Pyridiniums nucleophilic substitution

A 1-pyridinium substituent has an activating effect on nucleophilic substitution of pyrazines and s-triazines. °... 

Intramolecular nucleophilic displacement of the bromo group by an azine-nitrogen occurs in the cyclization of A-2-quinaldyl-2-bromo-pyridinium bromide (248) to give the naphthoimidazopyridinium ring system. The reaction of 2-bromopyridine and pyridine 1-oxide yields l-(2-pyridoxy)pyridinium bromide (249) which readily undergoes an intramolecular nucleophilic substitution in which departure of hydrogen as a proton presumably facilitates the formation of 250 by loss of the JV-oxypyridyl moiety. 

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. 

Pyridine has another useful attribnte, in that it behaves as a nncleophilic catalyst, forming an intermediate acylpyridinium ion, which then reacts with the nucleophile. Pyridine is more nucleophilic than the carboxylate anion, and the acylpyridinium ion has an excellent leaving group (pATa pyridinium 5.2). The reaction thus becomes a double nucleophilic substitution. 

The a-, f3- and y-halogeno substituents in pyridines and their benzo analogues are each more susceptible to nucleophilic substitution than is the case for halobenzenes because of the overall electron deficiency of the heteroaromatic ring. Furthermore, halogen substituents a and y to nitrogen are usually more reactive than /3-halogens and this is particularly so in pyridinium type systems. 

Of relevance to the results just described is the observation93 of the formation of significant proportions of 6,6 -dichloro-6,6 -di-deoxysucrose hexabenzoate and a monochloro-monodeoxy-mono-O-p-tolylsulfonylsucrose hexabenzoate, on treatment of 6,6 -di-0-p-tolylsulfonylsucrose with benzoyl chloride in pyridine at room temperature. These products arise by nucleophilic substitution of the p-tolylsulfonyloxy groups by the chloride ion of pyridinium chloride the isolation of a monochloro-monodeoxysucrose derivative indicated a difference in reactivity of the p-tolylsulfonyloxy groups at C-6 and C-6. ... 

Cyano, halo, amino, and nitro groups in the 2- or 4-position of pyridinium ions are susceptible to nucleophilic substitution. Treatment of these compounds with aqueous alkali gives the corresponding pyridones. Since this transformation is not the result of oxidation, it will not be further considered here. 

Most of the foregoing reactions really comprise only the first stage— the addition step—of what potentially is a nucleophilic substitution reaction. Under this heading, then, might also be included the reduction of pyridinium ions with sodium borohydride. With 3-substituted pyridines the 1,6-dihydro derivatives are apparently the main ones formed.331 (See also the article by Anderson and Lyle in this volume.)... 

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. 

Variously substituted 2-azido-pyridines have been irradiated on a preparative scale in the presence of alcohols or amines for the synthesis of the corresponding variously substituted 1,3-diazepines, in good to high yields. In the presence of halo substituents on the pyridinium moiety, a nucleophilic substitution by the ZH reagent can also occur [93]. Among others, representative examples of obtained target are reported in Figure 12.1 [91, 93]. 

The first step involves the formation of a pyridinium ion by reaction of a pyrylium ion with a primary amine the second step (dequaternization) has been studied more extensively than the first (amine + pyrylium). This important work on dequaternization deserves special mention because, besides the value for synthesis and understanding of steric acceleration, it sheds new light on the mechanism of aliphatic nucleophilic substitution (84CSR47). 

In addition, the transfer of N-substituents from pyridinium cations to nitroalkane anions involves an electron-transfer mechanism not of the normal radical chain variety (83JA90). Further studies delineating the boundaries of competitive, distinct pathways in these reactions would be of general interest for better understanding of nucleophilic substitutions (86CJC1161,86JA7295 87ACR(ip)). 

Various decomposition reactions of heterocyclic cations in aqueous solution are expected to proceed via pseudobase intermediates. These intermediates have been established for the alkaline decomposition of the pyridinium ring of nicotinamide adenine dinucleotide300 and for various solution transformations of flavin-derived cations.112,113,301-303 Nucleophilic substitution by hydroxide ion in various heteroaromatic cations almost certainly proceeds via the appropriate pseudobase tr-complexes.304,305... 

The thermal reactions of the pyridinium borate salts are likely to follow the same electron-transfer path. Experimental evidence for this conclusion is the fact that the 5cc-butyl transfer is substantially faster than methyl transfer although a nucleophilic substitution mechanism would predict the less hindered group to be transferred preferentially. The fast rates of 5cc-butyl transfer can be readily explained on the basis of the electron-transfer mechanism (Eqs. 69-71) by considering the different boron-carbon bond strength [189, 190] for the various alkylborates. The boron-carbon bond cleavage (Eq. 70) is apparently the critical step, and its relative rate [191] as compared to that of the back electron transfer determines the overall rate for thermal alkyl transfers in pyridinium tetraalkylborate salts. 

Although not officially a transformation involving carboxylate, the anion formed by two electron reduction of l-methyl-4-(methoxycarbonyl)pyridinium iodide has been extensively used as an electron transfer agent in the study of aliphatic nucleophilic substitution reactions [80]. 

In another study, the same group attached 4-phenyl-pyridinium /V-oxide as pendant groups to the polychloromethyl styrene and its block copolymer with polystyrene via nucleophillic substitution with chloride as leaving group. The obtained macrophotoinitiators were used to obtain graft copolymers by grafting from method of MMA (Scheme 11.19, path a), and hydroxyl functionalization (Scheme 11.19, path b) [53]. 

Radiolabeled 4-[ F]fluoropyridine can be synthesized by no-carrier-added nucleophilic aromatic substitution with K[ F]F-K222- In another instance, the nucleophilic substitution reaction was also employed for the synthesis of steroids-containing 4-fluoropyridine motif, and for the synthesis of 4-fluoropyridines annulated with pyrrole (azoindoles).Substantial difference in the reactivity of the pyridinium ring toward nucleophilic substitution in 5-iodo-2,4-difluorpyridine was effectively used for the preparation of 4-fluoropyridines 93 and 94 using difluoropyridine 92 as starting material (Scheme 6.31). 

Nucleophilic substitution reactions involving molten salts are well known. A number of esamples of molten pyridinium hydrochloride (mp 144 °C) being used in chemical synthesis, dating back to the 1940s, are known. Pyridinium chloride can act as both an acid and as a nucleophilic source of chloride. These properties are exploited in the dealkylation reactions of aromatic ethers [85]. An example involving the reaction of 2-methoxynaphthalene is given in Scheme 5.2-51 and a mechanistic explanation is given in Scheme 5.2-52. 

The use of pyridinium salts is also an effective method to activate pyridine rings toward nucleophilic substitution. Bennasar has reported the addition of cuprates into the 2-position of... 

DMAP and alkyl bromides are used to make homologs of l-alkyl-(NA -dimethylamino)pyridinium bromide salts by undergoing a simple nucleophilic substitution. These compounds were tested for antifungal and antibacterial capacities and show promising activity against bacterial strains such as Mycobacterium, E. coli, Staphylococcus, and Salmonella. 

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