2-苄基吲哚及硫色烯類化合物之合成

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(1)國立臺灣師範大學化學系 Department (Graduate institute) of Chemistry, National Taiwan Normal University. 碩士. 論文. 指導教授: 姚清發博士 (Dr. Ching-Fa Yao). 2-苄基吲哚及硫色烯類化合物之合成 Synthesis of 2-Benzylindoles and Thiochromenes. 研究生:楊偉傑 (Wei-Chieh Yang). 中華民國 101 年 6 月.

(2) 摘要. 本論文分為兩部分。第一部份探討利用銅催化，使 2-(2-halophenyl)chroman-3-amine 進行分子內胺化反應，建構出多種 2-((1H-indol-2-yl)methyl)phenol 衍生物。此合成策略可以在溫和的反應條件下，簡單的合成出廣泛的 2-benzyl-1H-indole 衍生物。第二部分是利用 2,2’-dithiodibenzaldehyde 及硝基苯乙烯來合成出多樣的硫色烯衍生物。此合成法具有簡單、有效率且符合綠色化學概念的特色。色烯類化合物具有多樣的生物活性，以及在醫藥上廣泛的應用，引起化學家對色烯類化合物的高度興趣；並嘗試以硫原子取代氧原子，期望可以提高分子的生物活性。. 關鍵字：2-苄基吲哚、吲哚、銅催化、分子內胺化、硫色烯. I.

(3) Abstract. The contents of this thesis divided into two parts summarizing the results based on the experimental works performed during the course of study. The first part of this thesis describes the copper-catalyzed intramolecular amination reaction of 2-(2-halophenyl)chroman-3-amine to construct a variety of 2-((1H-indol-2-yl)methyl)phenol derivatives. This method offers an easy access to a wide variety of 2-benzyl-1H-indole derivatives under mild reaction conditions in high yields. The second part focuses on the synthesis thio-nitrochromene derivatives from β-nitrostyrene and 2,2’-dithiodibenzaldehyde in the presence of organocatalyst. This method is a simple, efficient and environmentally friendly in line with the concept of green chemistry.. Keywords: 2-benzylindole 、 indole 、 copper-catalyzed 、 intramolecular amination、thiochromene. II.

(4) 1-1ǵ ǵ߻‫ق‬ ᚇᕉϯӝ‫ނ‬தख़ፄр౜ӧϺฅ‫ޑނ‬ମࢎύǴԶ‫ځ‬ғ‫׳܄ࢲނ‬ቶ‫ݱ‬ Ӧр౜ӧ୏ǵ෌‫کނ‬Γᜪ(ᛰ‫)ނ‬ύǴӕਔΨቶ‫ޑݱ‬೏ᔈҔӧཥᑫ‫ޑ‬ଯ ϩη‫׷‬਑‫࣬ک‬ᜢ‫ނޑ‬౛‫׷‬਑(ႝηǵӀᠼ໺ᒡ೛ഢ)ǹ‫܌‬а೭٤ᚇᕉϯ ӝ‫ޑނ‬ӝԋБ‫ݤ‬൩ᡉள਱Ѧ‫ޑ‬ख़ा 1Ƕ 1-1-1ǵ㞑㤺‫ޑ‬ϟಏ 㞑㤺(indole)ឦ‫ޱܭ‬३ᚇᕉ‫ޑ‬Ԗᐒϯӝ‫ނ‬ǴѬ‫ڀ‬Ԗᚈᕉ่ᄬǴҗ ΋ঁϤϡशᕉ(benzene)‫ک‬΋ঁϖϡ֖ේ‫ޑ‬㞓ࠗᕉ(pyrrole)ಔԋǹҗ‫ܭ‬ ේ΢‫ېޑ‬ჹႝηୖᆶӅਁǴ٬ள᏾ঁϩη‫ڀ‬Ԗ‫ޱ‬३ᕉ‫ޑ‬੝‫܄‬Ƕ. ӧ೚ӭϺฅ‫ނ‬Ϸᛰ‫ނ‬ύ೿‫ڀ‬Ԗ㞑㤺ϯӝ‫่ޑނ‬ᄬǴឦ‫ܭ‬΋ᅿғ‫ނ‬ ᡵ(alkaloid)ǹӧᛰ‫ނ‬ϩη΢ࢂ΋ख़ा‫ޑ‬ମࢎ่ᄬǶӧ 1950 ԃжǴ㞑㤺ᜪ‫ޑ‬ғ‫ނ‬ᡵᛰ‫ނ‬ǴӵճՈѳ(Resrpine)ёҔ‫ݯܭ‬ᕍଯՈᓸǵՎ΍Ⴅ ᆸᗂੱǵᆒઓੰ฻ύኰઓ࿶‫س‬಍Бय़‫ޑ‬੯ੰǴࢂ྽ਔ‫ޑ‬२ᒧᛰ‫ނ‬Ǵ1958 ԃ Woodward ௲௤аΓπӄӝԋ‫ޑ‬Б‫ݤ‬ԋфள‫ډ‬ճՈѳ 2Ƕ. 1. 1.

(5) ճՈѳӢ‫ڀ‬Ԗࢥ‫܄‬Ϸ೚ӭ‫ޑ‬ୋբҔǴ‫܌‬а೴ᅌӦ೏‫ځ‬дᛰ‫ڗ܌ނ‬ жǴࡺ 70 ԃжࡕ൳Я൩ؒԖӆ೏٬Ҕ‫ܭ‬ᎃ‫׉‬΢Ƕ‫ځ‬дᗋԖࡐӭ‫ڀ‬Ԗ 㞑㤺ମࢎ‫ޑ‬ғ‫ނ‬ᡵ೏ჴሞᔈҔӧᛰ‫ނ‬ϩη΢ǴႽࢂߏࡾӭᡫ(vindoline) ‫ڀ‬फ़ՈિϐфҔǵᐍ༝‫ދ‬ᅧᐋᡵ(ellipticine)‫ڀ‬Ԗߥៈ‫ط‬ᗐϷ‫ל‬ဍዦբ ҔǵN,N-dimethyltryptamine ࣁՅữ‫ޑ‬΋ᅿǴჹઓ࿶ଆᡉ๱բҔǴૈ კ 1.1)ǹ߈යϝԖࡐӭ‫ڀ‬Ԗ㞑㤺่ᄬ‫ޑ‬Ϻฅ‫ނ‬೏ว౜Ǵ ଺ࣁ଎Єᛰ 3(კ 2008 ԃǴவ໵݈ᐋ(Alstonia scholaris)ယηύ‫܌‬ϩᚆр scholarisine A4Ǵ ӧ 2012 ԃςҗ Amos B. Smith ௲௤ࣴ‫ز‬ი໗Ǵว߄ள‫ ډ‬scholarisine A5 ‫ޑ‬ӄӝԋൔᏤǶ೭ᜪ‫ڀ‬Ԗ㞑㤺ମࢎ‫ޑ‬ϯӝ‫ނ‬Ǵவ 20 Шइύ໒‫ډۈ‬౜ ӧ΋‫ޔ‬೿‫ࣽډڙ‬Ꮲৎॺ‫ޑ‬ख़ຎǴ‫܌‬аϯᏢৎ൩ଞჹ೭ᜪϯӝ‫ނ‬Ǵ຾Չ ෳ၂ࢂց‫ڀ‬Ԗғ‫܄ࢲނ‬Ǵ٠჋၂೛ीǵঅႬǴ‫׆‬ఈӧߥ੮চԖ‫ޑ‬ᛰ‫܄‬ ΠǴӝԋрཥᑉ‫ޑ‬ϯӝ‫่ނ‬ᄬǴ‫׆‬ఈૈჴሞᔈҔӧᛰ‫ނ‬ϩη΢Ǵ໒ว рჹΓᡏ໾্നλ‫ޑ‬ᛰ‫ނ‬Ƕ. კ 1.1ǵ֖Ԗ㞑㤺่ᄬ‫ޑ‬Ϻฅ‫ނ‬Ϸ‫ځ‬ᜪ՟‫ނ‬ 2. 2.

