JP6994299B2 - A method for purifying a dihydroxy compound having a fluorene skeleton - Google Patents

Description

本発明は、光学レンズや光学フィルムに代表される光学部材を構成する樹脂（光学樹脂）を形成するモノマーとして好適で、加工性、生産性に優れた新規なフルオレン骨格を有するジヒドロキシ化合物の精製方法に関する。 INDUSTRIAL APPLICABILITY The present invention is a method for purifying a dihydroxy compound having a novel fluorene skeleton, which is suitable as a monomer for forming a resin (optical resin) constituting an optical member represented by an optical lens or an optical film and has excellent processability and productivity. Regarding.

フルオレン骨格を有するジヒドロキシ化合物を原料モノマーとするポリカーボネート、ポリエステル、ポリアクリレート、ポリウレタン、エポキシなどの樹脂材料は、光学特性、耐熱性等に優れることから、近年、光学レンズや光学シートなどの新たな光学材料として注目されている。この中でも下記式（１） In recent years, new optics such as optical lenses and optical sheets have been used because resin materials such as polycarbonate, polyester, polyacrylate, polyurethane, and epoxy, which are made from a dihydroxy compound having a fluorene skeleton as a raw material monomer, have excellent optical properties and heat resistance. It is attracting attention as a material. Among these, the following formula (1)

で表される構造を有するジヒドロキシ化合物は、該ジヒドロキシ化合物から製造される樹脂が屈折率等の光学特性、耐熱性、耐水性、耐薬品性、電気特性、機械特性、溶解性等の諸特性に優れることから、特に光学樹脂の原材料として着目されている（例えば特許文献１～４）。

In the dihydroxy compound having the structure represented by, the resin produced from the dihydroxy compound has various properties such as optical properties such as refractive index, heat resistance, water resistance, chemical resistance, electrical properties, mechanical properties, and solubility. Since it is excellent, it is attracting particular attention as a raw material for optical resins (for example, Patent Documents 1 to 4).

上記式（１）で表されるジヒドロキシ化合物の製造方法としては、塩基触媒存在下、下記式（２） As a method for producing the dihydroxy compound represented by the above formula (1), the following formula (2) is used in the presence of a base catalyst.

で表されるフェノール化合物とエチレンオキサイドとを反応させる方法が知られている（特許文献２）。しかしながら、該方法で得られる上記式（１）で表されるジヒドロキシ化合物はその純度が低く、エチレンオキサイドが３分子以上付加した化合物（以下、多量体と称することもある）が多量に副生し、目的とする上記式（１）で表されるジヒドロキシ化合物を高純度で得ることは困難である。

A method of reacting a phenol compound represented by (Patent Document 2) with ethylene oxide is known (Patent Document 2). However, the dihydroxy compound represented by the above formula (1) obtained by the method has a low purity, and a large amount of a compound having three or more molecules of ethylene oxide added (hereinafter, also referred to as a multimer) is by-produced. It is difficult to obtain the target dihydroxy compound represented by the above formula (1) with high purity.

一方、上記式（１）で表されるジヒドロキシ化合物の改良製法として、酸触媒及びチオール類存在下、下記式（３） On the other hand, as an improved method for producing the dihydroxy compound represented by the above formula (1), the following formula (3) is used in the presence of an acid catalyst and thiols.

で表されるアルコールと９－フルオレノンとを反応させ上記式（１）で表されるジヒドロキシ化合物を得る方法が提案され（特許文献３）、また、該製法による着色の問題を改善する手法として、酸触媒及び９―フルオレノン類１００重量部に対して３重量部以上のチオール類存在下、上記式（３）で表されるアルコールと９―フルオレノンとを反応させ上記式（１）で表されるジヒドロキシ化合物を得る方法が提案されている（特許文献４）。

A method for obtaining a dihydroxy compound represented by the above formula (1) by reacting an alcohol represented by the above formula with 9-fluorenone has been proposed (Patent Document 3), and as a method for improving the problem of coloring by the production method, In the presence of 3 parts by weight or more of thiols with respect to 100 parts by weight of the acid catalyst and 9-fluorenone, the alcohol represented by the above formula (3) is reacted with 9-fluorenone and represented by the above formula (1). A method for obtaining a dihydroxy compound has been proposed (Patent Document 4).

しかしながら、該方法でもその着色改善は十分ではなく、また、反応時に多量のチオール類を必要とすることから、生成物からチオール類を完全に除去することが困難であり、該ジヒドロキシ化合物から樹脂を製造する際、チオール類に由来する硫黄分が樹脂の更なる着色を引き起こすといった問題がある。 However, even with this method, the improvement in coloring is not sufficient, and since a large amount of thiols are required at the time of reaction, it is difficult to completely remove the thiols from the product, and the resin is obtained from the dihydroxy compound. During production, there is a problem that the sulfur content derived from thiols causes further coloring of the resin.

また、本願発明者らが上記特許文献２～４に記載される方法を追試したところ、特許文献３記載の方法では反応が進行しないか、あるいは反応が進行したとしても、上記式（１）で表されるジヒドロキシ化合物を含むオイル状物が得られるのみで、結晶状の上記式（１）で表されるジヒドロキシ化合物は得られなかった。また、特許文献２及び４の追試では、得られる上記式（１）で表されるジヒドロキシ化合物の結晶は、反応や反応後の取り出し操作（晶析操作）で使用した溶媒（芳香族炭化水素類）を取り込み、包接体となることが判明した。 Further, when the inventors of the present application retested the methods described in Patent Documents 2 to 4, the reaction did not proceed by the method described in Patent Document 3, or even if the reaction proceeded, the above formula (1) was used. Only an oily substance containing the represented dihydroxy compound was obtained, and a crystalline dihydroxy compound represented by the above formula (1) was not obtained. Further, in the additional tests of Patent Documents 2 and 4, the obtained crystals of the dihydroxy compound represented by the above formula (1) are the solvent (aromatic hydrocarbons) used in the reaction and the removal operation (crystallization operation) after the reaction. ) Was taken up and it was found to be an inclusion body.

