WO2015166862A1 - Procede de production d'un compose de bispyrazole - Google Patents

Procede de production d'un compose de bispyrazole Download PDF

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WO2015166862A1
WO2015166862A1 PCT/JP2015/062283 JP2015062283W WO2015166862A1 WO 2015166862 A1 WO2015166862 A1 WO 2015166862A1 JP 2015062283 W JP2015062283 W JP 2015062283W WO 2015166862 A1 WO2015166862 A1 WO 2015166862A1
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compound
bispyrazole
formula
reaction
hydrazine
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優樹 小嶋
眞一 柿沼
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日本カーバイド工業株式会社
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

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  • the present invention relates to a method for producing a bispyrazole compound.
  • pyrazole compounds exhibit excellent performance due to their unique molecular structure, they are useful as various medical and agrochemical materials and their production intermediates, analytical reagents, dyes, pigments, optical materials, and electronic materials.
  • a compound having a plurality of pyrazole skeletons in the structural formula has an excellent feature of easily forming complexes with various metal ions because it has a plurality of coordinating nitrogen atoms in the molecule.
  • Non-Patent Document 1 describes that a compound having two pyrazole skeletons in a structural formula and a transition metal ion form a complex and can be used for various analytical reagents.
  • a method for synthesizing a compound having two pyrazole skeletons in such a structural formula bispyrazole compound
  • a formulation in which an intermediate containing a plurality of halogen atoms is reacted with hydrazine is known.
  • Non-Patent Document 1 discloses an intermediate [1a] having two 3-aryl-1,2-dibromo-3-oxopropyl groups in the structural formula and 15 equivalents of hydrazine.
  • Non-Patent Document 2 discloses a method for producing a bispyrazole compound [2b] by reacting 1,3-diketone intermediate [1b] with hydrazine as shown in the following reaction formula. .
  • the obtained bispyrazole compound has a low purity, and is oily even when purified using thin layer chromatography. This is because a side reaction occurs between the compound [1a] having two 3-aryl-1,2-dibromo-3-oxopropyl groups and hydrazine, and many by-products are produced. Therefore, the production method described in Non-Patent Document 1 requires a complicated purification step for the production of the high-purity bispyrazole compound [2a], and there is a problem as an industrial production method.
  • Non-Patent Document 2 uses sodium amide, which is water-inhibiting and pyrophoric, in the production of intermediate [1b] having a 1,3-diketone skeleton. Is a safety issue. Further, the method for producing the pyrazole compound [2b] has a problem that the yield is low.
  • the present invention has been made in view of the above.
  • the molar ratio of the compound [1a] having two 3-aryl-1,2-dibromo-3-oxopropyl groups to hydrazine is Since it is not controlled, the purity of the obtained bispyrazole compound [2a] decreases.
  • the inventors of the present invention have suppressed the side reaction by setting the molar ratio of the compound having two 3-aryl-1,2-dibromo-3-oxopropyl groups to hydrazine within a specific range, and having high purity. It has been found that a bispyrazole compound can be obtained.
  • An object of the present invention is to provide a production method capable of suppressing side reactions and obtaining a high-purity bispyrazole compound.
  • R 1 and R 2 in Formula (1) and Formula (2) are each independently an aryl group which may have a substituent.
  • the amount of the protic solvent is any one of [5] to [7], in the range of 3 to 100 parts by mass with respect to 1 part by mass of the compound represented by the formula (1). This is a method for producing a bispyrazole compound.
  • the side reaction can be suppressed and the manufacturing method from which a highly purified bispyrazole compound can be obtained can be provided.
  • the production method of the present invention since a high-purity bispyrazole compound is obtained, a complicated purification step is unnecessary, and crystals of the bispyrazole compound can be easily obtained. Furthermore, the production method of the present invention is industrially safe.
  • a method for producing a compound may be simply referred to as a method for producing a compound.
  • numerical ranges indicated using “to” indicate ranges including the numerical values described before and after “to” as the minimum value and the maximum value, respectively.
  • the present invention provides a compound comprising the compound represented by the formula (1) and the hydrazine.
  • the compound shown by Formula (1) may be called a chalcone compound or a chalcone compound (1).