(6) 1-1-2ǵ ǵ㞑㤺‫ޑ‬ӝԋᆶᔈҔ 㞑㤺‫ޑ‬ϯᏢᔈҔ࣬྽ቶ‫ݱ‬Ǵёа຾Չόӕᜪࠠ‫ޑ‬ϸᔈǶ‫ٯ‬ӵǺѬ ёауԋ‫܈୷⫾ډ‬ᅹ-ᅹόႫ‫ک‬ᗖ‫܈‬ᜪ՟‫୷ૈ۔‬ǵ‫ک‬ᒃႝη‫ޑ‬ᅹ(sp3) ϸᔈǵ‫ޔ‬ௗ‫ޑ‬຾Չ౎ϯ‫୷ޱ܈‬ϯǴ‫܈‬ӵ Diels-Alder ϸᔈ฻(კ 1.2) 6Ƕ. კ 1.2ǵ㞑㤺ё຾Չ‫ޑ‬ϸᔈᜪࠠ җ‫ܭ‬㞑㤺΢‫ޑ‬ႝ಻ϩѲ੝‫܄‬Ǵࡺό৒ܰ‫ޔ‬ௗӧ 2 ဦᅹ΢຾Չঅ ႬǴటӝԋ 2-‫ڗ‬ж‫ޑ‬㞑㤺೯தሡ೸ၸख़ཥࢎᄬ㞑㤺ύϖϡᕉ‫ޑ‬㞓ࠗᕉ ೽ϩǹၸѐӭ٬Ҕ໺಍‫ޑ‬Ԗᐒӝԋ‫ޑ‬Б‫ݤ‬Ǵ‫ځ‬੝ՅࣁǺᝄद‫ޑ‬ϸᔈచ ҹ(ଯྕǵமለமᡵᕉნ)ǵϸᔈਔ໔ߏǴ٠தՔᒿ๱࣬྽ӭໆ‫ޑ‬ୋౢ ‫ނ‬ౢғǶ๱Ӝ‫ޑ‬ΓӜϸᔈ 1 ӵ߄ ߄ 1.1 ‫܌‬ҢǺ 3. 3.

(7) ߄ 1.1ǵӝԋ㞑㤺‫ޑ‬ΓӜϸᔈ. 4. 4.

(8) ! ! ୷‫ܭ‬ᆘՅϯᏢ‫ۺཷޑ‬Ǵଓ‫؃‬ϯᏢϸᔈ‫ޑ‬ᙁൂǵБߡǵਏ౗฻੝‫܄‬Ǵ ၸѐத٬Ҕឦ‫ܭ‬ᝄद‫ޑ‬Ԗᐒ໽ϯ‫ޑ‬ϸᔈచҹǴςᅌᅌၨϿ೏ᔈҔӧӝ ԋ΢Ǵ‫ڗ‬Զжϐ‫ࢂޑ‬٬Ҕၸ෠ߎឦٰୖᆶϸᔈǴёаᡣϸᔈӧၨྕ‫ک‬ ‫ޑ‬ϸᔈచҹΠ຾ՉǴ٠Ъ಄ӝচη࿶ᔮ(atom economy)‫ۺཷޑ‬ǹԶԖ ᐒߎឦ‫ޑ‬ЇΕ‫׳‬ԋфӦ‫ׯ‬๓ၸѐᕷᚇǵᝄद‫ޑ‬Ԗᐒӝԋ฼ౣǶߎឦ⑵ (Pd)‫ޑ‬໽ϯ‫س‬಍ԿϞςว৖Α࣬྽‫ޑ‬ำࡋǴ٠‫ڗ‬ளΑёᢀ‫ޑ‬Ў᝘Ǵӧ ჴ፦‫ޑ‬ଅ᝘΢߾ࢂεৎԖҞӅ࿏Ƕ1989 ԃǴStille ‫ ک‬Rudisill ‫زࣴޑ‬ ი໗Ǵ२ԛൔᏤճҔशᕉ΢ӧᎃՏ‫ڀ‬ԖशΌᬨϷㄽữᜪ‫ޑ‬ϯӝ‫ނ‬Ǵӧ ߎឦ⑵‫ޑ‬໽ϯΠёள‫ڀډ‬Ԗ㞑㤺ࢎᄬ‫ޑ‬ϯӝ‫ ނ‬7 (Ԅ 1.1)Ƕ. (1.1). 1994 ԃǴYoshihisa Watanabe ࣴ‫ز‬ი໗ǴճҔशᕉ΢ӧᎃՏ‫ޑ‬ฮ ୷Ϸ౎୷ϯӝ‫ނ‬ǴӆуΕ΋਼ϯᅹǴճҔߎឦ⑵‫ک‬ᒴ(II)ёஒฮ୷຾ ՉᗋচϸᔈǴёள‫ډ‬ӭ‫ڗ‬ж‫ޑ‬㞑㤺ࢎᄬϯӝ‫ ނ‬8(Ԅ 1.2)Ƕ. (1.2). 5. 5.

(9) 2002 ԃǴYoshinori Yamamoto ࣴ‫ز‬ი໗ǴճҔ㶮ǵ౎ᜪ‫᠄ک‬ේ຾ ՉΟԋҽ΋ᗙϯ‫ޑ‬ϸᔈǴள‫ ډ‬N-cyanoindole ‫ޑ‬ౢ‫ ނ‬9(Ԅ 1.3)Ƕ. (1.3). 2009 ԃǴNing Jiao ࣴ‫ز‬ი໗ճҔशữ‫ک‬΍ᬨΒለΒҘ✊ӧ਼਻ ᆶ⑵‫ޑ‬Ӆӕ໽ϯΠǴӧଯྕ 120oC Πϸᔈ 12 λਔࡕǴள‫ډ‬ҘለҘ✊ ‫ڗ‬ж‫ޑ‬㞑㤺ࢎᄬϯӝ‫ ނ‬10(Ԅ 1.4)Ƕ. (1.4). ӧ 2010 ԃǴChing-Fa Yao ௲௤ࣴ‫ز‬ი໗ว߄ό΋ኬ‫ޑ‬ӝԋБ‫ݤ‬Ǵ ٬Ҕ㞑㤺‫ ک‬2-ฮ୷-ฮ୷शΌ౎຾ՉуԋϸᔈࡕǴճҔ៓ણ‫ک‬ᎉለӅ ໽ϯǴᗋচशᕉ΢‫ޑ‬ฮ୷ғԋशữࡕǴ຾Չϩηϣ‫ڗޑ‬жϸᔈಥѐฮ ୷Ǵᕉϯғԋ㞑㤺ࢎᄬϯӝ‫ ނ‬11(Ԅ 1.5)Ƕ. (1.5). 6. 6.

