2-Pyridone

2-Pyridone
2-Pyridone
2-Pyridone
2-Pyridone molecule (lactam form)
2-Pyridone molecule (lactim form)
Names
Preferred IUPAC name
Pyridin-2(1H)-one
Other names
2(1H)-Pyridinone
2(1H)-Pyridone
1H-Pyridine-2-one
2-Pyridone
1,2-Dihydro-2-oxopyridine
1H-2-Pyridone
2-Oxopyridone
2-Pyridinol
2-Hydroxypyridine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.005.019 Edit this at Wikidata
EC Number
  • 205-520-3
KEGG
RTECS number
  • UV1144050
UNII
  • InChI=1S/C5H5NO/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7) checkY
    Key: UBQKCCHYAOITMY-UHFFFAOYSA-N checkY
  • InChI=1/C5H5NO/c7-5-2-1-3-6-4-5/h1-4,7H
    Key: GRFNBEZIAWKNCO-UHFFFAOYAT
  • InChI=1/C5H5NO/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7)
    Key: UBQKCCHYAOITMY-UHFFFAOYAK
  • lactim: Oc1ccccn1
  • lactam: C1=CC=CNC(=O)1
Properties
C5H5NO
Molar mass 95.101 g·mol−1
Appearance Colourless crystalline solid
Density 1.39 g/cm3
Melting point 107.8 °C (226.0 °F; 380.9 K)
Boiling point 280 °C (536 °F; 553 K) decomp.
Solubility in other solvents Soluble in water,
methanol, acetone
Acidity (pKa) 11.65
UV-vis (λmax) 293 nm (ε 5900, H2O soln)
Structure
Orthorhombic
planar
4.26 D
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 irritating
GHS labelling:
GHS06: ToxicGHS07: Exclamation mark
Danger
H301, H315, H319, H335
P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability (yellow): no hazard codeSpecial hazards (white): no code
2
1
Flash point 210 °C (410 °F; 483 K)
Related compounds
Other anions
 2-Pyridinolate
Other cations
 2-Hydroxypyridinium-ion
alcohol, lactam, lactim,
pyridine, ketone
Related compounds
 pyridine, thymine, cytosine,
uracil, benzene
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkYX markN ?)

2-Pyridone is an organic compound with the formula C
5H
4NH(O). It is a colourless solid. It is well known to form hydrogen bonded dimers and it is also a classic case of a compound that exists as tautomers.

Tautomerism and aggregation

Pyridone is tautomeric with 2-hydroxypyridine:

tautomerism
tautomerism

Similar lactam-lactim tautomerism can also be exhibited in many related compounds.

The tautomerization has been exhaustively studied. The energy difference appears to be very small, and the dominant tautomer depends strongly on the phase of matter. The energy difference in the gas phase was measured by IR spectroscopy to be 2.43 to 3.3 kJ/mol for the solid state and 8.83 to 8.95 kJ/mol for the liquid state. The predominant solid state form is 2-pyridone, as confirmed by X-ray crystallography and IR spectroscopy.[citation needed] Non-polar solvents generally favour 2-hydroxypyridine whereas polar solvents such as alcohols and water favour the 2-pyridone.

In either case, the amide group can be involved in hydrogen bonding. 2-Pyridone, 2-hydroxypyridine, and substituted derivatives can form dimers with two hydrogen bonds...

dimer

...but X-ray crystallography indicates that the parent compounds do not so dimerize in the solid state; instead, the 2-pyridones form a helical structure. Contrariwise, some substituted 2-pyridones, for example 5-methyl-3-carbonitrile-2-pyridone, adopt solid-state dimers.

In solution the dimeric form is present; the ratio of dimerisation is strongly dependent on the polarity of the solvent. Polar and protic solvents can hydrogen-bond directly to pyridone, and the equilibrium shifts towards the monomer. Hydrophobic effects in non-polar solvents lead to a predominance of the dimer.

In any given system, all possible tautomers and dimers can be present and form an equilibrium, and the exact measurement of all the equilibrium constants is extremely difficult.

Tautomeric transition is generally believed to occur through multimolecular pathways. A monomolecular mechanism would require a forbidden 1-3 suprafacial transition state, and theoretical methods compute an energy barrier between 125 and 210 kJ/mol. Dimerisation, followed by double proton transfer and dissociation, is an autocatalytic path from one tautomer to the other. Protic solvents also mediate proton transfer during tautomerisation.

