JP2014076955A - Method for refining 3,3'-dinitro-4,4'-dihydroxydiphenyl ether and method for producing 3,3'-dinitro-4,4'-dihydroxydiphenyl ether composition - Google Patents
Method for refining 3,3'-dinitro-4,4'-dihydroxydiphenyl ether and method for producing 3,3'-dinitro-4,4'-dihydroxydiphenyl ether composition Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 21
- 239000000203 mixture Substances 0.000 title claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- 238000007670 refining Methods 0.000 title abstract 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 64
- 239000000725 suspension Substances 0.000 claims abstract description 19
- 239000000243 solution Substances 0.000 claims abstract description 15
- 239000012043 crude product Substances 0.000 claims abstract description 13
- 238000005406 washing Methods 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 8
- 239000012535 impurity Substances 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims description 11
- 238000000746 purification Methods 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 6
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 claims description 4
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000011541 reaction mixture Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000013078 crystal Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 238000002844 melting Methods 0.000 description 14
- 230000008018 melting Effects 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007795 chemical reaction product Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 6
- NZGQHKSLKRFZFL-UHFFFAOYSA-N 4-(4-hydroxyphenoxy)phenol Chemical compound C1=CC(O)=CC=C1OC1=CC=C(O)C=C1 NZGQHKSLKRFZFL-UHFFFAOYSA-N 0.000 description 5
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229910017604 nitric acid Inorganic materials 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 238000006396 nitration reaction Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- HDGNWRGKJBDMRZ-UHFFFAOYSA-N 4-(4-hydroxy-3-nitrophenoxy)-2-nitrophenol Chemical class C1=C([N+]([O-])=O)C(O)=CC=C1OC1=CC=C(O)C([N+]([O-])=O)=C1 HDGNWRGKJBDMRZ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
Abstract
Description
本発明は、耐熱性に優れる樹脂（耐熱性ポリマー）の原料モノマーの中間体となる３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテルの精製方法、およびその精製方法を含む３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル組成物の製造方法に関する。 The present invention relates to a method for purifying 3,3′-dinitro-4,4′-dihydroxydiphenyl ether, which is an intermediate of a raw material monomer of a resin (heat-resistant polymer) having excellent heat resistance, and 3,3 ′ including the purification method. -It relates to a method for producing a dinitro-4,4'-dihydroxydiphenyl ether composition.
ビス（４−ヒドロキシ−３−ニトロフェニル）エーテル類は、耐熱性ポリマー用の中間体として重要な化合物であり、かかるエーテル類を得る方法としては、４，４’−ジヒドロキシジフェニルエーテルを、ベンゼン−氷酢酸の混合溶媒下、硝酸にてニトロ化を行い、反応後、反応液を多量の水に投入し結晶化させることにより、収率７５％で３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテルを得られる方法（非特許文献１）が知られている。 Bis (4-hydroxy-3-nitrophenyl) ethers are important compounds as intermediates for heat-resistant polymers. As a method for obtaining such ethers, 4,4′-dihydroxydiphenyl ether is obtained by using benzene-ice. Nitration is performed with nitric acid in a mixed solvent of acetic acid, and after the reaction, the reaction solution is poured into a large amount of water and crystallized to obtain 3,3′-dinitro-4,4′-dihydroxy in a yield of 75%. A method for obtaining diphenyl ether (Non-Patent Document 1) is known.
しかしながら、非特許文献１に記載される方法で得られる結晶は、純度が低い（融点幅：１０℃）ため、高純度の結晶を得るためにエタノール溶媒にて５回の再結晶することが記載されている。この５回の再結晶処理後に得られた組成物でも、その融点幅は２℃であり、純度はまだ十分とはいえない。しかも、５回も再結晶を行うため収率を高めることは根本的に不可能である。したがって、非特許文献１に記載される精製処方は、純度が不十分であって、製品収率が低く、かつ大量の廃液が発生する方法である。それゆえ、この方法は工業的に大量生産には適さない。 However, since the crystal obtained by the method described in Non-Patent Document 1 has low purity (melting point width: 10 ° C.), it is described that recrystallization is performed five times with an ethanol solvent in order to obtain a high-purity crystal. Has been. Even in the composition obtained after the five recrystallization treatments, the melting point width is 2 ° C., and the purity is still not sufficient. Moreover, since recrystallization is performed five times, it is fundamentally impossible to increase the yield. Therefore, the refinement | purification prescription described in the nonpatent literature 1 is a method with which purity is inadequate, a product yield is low, and a large amount of waste liquid generate | occur | produces. Therefore, this method is not industrially suitable for mass production.
