CA1116607A - PROCESS FOR THE PREPARATION OF N-SUBSTITUTED .alpha.-HALOGENOACETANILIDES - Google Patents
PROCESS FOR THE PREPARATION OF N-SUBSTITUTED .alpha.-HALOGENOACETANILIDESInfo
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- CA1116607A CA1116607A CA000333393A CA333393A CA1116607A CA 1116607 A CA1116607 A CA 1116607A CA 000333393 A CA000333393 A CA 000333393A CA 333393 A CA333393 A CA 333393A CA 1116607 A CA1116607 A CA 1116607A
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C07C233/04—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C233/07—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D231/16—Halogen atoms or nitro radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
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- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
ABSTRACT OP THE DISCLOSURE
Herbicidally active N-substituted .alpha.-halogenoacetanilides of the general formula (XI), in which R represents an optionally substituted N-containing heterocyclic radical bonded via a ring nitrogen atom or represents the grouping an optionally substituted furyl or thiophenyl radical, alkenyl, alkynyl, alkoxy, alkylcarbonyl or an optionally substituted phonyl, phenoxy or phonylcarbonyl radical, A represents oxygen, sulphur or the grouping >NR3, B reprensents hydrogen, alkyl, halogenoalkyl, alkenyl, alkynyl, cycloalkyl, halogen, an optionally substituted aryl or aralkyl radical or the grouping -OR4, -SR4 or -NR3R4, R1 and R2, independently of one another, each represent hydrogen, alkyl, cycloalkyl, halogenoalkyl, alkoxyalkyl, alkenyl, alkynyl or optionally substituted phenyl, R3 represents hydrogen, alkyl or optionally substituted aryl, R4 represents hydrogen, alkyl, halogenoalkyl, alkenyl, alkvnyl, cycloalkyl or optionally substituted aralkyl, X1, X2 and X3 independently of one another, each represent hydrogon or alkyl and Hal roprosonts halogen, are prepared by a process, in which a haloacetanilide of the general formula in which Hal, X1, X2 and X3 have the above-mentioned meanings, is reacted with a compound of the general formula
Herbicidally active N-substituted .alpha.-halogenoacetanilides of the general formula (XI), in which R represents an optionally substituted N-containing heterocyclic radical bonded via a ring nitrogen atom or represents the grouping an optionally substituted furyl or thiophenyl radical, alkenyl, alkynyl, alkoxy, alkylcarbonyl or an optionally substituted phonyl, phenoxy or phonylcarbonyl radical, A represents oxygen, sulphur or the grouping >NR3, B reprensents hydrogen, alkyl, halogenoalkyl, alkenyl, alkynyl, cycloalkyl, halogen, an optionally substituted aryl or aralkyl radical or the grouping -OR4, -SR4 or -NR3R4, R1 and R2, independently of one another, each represent hydrogen, alkyl, cycloalkyl, halogenoalkyl, alkoxyalkyl, alkenyl, alkynyl or optionally substituted phenyl, R3 represents hydrogen, alkyl or optionally substituted aryl, R4 represents hydrogen, alkyl, halogenoalkyl, alkenyl, alkvnyl, cycloalkyl or optionally substituted aralkyl, X1, X2 and X3 independently of one another, each represent hydrogon or alkyl and Hal roprosonts halogen, are prepared by a process, in which a haloacetanilide of the general formula in which Hal, X1, X2 and X3 have the above-mentioned meanings, is reacted with a compound of the general formula
Description
11~66~7 - 1 - Type IVa The present invention relates to an unobvious process for the preparation of certain N-substituted ~-halogeno-acetanilides which have herbicidal and fungicidal proper-ties and most of which are known.
It has already been disclosed that N-substituted ~-halogenoacetanilides are obtained when anilines are re-acted, in a first stage, with correspondingly substituted halogenomethyl derivatives in the presence of an inert organic solvent and in the presence of an acid-binding agent, preferably at the boiling point of the solvent used, and the N-substituted anilines thus obtained are reacted in a second stage in the presence of an inert organic solvent and optionally in the presence of an acid-binding agent at temperatures between 20 and 100C with a halogenoacetyl-15 ating agent, for example halogenoacetyl chloride, inaccordance with the following reaction equation (see, inter alia, U.S. Patent Specifications 3,442,945, 3,780,090, 3,900,497, 3,946,045, 3,948,950, 4,001,325 and 4,032,657 and also German Offenlegungsschriften (German Published 20 Specification) 2,305,495, 2,311,897, 2,328,340, 2,350,944,
It has already been disclosed that N-substituted ~-halogenoacetanilides are obtained when anilines are re-acted, in a first stage, with correspondingly substituted halogenomethyl derivatives in the presence of an inert organic solvent and in the presence of an acid-binding agent, preferably at the boiling point of the solvent used, and the N-substituted anilines thus obtained are reacted in a second stage in the presence of an inert organic solvent and optionally in the presence of an acid-binding agent at temperatures between 20 and 100C with a halogenoacetyl-15 ating agent, for example halogenoacetyl chloride, inaccordance with the following reaction equation (see, inter alia, U.S. Patent Specifications 3,442,945, 3,780,090, 3,900,497, 3,946,045, 3,948,950, 4,001,325 and 4,032,657 and also German Offenlegungsschriften (German Published 20 Specification) 2,305,495, 2,311,897, 2,328,340, 2,350,944,
2,402,983 and 2,648,008):
X', X' ~ NH + Hal' Y~-R~ _ Base ~3_ x~3 (II) (I) X'~
\ / Y'-R' X~ ~ N + Hal'-CO-CH2Hal' I H (IV) X'3 (III) Le A 19 033 .
, .
11~.66~7 -HHal X 2-~ "
X' (~') C-CH2Hal' in which h rcpresents, amongst others, alkoxy, alkyl, alkenyl, alkynyl, dioxolanyl, dithiepanyl, a N-containing heterocyclic radical bonded by a ring nitrogen atom or a carboxylic acid ester radical, X1` , X2'and X3` each represent, amongst others, hydrogen, alkyl, alkoxy, halogenoalkyl, alkoxyalkyl, X1 , X2' and X3' being selected independently of each other, Y' represents alkylene or alkylidene, and Hal represents halogen.
This process has, however, a number of disadvantages.
Thus, the danger of side reactions in both process steps is very great and this can result in considerable losses in yield. Furthermore, during the alkylation of the anilines there is a possibility that both hydrogen atoms on the aniline nitrogen will react, which results in mix-tures of substances. Moreover, depending on the meaning of R', it is possible for the halogenoacetylation of the second stage to take place not only at the aniline nitrogen but, for example, also at a N-atom of the radical R\.
Furthermore, it has already been disclosed that, in particular, N-azolylmethyl-a-halogenoacetanilides can be obtained when anilines are reacted with paraformaldehyde in the presence of catalytic amounts of potassium hydroxide, a halogenoacetyl halide is added to the resulting phenyl-azom~ethines (see U.S. Patent Specifications 3,630,716 LE A 19 û33 6~7 ..
and 3,637,837) and the resulting M-halogenomethyl-~-halogenoacetanilides are reacted with appropriate hetero-cyclic compounds, optionally in the presence of an acid-binding agent and in the presence of an inert organic solvent at temperatures between 0 and 200C, in accord-ance with t~e following reaction equation (see also German Offenlegungsschrift (German Published Specification) 2,648,oo8);
X ', X,~
X~ ~ - NH2 + ~ (CH20)n3~ X~2 ~ _ N=CH2 X'3 x~3 (I) (VI) (VII) X~ CH2-Hal' Hal'-CO-CH2-Hal' - ~ X'2 ~ N\
(IV) X'~ C-CH2Hal' O (VIII) + H-A' Base ~ X'2 ~ / CH2-A' (IX) -HHal' X'~ lO 2 in which A' represents a N-containing heterocyclic radical bonded via a ring nitrogen atom, and Xl', X2', X3' and Hal' have the meanings stated above.
This process also has the disadvantage that it does not always proceed with satisfactory yields. The inter-mediate products formed are not always very stable and, because of their high reactivity, are difficult to isolate in a pure form, and this frequently results in highly con-taminated end products.
The present invention now provides a process for the preparation of a N-substituted a-halogenoacetanilide of the general formula :
Le A 19 033 6~7 2 R.
~ N / (XI) X C - CH2Hal O
in which R represents a pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,3,4-tetrazol-1-yl or pyrrol-l-yl radical, each of said radicals being optionally substituted by halogen, Cl 4 alkyl, Cl 4 alkoxy, Cl 4 alkylthio, phenyl, Cl 4 perfluoroalkyl, cyano, (Cl 4 alkyl)carbonyl, (Cl 4 alkoxy)carbonyl or hydroxycarbonyl bonded via a ring nitrogen atom, or rep-resents the grouping N - N
A B :~
or a furyl or thiophenyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms, alkenyl, alkynyl, alkoxy, alkylcarbonyl, or a phenyl, phenoxy or phenylcarbonyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
A is oxygen or the grouping = NR ;
B is hydrogen, alkyl haloalkyl, alkenyl, alkynyl, cycloalkyl or halogen, or an aryl or aralkyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms, and up to 5 halogen atoms, or the grouping -oR4, -SR4 or -NR3R4;
R and R are individually selected from hydrogen, alkyl, cycloalkyl, halo-alkyl, alkoxyalkyl, alkenyl or alkynyl, or a phenyl radical optionally sub-stituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl_2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
. .
1116~7 R3 is hydrogen or alkyl, or an aryl radical optionally substituted by halogen,Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
R is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl, or an aralkyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
Xl, X and X3 are individually selected from hydrogen or alkyl; and Hal is halogen; in which a halogenoacetanilide of the general formula -4a-6~7 x2 Xl H (XII), ~ - N /
X3 C ~ CH2 ~ Hal in which Hal, Xl, x2 and X3 have the above-mentioned meanings, is reacted with a compound of the general formula R (XIII), in which R, R1 and R2 have the above-mentioned meanings and Y represents halogen, aIkylsulphonyl or optionally substituted phenyl-sulphonyl, in the presen oe of an acid-binding agent and optionally in the presence of an organic solvent, it being possible optionally to use the campound of the formula (XIII) in the form of an acid addition salt.
It is to be regarded as extremely surprising that the reaction accord-ing to the invention pro oe eds in the indicated nanner. Under the given pro oe ss conditions, an anion is formed at the nitrogen atam of the halogenoaoe tanilides of the formula (XII) and this Lhen reacts well with the compounds of the formula (XIII) to give the oompounds, according to the invention, of the formula (XI).
However, there are a number of reaction possibilities which appear much more probable. It would be expected, for example, that the above-mentioned anion would react intramolecularly with the halogenomethyl group to give a three-membered ring or that an epoxide would be formed via the possible tautomeric form ill66~
fl ~ fl - N - C - CH - Hal ~ - N = C ~
0 2 ~ _ CH - Hal An intermolecular side reaction would also be expected, that is to say it would be expected that an O-alkylation would take place at the above-mentioned tautameric form instead of a N-alkylation at t~e halogenoaoe tanilide.
It is also surprising that in the case of the reaction according to the invention the halogenoa oe tanilide does not form 2,5-dioxo-1,4-diphenyl-piperazine ex dusively, in accordan oe with the follawing reactian equation (see also Journal fur Praktische Chemie 40, 426(1889)):
x2 X r~ - ~~~~~~~~ - ---H 1' CH I xl ~ x2 X3 C - OEI2 -LHal___________ _ _ H~ ~XII) (XII) ~ Xl x2 -2 3 ~al x ~ X ~ x (XIV) 10FurthermDre, when a~ueous sodium hydroxide solution is used as the acid-binding agent, nucleophilic replacement of the halogen by the hydroxyl group would also be can oe ivable, both in the case of the halogenoacetanilides of the formula (XII~ and in the case of the compounds of the formula (XIII).