  • the bispyrazole compound represented by the formula (2) may be referred to as a bispyrazole compound or a bispyrazole compound (2).
  • R 1 to Bisupirazoru compound represented by R 1 and formula compound represented comprises (2) Equation (1) is provided, also a compound represented by the formula (1) is provided with R 2 and the formula ( R 2 included in the bispyrazole compound represented by 2) is the same.
  • R ⁇ 1 > and R ⁇ 2 > in Formula (1) is an aryl group which may have a substituent each independently. Examples of the substituent include an alkyl group and an aryl group. Examples of the aryl group include a phenyl group, a naphthyl group, a pyrrolyl group, a pyridyl group, a furyl group, and a thienyl group. Further, R 1 and R 2 in the formula (1) may be the same or different from each other.
  • the hydrazine used in the production method of the present invention may be a hydrate. Hydrazine hydrate is also referred to as hydrated hydrazine.
  • the lower limit of the molar ratio of the compound represented by formula (1) to hydrazine is 1.0: 5.2.
  • the upper limit is 1.0: 11.7 or less, preferably 1.0: 7.8 or less, and more preferably 1.0: 6.9 or less.
  • the production method of the present invention includes a chalcone compound in the reaction system of chalcone compound (1) and hydrazine.
  • the reaction intermediate produced from (1) and the chalcone compound (1) hardly remains unreacted, and the production of by-products produced by side reactions can be suppressed, and the reaction of the bispyrazole compound in the reaction mixture after completion of the reaction Selectivity is improved. Further, when the molar ratio of the hydrazine when the molar ratio of the chalcone compound (1) is 1, the generation of by-products can be suppressed, and the bispyrazole compound in the reaction mixture after the reaction is completed. Selectivity is improved.
  • the molar ratio of hydrazine when the molar ratio of chalcone compound (1) is 1 may be referred to as the number of hydrazine equivalents or the number of hydrazine equivalents.
  • the production method of the present invention by setting the number of hydrazine equivalents in the range of 5.2 to 11.7, the production of bispyrazole compounds is increased and undesirable side reactions are suppressed, and a high-purity bispyrazole compound is obtained. Manufacturing method can be provided.
  • the high-purity bispyrazole compound obtained by the production method of the present invention is easily crystallized, various medical and agrochemical materials and their production intermediates, analytical reagents, dyes, pigments, optical materials, electronic materials, etc. It can be used industrially.
  • the purity of the bispyrazole compound (2) can be evaluated by an absolute calibration curve method by HPLC (high performance liquid chromatography).
  • the selectivity is defined as the ratio of the bispyrazole compound (2) to all components except specific components with a low purification load that can be easily removed in the HPLC analysis of the reaction solution.
  • the selectivity can be determined by analyzing the reaction solution sampled from the reaction system by HPLC, and specifically, the bispyrazole compound (2) with respect to the sum of all peak areas except a specific by-product peak. The peak area ratio can be obtained.
  • high purity means that the purity determined by the absolute calibration curve method by HPLC is 95% or more.
  • the theoretical value of the number of hydrazine equivalents is 2.0, and when combined with the number of equivalents of hydrazine required to keep the reaction system basic, it is 6.0. It is.
  • a method of increasing the amount of a target product by using an excessive amount of an inexpensive raw material is often performed.
  • the amount of bispyrazole compound (2) produced increases by using an excess amount of hydrazine.
  • the number of hydrazine equivalents exceeds 11.7, the selectivity of the reaction is lowered, and excess hydrazine remains in the reaction system, so that purification becomes complicated.
  • the production method of the present invention by setting the molar ratio of chalcone compound (1) to hydrazine within a specific range, side reactions are suppressed, industrially stable, and high-purity bispyrazole compound (2) is obtained. Obtainable.
  • the selectivity is low, purification of the reaction product obtained after the reaction becomes difficult, and the purity of the resulting bispyrazole compound (2) also decreases.
  • the purification of the low-purity bispyrazole compound (2) is not only economically disadvantageous, but also uses, for example, a generally known thin-layer chromatography as described in Non-Patent Document 1. Even in the refining method, it remains oily and the purity is not high, and industrial utilization is difficult. Therefore, in order to produce a high purity bispyrazole compound (2), it is important to obtain a high selectivity in the reaction.
