Synthesis of quinolines involving electrophilic amination of arenes with sodium azide in polyphosphoric acid

Full text of DOI:10.1007/s11172-011-0123-x

Russian Chemical Bulletin, International Edition, Vol. 60, No. 4, pp. 773—774, April, 2011
773
Synthesis of quinolines involving electrophilic amination of arenes
with sodium azide in polyphosphoric acid
A. S. Lyakhovnenko, M. M. Kugutov, and A. V. Aksenov
Stavropol State University, Department of Biology and Chemistry,
1
a ul. Pushkina, 355009 Stavropol, Russian Federation.
Fax: +7 (865 2) 35 4033. Eꢀmail: alexaks05@rambler.ru
Quinolines are wellꢀknown compounds for which
a considerable number of synthetic methods have been
developed. Nevertheless, no methods including the forꢀ
such a method, which is based on the recently found reꢀ
3
agent combination NaN /polyphosphoric acid (PPA*).
3
1
We showed that the reactions of phenol (1a) and anisole
mation of the N(1)—C(8a) and С(4)—C(4a) bonds were
known in the literature. In the present work, we proposed
(1b) with NaN in PPA at 55—60 °C for 3 h followed by
3
addition of 1,3ꢀdicarbonyl compound 2a,b and heating for
additional 3 h at 120—130 °C afford quinolines 3a—с in
yields of 31—42% (Scheme 1).
Scheme 1
The proposed mechanism of this transformation inꢀ
cludes the formation of triazene 4 according to the mechꢀ
anism analogous to that given in Ref. 3, the electrophilic
attack of 4 by 1,3ꢀdicarbonyl compound, cyclization of
intermediate 5 to compound 6, and decomposition of the
latter to yield azomethine 7, whose intramolecular alkylaꢀ
tion affords quinolines 3 (Scheme 2).
Thus, the consecutive reaction of sodium azide and
a 1,3ꢀdicarbonyl compound with an aromatic compound
in PPA results in quinolines through the oneꢀpot reaction.
In future, we intend to study to what extent this reaction is
general with respect to aromatic and heteroaromatic comꢀ
pounds.
i. 1) NaN /PPA; 2)
(2a,b)
3
R = H (1a), Me (1b); R´= Me (2a), Ph (2b); R = H, R´ = Ph (3a),
R = Me, R´= Ph (3b), R = R´ = Me (3c).
Scheme 2
i. NaN , PPA.
3
2
*
PPA containing 86% of P O , which has been prepared according to the published procedure, was used.
2 5
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 757—758, April, 2011.
066ꢀ5285/11/6004ꢀ773 © 2011 Springer Science+Business Media, Inc.
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774
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 4, April, 2011
Lyakhovenko et al.
NMR spectra were recorded on a Bruker WPꢀ200 (200 MHz)
6ꢀMethoxyꢀ2,4ꢀdimethylquinoline (3с) was obtained in a yield
of 0.058 g (31%) as an oil (cf. Ref. 6: oil). Found (%): C, 76.79;
H, 6.62; N, 7.09. C H NO. Calculated (%): C, 76.98; H, 7.00;
instrument using SiMe as the internal standard. The course of
4
the reaction and purity of the compounds synthesized were monꢀ
itored by TLC on Silufol UVꢀ254 plates using chloroform as
a solvent.
Synthesis of compounds 3a—c (general procedure). A mixture
of phenol (1a) or anisole (1b) (1 mmol) and NaN3 (0.072 g,
12
13
1
N, 7.48. H NMR (CDCl ), δ: 2.78 (s, 3 H, Me(4)); 2.82 (s, 3 H,
3
Me(2)); 3.87 (s, 3 H, OMe); 7. 58 (d.d, 1 H, H(7), J = 9.1 Hz,
J = 2.5 Hz); 7.65 (s, 1 Н, H (3)); 7.93 (d, 1 H, H(8), J = 9.1 Hz);
8.12 (d, 1 H, H(5), J = 2.5 Hz).
1
.1 mmol) in PPA (2—3 g) was thoroughly stirred at 55—60 °C
for 3 h (TLC control). The temperature was then raised to
20—130 °C and the mixture was stirred for an additional 1 h.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00193a).
1
Then, the corresponding 1,3ꢀdicarbonyl compound 2a,b (1 mmol)
was added and the mixture was stirred at the same temperature
for additional 4 h. The reaction mixture was cooled to 80 °C,
poured with stirring into cold water (30 mL), extracted with
ethyl acetate (3×50 mL), alkalified with aqueous ammonia to
pH ~8, and extracted with ethyl acetate (3×50 mL). This extract
was concentrated. Compounds 3a,b were purified by recrystalliꢀ
zation and compound 3с was purified by chromatography (the
eluent was chloroform).
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Engl. Transl.), 2009, 871].
1
2
3
(
6
ꢀHydroxyꢀ2,4ꢀdiphenylquinoline (3a) was obtained in a yield
4
5
6
. R. Leardini, D. Nanni, G. F. Pedulli, A. Tundo, G. J. Zanarꢀ
di, J. Chem. Sос., Perkin Trans. 1, 1986, 1591.
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of 0.131 g (34%), m.p. 222—223 °C (benzene—petroleum ether;
cf. Ref. 4: m.p. 222—223 °C). Found (%): C, 84.95; H, 5.03;
N, 4.67. C H NO. Calculated (%): C, 84.82; H, 5.08; N, 4.71.
21
15
1
H NMR (DMSOꢀd ), δ: 7. 21 (m, 1 H); 7.3—7.6 (m, 9 H); 7.74
6
(
s, 1 Н); 8.1—8.2 (m, 3 H).
6
ꢀMethoxyꢀ2,4ꢀdiphenylquinoline (3b) was obtained in a yield
of 0.131 g (42%), m.p. 121—122 °C (chloroform—petroleum ether;
cf. Ref. 5: m.p. 121—122 °C). Found (%): C, 85.05; H, 5.43;
N, 4.57. C H NO. Calculated (%): C, 84.86; H, 5.50; N, 4.50.
2
2
17
1
The H NMR spectrum was analogous to that given in Ref. 5.
Received May 28, 2010