Aminoquinolizinium salts

Either silver acetate (64JCS2760) or hot water <81H(15)213> may be used to convert 2-bromoquinolizinium bromide to the 2-hydroxy analog in excellent yield (Scheme 60). By far the most extensive application of this or any bromoquinolizinium salt has been in the preparation of AT-substituted 2-aminoquinolizinium salts (70JMC554). A similar reaction of 2-bromo-l-hydroxyquinolizinium bromide and arylamines has been patented... 

Through the reaction of 2-bromoquinolizinium ion or its 1-acetoxy analog with suitable amines, Alaimo and coworkers have produced a large number of 2-aminoquinolizinium salts having useful medicinal activity. Most, but by no means all, of these active compounds are 2-arylaminoquinolizinium salts (219 and 220). Best anthelmintic activity was found in (219) when R2 was alkoxy (< Bu) or dialkylamino (NMe2 or NEt2) and R3 = H (70JMC554). 

Collicutt and Jones24 have recently described the preparation of 1-aminoquinolizinium salts. Beckmann rearrangement of the oxime (14) of 1,2,3,4-tetrahydro-l-oxoquinolizinium bromide gave the 1-acetamido derivative, which on hydrolysis with concentrated hydrobromic acid afforded 1-aminoquinolizinium bromide hydrobromide (15). 

Nitrosation of 1-aminoquinolizinium salts gives furazano[3,4-a]quinolizines (645). The first formed product is probably a C-nitroso derivative which is subsequently oxidatively cyclized <68JCS(C)1088). 

In a much poorer yield, compound (8) was the product from the thermal decomposition of 5-(2-pyridyl)tetrazole (305) at 400°C/10 Torr (78HCA1755). Compound (305) was prepared by treating pyridine-2-carbonitrile with hydrazoic acid. [l,2,3]Triazolo[l,5-a]pyridines are also the products from the treatment of 1-aminoquinolizinium salts (306a) with nitrous acid in a process proceeding via (306b) (69TL1549). 

An examination of the scope and limitations of the synthesis due to Westphal et al.H (Eq. 2) was made by Hough and Jones9 in their attempts to prepare aminoquinolizinium salts. A possible steric inhibition was noted... 

Diazonium coupling to 1-hydroxyquinolizinium bromide 21 yields a highly insoluble red product which has been assigned structure 20. The diazonium salt from l-hydroxy-3-aminoquinolizinium bromide has been coupled with alkaline j3-naphthol.21... 

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