Synthesis

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

2-Pyridone synthesis from 2-pyran

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:

2-Pyridone synthesis from pyridine-N-oxide

In the Guareschi-Thorpe condensation cyanoacetamide reacts with a 1,3-diketone to a 2-pyridone. The reaction is named after Icilio Guareschi and Jocelyn Field Thorpe.

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. 2-Pyridone has a large effect on the reaction from activated esters with amines in nonpolar solvent, which is attributed to its tautomerisation and utility as a ditopic receptor. Proton transfer from 2-pyridone and its tautomer have been investigated by isotope labeling, kinetics and quantum chemical methods.

Coordination chemistry

2-Pyridone and some derivatives serve as ligands in coordination chemistry, usually as a 1,3-bridging ligand akin to carboxylate.

In nature

2-Pyridone is not naturally occurring, but a derivative has been isolated as a cofactor in certain hydrogenases.

Environmental behavior

2-Pyridone is rapidly degraded by microorganisms in the soil environment, with a half life less than one week.

Organisms capable of growth on 2-pyridone as a sole source of carbon, nitrogen, and energy have been isolated by a number of researchers. The most extensively studied 2-pyridone degrader is the gram-positive bacterium Arthrobacter crystallopoietes, a member of the phylum actinomycetota. Numerous actinomycetotes have been shown to degrade pyridine or alkyl-, carboxyl-, or hydroxyl-substituted derivatives.

2-Pyridone degradation is commonly initiated by mono-oxygenase attack, resulting in a diol, such as 2,5-dihydroxypyridine, which is metabolized via the maleamate pathway. Fission of the ring proceeds via action of 2,5-dihydroxypyridine monooxygenase, which is also involved in metabolism of nicotinic acid via the maleamate pathway. In the case of Arthrobacter crystallopoietes, at least part of the degradative pathway is plasmid-borne.

Analytical data

NMR spectroscopy

NMR data of 2-Pyridone

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):νmax (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 spectrometry