  • At least one of R 1 and R 2 in formula (1) is preferably a phenyl group. If at least any one phenyl group of R 1 and R 2 in the formula (1), at least one of R 1 and R 2 in the formula (2) is also a phenyl group. Furthermore, in the production method of the present invention, it is preferable that R 1 and R 2 in the formulas (1) and (2) are both phenyl groups.
  • the bispyrazole compound (2) obtained by the production method of the present invention is preferably a bispyrazole compound represented by the formula (3).
  • R 1 and R 2 in formula (3) are each independently an aryl group which may have a substituent. Examples of the aryl group include a phenyl group, a naphthyl group, a pyrrolyl group, a pyridyl group, a furyl group, and a thienyl group.
  • the compound represented by the formula (1) used in the production method of the present invention has two 3-aryl-1,2-dibromo-3-oxopropyl groups in the structural formula.
  • the bispyrazole compound (2) obtained by the production method of the present invention is: As shown in Formula (3), one pyrazolyl group and the other pyrazolyl group are preferable because they are located at the meta position. Thus, the bispyrazole compound (3) in which the pyrazolyl groups are located at the meta positions is preferable because a complex is easily formed with respect to various metal ions.
  • an organic solvent is preferably used as the reaction solvent.
  • the organic solvent that can be used in the present invention is not particularly limited as long as it does not inhibit the reaction between the chalcone compound (1) and hydrazine, and any of an aprotic solvent, a protic solvent, a polar solvent, and a nonpolar solvent. Can also be used.
  • a polar solvent is preferable in view of compatibility with hydrazine, and it is particularly preferable to use a protic solvent.
  • protic solvent examples include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutanol, and tert-butanol. These protic solvents may be used alone or in combination of two or more. In particular, it is preferable to use at least one of methanol and 2-propanol.
  • the lower limit amount of the protic solvent that can be used is preferably 3 parts by mass or more, more preferably 5 parts by mass or more, with respect to 1 part by mass of the chalcone compound.
  • the upper limit is preferably 100 parts by mass or less, particularly preferably 20 parts by mass or less. If the amount of the protic solvent is 3 parts by weight or more with respect to 1 part by mass of the chalcone compound, it is preferable because the selectivity of the reaction is improved. Moreover, if the amount of the protic solvent is 100 parts by mass or less, the solvent removal step after completion of the reaction is easy and preferable.
  • the reaction temperature in the production method of the present invention is not particularly limited, but the lower limit temperature is preferably 40 ° C or higher, particularly preferably 50 ° C or higher.
  • the upper limit temperature is preferably 100 ° C. or less, and particularly preferably 80 ° C. or less.
  • the reaction temperature of 40 ° C. or higher is preferable because the reaction rate does not decrease, and if the reaction temperature is 100 ° C. or lower, the chalcone compound (1), hydrazine and bispyrazole compound (2) are contained in the reaction system. It is preferable because it is difficult to decompose.
  • the method for adding hydrazine to the reaction system is not particularly limited, but a method of adding the entire amount of hydrazine to the reaction system before raising the temperature of the reaction system is preferable.
  • the reaction solution was subjected to solid-liquid separation with Nutsche, and the obtained crystals were washed with 707.1 g of methanol.
  • Nutsche solid-liquid separation with Nutsche
  • 2768 g of water and 556.7 g of the obtained crystals were added and stirred for 30 minutes.
  • the crystals were subjected to solid-liquid separation with Nutsche, and washed with 757.0 g of water and 925.5 g of methanol in this order.
  • the obtained wet crystals were vacuum-dried at 60 ° C. to obtain 534.7 g of powdery crystals of 3- (3-oxo-3-phenylpropenyl) chalcone.
  • the crude yield from isophthalaldehyde was 98%.
  • the reaction solution was subjected to solid-liquid separation with Nutsche, and the obtained crystal was washed with 157.1 g of cold CPME. 246.5 g of the obtained wet crystals were vacuum-dried at 60 ° C. to obtain ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone white 164.0 g of crystals were obtained. The yield was 45%.
  • the obtained reaction mixture was subjected to solid-liquid separation using Nutsche, and the precipitated solid was washed with 893.0 g of methanol to obtain 764.7 g of wet crystals.