かかる現状を鑑み、本発明は、下記式（１）に示される３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（本明細書において「ＮＨＰＥ」ともいう。）を主成分とする粗反応生成物などの粗生成物から、ＮＨＰＥの純度が高い組成物を得るための精製方法、およびその生成方法を備える高純度のＮＨＰＥ組成物の製造方法を提供することを目的とする。 In view of the current situation, the present invention is a crude reaction mainly composed of 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (also referred to as “NHPE” in the present specification) represented by the following formula (1). An object of the present invention is to provide a purification method for obtaining a composition having a high NHPE purity from a crude product such as a product, and a method for producing a high-purity NHPE composition provided with the production method.
上記課題を解決すべく本発明者らが鋭意検討した結果、３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）の粗生成物を、アセトンまたはアセトン水溶液にて懸濁洗浄することにより、高純度のＮＨＰＥを簡便に得られることを見出し、本発明を完成するに至った。 As a result of intensive studies by the present inventors to solve the above-mentioned problems, the crude product of 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) is suspended and washed with acetone or an aqueous acetone solution. Thus, it was found that high-purity NHPE can be easily obtained, and the present invention has been completed.
本発明によれば、高純度の３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）組成物を製造するにあたり、ＮＨＰＥを含む粗生成物を、アセトンまたはアセトン水溶液で懸濁洗浄処理することにより、高い収率で高純度品を得ること、および廃液量を少なくすることの少なくとも一方を達成でき、好ましい態様においては双方を実現できる。したがって、本発明により、高純度３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテルを工業的な製造方法として適用可能な程度に生産性良く製造する方法が提供される。 According to the present invention, in producing a high purity 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) composition, a crude product containing NHPE is suspended and washed with acetone or an acetone aqueous solution. By doing so, at least one of obtaining a high-purity product with high yield and reducing the amount of waste liquid can be achieved, and both can be realized in a preferred embodiment. Therefore, the present invention provides a method for producing high-purity 3,3'-dinitro-4,4'-dihydroxydiphenyl ether with high productivity to such an extent that it can be applied as an industrial production method.
以下、本発明の一実施形態について詳しく説明する。
３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）を含む粗生成物は、４，４’−ジヒドロキシジフェニルエーテル（本明細書において「ＨＰＥ」ともいう。）を芳香族炭化水素溶媒中、硝酸でニトロ化することにより、生産性高く得られる。このニトロ化の反応原料であるＨＰＥの製造方法は公知であり、また、市販もされており、比較的安価に手に入れることができる化合物である。ＨＰＥを含む材料を原料として使用するにあたり求められるＨＰＥの純度に特に制限はないが、通常、ＨＰＬＣ分析による純度としてＨＰＥの含有量が９７％以上の材料を使用することができる。
Hereinafter, an embodiment of the present invention will be described in detail.
A crude product containing 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) is obtained by converting 4,4′-dihydroxydiphenyl ether (also referred to herein as “HPE”) in an aromatic hydrocarbon solvent. It can be obtained with high productivity by nitration with nitric acid. A method for producing HPE, which is a reaction raw material for nitration, is known and commercially available, and is a compound that can be obtained at a relatively low cost. Although there is no particular limitation on the purity of HPE required when using a material containing HPE as a raw material, a material having an HPE content of 97% or more can be used as the purity by HPLC analysis.
本実施形態において懸濁洗浄溶媒として使用するアセトンまたはアセトン水溶液の濃度は、不純物の溶解性や、製品収率を考慮すると、アセトン水溶液の場合には５０重量％以上９５重量％以下が好ましく、特に７０重量％以上９５重量％以下が好ましい。アセトンについては、通常工業用途で入手可能な製品の純度（９９重量％程度）で十分である。 In the present embodiment, the concentration of acetone or an aqueous acetone solution used as a suspension cleaning solvent is preferably 50% by weight or more and 95% by weight or less in the case of an aqueous acetone solution, considering the solubility of impurities and the product yield. 70 to 95 weight% is preferable. For acetone, the purity of the product (about 99% by weight) usually available for industrial use is sufficient.
