JPWO2020059710A1 - Crystal of bisfluorene compound - Google Patents
Crystal of bisfluorene compound Download PDFInfo
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- JPWO2020059710A1 JPWO2020059710A1 JP2020548514A JP2020548514A JPWO2020059710A1 JP WO2020059710 A1 JPWO2020059710 A1 JP WO2020059710A1 JP 2020548514 A JP2020548514 A JP 2020548514A JP 2020548514 A JP2020548514 A JP 2020548514A JP WO2020059710 A1 JPWO2020059710 A1 JP WO2020059710A1
- Authority
- JP
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- Prior art keywords
- crystal
- crystals
- reaction
- fluorene
- bis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 168
- 150000001875 compounds Chemical class 0.000 title description 13
- 238000000113 differential scanning calorimetry Methods 0.000 claims abstract description 30
- HBTONAMIPDVQRI-UHFFFAOYSA-N 2-[4-[9-[4-(2-hydroxyethoxy)-3-phenylphenyl]fluoren-9-yl]-2-phenylphenoxy]ethanol Chemical compound OCCOC1=CC=C(C2(C3=CC=CC=C3C3=CC=CC=C32)C=2C=C(C(OCCO)=CC=2)C=2C=CC=CC=2)C=C1C1=CC=CC=C1 HBTONAMIPDVQRI-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000004519 manufacturing process Methods 0.000 claims abstract description 19
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- 210000003000 inclusion body Anatomy 0.000 claims description 29
- 238000002425 crystallisation Methods 0.000 claims description 26
- 230000008025 crystallization Effects 0.000 claims description 26
- 238000002844 melting Methods 0.000 claims description 22
- 230000008018 melting Effects 0.000 claims description 22
- 238000001035 drying Methods 0.000 claims description 20
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 abstract description 10
- -1 2-hydroxyethoxy Chemical group 0.000 abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 103
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
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- 230000000052 comparative effect Effects 0.000 description 23
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- 239000000126 substance Substances 0.000 description 18
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- 239000003960 organic solvent Substances 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
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- 239000003377 acid catalyst Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 8
- 239000013557 residual solvent Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000004817 gas chromatography Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- PTTPXKJBFFKCEK-UHFFFAOYSA-N 2-Methyl-4-heptanone Chemical compound CC(C)CC(=O)CC(C)C PTTPXKJBFFKCEK-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- 238000009835 boiling Methods 0.000 description 3
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- 239000007810 chemical reaction solvent Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 3
- 239000011964 heteropoly acid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- IYDGMDWEHDFVQI-UHFFFAOYSA-N phosphoric acid;trioxotungsten Chemical compound O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.O=[W](=O)=O.OP(O)(O)=O IYDGMDWEHDFVQI-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- CDPGQPIFOHITFN-UHFFFAOYSA-N 2-[4-[1-[4-(2-hydroxyethoxy)-3-phenylphenyl]-9H-fluoren-2-yl]-2-phenylphenoxy]ethanol Chemical compound OCCOC1=C(C=C(C=C1)C1=C(C=2CC3=CC=CC=C3C=2C=C1)C1=CC(=C(C=C1)OCCO)C1=CC=CC=C1)C1=CC=CC=C1 CDPGQPIFOHITFN-UHFFFAOYSA-N 0.000 description 2
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 2
- PBMQHMJOBMZOGU-UHFFFAOYSA-N 4-(9h-fluoren-1-yl)-2-phenylphenol Chemical compound OC1=CC=C(C=2C=3CC4=CC=CC=C4C=3C=CC=2)C=C1C1=CC=CC=C1 PBMQHMJOBMZOGU-UHFFFAOYSA-N 0.000 description 2
- YWFPGFJLYRKYJZ-UHFFFAOYSA-N 9,9-bis(4-hydroxyphenyl)fluorene Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C2=CC=CC=C21 YWFPGFJLYRKYJZ-UHFFFAOYSA-N 0.000 description 2
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 239000003426 co-catalyst Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
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- 238000010586 diagram Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003822 epoxy resin Substances 0.000 description 2
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 229920000647 polyepoxide Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- NOZAKUWNUGNDLI-UHFFFAOYSA-N 2-(2-phenylphenoxy)ethanol Chemical compound OCCOC1=CC=CC=C1C1=CC=CC=C1 NOZAKUWNUGNDLI-UHFFFAOYSA-N 0.000 description 1
- AIFZYIWZIDCFDV-UHFFFAOYSA-N 2-[4-(9h-fluoren-1-yl)-2-phenylphenoxy]ethanol Chemical compound OCCOC1=CC=C(C=2C3=C(C4=CC=CC=C4C3)C=CC=2)C=C1C1=CC=CC=C1 AIFZYIWZIDCFDV-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- UPDUATXRTAHXQQ-UHFFFAOYSA-N OCCOC(C=CC(C1(C(C(CC=C2)=O)=C2C2=CC=CC=C12)C(C=C1)=CC(C2=CC=CC=C2)=C1OCCO)=C1)=C1C1=CC=CC=C1 Chemical compound OCCOC(C=CC(C1(C(C(CC=C2)=O)=C2C2=CC=CC=C12)C(C=C1)=CC(C2=CC=CC=C2)=C1OCCO)=C1)=C1C1=CC=CC=C1 UPDUATXRTAHXQQ-UHFFFAOYSA-N 0.000 description 1
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- 235000007164 Oryza sativa Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
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- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
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- WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 1
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- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
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- 238000007561 laser diffraction method Methods 0.000 description 1
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- 238000000691 measurement method Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- KZCOBXFFBQJQHH-UHFFFAOYSA-N octane-1-thiol Chemical compound CCCCCCCCS KZCOBXFFBQJQHH-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
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- 238000007867 post-reaction treatment Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
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- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
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- 150000003839 salts Chemical class 0.000 description 1
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- 150000003613 toluenes Chemical class 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/40—Separation; Purification; Stabilisation; Use of additives by change of physical state, e.g. by crystallisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/205—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring the aromatic ring being a non-condensed ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
- C07C2603/18—Fluorenes; Hydrogenated fluorenes
Abstract
示差走査熱量分析による特定の吸熱ピークを有する９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体および、その結晶体の製造方法を提供することを課題とする。解決手段として、示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有することを特徴とする、９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体を提供する。 An object of the present invention is to provide a crystal of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene having a specific endothermic peak by differential scanning calorimetry, and a method for producing the crystal. do. As a solution, it is characterized by having at least one endothermic peak by differential scanning calorimetry in a temperature range of 158 ° C. or higher and lower than 161 ° C., 9,9-bis [4- (2-hydroxyethoxy) -3-phenyl. Phenyl] provides a crystal of fluorene.
Description
本発明は、示差走査熱量分析による特定の吸熱ピークを有する９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体および、その結晶体の製造方法に関する。 The present invention relates to a crystal of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene having a specific endothermic peak by differential scanning calorimetry, and a method for producing the crystal.
従来、９，９−ビス（４−ヒドロキシフェニル）フルオレン等のフルオレン骨格を有する化合物群は、耐熱性や光学特性等において優れていることから、ポリカーボネート樹脂等の熱可塑性合成樹脂原料、エポキシ樹脂等の熱硬化性樹脂原料、酸化防止剤原料、感熱記録体原料、感光性レジスト原料などの用途で用いられている。中でも、以下化学式（１）で表される化学構造を有する９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンから製造される樹脂は、光学特性に優れるとして着目されている（例えば、特許文献１、２等）。
上記化学式（１）で表される９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンとトルエンとの包接体と、特定の溶媒とを、溶解することなく混合させることにより、トルエンを除去する方法が知られている（特許文献５）が、得られる結晶はほとんど高融点であるため、融解や溶解させるためにエネルギーや時間が多く必要である。また、使用する溶媒によっては低融点の結晶が得られるが、当該結晶は、包接体を形成しているため、包接体から溶媒を除去するためのエネルギーが必要であるほか、嵩密度も低い。
高嵩密度の上記化学式（１）で表される９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶の製造方法が知られている（特許文献６）が、得られた結晶は包接体であり、加熱により当該包接体から結晶を保持したまま溶媒が除去できないか、あるいは除去できる場合でも包接体から溶媒を除去するためのエネルギーが必要であるという問題があった。
包接体ではない上記化学式（１）で表される９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンを得る製造方法も知られている（特許文献７）が、最も高融点の結晶は、融解して使用する場合は多くのエネルギーが必要である。また、低融点の結晶を得るには、極めて速い速度で冷却する必要があり、商業スケールでの実施は困難であるか、特殊な装置が必要なため、工業的規模での適用は容易ではない。そのほか、低融点の結晶は色相が悪く、光学用途への使用に問題があるほか、晶析に使用する溶媒の残存量が多いという問題もあった。
９，９−ビス（４−ヒドロキシフェニル）フルオレン等のフルオレン骨格を有する化合物群は、反応溶媒や精製に使用する溶媒との間で包接体を形成することが知られている一方で、包接された溶媒を除去するためには高温と多大な時間を要するために、工業的規模で適用することは困難であるほか、溶媒が包接されたフルオレン骨格を有する化合物は、エポキシ樹脂、ポリエステル等の製造原料やその他の用途において工業的に使用するには問題があることも知られている。Conventionally, a group of compounds having a fluorene skeleton such as 9,9-bis (4-hydroxyphenyl) fluorene is excellent in heat resistance, optical properties, etc., and therefore, a thermoplastic synthetic resin raw material such as a polycarbonate resin, an epoxy resin, etc. It is used in applications such as thermosetting resin raw materials, antioxidant raw materials, heat-sensitive recorder raw materials, and photosensitive resist raw materials. Among them, a resin produced from 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene having a chemical structure represented by the following chemical formula (1) has attracted attention as having excellent optical properties. (For example, Patent Documents 1, 2, etc.).
