WO1997008163A1 - Procede de production de derives thiochromane - Google Patents

Procede de production de derives thiochromane Download PDF

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Publication number
WO1997008163A1
WO1997008163A1 PCT/JP1996/002224 JP9602224W WO9708163A1 WO 1997008163 A1 WO1997008163 A1 WO 1997008163A1 JP 9602224 W JP9602224 W JP 9602224W WO 9708163 A1 WO9708163 A1 WO 9708163A1
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alkyl group
general formula
group
acid
derivative
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PCT/JP1996/002224
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English (en)
Japanese (ja)
Inventor
Ichiro Nasuno
Seiji Tomita
Mitsuru Shibata
Hiroshi Yamamoto
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Idemitsu Kosan Co., Ltd.
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Priority to AU66688/96A priority Critical patent/AU6668896A/en
Publication of WO1997008163A1 publication Critical patent/WO1997008163A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
    • C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides

Definitions

  • the present invention relates to a method for producing a thiochroman derivative used for producing a birazol derivative useful as a herbicide. * ⁇ Technology
  • a Grignard reaction must be carried out when synthesizing the alkoxythiochroman carboxylic acid, which is an intermediate for producing the virazole derivative, which is industrially difficult. It cannot be said that this is a useful method for producing a virazol derivative.
  • the Grignard reaction has high reactivity and may not be included 1 ′ depending on the kind of the substituent of the target intermediate. Disclosure of the invention
  • the ultimate object of the present invention is to provide an alkoxythiochroman carboxylic acid derivative used for industrially advantageously producing the above pyrazole derivative by a Grignard reaction or the like. It is an object of the present invention to provide a method for easily manufacturing without using expensive steps.
  • the method (a) of the present invention comprises a compound represented by the general formula (I)
  • R 1 is a C, to C 4 alkyl group;
  • X 1 is an alkyl group, a halogen atom or a C, to C, alkyl group;
  • m is 0 or an integer of 1 to 3;
  • X 2 is a halogen atom
  • the method (b) of the present invention comprises the general formula ( ⁇ )
  • R 1 is-alkyl group; R 2, RR 4, and R 5 is it that an independent Hydrogen atom ho ⁇ ( ⁇ alkyl group; 1 is 1 ⁇ 4 Arukiru group, C Wherein m is 0 or an integer of 1 to 3), wherein the phenylthiopropionic acid derivative represented by the general formula (IV)
  • R 1 is a C! -C 4 alkyl group
  • R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom or a C! -C., Alkyl group
  • X 1 is a C!-( ⁇ Alkyl group, halogen atom or C '.- C4 haloalkyl group
  • m is 0 or an integer of 1-3), which reduces the thiochromanone derivative represented by The general formula
  • R 6 is an alkyl group, an alkoxyalkyl group, or a CG haloalkyl group.
  • R 1 is a C, -C 4 alkyl group
  • R 2 , RR 4, and R 5 are each independently a hydrogen atom or an alkyl group
  • R 6 is a-( 6 alkyl group, !!! C alkoxyalkyl -, or C: be a ⁇ haloalkyl group
  • X ' is an C-C 4 alkyl group, a halogen atom or C ⁇ C. haloalkyl group
  • m is 0 or is an integer from 1 to 3
  • the alkoxythiochroman derivative represented by the general formula (VIII) is hydrolyzed. H ⁇ 2 C
  • R 2 , R : ′, RRRX 1 and m are as defined above).
  • the substance (w) of the present invention has the general formula (III-1)
  • R 1 is ( ⁇ -( 4 alkyl group; R 2 , R 3 , R 4 and R 5 are each independently a purple atom or C, -C 4 alkyl); X 1 - (4 alkyl group, a c androgenic atoms or (- ⁇ haloalkyl group; m 1 is a phenylene thio propionic acid derivative represented by a 1 to 3) integer.
  • the substance (X) of the present invention has the general formula (IV-1)
  • R 1 is an alkyl group;
  • R 2, RR 4 and R 5 are that it independent a hydrogen atom or a C C alkyl group;!
  • X 1 is Alkyl group, a C androgenic atom or ⁇ 4 haloalkyl group;
