JP4648546B2 - Novel naphthalene compounds having reactive groups and methods for producing them - Google Patents
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- 0 *c1c(cc(C(F)(F)F)cc2)c2cc(C(F)(F)F)c1 Chemical compound *c1c(cc(C(F)(F)F)cc2)c2cc(C(F)(F)F)c1 0.000 description 2
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- DRAHEMBRDIKAIK-UHFFFAOYSA-N OCc1cc(C(F)(F)F)cc2ccc(C(F)(F)F)cc12 Chemical compound OCc1cc(C(F)(F)F)cc2ccc(C(F)(F)F)cc12 DRAHEMBRDIKAIK-UHFFFAOYSA-N 0.000 description 1
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Description
【０００１】
【発明の属する技術分野】
本発明は、新規なナフタレン化合物類、特定的にはフッ素含有ナフタレン化合物類、及びそれらの製造方法に関する。本発明の新規化合物は、有機蛍光物質、液晶材料、染料の前駆体として有用であり、その他の各種中間体として広範な用途が期待されるものである。
【０００２】
【従来の技術】
本発明に係るナフタレン化合物類は新規であり、従ってそれらの化合物を製造するための方法も新規である。
【０００３】
【発明が解決しようとする課題】
本発明の目的は、下記一般式（Ｉ）で示される新規なナフタレン化合物類及びそれらの製造方法を提供することである。
【０００４】
【化６】
即ち、本発明は、下記の式（Ｖ）で示される新規な１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレン、その前駆体の式（ＩＩＩ）で示される１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレン〔１位のハロゲン原子は、Ｆ，Ｃｌ，Ｂｒ，またはＩ〕、及び式（ＩＶ）で示される１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンに関するものである。本発明によって提供される式（Ｖ）で示される新規な１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンは、活性メチレンを有することから各種化合物との反応性に富み、トリフルオロメチル基を有する有機蛍光物質、染料、液晶材料等を製造するための利用が期待される有用な中間体化合物である。また、式（ＩＩＩ）で示される１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレン及び式（ＩＶ）で示される１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンは、式（Ｖ）の化合物の前駆体として有用であるばかりでなく、それぞれが反応活性なハロゲン原子、ヒドロキシメチル基を有することから、トリフルオロメチル基を有する医農薬、機能性材料等等の製造のための中間体として、広い分野での応用が期待される有用な化合物である。
【０００６】
【化７】
【課題を解決するための手段】
本発明者等は、式（Ｖ）で示される新規な１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンを式（ＩＩ）で示される２，６−ビス（トリフルオロメチル）ナフタレンを原料として、これから式（ＩＩＩ）で示される１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレンと式（ＩＶ）で示される１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンとを経由して製造する方法を見出した。
【０００８】
本発明の新規化合物類の具体的な製造方法を以下に詳しく示す。
式（ＩＩ）で示される２，６−ビス（トリフルオロメチル）ナフタレンは、容易に入手可能な２，６−ナフタレンジカルボン酸をＳＦ4等のフッ素化剤でフッ素化することにより製造できる。
【０００９】
式（ＩＩ）で示される２，６−ビス（トリフルオロメチル）ナフタレンの直接ハロゲン化を行うことにより、式（ＩＩＩ）で示される新規なナフタレン化合物である１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。この直接ハロゲン化反応の収率及び次工程〔式（ＩＶ）の化合物の製造〕の収率を考慮すると、式（ＩＩＩ）で示される新規な１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレンの１位のハロゲンが臭素原子であることが、取扱上好ましく、推奨される。
【００１０】
