Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
  • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
  • C07D209/04—Indoles; Hydrogenated indoles
  • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
  • C07D209/32—Oxygen atoms
  • C07D209/34—Oxygen atoms in position 2
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
  • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
  • A01N43/38—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings

Definitions

• the preparation of compounds of formula (I) may, for. B. by reduction of 3 (-alkylsulfanyl) -1, 3-dihydro-2H-indol-2-ones done.
• the latter can be produced well on a laboratory scale.
• only methods have been described for their reduction, which can be handled poorly on an industrial scale. These are expensive and can also be demanding in terms of safety.
• Indole compounds of the formula (I) are disclosed in TJ Connolly, T. Durst, Synlett 1996, 663-664, in that PPh 3 can also be used in combination with p-TsOH as reagent.
• the known methods use either a heavy metal-containing
• Reagent or triphenylphosphine In the first case, waste containing heavy metals is produced. For ecological and economic reasons, this is not desirable. In the second case, the resulting from the triphenylphosphine reaction product must be separated from the reaction mixture. This separation is possible with additional effort usually only by chromatography. In addition, the respective reagent has a high molecular weight and must, however, be used stoichiometrically. This is disadvantageous for economic reasons.
• the methods known from the prior art are useful only on a laboratory scale and also have disadvantages due to the chemical properties of the metal compounds used as a reagent, with the disadvantages of using the method on an industrial scale even more effective.
• the object of the invention is to develop a process which allows the production of the compound of formula (I) on an industrial scale and does not have the disadvantages of the known from the prior art method.
• the object is achieved by a one-step process for preparing a compound of the formula (I)
• R 1 a to R 1d are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine and trifluoromethyl,
• Substituted substituent selected from the group consisting of (C 1 -C 4 ) alkoxy or (C 3 -C 7 ) cycloalkyl,
• (C 3 -C 7 ) -cycloalkyl where the cycloalkyl radical is unsubstituted or by one or more substituents selected from the group consisting of (C 1 -C 4 ) -alkyl or (C 3 -C 7 ) -cycloalkyl or (C 1 -C 4 ) -alkoxy, is substituted,
• (C 1 -C 6) -alkoxy where the alkoxy radical is branched or unbranched unsubstituted or substituted by one or more substituents selected from the group consisting of (C 1 -C 4 ) -alkoxy or (C 3 -C 7 ) -cycloalkyl,
• (C 1 -C 6) -alkylthio wherein the alkylthio radical is branched or unbranched unsubstituted or substituted by one or more substituents selected from the group consisting of (C 1 -C 4 ) -alkyl or (C 1 -C 4 ) -alkoxy,
• heteroaromatic ring having 1 to 2 heteroatoms, wherein the heteroatoms are independently selected from the group consisting of O or N and wherein the aryl or heteroaryl radical is unsubstituted or by one or more substituents selected from among (C 1 -C 4 ) -alkyl, (C 1 -C 4 ) -alkoxy or (C 3 -C 7 ) -cycloalkyl or (C 1 -C 4 ) -cycloalkyl or C 4 ) -Alkylthio existing group, starting from a compound of formula (II)
• R 2 is an unsubstituted or substituted (C 1 -C 4 ) -alkyl, (C 3 -C 7 ) -cycloalkyl, benzyl or a CH 2 -C (O) 0- (C 1 -C 6 ) -alkyl,
• reaction mixture is heated at a temperature which corresponds at most to the boiling point of the polar solvent, under reflux.
• the inventive method allows a simple, safe and cost-effective preparation of compounds of formula (I) from compounds of formula (II).
• the process can also be carried out safely on a company scale.
• the method can also be flexibly adapted to the apparatus requirements. It is particularly surprising and very advantageous that no odor-intensive exhaust gases are formed in the process according to the invention, as would actually be expected for such a reaction. This advantage is believed to be due to the fact that the sulfur-containing leaving group is bound in a non-volatile form.
• Preferred phenyl substituents R 1a , R 1 b , R 1c and R 1d are radicals which are selected independently of one another from the group consisting of hydrogen, (C 1 -C 6) -alkyl, (C 1 -C 6) -alkoxy, fluorine, chlorine, bromine and trifluoromethyl.
• Particularly preferred as phenyl substituents R 1 a , R 1 b , R 1c and R 1d radicals which are independently selected from the group consisting of
• radical R 2 is unsubstituted or substituted (C 1 -C 6 ) -alkyl, (C 3 -C 7 ) -cycloalkyl, benzyl or CH 2 -C (O) O- (C 1 -C 6 ) -alkyl, where the substituents are independently selected from the group consisting of
• a polar solvent is water, a (CrC 4 ) alcohol or a
• the sulfur-containing salt is selected from the group consisting of alkali metal or alkaline earth metal sulfite, alkali or alkaline earth bisulfite, alkali metal or alkaline earth metal dionite, alkali or alkaline earth dithionite or alkali metal or alkaline earth metal thiosulfate.
• Sodium salts ie the sulfur-containing salt is selected from the group consisting of Nat umbisulfit, Nat sulfite, Natriumthionit, Nat umdithionit and sodium thiosulfate.
• sulfur-containing salts are sodium bisulfite or
• Reaction mixture is heated to a temperature which is in a range whose lower limit is 40 ° C and whose upper limit corresponds to the reflux temperature of the solvent.
• Reaction temperature which corresponds approximately to the boiling point of the solvent used in each case.
• the reaction can also be carried out under elevated pressure in order to achieve a temperature which is up to 15 ° C above the boiling point of the respective solvent at atmospheric pressure.
• An elevated reaction temperature up to 15 ° C advantageously allows a shorter reaction time.
• Reaction mixture with stirring for the period of 1 to 48 hours Particularly preferred is heating the reaction mixture with stirring for the period of 1 to 24 hours, with a reaction time of 2 to 12 hours being most preferred.
• an antifoam or a mixture of different antifoams is added to the reaction mixture before reaching the boiling point of the particular solvent used.
• Suitable defoamers are, for example, Fluowet PL 80 or Korasilon LP-Si E 1051. The addition of the defoamer preferably takes place before the beginning of the heating of the reaction mixture. It is also within the scope of the invention that the
• a precipitant is added, wherein the precipitant is selected from the group of polar solvents consisting of water, a (CrC 4 ) alcohol or a mixture of water and a (CrC 4 ) alcohol.
• the addition of the precipitant has the particular advantage that the yield in the isolation by filtration is increased.
• reaction product of formula (I) may also be used without isolation, e.g. as a suspension or solution, further in the synthesis of fine chemicals and active ingredients in pharmacy and / or agriculture.
• a further aspect of the invention relates to the use of a compound of the formula (I) for the preparation of fine chemicals and of active compounds having a pharmaceutical or herbicidal action.

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• Organic Chemistry (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• Environmental Sciences (AREA)
• Engineering & Computer Science (AREA)
• Dentistry (AREA)
• General Health & Medical Sciences (AREA)
• Wood Science & Technology (AREA)
• Zoology (AREA)
• Plant Pathology (AREA)
• Pest Control & Pesticides (AREA)
• Agronomy & Crop Science (AREA)
• Indole Compounds (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Plural Heterocyclic Compounds (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)

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• 2011
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