  • m 1 is a Chiokuromanon derivative represented by a 1 to 3) integer.
  • the substance (y) of the present invention has the general formula (V)
  • R 1 is-alkyl group;
  • R 2, R 3, R 4 and R 5 is each independent hydrogen atom or ⁇ alkyl group;
  • X 1 is ⁇ 4 alkyl group, C port Gen atom or C, be ⁇ C 4 Soso Roarukiru group;
  • m is a hydroxy Chio chromans derivative represented by 0 or 1 of 3 integer).
  • the substance (2) of the present invention has the general formula (VII)
  • R 1 is a C! To C 4 alkyl group
  • R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom or a C! Ct alkyl group
  • R f ′ is ⁇ C 6 alkyl group, C alkoxyalkyl group or ( ⁇ ⁇ ( ⁇ noloalkyl group
  • X 1 is Ci ⁇
  • FIG. 1 is a reaction scheme showing the methods (a) to (e) of the present invention.
  • FIG. 2 is a process chart for producing a benzoic acid ester (I) used as a starting material in the method (a) of the present invention.
  • FIG. 3 is a process chart for producing ethyl 3,4-dichloro-6-methylbenzoate, which is the final product of Production Reference Example 1.
  • FIG. 4 is a process chart for producing the final target product of Production Reference Example 2, 3,4-difluoro-6-methylethyl benzoate.
  • FIG. 5 is a process chart for producing 8-chloro-6-hydroxypropyloxy-5-methyl-4-methoxythiochroman from 3,4-dichloro-6-methylbenzoate in Production Examples 1 to 5.
  • FIG. 6 is a process chart for producing 8-fluoro-6-ethoxycarbonyl 5-methylthiochroman-1-one from ethyl 3,4-difluoro-6-methylbenzoate in Production Examples 6 and 7. It is. Ming »The best form to apply
  • R 2 , R ⁇ R 4 and are each independently a hydrogen atom or a C, to C 4 alkyl group
  • R B is ( ⁇ ( "alkyl group, ( ⁇ ⁇ ( ⁇ alkoxyalkyl group, ( ⁇ ⁇ ( ⁇ c opening alkyl group, X 1 is c! ⁇ c 4 alkyl group, a halogen atom, c t ⁇ ⁇ 4 cutting edge alkyl group, m is 0 or an integer of 1 to 3, and X 2 is a halogen atom.
  • the method (a) of the present invention comprises condensing a benzoate (I) with a mercaptopropionic acid derivative (II) to obtain a phenylthiopropionic acid derivative (III).
  • Benzoic acid ester (I) used as a starting material has the general formula (1)
  • R 1 is ⁇ ( 4 alkyl group ';
  • X 1 is ⁇ ( ⁇ alkyl group, halogen
  • R ⁇ RR '1 and R 5 is represented by it it independently hydrogen or ( ⁇ ⁇ . ⁇ ! A ⁇ alkyl group).
  • the condensation reaction is carried out in a solvent inert to the reaction, such as toluene, N-methylpyrrolidone, N, N-dimethylformamide.
  • This reaction is preferably performed in the presence of a base, and examples of the base used include sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate.
  • the base is used in an amount of 2.0 to 5.0 equivalents, preferably 2.0 to 3.0 equivalents, based on the benzoate (I).
  • the reaction temperature ranges from room temperature to the reflux temperature of the solvent, but is preferably from 80 to 130 ° C.
  • the reaction time is generally 1 to 8 hours, preferably 1 to 3 hours.
  • the reaction solution is cooled to about 50 ° C, and an organic solvent such as ethyl acetate and water are added to remove the reaction solvent and neutral components.
  • the removal is performed by sequentially washing the aqueous layer with a polar organic solvent such as ethyl acetate and a non-polar organic solvent such as hexane. Further, a strong acid such as concentrated hydrochloric acid is added to the obtained aqueous layer to precipitate crystals. The precipitated crystals are collected by filtration and washed with water.
  • the obtained crystals are dissolved in a polar organic solvent such as ethyl acetate, and the solution is washed with a saturated saline solution and dried with anhydrous sodium sulfate. By evaporating the solvent, the desired phenylthiobrobionic acid derivative (III) is obtained.
  • the obtained phenylthiopropionic acid derivative has the general formula (I II)
  • the phenylthiopropionic acid derivative (III) may be further purified as necessary, but can usually be used in the method (b) of the present invention without purification.