特開平０７―１４９８８１号公報Japanese Unexamined Patent Publication No. 07-149881 特開２００１－１２２８２８号公報Japanese Unexamined Patent Publication No. 2001-122828 特開２００１－２０６８６３号公報Japanese Unexamined Patent Publication No. 2001-206863 特開２００９－２５６３４２号公報Japanese Unexamined Patent Publication No. 2009-256342

本発明の目的は、上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶から、包接された化合物（ゲスト分子）を除去又は低減させる方法を提供することにある。 An object of the present invention is to provide a method for removing or reducing an encapsulated compound (guest molecule) from a crystal of an inclusion body having a dihydroxy compound represented by the above formula (1) as a host molecule. ..

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、上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶と、メタノールとを接触させることによって、包接された化合物（ゲスト分子）を除去又は低減させることが可能であることを見出した。具体的には以下の発明を含む。 As a result of diligent research to solve the above-mentioned problems, the present inventors have brought the crystals of an inclusion body having the dihydroxy compound represented by the above formula (1) as a host molecule into contact with methanol. , Found that it is possible to remove or reduce the encapsulated compound (guest molecule). Specifically, the following inventions are included.

〔１〕
下記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶と、メタノールとを接触させる工程を含む、下記式 （１）で表されるジヒドロキシ化合物の結晶の精製方法。

[1]
A method for purifying a crystal of a dihydroxy compound represented by the following formula (1), which comprises a step of contacting a crystal of an inclusion body having a dihydroxy compound represented by the following formula (1) as a host molecule with methanol.

〔２〕
接触後、上記式（１）で表されるジヒドロキシ化合物の結晶とメタノールとを分離する工程を含む、〔１〕に記載のジヒドロキシ化合物の結晶の精製方法。 [2]
The method for purifying a crystal of a dihydroxy compound according to [1], which comprises a step of separating the crystal of the dihydroxy compound represented by the above formula (1) and methanol after contacting.

本発明によれば、上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶からゲスト分子を除去又は低減させることが可能となる。上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶を樹脂原料として使用すると、該結晶の溶融中に包接されていたゲスト分子が放出されるため、放出されたゲスト分子を安全に系外へと除去する必要があったり、包接されているゲスト分子の影響で、得られる樹脂の品質が一定とならない等の問題を引き起こすことがある。更には、上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶を保管や輸送する際、ゲスト分子に起因する引火可能性等を考慮する必要があり、より厳密な防災上の対策も必要となる。 According to the present invention, it is possible to remove or reduce the guest molecule from the crystal of the clathrate having the dihydroxy compound represented by the above formula (1) as the host molecule. When a crystal of an inclusion body having a dihydroxy compound represented by the above formula (1) as a host molecule is used as a resin raw material, the guest molecule encapsulated during the melting of the crystal is released, and thus the inclusion molecule is released. It may be necessary to safely remove guest molecules to the outside of the system, or the quality of the obtained resin may not be constant due to the influence of the included guest molecules. Furthermore, when storing or transporting the crystal of the inclusion body using the dihydroxy compound represented by the above formula (1) as the host molecule, it is necessary to consider the flammability caused by the guest molecule, which is more strict. Disaster prevention measures are also required.

本発明の精製方法に供することができる、上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶（以下、包接体の結晶と称することがある）は、包接可能な化合物をゲスト分子として有していても良い。ゲスト分子になり得る化合物として例えば、芳香族炭化水素類（具体的に例えばトルエン、キシレン、クロロベンゼン、ジクロロベンゼン等）、環状ケトン類（具体的に例えばシクロヘキサノン、シクロペンタノン、シクロオクタノン等）、エステル類（具体的に例えば酢酸エチル、酢酸ブチル、酢酸イソブチル等）が挙げられる。 A crystal of an inclusion body having a dihydroxy compound represented by the above formula (1) as a host molecule (hereinafter, may be referred to as a crystal of an inclusion body) that can be used in the purification method of the present invention is included. It may have a possible compound as a guest molecule. Examples of compounds that can be guest molecules include aromatic hydrocarbons (specifically, for example, toluene, xylene, chlorobenzene, dichlorobenzene, etc.), cyclic ketones (specifically, for example, cyclohexanone, cyclopentanone, cyclooctanone, etc.), and the like. Examples thereof include esters (specifically, for example, ethyl acetate, butyl acetate, isobutyl acetate, etc.).

結晶が包接体であるか否かは、例えば、ＴＧ－ＤＴＡ（熱重量・示差熱同時測定）分析、Ｘ線回折、ＮＭＲ分析といった方法の他、得られた結晶を、ゲスト分子の沸点以上となる条件で重量変化がない程度に十分に乾燥させた後、得られた結晶を溶媒に溶解させ、ガスクロマトグラフィーや高速液体クロマトグラフィーを用いて分析し、ゲスト分子に相当するピークが残存するか否かで判断することができる。また、前記ＴＧ－ＤＴＡ分析を用いる方法では、測定サンプルを一定の速度で昇温した際の重量変化と、それに伴う吸熱・発熱挙動を測定でき、重量変化と吸熱（又は発熱）とが同時に観測された時点で、ゲスト分子が放出されたことを判断することもできる。 Whether or not the crystal is an inclusion body is determined by, for example, TG-DTA (simultaneous measurement of thermal weight and differential heat) analysis, X-ray diffraction, NMR analysis, and the obtained crystal is above the boiling point of the guest molecule. After sufficiently drying to the extent that there is no change in weight under the above conditions, the obtained crystals are dissolved in a solvent and analyzed by gas chromatography or high-speed liquid chromatography, and a peak corresponding to a guest molecule remains. It can be judged by whether or not. Further, in the method using the TG-DTA analysis, the weight change when the temperature of the measurement sample is raised at a constant rate and the endothermic / exothermic behavior associated therewith can be measured, and the endothermic / heat absorption (or heat generation) can be observed at the same time. At that time, it can also be determined that the guest molecule has been released.

