WO2001040176A1 - Compose sulfure et procedes de fabrication de derives de thiochromane et de derives de dihydrobenzo-(b)-thiophene - Google Patents

Compose sulfure et procedes de fabrication de derives de thiochromane et de derives de dihydrobenzo-(b)-thiophene Download PDF

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WO2001040176A1
WO2001040176A1 PCT/JP2000/008504 JP0008504W WO0140176A1 WO 2001040176 A1 WO2001040176 A1 WO 2001040176A1 JP 0008504 W JP0008504 W JP 0008504W WO 0140176 A1 WO0140176 A1 WO 0140176A1
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general formula
carbon atoms
atom
alkyl group
derivative
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PCT/JP2000/008504
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English (en)
Japanese (ja)
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Masashi Sakamoto
Seiji Tomita
Yoriyuki Takashima
Hidetoshi Koga
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Idemitsu Kosan Co., Ltd.
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Priority claimed from JP34442699A external-priority patent/JP2001163853A/ja
Priority claimed from JP34442899A external-priority patent/JP2001163880A/ja
Priority claimed from JP34442799A external-priority patent/JP2001163881A/ja
Application filed by Idemitsu Kosan Co., Ltd. filed Critical Idemitsu Kosan Co., Ltd.
Priority to AU15564/01A priority Critical patent/AU1556401A/en
Publication of WO2001040176A1 publication Critical patent/WO2001040176A1/fr

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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
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
    • 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

Definitions

  • the present invention relates to an intermediate for producing a pyrazole derivative and a hexahexanedione derivative and a method for producing the same. More specifically, the present invention relates to a sulfide compound having high utility as an intermediate for producing a pyrazole derivative and a cyclohexanedione derivative, which are active ingredients of a herbicide, and a 6-acetylthiochroman derivative or 5-sulfide compound using the same.
  • Acetildihydrobenzo [b] A method for producing a thiophene derivative.
  • the present invention relates to a 6-acetylthiochroman derivative or a 5-acetylacetylhydrobenzo [b] thiophene derivative to a thiochroman-6-force rubonic acid derivative and a dihydrobenzo [b] thiophene-5-force rubonic acid.
  • the present invention relates to a method for manufacturing an inductor with low environmental load and low manufacturing cost.
  • the present invention provides a thiochroman-6-carboxylic acid derivative and dihydrobenzene derivative using a halogenated thiochroman-6-carboxylic acid derivative and a halogenated dihydrobenzene derivative [b] thiophen-15-carboxylic acid derivative.
  • the present invention relates to a method for producing a benzo [b] thiophene-5-carboxylic acid derivative with a low environmental load and a low production cost.
  • Herbicides are extremely important for labor saving of weed control work and improvement of productivity of agricultural and horticultural crops.Therefore, research and development of herbicides has been actively conducted for many years, and a wide variety of chemicals are currently in practical use. Has been However, even today, there is a need to develop new drugs with even more excellent herbicidal properties, especially those that can selectively control only the target weeds at low doses without causing phytotoxicity to cultivated crops. Is desired.
  • a thiophene-5-carboxylic acid derivative is prepared by reacting a thiophene-5-carboxylic acid derivative with a compound represented by the general formula (B) or (C) in the presence of a dehydrating agent and a base.
  • a thiophenol derivative represented by the general formula (F) is used as a starting material.
  • This thiophenol derivative can be produced by a known production method, for example, New Experimental Chemistry Course 14 Synthesis and Reaction of Organic Compounds III (Maruzen Co., Ltd., issued on February 20, 1986) 1 page 704 “via dithiocarbonate
  • the production method described in the section “Synthesizing method” describes that the production process is complicated and the production cost is high.
  • 1,4-dioxane is used as a solvent for the haloform reaction.
  • 1,4-dioxane it is difficult to collect and reuse 1,4-dioxane, increasing the amount of waste liquid from the manufacturing process, increasing the cost required for waste liquid treatment and increasing the environmental burden. There's a problem.
  • the compound in which X 4 in the above-mentioned thiochroman-6-carboxylic acid derivative and dihydrobenzo [b] thiophen-5-carboxylic acid derivative (A) is hydrogen is also useful as an active ingredient of the herbicide.
  • the thiophenol compound (F) in which X 4 is hydrogen is used as a starting material in steps 1 to 3 in the production method, the structure is a target structure in which the substituent X 1 is bonded to the 5-position of the thiochroman ring.
  • a first object of the present invention is to provide a sulfide compound having high utility as an intermediate for producing a pyrazole derivative and a cyclohexanedione derivative, which are active ingredients of a herbicide, and a 6-acetylthiophene using the sulfide compound. It is an object of the present invention to provide a method for producing a chroman derivative or 5-acetyldihydrobenzo [b] thiophene derivative easily and inexpensively.
  • a second object of the present invention is to reduce the environmental burden of thiochroman-6-carboxylic acid derivatives and dihydrobenzo [b] thiophene-5-carboxylic acid derivatives, and to reduce industrial costs. Provide an advantageous production method Is Rukoto.
  • the present inventors also oxidized a 6-acetylthiochroman derivative or a 5-acetyldihydrobenzo [b] thiophene derivative under a two-layer reaction solvent of water and an organic solvent to obtain a thiochroman derivative. It has been found that the above object can be achieved by using a 16-carboxylic acid derivative and dihydrobenzo [b] thiophene-15-carboxylic acid derivative.
  • the present inventors reduced the halogenated thiochroman-6-carboxylic acid derivative or the halogenated dihydrobenzo [b] thiophene-5-carboxylic acid derivative in an aqueous alkali solution to reduce the thiochroman-6-carboxylic acid derivative. It has been found that the above-mentioned object can be achieved by using an acid derivative and dihydrobenzo [b] thiophene-5-carboxylic acid derivative.
  • the present invention has been made based on these findings.
  • the gist of the present invention is as follows.
  • RR 2 independently represents a halogen atom or an alkyl group having 1 to 4 carbon atoms
  • R 3 , RR 5 , R 6 , and R 7 each independently represent a hydrogen atom or 1 to 4 carbon atoms.
  • R 5 and R 6 and R 6 and R 7 may be arbitrarily bonded to each other on a carbon atom to form a 3- to 7-membered hydrocarbon ring.
  • R 8 , R 9 , R 10 , R 11 , R 12 and R 13 each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • R 11 and R 12 and R 12 and R 13 may be arbitrarily bonded to each other on a carbon atom to form a 3- to 7-membered saturated hydrocarbon ring.
  • n indicates a queue or 0.
  • R 3 to R 7 are the same as described above, and X 2 represents a halogen atom.
  • a general formula (1) characterized by reacting a halogenated aryl compound represented by
  • R i R 7 is as defined above.
  • R 1 R 2 , R 8 to R 13 , and n are the same as described above, and m represents 1 or 2.
