Grant-in-Aid for Scientific Research (B).
|Allocation Type||Single-year Grants|
|Research Institution||HOKKAIDO UNIVERSITY|
TOKUDA Masao Hokkaido Univ.Grad.School of Eng., Prof., 大学院・工学研究科, 教授 (80001296)
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
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)
|Keywords||Anti-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|
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
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