本発明における、「上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶とメタノールとを接触させる」操作とは、包接体の結晶と、液体、または気体のメタノールとが接触することを言い、具体的に例えば、包接体の結晶と、メタノールとを容器に入れ、メタノール中で包接体の結晶を撹拌混合させる操作や、包接体の結晶にメタノールを混合した後乾燥機に入れ、メタノールを気化させながら除去する操作等が挙げられる。 In the present invention, the operation of "contacting methanol with a crystal of an inclusion body having a dihydroxy compound represented by the above formula (1) as a host molecule" means that the crystal of the inclusion body and liquid or gaseous methanol are used. Specifically, for example, an operation in which the crystals of the inclusion body and methanol are placed in a container and the crystals of the inclusion body are stirred and mixed in methanol, or methanol is added to the crystals of the inclusion body. Examples thereof include an operation in which methanol is removed while being vaporized by putting it in a dryer after mixing.

本発明の精製方法に供されるメタノールにはメタノール以外の有機化合物を含んでいてもよい。他の有機化合物を含む場合、全有機化合物（メタノール＋他の有機化合物）中のメタノール濃度は通常６０重量％以上、好ましくは７０重量％以上、更に好ましくは８０重量％以上である。他の有機化合物を用いる場合、本発明の精製方法を実施する際、他の有機化合物とメタノールとを予め混合したものを包接体の結晶と接触させてもよく、また、包接体の結晶と他の有機化合物とを含む混合液や懸濁体にメタノールを添加することで、包接体の結晶とメタノールとを接触させてもよい。 The methanol used in the purification method of the present invention may contain an organic compound other than methanol. When other organic compounds are contained, the concentration of methanol in the total organic compound (methanol + other organic compounds) is usually 60% by weight or more, preferably 70% by weight or more, and more preferably 80% by weight or more. When another organic compound is used, when the purification method of the present invention is carried out, a mixture of the other organic compound and methanol in advance may be brought into contact with the crystal of the inclusion body, or the crystal of the inclusion body may be used. Methanol may be brought into contact with the crystals of the clathrate by adding methanol to a mixed solution or suspension containing the above and other organic compounds.

なお、本発明の精製方法を実施する際、メタノール中に（他の有機化合物を含む場合、メタノール＋他の有機化合物の合計量に対し）水分が１０重量％より多く含まれていると、包接体でない上記式（１）で表されるジヒドロキシ化合物を得るために長時間を要する場合があることから、効率よく本発明の精製工程を実施するためには、メタノール中の水分を好ましくは１０重量％以下、より好ましくは５重量％以下とする。 When the purification method of the present invention is carried out, it is said that methanol contains more than 10% by weight of water (in the case of containing other organic compounds, the total amount of methanol + other organic compounds). Since it may take a long time to obtain the dihydroxy compound represented by the above formula (1) which is not a contact, in order to efficiently carry out the purification step of the present invention, the water content in methanol is preferably 10. By weight% or less, more preferably 5% by weight or less.

本発明におけるメタノールの使用量は、包接体の結晶がメタノールと接触することが可能であれば良く、具体的に例えば、包接体の結晶１重量部に対し０．２重量部以上、好ましくは０．５重量部以上、更に好ましくは１重量部以上であり、また上限量は上記式（１）で表されるジヒドロキシ化合物の前記有機化合物に対する溶解度によっても異なるが、通常３０重量部以下、好ましくは２０重量部以下、更に好ましくは１０重量部以下である。 The amount of methanol used in the present invention may be as long as the crystals of the inclusion body can come into contact with methanol, and specifically, for example, 0.2 parts by weight or more, preferably 0.2 parts by weight or more, based on 1 part by weight of the crystals of the inclusion body. Is 0.5 parts by weight or more, more preferably 1 part by weight or more, and the upper limit amount is usually 30 parts by weight or less, although it depends on the solubility of the dihydroxy compound represented by the above formula (1) in the organic compound. It is preferably 20 parts by weight or less, more preferably 10 parts by weight or less.

前述した本発明の精製方法を実施した後、上記式（１）で表されるジヒドロキシ化合物の結晶とメタノールとを分離しても良い。分離する方法として例えば、ろ過等の固液分離操作や、上記式（１）で表されるジヒドロキシ化合物の結晶とメタノールとの混合物を、メタノールの沸点以上の温度とすることで、上記式（１）で表されるジヒドロキシ化合物の結晶からメタノールを除去する方法等が挙げられる。 After carrying out the above-mentioned purification method of the present invention, the crystals of the dihydroxy compound represented by the above formula (1) and methanol may be separated. As a method for separation, for example, a solid-liquid separation operation such as filtration or a mixture of a crystal of a dihydroxy compound represented by the above formula (1) and methanol is set to a temperature equal to or higher than the boiling point of methanol to the above formula (1). ), And the like, a method of removing methanol from the crystals of the dihydroxy compound represented by).

上記式（１）で表されるジヒドロキシ化合物の結晶とメタノールとを分離した後、上記式（１）で表されるジヒドロキシ化合物の結晶にメタノールが付着している場合、得られた結晶を更に乾燥しても良い。具体的に例えば、分離して得られた上記式（１）で表されるジヒドロキシ化合物の結晶を風乾したり、該結晶をメタノールの沸点以上の温度で一定時間乾燥させる方法が挙げられる。 After separating the crystal of the dihydroxy compound represented by the above formula (1) and methanol, when methanol is attached to the crystal of the dihydroxy compound represented by the above formula (1), the obtained crystal is further dried. You may. Specific examples thereof include a method of air-drying the crystals of the dihydroxy compound represented by the above formula (1) obtained by separation, and a method of drying the crystals at a temperature equal to or higher than the boiling point of methanol for a certain period of time.