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

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References

See also

References

  1. ↑ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. P-44.4.1.8. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
  2. 1 2 3 Forlani L., Cristoni G., Boga C., Todesco P. E., Del Vecchio E., Selva S., Monari M. (2002). "Reinvestigation of tautomerism of some substituted 2-hydroxypyridines". Arkivoc. XI (11): 198–215. doi:10.3998/ark.5550190.0003.b18. hdl:2027/spo.5550190.0003.b18.
  3. ↑ Brown R. S., Tse A., Vederas J. C. (1980). "Photoelectro-Determined Core Binding Energies and Predicted Gas-Phase Basicities for the 2-Hydroxypyridine 2-Pyridone System". Journal of the American Chemical Society. 102 (3): 1174–1176. doi:10.1021/ja00523a050.
  4. ↑ Beak P. (1977). "Energies and Alkylation of Tautomeric Heterocyclic-Compounds - Old Problems New Answers". Acc. Chem. Res. 10 (5): 186–192. doi:10.1021/ar50113a006.
  5. 1 2 Abdulla H. I., El-Bermani M. F. (2001). "Infrared studies of tautomerism in 2-hydroxypyridine 2-thiopyridine and 2-aminopyridine". Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 57 (13): 2659–2671. Bibcode:2001AcSpA..57.2659A. doi:10.1016/S1386-1425(01)00455-3. PMID 11765793.
  6. 1 2 Yang H. W., Craven B. M. (1998). "Charge Density of 2-Pyridone". Acta Crystallogr. B. 54 (6): 912–920. doi:10.1107/S0108768198006545. PMID 9880899. S2CID 9505447.
  7. 1 2 Penfold B. R. (1953). "The Electron Distribution in Crystalline Alpha Pyridone". Acta Crystallogr. 6 (7): 591–600. Bibcode:1953AcCry...6..591P. doi:10.1107/S0365110X5300168X.
  8. 1 2 Ohms U., Guth H., Heller E., Dannöhl H., Schweig A. (1984). "Comparison of Observed and Calculated Electron-Density 2-Pyridone, C5H5NO, Crystal-Structure Refinements at 295K and 120K, Experimental and Theoretical Deformation Density Studies". Z. Kristallogr. 169: 185–200. doi:10.1524/zkri.1984.169.14.185. S2CID 97575334.
  9. 1 2 Almlöf J., Kvick A., Olovsson I. (1971). "Hydrogen Bond Studies Crystal Structure of Intermolecular Complex 2-Pyridone-6-Chloro-2-Hdroxypyridine". Acta Crystallogr. B. 27 (6): 1201–1208. doi:10.1107/S0567740871003753.
  10. ↑ Aue DH, Betowski LD, Davidson WR, Bower MT, Beak P (1979). "Gas-Phase Basicities of Amides and Imidates - Estimation of Protomeric Equilibrium-Constantes by the Basicity methode in the Gas-Phase". Journal of the American Chemical Society. 101 (6): 1361–1368. Bibcode:1979JAChS.101.1361A. doi:10.1021/ja00500a001.
  11. ↑ Frank J., Alan R. Katritzky (1976). "Tautomeric pyridines. XV. Pyridone-hydroxypyridine equilibria in solvents of different polarity". J Chem Soc Perkin Trans 2 (12): 1428–1431. doi:10.1039/p29760001428.
  12. 1 2 Fischer C. B., Steininger H., Stephenson D. S., Zipse H. (2005). "Catalysis of Aminolysis of 4-Nitrophenyl Acetate by 2-Pyridone". Journal of Physical Organic Chemistry. 18 (9): 901–907. doi:10.1002/poc.914.
  13. 1 2 L.-H. Wang, H. Zipse (1996). "Bifunctional Catalysis of Ester Aminolysis - A Computational and Experimental Study". Liebigs Ann. 1996 (10): 1501–1509. doi:10.1002/jlac.199619961003. Archived from the original on 2021-09-01. Retrieved 2021-09-01.
  14. 1 2 Hammes GG, Lillford PJ (1970). "A Kinetic and Equilibrium Study of Hydrogen Bond Dimerization of 2-Pyridone in Hydrogen Bonding Solvent". J. Am. Chem. Soc. 92 (26): 7578–7585. doi:10.1021/ja00729a012.
  15. 1 2 Rybakov V. R., Bush A. A., Babaev E. B., Aslanov L. A. (2004). "3-Cyano-4,6-dimethyl-2-pyridone (Guareschi Pyridone)". Acta Crystallogr E. 6 (2): o160–o161. Bibcode:2004AcCrE..60O.160R. doi:10.1107/S1600536803029295.
  16. 1 2 3 Gilchrist, T.L. (1997). Heterocyclic Chemistry ISBN 0-470-20481-8
  17. 1 2 Rawson J. M., Winpenny R. E. P. (1995). "The coordination chemistry of 2-pyridones and its derivatives". Coordination Chemistry Reviews. 139 (139): 313–374. doi:10.1016/0010-8545(94)01117-T.
  18. 1 2 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.
  19. 1 2 Sims, Gerald K., S (1985). "Degradation of Pyridine Derivatives in Soil". Journal of Environmental Quality. 14 (4): 580–584. Bibcode:1985JEnvQ..14..580S. doi:10.2134/jeq1985.00472425001400040022x.{{cite journal}}: CS1 maint: deprecated archival service (link)
  20. ↑ "Pyridin-N-oxydと酸無水物との反應" [Reaction between Pyridin-N-oxyd and acid anhydride]. Yakugaku Zasshi (in Japanese). 67 (3–4): 51–52. 1947. doi:10.1248/yakushi1947.67.3-4_51.
  21. ↑ Ochiai E (1953). "Recent Japanese Work on the Chemistry of Pyridine 1-Oxide and Related Compounds". The Journal of Organic Chemistry. 18 (5): 534–551. doi:10.1021/jo01133a010.
  22. ↑ Boekelheide V, Lehn WL (1961). "The Rearrangement of Substituted Pyridine N-Oxides with Acetic Anhydride1.2". The Journal of Organic Chemistry. 26 (2): 428–430. doi:10.1021/jo01061a037.
  23. ↑ I. Guareschi (1896). "Mem. Reale Accad. Sci. Torino II". {{cite journal}}: Cite journal requires |journal= (help)
  24. ↑ Baron, H., Remfry, F. G. P., Thorpe, J. F. (1904). "CLXXV.-The formation and reactions of imino-compounds. Part I. Condensation of ethyl cyanoacetate with its sodium derivative". J. Chem. Soc., Trans. 85: 1726–1761. doi:10.1039/ct9048501726. Archived from the original on 2020-09-14. Retrieved 2020-06-05.
  25. ↑ Fischer C. B., Polborn K., Steininger H., Zipse H. (2004). "Synthesis and Solid-State Structures of Alkyl-Substituted 3-Cyano-2-pyridones" (PDF). Zeitschrift für Naturforschung. 59 (59b): 1121–1131. doi:10.1515/znb-2004-1008. S2CID 98273691. Archived from the original (subscription required) on 2008-10-30. Retrieved 2006-11-07.
  26. ↑ Ensign JC, Rittenberg SC (1963). "A crystalline pigment produced from 2-hydroxypyridine by arthrobacter crystallopoietes n.sp". Archiv für Mikrobiologie. 47 (2): 137–153. Bibcode:1963ArMic..47..137E. doi:10.1007/BF00422519. PMID 14106078. S2CID 6389661.
  27. 1 2 Sims GK, O'Loughlin E, Crawford R (1989). "Degradation of pyridines in the environment" (PDF). CRC Critical Reviews in Environmental Control. 19 (4): 309–340. Bibcode:1989CRvEC..19..309S. doi:10.1080/10643388909388372. Archived from the original (PDF) on 2010-05-27.