(10) 1-1-3ǵ ǵਜ਼Ըୗϸᔈ (Ullmann reaction) ਜ਼ԸୗϸᔈЬाࢂճҔߎឦል໽ϯϸᔈǴᙖҗል(I)ӧଛՏ୷‫ک‬ᡵ ‫ޑ‬ᕉნΠԶ຾ՉҬඤଽӝϸᔈ (cross-coupling reaction)Ǵന߃ᔈҔӧ ࡌҥ sp ‫ޑ‬ᅹ-ᅹᗖ 12(Ԅ 1.6)ǹࡕٰԜӝԋ฼ౣΨ೏ᔈҔӧữϯϸᔈ(Ԅ 1.7)ǴҔаࡌҥཥ‫ޑ‬ᅹ-ේᗖǹ1997 ԃǴStephen L. Buchwald ௲௤ճҔ ⑵໽ϯ຾ՉữϯϸᔈǴஒữ‫ ک‬aryl bromide ຾Չଽӝϸᔈ 13(Ԅ 1.8)Ƕ. (1.6). (1.7). (1.8). 2008 ԃǴNobutaka Fujii ‫ ک‬Hiroaki Ohno ࣴ‫ز‬ი໗ǴճҔ༾‫ݢ‬ϸ ᔈǴΟಔԋ‫ޑ‬ଆ‫཮ނۈ‬Ӄ຾Չୗѭ‫׆‬ϸᔈ (Mannich-Type Reaction)Ǵ ӆӢࣁ࿚ϯ٥ል໽ϯΠଽӝǴள‫ډ‬㞑㤺ମࢎౢ‫ ނ‬14(Ԅ 1.9)Ƕ. (1.9). 7. 7.

(11) Զ L. Buchwald ௲௤Ǵଞჹӧል໽ϯΠ຾Չ‫ޑ‬ਜ਼Ըୗᜪࠠϸᔈ (Copper-Catalyzed Ullmann-Type Reactions)଺Αࡐӭ‫ޑ‬ჴᡍǴΨӧӚ යтว߄ΑࡐӭൔᏤǴ2010 ԃǴว߄Α΋ጇᜢ‫ܭ‬౛ፕ૶ᆉ‫ޑ‬ൔᏤǴ კ 1.3)ǴӧၸѐЎ᝘ൔᏤ᛾ܴ΋ठᇡࣁǴል(I) ௖૸ёૈ‫ޑ‬ϸᔈᐒ‫(ڋ‬კ ཮Ӄᆶ Ligand ‫ ک‬Nuc ଛՏǴՠࢂჹ‫ܭ‬ௗΠٰӵՖࢲϯ aryl halide ‫ޑ‬ ೽ϩ߾Ԗόӕ‫ޑ‬ཀ‫ـ‬Ǵന೏ε౲‫܌‬ௗ‫ޑڙ‬ϸᔈᐒ‫(ࢂڋ‬a)࿶җ਼ϯуԋ ள‫ډ‬ል(III)‫ޑ‬ύ໔‫ނ‬Ǵӆ຾Չᗋচಥѐ‫ޑ‬БԄ຾Չள‫ډ‬ౢ‫ނ‬Ǵ‫ځ‬Ѭଷ ೛‫ޑ‬ᐒ‫ڋ‬ӵǺ೸ၸ(b)ൂႝηᙯ౽(single-electron transfer)ǵ(c)চηᙯ౽ (atom transfer)‫(ک‬d)Ѥচη‫ ޑ‬σ-ᗖҬඤ(four-centered σ-bond metathesis) ฻ǴՠࢂࡕΟᅿϸᔈᐒ‫ڋ‬ѝԖϿኧ‫ޑ‬Ў᝘ൔᏤ 15Ƕ. კ 1.3 ਜ਼Ըୗϸᔈ‫ޑ‬ϸᔈᐒ‫ڋ‬. 8. 8.

(12) 2012 ԃǴAnny Jutand ‫ ک‬Ilaria Ciofini ௲௤ӧ Organometallics යт ว߄΋ጇЎകǴ௖૸ӧል໽ϯ‫سޑ‬಍Π຾ՉữϯϸᔈਔǴഛનǵữǵ ߎឦልϷଛՏ୷ǴѤ‫ޣ‬ӧϸᔈၸำύ‫ת܌‬ᄽ‫فޑ‬ՅǴ‫ک‬ၸำύ‫׎܌‬ԋ ‫ޑ‬ణᗖǴჹ᏾ঁଽӝϸᔈ‫ޑ‬ቹៜ٠ჹϸᔈᐒ‫଺ڋ‬΋‫س‬ӈֹ᏾‫ޑ‬௖૸ 16 (კ კ 1.4)ǹᇡࣁϸᔈᐒ‫ڋ‬ΨࢂữӃଛՏ‫ډ‬ል(I)ࡕǴӆ࿶җ਼ϯуԋϷ ᗋচ੃ѐ‫؁ޑ‬ᡯǴԶ‫ޱ‬३ᕉ΢‫ޑ‬ഛન҅ࢂቹៜϸᔈ຾Չ‫ޑ‬ЬӢϐ΋Ǵ ೸ၸ౛ፕ૶ᆉ‫ޑ‬᛾ܴǴᇡࣁ೭ঁϸᔈ‫ޑ‬ೲ౗،‫؁ۓ‬ᡯ (Rate-determining step, rds)Ǵ҅ࢂϸᔈၸำύ਼ϯуԋࡕಥѐഛન‫ޑ‬ ‫؁‬ᡯǴ೭ኬ‫ޑ‬ᖿ༈‫ޔ‬ௗϸᔈӧϸᔈ‫ޑ‬ਔ໔ߏอǴനࡕள‫ډ‬ഛન‫ޑ‬ϸᔈ ‫܄‬ᜢ߯ελࢂ࿚ > ྜྷ >> ෛǹϸᔈൻᕉӵკ კ 1.4 ‫܌‬኱ҢǶ. კ 1.4 ਜ਼Ըୗϸᔈൻᕉკ 9. 9.

