I wouldn’t say backfired, exactly (yet, touch wood!) but I have had some complete non-starters. That is, I have worked and worked, but been completely unable to make a molecule, or new reaction. Failure is never nice, and it can hard to admit defeat, but part of research is knowing when problem solving isn’t going to work, and you should change project. It’s sad to see a project go too- you really have high hopes for everything you start!