JP3909653B2 - Next generation chromatographic stationary phase with chemically bonded calixarene - Google Patents

Description

【００１０】
［式中、Ｒ¹及びＲ²は、少なくとも１個がCH₂＝CH(CH₂)_m-、トリアルコキシシリル-(CH₂)_m+2-又はポリシロキサン-(CH₂)_m+2-（ここで、ｍは１〜８の数を示す）を示し、残余が炭素数３以上のアルキル基を示し；
Ａｒは置換基を有していてもよい炭素数６〜１０の芳香族炭化水素基を示し；
ｎは２〜４の数を示す］
で表されるカリックスアレーン化合物を提供するものである。
【００１１】
また本発明は上記一般式（１）において、Ｒ¹及びＲ²の少なくとも１個がトリアルコキシシリル-(CH₂)_m+2-又はポリシロキサン-(CH₂)_m+2-である化合物を反応させるか又はコーティングしてなるクロマトグラフィー固定相を提供するものである。
【００１２】
【発明の実施の形態】
一般式（１）中、Ｒ¹及びＲ²の少なくとも１個はCH₂＝CH(CH₂)_m-、トリアルコキシシリル-(CH₂)_m+2-又はポリシロキサン-(CH₂)_m+2-である。ここで、Ｒ¹及びＲ²の少なくとも１個がCH₂＝CH(CH₂)_m-である化合物は、当該基がトリアルコキシシリル-(CH₂)_m+2-又はポリシロキサン-(CH₂)_m+2-である化合物の中間体である。ここでｍは１〜８の数を示すが、３〜８が好ましく、特に３〜６が好ましい。トリアルコキシシリル-(CH₂)_m+2-としては、トリ(Ｃ₁−Ｃ₆アルコキシ)シリル-(CH₂)_m+2-が好ましく、具体的にはトリメチルシリル-(CH₂)_m+2-、トリエチルシリル-(CH₂)_m+2-等が挙げられる。また、ポリシロキサン-(CH₂)_m+2-としては、ジメチルポリシロキサン-(CH₂)_m+2-が好ましい。ポリシロキサン-(CH₂)_m+2-において、-(CH₂)_m+2-基は、ポリシロキサンの側鎖として結合しているのが好ましく、例えば下記式（２）のように結合しているのがより好ましい。
【００１３】
【化３】

【００１４】
［式中、ｌ¹及びｌ³は１〜２０の数を示し、ｌ²は１〜４の数を示し、ｌ⁴は１０〜２０００の数を示し、ｍは前記と同じ］
【００１５】
Ｒ¹及びＲ²の残余の基は炭素数３以上のアルキル基であり、炭素数３〜１２のアルキル基が好ましく、３〜８のアルキル基がより好ましい。具体例としては、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、イソブチル基、ｎ−ペンチル基、ｎ−ヘキシル基等が挙げられる。
【００１６】
Ｒ¹及びＲ²のうち、少なくとも１つがトリアルコキシシリル-(CH₂)_m+2-又はポリシロキサン-(CH₂)_m+2-である化合物の場合、当該トリアルコキシシリル-(CH₂)_m+2-基又はポリシロキサン-(CH₂)_m+2-基は１〜２ｎ個まで置換し得るが、クロマトグラフィー固定相として用いるときに分子を捉えやすくする観点から、１〜ｎ個がより好ましい。
【００１７】
Ａｒは置換基を有していてもよい炭素数６〜１０の芳香族炭化水素基を示すが、当該芳香族炭化水素基としてはフェニル基、ナフチル基が好ましく、特にフェニル基が好ましい。当該芳香族炭化水素基に置換し得る基としては、アルキル基、ハロゲノアルキル基、アルコキシ基、シアノ基、ニトロ基、アミノ基、ジアルキルアミノ基、スルホニルオキシ基及び１個以上の不斉炭素原子を有する官能基が挙げられる。ここで、アルキル基としては、炭素数１〜２０、特に１〜１２のアルキル基が挙げられ、例えばメチル基、エチル基、イソプロピル基、ｎ−プロピル基、ｎ−ブチル基、ヘキシル基、デシル基、ドデシル基、テトラデシル基、ヘキサデシル基、オクタデシル基等が挙げられる。アルコキシ基としては、炭素数１〜８のアルコキシ基が挙げられ、例えばメトキシ基、エトキシ基、イソプロポキシ基等が挙げられる。ハロゲノアルキル基としては、ハロゲン原子が１〜３個置換した炭素数１〜６のアルキル基が挙げられ、例えばトリフルオロメチル基、１，１，１−トリクロロエチル基等が挙げられる。ジアルキルアミノ基としてはジ（Ｃ₁−Ｃ₆アルキル）アミノ基が挙げられ、ジメチルアミノ基、ジエチルアミノ基等が挙げられる。
【００１８】
Ａｒが、１個以上の不斉炭素原子を有する官能基が置換した芳香族炭化水素基である場合には、本発明化合物は、特にエナンチオマーの分離用固定相として有用である。ここで１個以上の不斉炭素原子を有する官能基の例としては、例えば次の式（３）〜（８）で示される基が挙げられる。
【００１９】
【化４】

【００２０】
［式中、Ｒ³はフェニル基、ナフチル基、イソプロピル基又はｔｅｒｔ−ブチル基を示し、ｐは０又は１の数を示し、Ｒ⁴はイソプロピル基、ｔｅｒｔ−ブチル基又はベンジル基を示し、そのときＲ⁵は水素原子を示し、また、Ｒ⁴とＲ⁵が一緒になってトリメチレン基を形成してもよい。*は不斉炭素原子を示す］
【００２１】
ｎは２〜４の数を示すが、２又は３が好ましく、２が特に好ましい。
【００２２】
本発明のカリックスアレーン化合物は、例えば次の反応式に従って製造することができる。
【００２３】
【化５】

【００２４】
【化６】

【００２５】
［式中、Ｒ^1a及びＲ^2aの少なくとも１個は水素原子であり、残余は炭素数３以上のアルキル基を示し、Ｒ^1b及びＲ^2bの少なくとも１個はCH₂＝CH(CH₂)_m-であり、残余は炭素数３以上のアルキル基を示し、Ｒ^1c及びＲ^2cの少くなくとも１個はトリアルコキシシリル-(CH₂)_m+2-又はポリシロキサン-(CH₂)_m+2-であり、残余は炭素数３以上のアルキル基を示し、ｎ及びｍは前記と同じ］
【００２６】
すなわち、ｐ−ｔｅｒｔ−ブチルフェノール（９）にアルカリ存在下にホルムアルデヒドを反応させることによりカリックスアレーン化合物（１０）を得、これに塩化アルミニウム及びフェノールを反応させてtert−ブチル基を除去することにより化合物（１１）を得、これをアルキルハライドを用いてフェノールの水酸基の一部をＯ−アルキル化して化合物（１２）とし、これをブロム化することにより化合物（１３）とし、残存するフェノールの水酸基をアルケニル化して化合物（１４）とし、次いでブロム基をジヒドロキシボラニル化した後アリル化すれば化合物（１Ａ）が得られる。得られた化合物（１Ａ）にハイドロジェンポリシロキサン又はトリアルコキシシランを反応させるヒドロシリル化に付すことにより化合物（１Ｓ₁）が得られる。
【００２７】
ここで、ｐ−ｔｅｒｔ−ブチルフェノール（９）からカリックスアレーン（１０）への変換反応は、水酸化ナトリウム、水酸化カリウム等のアルカリ存在下、あるいは酸触媒存在下、化合物（９）に対して、１．２倍モル以上のホルムアルデヒドあるいはパラホルムアルデヒドとともに加熱撹拌し、その後ジフェニルエーテル、キシレン等の溶媒中で加熱還流することにより行なわれる。カリックスアレーン（１０）のｔｅｒｔ−ブチル基脱離反応は、トルエン、ベンゼン等の芳香族炭化水素溶媒中、カリックスアレーン（１０）と塩化アルミニウム及びフェノールとを室温下で攪拌すればよい。化合物（１１）のアルキル化反応は、アセトニトリル、ジメチルホルムアミド等の溶媒中、炭酸カリウム、水素化ナトリウム等のアルカリ存在下、化合物（１１）とプロピルブロミド等の炭素数３以上のアルキルハライドを加熱還流すればよい。化合物（１２）のブロム化反応は、例えば、Ｎ−ブロムコハク酸イミド等のブロム化剤を用いて、メチルエチルケトン、トルエン等の溶媒中、室温条件で行なえばよい。化合物（１３）のアルケニル化反応は、アリルブロミド等のアルケニルハライドを用いて、水素化ナトリウム等の強アルカリの存在下、ジメチルホルムアミド、トルエン等の溶媒中、室温で行なえばよい。化合物（１４）は、ブチルリチウム、トリメトキシボラン、次いで塩酸を反応させることにより化合物（１５）とし、これを３−ヨウ化メチルベンゼン等のヨウ化アリール化合物とをトリフェニルホスフィン−パラジウム錯体の存在下、ベンゼン及び炭酸ナトリウム中加熱還流することにより化合物（１Ａ）が得られる。
化合物（１Ａ）のヒドロシリル化反応は、化合物（１Ａ）とハイドロジェンポリシロキサンあるいはトリアルコキシシランとを塩化白金酸、クロロトリス（トリフェニルホスフィン）ロジウム等の存在下トルエン、テトラヒドロフラン等の溶媒中で反応させることにより行なわれる。
【００２８】
一般式（１）中のＲ¹及びＲ²のうちの１個のみがCH₂＝CH(CH₂)_m-、ポリシロキサン-(CH₂)_m+2-、又はトリアルコキシシリル-(CH₂)_m+2-である化合物は、例えば次の反応式に従って製造することができる（一般式（１）中のｎが２の場合を例示）。
【００２９】
【化７】

