Basic alumina supported tandem synthesis of bridged polycyclic quinolino/isoquinolinooxazocines under microwave irradiation

Article abstract of DOI:10.1016/j.tetlet.2011.07.012

Basic alumina supported, solvent-free synthesis of novel oxazocines, medium size heterocycles, has been achieved in excellent yields by tandem C-alkylation followed by intramolecular O-alkylation of hydroxyquinoline/isoquinoline(s) with quinolinium salts under microwave irradiation. The method provides a facile and efficient route for the construction of polynuclear bridge-head oxazocines.

Full text of DOI:10.1016/j.tetlet.2011.07.012

Tetrahedron Letters 52 (2011) 4697–4700
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Basic alumina supported tandem synthesis of bridged polycyclic
quinolino/isoquinolinooxazocines under microwave irradiation
Shyamal Mondal, Rupankar Paira, Arindam Maity, Subhendu Naskar, Krishnendu B. Sahu, Abhijit Hazra,
⇑
Pritam Saha, Sukdeb Banerjee, Nirup B. Mondal
Department of Chemistry, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Basic alumina supported, solvent-free synthesis of novel oxazocines, medium size heterocycles, has been
achieved in excellent yields by tandem C-alkylation followed by intramolecular O-alkylation of hydroxy-
quinoline/isoquinoline(s) with quinolinium salts under microwave irradiation. The method provides a
facile and efficient route for the construction of polynuclear bridge-head oxazocines.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 13 May 2011
Revised 30 June 2011
Accepted 2 July 2011
Available online 8 July 2011
Keywords:
Basic alumina
Tandem reaction
Bridged heterocycle
Quinolino/isoquinolinooxazocines
Microwave irradiation
The modern trend in synthetic organic chemistry is to develop
new methodologies that afford products of greater structural
complexity with fewer synthetic steps,1 and of complex molecules
from relatively simple starting materials, employing operationally
simple, environmentally benign reaction conditions while ensuing
high yields.2 In this respect tandem reactions,3 where multiple
transformations take place in one-pot, have emerged as an efficient
tool for the synthesis of complex molecules. Significant develop-
ments in the area over the years have afforded a plethora of struc-
turally unique compounds.4 We have been performing tandem
reactions on quinolines/tetrahydroquinolines using different cata-
lytic systems because functionalized quinoline moiety is prevalent
in numerous biologically active compounds. In this endeavor we
have synthesized a number of linearly fused medium sized (seven
to nine-membered) tri, tetra, penta, and hexa-cyclic substituted
quinoline derivatives.5 We noted that oxazocines, eight-membered
oxa-aza-heterocycles, have received considerable attention due to
their pharmacological properties like antidepressant, antithrom-
botic, antipsychotic, and antibreast-cancer activities.6 The bridge-
head oxazocine core is also present in a number of natural
products, viz. ecteinascidine 743, bioxalomycin, tetrazomine, and
quinocarcins showing good antitumor and antimicrobial activity.7
The interesting biological activity of the bridgehead oxazocines
attracted our attention and prompted us to develop a convenient
protocol for easy access to this heterocyclic system utilizing the
scope of addition of nucleophilic reagents to quinolinium salts that
has already proved to be an efficient method for the synthesis of
useful quinoline derivatives.8
The microwave-irradiated solid-phase heterogeneous reactions
have become well-established9 as environmentally benign reaction
procedures that usually provide improved selectivity, enhanced
reaction rates, cleaner products, and manipulative simplicity. We re-
cently reported our efforts10 for fast and facile reaction strategies
that involved microwave energy as an unconventional energy
source in a two-component reaction. The present study was in-
tended to establish the viability of a two-component reaction
involving a 1,3-dinucleophilic tandem reaction between N-alkyl-
quinolinium salts and different bifunctional nucleophiles using
microwave energy. This strategy, if successful, would provide a fast,
one-pot synthesis of eight-membered rings in fused heterocycles
which otherwise are accessible only through multistep synthesis.
Here, in this communication, we wish to describe the first successful
application of this approach.
HO
N
OH
N
H3CO
H3CO
Al2O3 (basic)
Microwave
+
O
N
OH
10 min
N
CH3
1a
H3C
3a
2a
⇑
Corresponding author. Tel.: +91 33 2473 3491; fax: +91 33 2473 5197.