本発明の精製工程を実施することによって得られた、上記式（１）で表されるジヒドロキシ化合物の結晶は必要に応じ、吸着、水蒸気蒸留、再結晶などの操作を繰り返し実施して更に精製しても良い。 The crystals of the dihydroxy compound represented by the above formula (1) obtained by carrying out the purification step of the present invention are further purified by repeatedly carrying out operations such as adsorption, steam distillation and recrystallization as necessary. May be.

本発明の精製工程を実施することによって得られた、上記式（１）で表されるジヒドロキシ化合物の結晶は、包接された化合物（ゲスト分子）を有さないか、有していても微量であることから、ポリカーボネート、ポリエステル、ポリアクリレート、ポリウレタン、エポキシなどの樹脂材料として好適に用いられることは勿論のこと、包接しているゲスト分子が問題となる分野、例えば医農薬用の原料（中間体）としても好適に用いることができる。 The crystals of the dihydroxy compound represented by the above formula (1) obtained by carrying out the purification step of the present invention do not have or have a trace amount of the encapsulated compound (guest molecule). Therefore, it is not only suitably used as a resin material such as polycarbonate, polyester, polyacrylate, polyurethane, and epoxy, but also in fields where encapsulating guest molecules are a problem, for example, raw materials for medical and agricultural chemicals (intermediate). It can also be suitably used as a body).

以下に実施例等を挙げて本発明を具体的に説明するが、本発明はこれに何ら限定されるものではない。例中、各種測定は下記の方法で実施した。 Hereinafter, the present invention will be specifically described with reference to examples and the like, but the present invention is not limited thereto. In the example, various measurements were carried out by the following methods.

（１）ＨＰＬＣ純度
上記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶に含まれる、上記式（１）で表されるジヒドロキシ化合物のＨＰＬＣ純度は下記条件に基づく液体クロマトグラフィーの面積百分率である（但し、ゲスト分子由来のピークを除いた修正面百値に基づく）。
装置 ：島津製作所製 ＬＣ－２０１０Ａ、
カラム：ＳＵＭＩＰＡＸ ＯＤＳ Ａ－２１１（５μｍ、４．６ｍｍφ×２５０ｍｍ）、
移動相：純水／アセトニトリル（アセトニトリル３０％→１００％）、
流量 ：１．０ｍｌ／ｍｉｎ、カラム温度：４０℃、検出波長：ＵＶ ２５４ｎｍ。 (1) HPLC Purity The HPLC purity of the dihydroxy compound represented by the above formula (1) contained in the crystal of the inclusion body having the dihydroxy compound represented by the above formula (1) as a host molecule is a liquid based on the following conditions. Chromatographic area percentage (but based on modified surface percentage excluding peaks from guest molecules).
Equipment: LC-2010A manufactured by Shimadzu Corporation,
Column: SUIMPAX ODS A-211 (5 μm, 4.6 mm φ × 250 mm),
Mobile phase: pure water / acetonitrile (acetonitrile 30% → 100%),
Flow rate: 1.0 ml / min, column temperature: 40 ° C., detection wavelength: UV 254 nm.

（２）ゲスト分子の含量及びメタノール（又は他の有機化合物）含量の分析
ゲスト分子の含量、及びメタノール（又は他の有機化合物）の含量については下記条件に基づくガスクロマトグラフィーにより定量を行った。
装置 ：島津製作所製 ＧＣ－２０１４、
カラム：ＤＢ－１（０．２５μｍ、０．２５ｍｍＩＤ×３０ｍ）、
昇温：４０℃（１０分保持）→２０℃／ｍｉｎ→３００℃（２０分保持）、
Ｉｎｊ温度：２００℃、Ｄｅｔ温度：３００℃、スプリット比 １：１０、
キャリアー：窒素５５．０ｋＰａ（一定）、
サンプル調製方法：各製造例、実施例、または比較例で得られた包接体あるいは非包接体の結晶１００ｍｇを１０ｍｌメスフラスコに量り取り、そこへあらかじめ調製していた１，２－ジメトキシエタンのアセトニトリル溶液(１，２－ジメトキシエタン４００ｍｇをアセトニトリル２００ｍｌに溶解したもの)をホールピペットで５ｍｌ加え、アセトニトリルでメスアップさせ溶解したものを試料溶液とした。
一方、含量を測定したい有機化合物１０ｍｇを１０ｍｌメスフラスコに量り取り、上述と同量の１，２－ジメトキシエタンのアセトニトリル溶液を加え、アセトニトリルでメスアップさせ溶解したものを標準溶液とした。
試料溶液及び標準溶液を上述の条件にて分析し、得られた各成分のピーク面積をデータ処理装置で求め、各成分の含量（重量％、以下、断りのない限り％と表す。）を算出した（内部標準法）。
なお、精製を実施する際に有機化合物としてエタノールを用いた場合、上記の試料溶液および標準溶液の作成の際にアセトニトリルの代わりにトリエチレングリコールジメチルエーテルを用いた。 (2) Analysis of guest molecule content and methanol (or other organic compound) content The guest molecule content and methanol (or other organic compound) content were quantified by gas chromatography based on the following conditions.
Equipment: Shimadzu GC-2014,
Column: DB-1 (0.25 μm, 0.25 mm ID × 30 m),
Temperature rise: 40 ° C (hold for 10 minutes) → 20 ° C / min → 300 ° C (hold for 20 minutes),
Inj temperature: 200 ° C, Det temperature: 300 ° C, split ratio 1:10,
Carrier: Nitrogen 55.0 kPa (constant),
Sample preparation method: 100 mg of encapsulated or non-encapsulated crystals obtained in each Production Example, Example, or Comparative Example was weighed in a 10 ml volumetric flask, and 1,2-dimethoxyethane prepared in advance there. Acetonitrile solution (400 mg of 1,2-dimethoxyethane dissolved in 200 ml of acetonitrile) was added with a whole pipette in an amount of 5 ml, and the solution was prepared by measuring up with acetonitrile to prepare a sample solution.
On the other hand, 10 mg of the organic compound whose content was to be measured was weighed in a 10 ml volumetric flask, the same amount of 1,2-dimethoxyethane acetonitrile solution as described above was added, and the solution was prepared by measuring with acetonitrile and dissolving as a standard solution.
The sample solution and standard solution are analyzed under the above conditions, the peak area of each obtained component is determined by a data processing device, and the content of each component (% by weight, hereinafter referred to as% unless otherwise noted) is calculated. (Internal standard method).
When ethanol was used as the organic compound in the purification, triethylene glycol dimethyl ether was used instead of acetonitrile in the preparation of the above sample solution and standard solution.

