Pyridinium

Pyridinium
Names
Preferred IUPAC name
Pyridin-1-ium
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • InChI=1S/C5H5N/c1-2-4-6-5-3-1/h1-5H/p+1 Y
    Key: JUJWROOIHBZHMG-UHFFFAOYSA-O Y
  • InChI=1S/C5H5N/c1-2-4-6-5-3-1/h1-5H/p+1
  • InChI=1S/C5H5N/c1-2-4-6-5-3-1/h1-5H/p+1
    Key: JUJWROOIHBZHMG-UHFFFAOYSA-O
  • c1cc[nH+]cc1
Properties
[C5H5NH]+
Molar mass 80.110 g·mol−1
Acidity (pKa) ~5 [1][2]
Conjugate base Pyridine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Pyridinium refers to the charged cation of pyridine. The simplest being the conjugate acid [C5H5NH]+. Many related cations are known involving substituted pyridines, e.g. picolines, lutidines, collidines. They are prepared by treating pyridine with acids.[3]

As pyridine is often used as an organic base in chemical reactions, pyridinium salts are produced in many acid-base reactions. Its salts are often insoluble in the organic solvent, so precipitation of the pyridinium leaving group complex is an indication of the progress of the reaction.

Pyridinium cations are aromatic, as determined through Hückel's rule.[4] They are isoelectronic with benzene.

Other N-substitutions of pyridiniums exist. Exampels include N-alkyl, N-aryl and N-amino pyridinium species.

Occurrence in nature

Pyridiniums have also been isolated from natural sources. One pyridinium used in cellular metabolism is Nicotinamide adenine dinucleotide (NAD). Pachychaline A was isolated from caribbean marine sponge Pachychaline sp.[5] Desmosine is a biomarker for COPD.[6]

Applications

The permanently charged nature of N-alkyl pyridinium salts makes them useful in mass spectrometry. Examples in which pyridinium based charges were used includes peptides,[7] and fatty acids.[8] Pyridinium salts are also used for MALDI-MSI (mass spec imaging) to quantify metabolites in tissue slices.[9][10]

Alkyl and aryl substituted pyridiniums have been explored as ionic liquids.[11]

Various pyridinium species have found use as reagents or as intermediates for the synthesis of heterocycles.[12][13][14]

The pyridinium motive is present in the herbicide paraquat.[15]

Preparation

Various ways to prepare N-substituted pyridinium salts are known.[13] A straightforward way to prepare N-alkyl pyridiniums is to use the nucleophilic nature of the nitrogen lone pair to alkylate it with electrophilic alkylating reagents. Similarly, alkylated pyridinium salts may also be prepared by performing Michael addition to maleic acids.[16]

Analogously, N-amino pyridinium species may be prepared by reaction pyridines with electrophilic nitrogen reagents, in example Hydroxylamine-O-sulfonic acid.[14]

N-aryl pyridinium salts require different conditions to be made. Common approaches include the Zincke reaction or the reaction between pyrilium and anilines. Alternatively, denovo synthesis of the pyridine ring allows for incorporation of a N-aryl subtituent.[13]

Pyridine-N-oxide is readily prepared by oxidation of pyridine using peroxy acids.

Reactivity

In the presence of phosphines, N-alkyl pyridiniums are readily dealkylated to yield the coresponding pyridine.[17]

The electron poor nature of the pyridinium ring makes the pyridinium more reactive towards nucleophiles. Halogenated pyridinium salts readily undergo SnAr reactions. Mukaiyama´s reagent (2-Chloro-1-methylpyridinium Iodide) takes advantage of this reactivity, a carboxylate reacts at the halogenated C2 position forming the activated ester which may be substituted by various nucleophiles.[18][19]

Pyridinium species are also key intermediates in the Minisci reaction. In which the charged ring results in lowering of the LUMO, resulting in a better match with the SOMO of a nucleophilic radical, speeding up the reaction.[20] Depending on the substrate, the LUMO coefficients of pyridinium cations at C2/C6 and C4 differ slightly. This typically results in mixtures of regio isomers. One strategy to control the regiochemistry of the Minischi reaction is inclusion of a steric blocking group, preventing C2/C6 additions.[16][21]

Pyridinium species are also reactive towards conventional carbon nucleophiles, yielding N substituted 1,2- and 1,4-dihydropyridines. Examples include Grignard reagents and silyl enol ethers.[12][22][21][23] The regioselectivity is dependent on the substitution pattern of the pyridinium and the used nucleophile. Similarly, inclusion of a blocking group has been demonstrated to be an effective strategy for selective nucleophilic addition to the C4 position.[21]

When amines are used as the nucleophile, the pyridinium undergoes ring opening to yield linear conjugated imines, which may be hydrolysed to yield the aldehyde. These so called Zincke aldehydes are usefull intermediates is synthesis.

