One big difference is the dimensionality, of 2d vs 3d. Even within the 3d space, quantum chemistry effects produce an even higher order of "effective" dimension

One big difference is the dimensionality, of 2d vs 3d. Even within the 3d space, quantum chemistry effects produce an even higher order of "effective" dimensionality. Finding stable paths that don't interact in 2d is hard, but easier in 3d. Its even easier in hyper dimensional spaces where other chemical properties can be used to provide pathways for only specific reactions.