example, Pyricularia orvzae; Fusarium species, such as, for example, Fusarium culmorum; Botrytis species, such as, for example, Botrytis cinerea; Septoria species, such as, for example, Septoria nodorum, Leptosphaeria species, such as, for example, Leptosphaeria nodorum., Cercospora species, such as, for example, Cercospora canescens; Alternaria species, such as, for example, Alternaria brassicae; Pseudocercosporella species, such as, for example, Pseudocercosporella herpotricholdes.
The good toleration, by plants, of the active compounds, at the concentrations required for combating plant diseases. permits treatment of above--ground parts of plants. of vegetative propagation stock and seeds. and of the soil.
The active compounds can be converted into the customary formulations. such as solutions, emulsions, wettable powders, suspensions, powders, foams. pastes. -"ranules, tablets, aerosols, natural and synthetic materials impregnated with active compound. very fine capsules in polymeric substances, coating compositions for use on seed, and formulations used with burning equipment, such as fumigating cartridges. fumigating cans and fumigating coils, as well as ULV cold mist and warm mist formulations.
These formulations may be produced in kno%,,,,n manner, for example b%1 mixing the active compounds with extenders. that is to say liquid or liquefied gaseous or solid diluents or carriers. optionally with the use of surface-active agents. that is to say emulsi,in(_T auents and/or dispersing, agents and/or foam-forming, agents. In the case of the use of water as an extender. orgranic solvents can. for example. also be used as auxiliary solvents.
-Ls liquid solvents diluents or carriers, there are suitable in the main, aromatic hydro- a m ic or carbons such as x-..Iene. toluene or alkyl naphthalenes, chlorinated, ro at' chlorinated aliphatic hydrocarbons, such as clilorobenzenes. Lliloroetlivienes or methylene chloride. aliphatic hydrocarbons. such as cyclohexane or paraffins. for Nit 347- ForeiQn Countries example mineral oil fractions, alcohols, such as butanol or glycol as well as their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl-isobutyl ketone or cyclohexanone, or strongly polar solvents, such as dimethylformamide and dimethyl-sulphoxide, as well as water.
By liquefied gaseous diluents or carriers are meant liquids which would be gmseous at normal temperature and under normal pressure, for example aerosol propellants, such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide, As solid carriers there may be used ground natural minerals, such as kaolings, clays, talc, chalk, quartz, attapul-ite, montmorillonite or diatomaceous earth, and -round synthetic minerals, such as highly-dispersed silicic acid, alumina and silicates. As solid carriers for urranules there may be used crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inor- ganic and organic meals, and granules of organic material such as sawdust, coconut shells, maize cobs and tobacco stalks.
As emuisifying and/or foam-forming agents there may be used non-Ionic and anionic =1 __ 1=1 emulsifiers, such as polyoxyethylene-fatty acid esters, polyoxyethylene- fatty alcohol ethers, for example alkylaryl polyglycol ethers. alkyl sulphonates, alkyl sulphates. aryl sulphonates as well as albumin hydrolysis products.
Dispersing agents include, for example, lignin sulphite waste liquors and methylcellulose.
Adhesives such as carb oxymethyl cel I u lose and natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, can be used in the formulation.
It is possible to use colorants such as inorganic pigments. for example iron oxide, tita- W nium oxide and Prussian Blue, and organic dyestutTs, such as alizarin dyestuffs, azo Nit 347- ForeiQn Countries dyestuffs or metal phthalocyanine dyestuffs, and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.
The formulations in general contain from 0. 1 to 95 per cent by weight of active compound, preferably from 0.5 to 90 per cent by weight.
The active compounds according to the invention can be present in the formulations or in the various use forms as a mixture with other known active compounds, such as fungicides, bactericides, insecticides, acancides, nematicides, herbicides, bird repellents, growth factors, plant nutrients and agents for improving soil structure.