  • R Rs R 11 n are as defined above, X 3 represents a chlorine atom, a bromine atom or an iodine atom.
  • Z 1 is a general formula [10],
  • R 14 and R 15 each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms.
  • R 14 and R 15 each independently represent When both are an alkyl group having 1 to 4 carbon atoms or both are an alkoxy group having 1 to 4 carbon atoms, R 14 and R 15 are bonded to each other on an arbitrary carbon atom to form a spiro-type 3 to 7 Which may form a membered ring).
  • RR 8 to RH, X 3 , and n are the same as described above, and Z 2 is a group represented by the general formula (13) or (14),
  • R 16 and R 17 represents independently a hydrogen atom, an alkyl group or R 16 and R 17 are both alkoxy groups having 1 to 4 carbon atoms having 1 to 4 carbon atoms. Further, R 16 And R 17 are each independently an alkyl group having 1 to 4 carbon atoms or both When it is an alkoxy group having 1 to 4 carbon atoms, R 16 and R 17 are bonded to each other on an arbitrary carbon atom to form a spiro-type 3 to 7-membered saturated hydrocarbon ring or oxygen. A contained saturated hydrocarbon ring may be formed.
  • R 18 represents an oxygen atom, a sulfur atom or an alkoxyimino group having 1 to 4 carbon atoms.
  • the sulfide compound of the present invention has the general formula (1):
  • RR 2 independently represents a halogen atom or an alkyl group having 1 to 4 carbon atoms
  • R 3 , RR 5 , and RR 7 each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • R 5 and R 6 and R 6 and R 7 may be arbitrarily bonded to each other on a carbon atom to form a 3- to 7-membered hydrocarbon ring. ] Is represented.
  • the halogen atom represented by R 1 R 2 may be any of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • the alkyl group having 1 to 4 carbon atoms R ⁇ R 2 and R 3 to R 7 represent, methylcarbamoyl And propyl groups such as ethyl group, ethyl group, n-propyl group and i-propyl group, and founded / le groups such as n_butynole group, i-butynole group, sec-butynole group and t-butyl group.
  • this sulfide compound is a hydrocarbon having a 3- to 7-membered ring structure in which R 5 and R 6 and R 6 and R 7 in the general formula [1] are bonded to each other on an arbitrary carbon atom. It may have a structure forming a ring.
  • Shikuroarukeyuru groups which may be made form in this R 5 and R 6, Shikurobuteyuru group, Shikurobe Nteyuru group, cyclohexenyl group cycloheteroalkyl include Shikuroheputeyuru group.
  • cycloalkenyl group formed here may be substituted by one or more alkyl groups having 1 to 3 carbon atoms, and the total carbon number of the alkyl-substituted cycloalkenyl group may be 10 or less. .
  • Examples of the cycloalkyl group formed by R 6 and R 7 include a cyclopropyl group, a cyclobutynole group, a cyclopentynole group, a cyclohexynole group, and a cycloheptyl group.
  • the cycloalkyl group formed here may be substituted by one or more alkyl groups having 1 to 3 carbon atoms, and the alkyl-substituted cycloalkyl group may have a total carbon number of 9 or less. . ( ⁇ ) 6-acetylthiochroman derivative or 5
  • the sulfide compound represented by the general formula [1] is subjected to a cyclization reaction in the presence of protic acid to give 6-acetyl, which is more useful as an intermediate for producing an active ingredient of a herbicide.
  • a thiochroman derivative or 5-acetylethyl dibenzo [b] thiophene derivative can be produced.
  • Protonic acids that can be used in this cyclization reaction include mineral acids such as sulfuric acid and diphosphoric acid, sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid, and acidic ion exchange resins. Preferred is sulfuric acid.
  • the amount of protonic acid used here is 0.1 to 3 equivalents, preferably 0.2 to 1.2 equivalents, based on the above sulfide compound. If the amount of the protonic acid used is less than 0.1 equivalent to the above sulfide compound, the reaction may take a long time, and the amount of the protonic acid used may be long. Is on If the amount exceeds 3 equivalents to the sulfide compound, the amount of by-products may increase.
  • the solvent used here is not particularly limited as long as it does not hinder the reaction, and is a halogenated aliphatic hydrocarbon solvent such as methylene chloride or 1,2-dichloroethane, benzene, toluene, and xylene.
  • a halogenated aliphatic hydrocarbon solvent such as methylene chloride or 1,2-dichloroethane, benzene, toluene, and xylene.
  • aromatic hydrocarbon solvents such as nitrobenzene and nitrobenzene, with preference given to methylene chloride or 1,2-dichloromethane.
  • the reaction temperature in the case of carrying out this cyclization reaction is from 0 ° C to the reflux temperature of the solvent, preferably from 40 ° C to 60 ° C.
  • the reaction time is usually 1 to 96 hours, preferably 36 to 48 hours.
  • R 1 and R 2 have the same meaning as R 1 R 2 in the general formula [1].
  • a diaryl disulfide compound represented by, for example, di (4-acetinol- 1,2,5_dimethinolephenyl) disnorefide, or di (4-acetinol-2-cyclo-mouth _5-methinolefenole) Dishonolefide, di (4-acetinole-5-chloro-1- -2-methylmethyl) disulfide may be formed.
  • These diaryl disulfide compounds can be returned to the starting thiophenol compound by reduction.
  • the sulfide compound represented by the general formula [1] is subjected to a cyclization reaction in the presence of a Lewis acid and a protonic acid to thereby give a 6-acetylthiotaloman derivative or a 5-acetylethylhydrobenzo [ b) Tiofen induction
  • the body can be manufactured.
  • Examples of the Lewis acid used herein include aluminum chloride, iron chloride, zinc chloride and the like, with aluminum chloride being preferred.
  • the amount of the Lewis acid to be used is 1 to 7 equivalents, preferably 3 to 4.5 equivalents, based on the above sulfide compound. If the amount of the Lewis acid used is less than 1 equivalent relative to the sulfide compound, the reaction yield may be reduced, and the amount of the Lewis acid used may be less than the sulfide compound. If the amount exceeds 7 equivalents, the amount of by-products may increase.
  • the protonic acid used in combination with the Lewis acid functions as a catalyst.
  • Protonic acids suitable for use herein include sulfuric acid, mineral acids such as hydrochloric acid, carboxylic acids such as acetic acid and formic acid, and sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid.
  • alcohols such as hydrogen chloride gas, water, and methanol also act as co-catalysts.
  • hydrochloric acid and acetic acid are particularly preferably used.
  • the amount of the protonic acid to be used is 0.1 to 3 equivalents, preferably 0.2 to 1.2 equivalents, based on the above sulfide compound.
  • the reaction is also preferably carried out using a solvent.
  • a solvent for example, halogenated hydrocarbon solvents such as methylene chloride and 1,2-dichloroethane, and aromatic hydrocarbons such as benzene, dichlorobenzene, dichlorotonolene, and nitrobenzene.
