JP2005200344A - High-purity 1,2,3,4-tetrahydro-4-oxocarbazole compound and refining method therefor - Google Patents
High-purity 1,2,3,4-tetrahydro-4-oxocarbazole compound and refining method therefor Download PDFInfo
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本発明は、医薬中間体として有用な高純度１，２，３，４−テトラヒドロ−４−オキソカルバゾール類およびその精製方法に関し、さらに詳しくは、１,３−シクロヘキサンジオンモノフェニルヒドラゾン類を、塩化亜鉛および酢酸を用いてフィッシャー転移反応させて得られた、１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を含む反応液中から、高純度の１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を、効率良く工業的に有利に得る方法に関する。 The present invention relates to high-purity 1,2,3,4-tetrahydro-4-oxocarbazoles useful as pharmaceutical intermediates and a purification method thereof, and more particularly, 1,3-cyclohexanedione monophenylhydrazones are chlorinated. From a reaction solution containing 1,2,3,4-tetrahydro-4-oxocarbazole obtained by Fischer rearrangement reaction using zinc and acetic acid, high-purity 1,2,3,4-tetrahydro- The present invention relates to a method for obtaining 4-oxocarbazoles efficiently and industrially advantageously.
１,３−シクロヘキサンジオンモノフェニルヒドラゾン類を、フィッシャー転移により１，２，３，４−テトラヒドロ−４−オキソカルバゾール類に変える反応として、硫酸（非特許文献１）、トリフルオロ酢酸（非特許文献２、特許文献１）、イオン交換樹脂（非特許文献３）および酢酸中塩化亜鉛（特許文献２）を触媒として用いる方法が知られている。しかしながら、硫酸、トリフルオロ酢酸を用いた場合、不純物が多く収率、純度が低くなる欠点がある、また、トリフルオロ酢酸、イオン交換樹脂を用いた場合、触媒が高価であり経済面で問題がある。 As a reaction to convert 1,3-cyclohexanedione monophenylhydrazone to 1,2,3,4-tetrahydro-4-oxocarbazole by Fischer transfer, sulfuric acid (Non-patent Document 1), trifluoroacetic acid (Non-patent Document) 2, Patent Document 1), ion-exchange resin (Non-Patent Document 3) and zinc chloride in acetic acid (Patent Document 2) are known as catalysts. However, when sulfuric acid or trifluoroacetic acid is used, there are disadvantages in that there are many impurities and the yield and purity are low, and when trifluoroacetic acid and ion exchange resin are used, the catalyst is expensive and there is a problem in terms of economy. is there.
塩化亜鉛を用いた場合、不純物の生成が少なく、触媒も安価であるが、反応には理論量以上の塩化亜鉛を必要とすることが知られている（非特許文献４）。一方、目的物を回収するために、反応液を多量の（特許文献２では原料に対して５０重量倍もの）水中に添加し、結晶を析出、濾取している、そのため塩化亜鉛を含む多量の廃水が生成し、工業的規模の製造において、環境面、経済面で大きな問題がある。また、反応液を水中に添加した場合、目的物以外の原料、副生成物等の一部も同時に回収されるため、純度が低いという欠点がある。 When zinc chloride is used, the generation of impurities is small and the catalyst is inexpensive, but it is known that the reaction requires more than the theoretical amount of zinc chloride (Non-patent Document 4). On the other hand, in order to recover the target product, the reaction solution is added to a large amount of water (50 weight times the raw material in Patent Document 2), and crystals are precipitated and collected. Therefore, a large amount of zinc chloride is contained. Wastewater is generated, and there are significant environmental and economic problems in industrial scale manufacturing. Moreover, when a reaction liquid is added in water, since raw materials other than the target substance, a by-product, etc. are also collect | recovered simultaneously, there exists a fault that purity is low.
本発明は、１，２，３，４−テトラヒドロ−４−オキソカルバゾール類、塩化亜鉛、および酢酸を含む反応液中より、医薬中間体として有用な高純度の１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を、効率良く工業的に有利に得る精製方法を提供するものである。 The present invention relates to a highly pure 1,2,3,4-tetrahydro compound useful as a pharmaceutical intermediate from a reaction solution containing 1,2,3,4-tetrahydro-4-oxocarbazole, zinc chloride, and acetic acid. The present invention provides a purification method for efficiently obtaining industrially advantageous -4-oxocarbazoles.