The active compounds can be used as such or in the form of their formulations or the use forms prepared therefrom by further dilution, such as ready-to-use solutions, emulsions, suspensions, powders, pastes and granules. They are used in the customary manner, for example by watering,immersion, spraying, atomising, misting, vaporizing, injecting, forming a slurry, brushing on, dusting, scattering, dry dressing, moist dressing, wet dressing, slurry dressing or encrustin In the treatment of parts of plants, the active compound concentration in the use forms can be varied within a substantial range. They are. in general. from 1 to 0.0001 '//o by weight, preferably from 0.5 and 0.001 ',/o.
For the treatment of seed, amounts of active compound of 0.001 to 50 g, especially 0.0 1 to 10 lg , are generally employed per kilogram of seed.
For the treatment of soil, active compound concentrations, at the point of action. of 0.0000 1 to 0. 1 % by weight, especially of 0.000 1 to 0.02 01/6, are generally employed.
The preparation and use of the active compounds according to the invention can be seen from the following examples.
Nit 347- ForeiQn Countries Syrithesis Example 1 cl 0 17 ' CH3 N - N-Nr 1 cl H H 3: S CH 3 (Compound No, 4) (Process b):
A mixture of 3-acetyl-2,5-dimethylthiophene (0.46 g), 2,6dichloroisonicotinic acid hydrazide (0.62 g), p-toluenesulfonic acid (0. 1 g) and ethanol (50 ml) was refluxed for 8 hours. After being left for cooling, a product was collected by filtration and recrystallized from ethanol. 2,6-Dichlorolsonicotinic acid [l-(2,5-dimethyl)-3thienyl)ethvildene]-hvdrazide (0.92 was obtained in this manner.
Melting point: 223-225'C.
Svnthesis Example 2 c 1 0 N CH 1 N-N CH, cl H (Compound No. 23) H,CS CN S (Process a) A mixture of hydrazine monohvdrate (1.1 (g), 3-acetN-1---cyano-4-ineth%,I- '--(rnethvlthio)-thiophene (4.2,,) and ethanol (50 rni) vas heated Linder reflux for 8 hours. Ethanol was distilled off and the remaining product v, -as purified by column chromatography using silica gel (eluting solvents, chloroform: ethanol / 08:22). ',-.-\cetvi-5-4-meth-v.l-'-(meth%,Ith'o)- tll'en,,,ihvdrazone (3 S -,) was obtained in t1iis manner.
cyano - I I. - A toluene solution (20 in[) of' 3-acet,,,1-5-cvano-4-iiietii,1-.":.- (nietti.Itlilo)-tllleri,ihvdrazone (0.69 g) was.1,-,oroiisi\, stirred under coolinu, with ice. Then, a toillene solution Nit 347- ForeiQn Countries (10 ml) of 2,6-dichloroisonicotinoyl chloride (0.76 g) was added dropwise while keeping a temperature of 5'C or lower. The mixture was vigorously stirred for further 6 hours. The toluene layer was separated and dried over anhydrous sodium sulfate, and then the toluene was distilled off. The remaining product was purified by column chromatography using silica gel (eluting solvents, chloroform: ethanol / 98.2). 2,6-Di- I I chloroisonicotinic acid [1-((5-cyano-4-methyl-2-methylthio)-3-thienyllethylidene]hydrazide (0.82 g) was obtained in this manner. Melting point: 66-73'C.
Synthesis Example 3 cl 0 N H N-N cl H 1 S Br (Compound No. 32) Br (Process b): A mixture of '),5-dibromothlophene-2-carbaldehvde (0.81 Z), 2,6-dichloroisonicotinic acid hydrazide (0.62 g) and ethanol (50 ml) was refluxed for 8 hours. Ethanol was distilled off and the remaining product was purified by column chromatography using silica gel (eluting solvents, c h1oroform- ethanol / 98:2). 21,6-Dichlorolsonicotinic acid (3,5-dibromo2-thienyl)-methylidene hydrazide ( 1.3 g) was obtained in this manner. Melting point: >250'C (decomposed).
The following Table 2 shows compounds of the formula (1), which were s,,, nthesized according to the processes mentioned above.