＜製造例１＞
攪拌器、加熱冷却器、および温度計を備えたガラス製反応器に、９，９’－ビス（４－ヒドロキシ－３－フェニルフェニル）フルオレン１２０．０ｇ（０．２４０ｍｏｌ）、エチレンカーボネート４８．３ｇ（０．５４９ｍｏｌ）、炭酸カリウム２．４ｇ（０．０１８ｍｏｌ）およびトルエン１２０．０ｇを仕込み、１１０℃で１１時間撹拌し反応液を得た。
得られた反応液を８５℃まで冷却した後、水２０４ｇを加え、８０～８５℃で３０分撹拌し、静置後、水層を分離した。同じ操作を３回繰り返した後、得られた有機溶媒層をディーンスターク装置を用いて還流下で脱水することで晶析溶液を得た。
得られた晶析溶液を冷却した所、６５℃で結晶が析出し、結晶析出後、同温度で２時間撹拌した。更に２６℃まで冷却した後、濾過し、結晶を得た。得られた結晶を、１２時間、内圧１．１ｋＰａの減圧下、１１０℃～１１２℃で乾燥した。 <Manufacturing example 1>
In a glass reactor equipped with a stirrer, a heating cooler, and a thermometer, 120.0 g (0.240 mol) of 9.9'-bis (4-hydroxy-3-phenylphenyl) fluorene, 48.3 g of ethylene carbonate. (0.549 mol), 2.4 g (0.018 mol) of potassium carbonate and 120.0 g of toluene were charged and stirred at 110 ° C. for 11 hours to obtain a reaction solution.
After cooling the obtained reaction solution to 85 ° C., 204 g of water was added, the mixture was stirred at 80 to 85 ° C. for 30 minutes, allowed to stand, and then the aqueous layer was separated. After repeating the same operation three times, the obtained organic solvent layer was dehydrated under reflux using a Dean-Stark apparatus to obtain a crystallization solution.
When the obtained crystallization solution was cooled, crystals were precipitated at 65 ° C., and after the crystals were precipitated, the mixture was stirred at the same temperature for 2 hours. After further cooling to 26 ° C., the mixture was filtered to obtain crystals. The obtained crystals were dried at 110 ° C. to 112 ° C. for 12 hours under a reduced pressure of 1.1 kPa.

乾燥後、得られた結晶を上述した方法により分析した所、上記式（１）で表されるジヒドロキシ化合物をホスト分子とし、トルエンをゲスト分子とする包接体（包接体の結晶）であることを確認した。以下に分析結果を示す。
得られた結晶の重さ：１１８．２ｇ
ＨＰＬＣ純度：９７．２％
トルエン（ゲスト分子）含量：４．８３％ After drying, the obtained crystals were analyzed by the above-mentioned method, and found to be an inclusion body (crystal of the inclusion body) in which the dihydroxy compound represented by the above formula (1) was used as a host molecule and toluene was used as a guest molecule. It was confirmed. The analysis results are shown below.
Weight of obtained crystals: 118.2 g
HPLC purity: 97.2%
Toluene (guest molecule) content: 4.83%

＜製造例２＞
攪拌器、加熱冷却器、および温度計を備えたガラス製反応器に、９，９’－ビス（４－ヒドロキシ－３－フェニルフェニル）フルオレン９０．０ｇ（０．１８０ｍｏｌ）、エチレンカーボネート３６．０ｇ（０．４０８ｍｏｌ）、炭酸カリウム２．１ｇ（０．０１５ｍｏｌ）、およびシクロヘキサノン９０．０ｇを仕込み、１４０℃で７時間撹拌し反応液を得た。
得られた反応液を９０℃まで冷却した後、シクロヘキサノン６９ｇ、ノルマルヘプタン８１ｇを加え、有機溶媒層を９０℃に保ちながら洗浄水が中性となるまで水洗を行った。水洗後、得られた有機溶媒層をディーンスターク装置を用いて還流下で脱水することで、晶析溶液を得た。
その後、得られた晶析溶液を７０℃まで冷却し、７０℃で１時間保温することで結晶を析出させた後、同温度で２時間撹拌した。撹拌後、更に１９℃まで冷却した後、濾過し、結晶を得た。得られた結晶を内圧１．１ｋＰａの減圧下、９０℃で３時間乾燥した。 <Manufacturing example 2>
In a glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer, 90.0 g (0.180 mol) of 9,9'-bis (4-hydroxy-3-phenylphenyl) fluorene, 36.0 g of ethylene carbonate. (0.408 mol), 2.1 g (0.015 mol) of potassium carbonate, and 90.0 g of cyclohexanone were charged and stirred at 140 ° C. for 7 hours to obtain a reaction solution.
After cooling the obtained reaction solution to 90 ° C., 69 g of cyclohexanone and 81 g of normal heptane were added, and the mixture was washed with water until the washing water became neutral while keeping the organic solvent layer at 90 ° C. After washing with water, the obtained organic solvent layer was dehydrated under reflux using a Dean-Stark apparatus to obtain a crystallization solution.
Then, the obtained crystallization solution was cooled to 70 ° C. and kept at 70 ° C. for 1 hour to precipitate crystals, and then stirred at the same temperature for 2 hours. After stirring, the mixture was further cooled to 19 ° C. and then filtered to obtain crystals. The obtained crystals were dried at 90 ° C. for 3 hours under a reduced pressure of 1.1 kPa.

