:Zincke reaction

The first reaction is the formation of the N-2,4-dinitrophenyl-pyridinium salt (2). This salt is typically isolated and purified by recrystallization.

Image:Zincke Reaction Mechanism1.png

Upon heating a primary amine with the N-2,4-dinitrophenyl-pyridinium salt (2), the addition of the amine leads to the opening of the pyridinium ring. A second addition of amine leads to the displacement of 2,4-dinitroaniline (5) and formation of the König salt{{cite journal

| title = Über eine neue, vom Pyridin derivierende Klasse von Farbstoffen

| author = König, W.

| journal = Journal für Praktische Chemie

| volume = 69

| issue = 1

| pages = 105–137

| year = 1904

| url = https://zenodo.org/records/1428016/files/article.pdf

| doi = 10.1002/prac.19040690107}} (6a and 6b). The trans-cis-trans isomer of the König salt (6a) can react by either sigmatropic rearrangement or nucleophilic addition of a zwitterionic intermediate to give cyclized intermediate (7).{{cite journal

| title = A study on the mechanism of the reaction of N-(2,4-dinitrophenyl)-3-carbamoylpyridinium chloride with amines and amino acids with reference to effect of polyelectrolyte addition

|author1=Kunugi, S. |author2=Okubo, T. |author3=Ise, N. | journal = Journal of the American Chemical Society

| volume = 98

| issue = 1

| pages =2282–2287

| year = 1976

| url =

| doi = 10.1021/ja00424a047

| pmid=1254864|bibcode=1976JAChS..98.2282K }} This has been suggested to be the rate-determining step.{{cite journal | doi=10.1021/ja00722a016 | title=Formation of phenylpyridinium chloride from 5-anilino-N-phenyl-2,4-pentadienylideniminium chloride. Kinetics in basic media | date=1970 | last1=Marvell | first1=Elliot N. | last2=Caple | first2=Gerald | last3=Shahidi | first3=Iraj | journal=Journal of the American Chemical Society | volume=92 | issue=19 | pages=5641–5645 | bibcode=1970JAChS..92.5641M }}{{cite journal | doi=10.1021/ja00722a017 | title=Influence of para substituents on the rate of cyclization of 5-anilino-N-phenyl-2,4-pentadienylidenimine | date=1970 | last1=Marvell | first1=Elliot N. | last2=Shahidi | first2=Iraj | journal=Journal of the American Chemical Society | volume=92 | issue=19 | pages=5646–5649 | bibcode=1970JAChS..92.5646M }} After proton transfer and amine elimination, the desired pyridinium ion (9) is formed.

Image:Zincke Reaction Mechanism2.png

This mechanism can be referred to as an instance of the ANRORC mechanism: nucleophilic addition (A_N), ring opening and ring closing.

In one solid-phase synthesis application, the amine is covalently attached to Wang resin.{{cite journal | doi=10.1021/jo0001636 | title=The Solid-Phase Zincke Reaction: Preparation of ω-Hydroxy Pyridinium Salts in the Search for CFTR Activation | date=2000 | last1=Eda | first1=Masahiro | last2=Kurth | first2=Mark J. | last3=Nantz | first3=Michael H. | journal=The Journal of Organic Chemistry | volume=65 | issue=17 | pages=5131–5135 | pmid=10993337 }}

Image:ZinckeReactionSolidState.png

Another example is the synthesis of a chiral isoquinolinium salt.{{cite journal | doi=10.1021/jo961539b | title=New Chiral Isoquinolinium Salt Derivatives from Chiral Primary Amines via Zincke Reaction | date=1996 | last1=Barbier | first1=Denis | last2=Marazano | first2=Christian | last3=Das | first3=Bhupesh C. | last4=Potier | first4=Pierre | journal=The Journal of Organic Chemistry | volume=61 | issue=26 | pages=9596–9598 }}

Image:Zinckereactionchiral.png

{{Main|Zincke aldehyde}}

With secondary amines and not primary amines the Zincke reaction takes on a different shape forming so-called Zincke aldehydes in which the pyridine ring is ring-opened with the terminal iminium group hydrolyzed to an aldehyde:

Image:Zincke-Aldehyde.svg

This variation has been applied in the synthesis of novel indoles:{{cite journal | doi=10.1002/anie.200602996 | title=Synthesis of Nitrogen Heterocycles by the Ring Opening of Pyridinium Salts | date=2006 | last1=Kearney | first1=Aaron M. | last2=Vanderwal | first2=Christopher D. | journal=Angewandte Chemie International Edition | volume=45 | issue=46 | pages=7803–7806 | pmid=17072923 }}

Image:ZinckeAldehydeIndoleApplication.svg

with cyanogen bromide mediated pyridine activation.

