of 2-hydroxypyridine-N-oxide with triphosgene and pyridine, Scheme 2
The chemical structure of pyridine was determined decades after its discovery. (1869) and (1871) suggested that, in analogy between and , the structure of pyridine is derived from by substituting one C–H unit with a nitrogen atom. The suggestion by Körner and Dewar was later confirmed in an experiment where pyridine was reduced to with in . In 1876, combined and into pyridine in a iron-tube furnace. This was the first synthesis of a heteroaromatic compound.
Synthesis of Pyridine-n-oxide - Chempedia - LookChem
Wereport a practical and highly efficient protocol for the arylation of pyridine N-oxides with arylboronic acid through palladium-catalyzed Suzuki reaction in water. This ligand-free Suzuki reaction is performed in the presence of diisopropylamine and gives 2- or 3-arylated pyridyl N-oxide derivatives in good to excellent yields within 1 h.
TFA (0.016 ml, 0.22 mmol) was added to a solution of 2-aminopyridine N-oxide 1 (29.0 mg, 0.26 mmol) in CH2Cl2 (0.2 M). The reaction mixture was stirred for 10 min, then alkyne (0.027 ml, 0.22 mmol) and PicAuCl2 (8.7 mg, 0.022 mmol) were added. After stirring overnight at 40°C, Et3N (20µl) was added and the reaction mixture was concentrated under reduced pressure and purified by column chromatography to give pure imidazo[1,2-a]pyridine 2 (36.2 mg, 72%).
Pyridine-N-oxide is the heterocyclic compound with the formula CHNO
Substitutions to pyridine at the 2- or 4-position result in an energetically unfavorable σ complex. They can be promoted, however, using experimental techniques, such as conducting electrophilic substitution on the pyridine -oxide followed by deoxygenation of the nitrogen atom. Addition of oxygen reduces electron density on the nitrogen atom and promotes substitution at the 2- and 4-carbons. The oxygen atom can then be removed via several routes, most commonly with compounds of trivalent or divalent , which are easily oxidized. is a frequently used reagent, which is oxidized in this reaction to . The following paragraphs describe representative electrophilic substitution reactions of pyridine.
Pyridine N-oxide | Sigma-Aldrich
The first major synthesis of pyridine derivatives was described in 1881 by . The typically uses a 2:1:1 mixture of a β- (often ), an (often ), and or its salt as the nitrogen donor. First, a double pyridine is obtained, which is then oxidized to the corresponding pyridine derivative. showed that asymmetrically-substituted pyridine derivatives can be produced with this process.
Search results for Pyridine N-oxide at Sigma-Aldrich
Practical application of the traditional Chichibabin pyridine synthesis are limited by its consistently low yield, typically about 20%. This low yield, together with the high prevalence of byproducts, render unmodified forms of Chichibabin's method unpopular.
2-nitro pyridine | Sigma-Aldrich
The was reported in 1924 and is still in use in industry. In its general form, the reaction can be described as a of , , , or any combination of the above, in or . In particular, unsubstituted pyridine is produced from and , which are inexpensive and widely available. First, is formed in a from the acetaldehyde and formaldehyde. It is then with acetaldehyde and ammonia into , and then oxidized with a solid-state catalyst to pyridine. This process is carried out in a gas phase at 400–450 °C. The product consists of a mixture of pyridine, simple pyridines (), and ; its composition depends on the catalyst used and can be adapted to the needs of the manufacturer. The catalyst is usually a transition metal salt such as or , but and compounds can also be used. The recovered pyridine is separated from byproducts in a multistage process.