本発明者らは前記の課題を解決すべく鋭意研究を重ねた結果、式（１）
で表される１,３−シクロヘキサンジオンモノフェニルヒドラゾン類を、塩化亜鉛、および酢酸の存在下に反応して得られた、式（２）
（式中Ｒ１〜Ｒ７は水素原子または炭化水素基を示す）
で表される１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を含む反応液と、式（３）
で表されるアルコール類、または／および式（４）
で表されるケトン類を混合し、１，２，３，４−テトラヒドロ−４−オキソカルバゾール類の結晶を析出させることにより、塩化亜鉛を含む多量の廃水を生じることなく、また、従来法に比して簡単な操作で、効率良く高純度の１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を得ることができることを見出し、本発明を完成するに至った。
As a result of intensive studies to solve the above-mentioned problems, the present inventors have obtained the formula (1)
1,3-cyclohexanedione monophenylhydrazone represented by the formula (2) obtained by reacting in the presence of zinc chloride and acetic acid
(Wherein R1 to R7 represent a hydrogen atom or a hydrocarbon group)
A reaction solution containing 1,2,3,4-tetrahydro-4-oxocarbazole represented by formula (3)
Or / and formula (4)
By mixing the ketones represented by As a result, it has been found that high-purity 1,2,3,4-tetrahydro-4-oxocarbazoles can be obtained efficiently and with a simpler operation, and the present invention has been completed.
以下本発明についてさらに詳細に説明する。
本発明において用いられる１,３−シクロヘキサンジオンモノフェニルヒドラゾン類としては下式（１）で表される。
（式中Ｒ１〜Ｒ７は水素原子又は炭化水素基を示す）
The present invention will be described in further detail below.
The 1,3-cyclohexanedione monophenylhydrazone used in the present invention is represented by the following formula (1).
(Wherein R1 to R7 represent a hydrogen atom or a hydrocarbon group)
Ｒ１〜Ｒ７は特に限定されないが、好ましくは水素、アルキル基、アリール基又はアラルキル基であり、更に好ましくは水素又はアルキル基である。アルキル基の具体例としては、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ｔ−ブチル基、ｎ−ペンチル基、ネオペンチル基、ｎ−オクチル基、ｎ−ノニル基、シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基、メチルシクロペンチル基、メチルシクロヘキシル基等を挙げることができる。これらの中でも、メチル基、エチル基が特に好ましい。アリール基の具体例としては、フェニル基、ｏ−メチルフェニル、ｍ−メチルフェニル、ｐ−メチルフェニル、ｏ−メトキシフェニル、ｍ−メトキシフェニル、ｐ−メトキシフェニル、ｏ−ヒドロキシフェニル基、キシリル基、メシチル基等を挙げることができる。アラルキル基の具体例としては、ベンジル基、ｏ−メチルベンジル基、ｍ−メチルベンジル基、ｐ−メチルベンジル基、ｏ−アニシル基、ｍ−アニシル基、ｐ−アニシル基、ｏ−クロロベンジル基、ｍ−クロロベンジル基、ｐ−クロロベンジル基、ｏ−フルオロベンジル基、ｍ−フルオロベンジル基、ｐ−フルオロベンジル基、フェネチル基等を挙げることができる。 R1 to R7 are not particularly limited, but are preferably hydrogen, an alkyl group, an aryl group, or an aralkyl group, and more preferably hydrogen or an alkyl group. Specific examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, n-pentyl, neopentyl, n-octyl, n-nonyl, cyclo A propyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a methylcyclopentyl group, a methylcyclohexyl group, and the like can be given. Among these, a methyl group and an ethyl group are particularly preferable. Specific examples of the aryl group include a phenyl group, o-methylphenyl, m-methylphenyl, p-methylphenyl, o-methoxyphenyl, m-methoxyphenyl, p-methoxyphenyl, o-hydroxyphenyl group, xylyl group, A mesityl group etc. can be mentioned. Specific examples of the aralkyl group include benzyl group, o-methylbenzyl group, m-methylbenzyl group, p-methylbenzyl group, o-anisyl group, m-anisyl group, p-anisyl group, o-chlorobenzyl group, Examples thereof include m-chlorobenzyl group, p-chlorobenzyl group, o-fluorobenzyl group, m-fluorobenzyl group, p-fluorobenzyl group, phenethyl group and the like.