  • Into a 3000 ml four-necked flask different from the above flask 1600.3 g of water and 764.7 g of wet crystals were added, and then 2.0 g of concentrated hydrochloric acid was added with stirring.
  • the obtained crystal was subjected to solid-liquid separation using Nutsche, and washed with 406.2 g of water and 502.1 g of methanol in this order.
  • the obtained crystals were vacuum-dried at 60 ° C. to obtain 319.9 g of 3- (3-oxo-3-phenylpropenyl) chalcone powdery crystals.
  • the crude yield from isophthalaldehyde was 96%.
  • the obtained reaction solution was subjected to solid-liquid separation using a Nutsche, and the obtained crystal was washed with 283.0 g of MTBE.
  • the obtained wet crystals (122.0 g) were vacuum-dried at 60 ° C. to obtain ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone white 103.6 g of crystals were obtained.
  • the yield was 53%.
  • ⁇ Selection rate evaluation method> In a 450 mL screw cap bottle, 294.4 g of methanol and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone obtained in Production Example 5 were used. After charging 38 g (3.62 mmol, 1.0 eq.), The inside of the system was replaced with nitrogen gas. To this was added 3.27 g (52.3 mmol, 14.4 eq.) Of 80.0% by mass hydrated hydrazine, and then reacted at a reaction temperature of 60 ° C. for 24 hours.
  • the obtained reaction mixture was concentrated under reduced pressure using a rotary evaporator, and the solvent was distilled off.
  • 1.29 g was weighed into a 500 mL Erlenmeyer flask, dissolved by adding 260.5 g of MTBE and 100.4 g of water, liquid-separated, and removing the sample from the organic layer. Sampling and analysis using HPLC. The operation of washing the organic layer with water was repeated, and a change in composition in the organic layer was confirmed.
  • the area of the main peak and the reaction target product (1,3-bis (3-phenyl-5-pyrazolyl) benzene) is A
  • the area of the target peak is B
  • ratio (B / A) of A and B was calculated
  • Table 1 The results are shown in Table 1 below.
  • the two peaks with retention times of 0.33 minutes and 2.5 minutes in the HPLC analysis described in Table 1 are all derived from by-products.
  • the peak with a retention time of 2.5 minutes is derived from hydrazine hydrobromide.
  • the results in Table 1 indicate that these by-products can be removed by washing with water. These by-products can be easily removed by operations such as washing with water, separating and washing with a water-soluble reaction mixture dissolved in a water-insoluble organic solvent, and suspension washing with water of the reaction mixture from which the reaction solvent has been distilled off. Possible and very low purification load.
  • the selectivity refers to the peak of the bispyrazole compound with respect to the sum of all peak areas except the two peaks of retention times 0.33 minutes and 2.5 minutes shown in Table 1 in HPLC analysis of the reaction solution. It is the ratio of the area.
  • Example 1 is a method for producing a bispyrazole compound (2) in which the molar ratio of the chalcone compound (1) to hydrazine is 1.0: 6.0, that is, the hydrazine equivalent number is 6.0.
  • a 5000 mL four-necked flask equipped with a stirrer, thermometer and Dimroth 4001 g of methanol and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-) obtained in Production Example 2 and Production Example 3 were added.
  • the resulting reaction solution was cooled, concentrated to dryness, extracted with 1858 g of chloroform, and then washed with 2316 g of a 2% aqueous sodium hydroxide solution.
  • the aqueous layer was discarded, and 513 g of chloroform was added to the crystals obtained from the organic layer and the intermediate layer, and then washed with 1885 g of deionized water.
  • the aqueous layer was discarded, and the organic layer and the intermediate layer were separated into solid and liquid by Nutsche and dried to obtain 102 g of dried solid crystals.
  • the dried crystals were suspended in 1364 g of chloroform, and then 825 g of MTBE was added to obtain crystals.
  • the crystals were solid-liquid separated and washed with MTBE.
  • the obtained wet crystals were dried under reduced pressure to obtain 87.9 g of 1,3-bis (3-phenyl-5-pyrazolyl) benzene white crystals. Obtained.
  • the yield was 40%, and the purity of the obtained white crystals was 99.0% or more.
