1,2,4,5,6,116-Hexahydro isoquinoline, conformations

Conformational studies of c/5-6,11/)-H- and /rnns-6,ll/)-H-6-methyl-2,3,4,6,7,1 l/)-hexahydro-l//-pyrimido[6,l-n]isoquinolin-2-ones (136 and 137) by means of the MM2 method implemented in the HyperChem 4.5 suggested, that in the lowest-energy conformations heterocyclic moiety adopted trans-fu ed ring annotation in both cases, with a pseudo-equatorial and -axial methyl group, respectively (97LA1165). 

The relatively low chemical shift (1.30 ppm) of the 5-methyl group in hexahydro-4fl//-pyridazino[l,6-h]isoquinoline points to the presence of a trans-fused conformer 22 with an axial 5-methyl group (73JHC999). 

The trans-fused conformation of the heterorings of 9,10-dimethoxy-l 16-methyl-l,3,4,6,7,116-hexahydro[l,4]thiazino[3,4-a]isoquinoline was indicated by the appearance of Bohlmann bands in its IR spectrum (80JHC449). 

Of the six all-chair conformations of 2-methyl-l,3,4,6,7,llb-hexahydro-2//-pyrido[6,l-a]isoquinoline (60), the cis-Iax, cis-O, and cis-O x conformations could be discounted because they suffer from a number of nonbonded interactions (Scheme 11). The basic difference between the fram-fused and CIS-fused conformations is that in the tram-fused ring conformations (Teq and Tax) the perhydropyrimidine ring is fused onto the tetrahydropyridine... 

The coupling constants between llb-H and the C(l) methylene protons (14 and 6 Hz, and 9 and 3 Hz) for 9,10-dimethoxy-4-phenyl-l,6,7,llft-tetrahydro- and 1,3,4,6,7,llft-hexahydro-2//-pyrimido[6,l-a]isoquinolines indicate the predominance of the N-inside cis conformation (84JHC149). 

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