得られた結晶を上述した方法により分析した所、上記式（１）で表されるジヒドロキシ化合物をホスト分子とし、シクロヘキサノンをゲスト分子とする包接体（包接体の結晶）であることを確認した。以下に分析結果を示す。
得られた結晶の重さ：９９．６ｇ
ＨＰＬＣ純度：９７．５％
シクロヘキサノン（ゲスト分子）含量：１５．３％ When the obtained crystal was analyzed by the above-mentioned method, it was confirmed that the crystal was an inclusion body (crystal of the inclusion body) in which the dihydroxy compound represented by the above formula (1) was used as a host molecule and cyclohexanone was used as a guest molecule. did. The analysis results are shown below.
Weight of obtained crystals: 99.6 g
HPLC purity: 97.5%
Cyclohexanone (guest molecule) content: 15.3%

＜実施例１＞
攪拌器、加熱冷却器、および温度計を備えたガラス製反応器に、製造例１で得られた包接体の結晶１０ｇ、メタノール７０ｇを仕込んだ後、２５℃で１時間撹拌を行った。撹拌中、結晶は完全に溶解していなかった。
撹拌後、２５℃でろ過し、結晶を得た。得られた結晶を内圧１.３ｋＰａの減圧下、
９０℃で３時間乾燥し、上記式（１）で表されるジヒドロキシ化合物の結晶を得た。 <Example 1>
A glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer was charged with 10 g of the inclusion crystal and 70 g of methanol obtained in Production Example 1, and then stirred at 25 ° C. for 1 hour. The crystals were not completely dissolved during stirring.
After stirring, the mixture was filtered at 25 ° C. to obtain crystals. The obtained crystals are subjected to a reduced pressure of 1.3 kPa internal pressure.
The mixture was dried at 90 ° C. for 3 hours to obtain crystals of the dihydroxy compound represented by the above formula (1).

得られた上記式（１）で表されるジヒドロキシ化合物の結晶の各分析値は以下の通り。
得られた結晶の重さ：９．２ｇ
トルエン（ゲスト分子）含量：０．０１％
メタノール（精製で用いた有機化合物）含量：０．１０％ The analytical values of the obtained crystals of the dihydroxy compound represented by the above formula (1) are as follows.
Weight of obtained crystals: 9.2 g
Toluene (guest molecule) content: 0.01%
Methanol (organic compound used in purification) content: 0.10%

＜比較例１＞
メタノールをエタノールに変え、実施例１と同様に実施して上記式（１）で表されるジヒドロキシ化合物の結晶を得た。得られた上記式（１）で表されるジヒドロキシ化合物の結晶の各分析値は以下の通り。
得られた結晶の重さ：７．２ｇ
トルエン（ゲスト分子）含量：３．４１％
エタノール（精製で用いた有機化合物）含量：０．１５％ <Comparative Example 1>
Methanol was changed to ethanol, and the same procedure as in Example 1 was carried out to obtain crystals of the dihydroxy compound represented by the above formula (1). The analytical values of the obtained crystals of the dihydroxy compound represented by the above formula (1) are as follows.
Weight of obtained crystals: 7.2 g
Toluene (guest molecule) content: 3.41%
Ethanol (organic compound used in purification) Content: 0.15%

＜比較例２＞
製造例１で得られた包接体の結晶１ｇ、ジイソブチルケトン５ｇを撹拌子を入れた試験管に入れ、２５℃で１時間撹拌を行った。撹拌後、結晶をろ別し、乾燥した後、得られた結晶を上述した分析法により分析を行った。結果を表１に示す。
＜比較例３～７＞
撹拌温度、撹拌時間及び包接体の結晶と共に使用する有機化合物（又は水）を表１に示すものに変更した以外は比較例２と同様の方法にて実施した後、得られた結晶を上述した分析法により分析を行った。結果を表１に示す。 <Comparative Example 2>
1 g of the inclusion crystal and 5 g of the diisobutylketone obtained in Production Example 1 were placed in a test tube containing a stirrer, and the mixture was stirred at 25 ° C. for 1 hour. After stirring, the crystals were filtered off, dried, and then the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown in Table 1.
<Comparative Examples 3 to 7>
After carrying out in the same manner as in Comparative Example 2 except that the stirring temperature, stirring time and the organic compound (or water) used together with the inclusion crystal were changed to those shown in Table 1, the obtained crystals were described above. The analysis was performed by the analysis method used. The results are shown in Table 1.

＜実施例２＞
比較例７で得られた、上記式（１）で表されるジヒドロキシ化合物をホスト分子とし、トルエン及び酢酸イソブチルをゲスト分子とする結晶０．９ｇ、メタノール４．５ｇを、撹拌子を入れた試験管に入れ、２５℃で１時間撹拌を行った。撹拌後、結晶をろ別し、乾燥した後、得られた結晶を上述した分析法により分析を行った。結果を以下に示す。
トルエン（ゲスト分子）含量：０．１９％
酢酸イソブチル（ゲスト分子）含量：０．０５％
メタノール含量：０．２１％ <Example 2>
A test in which 0.9 g of crystals and 4.5 g of methanol having the dihydroxy compound represented by the above formula (1) as a host molecule and toluene and isobutyl acetate as guest molecules obtained in Comparative Example 7 were added with a stirrer. It was placed in a tube and stirred at 25 ° C. for 1 hour. After stirring, the crystals were filtered off, dried, and then the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown below.
Toluene (guest molecule) content: 0.19%
Isobutyl acetate (guest molecule) content: 0.05%
Methanol content: 0.21%

