WO2002012203A1 - Processus de préparation d'aryltriazolinones - Google Patents

Processus de préparation d'aryltriazolinones Download PDF

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WO2002012203A1
WO2002012203A1 PCT/JP2001/006543 JP0106543W WO0212203A1 WO 2002012203 A1 WO2002012203 A1 WO 2002012203A1 JP 0106543 W JP0106543 W JP 0106543W WO 0212203 A1 WO0212203 A1 WO 0212203A1
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acid
formula
iii
catalyst
aryl
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Japanese (ja)
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Tsunehiro Kido
Toshiharu Ohno
Hiroyuki Okita
Ken Morita
Masayuki Kusunoki
Satoshi Hobara
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Hokko Chemical Industry Co Ltd
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Hokko Chemical Industry Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms

Definitions

  • the present invention relates to a process for producing aryl-1,2,4-triazolin-15-ones, and more particularly, to aryl-1,2,4, a compound useful as a raw material or intermediate for the synthesis of pharmaceuticals and agricultural chemicals.
  • Aryl-1,2,4-triazolin-15-ones are compounds useful as synthetic raw materials or intermediates for pharmaceuticals and agricultural chemicals, and various production methods have been proposed.
  • n is 0 or an integer of 1 to 5
  • X may be the same or different and represents a halogen atom, a lower alkyl group, a lower haloalkyl group, or the like.
  • n is an integer of 1 to 3
  • R represents a halogen atom, an alkyl group, a haloalkyl group, and the like
  • X is each independently hydrogen, a halogen atom (Cl, Br, I), a lower alkyl group, etc.) is treated with a hypohalous acid or a hypohalite.
  • n is an integer of 1 to 3,; represents a halogen atom, an alkyl group, a haloalkyl group, and the like, and X independently represents hydrogen, a halogen atom, a lower alkyl group, and the like.
  • PCT International Publication WO93 / 233382 corresponds to Japanese Patent Publication No. 7-5033253,
  • R is a lower alkyl group
  • X is independently a halogen, lower alkyl, nitro, hydroxy, NHS_ ⁇ 2 R ', one N (S 0 2') 2 , one N (R ) S ⁇ 2 R ′ (where R ′ is lower alkyl) and n is an integer of 0 to 3.)
  • the tertiary butanol solvent is used.
  • halogens, hypohalous acids, or salts thereof used in the dehydrogenation reaction in the process for producing aryltriazolinones are corrosive or irritating and require care when handling large quantities. Therefore, there has been a demand for a method for producing aryltriazolinones without using these.
  • aryl hydrazones, cyanic acid, and cyanates are unstable in the dehydrogenation reaction step with halogens, hypohalous acid or a salt thereof, so that the formation reaction of aryl triazolidinones is performed. It is difficult to carry out the step and its dehydrogenation reaction step in parallel.
  • the present invention is intended to solve the problems associated with the prior art as described above, and the first invention is to use simpler and less costly reels by using less expensive raw materials. It is an object of the present invention to provide a novel method for producing aryl triazolinones that can produce triazolinones.
  • the second invention is intended to be able to produce aryltriazolinones safely and under mild conditions without using halogens, hypohalous acid and salts thereof, more easily and at low cost.
  • X represents a halogen atom or a lower alkyl group having 1 to 6 carbon atoms
  • n represents an integer of 0 to 5.
  • a plurality of Xs represent May be the same or different from each other.
  • the method is characterized by having a step of dehydrogenating aryltriazolidinone represented by the formula (1) with an oxidizing agent.
  • X represents a halogen atom, a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5.
  • a plurality of Xs represent May be the same or different from each other) to react with an alkali metal cyanate and an acid, preferably an organic acid, to form aryl triazolidinone represented by the above general formula (II).
  • an oxidizing agent to the reaction solution in the absence of a catalyst or in the presence of an oxidation catalyst. It is preferred to carry out a dehydration treatment step of triazolidinone (II) with an oxidizing agent.
  • the oxidizing agent may be a halogen, a hypohalous acid, a hypohalite, a permanganate, a hydrogen peroxide, a peracid, an alkyl hydroperoxide, a nitric acid, a dimethyl sulfoxide, or an oxygen. It is preferably any one of them, and more preferably a hypohalite or oxygen.
  • X represents a halogen atom, a lower alkyl group having 1 to 6 carbon atoms, and n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of Xs may be the same or different from each other.
  • aryl hydrazone represented by the above general formula (III). Without isolating the compound shown in (III), the obtained reaction solution containing aryl hydrazone (III) was added to an alkali metal cyanide metal salt and an acid.