(13) 1-4ǵ ǵჴᡍБ‫ݤ‬ 1-4-1ǵ΋૓ჴᡍБ‫ݤ‬ 1. ᅙᗺෳ‫سۓ‬ஒ‫ڰ‬ᡏኬࠔ࿼‫ܭ‬ЛಒᆅύǴ٬ҔMel−TEMP II ࠠᅙᗺ ෳ‫ۓ‬ሺෳ‫ۓ‬ϐǶ 2. ణਡᅶӅਁӀ᛼(1H-NMR)‫ک‬ᅹਡᅶӅਁӀ᛼(13C-NMR)߯٬Ҕ Bruker Avance 400ࠠ‫܈‬500ࠠਡᅶӅਁӀ᛼ሺǹ‫܌‬٬ҔྋᏊࣁ֖᤹ −ෛү(chloroform-d1, CDCl3)ǵ᤹−ΒҘ٥㿲(Dimethylsulfoxide-d6, DMSO-d6)ǶణਡᅶӅਁӀ᛼ϐϯᏢՏ౽΋૓߯а᤹−ෛү‫ූޑ‬੮ ෛү(CHCl3)‫ޑ‬ణ֎ԏঢ়δ = 7.26 ppm ‫܈‬ѤҘ୷‫ޖ‬₧δ = 0.00 ppm ࣁϣ୷ྗǴᅹਡᅶӅਁӀ᛼ϐϯᏢՏ౽΋૓߯а᤹−ෛү֎ԏঢ়δ = 77.23 ppm ࣁϣ୷ྗǶӀ᛼ൂՏ(δ)ࣁppmǴጠӝதኧൂՏ(Jȑࣁ Hzǹs (singlet)߄ൂ‫ݢ‬ঢ়ǹd (doublet)߄ᚈख़‫ݢ‬ঢ়ǹt (triplet)߄Οख़ ‫ݢ‬ঢ়ǹq (quartet)߄Ѥख़‫ݢ‬ঢ়ǹquint (quintet)߄ϖख़‫ݢ‬ঢ়ǹsext (sextet)߄Ϥख़‫ݢ‬ঢ়ǹbr (broadened)߄ቨ‫ݢ‬ঢ়ǹm (multiplet)߄ӭख़ ‫ݢ‬ঢ়Ƕ 3. ፦᛼ȐMSȑෳ‫߯ۓ‬٬ҔFinnigan TSQ 700 ࠠ‫࣬਻ޑ‬ቫ‫݋‬፦᛼ሺ‫܈‬ Finnigan MAT 95S ࠠ‫ޑ‬ଯਏૈ፦᛼ሺǴ໻ӈрமࡋεϷख़ा‫ޑ‬ှ ᚆ᎔ጕ(m/z)Ǵ‫࣬ځ‬ჹ୷ঢ়(base peak)‫ޑ‬ԭϩКமࡋӈӧࡴ۱ϣǴ ႝηናᔐෞᚆ‫(ݤ‬EI)ᚆηϯႝᓸࣁ70eVǶଯှ‫݋‬፦᛼(HRMS)߯௦ 28. 10.

(14) ҔFinnigan MAT 95SǵFinnigan MAT-95XL ‫܈‬ǵFinnigan/Thermo Quest MAT ଯਏૈ፦᛼ሺϷJEOL HR/LR FAB mass spectroscopy(ύѧࣴ‫ز‬ଣ)ෳ‫ۓ‬ϐǶ 4. ଯਏ౗నᄊՅቫϩ‫݋‬ሺ/፦᛼ሺ(LC-MS)௦ҔHewlett Packard Seris 1100MSD ࠠǶ 5. ύᓸᆅࢊՅቫϩᚆ‫(ݤ‬medium-pressure column chromatography)߯ ٬ҔE. Merck Art. 9385 Kieselgel 60 (230−400 mesh)ೕ਱Ǵ‫܈‬MNG SILICA GEL 60 (70-230 mesh)ೕ਱‫ޖޑ‬ጤࣁᓉ࣬֎ߕᏊǹᖓቫՅ ቫϩ‫(݋‬TLC)߯٬ҔE.Merck silica gel 60 F254 ࣒ࠠዟᖓТ‫ࢂ܈‬᎑ ТǶ 6. ؑගᏊ(eluent)ǵ৖໒Ꮚ(developing solvent)‫ک‬๧‫܌ڗ‬٬Ҕ‫ޑ‬ྋᏊΒ ෛҘ₧ǵෛүǵΌለΌ✊ǵ҅ρ₧ϷҘᎇࣣࣁACS ભǴ‫ࢂ܈‬аπ ཰ભྋᏊ຾ՉᇃᚖપϯᕇளǶ 7. ჴᡍ٬Ҕϐϸᔈ၂ᏊǴྋᏊ‫ک‬ଳᔿᏊନԖ੝ਸຏܴѦǴ֡ᖼԾ MerckǵTCIǵAcrosǵAlderichǵShow ‫܈‬Lancaster Ϧљ٠҂຾Չ પϯԶ‫ޔ‬ௗ٬ҔǹਡᅶӅਁϩ‫݋‬Ҕ֖᤹ྋᏊ߾ᖼԾMerck ᆶඳܴ ϯπϦљǶ 8. ൂ඲X-rayᙅ৔ࢂ٬ҔNonius Kappa CCD Axis (୯ҥᆵ᡼ৣጄε ᏢϯᏢ‫)س‬Ƕ 29. 11.

(15) 2-1ǵ ǵ߻‫ق‬ ೚ӭӧ෌‫ނ୏ࢂ܈ނ‬ύϩᚆԶள‫ޑ‬Ϻฅ‫ނ‬೏ว౜ёբࣁᛰ‫ނ‬ǴҔ а‫ݯ‬ᕍΓᜪ‫ޑ‬Ӛᅿ੯ੰǹϩ‫݋‬Ԝᜪϯӝ‫่ނ‬ᄬว౜ε೽ϩࢂ֖Ԗේǵ ਼ǵ౷‫ޑ‬ᚇᕉϯӝ‫ނ‬Ƕ೽ϩϺฅ‫ނ‬җ‫ܭ‬પϯϷϩᚆΜϩό৒ܰǴаϷ ค‫ݤ‬εໆ‫ڗ‬ள‫ޑ‬લᗺǴࡺϯᏢৎ‫׆‬ఈճҔаᙁൂ‫ޑ‬ԖᐒӝԋБԄǴ೛ ीӝԋр‫ڀ‬ԖԜᜪғ‫܄ࢲނ‬੝ਸ่ᄬ‫ޑ‬ᛰ‫ނ‬ϩηϷ‫़ځ‬ғ‫ނ‬Ƕ 2-1-1ǵՅ౎ᜪ़ғ‫(ނ‬chromene)‫ޑ‬ϟಏ Յ౎ᜪ़ғ‫(ނ‬chromene)ΞᆀࣁशԂ㞓ീ(benzopyran)Ǵаᚈᕉࣁ ਡЈх֖शᕉ(benzene ring)Ϸ਼֖ᚇᕉ‫ޑ‬㞓ീᕉ(pyran ring)़ғԶள ‫ޑ‬ᚈᕉϯӝ‫ނ‬Ǵ٩Ᏽ਼চη‫ޑ‬Տ࿼όӕёϩࣁ‫ٿ‬ᅿ่ᄬ౦ᄬ‫ނ‬Ǵϩձ ࣁՅ౎(chromene)Ϸ౦Յ౎(isochromene)ǴԶՅ౎٩Ᏽᚈᗖ‫ޑ‬Տ࿼ё ӆϩࣁ 2H-Յ౎(2-H chromene)Ϸ 4H-Յ౎(4-H chromene)‫ٿ‬ᅿǶ่ᄬ ӵკ კ 2.1 ‫܌‬ҢǶ. კ 2.1ǵ2H-Յ౎ǵ4H-Յ౎Ϸ౦Յ౎ϐ่ᄬ౦ᄬ‫ނ‬. Յ౎ᜪ़ғ‫ނ‬Ӹӧ‫ܭ‬෌‫ࣚނ‬ύǴ‫ځ‬ύ३‫ل‬ન(coumarin)़ғ‫ނ‬ന ࣁදၹǴҗ‫ܭ‬३‫ل‬નࢂ෌‫ނ‬ύ‫ڀ‬Ԗ३‫ނޑښ‬፦ǴࡺԐයதҔբࣁ‫ۓ‬३ 165 12.