そこで、式（ＩＩＩ）におけるハロゲンが臭素原子である１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレン〔式（ＶＩ）で示される化合物〕の製造方法を以下に説明する。
＜１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンの製造方法＞
下記式（ＩＩ）の原料化合物から式（ＶＩ）の目的化合物を製造する方法としては、鉄系触媒の存在下に、式（ＩＩ）の化合物を直接に臭素化することにより式（ＶＩ）の化合物を製造することができる。
【００１１】
【化８】
式（ＩＩ）で示される２，６−ビス（トリフルオロメチル）ナフタレンを無溶媒で、または溶媒を用いて所定温度、所定時間で鉄系触媒の存在下、臭素を滴下して、反応させることにより式（ＶＩ）で示される新規なナフタレン化合物である１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。
【００１３】
式（ＩＩ）で示される原料は、無溶媒で、あるいはジクロロメタン、クロロホルム等の塩素系溶媒で希釈して、使用するのが好ましい。その溶媒の使用量は、原料の重量１ｇに対して０〜２０ミリリットルである。この原料はナフタレン環上にトリフルオロメチル基を有するため臭素に対する反応性が乏しく触媒を用いる方が好ましい。触媒としては、鉄系の触媒が好ましく、鉄粉、臭化鉄（ＩＩＩ）等が使用できる。その使用量は、好ましくは原料に対して０〜０．２倍モル量である。臭素については、希釈しないでそのまま使用することができる。その使用量は、原料に対して０．９〜１．５倍モル量である。臭素は。０．５〜５時間で滴下するのが好ましく、必要であれば滴下終了後さらに１〜１０時間攪拌を続ける。臭素滴下時及び滴下後の反応温度は、０〜１５０℃の範囲で行うのが好ましい。この臭素化反応は常圧下で行えるが、加圧下で行ってもよい。反応終了後は、通常の後処理、精製を行うことにより、式（ＶＩ）で示される新規なナフタレン化合物である１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。
＜１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンの製造＞
前述の式（ＩＩ）で示される２，６−ビス（トリフルオロメチル）ナフタレンを原料として、これから式（ＩＩＩ）で示される１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレンを経由して式（ＩＶ）で示される１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンを製造する方法としては、不活性ガス雰囲気下で、式（ＩＩＩ）の化合物から有機金属化合物を調製して、これにホルムアルデヒドを反応させることにより製造できる。
【００１４】
ここで、式（ＩＩＩ）の化合物においてＸがＢｒであるものが、式（ＶＩ）で示される１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンであるが、この式（ＶＩ）の化合物から式（ＩＶ）の化合物を製造する方法としては、不活性ガス雰囲気下で、式（ＶＩ）の化合物から有機金属化合物を調製して、これにホルムアルデヒドを反応させることにより製造することができる。
【００１５】
【化９】
式（ＶＩ）で示される１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンを溶媒中、攪拌下、所定温度、所定時間で有機リチウム試薬あるいは金属マグネシウムを反応させることにより、有機金属化合物を含む溶液を調製し、その溶液とホルムアルデヒドとを攪拌下、所定温度、所定時間で反応させることによって、式（ＩＶ）で示される新規なナフタレン化合物である１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。本反応は、水分を嫌う反応であるため反応容器内は、窒素等の乾燥不活性ガス雰囲気下で行うことが好ましい。
【００１７】
この反応のための溶媒としては、ジエチルエーテル、テトラヒドロフラン等のエーテル系溶媒が使用できる。その使用量は、好ましくは原料１ｇに対して１〜１００ミリリットルである。
【００１８】
有機リチウム試薬を作用させる場合には、通常低温で行う必要がある。その温度は、−８０℃〜０℃が好ましい。金属マグネシウムを作用させる場合には−３０℃〜５０℃程度が好ましい。有機リチウム試薬及び金属マグネシウムの使用量は、好ましくは、原料１ｇに対して１〜２倍モル量である。調製された有機金属化合物を含む溶液は、ホルムアルデヒドと反応させるが、そのホルムアルデヒドとしては、パラホルムアルデヒド（固体）を直接に添加してもよいし、あるいは別容器にてパラホルムアルデヒドを熱分解して発生するホルムアルデヒド（気体）を用いてもよい。その使用量は、原料に対して１〜３倍モル量である。ホルムアルデヒドとの反応は−５０℃〜３０℃の温度で行うのが好ましい。反応時間は０．５〜５時間が好ましい。反応終了後、室温以下の温度で、希硫酸、希塩酸等を滴下し、通常の後処理、精製を行うことにより式（ＩＶ）で示される新規なナフタレン化合物である１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。