~ ne fact that the reactian according to the invention proceeds without complications is the more surprising in view of the possible and also probable courses of reactian.
,,~, ~ - .
~166~7 The process according to the invention has a nurnber of advantages.
Thus, both the halogenoacetanilides of the formula (XII), which are to be used as starting materials, and the compounds of the formula (XIII) are readily accessible and can be isolated virtually quantitatively and in pure form as stable substances. The conditions for carrying out the process according to the invention are very mild and in particular only very low temperatures are re-quired. The ccmpounds according to the invention can be o~tained in good yield and high purity. The fact that this process has broad applicability, since, in principle, all those compounds of the formula (XIII) in which the radical R
activates the replacement of the leaving group Y can be employed, is also to be singled out.
Formula (XI) gives a general definition of the N-substituted ~-halogenoaoe tanilides which can be prepared by the prooe ss according to the inven-tion. Preferably, in the formula (XI):
R represents an optionally substituted pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,3,4-tetrazol-1-yl or pyrrol-l-yl radical, preferred substituents being: halogen (especially fluorine, chlorine and branine), straight-chain or branched aIkyl with 1 to 4 carbon at~ns, alkoxy or alkylthio with, in either case, 1 to 4 carbon atoms, phenyl, perfluoroalkyl with 1 to 4 carbon atoms, cyano, alkylcarbonyl or alkoxycarbonyl with, in either case, 1 to 4 carbon atoms in the alkyl or alkoxy part, or hydroxycarbonyl, or R represents the grouping ~ A ~ B
in which A represents oxygen, sulphur or the grouping > NR , in which R represents hydrogen, straight-chain or branched alkyl with 1 to 4 carbon .....
.
~66~7 atoms or aryl with 6 to 10 carbon atoms (especially phenyl), it being possible for the aryl radical to carry one or more substituents selected from halogen, aIkyl with 1 to 4 carbon atoms, : - 7a -., ~
~.
~1~7 alkoxy with 1 or 2 carbon atoms~ alkylthio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine and chlorine), and B represents hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, halogenoalkyl with up to
X', X' ~ NH + Hal' Y~-R~ _ Base ~3_ x~3 (II) (I) X'~
\ / Y'-R' X~ ~ N + Hal'-CO-CH2Hal' I H (IV) X'3 (III) Le A 19 033 .
, .
11~.66~7 -HHal X 2-~ "
X' (~') C-CH2Hal' in which h rcpresents, amongst others, alkoxy, alkyl, alkenyl, alkynyl, dioxolanyl, dithiepanyl, a N-containing heterocyclic radical bonded by a ring nitrogen atom or a carboxylic acid ester radical, X1` , X2'and X3` each represent, amongst others, hydrogen, alkyl, alkoxy, halogenoalkyl, alkoxyalkyl, X1 , X2' and X3' being selected independently of each other, Y' represents alkylene or alkylidene, and Hal represents halogen.
This process has, however, a number of disadvantages.
Thus, the danger of side reactions in both process steps is very great and this can result in considerable losses in yield. Furthermore, during the alkylation of the anilines there is a possibility that both hydrogen atoms on the aniline nitrogen will react, which results in mix-tures of substances. Moreover, depending on the meaning of R', it is possible for the halogenoacetylation of the second stage to take place not only at the aniline nitrogen but, for example, also at a N-atom of the radical R\.
Furthermore, it has already been disclosed that, in particular, N-azolylmethyl-a-halogenoacetanilides can be obtained when anilines are reacted with paraformaldehyde in the presence of catalytic amounts of potassium hydroxide, a halogenoacetyl halide is added to the resulting phenyl-azom~ethines (see U.S. Patent Specifications 3,630,716 LE A 19 û33 6~7 ..
and 3,637,837) and the resulting M-halogenomethyl-~-halogenoacetanilides are reacted with appropriate hetero-cyclic compounds, optionally in the presence of an acid-binding agent and in the presence of an inert organic solvent at temperatures between 0 and 200C, in accord-ance with t~e following reaction equation (see also German Offenlegungsschrift (German Published Specification) 2,648,oo8);
X ', X,~
X~ ~ - NH2 + ~ (CH20)n3~ X~2 ~ _ N=CH2 X'3 x~3 (I) (VI) (VII) X~ CH2-Hal' Hal'-CO-CH2-Hal' - ~ X'2 ~ N\
(IV) X'~ C-CH2Hal' O (VIII) + H-A' Base ~ X'2 ~ / CH2-A' (IX) -HHal' X'~ lO 2 in which A' represents a N-containing heterocyclic radical bonded via a ring nitrogen atom, and Xl', X2', X3' and Hal' have the meanings stated above.
This process also has the disadvantage that it does not always proceed with satisfactory yields. The inter-mediate products formed are not always very stable and, because of their high reactivity, are difficult to isolate in a pure form, and this frequently results in highly con-taminated end products.
The present invention now provides a process for the preparation of a N-substituted a-halogenoacetanilide of the general formula :
Le A 19 033 6~7 2 R.
~ N / (XI) X C - CH2Hal O
in which R represents a pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,3,4-tetrazol-1-yl or pyrrol-l-yl radical, each of said radicals being optionally substituted by halogen, Cl 4 alkyl, Cl 4 alkoxy, Cl 4 alkylthio, phenyl, Cl 4 perfluoroalkyl, cyano, (Cl 4 alkyl)carbonyl, (Cl 4 alkoxy)carbonyl or hydroxycarbonyl bonded via a ring nitrogen atom, or rep-resents the grouping N - N
A B :~
or a furyl or thiophenyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms, alkenyl, alkynyl, alkoxy, alkylcarbonyl, or a phenyl, phenoxy or phenylcarbonyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
A is oxygen or the grouping = NR ;
B is hydrogen, alkyl haloalkyl, alkenyl, alkynyl, cycloalkyl or halogen, or an aryl or aralkyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms, and up to 5 halogen atoms, or the grouping -oR4, -SR4 or -NR3R4;
R and R are individually selected from hydrogen, alkyl, cycloalkyl, halo-alkyl, alkoxyalkyl, alkenyl or alkynyl, or a phenyl radical optionally sub-stituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl_2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
. .
1116~7 R3 is hydrogen or alkyl, or an aryl radical optionally substituted by halogen,Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
R is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl, or an aralkyl radical optionally substituted by halogen, Cl 4 alkyl, Cl 2 alkoxy, Cl 2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
Xl, X and X3 are individually selected from hydrogen or alkyl; and Hal is halogen; in which a halogenoacetanilide of the general formula -4a-6~7 x2 Xl H (XII), ~ - N /
X3 C ~ CH2 ~ Hal in which Hal, Xl, x2 and X3 have the above-mentioned meanings, is reacted with a compound of the general formula R (XIII), in which R, R1 and R2 have the above-mentioned meanings and Y represents halogen, aIkylsulphonyl or optionally substituted phenyl-sulphonyl, in the presen oe of an acid-binding agent and optionally in the presence of an organic solvent, it being possible optionally to use the campound of the formula (XIII) in the form of an acid addition salt.
It is to be regarded as extremely surprising that the reaction accord-ing to the invention pro oe eds in the indicated nanner. Under the given pro oe ss conditions, an anion is formed at the nitrogen atam of the halogenoaoe tanilides of the formula (XII) and this Lhen reacts well with the compounds of the formula (XIII) to give the oompounds, according to the invention, of the formula (XI).
However, there are a number of reaction possibilities which appear much more probable. It would be expected, for example, that the above-mentioned anion would react intramolecularly with the halogenomethyl group to give a three-membered ring or that an epoxide would be formed via the possible tautomeric form ill66~
fl ~ fl - N - C - CH - Hal ~ - N = C ~
0 2 ~ _ CH - Hal An intermolecular side reaction would also be expected, that is to say it would be expected that an O-alkylation would take place at the above-mentioned tautameric form instead of a N-alkylation at t~e halogenoaoe tanilide.
It is also surprising that in the case of the reaction according to the invention the halogenoa oe tanilide does not form 2,5-dioxo-1,4-diphenyl-piperazine ex dusively, in accordan oe with the follawing reactian equation (see also Journal fur Praktische Chemie 40, 426(1889)):
x2 X r~ - ~~~~~~~~ - ---H 1' CH I xl ~ x2 X3 C - OEI2 -LHal___________ _ _ H~ ~XII) (XII) ~ Xl x2 -2 3 ~al x ~ X ~ x (XIV) 10FurthermDre, when a~ueous sodium hydroxide solution is used as the acid-binding agent, nucleophilic replacement of the halogen by the hydroxyl group would also be can oe ivable, both in the case of the halogenoacetanilides of the formula (XII~ and in the case of the compounds of the formula (XIII).
~ ne fact that the reactian according to the invention proceeds without complications is the more surprising in view of the possible and also probable courses of reactian.
,,~, ~ - .
~166~7 The process according to the invention has a nurnber of advantages.
Thus, both the halogenoacetanilides of the formula (XII), which are to be used as starting materials, and the compounds of the formula (XIII) are readily accessible and can be isolated virtually quantitatively and in pure form as stable substances. The conditions for carrying out the process according to the invention are very mild and in particular only very low temperatures are re-quired. The ccmpounds according to the invention can be o~tained in good yield and high purity. The fact that this process has broad applicability, since, in principle, all those compounds of the formula (XIII) in which the radical R
activates the replacement of the leaving group Y can be employed, is also to be singled out.
Formula (XI) gives a general definition of the N-substituted ~-halogenoaoe tanilides which can be prepared by the prooe ss according to the inven-tion. Preferably, in the formula (XI):
R represents an optionally substituted pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,3,4-tetrazol-1-yl or pyrrol-l-yl radical, preferred substituents being: halogen (especially fluorine, chlorine and branine), straight-chain or branched aIkyl with 1 to 4 carbon at~ns, alkoxy or alkylthio with, in either case, 1 to 4 carbon atoms, phenyl, perfluoroalkyl with 1 to 4 carbon atoms, cyano, alkylcarbonyl or alkoxycarbonyl with, in either case, 1 to 4 carbon atoms in the alkyl or alkoxy part, or hydroxycarbonyl, or R represents the grouping ~ A ~ B
in which A represents oxygen, sulphur or the grouping > NR , in which R represents hydrogen, straight-chain or branched alkyl with 1 to 4 carbon .....
.
~66~7 atoms or aryl with 6 to 10 carbon atoms (especially phenyl), it being possible for the aryl radical to carry one or more substituents selected from halogen, aIkyl with 1 to 4 carbon atoms, : - 7a -., ~
~.