(16) ᏊǵಥૌᏊǶ߈ԃٰ೏ว౜‫ڀ‬ԖՅ౎่ᄬ‫़ޑ‬ғ‫ނ‬Ǵё೏ቶ‫ݱ‬ӦᔈҔ ӧᙴᛰБय़ǹӵ๮‫(݅ݤ‬warfarin)ёҔࣁ‫ל‬ᏉՈϐᛰ‫ނ‬Ǵ೸ၸ‫᠌طڋ׭‬ ္‫ޑ‬ሇનբҔǴ٬ᏉՈ䁙চѨѐфૈԶٛЗՈనᏉ‫ڰ‬ǹ౦๋޸߻चϣ ✊(marmesin)߾ࢂ΋ᅿύ૛ᛰǴ‫ڀ‬Ԗ‫ל‬๵ǵ‫ל‬ว‫ݹ‬ϐਏ݀1Ƕ ନΑ३‫ل‬ન़ғ‫ނ‬ѦǴ໳✉ᜪ(flavones)‫ޑ‬Ϻฅ‫ނ‬Ψ‫ڀ‬Ԗቶ‫ޑݱ‬ғ ‫܄ࢲނ‬2ǴԜԋϩӧύ૛ᛰ္ਔத೏ว౜Ƕ‫ٯ‬ӵլᛥь݅(cromakalim) ёբࣁՈᆅᘉ஭ᏊǴ೸ၸ௓‫ܭڋ‬ᡏϣATP‫໊ޑ‬-೯ၰǴҔ‫ݯܭ‬ᕍଯՈᓸ ஻‫ޣ‬1ǹҗഝ‫ف‬๸ύϩᚆԶள‫ޑ‬΋ᅿᡖ๵ࢥન(diversonol)Ǵૈ٬η৐ ԏᕭǵЗՈ3ǹ๼‫ل‬䯿ϡ(phaseolin)Ξᆀࣁ๼‫ل‬નǴӸӧ๼‫(ل‬phaseolus vulgaris)‫ޑ‬ᅿηύǴឦ‫ܭ‬Ϻฅύ૛ᛰ‫ޑ‬΋ᅿǴ‫ڀ‬Ԗ‫ל‬๵բҔǴ٠Ъё аҔٰ‫ڋ׭‬ᐘણ‫ޑ‬ϩှ4Ƕத‫ޑـ‬Յ౎ᜪ़ғ‫่ނ‬ᄬӵკ კ2.2‫܌‬ҢǶ. კ 2.2ǵՅ౎ᜪ़ғ‫ޑނ‬ϯӝ‫่ނ‬ᄬ 166 13.

(17) Perkinϸᔈࢂӝԋр३‫ل‬નϯӝ‫ޑނ‬࿶‫ڂ‬Б‫ݤ‬5Ƕ1877 ԃǴPerkin ࣴ‫ز‬ი໗ൔᏤ٬ҔᎃՏ‫ڀ‬Ԗ♏୷‫ޑ‬Нླྀ⾺ϷᎉለὢǴӧᎉለ໊Πϸᔈ ջёள‫ډ‬३‫ل‬ન่ᄬ‫ޑ‬ౢ‫(ނ‬Ԅ2.1)Ƕ. (2.1). ӝԋ໳✉ᜪϯӝ‫߾ނ‬аAllan–Robinsonϸᔈനࣁ๱Ӝ6Ƕ1924ԃǴ AllanϷRobinsonࣴ‫ز‬ი໗ൔᏤǴ٬ҔᎃՏ‫ڀ‬Ԗ♏୷‫ޑ‬शΌ✉ϷशҘለ ὢ຾ՉᕭӝϸᔈǴёаள‫ډ‬໳✉ᜪ‫़ޑ‬ғ‫(ނ‬Ԅ2.2)Ƕ. (2.2). ߈ԃٰԖࣴ‫ز‬ൔᏤࡰрǴӵ݀ஒՅ౎ᜪϯӝ‫ނ‬ύ਼֖㞓ീᕉ΢‫ޑ‬ ਼চη࿼ඤԋ౷চη(Sulfur)ਔǴёаගଯ‫ځ‬ғ‫܄ࢲނ‬Ъ‫ڀ‬Ԗ‫׳‬٫‫ޑ‬ ᛰਏ 7ǶൔᏤࡰр‫ޑޣٿ‬ৡ౦ӧ‫ܭ‬ǺӢࣁ౷‫ޑ‬ႝॄࡋ(electronegativity) ၨ਼ե(SǺ2.58ǹOǺ3.44ǹHǺ2.20)ǴӢԶफ़եΑϩη‫׎‬ԋణᗖ(H-Bond) ‫ૈޑ‬Κǹќ΋Бय़྽ϯӝ‫֖ނ‬Ԗ౷চηਔ཮ቚу‫ځ‬౧Н‫܄‬ (hydrophobic)Ǵჹ‫ܭ‬ᛰ‫ނ‬ϩηԶ‫ق‬ǴૈցғԋణᗖϷ౧Н‫࣬ࢂ܄‬྽ख़ ा‫ޑ‬ӢηǴӢԜ੝‫ޔ཮܄‬ௗቹៜ‫ځ‬ᆶၩᡏ࣬ϕ่ӝ(binding)‫ૈޑ‬ΚǶ 167 14.

(18) வᛰᏢ‫ޑ‬ᢀᗺٰ࣮Ǵ౷চη‫ޑ‬Ӹӧёа٬ϩη‫ڀ‬Ԗ‫׳‬٫‫✊ޑ‬ྋ‫܄‬ (lipophilic)Ǵ٬‫ځ‬೯ၸတՈᆅࡀም‫ޑ‬ᐒ౗εቚǶ(blood-brain barrierǴ ᙁᆀ BBBǴΨᆀࣁՈတࡀም‫܈‬ՈတምᏛǴࡰӧՈᆅ‫ک‬တϐ໔Ԗ΋ᅿ ᒧ᏷‫܄‬ӦߔЗࢌ٤‫ނ‬፦җՈ຾Εတ‫ޑ‬ȨࡀምȩǶ) კ 2.3 ‫܌‬Ңǹ़ғ‫ ނ‬1 ‫ڀ‬Ԗૈ‫ک‬ ൳ঁ‫ڀ‬ж߄‫ޑ܄‬౷Յ౎़ғ‫ނ‬ӵკ ΓᜪϷԴႵεတύ‫ޑ‬ӭЃữ D2ǴD3 Ϸ 5HTA1 ‫ڙ‬ᡏ่ӝ‫ޑ‬ᒃਡΚ 8ǹ़ ғ‫ ނ‬2 ߾ᡉҢр‫ڀ‬Ԗ‫ל‬ང෷(human Immunodeficiency virus)‫ޑ‬ወΚ 9ǹ ़ғ‫ ނ‬3 (Tertatolol) җ‫ݤ‬୯ᇙᛰϦљว౜Ǵࢂ β ‫ڙ‬ᡏߔᅉᏊǴҔ‫ݯܭ‬ ᕍଯՈᓸ‫ޑ‬ᛰ‫ނ‬ǴΨ೏᛾ܴૈբࣁ 5HTA1 ‫ڙ‬ᡏ‫ל࡮ޑ‬ᏊǴբҔᜪ՟‫ܭ‬ 㞑㤺ࢶᅟ(PindololǴѳᓸ኷)10Ƕ. კ 2.3ǵ౷Յ౎़ғ‫(ނ‬Thiochromenes)‫่ޑ‬ᄬ. 2-1-2ǵԖᐒ౷ϯ‫ޑނ‬ᇙഢ Ԗᐒ౷ϯ‫ނ‬ቶ‫ݱ‬ӦӸӧ‫ܭ‬ԾฅࣚύǴ‫ڀ‬Ԗܴᡉ‫ޑ‬ૌ‫ښ‬Ǵՠૌ‫ޑښ‬ ੝‫཮܄‬ᒿ๱ᅹኧቚуԶ෧১Ƕჹ‫܌‬Ԗ‫ޑ‬ғ‫ٰނ‬ᇥǴ౷ࢂ΋ঁࡐख़ाЪ 168 15.