Nit 347- Foreiqn Countries Table 2
R 4 0 N -)- N1 N==k,' '1 j R R R 2 R 3 (1) Com- Melting.
pound RI R2 R3 R4 R5 point No. (0 C) Me Me cl cl 96 j X 2 1 Me N3 cl cl 210-212 H 1 H Me C6; cl cl 260-262 1 4 H Me cl cl 223)-225 -l N Allyl Me N:=: cl cl 89-9') 1 \ 6 i-Pr Me N3 cl Cl 141-144 7 H Me 1 cl cl 266 GQ_ 8 H Me 1 k cl cl 217-219 I31 S ar MG 9 H Me S cl cl 213-215 1 \ H Me cl cl 229 S N% Nit 347- Foreiw Countries Table 2 (continued) Com- Melting point pound R' R 2 R M RS (" C) No.
11 1 X 203-204 113 H Me N cl cl e 12 b 177-178 1 H Me N cl cl Z% 13 W 224-225 -N H Me S cl cl 14 CN 165-167 H Me cl cl H 226 Me cl cl 16 -1, 237-239 H Me 0 cl cl 17 195-198 H Me me cl cl 18 249 H Me _--cts\Cr cl cl 19 1 \ 249-251 H Me 'I cl cl S CN 183-187 H Me m S Ph cl cl 21 1 H S cl cl 283-284 H Nit 347- Foreiqn Countries - 1 J Table 2 (continued) Commelting point pouna R' 2 R' R4 RS ('>C) R No.
M9 22 H Me N cl Cl 287-288 S- 2 J3 H Me x Cl Cl 66-73 3 mes", N \ 24 1 H Me 1 ns\ cl Cl 252-253 NO2 H Me cl Cl 252-254 clsx-cl 93r >250 26 H H If cl cl s\ (decomposed) - - me 27 H Me cl"{:, Cl Cl 285-286 S 28 H Me -^S" 11 -BU cl Cl 221-222 1 \ 29 H CH2CN 'IG\ cl Cl 252 S 1 \ H Et '15 cl Cl 197 S 1 X 31 H CF3 101 cl Cl 123-125 S Br > 250 32 H H cl cl S Br (decomposed) Nit 347- Foreim Countries Table 2 (continued) Com- Melting point pound R' 2 R3 p 4 R5 ("C) R No. - 1 \ 33 H t-Bu "G' cl Cl 155-156 1 34 H i-Pr \ cl cl 162-163 S 1 \ H i-Bu J31 cl cl 162-164 S 36 H CF3 Ph cl cl 139-142 W >250 37 H Me 1 X cl cl Me N (decomposed) H M 38 H Me cl Cl 264 a W "" 11/ 39 H H Cl N N Cl Cl 244-257 e Nit 347- Foreign Countries 1 Biological Test Examples Test Examifle A Test of foliar spray effect against rice blast Preparation of formulations of the compounds tested. Active compound: 30 - 40 parts by weight Carrier: mixture of diatornaceous earth and kaolin (L5), 55-65 parts by weight Emulsifier: polyoxyethylene alkyl phenyl ether, 5 parts by weight.
Each of the wettable powders is prepared by pulverizing, and mixing the above amounts of active compound, carrier and emulsifier. A portion of the wettable powder containing the prescribed amount of the active compound is diluted with water, followed by mixing.
Testing procedure Seedling 1 1 ing a ,s of paddy rice (cultivar: Kusabue) were cultured n plastic pots each hav 0 diameter of 7 cm. The previously prepared solution of the prescribed concentration of active compound was sprayed over the seedlings in the 3-4 leaf stage, at a rate of 50 ml per 3) pots. 5 days after the application, a suspension of artIficially cultured,Pvricularia orvzac spores was spray-inoculated twice on the seedlinus, and the seedlings were maintained at 25'C and 100% relative humidity for infection. 7 days after the inoculation, the degree of infection per pot was examined and rated accordina to the following criteria. Further, the control value (%) was calculated. IncidentiallY, the same evaluation of the dearee of infection and the same method for calculatin- the control value were employed in Test Examples B to D.
