Pyridine-N-oxide

Pyridine-N-oxide
Skeletal formula
Ball-and-stick model
Names
Preferred IUPAC name
1λ5-Pyridin-1-one
Other names
Pyridine-1-oxide
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.010.705 Edit this at Wikidata
EC Number
  • 211-774-6
UNII
  • InChI=1S/C5H5NO/c7-6-4-2-1-3-5-6/h1-5H checkY
    Key: ILVXOBCQQYKLDS-UHFFFAOYSA-N checkY
  • InChI=1/C5H5NO/c7-6-4-2-1-3-5-6/h1-5H
    Key: ILVXOBCQQYKLDS-UHFFFAOYAZ
  • c1cc[n+](cc1)[O-]
Properties
C5H5NO
Molar mass 95.101 g·mol−1
Appearance Colourless solid
Melting point 65 to 66 °C (149 to 151 °F; 338 to 339 K)
Boiling point 270 °C (518 °F; 543 K)
high
Acidity (pKa) 0.8 (of conjugate acid)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Pyridine-N-oxide is the heterocyclic compound with the formula C5H5NO. This colourless, hygroscopic solid is the product of the oxidation of pyridine. Its synthesis was first reported by Jakob Meisenheimer, who used peroxybenzoic acid as the oxidant. The compound is used infrequently as an oxidizing reagent in organic synthesis.

Structure

The structure of pyridine-N-oxide is very similar to that of pyridine with respect to the parameters for the ring. The molecule is planar. The N–O distance is 1.34 Å. The C–N–C angle is 124°, 7° wider than in pyridine.

Synthesis

The oxidation of pyridine can be achieved with a number of peroxy acids, including peracetic acid and peroxybenzoic acid. Oxidation can also be effected by a modified Dakin reaction using a urea–hydrogen peroxide complex, sodium perborate in acetic acid, catalytic methylrhenium trioxide (CH
3ReO
3) with sodium percarbonate or dimethyldioxirane.

Routes to pyridine-N-oxide.

Alternatively, glutaconaldehyde condenses with hydroxylamine to give pyridine N-oxide.: 51 

Reactions

Pyridine N-oxide is five orders of magnitude less basic than pyridine: the pKa of protonated pyridine-N-oxide is 0.8. Protonated derivatives are nevertheless isolable, e.g., [C5H5NOH]Cl. Further demonstrating its (feeble) basicity, pyridine-N-oxide also serves as a ligand in coordination chemistry. A host of transition metal complexes of pyridine-N-oxides are known.

Some electrophilic substitutions on pyridine rings are usefully effected using pyridine N-oxide followed by deoxygenation. The oxygen suppresses reaction at nitrogen atom and promotes substitution at the 2- and 4-carbons, particularly the 4 carbon.: 10–11, 14  For example, 4-nitropyridine can be prepared from nitrating pyridine-N-oxide and subsequent deoxygenation with PCl3. Deoxygenation can also be carried out with POCl3 to give 2-chloropyridines.

Preparation of 4-nitropyridine.

The ortho and para positions of pyridine-N-oxide derivatives are also active in nucleophilic substitution to a Polonovski reaction-like product.

Pyridine N-oxide is rather resistant to reduction. The electrochemical (half-wave) reduction potential is about -1.4 V relative to the saturated calomel electrode at neutral pH, rising to about -1.3 V at pH 3.5. For comparison, aliphatic and polyarene amine oxides are generally reduced between -0.2 and -0.8 V.: 91–93 

Pyridine-N-oxides are uncommon in nature. 2-(Methyldithio)pyridine-N-oxide and related compounds have been isolated from species of Allium.

The N-oxides of various pyridines are precursors to useful drugs:

Safety

The compound is a skin irritant.