(19) όёલϿ‫ޑ‬ϡનǴΨࢂữ୷ለϷೈқ፦‫ޑ‬ಔԋԋϩǶӧ 20 ᅿத‫ـ‬ữ ୷ለύǴҘ౷਽ለ(methionine)Ϸъા਽ለ(cysteine)Ǵ֖֡Ԗ౷চηǴ კ 2.4 ‫܌‬ҢǶҘ౷਽ለࣁว‫ߦػ‬຾ Զ߻‫׳ޣ‬ឦ‫ܭ‬Ѹሡữ୷ለǴ่ᄬӵკ ᏊϷ‫᠌ط‬ှࢥᏊǴऩલЮѬਔ཮Їଆ१ኅόਁ฻ੱ‫ރ‬Ƕ. კ 2.4ǵъા਽ለ(cysteine)ϷҘ౷਽ለ(methionine)‫่ޑ‬ᄬ. ౷ϡનᆶ਼ӕ௼Ǵࣣឦ‫ܭ‬ಃϤ௼Ǵ۶ԜԖ࣬՟‫ޑ‬ሽႝηቫ่ᄬǴ ՠ౷চηឦ‫ܭ‬ಃΟຼය‫ޑ‬ϡનǴᆶ਼চη࣬КǴ‫ڀ‬Ԗၨλ‫ޑ‬ႝॄࡋЪ চηъ৩ၨεǶᆶၸ਼ϯ‫࣬ނ‬՟Ǵ౷ϯ‫ނ‬Ψёғԋၸ౷ϯ‫(ނ‬R-O-O-R and R-S-S-R)ǴΞᆀࣁΒ౷ᗖǵᚈ౷ᗖǶΒ౷ᗖࢂᆢ࡭ೈқ፦‫ޜ‬໔่ ᄬ‫ޑ‬ख़ाϯᏢᗖϐ΋Ǵ౷ᎇᆶΒ౷ϯ‫ނ‬ӧғ‫ނ‬ᡏϣǴё࿶਼ϯᗋচϸ ᔈԶϕ࣬ᙯඤǴӵъા਽ለ(cysteine)Ϸા਽ለ(cystine)Ǵ࿶ၸ਼ϯᗋ চԶ࣬ϕᙯඤջࣁ΋‫ٯ‬Ǵӵკ კ 2.5 ‫܌‬ҢǶ. კ 2.5ǵъા਽ለ(cysteine)Ϸા਽ለ(cystine)࣬ϕᙯඤ. 169 16.

(20) ၸѐςԖ΋٤Ў᝘ൔᏤӵՖӝԋ౷Յ౎Ϸ‫़ځ‬ғ‫ނ‬Ǵՠࢂ࣬ၨ‫ܭ‬ ӵՖӝԋՅ౎़ғ‫ޑނ‬ጇኧٰᇥǴ߾ࢂ࣬ჹ‫ޑ‬ϿΑ೚ӭǴӢࣁ౷ϯ‫ނ‬ ‫ޑ‬ᇙഢࢂКၨ֚ᜤ‫ޑ‬Ƕ1987 ԃǴB. Ferreira ࣴ‫ز‬ი໗ճҔ౷⇌аϷ α,βόႫ‫ޑک‬ለǴӧ㥁ᾕ྽ᡵΠǴ२Ӄ཮Ӄ຾Չ 1,4-уԋǴௗ๱ӧӭᆫᕗ ለΠᆫӝǴёள‫ډ‬౷Յ✉़ғ‫ ނ‬11(Ԅ 2.3)Ƕ. (2.3). 1988 ԃǴAnna Arnoldi ‫زࣴޑ‬ი໗ൔᏤճҔ౷⇌़ғ‫کނ‬Βྜྷश Ό✉Ǵҗ࠶৸(Wittig)ϸᔈϷ‫ڗ‬жϸᔈள‫ ډ‬3-श୷౷Յ౎़ғ‫ ނ‬12(Ԅ 2.4)Ƕ. (2.4). 1999 ԃǴHoward Alper ‫زࣴޑ‬ი໗ௗ๱ൔᏤҗ 2-࿚౷⇌ǵೱ౎ Ϸ΋਼ϯᅹǴΟಔԋᙖҗߎឦ⑵໽ϯ຾ՉጠӝϸᔈǴள‫ډ‬౷Յ✉़ғ ‫ ނ‬13(Ԅ 2.5)Ƕ. (2.5). 170 17.

(21) 2009 ԃǴKee-Jung Lee ‫زࣴޑ‬ი໗ΨൔᏤǴҗᎃՏ‫ڀ‬Ԗཥ΍୷౷ ‫ڗ‬ж‫ޑ‬शҘ⾺Ϸ α,β-όႫ‫ک‬ϯӝ‫ނ‬Ǵ೸ၸၡܰγለࢲϯϸᔈǴёаள ‫ډ‬౷Յ౎़ғ‫ ނ‬14 (Ԅ 2.6)Ƕ. (2.6). ᆕӝ΢ॊਢ‫ٯ‬Ǵ‫ॺך‬ว౜ӧၸѐ‫ޑ‬ӝԋ౷Յ౎़ғ‫ޑނ‬ϸᔈచҹ ֡ឦ‫ܭ‬ၨᝄदЪ‫؁‬ᡯᕷᅥ‫ݩރޑ‬ǴεӭሡाӧଯྕΠϸᔈωૈள‫ډ‬౷ Յ౎़ғ‫ނ‬ǹ2006 ԃǴWang ௲௤ࣴ‫ز‬ი໗ൔᏤǴճҔ 2-౷⇌शҘ⾺ ᆶԺਦ⾺ϸᔈǴӧၨྕ‫ྕ࠻ޑک‬ϸᔈచҹջёᕇள౷Յ౎़ғ‫ ނ‬15 (Ԅ 2.7)Ƕ. (2.7). ՠࢂ 2-౷⇌शҘ⾺‫ޑ‬ᇙഢБ‫ݤ‬٠ό৒ܰǴ΋૓‫ޑ‬ӝԋ฼ౣࢂҗ౷ жНླྀለ(thiosalicylic acid)଺ࣁଆ‫ނۈ‬Ǵ೸ၸᗋচϸᔈள‫ ډ‬2-౷⇌श Ҙ⾺ 16ǶStafford ௲௤٬Ҕ౷жНླྀለ଺ࣁଆ‫ނۈ‬ǴӧᎋϷణϯ᎑᎖ ‫ޑ‬ᗋচΠ࿶Οঁ‫؁‬ᡯࡕள‫ ډ‬2-౷⇌शҘ⾺Ǵՠౢ౗ѝԖ 38 %(Ԅ 2.8)Ƕ. (2.8) 171 18.

