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Short Paper | Special issue | Vol 99, No. 1, 2019, pp.694-702
Published online, 19th October, 2018
DOI: 10.3987/COM-18-S(F)37
Selective Aromatic Nucleophilic Substitution of 4-(Dimethylamino)-2-methoxy-3-(trifluoroacetyl)quinoline with Thiols – DFT Calculation Study

Norio Ota, Yusuke Harada, Yasuhiro Kamitori, and Etsuji Okada*

*Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan


The nucleophilic aromatic substitution proceeds exclusively at the 4-position of 4-(dimethylamino)-2-methoxy-3-(trifluoroacetyl)quinoline 1 by the reaction with various thiols to give the corresponding N-S exchanged products solely, and no O-S exchange reactions at the 2-position are performed. Our DFT calculation study provides a rational explanation regarding this complete selectivity based on energies of the adducts 6, 7 which are corresponding to the O-protonated Meisenheimer complexes at carbonyl oxygen in 3-trifluoroacetyl group. It was also investigated about influences of the solvents on the present unique selective substitution with thiols referring the results for the analogous selective substitution on 1 using amines as a nucleophile.