  • Hydrogen solvents are exemplified. Of these, methylene chloride and 1,
  • 2-Jigu Roetane is mentioned as a particularly preferred one.
  • reaction temperature for carrying out this cyclization reaction is from 110 ° C to the reflux temperature of the solvent, and is preferably from 0 ° C to 20 ° C.
  • reaction time is usually
  • a hydrogen halide addition compound represented by, for example, (4-acetyl-12,5-dimethylphenyl) (3-chloro-1-3-methinolevbutane) szolefide, (4-acetinol-2-2-chloro-1-5-) Methinolephenyl) (3-chloro-3-methinolebutane) sulfide, (4-acetyl-1,2,5-dimethinolephenyl) (2-chloro-1--2-methinolepropane) snorelide,
  • RR 2 has the same meaning as RR 2 in the general formula [1].
  • These thioester compounds can be converted to the above-mentioned thiophenol compound by hydrolysis, and this thiophenol compound can be used as a raw material for producing a sulfide compound represented by the general formula [1].
  • RR 2, R 8 to R 13 and n have the same meaning as RR 2, R 8 to R 13 and n in formula (2).
  • These deacetyl compounds can be converted to the desired 6-acetylthiochroman derivative and 5-acetyldihydrobenzo [b] thiophene derivative by acetylating them.
  • R 3 to R 7 are the same as above, and X 2 represents a halogen atom.
  • X 2 represents a halogen atom.
  • the amount of the halogenated aryl compound to be added is 0.1 to 2 equivalents, preferably 0.2 to 1 equivalent, relative to the starting sulfide compound.
  • the 6-acetylthiochroman derivative and the 5-acetyldihydrobenzo (b) thiophene derivative obtained from the sulfide compound represented by the general formula (1) are represented by the following general formula (2):
  • RR 2 independently represents a halogen atom or an alkyl group having 1 to 4 carbon atoms as in the general formula [1]
  • R 8 , R 9 , R 10 , R 11 , R 12 And R 13 each independently represent a hydrogen atom or an alkyl group having 1 to 4 carbon atoms.
  • ⁇ ⁇ And! ⁇ May be arbitrarily bonded to each other on a carbon atom to form a 3- to 7-membered saturated hydrocarbon ring.
  • n represents 1 or 0.
  • examples of the halogen atom represented by R 1 and R 2 include a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and a carbon atom represented by RR 2 and R 8 to R 13
  • examples of the alkyl group of Formulas 1 to 4 include a propyl group such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a sec-butynole group, and a t-butynole group. Butyl group.
  • R 11 and R 12, and R 12 and R 13 may have a structure in which they are bonded to each other on an arbitrary carbon atom to form a 3- to 7-membered saturated hydrocarbon ring.
  • Examples of the cycloalkyl group in the case where R 11 and R 12 are bonded to each other include a cyclopeptizole group, a cyclopentyl group, a cyclohexynole group, and a cycloheptyl group.
  • the cycloalkyl group formed here may be substituted by one or more alkyl groups having 1 to 3 carbon atoms and the total number of carbon atoms of the alkyl-substituted cycloalkyl group is within 10 or less. Good.
  • spiro cycloalkyl groups which may be formed by the above R 12 and R 13, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group consequent opening include heptyl group cycloheteroalkyl. And formed here
  • the cycloalkyl group may be substituted by one or more alkyl groups having 1 to 3 carbon atoms, and the total number of carbon atoms in the alkyl-substituted alkyl group is 9 or less.
  • the first method for producing a sulfide compound is represented by the following reaction formula,
  • R 1 R 2 is the same as described above, X 1 represents a halogen atom, and M represents a hydrogen atom or an alkali metal. ]. That is, an acetophenone compound represented by the general formula [3], which is a starting material, is reacted with an alkali metal sulfide to obtain a thiophenol compound represented by the general formula [4] or an alkali metal salt thereof. Next, the obtained thiophenol compound or an alkali metal salt thereof is reacted with an aryl halide compound represented by the above general formula (5) to convert a target sulfide compound represented by the above general formula (1). How to get.
  • the thiophenol compound or its alkali metal salt obtained by the reaction of the acetophenone compound with the metal sulfide may be continuously reacted with the halogenated aryl compound without isolation.
  • the reaction between the thiophenol compound and the halogenated aryl compound in the presence of a base is carried out. May be performed.
  • the base used here is not particularly limited, but includes alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, sodium carbonate, potassium carbonate and the like.
  • alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, sodium carbonate, potassium carbonate and the like.
  • inorganic bases such as alkali metal carbonate, sodium hydrogencarbonate and potassium hydrogencarbonate
  • organic bases such as pyridine and triethylamine.
  • alkali metal sulfide examples include sodium hydrosulfide, rhodium hydrosulfide, sodium sulfide, potassium sulfide and the like, and preferably sodium hydrosulfide.
  • the amount of the alkali metal sulfide to be used is 1 to 4 equivalents, preferably 2 to 2.5 equivalents, relative to the acetophenone compound.
  • the solvent used here is not particularly limited as long as it does not interfere with the reaction.
  • Lower alcohols such as methanol, ethanol and propanol, ketones such as acetone and methyl isobutyl ketone, tetrahydrofuran, dioxane and dimethyl alcohol
  • ethers such as toxetane and diethylene glycol dimethyl ether
  • non-protonic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, and N-methylpyrrolidone.
  • Preferred are N, N —Non-protonic polar solvent such as dimethylformamide.
  • the reaction temperature for carrying out this reaction is from room temperature to 130 ° C., preferably from 80 ° C. to 100 ° C.
  • the reaction time is usually from 1 to 8 hours, preferably from 2 to 3 hours.
  • the diaryl disulfide compound may also be formed, but the diaryl disulfide compound can be converted to a thiophenol compound upon reduction.
  • the amount of the halogenated aryl compound used is 1 to 4 equivalents, preferably 1.2 equivalents to the acetate phenone compound. ⁇ 2 equivalents.
  • the solvent used in this reaction may be the solvent used in the previous reaction.
  • a non-protonic polar solvent such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, or acetonate may be used.
  • ketones such as methyl isobutyl ketone
  • halogenated hydrocarbon solvents such as methylene chloride and 1,2-dichloroethane
  • N, N-dimethylformamide docetone is preferably used.
  • the reaction temperature in the reaction between the thiophenol compound and the aryl halide compound is 0 ° C to 80 ° C, preferably 0 ° C to 50 ° C.
  • the reaction time is generally 0.5 to 4 hours, preferably 1 to 2 hours.
  • R 3 to R 7 have the same meaning as R 3 to R 7 in the general formula [1]. ]
  • di (3-methyl-2-butene) snolefidodidi (2-methinoly 2-propene) sulfide may be formed.
  • R 3 to R 7 have the same meaning as R 3 to R 7 in the general formula [1].
