Submit Manuscript | http://medcraveonline.com Abbreviations: MCPBA, chloroperbenzoic acid; p-TsOH, p-toluenesulphonic acid; FT, fourier transform; MS, mass spectra; TLC, layer chromatography Introduction 6-methoxy-2-tetralone has been selected as starting material for the synthesis of many steroidal compounds 1–3 2-aminotetalin derivatives 4 which exhibit antifungal activities, tetrahydro benzocycloheptane 5 and many terpenoid compounds. 6 6-methoxy-2-tetralone is more expensive, difficult to synthesize and unstable in comparison to 6-methoxy-1-tetralone. Therefore 6-methoxy-2-tetralone has attracted an array of impressive synthetic efforts. 7–13 The draw backs of the published methods are (i) Use of flammable material like trimethylsilyl cyanide and corro- sive product like zinc iodide 7 (ii) Use of bad smelling product like ethyl mercaptied 14 (iii) Long steps and complicated experimental procedure. 8,9 The overall yield of the most of the published procedures range from 39 to 42%. The importance of 6-methoxy 2-tetralone in organic synthesis encouraged us to develop an alternative approach of the same. The present paper describes the results of our efforts towards the synthesis of the title compound. The synthetic route is depicted in Scheme 1. Scheme 1 (i) 2,4-pentane diol, PTs; (ii) MCPBA, CH 2 Cl 2 ; (iii) Et OH, 10% H 2 SO 4 ; (iv) BF 3 .OEt 2 Results and discussion The commercially available 6-methoxy-1-tetralone 1 was converted 15 into the olefin 2 in 94% yield by heating under reflux with 2,4-pentanediol and a catalytic amount of p-toluenesulphonic acid (p-TsOH) who’s spectroscopic properties perfectly agree with structure assigned. The olefin 2 was also previously synthesized by different routes 14,16 but the yield was not high compared with the present procedure. Epoxidation of the olefin 2 was performed with m-chloroperbenzoic acid (MCPBA) in dichloromethane and without purification the resulting epoxide was heated under reflux for 3 hours with ethanolic sulfuric acid (10%) to afford the tetralone 3 in 39% yield (overall yield 36%). The reaction was attempted several times using different reaction conditions which included change of temperature, time of heating, amount of sulfuric acid etc., (Table 1) however the yield could not be further improved. The spectroscopic data (NMR and MS) lent support to the assigned structure. An attempt was made to purify the epoxides by column chromatography but could not be isolated due to tendency of decomposition as exhibited in TLC. Table 1 Brief description of conditions for experiments of compound 3 Time of heating Amount of H 2 SO 4 Changes of temperature Yield 1.5 hours 1mL (15%) 40–45° 12% 2 hours 2mL (15%) 50–60° 18% 3 hours 3mL (25%) 60–70° 20% 3 hours 3mL (10%) Reflux 39% The cleavage of the crude epoxide was also tried with freshly distilled borontrifluoride etherate [(BF 3 .Et 2 O)] at room temperature. The tetralone 3 was obtained in 36% (overall yield 35%). The opening of the epoxide was also attempted with sodium cyanoborohydride and borontrifluoride etherate. 17 A mixture of four products were obtained (evidenced by TLC) which on the basis of spectral data contained little if any of the desired product. In order to improve the yield, the olefin 2 was subjected to hydroboration-oxidation 18 reaction. As expected a mixture of alcohols were obtained as evidenced by 1 H NMR spectroscopy. Oxidation with Jones reagent 18,19 followed by MOJ Biorg Org Chem. 2018;2(1):32‒34. 32 © 2018 Jossblerys et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. A concise approach for the synthesis of 6-methoxy- 2-tetralone Volume 2 Issue 1 - 2018 Dasilva Jossblerys, 1 Liadis Bedoya, 1 Dioni A Arrieche, 1 Ajoy K Banerjee, 1 Po S Poon 2 1 Chemistry Center,Venezuelan Institute of Scientific Research (IVIC),Venezuela 2 Technological Development UNIT (UDT), University of Concepcion, Chile Correspondence: Ajoy K Banerjee, Centro de Química, IVIC, Apartado- 21827, Caracas-1020A,Venezuela, Tel +5802125041324, Fax +5802125041350, Email aabanerje@gmail.com Received: February 05, 2018 | Published: February 19, 2018 Abstract A three-step synthesis of 6-methoxy-2-tetralone, a potential intermediate for many terpenoids and steroidal compounds, has been developed. Keywords: 6-methoxy-1-tetralone, 2,4-pentanediol, MCPBA, PTS, hydroboration- oxidation MOJ Bioorganic & Organic Chemistry Research Article Open Access