Quinolinium salts reduction

Dihydro-1-methyIquinoline can be prepared by brief treatment of 1-methyl-quinolinium salts with sodium amalgam in water under alkaline conditions [87]. Reduction of quinolimum salts in acid solution gives dimeric compounds with structures analogous to 22, but with N-alkyl substituents [83]. 

IV. Complex Metal Hydride Reduction of Quinolines and Quinolinium Salts... 

A. Reductions with Sodium Borohydride Quinolinium salts are converted by sodium borohydride to the corresponding 1,2,3,4-tetrahydroquinolines as the major product. Usually, however, small amounts of 1,2-dihydroquinoline can be... 

The reduction of quinolinium salts or quinolines with lithium aluminum hydride gives predominantly the 1,2-dihydroquino-lines.78,92, 95- 97-103 The yield of product appears to depend upon the... 

Similar problems arise with quinolinium salts as both C2 and C4 are susceptible to radical addition. Where either of these positions is blocked by a substituent, reactions often proceed in high yield. For example, Minisci et al. have described a useful method of formylating heteroaromatic bases which begins with an iron(II) promoted reduction of /-butyl hydroperoxide <86JOC536>. The /-butyloxy radical thus produced abstracts a hydrogen atom from 1,3,5-trioxane 34 giving intermediate 33. Union of 33 and the quinolinium salt 35 next produces radical cation 36, which is oxidised to 32 by iron(III) (Scheme 14). 

Heteroaromatic cations undergo reduction when treated with 1,4-dihydronicotinamide. An early study showed that the 10-methylacridinium ion (87) was rapidly reduced in a redox reaction to the 9,10-dihydro adduct by 1,4-dihydronicotinamides (M Scheme 18). A variety of systems including py-ridines, isoquinolines, quinolines and phenanthridines have been studied using this and related procedures. The selective reduction of pyridinium and quinolinium salts with 1-benzyl-1,2-dihydro-isonicotinamide (89) has been achieved. The selective conversion to the thermodynamically more stable 1,4-dihydro species (90 Scheme 18) is rationalized by the reversibility in the formation of the kinetic products (i.e. the 1,2-adducts) in the presence of pyridinium ions. In the pyridinium case 1,6-di-hydro adducts were also observed in some cases. Reactivity in such systems is sometimes hindered due to hydration of the dihydropyridine system. This is particularly so in aqueous systems designed to replicate biological activity. Dihydroazines derived from isoquinolines and 3,5-disubstituted pyridines have been reported to overcome some of these difficulties. ... 

However, l-benzyl-3-cyanoquinolinium bromide (168) gives a 75% yield of the 1,4-dihydro adduct 169 when reduced with NBH and allowed to equilibrate in the presence of the parent quinolinium salt. 1,4-Dimethyl-2-methylaminoquinolinium iodide (170) undergoes hydride attack at the 2 position with borohydride to give the product 171 as an unstable yellow oil. Alstonilin or benz[ ]indolo[2,3-fl]chinolizidine-type alkaloids (173) have been successfully prepared in high yields from the isoquinolinium salt 172 via hydride reduction. ... 

Dihydroquinolines predominate as the major reduction product of quinolinium salts with LAH. As in the pyridine series, preferred attack occurs at the 2 position. 

A directed formation of the important chiral center at C-3 by reductive amination of diketo precursors A (see Scheme 4, Section IV,A,4), selectively at the aliphatic keto function—as proposed for the biosynthesis—could not be achieved chemically in the presence of the aromatic keto function, owing to the fast ring closure, for example, of 75 (cp. Scheme 20, Section V,C,3) to iso-quinolinium salts like 90. As this aromatic keto function could not be protected selectively, the biomimetic nitrogen incorporation was performed on the monoketone 110, readily available according to Scheme 14 (Section V,B). 

It has also been suggested that the reduction by 1,4-dihydropyri-dine derivatives proceeds by a one-step hydride transfer mechanism (HT-mechanism), which seems to be contrary to the ET-mechanism described above. This assertion is mostly based on the results from the reduction of cationic substrates such as quinolinium salts, acridinium salts, and protonated Schiff bases (Srinivasan et al. 1982). For example, Ostovic et al. (1983) reported that the value of the kinetic isotope effect does not change significantly for the reactions with a series of substrates with which equilibrium constants change widely. 

Asymmetric tetrahydroquinolines have been prepared from aminochalcones by profiting of the Bronsted acid catalysis action of quinolinium salts with an optically active anion. This photocyelization-reduction reaction has heen first carried out in hatch and then optimized in flow. ... 

The key intermediate 21 is in principle accessible in any of several ways. Thus reaction of thiophenecarbox-aldehyde with amninoacetal would lead to the Schiff base 20 treatment with acid would result in formation of the fused thiophene-pyridine ring (21). Alkylation of that intermediate with benzyl chloride gives the corresponding ternary imini urn salt 23. Treatment with sodium borohydride leads to reduction of the quinolinium ring and thus formation of ticlopidine (24). ... 

Quinolinium and isoquinolinium salts form predominantly 1,2-dihydro products with LAH reductions in aprotic solvents. With the latter the enamine system revealed is amenable to functionalization... 

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