  • a salt of an inorganic acid of aryl hydrazine may be used in place of the aryl hydrazine (IV) and treated with a base.
  • the reaction comprising the above three steps can be carried out in one pot (one reactor).
  • the reaction intermediates (111), (II) ) Is not required to be isolated and purified, and the reaction is allowed to proceed in a single vessel to produce the desired aryl triazolinones.
  • the present invention provides an industrially advantageous method for producing aryltriazolinones, for example, by obtaining (II).
  • the aryltriazolinones (I) thus obtained are useful as raw materials or intermediates for the synthesis of agricultural chemicals and pharmaceuticals.
  • X represents a halogen atom, a lower alkyl group having 1 to 6 carbon atoms, n represents an integer of 0 to 5. When n represents an integer of 2 or more, a plurality of Xs represent May be the same or different from each other.
  • X represents a halogen atom, a lower alkyl group having from 6 to 6 carbon atoms, n represents an integer from 0 to 5.
  • n represents an integer of 2 or more, a plurality of Xs represent They may be the same or different.
  • aryl hydrazone represented by the general formula (III)
  • the hydrazone (III) is isolated without adding an alkali metal cyanate and an acid, and further adding oxygen in the absence of a catalyst or in the presence of an oxidation catalyst to obtain an aryl group represented by the general formula (I). It is preferred to carry out the production of liazolinone.
  • a salt of an inorganic acid of arylhydrazine is used in place of the arylhydrazine (IV), and the salt is reacted with formaldehyde and a base to obtain a compound of the general formula (III)
  • the aryl hydrazone shown in (1) was generated, alkali metal cyanate and acid were added without isolating the aryl hydrazone ( ⁇ ⁇ ⁇ ) from the reaction solution, and further, in the absence of a catalyst or in the presence of an oxidation catalyst, It is also preferable to add oxygen to produce the aryltriazolinone represented by the general formula (I).
  • the reaction can be carried out in a one-pot (one reactor), and in that case, the reaction intermediates (III) and (II) generated in the course of the reaction are simply used. There is no need for separation and purification.
  • step of producing aryltriazolidinone (II) and the step of dehydrogenating aryltriazolidinone (II), which is the step of producing aryltriazolidinones (I), are performed in parallel.
  • an industrially advantageous method for producing aryl triazolinones can be provided, for example, the reaction time can be shortened.
  • the arylarylazolinone (I) thus obtained is useful as a raw material or an intermediate for the synthesis of agricultural chemicals and pharmaceuticals.
  • aryl triazolidinone represented by the following general formula (II) is subjected to a dehydrogenation treatment with an oxidizing agent, and is subjected to the following general formula (I).
  • the aryl triazolinones shown below are produced, in a preferred embodiment, the arylyl azolinones represented by the following formula (I) are produced through the following series of reaction steps, that is, the following first to third steps. It is manufactured (hereinafter, also referred to as the first manufacturing method).
  • X represents a halogen atom, a lower alkyl group having 1 to 6 carbon atoms, and n represents an integer of 0 to 5.
  • n represents an integer of 2 or more, a plurality of Xs may be the same or different.
  • halogen atom includes chlorine, bromine, fluorine and iodine atoms.
  • the lower alkyl group includes an alkyl group having 1 to 6 carbon atoms, and may be linear or branched. Examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-butyl, n-pentyl, isopentyl, 2-methylbutyl, neopentyl, n-hexyl, 4-methyl Pentyl-2,3-dimethylbutyl, 1-ethylbutyl, 1-ethyl-2-methylpropyl pill, 1-methyl-1-ethylpropyl, 1-methyl-2-ethylpropyl, 2-methyl-1-ethylpropyl, 2-methyl-1-ethylpropyl Or a 2-methyl-2-ethylpropyl group.
  • An aryl triazolidinone represented by the following general formula (II) is produced from an aryl triazolidinone represented by the following general formula (II) through a dehydrogenation reaction step by oxygen oxidation.
  • the first method for producing the aryltriazolinones (I) of the present invention In the “third step", the aryltriazolidinone represented by the general formula (II) is dehydrogenated with an oxidizing agent to produce aryl triazolinones represented by the general formula (I).
  • the arylarylazolidinone represented by the general formula (II) used in this case is, as shown in the above reaction formula, first, in the "first step", the arylarylhydrazine represented by the general formula (IV) Or the salt of an inorganic acid thereof) with formaldehyde (HC HO) to form aryl hydrazone represented by the general formula (III). It is preferable to synthesize by reacting with metal cyanate) and an acid.