  • the phenylthiopropionic acid derivative (III) obtained in the method (a) of the present invention is condensed and cyclized to obtain a thiochromanone derivative (IV).
  • the condensed cyclization method include (i) converting phenylthiopropionic acid derivative (III) to hydrogen fluoride, sulfuric acid, fuming sulfuric acid, phosphorus pentachloride, phosphoric acid, polyphosphoric acid, tin chloride, zinc chloride, or chloride.
  • a method of dehydration cyclization in the presence of an acid catalyst such as an acidic ion exchange resin represented by aluminum or Amberlyst; (ii) a phenylthiopropionic acid derivative (III) using a chlorine such as thionyl chloride; A method of reacting with an agent to form an acid chloride, and cyclizing in the presence of an acid catalyst similar to the method (i) above.
  • the solvent used in the reaction is not particularly limited as long as it is inert under the reaction conditions. However, hydrocarbon solvents such as pentane and hexane, and halogen solvents such as dichloromethane and 1,2-dichloroethane are used. preferable.
  • a method using polyphosphoric acid as a solvent and an acid catalyst is also suitable.
  • the acid catalyst is used in an amount of 0.01 to 20 equivalents, preferably 1.0 to 10 equivalents, based on the phenylthiopropionic acid derivative (III).
  • the reaction temperature is usually in the range of 0 e C ⁇ l 20 ° C, preferably 0 ° C ⁇ 100 ° C.
  • the reaction ⁇ 1, ./.] Is generally 30 minutes to 8 hours (3 ⁇ 4, but preferably 30 minutes to 2 hours.
  • the chlorinating agent is phenylthiopropion.
  • the acid derivative ( ⁇ ) is used in an amount of 1.0 to 3.0 equivalents, preferably 1.1 to 1.5 equivalents, and the reaction temperature of the acid chloride is usually in the range of 0 to 120 ° C.
  • the reaction time is usually 30 minutes to 8 hours, preferably 30 minutes to 2 hours, and the acid catalyst used in the cyclization method (ii) is an acid. It is used in an amount of 0.01 to 1.0 equivalent, preferably 0.1 to 1.0 equivalent, based on the chloride.
  • the reaction temperature of the acid-catalyzed reaction is usually from room temperature to 120 ° C., preferably room temperature.
  • the reaction time is generally 30 minutes to 8 hours, preferably 2 to 4 hours.
  • R 1 is C, ⁇ an alkyl group;.
  • R 2, R 3, R 4 and R 5 is it that independent a hydrogen atom or a C ⁇ C 4 alkyl group;!
  • X 1 is ⁇ 4 alkyl group, a C androgenic atom or C ⁇ C 4 Nono Roarukiru group;
  • m is represented by an integer of 0 or from 1 to 3).
  • R 1 is an alkyl group
  • X la and X lb are an alkyl group, a halogen atom or an alkyl group, which may be the same or different.
  • the thiochromanone derivative (IV) obtained in the method (b) of the present invention is reduced to obtain a hydroxythiochroman derivative (V).
  • the reduction method there are no particular restrictions on the reduction method, but (i) a method using a reducing agent such as sodium borohydride in a reaction inert solvent such as alcohol or dichloromethane, or (ii) a method using palladium or nickel or the like.
  • a method in which hydrogenation is carried out at normal pressure or under pressure in the presence of a reduction catalyst may be mentioned.
  • the reducing agent is used in an amount of 1.0 to 5.0 equivalents, preferably 1.1 to 2.0 equivalents, relative to the thiochromanone derivative (IV).
  • the reaction temperature is usually from 20 to 50, but preferably from 0 to 20 ° C.
  • the reaction time is usually from 30 minutes to 8 hours, preferably from 30 minutes to 2 hours.
  • the reduction catalyst is used in an amount of 1 to 50% by weight, preferably 10 to 20% by weight, based on the thiochromanone derivative (IV).
  • the hydrogen pressure is usually from normal pressure to 100 kg / cm 2 , preferably from 10 to 5 Okg / cm 2 .
  • the reaction temperature is from room temperature to 100 ° C, and the reaction time is from 1 to 8 hours.
  • a preferred embodiment of the method (c) of the present invention is a method in which ethanol and dichloromethane are used as a solvent and reduction is carried out using sodium borohydride.
