Whatever you do, skip Madisonville going to and from. That being said, be careful flying down OSR (old sorry road) some of the curves and bumps might catch you, and your gear, off guard.
45-OSR-39-21 is a zig zag and a good route, but he will be in 21 traffic. No use getting frustrated and causing a wreck by tailgating or passing, so I would advise just sit back and listen to some music.
45-75-21 is a good alternate if you don't want to do country roads, just be really really careful in Madisonville and OBEY the speed limit, especially on your way OUT of Madisonville. Also, that stretch between Madisonville and North Zulch is a killer road. People have died on those curves and passing when they shouldn't. Use this route going home as well. That way he will avoid the 21/45 junction that is a complete mess.
45-79-39-21 will put you going through some small towns that may pull you over if you are driving like a bat out of hell. A nice drive and pretty chill. Good chance you will have to pass a couple hay balers or trailers on 39 between Jewett and North Zulch.
I prefer the 45-OSR-39-21 route. I used to live in Normangee and my dad still ranches on 1452 so I feel like I know the area fairly well.
Just remind him to take it easy. There will be some looney toons on the road. The gas stations in Fairfield are going to be packed, as will Madisonville. Don't get gas at Exxon at 21/36, that guy is a horse's rear. Texas Burger has gone down hill so don't fall for the Nolan Ryan ads. Buc-ee's isn't worth the hassle unless it is really early morning or really late at night.