~1~7 alkoxy with 1 or 2 carbon atoms~ alkylthio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine and chlorine), and B represents hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, halogenoalkyl with up to
3 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine and chlorine and a specific example of halogenoalkyl being trifluoromethyl), alkenyl or alkynyl with in either case 2 to 4 carbon atoms, cycloalkyl with 5 to 7 carbon atoms, halogen (especially fluorine, chlorine or bromine), aryl with 6 to 10 carbon atoms (especially phenyl) [which aryl radical can optionally carry one or more substituents selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbcn atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine or chlorine and a specific example of halogenoalkyl being trifluoromethyl)], aralkyl with 6 to 10 carbon atoms in the aryl part and 1 to 4 carbon atoms in the alkyl part (especially benzyl)[it being possible for the aralkyl radical to carry one or more substituents in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylbhio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine or chlorine and a specific example of halogenoalkyl being trifluoromethyl)] or the grouping -oR4, -SR4 or -N R3R4, in which R3 represents hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms or aryl with 6 to 10 carbon atoms (especially phenyl),it being possible for the aryl radical to carry one or more substituents selected from Le A 19 033 1~66~)7 g halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine and chlorine), and R4 represents hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, halogenoalkyl with up to 3 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine and chlorine and 10 an example being trifluoromethyl), alkenyl or alkyny:l with, in either case, 2 to 4 carbon atoms, cycloalkyl with 5 to 7 carbon atoms or aralkyl with 6 to 10 carbon atoms in the aryl part and 1 to 4 carbon atoms in the alkyl pa:rt (especially benzyl)[it being possible for the aralkyl 15 radical to carry one or more substituents in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbon atoms and up to 5 identical or different halogen 20 atoms (preferred halogens being fluorine or chlorine and a specific example of halogenoalkyl being trifluoromethyl)], or R represents an optionally substituted furyl or thio-phenyl radical [preferred substituents being halogen, alkyl :~ 25 with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and halogeno-alkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine or chlorine and a specific example of halogenoalkyl being y 30 trifluoromethyl)], alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, alkoxy or alkylcarbonyl with, in either case, 1 to 4 carbon atoms in the alkyl part, or an option-ally substituted phenyl, phenoxy or phenylcarbonyl radical [possible substituents being halogen, alkyl with 1 to 4 35 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano 3 nitro and halogenoalkyl Le A 19 033 ~1~6~!i7 with up to 2 carbon atoms and up to 5 identical or different halogen atoms (preferred halogens being fluorine or chlorine and a specific example of halogenoalkyl being trifluonomethyl)], Rl and R2, which may be identical or different, each represent hydrogen, straight-chain or branched aIkyl with 1 to 4 carbon atoms, halogenoalkyl with up to 2 carbon atoms and 5 identical or different halogen atoms (preferred halogen atoms being fluorine and chlorine), aIkoxyaIkyl with 1 to 4 carbon atoms in the alkyl part and 1 to 4 carbon atoms in the aIkoxy part, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, or optionally substituted phenyl [preferred substituents being halogen, aIkyl with 1 to 4 carbon atoms, aIkoxy with 1 or 2 carbon atcn~s, aIkylthio with 1 or 2 carbon atoms, cyano, nitro and halogenoalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atcms (preferred halogens being fluorine or chlorine and a specific example of halogenoaIkyl being trifluoromethyl)], Xl, x2 and X3, which may be identical or different, each represent hydrogen or straight-chain or branched alkyl with 1 to 4 carbon atcms, and Hal represents fluorine, chlorine and bromine.
If, for example, 2-ethyl-6-methyl-chloroacetanilide and N-(l-chloro-methyl)-pyrazole hydrochloride are used as the starting materials, the course of the reaction of the process according to the invention can be represented by the following equation:
~C - CH Cl Cl - CH2 - N ~ x HCl Base 2 5 C 2 - N~
-- 11166~7 Formula (XII) gives a general definition of the halogenoacetanilides required as starting materials for carrying out the process according to the invention. In this formula, Hal, Xl, x2 and X3 preferably have those meanings which have already been mentioned as preferred, in the context of the description of the compounds of the formula (XI).
The halogenoacetanilides of the formula (XII) are generally known or can be obtained in a generally known manner, by reacting corresponding anilines with a halogeno-acetyl halide or halogenoacetic anhydride in the presence of an inert organic solvent, for example toluene or dimethylformamide, optionally in the presence of an acid-binding agent, for example potassium carbonate, at temperatures between 20 and 100C. Examples of compounds of the formula (XII) which may be mentioned are: chloro-(bromo)acetanilide, 2-methyl-chloro(bromo)acetanilide~
2-ethyl-chloro(bromo)acetanilidej 2-isopropyl-chloro(bromo)-acetanilide, 2-sec.-butyl-chloro(bromo)acetanilidej 2--tert.-butyl-chloro(bromo)acetanilide, 2,6-dimethyl-chloro(bromo)-acetanilide, 2,3-dimethyl-chloro(bromo)acetanilide, 2,5-di-methyl-chloro(bromo)acetanilide, 3,5-dimethyl-chloro(bromo)-acetanilide, 2,6-diethyl-chloro(bromo)acetanilide, 2-ethyl-6-methyl-chloro(bromo)acetanilide, 2,3,4-trimethyl-chloro-(bromo)acetanilide, 2,4,6-trimethyl-chloro(bromo)acet-anilide, 2,4,5-trimethyl-chloro(bromo)acetanilide, 2,3,5-trimethyl-chloro(bromo)acetanilide, 2-ethyl-4,6-dimethyl-chloro(bromo)acetanilide, 2,6-diethyl-4-methyl-chloro-(bromo)acetanilide and 2,6-diisopropyl-4-methyl-chloro-(bromo)acetanilide.
Formula (XIII) gives a general definition of thecompounds which are also to be used as starting materials for the reaction according to the invention. In this formula, R, Rl and R2 preferably have those meanings which have already been mentioned as preferred, in the context of the description of the compounds of the formula (XI).
Le A 19 033 66~7 Y preferably represents chlorine, bromine, iodine, alkylsulphonyl with l to 4 carbon atoms or optionally substituted phenylsulphonyl, preferred substituents being halogen and alkyl with 1 to 4 carbon atoms.
Most of the compounds of the formula (XIII) are known Compounds of the formula (XIII) not hitherto described in the literature are those in which R represents an optionally substituted heterocyclic radical bonded by a ring nitrogen atom and Rl represents hydrogen. They can be obtained by reacting a heterocyclic compound of the general formula , R5 H-N ~ 6 (XIV), R
in which R5 and R6 together with the nitrogen atom represent a heterocyclic ring which is optionally substituted and which optionally contains further N-atoms, with an aldehyde of the general formula 0=CH-R (XV) 9 in which R2 has the meaning stated above, optionally in the presence of an inert organic solvent, for example methylene chloride, at temperatures between -70 and +50C and reacting the resulting compounds of the general formula H0-CH-N~ 6 (XVI), in which R2, R5 and R6 have the meanings stated above, directly or optionally after isolation, with a chlorinating agent, for example thionyl chloride, or a sulphonating agent, for example methylsulphonyl chloride, optionally in the presence of an inert organic solvent, for example Le A 19 033 66~
- 13 ~
methylene chlo~ide, at temperatures between -70C and +50C.
In the compounds of the formula (XIV), R5 and R
together with the nitrogen atom preferably represent the optionally substituted azolyl radicals pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl and 1,2,3,4-tetrazol-1-yl or represent optionally substi-tuted pyrrol-l-yl, preferred substituents being halogen, especially fluorine, chlorine and bromine, straight-chain or branched alkyl with 1 to 4 carbon atoms, alkoxy or alkylthio with, in either case, 1 to 4 carbon atoms, phenyl, perfluoroalkyl with 1 to 4 carbon atoms, cyano, alkylcarbonyl or alkoxycarbonyl with, in either case, 1 to
If, for example, 2-ethyl-6-methyl-chloroacetanilide and N-(l-chloro-methyl)-pyrazole hydrochloride are used as the starting materials, the course of the reaction of the process according to the invention can be represented by the following equation:
~C - CH Cl Cl - CH2 - N ~ x HCl Base 2 5 C 2 - N~
-- 11166~7 Formula (XII) gives a general definition of the halogenoacetanilides required as starting materials for carrying out the process according to the invention. In this formula, Hal, Xl, x2 and X3 preferably have those meanings which have already been mentioned as preferred, in the context of the description of the compounds of the formula (XI).
The halogenoacetanilides of the formula (XII) are generally known or can be obtained in a generally known manner, by reacting corresponding anilines with a halogeno-acetyl halide or halogenoacetic anhydride in the presence of an inert organic solvent, for example toluene or dimethylformamide, optionally in the presence of an acid-binding agent, for example potassium carbonate, at temperatures between 20 and 100C. Examples of compounds of the formula (XII) which may be mentioned are: chloro-(bromo)acetanilide, 2-methyl-chloro(bromo)acetanilide~
2-ethyl-chloro(bromo)acetanilidej 2-isopropyl-chloro(bromo)-acetanilide, 2-sec.-butyl-chloro(bromo)acetanilidej 2--tert.-butyl-chloro(bromo)acetanilide, 2,6-dimethyl-chloro(bromo)-acetanilide, 2,3-dimethyl-chloro(bromo)acetanilide, 2,5-di-methyl-chloro(bromo)acetanilide, 3,5-dimethyl-chloro(bromo)-acetanilide, 2,6-diethyl-chloro(bromo)acetanilide, 2-ethyl-6-methyl-chloro(bromo)acetanilide, 2,3,4-trimethyl-chloro-(bromo)acetanilide, 2,4,6-trimethyl-chloro(bromo)acet-anilide, 2,4,5-trimethyl-chloro(bromo)acetanilide, 2,3,5-trimethyl-chloro(bromo)acetanilide, 2-ethyl-4,6-dimethyl-chloro(bromo)acetanilide, 2,6-diethyl-4-methyl-chloro-(bromo)acetanilide and 2,6-diisopropyl-4-methyl-chloro-(bromo)acetanilide.
Formula (XIII) gives a general definition of thecompounds which are also to be used as starting materials for the reaction according to the invention. In this formula, R, Rl and R2 preferably have those meanings which have already been mentioned as preferred, in the context of the description of the compounds of the formula (XI).
Le A 19 033 66~7 Y preferably represents chlorine, bromine, iodine, alkylsulphonyl with l to 4 carbon atoms or optionally substituted phenylsulphonyl, preferred substituents being halogen and alkyl with 1 to 4 carbon atoms.
Most of the compounds of the formula (XIII) are known Compounds of the formula (XIII) not hitherto described in the literature are those in which R represents an optionally substituted heterocyclic radical bonded by a ring nitrogen atom and Rl represents hydrogen. They can be obtained by reacting a heterocyclic compound of the general formula , R5 H-N ~ 6 (XIV), R
in which R5 and R6 together with the nitrogen atom represent a heterocyclic ring which is optionally substituted and which optionally contains further N-atoms, with an aldehyde of the general formula 0=CH-R (XV) 9 in which R2 has the meaning stated above, optionally in the presence of an inert organic solvent, for example methylene chloride, at temperatures between -70 and +50C and reacting the resulting compounds of the general formula H0-CH-N~ 6 (XVI), in which R2, R5 and R6 have the meanings stated above, directly or optionally after isolation, with a chlorinating agent, for example thionyl chloride, or a sulphonating agent, for example methylsulphonyl chloride, optionally in the presence of an inert organic solvent, for example Le A 19 033 66~
- 13 ~
methylene chlo~ide, at temperatures between -70C and +50C.
In the compounds of the formula (XIV), R5 and R
together with the nitrogen atom preferably represent the optionally substituted azolyl radicals pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl and 1,2,3,4-tetrazol-1-yl or represent optionally substi-tuted pyrrol-l-yl, preferred substituents being halogen, especially fluorine, chlorine and bromine, straight-chain or branched alkyl with 1 to 4 carbon atoms, alkoxy or alkylthio with, in either case, 1 to 4 carbon atoms, phenyl, perfluoroalkyl with 1 to 4 carbon atoms, cyano, alkylcarbonyl or alkoxycarbonyl with, in either case, 1 to
4 carbon atoms in the alkyl part or in the alkoxy part, and also hydroxycarbonyl.
In the aldehydes of the formula (XV), R preferably has the meaning which has already been mentioned as preferred, in the context of the description of the com-pounds of the formula (XI).
Both the heterocyclic compounds of the formula (XIV) 20 and the aldehydes of the formula (XV) are generally known.
