Tetrabutylammonium nitrate-trifluoroacetic anhydride, TBAN-TFAA, is a known nitrating agent for addition of NO2 to double bonds (J. Org. Chem., 2013, 78, 8442) and aromatic rings (Fieser and Fieser Reagents for Organic Synthesis, 2006).
A patent was issued last week (US Patent 10,028,962) that used TBAN-TFAA for the nitration 3-methylpyridine-2-carbonitrile that used 1.10 equiv TBAN and 1.12 equiv TFAA. This was a small scale reaction.
If this reaction would be considered for large scale, it may be worthwhile to consider using catalytic tetrabutylammonium salt (with a non-nucleophilic anion) and sodium nitrate in order to save the cost of the tetrabutylammonium salt. If any of you are aware if this has been tried and can disclose, please contact Marc Halpern of PTC Organics.
Tetrabutylammonium nitrate is made by ion exchange from an alkali nitrate with tetrabutylammonium chloride, bromide or hydrogen sulfate. Each of these quat salts has advantages and disadvantages from the standpoint of cost and thermodynamics, but the ion exchange unit operation costs money in all cases. A possible way to save money for a nitration using TBAN-TFAA would be to use a catalytic amount of tetrabutylammonium hydrogen sulfate and neutralize the proton with a non-aqueous base, then add stoichiometric sodium nitrate to the reaction (maybe potassium nitrate if the sodium salt doesn’t work due to lattice energy/structure).
As we teach in our 2-day course “Industrial Phase-Transfer Catalysis”, the affinity of a quaternary ammonium cation toward nitrate is about 1,000 times greater than for sulfate. That means that if we used, for example, 1 mole% tetrabutylammonium “sulfate” (neutralized hydrogen sulfate) and 1.1 equiv alkali metal nitrate, most of the tetrabutylammonium salt would be paired with nitrate and not with sulfate, even if the molar ratio of nitrate to sulfate were reversed at 1:100.
This is the basis for our speculation that the use of catalytic tetrabutylammonium hydrogen sulfate with just enough non-aqueous base to neutralize the proton (that will generate non-nucleophilic sulfate), plus the use of stoichiometric inorganic nitrate (with a cation that enables the nitrate anion to be physically available to the quat cation) has a good chance of forming tetrabutylammonium nitrate in situ under conditions that may not interfere with the trifluoroacetic anhydride.
If your company is continuously seeking ways to save money in commercial processes, now contact Marc Halpern of PTC Organics to explore opportunities to leverage highly specialized expertise in industrial phase-transfer catalysis with your internal company expertise to achieve low-cost high-performance green chemistry.
