:Chichibabin pyridine synthesis
{{Short description|Method for synthesizing pyridine rings}}
{{distinguish|Chichibabin reaction}}
{{Use dmy dates|date=November 2022}}
{{Reactionbox
| Name = Chichibabin pyridine synthesis
| Type = Ring forming reaction
| NamedAfter = Aleksei Chichibabin
| Section3 = {{Reactionbox Identifiers
| RSC_ontology_id = 0000526
}}
}}
The Chichibabin pyridine synthesis ({{IPAc-en|ˈ|tʃ|iː|tʃ|iː|ˌ|b|eɪ|b|iː|n}}) is a method for synthesizing pyridine rings. The reaction involves the condensation reaction of aldehydes, ketones, α,β-unsaturated carbonyl compounds, or any combination of the above, with ammonia.{{cite journal
|author1=Frank, R. L. |author2=Seven, R. P. | title = Pyridines. IV. A Study of the Chichibabin Synthesis
| journal = Journal of the American Chemical Society
| year = 1949
| volume = 71
| issue = 8
| pages = 2629–35
| doi = 10.1021/ja01176a008}} It was reported by Aleksei Chichibabin in 1924. name = 'AEC1924ori'>{{cite journal | author = Tschitschibabin, A. E. | title = Über Kondensation der Aldehyde mit Ammoniak zu Pyridinbasen | url = http://gallica.bnf.fr/ark:/12148/bpt6k90877m/f132.chemindefer | journal = Journal für Praktische Chemie | year = 1924 | volume = 107 | issue = 1–4 | pages = 122–8 | doi = 10.1002/prac.19241070110}}{{Cite book | title = Name Reactions | chapter = Chichibabin pyridine synthesis | pages = 107–9 | author = Li, J. J. | doi = 10.1007/978-3-642-01053-8_51 | year = 2009 | isbn = 978-3-540-40203-9}} Methyl-substituted pyridines, which show widespread uses among multiple fields of applied chemistry, are prepared by this methodology.{{cite journal |author1=Sagitullin, R. S. |author2=Shkil, G. P. |author3=Nosonova, I. I. |author4=Ferber, A. A. | title = Synthesis of pyridine bases by the Chichibabin method (review) | pages = 127–40 | journal = Chemistry of Heterocyclic Compounds | year = 1996 | volume = 32 | issue = 2 | doi = 10.1007/BF01165434|s2cid=93717043 }}
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- and 4-methylpyridine are produced as a mixture from acetaldehyde and ammonia. 3-Methylpyridine and pyridine are produced from acrolein and ammonia. Acrolein and propionaldehyde react with ammonia affords mainly 3-methylpyridine. 5-Ethyl-2-methylpyridine is produced from paraldehyde and ammonia.{{Ullmann|first1=S. |last1=Shimizu |first2=N. |last2=Watanabe |first3=T. |last3=Kataoka |first4=T. |last4=Shoji |first5=N. |last5=Abe |first6=S. |last6=Morishita |first7=H. |last7=Ichimura |title=Pyridine and Pyridine Derivatives |doi=10.1002/14356007.a22_399}}
=Mechanism and optimizations=
These syntheses involve many reactions such as imine synthesis, base-catalyzed aldol condensations, and Michael reactions.
Chichibabin pyridine synthesis
Many efforts have been made to improve the method.{{cite journal
| title = Acetic Acid—Ammonium Acetate Reactions. An Improved Chichibabin Pyridine Synthesis
| author = Weiss, M.
| journal = Journal of the American Chemical Society
| year = 1952
| pages = 200–2
| volume = 74
| issue = 1
| doi = 10.1021/ja01121a051}} Conducting the reaction in the gas phase in the presence of aluminium(III) oxide. zeolite (yield 98.9% at 500 K),{{ cite journal |author1= Krishna Mohan, K. V. V. |author2=Reddy, K. S. K. |author3=Narender, N. |author4=Kulkarni, S. J. | title = Zeolite Catalysed Synthesis of 5-Ethyl-2-methylpyridine under High Pressure | journal = Journal of Molecular Catalysis A: Chemical | year = 2008 | volume = 298 | issue = 1–2 | pages = 99–102 | doi = 10.1016/j.molcata.2008.10.010 }}
=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.
See also
References
{{Reflist}}
{{Organic reactions}}
{{DEFAULTSORT:Chichibabin Pyridine Synthesis}}
Category:Pyridine forming reactions