Nit 347- ForeiQn Countries Evaluation of the degree of infection Degree of Infection Percentage of lesion (spot) area (%) 0 0 0.5 less than 2 1 2 less than 5 2 5 - less than 10 3 10 - less than 20 4 20 - less than 40 5 not less than 40 control value (%) = ' 1 -(degree of infection in treated plot:degree of infection In non-treated plot) ik x 100 As a result, Compounds Nos. 5, 6, 16, 17, 19, 20, 21, 22, 23 24, 25, 26, 29, 31, n, 3 3 3 36, 37 and 38 exhibited a control value of 85 % or higher at an act ve ) 3, _) 4, _) 5, j 1 compound concentration of 500 ppm.
Test Example B Test of water surface application effect aggainst rice blast Testing procedure Seedlings of paddy rice (cultivar: Kusabue) in the 1.5 leaf stage were transplanted into irrigated plastic pots (100 CM2), one seedling per pot. 7 days after the transplanting (when the seedlings were in 3-4 leaf stage), the solution of the prescribed concentration of the active compound. which had been prepared in the manner similar to that of Test Example A, was dropped to the water surface with a pipette at a rate of 10 mI per pot. 10 days after the chemical treatment, a suspension of artificially' cultured spores of rice blast was spray-Inoculated twice on the seedlinus, and the seedling's 30 were maintained in the inoculation box at 25'C and 100% relative humidity for 12 hours for infection. Thereafter. the seedlin-urs were transferred to the greenhouse for Nit 347- Foreiqn Countries management. 10 days after the inoculation, the degree of infection per pot was evaluated, and further the control value (%) was calculated.
As a result, Compounds Nos. 4, 21, 22, 23, 25, 26, 28, 29, 31, 32, 336, 337 and 39 exhibited a control value of 85 % or higher at an active compound concentration of 4 kg/ha.
Test Example C Test of spray against tomato blight Testing procedure About 5 seeds of tomato (cultivar: Kurihara) were sown in each vinyl plastic pot of a diameter of 7 cm, and raised in a greenhouse (at 15- 25'C). The solution obtained by diluting the prepared formulation of the test compound to the prescribed concentration as mentioned above, was sprayed at a rate of 25 ml per.33 pots over small seedlings reaching 4 leaf stage. 5 days after the spraying, the zoosporangya formed on lesions, which had previously been infected and diseased with Phvtophthora infestans. were washed down with a writing-brush into distilled water to prepare a suspension. The suspension was spray- i nocu lated on the treated plants, and they were maintained - in a greenhouse at 15-20'C. 7 days after the inoculation, the degree of infection per pot was evaluated and the control value was calculated. The results are an average of I -) pots.
As a result, Compounds Nos. 4, 5, 6, 10, 11, 12, 14, 23 3, 30, 3 1, 3 2, 34 and 3 7 exhib ited a control value of 85 '//o or higher at an active compound concentration of 500 ppm, Test Example D Test of spray against cucumber mIldew Nit 347- Foreiqn Countries Testing procedure The solution obtained by diluting the test compound to the prescribed concentration, which had been prepared in the manner similar to that of Test Example A, was sprayed by using a spray epn over cucumber seedlings (cultivar: Tokiwatibai) which had been cultivated in each 7 cm plastic pot in the 2 leaf stage. 5 days after the spraying, a solution of spores of Sphaerotheca juligyinea was spray-inoculated, and the seedlings were left at a constant temperature chamber at 23'C. 10 days after the inoculation, the degree of infection per pot was evaluated and the control value was calculated. The results are an average of 3 pots. As a result, Compounds Nos. 10, 11, 12 and 30 exhibited control value of 85 % or higher at an active compound concen- tration of 250 ppm.
Formulation Examples no Formulation Example 1 (Granules) 25 parts by weight of water were added to a mixture of 10 parts by weight of Compound No..3) according to the invention, 30 paris by weight of bentonite (montmorillonite), 58 parts by weight of tale and 2 parts by weight of lignin sulphonic acid W salt. and the mixture was kneaded thorou,,hlv. The resulting product was granulated by means of an extrusion uranulator to form uranules havinu a size of from 10 to 40 meshes. The uranules were dried at a temperature between 40 and 5WC.