なお、ＨＰＥから３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）の製造方法を実施することによって得られたＮＨＰＥの粗生成物は、含水結晶として得られる場合もあり、この含水結晶に含まれる水分がアセトン水溶液における水分の由来となっていてもよい。すなわち、精製溶媒としてアセトンを用いた場合に、粗生成物に由来して水分が溶媒に追加され、結果的にアセトン水溶液によってＮＨＰＥの精製が行われてもよい。 In addition, the crude product of NHPE obtained by implementing the manufacturing method of 3,3'-dinitro-4,4'-dihydroxydiphenyl ether (NHPE) from HPE may be obtained as a water-containing crystal, and this water-containing The moisture contained in the crystal may be the origin of moisture in the acetone aqueous solution. That is, when acetone is used as the purification solvent, moisture is added to the solvent derived from the crude product, and as a result, NHPE may be purified with an aqueous acetone solution.
アセトンまたはアセトン水溶液の使用量は、３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）を含む粗反応生成物に対して２〜７倍（重量比）であり、好ましくは３〜５．５倍である。 The amount of acetone or the aqueous acetone solution used is 2 to 7 times (weight ratio) with respect to the crude reaction product containing 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE), preferably 3 to 3 times. 5.5 times.
本実施形態に係る精製方法によれば、固体状態にある（乾燥結晶でもよいし、含水結晶であってもよい。）ＮＨＰＥを、分散媒としてのアセトンまたはアセトン水溶液に投入し、得られた懸濁液（分散液）を攪拌することで懸濁洗浄し、その懸濁液をろ過して固体を回収するだけでＮＨＰＥの純度を高めることができる。この懸濁洗浄しろ過する方法は、再結晶のように、溶媒を加熱して粗生成物を溶解させ、次いで粗生成物が溶解してなる溶液を冷却して目的物を析出させるという煩雑な作業は不要である。また、粗生成物が溶解してなる溶液に、酸やアルカリ、貧溶媒などを投入して結晶を析出させる晶析に比べても、作業は容易である。なお、ろ過後の固体の洗浄に用いる液体は水でよい。水以外の洗浄液の成分としてメタノール、イソプロピルアルコールなどのアルコール類、アセトンなどのケトン類などが例示される。 According to the purification method of this embodiment, NHPE in a solid state (may be a dry crystal or a water-containing crystal) is added to acetone or an acetone aqueous solution as a dispersion medium, and the resulting suspension is obtained. It is possible to increase the purity of NHPE simply by suspending and washing the turbid liquid (dispersion) and filtering the suspension to recover the solid. This suspension washing and filtration method is a complicated method of heating the solvent to dissolve the crude product, and then cooling the solution in which the crude product is dissolved to precipitate the target product, as in recrystallization. No work is necessary. In addition, the operation is easy even when compared with crystallization in which an acid, an alkali, a poor solvent, or the like is added to a solution obtained by dissolving a crude product to precipitate crystals. The liquid used for washing the solid after filtration may be water. Examples of components of the cleaning liquid other than water include alcohols such as methanol and isopropyl alcohol, and ketones such as acetone.
このような簡便な懸濁洗浄による精製を行うだけで、得られたＮＨＰＥ組成物は、融点幅が０．５℃以下の範囲となる。この融点幅は、前述の非特許文献１に開示されるような５回もの再結晶を行って得られたＮＨＰＥ組成物における融点幅よりもはるかに狭く、本実施形態に係る精製方法を含む製造方法によって十分な純度のＮＨＰＥ組成物が得られることを示している。 By simply performing such purification by suspension washing, the obtained NHPE composition has a melting point range of 0.5 ° C. or less. This melting point width is much narrower than the melting point width in the NHPE composition obtained by performing recrystallization as many as five times as disclosed in the aforementioned Non-Patent Document 1, and includes the purification method according to this embodiment. It shows that the method gives a sufficiently pure NHPE composition.
