Elvia V. Cabrera, A. K. Banerjee
Oct 1, 2010
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0
Influential Citations
10
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Journal
Organic Preparations and Procedures International
Abstract
Substituted 1-tetralones play an important role in the synthesis of natural and non-natural products.1 8-Methoxy-1-tetralone 5 unlike 5-, 6-, and 7-methoxy-1 tetralones is not commercially available. It has recently been utilized for the synthesis2 of ARQ-501, a metabolite of human blood. In addition, tetralone 5 has been used in the synthesis of compounds for the study of dopamine (DA) and serotonin (5-HT) receptors.3 To the best of our knowledge, only four syntheses4–7 of 5 have been reported. In addition to the route described in references 4 and 5, the other two routes6,7 afford very poor yield of the tetralone 5. The synthetic approach5 which reports a good yield of tetralone 5 consists in the methylation of the 8-hydroxy-1-tetralone which was prepared8 by the catalytic hydrogenation of the commercially available naphthalene 1,8-diol. We have developed a facile synthesis of tetralone 5 (Scheme 1) which is described in the present communication. The previously reported9 acid 1 on bromination with bromine and acetic acid led to the formation of the bromoacid 2 in 93% yield. The bromoacid was subjected to cyclization with conc. sulfuric acid. The resulting ketone 3, obtained in 57% yield, underwent decarboxylation10 on heating with a mixture of sodium persulfate and silver nitrate in acetonitrile affording the bromotetralone 4 in 77% yield. The conversion of the bromotetralone into 8-methoxy-1-tetralone (5) in 97% yield was accomplished by catalytic hydrogenation over Pd/C (5%) in absolute methanol. The spectroscopic data (IR, 1H NMR, MS and 13C NMR) of 5 were consistent with the structure assigned. The overall yield from 1 was 40%. In conclusion, a convenient approach for the synthesis of 8-methoxy-1-tetralone has been developed. The starting material 1 can easily be prepared9 in large quantity from the commercially available m-methoxybenzaldehyde. All the intermediates were obtained in satisfactory yield and properly characterized. The published route4 describes a synthesis of the tetralone 5 in 41% yield from 2-methoxy-6-methylbenzoic acid via a clever use of tandem Michael-Dieckmann condensation and this is a noteworthy aspect of the synthesis