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general, clean, rapid, and efficient, providing an expedi-
tious access to the preparation of various quinolines.
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The reaction times, yields and melting points of quino-
lines 3 for the aqueous reaction of 2-aminoarylketone
or 2-aminoarylaldehyde 1 with a-methylene ketone 2
in a molar ratio of 1:1.2 in the presence of 1.0 equiv of
hydrochloric acid were collected in Table 2.
As seen from Table 2, the current protocol can be ap-
plied to 2-aminoarylketones (1a,b) or 2-aminoarylalde-
hyde (1c) and a wide range of a-methylene ketones
such as b-ketoester, cyclic ketones, acyclic and cyclic
1,3-diketones, and tolerate the presence of halogen,
ketone and ester groups. Interestingly, cyclic ketones
(2d–g) afforded the corresponding tricyclic quinolines.
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In conclusion, we have demonstrated that a straightfor-
ward, highly efficient and cost-effective synthesis of
biologically active quinolines can be achieved by
HCl-catalyzed Friedla¨nder reaction in pure water. The
current method presents a very appealing synthetic pro-
cess for quinolines because of the following advantages:
(1) use of water as environmentally benign reaction
media, (2) use of very cheap and readily available hydro-
chloric acid, (3) very high yield and short reaction time,
(4) straightforward and easy work-up procedure and (5)
no use of any metal catalyst or phase-transfer catalyst or
surfactant.
Acknowledgements
We are grateful for the financial support from National
Science Fund for Distinguished Young Scholars
(20125205), Fund for Innovative Research Groups of
National Science Foundation of China (20321101) and
Anhui Provincial Bureau of Human Resources
(2001Z019).
Supplementary data
Supplementary data associated with this article can be
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