懸濁洗浄処理温度は特に限定されないが、１０℃以上７０℃以下とすることが好ましい。処理温度が過度に低い場合には、満足のいく純度の製品を得ることができず、過度に高い場合には、３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）の収率が低下する傾向がみられる。ＮＨＰＥの純度が高い組成物をより高い収率で得る観点から、懸濁洗浄の処理温度は１０℃以上６０℃以下とすることが好ましく、１０℃以上５０℃以下とすることがより好ましい。 The suspension washing treatment temperature is not particularly limited, but is preferably 10 ° C. or higher and 70 ° C. or lower. If the processing temperature is too low, a product of satisfactory purity cannot be obtained, and if it is too high, the yield of 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) There is a tendency to decrease. From the viewpoint of obtaining a composition having a high purity of NHPE in a higher yield, the treatment temperature for suspension washing is preferably 10 ° C. or more and 60 ° C. or less, and more preferably 10 ° C. or more and 50 ° C. or less.
懸濁洗浄処理時間は特に限定されず、例えば、上記の処理温度に昇温後、０．５〜１０時間、好ましくは０．５〜５時間、さらに好ましくは１〜３時間撹拌を行えばよい。 The suspension washing treatment time is not particularly limited, and for example, after raising the temperature to the above treatment temperature, stirring may be performed for 0.5 to 10 hours, preferably 0.5 to 5 hours, more preferably 1 to 3 hours. .
懸濁洗浄処理後、結晶をろ過により分離し、ろ取した固体成分を水などを用いて洗浄し、洗浄後の固体成分を真空デシケータなどを用いて乾燥を行い、不純物含有量が低減された３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル組成物を得ることができる。 After suspension washing treatment, the crystals were separated by filtration, the solid component collected by filtration was washed with water, etc., and the washed solid component was dried using a vacuum desiccator, etc., and the impurity content was reduced. A 3,3′-dinitro-4,4′-dihydroxydiphenyl ether composition can be obtained.
次に実施例によって本発明をさらに詳細に説明するが、本発明がこれらの具体例にのみ限定されるものではない。なお、分析は下記条件の高速液体クロマトグラフィー（ＨＰＬＣ）により実施し、面積％により純度を評価した。 EXAMPLES Next, although an Example demonstrates this invention further in detail, this invention is not limited only to these specific examples. The analysis was performed by high performance liquid chromatography (HPLC) under the following conditions, and the purity was evaluated by area%.
（カラム）Ｌ−ｃｏｌｕｍｎ ＯＤＳ４．６ｍｍφ×１５０ｍｍ（（財）化学物質評価研究機構製）
（移動相）
Ａ：２０ｍｍｏｌ／Ｌのリン酸二水素カリウム溶液に、ＨＰＬＣ用リン酸を滴下してｐＨ３．０に調製する。
Ｂ：ＨＰＬＣ用メタノール（関東化学製）
（移動相組成）
Ａ／Ｂ：５０体積％／５０体積％（分析開始から２０分間）
：１０体積％／９０体積％（分析開始から２０分経過後４０分まで）
（移動相流量）１．０ｍＬ/ｍｉｎ
（測定波長）２５４ｎｍ
（カラム温度）４０℃
（注入量）１０μＬ
（サンプル調製法）３０ｍｇを５０ｍＬメスフラスコに秤量し、アセトニトリルでメスアップする。
(Column) L-column ODS 4.6 mmφ × 150 mm (manufactured by Chemical Substance Evaluation Research Organization)
(Mobile phase)
A: To a 20 mmol / L potassium dihydrogen phosphate solution, HPLC phosphoric acid is added dropwise to adjust to pH 3.0.
B: Methanol for HPLC (manufactured by Kanto Chemical)
(Mobile phase composition)
A / B: 50 vol% / 50 vol% (20 minutes from the start of analysis)
: 10 vol% / 90 vol% (until 40 minutes after 20 minutes from the start of analysis)
(Mobile phase flow rate) 1.0 mL / min
(Measurement wavelength) 254 nm
(Column temperature) 40 ° C
(Injection volume) 10 μL
(Sample preparation method) Weigh 30 mg into a 50 mL volumetric flask and make up with acetonitrile.