  • Example 2 is a production method different from Example 1 of the bispyrazole compound (2) having a hydrazine equivalent number of 6.0.
  • a 200 ml four-necked flask equipped with a thermometer and a stirrer was charged with 104.2 g of methanol and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) obtained in Production Example 2.
  • -10.38 g (15.77 mmol, 1.0 eq.) Of ⁇ , ⁇ -dihydrochalcone was added, and then 5.91 g (94.5 mmol, 6.0 eq.) Of 80.0% by mass hydrated hydrazine were added.
  • the crystals were separated into solid and liquid, washed with 10.3 g of MTBE, and the obtained wet crystals were dried under reduced pressure to obtain 0.998 g of 1,3-bis (3-phenyl-5-pyrazolyl) benzene crystals. Got. The yield was 33%, and the purity of the obtained white crystals was 99.0% or more.
  • Example 3 is a method for producing a bispyrazole compound (2) having a hydrazine equivalent number of 6.0 and using 2-propanol as an organic solvent.
  • a 100 ml four-necked flask equipped with a thermometer and a stirrer 52.5 g of 2-propanol and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenyl) obtained in Production Example 5 (Propenyl) - ⁇ , ⁇ -dihydrochalcone (5.20 g, 7.90 mmol, 1.0 eq.) was added, and then 2.0.0 g (47.5 mmol, 6.0 eq.) Of 80.0% by mass hydrated hydrazine was added. After the addition, the temperature was raised to 60 ° C. and reacted for 23 hours. The reaction was evaluated by measuring the HPLC of the reaction solution and determining the selectivity.
  • Example 4 is a manufacturing method of the bispyrazole compound (2) whose hydrazine equivalent number is 5.2.
  • a 6 mL screw cap vial 1.5 g of methanol and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone obtained in Production Example 5 were used.
  • 151 g (0.229 mmol, 1.0 eq.) was added, and then 0.0747 g (1.19 mmol, 5.2 eq.) Of 80.0% by mass hydrated hydrazine was added, and the temperature was raised to 60 ° C.
  • the reaction was performed for 24 hours. The reaction was evaluated by measuring the HPLC of the reaction solution and determining the selectivity.
  • Examples 5 to 9 are methods for producing a bispyrazole compound (2) in which the number of hydrazine equivalents was set to the values shown in Table 2, respectively.
  • Examples 5 to 8 were reacted in the same manner as in Example 4 except that the number of hydrazine equivalents was changed to the values shown in Table 2.
  • the reaction was carried out in the same manner as in Example 4 except that the number of hydrazine equivalents was changed to the value shown in Table 2 and the amount of methanol used was changed from 1.5 g to 0.75 g.
  • the reaction was evaluated by measuring the HPLC of the reaction solution and determining the selectivity.
  • Example 10 is a manufacturing method of the bispyrazole compound (2) whose hydrazine equivalent number is 6.9.
  • a 50 mL screw cap vial 10.3 g of methanol, ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone 1 obtained in Production Example 5 0.04 g (1.57 mmol, 1.0 eq.) was added, and then 0.675 g (10.8 mmol, 6.9 eq.) Of 80.0% by mass hydrated hydrazine was added. Reacted for hours. The reaction was evaluated by measuring the HPLC of the reaction solution and determining the selectivity.
  • Examples 11-12, Comparative Examples 1-2> The reaction was performed in the same manner as in Example 10 except that the number of hydrazine equivalents was changed, and HPLC of the reaction solution was measured. The reaction was evaluated by determining the selectivity.
  • Comparative Example 3 is a method for producing a bispyrazole compound (2) using triethylamine as a base compound other than hydrazine.
  • a 20 mL screw cap vial 6.8 g of methanol and 0.412 g (4.07 mmol, 4.0 eq.) Of triethylamine and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-) obtained in Preparation Example 5 were obtained.
  • Oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone was charged in an amount of 0.678 g (1.03 mmol, 1.0 eq.), And then 0.126 g (2.01 mmol, 2 eq.) Of 80.0 mass% hydrated hydrazine. 0.0 eq.), The temperature was raised to 60 ° C. and the reaction was allowed to proceed for 24 hours. The reaction was evaluated by measuring the HPLC of the reaction solution and determining the selectivity.
