A number of new 1-benzylisoquinoline derivatives have been synthesised. Attempts to perform oxidative coupling with some of these were unsucessful.IT has been suggested that the biosynthesis of aporphine alkaloids proceeds through intramolecular coupling of phenolic 1-benzylisoquino1ines.l Early attempts to simulate this process in the laboratory using laudanosoline failed because carbon-nitrogen coupling occurred in preference to the desired carbon-carbon c~u p l i n g .~~~ It has been further suggested that the removal of the basic properties of the nitrogen atom in laudanosoline or its methyl ethers, by acylation or quaternisation, would prevent carbon-nitrogen interaction occurring and make carbon-carbon interaction more favourable.2 No report of dehydrogenation experiments on any such modified materials had appeared and so it was decided to examine the action of various oxidising agents on a number of these compounds. The compounds chosen were of the first type and N-formyl was selected as the nitrogen blocking group.The synthesis of the N-formyl-l,2,3,4-tetrahydroisoquinolines was achieved directly from the corresponding 3,4-dihydroisoquinolines by a one-stage process involving reductive formylation with a mixture of formic acid and f~r m a m i d e .~ The yields obtained by this method were good and in most cases the products were obtained crystalline. It was essential to protect all hydroxyl groups by ether linkages because the presence of free hydroxyl groups appeared to inhibit the reduction completely. Formyl-1,2,3,4tetrahydro-7-hydroxy-1-(3hydroxy-4-methoxybenzyl)-6-methoxyisoquinoline (Vj) was prepared from the amine (Ia) and the acid (IIb). The latter was obtained by a modification of Schopf and Winterhalder's method.6 On reduction with lithium aluminium hydride the N-formyl compound (Vj) was converted into a base which was identical with an authentic sample of dl-reticuline (VIa) .' Attempted oxidation of the N-formyl compounds (Vh), (Vi), and (Vj) with alkaline potassium ferricyanide at Oo, chloranil or tetrachloro-o-quinone in ethanol or acetic acid, manganese dioxide in chloroform, or horseradish peroxidase and hydrogen peroxide at pH 9.3 * yielded only unchanged starting material. The failure of these compounds to M. Freifelder, J .
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