Pyridines 4-methylisoquinolines

As a further extension of photocyclization of the enamides prepared from 1-methylisoquinolines, Naito and Ninomiya (67) and Lenz (48) synthesized aza analogs of berbine, azaberbines, by irradiation of pyridine analogs of the parent enamides (27) (Scheme 57). 

Determinations of the ERE of quinoline from thermochemical data have given results which range from 47.3 to 69 kcal mole-1.49-271-272 There appear to be no corresponding estimates for isoquinoline, but a value of 48 9 kcal mole-1 has recently been deduced from a comparison of the equilibrium constants for pseudo-base formation of iV-methylisoquinoline cation and its dihydro analog 73.273 Comparison of these ERE values with those obtained for naphthalene (61-75 kcal mole-1) shows that they parallel the somewhat lower resonance energy of pyridine relative to that of benzene. 

Method (a) usually gives only trichloro or tribromo derivatives of N-hetero-cycles that contain active CH3 groups and it is not applicable to 3-methyl-pyridine, 3- or 4-methylquinoline, or 1-, 3-, or 4-methylisoquinoline further, 2- and 4-methylpyridine cannot be brominated by this method, although they can be thus chlorinated.755,757... 

Exceptionally, there is an example for simultaneous construction of both benzene and pyridine rings toward a perfluorinated isoquinoline. Feast et al. reported the synthesis of perfluoro-3-methylisoquinoline via the hetero Diels-Alder reaction of perflu-oro-l,4,6,7-tetrahydro-l,4-ethanonaphthalene with trifluoroacetonitrile followed by pyrolysis, which involved elimination of tetrafluoroethylene (Scheme 25) [93]. 

Fragmentation Similar to pyridine HCN elimination (Am 27) from M+, [M-l]+, and fragments. In methylquinolines and methylisoquinolines also CH3CN elimination (Am 41). In alkyl-substituted (C j) quinolines, benzylic eleavage dominates exeept when neighboring effeets of N play a role. For 2- and 8-alkylquinolines as well as 1- and 3-alkylisoquinolines, see rearrangements in pyridines. 

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