2-Pyridone

Chembox new
Name = 2-Pyridone
ImageFile = 2-pyridone.svg
ImageName = 2-Pyridone
IUPACName = 2-Pyridone
OtherNames = 2(1H)-Pyridinone,
2(1H)-Pyridone,
1-H-Pyridine-2-one,
1,2 Dihydro-2-oxopyridine,
1H-2-Pyridone, 2-Oxopyridone,
2-Pyridinol, 2-Hydroxypyridine
Section1 = Chembox Identifiers
SMILES = O=C1NC=CC=C1
CASNo = 142-08-5
RTECS = UV1144050
Section2 = Chembox Properties
Formula = C₅H₅NO
MolarMass = 95.10 g/mol
Appearance = Colourless crystalline solid
Density = 1.39 g/cm³, solid
Solvent = other solvents
SolubleOther = Soluble in water,
methanol, acetone
MeltingPt = 107.8 °C (381.0 K)
BoilingPt = 280 °C (553.2 K) decomposition
pKa = 11.65
pKb =
LambdaMax = 293 nm (ε 5900, H₂O soln)
Section3 = Chembox Structure
MolShape = planar
CrystalStruct = Orthorhombic
Dipole = 4.26 D
Section7 = Chembox Hazards
ExternalMSDS =
MainHazards = irritating
NFPA-H = 2
NFPA-F = 1
NFPA-R =
FlashPt = 210 °C
RPhrases = R36 R37 R38
SPhrases = S26 S37/39
Section8 = Chembox Related
OtherAnions = 2-Pyridinolate
OtherCations = 2-Hydroxypyridinium-ion
Function = functional groups
OtherFunctn = alcohol, lactam, lactim,
pyridine, ketone
OtherCpds = pyridine, thymine, cytosine,
uracil, benzene

2-Pyridone is an organic chemical compound with the formula chem|C|5|H|4|NH(O). This colourless crystalline solid is used in peptide synthesis. It is well known to form hydrogen bonded structures somewhat related to the base-pairing mechanism found in RNA and DNA. It is also a classic case of a molecule that exists as tautomers.

tructure

The most prominent feature of 2-pyridone is the amide group; a nitrogen with a hydrogen bound to it and a keto group next to it. In peptides, amino acids are linked by this pattern, a feature responsible for some remarkable physical and chemical properties. In this and similar molecules, the hydrogen bound to the nitrogen is suitable to form strong hydrogen bonds to other nitrogen- and oxygen-containing species.

Tautomerism

The hydrogen attached to the nitrogen can also move to the oxygen. Through movement of this hydrogen and electrons, the second tautomer form, 2-hydroxypyridine is formed. This lactam lactim tautomerism can also be found in other molecules with a similar structure.

Tautomerism in the solid state

The predominant solid state form is 2-pyridone. This has been confirmed by X-ray crystallography which shows that the hydrogen in solid state is closer to the nitrogen than to the oxygen (because of the low electron density at the hydrogen the exact positioning is difficult), and IR-spectroscopy, which shows that the C=O longitudinal frequency is present whilst the O-H frequencies are absent. [cite journal
author= Yang H. W., Craven B. M. | title=Charge Density of 2-Pyridone | journal= Acta Crystallogr. Ser. B54| year=1998 | pages=912–920|doi=10.1107/S0108768198006545 ] [cite journal
author= Penfold B. R. |title= The Electron Distribution in Crystalline Alpha-Pyridone | journal=Acta Crystallogr. | year=1953 | pages=591–600 | volume=6 |doi=10.1107/S0365110X5300168X ] [] []