  • di (3-methyl-2-butene) disulfide (2-methyl_2-propene) disulfide for example, di (3-methyl-2-butene) disulfide (2-methyl_2-propene) disulfide.
  • R 1 in the general formula [3] is a halogen atom
  • the S-arylisothiuronium salt represented by the general formula [6] is preferably produced by a method of producing by reacting a halogenated aryl compound represented by the general formula [5] with thiourea. is there.
  • the aryl halide compound represented by the general formula [5] is reacted with thiourea to form an S-arylisothiuronium salt.
  • a method of reacting an acetophenone compound with an alkali metal hydroxide may be employed.
  • a reaction between the halogenated aryl compound and thiourea may be employed.
  • a method of continuously reacting the product with an acetophenone compound and an alkali metal hydroxide without isolating the resulting S-arylisothiuronium salt may be employed.
  • a method may be employed in which a halogenated aryl compound is reacted with thiourea in the coexistence of an acetophenone compound, and then an alkali metal hydroxide is added thereto to cause a reaction.
  • the thiourea is used in this reaction in an amount of 0.5 to 1.5 equivalents, preferably 0.8 to 1.2 equivalents, based on the aryl halide compound.
  • the solvent used here is not particularly limited as long as it does not interfere with the reaction, and may be a two-layer system of water and an aromatic hydrocarbon solvent such as toluene or xylene and water. Examples of the solvent include ethanol, and preferred are ethanol and a two-layer solvent of an aromatic hydrocarbon solvent and water.
  • the reaction temperature for the reaction between the halogenated aryl compound and thiourea is from room temperature to the reflux temperature of the solvent, and is preferably from 50 ° C to 110 ° C.
  • the reaction time is generally 1 to 16 hours, preferably 1 to 3 hours.
  • the proportion of the S-arylisothiium mouth-metal salt used here is 1 to 4 relative to the acetofphenone compound.
  • Equivalent preferably Is 1.1 to 1.5 equivalents.
  • the use ratio of the alkali metal hydroxide used here is 2 to 8 equivalents, preferably 2.2 to 3 equivalents to the acetophenone compound.
  • the alkali metal hydroxide used in this reaction includes sodium hydroxide, potassium hydroxide and the like, and is usually used as an aqueous solution.
  • the solvent used in this reaction is not particularly limited, but non-protonones such as methanol, ethanol, and other phenols, N, N-dimethylformamide, N, N-dimethylinorea cetamide, and N-methylpyrrolidone.
  • phase transfer catalyst In a two-layer system composed of an aromatic hydrocarbon solvent and water, it is preferable to add a phase transfer catalyst to the two-layer system.
  • phase transfer catalyst suitable for use herein include tetra-n-butylammonium chloride, Examples include quaternary ammonium salts such as tetra-n-butylammonium bromide and quaternary phosphonium salts such as tetra-n-butylphosphonium chloride and tetra-n-butylphosphonium bromide.
  • the reaction temperature of the reaction of the acetophenone compound with the S-arylisothiuronium salt and the alkali metal hydroxide is from room temperature to the reflux temperature of the solvent, preferably from 50 ° C to 110 ° C. is there.
  • the reaction time is usually 1 to 12 hours, preferably 1 to 8 hours.
  • RR 2 and R 4 to R 7 have the same meaning as R 1 R 2 and R 4 to R 7 in the general formula [1].
  • Isomers of the double bond represented by, for example, (4-acetylino-1,2,5-dimethylphenyl) (3_methyl-11-butene) snoresulfide, and (4-acetylamino-1 2 _) Chloro-5-methylpheninole)
  • 6-carboxylic acid derivatives represented by the following formulas (thiochroman-16-carboxylic acid 1,1,1-dioxide having various substituents) and dihydrobenzene
  • Examples of the oxidizing agent used in the first production method include halogen, hypohalite and the like, and preferably, chlorine, bromine and sodium hypochlorite.
  • the oxidizing agent is used in an amount of 5 to 8 equivalents, preferably 5.5 to 6.5, based on the 6-acetylthiochroman derivative or the 5-acetylacetylhydrobenzo [b] thiophene derivative as a raw material. Is equivalent.
  • a halogen is used as the oxidizing agent, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide or an alkali metal carbonate such as sodium carbonate and potassium carbonate is added to the reaction system in advance. After the generation of the halogenous acid salt, the raw material compound may be added thereto and reacted, or a halogen may be introduced and reacted in the presence of the raw material compound and the alkali.
  • the phase transfer catalyst used in this oxidation reaction includes tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, benzyltriethylammonium chloride, and benzyltriethylammonium bromide.
  • Quaternary ammonium salts such as haem, phenyltrimethylammonium chloride, phenyltrimethylammonium bromide, octyltrimethylammonium chloride, tetra-n-butylphosphonium chloride, tetra-n-bromide
  • quaternary phosphonium salts such as butylphosphonium.
  • tetra n-butyl ammonium bromide is particularly preferably used.
  • the use ratio of this phase transfer catalyst is from 0.02 to 0.5 equivalent, preferably from 0.05 to 0.1 equivalent, based on the starting compound.
  • water-insoluble organic solvent used in the first production method examples include aliphatic hydrocarbon solvents such as methylene chloride, 1,2-dichloroethane and cyclohexane, tonolene, xylene, benzene, and chlorotonolene.
  • Aromatic hydrocarbon solvents such as methylene chloride, 1,2-dichloroethane and cyclohexane, tonolene, xylene, benzene, and chlorotonolene.
  • Aromatic hydrocarbon solvents 1,2-dichloroethane and toluene are particularly preferably used.
  • the reaction temperature for performing this oxidation reaction is 0 ° C to 60 ° C, preferably 20 ° C to 40 ° C.
  • the reaction time is generally 1 to 36 hours, preferably 8 to 16 hours.
  • R 1 R 2 , R 8 to R 13 and n have the same meaning as RR 2 , R 8 to R 13 and n in the general formula [2], and p represents 0 or 1.
  • the carboxylic acid compound represented by these is produced.
  • Examples of the carboxylic acid compound represented by the above general formula include 4,4,5,8-tetramethylthiochroman- 16-carboxylic acid and 2,3-dihydro-3,3,4,7-tetramethylbenzo [ b] Thiophene-5-carboxylic acid, 4,4,5,8-tetramethylthiochroman-6-carboxylic acid-11-oxide, 2,3-dihydro-1,3,3,4,7-tetramethylbenzo [b ] Thiophene-5-1-rubonic acid-1-oxide.
  • R 1 R 2 , R 8 -R 13 and n have the same meanings as R 1 R 2 , R 8 -R 13 and n in the general formula (2), and X 4 is a chlorine atom Or a bromine atom, k represents 0, 1 or 2, and q represents 1, 2 or 3. ] Is produced.