＜１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンの製造方法＞
式（ＩＩ）で示される２，６−ビス（トリフルオロメチル）ナフタレンを原料として、これから式（ＩＩＩ）で示される１−ハロゲノ−３，７−ビス（トリフルオロメチル）ナフタレンと式（ＩＶ）で示される１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンとを経由して、式（Ｖ）で示される新規な１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンを製造する方法としては、前述の方法ルートで式（ＩＩ）の化合物から式（ＩＶ）の化合物を製造し、さらに不活性雰囲気中で式（ＩＶ）の化合物の水酸基を脱離基に変換した後、シアン化物イオンと反応させることにより製造できる。
【００１９】
下記式（ＩＶ）化合物から式（Ｖ）化合物を製造する方法としては、不活性ガス雰囲気下、式（ＩＶ）の化合物の水酸基を脱離基に変換した後、シアン化物イオンと反応させることにより式（Ｖ）の新規ナフタレン化合物を製造できる。
【００２０】
【化１０】
式（ＩＶ）で示される１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンのヒドロキシ基（水酸基）を溶媒中、攪拌下、所定温度、所定時間で適当な試剤と反応させることにより脱離基に変換し、その溶液とシアン化物イオンとを攪拌下、所定温度、所定時間で反応させることにより式（Ｖ）で示される新規な１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。この反応は、水分を嫌う反応であるため、反応器内は、窒素等の乾燥不活性ガス雰囲気下で行うことが好ましい。
【００２２】
脱離基としては、ｐ−トルエンスルホニル基、メタンスルホニル基、トリフルオロメタンスルホニル基、ハロゲン原子等が好ましい。スルホニル化剤としては、それぞれに対応する酸クロリドや酸無水物が使用できる。ハロゲン化剤としては、ハロゲン化水素酸や無機酸のハロゲン化物等が使用できる。これらの試剤の使用量は、好ましくは原料に対して１〜３倍モル量である。スルホニル化反応においては、スルホニル化剤と同量あるいはやや過剰の塩基、例えばトリエチルアミン、ピリジンといった三級アミンの共存下で行うのが好ましい。スルホニル化、ハロゲン化の反応温度、反応時間は試剤により異なるが、通常は−２０℃〜１００℃といった温度で行うのが好ましい。
【００２３】
得られた脱離基を有する化合物は極性溶媒に溶解させてシアノ化剤と、反応させる。極性溶媒としては、ジメチルスルホキシド、ジメチルホルムアミド、Ｎ−メチルピロリドン、アセトン等が使用できる。その使用量は、好ましくは、脱離基を有する化合物１ｇに対して１〜１００ミリリットルである。シアノ化剤としては、シアン化ナトリウム、シアン化カリウム等が使用できる。その使用量は、好ましくは、脱離基を有する化合物に対して１〜２倍モル量である。シアノ化の反応温度は、０〜１５０℃が好ましい。反応時間は０．５〜５時間が好ましい。反応終了後、通常の後処理、精製を行うことにより、式（Ｖ）で表される新規なナフタレン化合物である１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンを製造することができる。
【００２４】
以下に本発明の実施例を示す。本発明における新規化合物類の製造方法は実施例に記載されたもののみに限定されるものではない。
【００２５】
【実施例】
１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンの製造
実施例1
油浴、還流冷却管、温度計及び圧力平衡管付き滴下ロートを備えた３００ｍｌガラス製フラスコに窒素雰囲気下、２，６−ビス（トリフルオロメチル）ナフタレン５０ｇ（０．１８９モル）と還元鉄粉１ｇ（０.０１９モル）とクロロホルム１００ｍｌを仕込んだ。加熱還流下、攪拌しながら、臭素３４.７ｇ（０.２１７モル）を２時間かけて滴下した。副生する臭化水素ガスは、アルカリスクラバーにより無害化処理した。滴下終了後、さらに５時間加熱還流下、攪拌を続けた。攪拌を止め、そのままの状態で反応液を室温まで冷却後、吸引濾過して濾液を５％亜硫酸ナトリウム水溶液１００ｍｌ及び飽和食塩水１００ｍｌで洗浄した。有機相は、無水硫酸ナトリウムで乾燥し、硫酸ナトリウムを濾別後、クロロホルムを減圧留去した。得られた粗生成物をシリカゲルクロマトグラフィーにより精製して、１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレンの淡黄色固体を得た。ＬＣ純度９８％、収量６２.１ｇ（収率９５.７％）。
【００２６】
生成物の構造は、核磁気共鳴分析等で確認した。核磁気共鳴分析［ＶＡＲＩＡＮ社製、Ｇｅｍｉｎｉ２００］の結果は以下の通りであった。
実施例２
