Institut Pasteur, URA 2128 CNRS-Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris cedex 15 (France), Fax: (+33) 145688404.
Chemistry. 2010 Apr 19;16(15):4669-77. doi: 10.1002/chem.200903442. Epub 2010 Mar 23.
Our program, which has focused on the preparation of new pyrazole derivatives, has led us to report here an original and simplified preparation of ethyl 3-ethoxy-1H-pyrazole-4-carboxylate. This is based on the reaction of hydrazine monohydrochloride and diethyl 2-(ethoxymethylene)malonate. Further transformations of this key compound allowed the preparation of the two possible iodinated isomers, namely, 3-ethoxy-4-iodo- and 3-ethoxy-5-iodo-1H-pyrazole. These compounds have opened the way to a quick access to many original pyrazole series. As an illustration, we report here on the selectivity of N-arylation, by using the Lam and Cham method, the C4- and C5-arylation of some of these 3-ethoxypyrazole derivatives by using the Suzuki-Miyaura reaction, and C5-benzylation reactions by means of the Negishi reaction. This was followed by hydrolysis of the ethoxy group, which led to the corresponding pyrazol-3-one derivatives. As a conclusion of this work, we conducted an investigation into the regiochemistry of the condensation between diethyl 2-(ethoxymethylene)malonate and the hydrochloride salts of methyl, benzyl, or phenyl hydrazine.
我们的项目专注于新吡唑衍生物的制备，在此我们报告了一种新颖且简化的制备方法，即通过盐酸肼和二乙基亚甲基丙二酸二乙酯反应，制备 3-乙氧基-1H-吡唑-4-羧酸乙酯。进一步对该关键化合物进行转化，可以制备两种可能的碘代异构体，即 3-乙氧基-4-碘代和 3-乙氧基-5-碘代-1H-吡唑。这些化合物为快速制备许多原始吡唑系列化合物开辟了道路。作为说明，我们在此报告了 N-芳基化的选择性，使用 Lam 和 Cham 方法，通过 Suzuki-Miyaura 反应对这些 3-乙氧基吡唑衍生物的 C4-和 C5-芳基化，以及通过 Negishi 反应进行 C5-苄基化反应。然后水解乙氧基，得到相应的吡唑-3-酮衍生物。作为这项工作的结论，我们对二乙基亚甲基丙二酸二乙酯与甲、苄基或苯基肼盐酸盐之间的缩合反应的区域化学进行了研究。
