Anion formation, Reissert compound

Among the great number of different approaches for the synthesis of phthal-ideisoquinoline alkaloids the application of Reissert compounds, developed first by Kerekes et al. (42,43), proved to be one of the most efficient and suitable methods (Scheme 24). Treatment of isoquinoline Reissert compounds 26 or 28 with sodium hydride in dimethylformamide resulted in the formation of the corresponding Reissert anions, which were reacted with dimethoxy- or meth-ylenedioxy-substituted o-formylbenzoic acid ester derivatives 178 and 179, respectively. The presumed mechanism of this reaction involves an initial reaction... 

The cyanide anion adds to C-1 in 2-benzoylisoquinolinium salts in water/DCM (dichloromethane), forming Reissert compounds then, just like their quinoline counterparts (see Section 3.2.3), the adducts can be deprotonated by a base with the loss of the iV-substituent and the formation of a 1-cyanoisoquinoline (Scheme 3.16). 

Analogously, although the enhanced reactivity of quinoline derivatives (relative to pyridine counterparts) in nucleophilic additions such as the formation of pseudobases and Reissert compounds probably relates to the relatively lower energy of the LUMO in the quinoline derivatives, the radicals from these heterocycles, in which the corresponding orbitals are singly occupied, are anionic thus, reactivity toward nucleophiles is also unlikely to be important. 

B. Reactions Involving the Formation of an Anion of the Reissert Compound... 

The anion 10, generated from the reaction of 3-benzoyl-3,4-dihydro-2-methylquinazoline-4-carbonitrile (a 2-methylquinazoline Reissert compound) with sodium hydride, undergoes both rearrangement and aromatization (cf. p 84), resulting in the formation of 4-benzoyl-2-methylquinazoline (32%), and 2-methylquinazoline-4-carbonitrile (20%). ... 

The formation of a Reissert anion (intermediate of type 16) is usually the introductory step in a great number of synthetic routes leading to isoquinoline as well as indole alkaloids and related compounds. On the one hand, the alkylation of a Reissert anion with alkyl halide followed by alkaline hydrolysis is the most frequently used method for the synthesis of 1-alkyl- or 1-arylalkylisoquinolines (20) (Scheme 4). On the other hand, Reissert anions react with aldehydes to form... 

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