Pyridine ring quaternary salts

Finally, a novel synthetic route involves formation of the pyridine ring from a fused pyran intermediate, e.g. (139) - (140) (70CB1250, 80JOC1918, 73JCS(P1)823). If a pyrylium salt is used, a quaternary pyridopyrimidinium salt such as (141) is formed 77KGS14S4). 

Most N-phenyl quaternary salts are not prepared by direct quater-nization but rather by introducing the nitrogen substituent before ring closure. It has recently been found that diphenyl iodonium boro-fluoride reacts smoothly with pyridine the phenyl carbonium ions formed give the 1-phenylpyridinium ion good yield. ... 

The introduction of a nitrogen atom into the benzene ring of indole affords a center, not present in indole itself, at which quaternary salt formation occurs readily, and the base 95 is converted into a quaternary salt (96) on the pyridine-type nitrogen atom. ... 

The only examples of ring oxidation are the one-electron anodic oxidation of Nl-aryl[l,2,4]triazolo[4,3-a]pyridines such as compound 143 to give quaternary salts (88ZC187), and the voltammetric oxidation of the anti-depressant Trazodone (Section V.A) (87MI1). 

Quatemization of the isoxazole nitrogen atom makes the ring particularly susceptible toward nucleophilic attack there is a certain analogy here with pyridine. The cleavage of the ring proceeds extremely readily in quaternary salts of isoxazole, even occurring by the action of such weak nucleophilic agents as the anions of carboxylic acids. 

Fig. 10.8 A where the R substituents are alkyl or heterocyclic radicals to give compounds such as cetyltrimethylammonium bromide (cetrimide), cetylpyridinium chloride and benzalkonium chloride. Inspection of the stmctures of these compounds (Fig. 10.8B) indicates the requirement for good antimicrobial activily of having a chain length in the range Cg to Cig in at least one of the R substituents. In the pyridinium compounds (Fig. 10.8C) three of the four covalent links may be satisfied by the nitrogen in a pyridine ring. Polymeric quaternary ammonium salts such as polyquatemium 1 are finding increasing use as preservatives.

Tetrahydrotetrazolo[l,5- ]pyridine 52 was reacted with dimethyl sulfate to give a mixture of quaternary salts 1-methyl 53 and 2-methyl compounds 54 from which the 1-alkyl compound was separated as a crystalline hexafluorophosphate salt 53 (A = PF6) in good yield. This salt when treated with potassium hydride in the presence of 18-crown-6 and KCN underwent deprotonation to give the saturated six-membered ring 55. 

Pyridine quaternary salts, uses for, 22 121 Pyridine ring syntheses, 22 108-112 from nonheterocyclic compounds, 22 108-110... 

Diazines are generally resistant to electrophilic attack on carbon, and, as for pyridine, addition on nitrogen is observed. Alkyl halides give mono-quaternary salts di-quatemary salts are not formed under normal conditions. Of conrse, if the diazine ring carries a snbstitnent that makes the starting... 

The pyridine ring is easily reduced in the form of its quaternary salts to give hexahydro derivatives by catalytic hydrogenation [446], and to tetrahydro and hexahydro derivatives by reduction with alane aluminum hydride) [447], sodium aluminum hydride [448], sodium bis 2-methoxyethoxy)aluminum hydride [448], sodium borohydride [447], potassium borohydride [449], sodium in ethanol [444, 450], and formic acid [318]. Reductions with hydrides give predominantly 1,2,5,6-tetrahydro derivatives while electroreduction and reduction with formic acid give more hexahydro derivatives [451,452]. 

As a first approximation, the reactions of pyridines with electrophiles can be compared with those of trimethylamine and benzene. Thus, pyridine reacts easily at the nitrogen atom with reagents such as proton acids, Lewis acids, metal ions, and reactive halides to form salts, coordination compounds, complexes, and quaternary salts, respectively. Under much more vigorous conditions it reacts at ring carbons to form C-substitution products in nitration, sulfonation, and halogenation reactions. 

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