In 2006 and again in 2007 the Zincke reaction was rediscovered by a research group from Japan {{cite journal |doi=10.1021/ol061585q |title=One-Pot Synthesis of N -Substituted Diaza[12]annulenes |date=2006 |last1=Yamaguchi |first1=Isao |last2=Gobara |first2=Yoshiaki |last3=Sato |first3=Moriyuki |journal=Organic Letters |volume=8 |issue=19 |pages=4279–4281 |pmid=16956206 }}{{Retracted|doi=10.1021/ol702583k|pmid=16956206|intentional=yes}} and a group from the USA.{{cite journal | doi=10.1002/anie.200702140 | title=[12]Annulene Gemini Surfactants: Structure and Self-Assembly | date=2007 | last1=Shi | first1=Lei | last2=Lundberg | first2=Dan | last3=Musaev | first3=Djamaladdin G. | last4=Menger | first4=Fredric M. | journal=Angewandte Chemie International Edition | volume=46 | issue=31 | pages=5889–5891 | pmid=17615610 }} Both groups claimed the synthesis of a 12 membered diazaannulene (structure 1) from an N-aryl pyridinium chloride and an amine, an aniline in the case of the Japanese group (depicted below) and an aliphatic amine (anticipating surfactant properties) in the case of the American group.

:Image:DiazaAnnulene.svg

In a letter to Angewandte Chemie, the German chemist Manfred Christl {{cite journal | doi=10.1002/anie.200704704 | title=1,7-Diaza[12]annulene Derivatives? 100-Year-Old Pyridinium Salts! | date=2007 | last1=Christl | first1=Manfred | journal=Angewandte Chemie International Edition | volume=46 | issue=48 | pages=9152–9153 | pmid=18046689 }} pointed out not only that the alleged new chemistry was in fact 100-year-old Zincke chemistry but also that the proposed structure for the reaction product was not the 12 membered ring but the 6 membered pyridinium salt (structure 2). Initially both groups conceded that they had ignored existing literature on Zincke but held on to the annulene structure based on their electrospray ionization (ESI) results which according to them clearly showed dimer. In his letter Christl remarked that in ESI measurements association of molecules is a common phenomenon. In addition, he noted similarities in melting point and NMR spectroscopy.

As of December 2007 the Japanese group retracted its paper in Organic Letters due to uncertainties regarding what products are formed in the reaction described and the US group added a correction to theirs in the Angewandte Chemie stating they wish(ed) to alter the proposed structure of (the) annulene.{{cite journal | doi=10.1002/anie.200790248 | title=[12]Annulene Gemini Surfactants: Structure and Self-Assembly | date=2007 | last1=Shi | first1=Lei | last2=Lundberg | first2=Dan | last3=Musaev | first3=Djamaladdin G. | last4=Menger | first4=Fredric M. | journal=Angewandte Chemie International Edition | volume=46 | issue=48 | pages=5889–5891 | pmid=17615610 }} The issue did receive some media coverage:{{in lang|de}} Ahnungslose Chemiker entdecken Verbindung zum zweiten Mal. Jens Lubbadeh Der Spiegel 6 December 2007 http://www.spiegel.de/wissenschaft/natur/0,1518,521646,00.html{{cite journal | title=Where have I seen that before? 103-year-old chemical reaction pops up again | first=Katharine |last=Sanderson |date=4 December 2007 | journal=Nature | doi=10.1038/news.2007.341| doi-access=free }}

{{Reflist}}

Category:Substitution reactions

Category:Name reactions