First, position. You have it heads up, you don't in 6-max. It makes a huge difference.
There's more to it, basically you need to play more to compensate for being in one of the blinds every hand. But, most of it is position. Consider the difference between what you should open UTG in 6-max and what you should open the button with. And, that is without having a discount and you need to get through 2 players.