Some predict a bright future for 2-methyltetrahydrofuran. At least one company is patenting MeTHF products. For process chemists, MeTHF offers at least one advantage over THF, i.e., MeTHF is immiscible with water. Well, mostly. Your water phase is going to have some MeTHF in it and some water in the MeTHF phase. You don’t have to salt up your water to get a phase boundary or worse, do a solvent exchange for an extraction. An aqueous quench of a MeTHF reaction mixture should phase separate with the aqueous wash and allow aqueous extraction. This is certainly convenient for the chemist, but at a price.
Last time I looked, MeTHF is about twice as expensive as THF. For small scale bench work, the cost differential isn’t too onerous. If you’re talking about filling a 5,000 liter reactor with it, the costs do add up. So, a defensible process improvement/change would have to yield at least the differential solvent cost and probably another 10-25 % to justify the cost of process validation and change management.
Some process changes will require customer approval and product validation on their side. Then, they’ll want a price concession for all of the trouble you put them through. So a switch to MeTHF over, say, THF will have to yield some bottom-line value to the manufacturer and the customer. It is always better to fold in your innovations before you submit your process to the plant people.
The other issue with MeTHF has to do with it’s chirality. For instance, MeTHF-metal complexes will be solvated by either or both enantiomers. The presence of diastereomeric complexes will only complicate in-process NMR checks of such processes. Though certainly not a show-stopper, it is a complication that the analytical crew will have to contend with.
Lamentations on Chemistry 
Disclosure: I am working for Penn Specialty Chemicals Inc. the dominant player in the MeTHF market
Another important advantage for MeTHF is the fact that it makes a rich azeotrope with water at atmospheric pressure.
In conclusion, MeTHF offers the combined advantage of the “THF-like” chemical properties and “toluene-like” physical properties.
In many cases, this will more than compensate for the MeTHF price on a solvent variable cost comparable basis.
A cost-benefit analysis has recently been published and is available for download from our web-site http://www.pschem.com
Thanks for the comment. I guess my post sounds more critical than I really am. I am a fan of MeTHF and would like to see it integrated into process chemistry to a much greater extent. The issue is, are there any home runs associated with MeTHF? Process chemists need to know about MeTHF so they can implement it into their development. As a former sales and marketing guy, I’d recommend that MeTHF manufacturers get grad students working with it. If they have good luck with it in their grad work, they’s have it in their tool box when they get into industry. That strategy is part of what is behind the stunning success of SAF, in my opinion at least.
Thank you for this suggestion. Point taken.
To respond to your question, 2-MeTHF is a home run today. In less than two years MeTHF has gained good market share at the loss of THF and the present market penetration rate is spectacular. Strong sales show that the solvent has real value.
Penn Specialty Chemicals has put together the little information available in the literature about MeTHF. We also tried to bridge some knowledge gaps with a well targeted R&D program. The results of these findings along with several articles published in the literature are concentrated on our website http://www.pschem.com
Nevertheless, you are right; the need for more knowledge sharing is a real one.
Unfortunately, in spite of hundreds of projects with MeTHF under current development inside the big pharma houses, there are no publications coming out for obvious reasons.
Gaussling, with your permission, I would like to bring this website to the attention of the scientists who are already working with MeTHF in the industrial labs. Some of them might choose to share information that is relevant for other users. I have on my Rolodex quite a few of them.
Is this OK with you?
You are free to do as you please, of course. I have personally met with the good folks at Penn Specialties at numerous trade shows. I write anonamously because I want the blog to be about ideas, not me. I have an interest in RMgX and am only too anxious to see new process solvents like MeTHF come into broader use. But it is the “cure looking for a disease” problem. Unless you can cite an example of the utility, folks are reluctant to try it. It is a common problem in the specialty chemical business.
I have been on a political jag lately that is just about spent. I guess there really is some interest in issues like this.
Cheers!