冷却浴、温度計及び圧力平衡管付き滴下ロートを備えた５００ｍｌガラス製フラスコに窒素雰囲気下、１−ブロモ−３，７−ビス（トリフルオロメチル）ナフタレン３０ｇ（０．０８７モル）と乾燥エーテル１５０ｍｌとを仕込んだ。−５０℃に冷却、攪拌下、ｎ−ブチルリチウムヘキサン溶液（１．５４Ｍ）６１．２ｍｌ（０．０９４モル）を３０分間かけて滴下した。次に、別のガラス製フラスコにて窒素雰囲気、攪拌下、パラホルムアルデヒド７．９ｇ（０．２６モル）を１００〜１８０℃に昇温加熱して発生させたホルムアルデヒドを乾燥窒素と共に主反応フラスコ内の気液界面付近へ、液温を−５０℃〜−３０℃の範囲内に制御しながら、３０分間かけて導入した。ホルムアルデヒドの発生が終了後、液温が１０℃以下となるように攪拌下、水１５０ｍｌ及び濃塩酸１０ｍｌをゆっくり滴下した。滴下終了後、エーテルを１００ｍｌ加えて抽出し、有機相を飽和食塩水１００ｍｌで洗浄した。有機相は無水硫酸ナトリウムで乾燥し、硫酸ナトリウムを濾別後、クロロホルムを減圧留去した。得られた粗生成物をシリカゲルクロマトグラフィーにより精製して、１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレンの白色固体を得た。ＬＣ純度９９％、収量１８．３ｇ（収率７１．１％）。
【００２７】
生成物の構造は、核磁気共鳴分析等で確認した。核磁気共鳴分析［ＶＡＲＩＡＮ社製、Ｇｅｍｉｎｉ２００］の結果は以下の通りであった。
1H−ＮＭＲ（溶媒：ＣＤＣｌ3、標準物質：テトラメチルシラン）
δ ８．４４ｐｐｍ（ｓ，１Ｈ，ＡｒＨ）
８．１６ｐｐｍ（ｓ，１Ｈ，ＡｒＨ）
８．０９ｐｐｍ（ｄ，Ｊ＝５．８４Ｈｚ，１Ｈ，ＡｒＨ）
７．８４ｐｐｍ（ｓ，１Ｈ，ＡｒＨ）
７．７９ｐｐｍ（ｄｄ，Ｊ＝１．６０，８．６０Ｈｚ，１Ｈ，ＡｒＨ）
５．２５ｐｐｍ（ｓ，２Ｈ，ＣＨ 2）
２．０５ｐｐｍ（ｂｓ，１Ｈ，ＯＨ）
19Ｆ−ＮＭＲ（溶媒：ＣＤＣｌ3、標準物質：ＣＦＣｌ3）
δ −６２．２６ｐｐｍ（ｓ，３Ｆ，ＣＦ 3）
−６２．６０ｐｐｍ（ｓ，３Ｆ，ＣＦ 3）
１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンの製造
実施例３
冷却浴、温度計及び圧力平衡管付き滴下ロートを備えた１００ｍｌガラス製フラスコに窒素雰囲気下、１−ヒドロキシメチル−３，７−ビス（トリフルオロメチル）ナフタレン５ｇ（０．０１７モル）とトリエチルアミン３．４５ｇ（０．０３４モル）とジクロロメタン２０ｍｌとを仕込んだ。約０℃に冷却、攪拌下、メタンスルホニルクロリド２．９５ｇ（０．０２６モル）を３０分間かけて滴下した。滴下終了後、さらに室温下３０分間攪拌をつづけた。再度０℃に冷却、攪拌下、飽和炭酸水素ナトリウム溶液２０ｍｌをゆっくり滴下し、ジクロロメタン２０ｍｌ加えて抽出した。滴下終了後、有機相を分取し、飽和食塩水２０ｍｌで洗浄した。有機相は無水硫酸ナトリウムで乾燥し、硫酸ナトリウムを濾別後、クロロホルムを減圧留去した。メタンスルホン酸エステル体を淡黄色固体として６．０ｇ得た。
【００２８】
次に、油浴、温度計及び圧力平衡管付き滴下ロートを備えた１００ｍｌがラス製フラスコに窒素雰囲気下、シアン化ナトリウム１．２５ｇ（０．０２６モル）とジメチルスルホキシド３０ｍｌとを仕込み、７０℃に加熱して均一溶液とした。ここに先に調製したメタンスルホン酸エステル体をジメチルスルホキシド１０ｍｌに溶解した溶液を全量速やかに添加した。添加後、７０℃でさらに３０分間攪拌した。放冷後、反応液にベンゼン１００ｍｌを加え、飽和食塩水５０ｍｌで洗浄した。有機相を分取して、無水硫酸ナトリウムで乾燥し、硫酸ナトリウムを濾別後、ベンゼンを減圧留去した。得られた粗生成物をシリカゲルクロマトグラフィーにより精製して、１−シアノメチル−３，７−ビス（トリフルオロメチル）ナフタレンの淡黄色固体を得た。ＬＣ純度９９％、収量２．９ｇ（収率５６．３％）。
【００２９】
生成物の構造は、核磁気共鳴分析等で確認した。核磁気共鳴分析［ＶＡＲＩＡＮ社製、Ｇｅｍｉｎｉ２００］の結果は以下の通りであった。
1H−ＮＭＲ（溶媒：ＣＤＣｌ3、標準物質：テトラメチルシラン）
δ ８．２６ｐｐｍ（ｓ，１Ｈ，ＡｒＨ）
８．２３ｐｐｍ（ｓ，１Ｈ，ＡｒＨ）
８．１７ｐｐｍ（ｄ，Ｊ＝８．６０Ｈｚ，１Ｈ，ＡｒＨ）
７．９０ｐｐｍ（ｓ，１Ｈ，ＡｒＨ）
７．８７ｐｐｍ（ｄ，Ｊ＝８．６０Ｈｚ，１Ｈ，ＡｒＨ）
４．２７ｐｐｍ（ｓ，１Ｈ，ＣＨ 2）
19Ｆ−ＮＭＲ（溶媒：ＣＤＣｌ3、標準物質：ＣＦＣｌ3）
δ −６２．３７ｐｐｍ（ｓ，３Ｆ，ＣＦ 3）
−６２．６２ｐｐｍ（ｓ，３Ｆ，ＣＦ 3）[0001]
BACKGROUND OF THE INVENTION
The present invention relates to novel naphthalene compounds, specifically fluorine-containing naphthalene compounds, and methods for producing them. The novel compounds of the present invention are useful as precursors for organic fluorescent materials, liquid crystal materials, and dyes, and are expected to be used in a wide variety of other intermediates.