Individual examples of compounds of the formula (XIII) which may be mentioned are: l-(l'-bromo(chloro)-ethyl)-pyrazol, l-(l'-bromo(chloro)ethyl)-4-chloro-pyrazole, l-(l`-bromo(chloro)ethyl)-2-methyl-pyrazole, l-(l'-bromo-(chloro)ethyl)-5-methyl-pyrazole, l-(l'-bromo(chloro)-ethyl)-3,5-dimethyl-pyrazole, 1-(1'-bromo(chloro)ethyl)-4-chloro-3,5-dimethyl-pyrazole~ 1-(1'-bromo(chloro)ethyl)-4-methoxy-pyrazole, l-(l`-bromo(chloro)propyl)-pyrazole, l-(l'-bromo(chloro)propyl)-4-chloro-pyrazole, l-(l'-bromo-(chloro)propyl)-3-methyl-pyrazole, 1-(1'-bromo(chloro)-propyl)-5-methyl-pyrazole, 1-(1'-bromo(chloro)propyl)-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)propyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)propyl)-4-methoxy-pyrazole, l-(l'-bromo(chloro)butyl)-pyrazole, l-(l'-bromo-(chloro)butyl)-4-chloro-pyrazole, l-(l'-bromo(chloro)-Le A 19 033 butyl)-2-methyl-pyrazole, 1-~ bromo(chloro)butyl)-5-methyl-pyrazole, l-(l'-bromo(chloro)butyl)-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)-butyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)butyl)-4-methoxy-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-4-chloro-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-3-methyl-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-5-methyl-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-3,5-dimethyl-pyrazole, 10 1-(1'-bromo(chloro)-2'-methyl-propyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)-2'-methyl-propyl)-4-methoxy-pyrazole, l-(l'-bromo(chloro)pentyl)-pyrazole, l-(l'-bromo(chloro)pentyl)-4-chloro-pyrazole, 1-(1'-bromo(chloro)pentyl)-3-methyl-pyrazole, l-(l'-bromo-(chloro)pentyl)-5-methylpyrazole, l-(l'-bromo(chloro)-pentyl)-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)pentyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)pentyl)-4-methoxy-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-4-chloro-20 pyrazole, 1-(bromo(chloro)-cyclopropyl-methyl)-3-methyl-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-5-methyl-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-3,5-dimethyl-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-4-chloro-3,5-dimethyl-pyrazole, l-(bromo(chloro)-cyclo-propyl-methyl)-4-methoxy-pyrazole, 1-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-pyrazole, l-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-4-chloro-pyrazole, l-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-3-methyl-pyrazole, l-(bromo-(chloro)-(2',4'-dichlorophenyl)-methyl)-5-methyl-pyrazole, 1-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-3,5-dimethyl-pyrazole, l-(bromo(chloro)-(2'4'-dichlorophenyl)-methyl)-4-chloro-3,5-dimethyl-pyrazole, l-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-4-methoxy-pyrazole, 1-(1',2',2',2'-tetrabromo(chloro)-ethyl)-pyrazole, 1-(1',2',2',2'-tetrabromo(chloro) ethyl)-4-chloro-pyrazole, 1-(1',2',2',2'-tetrabromo(chloro)-ethyl)-3-methyl-pyrazole, Le A 19 033 1~66~!7 1-(1',2',2~2~-tetrabromo(chloro)~ethyl)-5-methyl-pyrazole, 1-(1',2,',2',2'-tetrabromo(chloro)-ethyl)-3,5-dimethyl-pyrazole, l-(1',2~,2~,2'-tetrabromo(chloro)-ethyl)-4-chloro-3,5-dimethyl-pyrazole and 1-(1',2',2',2'-tetrabromo-(chloro)-ethyl)-4-methoxy-pyrazole.
Solvents which can be used for the reaction according to the invention are all inert organic solvents. These include, as preferences, ethers, such as diethyl ether;
aromatic hydrocarbons, such as benzene, toluene or xylene;
halogenated hydrocarbons, such as methylene chloride, carbon tetrachloride, chloroform or chlorobenzene; and esters, such as ethyl acetate.
The reaction according to the invention is carried out in the presence of an acid-binding agent. Acid-binding agents which can be used are any of the conventionalacid-binding agents. These include, as preferences~
inorganic bases, for example alkali metal hydroxides and alkali metal carbonates.
For carrying out the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the reaction is carried out at from -20C to 100C, preferably from 0C
to 80C.
When carrying out the process according to the invention, preferably 1 to 1.5 moles of the compound of the formula (XIII) and 1 to 3 moles of acid-binding agent are employed per 1 to 1.5 moles of the halogenoacetani-lide of the ~ormula (XII). m e compounds of the formula (XI) are isolated in a conventional manner.
In a preferred embodiment, the reaction according to the invention is carried out in a two-phase system, for example aqueous sodium hydroxide solution or potassium hydroxide solution/toluene or methylene chloride, optionally with the addition of 0.01-1 mol of a phase-transfer catalyst, for example an ammonium or phosphonium compound, examples of which are benzyl-dodecyl-dimethyl-ammonium chloride (Zephirol) and triethyl-benzyl-ammonium chloride.
Le A 19 033 :
When carrying out this variant of the process according to the invention, preferably 1 to 1.5 moles of the compound of the formula (XIII) and 1 to 10 moles of acid-binding agent are employed per 1 to 1.5 moles of the halogenoacetanilide of the formula (XII). The compounds of the formula (XI) are isolated in a conventional manner.
The active compounds of the formula (XI) which can be prepared according to the invention are, as is known, distinguished by very good herbicidal and also fungicidal activity (see the U.S. Patent Specifications and German Offenlegungsschriften (German Published Specificatiorls) cited above, in the context or discussion of the known state of the art).
Le A 19 033 11~66CI~
The process according to the invention is illustra,ed by the following preparative exa~ples.
Preparative Examples Example 1 CE~ /N=l - N / 2 ~ (1) 213 g (1 mol) of 2-ethyl-6-methyl-chloroacetanilide and 4 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 400 g of sodium hydroxide in 400 ml of water and 800 ml of methylene chloride and 170 g (1.1 mol) of N-chloro~ethylpyrazole hydrochloride were added in the course of 1 hour at 20 & to 25 &. The mixture was stirred for a further 3 hours at 25C, 500 ml of water were then added and the organic phase was separated off, washed several times with water, adjusted to pH 3 by adding citric acid and again washed with water, dried over sodium sulphate and concentrated in vacuo.
247 g (85% of theory) of N-pyrazol-l-yl-methyl-2-ethyl-6-methyl-chloro-acetanilide with a melting point of 57 & were obtained.
Exam~le 2 \C - CH Cl (2) 166~7 19.8 g (0.1 mol) of 2,6-dimethyl-chloroacetanilide and 0.5 g of tri-ethylbenzylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50%
strength sodium hydroxide solution and 150 ml of toluene and 13.1 g (0.11 mol) of propargyl bromide -~ere added dropwise at 20 to 30C, with vigorous stirring.
The mixture was stirred for a further 2 hours and the organic phase was then washed several times with water, dried over sodium sulphate and concentrated m vacuo. The crystalline crude product was recystallised from cyclohexane.
16.8 g (71.5% of theory) of N-propargyl-2,6-dimethyl-chloroacetanilide with a melting point of 82-84C were obtained.
Example 3 ~ \ C - C3 Cl ( ) 118.5 g (0.6 mol) of 2,6-dimethyl-chloroacetanilide and 1 g of tri-ethylbenzylammonium chloride were dissolved in a 2-phase mixture of 300 ml of 50% strength sodium hydroxide solution and 750 ml of toluene and 79.8 g (0.66 mol) of allyl brcmide were added dropwise at 20 to 30 & , with vigorous stirring.
The mixture was stirred for a further 3 hours and the organic phase was then washed several times with water, dried over sodium sulphate and concentrated.
115 g (81% of theory) of N-allyl-2,6-dimethyl-chloroacetanilide with a melting point of 62-67C were obtained.
- 20 Example 4 C - CH Cl C2~I5 1 2 (4) . ~
~1~66~7 21.3 g (0.1 mol) of 2~ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50% strength potassium hydroxide solution and 50 ml of methylene chloride and 8 g (0.1 mol) of monochlorodimethyl ether were added at 0C, whilst stirring. me te~,perature was allowed to rise to 25C and the mixture was stirred at this temperature for 12 hours. m e organic phase was then separated off and the aqueous phase was extracted three times by shaking with, in each case, 50 ml of methylene chloride. The combined organic phases were again washed with water, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. 100 ml of cyclohexane and then 200 ml of petroleum ether were added to the residue, any by-products and any starting material still pre-sent were filtered off and the filtrate was concentrated. The residue was dis-tilled. 18.4 g (72.2% of theory) of N-methoxymethyl-2-ethyl-6-methyl-chloro-acetanilide with a boiling point of 121C/0.1 mm Hg were thus obtained.
Example 5 C - CH Cl 10 g (0.047 mol) of 2-ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50% strength potassium hydroxide solution and 50 ml of methylene chloride and 6 g (0.052 mol) of 2-chloromethyl-furane were added at 0C, whilst stirring. The temperature was allcwed to rise to 25 & and the mixture was stirred at this temperature for 12 hours. m e organic phase was then separated off and the aqueous phase was extracted three times by shaking with, in each case, 50 ml . . .
lil66~7 . .
Or methylene chloride. The combined phases were again washed twice with, in each case~ 30 ml of water, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. 100 ml of cyclohexane and then 200 ml of petroleum ether were added to the residue, any by-products and any starting material still present were each filtered off and the filtrate was concentrated.
10.6 g (77% of theory) of N-(fur-2-yl-methyl)-2-ethyl-6-methyl-chloroacetanilide were obtained in the form of a viscous oil.
Example 6 ~ / 2 C2H~ ICI - CH2Cl (6) 10 g (0.047 mol) of 2-ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50% strength potassium hydroxide solution and 50 ml of methylene chloride and 6.5 g (0.05 mol) of 2-chloromethyl-thiophene were added at 0C, whilst stirring. The temperature was allowed to rise to 25C and the mixture was stirred at this temperature for 12 hours. The organic phase was then separated off and the aqueous phase was extracted three times by shaking wit;h, in each case, 50 ml of methylene chloride. The ~m-; bined organic phases were again washed with water, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. In each case 100 ml of cyclohexane andthen 200 ml of petroleum ether were added to the residue, any by-products and any starting material still present were each filtered off and the filtrate was concentrated.
The residue was treated several times with ligroin. The combined ligroin phases were dried over sodium sulphate and concentrated in vacuo. 11.9 g (82.5% of theory) of N-(thiophen-2-yl-methyl)-2-ethyl-6-methyl-chloroacetanilide were obtained in the form of a viscous oil.
Le A 19 033 .
. . .
~1166~7 . ~
- 21 _ xample 7 N/
o 42.2 g (0.2 mol) of 2-ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 100 ml of 50~ strength potassium hydroxide solution and 100 ml of methylene chlor-ide and 34.5 g (0.2 mol) of benzyl bromide were added at 0 C, whilst stirring. The temperature was allowed to rise to 25 C and the mixture was stirred at this temperat,ure for 12 hours. The organic phase was then separated off and the aqueous phase was extracted 3 times by shaking with, in each case, 50 ml of methylene chloride. The combined organic phase was again washed with 2 x 30 ml of water, dried over sodium sulphate and concentrated by distilling ff the solvent in vacuo. 300 ml of petroleum ether were added to the residue. Any by-products and any starting material still present were filtered off and the filtrate was concentrated. 51.8 g (86% of theory) of N-(benzy~-2-ethyl-6-methyl-chloroacetanilide were obtained in the form of a viscous oil.
The compounds listed in the following table were prepared in an analogous manner.
T a b 1 e R~ R2 X2 ~ \ (XI) X~ CH2Hal Le A 19 033 .
