Well, let's run the math- I'll figure for a 25 mph speed on a 26" bike- adjust accordingly.
A 26" bicycle covers 81.7" on one revolution or 6.8' (Pi x 26)
A mile is 5,280', so in 1 mile the wheel does 776 revolutions (5,280 / 6.8)
In 25 miles, the bike does 19,400 revolutions (776 x 25)
At 25 mph, that would equate to 323 revolutions per minute, rpm, of the wheel (19,400 / 60)
Now, the issue is to get the engine rpm reduced to 323 rpm to do 25 mph.
Figure a 25cc 2 stroke weed wacker would do 7,000 rpm (may be more, maybe less- adjust as needed)
To get 7,000 rpm to 323 rpm, divide 7,000 by 323 = 21.7
Total gear reduction needs to be 21.7:1- so here is the issue, for a chain and sprocket system without an intermediate reduction, we have a problem. A 10 tooth engine sprocket would require a 217 tooth wheel sprocket....that pretty big.
You would probably be better off with a friction drive. If you used a 1.25" engine roller with a 26" wheel, you have a reduction of 20.8:1 with nothing more needed.