A clathrate of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene represented by the above chemical formula (1) and toluene and a specific solvent are mixed without being dissolved. A method of removing toluene by allowing it to be removed is known (Patent Document 5), but since the obtained crystal has a high melting point, a large amount of energy and time are required to melt or dissolve it. Further, depending on the solvent used, a crystal having a low melting point can be obtained, but since the crystal forms an inclusion body, energy for removing the solvent from the inclusion body is required, and the bulk density is also high. Low.
A method for producing crystals of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene represented by the above chemical formula (1) having a high bulk density is known (Patent Document 6). The obtained crystal is an inclusion body, and the solvent cannot be removed from the inclusion body while retaining the crystal by heating, or even if it can be removed, energy for removing the solvent from the inclusion body is required. There was a problem.
A production method for obtaining 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene represented by the above chemical formula (1), which is not an inclusion body, is also known (Patent Document 7). , The crystal with the highest melting point requires a lot of energy when it is melted and used. Also, in order to obtain crystals with a low melting point, it is necessary to cool them at an extremely high speed, which is difficult to implement on a commercial scale or requires special equipment, so it is not easy to apply on an industrial scale. .. In addition, low melting point crystals have a poor hue, which causes problems in use in optical applications, and also has a problem in that the amount of residual solvent used for crystallization is large.
While compounds having a fluorene skeleton, such as 9,9-bis (4-hydroxyphenyl) fluorene, are known to form clathrates with reaction solvents and solvents used for purification, they are encapsulated. It is difficult to apply on an industrial scale because it takes a large amount of time and high temperature to remove the solvent in contact with the solvent, and compounds having a fluorene skeleton in which the solvent is included are epoxy resins and polyesters. It is also known that there is a problem in industrial use in manufacturing raw materials such as fluorene and other uses.
本発明は、上述した事情を背景としてなされたものであって、示差走査熱量分析による特定の吸熱ピークを有する９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体および、その結晶体の製造方法の提供を課題とする。 The present invention has been made in the context of the above circumstances, and is that of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene having a specific endothermic peak by differential scanning calorimetry. An object of the present invention is to provide a crystal body and a method for producing the crystal body.
本発明者らは、上述の課題解決のために鋭意検討した結果、特定の溶媒を用いて晶析することにより、示差走査熱量分析による特定の吸熱ピークを有する９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体が得られることを見出し、本発明を完成した。 As a result of diligent studies to solve the above-mentioned problems, the present inventors have 9,9-bis [4-(4), which has a specific endothermic peak by differential scanning calorimetry by crystallization using a specific solvent. We have found that a crystal of 2-hydroxyethoxy) -3-phenylphenyl] fluorene can be obtained, and completed the present invention.
本発明は以下の通りである。
１．示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有することを特徴とする、９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体。
２．包接体ではないことを特徴とする、１．に記載の結晶体。
３．アセトニトリルを用いて晶析する工程を含むことを特徴とする、１．または２．に記載の結晶体の製造方法。
４．さらに、晶析により得られた結晶を４５℃以上であって融点より低い温度条件下において乾燥する工程を含むことを特徴とする、３．に記載の製造方法。The present invention is as follows.
1. 1. Of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene, characterized by having at least one endothermic peak in the temperature range of 158 ° C. or higher and lower than 161 ° C. by differential scanning calorimetry. Crystal.
2. 1. It is not an inclusion body. The crystal according to.
3. 3. 1. It comprises a step of crystallization using acetonitrile. Or 2. The method for producing a crystal according to.
4. Further, the present invention comprises a step of drying the crystals obtained by crystallization under temperature conditions of 45 ° C. or higher and lower than the melting point. The manufacturing method described in.
本発明によれば、示差走査熱量分析による特定の吸熱ピークを有し、包接体ではない９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体および、その結晶体の製造方法が提供可能である。
９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンが有機溶媒等の化合物を包接している場合は、当該包接体と、例えば（メタ）アクリル酸等とを反応させる際に、包接している有機溶媒等の化合物が反応を阻害し、反応が進行しないという問題が発生する。また、当該包接体を溶融し樹脂原料として使用する際も、溶融中に発生する包接した有機溶媒等の化合物に由来する蒸気を反応装置から除去する必要があるほか、残存する有機溶媒等の化合物により目的とする樹脂の品質が低下する等の問題もあった。さらに、包接する有機溶媒等の化合物の引火点や発火点によっては、当該包接体の輸送や保管時における防災上の懸念もあった。
前述のとおり、示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有し、包接体ではない９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体は、未だ知られていない。しかも、従来の包接結晶から有機溶媒を除去するより、はるかに低い熱量により包接した有機溶媒を除去できるため、製造における消費エネルギーを抑えることができる。
すなわち、示差走査熱量分析による特定の吸熱ピークを有し、包接体ではない９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの新規な結晶体とその製造方法の提供は、樹脂原料等の工業的な使用において非常に有用である。According to the present invention, a crystal of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene which has a specific endothermic peak by differential scanning calorimetry and is not an inclusion body, and A method for producing the crystal can be provided.
When 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene encapsulates a compound such as an organic solvent, the inclusion body and, for example, (meth) acrylic acid and the like are mixed. During the reaction, a compound such as an inclusion organic solvent inhibits the reaction, causing a problem that the reaction does not proceed. Further, when the inclusion body is melted and used as a resin raw material, it is necessary to remove the vapor derived from the compound such as the inclusiond organic solvent generated during melting from the reactor, and the remaining organic solvent or the like is used. There is also a problem that the quality of the target resin is deteriorated by the compound of. Further, depending on the flash point or ignition point of the compound such as the organic solvent to be included, there is a concern about disaster prevention during transportation or storage of the inclusion body.
As described above, it has at least one endothermic peak in the temperature range of 158 ° C. or higher and lower than 161 ° C. by differential scanning calorimetry, and is not an inclusion body, 9,9-bis [4- (2-hydroxyethoxy) -3-. Phenylphenyl] Fluorene crystals are not yet known. Moreover, since the included organic solvent can be removed with a much lower amount of heat than the conventional organic solvent is removed from the included crystals, energy consumption in production can be suppressed.
That is, a novel crystal of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene which has a specific endothermic peak by differential scanning calorimetry and is not an inclusion body, and a method for producing the same. Is very useful in the industrial use of resin raw materials and the like.
以下、本発明を詳細に説明する。
本発明の９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンは下記化学式（１）で表される化合物である。
The 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene of the present invention is a compound represented by the following chemical formula (1).
＜合成方法について＞
本発明における、９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの合成方法については、特に制限はなく、例えば、前述の特許文献３に記載された公知製造方法を適用できる。
下記反応式に示す、化学式（２）で示される９−フルオレノンと化学式（３）で示されるアルコール類との反応について説明する。
反応に際して、酸触媒を使用することができる。使用する酸触媒は特に制限されず、公知の酸触媒を使用することができる。具体的な酸触媒としては、例えば、塩酸、塩化水素ガス、６０〜９８％硫酸、８５％リン酸等の無機酸、ｐ−トルエンスルホン酸、メタンスルホン酸、シュウ酸、蟻酸、トリクロロ酢酸またはトリフルオロ酢酸等の有機酸、ヘテロポリ酸等の固体酸等を挙げることができる。好ましくは リンタングステン酸等のヘテロポリ酸である。このような酸触媒の好適な使用量は反応条件によって異なるが、例えば、リンタングステン酸等のヘテロポリ酸の場合は、９−フルオレノン１００重量部に対して、１〜７０重量部の範囲、好ましくは、５〜４０重量部の範囲、より好ましくは１０〜３０重量部の範囲で用いられる。
反応に際して、酸触媒と共に必要に応じてチオール類等の助触媒を使用してもよい。使用により反応速度を加速させることができる。このようなチオール類としては、アルキルメルカプタン類やメルカプトカルボン酸類が挙げられ、好ましくは、炭素数１〜１２のアルキルメルカプタン類や炭素数１〜１２のメルカプトカルボン酸類である。炭素数１〜１２のアルキルメルカプタン類としては、例えば、メチルメルカプタン、エチルメルカプタン、ｎ−オクチルメルカプタン、ｎ−ドデシルメルカプタン等やそれらのナトリウム塩等のようなアルカリ金属塩が挙げられ、炭素数１〜１２のメルカプトカルボン酸類としては、例えば、チオ酢酸、β−メルカプトプロピオン酸等が挙げられる。また、これらは単独または２種類以上の組み合わせで使用できる。助触媒としてのチオール類の使用量は、原料の９−フルオレノンに対し通常１〜３０モル％の範囲、好ましくは２〜１０モル％の範囲で用いられる。<About synthesis method>
The method for synthesizing 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene in the present invention is not particularly limited, and for example, the known production method described in Patent Document 3 described above. Can be applied.
The reaction between 9-fluorenone represented by the chemical formula (2) and the alcohols represented by the chemical formula (3) shown in the following reaction formula will be described.
An acid catalyst can be used in the reaction. The acid catalyst used is not particularly limited, and a known acid catalyst can be used. Specific acid catalysts include, for example, inorganic acids such as hydrochloric acid, hydrogen chloride gas, 60-98% sulfuric acid and 85% phosphoric acid, p-toluenesulfonic acid, methanesulfonic acid, oxalic acid, formic acid, trichloroacetic acid or tri. Examples thereof include organic acids such as fluoroacetic acid and solid acids such as heteropolyacids. It is preferably a heteropolyacid such as phosphotungstic acid. The suitable amount of such an acid catalyst to be used varies depending on the reaction conditions. For example, in the case of a heteropolyacid such as phosphotungstic acid, the range is 1 to 70 parts by weight, preferably 1 to 70 parts by weight, based on 100 parts by weight of 9-fluorenone. , 5-40 parts by weight, more preferably 10-30 parts by weight.