【００３０】
【化８】

【００３１】
［式中、Ｂｎはベンジル基を示し、Ｒ⁶は炭素数３以上のアルキル基を示し、Ｒ⁷はポリシロキサン残基又はトリアルコキシシリル基を示し、ｍ及びＡｒは前記と同じ］
【００３２】
すなわち、カリックスアレーン（１０）をベンジル化してモノベンジル体（１７）を得、このｄｉｓｔａｌ位をアルキル化して化合物（１８）とし、ブロム化して化合物（１９）を得、さらに残りの水酸基をアルキル化して化合物（２０）とする。次に、脱ベンジル化して化合物（２１）とした後、アルケニル化して化合物（２２）とし、次いでジヒドロキシボラニル化した後アリール化すれば、化合物（１Ｂ）が得られる。化合物（１Ｂ）をヒドロシリル化反応に付して化合物（１Ｓ₂）を得る。
【００３３】
化合物（１６）のベンジル化反応は、ベンジルブロミド等のベンジルハライドを用い、炭酸カリウム、フッ化セシウム等のアルカリの存在下、アセトン、アセトニトリル等の溶媒中加熱還流することにより行なわれる。化合物（１７）のアルキル化反応は前記化合物（１１）のアルキル化と同様にして行なわれる。また、化合物（１８）のブロム化は、前記化合物（１２）のブロム化と同様にして行なわれる。化合物（１９）のアルキル化反応は、化合物（１１）のアルキル化と同様にしてもよいが、プロピルブロミド等を用い、水素化ナトリウム等の強アルカリの存在下に行なうのが好ましい。化合物（２０）の脱ベンジル化反応は、化合物（２０）とヨウ化トリメチルシリル等を、クロロホルム等の溶媒中で反応させることにより行なうことができる。化合物（２１）のアルケニル化、さらに化合物（２２）から化合物（１Ｓ₂）までの反応は、前記と同様にして行なうことができる。
【００３４】
かくして得られた本発明化合物（１）のうち、Ｒ¹及びＲ²の少なくとも１つがポリシロキサン-(CH₂)_m+2-又はトリアルコキシシリル-(CH₂)_m+2-である化合物は、種々のクロマトグラフィー固定相として有用である。ここで、クロマトグラフィーにはガスクロマトグラフィー、液体クロマトグラフィー、超臨界流体クロマトグラフィー、薄層クロマトグラフィー、キャピラリーガスクロマトグラフィー、電気クロマトグラフィー、キャピラリー電気泳動のいずれも含まれる。
【００３５】
本発明化合物（１）を反応させるか又はコーティングしてなるガスクロマトグラフィー用カラムは、例えば本発明化合物（１）のうち、Ｒ¹及びＲ²の少なくとも１つがポリシロキサン-(CH₂)_m+2-である化合物をペンタン、アセトン、塩化メチレン等の溶媒に溶解させ、これにケイソウ土系担体の代表的市販品であるクロモソルブＷやセライト５４５等を加え、その後減圧するなどして溶媒を除くことにより０．１〜３０重量％の範囲で担体表面に固定相をコーティングする。これをガラス、ステンレス等のパイプ状カラムに充填することにより得ることができる。また、キャピラリーガスクロマトグラフィー用カラムは、例えば本発明化合物（１）のうち、Ｒ¹及びＲ²の少なくとも１つがポリシロキサン-(CH₂)_m+2-である化合物をペンタン、アセトン、塩化メチレン等の溶媒に溶解させ、これを内面不活性化処理され市販されているシリカキャピラリーカラム（内径０．１〜１mm程度の中空パイプ）にスタティック法あるいはダイナミック法によりコーティングし、Ｎ₂ガスを通じてよく乾燥することにより得ることができる。また、液体クロマトグラフィー用カラムは、例えば本発明化合物（１）のうち、Ｒ¹及びＲ²の少なくとも１つがトリアルコキシシリル-(CH₂)_m+2-である化合物をトルエン、ヘプタン等の溶媒に溶解させ、これに予め酸処理した５〜１０μｌ程度の球状シリカゲルを加えて加熱還流し、濾過してよく乾燥し、これを市販品のステンレス、ガラス等のカラムに充填することにより得ることができる。
【００３６】
こうして得られたクロマトグラフィー用カラムを用いるクロマトグラフィーは通常のガスクロマトグラフィー、液体クロマトグラフィー等の手順に従って行なえばよい。
【００３７】
【実施例】
次に実施例を挙げて本発明をさらに詳細に説明するが、本発明は何らこれらに限定されるものではない。
【００３８】
実施例１
5,17-ビス(3-置換フェニル)-25,27-ジプロピルオキシ-26,28-ジアルケニルオキシカリックス[4]アレーンの合成
5,11,17,23-テトラ-tert-ブチル-25,26,27,28-テトラヒドロキシカリックス[4]アレーン(1)
窒素ガス導入管、メカニカルスターラーを備えた三ッ口フラスコに、4-tert-ブチルフェノール100 g (0.666 mol)、水酸化ナトリウム1.20 g (30.0 mmol)、37%ホルムアルデヒド水溶液(62 mL)を秤り取り、黄色アメ状になるまで120℃で約2時間メカニカルスターラーで撹拌した。これを室温まで冷却した後、冷却管を備えたディーンスターク型トラップを連結した。これにジフェニルエーテル(600 mL)を加え、窒素ガスを液面に吹き付けながら120℃で1時間撹拌後、さらに2時間還流した。放冷後、酢酸エチル(800 mL)を加え、得られた沈殿物を吸引ろ過により回収し、白色固体の(1) (Fw 648.92) を94.7 g 得た。収率88％; R_f = 0.46 (CHCl₃/hexane3:4); ¹H NMR (89.5 MHz, CDCl₃)δ10.38 (br s , 4H), 7.11 (s, 8H), 4.17 (br s, 4H), 3.57 (br s, 4H), 1.21 (s, 36H); IR (KBr, cm^-1) 3130 (OH).
【００３９】
25,26,27,28-テトラヒドロキシカリックス[4]アレーン(2)
窒素雰囲気下、塩化アルミニウム52.6 g (0.394 mol)、フェノール34.8 g (0.370 mol)(1) 50 g (77.1 mmol)、トルエン(400 mL)を混合し、室温で2時間撹拌した。反応終了後、水(500 mL) を加え30分間撹拌した後、有機相を分離し、これを無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(2) (Fw 424.47) を30.2 g 得た。収率92％; mp 313-314℃; R_f = 0.56 (hexane/chloroform 1:2); ¹H NMR ( 400 MHz, CDCl₃)δ10.21 (s, 4H),7.04 (d, 8H), 6.73(t, 4H), 4.4-3.3 (br d, 8H); ¹³C NMR (101 MHz, CDCl₃)δ148.74, 128.96, 128.21, 122.23, 31.68; IR(KBr, cm^-1) 3240(OH).
【００４０】
25,27-ジプロピルオキシ-26,28-ジヒドロキシカリックス[4]アレーン(3)
(2) 10.0 g (23.6 mmol)、炭酸カリウム3.59 g (25.96 mmol)、アセトニトリル(400 mL)を混合し、これにプロピルブロミド5.83 g (48.2 mmol)を加え15時間還流した。反応終了後、減圧濃縮により溶媒を留去し、クロロホルム(100 mL)を加え、これを水(100 mL)、1N塩酸水溶液(2×50 mL)、飽和食塩水(100 mL)で順に洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体 の(3) (Fw 508.66)を9.23 g 得た。収率77％; mp 271℃; R_f = 0.46 (hexane/ chloroform 4:3); ¹H NMR (400 MHz, CDCl₃) δ8.30 (s, 2H),7.04-6.62 (m, 12H), 4.32 (d, J = 13.0Hz, 4H), 3.94 (t, J = 6.28Hz, 4H), 3.36 (d, J = 13.0Hz, 4H), 2.06-2.01 (m, 4H), 1.29 (t, J = 7.36Hz, 6H); ¹³C NMR (101MHz, CDCl₃)δ153.35, 151.82, 134.19, 128.87, 128.41, 128.10, 125.26, 118.91, 78.25, 31.41,
10.90; IR(KBr, cm^-1) 3302(OH).
【００４１】
5,17-ジブロモ-25,27-ジプロピルオキシ-26,28-ジヒドロキシカリックス[4]アレーン(4)
(3) 10.0 g (19.7 mmol)、N-ブロモスクシンイミド7.00 g (39.3 mmol)を2-ブタノン(300 mL)に溶解し、室温で24時間撹拌した。反応終了後、減圧濃縮により溶媒を留去し、これに少量の熱メタノールを加えてN-ブロモスクシンイミドを完全に溶解させた。これをろ過して、白色固体の(4) (Fw 666.45)を11.6 g 得た。収率98％; mp >300℃; ¹H NMR (CDCl₃,400MHz) δ8.39 (s, 2H), 7.3-6.7 (m, 10H), 4.25 (d, J = 12.9 Hz, 4H), 3.95 (t, J = 6.20 Hz, 4H), 3.33 (d, J = 13.0Hz, 4H), 2.2-2.0 (m, 4H), 1.4-1.1 (m, 6H); IR(KBr, cm^-1) 3200(OH).
【００４２】
5,17-ジブロモ-25,27-ジプロピルオキシ-26,28-ジアリルオキシカリックス[4]アレーン(5a)
(4) 10.0 g (15.0 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、これに60％水素化ナトリウム-パラフィン3.60 g (90 mmol)を加え、室温で15分間撹拌した。これに3-ブロモプロペン9.05 g (75 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液(150 mL)を加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(5a)(Fw 746.58)を10.4 g得た。収率 93％; mp 216？C; ¹H NMR(CDCl₃)δ7.11-6.28 (m, 12H), 5.15-5.11 (m, 4H), 4.58-4.56 (m, 4H), 4.37 (d, J=13.44Hz, 4H), 3.75-3.69 (m, 4H), 3.09 (d, J=13.48Hz, 4H), 1.90-1.85 (m, 4H), 1.07-1.01 (m, 6H).
【００４３】
5,17-ジブロモ-25,27-ジプロピルオキシ-26,28-ビス(4-ペンテニルオキシ)カリックス[4]アレーン(5b)
(4) 10.0 g (15.0 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、これに60％水素化ナトリウム-パラフィン3.60 g (90 mmol)を加え、室温で15分間撹拌した後、5-ブロモ-1-ペンテン11.2 g (75.0 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液(150 mL)を加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(5b)(Fw 778.66)を8.8 g得た。収率 75％; mp 165？C; ¹H NMR(CDCl₃)δ6.82-6.44 (m, 10H), 5.85-5.83 (m, 2H), 5.08-4.98 (m, 4H), 4.38 (d, J=13.36Hz, 4H), 3.90-3.79 (m, 8H), 3.11 (d, J=13.40Hz, 4H), 2.18-2.16 (m, 4H), 1.99-1.87 (m, 8H), 1.00-0.93 (m, 6H).
【００４４】
25,27-ジプロピルオキシ-26,28-ジアリルオキシカリックス[4]アレーン-5,17-ジボロン酸(6a)
アルゴン雰囲気下、(5a) 2.00 g (2.58 mmol)を乾燥テトラヒドロフラン(40 mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液5.17 mL (7.74 mmol)を加え、-78℃で30分間撹拌した。これにトリメトキシボラン1.07g(10.32mmol)を加え、-78℃で1時間、室温で2時間撹拌した後、氷で冷却した2N塩酸水溶液(40 mL)を加えた。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(20 mL)を加えた。次の反応にはこの(6a)(Fw 608.53)の溶液をそのまま用いた。
【００４５】
25,27-ジプロピルオキシ-26,28-ビス(4-ペンテニルオキシ)カリックス[4]アレーン-5,17-ジボロン酸(6b)
アルゴン雰囲気下、(5b) 2.00 g (2.57mmol)を乾燥テトラヒドロフラン(40 mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液5.14 mL (7.71 mmol)を加え、-78℃で30分間撹拌した。これにトリメトキシボラン1.06 g (10.28 mmol)を加え、-78℃で1時間、室温で2時間撹拌した後、氷で冷却した2N塩酸水溶液(40 mL)を加えた。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(20 mL)を加えた。次の反応にはこの(6b)(Fw 731.52)の溶液をそのまま用いた。
【００４６】
5,17-ビス(3-メチルフェニル)-25,27-ジプロピルオキシ-26,28-ジアリルオキシカリックス[4]アレーン(7a)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードトルエン1.40 g (6.4 mmol)をベンゼン(30 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(6a) 1.57 g (2.58 mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン 1:4）により精製し、白色固体の(7a) (Fw 769.03)・0.25 CHCl₃を0.94 g得た。収率 61％; R_f=0.50 (hexane/ chloroform 1:1); ¹H NMR (400 MHz, CDCl₃) δ7.41-7.09 (m, 12H), 6.5-6.4 (m, 2H), 6.3-6.2 (m, 6H), 5.2-5.1 (m, 4H), 4.68 (d, 4H), 4.48 (d, J=13.3Hz, 4H), 3.74 (t, J=6.8Hz, 4H), 3.22 d, J=13.4Hz, 4H), 2.4 (s, 6H), 2.0-1.8 (m, 4H), 1.11 (t, J=7.4Hz, 6H); ¹³C NMR (100MHz, CDCl₃) δ156.70, 155.34, 141.14, 138.15, 137.47, 136.52, 133.08, 128.55, 127.70, 127.59, 127.37, 124.03, 122.18, 116.58, 76.70, 75.75, 31.41, 23.58, 21.60, 10.89.; Anal. Calcd for C₅₄H₅₆O₄・0.25CHCl₃: C,81.56; H,7.10. Found: C, 81.40;
H,7.13.
【００４７】
5,17-ビス(3-メチルフェニル)-25,27-ジプロピルオキシ-26,28-ビス(4-ペンテニルオキシ)カリックス[4]アレーン(7b)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.079 mmol)、3-ヨードトルエン1.39 g (6.38 mmol)をベンゼン(30 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(6b) 1.88 g (2.57 mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン 1:4）により精製し、白色固体の(7b) (Fw 801.12)を1.24 g得た。収率 60％; mp 63℃; R_f=0.64 (hexane/ chloroform 1:1); ¹H NMR (400 MHz, CDCl₃) δ7.31-6.32 (m, 18H), 5.90-5.84 (m, 2H), 5.08-4.98 (m, 4H), 4.49 (d, J=13.24Hz, 4H), 4.07 (t, J=7.8Hz, 4H), 3.76 (t, J=7.0Hz, 4H), 3.22 (d, J=13.31Hz, 4H), 2.37 (s, 6H), 2.13-1.90 (m, 12H), 1.09 (t, J=7.4Hz,6H); ¹³C NMR (100MHz, CDCl₃)δ157.04, 155.53, 141.13, 138.33, 138.02, 136.55, 134.88, 133.56, 128.44, 127.80, 127.62, 127.32, 123.95, 122.19, 114.96, 77.00, 74.57, 31.18, 30.43, 29.25, 23.53, 21.57, 10.84.; Anal. Calcd for C₅₆H₆₄O₄: C, 83.96; H, 8.05. Found: C, 84.16; H, 7.99.
【００４８】
5,17-ビス(3-トリフルオロメチルフェニル)-25,27-ジプロピルオキシ-26,28-ジアリルオキシカリックス[4]アレーン(7c)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードベンゾトリフルオライド1.82 g (6.7 mmol)を2-プロパノール(30 mL)に溶解し、これに炭酸カリウム2.4 g (17.4 mmol)と水(10 mL)を加えた。さらに、(6a) 1.57 g (2.58 mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム／ヘキサン 1:5）により精製し、白色固体の(7c) (Fw 876.98)を1.36 g得た。収率 58％; mp 237℃; R_f = 0.55 (hexane/ chloroform 1:1) ; ¹H NMR (400 MHz, CDCl₃) δ7.79-7.22 (m, 12H), 6.5-6.4 (m, 2H), 6.4-6.3 (m, 6H), 5.2-5.1 (m, 4H), 4.68 (d, 4H), 4.48(d, J = 13.2Hz, 4H), 3.78 (t, J = 7.0Hz, 4H), 3.24 (d, J = 13.4Hz, 4H), 2.0-1.9 (m, 4H), 1.11 (t, J = 7.4Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) 157.13, 155.62, 141.85, 137.57, 136.01, 133.53, 133.30, 131.38, 131.06, 130.74, 130.42, 130.06, 128.99, 127.77, 127.28, 125.67, 123.54, 123.50, 123.22, 123.18, 122.97, 122.29, 117.00, 76.70, 75.87, 31.39, 23.52, 10.79; IR(KBr, cm^-1)1341(CF₃); Anal. Calcd for C₅₄H₅₀O₄F₆: C,73.96; H,5.75. Found: C, 73.81; H,5.86.
【００４９】
5,17-ビス(3-トリフルオロメチルフェニル)-25,27-ジプロピルオキシ-26,28-ビス(4-ペンテニル)オキシカリックス[4]アレーン(7d)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードベンゾトリフルオライド1.81 g (6.67 mmol)を2-プロパノール(30 mL)に溶解し、これに炭酸カリウム2.4 g (17.4 mmol)と水(10 mL)を加えた。さらに、(6b) 1.88 g (2.57 mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン 1:5）により精製し、白色固体の(7d) (Fw 852.07)を1.27 g得た。収率 58％; mp 60℃; R_f = 0.75 (hexane/ chloroform 1:1); ¹H NMR (400 MHz, CDCl₃) δ7.51-6.58 (m, 18H), 5.89-5.85 (m, 2H), 5.09-5.00 (m, 4H), 4.5 (d, J=13.3Hz, 4H), 4.00-3.86 (m, 8H), 3.24 (d, J=13.4Hz, 4H), 2.24-2.18 (m, 4H), 2.08-1.94 (m, 8H), 1.06 (t, J=7.1Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ156.97, 156.27, 141.62, 138.13, 135.95, 134.51, 133.29, 130.71, 130.39, 130.07, 129.66, 128.74, 128.28, 126.92, 125.59, 123.17, 123.14, 122.97, 122.94, 122.30, 114.89, 76.90, 74.72, 31.13, 30.45, 29.34, 23.37, 10.64; IR(KBr, cm^-1)1342(CF₃); Anal. Calcd for C₅₆H₅₈O₄F₆: C, 73.94; H, 6.43. Found: C, 74.85; H, 6.48.
【００５０】
実施例２
5,17-ビス(3-置換フェニル)-25,27-ジアルケニルオキシ-26,28-ジプロピルオキシカリックス[4]アレーンの合成
25,27-ジアリルオキシ-26,28-ジヒドロキシカリックス[4]アレーン(8a)
(2) 10.0 g (23.6 mmol)、炭酸カリウム3.59 g (26.0 mmol)、アセトニトリル(400 mL)を混合し、これにアリルブロミド5.83 g (48.2 mmol)を加え15時間還流した。反応終了後、減圧濃縮により溶媒を留去し、クロロホルム(100 mL)を加え、これを水(100 mL)と1N塩酸水溶液(2×50 mL)、飽和食塩水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(8a) (Fw 504.23)を8.45 g得た。収率71%; R_f=0.14(hexane/ chloroform 1:1); mp 210-212℃ (lit. 187-188.5℃); ¹H NMR (400 MHz, CDCl₃) δ7.90 (s, 2H), 7.00-6.15 (m, 14H), 5.73-5.22 (m, 4H), 4.48 (m, 4H), 4.25 (d, J=13.0 Hz, 4H), 3.31 (d, J=13.0Hz, 4H); ¹³C NMR (101 MHz, CDCl₃)δ153.23, 151.70, 133.37, 132.75, 128.94, 128.44, 128.08, 125.41, 119.02, 117.92, 76.85, 31.42. IR(KBr, cm^-1)3328(OH)
【００５１】
25,27-ビス(4-ペンテニルオキシ)-26,28-ジヒドロキシカリックス[4]アレーン(8b)
(2) 10.0 g (23.6 mmol)、炭酸カリウム3.59 g (26.0 mmol)、アセトニトリル(400 mL)を混合し、これに5-ブロモ-1-ペンテン17.59 g (118 mmol)を加え15時間還流した。反応終了後、減圧濃縮により溶媒を留去し、クロロホルム(100 mL)を加え、これを水(100 mL)と1N塩酸水溶液(2×50 mL)、飽和食塩水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(8b) (Fw 560.73)を11.0 g得た。収率85%; R_f=0.17 (hexane/ chloroform 1:1); mp 178℃;¹H NMR (400 MHz, CDCl₃)δ8.20 (s, 2H), 7.06-6.63 (m, 12H), 5.95-5.93 (m, 2H), 5.21-5.04 (m, 4H), 4.31 (d, J=13.0Hz, 4H), 4.02-3.99 (m, 4H), 3.37 (d, J=13.0Hz, 4H), 2.56-2.51 (m, 4H), 2.19-2.13 (m, 4H).; ¹³C NMR(100MHz, CDCl₃)δ153.33，151.86，137.88，133.37，128.91，128.45，128.10，125.32，118.97，115.97，75.75，31.44，30.08，29.24．Anal. Calcd for C₃₈H₄₀O₄: C, 81.40; H, 7.19. Found:C, 80.95, H, 7.18. IR(KBr, cm^-1)3299(OH)
【００５２】
5,17-ジブロモ-25,27-ジアリルオキシ-26,28-ジヒドロキシカリックス[4]アレーン(9a)
(8b) 10.0g(19.8mmol)、N-ブロモスクシンイミド7.04 g (39.6 mmol)を2-ブタノン(300 mL)に溶解し、室温で24時間撹拌した。反応終了後、減圧濃縮により溶媒を留去し、これに少量の熱メタノールを加えN-ブロモスクシンイミドを完全に溶解させた。これをろ過して、白色固体の(9a) (Fw 664.43)を13.1 g得た。収率99%; mp 247℃; ¹H NMR (400 MH_Z, CDCl₃) δ8.10 (s, 2H), 7.01-6.76 (m, 10H), 6.24-6.23 (m, 2H), 5.79-5.41 (m, 4H), 4.52 (d, J=10.96Hz, 4H), 4.31-4.24 (m, 4H).IR(KBr, cm^-1)3271(OH)