Pyridinium ylides are also usefull intermediates in synthesis. Pyridinium ylides may be formed via deprotonation of the coresponding N-alkyl pyridinium or by the reaction between a pyridine and a carbene.[24] An example of the use of pyridinium ylides as a nucleophile is in the Kröhnke pyridine synthesis. Pyridinium ylides also readily undergo dipolar cycloadditions.[24][25][26]

Depending on the substitution pattern of the pyridinium ring, when put in the triplet state using a triplet sensitizer, N-N pyridinium ylides have been demonstrated to undergo [2+3] cycloaddition with the pyridinium ring itself or it transfers the heteroatom attached to the nitrogen.[27][28]

See also

References

  1. ^ Linnell, Robert (1960). "Notes – Dissociation Constants of 2-Substituted Pyridines". Journal of Organic Chemistry. 25 (2): 290. doi:10.1021/jo01072a623.
  2. ^ Pearson, Ralph G.; Williams, Forrest V. (1953). "Rates of Ionization of Pseudo Acids.1V. Steric Effects in the Base-catalyzed Ionization of Nitroethane". Journal of the American Chemical Society. 75 (13): 3073. doi:10.1021/ja01109a008.
  3. ^ George A. Olah; Michael Watkins (1978). "Fluorinations With Pyridinium Polyhydrogen Fluoride Reagent: 1-Fluoroadamantane". Org. Synth. 58: 75. doi:10.15227/orgsyn.058.0075.
  4. ^ "Aromatic Compounds" (PDF). Alex Roche, Rutgers University.
  5. ^ Laville, Rémi; Thomas, Olivier P.; Berrue, Fabrice; Reyes, Fernando; Amade, Philippe (January 2008). "Pachychalines A–C: Novel 3‐Alkylpyridinium Salts from the Marine Sponge Pachychalina sp". European Journal of Organic Chemistry. 2008 (1): 121–125. doi:10.1002/ejoc.200700741. ISSN 1434-193X.
  6. ^ Usuki, Toyonobu; Yamada, Haruka; Hayashi, Takahiro; Yanuma, Hiroto; Koseki, Yohei; Suzuki, Noriyuki; Masuyama, Yoshiro; Lin, Yong Y. (2012). "Total synthesis of COPD biomarker desmosine that crosslinks elastin". Chemical Communications. 48 (26): 3233. doi:10.1039/c2cc17958j. ISSN 1359-7345.
  7. ^ Waliczek, Mateusz; Kijewska, Monika; Rudowska, Magdalena; Setner, Bartosz; Stefanowicz, Piotr; Szewczuk, Zbigniew (2016-11-28). "Peptides Labeled with Pyridinium Salts for Sensitive Detection and Sequencing by Electrospray Tandem Mass Spectrometry". Scientific Reports. 6 (1) 37720. doi:10.1038/srep37720. ISSN 2045-2322. PMC 5125270. PMID 27892962.
  8. ^ Cao, Yanjing; Guan, Qing; Sun, Tuanqi; Qi, Wanshu; Guo, Yinlong (2016-09-21). "Charged tag founded in N-(1-chloroalkyl)pyridinium quaternization for quantification of fatty aldehydes". Analytica Chimica Acta. 937: 80–86. doi:10.1016/j.aca.2016.05.032. ISSN 0003-2670.
  9. ^ Shariatgorji, Mohammadreza; Nilsson, Anna; Fridjonsdottir, Elva; Vallianatou, Theodosia; Källback, Patrik; Katan, Luay; Sävmarker, Jonas; Mantas, Ioannis; Zhang, Xiaoqun; Bezard, Erwan; Svenningsson, Per; Odell, Luke R.; Andrén, Per E. (October 2019). "Comprehensive mapping of neurotransmitter networks by MALDI–MS imaging". Nature Methods. 16 (10): 1021–1028. doi:10.1038/s41592-019-0551-3. ISSN 1548-7105.
  10. ^ Huang, Meng; Qi, Xiaoyu; Zhu, Dafu; Zhou, Hao; Yuan, Jie; Mišić, Danijela; Soković, Marina; Xu, Hongxi; Sun, Lu; Ye, Yang; Liu, Jia (2025-12-03). "Recent Advances in On‐Tissue Chemical Derivatization Strategies for Enhancing MALDI‐MSI". Mass Spectrometry Reviews. doi:10.1002/mas.70016. ISSN 0277-7037.
  11. ^ pubs.acs.org. doi:10.1021/acs.energyfuels.5c01280 https://pubs.acs.org/action/cookieAbsent. Retrieved 2026-03-04. {{cite web}}: Missing or empty |title= (help)
  12. ^ a b Andersson, Hans; Olsson, Roger; Almqvist, Fredrik (2010-12-23). "Reactions between Grignard reagents and heterocyclic N-oxides: Stereoselective synthesis of substituted pyridines, piperidines, and piperazines". Organic & Biomolecular Chemistry. 9 (2): 337–346. doi:10.1039/C0OB00336K. ISSN 1477-0539.