(22) West ௲௤ൔᏤќ΋ᅿόӕ‫ޑ‬ӝԋ฼ౣǴࢂҗ 2-ฮ୷शҘ⾺଺ࣁ ଆ‫ނۈ‬Ǵ२Ӄᗋচฮ୷Ǵௗ๱Ҕ౷ణለႇ཮วғ‫ڗ‬жϸᔈǴനࡕёள ‫ ډ‬2-౷⇌शҘ⾺Ǵՠࢂౢ౗‫׳‬ৡѝԖ 17 % (Ԅ 2.9)Ƕ. (2.9). Kasmai ௲௤ൔᏤҗ౷жНླྀለ (thiosalicylic acid)଺ࣁଆ‫ނۈ‬Ǵ ೸ၸ LAH (lithium aluminium hydrideǴణϯ᎑᎖)ஒለᗋচԋᎇࡕǴӆ ٬Ҕ PCC (pyridinium chlorochromate)բࣁ਼ϯᏊǴёஒᎇᜪ਼ϯԋ⾺ ᜪǴள‫ډ‬Β౷ϯ‫ނ‬ǴӆᙖҗΟश୷ᕗ (PPh3)ஒ‫ځ‬ᗋচǴёаள‫ ډ‬2౷⇌शҘ⾺Ǵౢ౗ගଯࣁ 52 % (Ԅ 2.10)Ƕ. (2.10). 2010 ԃǴChemburkar ௲௤ࣴ‫ز‬ი໗ൔᏤǴҗ 2-ෛशҘ⾺଺ࣁଆ ‫ނۈ‬Ǵӧᡵ‫܄‬చҹΠуΕཥ΍୷౷ᎇ຾Չ‫ڗ‬жϸᔈǴಃΒ‫؁‬೸ၸణྜྷ ለϷᎉለϸᔈள‫ډ‬Β౷ϯ‫ ނ‬17Ǵౢ౗ቚуࣁ 75 % (Ԅ 2.11)Ƕ. (2.11) 172 19.

(23) 2004 ԃǴHartley ௲௤ࣴ‫ز‬ი໗ൔᏤǴҗ౷жНླྀለ(thiosalicylic acid)଺ࣁଆ‫ނۈ‬ǴӃᙖҗణϯ᎑᎖(lithium aluminium hydrideǴLiAlH4) ஒ♐ለᗋচԋᎇǴӆ೸ၸ IBX (o-iodoxybenzoic acid)‫਼ޑ‬ϯள‫⾺ډ‬ᜪ ‫ޑ‬Β౷ϯ‫ ނ‬18Ǵౢ౗ଯၲ 94 % (Ԅ 2.12)Ƕ. (2.12). ౷চηᆶ਼চηӧϯᏢ‫܄‬፦΢‫ޑ‬ৡ౦Ǵ౷жНླྀ⾺٠όႽНླྀ⾺ ΋ኬёаᛙ‫ۓ‬ӸӧǴ཮Ծρ‫׎‬ԋΒ౷ϯ‫(ނ‬2,2'-dithiodibenzaldehyde)Ǵ ሡाӆ೸ၸ΋٤ᗋচᏊ(ӵǺLiAlH4 ‫ ܈‬Ph3P)ஒ‫ځ‬ᗋচள‫ډ‬౷жНླྀ ⾺Ƕ2011 ԃǴ Lin ௲௤ว߄ൔᏤǴճҔ 2-ෛशҘ⾺଺ࣁଆ‫ނۈ‬Ǵ٠ ҔशㄽෛਂਆՐ౷ϯ‫ޑނ‬ύ໔‫ނ‬Ǵനࡕ‫׎‬ԋ౷চη೏शㄽ(Bz)ߥៈଆ ٰ‫ ޑ‬2-౷⇌शҘ⾺ 19 (Ԅ 2.13) Ƕ. (2.13). 2-1-3ǵ ǵ‫ن‬ٚථ-‫׆‬ᅟୗϸᔈ (Baylis-Hillman reaction) ϯᏢϸᔈ૸ፕ‫ޑ‬൩ࢂᅹ-ᅹᗖǵᅹ-ణᗖаϷᅹ-ᚇচηᗖ(ේǵ਼ǵ ౷฻)‫ޑ‬ғԋϷᘐ຋ǴّϞԖ೚ӭճҔၸ෠ߎឦୖᆶϸᔈ‫ޑ‬ΓӜϸᔈ ೏ቶ‫ݱ‬ᔈҔӧӝԋ฼ౣ΢ǹႽࢂ Suzuki couplingǵBuchwald-Hartwig 173 20.

(24) cross-coupling Ϸ Heck reaction ฻๱Ӝ‫ޑ‬ϸᔈǴ‫ॺך‬ᆀϐࣁԖᐒߎឦ ໽ϯϸᔈǹ೭٤ឦ‫ܭ‬ΓӜϸᔈӧӝԋϺฅ‫ނ‬΢ǴԖ๱ߚதख़ा‫ޑ‬ଅ᝘Ƕ ՠନΑԖᐒߎឦϸᔈаѦǴҔٰࡌᄬᅹ-ᅹᗖ‫ޑ‬ϸᔈԖ࣬྽ӭǴ аҘ୷Ό౎୷✉(methyl vinyl ketoneǴMVK)բࣁ‫ٯ‬ηǴԿϿԖϖᅿё ૈ‫ޑ‬ၡ৩ёаҔٰࡌҥཥ‫ޑ‬ᅹ-ᅹᗖǹёᙖҗ 1,2-уԋǵMichael уԋǵ კ 2.6ǹԶ೭٤ Aldol ϸᔈǵBaylis-Hillman Ϸ Diels-Alder ฻ϸᔈǴӵკ ϸᔈ࣬ၨ‫ܭ‬Ԗᐒߎឦϸᔈ೿ၨࣁᕉߥǴϸᔈచҹΨၨࣁྕ‫ک‬ǵ৒ܰ຾ ՉǴख़ᗺࢂ‫׳‬Ԗਏ౗аϷ಄ӝচη࿶ᔮ(atom-economic)Ǵ೭٤ϸᔈ‫ך‬ ॺᆀࣁ”Ԗᐒ໽ϯϸᔈ”(organocatalysis reactions)20ǹཀࡘࢂࡰǴӧϸ ᔈၸำύؒԖуΕҺՖ‫ߎޑ‬ឦ၂Ꮚٰ຾Չ໽ϯǴ໻ሡाճҔ΋٤֖Ԗ ේǵ਼ǵᕗ‫܈‬౷‫ޑ‬ϯӝ‫ނ‬Ǵ൩ёаߦ٬ϸᔈ‫ޑ‬วғǶ. კ 2.6ǵϖᅿёૈ‫ޑ‬ӝԋၡ৩ࡌᄬᅹ-ᅹᗖ. ‫ځ‬ύ‫ن‬ٚථ-‫׆‬ᅟୗϸᔈ(Baylis-Hillman reaction)Ǵࢂҗ α,β-όႫ ‫ک‬ϯӝ‫ނ‬ᆶᒃႝ၂Ꮚ(⾺ǵ✉)Ǵӧӝ፾‫ޑ‬໽ϯᏊբҔΠǴғԋ౎₩ αՏуԋౢ‫ޑނ‬ϸᔈǴғԋ‫౎ࣁނ‬Ч୷ᎇ (Ԅ 2.14) Ƕ 174 21.

