Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
  • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
  • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Definitions

• the present invention relates to a process for the preparation of 2-alkyl-3- (4,5-dihydroisoxazol-3-yl) halobenzenes.
• the object of the present invention was to provide an improved production process for 3-heterocyclyl-substituted benzoyl derivatives, as described, for example, in WO 98/31681.
• the production process for 2-alkyl-3- (4, 5-dihydroisoxazol-3-yl) -acylbenzenes described in WO 98/31681 and its precursor (2-alkyl-3- (4, 5-dihydroisoxazole) 3-yl) -bromobenzenes) is not optimal for the industrial production of these compounds, since the synthesis takes place over several stages and the yield of the respective end product, based on the starting products used in the first synthesis stage, is relatively low.
• the 3-heterocyclyl-substituted benzoyl derivatives or their various precursors can be prepared in good yield and on an advantageous economic scale by the process according to the invention.
• the process according to the invention has the advantage that the overall yield of the respective end products, based on the starting materials used, is higher than the yield according to the processes described in WO 98/31681.
• the starting materials are easy to produce or can be obtained in large quantities from several independent raw material suppliers, so that overall a more cost-effective, economical and safe large-scale process for the production of herbicidal active substances is available.
• the present invention relates to a process for the preparation of the compounds of the formula I.
• n 0.1 or 2;
• R 3 , R 4 , R 5 are hydrogen, Cx-C ⁇ -alkyl, in particular methyl, or R 4 and R 5 together form a bond;
• radicals R 1 can in each case be the same or different and have the given meaning, with halogens, in particular chlorine or bromine, to give the 3,6-dihalo-1,2-di-alkylbenzenes of the formula III
• R 1 and R 3 to R 6 have the meanings given in claim 1;
• R 1 to R 6 have the meanings given in claim 1;
• C 1 -C 6 -alkyl denotes a straight-chain or branched alkyl group with 1 - 6 C atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl or n -Hexyl.
• R 4 and R 5 together can also represent a bond, so that the corresponding isoxazole derivatives result.
• R 3 is preferably hydrogen.
• halogenation is carried out according to methods known from the literature, preferably using chlorine gas.
• Suitable solvents are alcohols, such as Ethanol.
• Solvents which are inert during the bromination such as: benzene, t. -Butylbenzene, t.-Amylbenzene, halogenated hydrocarbons, such as methylene chloride, chloroform, chlorobenzene 1, 2-dichloroethane, carbon tetrachloride, dichlorobenzene or trichlorobenzene. Mixtures of these solvents are also possible.
• Brominating agent bromine, or bromine salts e.g. Bromine salts, HBr, preferably in its aqueous solution. Technical azeotropic mixtures of HBr can also be used with particular preference.
• oxidizing agents such as peracids, peroxides, hypochlorite, chlorine, sodium bromate and potassium peroxodisulfate, and hydrogen peroxide is particularly suitable.
• alkyl and benzyl halides are added to the corresponding carbonyl Can oxidize compounds with amine oxides of tertiary amines or pyridine. The reaction takes place under the following conditions: amine oxides: amine oxides with aliphatic, cycloaliphatic and aromatic residues such as trimethylamine, dirthylcyclopentylamine, dimethylamine.
• amine oxides with cycloaliphatic radicals which are interrupted by heteroatoms (0; N).
• N-alkyl and N-aryl substituted piperidines, piperazines and morpholines are particularly suitable.
• allyl halides can be reacted with alkali metal nitrates to give the corresponding aldehydes.
• the conditions are for example the following: Solvents: alcohols such as methanol, ethanol, isopropanol, ethers such as dioxane, THF, dipolar aprotic solvents such as e.g. N, N-dialkylformamides, -acetamides, N-methylpyrrolidone, dirnethylpropyleneurea; Tetramethyl urea, DMF, NMP, acetonitrile.
• solvents alcohols such as methanol, ethanol, isopropanol
• ethers such as dioxane, THF
• dipolar aprotic solvents such as e.g. N, N-dialkylformamides, -acetamides, N-methylpyrrolidone, dirnethylpropyleneurea
• Tetramethyl urea DMF, NMP
• the nitronates are produced as follows: reaction of lower nitroalkanes with alkali metal hydroxides (aqueous NaOH or KOH) or reaction of lower nitroalkanes with alkali metal alcoholates such as KotBu in butanol or sodium methylate in methanol.
• alkali metal hydroxides aqueous NaOH or KOH
• alkali metal alcoholates such as KotBu in butanol or sodium methylate in methanol.
