Synthesis of Indeno[1,2-b]quinolin-10-ones via Pd/C-Assisted Dehydrogenation of 4b,5,10a,11-Tetrahydroindeno[1,2-b]quinolin-10-ones

Abstract

Recently, we have reported the synthesis of 4b,5,10a,11tetrahydroindeno[1,2-b]quinolin-10-ones starting from the acetates of Baylis-Hillman adducts as in Scheme 1. Indenoquinoline derivatives showed a wide range of biological activities such as 5-HT-receptor binding activity, antiinflammatory activity, and also act as antitumor agents, inhibitor for steroid reductase, acetylcholinesterase inhibitors, and antimalarials. These compounds could be synthesized via the aza-Bergman cyclization or via the radical cyclization of isonitrile derivatives. In these contexts, development of a facile synthetic method of indeno[1,2-b]quinoline derivatives would be very important. Thus, we examined the possibility for the synthesis of a variety of indenoquinolines from 4b,5,10a,11-tetrahydroindeno[1,2-b]quinolin-10-one (1a) as shown in Scheme 2. Oxidation of 1a with iodine in methanol would produce 10methoxy-11H-indeno[1,2-b]quinoline. Treatment of 1a with POCl3 followed by dehydrogenation would generate 10chloro-11H-indeno[1,2-b]quinoline. Dehydrogenation of 1a with Pd/C or with related oxidant might produce indeno[1,2b]quinolin-10-one (Scheme 2). Treatment of 1a with POCl3 showed the formation of intractable mixtures, unfortunately. Oxidation of 1a with FeCl3 in methanol (reflux, 3 days) produced low yield of indeno[1,2-b]quinolin-10-one (2a, 21%). The use of 2.5 equivalents of DDQ (benzene, reflux, 10 h) for the oxidation of 1a showed moderate yield of 2a (52%). After many trials, we found that dehydrogenation conditions using Pd/C in refluxing decaline generate 2a in good yield (83%). As shown in Table 1, we prepared some indeno[1,2-b]quinolines 2b-e similarly by using Pd/C. It is noteworthy that dechlorination occurred simultaneously for the chlorinesubstituted compounds 1c and 1e at refluxing temperature to give 2a as the major product instead of the desired 2c and 2e. But, fortunately, we could obtain the desired products 2c and 2e without dechlorination in good yields (75 and 68%, respectively) when we carried out the reaction at lower temperature (140 C). We tried next the oxidation of 1a with iodine in methanol, which resulted in the formation of iodinated compound 3a (49%) instead of the expected 10-