＜実施例３＞
製造例１で得られた、包接体の結晶１ｇ、トルエン０．４ｇ、メタノール１．６ｇを、撹拌子を入れた試験管に入れ、２５℃で３時間撹拌を行った。撹拌中、結晶は完全に溶解していなかった。
撹拌後、結晶をろ別し、乾燥し、得られた結晶を上述した分析法により分析を行った。結果を以下に示す。
トルエン（ゲスト分子）含量：０．１１％
メタノール含量：０．２７％ <Example 3>
1 g of the inclusion crystal, 0.4 g of toluene, and 1.6 g of methanol obtained in Production Example 1 were placed in a test tube containing a stirrer and stirred at 25 ° C. for 3 hours. The crystals were not completely dissolved during stirring.
After stirring, the crystals were filtered off, dried, and the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown below.
Toluene (guest molecule) content: 0.11%
Methanol content: 0.27%

＜実施例４＞
製造例１で得られた、包接体の結晶１ｇ、メタノール４．４ｇ、水０．６を、撹拌子を入れた試験管に入れ、２５℃で１２時間撹拌を行った。撹拌後、結晶をろ別し、乾燥した後、得られた結晶を上述した分析法により分析を行った。結果を以下に示す。
トルエン（ゲスト分子）含量：２．４３％
メタノール含量：０．１２％
上記結晶０．９ｇ、メタノール３．９６ｇ、水０．５４ｇを、撹拌子を入れた試験管に入れ、２５℃で４８時間撹拌を行った。撹拌後、結晶をろ別し、乾燥した後、得られた結晶を上述した分析法により分析を行った。結果を以下に示す。
トルエン（ゲスト分子）含量：０．１２％
メタノール含量：０．１２％ <Example 4>
1 g of the inclusion crystal, 4.4 g of methanol, and 0.6 of water obtained in Production Example 1 were placed in a test tube containing a stirrer and stirred at 25 ° C. for 12 hours. After stirring, the crystals were filtered off, dried, and then the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown below.
Toluene (guest molecule) content: 2.43%
Methanol content: 0.12%
0.9 g of the above crystals, 3.96 g of methanol, and 0.54 g of water were placed in a test tube containing a stirrer, and the mixture was stirred at 25 ° C. for 48 hours. After stirring, the crystals were filtered off, dried, and then the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown below.
Toluene (guest molecule) content: 0.12%
Methanol content: 0.12%

＜実施例５＞
製造例１で得られた、包接体の結晶１ｇ、メタノール４．６ｇ、水０．４ｇを、撹拌子を入れた試験管に入れ、２５℃で８時間撹拌を行った。撹拌後、結晶をろ別し、乾燥した後、得られた結晶を上述した分析法により分析を行った。結果を以下に示す。
トルエン（ゲスト分子）含量：０．１１％
メタノール含量：０．１３％ <Example 5>
1 g of the inclusion crystal, 4.6 g of methanol, and 0.4 g of water obtained in Production Example 1 were placed in a test tube containing a stirrer and stirred at 25 ° C. for 8 hours. After stirring, the crystals were filtered off, dried, and then the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown below.
Toluene (guest molecule) content: 0.11%
Methanol content: 0.13%

＜実施例６＞
製造例１で得られた、包接体の結晶１０ｇの上からメタノール５ｇを振りかけた後、攪拌器、加熱冷却器、減圧器を備えたガラス製反応器に該包接体を入れ、加熱冷却器温度を９０℃、内圧１．１ｋPaとして１時間撹拌しながらメタノールを系外へ除去した。その後、得られた結晶を上述した分析法により分析を行った。結果を以下に示す。
トルエン（ゲスト分子）含量：０．０１％
メタノール含量：検出されず <Example 6>
After sprinkling 5 g of methanol on 10 g of the crystals of the inclusion body obtained in Production Example 1, the inclusion body is placed in a glass reactor equipped with a stirrer, a heating / cooling device, and a decompressor, and heated and cooled. Methanol was removed from the system while stirring at a vessel temperature of 90 ° C. and an internal pressure of 1.1 kPa for 1 hour. Then, the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown below.
Toluene (guest molecule) content: 0.01%
Methanol content: not detected

＜比較例８～１０＞
製造例１で得られた、包接体の結晶に振りかけた有機化合物を表２に示すものに変更した以外は実施例６と同様の方法にて実施し、得られた結晶を上述した分析法により分析を行った。結果を表２に示す。 <Comparative Examples 8 to 10>
The same method as in Example 6 was carried out except that the organic compound sprinkled on the crystals of the inclusion body obtained in Production Example 1 was changed to the one shown in Table 2, and the obtained crystals were subjected to the above-mentioned analytical method. Was analyzed by. The results are shown in Table 2.

＜実施例７＞
攪拌器、加熱冷却器、および温度計を備えたガラス製反応器に、製造例２で得られた、包接体の結晶１０ｇ、メタノール５０ｇを仕込んだ後、２５℃で３時間撹拌を行った。
撹拌後、２５℃でろ過し、結晶を得た。得られた結晶を内圧１．１ｋＰａの減圧下、９０℃で３時間乾燥し、上記式（１）で表されるジヒドロキシ化合物の結晶を得た。 <Example 7>
A glass reactor equipped with a stirrer, a heating / cooling device, and a thermometer was charged with 10 g of inclusion crystal and 50 g of methanol obtained in Production Example 2, and then stirred at 25 ° C. for 3 hours. ..
After stirring, the mixture was filtered at 25 ° C. to obtain crystals. The obtained crystals were dried at 90 ° C. for 3 hours under a reduced pressure of 1.1 kPa to obtain crystals of the dihydroxy compound represented by the above formula (1).