  • aryl triazolidinone (II) In the reaction of aryl triazolidinone (II) with an oxidizing agent, which is an oxidation reaction in the first production method of the present invention, it is also obtained by treating aryl hydrazone (III) with an alkali metal salt of cyanate and an acid.
  • the third-stage reaction may be carried out by directly adding an oxidizing agent to the reaction mixture containing aryltriazolidinone (II) in the absence of a catalyst or in the presence of an oxidation catalyst.
  • these series of reactions are performed in the presence of a solvent.
  • a solvent it does not adversely affect the reaction, and preferably —Solvents described below are used in which ruhydrazone (III) and aryltriazolidinone (II) are at least partially soluble.
  • the series of reactions consisting of the first to third steps proceed at a relatively low temperature, are completed in a short time, and have a high yield of the target compound.
  • the reaction step will be described in more detail. That is, in the first step of the reaction preferably used in the first process for producing the aryltriazolinones (I) of the present invention, the arylhydrazine (IV) (or a salt of an inorganic acid thereof) and formaldehyde are used.
  • the reaction is carried out in a solvent without a catalyst, in the presence of an acid catalyst or in the presence of a base catalyst to produce the corresponding arylhydrazone (III).
  • arylhydrazine (IV) in place of arylhydrazine (IV), an organic salt of arylhydrazine can be used, and a base such as sodium hydroxide and formaldehyde can be used without a catalyst, in the presence of an acid catalyst, or in the presence of a base catalyst.
  • a base such as sodium hydroxide and formaldehyde
  • the reaction can be performed below.
  • Such a first-stage reaction is usually carried out in a temperature range from 110 ° C. to the “boiling point of the solvent used”, preferably at about 0 ° (at a temperature of about + 40 ° C. for 10 minutes.
  • the reaction is carried out under normal pressure for up to 24 hours, preferably for 30 minutes to 5 hours ..
  • arylhydrazine (IV) and formaldehyde are used (reaction) in a theoretically equimolar amount.
  • formaldehyde is used in an amount of 1.0 to 2.0 moles, preferably 1.0 to 1.2 moles, per mole of arylhydrazine (IV).
  • formaldehyde is used in an amount of formaldehyde in an amount of 1.0 to 2.0 moles, preferably 1.0 to 1.2 moles, per mole of arylhydrazine (IV).
  • formaldehyde is used in an amount of formaldehyde is used.
  • the arylhydrazine represented by the general formula (IV) or a salt of an inorganic acid thereof used as a starting material is widely commercially available or It can be easily synthesized according to a known method, for example, the method described in "Organic Synthesis (Collective Volume) I, 442 to 445 (.1956)".
  • Examples of the base used for the base treatment of the above-mentioned inorganic acid salt J of arylhydrazine include, for example, sodium hydroxide, potassium hydroxide, sodium hydrogen carbonate, sodium carbonate, potassium carbonate, Examples thereof include barium hydroxide and the like, and preferably, sodium hydroxide, rhodium hydroxide, etc. These bases may be used in an equimolar amount in theory with “salt of inorganic acid of arylhydrazine”. Usually, the base is used in an amount of 1.0 to 2.0 mol, preferably 1.0 to 1.2 mol, per 1 mol of the “salt of the inorganic acid of arylhydrazine”. .
  • Examples of the acid catalyst used for reacting the above arylhydrazine (IV) with formaldehyde include, for example, mineral acids such as hydrochloric acid and sulfuric acid; organic acids such as formic acid and acetic acid; Sulfonic acids such as p-toluenesulfonic acid; Phosphoric acids such as phosphoric acid, phosphoric acid and pyrophosphoric acid; sodium phosphonate, potassium phosphonate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, sodium pyrophosphate, potassium pyrophosphate Any acidic phosphates and the like can be mentioned.
  • the base catalyst examples include inorganic bases such as sodium hydroxide, potassium hydroxide, and sodium carbonate; and amines such as triethylamine, pyridine, and 1,8-diazabicyclo [5,4,0] panda-7-ene. No. These catalysts are usually used in an amount of 0.01 to 10 mol% based on arylhydrazine.
  • examples of the solvent include methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, methoxyethyl alcohol, n-butyl alcohol, sec-butyl alcohol, Alcohols such as sobutyl alcohol and t-butyl alcohol; ethers such as tetrahydrofuran and dioxane; nitriles such as acetonitrile and propionitrile; organic acids such as formic acid and acetic acid; A solvent can be used, and a mixed solvent of t-butyl alcohol and water is preferably used. These solvents are used in an amount of, for example, 100 to 400 m 1 per mole of arylhydrazine (IV).