(25) (2.14). 1968 ԃǴനԐҗВҁϯᏢৎහҖ଼΋(Ken-ichi Morita)ว౜Ǵ٬ ҔΟख़ᕗ(tricyclohexylphosphine)଺ࣁ໽ϯᏊǴёа٬ϸᔈวғ 21Ƕ 1972 ԃǴम୯ϯᏢৎӼܿѭ-‫ن‬ٚථ(Anthony B. Baylis)Ϸቺ୯ϯᏢৎ ఘᆢᅟ-‫׆‬ᅟୗ(Melville E. D. Hillman)‫ׯ‬๓Αჴᡍచҹ 22Ǵ٬Ҕࢥ‫܄‬ၨ ১‫ޑ‬Οભữ଺ࣁ໽ϯᏊ຾ՉϸᔈǴத‫ޑـ‬໽ϯᏊёаୖԵკ კ 2.723Ƕ‫܌‬ аΞᆀࣁහҖ-‫ن‬ٚථ-‫׆‬ᅟୗϸᔈ(Morita-Baylis-Hillman reaction)Ǵ‫܈‬ ‫ޣ‬ᙁᆀࣁ MBH ϸᔈ(MBH reaction)Ƕ. კ 2.7ǵதҔ‫ޑ‬Οભữ໽ϯᏊ 175 22.

(26) 2-4ǵ ǵჴᡍБ‫ݤ‬ 2-4-1ǵ΋૓ჴᡍБ‫ݤ‬ 1. ᅙᗺෳ‫سۓ‬ஒ‫ڰ‬ᡏኬࠔ࿼‫ܭ‬ЛಒᆅύǴ٬ҔMel−TEMP II ࠠᅙᗺ ෳ‫ۓ‬ሺෳ‫ۓ‬ϐǶ 2. ణਡᅶӅਁӀ᛼(1H-NMR)‫ک‬ᅹਡᅶӅਁӀ᛼(13C-NMR)߯٬Ҕ Bruker Avance 400ࠠ‫܈‬500ࠠਡᅶӅਁӀ᛼ሺǹ‫܌‬٬ҔྋᏊࣁ֖᤹ −ෛү(chloroform-d1, CDCl3)ǵ᤹−ΒҘ٥㿲(Dimethylsulfoxide-d6, DMSO-d6)ǶణਡᅶӅਁӀ᛼ϐϯᏢՏ౽΋૓߯а᤹−ෛү‫ූޑ‬੮ ෛү(CHCl3)‫ޑ‬ణ֎ԏঢ়δ = 7.26 ppm ‫܈‬ѤҘ୷‫ޖ‬₧δ = 0.00 ppm ࣁϣ୷ྗǴᅹਡᅶӅਁӀ᛼ϐϯᏢՏ౽΋૓߯а᤹−ෛү֎ԏঢ়δ = 77.23 ppm ࣁϣ୷ྗǶӀ᛼ൂՏ(δ)ࣁppmǴጠӝதኧൂՏ(Jȑࣁ Hzǹs (singlet)߄ൂ‫ݢ‬ঢ়ǹd (doublet)߄ᚈख़‫ݢ‬ঢ়ǹt (triplet)߄Οख़ ‫ݢ‬ঢ়ǹq (quartet)߄Ѥख़‫ݢ‬ঢ়ǹquint (quintet)߄ϖख़‫ݢ‬ঢ়ǹsext (sextet)߄Ϥख़‫ݢ‬ঢ়ǹbr (broadened)߄ቨ‫ݢ‬ঢ়ǹm (multiplet)߄ӭख़ ‫ݢ‬ঢ়Ƕ 3. ፦᛼ȐMSȑෳ‫߯ۓ‬٬ҔFinnigan TSQ 700 ࠠ‫࣬਻ޑ‬ቫ‫݋‬፦᛼ሺ‫܈‬ Finnigan MAT 95S ࠠ‫ޑ‬ଯਏૈ፦᛼ሺǴ໻ӈрமࡋεϷख़ा‫ޑ‬ှ ᚆ᎔ጕ(m/z)Ǵ‫࣬ځ‬ჹ୷ঢ়(base peak)‫ޑ‬ԭϩКமࡋӈӧࡴ۱ϣǴ ႝηናᔐෞᚆ‫(ݤ‬EI)ᚆηϯႝᓸࣁ70eVǶଯှ‫݋‬፦᛼(HRMS)߯௦ 192 23.

(27) ҔFinnigan MAT 95SǵFinnigan MAT-95XL ‫܈‬ǵFinnigan/Thermo Quest MAT ଯਏૈ፦᛼ሺϷJEOL HR/LR FAB mass spectroscopy(ύѧࣴ‫ز‬ଣ)ෳ‫ۓ‬ϐǶ 4. ଯਏ౗నᄊՅቫϩ‫݋‬ሺ/፦᛼ሺ(LC-MS)௦ҔHewlett Packard Seris 1100MSD ࠠǶ 5. ύᓸᆅࢊՅቫϩᚆ‫(ݤ‬medium-pressure column chromatography)߯ ٬ҔE. Merck Art. 9385 Kieselgel 60 (230−400 mesh)ೕ਱Ǵ‫܈‬MNG SILICA GEL 60 (70-230 mesh)ೕ਱‫ޖޑ‬ጤࣁᓉ࣬֎ߕᏊǹᖓቫՅ ቫϩ‫(݋‬TLC)߯٬ҔE.Merck silica gel 60 F254 ࣒ࠠዟᖓТ‫ࢂ܈‬᎑ ТǶ 6. ؑගᏊ(eluent)ǵ৖໒Ꮚ(developing solvent)‫ک‬๧‫܌ڗ‬٬Ҕ‫ޑ‬ྋᏊΒ ෛҘ₧ǵෛүǵΌ⾸ǵΌለΌ✊ǵ҅ρ₧ϷҘᎇࣣࣁACS ભǴ‫܈‬ ࢂаπ཰ભྋᏊ຾ՉᇃᚖપϯᕇளǶ 7. ჴᡍ٬Ҕϐϸᔈ၂ᏊǴྋᏊ‫ک‬ଳᔿᏊନԖ੝ਸຏܴѦǴ֡ᖼԾ MerckǵTCIǵAcrosǵAlderichǵShow ‫܈‬Lancaster Ϧљ٠҂຾Չ પϯԶ‫ޔ‬ௗ٬ҔǹਡᅶӅਁϩ‫݋‬Ҕ֖᤹ྋᏊ߾ᖼԾMerck ᆶඳܴ ϯπϦљǶ 8. ൂ඲X-rayᙅ৔ࢂ٬ҔNonius Kappa CCD Axis (୯ҥᆵ᡼ৣጄε ᏢϯᏢ‫)س‬Ƕ 193 24.

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