~;116&~
Ex- Melting ample pgint . Xl X2 X3 R R~ R2 Hal ( C) 8 CH3 6-C2H5 H-N~ ~ H CH3 Cl 87 9 CH3 6-CH~ /N -I H CH3 Cl 90 C2H5 6-C2H5 H -N ~ H CH3 Cl 80 11 C2H~ 6-C2H5 H - ~ H H Cl 67 12 C2H5 6-C2H~ H ~ N H H Cl 112 13 C2H5 4-CH3 6-C2Hs -N ¦ H H Cl 78 ~N=~
14 i-C3H7 H H -N I H H Cl 118 ~1 15 i-C3H7 H H -N I H H Cl Oil ~-N
16 CH3 6-C2H5 H -N ¦ H H Cl Oil 17 C(CH3 )3 H/N~ H H Cl Oil 18 C(CH3)3 H\_ ~ H H Cl 118 /N -I- Cl 19 C2H5 6-C2H5 H - \=: I H H Cl 110 ' /N- CH3 ; 20 CH3 6-C2H5 H -N H H Cl 90 Le A 19 033 : "
1~66~7 ,., - 23 ~
T a b l e 1 (continued) Melting Example pgint __ _ X~ R _ H~l ( C) 21 C2H5 6-C2H5 H -N ~ H H Cl 89 22 CH3 6~C2Hs H ~ ~o~ CH H H Cl 67-70 23 C2Hs 6-C2~s H ~ ~N ~ SCH3 H H Cl 121-23 CH~
24 C2H5 6-C2H~ H ~~ o ~ CH3 H H Cl 79-82 CH~ 6-CH3 N - ~ H H Cl 91-93 26 C(CH3)~ H H ~ 0 ~ CH3 H H Cl 102-04 27 C2H5 6-C2H5 H -~ 0 ~ CH3 H H Br 80 28 CH~ H H -C0 ~ H H Cl 138 29 C2H, 6-C2H~ H -C0 ~ H H Cl 116 30 CH~ 6-CH~ H -C0 ~ H H Cl 100 31 CH3 6-CH3 H -C0-CH~ CH3 H Cl 104 32 CH3 6-CH3 H -C0 ~ F H H Cl 104 33 C2H5 6-C2H5 H -OCH3 H H Cl 40-41 Le A 19 033 , ~ ~
~116~7 Preparation of the oompounds of the formula (XII) Example XII - 1 _ ~ 3 /H
C2H5 o 152 g (1.1 mol) of potassium carbonate were added to 135.2 g (1 mol) of 2-ethyl-6-methyl-aniline in 1000 ml of toluene. 113 g (l mol) of chloroa oe tyl chloride were added dropwise to this mixture, whilst stirring. After the exothermic reaction had subsided, the reaction mixture was stirred for a further 2 hours under reflux. m e reaction mixture was then filtered and the filtrate was concentrated to 500 ml in vacuo. The resulting crystals were filtered off and washed with petroleum ether. 189.6 g (98% of theory) of 2-ethyl-6-methyl-chloroa oe tanilide were obtained in the form of w~te crystals with a melting point of 120 &.
The compounds of the formula (XII) listed in Table 2 below were ob-tained in an analogous m~nner.
T a b 1 e 2 x2 O (XII) " ~166~7 Ex- Melting ample Xl x2 X Hal point No. (C) . .
XII-2 CH3 6-CH3 H Cl 148 XII-3 C2E15 6-C2H5 H Cl 133 XII-4 i-C3H7 H H Cl 79 XII-5 tert--C4H9 H H Cl 96 XII-6 C2H5 H H Cl 103 XII-7 CH3 H H Cl 109 XII-8 CH3 3-CH3 H Cl 135 XII-9 CH3 5-CH3 H Cl 154 XII-10 CH3 4-CH3 6-CH3 Cl 177 XII-ll C2H5 4-CH3 6-CH3 Cl 134 XII-12 se .-C4Hg H H Cl Oil XII-13 H H H Cl 132 Preparation of compounds of the form~la (XIII):
Example XIII - 1 Cl - CH - N ~ x HCl 250 g (5.7 mol) of acetaldehyde were added dropwise in the course of one hour, at 0 to 5C to 340 g (5 mol) of pyrazole in 1200 ml of methylene chloride. m e mixture was stirred for about a further 1 hour at 0C. The re-sulting N-(l-hydroxyethyl)-pyrazole was not isolated, but the reaction solution was added dropwise direct, at 0 to 5 & , in the course of one hour to 1250 g (10.5 mol) of thionyl chloride. The resulting mixture was stirred for a further - 2~ -: :
~: `
11166~7 1 hour at 20 C and was then conoentrated in vacuo at 40C. After adding 300 ml of methylene chloride, the mixture was concentrated again. m e residue was dis-tilled ln vacuo. 620.3 g (75~ of theory) of N-(l-chloroethyl)-pyrazole hydro-chloride with a boiling point of 55C/18 mm Hg were obtained.
Example XIII - 2 ~\
N - CH - Cl x HCl CH3 ~CH3 220 g (3.2 mol) of isobutyl aldehyde were added dropwise at 0 - 5 C
to 204 g (3 mol) of pyrazole dissolved in 400 ml of methylene chloride. After the addition had ended, the mixture was stirred for a further two hours at 0C
and the solution was then added dropwise at 0 - 5C to 750 g (6.3 mDl) of thionyl chloride. m e reaction mixture was then allowed to warm to room tempera-ture and was stirred for a further 12 hours. m e solvent was then stripped off m vacuo and the residue was taken up in carbon tetrachloride and crystallised.
m e crystals were filtered off, the mother liquor was concentrated and the residue was crystallised. The solid thus obtained was oombined with the first fraction and stirred thoroughly with 200 ml of carbon tetrachloride. m e solid was then filtered off, rinsed with 100 ml of carbon tetrachloride and dried at 40 & in vacuo. 530 g (91~ of theory) of l-(l'-chloro-isobutyl)-pyrazole hydro-chloride with a melting point of 110-114C were obtained.
Example XIII - 3 Cl - CH - N ~ x HCl 170 g (content ca. 1.2 mol) of chloral were added dropwise in the course of one hour, at 0 to 5C, to 68 g (1 m~l) of pyrazole in 400 ml of methylene chloride. m e mixture was stirred for a further 3 hours at 25C and the crystalline product was filtered off. The mother liquor was conoentrated and the crystalline product was again filtered off. m e co~bined crystalline products were dissolved in methylene chloride and the solution was added at 10C
in the course of half an hour to 250 g (2.1 mol) of thionyl chloride in 500 ml of methylene chloride. me mixture was stirred for a further 18 hours at room temperature. The reaction mlxture was then concentrated in vacuo at 50 &.
200 ml of chloroform were added to the residue and the resulting mixture was again concentrated. After adding 200 ml of carbon tetrachloride, the product crystallised out; it was filtered off and dried. 178 g (66% of theory) of N-(1,2,2,2-tetrachloroethyl)-pyrazole hydrcchloride with a melting point of 95C
were obtained.
m ose comFounds which are listed in Table 3 below were obtained in a corresponding manner.
T a b 1 e 3 Rl ~ R
- CH - Y
R2 ~ ~ (XIII) R
i6~7 ., .
Eample R R R2 R3 y Melting point (OC) No. Boiling point ( C) XIII 2 -i-C3H7 H H H Cl ~el~ing point:
114 (x HCl) XIII 3 -CC13 H H H Cl MeOting point:
95 C (x HCl) XIII 4 -CH3 CH3 Cl CH3 Cl Oil (x HCl) XIII 5 -CH3 H Cl H Cl Boiling point:
60-62/20 mbars (x HCl) XIII 6 -C2H5 H H H Cl Oil (x HCl) XIII 7 -n-C3H7 H H H Cl Oil (x HCl) XIII 8 -CH3 H H H Br Boiling point:
60-65/20 mbars XIII 9 -CH3 H H H Cl Boiling point:
50-55/18 mbars 'i~'' .
In the aldehydes of the formula (XV), R preferably has the meaning which has already been mentioned as preferred, in the context of the description of the com-pounds of the formula (XI).
Both the heterocyclic compounds of the formula (XIV) 20 and the aldehydes of the formula (XV) are generally known.
Individual examples of compounds of the formula (XIII) which may be mentioned are: l-(l'-bromo(chloro)-ethyl)-pyrazol, l-(l'-bromo(chloro)ethyl)-4-chloro-pyrazole, l-(l`-bromo(chloro)ethyl)-2-methyl-pyrazole, l-(l'-bromo-(chloro)ethyl)-5-methyl-pyrazole, l-(l'-bromo(chloro)-ethyl)-3,5-dimethyl-pyrazole, 1-(1'-bromo(chloro)ethyl)-4-chloro-3,5-dimethyl-pyrazole~ 1-(1'-bromo(chloro)ethyl)-4-methoxy-pyrazole, l-(l`-bromo(chloro)propyl)-pyrazole, l-(l'-bromo(chloro)propyl)-4-chloro-pyrazole, l-(l'-bromo-(chloro)propyl)-3-methyl-pyrazole, 1-(1'-bromo(chloro)-propyl)-5-methyl-pyrazole, 1-(1'-bromo(chloro)propyl)-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)propyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)propyl)-4-methoxy-pyrazole, l-(l'-bromo(chloro)butyl)-pyrazole, l-(l'-bromo-(chloro)butyl)-4-chloro-pyrazole, l-(l'-bromo(chloro)-Le A 19 033 butyl)-2-methyl-pyrazole, 1-~ bromo(chloro)butyl)-5-methyl-pyrazole, l-(l'-bromo(chloro)butyl)-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)-butyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)butyl)-4-methoxy-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-4-chloro-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-3-methyl-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-5-methyl-pyrazole, 1-(1'-bromo(chloro)-2'-methyl-propyl)-3,5-dimethyl-pyrazole, 10 1-(1'-bromo(chloro)-2'-methyl-propyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)-2'-methyl-propyl)-4-methoxy-pyrazole, l-(l'-bromo(chloro)pentyl)-pyrazole, l-(l'-bromo(chloro)pentyl)-4-chloro-pyrazole, 1-(1'-bromo(chloro)pentyl)-3-methyl-pyrazole, l-(l'-bromo-(chloro)pentyl)-5-methylpyrazole, l-(l'-bromo(chloro)-pentyl)-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)pentyl)-4-chloro-3,5-dimethyl-pyrazole, l-(l'-bromo(chloro)pentyl)-4-methoxy-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-4-chloro-20 pyrazole, 1-(bromo(chloro)-cyclopropyl-methyl)-3-methyl-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-5-methyl-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-3,5-dimethyl-pyrazole, l-(bromo(chloro)-cyclopropyl-methyl)-4-chloro-3,5-dimethyl-pyrazole, l-(bromo(chloro)-cyclo-propyl-methyl)-4-methoxy-pyrazole, 1-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-pyrazole, l-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-4-chloro-pyrazole, l-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-3-methyl-pyrazole, l-(bromo-(chloro)-(2',4'-dichlorophenyl)-methyl)-5-methyl-pyrazole, 1-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-3,5-dimethyl-pyrazole, l-(bromo(chloro)-(2'4'-dichlorophenyl)-methyl)-4-chloro-3,5-dimethyl-pyrazole, l-(bromo(chloro)-(2',4'-dichlorophenyl)-methyl)-4-methoxy-pyrazole, 1-(1',2',2',2'-tetrabromo(chloro)-ethyl)-pyrazole, 1-(1',2',2',2'-tetrabromo(chloro) ethyl)-4-chloro-pyrazole, 1-(1',2',2',2'-tetrabromo(chloro)-ethyl)-3-methyl-pyrazole, Le A 19 033 1~66~!7 1-(1',2',2~2~-tetrabromo(chloro)~ethyl)-5-methyl-pyrazole, 1-(1',2,',2',2'-tetrabromo(chloro)-ethyl)-3,5-dimethyl-pyrazole, l-(1',2~,2~,2'-tetrabromo(chloro)-ethyl)-4-chloro-3,5-dimethyl-pyrazole and 1-(1',2',2',2'-tetrabromo-(chloro)-ethyl)-4-methoxy-pyrazole.
