Quaternary Quinolinium and Isoquinolinium Salts

The predominant property of these salts is the ease with which nucleophiles add to the quinolinium-2-and the isoquinolinium-1-positions. Such additions are favoured in these bicyclic compounds since the products retain a complete aromatic benzene ring. Hydroxide, hydride and organometaUic nucleophiles aU add with facility, though the resulting dihydroaromatic products require careful handling if they are not to disproportionate or be oxidised. This approach can give 2-nifluoromethyl-quinolines CFj carbanion (from trifluoro(trimethylsilyl)methane and fluoride) is added to an A -(para-methoxybenzyl)-quinolinium salt, then the A -substituent is removed and oxidation to the aromatic level achieved with ceric ammonium nitrate.  

The position of fastest addition to quinohnium salts is C-2, but with reversible reactions, a thermodynamic adduct with the addend at C-4 and the residual double bond in conjugation with the nitrogen, can be obtained.  

The Zincke salt (A -(2,4-dmitrophenyl) salt) of isoquinoline is easily transformed into chiral isoquinolinium salts on reaction with chiral amines - an ANRORC sequence in which the ninogen of the chiral amine ends up as the nitrogen of the isoquinolinium product - nucleophilic addition of Grignard reagents to these salts shows good stereoselectivity.  

More practically significant, are the many examples of nucleophilic addition to salts in which an N-substituent conjugates with the nitrogen, and thus stabilizes the product - Reissert compounds were the first examples. These are produced by cyanide addition to an iV -acyl-quinolinium or -isoquinolinium salt in the classical process the acylating agent is benzoyl chloride. Reissert compounds are traditionally prepared using a dichloromethane-water two-phase medium improvements include utilising phase-transfer 

Reissert compounds have utility in a number of ways deprotonation, alkylation and removal of acyl and cyanide groups leads to the corresponding substituted heterocycles. Af-Sulfonyl analogues of Reissert adducts easily eliminate arylsulfinate, thus providing a method for the introduction of a cyano group.  

The predominant property of these salts is the ease with which nucleophiles add to the quinolinium-2- and the isoquinolinium-1-positions. Hydroxide, hydride and organometallic nucleophiles all add with facility, though the resulting dihydroaromatic products require careful handling if they are not to disproportionate (see also section 6.7) or be oxidised.  

Treatment of quinoline and isoquinoline with sodium borohydride in a mixture of acetic acid and acetic anhydride gives good yields of -acetyl-1,2-dihydro-derivatives. 

Reissert compoimds have utility in a number of ways deprotonation, alkylation and removal of acyl and cyanide groups leads to the corresponding substituted 

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Organomagnesium compounds react with enamine salts to give bases substituted on the a-carbon atom. These reactions may be regarded as an extension of Freund s observations on quaternary quinolinium and isoquinolinium salts. The reaction of hydrastinine with methylmagnesium bromide 318 (Eq. 10) is a typical example. The... 

At pH 13.0, most quats are titrated, but those with the quaternary nitrogen in an aromatic ring (pyridinium, quinolinium, isoquinolinium and biguanidinium salts) are not. These materials cause a small positive error at pH 13.0, which is overcome by heating the alkaline solution. This opens the ring and destroys the quaternary nitrogen function ... 

The use of 2,4-dinitroi enyl aromatic quaternary salts prepared directly from the parent isoquinoline compound and 2,4-dinitrophenyl bromide or chloride enhances the electron-deficient nature of the iso-quinolinium salts, accelerates the rate of their [4 + 2] cycloaddition reactions with electron-rich alkenes, and has permitted the use of isoquinolinium s ts previously regarded as unmanageable. The application of these observations in the total syntheses of methylamottianamide and 14-epicorynoline is summarized in Scheme 26. ... 

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