  • Comparative Example 4 is a method for producing a bispyrazole compound (2) using sodium carbonate as a base compound other than hydrazine.
  • a bispyrazole compound (2) using sodium carbonate as a base compound other than hydrazine.
  • 1.5 g of methanol and 0.0518 g (0.489 mmol, 4.3 eq.) Of sodium carbonate and ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3) obtained in Production Example 5 were added.
  • Comparative Example 5 is based on the reaction conditions described in Non-Patent Document 1.
  • a reaction vessel 294.2 g of methanol and 2.37 g (3.60 mmol, 1.60) of ⁇ , ⁇ -dibromo-3- (1,2-dibromo-3-oxo-3-phenylpropenyl) - ⁇ , ⁇ -dihydrochalcone. 0 eq.)
  • the inside of the system was replaced with nitrogen gas.
  • 3.28 g (52.4 mmol, 15 eq.) Of 80.0% by mass hydrated hydrazine was added, followed by reaction at a reaction temperature of 60 ° C. for 24 hours.
  • the reaction was evaluated by measuring the HPLC of the resulting reaction solution and determining the selectivity.
  • the selectivity was 25.7% at a wavelength of 215 nm and 55.3% at a wavelength of 254 nm.
  • the reaction solution is cooled and concentrated to dryness, and 155.0 g of chloroform and 100.0 g of water are added and extracted three times. Then, the organic layer is concentrated to dryness, redissolved with 22.0 g of chloroform, and 2% aqueous sodium hydroxide solution. Washing was performed 3 times with 13.0 g. The aqueous layer was discarded, and 22.1 g of MTBE was added to the chloroform suspension for crystallization.
  • the slurry was separated into solid and liquid, washed with MTBE, and the resulting wet crystals were dried to obtain 0.23 g of 1,3-bis (3-phenyl-5-pyrazolyl) benzene crystals.
  • the yield was 18% and the purity was 49%.
  • Table 2 summarizes the reaction conditions and selectivities of Examples 1 to 12 and Comparative Examples 1 to 5.
  • the highly pure bispyrazole compound can be produced by the production method of the present invention.
  • the high-purity bispyrazole compound obtained by the production method of the present invention can be suitably used for various medical and agrochemical materials and their production intermediates, analytical reagents, dyes, pigments, optical materials and electronic materials.

Abstract

La présente invention concerne un procédé de production permettant de produire un composé de bispyrazole de grande pureté et de prévenir la survenue d'une réaction secondaire. Le procédé de production d'un composé de bispyrazole représenté par la formule (2) consiste à mettre à réagir un composé représenté par la formule (1) avec de l'hydrazine, le rapport molaire du composé représenté par la formule (1) sur l'hydrazine se situant dans la plage de 1,0 : 5,2 à 1,0 : 11.7.[Dans la formule (1) et la formule (2), R1 et R2 représentent indépendamment un groupe aryle pouvant comporter un substituant].
PCT/JP2015/062283 2014-04-30 2015-04-22 Procede de production d'un compose de bispyrazole WO2015166862A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3122261A1 (de) * 1981-06-04 1982-12-23 Bayer Ag, 5090 Leverkusen Verfahren zur herstellung von pyrazolen
JPH08301854A (ja) * 1995-05-01 1996-11-19 Nippon Hidorajin Kogyo Kk ピラゾロン類の製造法
WO2009027346A2 (fr) * 2007-08-25 2009-03-05 Universität des Saarlandes Inhibiteurs 17bêta-hydroxystéroïd-déhydrogénase de type 1 pour traiter des maladies hormono-dépendantes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3122261A1 (de) * 1981-06-04 1982-12-23 Bayer Ag, 5090 Leverkusen Verfahren zur herstellung von pyrazolen
JPH08301854A (ja) * 1995-05-01 1996-11-19 Nippon Hidorajin Kogyo Kk ピラゾロン類の製造法
WO2009027346A2 (fr) * 2007-08-25 2009-03-05 Universität des Saarlandes Inhibiteurs 17bêta-hydroxystéroïd-déhydrogénase de type 1 pour traiter des maladies hormono-dépendantes

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