Pyridinium salts nucleophilic addition

The Zincke reaction is an overall amine exchange process that converts N- 2,A-dinitrophenyl)pyridinium salts (e.g, 1), known as Zincke salts, to iV-aryl or iV-alkyl pyridiniums 2 upon treatment with the appropriate aniline or alkyl amine. The Zincke salts are produced by reaction of pyridine or its derivatives with 2,4-dinitrochlorobenzene. This venerable reaction, first reported in 1904 and independently explored by Konig, proceeds via nucleophilic addition, ring opening, amine exchange, and electrocyclic reclosure, a sequence that also requires a series of proton transfers. By... 

Reactions of highly electron-rich organometalate salts (organocuprates, orga-noborates, Grignard reagents, etc.) and metal hydrides (trialkyltin hydride, triethylsilane, borohydrides, etc.) with cyano-substituted olefins, enones, ketones, carbocations, pyridinium cations, etc. are conventionally formulated as nucleophilic addition reactions. We illustrate the utility of donor/acceptor association and electron-transfer below. 

A new approach to ( )-deserpidine has been published by Wenkert (264) in preliminary form. The characteristic feature of the synthesis is the addition of a nucleophile to a pyridinium salt, followed by acid-induced ring closure. For the preparation of the desired pyridinium salt 532, nicotinaldehyde was condensed with methyl methoxyacetate, and the methyl acrylate derivative 531 was alky-... 

AUenyl pyridinium salts 303 are a class of electron-deficient allenes, of which the center carbon atom can accept nucleophilic addition of diethylamine and pyridine derivatives [147, 148]. 

Silylcuprates have been reported to undergo reactions with a number of miscellaneous Michael acceptors [65]. Conjugate addition to 3-carbomethoxy acyl pyri-dinium salts [65a] affords 4-silyl-l,4-dihydropyridines. Oxidation with p-chlorand generates a 4-acyl pyridinium salt that gives the 4-silylnicotinate upon quenching with water, and methyl 4-silyl-2-substituted dihydronicotinates upon quenching with nucleophiles (nucleophilic addition at the 6-position). The stabilized anion formed by conjugate addition to an a, j8-unsaturated sulfone could be trapped intramolecularly by an alkyl chloride [65b]. 

The reaction of nucleophiles with pyridinium salts leads to addition, giving dihydropyridines. Attack... 

The reasons why nucleophilic additions occur readily, particularly in the case of pyridinium salts... 

Nucleophilic addition readily takes place with pyridinium salts attack is normally easier at the C-2(6) position, since the inductive effect of the positively charged nitrogen atom is greatest here (Scheme 2.28). When the sites adjacent to the nitrogen are blocked, however, attack occurs at C-4. The products are dihydropyridines. 

Pyridinium salts are susceptible to addition reactions with nucleophiles and to reduction. 

Nucleophiles react particularly easily with quaternized azines and with pyrylium and thiopyrylium slats (cf. equation 23) typical examples, including the well-known reaction of pyridinium salts with hydroxide in the presence of potassium ferricyanide to give 2-pyridones, are summarized in equations (34)-(36) (note the rather unusual orientation of addition in the last case reaction normally occurs essentially exclusively a to the heteroatom if the position is free or occupied by a leaving group). 

The Lewis acid-catalyzed three-component reaction of dihydropyridines, aldehydes, and />-substituted anilines efficiently yields highly substituted tetrahydroquinolines in a stereoselective manner, through a mechanism believed to be imine formation followed by formal [4-1-2] cycloaddition (Scheme 41). The 1,4-dihydropyridine starting materials were also prepared in situ by the nucleophilic addition of cyanide to pyridinium salts, creating in effect a one-pot four-component reaction <20030L717>. 

X -phosphorins have physical properties which are rather similar to those of pyridines. But the chemistry of X -phosphorins is very different, due mainly to the phosphorus atom which can easily lose one electron to produce a stable radical cation, or accept one or more electrons to yield a radical anion, dianion or radical trianion. Nucleophiles add to stable X -phosphorin anions. In contrast to pyridine chemistry, no stable X -phosphorinium compound (corresponding to a N-alkyl-pyridinium salt) could be isolated. Instead the electron shell of phosphorus is enlarged by addition of an electrophile yielding a X -phosphorine derivative. 

Nucleophilic addition at the 2-position of pyrylium salts (223) occurs readily under mild conditions and when ammonia or primary amines are used the subsequent ring-opening/ring-closure sequences give pyridines (224) and pyridinium salts (222), respectively (Section 3.2.1.6.4.iii). The process is most useful for the synthesis of 2,4,6-trisubstituted pyridine derivatives. Thiinium salts (226) are conveniently prepared from pyrylium salts (225) by treatment with sodium sulfide (Section 3.2.1.6.5), Thiinium salts (226) react with ammonia and amines similarly to their pyrylium analogues. 

The highly nucleophilic 3,4-dimethoxyfuran, when treated with arene diazonium salts in aqueous pyridine, undergoes 1,4-addition to afford pyridinium salts (51). The pyridine is easily displaced by nucleophiles including alcohols and phenols, thereby affording 5-alkoxy or 5-phenoxy derivatives of 3,4-dimethoxyfuran-2(5H)-one (52 Scheme 19) (78HCA1033). 

Two examples of the preparation of dihydropyridinones from pyridines via Grignard nucleophilic addition to acyl pyridinium salts <07TL8536 07BMC1106> were published in the literature this year. 

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