Isoquinoline, bromination nitration

Electrophilic substitution (bromination, nitration) of 2-substituted 1,2,3,6,7,116-hexahydro-4//-pyrazino[2,l -a]isoquinolin-4-ones occurred on the aromatic moiety to give either 11- or 8-substituted derivatives the site was not determined (76GEP2441261). The nitro group was reduced to an amino group, which was alkylated, acylated, and converted to different groups via a diazonium group, and involved in diazonium coupling. 

Bromination and nitration of some annulated thieno[3,2-6]pyridines were investigated. The reaction of thieno[3,2-c]isoquinoline A-oxide (181) with bromine yields 2,3-disubstituted product 182, whereas treatment of 181 with HN03 affords 2-nitro derivative 183 (1989CS305, 1989CS309). 

The nitration of isoquinoline also occurs predominantly at the 5- and 8-positions and may be achieved in tandem with bromination to give access to bromonitroisoquinolines in a one-pot procedure <20050S98>. Isoquinoline is selectively brominated at the 5-position using A-bromosuccinimide (NBS) in sulfuric acid and nitration, without isolation of 5-bromoisoquinoline, occurs on addition of potassium nitrate to afford moderate yields of 5-bromo-8-nitroisoquinoline 6 (Equation 3). 

A solution of 387 g. (3.0 moles) of isoquinoline in 350 ml. of 48% hydrobromic acid is evaporated to near dryness, and 480 g. (3.0 moles) of bromine is added slowly. (Hood.) The resulting mixture is heated under an air reflux condenser at 180-190° for 7 hours, during which evolution of hydrogen bromide is complete. After cooling, excess sodium hydroxide solution is added and the mixture is steam-distilled. Water is decanted from the distillate until approximately 5 1. remains, and nitric acid is added to the hot mixture until the bromoisoquinoline is in solution. Upon cooling the nitrate salt precipitates and is filtered off and redissolved in hot water. Addition of excess ammonium hydroxide precipitates the 4-bromoisoquinoline which upon recrystallization from ether melts at 39-40°. The yield varies between 45% and 74%. 

SeAi reactions occur preferentially in the 5- or 8-position of isoquinoline. Nitration with HNO3/H2SO4 at 25°C affords the 5- and 8-nitro compounds 1 and 2, bromination in the presence of strong protic acids or of AICI3 leads to the 5-bromo compound 3, and sulfonation with oleum at temperatures up to 180°C yields the 5-sulfonic acid 4 ... 

Isoquinolines may be converted into the 5- or 8-bromo derivatives by reaction with a brominating reagent, e.g. NBS, and an acidic catalyst, like chlorosulfonic or sulfuric acid. The selectivity for producing the 5- rather than the 8-isomer increased with the acidity of the catalyst. Nitration may also be achieved by... 

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