pyridine-N-oxide

{{chembox

| Watchedfields = changed

| Name =Pyridine-N-oxide

| verifiedrevid = 464376916

| ImageFileL1 = Pyridine-N-oxide.png

| ImageSizeL1 = 80

| ImageAltL1 = Skeletal formula

| ImageFileR1 = Pyridine-N-oxide-3D-balls.png

| ImageSizeR1 = 120

| ImageAltR1 = Ball-and-stick model

| PIN = 1λ⁵-Pyridin-1-one

| OtherNames = Pyridine-1-oxide

|Section1={{Chembox Identifiers

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 694-59-7

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 29136

| ChEMBL = 3278446

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 12229

| EINECS = 211-774-6

| PubChem = 12753

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 91F12JJJ4H

| InChI = 1/C5H5NO/c7-6-4-2-1-3-5-6/h1-5H

| InChIKey = ILVXOBCQQYKLDS-UHFFFAOYAZ

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C5H5NO/c7-6-4-2-1-3-5-6/h1-5H

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = ILVXOBCQQYKLDS-UHFFFAOYSA-N

| SMILES = c1cc[n+](cc1)[O-]

}}

|Section2={{Chembox Properties

| C=5 | H=5 | N=1 | O=1

| Appearance = Colourless solid

| Density =

| MeltingPtC = 65 to 66

| MeltingPt_notes =

| BoilingPtC = 270

| Solubility = high

| pKa = 0.8 (of conjugate acid)

}}

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.{{cite journal|first = Jakob|last = Meisenheimer|authorlink = Jakob Meisenheimer|title = Über Pyridin-, Chinolin- und Isochinolin-N-oxyd|language = German|journal = Ber. Dtsch. Chem. Ges.|volume = 59|pages = 1848–1853|doi = 10.1002/cber.19260590828|year = 1926|issue = 8}} The compound is used infrequently as an oxidizing reagent in organic synthesis.{{cite encyclopedia|first1 = S. Nicholas|last1 = Kilényi|first2 = James J.|last2 = Mousseau|date = 20 September 2015|doi = 10.1002/047084289X.rp283.pub2|title = Pyridine N-Oxide |pages = 1–6|encyclopedia = Encyclopedia of Reagents for Organic Synthesis|publisher = John Wiley & Sons|isbn = 9780470842898}}

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{{nbsp}}Å. The C–N–C angle is 124°, 7° wider than in pyridine.{{cite journal |doi=10.1107/S0567740871002334|title=The Crystal Structure of Pyridine 1-oxide |year=1971 |last1=Ülkü |first1=D. |last2=Huddle |first2=B. P. |last3=Morrow |first3=J. C. |journal=Acta Crystallographica Section B: Structural Crystallography and Crystal Chemistry |volume=27 |issue=2 |pages=432–436 |bibcode=1971AcCrB..27..432U }}

Synthesis

The oxidation of pyridine can be achieved with a number of peroxy acids, including peracetic acid and peroxybenzoic acid.{{cite journal|first1 = H. S.|last1 = Mosher|first2 = L.|last2 = Turner|first3 = A.|last3 = Carlsmith|title = Pyridine-N-oxide |journal=Org. Synth.|year = 1953 |volume=33 |page=79 |doi = 10.15227/orgsyn.033.0079}} Oxidation can also be effected by a modified Dakin reaction using a urea–hydrogen peroxide complex,{{cite journal |title = The Urea−Hydrogen Peroxide Complex: Solid-State Oxidative Protocols for Hydroxylated Aldehydes and Ketones (Dakin Reaction), Nitriles, Sulfides, and Nitrogen Heterocycles|first1 = Rajender S.|last1 = Varma|first2 = Kannan P.|last2 = Naicker|journal = Org. Lett.|year = 1999 |volume = 1|issue = 2|pages = 189–192|doi = 10.1021/ol990522n}} and sodium perborate{{cite journal|journal = Tetrahedron|volume = 45|issue = 11 |year = 1989|pages = 3299–3306|title = Further functional group oxidations using sodium perborate|first1 = Alexander|last1 = McKillop|first2 = Duncan|last2 = Kemp|doi = 10.1016/S0040-4020(01)81008-5}} or, using methylrhenium trioxide ({{chem|CH|3|ReO|3}}) as catalyst, with sodium percarbonate.{{cite journal|title = Rhenium-Catalyzed Highly Efficient Oxidations of Tertiary Nitrogen Compounds to N-Oxides Using Sodium Percarbonate as Oxygen Source|first1 = Suman L.|last1 = Jain|first2 = Jomy K.|last2 = Joseph|first3 = Bir|last3 = Sain|journal = Synlett|volume = 2006|issue = 16|year = 2006|pages = 2661–2663|doi = 10.1055/s-2006-951487}}

Reactions

Pyridine N-oxide is five orders of magnitude less basic than pyridine: the pK_a of protonated pyridine-N-oxide is 0.8.{{cite journal |doi=10.1016/0003-2670(95)00594-3 |title=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 |year=1996 |last1=Chmurzyński |first1=L. |journal=Analytica Chimica Acta |volume=321 |issue=2–3 |pages=237–244 }} Protonated derivatives are 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.

Treatment of the pyridine-N-oxide with phosphorus oxychloride gives 4- and 2-chloropyridines.{{cite book|first = E. F. V.|last = Scriven|title = Comprehensive Heterocyclic Chemistry: The Structure, Reactions, Synthesis and Uses of Heterocyclic Compounds|editor1-first = Alan R.|editor1-last = Katritzky|editor1-link = Alan R. Katritzky|editor2-first = Charles Wayne|editor2-last = Rees|editor2-link = Charles Rees|editor3-first = Otto|editor3-last = Meth-Cohn|publisher = Pergamon Press|year = 1984|chapter = Pyridines and their Benzo Derivatives: (ii) Reactivity at Ring Atoms|volume = 2|pages = 165–314|doi = 10.1016/B978-008096519-2.00027-8|isbn = 9780080307015}}

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.{{cite journal |doi=10.1021/np800572r |title=Bioactive Pyridine- N -oxide Disulfides from Allium stipitatum |date=2009 |last1=o'Donnell |first1=Gemma |last2=Poeschl |first2=Rosemarie |last3=Zimhony |first3=Oren |last4=Gunaratnam |first4=Mekala |last5=Moreira |first5=Joao B. C. |last6=Neidle |first6=Stephen |last7=Evangelopoulos |first7=Dimitrios |last8=Bhakta |first8=Sanjib |last9=Malkinson |first9=John P. |last10=Boshoff |first10=Helena I. |last11=Lenaerts |first11=Anne |last12=Gibbons |first12=Simon |journal=Journal of Natural Products |volume=72 |issue=3 |pages=360–365 |pmid=19093848 |pmc=2765505 |bibcode=2009JNAtP..72..360O }}

The N-oxides of various pyridines are precursors to useful drugs:{{Ullmann|doi=10.1002/14356007.a22_399|chapter=Pyridine and Pyridine Derivatives|year=2000|last1= Shimizu|first1=Shinkichi|last2=Watanabe|first2=Nanao|last3=Kataoka|first3 =Toshiaki|last4=Shoji|first4=Takayuki|last5=Abe|first5=Nobuyuki|last6=Morishita|first6=Sinji|last7=Ichimura|first7=Hisao|isbn=3527306730}}

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.

References

Category:Amine oxides

Category:Pyridinium compounds

Category:Oxidizing agents