【００５３】
5,17-ジブロモ-25,27-ビス(4-ペンテニルオキシ)-26,28-ジヒドロキシカリックス[4]アレーン(9b)
(8b) 10.0g(17.8 mmol)、N-ブロモスクシンイミド9.52 g (53.5 mmol)を2-ブタノン(300 mL)に溶解し、室温で24時間撹拌した。反応終了後、減圧濃縮により溶媒を留去した。これに少量の熱メタノールを加え、N-ブロモスクシンイミドを完全に溶解させた。これをろ過して、白色固体の(9b) (Fw 718.52)を10.23 g得た。収率80%。
【００５４】
5,17-ジブロモ-25,27-ジアリルオキシ-26,28-ジプロピルオキシカリックス[4]アレーン(10a)
(9a) 10.0 g (15.0 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、これに60％水素化ナトリウム-パラフィン3.01 g (75 mmol)を加え、室温で15分撹拌した。さらにプロピルブロミド9.30 g (75 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液150 mLを加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(10a) (Fw 746.58)を6.72 g得た。収率60%; R_f=0.62(hexane/ chloroform 1:1);mp 153-154℃; ¹H NMR(400MHz, CDCL₃) δ7.23-6.87 (m, 6H), 6.46-6.16 (m, 6H), 5.14-5.11 (m, 4H), 4.60 (d, J = 13.2Hz , 4H), 4.39 (d, J = 11.2Hz, 4H), 3.71 (t, J = 10.8Hz, 4H), 3.13 (d, J = 13.2Hz, 4H), 1.93-1.88 (m, 4H), 1.50-1.04 (m, 4H); ¹³C NMR(100 MHz, CDCl₃) δ156.90, 154.63, 136.15, 135.92, 135.78, 130.29, 128.92, 122.95, 117.00, 115.67, 77.02, 75.70, 31.29, 23.00, 10.86. Anal. Calcd for C₄₀H₄₂O₄Br₂: C, 64.35; H,5.67. Found: C, 64.84, H, 5.74.
【００５５】
5,17-ジブロモ-25,27-ビス(4？ペンテニルオキシ)-26,28-ジプロピルオキシカリックス[4]アレーン(10b)
(9b) 10.0 g (13.9 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、これに60％水素化ナトリウム-パラフィン2.78 g (70 mmol)を加え、室温で15分撹拌した。さらにプロピルブロミド8.40 g (70 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液150 mLを加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(10b) (Fw 778.66)を6.28g得た。収率63％。
【００５６】
25,27-ジアリルオキシ-26,28-ジプロピルオキシカリックス[4]アレーン-5,17-ジボロン酸 (11a)
アルゴン雰囲気下、(10a) 2.00 g (2.58 mmol)を乾燥テトラヒドロフラン(40 mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液5.17 mL (7.74 mmol)を加え、-78℃で30分間撹拌した。これにトリメトキシボラン1.07g(10.32mmol)を加え、-78℃で1時間、室温で2時間撹拌した後、氷で冷却した2N塩酸水溶液(40 mL)を加えた。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(20 mL)を加えた。次の反応にはこの(11a) (Fw 608.53) の溶液をそのまま用いた。
【００５７】
25,27-ビス(4-ペンテニルオキシ)-26,28-ジプロピルオキシカリックス[4]アレーン-5,17-ジボロン酸 (11b)
アルゴン雰囲気下、(10b) 2.00 g (2.57 mmol)を乾燥テトラヒドロフラン(40 mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液5.14 mL (7.71 mmol)を加え、-78℃で30分間撹拌した。これにトリメトキシボラン1.06 g (10.28 mmol)を加え、-78℃で1時間、室温で2時間撹拌した後、氷で冷却した2N塩酸水溶液(40 mL)を加えた。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(20 mL)を加えた。次の反応にはこの(11b) (Fw 731.52) の溶液をそのまま用いた。
【００５８】
5,17-ビス(3-メチルフェニル)-25,27-ジアリルオキシ-26,28-ジプロピルオキシカリックス[4]アレーン(12a)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードトルエン1.40 g (6.4 mmol)をベンゼン(30 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(11a) 1.57 g (2.58 mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン1:4）により精製し、白色固体の(12a) (Fw 769.03)を1.44 g得た。収率70%; R_f=0.48 (hexane/ chloroform 1:1); mp 65℃; ¹H NMR(400MHz, CDCL₃) δ7.77-6.67 (m, 18H), 6.43-6.41 (m, 2H), 5.27-5.17 (m, 4H), 4.61-4.51 (m, 4H), 4.47 (d, J = 13.2Hz , 4H), 3.86-3.83 (m, 4H), 4.39 (d, J = 11.2Hz, 4H), 3.21 (d, J = 13.2Hz, 4H), 2.16 (s, 6H), 1.98-1.91 (m, 4H), 1.98-1.91 (m, 4H), 1.06-1.01 (m, 6H); ¹³C NMR(100 MHz, CDCl₃) δ156.00, 155.85, 141.08, 137.53, 135.98, 135.66, 135.17, 134.54, 128.41, 128.05, 127.37, 126.77, 123.70, 122.48, 116.61, 77.21, 75.74, 31.36, 23.38, 21.43, 10.50. Anal. Calcd for C₄₀H₄₂O₄Br₂: C, 64.35; H,5.67. Found: C, 64.84, H, 5.74. Anal. Calcd for C₅₄H₅₆O₄: C, 84.34; H, 7.34. Found: C, 83.95; H, 7.47.
【００５９】
5,17-ビス(3-メチルフェニル)-25,27-ビス(4-ペンテニルオキシ)-26,28-ジプロピルオキシカリックス[4]アレーン(12b)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092g (0.079mmol)、3-ヨードトルエン1.39g (6.38mmol)をベンゼン(30 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(11b) 1.88 g (2.57 mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン1:4）により精製し、白色固体の(12b) (Fw 801.12)を1.19g得た。収率58％。
【００６０】
5,17-ビス(3-トリフルオロメチルフェニル)-25,27-ジアリルオキシ-26,28-ジプロピルオキシカリックス[4]アレーン(12c)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードベンゾトリフルオライド1.82 g (6.7 mmol)を2-プロパノール(30 mL)に溶解し、これに炭酸カリウム2.4 g (17.4 mmol)と水(10 mL)を加えた。さらに、(11a) 1.57 g (2.58 mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン1:5）により精製し、白色固体の(12b) (Fw 876.98)を1.24 g得た。収率55%; mp 138℃; R_f=0.61 (hexane/ chloroform 1:1)、¹H NMR (400MHz, CDCl₃)δ7.16-6.45 (m, 20H), 5.20-5.18 (m, 4H), 4.70-4.68 (m, 4H), 4.49 (d, J=13.3Hz, 4H), 3.77 (t, J= 7.08Hz, 4H), 3.23 (d, J= 13.4Hz, 4H), 1.99-1.92(m, 4H), 1.11-1.04 (m, 6H); ¹³C NMR(100MHz, CDCl₃)δ156.50, 155.98, 141.38, 136.63, 136.15, 134.28, 133.36, 129.15, 128.87, 128.38, 126.30, 122.72, 122.66, 116.87, 76.69, 75.73, 31.34, 23.51, 10.74. Anal. Calcd for C₅₄H₅₀O₄F₆: C,73.96; H5.75. Found: C, 74.22; H, 5.91; IR(KBr, cm^-1)1342(CF₃).
【００６１】
5,17-ビス(3-トリフルオロメチルフェニル)-25,27-ビス(4-ペンテニルオキシ)-26,28-ジプロピルオキシカリックス[4]アレーン(12d)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードベンゾトリフルオライド1.82 g (6.7 mmol)を2-プロパノール(30 mL)に溶解し、これに炭酸カリウム2.4 g (17.4 mmol)と水(10 mL)を加えた。さらに、(11b) 1.57 g (2.58 mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン1:5）により精製し、白色固体の(12d) (Fw 852.07)を1.21g得た。収率55％。
【００６２】
実施例３
5,17-ビス(3-置換フェニル)-25-アルケニルオキシ-26,27,28-トリプロピルオキシカリックス[4]アレーンの合成
25-ベンジルオキシ-26,27,28-トリヒドロキシカリックス[4]アレーン(13)
(2) 10.0 g (23.6 mmol)、炭酸カリウム1.63 g (11.8 mmol)、アセトン(400 mL)を混合し、これにベンジルブロミド4.84 g (28.3 mmol)を加え5時間還流した。反応終了後、減圧濃縮により溶媒を留去し、クロロホルム(100 mL)を加え、これを水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(13) (Fw 514.62)を6.12 g得た。収率51 ％; mp 240℃; R_f= 0.13 (hexane/ chloroform); ¹H NMR (400 MHz, CDCl₃) δ9.56 (s, 1H), 9.22 (s, 1H), 7.74-6.63 (m, 17H), 5.91 (s, 2H), 4.34 (d, J=13.0Hz, 2H), 4.22 (d, J=13.2Hz, 2H), 3.43 (d, J=13.0Hz, 2H), 3.42 (d, J=13.8Hz, 2H); ¹³C NMR(CDCl₃, 100MHz)δ151.25, 150.81, 149.51, 135.51, 134.35, 129.44, 129.07, 128.99, 128.98, 128.79, 128.75, 128.39, 128.34, 128.30, 126.31, 121.93, 120.87, 79.32, 31.87, 31.62.; Anal. Calcd for C₃₅H₃₀O₄・0.1CHCl₃: C, 80.06; H, 5.76. Found: C,80.65; H, 6.00. IR(KBr, cm^-1)3268(OH)
【００６３】
25-ベンジルオキシ-26,28-ジヒドロキシ-27-プロピルオキシカリックス[4]アレーン(14)
(13) 5.0 g (9.72 mmol)、炭酸カリウム1.48 g (10.7 mmol)、アセトニトリル(100 mL)を混合し、これにプロピルブロミド2.41 g (19.9 mmol)を加え15時間還流した。反応終了後、減圧濃縮により溶媒を留去し、クロロホルム(100 mL)を加え、これを水(50 mL)、飽和食塩水(100 mL)の順で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(14) (Fw 556.70)を3.90 g 得た。収率72％; mp 233℃; R_f=0.20 (hexane/ chloroform); ¹H NMR (89.5 MHz, CDCl₃) δ8.14 (s, 2H), 7.80-7.37 (m, 5H), 7.06-6.62 (m, 12H), 5.06 (s, 2H), 4.37-4.27 (m, 4H), 3.72 (m, 2H), 3.39-3.32 (m, 4H), 2.09-2.00 (m, 2H), 1.24 (t, J= 7.4Hz, 3H); ¹³C NMR (100MHz, CDCl₃)δ153.36, 151.84, 151.67, 136.78, 133.45, 133.39, 129.05, 128.92, 128.57, 128.48, 128.40, 128.07, 128.07, 128.03, 128.02, 127.50, 125.58, 125.28, 118.95, 78.36, 78.28, 31.44, 23.49, 11.03. Anal. Calcd for C₃₈H₃₆O₄: C, 81.99; H, 6.52. Found: C, 81.77; H, 6.53; IR(KBr,cm^-1) 3336(OH)
【００６４】
5,17-ジブロモ-25-ベンジルオキシ-26,28-ジヒドロキシ-27-プロピルオキシカリックス[4]アレーン(15)
(14) 5.0 g (9.00 mmol)、N-ブロモスクシンイミド3.52 g (19.8 mmol)を2-ブタノン(150 mL)に溶解し、室温で24時間撹拌した。反応終了後、減圧濃縮により溶媒を留去し、これに少量の熱メタノールを加え、N-ブロモスクシンイミドを完全に溶解させた。これをろ過して、白色固体の(4a) (Fw 714.49) を6.10 g得た。収率95％; mp >300？C; ¹H NMR(CDCl₃, 400MHz)δ8.21 (s, 2H), 7.87-6.80 (m, 15H), 5.04 (s, 2H), 4.29-4.24 (q, 4H), 3.94-3.91 (m, 2H), 3.39-3.26 (q, 4H), 2.07-2.00 (m, 2H), 1.23-1.20 (m, 3H); IR(KBr, cm^-1)3247(OH).
【００６５】
5,17-ジブロモ-25-ベンジルオキシ-26,27,28-トリプロピルオキシカリックス[4]アレーン(16)
(15) 3.5 g (4.88 mmol)をN,N-ジメチルホルムアミド(100 mL)に溶解し、これに60％水素化ナトリウム-パラフィン1.17 g (29.3 mmol)を加え、室温で15分間撹拌した後、プロピルブロミド2.95 g (24.4 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液(100 mL)を加え、クロロホルム(3×100 mL)で抽出し、合わせた有機相を水(2×50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(5a) (Fw 798.65)・0.1CHCl₃ 3.54 g を得た。収率91％; R_f=0.72 (hexane/ chloroform 1:1); mp 78℃; ¹H NMR(CDCl₃, 500MHz)δ7.39-6.51 (m, 15H), 4.86 (s, 2H), 4.40-4.27 (q, 4H), 3.83-3.76 (m, 6H), 3.12-3.01 (q, 4H), 1.93-1.76 (m, 6H), 1.03-0.81 (m, 9H); ¹³C NMR(CDCl₃, 100MHz)δ156.09, 155.93, 154.88, 137.76, 137.61, 137.48, 134.10, 133.83, 130.92, 129.47, 128.58, 128.27, 128.18, 128.10, 128.03, 122.82, 122.43, 114.56, 76.81, 30.91, 30.85, 23.32, 22.99, 10.47, 9.98; Anal. Calcd for C₄₄H₄₆O₄Br₂・0.1CHCl₃: C65.35; H5.73. Found: C, 65.26; H, 5.80.
【００６６】
5,17-ジブロモ-25-ヒドロキシ-26,27,28-トリプロピルオキシカリックス[4]アレーン(17)
アルゴン雰囲気下、(16) 2.00 g (2.50 mmol)を乾燥クロロホルム(150 mL)に溶解し、これにトリメチルシリルヨージド1.07 mL (7.52 mmol)を加えた。これを室温で3.5時間撹拌した。反応終了後、水(100mL) で希釈した。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去し、フラッシュクロマトグラフィー(silica gel 100 g ,クロロホルム/ヘキサン 1:2)により精製し、白色固体の(17) (Fw 708.53)・0.1CHCl₃を1.14 g で得た。収率64％; R_f=0.62 (hexane/ chloroform 1:1); mp 218℃; ¹H NMR(CDCl₃, 400MHz)δ7.29-6.48 (m, 10H), 4.63 (s, 1H), 4.37-4.30 (q, 4H), 3.82-3.69 (m, 6H), 3.29-3.17 (q, 4H), 2.24-2.18 (m, 2H), 1.91-1.84 (m, 4H), 1.12-1.09 (m, 6H), 1.09-0.89 (m, 3H); ¹³C NMR(CDCl₃, 100MHz)δ156.62, 153.59, 153.02, 136.39, 135.39, 135.74, 134.99, 130.70, 130.50, 130.23, 129.48, 128.71, 123.67, 119.83, 116.08, 77.62, 76.63, 30.63, 30.59, 23.37, 22.33, 10.78, 9.54; Anal. Calcd for C₃₇H₄₀O₄Br₂・0.1CHCl₃: C, 61.85; H, 5.61. Found: C, 61.48; H, 5.57; IR(KBr,cm^-1) 3553(OH)
【００６７】
5,17-ジブロモ-25-アリルオキシ-26,27,28-トリプロピルオキシカリックス[4]アレーン(18a)
(17) 1.0 g (1.41mmol)をN,N-ジメチルホルムアミド50mLに溶解し、これに60％水素化ナトリウム-パラフィン0.169g(4.23mmol)を加え、室温で15分間撹拌した後3-ブロモプロペン0.85 g (7.05 mmol)を加え、室温で5時間撹拌した。反応終了後、1Ｎ塩酸(30mL)を加え、クロロホルム(3×50mL)で抽出し、合わせた有機相を水(2×100mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(18a)(Fw 748.59)を0.68 gで得た．収率64％; ¹H NMR(CDCl₃, 400MHz)δ6.86-6.57 (m, 10H), 6.40-6.34 (m, 1H), 5.18-5.13 (m, 2H), 4.01 (d, 2H), 4.42-4.35 (m, 4H), 3.95-3.72 (m, 6H), 3.14-3.10 (m, 4H), 1.95-1.86 (m, 6H), 1.05-0.90 (m, 9H).
【００６８】
5,17-ジブロモ-25-(4-ペンテニルオキシ)-26,27,28-トリプロピルオキシカリックス[4]アレーン(18b)
(17) 0.7 g (0.99mmol)をN,N-ジメチルホルムアミド50mLに溶解し、これに60％水素化ナトリウム-パラフィン0.12g(2.96mmol)を加え、室温で15分間撹拌した後5-ブロモ-1-ペンテン0.74 g (4.94 mmol)を加え、室温で5時間撹拌した。反応終了後、1Ｎ塩酸(30mL)を加え、クロロホルム(3×50mL)で抽出し、合わせた有機相を水(2×100mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(18b)(Fw 776.65)を0.34 g得た。収率44％; ¹H NMR(CDCl₃, 400MHz)δ6.73-6.60 (m, 10H), 5.82-5.71 (m, 1H), 5.12-4.93 (m, 2H), 4.46-4.31 (m, 4H), 3.88-3.71 (m, 8H), 3.18-3.03 (m, 4H), 2.19-1.69 (m, 10H), 1.07-0.37 (m, 9H).
【００６９】
25-アリルオキシ-26,27,28-トリプロピルオキシカリックス[4]アレーン-5,17-ジボロン酸(19a)
アルゴン雰囲気下、(18a) 0.5 g (0.668 mmol)を乾燥テトラヒドロフラン(10mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液1.26mL（2.00 mmol）を加え、-78℃で30分間撹拌した。さらにトリメトキシボラン0.28 g (2.67 mmol)を加え、-78℃で1時間、室温で２時間撹拌した後、氷で冷却した2N塩酸水溶液(10 mL)を加えた。これをクロロホルム(2×50 mL)で抽出し、合わせた有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(10 mL)を加えた。次の反応にはこの(19a) (Fw 678.43)の溶液をそのまま用いた。
【００７０】
25-(4-ペンテニルオキシ)-26,27,28-トリプロピルオキシカリックス[4]アレーン-5,17-ジボロン酸(19b)
アルゴン雰囲気下、(18b) 0.5 g (0.644 mmol)を乾燥テトラヒドロフラン(10mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液1.29mL（1.93 mmol）を加え、-78℃で30分間撹拌した。さらにトリメトキシボラン0.27 g (2.67 mmol)を加え、-78℃で1時間、室温で２時間撹拌した後、氷で冷却した2N塩酸水溶液(10 mL)を加えた。これをクロロホルム(2×50 mL)で抽出し、合わせた有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(5 mL)を加えた。次の反応にはこの(19b)(Fw 706.49)の溶液をそのまま用いた。
【００７１】
5,17-ビス(3-メチルフェニル)-25-アリルオキシ-26,27,28-トリプロピルオキシカリックス[4]アレーン(20a)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.022g(0.019mmol)及び3-ヨードトルエン0.35g(1.62mmol)をベンゼン(10 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(19a)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×10 mL)で抽出し、有機相を水(10 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（クロロホルム／ヘキサン 1:4）により精製し、白色固体の(20a)(Fw 771.05)を0.31g 得た。収率62％。
【００７２】
5,17-ビス(3-メチルフェニル)-25-(4-ペンテニルオキシ)-26,27,28-トリプロピルオキシカリックス[4]アレーン (20b)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.022g(0.019mmol)及び3-ヨードトルエン0.35g(1.62mmol)をベンゼン(10 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、（19b）0.45g(0.64mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×10 mL)で抽出し、有機相を水(10 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（クロロホルム／ヘキサン 1:4）により精製し、白色固体の(20b)(Fw 799.10)を0.30g得た。収率59％。