Formulation Exampie 11 (Granules) parts by weight of a clay mineral having a particle size distribution Xvithin a range of from 0.2 to 2 mm were introduced into a rotary mixer. This product was uniformly wetted by spraying thereto under rotation a mixture of 5 parts by weight of Cornpound No. 1 according to the invention and a liquid diluent. The granules obtained in this manner x,,, ere dried at a temperature between 40 and 500C, Formulation Example 111 (Emulsion) An emulsion -,vas obtained by mixting, 30 parts by weight ofCornpound No 3 according to the invention. 5 parts by %vet(-,ht ot'xvlene. 8 parts bv wcluht of pol,,.ox.etli-,.,lene Nit 347- Foreicin Countries alkyl phenyl ether, 7 parts by weight of calcium alkylbenzene sulphonate and 50 pans by weight of water with stirring.
Formulation Exarnple IV (Wettable Powder) A wettable powder was prepared by thoroughly mixing 15 parts by weight of Com pound No. 5 according to the invention, 80 parts by weight of a mixture (1:5) of White Carbon (fine powder of hydrated non-crystalline silicon oxide) and powdery clay, 2 parts by weight of sodium alkylbenzene sulphonate and 3 parts by weight of a condensate of sodium alkylnaphthalene sulphonate and formaldehyde in powdery state.
Formulation Example V (Wettable Granules) parts by weight of Compound No. 2 according to the 30 parts by weight Z) 1= of sodium lignin sulphonate, 15 parts by weight of bentonite and 3 5 parts by weight of calcined diatomaceous earth powder were thoroughly mixed with water. The resulting product was granulated by means of extrusion through a 0.3 mm screen. After drying the product, wettable granules were obtained.
It will of course be understood that the present invention has been described above purely by way of example, and that modifications of detail can be made within the scope of this invention.
Nit 347- Foreiqn Countries
Claims (1)
- Patent ClaimsIsonicotinic acid hydrazide derivatives of the formula 4 0 N RN N= R 5 R 1/ R R- R 3 in which RI is hydro,-,en. alkA or alkenvi, R2 is hydrogen. alkyl, haloalkyl or cyanoalkyl.R3 is optionally substituted phenyl, or is an optionally substituted 5- or 6membered heterocyclic radical, or is an optionally substituted benzoftised heterocyclic radical comprising a 5- or 6-membered heterocycle, and R4 and C independently of each other are hydrogen. halogen. hydroxy or alkox.2. Isonicotinic acid hydrazide derivatives of the fiormula (1) according to claim 1, in which RI is hydrogen. C 1-4 alkyl Or C-2-4 alkeni, R2 is hydro-gen. C 1-4 alkvl, C 1-4 lialoalkyl or C 1 -4 c,,.-,inoaik\.].R3 is plienyL or is py,r,d.,,1. thlen\,[, 1)y.rrol.,.[, tli,azoi\,1. 1'urvi. 1)Yrazol\ll.pyrazinyl, 1),..rimidin\.1, benz[blthien,,..1, quinolyl or isoquinol\,1. each of' Nit-347- Fcweittn,C. ories which may be substituted by up to 3 substituents selected from halo- gen, cyano, nitro, Cl-4 alkyl, Cl-4 alkoxy, Cl-4 alkylthio, amino, C1-4 1 alkylamino, di(C 1-4 alkyl)an-iino and phenyl, and -10 R4 and R5 independently of each other represent hydrogen, chlorine, hydroxy or methoxy.Isonicotinic acid hydraziole derivatives of the formula (I) according to claim 1, in which RI 1. drogen, C, s hy -4 alkyl or C2-4 alkenvi, R2 is hydrogen, C 1-4 alkyl, C 1-4 haloalkyl or C 1-4 cyanoalkyl, R3 is pyridyl, thienyl, pyrrolyl, thiazolyl, furyl, pyrazolyl, pyrazinyl, pyrimidinyl, benzo[blthienyi, quinolyl or isoquinolyl, each of which may be substituted by up to 3 substituents selected from fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, see-butyl, methoxy, ethoxy, methylthio. ethylthio, amino, dimethvlamino and phenyl and R4 and C independently of each other represent hydrogen, chlorine. hydroxy or methoxy.4, Process for the preparation of