（参考例１）
温度計、ジムロート冷却器および攪拌機を備えた３００ｍＬ四つ口フラスコに、４，４’−ジヒドロキシジフェニルエーテル（ＨＰＥ）４０．２ｇ（０．２モル）およびトルエン１２１．２ｇを加えて、フラスコ内の反応混合物を撹拌し、０℃に冷却した。続いて、反応混合物の温度を０〜５℃を保持しながら、６１質量％硝酸４２．０ｇ（反応原料に対する理論モル比：２．０）を４時間かけて滴下した。滴下終了後の反応混合物を０〜５℃の範囲に保持しながら１時間撹拌した後、反応混合物の温度を室温まで徐々に昇温した。室温となった反応混合物をさらに攪拌しながら、反応終点（ＨＰＬＣによる面積百分率で反応原料の濃度が２％以下）の確認を行った。その結果、攪拌開始から１時間後に反応終点に到達したことを確認した。反応終点に到達した反応混合物をろ過し、ろ過ケーキを水１００ｇで洗浄してウェットケーキを得た。このウェットケーキを真空乾燥機で乾燥し、３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）を含む粗反応生成物４２．２ｇを橙色結晶として得た。収率は、６２．５モル％であり、純度は８６．４％であった。
(Reference Example 1)
40.2 g (0.2 mol) of 4,4′-dihydroxydiphenyl ether (HPE) and 121.2 g of toluene were added to a 300 mL four-necked flask equipped with a thermometer, a Dimroth condenser and a stirrer, and the reaction in the flask The mixture was stirred and cooled to 0 ° C. Subsequently, 42.0 g of 61% by mass nitric acid (theoretical molar ratio to the reaction raw material: 2.0) was dropped over 4 hours while maintaining the temperature of the reaction mixture at 0 to 5 ° C. The reaction mixture after completion of the dropwise addition was stirred for 1 hour while maintaining the temperature in the range of 0 to 5 ° C, and then the temperature of the reaction mixture was gradually raised to room temperature. While further stirring the reaction mixture that had reached room temperature, the reaction end point (concentration of the reaction raw material was 2% or less in terms of area percentage by HPLC) was confirmed. As a result, it was confirmed that the reaction end point was reached after 1 hour from the start of stirring. The reaction mixture that reached the reaction end point was filtered, and the filter cake was washed with 100 g of water to obtain a wet cake. This wet cake was dried with a vacuum dryer to obtain 42.2 g of a crude reaction product containing 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) as orange crystals. The yield was 62.5 mol%, and the purity was 86.4%.
（実施例１）
温度計、ジムロート冷却器および攪拌機を備えた１００ｍＬ四つ口フラスコに、参考例１で得た３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）を含む粗反応生成物１０ｇ（０．１モル）および８８重量％アセトン水溶液３４ｇを加えて、フラスコ内の反応混合物を撹拌し、５０℃に昇温した。内温を５０℃に保持しながら１時間撹拌した後、反応混合物の温度を１０℃まで徐々に冷却した。懸濁液をろ過し、ろ過ケーキをアセトン１０ｇ、次いで水２０ｇで洗浄してウェットケーキ８．６ｇを得た。このウェットケーキを真空乾燥機で乾燥し、乾燥品７．７ｇを橙色結晶として得た。製品収率は８７．３モル％であり、純度は９８．６％であった。
Example 1
In a 100 mL four-necked flask equipped with a thermometer, a Dimroth cooler, and a stirrer, 10 g of crude reaction product containing 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) obtained in Reference Example 1 (0 0.1 mol) and 34 g of 88 wt% acetone aqueous solution were added, and the reaction mixture in the flask was stirred and heated to 50 ° C. After stirring for 1 hour while maintaining the internal temperature at 50 ° C, the temperature of the reaction mixture was gradually cooled to 10 ° C. The suspension was filtered, and the filter cake was washed with 10 g of acetone and then with 20 g of water to obtain 8.6 g of a wet cake. This wet cake was dried with a vacuum dryer to obtain 7.7 g of a dried product as orange crystals. The product yield was 87.3 mol% and the purity was 98.6%.
