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

电化学固定二氧化碳合成抗炎剂

• 批准号: 10555314
• 负责人: TOKUDA Masao
• 金额: $ 6.91万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10555314/
• 关键词: 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 … 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 AgentsElectrochemical 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 CarboxylationElectrochemical 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 ReactionHighly 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

1.抗炎剂及其前体的合成(1)在大气压二氧化碳存在下，用铂阴极和镁阳极电解相应的芳基取代的溴乙烯在DMF中，高收率地电化学羧化卤代乙烯-2-芳基-2-丙烯酸。 2-芳基-2-丙烯酸是布洛芬、萘普生和酮洛芬等多种抗炎药物的前体，实际上通过这种电化学羧化反应可以高产率地制备出2-芳基-2-丙烯酸，并且可以通过对映选择性氢化很容易地将其转化为抗炎活性化合物。(2)芳基甲基酮的电化学羧化 -芳基甲基酮的类似电化学羧化反应以高产率产生 2-芳基-2-羟基丙酸（抗炎剂的前体）。该方法被发现对于洛索洛芬的合成非常有用。(3)取代苄基卤化物的电化学羧化-Sim ... More 1-芳基-1-卤代乙烷的电化学羧化得到了高产率的外消旋抗炎剂混合物。2．超临界二氧化碳在抗炎剂合成中的应用当超临界二氧化碳同时用作试剂和反应介质时，二氧化碳可以有效地电化学固定在溴乙烯、芳基甲基酮和苄基卤上，从而得到各种抗炎剂。 3．通过电化学羧化合成有用的羧酸芳基取代的乙烯基三氟甲磺酸酯、脂肪族乙烯基三氟甲磺酸酯和苯基取代的烯烃的电化学羧化得到相应的α、β-不饱和酸、β-酮基羧酸和2-苯基琥珀酸。 产量.4。微波诱导反应高效立体选择性合成卤代乙烯利用微波诱导反应，在短反应时间（1-2 分钟）内实现了（E）-和（Z）-卤代乙烯的高效立体选择性合成，（E）-和（Z）-卤代乙烯是合成抗炎剂的起始化合物。较少的

项目成果

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)

H. Senboku 等人：“有机电合成的新趋势”，S. Tori（撰稿人）编辑，“通过电化学羧化作用的 3-亚甲基-4-戊烯酸的新且方便的合成”Springer-Verlag，东京 461（ 243-244) (1998)

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)

H.Kamekawa、H.Senboku 和 M.Tokuda：“乙烯基三氟甲磺酸酯的新型电化学羧化 - β-酮羧酸的合成”Tetrahedron Lett.. 39. 1591-1594 (1998)

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)

H.Senboku、H.Komatsu、Y.Fujimura 和 M.Tokuda：“苯基取代烯烃的高效电化学二羧化：1-苯基烷烃-1, 2-二羧酸的合成”Synlett。

H.Senboku, H.Kanaya, and M.Tokuda: "Stereochemical Study on Electrochemical Carboxylation of Vinyl Triflates"J.Electroanal.Chem.. (in press.).

H.Senboku、H.Kanaya 和 M.Tokuda：“乙烯基三氟甲磺酸酯电化学羧化的立体化学研究”J.Electroanal.Chem..（印刷中）。

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)

A.Sakaki、H.Kudoh、H.Senboku 和 M.Tokuda：“超临界二氧化碳中几种有机卤化物的电化学羧化”Novel Torends in Electroorganic Synthesis，S.Torii 编，Springer-Verlag Tokyo。