22" is probably the standard track size you can use. However, i'd encourage you to get the largest possible curve radious in your layout, regardless of what locomotives you may or may not use. You can use flex track to accomplish this.
besides, there is no reason a C40-8W can't be run on your layout, its just that its a larger horsepower Roadswitcher, so it wouldn't normally be doing any of the dirty work. You'll be set with a GP40-2/GP38-2, or locomotives like Atlas's recent B30-7s, anything with 4 wheels to a truck.
do you have a picture of this 3x6? most likely, if its in a smaller scale or size, it can be remade bigger and maybe improoved.