HINDERED ROTATION IN SUBSTITUTED 1,2,3,4-TETRAHYDRO-6,7-DIMETHOXYISOQUINOLINES

Conformational information concerning 1- and 2-substituted l,2,3,4-tetrahydro-6,7-dimethoxyisoquinolines can be obtained by examination of the proton magnetic resonance (pmr) spectra of a suitable series of these compounds. The pmr spectra of 1,2,3,4-tetrahydro-2-acetyl-6,7-dimethoxyisoquinoline and its C-1 derivatives indicate the presence of unequal populations of two conformers at room temperature. The rates of exchange between the conformers were, in several cases, obtained from a match of experimental line widths (expanded sweeps) and calculated line widths as derived from the Gutowsky-Holm line shape equation. In the case of 1-benzyl-2-acetyl-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline the rates were obtained from the methoxy, acetyl, and aromatic resonances and each gave Arrhenius activation energies of 20.6 ±0.5 kcal/mole. The collective data for this series suggest that the two conformations observed reflect the two minimum energy conformations of N,N-disubsti-tuted amides resulting from rotation of the N-acetyl group. This conclusion, as well as that concerning the value of the activation energy for the exchange process, differs markedly from that previously reached. Finally, in 2-substituted 1-(o-aminobenzyl)-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinolines, the location of the C-1 benzyl group appears to be a function of the size of the substituent in the 2 position. © 1969, American Chemical Society. All rights reserved.