【００７３】
5,17-ビス(3-トリフルオロメチルフェニル)-25-アリルオキシ-26,27,28-トリプロピルオキシカリックス[4]アレーン (20c)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.019 g (0.016 mmol)、3-ヨードベンゾトリフルオライド0.36 g (1.34 mmol)を2-プロパノール(10 mL)に溶解し、炭酸カリウム0.6 g (4.34 mmol)と水(3 mL)を加えた。これに、(19a) 0.45 g (0.668mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×10 mL)で抽出し、有機相を水(10 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 60g, クロロホルム／ヘキサン 1:3）により精製し、白色固体の(20c)(Fw 878.99)を0.338 g 得た。収率 58％; ¹H NMR(CDCl₃, 400MHz)δ7.23-6.65 (m, 18H), 6.48-6.37 (m, 1H), 5.20-5.18 (m, 2H), 4.60-4.47 (m, 6H), 4.02-3.80 (m, 6H), 3.25-3.21 (m, 4H), 2.01-1.94 (m, 6H), 1.085-0.99 (m, 9H).
【００７４】
5,17-ビス(3-トリフルオロメチルフェニル)-25-(4-ペンテニルオキシ)-26,27,28-トリプロピルオキシカリックス[4]アレーン (20d)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.019g(0.016mmol)及び3-ヨードベンゾトリフルオライド0.36g(1.34mmol)を2-プロパノール(10 mL)に溶解し、炭酸カリウム0.6 g (4.34 mmol)と水(3 mL)を加えた。これに、(19b)0.45g(0.64mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×10 mL)で抽出し、有機相を水(10 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 60g, クロロホルム／ヘキサン 1:3）により精製し、白色固体の(20d)(Fw 907.05)を0.31g得た。収率53％。
【００７５】
実施例４
5,17-ビス(3-置換フェニル)-25,26,27-トリプロピルオキシ-28-アルケニルオキシカリックス[4]アレーンの合成
5,17-ジブロモ-25,26,27-トリプロピルオキシ-28-ヒドロキシカリックス[4]アレーン(21)
(4) 10.0 g (15.0 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、さらに60％水素化ナトリウム-パラフィン1.20 g (30.0 mmol)を加え、室温で15分間撹拌した。これにプロピルブロミド3.63 g (30.0 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液(150 mL)を加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー(silica gel 100 g, クロロホルム/ヘキサン 1:4 )により、白色固体の(21)(Fw 708.53)を7.60 g得た。収率 72％; ¹H NMR (CDCl₃, 400MHz)δ7.30-7.22 (m, 4H), 6.47-6.34 (m, 6H), 4.80 (s, 1H), 4.37-4.28 (m, 4H), 3.82-3.78 (m, 2H), 3.72-3.69 (m, 4H), 3.26-3.14 (q, 4H), 2.25-2.18 (m, 2H), 1.93-1.84 (m, 4H), 1.12-1.08 (m, 6H), 0.94-0.90 (m, 3H); ¹³C NMR(CDCl₃, 100MHz)δ155.94, 154.32, 152.45, 139.15, 132.84, 132.63, 131.83, 130.78, 128.23, 128.10, 123.27, 115.43, 111.25, 77.65, 76.62, 30.57, 30.53, 23.41, 22.28, 10.77, 9.52; IR(KBr, cm^-1)3537(OH).
【００７６】
5,17-ジブロモ-25,26,27-トリプロピルオキシ-28-アリルオキシカリックス[4]アレーン(22a)
(21) 5.0 g (7.06 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、さらに60％水素化ナトリウム-パラフィン0.85 g (21.2 mmol)を加え、室温で15分間撹拌した。これに3-ブロモプロペン2.56 g (21.2 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液(150 mL)を加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、再結晶(クロロホルム/メタノール)により、白色固体の(22a)(Fw 748.59)を3.92 g得た。収率 74％。
【００７７】
5,17-ジブロモ-25,26,27-トリプロピルオキシ-28- (4-ペンテニルオキシ)カリックス[4]アレーン(22b)
(21a) 5.0 g (7.06 mmol)をN,N-ジメチルホルムアミド(200 mL)に溶解し、さらに60％水素化ナトリウム-パラフィン0.85 g (21.2 mmol)を加え、室温で15分間撹拌した。これに5-ブロモ-1-ペンテン5.26 g (35.3 mmol)を加え、室温で5時間撹拌した。反応終了後、1N塩酸水溶液(150 mL)を加え、クロロホルム(3×150 mL)で抽出し、合わせた有機相を水(2×100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラシュクロマトグラフィー(クロロホルム/ヘキサン)により、白色固体の(22b)(Fw 776.65)を3.47g得た。収率 63％; R_f = 0.60 (hexane: chloroform 1:1); mp 60℃; ¹H NMR(CDCl₃, 400MHz)δ7.35-6.52 (m, 10H), 5.92-5.81 (m, 1H), 5.07-5.01 (m, 2H), 4.41-4.37 (q, 4H), 3.90-3.79 (m, 8H), 3.12-3.09 (q, 4H), 2.17-2.15 (m, 2H), 2.00-1.86 (m, 8H), 1.02-0.94 (m, 9H); ¹³C NMR(CDCl₃, 100MHz)δ156.24, 155.73, 155.69, 139.09, 138.00, 137.33, 135.78, 134.21, 132.70, 131.36, 130.81, 128.38, 128.35, 122.48, 114.93, 114.77, 114.69, 76.83, 74.66, 30.84, 30.82, 30.40, 29.21, 23.23, 23.18, 10.34, 10.27.
【００７８】
25,26,27-トリプロピルオキシ-28-アリルオキシカリックス[4]アレーン-5,17-ジボロン酸(23a)
アルゴン雰囲気下、(22a) 2.00 g (2.66 mmol)を乾燥テトラヒドロフラン(40 mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液5.32 mL (7.98 mmol)を加え、-78℃で30分間撹拌した。これにトリメトキシボラン1.10 g(10.64 mmol)を加え、-78℃で1時間、室温で2時間撹拌した後、氷で冷却した2N塩酸水溶液(40 mL)を加えた。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(20 mL)を加えた。次の反応にはこの(22a)の溶液をそのまま用いた。
【００７９】
25,26,27-トリプロピルオキシ-28-(4-ペンテニルオキシ)カリックス[4]アレーン-5,17-ジボロン酸(23b)
アルゴン雰囲気下、(21b) 2.00 g (2.56mmol)を乾燥テトラヒドロフラン(40 mL)に溶解し、-78℃に冷却した。これに1.5M n-ブチルリチウム-n-ヘキサン溶液5.12 mL (7.69 mmol)を加え、-78℃で30分間撹拌した。これにトリメトキシボラン1.06 g (10.24 mmol)を加え、-78℃で1時間、室温で2時間撹拌した後、氷で冷却した2N塩酸水溶液(40 mL)を加えた。これをクロロホルム(2×100 mL)で抽出し、合わせた有機相を水(100 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を10 mLまで留去し、次の反応で用いる溶媒(20 mL)を加えた。次の反応にはこの(23b)の溶液をそのまま用いた。
【００８０】
5,17-ビス(3-メチルフェニル)-25,26,27-ジプロピルオキシ-28-アリルオキシカリックス[4]アレーン(24a)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードトルエン1.39 g (6.36 mmol)をベンゼン(30 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(23a) 1.80 g (2.66 mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン 1:3）により精製し、白色固体の(24a)を1.06 g得た。収率 58％。
【００８１】
5,17-ビス(3-メチルフェニル)-25,26,27-トリプロピルオキシ-28-(4-ペンテニルオキシ)カリックス[4]アレーン(24b)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.079 mmol)、3-ヨードトルエン1.39g(6.36mmol)をベンゼン(30 mL)に溶解し、これに2M炭酸ナトリウム水溶液(20 mL)を加えた。さらに、(23b)2.07g(2.66mmol)を含む前述の溶液を加え20時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン 1:4）により精製し、白色固体の(24b)(Fw 799.10)を1.84g得た。収率51％。
【００８２】
5,17-ビス(3-トリフルオロメチルフェニル)-25,26,27-トリプロピルオキシ-28-アリルオキシカリックス[4]アレーン(24c)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードベンゾトリフルオライド0.91g(3.85mmol)を2-プロパノール(30 mL)に溶解し、これに炭酸カリウム1.2g(8.7mmol)と水(10 mL)を加えた。さらに、(23a)1.80g(2.66mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム／ヘキサン 1:5）により精製し、白色固体の(24c)(Fw 878.99)を1.24g得た。収率53％。
【００８３】
5,17-ビス(3-トリフルオロメチルフェニル)-25,26,27-トリプロピルオキシ-28-(4-ペンテニル)オキシカリックス[4]アレーン(24d)
アルゴン雰囲気下、テトラキス（トリフェニルホスフィン）パラジウム0.092 g (0.080 mmol)、3-ヨードベンゾトリフルオライド0.91g(3.85mmol)を2-プロパノール(30 mL)に溶解し、これに炭酸カリウム1.2g(8.7mmol)と水(10 mL)を加えた。さらに、(23b)2.07g(2.66mmol)を含む前述の溶液を加え4時間還流した。反応終了後、クロロホルム(2×50 mL)で抽出し、有機相を水(50 mL)で洗浄した。この有機相を無水硫酸マグネシウムで脱水し、減圧濃縮により溶媒を留去した後、フラッシュクロマトグラフィー（silica gel 120g, クロロホルム/ヘキサン 1:5）により精製し、白色固体の(24d)(Fw 907.05)を1.18g得た。収率49％。
【００８４】
実施例５
カリックスアレーンを化学結合させたポリシロキサンの合成
アルゴン雰囲気下、テフロンフラスコで(24b)1.0 g( 1.25mmol)とSi-H結合を4％含有するヒドロメチルポリシロキサン0.60 g (Si-H 1.25mmol)を乾燥トルエン(40 mL)に溶解し、85-90℃で1時間撹拌した。これに1％塩化白金酸(THF-エタノール溶液)132.5μL を加え，85-90℃で72時間撹拌した後、1-オクテン132.5μL(0.85 mmol) 加え一晩撹拌した。空気にさらして放冷後、遠心分離により大部分の触媒を取り除き、フラッシュクロマトグラフィー(silica gel 50 g, 酢酸エチル/ヘキサン 1:10)により精製し、目的化合物を1.18g得た。
【００８５】
実施例６
カリックスアレーンを化学結合させたポリシロキサンの合成
アルゴン雰囲気下、テフロンフラスコで(24b)1.0g (1.25mmol)とメチルジクロロシラン7.82 g (67.95 mmol)を乾燥ベンゼン(20 mL)に溶解し、0.1M 塩化白金酸(THF-エタノール溶液)160.3μLを加え40℃で20時間撹拌した。減圧濃縮により溶媒を留去した後、アルゴン雰囲気下ポリジメチルシロキサン(M_n=550)1.41 g (2.56mmol)と乾燥ベンゼン(20 mL)を加え、50℃で10時間撹拌した。さらにトリメチルクロロシラン2.23 g (20.51mmol)を加え、50℃で10時間撹拌した。これを減圧濃縮により溶媒を留去した後、ジクロロメタン(40mL)に溶解し、メタノール-水(1:1 v/v)で洗浄した。減圧濃縮により溶媒を留去し、目的生成物を得た。
【００８６】
実施例７
カリックスアレーンを化学結合させたトリエトキシシランの合成
アルゴン雰囲気下、(7a) 1.00g (1.30mmol)とトリフェニルホスフィンロジウムクロライド0.025 g (0.027mmol)、トリエトキシシラン5.91mL(32.03mmol)を混合し、凍結脱気法により脱気した。これに乾燥トルエン(40mL)を加え、90℃で6時間撹拌した。放冷後、減圧濃縮により溶媒を留去し、フラッシュクロマトグラフィー (silica gel 80 g, クロロホルム/ヘキサン 6:4)により精製し、目的化合物を0.65g 得た。
【００８７】
実施例８
実施例５で得られたカリックスアレーンが化学結合したポリシロキサンを、フューズドシリカキャピラリー(内径0.25 mm×8.7 m)の内表面にコーティングしてカラムを作製した。その結果、従来のカラムでは比較的分離が難しい、ベンゼン誘導体のメタ異性体とパラ異性体との分離において改善が認められた。
【００８８】
【発明の効果】
本発明のカリックスアレーン化合物（１）は、包接能及び分離能に優れており、クロマトグラフィー用カラムとして有用である。特にカリックスアレーン骨格の包接場である上縁部の向かい合わせの位置に平面構造を有する芳香族炭化水素基があることにより、分子全体が試料分子を包接し易くなっている。また、固定相の骨格となるポリシロキサン側鎖と結合していることから、カラムブリードを防ぐ効果も有する。本発明のクロマトグラフィー固定相は、カリックスアレーン化合物（１）の優れた分離能により、エナンチオマーの分離に対しても有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to calixarene compounds useful as materials for various chromatographic stationary phases.
[0002]
[Prior art]
Chromatography, which was founded by Tswett in 1903, is now firmly established as an excellent method for separation and analysis. However, the separation principle using the bulk property of a polymer as a stationary phase has come to a limit, so that clathrate compounds that have been widely applied in various fields have begun to attract attention around 1980.
[0003]
In particular, in 1980, examples of the application of crown ether, a first generation clathrate compound, to a liquid chromatography stationary phase were reported one after another. Since crown ethers form stable complexes with various metal cations, we succeeded in separating metal ions by matching the cation size with the ring size of crown ether. Furthermore, in the early 1990s, it began to be used as a column stationary phase for gas chromatography, and showed a unique selectivity for separation into polar compounds and aromatic hydrocarbons, particularly positional isomers.
[0004]
In 1990, a cyclodextrin, a second generation inclusion compound, was chemically bonded to a polysiloxane skeleton, and this application was reported. Cyclodextrins are mainly used for gas chromatography. In 1993, cyclodextrin was successfully separated for the first time without derivatizing a chiral diol. In the same year, Jung et al. Achieved excellent enantiomeric resolution by replacing part of the methyl group of permethylated β-cyclodextrin with a trifluoroacetyl group. As described above, the separation analysis technique using an inclusion compound has brought a breakthrough in the field of analytical chemistry and is now widely used. However, these methods also have drawbacks. For example, crown ethers are excellent for separation based on ion-dipole interactions, that is, separation of ions in liquid chromatography, but are not suitable for other separations. In addition, cyclodextrin shows excellent selectivity for various compounds compared to crown ether, but problems remain in its heat resistance and difficulty in chemical modification.
[0005]
In order to overcome these problems, the third generation inclusion compound, calixarene, has recently attracted attention. Calixarene can be expected to have superior resolution for various compounds than cyclodextrin because of its heat resistance, its various interactions, and the ease of chemical modification. In 1995, Munk et al. Reported a packed column in which p-tert-butylcalix [4] arene was physically adsorbed on a gas chromatography packing. However, this resulted in stationary phase bleeding due to physical adsorption, and the resolution was low. Therefore, in 1996, an improved column was reported in which the inner surface of a capillary column coated with polysiloxane was further coated with calixarene. This also did not show the expected resolution due to the difficulty of column coating and the high melting point of calixarene. Thus, in 1999, Wu et al. Succeeded in dramatically improving resolution by directly bonding a calixarene having a tert-butyl group to a polysiloxane skeleton (Chromatographia, 1999, 50, 82; J. Chromatogra. A 1999). , 840, 225). Furthermore, it exhibits thermal stability at a high temperature of 320 ° C., and is the most successful example of a column using calixarene.
[0006]
[Problems to be solved by the invention]
However, the separation ability of these conventional calixarene compounds is not yet satisfactory, and the development of a calixarene compound useful as a chromatographic stationary phase that is further excellent in inclusion ability and separation ability is desired.
[0007]
[Means for Solving the Problems]
Therefore, the present inventor has studied to solve the above problems, and the Wu et al. Calixarene compound has a bulky substituent tert-butyl group at the upper edge of the calixarene serving as an inclusion field. However, the inclusion ability is not fully utilized, whereas an aromatic hydrocarbon group having a planar structure is introduced at the upper edge of the calixarene, and the polysiloxane side chain or the lower chain via an alkyl chain The inventors have found that a novel compound bonded to a trialkoxysilyl group is excellent in inclusion and separation ability and useful as a chromatographic stationary phase, and completed the present invention.
[0008]
That is, the present invention provides the following general formula (1)
[0009]
[Chemical formula 2]