E-mail address: nirup@iicb.res.in (N.B. Mondal).
Scheme 1. Microwave mediated synthesis of quinolinooxazocine (3a) catalyzed by
alumina.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.012

4698
S. Mondal et al. / Tetrahedron Letters 52 (2011) 4697–4700
It was reasoned that basic alumina can be used as a basic
catalyst under microwave energy for activation of the hydroxy-
quinoline, which could participate in a 1,3-dinucleophilic addition
reaction with N-alkyl quinolinium salts. On the basis of that rea-
soning, we chose N-alkyl quinolinium salt 1a (1 mmol) and
hydroxyquinoline 2a (1.2 equiv) as reactants of this study. Those
were mixed with basic alumina (0.5 g) and irradiated in a mono-
mode Discover microwave reactor (CEM Corp., Matthews, NC,
USA) at 100 °C for 10 min. Usual work-up with ethyl acetate
followed by chromatographic purification afforded the reaction
product 3a in 92% yield. The molecular formula was deduced to
be C20H18N2O3 by elemental and high resolution mass spectral
analysis, indicating the annulation of the reactants to form the
desired quinolinooxazocine (Scheme 1). The 1H NMR spectrum of
3a exhibited two characteristic11 peaks (d 2.03 and d 2.13) for
the geminal aliphatic methylene protons, two 3H singlets assigned
to N–CH3 (d 3.09) and O–CH3 protons (d 3.64), two broad singlets
for N–CH–O and the benzylic protons (d 5.89 and d 4.13), and a
peak for phenolic OH proton at d 11.35. The 13C NMR spectrum
of 3a showed 20 distinct peaks in agreement with the proposed
structure. 13C DEPT data established a peak at d 25.1 for the meth-
ylene carbon, one peak at d 36.9 for N–CH3, and one for the meth-
oxy carbon at d 55.3. Of the rest 17 peaks, nine were assigned to
aromatic methine carbons and other eight peaks were identified
for quaternary carbons. The bridged structure was eventually fully
elucidated by single crystal X-ray analysis. The ORTEP representa-
tion of the compound 3a, indicating the molecular structure, is de-
picted in Figure 1. When the 2-methyl quinolinium salt 1d was
used as the starting material, the product 3d displayed in its 1H
NMR spectrum signals resembling those of 3a except for the disap-
pearance of the signal at d 5.89; instead a singlet at d 1.90 was ob-
served for the methyl group.
Figure 1. ORTEP diagram of quinolinooxazocine (3a).
Table 1
Tandem reactiona of 1a and 2a under thermal condition
Entry
Solvent
Base
Yieldb of 3a (%)
1
2
3
4
5
6
7
8
9c
Methanol
THF
CH3CN
Pyridine
Methanol
THF
CH3CN
Pyridine
Nil
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Basic Al2O3
Basic Al2O3
Basic Al2O3
Basic Al2O3
Basic Al2O3
60
55
75
80
54
50
56
65
92
We conducted several reactions with or without basic alumina
but in conjugation with other bases and in different organic sol-
vents to study the effectiveness of basic alumina. When the reac-
tion was carried out thermally with quinolinium salt 1a
(1 mmol), hydroxyquinoline 2a (1.2 equiv) and cesium carbonate
a
Reactions were carried using 1 mmol of quinolinium salt, 1.2 equiv of
hydroxyquinoline and 1 g basic alumina.
b
Isolated yields.
c
Basic alumina was activated at 450 °C for 12 h and then the reaction was carried
out according to Scheme 1.
