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. 2022 Apr 19;28(22):e202200472.
doi: 10.1002/chem.202200472. Epub 2022 Mar 15.

Controlling Tautomerization in Pyridine-Fused Phosphorus-Nitrogen Heterocycles

J Nolan McNeill  1 , Lucas J Karas  2 , Jeremy P Bard  1 , Kevin Fabrizio  1 , Lev N Zakharov  3 , Samantha N MacMillan  4 , Carl K Brozek  1 , Judy I Wu  2 , Darren W Johnson  1 , Michael M Haley  1
Affiliations

Controlling Tautomerization in Pyridine-Fused Phosphorus-Nitrogen Heterocycles

J Nolan McNeill et al. Chemistry. .

Abstract

Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This tautomerization, initially observed in the solid state through X-ray crystallography, is also explained by computational analysis. We prepared an electron deficient analogue (2 e) with a fluorine on the pyridine ring and showed that the weakly basic pyridine resisted tautomerization, providing key insights to why the transformation occurs. To study the difference in solution vs. solid-state heterocycles, alkylated analogues that lock in the quinoidal tautomer were synthesized and their different 1 H NMR and UV/Vis spectra studied. Ultimately, we determined that all heterocycles are the aromatic tautomer in solution and all but 2 e switch to the quinoidal tautomer in the solid state. Better understanding of this transformation and under what circumstances it occurs suggest future use in a switchable on/off hydrogen-bond-directed receptor that can be tuned for complementary hydrogen bonding.

Keywords: NICS calculations; PN-heterocycles; X-ray crystallography; quinoidal; tautomerization.

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