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
CAS Number	694-59-7 ;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:29136 ;
ChEMBL	ChEMBL3278446;
ChemSpider	12229 ;
EC Number	211-774-6;
PubChem CID	12753;
UNII	91F12JJJ4H ;
	InChI InChI=1S/C5H5NO/c7-6-4-2-1-3-5-6/h1-5H Key: ILVXOBCQQYKLDS-UHFFFAOYSA-N ; InChI=1/C5H5NO/c7-6-4-2-1-3-5-6/h1-5H Key: ILVXOBCQQYKLDS-UHFFFAOYAZ;
	SMILES c1cc[n+](cc1)[O-];
Properties
Chemical formula	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)
Solubility in water	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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	Infobox references

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.^[1] The compound is used infrequently as an oxidizing reagent in organic synthesis.^[2]

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.^[3]

Synthesis

The oxidation of pyridine can be achieved with a number of peroxy acids, including peracetic acid and peroxybenzoic acid.^[4] Oxidation can also be effected by a modified Dakin reaction using a urea–hydrogen peroxide complex^[5], sodium perborate in acetic acid^[6], catalytic methylrhenium trioxide (CH₃ReO₃) with sodium percarbonate^[7] or dimethyldioxirane.^[8]

Reactions

Pyridine N-oxide is five orders of magnitude less basic than pyridine: the pK_a of protonated pyridine-N-oxide is 0.8.^[9] Protonated derivatives are isolable, e.g., [C₅H₅NOH]Cl.^[4] 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. Addition of oxygen suppresses further reactions at nitrogen atom and promotes substitution at the 2- and 4-carbons.^[10] For example, 4-nitropyridine can be prepared from nitrating pyridine-N-oxide and subsequent deoxygenation with PCl₃.^[11] Deoxygenation can also be carried out with POCl₃ to give 2-chloropyridines.^[12]

Related pyridine-N-oxides

Pyridine-N-oxides are uncommon in nature. 2-(Methyldithio)pyridine-N-oxide and related compounds have been isolated from species of Allium.^[13]

The N-oxides of various pyridines are precursors to useful drugs:^[14]

Nicotinic acid N-oxide, derived from nicotinic acid is a precursor to niflumic acid and pranoprofen.
2,3,5-Trimethylpyridine N-oxide is a precursor to the drug omeprazole
2-Chloropyridine N-oxide is a precursor to the fungicide zinc pyrithione

Safety

The compound is a skin irritant.^[2]

References

↑ Meisenheimer, Jakob (1926). "Über Pyridin-, Chinolin- und Isochinolin-N-oxyd" (in German). Ber. Dtsch. Chem. Ges. 59 (8): 1848–1853. doi:10.1002/cber.19260590828.
↑ ^2.0 ^2.1 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.
↑ 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. doi:10.1107/S0567740871002334. Bibcode: 1971AcCrB..27..432U.
↑ ^4.0 ^4.1 Mosher, H. S.; Turner, L.; Carlsmith, A. (1953). "Pyridine-N-oxide". Org. Synth. 33: 79. doi:10.15227/orgsyn.033.0079.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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. https://doi.org/10.3184/174751915X14269588490798.
↑ Jung, Jae-Chul; Jo, Young-Jo; Park, Oee-Sook (9th November 2006). "Preparation of 2-chloropyridine". Synthetic Communications 31 (16): 2507-2511. https://doi.org/10.1081/SCC-100105130.
↑ o'Donnell, Gemma; Poeschl, Rosemarie; Zimhony, Oren; Gunaratnam, Mekala; Moreira, Joao B. C.; Neidle, Stephen; Evangelopoulos, Dimitrios; Bhakta, Sanjib et al. (2009). "Bioactive Pyridine- N -oxide Disulfides from Allium stipitatum". Journal of Natural Products 72 (3): 360–365. doi:10.1021/np800572r. PMID 19093848. Bibcode: 2009JNAtP..72..360O.
↑ Shimizu, Shinkichi; Watanabe, Nanao; Kataoka, Toshiaki; Shoji, Takayuki; Abe, Nobuyuki; Morishita, Sinji; Ichimura, Hisao (2000). "Ullmann's Encyclopedia of Industrial Chemistry". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399.

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[1] Meisenheimer, Jakob (1926). "Über Pyridin-, Chinolin- und Isochinolin-N-oxyd" (in German). Ber. Dtsch. Chem. Ges. 59 (8): 1848–1853. doi:10.1002/cber.19260590828.

[eEROS-2] 2.0 ^2.1 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. doi:10.1107/S0567740871002334. Bibcode: 1971AcCrB..27..432U.

[pyridine-N-oxide_hydrochloride-4] 4.0 ^4.1 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] 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.

[SEAr-10] 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.

[11] 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. https://doi.org/10.3184/174751915X14269588490798.

[12] Jung, Jae-Chul; Jo, Young-Jo; Park, Oee-Sook (9th November 2006). "Preparation of 2-chloropyridine". Synthetic Communications 31 (16): 2507-2511. https://doi.org/10.1081/SCC-100105130.

[13] 'Donnell, Gemma; Poeschl, Rosemarie; Zimhony, Oren; Gunaratnam, Mekala; Moreira, Joao B. C.; Neidle, Stephen; Evangelopoulos, Dimitrios; Bhakta, Sanjib et al. (2009). "Bioactive Pyridine- N -oxide Disulfides from Allium stipitatum". Journal of Natural Products 72 (3): 360–365. doi:10.1021/np800572r. PMID 19093848. Bibcode: 2009JNAtP..72..360O.

[14] Shimizu, Shinkichi; Watanabe, Nanao; Kataoka, Toshiaki; Shoji, Takayuki; Abe, Nobuyuki; Morishita, Sinji; Ichimura, Hisao (2000). "Ullmann's Encyclopedia of Industrial Chemistry". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399.

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