  • halide represented by the above general formula examples include, for example, 6-chloroacetyl 1,4-, 5,8-tetramethylthiochromane, 6,4-dichloroacetinole 4,4,5,8-tetramethylthiochromane, 4,4,5,8-tetramethine 6-trichloroacetinole Thiochroman, 6-Chloroacetylenole-4,4,5,8-Tetramethylthiochroman-11-oxide, 6-Dichloroacetyl-4,4,5,8-Tetramethylthiochroman_1-oxide, 4,4,5,8 —Tetramethyl-1-6-trichloroacetylthiochroman-1-oxide, 6-chloroacetinol 4,4,5,8-tetramethinorethiochroman-1,1,1-dioxide, 6-dichloroacetyl_4,4,5,5 Examples include 8-tetramethylthiochroman-1,1-dioxide and 4,4,5
  • the carboxylic acid compound and halide as the by-products are further oxidized to convert them into the desired thiochroman 16-carboxylic acid derivative and dihydrobenzo [b] thiophene 15-carboxylic acid derivative. It is possible. Further, when 1,2-dichloroethane is used as a reaction solvent, the following formula:
  • R 1 R 2 , R 8 to R 13 and n have the same meaning as R 1 R 2 , R 8 to R 13 and n in the general formula (2), and k is 0, 1 Or 2 is indicated. ] The ester compound represented by these is produced.
  • ester compound represented by the above general formula examples include, for example, 4,4,5,8-tetramethinolethiochroman-1-6-force olevonic acid 2-cocculo lochinoreestenole, 2,3-dihydro-3 , 3,4,7-Tetramethylbenzo [b] thiophene-5-potty olevonic acid 2-chloroethynoleestenole, 4,4,5,8-Tetramethinolethiothaloman-1-6-potty olevonic acid 1 1 —Oxide 2-chloroethynolester, 2,3-dihydro-1,3,4,7-tetramethylbenzo [b] thiophen-1 5-potassolenovonic acid 1-oxide 2-chloroethynoleestenole , 4,4,5,8-Tetramethylthiochroman-1-6-Rubonic acid-1,1,1-dioxo Examples include sid2_cloethyl ester, 2,
  • ester compounds can be converted to the desired thiochroman 16-carboxylic acid derivative and dihydrobenzo [b] thiophene 15-carboxylic acid derivative by hydrolysis and, if necessary, further oxidation. is there.
  • the 6-acetylthiochroman derivative or 5-acetyldihydrobenzo [b] thiophene derivative represented by the general formula [2] as a raw material is converted into the first oxidation in the first step.
  • RR 2 , R 8 to R 13 , and n are the same as those in the general formula [2], and m represents 1 or 2.
  • these compounds are oxidized using a second oxidizing agent in a two-layer system of water and an organic solvent to obtain the desired chiochroman 1-
  • This is a method for producing a dicarboxylic acid derivative and dihydrobenzo [b] thiophene-15-carboxylic acid derivative.
  • the first oxidizing agent examples include hydrogen peroxide, peracetic acid, sodium periodate and the like. Of these, hydrogen peroxide is particularly preferred.
  • the usage ratio of the first oxidizing agent is 1 to 3 equivalents to the starting compound.
  • the amount when a sulfoxide compound is obtained, the amount is preferably 1 to 1.1 equivalents.
  • the amount is preferably 2 to 2.2 equivalents.
  • hydrogen peroxide is used, acetic acid is preferably added, and the acetic acid is preferably used in an amount of 0.2 to 2 equivalents relative to hydrogen peroxide.
  • Examples of the solvent used in the previous reaction include aliphatic hydrocarbon solvents such as methylene chloride, 1,2-dichloroethane, and cyclohexane, and aromatic solvents such as toluene, xylene, chlorobenzene, and chlorotoluene. Examples include hydrocarbon solvents. Among these solvents, 1,2-dichloroethane and toluene are preferred.
  • the reaction temperature in the preceding reaction can be in the range of 0 ° C. to the reflux temperature of the solvent.
  • the range is more preferably 0 ° C to 20 ° C, and when the sulfone compound is obtained, the range is more preferably 70 ° C to 90 ° C. preferable.
  • the reaction time is usually 1 to 5 hours, preferably 2 to 3 hours.
  • the sulfoxide compound or the sulfone compound represented by the general formula (8) is oxidized using a second oxidizing agent in a two-layer system of water and an organic solvent, and Thiochroman-6-carboxylic acid derivatives or dihydrobenzo [b] Thiophene-15-carboxylic acid derivatives are produced.
  • the second oxidizing agent examples include halogen, hypohalite, etc., preferably chlorine, bromine and sodium hypochlorite.
  • the use ratio of this oxidizing agent is 3 to 8 equivalents to the above-mentioned sulfoxide compound or sulfone compound as a raw material, preferably 4 to 5 equivalents when the raw material is a sulfoxide compound, and Is preferably 3 to 4 equivalents.
  • an alkali hydroxide such as sodium hydroxide or sodium hydroxide
  • an alkali carbonate such as sodium carbonate or potassium carbonate is added to the reaction system in advance.
  • the raw material sulfoxide compound or sulfone compound may be added thereto and reacted, or halogen may be introduced in the presence of the raw material sulfoxide compound or sulfone compound and an alkali. Reaction.
  • phase transfer catalyst examples include tetra-n-butylammonium chloride, tetra-n-butylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide, Quaternary ammonium salts such as phenyltrimethylammonium chloride, phenyltrimethylammonium bromide and octyltrimethylammonium chloride; quaternary phosphonium such as tetra-n-butylphosphonium chloride and tetra-n-butylphosphonium bromide Salts.
  • phase transfer catalyst is from 0.02 to 0.5 equivalent, preferably from 0.05 to 0.1 equivalent, based on the starting sulfoxide compound or sulfone compound.
  • water-insoluble organic solvent used in this reaction examples include aliphatic hydrocarbon solvents such as methylene chloride, 1,2-dichloroethane, and cyclohexane; toluene, xylene, benzene, and benzene. Aromatic hydrocarbon solvents. Among these solvents, 1,2-dichloroethane-toluene is particularly preferably used. Further, in this production method, the solvent used in the previous step is used without isolation, without isolating the sulfoxide compound or sulfone compound represented by the general formula [8] produced in the previous step. be able to.
  • aliphatic hydrocarbon solvents such as methylene chloride, 1,2-dichloroethane, and cyclohexane
  • toluene xylene
  • benzene benzene
  • Aromatic hydrocarbon solvents 1,2-dichloroethane-toluene is particularly preferably used.
  • the reaction temperature for performing this oxidation reaction is 0 ° C to 60 ° C, preferably 20 ° C to 40 ° C.
  • the reaction time is generally 0.5 to 36 hours, preferably 1 to 16 hours.
  • R 1 RR 11 n is the same as above, X 3 represents a chlorine atom, a bromine atom or an iodine atom, and Z 1 represents a general formula (10),
  • R 14 and R 15 each independently represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms.