  • the amount of the solvent may be determined in the second step, which is the reaction step between the aryl hydrazone (III) and the alkali metal cyanate, or the reaction step in the following reaction, where the aryl azolidinone (II) is reacted with the oxidizing agent. It can be appropriately changed according to individual reactants, reaction conditions, etc., such as the third step, which is not determined unconditionally.
  • the aryl hydrazone (III) and the alkali metal cyanate (alkali metal) are used.
  • Cyanate) and an acid, preferably an organic acid, as a source of protons are reacted in a solvent to form allyl triazolidinone (II).
  • Such a reaction is carried out batchwise by adding an alkali metal cyanate and an organic acid as a proton source to a reaction solution containing aryl hydrazone (III) obtained in the first step. Can be performed efficiently.
  • This second stage reaction is carried out at a temperature of about 10 ° C. (: up to + 60 ° C., preferably about 0 ° C. to 104 ° C., for 1 to 24 hours, preferably Performed under normal pressure for ⁇ 5 hours.
  • the above aryl hydrazone (III) and the alkali metal cyanate may theoretically be used in equimolar amounts, but usually the aryl hydrazone (III)
  • the alkali metal cyanate is used in an amount of 1.0 to 3.0 mol, preferably 1.0 to 1.5 mol, per 1 mol.
  • alkali metal cyanate examples include sodium cyanate, potassium cyanate, calcium cyanate and the like, and sodium cyanate (sodium cyanate) is preferable.
  • Examples of the acid as a proton source include phosphoric acids such as phosphonic acid, phosphoric acid, and pyrophosphoric acid; sodium phosphonate, potassium phosphonate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, and sodium pyrophosphate. And acidic phosphates such as potassium pyrophosphate; organic acids such as formic acid, acetic acid, propionic acid and butyric acid; and organic acids are preferable.
  • the acid such as an organic acid may be used in an equivalent amount to the alkali metal cyanate, and the acid, preferably the organic acid, is usually 1 to 1.2 with respect to 1 equivalent of the alkali metal cyanate. Equivalents (equivalent excess to about 20%), preferably used at 1.00 to: L.10 equivalents.
  • the same solvent as used in the first step is used.
  • the mixing ratio of the organic solvent and water is by volume, and the organic solvent: water can be used in a range of 100: 1 to 500.
  • the organic solvent is used.
  • Water 100: Used in the range of 20 to 200. These solvents are used in an amount of 100 ml to 5000 ml per 1 mol of arylhydrazone (III).
  • the aryltriazolidinone (II) and an oxidizing agent are used in the absence of a catalyst or oxidation.
  • the reaction is carried out in a solvent in the presence of a catalyst to form the desired aryltriazolinones (I).
  • the reaction is usually carried out at a temperature of about -10 to 60 ° C, preferably about 0 to 40 ° C.
  • the reaction is usually carried out under normal pressure for 1 to 24 hours, preferably 2 to 8 hours.
  • the oxidizing agent include halogen, hypohalous acid, hypohalite, permanganate, hydrogen peroxide, peracids, alkyl hydroperoxide, nitric acid, dimethyl sulfoxide, and oxygen. It can also be used in the presence of an oxidation catalyst.
  • Halogen includes chlorine, bromine, iodine, and fluorine.
  • sodium hypochlorite among the hypohalites is preferred.
  • the oxidation catalyst used may be ferrous chloride, ferrous bromide, ferrous sulfate, cobalt chloride, bromide.
  • Iron group salts such as cobalt, cobalt sulfate, cobalt nitrate, and cobalt acetate;
  • Copper salts such as copper chloride (1), copper bromide (1), copper chloride (11), copper bromide (11), copper sulfate, copper acetate;
  • Examples thereof include divanadium pentoxide, osmium oxide, selenium oxide, tandane oxide, sodium tungstate, molybdenum oxide, sodium molybdate, titanium tetrachloride, and chromium oxide.
  • the oxidation catalyst to be used includes ferrous chloride, ferric chloride, ferrous bromide, ferric bromide, ferrous sulfate, and ferrous sulfate.