[0010]
[Wherein R¹And R²Is at least one CH₂= CH (CH₂)_m-, Trialkoxysilyl- (CH₂)_{m + 2}-Or polysiloxane- (CH₂)_{m + 2}-(Wherein m represents a number of 1 to 8), and the remainder represents an alkyl group having 3 or more carbon atoms;
Ar represents an aromatic hydrocarbon group having 6 to 10 carbon atoms which may have a substituent;
n represents a number from 2 to 4]
The calixarene compound represented by these is provided.
[0011]
In the general formula (1), the present invention relates to R¹And R²At least one of trialkoxysilyl- (CH₂)_{m + 2}-Or polysiloxane- (CH₂)_{m + 2}A chromatographic stationary phase obtained by reacting or coating a compound which is-.
[0012]
DETAILED DESCRIPTION OF THE INVENTION
In general formula (1), R¹And R²At least one of CH₂= CH (CH₂)_m-, Trialkoxysilyl- (CH₂)_{m + 2}-Or polysiloxane- (CH₂)_{m + 2}-That's it. Where R¹And R²At least one of CH₂= CH (CH₂)_mA compound in which the group is trialkoxysilyl- (CH₂)_{m + 2}-Or polysiloxane- (CH₂)_{m + 2}It is an intermediate of a compound that is-. Here, m represents a number of 1 to 8, preferably 3 to 8, and particularly preferably 3 to 6. Trialkoxysilyl- (CH₂)_{m + 2}-As the bird (C₁-C₆Alkoxy) silyl- (CH₂)_{m + 2}-Is preferred, specifically, trimethylsilyl- (CH₂)_{m + 2}-, Triethylsilyl- (CH₂)_{m + 2}-Etc. Polysiloxane- (CH₂)_{m + 2}-As dimethylpolysiloxane- (CH₂)_{m + 2}-Is preferred. Polysiloxane- (CH₂)_{m + 2}-,-(CH₂)_{m + 2}The-group is preferably bonded as a side chain of the polysiloxane, for example, more preferably bonded as shown in the following formula (2).
[0013]
[Chemical Formula 3]

