The Chichibabin pyridine synthesis () is a method for synthesizing

pyridine Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a d ...

rings. The reaction involves the

condensation reaction In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a ...

aldehydes In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl group ...

ketones In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bon ...

α,β-Unsaturated carbonyl compound In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...

s, or any combination of the above, with

ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous was ...

. It was reported by

Aleksei Chichibabin Alekséy Yevgényevich Chichibábin (russian: Алексей Евгеньевич Чичибабин) was a Soviet Union, Soviet/Russian organic chemist, born , Kuzemin village, current Sumy Oblast, Ukraine, died in Paris, France, 15 August 1945. H ...

in 1924. Methyl-substituted pyridines, which show widespread uses among multiple fields of applied chemistry, are prepared by this methodology.

Representative syntheses

The syntheses are presently conduced commercially in the presence of oxide catalysts such as modified alumina (Al₂O₃) or silica (SiO₂). The reactants are passed over the catalyst at 350-500 °C.

2-Methylpyridine 2-Methylpyridine, or 2-picoline, is the compound described with formula C6H7N. 2-Picoline is a colorless liquid that has an unpleasant odor similar to pyridine. It is mainly used to make vinylpyridine and the agrichemical nitrapyrin. Synthesis 2 ...

- and

4-methylpyridine 4-Methylpyridine is the organic compound with the formula CH3C5H4N. It is one of the three isomers of methylpyridine. This pungent liquid is a building block for the synthesis of other heterocyclic compounds. Its conjugate acid, the 4-methylpyrid ...

are produced as a mixture from acetaldehyde and ammonia.

3-Methylpyridine 3-Methylpyridine or 3-picoline, is an organic compound with formula 3-CH3C5H4N. It is one of three positional isomers of methylpyridine, whose structures vary according to where the methyl group is attached around the pyridine ring. This colorles ...

and pyridine are produced from acrolein and ammonia. Acrolein and propionaldehyde react with ammonia affords mainly 3-methylpyridine.

5-Ethyl-2-methylpyridine 5-Ethyl-2-methylpyridine is an organic compound with the formula (C2H5)(CH3)C5H3N. One of several isomeric pyridines with this formula, this derivative is of interest because it is efficiently prepared from simple reagents and it is a convenient ...

is produced from

paraldehyde Paraldehyde is the cyclic trimer of acetaldehyde molecules. Formally, it is a derivative of 1,3,5-trioxane, with a methyl group substituted for a hydrogen atom at each carbon. The corresponding tetramer is metaldehyde. A colourless liquid, it ...

and ammonia.

Mechanism and optimizations

These syntheses involve many reactions such as imine synthesis, base-catalyzed

aldol condensation An aldol condensation is a condensation reaction in organic chemistry in which two carbonyl moieties (of aldehydes or ketones) react to form a β-hydroxyaldehyde or β-hydroxyketone (an aldol reaction), and this is then followed by dehydration to ...

s, and

Michael reaction In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a carbon ...

Many efforts have been made to improve the method. Conducting the reaction in the gas phase in the presence of aluminium(III) oxide.

zeolite Zeolites are microporous, crystalline aluminosilicate materials commonly used as commercial adsorbents and catalysts. They mainly consist of silicon, aluminium, oxygen, and have the general formula ･y where is either a metal ion or H+. These pos ...

(yield 98.9% at 500 K),

From nitriles

Of the many variations have been explored. one approach employs nitriles as the nitrogen source. For example, acrylonitrile and acetone affords 2-methylpyridine uncontaminated with the 4-methyl derivative. In another variation, alkynes and nitriles react in the presence of organocobalt catalysts, a reaction inspired by

alkyne trimerization In organic chemistry, an alkyne trimerisation is a +2+2nbsp;cycloaddition reaction in which three alkyne units () react to form a benzene ring. The reaction requires a metal catalyst. The process is of historic interest as well as being applicab ...

References

{{DEFAULTSORT:Chichibabin Pyridine Synthesis Pyridine forming reactions Heterocycle forming reactions Name reactions Soviet inventions

Representative syntheses

Mechanism and optimizations

From nitriles

See also

References