（実施例２）
温度計、ジムロート冷却器および攪拌機を備えた１００ｍＬ四つ口フラスコに、参考例１で得た３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテルを含む粗反応生成物１０ｇ（０．１モル）および９３重量％％アセトン水溶液５４ｇを加えて、フラスコ内の反応混合物を撹拌し、２５℃に昇温した。内温を２５℃に保持しながら１時間撹拌した。懸濁液をろ過し、ろ過ケーキをアセトン１０ｇ、次いで水２０ｇで洗浄してウェットケーキ９．８ｇを得た。このウェットケーキを真空乾燥機で乾燥し、乾燥品７．０ｇを黄色の粉末結晶として得た。製品収率は７９．６モル％であり、純度は９８．３％であった。
(Example 2)
10 g (0.1 mol) of a crude reaction product containing 3,3′-dinitro-4,4′-dihydroxydiphenyl ether obtained in Reference Example 1 was added to a 100 mL four-necked flask equipped with a thermometer, a Dimroth condenser and a stirrer. ) And 54 g of 93% by weight aqueous acetone solution were added, and the reaction mixture in the flask was stirred and heated to 25 ° C. The mixture was stirred for 1 hour while maintaining the internal temperature at 25 ° C. The suspension was filtered, and the filter cake was washed with 10 g of acetone and then with 20 g of water to obtain 9.8 g of a wet cake. The wet cake was dried with a vacuum dryer to obtain 7.0 g of a dried product as yellow powder crystals. The product yield was 79.6 mol% and the purity was 98.3%.
（実施例３）
温度計、ジムロート冷却器および攪拌機を備えた３００ｍＬ四つ口フラスコに、４，４’−ジヒドロキシジフェニルエーテル４０．４ｇ（０．２モル）およびトルエン１２１．２ｇを加えて、フラスコ内の反応混合物を撹拌し、０℃に冷却した。続いて、反応混合物の温度を０〜５℃を保持しながら、６９質量％硝酸３６．５ｇ（反応原料に対する理論モル比：２．０）を２時間かけて滴下した。滴下終了後の反応混合物を０〜５℃の範囲に保持しながら１時間撹拌した後、反応混合物の温度を室温まで徐々に昇温した。室温となった反応混合物をさらに攪拌しながら、反応終点（ＨＰＬＣによる面積百分率で反応原料の濃度が２％以下）の確認を行った。その結果、攪拌開始から１時間後に反応終点に到達したことを確認した。反応終点に到達した反応混合物をろ過し、ろ過ケーキを水１２１ｇで洗浄して粗反応生成物の含水結晶５０．２ｇを得た。結晶を一部採取し、含水率、純度を測定したところ、含水率は２６．１％、純度は８５．５％であった。
温度計、ジムロート冷却器および攪拌機を備えた３００ｍＬ四つ口フラスコに、粗反応生成物の含水結晶５０．２ｇ（Ｄｒｙ換算：３７．１ｇ）およびアセトン１１２．２ｇを加えて、フラスコ内の反応混合物を撹拌し、５０℃に昇温した。内温を５０℃に保持しながら１時間撹拌した後、反応混合物の温度を１０℃まで徐々に冷却した。懸濁液をろ過し、ろ過ケーキをアセトン３７ｇ、次いで水７４ｇで洗浄してウェットケーキ３５．０ｇを得た。このウェットケーキを真空乾燥機で乾燥し、乾燥品２６．０ｇを黄色の粉末結晶として得た。製品収率は８０．９モル％であり、純度は９８．８％であった。なお、得られた結晶の融点を測定した結果（融点近傍での加熱速度：２℃／分）、融点は１５８．８℃から１５９．２℃の範囲となった。
(Example 3)
To a 300 mL four-necked flask equipped with a thermometer, a Dimroth condenser, and a stirrer, 40.4 g (0.2 mol) of 4,4′-dihydroxydiphenyl ether and 121.2 g of toluene were added, and the reaction mixture in the flask was stirred. And cooled to 0 ° C. Subsequently, 36.5 g of 69% by mass nitric acid (theoretical molar ratio to the reaction raw material: 2.0) was added dropwise over 2 hours while maintaining the temperature of the reaction mixture at 0 to 5 ° C. The reaction mixture after completion of the dropwise addition was stirred for 1 hour while maintaining the temperature in the range of 0 to 5 ° C, and then the temperature of the reaction mixture was gradually raised to room temperature. While further stirring the reaction mixture that had reached room temperature, the reaction end point (concentration of the reaction raw material was 2% or less in terms of area percentage by HPLC) was confirmed. As a result, it was confirmed that the reaction end point was reached after 1 hour from the start of stirring. The reaction mixture that reached the end point of the reaction was filtered, and the filter cake was washed with 121 g of water to obtain 50.2 g of hydrous crystals of the crude reaction product. A portion of the crystals was collected and the water content and purity were measured. The water content was 26.1% and the purity was 85.5%.
