Pyridinium salts nucleophilic substitution

In 1904, Zincke reported that treatment of Al-(2,4-dinitrophenyl)pyridinium chloride (1) with aniline provided a deep red salt that subsequently transformed into A-phenyl pyridinium chloride 5 (Scheme 8.4.2). Because the starting salt 1 was readily available from the nucleophilic aromatic substitution reaction of pyridine with 2,4-dinitrochlorobenzene, the Zincke reaction provided access to a pyridinium salt (5) that would otherwise require the unlikely substitution reaction between pyridine and... 

The nitration of l,2,5-selenadiazolo[3,4-/] quinoline 77 with benzoyl nitrate affords the 8-nitro derivative 78, whereas methylation with methyl iodide or methyl sulfate afforded the corresponding 6-pyridinium methiodide 79 or methosulfate 80, respectively (Scheme 29). The pyridinium salt 80 was submitted to oxidation with potassium hexacyanoferrate and provided 7-oxo-6,7-dihydro derivative 81 or, by reaction of pyridinium salt 79 with phenylmagnesium bromide, the 7-phenyl-6,7-dihydro derivative 82. Nucleophilic substitution of the methiodide 79 with potassium cyanide resulted in the formation of 9-cyano-6,9-dihydroderivative 83, which can be oxidized by iodine to 9-cyano-l,2,5-selenadiazolo [3,4-/]quinoline methiodide 84. All the reactions proceeded in moderate yields (81IJC648). 

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

Spurred by our desire to avoid use of expensive dipolau aprotic solvents in nucleophilic aromatic substitution reactions, we have developed two alternative phase transfer systems, which operate in non-polar solvents such as toluene, chlorobenzene, or dichlorobenzene. Poleu polymers such as PEG are Inexpensive and stable, albeit somewhat inefficient PTC agents for these reactions. N-Alkyl-N, N -Dialkylaminopyridinium salts have been identified as very efficient PTC agents, which are about 100 times more stable to nucleophiles than Bu NBr. The bis-pyridinium salts of this family of catalysts are extremely effective for phase transfer of dianions such as bis-phenolates. 

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 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>. 

The /V-(2,6-dimethy 1-4-oxopyridin-1 -yl)pyridinium salts (15)24 have proved to be versatile intermediates for the regiospecific synthesis of 4-substituted pyridines (17) via attack by the appropriate carbon nucleophiles, e.g. ionized ketones,90 nitroalkanes,91 esters and nitriles,92 and a-diketones, a-keto esters, a-diesters, disulfones etc. (Scheme 10).93 Aromatization of the intermediate 1,4-dihydro adduct (16) was generally achieved under free radical conditions. 

Again, as expected, pyridine A-oxides are very susceptible to nucleophilic attack. Unlike the situation usually prevalent with the quaternary pyridinium salts, the elimination stage of the two-step nucleophilic substitution can occur with relative ease, the oxide grouping serving as a good sink for the leaving hydride ion electron-pair and being itself eliminated in the process. Considerably more work has been carried out on quinoline and isoquinoline A-oxides than on pyridine A-oxide derivatives. 

Fused dihydrooxazolium compounds react readily by nucleophilic displacement of the oxygen from the azine ring. Thus, 2-carboxy-2,3-dihydrooxazolo[2,3-a]pyridinium bromide reacts with oxygen or nitrogen nucleophiles to form 2-oxo- or 2-imino-l(2ff)-pyridinelactic acids (204) (52JA4906). Similarly, the pyridinium salt (205) reacts by substitution in potassium hydroxide solution, whereas potassium t-butoxide causes proton abstraction and formation of the JV-vinyl derivative (206) (79JA3607). 

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