本発明において用いられる塩化亜鉛、および酢酸の量は、特に限定されるものではないが、使用する塩化亜鉛の量は、１,３−シクロヘキサンジオンモノフェニルヒドラゾン類に対して、通常２〜１０モル倍量、好ましくは３〜７モル倍量である。この量が少なすぎると収率が低下し、逆に多すぎても使用量に相応した著しい効果は認められない。使用する酢酸の量は、１,３−シクロヘキサンジオンモノフェニルヒドラゾン類に対して、通常１〜１５重量倍量、好ましくは１〜１０倍量、さらに好ましくは１〜６倍量である。この量が少なすぎると反応時の攪拌が困難になり、逆に多すぎると結晶析出時の収率が低下する。 The amount of zinc chloride and acetic acid used in the present invention is not particularly limited, but the amount of zinc chloride used is usually 2 to 10 mol with respect to 1,3-cyclohexanedione monophenylhydrazone. Double amount, preferably 3 to 7 mole times. If this amount is too small, the yield decreases, and conversely, if it is too large, no significant effect corresponding to the amount used is observed. The amount of acetic acid to be used is usually 1 to 15 times by weight, preferably 1 to 10 times, more preferably 1 to 6 times the amount of 1,3-cyclohexanedione monophenylhydrazone. If this amount is too small, stirring during the reaction becomes difficult. Conversely, if it is too large, the yield at the time of crystal precipitation decreases.
本発明における反応条件は、特に限定されるものではないが、一般的なフィッシャー転移反応と同条件で実施可能である。例えば、窒素雰囲気下または気流下、１,３−シクロヘキサンジオンモノフェニルヒドラゾン類、塩化亜鉛、および酢酸を８０〜１１０℃の温度範囲で、４〜８時間加熱攪拌することにより１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を含む反応液を得ることができる。 Although the reaction conditions in this invention are not specifically limited, It can implement on the same conditions as a general Fisher transfer reaction. For example, 1,3-cyclohexanedione monophenylhydrazone, zinc chloride, and acetic acid are heated and stirred in a temperature range of 80 to 110 ° C. for 4 to 8 hours in a nitrogen atmosphere or in an air stream. A reaction solution containing 4-tetrahydro-4-oxocarbazole can be obtained.
本発明において、上記反応液と一般式（２）、（３）で示される、アルコール類、および／またはケトン類を混合することにより、目的物を結晶として析出させることができる。反応液と混合するアルコール類、および／またはケトン類としては、目的物の溶解度が低く、塩化亜鉛の溶解度が高いものが好ましい、アルコール類の具体例としては、メタノール、エタノール、プロパノール、イソプロパノール、ブタノール、イソブタノール、ｔ−ブタノールが挙げられる。ケトン類の具体例としては、アセトン、メチルエチルケトン、メチルプロピルケトン、ジエチルケトン、ジプロピルケトン、ジイソプロピルケトンが挙げられる。これらの中で目的物の回収率が高いことから、特にメタノール、エタノール、アセトンが好ましい。これらのアルコール類、および／またはケトン類は単独で使用しても良く、２種以上の混合物として使用することもできる。 In the present invention, the target product can be precipitated as crystals by mixing the reaction solution and alcohols and / or ketones represented by the general formulas (2) and (3). As alcohols and / or ketones to be mixed with the reaction solution, those having low solubility of the target product and high solubility of zinc chloride are preferable. Specific examples of alcohols include methanol, ethanol, propanol, isopropanol, and butanol. , Isobutanol and t-butanol. Specific examples of ketones include acetone, methyl ethyl ketone, methyl propyl ketone, diethyl ketone, dipropyl ketone, and diisopropyl ketone. Among these, methanol, ethanol, and acetone are particularly preferable because of the high recovery rate of the target product. These alcohols and / or ketones may be used alone or as a mixture of two or more.