To a 300 mL four-necked flask equipped with a thermometer, a Dimroth cooler, and a stirrer was added 50.2 g of crude crystals of the reaction product (Dry conversion: 37.1 g) and 112.2 g of acetone, and the reaction mixture in the flask The mixture was stirred and heated to 50 ° C. After stirring for 1 hour while maintaining the internal temperature at 50 ° C, the temperature of the reaction mixture was gradually cooled to 10 ° C. The suspension was filtered, and the filter cake was washed with 37 g of acetone and then 74 g of water to obtain 35.0 g of a wet cake. This wet cake was dried with a vacuum dryer to obtain 26.0 g of a dried product as yellow powder crystals. The product yield was 80.9 mol% and the purity was 98.8%. As a result of measuring the melting point of the obtained crystal (heating rate in the vicinity of the melting point: 2 ° C./min), the melting point was in the range of 158.8 ° C. to 159.2 ° C.
（実施例４）
温度計、ジムロート冷却器および攪拌機を備えた３００ｍＬ四つ口フラスコに、４，４’−ジヒドロキシジフェニルエーテル（ＨＰＥ）２０．２ｇ（０．１モル）およびトルエン１６２ｇを加えて、フラスコ内の反応混合物を撹拌し反応混合物を０℃に冷却した。続いて、反応混合物の温度を０〜３℃の範囲に保持しながら、６９質量％硝酸１８．３ｇ（反応原料に対する理論モル比：２．０）を１．０時間かけて滴下した。滴下終了後の反応混合物を０〜３℃に保持しながら２時間撹拌した。攪拌後の反応液の分析の結果、ＨＰＬＣによる面積百分率で反応液中の反応原料の濃度が２％以下であることを確認した。そこで、この時点で反応終点に到達していると判断して、反応混合物をろ過し、ろ過ケーキを水６０ｇで洗浄してウェットケーキ２８．０ｇを得た。このウェットケーキを真空乾燥機で乾燥し、粗反応生成物の乾燥品２０．６ｇを、やや黒みがかった黄色の粉末結晶として得た。収率は、６０．７モル％であり、純度は８６．０％であった。
温度計、ジムロート冷却器および攪拌機を備えた１００ｍＬ四つ口フラスコに、粗反応生成物の乾燥品１０．０ｇおよびアセトン３０．０ｇを加えて、フラスコ内の反応混合物を撹拌し、５０℃に昇温した。内温を５０℃に保持しながら１時間撹拌した後、反応混合物の温度を１０℃まで徐々に冷却した。懸濁液をろ過し、ろ過ケーキを水２０ｇで洗浄しウェットケーキを得た。このウェットケーキを真空乾燥機で乾燥し、乾燥品７．５ｇを黄色の粉末結晶として得た。製品収率は８６．５モル％であり、純度は９８．８％であった。なお、得られた結晶の融点を測定した結果（融点近傍での加熱速度：２℃／分）、融点は１５８．４℃から１５８．８℃の範囲となった。
(Example 4)
To a 300 mL four-necked flask equipped with a thermometer, a Dimroth condenser, and a stirrer was added 20.2 g (0.1 mol) of 4,4′-dihydroxydiphenyl ether (HPE) and 162 g of toluene, and the reaction mixture in the flask was Stir and cool the reaction mixture to 0 ° C. Subsequently, 18.3 g of 69% by mass nitric acid (theoretical molar ratio to the reaction raw material: 2.0) was added dropwise over 1.0 hour while maintaining the temperature of the reaction mixture in the range of 0 to 3 ° C. The reaction mixture after completion of the dropwise addition was stirred for 2 hours while maintaining at 0 to 3 ° C. As a result of analysis of the reaction solution after stirring, it was confirmed that the concentration of the reaction raw material in the reaction solution was 2% or less by area percentage by HPLC. Therefore, it was judged that the reaction end point was reached at this time, and the reaction mixture was filtered, and the filter cake was washed with 60 g of water to obtain 28.0 g of a wet cake. This wet cake was dried with a vacuum dryer, and 20.6 g of a dried product of the crude reaction product was obtained as slightly blackish yellow powder crystals. The yield was 60.7 mol% and the purity was 86.0%.
