Two procedures for the synthesis of barely accessible 8-chloro-3,4-dihydroisoquinoline were investigated. The first approach is based on a directed ortho-lithiation of N-pivaloyl meta-chlorophenylethylamine, followed by formylation and subsequent ring closure under acidic conditions. In the second, more advantageous variant, the N-hydroxyethyl ortho-chlorobenzylamine intermediate undergoes a Friedel-Crafts reaction, and the resulting tetrahydro derivative is oxidized with N-bromosuccinimide. The 8-chloro-3,4-dihydroisoquinoline key intermediate is then applied in Suzuki reactions to give various 8-aryl-3,4-dihydroisoquinolines, which are finally treated with alkyl or aryllithiums to give 1-substituted 8-aryl-1,2,3,4-tetrahydroisoquinolines. These novel 1,2,3,4-tetrahydroisoquinoline derivatives can be used as building blocks in the synthesis of potential drug candidates.

研究了两种几乎无法获得的8-氯-3,4-二氢异喹啉的合成方法。第一种方法基于N-新戊酰基间-氯苯基乙胺的定向邻位锂化，然后进行甲酰化和随后在酸性条件下闭环。在第二个更有利的变体中，使N-羟乙基邻氯苄胺中间体进行弗里德-克来福特反应，并且将所得的四氢衍生物用N氧化。-溴代琥珀酰亚胺。然后将8-氯-3,4-二氢异喹啉关键中间体应用于Suzuki反应中，得到各种8-芳基-3,4-二氢异喹啉，最后用烷基或芳基锂处理得到1-取代的8-芳基-1， 2,3,4-四氢异喹啉。这些新颖的1,2,3,4-四氢异喹啉衍生物可用作潜在候选药物合成的基础。