  • the reaction temperature is preferably 0 ° C. to room temperature, and the reaction time is preferably 30 30 to 2 hours.
  • R 1 is a ( ⁇ - ⁇ alkyl group;
  • R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom or a C! Ca alkyl group;
  • X 1 is a -alkyl group
  • Nono port Gen atom or C be ⁇ C 4 haloalkyl group;
  • m is 3 ⁇ 4 by an integer of 0 or from 1 to 3).
  • the hydroxythiochroman derivative (V) obtained in the method (c) of the present invention is dehydrated and condensed with an alcohol (VI) to obtain an alkoxythiochroman derivative (VII).
  • R 6 is represented by —C c alkyl group, C; —C 6 alkoxyalkyl group, or C! — (A 6- alkyl group).
  • reaction solvent used in the dehydration condensation reaction an aromatic hydrocarbon solvent such as benzene, toluene, xylene and the like, and a halogenated hydrocarbon solvent such as 1,2-dichloroethane and carbon tetrachloride can be used.
  • Alcohol (VI) which is a reaction reagent, can be used in excess as a solvent.
  • an acid catalyst such as sulfuric acid, -aromatic sulfonic acid, sulfonic acid halide, boron trifluoride, and aluminum chloride is used.
  • the acid catalyst is used in an amount of 0.01 to 0.2 equivalent relative to the hydroxythiochroman derivative (V).
  • the reaction temperature is usually in the range of 60 E C to the boiling point of the solvent, but preferably the reflux temperature of the solvent used or the alcohol (VI) used also as the solvent.
  • reaction solution is poured into a large excess of ice water, and extracted with an organic solvent such as ethyl acetate and dichloromethane.
  • organic solvent such as ethyl acetate and dichloromethane.
  • the obtained organic layer is sequentially washed with a 5% aqueous potassium carbonate solution and saturated saline, and dried over anhydrous sodium sulfate. By distilling off the solvent, a crude product of interest can be obtained.
  • R 1 is a C! CA alkyl group
  • R 2 , R 3 , R 4 and R 3 are each independently a hydrogen atom or a C! -C 4 alkyl group
  • R 6 is a C! ! ⁇ C 6 alkyl group, C, be -C G alkoxyalkyl group or C 1 -C 6 Nono Roarukiru group
  • X 1 is ( ⁇ ⁇ C. alkyl group, a halogen atom or the C: ⁇ C 4 Nono Roarukiru group Yes
  • 111 is 0 or an integer of 1 to 3).
  • the process (e) of the present invention comprises hydrolyzing the alkoxythiochroman derivative (VII) obtained by the process (d) of the present invention to obtain an alkoxythiochroman carboxylic acid derivative (VIII) as the final product. is there.
  • the hydrolysis reaction can be achieved under both acidic conditions and basic conditions.
  • the reaction is carried out using a base catalyst such as sodium hydroxide in the presence of a large excess of water.
  • the acid catalyst or the base catalyst is used in an amount of 0.01 to 1 equivalent, preferably 0.1 to 1 equivalent, relative to the alkoxythiochroman derivative (VII).
  • Reaction temperature is usually room temperature
  • the reaction time is generally 1 to 8 hours, preferably 1 to 4 hours.
  • the solvent is distilled off from the reaction solution, ice water is added to the obtained residue, and neutral impurities are removed with an organic solvent such as ethyl acetate or dichloromethane.
  • the obtained aqueous layer is neutralized with concentrated hydrochloric acid, and extracted with an organic solvent such as ethyl acetate and dichloromethane.
  • the obtained organic layer is washed with a saturated saline solution, dried over anhydrous sodium sulfate or the like, and the solvent is distilled off, whereby a crude product of the desired product can be obtained.
  • the alkoxythiochroman carboxylic acid thus obtained is the final product and has the general formula (VIII)
  • R 2 , R 3 ,: 4 and R 5 are each independently a hydrogen atom or R B is a Ct Cs alkyl group, a C 1 -C 6 alkoxyalkyl group or a C! -C 6 haloalkyl group;
  • X 1 is a C! -C 4 alkyl group, a halogen atom or
  • ⁇ To ⁇ is a 4- alkyl group;
  • m is 0 or an integer of 1 to 3).
  • the benzoate (I) used as a starting material in the method (a) of the present invention can be produced by various known methods.