Further reading

General

  1. Engdahl K., Ahlberg P. (1977). Journal of Chemical Research: 340–341. {{cite journal}}: Missing or empty |title= (help)
  2. Bensaude O, Chevrier M, Dubois J (1978). "Lactim-Lactam Tautomeric Equilibrium of 2-Hydroxypyridines. 1.Cation Binding, Dimerization and Interconversion Mechanism in Aprotic Solvents. A Spectroscopic and Temperature-Jump Kinetic Study". J. Am. Chem. Soc. 100 (22): 7055–7066. Bibcode:1978JAChS.100.7055B. doi:10.1021/ja00490a046.
  3. Bensaude O, Dreyfus G, Dodin G, Dubois J (1977). "Intramolecular Nondissociative Proton Transfer in Aqueous Solutions of Tautomeric Heterocycles: a Temperature-Jump Kinetic Study". J. Am. Chem. Soc. 99 (13): 4438–4446. Bibcode:1977JAChS..99.4438B. doi:10.1021/ja00455a037.
  4. Bensaude O, Chevrier M, Dubois J (1978). "Influence of Hydration upon Tautomeric Equilibrium". Tetrahedron Lett. 19 (25): 2221–2224. doi:10.1016/S0040-4039(01)86850-7.
  5. Hammes GG, Park AC (1969). "Kinetic and Thermodynamic Studies of Hydrogen Bonding". J. Am. Chem. Soc. 91 (4): 956–961. Bibcode:1969JAChS..91..956H. doi:10.1021/ja01032a028.
  6. Hammes GG, Spivey HO (1966). "A Kinetic Study of the Hydrogen-Bond Dimerization of 2-Pyridone". J. Am. Chem. Soc. 88 (8): 1621–1625. Bibcode:1966JAChS..88.1621H. doi:10.1021/ja00960a006. PMID 5942979.
  7. Beak P, Covington JB, Smith SG (1976). "Structural Studies of Tautomeric Systems: the Importance of Association for 2-Hydroxypyridine-2-Pyridone and 2-Mercaptopyridine-2-Thiopyridone". J. Am. Chem. Soc. 98 (25): 8284–8286. Bibcode:1976JAChS..98.8284B. doi:10.1021/ja00441a079.
  8. Beak P, Covington JB, White JM (1980). "Quantitave Model of Solvent Effects on Hydroxypyridine-Pyridone and Mercaptopyridine-Thiopyridone Equilibria: Correlation with Reaction-Field and Hydrogen-Bond Effects". J. Org. Chem. 45 (8): 1347–1353. doi:10.1021/jo01296a001.
  9. Beak P, Covington JB, Smith SG, White JM, Zeigler JM (1980). "Displacement of Protomeric Equilibria by Self-Association: Hydroxypyridine-Pyridone and Mercaptopyridine-Thiopyridone Isomer Pairs". J. Org. Chem. 45 (8): 1354–1362. doi:10.1021/jo01296a002.

Tautomerism