Introduction

2-Hydroxypyridine (Figure 1), also known as 2-Pyridinol, is an important intermediate in organic synthesis, which has a wide range of applications in medicine, pesticides and so on. For example, it is an important intermediate for the synthesis of penicillin, as well as an important raw material for the synthesis of polyvinyl chloride pyridine resin, N-palladium dichloride bis (2-hydroxypyridine), 2-hydroxy-3,5-dinitropyridine copper salt and other catalysts. Pyridine is a class of N-heterocyclic organic pollutants which has high biological toxicity and long existed in the environment. 2-Hydroxypyridine is an important pyridine derivative and intermediate metabolite in the biodegradation of N-heterocyclic organic compounds such as pyridine and nicotine. It is more water soluble,more mobile,and more leachable into groundwater,soil,which causes widespread contamination in environment and threatens ecological environment and human health. Microbial degradation with the characteristics of high efficiency，low cost，no secondary pollution is an effective measure to remove the environment pollution of 2-hydroxypyridine, which has a good application prospect.[1-2]

Synthesis of 2-Hydroxypyridine

2-Hydroxypyridine was prepared by diazotization of 2-aminopyridine, dissoving in 20% sulfurie acid solution and putting NaNO₂, solution in excess of about 10% into the solution. The appropriate temperature of diazotization is 0~5℃, followed by an alkaline hydrolysis process in Na₂CO₃ solution. Thus, 2-hydroxypyridine was gained together with sodium sulfate. To purify the 2-hydroxypyridine needs methods of crystallization and recrystallization for extraction. At last high quality of 2-hydroxypyridine was synthesized with 98% content. And the yield could be satisfied as high as 78% or so. The time needed by the route is much shorter than that of the references, and has simpler operation than others. The process is very suitable for industrial.[1]

Why is 2-hydroxypyridine soluble in water but not 3-hydroxypyridine?

Molecular mechanics and semiempirical calculations using HyperChem 5 were carried out to investigate whether the results obtained can explain why2-hydroxypyridine is far more soluble in water than 3-hydroxypyridine. The results of molecular mechanics calculations show that in solution in water the total energy of 2-hydroxypyridine in the oxo form is less than that of 3-hydroxypyridine in the zwitterionic form by 2.14 kcal/mol. The difference is much greater for the AM1 optimized H-bonded molecules. The greater amount of energy released in dissolution and H-bond formation by 2-hydroxypyridine than by 3-hydroxypyridine together with a higher crystal lattice energy for the latter provide an explanation as to why 3-hydroxypyridine is much less soluble in water than 2-hydroxypyridine. When the predicted electronic spectral lines of the compounds were compared with the observed λmax values, it is found that generally the results obtained using AM1 agree more closely with the experimentally observed values.[3]

Photoionization of 2-hydroxypyridine

Researchers studied the photoionization of 2-pyridone and its tautomer, 2-hydroxypyridine by means of VUV synchrotron radiation coupled to a velocity map imaging electron/ion coincidence spectrometer. The photoionization efficiency (PIE) spectrum is composed of steps. The state energies of the [2-pyridone]+ cation in the x ground and ? excited electronic states,as well as of the [2-hydroxypyridine]+ cation in the electronic ground state, are determined.The slow photoelectron spectra (SPES) are dominated by the 00 transitions to the corresponding electronic states together with several weaker bands corresponding to the population of the pure or combination vibrational bands of the cations. These vibrationally-resolved spectra compare very well with state-of-the-art calculations. Close to the ionization thresholds, the photoionization of these molecules is found to be mainly dominated by a direct process whereas the indirect route (autoionization) may contribute at higher energies.[4]

Exploiting 2-hydroxypyridine as a design element

The unique primary and secondary coordination environments surrounding the active site of hydrogenase enzymes play a crucial role in H2 activation and transfer reactions. [Fe]-hydrogenase contains a 2-hydroxypyridine ligand motif, and many researchers have incorporated this design element into synthetic catalysts. Transition metal complexes supported by2-hydroxypyridine scaffolds are catalysts for chemical conversion schemes relevant to alternative energy applications and, in addition to hydrogenase-type reactivity, find new uses in other chemical domains. Catalysts incorporating the 2-hydroxypyridine motif use the pendent pyridinoate groups to aid in H+ and e transfer steps for catalytic hydrogenation, dehydrogenation and water oxidation.Barriers to H+ transfer can be minimized with an appropriate orientation of the pyridinoate groups to circumvent Grotthuss-type H+ transfer mechanisms, and thus, lower the entropic contributions to rate-determining steps in catalytic cycles. The principles described for hydrogenation/dehydrogenation will likely be adapted for hydrofunctionalization catalysis, or alternatively, many other reaction types that feature acidic/basic partners, as they may be cooperatively activated/transferred by 2-hydroxypyridine type units. Future frontiers in 2-hydroxypyridine-derived catalysis will involve the development of catalysts featuring earth-abundant metals,structurally faithful model complexes that exhibit catalytic reactivity of the native enzyme, and the expansion of 2-hydroxypyridine ligands into other catalytic reactions.[5]

References

[1]Xie L,et al. Study on Synthesis of 2-Hydroxypyridine[J].Shandong Chemical Industry,2014,43(09):13-15.DOI:10.19319/j.cnki.issn.1008-021x.2014.09.008.

[2]Lu P,et al. Advances in microbiological degradation of 2-hydroxypyridine[J].Journal of Biology,2020,37(02):78-82.

[3]Huq F, Yu JQ. Molecular modeling analysis: "Why is 2-hydroxypyridine soluble in water but not 3-hydroxypyridine?". J Mol Model. 2002;8(3):81-86. doi:10.1007/s00894-002-0073-1

[4]Poully JC, Schermann JP, Nieuwjaer N, et al. Photoionization of 2-pyridone and 2-hydroxypyridine. Phys Chem Chem Phys. 2010;12(14):3566-3572. doi:10.1039/b923630a

[5]Moore CM, Dahl EW, Szymczak NK. Beyond H?: exploiting 2-hydroxypyridine as a design element from [Fe]-hydrogenase for energy-relevant catalysis. Curr Opin Chem Biol. 2015;25:9-17. doi:10.1016/j.cbpa.2014.11.021