[0002]
[Prior art]
The naphthalene compounds according to the present invention are novel and therefore the process for producing these compounds is also novel.
[0003]
[Problems to be solved by the invention]
An object of the present invention is to provide novel naphthalene compounds represented by the following general formula (I) and a method for producing them.
[0004]
[Chemical 6]
That is, the present invention relates to a novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the following formula (V), a precursor 1-halogeno-3 represented by the formula (III), 7-bis (trifluoromethyl) naphthalene [the halogen atom at the 1-position is F, Cl, Br, or I] and 1-hydroxymethyl-3,7-bis (trifluoromethyl) represented by the formula (IV) It relates to naphthalene. Since the novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (V) provided by the present invention has active methylene, it is rich in reactivity with various compounds. It is a useful intermediate compound expected to be used for producing an organic fluorescent substance having a group, a dye, a liquid crystal material and the like. Further, 1-halogeno-3,7-bis (trifluoromethyl) naphthalene represented by the formula (III) and 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV) are: Not only is it useful as a precursor of the compound of formula (V), but each has a reactive halogen atom and a hydroxymethyl group, so that it can be used for the production of medical pesticides, functional materials, etc. having a trifluoromethyl group. Therefore, it is a useful compound that is expected to be applied in a wide range of fields.
[0006]
[Chemical 7]
[Means for Solving the Problems]
The present inventors converted a novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (V) into 2,6-bis (trifluoromethyl) naphthalene represented by the formula (II). As raw materials, 1-halogeno-3,7-bis (trifluoromethyl) naphthalene represented by the formula (III) and 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV) And found a method of manufacturing via.
[0008]
Specific production methods of the novel compounds of the present invention are shown in detail below.
2,6-bis (trifluoromethyl) naphthalene represented by the formula (II) can be produced by fluorinating a readily available 2,6-naphthalenedicarboxylic acid with a fluorinating agent such as SF 4 .
[0009]
By directly halogenating 2,6-bis (trifluoromethyl) naphthalene represented by the formula (II), a novel naphthalene compound represented by the formula (III), 1-halogeno-3,7-bis ( Trifluoromethyl) naphthalene can be produced. Considering the yield of this direct halogenation reaction and the yield of the next step [production of compound of formula (IV)], a novel 1-halogeno-3,7-bis (trifluoromethyl) represented by formula (III) ) It is preferable and recommended that the halogen at the 1-position of naphthalene is a bromine atom.
[0010]
Therefore, a method for producing 1-bromo-3,7-bis (trifluoromethyl) naphthalene [compound represented by formula (VI)] in which the halogen in formula (III) is a bromine atom will be described below.
<Method for Producing 1-Bromo-3,7-bis (trifluoromethyl) naphthalene>
As a method for producing the target compound of the formula (VI) from the raw material compound of the following formula (II), the compound of the formula (VI) is obtained by directly brominating the compound of the formula (II) in the presence of an iron-based catalyst. Compounds can be produced.
[0011]
[Chemical 8]
Reacting 2,6-bis (trifluoromethyl) naphthalene represented by the formula (II) by adding bromine dropwise in the presence of an iron-based catalyst without solvent or at a predetermined temperature and for a predetermined time using a solvent. Thus, 1-bromo-3,7-bis (trifluoromethyl) naphthalene, which is a novel naphthalene compound represented by the formula (VI), can be produced.
[0013]
The raw material represented by the formula (II) is preferably used without a solvent or diluted with a chlorinated solvent such as dichloromethane or chloroform. The amount of the solvent used is 0 to 20 ml per 1 g of the raw material. Since this raw material has a trifluoromethyl group on the naphthalene ring, the reactivity with bromine is poor, and it is preferable to use a catalyst. As the catalyst, iron-based catalysts are preferable, and iron powder, iron (III) bromide, and the like can be used. The amount used is preferably 0 to 0.2 times the molar amount of the raw material. Bromine can be used as it is without dilution. The amount used is 0.9 to 1.5 times the molar amount of the raw material. Bromine. It is preferable to drop in 0.5 to 5 hours, and if necessary, stirring is continued for 1 to 10 hours after the dropping is completed. The reaction temperature at the time of dropping bromine and after dropping is preferably in the range of 0 to 150 ° C. This bromination reaction can be performed under normal pressure, but may be performed under pressure. After completion of the reaction, 1-bromo-3,7-bis (trifluoromethyl) naphthalene, which is a novel naphthalene compound represented by the formula (VI), can be produced by performing ordinary post-treatment and purification. .
<Production of 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene>
Using 2,6-bis (trifluoromethyl) naphthalene represented by the above-mentioned formula (II) as a raw material, from now on via 1-halogeno-3,7-bis (trifluoromethyl) naphthalene represented by the formula (III) As a method for producing 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV), an organometallic compound is prepared from the compound of the formula (III) under an inert gas atmosphere. And it can manufacture by making formaldehyde react with this.