使用するアルコール類、および／またはケトン類の量は、１,３−シクロヘキサンジオンモノフェニルヒドラゾン類に対して、通常０．７〜１３重量倍量、好ましくは１.０〜８倍量、さらに好ましくは１．３〜５倍量である。この量が少なすぎると、目的物が結晶として析出しない場合があり、また、結晶が析出した場合でも、目的物を濾取する際の濾過性が著しく悪化する。逆に多すぎると目的物の収率が低下する。 The amount of alcohols and / or ketones used is usually 0.7 to 13 times by weight, preferably 1.0 to 8 times, more preferably 1,3-cyclohexanedione monophenylhydrazone. Is 1.3 to 5 times the amount. If the amount is too small, the target product may not be precipitated as crystals, and even when crystals are precipitated, the filterability when the target product is filtered is significantly deteriorated. On the other hand, if the amount is too large, the yield of the target product decreases.
反応液とアルコール類、および／またはケトン類の混合は、反応液中にアルコール類、および／またはケトン類を加えても良く、逆に、アルコール類、および／またはケトン類中に反応液を加えることもできるが、反応液が粘性液体であるため、操作性の面から、反応液中にアルコール類、および／またはケトン類を加える方が好ましい。アルコール類、および／またはケトン類を混合する温度は特に限定されないが、混合時発熱を伴うため、６０℃以下に冷却後行なうのが好ましい。アルコール類、および／またはケトン類を混合後、攪拌下室温付近、場合によってはそれ以下の温度まで冷却し、析出した結晶を濾取することにより、高純度の目的物を得ることができる。また、必要に応じて、濾過後アルコール類、ケトン類または水等で洗浄することにより、さらに高純度の目的物を得ることができる。 In mixing the reaction solution with alcohols and / or ketones, the alcohols and / or ketones may be added to the reaction solution, and conversely, the reaction solution is added to the alcohols and / or ketones. However, since the reaction solution is a viscous liquid, it is preferable to add alcohols and / or ketones to the reaction solution from the viewpoint of operability. The temperature at which the alcohols and / or ketones are mixed is not particularly limited, but it is preferably performed after cooling to 60 ° C. or lower because it generates heat during mixing. After mixing the alcohols and / or ketones, the mixture is cooled to room temperature with stirring, or in some cases, to a temperature lower than that, and the precipitated crystals are collected by filtration to obtain a high-purity target product. Further, if necessary, the product of higher purity can be obtained by washing with alcohol, ketones or water after filtration.
本発明の方法によれば１,３−シクロヘキサンジオンモノフェニルヒドラゾン類の、塩化亜鉛および酢酸を用いたフィッシャー転移反応により得られた、１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を含む反応液中から高純度の１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を効率良く工業的有利に得ることができる。 According to the method of the present invention, 1,2,3,4-tetrahydro-4-oxocarbazole obtained by Fischer rearrangement reaction of 1,3-cyclohexanedione monophenylhydrazone using zinc chloride and acetic acid is obtained. High-purity 1,2,3,4-tetrahydro-4-oxocarbazoles can be efficiently and advantageously obtained industrially from the contained reaction liquid.
以下に実施例を挙げて、本発明を更に詳細に説明するが、本発明はこれに限定されるものではない。 The present invention will be described in more detail with reference to examples below, but the present invention is not limited thereto.
反応容器に１,３−シクロヘキサンジオンモノフェニルヒドラゾン２６．３ｇ、酢酸５２．６ｇ、および塩化亜鉛７９．１ｇを入れ、窒素気流下９５〜１００℃で７時間反応を行ない、赤褐色の反応液を得た。この反応液を５０℃まで冷却した後、反応液中にメタノール４３．７ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌した。析出した結晶を濾別し、メタノール、ついで水でリンス洗浄後、乾燥させ、淡黄色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１５．５ｇ（収率６５.０％）を得た。この結晶をＬＣで分析した結果、純度９９．９％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分２１ｐｐｍであった。 A reaction vessel was charged with 26.3 g of 1,3-cyclohexanedione monophenylhydrazone, 52.6 g of acetic acid, and 79.1 g of zinc chloride, and reacted at 95-100 ° C. for 7 hours under a nitrogen stream to obtain a reddish brown reaction solution. It was. After cooling the reaction solution to 50 ° C., 43.7 g of methanol was added to the reaction solution, gradually cooled to room temperature, and stirred at room temperature for about 2 hours. The precipitated crystals were separated by filtration, rinsed with methanol and then with water and dried, and 15.5 g (yield 65.0%) of pale yellow 1,2,3,4-tetrahydro-4-oxocarbazole crystals were obtained. Obtained. As a result of analyzing the crystals by LC, the purity was 99.9%. Moreover, as a result of measuring the zinc content in the crystal by atomic absorption, the zinc content was 21 ppm.
