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Synthesis of Anti-inflammatory Agents by Electrochemical Fixation of Carbon Dioxide

Research Project

Project/Area Number 10555314
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section展開研究
Research Field 有機工業化学
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

TOKUDA Masao  Hokkaido Univ.Grad.School of Eng., Prof., 大学院・工学研究科, 教授 (80001296)

Co-Investigator(Kenkyū-buntansha) 佐々木 皇美  通産省, 工業技術院北海道工業技術研究所・資源エネルギー基礎工学部, 技官(研究職)
SENBOKU Hisanori  Hokkaido Univ.Grad.School of Eng., Inst., 大学院・工学研究科, 助手 (50241360)
ORITO Kazuhiko  Hokkaido Univ.Grad.School of Eng., Asso.Prof., 大学院・工学研究科, 助教授 (20109482)
佐々木 〓美  通産省, 工技院・北海道工業技術・研究所資源エネルギー基礎工学部, 技官
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsAnti-inflammatory Agent / Ibuprofen / Naproxen / Loxoprofen / Fixation of Carbon Dioxide / Electroorganic Synthesis / Carboxylation / Microwave Irradiation / インドプロフェン / シクロプロフェン / フルルビプロフェン / ハロゲン化ビニル / ビニルトリフラート
Research Abstract

1. Synthesis of Anti-inflammatory Agents and Their Precursors
(1)Electrochemical carboxylation of vinyl halides -2-Aryl-2-propenoic acids were prepared in high yields by electrolysis of the corresponding aryl-substituted vinyl bromides in DMF in the presence of atmospheric pressure of carbon dioxide with a platinum cathode and a magnesium anode. 2-Aryl-2-propenoic acids, precursors of various anti-inflammatory agents such as ibuprofen, naproxen, and ketoprofen, were actually prepared in high yields by using this electrochemical carboylation and can readily be transformed into anti-inflammatory active compounds by enantioselectiev hydrogenation.
(2)Electrochemical carboxylation of aryl methyl ketones -Similar electrochemical carboxylation of aryl methyl ketones gave 2-aryl-2-hydroxypropanoic acids, precursors of anti-inflammatory agents, in high yields. This method was found to be very useful for a synthesis of loxoprofen.
(3)Electrochemical carboxylation of substituted benzyl halides -Sim … More ilar electrochemical carboxylation of 1-aryl-1-haloethanes gave a racemic mixture of anti-inflammatory agents in high yields.
2. Use of Supercritical Carbon Dioxide in the Synthesis of Anti-inflammatory Agents
Electrochemical fixation of carbon dioxide to vinyl bromides, aryl methyl ketones, and benzylic halides took place efficiently to give various anti-inflammatory agents when supercritical carbon dioxide was used both as a reagent and-a reaction medium.
3. Synthesis of Useful Carboxylic Acids by Electrochemical Carboxylation
Electrochemical carboxylation of aryl-substituted vinyl triflates, aliphatic vinyl triflates, and phenyl-substituted alkenes gave the corresponding α, β-unsaturated acids, β-keto carboxylic acids, and 2-phenylsuccinic acids in high yields.
4. Highly Efficient and Stereoselective Synthesis of Vinyl Halides by Microwave-induced Reaction
Highly efficient and stereoselective synthesis of(E)-and(Z)-vinyl halides, which are starting compounds for a synthesis of anti-inflammatory agents, was achieved in a short reaction time(1-2 min)by using microwave-induced reaction. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] H.Kamekawa,M.Tokuda et al.: "New Electrochemical Carboxylation of Vinyl Triflates. New Synthesis of β-Ketocarboxylic Acids"Tetrahedron Lett.. 39. 1591-1594 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 徳田昌生: "超臨界二酸化炭素を用いた電解合成"Electrochemistry. 67(10). 993-996 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 仙北久典,徳田昌生: "超臨界CO_2流体を利用した電解合成プロセス"化学装置. 41(2). 55-59 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku,M.Tokuda et al.: "Divergent Electrochemical Carboxylation of Vinyl Triflates : New Electrochemical Synthesis of Phenyl-substituted α,β-unsaturated Carboxylic Acids and Aliphatic β-Ketocarboxylic Acids"Electrochimica Acta. 45. 2995-3003 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] C.Kuang,M.Tokuda et al.: "Stereoselective Synthesis of (E)-β-Arylvinyl Halides by Microwave-Induced Hunsdiecker Reaction"Synlett. No.10. 