[0014]
Here, in the compound of the formula (III), X is Br, which is 1-bromo-3,7-bis (trifluoromethyl) naphthalene represented by the formula (VI). As a method for producing a compound of the formula (IV) from a compound, it can be produced by preparing an organometallic compound from a compound of the formula (VI) under an inert gas atmosphere and reacting it with formaldehyde. .
[0015]
[Chemical 9]
An organometallic compound is prepared by reacting 1-bromo-3,7-bis (trifluoromethyl) naphthalene represented by the formula (VI) with a organolithium reagent or magnesium at a predetermined temperature and a predetermined time in a solvent while stirring. Is prepared, and the solution and formaldehyde are reacted with stirring at a predetermined temperature for a predetermined time, whereby 1-hydroxymethyl-3,7-bis, which is a novel naphthalene compound represented by formula (IV), is reacted. (Trifluoromethyl) naphthalene can be produced. Since this reaction is a reaction which dislikes moisture, the reaction vessel is preferably carried out in an atmosphere of dry inert gas such as nitrogen.
[0017]
As a solvent for this reaction, ether solvents such as diethyl ether and tetrahydrofuran can be used. The amount used is preferably 1 to 100 ml per 1 g of raw material.
[0018]
When an organolithium reagent is allowed to act, it is usually necessary to carry out at a low temperature. The temperature is preferably -80 ° C to 0 ° C. When metal magnesium is allowed to act, it is preferably about -30 ° C to 50 ° C. The amount of the organic lithium reagent and metal magnesium used is preferably 1 to 2 times the molar amount of 1 g of the raw material. The prepared solution containing the organometallic compound is reacted with formaldehyde. As the formaldehyde, paraformaldehyde (solid) may be added directly, or it is generated by thermal decomposition of paraformaldehyde in a separate container. Formaldehyde (gas) may be used. The amount used is 1 to 3 times the molar amount of the raw material. The reaction with formaldehyde is preferably carried out at a temperature of -50 ° C to 30 ° C. The reaction time is preferably 0.5 to 5 hours. After completion of the reaction, 1-hydroxymethyl-3,7 which is a novel naphthalene compound represented by the formula (IV) is obtained by adding dilute sulfuric acid, dilute hydrochloric acid or the like dropwise at room temperature or lower, and performing normal post-treatment and purification. -Bis (trifluoromethyl) naphthalene can be produced.
<Method for Producing 1-Cyanomethyl-3,7-bis (trifluoromethyl) naphthalene>
Starting from 2,6-bis (trifluoromethyl) naphthalene represented by formula (II), 1-halogeno-3,7-bis (trifluoromethyl) naphthalene represented by formula (III) and formula (IV) A novel 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (V) via 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by As a production method, the compound of formula (IV) is produced from the compound of formula (II) by the above-mentioned method route, and further, the hydroxyl group of the compound of formula (IV) is converted into a leaving group in an inert atmosphere. Can be produced by reacting with cyanide ions.
[0019]
As a method for producing the compound of the formula (V) from the compound of the following formula (IV), after converting the hydroxyl group of the compound of the formula (IV) into a leaving group in an inert gas atmosphere, the compound is reacted with cyanide ions. A novel naphthalene compound of formula (V) can be produced.
[0020]
Embedded image
By reacting the hydroxy group (hydroxyl group) of 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene represented by the formula (IV) with a suitable reagent in a solvent at a predetermined temperature for a predetermined time. A novel 1-cyanomethyl-3,7-bis (trifluoromethyl) represented by the formula (V) is obtained by converting into a leaving group and reacting the solution and cyanide ion with stirring at a predetermined temperature for a predetermined time. ) Naphthalene can be produced. Since this reaction is a reaction that dislikes moisture, the reaction is preferably performed in a dry inert gas atmosphere such as nitrogen.
[0022]
As the leaving group, a p-toluenesulfonyl group, a methanesulfonyl group, a trifluoromethanesulfonyl group, a halogen atom and the like are preferable. As the sulfonylating agent, corresponding acid chlorides and acid anhydrides can be used. As the halogenating agent, a hydrohalic acid, a halide of an inorganic acid, or the like can be used. The amount of these reagents used is preferably 1 to 3 times the molar amount of the raw material. The sulfonylation reaction is preferably carried out in the presence of the same amount or a slight excess of a base such as a tertiary amine such as triethylamine or pyridine. The reaction temperature and reaction time for sulfonylation and halogenation vary depending on the reagent, but it is usually preferable to carry out at a temperature of -20 ° C to 100 ° C.