実施例１と同様に反応を行ない、得られた反応液を５０℃まで冷却した後、エタノール６５．６ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌した。析出した結晶を濾別し、エタノールついで水で洗浄後、乾燥させ、淡黄色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１５．０ｇ（収率６３.１％）を得た。この結晶をＬＣで分析した結果、純度９９．９％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分５６ｐｐｍであった。 The reaction was carried out in the same manner as in Example 1. The obtained reaction solution was cooled to 50 ° C., 65.6 g of ethanol was added, the solution was gradually cooled to room temperature, and stirred at room temperature for about 2 hours. The precipitated crystals were separated by filtration, washed with ethanol and then water and dried to obtain 15.0 g of light yellow 1,2,3,4-tetrahydro-4-oxocarbazole crystals (yield 63.1%). . As a result of analyzing the crystals by LC, the purity was 99.9%. Further, the zinc content in the crystal was measured by atomic absorption, and as a result, the zinc content was 56 ppm.
実施例１と同様に反応を行ない、得られた反応液を５０℃まで冷却した後、アセトン４４．２ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌した。析出した結晶を濾別し、アセトンついで水で洗浄後、乾燥させ、淡黄色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１４．４ｇ（収率６１．２％）を得た。この結晶をＬＣで分析した結果、純度９９．７％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分３０ｐｐｍであった。 The reaction was carried out in the same manner as in Example 1. The obtained reaction solution was cooled to 50 ° C., 44.2 g of acetone was added, the mixture was gradually cooled to room temperature, and stirred at room temperature for about 2 hours. The precipitated crystals were separated by filtration, washed with acetone and then with water and dried to obtain 14.4 g (yield 61.2%) of pale yellow 1,2,3,4-tetrahydro-4-oxocarbazole crystals. . As a result of analyzing the crystals by LC, the purity was 99.7%. Moreover, as a result of measuring the zinc content in the crystal by atomic absorption, the zinc content was 30 ppm.
実施例１と同様に反応を行ない、得られた反応液を５０℃まで冷却した後、イソプロパノール４３．７ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌した。析出した結晶を濾別し、イソプロパノールついで水で洗浄後、乾燥させ、淡黄色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１５．１ｇ（収率６３．３％）を得た。この結晶をＬＣで分析した結果、純度９８．５％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分２３０ｐｐｍであった。 The reaction was carried out in the same manner as in Example 1. The obtained reaction solution was cooled to 50 ° C., 43.7 g of isopropanol was added, the solution was gradually cooled to room temperature, and stirred at room temperature for about 2 hours. The precipitated crystals were separated by filtration, washed with isopropanol and then with water, and then dried to obtain 15.1 g (yield 63.3%) of pale yellow 1,2,3,4-tetrahydro-4-oxocarbazole crystals. . As a result of analyzing the crystals by LC, the purity was 98.5%. Moreover, as a result of measuring the zinc content in the crystal by atomic absorption, the zinc content was 230 ppm.
実施例１と同様に反応を行ない、得られた反応液を５０℃まで冷却した後、メタノール１３１．１ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌した。析出した結晶を濾別し、メタノールついで水で洗浄後、乾燥させ、淡黄色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１１．８ｇ（収率４９．７％）を得た。この結晶をＬＣで分析した結果、純度９９．９％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分４ｐｐｍであった。
The reaction was carried out in the same manner as in Example 1. The obtained reaction solution was cooled to 50 ° C., 131.1 g of methanol was added, the solution was gradually cooled to room temperature, and stirred at room temperature for about 2 hours. The precipitated crystals were separated by filtration, washed with methanol and then water, and dried to obtain 11.8 g (yield 49.7%) of pale yellow 1,2,3,4-tetrahydro-4-oxocarbazole crystals. . As a result of analyzing the crystals by LC, the purity was 99.9%. Moreover, as a result of measuring the zinc content in the crystal by atomic absorption, the zinc content was 4 ppm.
