Benzyl Chloride → Benzaldehyde, 3,5-dimethoxy-4-(phenylmethoxy)-

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Reaction Steps

4-Benzyloxy-3,5-dimethoxybenzaldehyde (13j) was prepared by the reaction of syringaldehyde with benzyl chloride in the presence of K2CO3 in boiling acetone. Similarly, reaction of t-butyldimethylsilyl chloride with syringaldehyde in DMF in the presence of N,N-diisopropylethylamine gave 4-(t-butyldimethylsilyl)-oxy-3,5-dimethoxybenzaldehyde (13k) (Scheme VII). Wittig reaction of phosphonium bromides 14a-b with benzaldehydes 13a-k in THF in the presence of sodium hydride followed by preparative thin-layer chromatographic separation of the crude products afforded the cis stilbenes 15a-k and trans stilbenex 16a-k (Scheme VIII). Reaction of compounds 15k and 16k with tetra-n-butylammonium fluoride and in situ acetylation of the phenols with acetic anhydride gave the acetoxy compounds 15l and 16l (Scheme IX). The cis and trans geometries of the stilbenes were assigned by the characteristic 1H NMR coupling constants of the olefinic protons. Catalytic hydrogenation of stilbenes 15 and 16 at about 40 psi in the presence of 10% palladium on charcoal gave the dihydrostilbenes 17a-e (Scheme XIII). The amino ethers 17f-g were prepared by the reaction of 1-(4-hydroxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethane (18) with dialkylaminoethyl chlorides 19a-b in refluxing acetone in the presence of K2CO 3 (Scheme X). Compounds 17h and 17i were prepared by the alkylation of 3,4,5-trimethoxyphenyl-acetonitrile (20a) and 4-methoxyphenylacetonitrile (20b) with 4-methoxybenzyl bromide (21a) and 3,4,5-trimethoxybenzyl bromide (21b), respectively, using LDA as the base (Scheme XI). Similarly, alkylation of methyl 4-methoxyphenylacetate (20b) with 3,4,5-trimethoxybenzyl bromide 21b gave product 17j.

Provenance & Evidence