An efficient synthesis of 7-methoxy-8-methyl-α-tetralone

Abstract

with Jones reagent. The conversion of the compound 5 to the target molecule 7 in 64% yield was also achieved by employing different condition 8 which involved the addition of a solution of chromic acid and periodic acid in acetonitrile to solution of the compound 5 in dichloromethane. These conditions not only led to desilylation but also oxidation of the resulting alcohol, thus shortening the reaction sequence by one step.In summary we have developed an alternative route for the synthesis of 7-methoxy-8-methyl-a-tetralone 1. The yields of all new compounds are high. The overall yield of our method is 20.4% whereas the overall yield of the published procedure 2 is 16.0%. The experimental conditions selected for the present procedure afforded a very clean product in each step and all the experiments can be reproduced. ExperimentalUnless otherwise stated, IR spectra were obtained with a Nicolet Fourier transform (FT). NMR spectra were recorded on a Bruker 300 MHz spectrometer in CDCl 3 . Mass spectra were recorded on a Thermo Finnigan TSQ Quantum Ultra AM mass spectrometer. All organic extracts were dried over MgSO 4 and evaporated under reduced pressure. Column chromatography was carried out on Silica gel 60 (Merck), grade 60, 70-230 mesh, and TLC plates were coated with silica gel 60 F 254 , layer thickness 0.2 mm and the spots were located by exposing the plate to UV light. Microanalyses were carried out in the Department of Chemistry, IVIC.8-Bromo-7-methoxy-a-tetralone (2); first approach: A mixture of 7-methoxy-1-tetralone 1 (4.71 g, 26.78 mmol), N-bromosuccinimide (4.76 g, 26.78 mmol) and acetonitrile (25 mL) was stirred at room temperature for 16 h. The solvent was evaporated and chromatographed to give the tetralone 2 (67%, 4.57 g) as a yellow solid, m.p. 92-94 °C, IR (cm -1 ): 1688 (CO); 1 H NMR d: 1.89-1.97 (m, 2H, C3-2H), 2.54 (t, 2H, C4-2H, J = 6.54 Hz), 2.76 (t, 2H, C2-2H, J = 6.24 Hz), 3.76 (s, 3H, OCH 3 ), 6.88 (d, 1H, ArH, J = 8.43 Hz), 7.03 (d, 1H, ArH, J = 8.43 Hz);The title compound tetralone 7 which is a potential intermediate in the preparation of lactones 1 related to desmotroposantonin has been synthesised 2 by Chatterjee and Banerjee. The starting material selected by these authors is not easily accessible. During its transformation to the tetralone 7 most of the intermediate steps produced isomeric products and thus required very careful purification to give the pure intermediates. The yield of the penultimate product was also not high. Our recent studies 3 on the transformation of 6-methoxytetralin prompted us to explore an alternative route for the title compound. Results and discussionThe commercially available 7-methoxy-a-tetralone 1 on bromination 4 with N-bromosuccinimide (NBS) in acetone yielded the bromotetralone 2 in 67% yield.The bromotetralone 2 was obtained in 37% yield when the bromination was carried out with NBS in water under solvent free condition. 5 Reduction of 2 with sodium borohydride in anhydrous ethanol afforded the tetrahydronaphthol 3 in 94% yield. The tert-butyldim...