  • R 14 and R 15 each independently represent When both are an alkyl group having 1 to 4 carbon atoms or both are an alkoxy group having 1 to 4 carbon atoms, R 14 and R 15 are bonded to each other on an arbitrary carbon atom to form a spiro-type 3 to 7 Which may form a membered ring).
  • the alkoxy group having 1 to 4 carbon atoms represented by R 14 and R 15 in the general formula [10] includes a propoxy group such as a methoxy group, an ethoxy group, an n_propoxy group, an i_propoxy group, and an n-butoxy group. Butoxy groups such as i-butoxy group, sec-butoxy group and t-butoxy group.
  • R 14 and R 15 are each independently an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, they are bonded to each other on any carbon atom to form a spiro-type 3 Or a 7-membered ring may be formed.
  • the cycloalkyl group may be a cyclopropyl group, a cyclopentinole group, a cyclopentyl group, or a cyclohexyl group.
  • the cycloalkyl group formed here may be substituted with an alkyl group having 1 to 3 carbon atoms, and the alkyl group of the alkyl-substituted alkyl group may have up to 9 carbon atoms.
  • examples of the cyclic acetal group include an ethylenedioxy group, a propylenedioxy group, and a petylenedioxy group.
  • the cyclic acetal group formed here may be substituted by an alkyl group having 1 to 3 carbon atoms, and the total number of carbon atoms of the alkyl-substituted cyclic acetal group may be 9 or less.
  • the halide represented by the above general formula [9], that is, the 8_halogenochromone 6-hydrorubonic acid derivative or the 7-halogenodihydrobenzen [b] thiophen-15-hydrorubonic acid derivative is represented by the above (IV) Or the above-mentioned international application WO 93/18031, international application WO 94/01431, international application WO 96/2541 It can be manufactured by the manufacturing method described in Japanese Patent Publication No.
  • the thiochroman-6-carboxylic acid derivative represented by the above general formula [11] is reduced by reducing the halide represented by the above general formula [9] with zinc in an aqueous alkali solution ( Various substituents S-thiochroman-6-caprolubonic acid-1,1,1-dioxide) and dihydrobenzo [b] thiophen-5-caprolubonic acid derivatives (may have various substituents) To produce dihydrobenzo [b] thiophene-5-potassolenoic acid (1,1,1-dioxide).
  • alkali compound used for preparing the above-mentioned aqueous alkali solution include hydroxides such as sodium hydroxide and potassium hydroxide, and carbonates such as sodium carbonate and carbonic acid lime. Among these compounds, sodium hydroxide or potassium hydroxide is particularly preferred.
  • the use ratio of the alkali compound is 2 to 5 equivalents, preferably 3 to 4 equivalents, to the halide represented by the general formula [9] of the raw material. It is preferable to use an aqueous solution having a concentration of 5 to 30% by weight.
  • the ratio of zinc used here is 1 2 to 2 equivalents, preferably 1.5 to 2 equivalents. If the proportion of zinc used is less than 1 equivalent to the halide of the raw material, the raw material may remain in the product, and the proportion of zinc used may be 2.equivalent to the halide of the raw material. It is desirable to keep the amount within the above-mentioned range, since the effect equivalent to that is not obtained even if it is used beyond the limit.
  • an alcohol-based solvent such as methanol or ethanol may be added at a ratio of 10 equivalents or less, preferably 4 to 8 equivalents to the halide.
  • the reaction temperature in this reduction reaction is from 20 ° C. to the reflux temperature of the solvent, preferably from 50 ° C. (° 80 ° C.).
  • the reaction time is usually from 1 to 16 hours, but is preferably from 1 to 16 hours. Is 5 to 10 hours.
  • RR 8 to Rn, Z 1 and n have the same meaning as R 1 R 8 to RH, Z 1 and n in the general formula [9].
  • Such compounds include, for example, 8,8'-bi (4,4,5-trimethylthiochroman-16_carboxylic acid-1-1,1dioxide), 7,7'-bi
  • R 1 R 8 ⁇ RH, X 3 n are the same as in the general formula (9), Z 2 2 is Eta ⁇ -.
  • R 16 and R 17 each independently represent a hydrogen atom, alkyl group or alkoxy group
  • R 16 and R 17 are both 1 to 4 carbon atoms of 1 to 4 carbon atoms.
  • R 16 And R 17 are each independently an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, R 16 and R 17 are bonded to each other on an arbitrary carbon atom.
  • Examples of the alkoxy group having 1 to 4 carbon atoms represented by R 16 and R 17 in the general formula [13] include a methoxy group, an ethoxy group, a propoxy group such as an n-propoxy group, an i_propoxy group, and an n-butoxy group. , I-butoxy group, sec-butoxy And butoxy groups such as t-butoxy group.
  • Examples of the alkoxyimino group having 1 to 4 carbon atoms represented by R 18 in the general formula [14] include a propoxyimino group such as a methoxyimino group, an ethoxyimino group, an n-propoxyimino group, and an i-propoxyimino group. And butoxyimino groups such as n-butoxyimino group, i-butoxyimino group, sec_butoxyimino group and t-butoxyimino group.
  • R 16 and R 17 in the general formula (13) are each independently an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms, It may combine with each other on the atom to form a spiro-type 3- to 7-membered ring.
  • examples of the cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cycloheptyl group.
  • Can be The cycloalkyl group formed here may be substituted with an alkyl group having 1 to 3 carbon atoms, and the alkyl-substituted alkyl group may have up to 9 carbon atoms.
  • examples of the cyclic acetal group include an ethylenedioxy group, a propylenedioxy group, and a butylenedioxy group.
  • the cyclic acetal group formed here may be substituted by an alkyl group having 1 to 3 carbon atoms, and the total number of carbon atoms of the alkyl-substituted cyclic acetal group may be 9 or less.
  • the halide represented by the general formula [12] of the raw material that is, the 8-halogenothiochroman-16-carboxylic acid derivative or the 7-halogenodihydrobenzo [b] thiophene-5-potassium sulfonic acid derivative can be obtained by the above (IV) ) Or the above-mentioned international application WO 93/18031, international application WO 94/01431, international application WO 96/254 1 It can be manufactured by the manufacturing method described in Japanese Patent Publication No.
  • the alkaline aqueous solution used here may be the same as the alkaline aqueous solution in the method for producing the compound of the general formula (11).
  • the metal catalyst used here includes base metals such as Raney nickel and nickel diatomaceous earth.
  • a catalyst or a noble metal catalyst such as palladium or platinum oxide is used.
  • noble metal catalysts are preferable, and among them, palladium catalyst is particularly preferable.
  • a carrier such as activated carbon, alumina, silica gel, and barium sulfate.
  • activated carbon is particularly preferably used.