1439-1442 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku,M.Tokuda et al.: "Efficient Electrochemical Dicarboxylation of Phenyl-substituted Alkenes : Synthesis of 1-Phenylalkane-1,2-dicarboxylic Acids"Synlett. No.3. 418-420 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 仙北久典,徳田昌生: "超臨界二酸化炭素中での電気化学的手法による有機合成(総説)"Jasco Report. 特集第4号. 1-6 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku,M.Tokuda et al.: "Stereochemical Study on Electrochemical Carboxylation of Vinyl Triflates"J.Electroanal.Chem.. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tokuda et al.: "「Novel Trends in Electroorganic Synthesis」, ed.by S.Tori(分担)"Synthesis of α,β-Unsaturated Carboxylic Acids by Electrochemical Carboxylation of Vinyl Bromides and Its Application to the Synthesis of Anti-inflammatory Agents""Springer-Verlag, Tokyo. 461(239-242) (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku et al.: "「Novel Trends in Electroorganic Synthesis」,ed.by S.Tori(分担)"New and Convenient Synthesis of 3-Methylene-4-pentenoic Acid by Electrochemical Carboxylation""Springer-Verlag, Tokyo. 461(243-244) (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Sasaki et al.: "「Novel Trends in Electroorganic Synthesis」,ed.by S.Tori(分担)"Electrochemical Carboxylation of Several Organic Halides in Supercritical Carbon Dioxide""Springer-Verlag, Tokyo. 461(245-246) (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Kamekawa et al.: "「Novel Trends in Electroorganic Synthesis」,ed.by S.Tori(分担)"Synthesis of β-Keto Acids by Electrochemical Carboxylation of Vinyl Triflates""Springer-Verlag, Tokyo. 461(247-248) (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 徳田昌生,仙北久典: "「超臨界流体プロセスの実用化」(分担執筆)有機カルボン酸の高効率合成"技術情報協会. 214(104-109) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 徳田昌生: "「電気化学便覧,第5版」(分担執筆)有機電解法"丸善. 756(281-285) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Kamekawa, H.Senboku, and M.Tokuda: "New Electrochemical Carboxylation of Vinyl Triflates-Synthesis of β-Keto Carboxylic Acids"Tetrahedron Lett.. 39. 1591-1594 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tokuda: "Electrosynthesis Using Supercritical Carbon Dioxide"Electrochemistry. 67. 993-996 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku and M.Tokuda: "Synthetic Process by Electrolysis using Supercritical Carbon Dioxide"KAGAKU SOUCHI(Plant and Process). 41(2). 55-59 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku, Y.Fujimura, H.Kamekawa, and M.Tokuda: "Divergent Electrochemical Carboxylation of Vinyl Triflates : New Electrochemical Synthesis of Phenyl-substituted α, β-Unsaturated Carboxylic Acids and Aliphatic β-Ketocarboxylic Acids"Electrochimica Acta. 45. 2995-3003 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] C.Kuang, H.Senboku, and M.Tokuda: "Stereoselective Synthesis of(E)-β-Arylvinyl Halides by Microwave-induced Hunsdiecker Reaction"Synlett. 1439-1442 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku, H.Komatsu, Y.Fujimura, and M.Tokuda: "Efficient Electrochemical Dicarboxylation of Phenyl-substituted Alkenes : Synthesis of 1-Phenylalkane-1, 2-dicarboxylic Acids"Synlett. 418-420 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku, H.Kanaya, and M.Tokuda: "Stereochemical Study on Electrochemical Carboxylation of Vinyl Triflates"J.Electroanal.Chem.. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku and M.Tokuda: "Organic Synthesis in Supercritical Carbon Dixoide by means of Electrochemical Method"Jasco Report, Special Issue. No.4. 1-6 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tokuda, H.Kamekawa, and H.Senboku: "Synthesis of α, β-Unsaturated Carboxylic Acids by Electrochemical Carboxylation of Vinyl Bromides and Its Application to the Synthesis of Anti-inflammatory Agents"Novel Trends in Electroorganic Synthesis, ed.by S.Torii, Springer-Verlag Tokyo. 