Pyridinium salts formation

Triflates are more reactive than mesylates and tosylates. Triflates are generally prepared by the reaction of alcohols with triflic anhydride in the presence of pyridine at low temperature. In the case where concomitant pyridinium salt formation lowers the yield of the desired triflate, more-hindered bases such as (94) have been used (Scheme 37). ... 

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). 

Quaternization of harman (235) with ethyl bromoacetate, followed by cyclization of the pyridinium salt 236 with 1,2-cyclohexane-dione in refluxing ethanol yielded an ester which on hydrolysis gave the pseudo-cross-conjugated mesomeric betaine 237. Decarboxylation resulted in the formation of the alkaloid Sempervirine (238). The PCCMB 237 is isoconjugate with the 11/7-benzo[u]fluorene anion—an odd nonalternant hydrocarbon anion—and belongs to class 14 of heterocyclic mesomeric betaines (Scheme 78). 

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. 

Quinolizinium and other fused pyridinium salts are formed when a-methylheterocycles react with 2,4,6-triphenylpyrylium, which thus behaves as a C3-synthon <96MC99>. Pyrylium salts also feature in a stereocontroUed route to conjugated dienynes which has led to a synthesis of Carduusyne A, a marine metabolic fatty acid <96TL1913> and in the formation of pyridinium containing crown ethers <96LA9S9>. 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

This is the most convenient way to prepare quinuclidone hydrochloride. The second step illustrates the conversion of an N-alkyl-pyridinium salt to an N-alkylpiperidine. The third step illustrates the formation of a bicydic system by the Dieckmann condensation. 

Using a different set of hydrogen bonding fragments Kruger and Martin have reported the formation and structural characterization of the double helicate 71 [93]. This helical structure can be prepared by assembling 72 diammonium-bis-pyridinium salt around two chloride anions (see Scheme 36). 

The oxidation of A -phenylhydrazones in the presence of pyridine leads to the formation of 5-triazolo[4,3a]pyridinium salts hy attack of pyridine as a nucleophile on the nitrilimine intermediate (Scheme 54) [77]. 

This may be caused by two factors. First of all, in the case of pyridinium salts there may be a contribution from the hydrophobic interactions between neighbouring bound headgroups (an effect which would not contribute to the free energy of micelle formation). Secondly, a steric hindrance effect may prevent the positive chrge on the trlmethylammonium head group from approaching close to the polylon charge. 

When mechanical vibration of bis(pyridinium) salts (see Scheme 5.5) was conducted with a stainless steel ball in a stainless steel blender at room temperature under strict anaerobic conditions, the powdery white snrface of the dicationic salts turned deep blue-purple (Kuzuya et al. 1993). Single-line ESR spectra were recorded in the resnlting powder. No ESR spectra were observed in any of the dipyridinium salts when mechanical vibration was conducted with a Teflon-made ball in a Teflon-made blender nnder otherwise identical conditions. When observed, the ESR signals were quickly quenched on exposnre to air and the starting dicationic salts were recovered. Each of the resulting powders was dissolved in air-free acetonitrile, and the ESR spectra of the solution were recorded after the material had been milled nnder anaerobic conditions. Analysis of the signal hyperflne structure confirmed the formation of the corresponding cation-radicals, which are depicted in Scheme 5.5. 

The same group expanded the scope of the aza-Diels-Alder reaction of electron-rich dienes to Brassard s diene 97 (Scheme 37) [60]. In contrast to Danishefsky s diene, it is more reactive, but less stable. Akiyama et al. found chiral BINOL phosphate (R)-3m (3 mol%, R = 9-anthryl) with 9-anthryl substituents to promote the [4 + 2] cycloaddition of A-arylated aldimines 94 and Brassard s diene 97. Subsequent treatment with benzoic acid led to the formation of piperidinones 98. Interestingly, the use of its pyridinium salt (3 mol%) resulted in a higher yield (87% instead of 72%) along with a comparable enantioselectivity (94% ee instead of 92% ee). This method furnished cycloadducts 98 derived from aromatic, heteroaromatic, a,P-unsaturated, and aliphatic precursors 94 in satisfactory yields (63-91%) and excellent enantioselectivities (92-99% ee). NMR studies revealed that Brassard s diene 97 is labile in the presence of phosphoric acid 3m (88% decomposition after 1 h), but comparatively stable in the presence of its pyridinium salt (25% decomposition after 1 h). This observation can be explained by the fact that the pyridinium salt is a weak Brpnsted acid compared to BINOL phosphate 3m. 

When 4-unsubstituted pyridinium salts were used, simultaneous chlorination accompanies the dithiazolium rings formation to give chlorinated salts 114 and radicals 115 after reduction in high yields (2002CC2562,2003JA14394 Scheme 57). 

A surprising synthesis of 1,2-fused pyridinium salts (type 230) is exemplified by the formation of derivative 252 from dihydrofuran 251 (83CL21). Amide 253 undergoes, in analogy with homoberbine syntheses, twofold cyclization to achieve enamine 254 (03WO84963). 

This protective group is introduced by an acid-catalyzed addition of the alcohol to the vinyl ether moiety in dihydropyran. />-Toluenesulfonic acid or its pyridinium salt is used most frequently as the catalyst,3 although other catalysts are advantageous in special cases. The THP group can be removed by dilute aqueous acid. The chemistry involved in both the introduction and deprotection stages is the reversible acid-catalyzed formation and hydrolysis of an acetal (see Part A, Section 8.1). 

The rates of H-D exchange at the a-positions have been determined for a series of N- substituted pyridinium salts and pyridine 1-oxides in D20 at 75 °C (Scheme 197) (70JA7547). The rates give a good correlation with the Taft inductive parameter <77 pi = 15). The positively charged nitrogen in a ring has been estimated to activate the a-position towards deprotonation and ylide formation by a factor of 1014 16. 

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