Tautomerism in solution

The determination of which of the two tautomeric forms is present in solution has been the subject of many publications. The energy difference appears to be very small and is dependent on the polarity of the solvent. Non-polar solvents favour the formation of 2-hydroxypyridine whereas polar solvents such as alcohols and water favour the formation of 2-pyridone.cite journal
author= Forlani L., Cristoni G., Boga C., Todesco P. E., Del Vecchio E., Selva S., Monari M. | title=Reinvestigation of tautomerism of some substituted 2-hydroxypyridines | journal=ARKIVOC | year = 2002 | pages =198–215 | volume=XI |url = http://arkat-usa.org/home.aspx?VIEW=MANUSCRIPT&MSID=590&SEARCH=2-hydroxypyridines | format=Dead link|date=May 2008 ] [cite journal
author= Vögeli U., von Philipsborn W.| title=C-13 and H-1 NMR Spectroscopie Studies on Structure of N-Methyle-3-Pyridone and 3-Hydroypyridine | journal= Org Magn Reson| year=1973| pages= 551–559| doi=10.1002/mrc.1270051202] [cite journal
author= Specker H., Gawrosch H.| title=Ultraviolet absorption of benztriaxole, pryridone and its salts. | journal= Chem. Ber.| year=1942| pages= 1338–1348| issue=75] [ cite journal
author= Leis D. G., Curran B. C. | title = Electric Moments of Some Gamma-Substituted Pyridines | journal=Journal of the American Chemical Society | year=1945 | pages=79–81 | issue=67 |doi = 10.1021/ja01217a028] [cite journal
author= Albert A., Phillips J. N.| title=Ionisation Constants of Heterocyclic Substances Hydroxy-Derivates of Nitrogenous Six-Membered Ring-Compounds
journal=J. Chem. Soc. | year=1956| pages= 1294–1304| doi=10.1039/jr9560001294] [cite journal
author= Cox R. H., Bothner-By A. A| title=Proton Magnetic Resonance Spectra of Tautomeric Substituted Pyridines and Their Conjugated Acides | journal=J. Phys. Chem. | year=1969 | pages=2465–2468 | issue=73|doi=10.1021/j100842a001 ] [cite journal
author=Aksnes DW, Kryvi | title=Substituent and Solvent Effects in Proton Magnetic -Resonance (PMR) Spectra of 6 2-Substituted Pyridines
journal=Acta. Chem. Scand. | year=1972| pages=2255–2266 | issue=26] [cite journal
author= Aue DH, Betowski LD, Davidson WR, Bower MT, Beak P| title=Gas-Phase Basicities of Amides and Imidates - Estimation of Protomeric Equilibrium-Constantes by the Basicity methode in the Gas-Phase | journal=Journal of the American Chemical Society | year=1979 | pages=1361–1368 | issue=101|doi=10.1021/ja00500a001] [cite journal
author=Frank J., Alan R. Katritzky | title= Tautomeric pyridines. XV. Pyridone-hydroxypyridine equilibria in solvents of different polarity| journal= J Chem Soc Perkin Trans 2 | year=1976 | pages=1428–1431 | doi= 10.1039/p29760001428]

The energy difference for the two tautomers in the gas phase was measured by IR-spectroscopy to be 2.43 to 3.3 kJ/mol for the solid state and 8.95 kJ/mol and 8.83 kJ/mol for the liquid state. [ cite journal
author=Brown R. S., Tse A., Vederas J. C. | title=Photoelectro-Determined Core Binding Energies and Predicted Gas-Phase Basicities for the 2-Hydroxypyridine 2-Pyridone System | journal=Journal of the American Chemical Society | year= 1980| pages= 1174–1176| issue=102|doi=10.1021/ja00523a050] [cite journal
author= Beak P.| title=Energies and Alkylation of Tautomeric Heterocyclic-Compounds - Old Problems New Answers | journal=Acc. Chem. Res. | year=1977 | pages=186–192 | issue=10|doi=10.1021/ar50113a006] []

Tautomerisation mechanism A

The single molecular tautomerisation has a forbidden 1-3 suprafacial transition state and therefore has a high energy barrier for this tautomerisation, which was calculated with theoretical methods to be 125 or 210 kJ/mol. The direct tautomerisation is energetically not favoured. There are other possible mechanisms for this tautomerisation. ^[16]