In the reaction, a co-catalyst such as thiols may be used together with the acid catalyst, if necessary. The reaction rate can be accelerated by use. Examples of such thiols include alkyl mercaptans and mercaptocarboxylic acids, preferably alkyl mercaptans having 1 to 12 carbon atoms and mercaptocarboxylic acids having 1 to 12 carbon atoms. Examples of alkyl mercaptans having 1 to 12 carbon atoms include alkali metal salts such as methyl mercaptan, ethyl mercaptan, n-octyl mercaptan, n-dodecyl mercaptan, and sodium salts thereof, and have 1 to 12 carbon atoms. Examples of the 12 mercaptocarboxylic acids include thioacetic acid and β-mercaptopropionic acid. In addition, these can be used alone or in combination of two or more types. The amount of thiols used as a co-catalyst is usually in the range of 1 to 30 mol%, preferably in the range of 2 to 10 mol% with respect to the raw material 9-fluorenone.
反応に際して反応溶媒は使用しなくてもよいが、工業的生産時の操作性や反応速度の向上などの理由で使用してもよい。反応溶媒としては、反応温度において反応器から留出せず、反応に不活性であれば特に制限はないが、例えば、トルエン、キシレン等の芳香族炭化水素、メタノール、エタノール、１−プロパノール、２−プロパノール等の低級脂肪族アルコール、ヘキサン、ヘプタン、シクロヘキサン等の飽和脂肪族炭化水素等の有機溶媒や水またはこれらの混合物が挙げられる。これらのうち、芳香族炭化水素が好ましく用いられる。
反応温度は、使用する酸触媒の種類により異なるが、酸触媒としてリンタングステン酸等のヘテロポリ酸を使用する場合は、通常２０〜２００℃、好ましくは４０〜１７０℃、さらに好ましくは５０〜１２０℃の範囲である。反応圧力は、使用する有機溶媒の沸点によっては、反応温度が前記範囲内になるように加圧または減圧下で行ってもよく、生成する水を除去しながら反応を行ってもよい。
反応時間は、使用する酸触媒の種類や、反応温度等の反応条件により異なるが、通常１〜３０時間程度で終了する。
反応の終点は、液体クロマトグラフィーまたはガスクロマトグラフィー分析にて確認することができる。未反応の９−フルオレノンが消失し、目的物の増加が認められなくなった時点を反応の終点とするのが好ましい。The reaction solvent may not be used in the reaction, but it may be used for reasons such as operability during industrial production and improvement of the reaction rate. The reaction solvent is not particularly limited as long as it is not distilled from the reactor at the reaction temperature and is inactive in the reaction. For example, aromatic hydrocarbons such as toluene and xylene, methanol, ethanol, 1-propanol and 2- Examples thereof include lower aliphatic alcohols such as propanol, organic solvents such as saturated aliphatic hydrocarbons such as hexane, heptane and cyclohexane, water, and mixtures thereof. Of these, aromatic hydrocarbons are preferably used.
The reaction temperature varies depending on the type of acid catalyst used, but when a heteropolyacid such as phosphotungstic acid is used as the acid catalyst, it is usually 20 to 200 ° C, preferably 40 to 170 ° C, and more preferably 50 to 120 ° C. Is the range of. The reaction pressure may be pressurized or reduced under pressure so that the reaction temperature is within the above range, depending on the boiling point of the organic solvent used, or the reaction may be carried out while removing the water to be produced.
The reaction time varies depending on the type of acid catalyst used and reaction conditions such as reaction temperature, but is usually completed in about 1 to 30 hours.
The end point of the reaction can be confirmed by liquid chromatography or gas chromatography analysis. It is preferable that the end point of the reaction is the time when the unreacted 9-fluorenone disappears and the increase of the target substance is no longer observed.
＜反応の後処理について＞
このような反応の終了後に、公知の後処理方法を適用することができる。例えば、反応終了液に、酸触媒を中和するために、水酸化ナトリウム水溶液、アンモニア水溶液等のアルカリ水溶液を加える。中和した反応混合液を静置し、必要に応じて水と分離する溶媒を加えて、水層を分離除去する。必要に応じて得られた油層に蒸留水を加え、撹拌して水洗した後、水層を分離除去する操作を１回乃至複数回繰り返し行い中和塩を除去し、得られた油層をそのまま冷却して結晶が析出すれば、析出した結晶を分離して粗結晶を得ることができる。また、得られた油層から溶媒や余剰の上記化学式（３）で示されるアルコール類を、蒸留により除去して、得られた残渣に芳香族炭化水素等の溶媒を加えて均一の溶液とし、冷却して析出した結晶を分離して粗結晶を得てもよい。この粗結晶や前記残渣は、本発明の晶析する工程を経ることにより、示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有し、包接体ではない９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体を得ることができる。<Post-treatment of reaction>
After completion of such a reaction, a known post-treatment method can be applied. For example, an alkaline aqueous solution such as a sodium hydroxide aqueous solution or an ammonia aqueous solution is added to the reaction completion solution in order to neutralize the acid catalyst. The neutralized reaction mixture is allowed to stand, and if necessary, a solvent that separates from water is added to separate and remove the aqueous layer. If necessary, distilled water is added to the obtained oil layer, stirred and washed with water, and then the operation of separating and removing the water layer is repeated once or multiple times to remove the neutralized salt, and the obtained oil layer is cooled as it is. When the crystals are precipitated, the precipitated crystals can be separated to obtain crude crystals. Further, the solvent and excess alcohols represented by the above chemical formula (3) are removed from the obtained oil layer by distillation, and a solvent such as an aromatic hydrocarbon is added to the obtained residue to prepare a uniform solution, which is cooled. The precipitated crystals may be separated to obtain crude crystals. The crude crystals and the residue have at least one endothermic peak in the temperature range of 158 ° C. or higher and lower than 161 ° C. by differential scanning calorimetry by undergoing the crystallization step of the present invention, and are not inclusion bodies. , 9-Bis [4- (2-Hydroxyethoxy) -3-phenylphenyl] fluorene crystals can be obtained.
＜晶析する工程について＞
本発明の製造方法は、アセトニトリルを用いて晶析する工程（以下、晶析工程ともいう。）を含むことを特徴とするものである。ここで、使用可能なアセトニトリルとしては、特に限定されることなく、一般的に市販されているアセトニトリルを使用することができる。
晶析工程に使用するアセトニトリルの量は、反応の後処理により得られた残渣または粗結晶に含まれる９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレン１００重量部に対して、１５０〜６００重量部が好ましく、２００〜５００重量部がより好ましく、２５０〜４００重量部がさらに好ましく、中でも、３００〜３５０重量部が最も好ましい。使用するアセトニトリルの量が多いと、得られる結晶量が低下してしまい、少ないと目的物の純度が低下し好ましくない。さらに、使用するアセトニトリルの量が少ないと、晶析工程に使用する反応後処理工程により得られた残渣または粗結晶に含まれる溶媒、例えば、トルエン等の芳香族炭化水素を包接する９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンが増加してしまうため好ましくない。
本発明の晶析工程においては、アセトニトリル以外の溶媒を使用すると、示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有し、包接体ではない９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体を得ることができないために、好ましくない。
本発明の晶析工程では、使用する反応後処理後の残渣または粗結晶に、アセトニトリルを添加し、常圧または加圧下でアセトニトリルの沸点以下まで加温して完溶させて均一な溶液とした後、冷却して析出する結晶を得ることができる。加温して均一な溶液とした後、冷却する場合には、１時間あたり１〜１０℃、好ましくは１時間あたり３〜７℃で、冷却して結晶を析出させる。結晶を析出させる温度としては、４０〜５８℃の温度範囲が好ましく、４５〜５５℃の温度範囲がより好ましく、中でも５０℃程度の温度が結晶析出温度としては適している。また、結晶を析出させる際には、種晶を使用しても良い。結晶が析出開始した後は、０〜５時間同温度で保持し、前記冷却速度で、０〜４０℃、好ましくは１０〜３５℃、より好ましくは２０〜３０℃まで冷却して、０〜３時間同温度で保持した後、析出した結晶を濾過操作等により分離することが好ましい。<About the crystallization process>
The production method of the present invention is characterized by including a step of crystallization using acetonitrile (hereinafter, also referred to as a crystallization step). Here, the acetonitrile that can be used is not particularly limited, and generally commercially available acetonitrile can be used.
The amount of acetonitrile used in the crystallization step is 100 parts by weight of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene contained in the residue or crude crystal obtained by the post-treatment of the reaction. On the other hand, 150 to 600 parts by weight is preferable, 200 to 500 parts by weight is more preferable, 250 to 400 parts by weight is further preferable, and 300 to 350 parts by weight is most preferable. If the amount of acetonitrile used is large, the amount of crystals obtained will decrease, and if it is small, the purity of the target product will decrease, which is not preferable. Further, when the amount of acetonitrile used is small, the solvent contained in the residue or crude crystal obtained by the reaction post-treatment step used in the crystallization step, for example, an aromatic hydrocarbon such as toluene is encapsulated 9,9-. Bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene increases, which is not preferable.
In the crystallization step of the present invention, when a solvent other than acetonitrile is used, it has at least one endothermic peak by differential scanning calorimetry in the temperature range of 158 ° C. or higher and lower than 161 ° C., and is not an inclusion body 9,9-. It is not preferable because crystals of bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene cannot be obtained.
