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Facile Synthesis, Isolation and Characterization of 1-(4-Hydroxy-3-methoxyphenyl)ethanone (Acetovanillone) and its Isomeric Related Substances as Key Starting Materials for an Antipsychotic Drug: Iloperidone
Corresponding Author(s) : S. Boodida
Asian Journal of Chemistry,
Vol. 34 No. 5 (2022): Vol 34 Issue 5, 2022
Abstract
Three isomeric and one process related substances of acetovanillone 1-(4-hydroxy-3-methoxyphenyl)ethanone (I) were isolated and characterized while developing a laboratory process and pilot scale synthesis of acetovanillone. These impurities namely, 1-(3-hydroxy-4-methoxyphenyl)ethanone (Imp 1) (isoacetovanillone impurity), 1-(4-hydroxy-3-methoxyphenyl)-propan-1-one) (Imp 2) (propiovanillone impurity), 1-(3-hydroxy-2-methoxyphenyl)ethanone (Imp 3) (O-acetoisovanillone impurity-1), 1-(2-hydroxy-3-methoxyphenyl)ethanone (Imp 4) (O-acetoisovanillone impurity-2) have been synthesized and reported for the first time. The spectral characteristics of the synthesized impurities were confirmed with FTIR, 1H NMR and mass spectrometry.
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References
B.A. ‘T Hart, J.M. Simons, K.-S. Shoshan, N.P.M. Bakker and R.P. Labadie, Free Radic. Biol. Med., 9, 127 (1990); https://doi.org/10.1016/0891-5849(90)90115-Y
J. Stolk, J.H. Hiltermann, J.H. Dijkman and A.J. Verhoeven, Am. J. Respir. Cell Mol. Biol., 11, 95 (1994); https://doi.org/10.1165/ajrcmb.11.1.8018341
E.V. Worm, C.J. Benkelman, A.J.J. Van den Berg, B.H. Kroes, R.P. Labadie and H.V. Dijk, Eur. J. Pharmacol., 433, 225 (2001); https://doi.org/10.1016/s0014-2999(01)01516-3
M. Salmon, H. Koto, O.T. Lynch, E.-B. Haddad, N.J. Lamb, G.J. Quinlan, P.J. Barnes and K.F. Chung, Am. J. Respir. Crit. Care Med., 157, 970 (1998); https://doi.org/10.1164/ajrccm.157.3.9704067
D.J. Crouse, S.L. Hurlbut and D.M.S. Wheeler, J. Org. Chem., 46, 374 (1981); https://doi.org/10.1021/jo00315a028
R. Martin, Handbook of Hydroxyacetophenones: Preparation and Physical Properties, Springer (2005).
G.A. Olah, Fridal-Crafts Chemistry, Wiley-Interscience: New York (1973).
C.E. Coulthard, J. Marshall and F.L. Pyman, J. Chem. Soc., 280 (1930); https://doi.org/10.1039/JR9300000280
J.A. Dodge, M.G. Stocksdale, K.J. Fahey and C.D. Jones, J. Org. Chem., 60, 739 (1995); https://doi.org/10.1021/jo00108a046
S. Karagoz, T. Bhaskar, A. Muto and Y. Sakata, Fuel, 84, 875 (2005); https://doi.org/10.1016/j.fuel.2005.01.004
Z.S. Yuan, S.N. Cheng, M. Leitch and C.B. Xu, Bioresour. Technol., 101, 9308 (2010); https://doi.org/10.1016/j.biortech.2010.06.140
N.N. Duong, B. Wang, T. Sooknoi, S.P. Crossley and D.E. Resasco, ChemSusChem, 10, 2823 (2017); https://doi.org/10.1002/cssc.201700394
H. Persson and W. Yang, Fuel, 252, 200 (2019); https://doi.org/10.1016/j.fuel.2019.04.087
C. Padro, J. Catal., 226, 308 (2004); https://doi.org/10.1016/j.jcat.2004.05.030
M.K. Montañez-Valencia, C.L. Padró and M.E. Sad, Appl. Catal. B, 278, 119317 (2020); https://doi.org/10.1016/j.apcatb.2020.119317
E. Kozhevnikova, Appl. Catal. A Gen., 245, 69 (2003); https://doi.org/10.1016/S0926-860X(02)00618-X
K. Nakazawa, Yakugaku Zasshi, 74, 836 (1954); https://doi.org/10.1248/yakushi1947.74.8_836
H.O. Mottern, J. Am. Chem. Soc., 56, 2107 (1934); https://doi.org/10.1021/ja01325a033
J.A. Dodge, M.G. Stocksdale, K.J. Fahey and C.D. Jones, J. Org. Chem., 60, 739 (1995); https://doi.org/10.1021/jo00108a046
International Conference on Harmonization (ICH) Guidelines Q2B Validation of Analytical Procedure: Methodology, Geneva, Switzerland (1996).
C. Schuerch Jr., J. Am. Chem. Soc., 70, 2293 (1948); https://doi.org/10.1021/ja01186a514
V.K. Ahluwalia, P. Bhagat, R. Aggarwal and R. Chandra, Intermediates for Organic Synthesis, Kindle Edition (2005).