（比較例１）
実施例１と同様に反応を行ない、得られた反応液を７０℃まで冷却した後、水６４７ｇ中に反応液を徐々に加えて結晶を析出させた。これを室温で約２時間攪拌した後濾別し、水で洗浄後、乾燥させ、黄緑色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１８．９ｇ（収率７９．２％）を得た。この結晶をＬＣで分析した結果、純度７０．３％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分４７００ｐｐｍであった。
(Comparative Example 1)
The reaction was carried out in the same manner as in Example 1. The obtained reaction solution was cooled to 70 ° C., and then the reaction solution was gradually added to 647 g of water to precipitate crystals. The mixture was stirred at room temperature for about 2 hours, filtered, washed with water, dried, and 18.9 g of yellowish green 1,2,3,4-tetrahydro-4-oxocarbazole crystals (yield 79.2%). ) As a result of analyzing the crystals by LC, the purity was 70.3%. Moreover, as a result of measuring the zinc content in the crystal by atomic absorption, the zinc content was 4700 ppm.
（比較例２）
実施例１と同様に反応を行ない、得られた反応液を５０℃まで冷却した後、イソアミルアルコール４３．７ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌した。析出した結晶を濾別し、イソアミルアルコールついで水で洗浄後、乾燥させ、淡黄色の１，２，３，４−テトラヒドロ−４−オキソカルバゾール結晶１３．５ｇ（収率５６．７％）を得た。この結晶をＬＣで分析した結果、純度６１．０％であった。また、結晶中の亜鉛分を原子吸光で測定した結果、亜鉛分５１００ｐｐｍであった。
(Comparative Example 2)
The reaction was carried out in the same manner as in Example 1. The obtained reaction solution was cooled to 50 ° C., 43.7 g of isoamyl alcohol was added, the solution was gradually cooled to room temperature, and stirred at room temperature for about 2 hours. The precipitated crystals were separated by filtration, washed with isoamyl alcohol and then with water, and then dried to obtain 13.5 g (yield 56.7%) of pale yellow 1,2,3,4-tetrahydro-4-oxocarbazole crystals. It was. As a result of analyzing the crystals by LC, the purity was 61.0%. Moreover, as a result of measuring the zinc content in the crystal by atomic absorption, the zinc content was 5100 ppm.
（比較例３）
実施例１と同様に反応を行ない、得られた反応液を５０℃まで冷却した後、ジイソブチルケトン４３．７ｇを加えて室温まで徐々に冷却、室温で約２時間攪拌したが結晶は析出しなかった。
(Comparative Example 3)
The reaction was carried out in the same manner as in Example 1. After cooling the resulting reaction solution to 50 ° C., 43.7 g of diisobutyl ketone was added, and the mixture was gradually cooled to room temperature and stirred at room temperature for about 2 hours, but no crystals precipitated. It was.
Claims (5)
で表される１,３−シクロヘキサンジオンモノフェニルヒドラゾン類を塩化亜鉛および酢酸の存在下に反応させて得られた、式（２）
で表される１，２，３，４−テトラヒドロ−４−オキソカルバゾール類を含む反応液と、式（３）
で表されるアルコール類、または／および式（４）
で表されるケトン類を混合し、１，２，３，４−テトラヒドロ−４−オキソカルバゾール類の結晶を析出させることを特徴とする１，２，３，４−テトラヒドロ−４−オキソカルバゾール類の精製方法。 Formula (1)
Obtained by reacting 1,3-cyclohexanedione monophenylhydrazone represented by the formula (2) in the presence of zinc chloride and acetic acid.
A reaction solution containing 1,2,3,4-tetrahydro-4-oxocarbazole represented by formula (3)
Or / and formula (4)
1,2,3,4-Tetrahydro-4-oxocarbazole is precipitated by mixing the ketones represented by formula (1), and the 1,2,3,4-tetrahydro-4-oxocarbazole is precipitated. Purification method.
The amount of alcohols and / or ketones used is 0.7 to 13 times by weight with respect to 1,3-cyclohexanedione monophenylhydrazones. Purification method.
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