Prenyl Monohydric Phenols

Although strictly outside the reactions of prenyiphenolic compounds the extensive work on the regiospecific general synthesis of chrom-3-enes (2H-benzo[b]pyrans), in particular2,2-dimethylchromenes, from the reaction of metal phenoxides with 3-methylbut-3-enal is very noteworthy. In the general procedure a solution of titanium tetraethoxide (0.025 mol) in toluene was treated with the phenol (0.1 mol) in toluene and the ethanol formed removed by distillation over 

5 hours following which the mixture was cooled to ambient temperature and 

3-methylbut-2-enal (0.15 mol) in toluene introduced. After the addition of more toluene the mixture was refluxed for 8 hours and finally upon cooling, quenched with aqueous ammonium chloride. In this way, phenol (R = = R = = H) 

2-isoPrenylphenols obtained from isoprene, 2-methylbut-3-ene-2-ol or 3-methylbut-2-enol readily furnished 2,2-dimethylchroman products by cyclisation under mild conditions. Thus reaction with 90% formic acid (ref.4) at water-bath temperature over 1-2 hours followed by TLC purification afforded the chroman. For example, 2-isoprenyl-1-naphthol (ref. 4) and its isomer 1-isoprenyl-2-naphthol afforded chromans. Formation of the more stabilised carbocation of the 2-prenylphenol or naphthol and attack by the oxygen of the phenolic OH group results in production of the six- and not the five-membered ring. 

Under severe acid-catalysed reactions of isoprene with phenols, chromans always accompanied the 2- and 4-alkenylphenols (ref. 2). 

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Claisen had reported that the proportion of C- to O-alkylation could be greatly enhanced by the use of sodium phenoxides in benzene suspension and indeed this method has been beneficially employed for o-C-isoprenylation. In a general procedure (ref.9), an ethereal solution of the phenol (0.05 mole), was treated with metallic sodium (0.2 mole) and after 1.5 hours the prenyl chloride (RCI) was introduced. Upon refluxing for 10 hours, removal of excess sodium and acidic work-up, monohydric phenols afforded yields from 66-90%. For example, 2-methylphenolwith3-methylbuten-2-ylchloridegave2-methyl-6-(3-methylbuten-2-... 

As with prenylphenols in the monohydric series mild acid-catalysed procedures have been developed for the prenylation of polyhydric phenols. Thus a variety of these compounds have been condensed with 3-methylbut-2-enol and with 2-methylbut-3-en-2-ol in dilute aqueous formic acid. Hydroquinone for example afforded isopentenylhydroquinone, 4-hydroxy-2-(3-methylbuten-2-yl)phenol (ref. 15). 

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