[0014]
[Where l¹And l^ThreeIndicates a number from 1 to 20, l²Indicates a number from 1 to 4, l^FourRepresents a number from 10 to 2000, m is the same as above]
[0015]
R¹And R²The remaining group is an alkyl group having 3 or more carbon atoms, preferably an alkyl group having 3 to 12 carbon atoms, and more preferably an alkyl group having 3 to 8 carbon atoms. Specific examples include n-propyl group, isopropyl group, n-butyl group, isobutyl group, n-pentyl group, n-hexyl group and the like.
[0016]
R¹And R²Of which at least one is trialkoxysilyl- (CH₂)_{m + 2}-Or polysiloxane- (CH₂)_{m + 2}In the case of a compound that is-, the trialkoxysilyl- (CH₂)_{m + 2}-Group or polysiloxane- (CH₂)_{m + 2}-Although 1-2n group can be substituted, 1-n is more preferable from a viewpoint which makes it easy to catch a molecule | numerator when using as a chromatography stationary phase.
[0017]
Ar represents an aromatic hydrocarbon group having 6 to 10 carbon atoms which may have a substituent, and as the aromatic hydrocarbon group, a phenyl group and a naphthyl group are preferable, and a phenyl group is particularly preferable. Examples of the group that can be substituted for the aromatic hydrocarbon group include an alkyl group, a halogenoalkyl group, an alkoxy group, a cyano group, a nitro group, an amino group, a dialkylamino group, a sulfonyloxy group, and one or more asymmetric carbon atoms. The functional group which has is mentioned. Here, as an alkyl group, a C1-C20, especially 1-12 alkyl group is mentioned, for example, a methyl group, an ethyl group, isopropyl group, n-propyl group, n-butyl group, hexyl group, decyl group. , Dodecyl group, tetradecyl group, hexadecyl group, octadecyl group and the like. As an alkoxy group, a C1-C8 alkoxy group is mentioned, For example, a methoxy group, an ethoxy group, an isopropoxy group etc. are mentioned. Examples of the halogenoalkyl group include an alkyl group having 1 to 6 carbon atoms in which 1 to 3 halogen atoms are substituted, and examples thereof include a trifluoromethyl group and a 1,1,1-trichloroethyl group. As the dialkylamino group, di (C₁-C₆Alkyl) amino group, and examples thereof include dimethylamino group and diethylamino group.
[0018]
When Ar is an aromatic hydrocarbon group substituted with a functional group having one or more asymmetric carbon atoms, the compound of the present invention is particularly useful as a stationary phase for separation of enantiomers. Here, examples of the functional group having one or more asymmetric carbon atoms include groups represented by the following formulas (3) to (8).
[0019]
[Formula 4]

[0020]
[Wherein R^ThreeRepresents a phenyl group, a naphthyl group, an isopropyl group or a tert-butyl group, p represents a number of 0 or 1, and R^FourRepresents an isopropyl group, a tert-butyl group or a benzyl group.^FiveRepresents a hydrogen atom, and R^FourAnd R^FiveTogether may form a trimethylene group. * Indicates an asymmetric carbon atom]
[0021]
Although n shows the number of 2-4, 2 or 3 is preferable and 2 is especially preferable.
[0022]
The calixarene compound of the present invention can be produced, for example, according to the following reaction formula.
[0023]
[Chemical formula 5]

[0024]
[Chemical 6]

[0025]
[Wherein R^1aAnd R^2aAt least one of them represents a hydrogen atom, and the remainder represents an alkyl group having 3 or more carbon atoms, and R^1bAnd R^2bAt least one of CH₂= CH (CH₂)_m-The remainder represents an alkyl group having 3 or more carbon atoms, and R^1cAnd R^2cAt least one of the trialkoxysilyl- (CH₂)_{m + 2}-Or polysiloxane- (CH₂)_{m + 2}And the remainder represents an alkyl group having 3 or more carbon atoms, and n and m are the same as above]
[0026]
That is, by reacting p-tert-butylphenol (9) with formaldehyde in the presence of alkali, calixarene compound (10) is obtained, and this is reacted with aluminum chloride and phenol to remove the tert-butyl group. (11) is obtained, and a part of the hydroxyl group of phenol is O-alkylated using an alkyl halide to obtain a compound (12), which is brominated to obtain a compound (13). Alkenylation to compound (14), followed by dihydroxyboranylation of the bromo group followed by allylation gives compound (1A). By subjecting the obtained compound (1A) to hydrosilylation in which hydrogenpolysiloxane or trialkoxysilane is reacted, compound (1S₁) Is obtained.
[0027]
Here, the conversion reaction from p-tert-butylphenol (9) to calixarene (10) is carried out with respect to compound (9) in the presence of an alkali such as sodium hydroxide or potassium hydroxide, or in the presence of an acid catalyst. It is carried out by heating and stirring together with 1.2 times mole or more of formaldehyde or paraformaldehyde, and then heating and refluxing in a solvent such as diphenyl ether or xylene. In the tert-butyl group elimination reaction of calixarene (10), calixarene (10), aluminum chloride and phenol may be stirred at room temperature in an aromatic hydrocarbon solvent such as toluene and benzene. In the alkylation reaction of compound (11), compound (11) and an alkyl halide having 3 or more carbon atoms such as propyl bromide are heated to reflux in a solvent such as acetonitrile or dimethylformamide in the presence of an alkali such as potassium carbonate or sodium hydride. do it. The bromination reaction of the compound (12) may be performed at room temperature in a solvent such as methyl ethyl ketone and toluene using a brominating agent such as N-bromosuccinimide. The alkenylation reaction of compound (13) may be performed at room temperature in a solvent such as dimethylformamide or toluene in the presence of a strong alkali such as sodium hydride using an alkenyl halide such as allyl bromide. Compound (14) is compound (15) by reacting butyllithium, trimethoxyborane, and then hydrochloric acid, and this is combined with an aryl iodide compound such as 3-iodomethylbenzene to the presence of a triphenylphosphine-palladium complex. The compound (1A) is obtained by heating to reflux in benzene and sodium carbonate.
In the hydrosilylation reaction of compound (1A), compound (1A) is reacted with hydrogenpolysiloxane or trialkoxysilane in a solvent such as toluene or tetrahydrofuran in the presence of chloroplatinic acid, chlorotris (triphenylphosphine) rhodium or the like. Is done.
[0028]
R in general formula (1)¹And R²Only one of them is CH₂= CH (CH₂)_m-, Polysiloxane- (CH₂)_{m + 2}-Or trialkoxysilyl- (CH₂)_{m + 2}The compound which is-can be produced, for example, according to the following reaction formula (illustrated when n in general formula (1) is 2).
[0029]
[Chemical 7]

[0030]
[Chemical 8]