In the crystallization step of the present invention, acetonitrile is added to the residue or crude crystals after the post-reaction treatment to be used, and the mixture is heated to below the boiling point of acetonitrile under normal pressure or pressure to completely dissolve the solution to obtain a uniform solution. After that, it can be cooled to obtain crystals that precipitate. When the solution is heated to obtain a uniform solution and then cooled, the crystals are precipitated by cooling at 1 to 10 ° C. per hour, preferably 3 to 7 ° C. per hour. As the temperature for precipitating crystals, a temperature range of 40 to 58 ° C. is preferable, a temperature range of 45 to 55 ° C. is more preferable, and a temperature of about 50 ° C. is particularly suitable as a crystal precipitation temperature. Further, when precipitating crystals, seed crystals may be used. After the crystals start to precipitate, they are kept at the same temperature for 0 to 5 hours, cooled to 0 to 40 ° C., preferably 10 to 35 ° C., more preferably 20 to 30 ° C. at the above cooling rate, and 0 to 3 After holding at the same temperature for a time, it is preferable to separate the precipitated crystals by a filtration operation or the like.
＜乾燥する工程について＞
乾燥する工程（以下、乾燥工程ともいう。）を実施することにより、本発明の晶析工程において使用したアセトニトリルを完全に除去することができる。本発明の乾燥工程は、晶析工程により得られた結晶を、４５℃以上であって融点より低い温度条件下で実施することができるが、７０℃以上が好ましく、９０℃以上がより好ましく、１００℃以上が特に好ましい。また、その他の条件等によっては熱により結晶の色相が悪化する可能性もあるため、１５０℃以下が好ましく、１３０℃以下がより好ましい。４５℃より低い温度では、晶析工程において使用したアセトニトリルを除去できないか、除去できたとしても非常に多くの時間が必要となり好ましくない。
乾燥工程を実施する際は常圧でも減圧下でも良いが、工業的に実施する場合には、減圧下において実施する方がより効率的に、晶析工程において使用したアセトニトリルを除去できることからも好適である。その他、乾燥工程は、窒素等の不活性ガス雰囲気中で行うことがより好ましい。<About the drying process>
By carrying out a drying step (hereinafter, also referred to as a drying step), acetonitrile used in the crystallization step of the present invention can be completely removed. In the drying step of the present invention, the crystals obtained by the crystallization step can be carried out under temperature conditions of 45 ° C. or higher and lower than the melting point, but 70 ° C. or higher is preferable, 90 ° C. or higher is more preferable. 100 ° C. or higher is particularly preferable. Further, depending on other conditions and the like, the hue of the crystal may be deteriorated by heat, so 150 ° C. or lower is preferable, and 130 ° C. or lower is more preferable. At a temperature lower than 45 ° C., acetonitrile used in the crystallization step cannot be removed, or even if it can be removed, a very large amount of time is required, which is not preferable.
The drying step may be carried out under normal pressure or reduced pressure, but when carried out industrially, it is more efficient to carry out under reduced pressure because acetonitrile used in the crystallization step can be removed. Is. In addition, the drying step is more preferably performed in an atmosphere of an inert gas such as nitrogen.
＜本発明の結晶体＞
本発明の９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体は、示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有することを特徴とする。示差走査熱量分析による吸熱ピークは、１５９℃以上１６１℃未満の温度範囲がより好ましく、１６０℃以上１６１℃未満の温度範囲がさらに好ましい。さらに、本発明の９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの結晶体は包接体ではない、すなわち、有機溶媒等の化合物を包接しない結晶体である。
本発明における、有機溶媒等の化合物を包接しない結晶体としては、残存する有機溶媒の含量が１重量％以下である結晶体が好ましく、０．５重量％以下である結晶体がより好ましく、０．３重量％以下である結晶体がさらに好ましく、０．１重量％以下が特に好ましい。また、本発明における、有機溶媒等の化合物を包接しない結晶体は、ゆるみ嵩密度が０．３５〜０．４５ｇ／ｃｍ３の範囲であることが好ましい。<Crystal of the present invention>
The crystal of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene of the present invention has at least one endothermic peak in the temperature range of 158 ° C. or higher and lower than 161 ° C. by differential scanning calorimetry. It is characterized by having. The endothermic peak by differential scanning calorimetry is more preferably in the temperature range of 159 ° C. or higher and lower than 161 ° C., and further preferably in the temperature range of 160 ° C. or higher and lower than 161 ° C. Furthermore, the crystal of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene of the present invention is not a clathrate, that is, a crystal that does not clasp a compound such as an organic solvent. be.
In the present invention, as the crystal body that does not include a compound such as an organic solvent, a crystal body having a residual organic solvent content of 1% by weight or less is preferable, and a crystal body having a residual organic solvent content of 0.5% by weight or less is more preferable. Crystals of 0.3% by weight or less are more preferable, and 0.1% by weight or less is particularly preferable. Further, the crystal body in the present invention that does not include a compound such as an organic solvent preferably has a loose bulk density in the range of 0.35 to 0.45 g / cm 3.
以下、本発明を実施例により具体的に説明するが、本発明はこれら実施例に限定されるものではない。
分析方法は以下の通りである。
＜分析方法＞
１．示差走査熱量分析（ＤＳＣ）
結晶体５ｍｇをアルミパンに秤量し、示差走査熱量測定装置（（株）島津製作所製：ＤＳＣ−６０）を用いて、酸化アルミニウムを対照として下記操作条件により測定した。
（操作条件）
昇温速度：１０℃／分
測定温度範囲：３０〜２００℃
測定雰囲気：開放、窒素５０ｍＬ／分
２．示差熱・熱重量分析（ＤＴＧ）
結晶体８ｍｇをアルミパンに秤量し、示差熱・熱重量分析装置（（株）島津製作所製：ＤＴＧ−６０Ａ）を用いて、下記操作条件により測定した。
（操作条件）
昇温速度：１０℃／分
測定温度範囲：３０〜３００℃
測定雰囲気：開放、窒素５０ｍＬ／分Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited to these Examples.
The analysis method is as follows.
<Analysis method>
1. 1. Differential scanning calorimetry (DSC)
5 mg of the crystal was weighed in an aluminum pan, and measured using a differential scanning calorimetry device (manufactured by Shimadzu Corporation: DSC-60) under the following operating conditions using aluminum oxide as a control.
(Operating conditions)
Temperature rise rate: 10 ° C / min Measurement temperature range: 30-200 ° C
Measurement atmosphere: open, nitrogen 50 mL / min 2. Differential thermal / thermogravimetric analysis (DTG)
8 mg of the crystal was weighed on an aluminum pan and measured using a differential thermal / thermogravimetric analyzer (manufactured by Shimadzu Corporation: DTG-60A) under the following operating conditions.
(Operating conditions)
Temperature rise rate: 10 ° C / min Measurement temperature range: 30 to 300 ° C
Measurement atmosphere: open, nitrogen 50 mL / min
３．ＨＳ−ＧＣ（残存溶媒分析）
「ＨＳ−ＧＣ」とは、気相部分（ヘッドスペース、ＨＳ）をガスクロマトグラフ（ＧＣ）に導入して分析する手法である。バイアルに封入された試料を一定時間保温することで気相と試料を平衡状態として気相部分を分析することにより、結晶中に残存する溶媒量を測定した。具体的には、結晶体０．５ｇを秤量し、そこにＮ−メチルピロリドンを精秤しながら添加して全体を１０ｇにする。この溶液をＨＳ用バイアルに約３ｇを秤量して、漏れないようにクランプして下記条件で測定した。
（ＧＣ分析条件）
装置：（株）島津製作所製：ＧＣ−２０１０ｐｌｕｓ
カラム：ＴＣ−１ ６０ｍ×０．２５ｍｍΦ、膜厚０．２５μｍ
検出器：ＦＩＤ
ＩＮＪ温度：３００℃、ＦＩＤ温度：３１０℃
昇温条件：４０℃（２５分）→２０℃／分→３００℃（５分）
カラム線速度：１９．９ｃｍ／秒
（ＨＳ分析条件）
機器：ＴｕｒｂｏＭａｔｒｉｘ ＨＳ ４０（パーキンエルマー社）
キャリアガス圧：１５４ｋＰａ
バイアル加熱温度：１００℃
注入時間：０．０５分3. 3. HS-GC (residual solvent analysis)
"HS-GC" is a method of introducing a gas phase portion (head space, HS) into a gas chromatograph (GC) for analysis. The amount of solvent remaining in the crystal was measured by analyzing the gas phase portion with the gas phase and the sample in an equilibrium state by keeping the sample enclosed in the vial warm for a certain period of time. Specifically, 0.5 g of the crystal is weighed, and N-methylpyrrolidone is added thereto while being weighed to make the whole amount 10 g. About 3 g of this solution was weighed in an HS vial, clamped so as not to leak, and measured under the following conditions.
