669. Synthesis and oxidation of some 1-benzylisoquinoline derivatives

Abstract

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 . -

Synthesis and Characterization of Liquid Crystalline Perylene Diimides

“…Both pathways began with formation of the polyoxyethylene-substituted alcohols 7 . The most reproducible preparations of 7 involved alkylation of the phenolic groups of 6 with appropriate alkyl chlorides 5 , a procedure derived from reported preparations of polyoxyethylene derivatives of catechol and resorcinol. , The first synthetic pathway (Scheme ) was based on a well-established synthetic route to phenethylamines involving β-nitrostyrene intermediates. , Thus, alcohols 7 were efficiently converted to aldehydes 8 by Collins oxidation to yield the required phenethylamines 3 ph .…”

New potential mammalian lignan metabolites of environmental phytoestrogens

“…Diphenylthioacetals 17a-e, starting materials for the three component reaction, were prepared in excellent yields by treating the corresponding OBn or OMe benzaldehydes with PhSH and Me 3 SiCl (Stütz and Stadler 1977). Benzylic bromides 19a-e were prepared in high yield by treating the corresponding substituted benzylic alcohols with PBr 3 (Baxter et al 1965) (Table 1). …”

On the Actions of Compounds Related to Dopamine at a Neurosecretory Synapse

“…N-acetyldopamine (25) was prepared from protocatechualdehyde, which was protected by benzylation and converted to the co-nitro-styrene (Baxter et al, 1965). Reduction with lithium aluminium hydride gave 3,4-dibenzyloxyphenethylamine which was isolated as its hydrochloride.…”

“…Treatment with methylamine and demethylation with hydrobromic acid then gave epinine hydrobromide (5). For 3-hydroxy-4-methoxyand 4-hydroxy-3-methoxy-phenethylmethylamine hydrochlorides (6 and 7) isovanillin and vanillin, respectively, were first protected by benzylation (Baxter et al, 1965) converted to their w-nitrostyrenes and reduced with lithium aluminium hydride to the primary amines. These were then converted to the N-monomethyl compounds by reaction with benzaldehyde, N-methylation with dimethyl sulphate and hydrolysis of the benzal group (Kirkwood & Marion, 1950).…”

“…Dopamine hydrochloride (1, Table 1) was obtained from Koch-Light and re-crystallized. 3-hydroxy-4-methoxyphenethylamine hydrochloride (2) was prepared from isovanillin by reaction with nitromethane to give the w-nitro-styrene (Baxter, Allan & Swan, 1965) which was then reduced with lithium aluminium hydride (Fennoy, 1961). 4-Hydroxy-3-methoxyphenethylamine hydrochloride (3) was prepared by a similar method from vanillin.…”