[0031]
[Wherein Bn represents a benzyl group, R⁶Represents an alkyl group having 3 or more carbon atoms, and R⁷Represents a polysiloxane residue or a trialkoxysilyl group, and m and Ar are the same as above]
[0032]
Namely, the calixarene (10) is benzylated to obtain a monobenzyl compound (17), the distal position is alkylated to obtain a compound (18), and brominated to obtain a compound (19), and the remaining hydroxyl group is alkylated. Compound (20). Next, after debenzylation to compound (21), alkenylation to compound (22), followed by dihydroxyboranylation and arylation, compound (1B) is obtained. Compound (1B) is subjected to a hydrosilylation reaction to give compound (1S₂)
[0033]
The benzylation reaction of the compound (16) is carried out by using a benzyl halide such as benzyl bromide and heating to reflux in a solvent such as acetone or acetonitrile in the presence of an alkali such as potassium carbonate or cesium fluoride. The alkylation reaction of compound (17) is carried out in the same manner as the alkylation reaction of compound (11). The bromination of compound (18) is performed in the same manner as the bromination of compound (12). The alkylation reaction of the compound (19) may be the same as the alkylation of the compound (11), but is preferably performed using propyl bromide or the like in the presence of a strong alkali such as sodium hydride. The debenzylation reaction of compound (20) can be carried out by reacting compound (20) with trimethylsilyl iodide in a solvent such as chloroform. Alkenylation of compound (21) and further from compound (22) to compound (1S₂The reaction up to) can be carried out in the same manner as described above.
[0034]
Of the compound (1) of the present invention thus obtained, R¹And R²At least one of the polysiloxane- (CH₂)_{m + 2}-Or trialkoxysilyl- (CH₂)_{m + 2}Compounds that are-are useful as various chromatographic stationary phases. Here, the chromatography includes any of gas chromatography, liquid chromatography, supercritical fluid chromatography, thin layer chromatography, capillary gas chromatography, electrochromatography, and capillary electrophoresis.
[0035]
The column for gas chromatography obtained by reacting or coating the compound (1) of the present invention is, for example, R among the compounds (1) of the present invention.¹And R²At least one of the polysiloxane- (CH₂)_{m + 2}Dissolve the compound-in a solvent such as pentane, acetone, methylene chloride, etc., and add chromosolve W or Celite 545, which are typical commercially available diatomaceous earth carriers, and then remove the solvent by reducing the pressure. The stationary phase is coated on the surface of the carrier in the range of 0.1 to 30% by weight. This can be obtained by filling a pipe column such as glass or stainless steel. The column for capillary gas chromatography is, for example, R of the present compound (1).¹And R²At least one of the polysiloxane- (CH₂)_{m + 2}-Is dissolved in a solvent such as pentane, acetone, methylene chloride, etc., and this is applied to a commercially available silica capillary column (hollow pipe with an inner diameter of about 0.1 to 1 mm) by static or dynamic method. Coated with N₂It can be obtained by drying well through gas. The column for liquid chromatography is, for example, R of the present compound (1).¹And R²At least one of trialkoxysilyl- (CH₂)_{m + 2}-Is dissolved in a solvent such as toluene, heptane, etc., and 5 to 10 μl of spherical silica gel previously treated with acid is added thereto, heated to reflux, filtered and dried, and this is commercially available stainless steel, glass. It can be obtained by packing in a column.
[0036]
Chromatography using the chromatography column thus obtained may be performed according to procedures such as ordinary gas chromatography and liquid chromatography.
[0037]
【Example】
EXAMPLES Next, although an Example is given and this invention is demonstrated further in detail, this invention is not limited to these at all.
[0038]
Example 1
Synthesis of 5,17-bis (3-substituted phenyl) -25,27-dipropyloxy-26,28-dialkenyloxycalix [4] arene
5,11,17,23-Tetra-tert-butyl-25,26,27,28-tetrahydroxycalix [4] arene (1)
In a three-necked flask equipped with a nitrogen gas inlet tube and mechanical stirrer, weigh 4-tert-butylphenol 100 g (0.666 mol), sodium hydroxide 1.20 g (30.0 mmol), and 37% formaldehyde aqueous solution (62 mL). The mixture was stirred with a mechanical stirrer at 120 ° C. for about 2 hours until it became yellowish. After cooling to room temperature, a Dean-Stark trap equipped with a cooling tube was connected. Diphenyl ether (600 mL) was added thereto, and the mixture was stirred at 120 ° C. for 1 hour while blowing nitrogen gas to the liquid surface, and further refluxed for 2 hours. After allowing to cool, ethyl acetate (800 mL) was added, and the resulting precipitate was collected by suction filtration to obtain 94.7 g of (1) (Fw 648.92) as a white solid. Yield 88%; R_f = 0.46 (CHCl_Three/ hexane3: 4);¹H NMR (89.5 MHz, CDCl_Three) δ 10.38 (br s, 4H), 7.11 (s, 8H), 4.17 (br s, 4H), 3.57 (br s, 4H), 1.21 (s, 36H); IR (KBr, cm^-1) 3130 (OH).
[0039]
25,26,27,28-Tetrahydroxycalix [4] arene (2)
Under a nitrogen atmosphere, 52.6 g (0.394 mol) of aluminum chloride, 34.8 g (0.370 mol) of phenol (1) 50 g (77.1 mmol) and toluene (400 mL) were mixed and stirred at room temperature for 2 hours. After completion of the reaction, water (500 mL) was added and stirred for 30 minutes, and then the organic phase was separated. The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was removed by concentration under reduced pressure, and recrystallization (chloroform / methanol) As a result, 30.2 g of (2) (Fw 424.47) was obtained as a white solid. Yield 92%; mp 313-314 ° C; R_f= 0.56 (hexane / chloroform 1: 2);¹H NMR (400 MHz, CDCl_Three) δ 10.21 (s, 4H), 7.04 (d, 8H), 6.73 (t, 4H), 4.4-3.3 (br d, 8H);¹³C NMR (101 MHz, CDCl_Three) δ148.74, 128.96, 128.21, 122.23, 31.68; IR (KBr, cm^-1) 3240 (OH).
[0040]
25,27-dipropyloxy-26,28-dihydroxycalix [4] arene (3)
(2) 10.0 g (23.6 mmol), potassium carbonate 3.59 g (25.96 mmol), and acetonitrile (400 mL) were mixed, and propyl bromide 5.83 g (48.2 mmol) was added thereto and refluxed for 15 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, chloroform (100 mL) was added, and this was washed in turn with water (100 mL), 1N aqueous hydrochloric acid (2 × 50 mL), and saturated brine (100 mL). . This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 9.23 g of (3) (Fw 508.66) as a white solid. Yield 77%; mp 271 ° C; R_f= 0.46 (hexane / chloroform 4: 3);¹H NMR (400 MHz, CDCl_Three) δ8.30 (s, 2H), 7.04-6.62 (m, 12H), 4.32 (d, J = 13.0Hz, 4H), 3.94 (t, J = 6.28Hz, 4H), 3.36 (d, J = 13.0 Hz, 4H), 2.06-2.01 (m, 4H), 1.29 (t, J = 7.36Hz, 6H);¹³C NMR (101MHz, CDCl_Three) δ153.35, 151.82, 134.19, 128.87, 128.41, 128.10, 125.26, 118.91, 78.25, 31.41,
10.90; IR (KBr, cm^-1) 3302 (OH).
[0041]
5,17-Dibromo-25,27-dipropyloxy-26,28-dihydroxycalix [4] arene (4)
(3) 10.0 g (19.7 mmol) and N-bromosuccinimide 7.00 g (39.3 mmol) were dissolved in 2-butanone (300 mL) and stirred at room temperature for 24 hours. After completion of the reaction, the solvent was distilled off by concentration under reduced pressure, and a small amount of hot methanol was added thereto to completely dissolve N-bromosuccinimide. This was filtered to obtain 11.6 g of (4) (Fw 666.45) as a white solid. Yield 98%; mp> 300 ° C;¹H NMR (CDCl_Three, 400MHz) δ8.39 (s, 2H), 7.3-6.7 (m, 10H), 4.25 (d, J = 12.9 Hz, 4H), 3.95 (t, J = 6.20 Hz, 4H), 3.33 (d, J = 13.0Hz, 4H), 2.2-2.0 (m, 4H), 1.4-1.1 (m, 6H); IR (KBr, cm^-1) 3200 (OH).
[0042]
5,17-Dibromo-25,27-dipropyloxy-26,28-diallyloxycalix [4] arene (5a)
(4) 10.0 g (15.0 mmol) was dissolved in N, N-dimethylformamide (200 mL), 60% sodium hydride-paraffin 3.60 g (90 mmol) was added thereto, and the mixture was stirred at room temperature for 15 minutes. To this was added 9.05 g (75 mmol) of 3-bromopropene, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid aqueous solution (150 mL) was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 10.4 g of white solid (5a) (Fw 746.58). Yield 93%; mp 216? C;¹H NMR (CDCl_Three) 7.11-6.28 (m, 12H), 5.15-5.11 (m, 4H), 4.58-4.56 (m, 4H), 4.37 (d, J = 13.44Hz, 4H), 3.75-3.69 (m, 4H) , 3.09 (d, J = 13.48Hz, 4H), 1.90-1.85 (m, 4H), 1.07-1.01 (m, 6H).
[0043]
5,17-Dibromo-25,27-dipropyloxy-26,28-bis (4-pentenyloxy) calix [4] arene (5b)
(4) 10.0 g (15.0 mmol) was dissolved in N, N-dimethylformamide (200 mL), 60% sodium hydride-paraffin 3.60 g (90 mmol) was added thereto, and the mixture was stirred at room temperature for 15 minutes. 5-Bromo-1-pentene (11.2 g, 75.0 mmol) was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid aqueous solution (150 mL) was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then recrystallization (chloroform / methanol) gave 8.8 g of white solid (5b) (Fw 778.66). Yield 75%; mp 165? C;¹H NMR (CDCl_Three) δ6.82-6.44 (m, 10H), 5.85-5.83 (m, 2H), 5.08-4.98 (m, 4H), 4.38 (d, J = 13.36Hz, 4H), 3.90-3.79 (m, 8H) , 3.11 (d, J = 13.40Hz, 4H), 2.18-2.16 (m, 4H), 1.99-1.87 (m, 8H), 1.00-0.93 (m, 6H).
[0044]
25,27-Dipropyloxy-26,28-diallyloxycalix [4] arene-5,17-diboronic acid (6a)
Under an argon atmosphere, 2.00 g (2.58 mmol) of (5a) was dissolved in dry tetrahydrofuran (40 mL) and cooled to -78 ° C. To this was added 5.17 mL (7.74 mmol) of 1.5M n-butyllithium-n-hexane solution, and the mixture was stirred at -78 ° C for 30 minutes. To this was added 1.07 g (10.32 mmol) of trimethoxyborane, and the mixture was stirred at −78 ° C. for 1 hour and at room temperature for 2 hours, and then 2N aqueous hydrochloric acid (40 mL) cooled with ice was added. This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (20 mL) was added. The solution of (6a) (Fw 608.53) was used as it was for the next reaction.
[0045]
25,27-Dipropyloxy-26,28-bis (4-pentenyloxy) calix [4] arene-5,17-diboronic acid (6b)
Under an argon atmosphere, 2.00 g (2.57 mmol) of (5b) was dissolved in dry tetrahydrofuran (40 mL) and cooled to -78 ° C. To this, 5.14 mL (7.71 mmol) of 1.5M n-butyllithium-n-hexane solution was added and stirred at -78 ° C for 30 minutes. To this was added 1.06 g (10.28 mmol) of trimethoxyborane, and the mixture was stirred at -78 ° C for 1 hour and at room temperature for 2 hours, and then 2N hydrochloric acid aqueous solution (40 mL) cooled with ice was added. This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (20 mL) was added. The solution of (6b) (Fw 731.52) was used as it was for the next reaction.
[0046]
5,17-bis (3-methylphenyl) -25,27-dipropyloxy-26,28-diallyloxycalix [4] arene (7a)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.40 g (6.4 mmol) of 3-iodotoluene are dissolved in benzene (30 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Furthermore, the above-mentioned solution containing 1.57 g (2.58 mmol) of (6a) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 4) to obtain a white solid (7a) (Fw 769.03)・ 0.25 CHCl_Three0.94 g was obtained. Yield 61%; R_f= 0.50 (hexane / chloroform 1: 1);¹H NMR (400 MHz, CDCl_Three) δ7.41-7.09 (m, 12H), 6.5-6.4 (m, 2H), 6.3-6.2 (m, 6H), 5.2-5.1 (m, 4H), 4.68 (d, 4H), 4.48 (d, J = 13.3Hz, 4H), 3.74 (t, J = 6.8Hz, 4H), 3.22 d, J = 13.4Hz, 4H), 2.4 (s, 6H), 2.0-1.8 (m, 4H), 1.11 (t , J = 7.4Hz, 6H);¹³C NMR (100MHz, CDCl_Three) δ156.70, 155.34, 141.14, 138.15, 137.47, 136.52, 133.08, 128.55, 127.70, 127.59, 127.37, 124.03, 122.18, 116.58, 76.70, 75.75, 31.41, 23.58, 21.60, 10.89 .; Anal. Calcd for C₅₄H₅₆O_Four・ 0.25CHCl_Three: C, 81.56; H, 7.10. Found: C, 81.40;
H, 7.13.
[0047]
5,17-bis (3-methylphenyl) -25,27-dipropyloxy-26,28-bis (4-pentenyloxy) calix [4] arene (7b)
Under an argon atmosphere, 0.092 g (0.079 mmol) of tetrakis (triphenylphosphine) palladium and 1.39 g (6.38 mmol) of 3-iodotoluene are dissolved in benzene (30 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Further, the above solution containing 1.88 g (2.57 mmol) of (6b) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 4) to obtain a white solid (7b) (Fw 801.12) 1.24 g was obtained. Yield 60%; mp 63 ° C; R_f= 0.64 (hexane / chloroform 1: 1);¹H NMR (400 MHz, CDCl_Three) δ7.31-6.32 (m, 18H), 5.90-5.84 (m, 2H), 5.08-4.98 (m, 4H), 4.49 (d, J = 13.24Hz, 4H), 4.07 (t, J = 7.8Hz , 4H), 3.76 (t, J = 7.0Hz, 4H), 3.22 (d, J = 13.31Hz, 4H), 2.37 (s, 6H), 2.13-1.90 (m, 12H), 1.09 (t, J = 7.4Hz, 6H);¹³C NMR (100MHz, CDCl_Three) 157.04, 155.53, 141.13, 138.33, 138.02, 136.55, 134.88, 133.56, 128.44, 127.80, 127.62, 127.32, 123.95, 122.19, 114.96, 77.00, 74.57, 31.18, 30.43, 29.25, 23.53, 21.57, 10.84 .; Anal. Calcd for C₅₆H₆₄O_Four: C, 83.96; H, 8.05. Found: C, 84.16; H, 7.99.
[0048]
5,17-Bis (3-trifluoromethylphenyl) -25,27-dipropyloxy-26,28-diallyloxycalix [4] arene (7c)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.82 g (6.7 mmol) of 3-iodobenzotrifluoride were dissolved in 2-propanol (30 mL), and 2.4 g of potassium carbonate (17.4 mmol) and water (10 mL) were added. Further, the above solution containing 1.57 g (2.58 mmol) of (6a) was added and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 5) to obtain a white solid (7c) (Fw 876.98) 1.36 g was obtained. Yield 58%; mp 237 ° C; R_f= 0.55 (hexane / chloroform 1: 1);¹H NMR (400 MHz, CDCl_Three) δ 7.79-7.22 (m, 12H), 6.5-6.4 (m, 2H), 6.4-6.3 (m, 6H), 5.2-5.1 (m, 4H), 4.68 (d, 4H), 4.48 (d, J = 13.2Hz, 4H), 3.78 (t, J = 7.0Hz, 4H), 3.24 (d, J = 13.4Hz, 4H), 2.0-1.9 (m, 4H), 1.11 (t, J = 7.4Hz, 6H);¹³C NMR (100 MHz, CDCl_Three) 157.13, 155.62, 141.85, 137.57, 136.01, 133.53, 133.30, 131.38, 131.06, 130.74, 130.42, 130.06, 128.99, 127.77, 127.28, 125.67, 123.54, 123.50, 123.22, 123.18, 122.97, 122.29, 117.00, 8770 , 31.39, 23.52, 10.79; IR (KBr, cm^-1) 1341 (CF_Three); Anal. Calcd for C₅₄H₅₀O_FourF₆: C, 73.96; H, 5.75. Found: C, 73.81; H, 5.86.
[0049]
5,17-bis (3-trifluoromethylphenyl) -25,27-dipropyloxy-26,28-bis (4-pentenyl) oxycalix [4] arene (7d)
Under argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.81 g (6.67 mmol) of 3-iodobenzotrifluoride were dissolved in 2-propanol (30 mL), and 2.4 g of potassium carbonate (17.4 mmol) and water (10 mL) were added. Further, the above solution containing 1.88 g (2.57 mmol) of (6b) was added and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 5) to obtain a white solid (7d) (Fw 852.07) 1.27 g was obtained. Yield 58%; mp 60 ° C; R_f= 0.75 (hexane / chloroform 1: 1);¹H NMR (400 MHz, CDCl_Three) δ7.51-6.58 (m, 18H), 5.89-5.85 (m, 2H), 5.09-5.00 (m, 4H), 4.5 (d, J = 13.3Hz, 4H), 4.00-3.86 (m, 8H) , 3.24 (d, J = 13.4Hz, 4H), 2.24-2.18 (m, 4H), 2.08-1.94 (m, 8H), 1.06 (t, J = 7.1Hz, 6H);¹³C NMR (100 MHz, CDCl_Three) δ156.97, 156.27, 141.62, 138.13, 135.95, 134.51, 133.29, 130.71, 130.39, 130.07, 129.66, 128.74, 128.28, 126.92, 125.59, 123.17, 123.14, 122.97, 122.94, 122.30, 114.89, 76.90, 74.72, 31. , 30.45, 29.34, 23.37, 10.64; IR (KBr, cm^-1) 1342 (CF_Three); Anal. Calcd for C₅₆H₅₈O_FourF₆: C, 73.94; H, 6.43. Found: C, 74.85; H, 6.48.
[0050]
Example 2
Synthesis of 5,17-bis (3-substituted phenyl) -25,27-dialkenyloxy-26,28-dipropyloxycalix [4] arene
25,27-diallyloxy-26,28-dihydroxycalix [4] arene (8a)
(2) 10.0 g (23.6 mmol), potassium carbonate 3.59 g (26.0 mmol), and acetonitrile (400 mL) were mixed, and allyl bromide 5.83 g (48.2 mmol) was added thereto, followed by refluxing for 15 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, chloroform (100 mL) was added, and this was washed with water (100 mL), 1N aqueous hydrochloric acid (2 × 50 mL), and saturated brine (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 8.45 g of (8a) (Fw 504.23) as a white solid. Yield 71%; R_f= 0.14 (hexane / chloroform 1: 1); mp 210-212 ° C (lit. 187-188.5 ° C);¹H NMR (400 MHz, CDCl_Three) δ7.90 (s, 2H), 7.00-6.15 (m, 14H), 5.73-5.22 (m, 4H), 4.48 (m, 4H), 4.25 (d, J = 13.0 Hz, 4H), 3.31 (d , J = 13.0Hz, 4H);¹³C NMR (101 MHz, CDCl_Three) δ153.23, 151.70, 133.37, 132.75, 128.94, 128.44, 128.08, 125.41, 119.02, 117.92, 76.85, 31.42.IR (KBr, cm^-1) 3328 (OH)
[0051]
25,27-bis (4-pentenyloxy) -26,28-dihydroxycalix [4] arene (8b)
(2) 10.0 g (23.6 mmol), potassium carbonate 3.59 g (26.0 mmol), and acetonitrile (400 mL) were mixed. To this, 17.59 g (118 mmol) of 5-bromo-1-pentene was added and refluxed for 15 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, chloroform (100 mL) was added, and this was washed with water (100 mL), 1N aqueous hydrochloric acid (2 × 50 mL), and saturated brine (100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 11.0 g of (8b) (Fw 560.73) as a white solid. Yield 85%; R_f= 0.17 (hexane / chloroform 1: 1); mp 178 ° C;¹H NMR (400 MHz, CDCl_Three) δ8.20 (s, 2H), 7.06-6.63 (m, 12H), 5.95-5.93 (m, 2H), 5.21-5.04 (m, 4H), 4.31 (d, J = 13.0Hz, 4H), 4.02 -3.99 (m, 4H), 3.37 (d, J = 13.0Hz, 4H), 2.56-2.51 (m, 4H), 2.19-2.13 (m, 4H);¹³C NMR (100MHz, CDCl_Three) 153.33, 151.86, 137.88, 133.37, 128.91, 128.45, 128.10, 125.32, 118.97, 115.97, 75.75, 31.44, 30.08, 29.24. Anal. Calcd for C₃₈H₄₀O_Four: C, 81.40; H, 7.19. Found: C, 80.95, H, 7.18.IR (KBr, cm^-1) 3299 (OH)
[0052]
5,17-Dibromo-25,27-diallyloxy-26,28-dihydroxycalix [4] arene (9a)
(8b) 10.0 g (19.8 mmol) and N-bromosuccinimide 7.04 g (39.6 mmol) were dissolved in 2-butanone (300 mL), and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, and a small amount of hot methanol was added thereto to completely dissolve N-bromosuccinimide. This was filtered to obtain 13.1 g of white solid (9a) (Fw 664.43). Yield 99%; mp 247 ° C;¹H NMR (400 MH_Z, CDCl_Three) δ8.10 (s, 2H), 7.01-6.76 (m, 10H), 6.24-6.23 (m, 2H), 5.79-5.41 (m, 4H), 4.52 (d, J = 10.96Hz, 4H), 4.31 -4.24 (m, 4H) .IR (KBr, cm^-13271 (OH)
[0053]
5,17-Dibromo-25,27-bis (4-pentenyloxy) -26,28-dihydroxycalix [4] arene (9b)
(8b) 10.0 g (17.8 mmol) and N-bromosuccinimide 9.52 g (53.5 mmol) were dissolved in 2-butanone (300 mL), and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure. A small amount of hot methanol was added thereto to completely dissolve N-bromosuccinimide. This was filtered to obtain 10.23 g of white solid (9b) (Fw 718.52). Yield 80%.
[0054]
5,17-Dibromo-25,27-diallyloxy-26,28-dipropyloxycalix [4] arene (10a)
(9a) 10.0 g (15.0 mmol) was dissolved in N, N-dimethylformamide (200 mL), 60% sodium hydride-paraffin (3.01 g, 75 mmol) was added thereto, and the mixture was stirred at room temperature for 15 minutes. Further, 9.30 g (75 mmol) of propyl bromide was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 150 mL of 1N hydrochloric acid aqueous solution was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 6.72 g of (10a) (Fw 746.58) as a white solid. Yield 60%; R_f= 0.62 (hexane / chloroform 1: 1); mp 153-154 ° C;¹H NMR (400MHz, CDCL_Three) δ7.23-6.87 (m, 6H), 6.46-6.16 (m, 6H), 5.14-5.11 (m, 4H), 4.60 (d, J = 13.2Hz , 4H), 4.39 (d, J = 11.2Hz, 4H), 3.71 (t, J = 10.8Hz, 4H), 3.13 (d, J = 13.2Hz, 4H), 1.93-1.88 (m, 4H), 1.50 -1.04 (m, 4H);¹³C NMR (100 MHz, CDCl_Three) δ156.90, 154.63, 136.15, 135.92, 135.78, 130.29, 128.92, 122.95, 117.00, 115.67, 77.02, 75.70, 31.29, 23.00, 10.86. Anal.Calcd for C₄₀H₄₂O_FourBr₂: C, 64.35; H, 5.67. Found: C, 64.84, H, 5.74.
[0055]
5,17-Dibromo-25,27-bis (4-pentenyloxy) -26,28-dipropyloxycalix [4] arene (10b)
(9b) 10.0 g (13.9 mmol) was dissolved in N, N-dimethylformamide (200 mL), 60% sodium hydride-paraffin 2.78 g (70 mmol) was added thereto, and the mixture was stirred at room temperature for 15 minutes. Further, 8.40 g (70 mmol) of propyl bromide was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 150 mL of 1N hydrochloric acid aqueous solution was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then recrystallization (chloroform / methanol) gave 6.28 g of (10b) (Fw 778.66) as a white solid. Yield 63%.
[0056]
25,27-diallyloxy-26,28-dipropyloxycalix [4] arene-5,17-diboronic acid (11a)
Under an argon atmosphere, 2.00 g (2.58 mmol) of (10a) was dissolved in dry tetrahydrofuran (40 mL) and cooled to -78 ° C. To this was added 5.17 mL (7.74 mmol) of 1.5M n-butyllithium-n-hexane solution, and the mixture was stirred at -78 ° C for 30 minutes. To this was added 1.07 g (10.32 mmol) of trimethoxyborane, and the mixture was stirred at −78 ° C. for 1 hour and at room temperature for 2 hours, and then 2N aqueous hydrochloric acid (40 mL) cooled with ice was added. This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (20 mL) was added. The solution of (11a) (Fw 608.53) was used as it was for the next reaction.
[0057]
25,27-bis (4-pentenyloxy) -26,28-dipropyloxycalix [4] arene-5,17-diboronic acid (11b)
Under an argon atmosphere, 2.00 g (2.57 mmol) of (10b) was dissolved in dry tetrahydrofuran (40 mL) and cooled to -78 ° C. To this, 5.14 mL (7.71 mmol) of 1.5M n-butyllithium-n-hexane solution was added and stirred at -78 ° C for 30 minutes. To this was added 1.06 g (10.28 mmol) of trimethoxyborane, and the mixture was stirred at -78 ° C for 1 hour and at room temperature for 2 hours, and then 2N hydrochloric acid aqueous solution (40 mL) cooled with ice was added. This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (20 mL) was added. The solution of (11b) (Fw 731.52) was used as it was for the next reaction.
[0058]
5,17-bis (3-methylphenyl) -25,27-diallyloxy-26,28-dipropyloxycalix [4] arene (12a)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.40 g (6.4 mmol) of 3-iodotoluene are dissolved in benzene (30 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Furthermore, the above-mentioned solution containing (11a) 1.57 g (2.58 mmol) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 4) to obtain a white solid (12a) (Fw 769.03) 1.44 g was obtained. Yield 70%; R_f= 0.48 (hexane / chloroform 1: 1); mp 65 ° C;¹H NMR (400MHz, CDCL_Three) δ7.77-6.67 (m, 18H), 6.43-6.41 (m, 2H), 5.27-5.17 (m, 4H), 4.61-4.51 (m, 4H), 4.47 (d, J = 13.2Hz , 4H), 3.86-3.83 (m, 4H), 4.39 (d, J = 11.2Hz, 4H), 3.21 (d, J = 13.2Hz, 4H), 2.16 (s, 6H), 1.98-1.91 (m, 4H), 1.98-1.91 (m, 4H), 1.06-1.01 (m, 6H);¹³C NMR (100 MHz, CDCl_Three) δ156.00, 155.85, 141.08, 137.53, 135.98, 135.66, 135.17, 134.54, 128.41, 128.05, 127.37, 126.77, 123.70, 122.48, 116.61, 77.21, 75.74, 31.36, 23.38, 21.43, 10.50. Anal. Calcd for C₄₀H₄₂O_FourBr₂: C, 64.35; H, 5.67. Found: C, 64.84, H, 5.74. Anal. Calcd for C₅₄H₅₆O_Four: C, 84.34; H, 7.34. Found: C, 83.95; H, 7.47.
[0059]
5,17-bis (3-methylphenyl) -25,27-bis (4-pentenyloxy) -26,28-dipropyloxycalix [4] arene (12b)
Under argon atmosphere, 0.092 g (0.079 mmol) of tetrakis (triphenylphosphine) palladium and 1.39 g (6.38 mmol) of 3-iodotoluene are dissolved in benzene (30 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Furthermore, the above-mentioned solution containing (11b) 1.88 g (2.57 mmol) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 120g, chloroform / hexane 1: 4) to obtain a white solid (12b) (Fw 801.12) 1.19 g was obtained. Yield 58%.
[0060]
5,17-bis (3-trifluoromethylphenyl) -25,27-diallyloxy-26,28-dipropyloxycalix [4] arene (12c)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.82 g (6.7 mmol) of 3-iodobenzotrifluoride were dissolved in 2-propanol (30 mL), and 2.4 g of potassium carbonate (17.4 mmol) and water (10 mL) were added. Furthermore, the above-mentioned solution containing (11a) 1.57 g (2.58 mmol) was added and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 5) to obtain a white solid (12b) (Fw 876.98) 1.24 g was obtained. Yield 55%; mp 138 ° C; R_f= 0.61 (hexane / chloroform 1: 1),¹H NMR (400MHz, CDCl_Three) δ7.16-6.45 (m, 20H), 5.20-5.18 (m, 4H), 4.70-4.68 (m, 4H), 4.49 (d, J = 13.3Hz, 4H), 3.77 (t, J = 7.08Hz , 4H), 3.23 (d, J = 13.4Hz, 4H), 1.99-1.92 (m, 4H), 1.11-1.04 (m, 6H);¹³C NMR (100MHz, CDCl_Three) δ156.50, 155.98, 141.38, 136.63, 136.15, 134.28, 133.36, 129.15, 128.87, 128.38, 126.30, 122.72, 122.66, 116.87, 76.69, 75.73, 31.34, 23.51, 10.74. Anal. Calcd for C₅₄H₅₀O_FourF₆: C, 73.96; H5.75. Found: C, 74.22; H, 5.91; IR (KBr, cm^-1) 1342 (CF_Three).