Solvents which can be used for the reaction according to the invention are all inert organic solvents. These include, as preferences, ethers, such as diethyl ether;
aromatic hydrocarbons, such as benzene, toluene or xylene;
halogenated hydrocarbons, such as methylene chloride, carbon tetrachloride, chloroform or chlorobenzene; and esters, such as ethyl acetate.
The reaction according to the invention is carried out in the presence of an acid-binding agent. Acid-binding agents which can be used are any of the conventionalacid-binding agents. These include, as preferences~
inorganic bases, for example alkali metal hydroxides and alkali metal carbonates.
For carrying out the process according to the invention, the reaction temperatures can be varied within a relatively wide range. In general, the reaction is carried out at from -20C to 100C, preferably from 0C
to 80C.
When carrying out the process according to the invention, preferably 1 to 1.5 moles of the compound of the formula (XIII) and 1 to 3 moles of acid-binding agent are employed per 1 to 1.5 moles of the halogenoacetani-lide of the ~ormula (XII). m e compounds of the formula (XI) are isolated in a conventional manner.
In a preferred embodiment, the reaction according to the invention is carried out in a two-phase system, for example aqueous sodium hydroxide solution or potassium hydroxide solution/toluene or methylene chloride, optionally with the addition of 0.01-1 mol of a phase-transfer catalyst, for example an ammonium or phosphonium compound, examples of which are benzyl-dodecyl-dimethyl-ammonium chloride (Zephirol) and triethyl-benzyl-ammonium chloride.
Le A 19 033 :
When carrying out this variant of the process according to the invention, preferably 1 to 1.5 moles of the compound of the formula (XIII) and 1 to 10 moles of acid-binding agent are employed per 1 to 1.5 moles of the halogenoacetanilide of the formula (XII). The compounds of the formula (XI) are isolated in a conventional manner.
The active compounds of the formula (XI) which can be prepared according to the invention are, as is known, distinguished by very good herbicidal and also fungicidal activity (see the U.S. Patent Specifications and German Offenlegungsschriften (German Published Specificatiorls) cited above, in the context or discussion of the known state of the art).
Le A 19 033 11~66CI~
The process according to the invention is illustra,ed by the following preparative exa~ples.
Preparative Examples Example 1 CE~ /N=l - N / 2 ~ (1) 213 g (1 mol) of 2-ethyl-6-methyl-chloroacetanilide and 4 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 400 g of sodium hydroxide in 400 ml of water and 800 ml of methylene chloride and 170 g (1.1 mol) of N-chloro~ethylpyrazole hydrochloride were added in the course of 1 hour at 20 & to 25 &. The mixture was stirred for a further 3 hours at 25C, 500 ml of water were then added and the organic phase was separated off, washed several times with water, adjusted to pH 3 by adding citric acid and again washed with water, dried over sodium sulphate and concentrated in vacuo.
247 g (85% of theory) of N-pyrazol-l-yl-methyl-2-ethyl-6-methyl-chloro-acetanilide with a melting point of 57 & were obtained.
Exam~le 2 \C - CH Cl (2) 166~7 19.8 g (0.1 mol) of 2,6-dimethyl-chloroacetanilide and 0.5 g of tri-ethylbenzylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50%
strength sodium hydroxide solution and 150 ml of toluene and 13.1 g (0.11 mol) of propargyl bromide -~ere added dropwise at 20 to 30C, with vigorous stirring.
The mixture was stirred for a further 2 hours and the organic phase was then washed several times with water, dried over sodium sulphate and concentrated m vacuo. The crystalline crude product was recystallised from cyclohexane.
16.8 g (71.5% of theory) of N-propargyl-2,6-dimethyl-chloroacetanilide with a melting point of 82-84C were obtained.
Example 3 ~ \ C - C3 Cl ( ) 118.5 g (0.6 mol) of 2,6-dimethyl-chloroacetanilide and 1 g of tri-ethylbenzylammonium chloride were dissolved in a 2-phase mixture of 300 ml of 50% strength sodium hydroxide solution and 750 ml of toluene and 79.8 g (0.66 mol) of allyl brcmide were added dropwise at 20 to 30 & , with vigorous stirring.
The mixture was stirred for a further 3 hours and the organic phase was then washed several times with water, dried over sodium sulphate and concentrated.
115 g (81% of theory) of N-allyl-2,6-dimethyl-chloroacetanilide with a melting point of 62-67C were obtained.
- 20 Example 4 C - CH Cl C2~I5 1 2 (4) . ~
~1~66~7 21.3 g (0.1 mol) of 2~ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50% strength potassium hydroxide solution and 50 ml of methylene chloride and 8 g (0.1 mol) of monochlorodimethyl ether were added at 0C, whilst stirring. me te~,perature was allowed to rise to 25C and the mixture was stirred at this temperature for 12 hours. m e organic phase was then separated off and the aqueous phase was extracted three times by shaking with, in each case, 50 ml of methylene chloride. The combined organic phases were again washed with water, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. 100 ml of cyclohexane and then 200 ml of petroleum ether were added to the residue, any by-products and any starting material still pre-sent were filtered off and the filtrate was concentrated. The residue was dis-tilled. 18.4 g (72.2% of theory) of N-methoxymethyl-2-ethyl-6-methyl-chloro-acetanilide with a boiling point of 121C/0.1 mm Hg were thus obtained.
Example 5 C - CH Cl 10 g (0.047 mol) of 2-ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50% strength potassium hydroxide solution and 50 ml of methylene chloride and 6 g (0.052 mol) of 2-chloromethyl-furane were added at 0C, whilst stirring. The temperature was allcwed to rise to 25 & and the mixture was stirred at this temperature for 12 hours. m e organic phase was then separated off and the aqueous phase was extracted three times by shaking with, in each case, 50 ml . . .
lil66~7 . .
Or methylene chloride. The combined phases were again washed twice with, in each case~ 30 ml of water, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. 100 ml of cyclohexane and then 200 ml of petroleum ether were added to the residue, any by-products and any starting material still present were each filtered off and the filtrate was concentrated.
10.6 g (77% of theory) of N-(fur-2-yl-methyl)-2-ethyl-6-methyl-chloroacetanilide were obtained in the form of a viscous oil.
Example 6 ~ / 2 C2H~ ICI - CH2Cl (6) 10 g (0.047 mol) of 2-ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 50 ml of 50% strength potassium hydroxide solution and 50 ml of methylene chloride and 6.5 g (0.05 mol) of 2-chloromethyl-thiophene were added at 0C, whilst stirring. The temperature was allowed to rise to 25C and the mixture was stirred at this temperature for 12 hours. The organic phase was then separated off and the aqueous phase was extracted three times by shaking wit;h, in each case, 50 ml of methylene chloride. The ~m-; bined organic phases were again washed with water, dried over sodium sulphate and concentrated by distilling off the solvent in vacuo. In each case 100 ml of cyclohexane andthen 200 ml of petroleum ether were added to the residue, any by-products and any starting material still present were each filtered off and the filtrate was concentrated.
The residue was treated several times with ligroin. The combined ligroin phases were dried over sodium sulphate and concentrated in vacuo. 11.9 g (82.5% of theory) of N-(thiophen-2-yl-methyl)-2-ethyl-6-methyl-chloroacetanilide were obtained in the form of a viscous oil.
Le A 19 033 .
. . .
~1166~7 . ~
- 21 _ xample 7 N/
o 42.2 g (0.2 mol) of 2-ethyl-6-methyl-chloroacetanilide and 1 ml of benzyl-dodecyl-dimethylammonium chloride were dissolved in a 2-phase mixture of 100 ml of 50~ strength potassium hydroxide solution and 100 ml of methylene chlor-ide and 34.5 g (0.2 mol) of benzyl bromide were added at 0 C, whilst stirring. The temperature was allowed to rise to 25 C and the mixture was stirred at this temperat,ure for 12 hours. The organic phase was then separated off and the aqueous phase was extracted 3 times by shaking with, in each case, 50 ml of methylene chloride. The combined organic phase was again washed with 2 x 30 ml of water, dried over sodium sulphate and concentrated by distilling ff the solvent in vacuo. 300 ml of petroleum ether were added to the residue. Any by-products and any starting material still present were filtered off and the filtrate was concentrated. 51.8 g (86% of theory) of N-(benzy~-2-ethyl-6-methyl-chloroacetanilide were obtained in the form of a viscous oil.
The compounds listed in the following table were prepared in an analogous manner.
T a b 1 e R~ R2 X2 ~ \ (XI) X~ CH2Hal Le A 19 033 .
~;116&~
Ex- Melting ample pgint . Xl X2 X3 R R~ R2 Hal ( C) 8 CH3 6-C2H5 H-N~ ~ H CH3 Cl 87 9 CH3 6-CH~ /N -I H CH3 Cl 90 C2H5 6-C2H5 H -N ~ H CH3 Cl 80 11 C2H~ 6-C2H5 H - ~ H H Cl 67 12 C2H5 6-C2H~ H ~ N H H Cl 112 13 C2H5 4-CH3 6-C2Hs -N ¦ H H Cl 78 ~N=~
14 i-C3H7 H H -N I H H Cl 118 ~1 15 i-C3H7 H H -N I H H Cl Oil ~-N
16 CH3 6-C2H5 H -N ¦ H H Cl Oil 17 C(CH3 )3 H/N~ H H Cl Oil 18 C(CH3)3 H\_ ~ H H Cl 118 /N -I- Cl 19 C2H5 6-C2H5 H - \=: I H H Cl 110 ' /N- CH3 ; 20 CH3 6-C2H5 H -N H H Cl 90 Le A 19 033 : "
1~66~7 ,., - 23 ~
T a b l e 1 (continued) Melting Example pgint __ _ X~ R _ H~l ( C) 21 C2H5 6-C2H5 H -N ~ H H Cl 89 22 CH3 6~C2Hs H ~ ~o~ CH H H Cl 67-70 23 C2Hs 6-C2~s H ~ ~N ~ SCH3 H H Cl 121-23 CH~
24 C2H5 6-C2H~ H ~~ o ~ CH3 H H Cl 79-82 CH~ 6-CH3 N - ~ H H Cl 91-93 26 C(CH3)~ H H ~ 0 ~ CH3 H H Cl 102-04 27 C2H5 6-C2H5 H -~ 0 ~ CH3 H H Br 80 28 CH~ H H -C0 ~ H H Cl 138 29 C2H, 6-C2H~ H -C0 ~ H H Cl 116 30 CH~ 6-CH~ H -C0 ~ H H Cl 100 31 CH3 6-CH3 H -C0-CH~ CH3 H Cl 104 32 CH3 6-CH3 H -C0 ~ F H H Cl 104 33 C2H5 6-C2H5 H -OCH3 H H Cl 40-41 Le A 19 033 , ~ ~
~116~7 Preparation of the oompounds of the formula (XII) Example XII - 1 _ ~ 3 /H
C2H5 o 152 g (1.1 mol) of potassium carbonate were added to 135.2 g (1 mol) of 2-ethyl-6-methyl-aniline in 1000 ml of toluene. 113 g (l mol) of chloroa oe tyl chloride were added dropwise to this mixture, whilst stirring. After the exothermic reaction had subsided, the reaction mixture was stirred for a further 2 hours under reflux. m e reaction mixture was then filtered and the filtrate was concentrated to 500 ml in vacuo. The resulting crystals were filtered off and washed with petroleum ether. 189.6 g (98% of theory) of 2-ethyl-6-methyl-chloroa oe tanilide were obtained in the form of w~te crystals with a melting point of 120 &.