Table 2
Synthesis of quinolino/isoquinolinooxazocines under microwave irradiation
OH
OH
HO
2b
2a
N
N
N
R2
Alumina (basic)
Microwave
N
OH
R2
R2
Alumina (basic)
R1
O
Microwave
10 min
N
CH3
O
N
N
10 min
H3C
R1
H3C
R1
3g-l
1a-f
R1 = H, CH3
3a-f
R2 = H, CH3, OCH3
Entrya
Quinolinium salts
Hydroxyquinoline/isoquinolines
Products
Yieldsb (%)
R2
OH
HO
N
N
R2
N
CH3
R1
N
OH
O
H3C
R1
1
2
3
4
5
1a (R1 = H, R2 = OCH3)
1b (R1 = H, R2 = CH3)
1c (R1 = H, R2 = H)
2a
2a
2a
2a
2a
3a
3b
3c
3d
3e
92
90
90
88
87
1d (R1 = CH3, R2 = OCH3)
1e (R1 = CH3, R2 = CH3)

S. Mondal et al. / Tetrahedron Letters 52 (2011) 4697–4700
4699
Table 2 (continued)
Entrya
6
Quinolinium salts
Hydroxyquinoline/isoquinolines
Products
Yieldsb (%)
1f (R1 = CH3, R2H)
2a
3f
87
R2
OH
N
R2
N
CH3
R1
N
O
N
H3C
R1
7
8
9
10
11
12
1a
1b
1c
1d
1e
1f
2b
2b
2b
2b
2b
2b
3g
3h
3i
3j
3k
3l
88
89
88
86
86
85
a
Reactions were carried using 1 mmol of quinolinium salt, 1.2 equiv of hydroxyquinoline and 0.5 g basic alumina under microwave irradiation.
Isolated pure yield.
b
(used as base in lieu of basic alumina) for 5 h in solvents like
MeOH, THF, or CH3CN, considerable decrease in yield was observed
(Table 1, entry 1–3). However, when the same was performed in
dry pyridine with cesium carbonate as base, it afforded somewhat
better yield of the quinolinooxazocine (entry 4). The thermal reac-
tion of 1a and 2a in other organic solvents in combination with ba-
sic alumina also lowered the yield of 3a (entries 5–8).
After achieving the optimal reaction condition for the tandem
synthesis of quinolinooxazocine 3a,12 we carried out reactions of
other quinolinium salts (1b–f) with hydroxyquinoline (2a) under
the protocol to afford 3b–f in excellent yields (Table 2). The
remarkable advantage of this solid-phase reaction is that the reac-
tion products were separated from alumina by simple extraction
with ethyl acetate.
Acknowledgments
The authors express their gratitude to the Director, IICB for lab-
oratory facilities, the Council of Scientific and Industrial Research
(CSIR) for providing the funding and fellowships to S.M., A.M.,
S.N., R.P., A.H., K.B.S., and P.S. We are indebted to Dr. R. Mukherjee
and Mr. K. Sarkar for recording the spectra and Dr. B. Achari, Emer-
itus Scientist, CSIR, for his valuable suggestions.
Supplementary data
Crystallographic data in CIF format are available free of charge via
the internet at CCDC 825258. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the
CambridgeCrystallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, UK. Fax: +44 1223 336033; or deposit@ccdc.cam.ac.uk).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.07.012.
To extend the scope of the reaction further, the alumina
catalyzed solid phase reaction was carried out with 1a and 2b un-
der microwave irradiation (entry 7, Table 2) to afford iso-
quinolinooxazocine 3g in 88% yield (Scheme 2).
However, an attempt to carry the tandem reaction with
2-hydroxyquinoline, 4-hydroxyquinoline, and 3-hydroxyisoquino-
line under identical conditions failed to produce any result. We
presume the failure was probably due to keto-amine tautomerism
in the quinoline molecules. As described in the report of Moghaddam
et al.11e the mechanism possibly involves the formation of an
iminium intermediate via C-alkylation followed by intramolecular
cyclization to give the desired product.
The usefulness of this methodology lies in the fact that the tan-
dem reaction is carried out rapidly under microwave promoted
environmentally benign, solvent-free condition to give quinolino/
isoquinolinooxazocines (entry 3a–l)13 in excellent yields. The cata-
lytic effect of basic alumina was found to be more prominent in
solid phase reactions than liquid phase reactions (Table 2). The
reaction is compatible with various substituents. In conclusion
the methodology is expected to provide a general route for the
References and notes
1. Trost, B. M. Science 1991, 254, 1471; Hall, N. Science 1994, 266, 32.
2. Parenty, A. D. C.; Smith, L. V.; Pickering, A. L.; Long, D. L.; Cronin, L. J. Org. Chem.
2004, 69, 5934.
3. (a) Tietze, L. F. Chem. Rev. 1996, 96, 115; (b) Arai, S.; Nakayama, K.; Hatano, K.;
Shioiri, T. J. Org. Chem. 1998, 63, 9572.
