Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
  • C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
  • C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings 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

Definitions

• the present invention relates to a new process for the preparation of the known 3,4-dichloro-N- (2-cyano-phenyl) -5-isothiazole carboxamide, which can be used as an active ingredient with microbicidal properties.
• the method according to the invention is characterized by a number of advantages.
• Suitable acid acceptors when carrying out the first stage of the process according to the invention are preferably tertiary amines.
• tertiary amines examples include trimethylamine, triemylarnine, tributylamine, N, N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclooctane (DABCO), diazabicyclonones (DBN) or diazabicycloundecene (DBU ).
• Halogenated aromatic hydrocarbons such as toluene or chlorobenzene
• chlorinated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane
• amides such as dimethylformamide and dimethylacetamide. Dimethylformamide is particularly preferred.
• Suitable dehydrating agents for carrying out the second stage of the process according to the invention are all those reagents which are suitable for eliminating water from A iden.
• Mixtures of dimethylformamide and thionyl chloride, phosphorus oxychloride, phosgene or CMormethylene-dimethylammmonium chloride can preferably be used.
• All customary aprotic, organic solvents can be used as diluents when carrying out the second stage of the process according to the invention.
• Halogenated aromatic hydrocarbons such as toluene or chlorobenzene, can preferably be used, furthermore chlorinated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride, dichloroethane or
• Trichloroethane and also amides such as dimethylformamide and dimethylacetamide.
• Dimethylformamide is particularly preferred.
• the temperatures can be varied within a substantial range when carrying out the process according to the invention.
• the first stage is carried out at temperatures between 0 ° C. and 160 ° C., preferably between 0 ° C. and 120 ° C.
• work is generally carried out at temperatures between -20 ° C. and + 80 ° C., preferably between 0 ° C. and 60 ° C.
• reaction in the first stage and the second stage is generally carried out under atmospheric pressure. However, it is also possible to work under increased pressure.
• N- [2- (aminocarbonyl) phenyl] -3,4-dichloro-5-isothiazolecarboxamide of the formula (TV) are generally employed of dehydrating agent and optionally an excess of dimethylformamide.
• the preparation Processing takes place according to customary methods, in general the procedure is followed by adding water to the reaction mixture and suctioning off, washing and drying the resulting solids.
• the method according to the invention can be carried out as a one-pot reaction.
• 3,4-dichloroisothiazole-5-carboxylic acid chloride of the formula (LT) is first reacted with anthranilic acid amide of the formula (HI) in the presence of acid acceptor and then added without prior isolation of the N- [2- (ammocarbonyl) phenyl] -3,4-dicMor-isothiazolcarboxamids of formula (TV) add the dehydration reagent.
• the processing is again carried out according to the usual
• a solution of 4.33 g (22 mmol) of 3,4-dichloroisothiazolecarboxylic acid chloride is added to a mixture of 15 ml of dimethylformamide, 3 g (22 mmol) of anthranilic acid amide and 2.23 g (22 mmol) of triethylamine at 60 ° C. while stirring dripped.
• the reaction mixture is then stirred for a further hour at 60 ° C. and then concentrated under reduced pressure.
• the remaining residue is stirred with 35 ml of water and then suction filtered.
• the resulting, still moist solid is boiled with isopropanol, cooled to room temperature, suction filtered and dried.
• Triethylamine in 24 g of dimethylformamide is added dropwise at room temperature with stirring, a solution of 8.66 g (40 mmol) of 3,4-dichloroisothiazole-5-carboxylic acid chloride in 20 g of dimethylformamide.
• the reaction mixture is stirred at 20 ° C. for one hour.
• 6.67 g (56 mmol) of thionyl chloride are added dropwise to the resulting suspension with stirring.
• reaction mixture is stirred for a further 2 hours at room temperature, then 80 ml of water are added and the mixture is stirred for a further 15 minutes.
• the resulting solid is filtered off, washed twice with 40 ml of water and dried.
• the product obtained is boiled in 30 ml of isopropanol for 30 minutes. After cooling to room temperature, the resulting solid is suctioned off, twice with 10 ml each
• Triethylamine in 12 g of dimethylformamide is added dropwise at room temperature with stirring, a solution of 4.33 g (20 mmol) of 3,4-dichloroisothiazole-5-carboxylic acid chloride in 10 g of dimethylformamide.
• the reaction mixture is stirred at 20 ° C. for one hour.
• 4.3 g (28 mmol) of phosphorus oxychloride are added dropwise to the resulting suspension at 0 ° C. while stirring.
• the reaction mixture is stirred for a further 2 hours at 0 ° C., then mixed with 40 ml of water and stirred for a further 15 minutes.
• a solution of 8.66 g (40 mmol) of 3,4-dichloroisothiazole-5 is added to a solution of 6 g (44 mmol) of anthranilic acid amide and 4.46 g (44 mmol) of triethylamine in 24 g of dimethylformamide at room temperature with stirring -carboxylic acid chloride added dropwise in 20 g of dimethylformamide.
• the reaction mixture is stirred at 20 ° C. for one hour.
• 5.6 g (56 mmol) of phosgene are introduced into the resulting suspension at 20-25 ° C. with stirring.
• reaction mixture is stirred for a further 2 hours at room temperature, then 80 ml of water are added while cooling with ice and the mixture is stirred for a further 15 minutes.
• the resulting solid is filtered off, washed twice with 40 ml of water and dried. The received
• the aqueous phase is separated off from the two-phase filtrate and extracted twice with 150 ml of ethyl acetate each time.
• the combined organic phases are dried over sodium sulfate and then concentrated under reduced pressure.
• the remaining residue is stirred with 100 ml of petroleum ether and 25 ml of ethyl acetate.
• the resulting solid is filtered off, washed with ethyl acetate and dried.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Thiazole And Isothizaole Compounds (AREA)
• Plural Heterocyclic Compounds (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (6)

Applications Claiming Priority (2)

Publications (1)

Family

ID=29723489

Family Applications (1)

Country Status (9)

Cited By (4)

Citations (1)

Family Cites Families (2)

• 2002
  • 2002-06-27 DE DE10228732A patent/DE10228732A1/de not_active Withdrawn
• 2003
  • 2003-06-17 AT AT03732578T patent/ATE308530T1/de not_active IP Right Cessation
  • 2003-06-17 JP JP2004516609A patent/JP4551762B2/ja not_active Expired - Lifetime
  • 2003-06-17 AU AU2003238510A patent/AU2003238510A1/en not_active Abandoned
  • 2003-06-17 KR KR1020047021038A patent/KR101069222B1/ko not_active Expired - Lifetime
  • 2003-06-17 CN CNB038203294A patent/CN1325483C/zh not_active Expired - Lifetime
  • 2003-06-17 WO PCT/EP2003/006360 patent/WO2004002968A1/de not_active Ceased
  • 2003-06-17 DE DE50301572T patent/DE50301572D1/de not_active Expired - Lifetime
  • 2003-06-17 EP EP03732578A patent/EP1519926B1/de not_active Expired - Lifetime
  • 2003-06-26 TW TW092117350A patent/TWI266766B/zh not_active IP Right Cessation

Patent Citations (1)

Also Published As

Similar Documents

Legal Events