[0061]
5,17-bis (3-trifluoromethylphenyl) -25,27-bis (4-pentenyloxy) -26,28-dipropyloxycalix [4] arene (12d)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.82 g (6.7 mmol) of 3-iodobenzotrifluoride were dissolved in 2-propanol (30 mL), and 2.4 g of potassium carbonate (17.4 mmol) and water (10 mL) were added. Furthermore, the above-mentioned solution containing (11b) 1.57 g (2.58 mmol) was added and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 5) to obtain a white solid (12d) (Fw 852.07) 1.21 g was obtained. Yield 55%.
[0062]
Example 3
Synthesis of 5,17-bis (3-substituted phenyl) -25-alkenyloxy-26,27,28-tripropyloxycalix [4] arene
25-Benzyloxy-26,27,28-trihydroxycalix [4] arene (13)
(2) 10.0 g (23.6 mmol), potassium carbonate 1.63 g (11.8 mmol), and acetone (400 mL) were mixed, and benzyl bromide 4.84 g (28.3 mmol) was added thereto, followed by refluxing for 5 hours. After completion of the reaction, the solvent was distilled off by concentration under reduced pressure, chloroform (100 mL) was added, and this was washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 6.12 g of (13) (Fw 514.62) as a white solid. Yield 51%; mp 240 ° C; R_f= 0.13 (hexane / chloroform);¹H NMR (400 MHz, CDCl_Three) δ9.56 (s, 1H), 9.22 (s, 1H), 7.74-6.63 (m, 17H), 5.91 (s, 2H), 4.34 (d, J = 13.0Hz, 2H), 4.22 (d, J = 13.2Hz, 2H), 3.43 (d, J = 13.0Hz, 2H), 3.42 (d, J = 13.8Hz, 2H);¹³C NMR (CDCl_Three, 100MHz) δ151.25, 150.81, 149.51, 135.51, 134.35, 129.44, 129.07, 128.99, 128.98, 128.79, 128.75, 128.39, 128.34, 128.30, 126.31, 121.93, 120.87, 79.32, 31.87, 31.62 .; Anal. Calcd for C₃₅H₃₀O_Four・ 0.1CHCl_Three: C, 80.06; H, 5.76. Found: C, 80.65; H, 6.00. IR (KBr, cm^-1) 3268 (OH)
[0063]
25-Benzyloxy-26,28-dihydroxy-27-propyloxycalix [4] arene (14)
(13) 5.0 g (9.72 mmol), 1.48 g (10.7 mmol) of potassium carbonate, and acetonitrile (100 mL) were mixed, and 2.41 g (19.9 mmol) of propyl bromide was added thereto and refluxed for 15 hours. After completion of the reaction, the solvent was removed by concentration under reduced pressure, chloroform (100 mL) was added, and this was washed with water (50 mL) and saturated brine (100 mL) in this order. The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 3.90 g of (14) (Fw 556.70) as a white solid. Yield 72%; mp 233 ° C; R_f= 0.20 (hexane / chloroform);¹H NMR (89.5 MHz, CDCl_Three) δ8.14 (s, 2H), 7.80-7.37 (m, 5H), 7.06-6.62 (m, 12H), 5.06 (s, 2H), 4.37-4.27 (m, 4H), 3.72 (m, 2H) , 3.39-3.32 (m, 4H), 2.09-2.00 (m, 2H), 1.24 (t, J = 7.4Hz, 3H);¹³C NMR (100MHz, CDCl_Three) δ153.36, 151.84, 151.67, 136.78, 133.45, 133.39, 129.05, 128.92, 128.57, 128.48, 128.40, 128.07, 128.07, 128.03, 128.02, 127.50, 125.58, 125.28, 118.95, 78.36, 78.28, 31.44, 23.49, 11.03 Anal. Calcd for C₃₈H₃₆O_Four: C, 81.99; H, 6.52. Found: C, 81.77; H, 6.53; IR (KBr, cm^-1) 3336 (OH)
[0064]
5,17-Dibromo-25-benzyloxy-26,28-dihydroxy-27-propyloxycalix [4] arene (15)
(14) 5.0 g (9.00 mmol) and N-bromosuccinimide 3.52 g (19.8 mmol) were dissolved in 2-butanone (150 mL), and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the solvent was distilled off by concentration under reduced pressure, and a small amount of hot methanol was added thereto to completely dissolve N-bromosuccinimide. This was filtered to obtain 6.10 g of white solid (4a) (Fw 714.49). Yield 95%; mp> 300? C;¹H NMR (CDCl_Three, 400MHz) δ8.21 (s, 2H), 7.87-6.80 (m, 15H), 5.04 (s, 2H), 4.29-4.24 (q, 4H), 3.94-3.91 (m, 2H), 3.39-3.26 ( q, 4H), 2.07-2.00 (m, 2H), 1.23-1.20 (m, 3H); IR (KBr, cm^-1) 3247 (OH).
[0065]
5,17-Dibromo-25-benzyloxy-26,27,28-tripropyloxycalix [4] arene (16)
(15) 3.5 g (4.88 mmol) was dissolved in N, N-dimethylformamide (100 mL), 60% sodium hydride-paraffin 1.17 g (29.3 mmol) was added thereto, and the mixture was stirred at room temperature for 15 minutes. 2.95 g (24.4 mmol) of propyl bromide was added and stirred at room temperature for 5 hours. After completion of the reaction, 1N aqueous hydrochloric acid solution (100 mL) was added, extracted with chloroform (3 × 100 mL), and the combined organic phase was washed with water (2 × 50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then recrystallization (chloroform / methanol) gave (5a) (Fw 798.65) .0.1 CHCl as a white solid._Three 3.54 g was obtained. Yield 91%; R_f= 0.72 (hexane / chloroform 1: 1); mp 78 ° C;¹H NMR (CDCl_Three, 500MHz) δ7.39-6.51 (m, 15H), 4.86 (s, 2H), 4.40-4.27 (q, 4H), 3.83-3.76 (m, 6H), 3.12-3.01 (q, 4H), 1.93- 1.76 (m, 6H), 1.03-0.81 (m, 9H);¹³C NMR (CDCl_Three, 100MHz) δ156.09, 155.93, 154.88, 137.76, 137.61, 137.48, 134.10, 133.83, 130.92, 129.47, 128.58, 128.27, 128.18, 128.10, 128.03, 122.82, 122.43, 114.56, 76.81, 30.91, 22.85, 23.32, 22. , 10.47, 9.98; Anal. Calcd for C₄₄H₄₆O_FourBr₂・ 0.1CHCl_Three: C65.35; H5.73. Found: C, 65.26; H, 5.80.
[0066]
5,17-Dibromo-25-hydroxy-26,27,28-tripropyloxycalix [4] arene (17)
Under an argon atmosphere, 2.00 g (2.50 mmol) of (16) was dissolved in dry chloroform (150 mL), and 1.07 mL (7.52 mmol) of trimethylsilyl iodide was added thereto. This was stirred at room temperature for 3.5 hours. After completion of the reaction, it was diluted with water (100 mL). This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and purified by flash chromatography (silica gel 100 g, chloroform / hexane 1: 2) to obtain a white solid (17) (Fw 708.53)・ 0.1CHCl_ThreeWas obtained in 1.14 g. Yield 64%; R_f= 0.62 (hexane / chloroform 1: 1); mp 218 ° C;¹H NMR (CDCl_Three, 400MHz) δ7.29-6.48 (m, 10H), 4.63 (s, 1H), 4.37-4.30 (q, 4H), 3.82-3.69 (m, 6H), 3.29-3.17 (q, 4H), 2.24- 2.18 (m, 2H), 1.91-1.84 (m, 4H), 1.12-1.09 (m, 6H), 1.09-0.89 (m, 3H);¹³C NMR (CDCl_Three, 100MHz) δ156.62, 153.59, 153.02, 136.39, 135.39, 135.74, 134.99, 130.70, 130.50, 130.23, 129.48, 128.71, 123.67, 119.83, 116.08, 77.62, 76.63, 30.63, 30.59, 23.37, 22.33, 10.78, 9.54 ; Anal. Calcd for C₃₇H₄₀O_FourBr₂・ 0.1CHCl_Three: C, 61.85; H, 5.61. Found: C, 61.48; H, 5.57; IR (KBr, cm^-1) 3553 (OH)
[0067]
5,17-Dibromo-25-allyloxy-26,27,28-tripropyloxycalix [4] arene (18a)
(17) 1.0 g (1.41 mmol) was dissolved in 50 mL of N, N-dimethylformamide, and 0.169 g (4.23 mmol) of 60% sodium hydride-paraffin was added thereto, followed by stirring at room temperature for 15 minutes, and then 3-bromopropene. 0.85 g (7.05 mmol) was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid (30 mL) was added, extracted with chloroform (3 × 50 mL), and the combined organic phases were washed with water (2 × 100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave (18a) (Fw 748.59) as a white solid in 0.68 g. Yield 64%;¹H NMR (CDCl_Three, 400MHz) δ6.86-6.57 (m, 10H), 6.40-6.34 (m, 1H), 5.18-5.13 (m, 2H), 4.01 (d, 2H), 4.42-4.35 (m, 4H), 3.95- 3.72 (m, 6H), 3.14-3.10 (m, 4H), 1.95-1.86 (m, 6H), 1.05-0.90 (m, 9H).
[0068]
5,17-Dibromo-25- (4-pentenyloxy) -26,27,28-tripropyloxycalix [4] arene (18b)
(17) 0.7 g (0.99 mmol) was dissolved in 50 mL of N, N-dimethylformamide, and 0.12 g (2.96 mmol) of 60% sodium hydride-paraffin was added thereto, followed by stirring at room temperature for 15 minutes, and then 5-bromo- 1-Pentene 0.74 g (4.94 mmol) was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid (30 mL) was added, extracted with chloroform (3 × 50 mL), and the combined organic phases were washed with water (2 × 100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and recrystallization (chloroform / methanol) gave 0.34 g of white solid (18b) (Fw 776.65). Yield 44%;¹H NMR (CDCl_Three, 400MHz) δ6.73-6.60 (m, 10H), 5.82-5.71 (m, 1H), 5.12-4.93 (m, 2H), 4.46-4.31 (m, 4H), 3.88-3.71 (m, 8H), 3.18-3.03 (m, 4H), 2.19-1.69 (m, 10H), 1.07-0.37 (m, 9H).
[0069]
25-allyloxy-26,27,28-tripropyloxycalix [4] arene-5,17-diboronic acid (19a)
Under an argon atmosphere, 0.5 g (0.668 mmol) of (18a) was dissolved in dry tetrahydrofuran (10 mL) and cooled to -78 ° C. To this was added 1.26 mL (2.00 mmol) of 1.5M n-butyllithium-n-hexane solution, and the mixture was stirred at -78 ° C for 30 minutes. Further, 0.28 g (2.67 mmol) of trimethoxyborane was added, and the mixture was stirred at −78 ° C. for 1 hour and at room temperature for 2 hours, and then 2N hydrochloric acid aqueous solution (10 mL) cooled with ice was added. This was extracted with chloroform (2 × 50 mL) and the combined organic phases were washed with water (50 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (10 mL) was added. The solution of (19a) (Fw 678.43) was used as it was for the next reaction.
[0070]
25- (4-Pentenyloxy) -26,27,28-tripropyloxycalix [4] arene-5,17-diboronic acid (19b)
Under an argon atmosphere, 0.5 g (0.644 mmol) of (18b) was dissolved in dry tetrahydrofuran (10 mL) and cooled to -78 ° C. To this was added 1.29 mL (1.93 mmol) of 1.5M n-butyllithium-n-hexane solution, and the mixture was stirred at -78 ° C for 30 minutes. Further, 0.27 g (2.67 mmol) of trimethoxyborane was added, and the mixture was stirred at −78 ° C. for 1 hour and at room temperature for 2 hours, and then 2N hydrochloric acid aqueous solution (10 mL) cooled with ice was added. This was extracted with chloroform (2 × 50 mL) and the combined organic phases were washed with water (50 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (5 mL) was added. The solution of (19b) (Fw 706.49) was used as it was for the next reaction.
[0071]
5,17-bis (3-methylphenyl) -25-allyloxy-26,27,28-tripropyloxycalix [4] arene (20a)
Under an argon atmosphere, 0.022 g (0.019 mmol) of tetrakis (triphenylphosphine) palladium and 0.35 g (1.62 mmol) of 3-iodotoluene are dissolved in benzene (10 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Further, the above solution containing (19a) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 10 mL), and the organic phase was washed with water (10 mL). The organic phase was dehydrated with anhydrous magnesium sulfate and the solvent was removed by concentration under reduced pressure. The residue was purified by flash chromatography (chloroform / hexane 1: 4) to obtain 0.31 g of white solid (20a) (Fw 771.05). It was. Yield 62%.
[0072]
5,17-bis (3-methylphenyl) -25- (4-pentenyloxy) -26,27,28-tripropyloxycalix [4] arene (20b)
Under an argon atmosphere, 0.022 g (0.019 mmol) of tetrakis (triphenylphosphine) palladium and 0.35 g (1.62 mmol) of 3-iodotoluene are dissolved in benzene (10 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Further, the above solution containing 0.45 g (0.64 mmol) of (19b) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 10 mL), and the organic phase was washed with water (10 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, and the solvent was distilled off by concentration under reduced pressure, followed by purification by flash chromatography (chloroform / hexane 1: 4) to obtain 0.30 g of white solid (20b) (Fw 799.10). It was. Yield 59%.
[0073]
5,17-Bis (3-trifluoromethylphenyl) -25-allyloxy-26,27,28-tripropyloxycalix [4] arene (20c)
Under argon atmosphere, tetrakis (triphenylphosphine) palladium 0.019 g (0.016 mmol) and 3-iodobenzotrifluoride 0.36 g (1.34 mmol) are dissolved in 2-propanol (10 mL), and potassium carbonate 0.6 g (4.34 mmol) And water (3 mL) were added. To this was added the above solution containing 0.45 g (0.668 mmol) of (19a) and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 10 mL), and the organic phase was washed with water (10 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 60 g, chloroform / hexane 1: 3) to obtain a white solid (20c) (Fw 878.99) 0.338 g was obtained. Yield 58%;¹H NMR (CDCl_Three, 400MHz) δ7.23-6.65 (m, 18H), 6.48-6.37 (m, 1H), 5.20-5.18 (m, 2H), 4.60-4.47 (m, 6H), 4.02-3.80 (m, 6H), 3.25-3.21 (m, 4H), 2.01-1.94 (m, 6H), 1.085-0.99 (m, 9H).
[0074]
5,17-bis (3-trifluoromethylphenyl) -25- (4-pentenyloxy) -26,27,28-tripropyloxycalix [4] arene (20d)
Under an argon atmosphere, 0.019 g (0.016 mmol) of tetrakis (triphenylphosphine) palladium and 0.36 g (1.34 mmol) of 3-iodobenzotrifluoride are dissolved in 2-propanol (10 mL), and 0.6 g (4.34 mmol) of potassium carbonate. And water (3 mL) were added. To this was added the above solution containing 0.45 g (0.64 mmol) of (19b) and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 10 mL), and the organic phase was washed with water (10 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 60 g, chloroform / hexane 1: 3) to obtain a white solid (20d) (Fw 907.05) 0.31 g was obtained. Yield 53%.
[0075]
Example 4
Synthesis of 5,17-bis (3-substituted phenyl) -25,26,27-tripropyloxy-28-alkenyloxycalix [4] arene
5,17-Dibromo-25,26,27-tripropyloxy-28-hydroxycalix [4] arene (21)
(4) 10.0 g (15.0 mmol) was dissolved in N, N-dimethylformamide (200 mL), 60% sodium hydride-paraffin 1.20 g (30.0 mmol) was added, and the mixture was stirred at room temperature for 15 minutes. To this was added 3.63 g (30.0 mmol) of propyl bromide, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid aqueous solution (150 mL) was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, and the solvent was distilled off by concentration under reduced pressure.After flash chromatography (silica gel 100 g, chloroform / hexane 1: 4), (21) (Fw 708.53) as a white solid was obtained. 7.60 g was obtained. Yield 72%;¹H NMR (CDCl_Three, 400MHz) δ7.30-7.22 (m, 4H), 6.47-6.34 (m, 6H), 4.80 (s, 1H), 4.37-4.28 (m, 4H), 3.82-3.78 (m, 2H), 3.72- 3.69 (m, 4H), 3.26-3.14 (q, 4H), 2.25-2.18 (m, 2H), 1.93-1.84 (m, 4H), 1.12-1.08 (m, 6H), 0.94-0.90 (m, 3H );¹³C NMR (CDCl_Three, 100MHz) δ155.94, 154.32, 152.45, 139.15, 132.84, 132.63, 131.83, 130.78, 128.23, 128.10, 123.27, 115.43, 111.25, 77.65, 76.62, 30.57, 30.53, 23.41, 22.28, 10.77, 9.52; IR (KBr , cm^-1) 3537 (OH).
[0076]
5,17-Dibromo-25,26,27-tripropyloxy-28-allyloxycalix [4] arene (22a)
(21) 5.0 g (7.06 mmol) was dissolved in N, N-dimethylformamide (200 mL), and 0.85 g (21.2 mmol) of 60% sodium hydride-paraffin was further added, followed by stirring at room temperature for 15 minutes. To this was added 2.56 g (21.2 mmol) of 3-bromopropene, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid aqueous solution (150 mL) was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then recrystallization (chloroform / methanol) gave 3.92 g of white solid (22a) (Fw 748.59). Yield 74%.
[0077]
5,17-Dibromo-25,26,27-tripropyloxy-28- (4-pentenyloxy) calix [4] arene (22b)
(21a) 5.0 g (7.06 mmol) was dissolved in N, N-dimethylformamide (200 mL), 60% sodium hydride-paraffin 0.85 g (21.2 mmol) was further added, and the mixture was stirred at room temperature for 15 minutes. To this was added 5.26 g (35.3 mmol) of 5-bromo-1-pentene, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, 1N hydrochloric acid aqueous solution (150 mL) was added, extracted with chloroform (3 × 150 mL), and the combined organic phase was washed with water (2 × 100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and 3.47 g of white solid (22b) (Fw 776.65) was obtained by flash chromatography (chloroform / hexane). Yield 63%; R_f = 0.60 (hexane: chloroform 1: 1); mp 60 ° C;¹H NMR (CDCl_Three, 400MHz) δ7.35-6.52 (m, 10H), 5.92-5.81 (m, 1H), 5.07-5.01 (m, 2H), 4.41-4.37 (q, 4H), 3.90-3.79 (m, 8H), 3.12-3.09 (q, 4H), 2.17-2.15 (m, 2H), 2.00-1.86 (m, 8H), 1.02-0.94 (m, 9H);¹³C NMR (CDCl_Three, 100MHz) δ156.24, 155.73, 155.69, 139.09, 138.00, 137.33, 135.78, 134.21, 132.70, 131.36, 130.81, 128.38, 128.35, 122.48, 114.93, 114.77, 114.69, 76.83, 74.66, 30.84, 29.82, 30.40, 29. , 23.23, 23.18, 10.34, 10.27.
[0078]
25,26,27-Tripropyloxy-28-allyloxycalix [4] arene-5,17-diboronic acid (23a)
Under an argon atmosphere, 2.00 g (2.66 mmol) of (22a) was dissolved in dry tetrahydrofuran (40 mL) and cooled to -78 ° C. To this was added 5.32 mL (7.98 mmol) of 1.5M n-butyllithium-n-hexane solution, and the mixture was stirred at -78 ° C for 30 minutes. To this was added 1.10 g (10.64 mmol) of trimethoxyborane, and the mixture was stirred at −78 ° C. for 1 hour and at room temperature for 2 hours, and then 2N hydrochloric acid aqueous solution (40 mL) cooled with ice was added. This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (20 mL) was added. In the next reaction, the solution of (22a) was used as it was.
[0079]
25,26,27-Tripropyloxy-28- (4-pentenyloxy) calix [4] arene-5,17-diboronic acid (23b)
Under an argon atmosphere, 2.00 g (2.56 mmol) of (21b) was dissolved in dry tetrahydrofuran (40 mL) and cooled to -78 ° C. To this was added 5.12 mL (7.69 mmol) of 1.5M n-butyllithium-n-hexane solution, and the mixture was stirred at -78 ° C for 30 minutes. To this was added 1.06 g (10.24 mmol) of trimethoxyborane, and the mixture was stirred at −78 ° C. for 1 hour and at room temperature for 2 hours, and then 2N hydrochloric acid aqueous solution (40 mL) cooled with ice was added. This was extracted with chloroform (2 × 100 mL) and the combined organic phases were washed with water (100 mL). The organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off to 10 mL by concentration under reduced pressure, and the solvent used in the next reaction (20 mL) was added. The solution of (23b) was used as it was for the next reaction.
[0080]
5,17-bis (3-methylphenyl) -25,26,27-dipropyloxy-28-allyloxycalix [4] arene (24a)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 1.39 g (6.36 mmol) of 3-iodotoluene are dissolved in benzene (30 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Furthermore, the above-mentioned solution containing (23a) 1.80 g (2.66 mmol) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and purified by flash chromatography (silica gel 120g, chloroform / hexane 1: 3) to obtain 1.06 g of white solid (24a). It was. Yield 58%.
[0081]
5,17-bis (3-methylphenyl) -25,26,27-tripropyloxy-28- (4-pentenyloxy) calix [4] arene (24b)
Under argon atmosphere, 0.092 g (0.079 mmol) of tetrakis (triphenylphosphine) palladium and 1.39 g (6.36 mmol) of 3-iodotoluene are dissolved in benzene (30 mL), and 2M aqueous sodium carbonate solution (20 mL) is added thereto. It was. Further, the above solution containing 2.07 g (2.66 mmol) of (23b) was added and refluxed for 20 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 4) to obtain a white solid (24b) (Fw 799.10) 1.84 g was obtained. Yield 51%.
[0082]
5,17-Bis (3-trifluoromethylphenyl) -25,26,27-tripropyloxy-28-allyloxycalix [4] arene (24c)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 0.91 g (3.85 mmol) of 3-iodobenzotrifluoride were dissolved in 2-propanol (30 mL). mmol) and water (10 mL) were added. Further, the above-mentioned solution containing (23a) 1.80 g (2.66 mmol) was added and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 5) to give a white solid (24c) (Fw 878.99) 1.24 g was obtained. Yield 53%.
[0083]
5,17-bis (3-trifluoromethylphenyl) -25,26,27-tripropyloxy-28- (4-pentenyl) oxycalix [4] arene (24d)
Under an argon atmosphere, 0.092 g (0.080 mmol) of tetrakis (triphenylphosphine) palladium and 0.91 g (3.85 mmol) of 3-iodobenzotrifluoride were dissolved in 2-propanol (30 mL). mmol) and water (10 mL) were added. Furthermore, the above-mentioned solution containing (23b) 2.07 g (2.66 mmol) was added and refluxed for 4 hours. After completion of the reaction, the mixture was extracted with chloroform (2 × 50 mL), and the organic phase was washed with water (50 mL). This organic phase was dehydrated with anhydrous magnesium sulfate, the solvent was distilled off by concentration under reduced pressure, and then purified by flash chromatography (silica gel 120 g, chloroform / hexane 1: 5) to obtain a white solid (24d) (Fw 907.05) 1.18 g was obtained. Yield 49%.
[0084]
Example 5
Synthesis of polysiloxane with chemically bonded calixarene
Under argon atmosphere, 1.0 g (1.25 mmol) of (24b) and 0.60 g of hydromethylpolysiloxane (Si-H 1.25 mmol) containing 4% Si-H bond were dissolved in dry toluene (40 mL) in a Teflon flask. Stir at 85-90 ° C. for 1 hour. To this was added 132.5 μL of 1% chloroplatinic acid (THF-ethanol solution), and the mixture was stirred at 85-90 ° C. for 72 hours, and then 132.5 μL (0.85 mmol) of 1-octene was added and stirred overnight. After cooling by exposure to air, most of the catalyst was removed by centrifugation and purified by flash chromatography (silica gel 50 g, ethyl acetate / hexane 1:10) to obtain 1.18 g of the desired compound.
[0085]
Example 6
Synthesis of polysiloxane with chemically bonded calixarene
In a Teflon flask under argon, (24b) 1.0 g (1.25 mmol) and methyldichlorosilane 7.82 g (67.95 mmol) were dissolved in dry benzene (20 mL), and 0.1M chloroplatinic acid (THF-ethanol solution) 160.3 μL And stirred at 40 ° C. for 20 hours. After distilling off the solvent by concentration under reduced pressure, polydimethylsiloxane (M_n= 550) 1.41 g (2.56 mmol) and dry benzene (20 mL) were added, and the mixture was stirred at 50 ° C. for 10 hours. Further, 2.23 g (20.51 mmol) of trimethylchlorosilane was added and stirred at 50 ° C. for 10 hours. The solvent was removed by concentration under reduced pressure, and the residue was dissolved in dichloromethane (40 mL) and washed with methanol-water (1: 1 v / v). The solvent was removed by concentration under reduced pressure to obtain the desired product.
[0086]
Example 7
Synthesis of triethoxysilane chemically bonded to calixarene
Under an argon atmosphere, 1.00 g (1.30 mmol) of (7a), 0.025 g (0.027 mmol) of triphenylphosphine rhodium chloride and 5.91 mL (32.03 mmol) of triethoxysilane were mixed and degassed by freeze degassing. To this was added dry toluene (40 mL), and the mixture was stirred at 90 ° C. for 6 hours. After allowing to cool, the solvent was distilled off by concentration under reduced pressure, and the residue was purified by flash chromatography (silica gel 80 g, chloroform / hexane 6: 4) to obtain 0.65 g of the objective compound.
[0087]
Example 8
A column was prepared by coating the inner surface of a fused silica capillary (inner diameter 0.25 mm × 8.7 m) with the polysiloxane chemically bonded to the calixarene obtained in Example 5. As a result, an improvement was observed in the separation of meta-isomers and para-isomers of benzene derivatives, which is relatively difficult to separate with conventional columns.
[0088]
【The invention's effect】
The calixarene compound (1) of the present invention is excellent in inclusion ability and separation ability, and is useful as a chromatography column. In particular, the presence of an aromatic hydrocarbon group having a planar structure at the position facing the upper edge, which is the inclusion field of the calixarene skeleton, makes it easy for the entire molecule to include the sample molecule. In addition, since it is bonded to the polysiloxane side chain that is the skeleton of the stationary phase, it also has an effect of preventing column bleed. The chromatographic stationary phase of the present invention is also useful for the separation of enantiomers due to the excellent resolution of the calixarene compound (1).

Claims (4)

General formula (1)

[In the formula, at least one of R ¹ and R ² is CH ₂ ═CH (CH ₂ ) _m- , trialkoxysilyl- (CH ₂ ) _{m + 2} -or polysiloxane- (CH ₂ ) _{m + 2-} (Where m represents a number of 1 to 8), and the remainder represents an alkyl group having 3 or more carbon atoms;
Ar represents an aromatic hydrocarbon group having 6 to 10 carbon atoms which may have a substituent;
n represents a number from 2 to 4]
A calixarene compound represented by: 1 or 2 wherein Ar is selected from an alkyl group, a halogenoalkyl group, an alkoxy group, a cyano group, a nitro group, an amino group, a dialkylamino group, a sulfonyloxy group and a functional group having one or more asymmetric carbon atoms The calixarene compound according to claim 1, which is a substituted phenyl group or naphthyl group. The calixarene compound according to claim 1 or ² , wherein at least one of R ¹ and R ² is trialkoxysilyl- (CH ₂ ) _{m + 2} -or polysiloxane- (CH ₂ ) _{m + 2-} . A chromatographic stationary phase obtained by reacting or coating the calixarene compound according to claim 3.