• the nitronates thus obtained are reacted with the benzyl halides.
• the reaction takes place at temperatures between -10? and 80 ° C preferably at 0 ° C to 50? C.
• the work-up is aqueous.
• reaction of the benzaldoxime of the formula VI with alkenes of the formula VII to give compounds of the formula VIII proceeds via various intermediate stages. Since the first reaction step is the formation of an intermediate hydroxamic acid halide, a suitable oxidizing reagent and a halogen source or the halogen itself must be present. The second step is the elimination of hydrogen halide to nitrile oxide, which requires basic conditions. The third is the cycloaddition of the nitrile oxide to the alkene.
• this sequence can be carried out step by step, with the formation of the hydroxamic acid z.
• the free halogens bromine or chlorine can be used. Since the hydroxamic acid halides tend to decompose, they will soon have to be converted further with a base into the even more sensitive nitrile oxides, which are mostly trapped in situ with the alkene.
• a solvent such as, for example, haloalkanes such as dichloroethane and methylene chloride or aromatics such as benzene, toluene, chlorobenzene, nitrobenzene or xylene is used, which dissolves the organic component but does not itself interfere with the reaction.
• An aqueous alkali metal hypohalide solution preferably 1-2 equivalents of commercially available sodium hypochloride solution, is added as the halogenating agent and at the same time as the base, the alkene being added in parallel or immediately thereafter.
• the reaction mixture is therefore usually in two phases, since the organic solvent mixes only incompletely with the alkali metal hypohalide solution. It may be advantageous to add 3-50% sodium or potassium acetate to complete the conversion, but this is not absolutely necessary. Gaseous alkenes of the formula are introduced, and liquid alkenes are metered in accordingly.
• the alkenes are generally used in a molar ratio of 1 to 5: 1 with respect to the oxime VI.
• the reaction is carried out at temperatures from 0 to 80 ° C., preferably at temperatures between 20 and 50 ° C.
• the reaction is carried out under a pressure of 0 to 20 bar, preferably at 0 to 6 bar.
• Solvents alcohols such as methanol, ethanol, propanol, t-butanol, water, ethers such as dioxane, THF, polar aprotic solvents, e.g. N, N-dialkylformamides, acetamides, N-methylpyrrolidone, dirnethylpropyleneurea; Tetramethyl urea, acetonitrile, propionitrile, dimethyl sulfoxide; preferred: methanol, DMF, NMP.
• Temperature 0 ° C to 170 ° C, preferably 30 ° C to 120 ° C, particularly preferably 40 ° C to 100 ° C.
• the alkali thioalkylate for example sodium thiomethylate
• the alkali thioalkylate can be used as a solid, as an aqueous or methanolic solution or in si tu from the alkyl mercaptan, for.
• sodium methylate, potassium ethylate, sodium hydroxide or potassium hydroxide can be produced and used.
• the reaction can also be carried out in vacuo by additionally adding a high-boiling dipolar aprotic solvent with distillation of the low-boiling solvent, for example water or methanol.
• copper powder as a catalyst 0.01-10 mol%, the completion and acceleration of the reaction can often be achieved.
• the thioalkylation is generally at 0 to 100 ° C, preferably at 20 - 80 ° C. carried out .
• the reaction mixture is poured into 2.5 l of water, adjusted to pH 7.0 with 10% HCl, extracted three times with 1 l of ethyl acetate, combined organic phases, washed twice with 500 ml of saturated NaCl solution and dried over Na 2 SO 4 , and concentrated in vacuo:
• the 161.0 g of the crude product were distilled through a 10 cm column with 10 mm Raschig rings.
• the crystals from the last fractions were filtered. 25 9.8 g of 85.9% of the desired product, 4.5% and 6.9% of isomers. Yield: 9.7%.
• the residue was distilled through a canned column, and 3.2 g of 94.3% product were obtained again.
• N-methylmorpholine-N-oxide and 280 ml acetonitrile are added within 25 min at 0-5 ° C and stirred for 1 h at 0-8 ° C.
• the precipitate is filtered off with suction, taken up in 280 ml of acetonitrile and then 250 g (0.42 mol) of 20% NMO in acetonitrile are added at 40 ° C.
• the reaction mixture is at 1 h
• 35 action mixture is stirred into 250 ml of water and extracted three times with 100 ml of toluene. The combined organic phases are washed once with 100 ml of water and then concentrated in vacuo. 17.5 g of dark oil are obtained.
• GC / MS contains 52.3% of the desired product in addition to other isomers. 0 MSm / z: 287.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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