Dimerisation

2-Pyridone and 2-hydroxypyridine can form dimers with two hydrogen bonds. [cite journal| author= Hammes GG, Lillford PJ| title=A Kinetic and Equilibrium Study of Hydrogen Bond Dimerization of 2-Pyridone in Hydrogen Bonding Solvent | journal=J. Am. Chem. Soc. | year=1970 | pages=7578–7585 | issue=92| doi=10.1021/ja00729a012]

Aggregation in the solid state

In the solid state the dimeric form is not present; the 2-pyridones form a helical structure over hydrogen bonds. Some substituted 2-pyridones form the dimer in solid state, for example the 5-methyl-3-carbonitrile-2-pyridone. The determination of all these structures was done by X-ray crystallography.In the solid state the hydrogen is located closer to the oxygen so it could be considered to be right to call the colourless crystals in the flask 2-pyridone. ^[1-5]

Aggregation in solution

In solution the dimeric form is present; the ratio of dimerisation is strongly dependent on the polarity of the solvent. Polar and protic solvents interact with the hydrogen bonds and more monomer is formed. Hydrophobic effects in non-polar solvents lead to a predominance of the dimer. The ratio of the tautomeric forms is also dependent on the solvent. All possible tautomers and dimers can be present and form an equilibrium, and the exact measurement of all the equilibrium constants in the system is extremely difficult. ^[17-27]

(NMR-spectroscopy is a slow method, high resolution IR-spectroscopy in solvent is difficult, the broad absorption in UV-spectroscopy makes it hard to discriminate 3 and more very similar molecules).

Some publications only focus one of the two possible patterns, and neglect the influence of the other. For example, to calculation of the energy difference of the two tautomers in a non-polar solution will lead to a wrong result if a large quantity of the substance is on the side of the dimer in an equilibrium.

Tautomerisation mechanism B

The direct tautomerisation is not energetically favoured, but a dimerisation followed by a double proton transfer and dissociation of the dimer is a self catalytic path from one tautomer to the other. Protic solvents also mediate the proton transfer during the tautomerisation.

ynthesis

2-Pyrone can be obtained by a cyclisation reaction (above), and converted to 2-pyridone via an exchange reaction with ammonia.

Pyridine forms an N-oxide with some oxidation agents such as hydrogen peroxide. This pyridine-N-oxide undergoes a rearrangement reaction to 2-pyridone in acetic anhydride (above).

In the Guareschi-Thorpe condensation cyanoacetamide reacts with a 1,3-diketone to a 2-pyridone. [Gilchrist, T.L. (1997). Heterocyclic Chemistry ISBN 0470204818] [cite journal | author= Rybakov V. R., Bush A. A., Babaev E. B., Aslanov L. A. | title= 3-Cyano-4,6-dimethyl-2-pyridone (Guareschi Pyridone)| journal= Acta Crystallogr E | year=2004 | pages=o160-o161 | volume=6 |doi=10.1107/S1600536803029295 ] The reaction is named after Icilio Guareschi and Jocelyn Field Thorpe. [cite journal | author= I. Guareschi| journal= Mem. Reale Accad. Sci. Torino II | title=.| | volume= 46, 7, 11, 25 | year= 1896] [cite journal | author= Baron, H.; Remfry, F. G. P.; Thorpe, Y. F.| title=.| journal = J. Chem. Soc. 85 | volume= 1726 | year= 1904]