The compounds of the formula (XII) listed in Table 2 below were ob-tained in an analogous m~nner.
T a b 1 e 2 x2 O (XII) " ~166~7 Ex- Melting ample Xl x2 X Hal point No. (C) . .
XII-2 CH3 6-CH3 H Cl 148 XII-3 C2E15 6-C2H5 H Cl 133 XII-4 i-C3H7 H H Cl 79 XII-5 tert--C4H9 H H Cl 96 XII-6 C2H5 H H Cl 103 XII-7 CH3 H H Cl 109 XII-8 CH3 3-CH3 H Cl 135 XII-9 CH3 5-CH3 H Cl 154 XII-10 CH3 4-CH3 6-CH3 Cl 177 XII-ll C2H5 4-CH3 6-CH3 Cl 134 XII-12 se .-C4Hg H H Cl Oil XII-13 H H H Cl 132 Preparation of compounds of the form~la (XIII):
Example XIII - 1 Cl - CH - N ~ x HCl 250 g (5.7 mol) of acetaldehyde were added dropwise in the course of one hour, at 0 to 5C to 340 g (5 mol) of pyrazole in 1200 ml of methylene chloride. m e mixture was stirred for about a further 1 hour at 0C. The re-sulting N-(l-hydroxyethyl)-pyrazole was not isolated, but the reaction solution was added dropwise direct, at 0 to 5 & , in the course of one hour to 1250 g (10.5 mol) of thionyl chloride. The resulting mixture was stirred for a further - 2~ -: :
~: `
11166~7 1 hour at 20 C and was then conoentrated in vacuo at 40C. After adding 300 ml of methylene chloride, the mixture was concentrated again. m e residue was dis-tilled ln vacuo. 620.3 g (75~ of theory) of N-(l-chloroethyl)-pyrazole hydro-chloride with a boiling point of 55C/18 mm Hg were obtained.
Example XIII - 2 ~\
N - CH - Cl x HCl CH3 ~CH3 220 g (3.2 mol) of isobutyl aldehyde were added dropwise at 0 - 5 C
to 204 g (3 mol) of pyrazole dissolved in 400 ml of methylene chloride. After the addition had ended, the mixture was stirred for a further two hours at 0C
and the solution was then added dropwise at 0 - 5C to 750 g (6.3 mDl) of thionyl chloride. m e reaction mixture was then allowed to warm to room tempera-ture and was stirred for a further 12 hours. m e solvent was then stripped off m vacuo and the residue was taken up in carbon tetrachloride and crystallised.
m e crystals were filtered off, the mother liquor was concentrated and the residue was crystallised. The solid thus obtained was oombined with the first fraction and stirred thoroughly with 200 ml of carbon tetrachloride. m e solid was then filtered off, rinsed with 100 ml of carbon tetrachloride and dried at 40 & in vacuo. 530 g (91~ of theory) of l-(l'-chloro-isobutyl)-pyrazole hydro-chloride with a melting point of 110-114C were obtained.
Example XIII - 3 Cl - CH - N ~ x HCl 170 g (content ca. 1.2 mol) of chloral were added dropwise in the course of one hour, at 0 to 5C, to 68 g (1 m~l) of pyrazole in 400 ml of methylene chloride. m e mixture was stirred for a further 3 hours at 25C and the crystalline product was filtered off. The mother liquor was conoentrated and the crystalline product was again filtered off. m e co~bined crystalline products were dissolved in methylene chloride and the solution was added at 10C
in the course of half an hour to 250 g (2.1 mol) of thionyl chloride in 500 ml of methylene chloride. me mixture was stirred for a further 18 hours at room temperature. The reaction mlxture was then concentrated in vacuo at 50 &.
200 ml of chloroform were added to the residue and the resulting mixture was again concentrated. After adding 200 ml of carbon tetrachloride, the product crystallised out; it was filtered off and dried. 178 g (66% of theory) of N-(1,2,2,2-tetrachloroethyl)-pyrazole hydrcchloride with a melting point of 95C
were obtained.
m ose comFounds which are listed in Table 3 below were obtained in a corresponding manner.
T a b 1 e 3 Rl ~ R
- CH - Y
R2 ~ ~ (XIII) R
i6~7 ., .
Eample R R R2 R3 y Melting point (OC) No. Boiling point ( C) XIII 2 -i-C3H7 H H H Cl ~el~ing point:
114 (x HCl) XIII 3 -CC13 H H H Cl MeOting point:
95 C (x HCl) XIII 4 -CH3 CH3 Cl CH3 Cl Oil (x HCl) XIII 5 -CH3 H Cl H Cl Boiling point:
60-62/20 mbars (x HCl) XIII 6 -C2H5 H H H Cl Oil (x HCl) XIII 7 -n-C3H7 H H H Cl Oil (x HCl) XIII 8 -CH3 H H H Br Boiling point:
60-65/20 mbars XIII 9 -CH3 H H H Cl Boiling point:
50-55/18 mbars 'i~'' .
Claims (35)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. Process for the preparation of an N-substituted .alpha.-haloacetanilide compound of the formula (XI) wherein R is pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,3,4-tetrazol-1-yl or pyrrol-1-yl radical, each of said radicals being optionally substituted by halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, phenyl, C1-4 perfluoroalkyl, cyano, (C1-4 alkyl)carbonyl, (C1-4 alkoxy) carbonyl or hydroxycarbonyl bonded via a ring nitrogen atom, or the grouping , or a furyl or thiophenyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms, alkenyl, alkynyl, alkoxy, alkylcarbonyl, or a phenyl, phenoxy or phenylcarbonyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
A is oxygen or the grouping ;
B is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl or halogen, or an aryl or aralkyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or halo-alkyl having up to 2 carbon atoms and up to 5 halogen atoms, or the grouping -OR4, -SR4 or -NR3R4;
R1 and R2 are individually selected from hydrogen, alkyl, cycloalkyl, haloalkyl, alkoxyalkyl, alkenyl or alkynyl, or a phenyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
R3 is hydrogen or alkyl, or an aryl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
R4 is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl, or an aralkyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
X1, X2 and X3 are individually selected from hydrogen or alkyl; and Hal is halogen;
which process comprises reacting a haloacetanilide of the formula (XII), wherein Hal, X1, X2 and X3, defined as above, with a compound of the formula (XIII), wherein R, R1 and R2, are as defined above, and Y is halogen or alkylsulphonyl, or a phenylsulphonyl radical optionally substituted by halogen or C1-4 alkyl, which compound of the formula (XIII) can be in the form of an acid addition salt thereof, in the presence of an acid-binding agent.
A is oxygen or the grouping ;
B is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl or halogen, or an aryl or aralkyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or halo-alkyl having up to 2 carbon atoms and up to 5 halogen atoms, or the grouping -OR4, -SR4 or -NR3R4;
R1 and R2 are individually selected from hydrogen, alkyl, cycloalkyl, haloalkyl, alkoxyalkyl, alkenyl or alkynyl, or a phenyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
R3 is hydrogen or alkyl, or an aryl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
R4 is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl or cycloalkyl, or an aralkyl radical optionally substituted by halogen, C1-4 alkyl, C1-2 alkoxy, C1-2 alkylthio, cyano, nitro or haloalkyl having up to 2 carbon atoms and up to 5 halogen atoms;
X1, X2 and X3 are individually selected from hydrogen or alkyl; and Hal is halogen;
which process comprises reacting a haloacetanilide of the formula (XII), wherein Hal, X1, X2 and X3, defined as above, with a compound of the formula (XIII), wherein R, R1 and R2, are as defined above, and Y is halogen or alkylsulphonyl, or a phenylsulphonyl radical optionally substituted by halogen or C1-4 alkyl, which compound of the formula (XIII) can be in the form of an acid addition salt thereof, in the presence of an acid-binding agent.
2. A process as claimed in claim 1 wherein the reaction is effected at a temperature of from -20°C to +100°C.
3. A process as claimed in claim 1 wherein the reaction is effected at a temperature of from 0°C to 80°C.
4. A process as claimed in claim 1 wherein the acid-binding agent is an alkali metal hydroxide or an alkali metal carbonate.
5. A process as claimed in claim 1 wherein the molar ratio of the haloacetanilide of formula (XII) to the compound of formula (XIII) is from 1 : 1.5 to 1.5 : 1.
6. A process as claimed in claim 1 wherein the reaction is effected in an inert organic solvent.
7. A process as claimed in claim 1 wherein the reaction is carried out in a two-phase system in the presence of a phase-transfer catalyst.
8. A process as claimed in claim 7 wherein an ammonium or phosphonium compound is employed as the phase transfer catalyst.
9. A process as claimed in claim 8 wherein the phase transfer catalyst employed is triethylbenzylammonium chloride or benzyl-dodecyl-dimethyl-ammonium chloride.
10. A process as claimed in claim 7 wherein the two-phase system comprises (a) an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution, and (b) toluene or methylene chloride.
11. A process as claimed in claim 1 for the preparation of N-pyrazol-1-yl-methyl-2-ethyl-6-methyl-chloroacetanilide which comprises reacting 2-ethyl-6-methyl-chloroacetanilide with an N-(Y-methyl)-pyrazole or an acid addition salt thereof, in the presence of an acid-binding agent.
12. A process as claimed in claim 1 for the preparation of N-pyrazol-l-yl-methyl-2,6-diethyl-chloroacetanilide which comprises reacting 2,6-diethyl-chloroacetanilide with an N-(Y-methyl)-pYrazole or an acid-addition salt thereof, in the presence of an acid-binding agent.
13. A process as claimed in claim 1 for the preparation of N-(3,5-dimethylpyrazol-1-yl)-methyl-2-ethyl-6-methyl-chloroacetanilide which com-prises reacting 2-ethyl-6-methyl-chloroacetanilide with an N-(Y-methyl)-3,5-dimethylpyrazole or an acid-addition salt thereof, in the presence of an acid-binding agent.
14. A process as claimed in claim 1 for the preparation of N-(3-methyl-pyrazol-1-yl)-methyl-2,6-diethyl-chloroacetanilide, which comprises reacting 2,6-diethyl-chloroacetanilide with an N-(Y-methyl)-3-methylpyrazole or an acid-addition salt thereof in the presence of an acid-binding agent.
15. A process as claimed in claim 1 for the preparation of N-methoxy-methyl-2,6-diethyl-chloroacetanilide which comprises reacting 2,6-diethyl-chloroacetanilide with a mono-(Y)-dimethyl ether, in the presence of an acid-binding agent.
