ISSN 1070-4280, Russian Journal of Organic Chemistry, 2018, Vol. 54, No. 1, pp. 95–101. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © Yu.S. Rozhkova, T.S. Vshivkova, I.V. Plekhanova, Yu.V. Shklyaev, 2018, published in Zhurnal Organicheskoi Khimii, 2018, Vol. 54,
No. 1, pp. 97–102.
Dedicated to Corresponding Member of the Russian Academy of Sciences
V.F. Mironov on his 60th anniversary
Synthesis of New 1,2,3,4-Tetrahydroisoquinoline Derivatives.
Yu. S. Rozhkova,* T. S. Vshivkova, I. V. Plekhanova, and Yu. V. Shklyaev
Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences,
ul. Akad. Koroleva 3, Perm, 614013 Russia
Received July 5, 2017
Abstract—A four-step procedure has been developed for the synthesis of new 2-(2,3,3-trimethyl-1,2,3,4-
tetrahydroisoquinolin-1-yl)anilines by acylation of 2-(3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)anilines at the
amino group with isobutyryl chloride, reduction of the endocyclic C=N bond in N-[2-(3,3-dimethyl-3,4-di-
hydroisoquinolin-1-yl)phenyl]isobutyramides, N-alkylation of N-[2-(3,3-dimethyl-1,2,3,4-tetrahydroisoquino-
lin-1-yl)phenyl]isobutyramides to N-[2-(2,3,3-trimethyl-1,2,3,4-tetrahydroisoquinolin-1-yl)phenyl]isobutyr-
amides, and acid hydrolysis of the latter.
R = MeO (a), H (b).
Isoquinoline derivatives of both natural and syn-
thetic origin attract interest primarily due to broad
spectrum of their biological activity. Among these
compounds, the highest activity has been revealed in
1,2,3,4-tetrahydroisoquinolines [1–10]. Therefore,
development of methods for the synthesis of new
functionalized 1,2,3,4-tetrahydroisoquinolines suitable
for further structural modifications with the goal of
creating libraries of biologically active compounds is
an important problem.
The present study was aimed at developing a proce-
dure for the synthesis of previously unknown 2,3,3-tri-
a 2-aminophenyl substituent on C
. Interest in these
compounds arises from the fact that some N-alkyl-3,3-
dimethyl-1,2,3,4-tetrahydroisoquinolines were found
to exhibit antiplatelet , anticoagulant , antiar-
rhythmic [8, 10], hypotensive , and β-adrenergic
blocking activities . This makes it reasonable to
search for new compounds of that series, especially for
those containing groups capable of undergoing further
We selected 2-(3,3-dimethyl-3,4-dihydroisoquino-
lin-1-yl)anilines 1a and 1b as starting materials for the
synthesis of the target structure. 3,4-Dihydroiso-
quinoline 1a was synthesized for the first time by one-
pot three-component condensation of 1,2-dimethoxy-
benzene with isobutyraldehyde and 2-aminobenzo-
nitrile in concentrated sulfuric acid, which was
developed by us previously . Compound 1b was