239-242 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku, Y.Fujimura, A.Yoshikawa, H.Suginome, and M.Tokuda: "New and Convenient synthesis of 3-Methylene-4-pentenoic Acid by Electrochemical Carboxylation"Novel Trends in Electroorganic Synthesis, ed.by S.Torii, Springer-Verlag Tokyo. 2243-24* (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] A.Sakaki, H.Kudoh, H.Senboku, and M.Tokuda: "Electrochemical Carboxylation of Several Organic Halides in Supercritical Carbon Dioxide"Novel Torends in Electroorganic Synthesis, ed.by S.Torii, Springer-Verlag Tokyo. 245-246 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Kamekawa, H.Senboku, and M.Tokuda: "Synthesis of β-Keto Acids by Electrochemical Carboxylation of Vinyl Triflates"Novel Trends in Electroorganic Synthesis, ed.by S.Torii, Springer-Verlag Tokyo. 247-248 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tokuda and H.Senboku: "Highly Efficient Synthesis of Various Carboxylic Acids"Practical Application of Chemical Process in Spercritical Fluids, Gijutsu Jouhou Kyoukai. 104-109 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Tokuda: "Experimental Method in Organic Electrochemistry"Denkikagaku Binran, Maruzen. 281-285 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H.Senboku, M.Tokuda et al.: "Divergent Electrochemical Carboxylation of Vinyl Triflates : New Electro-Chemical Synthesis of Phenyl-substituted α, β-Unsaturated Carboxylic Acids and Aliphatic β-Ketocarboxylic Acids"Electrochimica Acta. 45. 2995-3003 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.Senboku, M.Tokuda et al.: "Stereochemical Study on Electrochemical Carboxylation of Vinyl Triflates"J.Electroanal.Chem.. (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] H.senboku, M.Tokuda et al.: "Efficient Electrochemical Dicarboxylation of Phenyl-substituted Alkenes : Synthesis of 1-Phenylalkane-1, 2-dicarboxylic Acids"Synlett. No.3. 418-420 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] C.kuang, M.Tokuda et al.: "Stereoselective Synthesis of (E)-β-Arylvinyl Halides by Microwave-Induced Hunsdiecker Reaction"Synlett. No.10. 1439-1442 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 仙北久典,徳田昌生: "超臨界二酸化炭素中での電気化学的手法による有機合成(総説)"Jasco Report. 特集第4号. 1-6 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 徳田昌生,仙北久典: "「超臨界流体プロセスの実用化」(分担執筆)有機カルボン酸の高効率合成"技術情報協会. 214(104-109) (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H. Senboku, M. Tokuda: "Divergent Electrochemical Carboxylation of Vinyl Triflates : New Electrochemical Synthesis of Phenyl-Substituted α,β-Unsaturated Carboxyicl Acids and Aliphatic β-Keto Carboxylic Acids"Electrochimica Acta. (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 徳田 昌生: "超臨界二酸化炭素を用いた電解合成"Electrochemistry. 67(10). 993-996 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Orito, M. Tokuda: "Synthesis of Phthalideisoquinoline and Protoberberine Alkaloids and Indclo[2,1-a]isoquinolines in a Divergent Route Involving Palladium(o)-catalyzed Carbonylation"J.Org.Chem. 64(18). 6583-6596 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 仙北久典,徳田昌生: "超臨界CO_2流体を利用した電解合成プロセス"化学装置. (2). 55-59 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H.Kamekawa: "New Electrochemical Carboxylation of Vinyl Triflates. Synthesis of β-Keto Carboxylic Acids" Tetrahedron Letters. 39. 1591-1594 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Senboku: "Divergent Electrochamical Carboxylation of Vinyl Triflates:New Electrochemical Synthesis of Phenyl-substituted α,β-Unsaturated Carboxylic Acids and aliphatic β-keto Carboxylic Acids" Electrochimica Acta. 44(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 仙北 久典: "超臨界CO_2流体を利用した電解合成プロセス" 化学装置. 41-2. 55-59 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Torii Ed.,: "「Novel Trends in Electroorganic Synthesis」(分担)“Synthesis of α,β-Unsaturated Carboxylic Acids by Electrochamical Carboxylation of Vinyl Bromides and Its Application to the Synthesis of Anti-inflammatory Agents"" Springer-Verlag, 461 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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