  • the benzoate (I) may be produced through the steps (1) to (3) shown in FIG. Can be manufactured.
  • R 1 is a C i -C 4 alkyl group
  • X 1 is a ( ⁇ -( ⁇ alkyl group, a halogen atom, ( ⁇ -( ⁇ a haloalkyl group, m is 0 or 1-
  • X is an integer of 3
  • X 2 is a halogen atom
  • L is a chlorine atom, a bromine atom, a 10H group or an OCOCH 3 .
  • a halogen-substituted benzene derivative represented by the formula (i) (hereinafter referred to as a halogen-substituted benzene (i)) is acetylated with an acetylating agent in the presence of an acid catalyst, and an acetophenone derivative represented by the formula (ii) Acetophenone (ii)).
  • the acid catalyst include hydrogen fluoride, sulfuric acid, phosphorus pentachloride, phosphoric acid, polyphosphoric acid, tin chloride, zinc chloride, and aluminum chloride.
  • the acid catalyst is used in an amount of 0.1 to 5.0 equivalents, preferably 1.0 to 3.0 equivalents, based on the halogen-substituted benzene (i).
  • Examples of the acetylating agent include acetic acid, acetic anhydride, acetyl chloride and the like.
  • the acetylating agent is used in an amount of 1.0 to 5.0 equivalents, preferably 1.1 to 1.5 equivalents, based on the halogen-substituted benzene (i).
  • the reaction solvent is not particularly limited as long as it is inert under the reaction conditions. However, hydrocarbon solvents such as pentane and hexane, and halogen solvents such as dichloromethane and 1,2-dichloroethane are preferred.
  • the reaction temperature is not particularly limited within the range of 178 ° C to the reflux temperature of the solvent, but is preferably about 0 to 80 ° C.
  • the reaction time is usually 1 to 20 hours, preferably 2 to 8 hours.
  • reaction solution is poured into ice water, extracted with an organic solvent such as dichloromethane, and the obtained organic layer is washed successively with water, a 5% aqueous potassium carbonate solution and saturated saline, and then sulfuric anhydride is added. Dry with sodium. By distilling off the solvent, a crude product of the desired product can be obtained.
  • organic solvent such as dichloromethane
  • acetophenone ( ⁇ ) is oxidatively cleaved to obtain a benzoic acid derivative represented by the formula (iii) (hereinafter, referred to as benzoic acid derivative (iii)).
  • Examples of the oxidative cleavage method include (a) a method using carbon tetrachloride and lithium hydroxide (haloform reaction), (mouth) a method using sodium hydroxide and chlorine (haloform reaction), and (c) iodine. Examples thereof include a method using pyridine (King reaction), and (2) a method using an oxidizing agent such as sodium hypochlorite and potassium hypochlorite (haloform reaction).
  • the solvent for example, dioxane, water, black holem, or the like can be used.
  • the oxidizing agent is used in an amount of 3.0 to 5.0 equivalents to acetophenone (ii).
  • the reaction temperature is usually from 120 to 60 ° C, preferably from 0 to 20 ° C.
  • the reaction time is usually 1 to 8 hours, but preferably 2 to 4 hours.
  • an organic solvent such as dichloromethane is added for washing to remove the organic solvent and neutral components used in the reaction.
  • the remaining aqueous layer is made acidic by adding concentrated hydrochloric acid or the like, and the crystals are precipitated.
  • the obtained crystals are filtered and dried, or extracted with an organic solvent, dried over anhydrous sodium sulfate, and then the solvent is distilled off to obtain the desired product.
  • the benzoic acid derivative (iii) is condensed with an alcohol represented by the formula (iv) (hereinafter, referred to as alcohol (iv)) to obtain a benzoic acid ester (iv)
  • Preferred examples of the condensation method include (i) a method in which a benzoic acid derivative (iii) is reacted with a chlorinating agent such as thionyl chloride to react with an alcohol (iv) as an acid chloride, (mouth) sulfuric acid, p-toluene In the presence of an acid catalyst such as sulfonate, a method of dehydrating and condensing with an alcohol (iv) may be mentioned.