  13. ^ a b c Sowmiah, Subbiah; Esperança, José M. S. S.; Rebelo, Luís P. N.; Afonso, Carlos A. M. (2018-01-30). "Pyridinium salts: from synthesis to reactivity and applications". Organic Chemistry Frontiers. 5 (3): 453–493. doi:10.1039/C7QO00836H. ISSN 2052-4129.
  14. ^ a b Roychowdhury, Pritam; Samanta, Samya; Tan, Hao; Powers, David C. (2023-05-16). "N-Amino pyridinium salts in organic synthesis". Organic Chemistry Frontiers. 10 (10): 2563–2580. doi:10.1039/D3QO00190C. ISSN 2052-4129.
  15. ^ Shimizu, Shinkichi; Watanabe, Nanao; Kataoka, Toshiaki; Shoji, Takayuki; Abe, Nobuyuki; Morishita, Sinji; Ichimura, Hisao (2007). "Pyridine and Pyridine Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a22_399. ISBN 978-3-527-30673-2.
  16. ^ a b pubs.acs.org. doi:10.1021/jacs.1c05278. PMC 8721863. PMID 34318659 https://pubs.acs.org/action/cookieAbsent. Retrieved 2026-03-05. {{cite web}}: Missing or empty |title= (help)
  17. ^ pubs.acs.org. doi:10.1021/jo00877a023 https://pubs.acs.org/action/cookieAbsent. Retrieved 2026-03-05. {{cite web}}: Missing or empty |title= (help)
  18. ^ Mukaiyama, Teruaki; Usui, Masahiro; Shimada, Eiichiro; Saigo, Kazuhiko (1975-10-05). "A CONVENIENT METHOD FOR THE SYNTHESIS OF CARBOXYLIC ESTERS". Chemistry Letters. 4 (10): 1045–1048. doi:10.1246/cl.1975.1045. ISSN 0366-7022.
  19. ^ Armstrong, Alan; Wang, Yun; Wang, Pengfei (2008-09-15), John Wiley & Sons, Ltd (ed.), "2-Chloro-1-methylpyridinium Iodide", Encyclopedia of Reagents for Organic Synthesis, Chichester, UK: John Wiley & Sons, Ltd, doi:10.1002/047084289X.rc126.pub2, ISBN 978-0-471-93623-7, retrieved 2026-03-05{{citation}}: CS1 maint: work parameter with ISBN (link)
  20. ^ Tauber, Johannes; Imbri, Dennis; Opatz, Till (2014-10-10). "Radical Addition to Iminium Ions and Cationic Heterocycles". Molecules. 19 (10): 16190–16222. doi:10.3390/molecules191016190. ISSN 1420-3049. PMC 6270771. PMID 25310148.
  21. ^ a b c Wenbo, H. Liu (2024). "Unified ionic and radical C-4 alkylation and arylation of pyridines". Chemical Science. 15: 12442–12450. doi:10.1039/d4sc03739a. {{cite journal}}: line feed character in |title= at position 45 (help)
  22. ^ Knight, Brian J.; Tolchin, Zachary A.; Smith, Joel M. (2021-03-11). "A predictive model for additions to N-alkyl pyridiniums". Chemical Communications. 57 (21): 2693–2696. doi:10.1039/D1CC00056J. ISSN 1364-548X. PMID 33595047. S2CID 231945207.
  23. ^ Grigolo, Thiago A.; Subhit, Ariana R.; Smith, Joel M. (2021-09-03). "Regioselective Asymmetric Alkynylation of N-Alkyl Pyridiniums". Organic Letters. 23 (17): 6703–6708. doi:10.1021/acs.orglett.1c02276. ISSN 1523-7060. PMID 34474575. S2CID 237401193.
  24. ^ a b Padwa, Albert; Austin, David J.; Precedo, Laura; Zhi, Lin (February 1993). "Cycloaddition reactions of pyridinium and related azomethine ylides". The Journal of Organic Chemistry. 58 (5): 1144–1150. doi:10.1021/jo00057a029. ISSN 0022-3263.
  25. ^ Zhou, Xueting; Shi, Jun; Song, Jun‐Rong; Pan, Wei‐Dong; Ren, Hai; Wu, Wei (2023-10-02). "Catalyst‐Free [3+2] Cycloaddition of Isoquinolinium/Pyridinium Ylides and Electron‐Deficient Alkenes". European Journal of Organic Chemistry. 26 (37). doi:10.1002/ejoc.202300563. ISSN 1434-193X.
  26. ^ Dong, Shanliang; Fu, Xiang; Xu, Xinfang (August 2020). "[3+2]‐Cycloaddition of Catalytically Generated Pyridinium Ylide: A General Access to Indolizine Derivatives". Asian Journal of Organic Chemistry. 9 (8): 1133–1143. doi:10.1002/ajoc.202000276. ISSN 2193-5807.
  27. ^ Lee, Wooseok; Koo, Yejin; Jung, Hoimin; Chang, Sukbok; Hong, Sungwoo (August 2023). "Energy-transfer-induced [3+2] cycloadditions of N–N pyridinium ylides". Nature Chemistry. 15 (8): 1091–1099. doi:10.1038/s41557-023-01258-2. ISSN 1755-4349.
  28. ^ Lee, Wooseok; Kim, Changha; Jang, Ahyoung; Hong, Sungwoo (2025-11-28). "Pyridinium ylides as photocatalytic atom transfer reagents". Nature Communications. 16 (1): 10716. doi:10.1038/s41467-025-65740-w. ISSN 2041-1723. PMC 12663387. PMID 41315320.
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