4. (a) Yavari, I.; Karimi, E. Tetrahedron Lett. 2008, 49, 6433; (b) Hashmi, A. S. K.
Chem. Rev. 2007, 107, 3180; (c) Tietze, L. F.; Rackelman, N. In Multi-component
Reactions; Zhu, J., Bienayme, I., Eds.; Wiley-VCH: Weinheim, 2005; (d)
Overman, L. E.; Velthuisen, E. J. J. Org. Chem. 2006, 71, 1581; (e) Wang, K. K.
Chem. Rev. 1996, 96, 207; (f) Ho, T. L. Tandem Organic Reactions; Wiley and Sons:
New York, NY, 1992.
5. (a) Hazra, A.; Mondal, S.; Maity, A.; Naskar, S.; Saha, P.; Paira, R.; Sahu, K. B.;
Paira, P.; Ghosh, S.; Sinha, C.; Samanta, A.; Banerjee, S.; Mondal, N. B. Eur. J. Med.
Chem. 2011, 46, 2132; (b) Paira, R.; Maity, A.; Naskar, S.; Mondal, S.; Paira, P.;
Hazra, A.; Sahu, K. B.; Saha, P.; Banerjee, S.; Mondal, N. B. Synthesis 2010, 3520;
(c) Naskar, S.; Paira, P.; Paira, R.; Mondal, S.; Maity, A.; Hazra, A.; Sahu, K. B.;
Saha, P.; Banerjee, S.; Luger, P.; Weber, M.; Mondal, N. B. Tetrahedron 2010, 66,
5196; (d) Hazra, A.; Paira, P.; Sahu, K. B.; Naskar, S.; Saha, P.; Paira, R.; Mondal,
S.; Maity, A.; Luger, P.; Weber, M.; Mondal, N. B.; Banerjee, S. Tetrahedron Lett.
2010, 51, 1585; (e) Deb, I.; Paira, P.; Hazra, A.; Banerjee, S.; Dutta, P. K.; Mondal,
N. B.; Das, S. Bioorg. Med. Chem. 2009, 17, 5782; (f) Paira, P.; Hazra, A.; Kumar,
S.; Paira, R.; Sahu, K. B.; Naskar, S.; Saha, P.; Mondal, S.; Maity, A.; Banerjee, S.;
Mondal, N. B. Bioorg. Med. Chem. Lett. 2009, 19, 4786; (g) Palit, P.; Paira, P.;
Hazra, A.; Banerjee, S.; Das Gupta, A.; Dastidar, S. G.; Mondal, N. B. Eur. J. Med.
Chem. 2009, 44, 845.
facile, one-pot synthesis of
isoquinolinooxazocines.
a
wide range of quinolino/
OH
N
H3CO
H3CO
Al2O3 (basic)
+
6. (a) Mishra, J. K.; Samanta, K.; Jain, M.; Dikshit, M.; Panda, G. Bioorg. Med. Chem.
Lett. 2010, 20, 244; (b) Díaz-Gavilàn, M.; Rodríguez-Serrano, F.; Gómez-Vidal, J.
A.; Marchal, J. A.; Arànega, A.; Gallo, M. Á.; Espinosa, A.; Campos, J. M.
Tetrahedron 2004, 60, 11547; (c) Xu, Y. J.; Liu, H.; Pan, W.; Chen, X.; Wong, W.
C.; Labelle, M. Tetrahedron Lett. 2005, 46, 7523; (d) Seto, S.; Tanioka, A.; Ikeda,
M.; Izawa, S. Bioorg Med. Chem. Lett. 2005, 15, 1485; (e) Liao, Y.; Venhuis, B. J.;
Rodenhuis, N.; Timmerman, W.; Wikstrom, H.; Meire, E.; Bartoszyk, G. D.;
Bottcher, H.; Seyfried, C. A.; Sundell, S. J. Med. Chem. 1999, 42, 2235.
O
N
Microwave
10 min
N
CH3
N
H3C
3g
1a
2b
Scheme 2. Microwave mediated synthesis of isoquinolinooxazocine (3g) catalyzed
by alumina.