  • the chlorinating agent is used in an amount of 1.0 to 5.0 equivalents, preferably 1.2 to 2.0 equivalents, relative to the benzoic acid derivative (iii).
  • the alcohol (iv) is allowed to react with the obtained acid compound in an amount of 1.0 to 100 equivalents, preferably 5 to 50 equivalents.
  • the reaction solvent include solvents inert to the reaction, such as dichloromethane and 1.2-dichloroethane.
  • the reaction temperature is usually 0 to 100 ° C, preferably 0 to the reflux temperature of the solvent.
  • the reaction time is usually 30 minutes to 8 hours, preferably 2 to 4 hours.
  • the acid catalyst is used in an amount of 0.01 to 5.0 equivalents, preferably 0.05 to 1 equivalent, relative to the benzoic acid derivative (iii).
  • the alcohol (iv) is reacted with the benzoic acid derivative (iii) in an amount of 1 to 100 ff, preferably 5 to 20:
  • the reaction solvent used is the alcohol used for the reaction.
  • the reaction temperature is usually from 0 to the reflux temperature of the solvent, preferably from 20 to 80 ° C.
  • the reaction time is generally 1-24 hours, preferably 2-8 hours.
  • the solvent was distilled off under reduced pressure, ice water was added to the reaction residue, and the mixture was extracted with ethyl acetate.
  • the obtained organic layer is washed successively with an aqueous sodium carbonate solution and a saturated saline solution, and dried over anhydrous sodium sulfate. By evaporating the solvent under reduced pressure, a crude product of the desired product can be obtained.
  • the phenylthiopropionic acid of the substance (w) of the present invention is represented by the general formula (III-1).
  • R 1 is an alkyl group.
  • the CCA alkyl group include a methyl group, an ethyl group, a propyl group and a butyl group, and the propyl group and the butyl group may have a branch. Preferably it is an ethyl group.
  • R 2 , R 3 , R 4 and R 5 are each independently a hydrogen atom or a C, -C 4 alkyl group. Specific examples of the C 1 to C 4 alkyl groups are as described above.
  • X 1 is a C i -C 4 alkyl group, a halogen atom or C! To C 4 peroxyalkyl group, preferably C: to C 4 alkyl group or Happagen atom.
  • C! Examples of ⁇ C 4 alkyl group is as defined above, preferably a methyl group.
  • Specific examples of the halogen atom include a chlorine atom, a fluorine atom, a bromine atom, an iodine atom and the like, and a chlorine atom or a fluorine atom is preferable.
  • Ci ⁇ C 4 haloalkyl groups are those substituted with at least one halogen atom of the ( ⁇ - ( ⁇ hydrogen atom in the alkyl group, C i - C 6 Nono Roarukiru groups described below as specific examples Among them, those having 1 to 4 carbon atoms are mentioned.
  • m 1 represents the number of substitutions of X 1 and is an integer of 1 to 3, preferably 1 or 2.
  • the substitution position of X 1 is susceptible to 5, 7 and 8 positions of Chiokuroman ring, it is preferred properly is 5 and / or 8-position. That is, when m 1 is 1, the substitution position of X 1 is preferably at position 5 or 8 of the chiochroman ring, and when m 1 is 2, the substitution position of two X 1 is preferably at positions 5 and 8.
  • m 1 is 2 or 3, two or three X 1 may be the same or different.
  • the thiochromanone derivative which is the substance (X) of the present invention is represented by the general formula (IV-1).
  • R ′ to R 5 , X 1 and m 1 in the above formula (IV-1) are as described in the phenylthiopionic acid derivative of the formula ( ⁇ -1).
  • a particularly preferred embodiment of the substance (X) of the present invention is represented by the general formula (VI-la)
  • alkoxythiochroman derivative of the present invention (z) is represented by the general formula (VII)
  • R 6 is a C i -C G alkyl group, a C! -C 6 alkoxyalkyl group or a C! -C 6 haloalkyl group, preferably a -alkyl group.
  • C Cc alkoxyalkyl group examples include, for example, a methoxy-substituted 5-alkyl group such as a methoxymethyl group, a methoxethyl group and a methoxypropyl group; an ethoxy-substituted group such as an ethoxymethyl group, an ethoxyshethyl group and an ethoxypropyl group.