  • Iron group salts such as ferrous iron, cobalt chloride, cobalt bromide, cobalt sulfate, cobalt nitrate, cobalt acetate, nickel chloride;
  • Iron group complexes such as iron (III) acetyl acetatetonate, cobalt (II) acetyl acetatetonate, cobalt (II) bis (salicylidene) ethylenediamine, hexamminenickel (II) chloride;
  • Platinum group such as platinum and palladium
  • Platinum group salts such as palladium chloride, palladium acetate, and platinum oxide; black (triphenylphosphine) rhodium, dichlorobis (trif Phenylphosphine) platinum group complexes such as ruthenium;
  • Copper salts such as copper chloride (1), copper bromide (1), copper chloride (11), copper bromide (11), copper sulfate, copper acetate;
  • Zinc salts such as zinc chloride
  • Zinc complexes such as tris (ethylenediamine) zinc; vanadium complexes such as vanadium acetyl acetonate; rare earth salts such as cerium chloride and samarium iodide; These catalysts are used alone or in combination of two or more.
  • the above-mentioned aryl triazolidinone (II) and the oxidizing agent may be used in an equimolar amount in theory, but usually, the oxidizing agent is used per 1 mole of the aryl triazolidinone (II). Is usually used in an amount of 1.0 to 1.40 mol, preferably 1.0 to 1.10 mol.
  • an aqueous solution of sodium hypochlorite having a concentration of about 5 to 25% (weight / weight), preferably about 5 to 15% can be used.
  • the oxidation catalyst optionally used is usually 0.01 to 10 mol%, preferably 0.1 to 1 mol%, relative to 100 mol% of aryl triazolidinone ( ⁇ ). Used in quantity.
  • the solvent those similar to those used in the first and second steps are used. Even in the case of a mixed solvent of an organic solvent and water, the same mixture ratio is used. Such a solvent is used in an amount of 100 to 6 000 ml per 1 mol of aryltriazolidinone (II).
  • the reaction solution in each of the first to third steps is preferably at least It is preferable to stir gently.
  • the organic solvent in the above-mentioned mixed solvent (a mixed solvent of an organic solvent and water) is distilled off from the reaction mixture and reused in the next production of aryltriazolinones (I) It is possible.
  • the desired aryltriazolinones (I) are isolated through a usual extraction and separation operation, or after the organic solvent is distilled off, the desired product is precipitated in water and separated by filtration.
  • an organic solvent in the reaction mixture is distilled off, and then the target aryltriazolinone (I) is dissolved in an aqueous base solution such as sodium hydroxide. A salt is formed, which is washed with an organic solvent.
  • the desired arylarylazolinones (I) are precipitated by adding and neutralizing a mineral acid such as hydrochloric acid.
  • a mineral acid such as hydrochloric acid.
  • High-purity aryltriazolinones (I) can be obtained by filtering and washing the precipitated crystals with water.
  • the obtained target product may be further purified, if necessary, by means of washing with an organic solvent, column chromatography, recrystallization, or the like.
  • the aryl triazolinones (I) thus obtained are suitably used as raw materials for producing agricultural chemicals and pharmaceuticals.
  • aryltriazolinones (I) the second process for producing the aryltriazolinones (I) according to the present invention. That is, in the second production method of the present invention, a step of producing an aryltriazolidinone represented by the general formula (II) from an arylarylhydrazone represented by the general formula (III) (hereinafter referred to as an aryltriazolidinone ( ⁇ )) Simultaneously with the addition of oxygen in the absence of a catalyst or an oxidation catalyst, and a dehydrogenation reaction of aryltriazolidinone (II) by oxygen oxidation is carried out. ) Manufacture nons.
  • arylhydrazine (or a salt of an inorganic acid thereof) represented by the general formula (IV) is converted to formaldehyde.
  • the reaction is carried out to form an arylhydrazone represented by the general formula (III), followed by reaction with an alkali metal cyanate (alkali metal cyanate) and an acid.
  • aryltriazolidinone (II) is carried out in the absence of an oxidation catalyst or simultaneously with the addition of an alkali metal cyanate and an acid to aryl hydrazone represented by the general formula (III).
  • the reaction is carried out by adding oxygen and introducing oxygen into the reaction solution.
  • these series of reactions are usually performed in the presence of a solvent.
  • the reaction is carried out in a solvent which does not adversely influence the reaction, and is preferably at least partially soluble in arylhydrazone (III) and aryltriazolidinone (II).
  • the second production method of the present invention the above series of reactions is completed in a relatively short time, and the aryltriazolinones (I) can be obtained in high yield.
  • the second production method of the aryl triazolinones (I) according to the present invention will be described focusing on the differences from the first production method of the aryl triazolinones (I).
  • the production method of raw materials will be described in detail.