  • the metal catalyst is used in an amount of 0.1 to 3% by weight, preferably 0.35 to 1% by weight, based on the halide represented by the general formula [12] as a raw material. .
  • the hydrogen used for the reduction reaction may be supplied to the reaction system at normal pressure or under pressure. Preferred is a pressurizing condition in which the hydrogen pressure is 4 MPa or less.
  • the reaction temperature at the time of performing this reduction reaction is 20 ° C. to the reflux temperature of water, preferably 70 ° C. to 80 ° C. in the case of the reaction under normal pressure, and 20 ° C. in the case of pressurization.
  • ° C to 150 ° C preferably 50 ° C to 120 ° C.
  • the reaction time is generally 1 to 16 hours, preferably 5 to 10 hours.
  • an alcohol solvent such as methanol or ethanol may be added to the reaction system.
  • RR 8 ⁇ Rn, Z 2 and n have the RR 8 to R, the same meaning as Z 2, and n in the general formula [1 2].
  • the dimer of the raw material represented by the formula may be formed.
  • Such compounds include, for example, 8,8'-bi (4-methoximino-15-methylthiochroman-16_potassolenoic acid-1,1,1-dioxide), 7,7,1-bi (2,3- Dihydro-3-methoxyimino-4-methylbenzo [b] thiophen-5-carboxylic acid 1,1,1-dioxide), 8,8, -bi (6-carboxy-1,3,3,5-trimethylthiochroman-1 4 _One-1,1,1-dioxide), 7,7'-bi (5_carboxy_2,3-dihydro-1,2,2,4-trimethylbenzo [b] thiophen-1,3-one-1,1-dioxy C).
  • the reaction mixture containing the thiophenol compound obtained in the above (1) was cooled to 10 to 15 ° C, and 1-chloro-13-methyl-2-butene 44.3 mm was added as an aryl halide compound. Little (393 mmol, 1.5 equivalents) was added dropwise over 43 minutes while maintaining 10-15 ° C. After the dropwise addition, the temperature of the reaction solution was returned to room temperature, and the reaction was performed with stirring for 2 hours.
  • Table 1 shows the structural formula and 1 H_NMR data of the obtained compound.
  • a thiophenol compound was produced in the same manner as in (1).
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • the compound was identified as di (4-acetinol-1-2-chloro-5-methinolephenyl) snorefide.
  • reaction product was cooled to room temperature, 60 ml of n-hexane was added to precipitate a solid, and the solid was separated by filtration and dried to obtain 3-methyl ⁇ 2-butyrisothiuronic chloride. 15.5 g (86% yield) were obtained.
  • acetophenone compound 8.3 g (41 mmol) of 2,4-dichloro-1-methylacetophenone was used, and this was used together with the 3-methylphenol-2-butylisothiuronium chloride obtained in the above (1). 8.2 g (45 mmol, 1.1 eq.) And 1.4 g (4.3 mmol, 0.1 eq.) Of tetra-n-butylammonium bromide as a phase transfer catalyst were added to 25 ml of toluene.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Example 3 was repeated except that 1-chloro-2-3-methyl-2-propene was used in place of 1-chloro-3-3-methyl-2-butene used in (1) of Example 3.
  • Example 3 (2) except that 3-methyl-12-butyrisothiuronium chloride used in Example 3 (2) was replaced with 2-methyl-12-propenylisothiuronium chloride.
  • the desired (4-acetyl-5-chloro-2-methinolepheninole) (2-methinole-1-propene) snorerefide was obtained in a yield of 70%.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Example 6 instead of the (4-acetyl-1,2,5-dimethylphenyl) (3-methyl-12-butene) sulfide used as a raw material, (4-acetyl-2-cyclobutane-5-methyl) was used. Noreffenore) (3_methyl_2-butene) The procedure was as in Example 6, except that snorefide was used.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • the obtained reaction solution was added to ice, and extracted twice with 1,2-dichloroethane.
  • the obtained extract was washed twice with an aqueous sodium hydroxide solution and then dried over anhydrous sodium sulfate.
  • the solvent is distilled off under reduced pressure, and the obtained crude product is purified by silica gel column chromatography, thereby obtaining the desired 6-acetyl-5-chloro mouth_4,4,8-trimethinolethiol 0.660 g (30% yield) of chroman was obtained.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • the sodium hydroxide washing solution was acidified with concentrated hydrochloric acid, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.52 g of a by-product (yield). 3 5%).
  • the obtained by-product was analyzed by 1 H-NMR (double-mouthed form solvent; TMS standard). As a result, 2.30 (s, 3H) ppm, 2.63 (s, 3H) ppm, 3.50 (s, 1H) ppm N Absorption peak was observed at 7.30 (s, 1H) ppm and 7.52 (s, 1H) ppm.
  • Example 8 In place of the (4-acetyl-1-5-chloro-12-methylphenyl) (3-methyl-12-butene) sulfide used as a raw material in Example 8, (4-acetyltin-2,5-dimethinolephenyl) ( Example 8 was repeated except that 2- (methyl-2-propene) sulfide was used and 1-chloro-12-methyl-12-propene was used as the aryl halide compound added to suppress the generation of by-products. As well as Thus, the desired 5_acetyl-2,3-dihydro3,3,4,7-tetramethylbenzo [b] thiophene was obtained in a yield of 83%.
  • Table 1 shows the structural formula and 1 H-NMR data of the obtained compound.
  • reaction mixture was added to ice, extracted twice with 1,2-dichloroethane, and dried over anhydrous sodium sulfate. Furthermore, the solvent was distilled off under reduced pressure, and the crude product was purified by silica gel column chromatography to obtain the desired 5-acetyl-7-chloro-2,3-dihydro-1,3,3,4-trimethylbenzo [ b] 1.36 g (yield 68%) of thiophene was obtained.
  • Table 1 shows the structural formula and 1 H_NMR data of the obtained compound.
  • 2,4-Dichloro-5-methylacetophenone used in this example was produced by the following method.
  • sodium hypochlorite 3 2.79 g (58 millimoles, 6.0 equivalents) was used as an oxidizing agent, cooled in an ice-water bath, and further added with 20% by weight water. An aqueous solution of sodium oxide, 3.2 milliliters (19 mmol, 2.0 equivalents), was added dropwise while maintaining the temperature at 10 ° C or lower.
  • Table 2 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Table 2 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Example 1 5 7-Chloro-1,2,3-dihydro 3,3,4_trimethinolebenzo [b] Thiophene-1 5-Carboxylic acid- 1,1-dioxide
  • the starting material 5-acetyl-1 7-chloro-1,2,3-dihydro-3,3,4-trimethylbenzo [b] thiophene 1.8 g (7.1 millimol) was dissolved in 9 milliliters of 1,2-dichloroethane.
  • Table 2 shows the structural formula and 1 H—NMR data of the obtained compound.