(GC analysis conditions)
Equipment: Shimadzu Corporation: GC-2010plus
Column: TC-1 60m x 0.25mmΦ, film thickness 0.25μm
Detector: FID
INJ temperature: 300 ° C, FID temperature: 310 ° C
Heating conditions: 40 ° C (25 minutes) → 20 ° C / min → 300 ° C (5 minutes)
Column linear velocity: 19.9 cm / sec (HS analysis conditions)
Equipment: TurboMatrix HS 40 (PerkinElmer)
Carrier gas pressure: 154 kPa
Vial heating temperature: 100 ° C
Injection time: 0.05 minutes
４．ゆるみ嵩密度
多機能型粉体物性測定器マルチテスター（ＭＴ―１００１型／（株）セイシン企業製）を用い、容量２０ｃｍ３の測定用セルに、空気の隙間ができないように篩を通して結晶を静かに投入し、前記測定用セルが結晶で充填した時のセル内の結晶の重量ａ（ｇ）を測定し、下記計算式よりゆるみ嵩密度を算出した。
［計算式］
ゆるみ嵩密度（ｇ／ｃｍ３）＝結晶体の重量ａ（ｇ）÷２０ｃｍ３
５．粉末Ｘ線回析（ＸＲＤ）分析
結晶体０．１ｇをガラス試験板の試料充填部に充填し、下記粉末Ｘ線回析装置を用いて、下記条件により測定した。
装置：（株）リガク製：ＳｍａｒｔＬａｂ
Ｘ線源：ＣｕＫα
スキャン軸：２θ／θ
モード：連続
測定範囲：２θ＝５°〜７０°
ステップ：０．０１°
スピード計測時間：２θ＝２°／ｍｉｎ
ＩＳ：１／２
ＲＳ：２０．００ｍｍ
出力：４０ｋＶ−３０ｍＡ
６．粒度分布
結晶０．１ｇに、分散溶媒として水０．１ｇ、分散剤(中性洗剤)一滴を加えて混合し、これを装置に投入し、超音波処理（３分）後、測定した。
装置：（株）島津製作所製：ＳＡＬＤ−２２００
測定方式：レーザー回析方式
７．ＹＩ値（黄色度）
結晶２．０ｇを、純度９９重量％以上の１，４ジオキサン１８．０ｇに溶解させ、以下の条件で得られた１，４−ジオキサン溶液のＹＩ値（黄色度）を測定した。
装置：色差計（日本電色工業社製，ZE6000）
使用セル：ガラス試験管（直径２４ｍｍ）
なお、測定に使用する１，４−ジオキサン自身の着色が測定値に影響を与えないよう、事前に１，４−ジオキサンの色相を測定して補正した。(ブランク測定)。このブランク測定を実施したうえで、サンプルを測定した値を本発明におけるＹＩ値（黄色度）とした。4. Loose bulk density Using a multi-function measuring instrument multi-tester (MT-1001 type / manufactured by Seishin Co., Ltd.), pass a sieve through a measuring cell with a capacity of 20 cm 3 so that there are no gaps in the air, and quietly crystallize the crystals. The weight a (g) of the crystal in the cell when the measurement cell was filled with crystals was measured, and the loose bulk density was calculated from the following formula.
[a formula]
Loose bulk density (g / cm 3 ) = Crystal weight a (g) ÷ 20 cm 3
5. Powder X-ray Diffraction (XRD) Analysis 0.1 g of the crystal was filled in the sample filling part of the glass test plate, and the measurement was carried out under the following conditions using the following powder X-ray diffractometer.
Equipment: Made by Rigaku Co., Ltd .: SmartLab
X-ray source: CuKα
Scan axis: 2θ / θ
Mode: Continuous measurement range: 2θ = 5 ° to 70 °
Step: 0.01 °
Speed measurement time: 2θ = 2 ° / min
IS: 1/2
RS: 20.00mm
Output: 40kV-30mA
6. Particle size distribution To 0.1 g of crystals, 0.1 g of water as a dispersion solvent and one drop of a dispersant (neutral detergent) were added and mixed, and this was put into an apparatus, ultrasonically treated (3 minutes), and then measured.
Equipment: Shimadzu Corporation: SALD-2200
Measurement method: Laser diffraction method 7. YI value (yellowness)
2.0 g of crystals were dissolved in 18.0 g of 1,4 dioxane having a purity of 99% by weight or more, and the YI value (yellowness) of the 1,4-dioxane solution obtained under the following conditions was measured.
Equipment: Color difference meter (manufactured by Nippon Denshoku Kogyo Co., Ltd., ZE6000)
Cell used: Glass test tube (diameter 24 mm)
The hue of 1,4-dioxane was measured and corrected in advance so that the coloring of 1,4-dioxane itself used for the measurement did not affect the measured value. (Blank measurement). After performing this blank measurement, the value measured by the sample was taken as the YI value (yellowness) in the present invention.
＜合成例＞
９，９−ビス［４−（２−ヒドロキシエトキシ）−３−フェニルフェニル］フルオレンの合成
温度計、撹拌機、冷却管を備えた１リットル４つ口フラスコ内を窒素置換し、９−フルオレノン７６．３ｇ（０．４２３モル）、化学式（３）で示されるアルコール類９０７．０ｇ（４．２４モル）、リンタングステン酸１３．７ｇ、トルエン３８８．７ｇを仕込み、反応温度１００℃、圧力４２ｋＰａにおいて、反応生成水を除去しながら反応を行った。液体クロマトグラフィー分析により原料消失を確認し、反応終了とした。反応液を８０℃にまで冷却し、トルエン３３９．１ｇ、１５％水酸化ナトリウム水溶液２６．６９ｇ、蒸留水２５０ｇを加えて反応液を中和して静置し、水層を除去した。得られた油層に蒸留水２５０ｇを加えて撹拌後静置し、水層を除去する水洗操作を４回実施した。得られた油層から、蒸留により溶媒等の低沸点物質と未反応の化学式（３）で示されるアルコール類を取り除いた後、残渣をトルエン１５００ｇで溶解した。このトルエン溶液を２５℃にまで冷却し、析出した結晶を濾過し、目的物のトルエン包接体２３２．０ｇ（高速液体クロマトグラフィー分析による純度９８．０％、トルエン５重量％包接）を得た。<Synthesis example>
Synthesis of 9,9-bis [4- (2-hydroxyethoxy) -3-phenylphenyl] fluorene The inside of a 1-liter four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen to make 9-fluorenone 76. .3 g (0.423 mol), 907.0 g (4.24 mol) of alcohols represented by the chemical formula (3), 13.7 g of phosphotungstate, and 388.7 g of toluene were charged, and the reaction temperature was 100 ° C. and the pressure was 42 kPa. , The reaction was carried out while removing the reaction-generated water. The disappearance of the raw materials was confirmed by liquid chromatography analysis, and the reaction was terminated. The reaction mixture was cooled to 80 ° C., and 339.1 g of toluene, 26.69 g of a 15% aqueous sodium hydroxide solution, and 250 g of distilled water were added to neutralize the reaction solution and allowed to stand to remove the aqueous layer. 250 g of distilled water was added to the obtained oil layer, and the mixture was stirred and allowed to stand, and a water washing operation for removing the aqueous layer was carried out four times. A low boiling point substance such as a solvent and unreacted alcohols represented by the chemical formula (3) were removed from the obtained oil layer by distillation, and then the residue was dissolved in 1500 g of toluene. This toluene solution is cooled to 25 ° C., and the precipitated crystals are filtered to obtain 232.0 g of the target toluene clathrate (purity 98.0% by high performance liquid chromatography analysis, 5 wt% toluene inclusion). rice field.
＜実施例１＞
（晶析工程）
温度計、撹拌機、冷却管を備えた２００ミリリットル４つ口フラスコに、上記「合成例」で得られた白色結晶１０ｇとアセトニトリル３０ｇを入れて、６０℃で溶解後、１時間あたり５℃の速度で冷却すると、５０℃付近で結晶が析出した。その後、同じ冷却速度でさらに２５℃まで冷却して、析出した結晶を濾過した。
（乾燥工程）
晶析工程により得られた結晶を、温度２０℃、１．２ｋＰａで２時間乾燥させた。得られた結晶は、ＨＳ−ＧＣ分析により残存溶媒がトルエン０．０５重量％、アセトニトリル３．６重量％であった。さらに、同一条件でこの結晶を４時間乾燥したが、残存溶媒の含有量に変化はなかった。このことから、晶析工程で得られた結晶は、アセトニトリル包接体であることが明らかになった。このアセトニトリル包接体について示差熱・熱重量分析（ＤＴＧ）を行った結果、包接するアセトニトリルを除去する熱量は約４０Ｊ／ｇであることが確認された。このアセトニトリル包接体の示差熱・熱重量分析（ＤＴＧ）曲線を示す図を図１に示す。
このアセトニトリル包接体を温度１００℃、圧力１．２ｋＰａの環境で４時間乾燥し、包接体ではない結晶９．０ｇが得られた。
（分析結果）
乾燥工程により得られた結晶は、高速液体クロマトグラフィー分析による純度が９８．７％であり、ＨＳ−ＧＣ分析により残存溶媒がトルエン０．０５重量％、アセトニトリル０．２重量％であることが確認できた。
上記分析を行った、包接体ではない結晶の示差走査熱量測定（ＤＳＣ）曲線を示す図を図２に示す。<Example 1>
(Crystalization process)
In a 200 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube, 10 g of the white crystals and 30 g of acetonitrile obtained in the above "Synthesis Example" were placed, dissolved at 60 ° C., and then dissolved at 5 ° C. per hour. When cooled at a rate, crystals were precipitated at around 50 ° C. Then, it was further cooled to 25 ° C. at the same cooling rate, and the precipitated crystals were filtered.
(Drying process)
The crystals obtained by the crystallization step were dried at a temperature of 20 ° C. and 1.2 kPa for 2 hours. The obtained crystals had a residual solvent of 0.05% by weight of toluene and 3.6% by weight of acetonitrile by HS-GC analysis. Further, the crystals were dried under the same conditions for 4 hours, but the content of the residual solvent did not change. From this, it was clarified that the crystal obtained in the crystallization step was an acetonitrile clathrate. As a result of differential thermal analysis (DTG) of this acetonitrile inclusion body, it was confirmed that the amount of heat for removing the acetonitrile to be included was about 40 J / g. The figure which shows the differential thermal analysis (DTG) curve of this acetonitrile inclusion body is shown in FIG.