  • a methoxy-substituted 5-alkyl group such as a methoxymethyl group, a methoxethyl group and a methoxypropyl group
  • an ethoxy-substituted group such as an ethoxymethyl group, an ethoxyshethyl group and an ethoxypropyl group.
  • a haloalkyl group is one in which at least one of the hydrogen atoms in the C 1 -C 5 alkyl group has been replaced by a halogen atom (eg, a chlorine atom, a fluorine atom, a bromine atom, an iodine atom).
  • a halogen atom eg, a chlorine atom, a fluorine atom, a bromine atom, an iodine atom.
  • FIG. 3 shows a manufacturing process diagram of Production Reference Example 1.
  • Step (1) Synthesis of 3,4-dichloro-6-methylacetophenone (equivalent to acetophenone derivative (ii))
  • the obtained aqueous layer was extracted with ethyl acetate, and the obtained organic layer was combined with the concentrated organic layer.
  • the organic layer was washed once with 5% hydrochloric acid, twice with an aqueous solution of sodium carbonate and once with a saturated saline solution, and then dried over anhydrous sodium sulfate.
  • the solvent was distilled off under reduced pressure to obtain a crude product of 3,4-dichloro-6-methylacetophenone 125.1-(yield 86%).
  • the 3,4-dichloro-6-methylbenzoic acid 92.1 (42 lmmo 1) obtained in the above step (2) was dissolved in 550 ml of ethanol corresponding to the alcohol (iv) and also as a solvent. 20 ml of concentrated sulfuric acid as a catalyst was added, and the mixture was heated under reflux for 7 hours. After the ethanol was distilled off under reduced pressure, ice water was added thereto, and the mixture was extracted twice with ethyl acetate. The obtained organic layer was washed successively with an aqueous solution of sodium carbonate and a saturated saline solution, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 103.4 g of a crude product of ethyl 3,4-dichloro-6-methylbenzoate (97% yield).
  • FIG. 4 shows a production process diagram of Production Reference Example 2.
  • Step (1) Synthesis of 3,4-difluoro-6-methylacetophenone (corresponding to acetophenone derivative (ii))
  • the obtained aqueous layer was extracted with methylene chloride, and the obtained organic layer was combined with the concentrated organic layer.
  • the organic layer was washed once with 5% hydrochloric acid, twice with an aqueous sodium hydrogen carbonate solution and once with a saturated saline solution, and then dried over anhydrous sodium sulfate.
  • the solvent is distilled off under reduced pressure
  • Production Example 1 Production of 3- (2-chloro-4-ethoxyethoxycarbonyl-5-methylphenylthio) propionic acid (phenylthiopropionic acid (III-1)) corresponding to the method (a) of the present invention
  • the reaction solution was cooled to about 50 e C and, after addition of acetic acid Echiru and water, to remove the DMF and neutral components, four times, hexane with 1 Kaiarai ⁇ was to in acetic acid Echiru.
  • Concentrated hydrochloric acid was added to the obtained aqueous layer to precipitate crystals. After leaving for a while, the crystals were collected by filtration and washed three times with water. The obtained crystals were dissolved in ethyl acetate, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 50.4 g (yield: 60%) of a crude product of 3- (2-chloro-4-ethoxycarbonyl-5-methylphenylthio) propionic acid (III).
  • reaction solution was poured into 40% of 5% aqueous hydrochloric acid, extracted with 900 ml of dichloromethane, and the obtained organic layer was washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off to obtain 86.8 g (97% yield) of 8-chloro-6-ethoxycarbone-5-methylthiochroman-1-ol (V).
  • Figure 6 shows the manufacturing process diagrams of Production Examples 6 and 7. .
  • Production Example 6 Production example of 3- (2-fluoro-4-ethoxycarboxy-5-methylphenylthio) propionic acid (corresponding to phenylthiopropionic acid (III)) corresponding to the method (a) of the present invention.
  • virazole derivatives having a thiochroman ring useful as herbicides According to the present findings, virazole derivatives having a thiochroman ring useful as herbicides