得られた上記式（１）で表されるジヒドロキシ化合物の結晶の各分析値は以下の通り。
得られた結晶の重さ：８．１ｇ
シクロヘキサノン（ゲスト分子）含量：１．５６重量％
メタノール含量：０．１０重量％ The analytical values of the obtained crystals of the dihydroxy compound represented by the above formula (1) are as follows.
Weight of obtained crystals: 8.1 g
Cyclohexanone (guest molecule) content: 1.56% by weight
Methanol content: 0.10% by weight

＜実施例８＞
撹拌温度を７０℃とする以外は実施例７と同様に実施し、上記式（１）で表されるジヒドロキシ化合物の結晶を得た。得られた上記式（１）で表されるジヒドロキシ化合物の結晶の各分析値は以下の通り。
得られた結晶の重さ：８．０ｇ
シクロヘキサノン（ゲスト分子）含量：０．２１％
メタノール含量：０．１５％ <Example 8>
The same procedure as in Example 7 was carried out except that the stirring temperature was 70 ° C. to obtain crystals of the dihydroxy compound represented by the above formula (1). The analytical values of the obtained crystals of the dihydroxy compound represented by the above formula (1) are as follows.
Weight of obtained crystals: 8.0 g
Cyclohexanone (guest molecule) content: 0.21%
Methanol content: 0.15%

＜比較例１１＞
メタノールをエタノールに変更する以外は実施例７と同様に実施し、上記式（１）で表されるジヒドロキシ化合物の結晶を得た。得られた上記式（１）で表されるジヒドロキシ化合物の結晶の各分析値は以下の通り。
得られた結晶の重さ：６．４ｇ
シクロヘキサノン（ゲスト分子）含量：１３．３％
エタノール含量：０．１５％ <Comparative Example 11>
The same procedure as in Example 7 was carried out except that methanol was changed to ethanol, and crystals of the dihydroxy compound represented by the above formula (1) were obtained. The analytical values of the obtained crystals of the dihydroxy compound represented by the above formula (1) are as follows.
Weight of obtained crystals: 6.4 g
Cyclohexanone (guest molecule) content: 13.3%
Ethanol content: 0.15%

＜比較例１２＞
製造例２で得られた、包接体の結晶１ｇ、ジイソブチルケトン５ｇを撹拌子を入れた試験管に入れ、２５℃で１時間撹拌を行った。撹拌後、結晶をろ別し、乾燥した後、得られた結晶を上述した分析法により分析を行った。結果を表３に示す。
＜比較例１３～１４＞
包接体の結晶と共に使用する有機化合物を表３に示すものに変更した以外は比較例１２と同様の方法にて実施した後、得られた結晶を上述した分析法により分析を行った。結果を表３に示す。 <Comparative Example 12>
1 g of the inclusion crystal and 5 g of the diisobutylketone obtained in Production Example 2 were placed in a test tube containing a stirrer, and the mixture was stirred at 25 ° C. for 1 hour. After stirring, the crystals were filtered off, dried, and then the obtained crystals were analyzed by the above-mentioned analytical method. The results are shown in Table 3.
<Comparative Examples 13 to 14>
After the same method as in Comparative Example 12 was carried out except that the organic compound used together with the inclusion crystal was changed to the one shown in Table 3, the obtained crystal was analyzed by the above-mentioned analytical method. The results are shown in Table 3.

＜参考例１＞
スケールを１０分の１とする以外は特開２００１－２０６８６３号の実施例６に記載されている方法で仕込・反応を行い、６５℃で１時間撹拌した段階で反応液を高速液体クロマトグラフィーで分析したが、上記式（１）で表されジヒドロキシ化合物は殆ど生成しておらず、原料の９－フルオレノンが９８％残存していた。そこで更に同温度で７時間撹拌を継続し、反応液を高速液体クロマトグラフィーで分析したが、やはり反応は殆ど進行しておらず、原料の９－フルオレノンが９７％残存していた。
そこで特開２００１－２０６８６３号〔００１９〕の記載に基づき、反応温度を６５℃から１００℃へと変更し同温度で撹拌を継続したところ、原料である９－フルオレノンの消失までに７３時間必要であった。
該文献記載に基づく後処理を実施するため、得られた反応液を２分割し、一方にメタノール１０ｇ、もう一方にイソプロピルアルコール１０ｇを加え６０℃まで加温し、１時間撹拌を継続した後、それぞれ純水３０ｇを加え、３０℃まで冷却したが、いずれも結晶は析出せず、それぞれ水と分離したタール状の液体が得られた。 <Reference example 1>
The reaction solution was subjected to high performance liquid chromatography at the stage where the preparation and reaction were carried out by the method described in Example 6 of Japanese Patent Laid-Open No. 2001-206863 except that the scale was reduced to 1/10, and the mixture was stirred at 65 ° C. for 1 hour. As a result of analysis, almost no dihydroxy compound represented by the above formula (1) was produced, and 98% of the raw material 9-fluorenone remained. Therefore, stirring was continued at the same temperature for 7 hours, and the reaction solution was analyzed by high performance liquid chromatography. However, the reaction hardly proceeded, and 97% of the raw material 9-fluorenone remained.
Therefore, when the reaction temperature was changed from 65 ° C. to 100 ° C. and stirring was continued at the same temperature based on the description of Japanese Patent Application Laid-Open No. 2001-206863, it took 73 hours for the raw material 9-fluorenone to disappear. there were.
In order to carry out the post-treatment based on the document, the obtained reaction solution was divided into two parts, 10 g of methanol was added to one of them, and 10 g of isopropyl alcohol was added to the other, and the mixture was heated to 60 ° C. and stirred for 1 hour. Although 30 g of pure water was added and cooled to 30 ° C., no crystals were precipitated in any of them, and a tar-like liquid separated from water was obtained.

Claims (1)

下記式（１）で表されるジヒドロキシ化合物をホスト分子とする包接体の結晶と、メタノールとを混合した後、ろ過することなくメタノールを気化させながら除去する工程を含む、下記式 （１）で表されるジヒドロキシ化合物の結晶の精製方法。

The following formula (1) includes a step of mixing methanol with a crystal of an inclusion body having a dihydroxy compound represented by the following formula (1) as a host molecule, and then removing the methanol while vaporizing it without filtering. ) Is a method for purifying crystals of a dihydroxy compound.