See also

Further reading

References

  1. ↑ Meisenheimer, Jakob (1926). "Über Pyridin-, Chinolin- und Isochinolin-N-oxyd". Ber. Dtsch. Chem. Ges. (in German). 59 (8): 1848–1853. doi:10.1002/cber.19260590828.
  2. 1 2 Kilényi, S. Nicholas; Mousseau, James J. (20 September 2015). "Pyridine N-Oxide". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. pp. 1–6. doi:10.1002/047084289X.rp283.pub2. ISBN 9780470842898.
  3. ↑ Ülkü, D.; Huddle, B. P.; Morrow, J. C. (1971). "The Crystal Structure of Pyridine 1-oxide". Acta Crystallographica Section B: Structural Crystallography and Crystal Chemistry. 27 (2): 432–436. Bibcode:1971AcCrB..27..432U. doi:10.1107/S0567740871002334.
  4. 1 2 Mosher, H. S.; Turner, L.; Carlsmith, A. (1953). "Pyridine-N-oxide". Org. Synth. 33: 79. doi:10.15227/orgsyn.033.0079.
  5. ↑ Varma, Rajender S.; Naicker, Kannan P. (1999). "The Urea−Hydrogen Peroxide Complex: Solid-State Oxidative Protocols for Hydroxylated Aldehydes and Ketones (Dakin Reaction), Nitriles, Sulfides, and Nitrogen Heterocycles". Org. Lett. 1 (2): 189–192. doi:10.1021/ol990522n.
  6. ↑ McKillop, Alexander; Kemp, Duncan (1989). "Further functional group oxidations using sodium perborate". Tetrahedron. 45 (11): 3299–3306. doi:10.1016/S0040-4020(01)81008-5.
  7. ↑ Jain, Suman L.; Joseph, Jomy K.; Sain, Bir (2006). "Rhenium-Catalyzed Highly Efficient Oxidations of Tertiary Nitrogen Compounds to N-Oxides Using Sodium Percarbonate as Oxygen Source". Synlett. 2006 (16): 2661–2663. doi:10.1055/s-2006-951487.
  8. ↑ Ferrer, Marta; Sánchez-Baeza, Francisco J.; Messeguer, Angel (17 November 1997). "On the preparation of amine N-oxides by using dioxiranes". Tetrahedron. 53 (46): 15877–15888.
  9. 1 2 3 4 Ochiai Eiji (1967). Aromatic Amine Oxides. Translated by Mizoguchi, Dorothy U. Amsterdam: Elsevier. p. 11. LCCN 66-25764.
  10. ↑ Chmurzyński, L. (1996). "Studies on correlations of acid-base properties of substituted pyridine N-oxides in solutions. Part 1. Correlations of the p Ka values in non-aqueous solvents and water". Analytica Chimica Acta. 321 (2–3): 237–244. doi:10.1016/0003-2670(95)00594-3.
  11. ↑ Campeau, Louis-Charles; Fagnou, Keith (2011). "Synthesis of 2-aryl Pyridines By Palladium-catalyzed Direct Arylation of Pyridine N-oxides". Org. Synth. 88: 22. doi:10.15227/orgsyn.088.0022.
  12. ↑ Wan, Zhidong; Fang, Zheng; Yang, Zhao; Lie, Chengkou; Gu, Jiajia; Guo, Kai (April 2015). "A two-step continuous flow synthesis of 4-nitropyridine". Journal of Chemical Research. 39 (4): 209–212.
  13. ↑ Jung, Jae-Chul; Jo, Young-Jo; Park, Oee-Sook (9 November 2006). "Preparation of 2-chloropyridine". Synthetic Communications. 31 (16): 2507–2511.
  14. ↑ o'Donnell, Gemma; Poeschl, Rosemarie; Zimhony, Oren; Gunaratnam, Mekala; Moreira, Joao B. C.; Neidle, Stephen; Evangelopoulos, Dimitrios; Bhakta, Sanjib; Malkinson, John P.; Boshoff, Helena I.; Lenaerts, Anne; Gibbons, Simon (2009). "Bioactive Pyridine- N -oxide Disulfides from Allium stipitatum". Journal of Natural Products. 72 (3): 360–365. Bibcode:2009JNAtP..72..360O. doi:10.1021/np800572r. PMC 2765505. PMID 19093848.
  15. ↑ Shimizu, Shinkichi; Watanabe, Nanao; Kataoka, Toshiaki; Shoji, Takayuki; Abe, Nobuyuki; Morishita, Sinji; Ichimura, Hisao (2000). "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399. ISBN 3527306730.