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé permettant de simplifier la production d'acides alcoxythiochromane-carboxyliques utilisés pour la production de dérivés pyrazole comportant un anneau thiochromane et convenant particulièrement comme herbicide via l'hydrolyse d'esters d'acides alcoxythiochromane-carboxyliques, sans avoir recours à une opération coûteuse telle que la réaction de Grignard.
PCT/JP1996/002224 1995-08-31 1996-08-07 Procede de production de derives thiochromane WO1997008163A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU66688/96A AU6668896A (en) 1995-08-31 1996-08-07 Process for producing thiochroman derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP22345795 1995-08-31
JP7/223457 1995-08-31

Publications (1)

Publication Number Publication Date
WO1997008163A1 true WO1997008163A1 (fr) 1997-03-06

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1996/002224 WO1997008163A1 (fr) 1995-08-31 1996-08-07 Procede de production de derives thiochromane

Country Status (3)

Country Link
AR (1) AR003379A1 (fr)
AU (1) AU6668896A (fr)
WO (1) WO1997008163A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105924425A (zh) * 2016-04-29 2016-09-07 浙江师范大学 一种制备二氢硫色满衍生物的方法
CN115028596A (zh) * 2021-03-03 2022-09-09 帕潘纳(北京)科技有限公司 制备苯唑草酮中间体的方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03505204A (ja) * 1988-06-20 1991-11-14 フアルミタリア・カルロ・エルバ・エツセ・エルレ・エルレ ３環式３―オキソ―プロパンニトリル誘導体およびその調製方法
WO1993018031A1 (fr) * 1992-03-03 1993-09-16 Idemitsu Kosan Co., Ltd. Derive de pyrazole
WO1995004054A1 (fr) * 1993-08-02 1995-02-09 Idemitsu Kosan Co., Ltd. Derive de pyrazole
JPH0826914A (ja) * 1994-07-15 1996-01-30 Idemitsu Kosan Co Ltd トリケトン誘導体
WO1996025412A1 (fr) * 1995-02-13 1996-08-22 Idemitsu Kosan Co., Ltd. Derives de pyrazole

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH03505204A (ja) * 1988-06-20 1991-11-14 フアルミタリア・カルロ・エルバ・エツセ・エルレ・エルレ ３環式３―オキソ―プロパンニトリル誘導体およびその調製方法
WO1993018031A1 (fr) * 1992-03-03 1993-09-16 Idemitsu Kosan Co., Ltd. Derive de pyrazole
WO1995004054A1 (fr) * 1993-08-02 1995-02-09 Idemitsu Kosan Co., Ltd. Derive de pyrazole
JPH0826914A (ja) * 1994-07-15 1996-01-30 Idemitsu Kosan Co Ltd トリケトン誘導体
WO1996025412A1 (fr) * 1995-02-13 1996-08-22 Idemitsu Kosan Co., Ltd. Derives de pyrazole

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105924425A (zh) * 2016-04-29 2016-09-07 浙江师范大学 一种制备二氢硫色满衍生物的方法
CN115028596A (zh) * 2021-03-03 2022-09-09 帕潘纳(北京)科技有限公司 制备苯唑草酮中间体的方法

Also Published As

Publication number Publication date
AU6668896A (en) 1997-03-19
AR003379A1 (es) 1998-07-08

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