To a 100 mL four-necked flask equipped with a thermometer, a Dimroth condenser, and a stirrer, 10.0 g of a dried crude reaction product and 30.0 g of acetone are added, and the reaction mixture in the flask is stirred and heated to 50 ° C. Warm up. After stirring for 1 hour while maintaining the internal temperature at 50 ° C, the temperature of the reaction mixture was gradually cooled to 10 ° C. The suspension was filtered, and the filter cake was washed with 20 g of water to obtain a wet cake. The wet cake was dried with a vacuum dryer to obtain 7.5 g of a dried product as yellow powder crystals. The product yield was 86.5 mol% and the purity was 98.8%. In addition, as a result of measuring melting | fusing point of the obtained crystal | crystallization (heating rate in the vicinity of melting | fusing point: 2 degree-C / min), melting | fusing point became the range of 158.4 degreeC to 158.8 degreeC.
（比較例１）
温度計、ジムロート冷却器および攪拌機を備えた１００ｍＬ四つ口フラスコに、参考例１で得た３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテルを含む粗反応生成物１０ｇ（０．１モル）および９３％メタノール水溶液５４ｇを加えて、フラスコ内の反応混合物を撹拌し、２５℃に昇温した。内温を２５℃に保持しながら１時間撹拌した。懸濁液をろ過し、ろ過ケーキをメタノール１０ｇ、次いで水２０ｇで洗浄してウェットケーキ１３．６ｇを得た。このウェットケーキを真空乾燥機で乾燥し、乾燥品９．６ｇを橙色結晶として得た。製品収率は、９８．０モル％であり、純度は８８．０％であった。なお、得られた結晶の融点を測定した結果（融点近傍での加熱速度：２℃／分）、融点は１５２．２℃から１５７．０℃の範囲となった。
(Comparative Example 1)
10 g (0.1 mol) of a crude reaction product containing 3,3′-dinitro-4,4′-dihydroxydiphenyl ether obtained in Reference Example 1 was added to a 100 mL four-necked flask equipped with a thermometer, a Dimroth condenser and a stirrer. ) And 54 g of 93% methanol aqueous solution were added, and the reaction mixture in the flask was stirred and heated to 25 ° C. The mixture was stirred for 1 hour while maintaining the internal temperature at 25 ° C. The suspension was filtered, and the filter cake was washed with 10 g of methanol and then with 20 g of water to obtain 13.6 g of a wet cake. This wet cake was dried with a vacuum drier to obtain 9.6 g of a dried product as orange crystals. The product yield was 98.0 mol% and the purity was 88.0%. As a result of measuring the melting point of the obtained crystal (heating rate in the vicinity of the melting point: 2 ° C./min), the melting point was in the range of 152.2 ° C. to 157.0 ° C.
本発明によれば、３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）の粗生成品に対して、アセトンまたはアセトン水溶液にて懸濁洗浄する精製方法を含む工程を実施することによって、不純物含有量が低減された３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル（ＮＨＰＥ）組成物を、高収率で簡便に得ることができる。 According to the present invention, a process including a purification method in which a crude product of 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) is suspended and washed with acetone or an acetone aqueous solution is performed. Thus, a 3,3′-dinitro-4,4′-dihydroxydiphenyl ether (NHPE) composition having a reduced impurity content can be easily obtained in a high yield.
Claims (4)
前記攪拌後の懸濁液をろ過し、
前記ろ過により得られた固体成分を洗浄し、
前記洗浄後の固体成分を乾燥して、不純物含有量が低減された３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル組成物を得ること
を特徴とする、３，３’−ジニトロ−４，４’−ジヒドロキシジフェニルエーテル組成物の製造方法。 The crude product of 3,3′-dinitro-4,4′-dihydroxydiphenyl ether was suspended in acetone or an aqueous acetone solution, and the resulting suspension was stirred.
The suspension after stirring is filtered,
Washing the solid component obtained by the filtration,
The washed solid component is dried to obtain a 3,3′-dinitro-4,4′-dihydroxydiphenyl ether composition having a reduced impurity content, 3,3′-dinitro-4 , 4′-Dihydroxydiphenyl ether composition production method.
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| WO2022019305A1 (en) * | 2020-07-20 | 2022-01-27 | 株式会社トクヤマ | Method for producing triazolinedione adduct |
| CN114702390A (en) * | 2022-03-08 | 2022-07-05 | 常州佳德医药科技有限公司 | Preparation method of 4-chloro-3-nitrobenzyl ether |
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