The acetonitrile inclusion body was dried in an environment of a temperature of 100 ° C. and a pressure of 1.2 kPa for 4 hours to obtain 9.0 g of crystals that were not inclusion bodies.
(result of analysis)
The crystals obtained by the drying step were confirmed to have a purity of 98.7% by high performance liquid chromatography analysis and a residual solvent of 0.05% by weight of toluene and 0.2% by weight of acetonitrile by HS-GC analysis. did it.
FIG. 2 shows a differential scanning calorimetry (DSC) curve of a non-inclusion crystal that has undergone the above analysis.
＜実施例２＞
（晶析工程）
温度計、撹拌機、冷却管を備えた１リットル四つ口フラスコに、上記「合成例」で得られた白色結晶２０８．７ｇとアセトニトリル６２６．１ｇを入れて６０℃で溶解後、１時間あたり５℃の冷却速度で冷却し、実施例１で得られた種結晶概略０．１ｇを５５℃で添加したところ、５０℃で析出結晶の増加を確認できた。同じ冷却速度で２５℃まで冷却し、２５℃で２時間保持し、析出した結晶を濾別した。
（乾燥工程）
晶析工程により得られた結晶を、温度２０℃、圧力１．２ｋＰａの環境で２時間乾燥させた。得られた結晶は、ＨＳ−ＧＣ分析により残存溶媒がトルエン０．０８重量％、アセトニトリル３．７重量％であった。さらに、同一条件でこの結晶を２時間乾燥したが、残存溶媒の含有量に変化はなかった。このことから、晶析工程により得られた結晶は、アセトニトリル包接体であることが明らかとなった。このアセトニトリル包接体について示差熱・熱重量分析（ＤＴＧ）を行った結果、包接するアセトニトリルを除去する熱量は約９４Ｊ／ｇであることが確認された。
アセトニトリル包接体を、温度１００℃、圧力１．２ｋＰａの環境で１４時間乾燥させることにより、包接体ではない結晶１５６．６ｇが得られた。
（分析結果）
乾燥工程により得られた結晶は、高速液体クロマトグラフィー分析による純度が９８．８％であり、ＨＳ−ＧＣ分析により残存溶媒がトルエン０．０８重量％、アセトニトリル０．００３重量％であること、さらに、示差走査熱量分析による吸熱ピークトップ温度は１６０℃、ＹＩ値（黄色度）は、０．４７、ゆるみ嵩密度０．４ｇ／ｃｍ３であることが確認できた。また、得られた結晶のメディアン径（Ｄ５０）は３４．０μｍ、モード径は３９．６μｍであった。
上記分析を行った、包接体ではない結晶の示差走査熱量測定（ＤＳＣ）曲線を示す図を図３に示す。また、上記付着溶媒を除去して得られた結晶の示差熱・熱重量分析（ＤＴＧ）曲線を示す図を図４に示し、粉末Ｘ線の主なピーク（５％を超える相対積分強度を有するもの）を表１に列挙する。<Example 2>
(Crystalization process)
208.7 g of white crystals and 626.1 g of acetonitrile obtained in the above "Synthesis Example" were placed in a 1-liter four-necked flask equipped with a thermometer, a stirrer, and a cooling tube and dissolved at 60 ° C. per hour. When the mixture was cooled at a cooling rate of 5 ° C. and approximately 0.1 g of the seed crystal obtained in Example 1 was added at 55 ° C., an increase in precipitated crystals was confirmed at 50 ° C. The crystals were cooled to 25 ° C. at the same cooling rate, held at 25 ° C. for 2 hours, and the precipitated crystals were filtered off.
(Drying process)
The crystals obtained by the crystallization step were dried in an environment at a temperature of 20 ° C. and a pressure of 1.2 kPa for 2 hours. The obtained crystals were found to have a residual solvent of 0.08% by weight of toluene and 3.7% by weight of acetonitrile by HS-GC analysis. Further, the crystals were dried under the same conditions for 2 hours, but the content of the residual solvent did not change. From this, it was clarified that the crystal obtained by the crystallization step was an acetonitrile clathrate. As a result of differential thermal analysis (DTG) of this acetonitrile inclusion body, it was confirmed that the calorific value for removing the acetonitrile included was about 94 J / g.
The acetonitrile inclusion body was dried in an environment of a temperature of 100 ° C. and a pressure of 1.2 kPa for 14 hours to obtain 156.6 g of crystals that were not inclusion bodies.
(result of analysis)
The crystals obtained by the drying step have a purity of 98.8% by high performance liquid chromatography analysis, a residual solvent of 0.08% by weight of toluene and 0.003% by weight of acetonitrile by HS-GC analysis, and further. It was confirmed that the heat absorption peak top temperature was 160 ° C., the YI value (yellowness) was 0.47, and the loose bulk density was 0.4 g / cm 3 by the differential scanning calorific value analysis. The median diameter (D50) of the obtained crystal was 34.0 μm, and the mode diameter was 39.6 μm.
FIG. 3 shows a differential scanning calorimetry (DSC) curve of a non-inclusion crystal that has undergone the above analysis. Further, FIG. 4 shows a diagram showing a differential thermal / thermogravimetric analysis (DTG) curve of the crystal obtained by removing the adhesive solvent, and has a main peak of powder X-rays (relative integrated intensity exceeding 5%). Things) are listed in Table 1.
これらの分析により、得られた結晶体は、示差走査熱量分析による吸熱ピークを１５８℃以上１６１℃未満の温度範囲に少なくとも１つ有する結晶体であり、さらには、包接体ではない結晶体であることが明らかとなった。 The crystals obtained by these analyzes are crystals having at least one endothermic peak in the temperature range of 158 ° C. or higher and lower than 161 ° C. by differential scanning calorimetry, and further, a crystal that is not an inclusion body. It became clear that there was.
＜比較例１＞
上記特許文献４の実施例１に記載された製造方法について、追試験を行った。
詳しくは、撹拌機、冷却管、および温度計を備えた１リットル４つ口フラスコ内を窒素置換し、９，９’−ビス（４−ヒドロキシ−３−フェニルフェニル）フルオレン７５ｇ（０．１４９ｍｏｌ）、炭酸カリウム１．７ｇ、エチレンカーボネート３０．０５ｇ（０．３４１ｍｏｌ）、トルエン１１２．５ｇ、およびメチルトリグライム７．５ｇを仕込み、１１０℃まで昇温し、同温度で１６時間撹拌後、高速液体クロマトグラフィー（以下ＨＰＬＣ）測定にて原料が消失していることを確認した。
その後、水３．０７g添加し、１００℃で５時間加水分解を行った。
得られた反応液を９０℃まで冷却した後、水１１３ｇを加え、８０〜８５℃で３０分撹拌し、静置後、水層を分離した。同じ水洗操作を３回繰り返した後、得られた有機溶媒層から溶媒を除去し、濃縮物を得た。得られた濃縮物にトルエン９２ｇ、メタノール３４８ｇを添加し晶析溶液を得た。得られた晶析溶液を６５℃まで昇温し、同温度で１時間撹拌して結晶を完溶させた後、１分あたり０．１℃で冷却することにより５０℃で結晶を析出させ、同温度で２時間撹拌した。更に２２℃まで冷却した後、濾過し結晶を得た。
得られた結晶を１．３ｋＰａの減圧下、５５℃で３時間乾燥した後、結晶の一部をＨＳ-ＧＣで分析した。その結果、晶析工程で用いた溶媒であるメタノールを３．５重量％含有していることが確認された。更に同条件で３時間乾燥を継続し分析しても、メタノールの含有量が４重量％と減少しなかった。この結晶から、包接した溶媒を除去するのに必要な熱量をＤＴＧで測定した結果、約８７５Ｊ／ｇであった。この結晶を内圧１．３ｋＰａの減圧下、内温を９０℃に昇温し、更に３時間乾燥した。メタノールの含有量が０．０２重量％となった為、乾燥終了とした。
得られた結晶の示差熱・熱重量分析（ＤＴＧ）曲線を示す図を図５に、各分析値を下記に示す。
得られた結晶の重さ：７７．９ｇ（収率：８８％）
ＨＰＬＣ純度：９８．６％
トルエン含量：０．０１重量％
メタノール含量：０．０２重量％
比較例２の結果より、メタノール包接体からメタノールを除去するためには、概略９００Ｊ／ｇ程度のエネルギーが必要であることが確認された。
また、得られた結晶のメディアン径（Ｄ５０）は１８．５μｍ、モード径は２１．２μｍであった。<Comparative example 1>
A follow-up test was performed on the production method described in Example 1 of Patent Document 4.
Specifically, the inside of a 1-liter four-necked flask equipped with a stirrer, a cooling tube, and a thermometer was substituted with toluene, and 75 g (0.149 mol) of 9,9'-bis (4-hydroxy-3-phenylphenyl) fluorene was substituted. , 1.7 g of potassium carbonate, 30.05 g (0.341 mol) of ethylene carbonate, 112.5 g of toluene, and 7.5 g of methyl triglime were charged, heated to 110 ° C., stirred at the same temperature for 16 hours, and then a high performance liquid. It was confirmed by chromatography (hereinafter referred to as HPLC) measurement that the raw material had disappeared.
Then, 3.07 g of water was added, and hydrolysis was carried out at 100 ° C. for 5 hours.
The obtained reaction solution was cooled to 90 ° C., 113 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 washing operation three times, the solvent was removed from the obtained organic solvent layer to obtain a concentrate. To the obtained concentrate, 92 g of toluene and 348 g of methanol were added to obtain a crystallization solution. The obtained crystallization solution was heated to 65 ° C. and stirred at the same temperature for 1 hour to completely dissolve the crystals, and then cooled at 0.1 ° C. per minute to precipitate the crystals at 50 ° C. The mixture was stirred at the same temperature for 2 hours. After further cooling to 22 ° C., the crystals were obtained by filtration.