  • Table 2 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Table 3 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Example 17 the 8-chloro-1,4-dioxoxide used in place of the 8,4-chloro-1,4,5-trimethylthiochroman-6-potassium 1,1-dioxide used as the raw material was replaced with 8-chloro-14-methoxy-5- The procedure was similar to that of Example 17 except that methinorethiochroman-1-butanoic acid 1,1,1-dioxide was used and ethanol (6.8 equivalents to the starting material) was added as a solvent. Methoxy-5-methylthiochroman-1-6-rhubonic acid 1,1,1-dioxide was obtained in a yield of 98%.
  • Table 3 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Example 17 the 5,8-dichroic port_4,4-dimethylthiochromane was used in place of the 8,4-chloro-1,4,5-trimethylthiochroman-6-carboxylic acid_1,1-dioxide used as a raw material.
  • 5-Chloro-4,4-dimethinolethiochroman _ 6 was prepared in the same manner as in Example 17 except that 1,1-dioxide of 1,6-dicarboxylic acid was used and the reaction temperature was set to 50 ° C. —Power 1,1-dioxide of norlevonic acid was obtained in a yield of 72%.
  • Table 3 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Table 3 shows the structural formula and 1 H-NMR data of the obtained compound.
  • Example 21 instead of the 7-chloro-1,2,3-dihydro-13,4-dimethylbenzo [b] thiophene-15-carboxylic acid-11,1-dioxide used as a starting material, 8 4-Chloro-4-methoxyethoxymino-5-methylthiochroman-6-carboxylic acid 1,1,1-dioxide was used, and the reaction temperature was 60 ° C. 'Methoxyimino-5-methylthiochroman-16-carboxylic acid-11,1-dioxide was obtained in a yield of 66%. Table 3 shows the structural formula and 1 H—NMR data of the obtained compound.
  • the sulfide compound of the present invention is useful as a 6-acetylthiochroman derivative or 5-acetyldihydrobenzo (b) thiophene derivative, which is useful as an intermediate for producing a pyrazole derivative and a cyclohexanedione derivative as active ingredients of a herbicide.
  • a 6-acetylthiochroman derivative or 5-acetyldihydrobenzo (b) thiophene derivative which is useful as an intermediate for producing a pyrazole derivative and a cyclohexanedione derivative as active ingredients of a herbicide.
  • the thiochroman 6-potassium sulfonic acid derivative or dihydrobenzene (b) thiophene-5-carboxylic acid derivative can be efficiently produced at a low environmental load and at low cost. Can be manufactured.

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Abstract

L'invention concerne un composé sulfuré représenté par la formule générale (1) dans laquelle R1 et R2 représentent chacun un halogène ou un C¿1-4?-alkyle, et R?3 à R7¿ représentent chacun de l'hydrogène ou un C¿1-4?-alkyle, R?5 et R6¿ étant liés et R6 et R7 étant liés l'un à l'autre pour former un cycle hydrocarbure ayant de 3 à 7 éléments. Ledit composé sert à fabriquer un dérivé de 6-acétylthiochromane ou un dérivé de 5-acétyldihydrobenzo-(b)-thiophène, et à fabriquer un dérivé d'acide thiochromane-6-carboxylique ou un dérivé d'acide dihydrobenzo-(b)-thiophène-5-carboxylique. L'invention concerne également des procédés industriels avantageux destinés à la fabrication des deux dérivés d'acide carboxylique, ces procédés représentant une charge réduite pour l'environnement.
PCT/JP2000/008504 1999-12-03 2000-12-01 Compose sulfure et procedes de fabrication de derives de thiochromane et de derives de dihydrobenzo-(b)-thiophene WO2001040176A1 (fr)

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JP11/344426 1999-12-03
JP34442699A JP2001163853A (ja) 1999-12-03 1999-12-03 スルフィド化合物及び６−アセチルチオクロマン誘導体又は５−アセチルジヒドロベンゾ〔ｂ〕チオフェン誘導体の製造法
JP34442899A JP2001163880A (ja) 1999-12-03 1999-12-03 チオクロマン−６−カルボン酸誘導体またはジヒドロベンゾ〔ｂ〕チオフェン−５−カルボン酸誘導体の製造法
JP11/344427 1999-12-03
JP11/344428 1999-12-03
JP34442799A JP2001163881A (ja) 1999-12-03 1999-12-03 チオクロマン−６−カルボン酸誘導体またはジヒドロベンゾ〔ｂ〕チオフェン−５−カルボン酸誘導体の製造法

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Cited By (3)

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Publication number Priority date Publication date Assignee Title
WO2013072402A1 (fr) 2011-11-16 2013-05-23 Basf Se Composés 1,2,5-oxadiazole substitués et leur utilisation comme herbicides agissant au niveau du photosystème ii
WO2013076315A2 (fr) 2012-04-27 2013-05-30 Basf Se Composés substitués de n-(tétrazol-5-yl)- et n-(triazol-5-yl) arylcarboxamides et leur utilisation comme herbicides
WO2014184019A1 (fr) 2013-05-15 2014-11-20 Basf Se Composés de n-(1,2,5-oxadiazol-3-yl)carboxamide et leur utilisation en tant qu'herbicides

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EP0270227A1 (fr) * 1986-11-10 1988-06-08 W.R. Grace & Co. Emballage pour aliments non souillant et procédé pour sa fabrication
EP0712853A1 (fr) * 1993-08-02 1996-05-22 Idemitsu Kosan Company Limited Derive de pyrazole
EP0810226A1 (fr) * 1995-02-13 1997-12-03 Idemitsu Kosan Company Limited Derives de pyrazole
EP0818455A1 (fr) * 1995-03-28 1998-01-14 Idemitsu Kosan Company Limited Derives de pyrazole

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0270227A1 (fr) * 1986-11-10 1988-06-08 W.R. Grace & Co. Emballage pour aliments non souillant et procédé pour sa fabrication
EP0712853A1 (fr) * 1993-08-02 1996-05-22 Idemitsu Kosan Company Limited Derive de pyrazole
EP0810226A1 (fr) * 1995-02-13 1997-12-03 Idemitsu Kosan Company Limited Derives de pyrazole
EP0818455A1 (fr) * 1995-03-28 1998-01-14 Idemitsu Kosan Company Limited Derives de pyrazole

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013072402A1 (fr) 2011-11-16 2013-05-23 Basf Se Composés 1,2,5-oxadiazole substitués et leur utilisation comme herbicides agissant au niveau du photosystème ii
WO2013076315A2 (fr) 2012-04-27 2013-05-30 Basf Se Composés substitués de n-(tétrazol-5-yl)- et n-(triazol-5-yl) arylcarboxamides et leur utilisation comme herbicides
WO2014184019A1 (fr) 2013-05-15 2014-11-20 Basf Se Composés de n-(1,2,5-oxadiazol-3-yl)carboxamide et leur utilisation en tant qu'herbicides

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