[0023]
The obtained compound having a leaving group is dissolved in a polar solvent and reacted with a cyanating agent. As the polar solvent, dimethyl sulfoxide, dimethylformamide, N-methylpyrrolidone, acetone or the like can be used. The amount used is preferably 1 to 100 ml with respect to 1 g of the compound having a leaving group. As the cyanating agent, sodium cyanide, potassium cyanide and the like can be used. The amount used is preferably 1 to 2 times the molar amount of the compound having a leaving group. The reaction temperature for cyanation is preferably 0 to 150 ° C. The reaction time is preferably 0.5 to 5 hours. After completion of the reaction, 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene, which is a novel naphthalene compound represented by the formula (V), can be produced by performing normal post-treatment and purification. .
[0024]
Examples of the present invention are shown below. The production method of the novel compounds in the present invention is not limited to those described in the Examples.
[0025]
【Example】
Preparation of 1-bromo-3,7-bis (trifluoromethyl) naphthalene Example 1
In a 300 ml glass flask equipped with an oil bath, a reflux condenser, a thermometer and a dropping funnel with a pressure balance tube, 50 g (0.189 mol) of 2,6-bis (trifluoromethyl) naphthalene and reduced iron powder in a nitrogen atmosphere 1 g (0.019 mol) and 100 ml of chloroform were charged. While heating under reflux, 34.7 g (0.217 mol) of bromine was added dropwise over 2 hours with stirring. The by-produced hydrogen bromide gas was detoxified with an alkali scrubber. After completion of the dropwise addition, stirring was continued under heating and reflux for another 5 hours. Stirring was stopped, the reaction solution was cooled to room temperature as it was, and then suction filtered, and the filtrate was washed with 100 ml of 5% aqueous sodium sulfite solution and 100 ml of saturated brine. The organic phase was dried over anhydrous sodium sulfate, sodium sulfate was filtered off, and chloroform was distilled off under reduced pressure. The obtained crude product was purified by silica gel chromatography to obtain a light yellow solid of 1-bromo-3,7-bis (trifluoromethyl) naphthalene. LC purity 98%, yield 62.1 g (yield 95.7%).
[0026]
The structure of the product was confirmed by nuclear magnetic resonance analysis and the like. The results of nuclear magnetic resonance analysis [manufactured by Varian, Gemini 200] were as follows.
In a 500 ml glass flask equipped with a cooling bath, a thermometer and a dropping funnel equipped with a pressure balance tube, under a nitrogen atmosphere, 30 g (0.087 mol) of 1-bromo-3,7-bis (trifluoromethyl) naphthalene and 150 ml of dry ether And charged. While cooling to −50 ° C. and stirring, 61.2 ml (0.094 mol) of n-butyllithium hexane solution (1.54M) was added dropwise over 30 minutes. Next, in a separate glass flask, 7.9 g (0.26 mol) of paraformaldehyde was heated to 100 to 180 ° C. with stirring under a nitrogen atmosphere, and the formaldehyde generated with dry nitrogen was added to the main reaction flask. The liquid temperature was introduced into the vicinity of the gas-liquid interface over 30 minutes while controlling the liquid temperature within the range of −50 ° C. to −30 ° C. After the generation of formaldehyde was completed, 150 ml of water and 10 ml of concentrated hydrochloric acid were slowly added dropwise with stirring so that the liquid temperature became 10 ° C. or lower. After completion of the dropwise addition, 100 ml of ether was added for extraction, and the organic phase was washed with 100 ml of saturated brine. The organic phase was dried over anhydrous sodium sulfate, sodium sulfate was filtered off, and chloroform was distilled off under reduced pressure. The obtained crude product was purified by silica gel chromatography to obtain a white solid of 1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene. LC purity 99%, yield 18.3 g (yield 71.1%).
[0027]
The structure of the product was confirmed by nuclear magnetic resonance analysis and the like. The results of nuclear magnetic resonance analysis [manufactured by Varian, Gemini 200] were as follows.
1 H-NMR (solvent: CDCl 3 , standard substance: tetramethylsilane)
δ 8.44ppm (s, 1H, Ar H)
8.16 ppm (s, 1H, Ar H )
8.09 ppm (d, J = 5.84 Hz, 1H, Ar H )
7.84 ppm (s, 1 H, Ar H )
7.79 ppm (dd, J = 1.60, 8.60 Hz, 1H, Ar H )
5.25 ppm (s, 2H, C H 2 )
2.05ppm (bs, 1H, O H )
19 F-NMR (solvent: CDCl 3 , standard substance: CFCl 3 )
δ −62.26 ppm (s, 3F, C F 3 )
−62.60 ppm (s, 3F, C F 3 )
Production Example 1 of 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene
1-hydroxymethyl-3,7-bis (trifluoromethyl) naphthalene 5 g (0.017 mol) and triethylamine 3 in a 100 ml glass flask equipped with a cooling bath, a thermometer and a dropping funnel equipped with a pressure balance tube in a nitrogen atmosphere .45 g (0.034 mol) and 20 ml of dichloromethane were charged. While cooling to about 0 ° C. and stirring, 2.95 g (0.026 mol) of methanesulfonyl chloride was added dropwise over 30 minutes. After completion of the dropwise addition, stirring was continued for 30 minutes at room temperature. The solution was cooled again to 0 ° C., and 20 ml of saturated sodium bicarbonate solution was slowly added dropwise with stirring, followed by extraction with 20 ml of dichloromethane. After completion of the dropwise addition, the organic phase was separated and washed with 20 ml of saturated brine. The organic phase was dried over anhydrous sodium sulfate, sodium sulfate was filtered off, and chloroform was distilled off under reduced pressure. 6.0 g of a methanesulfonic acid ester was obtained as a pale yellow solid.