16. Process as claimed in claim 1 wherein in said formulae R is an optionally substituted pyrazol-l-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, or 1,2,3,4-tetrazol-1-yl radical, the substituents being selected from halogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, alkoxy or alkylthio with, in either case, 1 to 4 carbon atoms, phenyl, perfluoroalkyl with 1 to 4 carbon atoms, cyano, alkylcarbonyl or alkoxycarbonyl with, in either case, 1 to 4 carbon atoms in the alkyl or alkoxy part, or hydroxycarbonyl, or R is the grouping IMG>
wherein A is oxygen or the grouping , in which R3 is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms or aryl with 6 to 10 carbon atoms optionally substituted with at least one substituent selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; and B is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, haloalkyl with up to 3 carbon atoms and up to 5 identical or different halogen atoms, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, cycloalkyl with 5 to 7 carbon atoms, halogen, aryl with 6 to 10 carbon atoms optionally substituted with at least one substituent selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; aralkyl with 6 to 10 carbon atoms in the aryl part and 1 to 4 carbon atoms in the alkyl part optionally substituted with at least one sub-stituent in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; or the grouping -OR4, -SR4 or -NR3R4, wherein R3 is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms or aryl with 6 to 10 carbon atoms optionally substituted with at least one substituent in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 car-bon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; and R4 is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, haloalkyl with up to 3 carbon atoms and up to 5 identical or different halogen atoms, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, cycloalkyl with 5 to 7 carbon atoms or aralkyl with 6 to 10 carbon atoms in the aryl part and 1 to 4 carbon atoms in the alkyl part radical being able to carry one or more substituents in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms, or R is an optionally substituted furyl or thiophenyl radical wherein the substituent are selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, alkoxy or alkylcarbonyl with, in either case, 1 to 4 carbon atoms in the alkyl part, or an optionally substituted phenyl, phenoxy or phenylcarbonyl radical wherein the substitutent are selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms, R1 and R2 are individually selected from hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, haloalkyl with up to 2 carbon atoms and 5 identical or different halogen atoms, alkoxyalkyl with 1 to 4 carbon atoms in the alkyl part and 1 to 4 carbon atoms in the alkoxy part, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, or optionally substituted phenyl wherein the substituents are selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 ident-ical or different halogen atoms;
X1, X2 and X3 are individually selected from hydrogen or straight-chain or branched alkyl with 1 to 4 carbon atoms; and Hal is fluorine, chlorine and bromine.
wherein A is oxygen or the grouping , in which R3 is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms or aryl with 6 to 10 carbon atoms optionally substituted with at least one substituent selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; and B is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, haloalkyl with up to 3 carbon atoms and up to 5 identical or different halogen atoms, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, cycloalkyl with 5 to 7 carbon atoms, halogen, aryl with 6 to 10 carbon atoms optionally substituted with at least one substituent selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; aralkyl with 6 to 10 carbon atoms in the aryl part and 1 to 4 carbon atoms in the alkyl part optionally substituted with at least one sub-stituent in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; or the grouping -OR4, -SR4 or -NR3R4, wherein R3 is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms or aryl with 6 to 10 carbon atoms optionally substituted with at least one substituent in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 car-bon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; and R4 is hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, haloalkyl with up to 3 carbon atoms and up to 5 identical or different halogen atoms, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, cycloalkyl with 5 to 7 carbon atoms or aralkyl with 6 to 10 carbon atoms in the aryl part and 1 to 4 carbon atoms in the alkyl part radical being able to carry one or more substituents in the aryl part selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms, or R is an optionally substituted furyl or thiophenyl radical wherein the substituent are selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms; alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, alkoxy or alkylcarbonyl with, in either case, 1 to 4 carbon atoms in the alkyl part, or an optionally substituted phenyl, phenoxy or phenylcarbonyl radical wherein the substitutent are selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 identical or different halogen atoms, R1 and R2 are individually selected from hydrogen, straight-chain or branched alkyl with 1 to 4 carbon atoms, haloalkyl with up to 2 carbon atoms and 5 identical or different halogen atoms, alkoxyalkyl with 1 to 4 carbon atoms in the alkyl part and 1 to 4 carbon atoms in the alkoxy part, alkenyl or alkynyl with, in either case, 2 to 4 carbon atoms, or optionally substituted phenyl wherein the substituents are selected from halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 or 2 carbon atoms, alkylthio with 1 or 2 carbon atoms, cyano, nitro and haloalkyl with up to 2 carbon atoms and up to 5 ident-ical or different halogen atoms;
X1, X2 and X3 are individually selected from hydrogen or straight-chain or branched alkyl with 1 to 4 carbon atoms; and Hal is fluorine, chlorine and bromine.
17. Process as claimed in claim 1 wherein R is a pyrazol-1-yl, 1,2,4-triazol-1-yl, 1,2,3-triazol-1-yl, 1,3,4-triazol-1-yl, 1,2,3,4-tetrazol-1-yl or pyrrol-l-yl radical, each of said radicals being optionally substituted by halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, phenyl, C1-4 perfluoroalkyl, cyano, (C1-4 alkyl)carbonyl, (C1-4 alkoxy)carbonyl or hydroxycarbonyl bonded via a ring nitrogen atom.
18. Process as claimed in claim 1 wherein R is the grouping
19. Process as claimed in claim l wherein R is optionally substituted furyl.
20. Process as claimed in claim 1 wherein R is optionally substituted thiophenyl.
21. Process as claimed in claim 1 wherein R is alkenyl or alkynyl.
22. Process as claimed in claim 1 wherein R is alkoxy.
23. Process as claimed in claim 1 wherein R is alkylcarbonyl.
24. Process as claimed in claim 1 wherein R is optionally substituted phenyl, phenoxy or phenylcarbonyl.
25. Process as claimed in claim 18 wherein R is the grouping wherein A is oxygen.
26. Process as claimed in claim 18 wherein R is the grouping wherein A is NR3.
27. Process as claimed in claim 18 wherein R is the grouping wherein B is C1-4 alkyl or alkylthio.
28. Process as claimed in claim 18 wherein R is the grouping wherein B is OR4.
29. Process as claimed in claim 18 wherein R is the grouping wherein B is SR4.
30. Process as claimed in claim 18 wherein R is the grouping wherein B is NR3R4.
31. Process as claimed in claim 1 wherein R1 and R2 are both hydrogen.
32. Process as claimed in claim 1 wherein X1, X2 and X3 are hydrogen.
33. Process as claimed in claim 1 wherein two of X1 and X2 are alkyl.
34. Process as claimed in claim 1 wherein said process is carried out in the presence of an organic solvent.
35. Process as claimed in claim 1 wherein said compound of the formula (XIII) is in the form of an acid addition salt thereof.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782835157 DE2835157A1 (en) | 1978-08-10 | 1978-08-10 | METHOD FOR PRODUCING N-SUBSTITUTED ALPHA -HALOGENACETANILIDES |
| DEP2835157.7 | 1978-08-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1116607A true CA1116607A (en) | 1982-01-19 |
Family
ID=6046745
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000333393A Expired CA1116607A (en) | 1978-08-10 | 1979-08-08 | PROCESS FOR THE PREPARATION OF N-SUBSTITUTED .alpha.-HALOGENOACETANILIDES |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP0008057B1 (en) |
| JP (1) | JPS5524194A (en) |
| AT (1) | ATE1009T1 (en) |
| BR (1) | BR7905112A (en) |
| CA (1) | CA1116607A (en) |
| CS (1) | CS214801B2 (en) |
| DE (2) | DE2835157A1 (en) |
| DK (1) | DK333479A (en) |
| ES (1) | ES483280A1 (en) |
| IL (1) | IL57998A (en) |
| ZA (1) | ZA794144B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4599448A (en) * | 1981-05-26 | 1986-07-08 | Bayer Aktiengesellschaft | Novel N-(1-alkenyl)-chloroacetanilides as herbicides and plant growth regulators |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4258196A (en) * | 1978-04-17 | 1981-03-24 | Monsanto Company | Process for the production of tertiary 2-haloacetamides |
| EP0029011A1 (en) * | 1979-11-13 | 1981-05-20 | Ciba-Geigy Ag | N-(Azolyl-1-eth-1'-yl)-halogenacetanilides, their preparation and their use as herbicides |
| DE3011084A1 (en) * | 1980-03-22 | 1981-10-01 | Bayer Ag, 5090 Leverkusen | METHOD FOR PRODUCING SUBSTITUTED N-AZOLYLMETHYL HALOGEN ACETANILIDES |
| US4260782A (en) * | 1980-06-09 | 1981-04-07 | Ciba-Geigy Corporation | Process for the preparation of N-(1'-alkoxycarbonylethyl)-2,6-dialkylanilines |
| US4266071A (en) * | 1980-06-09 | 1981-05-05 | Ciba-Geigy Corporation | Process for the preparation of N-(1-alkoxycarbonylethyl)-2,6-dialkylanilines |
| HU190681B (en) * | 1982-01-15 | 1986-10-28 | Eszakmagyar Vegyimuevek | Process for production of n-alcoxi-alkyl-2,6-dialkylchlor-acetanilids |
| JPS604181A (en) * | 1983-06-22 | 1985-01-10 | Tokuyama Soda Co Ltd | N-substituted-chloroacetanilide |
| DE3572809D1 (en) * | 1984-05-23 | 1989-10-12 | Ciba Geigy Ag | MICROBICIDAL 1-FLUORO-1-AZOLYL-2,2-DIARYLETHANE DERIVATIVES |
| FI102748B (en) * | 1992-06-19 | 1999-02-15 | Daiichi Seiyaku Co | Process for the preparation of N- (2,6-dialkyl) -2- (2-oxo-1-pyrrolidinyl) acetamide derivatives |
| TW201033163A (en) * | 2008-10-20 | 2010-09-16 | Sumitomo Chemical Co | Method for manufacturing oxadiazolinone compound and intermediate thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1019752A (en) * | 1973-02-12 | 1977-10-25 | Sidney B. Richter | Heterocyclic anilids |
| US3901917A (en) * | 1974-11-04 | 1975-08-26 | Velsicol Chemical Corp | N-thienylalkylacetanilides |
| DE2648008C3 (en) * | 1976-10-23 | 1980-09-04 | Basf Ag, 6700 Ludwigshafen | Acetanilide |
| DE2704281A1 (en) * | 1977-02-02 | 1978-08-03 | Bayer Ag | Herbicidal N-heterocyclyl-methyl-halo-acetanilide derivs. - prepd. from a N-halomethyl-chloro:acetanilide and a heterocycle |
-
1978
- 1978-08-10 DE DE19782835157 patent/DE2835157A1/en not_active Withdrawn
-
1979
- 1979-07-30 AT AT79102706T patent/ATE1009T1/en not_active IP Right Cessation
- 1979-07-30 DE DE7979102706T patent/DE2962806D1/en not_active Expired
- 1979-07-30 EP EP79102706A patent/EP0008057B1/en not_active Expired
- 1979-08-07 IL IL57998A patent/IL57998A/en unknown
- 1979-08-08 CA CA000333393A patent/CA1116607A/en not_active Expired
- 1979-08-09 DK DK333479A patent/DK333479A/en unknown
- 1979-08-09 JP JP10082779A patent/JPS5524194A/en active Pending
- 1979-08-09 CS CS795458A patent/CS214801B2/en unknown
- 1979-08-09 ES ES483280A patent/ES483280A1/en not_active Expired
- 1979-08-09 ZA ZA00794144A patent/ZA794144B/en unknown
- 1979-08-09 BR BR7905112A patent/BR7905112A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4599448A (en) * | 1981-05-26 | 1986-07-08 | Bayer Aktiengesellschaft | Novel N-(1-alkenyl)-chloroacetanilides as herbicides and plant growth regulators |
Also Published As
| Publication number | Publication date |
|---|---|
| BR7905112A (en) | 1980-05-06 |
| IL57998A0 (en) | 1979-12-30 |
| EP0008057A1 (en) | 1980-02-20 |
| ZA794144B (en) | 1980-09-24 |
| DK333479A (en) | 1980-02-11 |
| JPS5524194A (en) | 1980-02-21 |
| DE2962806D1 (en) | 1982-07-01 |
| CS214801B2 (en) | 1982-06-25 |
| ATE1009T1 (en) | 1982-05-15 |
| DE2835157A1 (en) | 1980-02-21 |
| EP0008057B1 (en) | 1982-05-12 |
| IL57998A (en) | 1982-08-31 |
| ES483280A1 (en) | 1980-04-16 |
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