The obtained crystals were dried at 55 ° C. for 3 hours under a reduced pressure of 1.3 kPa, and then a part of the crystals was analyzed by HS-GC. As a result, it was confirmed that the solvent used in the crystallization step, methanol, was contained in an amount of 3.5% by weight. Further, even when the drying was continued for 3 hours under the same conditions and analyzed, the methanol content did not decrease to 4% by weight. The amount of heat required to remove the included solvent from this crystal was measured by DTG and found to be about 875 J / g. The crystals were heated to 90 ° C. under a reduced pressure of 1.3 kPa and further dried for 3 hours. Since the content of methanol was 0.02% by weight, drying was completed.
The figure showing the differential thermal / thermogravimetric analysis (DTG) curve of the obtained crystal is shown in FIG. 5, and each analysis value is shown below.
Weight of obtained crystals: 77.9 g (yield: 88%)
HPLC purity: 98.6%
Toluene content: 0.01% by weight
Methanol content: 0.02% by weight
From the results of Comparative Example 2, it was confirmed that about 900 J / g of energy was required to remove methanol from the methanol inclusion body.
The median diameter (D50) of the obtained crystal was 18.5 μm, and the mode diameter was 21.2 μm.
上記特許文献５の比較例１、実施例８、１２、１７、１９、２０に記載された製造方法について、追試験を行った。
＜参考例１＞
（特許文献５の比較例１）
撹拌器、加熱冷却器、および温度計を備えた１リットル４つ口フラスコ内を窒素置換し、９，９’−ビス（４−ヒドロキシ−３−フェニルフェニル）フルオレン６０ｇ（０．１１９ｍｏｌ）、炭酸カリウム１．２ｇ、エチレンカーボネート２４．１５ｇ（０．２７４ｍｏｌ）、およびトルエン６０ｇを仕込み、１１０℃で３４時間撹拌した。次いで水４．８６g添加し、１００℃で１１時間反応（加水分解）を行った。得られた反応液を８５℃まで冷却した後、トルエン３０gと水１０２ｇを加え、８０〜８５℃で３０分撹拌し、静置後、水層を分離した。同じ水洗操作を３回繰り返した後、得られた有機溶媒層からディーンスターク装置を用いて還流下で水を除去し、冷却により７５℃で結晶が析出し、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。
得られた結晶を上述した方法により分析した結果、トルエン包接体であることを確認した。
得られた結晶の分析結果を下記に示す。
得られた結晶の重さ：６８．５ｇ
ＨＰＬＣ純度：９７．５％
トルエン（ゲスト分子）含量：４．４６重量％A follow-up test was performed on the production methods described in Comparative Example 1, Examples 8, 12, 17, 19, and 20 of Patent Document 5.
<Reference example 1>
(Comparative Example 1 of Patent Document 5)
Nitro was substituted in a 1-liter 4-neck flask equipped with a stirrer, a heating / cooling device, and a thermometer, and 60 g (0.119 mol) of 9,9'-bis (4-hydroxy-3-phenylphenyl) fluorene, carbonic acid. 1.2 g of potassium, 24.15 g (0.274 mol) of ethylene carbonate, and 60 g of toluene were charged and stirred at 110 ° C. for 34 hours. Then, 4.86 g of water was added, and the reaction (hydrolysis) was carried out at 100 ° C. for 11 hours. After cooling the obtained reaction solution to 85 ° C., 30 g of toluene and 102 g of water were added, and 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 washing operation three times, water was removed from the obtained organic solvent layer under reflux using a Dean-Stark apparatus, crystals were precipitated at 75 ° C. by cooling, and the mixture was stirred at the same temperature for 2 hours. After further cooling to 26 ° C., it 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.
As a result of analyzing the obtained crystals by the above-mentioned method, it was confirmed that they were toluene inclusions.
The analysis results of the obtained crystals are shown below.
Weight of obtained crystals: 68.5 g
HPLC purity: 97.5%
Toluene (guest molecule) content: 4.46% by weight
＜比較例２＞
（特許文献５の実施例８：イソブチルケトン）
上記参考例２で得られたトルエン包接体の結晶５ｇとジイソブチルケトン２５ｇを撹拌子の入った試験管に入れ、１００℃で５時間撹拌し、そのまま冷却せずに濾過した。その後、窒素気流中で２時間乾燥した。
得られた結晶の示差走査熱量測定（ＤＳＣ）曲線を示す図を図６に、各分析値を下記に示す。
ＨＰＬＣ純度：９８．４０％
トルエン（ゲスト分子）含量：検出限界以下（ＨＳ−ＧＣ）
融点：１９２℃
ゆるみ嵩密度：０．３１ｇ／ｃｍ３
なお、上記ゆるみ嵩密度は、試験管での簡易試験によるデータである。
比較例３の結果より、上記特許文献５の実施例８により得られる結晶は、融点が１９２℃と高融点結晶であることが、さらに、ゆるみ嵩密度は０．３１ｇ／ｃｍ３と低いことも確認された。<Comparative example 2>
(Example 8 of Patent Document 5: Isobutyl Ketone)
5 g of the toluene clathrate crystal obtained in Reference Example 2 and 25 g of the diisobutyl ketone were placed in a test tube containing a stirrer, stirred at 100 ° C. for 5 hours, and filtered without cooling. Then, it was dried in a nitrogen stream for 2 hours.
The figure showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in FIG. 6, and each analytical value is shown below.
HPLC purity: 98.40%
Toluene (guest molecule) content: below detection limit (HS-GC)
Melting point: 192 ° C
Loose bulk density: 0.31 g / cm 3
The loose bulk density is data obtained by a simple test in a test tube.
From the results of Comparative Example 3, the crystal obtained in Example 8 of Patent Document 5 has a melting point of 192 ° C., which is a high melting point crystal, and further, the loose bulk density is as low as 0.31 g / cm 3. confirmed.
＜比較例３＞（特許文献５の実施例１２：ヘプタン）
上記参考例２で得られたトルエン包接体の結晶５ｇとへプタン２５ｇを撹拌子の入った試験管に入れ、１００℃で２時間撹拌し、そのまま冷却せずに濾過した。その後、窒素気流中で２時間乾燥した。
得られた結晶の示差走査熱量測定（ＤＳＣ）曲線を示す図を図７に、各分析値を下記に示す。
ＨＰＬＣ純度：９８．７４％
トルエン（ゲスト分子）含量：検出限界以下（ＨＳ−ＧＣ）
融点：１９１℃
ゆるみ嵩密度：０．３８ｇ／ｃｍ３
なお、上記ゆるみ嵩密度は、試験管での簡易試験によるデータである。
比較例４の結果より、上記特許文献５の実施例１２により得られる結晶は、融点が１９１℃と高融点結晶であることが確認された。<Comparative Example 3> (Example 12 of Patent Document 5: Heptane)
5 g of the toluene clathrate crystal obtained in Reference Example 2 and 25 g of heptane were placed in a test tube containing a stirrer, stirred at 100 ° C. for 2 hours, and filtered without cooling. Then, it was dried in a nitrogen stream for 2 hours.
The figure showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in FIG. 7, and each analytical value is shown below.
HPLC purity: 98.74%
Toluene (guest molecule) content: below detection limit (HS-GC)
Melting point: 191 ° C
Loose bulk density: 0.38 g / cm 3
The loose bulk density is data obtained by a simple test in a test tube.
From the results of Comparative Example 4, it was confirmed that the crystal obtained in Example 12 of Patent Document 5 had a melting point of 191 ° C. and was a high melting point crystal.
＜比較例４＞
（特許文献５の実施例１７：ジブチルエーテル）
上記参考例２で得られたトルエン包接体の結晶５ｇとジブチルエーテル２５ｇを撹拌子の入った試験管に入れ、１００℃で５時間撹拌し、そのまま冷却せずに濾過した。その後、窒素気流中で２時間乾燥した。
得られた結晶の示差走査熱量測定（ＤＳＣ）曲線を示す図を図８に、各分析値を下記に示す。
ＨＰＬＣ純度：９７．８８％
トルエン（ゲスト分子）含量：検出限界以下（ＨＳ−ＧＣ）
融点：１９２℃
ゆるみ嵩密度：０．３５ｇ／ｃｍ３
なお、上記ゆるみ嵩密度は、試験管での簡易試験によるデータである。
比較例５の結果より、上記特許文献５の実施例１７により得られる結晶は、融点が１９２℃と高融点結晶であることが確認された。<Comparative example 4>
(Example 17 of Patent Document 5: dibutyl ether)
5 g of the toluene clathrate crystal obtained in Reference Example 2 and 25 g of dibutyl ether were placed in a test tube containing a stirrer, stirred at 100 ° C. for 5 hours, and filtered without cooling. Then, it was dried in a nitrogen stream for 2 hours.
The figure showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in FIG. 8, and each analytical value is shown below.
HPLC purity: 97.88%
Toluene (guest molecule) content: below detection limit (HS-GC)
Melting point: 192 ° C
Loose bulk density: 0.35 g / cm 3
The loose bulk density is data obtained by a simple test in a test tube.
From the results of Comparative Example 5, it was confirmed that the crystal obtained in Example 17 of Patent Document 5 had a melting point of 192 ° C. and was a high melting point crystal.