[0028]
Next, 100 ml equipped with an oil bath, a thermometer and a dropping funnel equipped with a pressure balance tube was charged with 1.25 g (0.026 mol) of sodium cyanide and 30 ml of dimethyl sulfoxide in a glass flask under a nitrogen atmosphere. To a homogeneous solution. A total amount of a solution prepared by dissolving the previously prepared methanesulfonic acid ester in 10 ml of dimethyl sulfoxide was quickly added thereto. After the addition, the mixture was further stirred at 70 ° C. for 30 minutes. After allowing to cool, 100 ml of benzene was added to the reaction solution and washed with 50 ml of saturated brine. The organic phase was separated, dried over anhydrous sodium sulfate, sodium sulfate was filtered off, and benzene was distilled off under reduced pressure. The obtained crude product was purified by silica gel chromatography to obtain a light yellow solid of 1-cyanomethyl-3,7-bis (trifluoromethyl) naphthalene. LC purity 99%, yield 2.9 g (56.3% yield).
[0029]
The structure of the product was confirmed by nuclear magnetic resonance analysis and the like. The results of nuclear magnetic resonance analysis [manufactured by Varian, Gemini 200] were as follows.
1 H-NMR (solvent: CDCl 3, standard: tetramethylsilane)
δ 8.26 ppm (s, 1 H, Ar H )
8.23 ppm (s, 1 H, Ar H )
8.17 ppm (d, J = 8.60 Hz, 1H, Ar H )
7.90 ppm (s, 1 H, Ar H )
7.87 ppm (d, J = 8.60 Hz, 1H, Ar H )
4.27 ppm (s, 1 H, C H 2 )
19 F-NMR (solvent: CDCl 3 , standard substance: CFCl 3 )
δ −62.37 ppm (s, 3F, C F 3 )
−62.62 ppm (s, 3F, C F 3 )
Claims (5)
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3939198A (en) * | 1966-02-23 | 1976-02-17 | Marathon Oil Company | Chlorinated naphthalene esters |
| US4022827A (en) * | 1970-05-06 | 1977-05-10 | Marathon Oil Company | Heptachloro-alpha-naphthoyl chloride |
| JPH02502728A (en) * | 1987-12-23 | 1990-08-30 | アメリカン・ホーム・プロダクツ・コーポレイション | N-naphthoylglycine as an aldose reductase inhibitor |
| JPH02502727A (en) * | 1987-12-23 | 1990-08-30 | アメリカン・ホーム・プロダクツ・コーポレイション | N-acyl-N-naphthoylglycine as an aldose reductase inhibitor |
| JP2000186146A (en) * | 1998-12-22 | 2000-07-04 | Sumitomo Bakelite Co Ltd | Polybenzoxazole precursor and polybenzoxazole resin |
| WO2002012208A1 (en) * | 2000-08-04 | 2002-02-14 | Taiho Industries, Co., Ltd | Nile-red luminescent compound, process for producing the same, and luminescent element utilizing the same |
-
2001
- 2001-01-10 JP JP2001002442A patent/JP4648546B2/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3939198A (en) * | 1966-02-23 | 1976-02-17 | Marathon Oil Company | Chlorinated naphthalene esters |
| US4022827A (en) * | 1970-05-06 | 1977-05-10 | Marathon Oil Company | Heptachloro-alpha-naphthoyl chloride |
| JPH02502728A (en) * | 1987-12-23 | 1990-08-30 | アメリカン・ホーム・プロダクツ・コーポレイション | N-naphthoylglycine as an aldose reductase inhibitor |
| JPH02502727A (en) * | 1987-12-23 | 1990-08-30 | アメリカン・ホーム・プロダクツ・コーポレイション | N-acyl-N-naphthoylglycine as an aldose reductase inhibitor |
| JP2000186146A (en) * | 1998-12-22 | 2000-07-04 | Sumitomo Bakelite Co Ltd | Polybenzoxazole precursor and polybenzoxazole resin |
| WO2002012208A1 (en) * | 2000-08-04 | 2002-02-14 | Taiho Industries, Co., Ltd | Nile-red luminescent compound, process for producing the same, and luminescent element utilizing the same |
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