Reduction question

I've tried researching things like cyclisation, nitro reduction and all I've found is little to nothing. I know that for the 1st arrow I need to protect the carbonyl and the 2nd arrow is the carboxylic acid but I'm not sure how to go about with the reaction or mechanism. Can you someone guide me along please?


1 Answer 1


For the first arrow you are correct that you need to protect the ketone before reducing the nitro group. For this I would use a dimethyl ketal. There are many sets of conditions for this; trimethyl orthoformate in refluxing MeOH with catalytic PTSA is a good bet. This will also give the methyl ester of the carboxylic acid but that is of no consequence as it will be reacted in the next step. Your next step is then the nitro group reduction. I see no reason why you should not use hydrogenation, just don't have any acid present as that may remove the ketal and you still need that for step 3. The aniline thus produced will cyclise easily, just heat it in neutral solvent if it does not spontaneously cyclise. Step 3 is reduction of the amide, LiAlH4 should do this. Finally you deprotect the ketone with a mild acid hydrolysis.

For the second arrow reduction of the nitro group by hydrogenation will give indole-2-carboxylic acid by spontaneous cyclisation as formation of the aromatic [5] is favoured over the non-aromatic [6]. This has been reduced to your target indoline-2-carboxylic acid by sodium/liquid ammonia https://patents.google.com/patent/US4485241


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