  • the aryl hydrazone (III) used for producing the aryl triazolidinone (II) is the same as the above-mentioned first aryl azolidinone (III) according to the present invention. It is synthesized in the same manner as in the preparation of arylhydrazone (III).
  • arylhydrazine (IV) (or a salt of an inorganic acid thereof) and formaldehyde are reacted in a solvent without a catalyst, in the presence of an acid catalyst or in the presence of a base catalyst, to give arylhydrazine (III). ) Is synthesized.
  • aryl hydrazine inorganic material may be used instead of aryl hydrazone (III).
  • An acid salt can be used.
  • a base is reacted with formaldehyde and an inorganic salt of arylhydrazine. It is preferable to use the reaction solution for synthesizing the following aryltriazolinones (I) without isolating the arylhydrazone (III) from the obtained reaction solution containing arylhydrazone (III).
  • aryl hydrazine (IV) or a salt thereof, a base, an acid catalyst and a solvent thereof described in “Synthesis of aryl hydrazine (III)” in the first production method described above were used under the same conditions. Can be used. However, these reaction solvents are preferably used in the range of 300 to 300 ml per mole of arylhydrazine (IV).
  • aryl triazolinones (I) Preferred in the first method for producing aryl triazolinones (I) according to the present invention.
  • the alkali metal cyanate alkali metal cyanate
  • an acid preferably an organic acid, as a proton source, and oxygen is introduced (added) to the reaction solution in the absence of a catalyst or in the presence of an oxidation catalyst for the dehydrogenation reaction step.
  • the desired aryltriazolinones (I) are produced.
  • the process for producing the aryl triazolinones (I) is carried out at a temperature of about ⁇ 10 ° C. to about 110 ° C., preferably at a temperature of about 0 ° C. to about 60 ° C., for 1 to 24 hours. Preferably, it is carried out in about 1 to 10 hours.
  • the aryl hydrazone (III) and the alkali metal cyanate may be used in an equimolar amount in theory.
  • the alkali metal cyanate is usually used with respect to 1 mol of aryl hydrazone (III). , 1 to 5 mol, preferably 1 to 3 mol.
  • alkali metal cyanate examples include the same as those used in the synthesis process of aryl triazolidinone (II) in the first production method.
  • sodium cyanate sodium cyanate
  • cyanic acid cyanic acid
  • Potassium potassium cyanate
  • Examples of the acid as the proton source include the same acids as those used in the step of synthesizing allyl triazolidinone (II) in the first production method. These acids may be used in the same theoretical amount as the alkali metal cyanate, but usually 0.5 to 3.0 mol, preferably 1 mol, per mol of the alkali metal cyanate. It is used in a molar amount of 0.5 to 1.1.
  • the oxidation catalyst examples include, for example, ferrous chloride, ferric chloride, ferrous bromide, ferric bromide, ferrous sulfate, ferric sulfate, and ferric chloride.
  • Iron group salts such as baltic, cobalt bromide, cobalt sulfate, cobalt nitrate, cobalt acetate, nickel chloride;
  • Iron group complexes such as iron (I 11) acetyl acetate, cobalt (II) acetyl acetate, cobalt (II) bis (salicylidene) ethylenediamine, hexamminenickel (II) chloride;
  • Platinum group such as platinum and palladium
  • Platinum group salts such as palladium chloride, palladium acetate and platinum oxide;
  • Platinum group complexes such as rhodium (triphenylphosphine) rhodium and dichlorobis (triphenylphosphine) ruthenium;
  • Copper salts such as copper chloride (1), copper bromide (1), copper chloride (11), copper bromide (11), copper sulfate, copper acetate;
  • Copper (II) acetylacetonate copper complexes such as bisethylenediamine copper; zinc salts such as zinc chloride;
  • Tris (ethylenediamine) zinc complexes such as zinc; vanadium complexes such as vanadium acetyl acetonate; rare earth salts such as cerium chloride and samarium iodide.
  • These catalysts are used alone or in combination of two or more.
  • divalent copper salts that is, copper sulfate, copper acetate and the like are preferable.
  • These oxidation catalysts are used in an amount of 0.0 :! to 10 mol%, preferably 0.1 to: ! mol, based on 100 mol% of arylhydrazone (III). It is used in mol% amounts.
  • the introduction (addition) of oxygen in the above dehydrogenation reaction step is carried out by replacing the reaction system under an oxygen atmosphere, by blowing oxygen into the reaction solution, or by blowing air into the reaction solution.