＜比較例５＞
温度計、撹拌機、冷却管を備えた５００ミリリットル４つ口フラスコを窒素置換し、そこに、上記「合成例」で得られたトルエン包接体１４．１ｇ(ＹＩ値０．８０)とメチルイソブチルケトン６０ｇとへプタン２４gを仕込み、１００℃まで昇温し、３０分間撹拌して結晶をすべて溶解させた。得られた溶液を１分間あたり０．８℃の速度で冷却することにより６５℃で結晶が析出した。同温度で２時間撹拌後、２０℃ まで冷却し、ろ過を行った。得られた結晶を１．３ｋＰａの減圧下、９０℃で３時間乾燥し、下記品質の結晶１０．６ｇを得た。
ＨＰＬＣ純度:９９．３％
残存トルエン:１１２ｐｐｍ
残存メチルイソブチルケトン:１６８０ｐｐｍ
残存へプタン:３２１ｐｐｍ
ＹＩ値：１．２６（１０％ジオキサン溶液）
ＤＳＣ融解吸熱最大温度：１７１℃<Comparative example 5>
A 500 ml four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 14.1 g (YI value 0.80) of the toluene clathrate obtained in the above "Synthesis Example" and methyl were added thereto. 60 g of isobutyl ketone and 24 g of heptane were charged, the temperature was raised to 100 ° C., and the mixture was stirred for 30 minutes to dissolve all the crystals. Crystals were precipitated at 65 ° C. by cooling the resulting solution at a rate of 0.8 ° C. per minute. After stirring at the same temperature for 2 hours, the mixture was cooled to 20 ° C. and filtered. The obtained crystals were dried at 90 ° C. for 3 hours under a reduced pressure of 1.3 kPa to obtain 10.6 g of crystals having the following quality.
HPLC purity: 99.3%
Residual toluene: 112 ppm
Residual Methyl Isobutyl Ketone: 1680 ppm
Residual heptane: 321 ppm
YI value: 1.26 (10% dioxane solution)
DSC melting endothermic maximum temperature: 171 ° C
上記特許文献６の実施例１、２に記載された製造方法について、追試験を行った。
＜比較例６＞
（特許文献６の実施例１）
温度計、撹拌機、冷却管を備えた１リットル４つ口フラスコ内を窒素置換し、９−フルオレノン１８．０ｇ（０．１モル）、２−［（２−フェニル）フェノキシ］エタノール５３．５ｇ（０．２５モル）、３−メルカプトプロピオン酸１ｇ、トルエン６０ｍＬを仕込み、６５℃で溶解させてから、９８％硫酸２５ｍＬを１時間かけて滴下した。その後６５℃で６時間撹拌して反応させた。反応終了後、水酸化ナトリウム溶液を加えて中和し、さらに、トルエン１００ｇ、水５０ｇ加えて撹拌し、静置後、水層を除去した。得られた有機層に水６０ｇを加えて撹拌して静置後、水層を除去する操作を４回実施した。
洗浄した有機層を１０℃／時間で冷却して晶析し、２５℃で１５時間撹拌後、濾過して９，９−ビス［３−フェニル−４−（２−ヒドロキシエトキシ）フェニル］フルオレンの粗生成物を得た。
この粗生成物２０．２ｇをトルエン６０．６ｇで溶解後、冷却して晶析を行い、２５℃で濾過し、９，９−ビス［３−フェニル−４−（２−ヒドロキシエトキシ）フェニル］フルオレンの結晶を得た。その後、８０℃、１．３ｋＰａで６時間乾燥して結晶１１ｇを得た。（収率１９．０％）
結晶をＨＰＬＣで分析した結果、その純度は９２．８％であった。
得られた結晶の示差熱・熱重量分析（ＤＴＧ）曲線を示す図を図９に示す。
図９より、融点以上の温度において結晶重量が減少していることから、上記特許文献６の実施例１により得られる結晶は、トルエン包接体であることが明らかとなった。A follow-up test was performed on the production methods described in Examples 1 and 2 of Patent Document 6.
<Comparative Example 6>
(Example 1 of Patent Document 6)
The inside of a 1-liter four-necked flask equipped with a thermometer, a stirrer, and a cooling tube was replaced with nitrogen, and 9-fluorenone 18.0 g (0.1 mol), 2-[(2-phenyl) phenoxy] ethanol 53.5 g. (0.25 mol), 1 g of 3-mercaptopropionic acid and 60 mL of toluene were charged and dissolved at 65 ° C., and then 25 mL of 98% sulfuric acid was added dropwise over 1 hour. Then, the reaction was carried out by stirring at 65 ° C. for 6 hours. After completion of the reaction, a sodium hydroxide solution was added for neutralization, 100 g of toluene and 50 g of water were added and stirred, and the mixture was allowed to stand and the aqueous layer was removed. After adding 60 g of water to the obtained organic layer, stirring and allowing it to stand, the operation of removing the aqueous layer was carried out four times.
The washed organic layer is cooled at 10 ° C./hour for crystallization, stirred at 25 ° C. for 15 hours, and then filtered through 9,9-bis [3-phenyl-4- (2-hydroxyethoxy) phenyl] fluorene. A crude product was obtained.
20.2 g of this crude product is dissolved in 60.6 g of toluene, cooled to perform crystallization, filtered at 25 ° C., and 9,9-bis [3-phenyl-4- (2-hydroxyethoxy) phenyl]. Fluorene crystals were obtained. Then, it was dried at 80 ° C. and 1.3 kPa for 6 hours to obtain 11 g of crystals. (Yield 19.0%)
As a result of analyzing the crystals by HPLC, the purity was 92.8%.
The figure which shows the differential thermal analysis (DTG) curve of the obtained crystal is shown in FIG.
From FIG. 9, since the crystal weight decreases at a temperature equal to or higher than the melting point, it was clarified that the crystal obtained in Example 1 of Patent Document 6 is a toluene clathrate.
＜比較例７＞
（特許文献６の実施例２）
上記比較例８の結晶１０ｇをエタノール６０ｇで溶解後、冷却して晶析を行い、２５℃で濾過し、結晶を得た。２５℃、１．３ｋＰａで３時間乾燥した後、ＨＳ−ＧＣで分析した結果、エタノールの含有量が６．０重量％であった。この結晶について示差熱・熱重量分析（ＤＴＧ）を行った結果、包接するエタノールを除去する熱量は約１４７Ｊ／ｇであることが確認された。この結晶の示差熱・熱重量分析（ＤＴＧ）曲線を示す図を図１０に示す。
さらに、この結晶を８０℃、１．３ｋＰａで６時間乾燥した結果、エタノールの含有量が０．１４重量％の結晶６．９ｇが得られた。（収率６９％）
得られた結晶の示差走査熱量測定（ＤＳＣ）曲線を示す図を図１１に、各分析値を下記に示す。
ＨＰＬＣ純度：９４．５％
エタノール含量：０．１４重量％（ＨＳ−ＧＣ）
トルエン含量：検出限界以下（ＨＳ−ＧＣ）
融点：１３２℃
ゆるみ嵩密度：０．３３ｇ／ｃｍ３
なお、上記ゆるみ嵩密度は、試験管での簡易試験によるデータである。また、ＨＰＬＣ純度が特許文献６に記載された数値より低いのは、実施例６には、硫酸滴下温度等の詳細が説明されていないので、反応条件が完全に一致していないことも理由として考えられる。
また、得られた結晶のメディアン径（Ｄ５０）は２０．７μｍ、モード径は２６．１μｍであった。得られた結晶は、本発明の結晶混合体に比べて粒子径が非常に細かく、また、上記「比較例２」のメタノール包接体から得られた結晶に比べて流動性が向上した様子は確認されなかった。
比較例９の結果より、エタノール包接体からエタノールを除去するためには、概略１５０Ｊ／ｇ程度のエネルギーが必要であることが、さらに、包接体からエタノールを除去した結晶の融点は１３２℃であることが確認された。
<Comparative Example 7>
(Example 2 of Patent Document 6)
After dissolving 10 g of the crystals of Comparative Example 8 in 60 g of ethanol, the crystals were cooled, crystallized, and filtered at 25 ° C. to obtain crystals. After drying at 25 ° C. and 1.3 kPa for 3 hours, the analysis by HS-GC revealed that the ethanol content was 6.0% by weight. As a result of differential thermal analysis (DTG) of this crystal, it was confirmed that the calorific value for removing the inclusion ethanol was about 147 J / g. A diagram showing a differential thermal / thermogravimetric analysis (DTG) curve of this crystal is shown in FIG.
Further, as a result of drying the crystals at 80 ° C. and 1.3 kPa for 6 hours, 6.9 g of crystals having an ethanol content of 0.14% by weight was obtained. (Yield 69%)
The figure showing the differential scanning calorimetry (DSC) curve of the obtained crystal is shown in FIG. 11, and each analytical value is shown below.
HPLC purity: 94.5%
Ethanol content: 0.14% by weight (HS-GC)
Toluene content: below detection limit (HS-GC)
Melting point: 132 ° C
Loose bulk density: 0.33 g / cm 3
The loose bulk density is data obtained by a simple test in a test tube. Further, the reason why the HPLC purity is lower than the numerical value described in Patent Document 6 is that the reaction conditions are not completely matched because the details such as the sulfuric acid dropping temperature are not described in Example 6. Conceivable.
The median diameter (D50) of the obtained crystal was 20.7 μm, and the mode diameter was 26.1 μm. The obtained crystals have a very fine particle size as compared with the crystal mixture of the present invention, and the fluidity is improved as compared with the crystals obtained from the methanol clathrate of "Comparative Example 2". Not confirmed.
From the results of Comparative Example 9, it is found that energy of about 150 J / g is required to remove ethanol from the ethanol inclusion body, and further, the melting point of the crystal obtained by removing ethanol from the inclusion body is 132 ° C. It was confirmed that.
Claims (4)
The production method according to claim 3, further comprising a step of drying the crystals obtained by crystallization under a temperature condition of 45 ° C. or higher and lower than the melting point.
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