Why would you want to make 2D animation look like 3D? Why not just do it in 3D? What’s the point of making 2D animation look like 3D? And it’s not possible anyway–it’ll take far too long as you’d need to paint every single frame and that’s just not feasible, unless you want to spend many decades on one single animation. There’s a reason why no one’s done it–it’s pretty much impossible, or very impractical.
If you want to learn how to paint realistic 2D, then that’s something different. Because we’re talking just one single image. If you want to do that, then this is what you need to do:
Have you actually tried to paint from reality or photo references before? If you’ve never even done it, then you need to start doing it, and lots of it.
There are specific ways different materials reflect light (plastic, metal, wood, skin, silk, etc.), as well as different types of textures. You need to actually try to paint those different materials convincingly in order to learn how to depict them accurately. So for example, you need to actually do some digital still life paintings of various types of objects in front of you, like these:
When you have painted enough of those, you’ll have experience depicting a wide range of different surface materials and forms. Ideally you’ll also vary the lighting on each too so you can also learn different how to depict lighting too, because the direction and quality of light can drastically alter how things appear.
If you don’t have a space where you can control the lighting and keep it consistent (such as using indoor light only, since outdoor light will constantly change throughout the day, and these still life studies can take many hours or days to complete), using good photo references is a good alternative (emphasis on “good” references with proper exposure, good lighting, good choice of subjects), such as these:
Other than still life, you’ll also want to tackle other subjects like people, animals, landscape, architecture, vehicles, etc. Do painting studies of those and you’ll become more familiar with different types of surfaces materials and forms and lighting.
Beyond doing those still life painting studies (study means you actually paint them, not just look at them), you’ll also need to learn about the foundations of visual art related to lighting, values, colors, shapes, forms, etc. There are very specific reasons why lighting works the way it does, or why different levels of specularity appear differently, or how color bleeds in radiosity, how shadows are cast, how to maintain value coherency, how the way you render values alters the way the form reads, etc. I actually teach all this (and so much more) in my online workshop, Becoming a Better Artist:
By combining foundation knowledge with painting studies, you’ll eventually be able to paint the kind of 2D works that have the realism of 3D works.
Now, if you apply that to your question about making 2D animation look like realistic 3D animation, imagining having to paint 24 frames of realistic digital painting for every second of animation. Just one frame will take you several hours to paint. Add up all those seconds for however long your animation will be–it’ll take you far too long. And also, you can’t just change your mind during the production about certain details like you can in 3D animation. In 3D you can swap out an entire character, change design, swap out materials, change colors and lighting, alter the animation, alter the camera movement, etc., and all you have to do is redo the renders. If you do it in 2D, you’d have to completely repaint everything that needs to be changed.