  • the pressure of the reaction system at the time oxygenation usually from 1 to 1 0 atm (l X 1 0 3 ⁇ l X 1 0 4 h Pa), preferably 1 to 3 atm (1 X 1 0 3 ⁇ 3 X 1 0 is a 3 hPa).
  • the solvent examples include the aryltriazolidinone of the first production method.
  • the same solvent as that used in the synthesis step (II) can be used.
  • the same mixed solvent of an organic soot and water is used.
  • These solvents are used in an amount of 100 to 500 ml, preferably 300 to 400 ml, per 1 mol of arylhydrazone (111).
  • the step of producing such aryltriazolinones (I) is desirably carried out in a so-called batch system by sequentially adding the components required in each reaction step to the same reactor.
  • the organic solvent in the mixed solvent used is distilled off from the reaction mixture, and can be reused in the next production of aryltriazolinones (I).
  • the desired aryltriazolinones (I) are isolated through a usual liquid separation operation, or after evaporating the organic solvent, the desired product (I) is precipitated in water and separated by filtration. .
  • the obtained target product (I) may be further purified, if necessary, by means such as column chromatography or recrystallization.
  • arylated liazolinones (I) are added to water. After dissolution, this is washed with an organic solvent. Thereafter, a desired acid (I) is precipitated by adding a mineral acid such as hydrochloric acid to neutralize the salt of the aryltriazolinones (I). By filtering and washing the precipitated crystals with water, high purity aryltriazolinones (I) can be obtained.
  • a mineral acid such as hydrochloric acid
  • the aryl triazolinones (I) thus obtained are suitably used as raw materials for producing agricultural chemicals and pharmaceuticals.
  • the reaction proceeds at a relatively low temperature and is completed in a short time, and the aryl triazolinones (I) of the target compound are obtained in high yield. I) can be obtained.
  • Isolation of certain aryl triazolinones (I) is easily performed, for example, by distilling off the solvent.
  • aryltriazolinone when all of the above steps (first to third steps) are carried out in a pot, it can be carried out using a small amount of energy, and as a result, purification can be performed at low cost. It is possible to provide an aryltriazolinone as a target compound. Further, the method for producing aryltriazolinones of the present invention is suitable for large-scale industrial implementation and is an industrially advantageous method.
  • the second production method of the aryl triazolinones (I) according to the present invention uses an oxygen oxidation reaction in the dehydrogenation step, thereby allowing a conventional oxidation reaction with a hypohalite, a halogen, or the like.
  • the desired compound aryl triazolinones (I) can be obtained easily and at low cost under safer and milder conditions.
  • the dehydrogenation reaction step by oxygen oxidation can be performed in parallel with the production step of the target compound intermediate, aryltriazolidinone (II), in the same vessel, thereby shortening the reaction time. It is suitable for large-scale industrial implementation and is an industrially advantageous method.
  • reaction mixture was cooled to 5 ° C., and 39 g of acetic acid was added dropwise over 10 minutes. After the dropwise addition, the ice-water cooling bath was removed, and the reaction mixture was stirred at room temperature (24 ° C) for about 2 hours.
  • reaction mixture After stirring for 2 hours, the reaction mixture was cooled to about 10 ° C., and a 12% solution of sodium hypochlorite prepared from an aqueous solution of 39 g of chlorine gas and 44.3 g of sodium hydroxide 3 3 5 g was added dropwise over 50 minutes. After the dropwise addition, the reaction mixture was stirred for 60 minutes while cooling with ice and water, and further stirred at room temperature for 5 hours.
  • reaction mixture After stirring for 3 hours, the reaction mixture was cooled to about 10 ° C., and 100 g of a 12% solution of sodium hypochlorite was added dropwise over 90 minutes. After the dropwise addition, the reaction mixture was stirred for 60 minutes while cooling with ice water, and further stirred at room temperature for 5 hours. Next, the tertiary butanol was distilled off from the reaction mixture by gradually heating the reaction mixture to about 10 ° C. under stirring, and the mixture was concentrated. After a while the residue which solidified was collected by filtration and washed with 100 ml of water. The obtained crude crystals were dried and further washed with 500 ml of diisopropyl ether to obtain the title compound (207 g, yield 79%). Melting point: 148-149 ° C.
  • reaction vessel was replaced with oxygen, and immediately a mixture of acetic acid (109 g) and water (100 ml) was added dropwise over 20 minutes. After completion of the dropwise addition, the mixture was stirred at 10 under an oxygen atmosphere for 5 hours, and further stirred at 55 ° C for 3 hours.
