Quaternary pyridinium salt

The main features of the reactivity of pyridinium salts are (i) the greatly enhanced susceptibility to nucleophilic addition and displacement at the a- and 7-positions, sometimes followed by ring opening and (ii) the easy deprotonation of a- and 7-alkyl groups (see also section 5.11). 

The oxidation of pyridinium salts to pyridones by alkaline ferricyanide is presumed to involve a very small concentration of hydroxide adduct. 3-Substituted pyridinium ions are transformed into mixtures of 2- and 6-pyridones, for example oxidation of 1,3-dimethylpyridinium iodide gives a 9 1 ratio of 2- and 6-pyridones. 

7V-Acyl, particularly A-alkoxy- or iV-aryloxycarbonylpyridiniums can be reduc-tively trapped as dihydro-derivatives by borohydride no further reduction occurs because the immediate product is an enamide and not an enamine and therefore does not protonate under the conditions of the reduction.The 1,2-dihydro-isomers, which can be produced essentially exclusively by reduction at -70 °C in methanol, serve as dienes in Diels-Alder reactions. Irradiation causes conversion into 2-azabicyclo[2.2.0]hexenes removal of the carbamate and A-alkylation gives derivatives which are synthons for unstable A-alkyldihydropyridines, and convertible into the latter thermally.  

The easy specific reduction of 3-acylpyridinium salts giving stable 3-acyl-1,4-dihydropyridines using sodium dithionite is often quoted, because of its perceived relevance to nicotinamide coenzyme activity the mechanism involves addition of sulfur at C-4 as its first step, as shown below.1,4-Dihydropyridines are normally air-sensitive, easily rearomatised molecules the stability of 3-acyl-1,4-dihydropyr-idines is related to the conjugation between ring nitrogen and side-chain carbonyl group (see also Hantzsch synthesis, section 5.15.1.2). However, even simple pyridinium salts, provided the A-substituent is larger than propyl, or for example benzyl, can be reduced to 1,4-dihydropyridines with sodium dithionite.  

Organometallic reagents add very readily to A-alkyl-, A-aryl- and with important synthetic significance, A-acylpyridinium salts. In the simplest cases, addition is to an a-carbon the resulting 2-substituted-l,2-dihydropyridine can be handled and spectroscopically identified, with care, but more importantly can be easily oxidised to a 2-substituted pyridinium salt.  

A further consequence of the stabilisation of carbanionic centres at pyridine a- and y-positions is the facility with which vinylpyridines, and alkynyl-pyridines, add nucleophiles, in Michael-like processes (mercury-catalysed hydration goes in the opposite sense Complimentarily, pyridin-2-yl- and 4-ylethyl esters, sulfides or sulfones can serve as protecting groups, being readily and mildly removed by pyridine quatemisation (iodomethane), causing elimination of the vinylpyridinium salt.  

12 PYRIDINE ALDEHYDES, KETONES, CARBOXYLIC ACIDS AND ESTERS 

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Reactive halogen compounds, alkyl haUdes, and activated alkenes give quaternary pyridinium salts, such as (12). Oxidation with peracids gives pyridine Akoxides, such as pyridine AJ-oxide itself [694-59-7] (13), which are useful for further synthetic transformations (11). 

Fulvene-type enamines, which possess some nonbenzenoid aromatic character, have been synthesized by treating cyclopentadienylsodium with an amide-dimethyl sulfate eomplex (117aJ17b) or quaternary pyridinium salts (117c). One of the simplest ones produced is 6-(dimethylamino)fulvene (117a,117d). 

Partial hydrogenation of the quaternary pyridinium salts in the presence of triethylamine on palladium in methanol has been used for the synthesis of a large number of alkaloids. The tetrahydropyridine derivatives thus formed undergo various cyclization reactions in acidic media (89). 

Of derivatives of compound 3, the zwitterions 245 react with DMAD if magnesium bromide is added to give aminopyridine derivatives (00H(53)265). Compounds such as 102 are opened by acid to give quaternary pyridinium salts (92LA885). There are various interconversions of 2-substituted triazolopyridin-3-ones into 1-substituted zwitterions. An example is the reaction of 246 (83BCSJ2969) the reverse conversion is also reported. 

With the two starting compounds, the picolylsulfone and the a-bromoketone we applied the well known Tschitschibabin synthesis (ref. 10). The first step of this synthesis is the formation of a quaternary pyridinium salt. 

N Bodor, E Shek, T Higuchi. Delivery of a quaternary pyridinium salt across the blood-brain barrier by its dihydropyridine derivative. Science 190 155-156, 1975. 

Zinc(II) phthalocyanines with quaternary pyridinium salt substituents are effective photobactericides for both Gram + ve (Enterococcus seriolicida) and Gram —ve (Escherichia coli Pseudomonas aeruginosa) bacteria.262... 