isonicotinic acid hydrazide deri".,ati-, -es of the formula (1) according to claim 1, characterized in that a) isonicotinic acid derivatives of the formula Nit 347- Foreiqn Countries R 4 0 N cl 1 1 D__1 (II) in which R4 and R5 have the above-mentioned meanings, W o _w are reacted with hydrazine derivatives of the formula R 2 R 1 in which H N-N--. R 3 OID RI, R2 and R3 have the above-mentioned meanings, if appropriate in the presence of an acid-binding acent and if 1 - appropriate in the presence of a diluent, or b) reacting 1sonicotinic acid hydrazides of the formula R 4 0 N-NH, N1 R 5 R 1/ in which Nit 347Foreicin Countries ([V) RI, R4 and R5 have the above-mentioned meanings, are reacted with carbonyl compounds of the formula o=c / R 2 (V) \ R 3 in which R2 and R3 have the above-mentioned meanings, c if appropriate in the presence of an acid catalyst and if appropriate in the presence of a diluent.5. Microbicidal compositions, characterized in that they contain at least one ISO- nicotinic acid hydrazide derivative of the formula (I) according to claim I plus extenders and/or surface active a(yents.6. Process for combatin- undesired microoruanisms, characterized in that iso- nicotinic acid hydrazide derivatives of the formula (1) according to claim I are applied to the microorganisms and/or to their habitat.7. Use of isonicotinic acid hydrazide derivatives of the formula (I) accordinu to claim 1 for combating undesired microorganisms.Process for the preparation of microbicidal compositions. characterized in that isonicotinic acid hydrazide derivatives of the formula (1) according to claim I are mixed with extenders and/or surface active agents.Nit 347- Foreign Countries 9. Isonicotinic acid hydrazide derivative according to claim 1, as hereinbefore specifically identified.10. Process for the production of an isonicotinic acid hydrazide derivative according to claim 1, when carried out substantially as described in any one of Synthesis Examples 1 to 3.11. Isonicotinic acid hydrazide derivative according to claim 1, when prepared by the process of claim 4 or 10.Use of isonicotinic acid hydrazide derivative according to claim 9 or 11 for combating undesired microorganisms.Nit 347- Foreiqn Counihies
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Cited By (3)
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| WO2011069039A1 (en) * | 2009-12-04 | 2011-06-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Hydrazone and diacyl hydrazine compounds and methods of use |
| CN104356062A (en) * | 2014-10-22 | 2015-02-18 | 玉林师范学院 | Preparation method of p-hydroxybenzaldehyde condensed isoniazide and application thereof |
| US11603364B2 (en) | 2020-08-27 | 2023-03-14 | Alterity Therapeutics Limited | Acyl hydrazone derivative compounds for treating disease |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011069039A1 (en) * | 2009-12-04 | 2011-06-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Hydrazone and diacyl hydrazine compounds and methods of use |
| US8518968B2 (en) | 2009-12-04 | 2013-08-27 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Hydrazone and diacyl hydrazine compounds and methods of use |
| CN104356062A (en) * | 2014-10-22 | 2015-02-18 | 玉林师范学院 | Preparation method of p-hydroxybenzaldehyde condensed isoniazide and application thereof |
| US11603364B2 (en) | 2020-08-27 | 2023-03-14 | Alterity Therapeutics Limited | Acyl hydrazone derivative compounds for treating disease |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2764290A1 (en) | 1998-12-11 |
| JPH10338673A (en) | 1998-12-22 |
| DE19822889A1 (en) | 1998-12-10 |
| GB9811957D0 (en) | 1998-07-29 |
| GB2325932B (en) | 2001-06-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20030603 |