  • t_butyl alcohol was distilled off under reduced pressure and concentrated. To this, add 200 ml of toluene, extract 3 times with 60 ml of 40% aqueous sodium hydroxide solution, wash the aqueous layer twice with 200 ml of toluene, and add 200 ml of concentrated hydrochloric acid.
  • the number before the element or alkyl group refers to the number of the heterocyclic ring in the above formula.
  • nPr Normal B-Bil group
  • iPr Isopropyl group Industrial applicability
  • the method can be carried out more easily and at lower cost using less expensive raw materials. It is useful as a method for producing reel triazolinones, and the second method is a method for producing aryl triazolinones that can be carried out more easily and at low cost under safe and mild conditions. Useful.
  • the first and second production methods are suitable for large-scale industrial implementation of aryltriazolinones suitably used as raw materials for producing agricultural chemicals and pharmaceuticals.

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

Abstract

La présente invention concerne un nouveau processus par lequel on peut facilement préparer des aryltriazolinones à partir de produits primaires bruts bon marché et à faible coût, et un nouveau processus par lequel on peut facilement et simplement préparer des aryltriazolinones dans des conditions plus sûres et plus douces et ce, à faible coût. Cette invention concerne plus particulièrement un processus de préparation d'aryltriazolinones (I) qui consiste à déshydrogéner un aryltriazolinone (II) avec un agent oxydant, et un processus de préparation d'aryltriazolinones (I), qui consiste à ajouter un cyanate de métal alcalin et un acide à un arylhydrazone (III) puis à ajouter de l'oxygène à ce mélange en présence ou non d'un catalyseur d'oxydation. (I) (II) (III) (Dans la formule générale, X est halogène ou alkyle inférieur en C1-6, n est un entier allant de 0 à 5, sous réserve que lorsque n est supérieur ou égal à 2, les X puissent être semblables ou différents entre eux.)
PCT/JP2001/006543 2000-08-08 2001-07-30 Processus de préparation d'aryltriazolinones Ceased WO2002012203A1 (fr)

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JP2000-239566 2000-08-08
JP2001193655A JP3863736B2 (ja) 2000-08-08 2001-06-26 アリールトリアゾリノン類の製造法
JP2001-193655 2001-06-26

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009088025A1 (fr) * 2008-01-10 2009-07-16 Hokko Chemical Industry Co., Ltd. Procédé de fabrication de phényltriazolinone
WO2014202510A1 (fr) 2013-06-20 2014-12-24 Bayer Cropscience Ag Dérivés d'arylsulfure et d'arylsulfoxyde utilisés comme acaricides et insecticides

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104672157B (zh) * 2015-02-12 2017-06-27 山东潍坊润丰化工股份有限公司 一种芳基三唑啉酮的制备方法
CN109912522B (zh) * 2017-12-12 2021-04-13 北京颖泰嘉和生物科技股份有限公司 制备三唑啉硫酮化合物的方法

Citations (3)

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WO1991003470A1 (fr) * 1989-09-08 1991-03-21 Fmc Corporation Production de triazolinones
WO1993023382A1 (fr) * 1992-05-13 1993-11-25 Fmc Corporation Formation cyclique de triazolinones dans le tert-butanol
WO1998038176A1 (fr) * 1997-02-26 1998-09-03 Hokko Chemical Industry Co., Ltd. Derives de 4-carbamoyl-1,2,4-triazol-5-one substitue en 1 utilises en tant qu'herbicide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991003470A1 (fr) * 1989-09-08 1991-03-21 Fmc Corporation Production de triazolinones
WO1993023382A1 (fr) * 1992-05-13 1993-11-25 Fmc Corporation Formation cyclique de triazolinones dans le tert-butanol
WO1998038176A1 (fr) * 1997-02-26 1998-09-03 Hokko Chemical Industry Co., Ltd. Derives de 4-carbamoyl-1,2,4-triazol-5-one substitue en 1 utilises en tant qu'herbicide

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009088025A1 (fr) * 2008-01-10 2009-07-16 Hokko Chemical Industry Co., Ltd. Procédé de fabrication de phényltriazolinone
JP5167283B2 (ja) * 2008-01-10 2013-03-21 北興化学工業株式会社 フェニルトリアゾリノン類の製造法
WO2014202510A1 (fr) 2013-06-20 2014-12-24 Bayer Cropscience Ag Dérivés d'arylsulfure et d'arylsulfoxyde utilisés comme acaricides et insecticides

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JP2002179655A (ja) 2002-06-26
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