The effects of electron withdrawal by ring nitrogen are increased in pyridinium and related cations. Hence AAprotonation, AAalkylation or AAoxide formation results in greater substituent reactivity at the a- and y-positions. In quaternary pyridinium salts, e.g. (7),... 

N. Bodor, R. G. Roller, and S. J. Selk, Elimination of a quaternary pyridinium salt delivered as its dihydropyridine derivative from brain of mice, J. Pharm. Sci. 67 685 (1978). 

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. 

More than 130 different organic chemicals are currently employed as herbicides in the U.S. All of the main families of organic compounds are represented aromatic, aliphatic, and heterocyclic. Herbicidal activity is found in a variety of classes of compounds haloaliphatic, phenoxy, and benzoic acids carbamates dinitroanilines acetanilides amino triazines quaternary pyridinium salts uracils and ureas. A few selected key examples are reviewed below. 

Reduction of quaternary pyridine salts with sodium amalgam afford the 1,2-dihydro whereas sodium hydrosulphite gives the 1,4-dihydro derivative, respectively362. From a preparative point of view, partial hydrogenation of quaternary pyridinium salts in alkaline media to give substituted 1-methyl-A2-piperideines is very important363,364. 

Piperideines unsubstituted at the nitrogen atom may be prepared from the corresponding pyridine compounds by partial reduction with sodium and boiling alcohols (the Ladenburg reduction), by electrolytic reduction, or, preferably, by reduction with aluminum hydride. l-Alkyl-3-piperideines are prepared by reduction of quaternary pyridinium salts with formic acid (the Lukes reduction) or with complex hydrides. 

Electrolytic reductions of quaternary pyridinium salts, especially of methyl methosulfates, lead to mixtures of 1-methylpiperidines and... 

Somewhat less useful is the aluminum hydride reduction of quaternary pyridinium salts. Reduction of the salts may be more conveniently performed by the use of sodium borohydride (see Section II, B, 6). Moreover, the aluminum hydride reductions of some dialkyl-pyridinium salts are accompanied by reductive cleavage of the pyridine ring,77 For example, methiodides of 2,5-dimethylpyridine,77 2-methyl-5-ethylpyridine,77 and 2-ethyl-5-methylpyridine61 afford mixtures of the corresponding tetrahydro and hexahydro bases along with a secondary amine, viz., 5-methylaminomethyl-2,4-hexadiene, 5-methylaminomethyl-2,4-heptadiene, and 7-methylamino-6-methyl-2,4-heptadiene, respectively. 

Reductions of quaternary pyridinium salts to 1-alkyl-3-piperideines may be performed preferably with the use of sodium or potassium borohydride in aqueous or alcoholic solutions. Lithium aluminum... 

In contrast to aluminum hydride reductions (see Section II, B, 4), no ring openings have been observed in reductions of quaternary pyridinium salts by means of sodium borohydride. Whenever possible, both isomeric tetrahydropyridines are formed, as it may be seen from the following examples (aluminum hydride, electrolytic, and formic acid reductions are included for comparison). 

Preparation of reagent Even in the absence of water a reagent consisting of iodine, sulfur dioxide, pyridine, and methanol undergoes rapid initial loss in strength, followed by slower change. The reactions involve the formation of quaternary pyridinium salts and pyridinium iodide, for example,... 

Nitrosobenzene, CjHsNO, which is obtained by the oxidation of phenylhydroxylamine, and p>nitrosodimethylaniline, p-(CH3)2NCjH4NO, which is easily prepared by the nitrosation of dimethylaniline, are fairly specific oxidizing agents for the preparation of aromatic aldehydes from benzyl halides or tosylates and of a-dicarbonyl compounds from from a-halo ketones [984, 985]. Also, a methylene group flanked by two carbonyls can be oxidized to a carbonyl group by nitrosodimethylaniline [986]. Pyridine is frequently used to form quaternary pyridinium salts from reactive halides prior to their oxidation to aromatic aldehydes, a-ketoaldehydes, or a-diketones [984] (equations 22 and 23). 

Piperidines are formed by the hydrogenation of pyridines over platinum catalysts in acid solution, generally at room temperature under 3-4 atmospheres of hydrogen (Eqn. 17.32). Acid is used in this reaction since the pyridinium salt is more easily hydrogenated than the free base. A quaternary pyridinium salt gives the N-alkyl piperidine in ethanol, without added acid, under these same... 

Isolation of xestamines D-H (22-26) from Calyx podatypa yielded two fractions, xestamines and their corresponding A -methylpyridinium salts [14]. It is interesting that these quaternary pyridinium salts exerted a moderate antibacterial activity against bacteria, that was about 40 times greater than the activity of the corresponding tertiary amines. 

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