carbocations are frustrating

While looking for ways to update our organic lab curriculum, I came across an article in an article in J. Chem. Educ.that is a modification of a classic experiment in Williamson's Macroscale and Microscale Organic Experiments (Heath).

Williamson's experiment is an alkylation of 1,4-dimethoxybenzene with tert-butanol catalyzed by sulfuric acid. This reaction is a nice alternative EAS reaction to more traditional Friedel-Crafts alkylations for several reasons. It ties the chemistry of aromatic compounds to the chemistry of alcohols and carbocations. It is also similar to how such alkylations might be done on a larger scale industrially. Finally, it avoids using AlCl₃, which I would rather not use for many reasons. The only downside is the use of concentrated sulfuric acid.

The modification by Polito, Hamman, and Rhile in J. Chem. Educ. adds a nice twist: carbocation rearrangement. Instead of tert-butanol, they used 2-methyl-2-butanol and 3-methyl-2-butanol. They also leave the surprise for the students by not telling them that the products of both reactions are the same:



I was hoping to get similar results with tert-butanol and isobutanol, since we already had a lot of both, and isobutanol, the rearranging alcohol is way cheaper than 3-methyl-2-butanol ($60 per litre vs. $60 per 100 mL).

My student assistants and I tried the procedure as written (addition of H₂SO₄ over 15 minutes to 1,4-dimethoxybenzene and isobutanol in acetic acid on ice followed by 20 minutes stirring at RT) with isobutanol. The reaction was very uneventful. We isolated a very nice white solid that we recrystallized from ethanol. Sadly, our "product" (MP 54.0-55.0 ^oC) was 1,4-dimethoxybenzene (MP 56 ^oC).

We then repeated the experiment but left out the ice bath. The reaction mixture became warm to the touch and turned a deep red, which we hoped was the cyclohexadienyl carbocation intermediate. After work up, we isolated a slightly yellow solid that had a fruity smell (likely isobutyl acetate, the Fischer Esterification side product). After recrystallization from 1:1 ethanol:water, we were sad to discover that we had once again discovered a really complicated way to purify 1,4-dimethoxybenzene. The melting points of the crude solids also indicated acceptable purity 1,4-dimethoxybenzene.

Likely, isobutanol will require significantly more oomph to undergo this reaction since it is a primary alcohol. However, heating the reaction will increase conversion of isobutanol to isobutyl acetate and isobutylene, both of which are detrimental. 3-Methyl-2-butanol is a secondary alcohol, which is likely why it works.

Is this green enough? NO! While the procedure avoids organicky solvents (plus), it does use more than a full equivalent of concentrated sulfuric acid (minus). Purification may not be necessary (plus), but the reaction doesn't work (FAIL!). It doesn't matter what you do if you can't get that last one.