Pyridinium compounds substitution

A proposed explanation of the reactivity of the 4-position versus that of the 2-position in pyridinium compounds has been advanced by Kosower and Klinedinst nucleophiles which are expected to form charge-transfer complexes will tend to substitute at the 4-position. However, it is not clear why this (usually unknown) property should govern the site of substitution, except for a bifunctional nucleophile such as hydrosulfite ion which can form a suitable bridge from the nitrogen to the 4-position. 

In addition to the chain length, the hydrocarbon chain unsaturation also plays a very important role. This is clearly shown by the data on cationic PCs, which demonstrate drastic transfection increase with increase of the number of double bonds per lipid from 0 to 2 (Fig. 13a). Studies on double chained pyridinium compounds SAINT (Synthetic Amphiphile INTeraction) (Fig. 17, inset) have shown that, while elongation of the saturated alkyl chains from 06 0/06 0 to 08 0/08 0 resulted in a reduction by a factor of about two in the transfection efficiency, introduction of double bonds reversed this effect and resulted in very strong increase of the transfection efficiency (Fig. 17). When substituting only one of the saturated 08 0 alkyl chains for unsaturated 08 1 chain, the transfection efficiency increased by an order of magnitude, while the diunsaturated compound,... 

The 2-halo-substituted benzimidazoles, then, more or less readily react with ammonia, amines and hydrazines (80AHC 27)241,70AHC(12)103,74CRV279), It is likely that the formation of the 2-pyridinium compound (123) when cycloheptimidazolin-2(l//)-one reacts with phosphoryl chloride in pyridine occurs via the 2-chloro intermediate (Scheme 56). The sulfur function of benzimidazole-2-sulfonic acid can be displaced by amino or alkylamino groups. 

Katritzky and coworkers have extensively developed the activation of amines by reaction with pyry-lium salts to provide (V-alkyl (or N-aryl) pyridinium compounds. When buttressing substituents were present to discourage attack on the pyridine ring, the N-alkyl substituent was subject to displacement and elimination processes. In general, primary alkyl substituents reacted with most nucleophiles in a normal 5n2 process as shown in Scheme 12, whereas competition between substitution and elimination took place with the secondary analogs, with elimination dominating the reactions starting from cycloalkyl-amines. 

NMR experiments on the reactions of halophosphates esters with pyridine showed that equilibria involving the formation of pyridinium salts in these reactions are almost entirely shifted to the left for chloro- and bromo-phosphates and to the right for the corresponding iodophosphates. This explains dramatic differences in chemical reactivity between these compounds. Substituted medium-sized and large N-heterocycles (117) have been prepared via an extension of the Suzuki reaction involving the palladium-catalysed coupling of vinyl-phosphates (118) with aryl or heteroaryl boronic acids (Scheme 27). ... 

Table 1 indicates that phosphyloximes of 2-substituted pyridinium compounds are very... 

The carboxamide is skewed from planarity by 23° in nicotinamide and the nitrogen is oriented toward C-2. In N-substituted pyridinium compounds and... 

Coniceine is most readily obtained by the action of alkalies on iodoconiine and also by the action of hydriodic acid on conhydrine (132). It is a dextrorotatory oil, [aJo - - 42°, b.p. 150-151°, which forms crystalline salts (Table 3). Alpha-substituted pyridine containing a halogen atom in the side chain can rearrange to pyridinium compounds (201). This same... 

Similarly, MI-542 reacts with a-bromoacrylonitrile to give the 3-cyano derivatives and with a-bromo-a-unsaturated acids by trans addition to form substituted 3-carboxyldihydrothiazolo[3,2-fl]pyridinium compounds that are readily decarboxylated, Under these conditions MI-542 does not react with )3-bromostyrene. 

B. Brominating agents Pyridinium hydrotribromide (pyridinium hydrobromide perbromide) Dioxane-bromine complex A-Bromosuccinimide 2,4,4,6-Tetrabromocyclohexadienone Benzyltrimethylammonium tribromide Substitute for bromine when increased selectivity or mild reaction conditions are required Same as for pyridinium hydrotribromide Substitute for bromine when low Br concentration is required Selective bromination of polyolefins and cyclization induced by Br+ Selective bromination of alkenes and carbonyl compounds... 

An interesting intermediate 30 was proposed to result from the sequential addition of pyridine to tetrachlorocyclopropene (31). Compound 30 represents an alkyl nitrogen ylide with two 1-chloroalkyl pyridinium moieties in the same molecule. Pyridines with electron-withdrawing groups and heterocycles with an electron-deficient nitrogen, for example, pyridine-3-carbaldehyde or quinoline, react with 31 to yield the corresponding mono-substituted products 32a and 32b (83JOC2629) (Scheme 8). 

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