A-Pyridinium methyl ketone salts

Pyridines from a-pyridinium methyl ketone salts and a,P-unsaturated ketones. 

KrOhnke annulation involves the condensation reaction of an a-pyridinium methyl ketone salt such as phenacylpyridinium bromide 191 to an enones such as benzalacetophenone 193 to afford 2,4,6-triphenylpyridine 194 in 90% yield. Krdhnke found that glacial acetic acid and ammonium acetate were the ideal conditions to promote the desired Michael addition. 

Michael addition, q.v., of oc-pyridinium methyl ketone salts to a,p-unsaturated ketones, generating the 1,5-dicarbonyl compounds which undergo ammonium acetate-promoted ring closure, to yield substituted pyridines ... 

Methyl aryl ketones react with iodine in the presence of excess pyridine to give pyridinium salts. Cleavage of the salts is readily accomplished by heating with aqueous-alcoholic sodium hydroxide. Over-all yields of 60-83% are reported. This two-step procedure affords a method similar to the haloform reaction for degradation of certain methyl ketones to acids with one less carbon-atom. 

Aryl methyl ketones can be converted to a-keto dithioates, as shown in Scheme 11 [43]. Therefore, on treatment with iodine and pyridine, the ketone 44 yields pyridinium salt 45, and 45 can then be treated first with elemental sulfur in the presence of triethylamine in DMSO and DMF and then with methyl iodide to give S-methyl a-keto dithioate 46. The reaction of l-(diethylamino)-2-(phenylthio)acetylene (47) with elemental sulfur in refluxing chlorobenzene gives compound 48 in which the dithioester and thioamide groups directly connected to each other (Eq. 17) [44]. 

An interesting formation of highly substituted trihydroxybenzenes (36) and (37) together with the simpler phenol (38) involves the transfer of a methyl group from O to induced by a pyridinium halide, and the similarly congested 2,4,6-tris-(4-t-butylphenyl)-phenol (39) results from the pyrylium salt (40) (Scheme 6) formed by the reaction of 2 moles of the aldehyde Bu C6H4CHO with 1 of the ketone Bu CeH4COMe. 

Support-bound alkylating agents have been used to N-alkylate pyridines and dihydropyridines (Entries 7 and 8, Table 15.21). Similarly, resin-bound pyridines can be N-alkylated by treatment with a-halo ketones (DMF, 45 °C, 1 h [267]) or other alkylating agents [246]. Polystyrene-bound l-[(alkoxycarbonyl)methyl]pyridinium salts can be prepared by N-alkylating pyridine with immobilized haloacetates (Entry 8, Table 15.21). These pyridinium salts react with acceptor-substituted alkenes to yield cyclopropanes (Section 5.1.3.6). Pyridinium salts have also been prepared by reaction of resin-bound primary amines with /V-(2,4-dinitrophenyl)pyridinium salts [268,269]. 

A mixture of three products is obtained, in which the 7-methylated indole (62, R7 = Me) predominates (when methyl ethyl ketone is the ketone used), and predominates greatly when a substituent is present at position 4.64 The reaction mechanism is extremely complex, and the 7-methyl group is claimed to arise from the ethyl group of the ketimine. The synthesis is general, but gives a mixture of polyalkylated indoles in poor yield. Instead of a preformed alkylimine, a simple mixture of a dialkyl ketone and a primary alkylamine can be used. The N atom of the indole is provided by the alkylamine the N atom of the pyridinium salt is eliminated, along with the nitro group.65 67... 

A simpler large scale method to obtain pyrantel, morantel (10a,b) and oxantel (11) involves condensation of 23 with an aryl aldehyde in presence of a base. Water is removed by azeotropic distillation or by using a chemical scavenger like methyl/ethyl formate, which reacts with water to push the reaction in the forward direction (Scheme 3). Other methods to prepare pyrantel and its derivatives are also reported [5,6,13-17]. The l-(2-arylvinyl)pyridium salts (18,19), structural congeners of pyrantel/moratel, are prepared by quaternisation of pyridine with the appropriate bromomethylaryl ketones (27) to afford 28. The latter is reduced with sodium boro-hydride to give the carbinol 29, which on dehydration leads to the formation of l-(2-arylvinyl)pyridinium bromides (18,19) [8]. 

Naphthoic acid Methyl 1-naphthyl ketone is dissolved in glacial acetic acid (5-10 parts) and treated with the calculated amount of bromine in the cold. The mixture is warmed gently on a water-bath and then poured into water containing a little sulfur dioxide the precipitated crystals of bromomethyl 1-naphthyl ketone are filtered off and pressed on porous plate they are then treated with an excess of pyridine and, when reaction has set in, the mixture is heated for a short time on the water-bath, after which the whole is dissolved in alcohol and the l-(l-naphthoylmethyl)pyridinium bromide is precipitated by ether. If recrystallized from water (10 parts), this salt melts at 170°. For hydrolysis, the bromide (0.5 g) is dissolved in water (40 g) and ethanol (12 ml), 10% sodium hydroxide solution (2 ml) is added, and the whole is heated for 12 min on a water-bath. Acidification then precipitates the 1-naphthoic acid. 

The interest in functionalized ionic liquids is growing because ionic liquids bearing ether, amino or alcohol functionalities have been shown to display special properties, including the ability to dissolve a larger amoimt of metal halide salts and to extract heavy metal ions from aqueous solutions. Imidazolium-based ionic liquids with ether and hydroxyl (see Section 2.2.1), thiourea, thioether and urea (see Section 2.2.8) " have been prepared following the standard quatemization procedure. A straightforward approach has been described for the preparation of imidazolium (as well as pyridinium) cations with ester, ketone or cyanide functionalities 1-methylimidazole reacts with methanesulfonic acid to provide the imidazolium salt 11, which undergoes a Michael-type reaction with methyl vinyl ketone as a ,j8-unsaturated compound to produce the ionic liquid 12 (Scheme 5). ... 

The uses of the versatile oxidant pyridinium chlorochromate have been reviewed. Pyridinium chlorochromate has been used for the oxidation of methyl 5-hydroxypentanoate to the aldehyde, an intermediate useful in the synthesis of leukotrienes, and the same reagent oxidatively cleaves secondary vicinal diols to the corresponding aldehydes. The reactivity of the chlorochromate ion as an oxidant can be influenced by the counter-ion. For example, the 4-dimethylaminopyridinium salt is a mild, selective reagent for the oxidation of allylic and benzylic alcohols. Pyridinium fluorochromate oxidizes primary and secondary alcohols to aldehydes and ketones respectively in dichloromethane solution, and shows a less pronounced acidity compared with the chloro-... 

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