El-Gendy Adel A, Said Mohamed M, Ghareb Nagat, Mostafa Yasser M, El-Ashry El Sayed H
Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Arch Pharm (Weinheim). 2008 May;341(5):294-300. doi: 10.1002/ardp.200700161.
Condensation of aryl hydrazines with ethyl pyruvate gave the respective hydrazones 4-6; Fischer indolization led to substituted-1H-indole-2-carboxylic acid ethyl esters 7-9. The Mannich reaction of these compounds with formaldehyde and morpholine yielded ethyl 3-(morpholinomethyl)-substituted-1H-indole-2-carboxylates 10-12. The 5,7-dichloro-1H-indole-2-carbohydrazide 13 was cyclized with methyl orthoformate in DMF to give 6,8-dichloro[1,2,4]triazino[4,5-a]indol-1(2H)-one 14. Vilsmeier-Haack formylation of 7-9 gave ethyl 3-formyl-substituted-1H-indole-2-carboxylates 15-17 whose 2,2'-((5-chloro-2-(ethoxycarbonyl)-1H-indol-3-yl)methylene)bis-(sulfanediyl) diacetic acid 18 was prepared. The reaction of 15 and 16 with substituted anilines by conventional and microwave methods gave ethyl 3-(N-aryliminomethyl)-5-halo-1H-indole-2-carboxylates 19-29. In a cyclocondensation reaction of 19-25 with thiolactic acid or thioglycolic acid substituted indolylthiazolidinones 30-33 were prepared. Reaction of hydrazine hydrate with 15-17 did not give the respective hydrazones but directly led to the cyclized products substituted-3H-pyridazino[4,5-b]indol-4(5H)-ones 34-36, while a reaction with 2,4-dichlorophenylhydrazine yielded the uncyclized hydrazones. The chlorination of 35 and 36 with POCl3 gave pyridazino[4,5-b]indoles 39 and 40, respectively; reaction of the latter compounds with morpholine gave 4-(substituted-5H-pyridazino[4,5-b]indol-4-yl)morpholine 41 and 42. Mannich reaction of 34 with formaldehyde and N-ethylpiperazine gave 8-chloro-3-((4-ethylpiperazin-1-yl)methyl)-3H-pyridazino[4,5-b]indol-4(5H)-one 43. The microwave assistance of selected reactions has a profound effect on the reaction speed. The structures of the new compounds were confirmed by both analytical and spectral data. Some compounds were subjected to investigations concerning their antimicrobial, tranquilizing, and anticonvulsant activities.
芳基肼与丙酮酸乙酯缩合得到相应的腙4 - 6；费歇尔吲哚合成反应生成取代的1H - 吲哚 - 2 - 羧酸乙酯7 - 9。这些化合物与甲醛和吗啉进行曼尼希反应，得到3 -（吗啉甲基）取代的1H - 吲哚 - 2 - 羧酸乙酯10 - 12。5,7 - 二氯 - 1H - 吲哚 - 2 - 碳酰肼13与原甲酸甲酯在N,N - 二甲基甲酰胺中环化，得到6,8 - 二氯[1,2,4]三嗪并[4,5 - a]吲哚 - 1(2H) - 酮14。7 - 9经维尔斯迈尔 - 哈克甲酰化反应得到3 - 甲酰基取代的1H - 吲哚 - 2 - 羧酸乙酯15 - 17，其2,2'-((5 - 氯 - 2 -（乙氧羰基）- 1H - 吲哚 - 3 - 基）亚甲基）双 -（硫代二基）二乙酸18被制备出来。15和16与取代苯胺通过常规方法和微波方法反应，得到3 -（N - 芳基亚氨基甲基）- 5 - 卤代 - 1H - 吲哚 - 2 - 羧酸乙酯19 - 29。在19 - 25与硫代乳酸或硫代乙醇酸的环缩合反应中，制备出取代的吲哚基噻唑烷酮30 - 33。水合肼与15 - 17反应没有得到相应的腙，而是直接生成环化产物取代的3H - 哒嗪并[4,5 - b]吲哚 - 4(5H) - 酮34 - 36，而与2,4 - 二氯苯肼反应则生成未环化的腙。35和36用三氯氧磷氯化分别得到哒嗪并[4,5 - b]吲哚39和40；后两种化合物与吗啉反应得到4 -（取代的5H - 哒嗪并[4,5 - b]吲哚 - 4 - 基）吗啉41和42。34与甲醛和N - 乙基哌嗪进行曼尼希反应得到8 - 氯 - 3 -（（4 - 乙基哌嗪 - 1 - 基）甲基）- 3H - 哒嗪并[4,5 - b]吲哚 - 4(5H) - 酮43。所选反应的微波辅助对反应速度有深远影响。新化合物的结构通过分析和光谱数据得以确证。一些化合物进行了抗菌、镇静和抗惊厥活性的研究。