Chemical properties

Catalytic activity

2-Pyridone catalyses a variety of proton-dependent reactions, for example the aminolysis of esters. In some cases, molten 2-pyridone is used as a solvent. The mutarotation of sugars and that 2-pyridone has a large effect on the reaction from activated esters with amines in nonpolar solvent, which is attributed to its tautomerisation and ability to as a ditopic receptor. Current interest focuses on proton transfer from 2-pyridone and its tautomer, using isotope labeling, kinetics and quantum chemical methods were used on the mechanism to determine the rate determining step in the reaction. [cite journal
author= Fischer C. B., Steininger H., Stephenson D. S., Zipse H. | title=Catalysis of Aminolysis of 4-Nitrophenyl Acetate by 2-Pyridone | journal= Journal for Physical Organic Chemistry | year= 2005 | pages= 901–907|volume =18|issue=9 |doi=10.1002/poc.914] [cite journal
author= Fischer C. B., Polborn K., Steininger H., Zipse H. | title= Synthesis and Solid-State Structures of Alkyl-Substituted 3-Cyano-2-pyridones| journal=Zeitschrift für Naturforschung | year=2004 | pages=1121–1131 |issue=59b|url = http://www.znaturforsch.com/sb/s59b1121.pdf | format= subscription required ] [cite journal
author= L.-H. Wang, H. Zipse | title= Bifunctional Catalysis of Ester Aminolysis - A Computational and Experimental Study| journal=Lieb. Ann. | year=1996 | pages=1501-1509 |issue=10|url = http://www3.interscience.wiley.com/cgi-bin/fulltext/112345691/PDFSTART | format= subscription required ))]

Molecular recognition

The structures shown in the figure above are reminiscent of the base pairs found in the DNA or RNA. These dimers are sometimes used as simple models for base pairs in experimental and theoretical studies.

Coordination chemistry

2-Pyridone and some derivatives serve as ligands in coordination chemistry, usually as a 1,3-bridging ligand akin to carboxylate. [cite journal
author= Rawson J. M., Winpenny R. E. P.| title=The coordination chemistry of 2-pyridones and its derivatives| journal=Coordination Chemistry Reviews | year=1995 | pages=313–374| issue=139|doi=10.1016/0010-8545(94)01117-T]

In nature

2-Pyridone is not naturally occurring, but a derivative has been isolated as a cofactor in certain hydrogenases. [Shima, S.; Lyon, E. J.; Sordel-Klippert, M.; Kauss, M.; Kahnt, J.; Thauer, R. K.; Steinbach, K.; Xie, X.; Verdier, L. and Griesinger, C., "Structure elucidation: The cofactor of the iron-sulfur cluster free hydrogenase Hmd: structure of the light-inactivation product", Angew. Chem., Int. Ed., 2004, 43, 2547-2551.]

Analytical data

NMR spectroscopy

¹H-NMR

¹H-NMR (400 MHz, CD₃OD): /ρ = 8.07 (dd,³J = 2.5 Hz,⁴J = 1.1 Hz, 1H, C-6), 7.98 (dd,³J = 4.0 Hz,³J = 2.0 Hz, 1H, C-3), 7.23 (dd,³J = 2.5 Hz,³J = 2.0 Hz, 1H, C-5), 7.21 (dd,³J = 4.0 Hz,⁴J = 1.0 Hz, 1H, C-4).

¹³C-NMR

(100.57 MHz, CD₃OD): ρ = 155.9 (C-2), 140.8 (C-4), 138.3 (C-6), 125.8 (C-3), 124.4 (C-5)

UV/Vis spectroscopy

(MeOH):ν_max (lg ε) = 226.2 (0.44), 297.6 (0.30).

IR spectroscopy

(KBr): ν = 3440 cm^-1–1 (br, m), 3119 (m), 3072 (m), 2986 (m), 1682 (s), 1649 (vs), 1609 (vs), 1578 (vs), 1540 (s), 1456 (m), 1433 (m), 1364 (w), 1243 (m), 1156 (m), 1098 (m), 983 (m), 926 (w), 781 (s), 730 (w), 612 (w), 560 (w), 554 (w), 526 (m), 476 (m), 451 (w).

Mass-spectroscopy

EI-MS (70 eV): m/z (%) = 95 (100) [M⁺] , 67 (35) [M⁺ - CO] , 51 (4) [C₄H₃⁺] .

References

General references

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