4700
S. Mondal et al. / Tetrahedron Letters 52 (2011) 4697–4700
7. (a) Flanagan, M. E.; Williams, R. M. J. Org. Chem. 1995, 60, 6791; (b) Fujimoto,
K.; Oka, T.; Morimoto, M. Cancer Res. 1987, 47, 1516; (c) Sato, T.; Hirayama, F.;
Saito, T.; Kaniwa, H. J. Antibiot. 1991, 44, 1367; (d) Suzuki, K.; Sato, T.; Morioka,
M.; Nagai, K.; Abe, K.; Yamaguchi, H.; Saito, T.; Ohmi, Y.; Susaki, K. J. Antibiot.
1991, 44, 479.
8. (a) Yavari, I.; Mirzaei, A.; Moradi, L.; Hosseini, N. Tetrahedron Lett. 2008, 49,
2355; (b) Paira, P.; Hazra, A.; Sahu, K. B.; Banerjee, S.; Mondal, B.; Sahu, N. P.;
Weber, M.; Luger, P. Tetrahedron 2008, 64, 4026; (c) Liu, Y.; Hu, H. Y.; Liu, Q. J.;
Hu, H. W.; Xu, J. H. Tetrahedron 2007, 63, 2024; (d) Fakhfakh, M. A.; Franck, X.;
Fournet, A.; Hocquemiller, R.; Figadere, B. Tetrahedron Lett. 2001, 41, 3847; (e)
Yue, G.; Wan, Y.; Song, S.; Yang, G.; Chen, Z. Bioorg. Med. Chem. 2005, 15, 453; (f)
Takamura, M.; Funabashi, K.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2000,
122, 6327.
evaporated to dryness and the residue was chromatographed over a column of
silica gel (60–120 mess) eluting with a mixture of hexane and ethyl acetate in
different ratios to yield the products 3a–l.
13. (a) Spectral data for 3a: White crystals (yield: 92%); mp 171–172 °C; 1H NMR
(600 MHz, DMSO-d6): d 2.03 (d, 1H, J = 12.6 Hz, CH2), 2.13 (d, 1H, J = 12.6 Hz,
CH2), 3.09 (s, 3H, CH3), 3.64 (s, 3H, CH3), 4.13 (bs, 1H, CH), 5.89 (bs, 1H, CH),
6.62 (m, 2H, CH), 6.95 (d, 1H, J = 2.4 Hz, CH), 7.14 (t, 1H, J = 7.8 Hz, CH), 7.23 (d,
1H, J = 7.2 Hz, CH), 7.43 (m, 1H), 7.76 (d, 1H, J = 7.2 Hz, CH), 11.35 (s, 1H, –OH);
13C NMR (150 MHz, DMSO-d6): d 25.1 (CH2), 26.8 (CH), 36.9 (CH3), 55.3 (CH3),
85.3 (CH), 110.9 (C), 111.1 (CH), 111.7 (CH), 114.0 (CH), 114.3 (C), 115.1 (CH),
121.3 (CH), 122.1 (CH), 127.7 (C), 130.2 (CH), 135.7 (C), 137.0 (C), 151.2 (C),
155.9 (C), 161.5 (C). ESI-MS: m/z 335 [M+H]+, 357 [M+Na]+, HRMS: calcd for
C
20H18N2O3Na; 357.1215; [M+Na]+; found 357.1212; (b) Spectral data for 3b:
9. (a) Varma, R. S. In Microwaves: Theory and Application in Material Processing IV;
Clark, D. E., Sutton, W. H., Lewis, D. A., Eds.; American Ceramic Society:
Westerville, OH, 1997; p 357; (b) Varma, R. S.; Dahiya, R. Tetrahedron 1998, 54,
6293; (c) Varma, R. S.; Meshram, H. M. Tetrahedron Lett. 1997, 38, 7973; (d)
Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett. 2000, 41, 531; (e) Kabalka, G. W.;
Wang, L.; Pagni, R. M. Synlett 2001, 676; (f) Bose, A. K.; Manhas, M. S.; Sharma,
A. K.; Banik, B. K. Synthesis 2002, 1578.
10. (a) Paira, R.; Maity, A.; Mondal, S.; Naskar, S.; Sahu, K. B.; Saha, P.; Hazra, A.;
Padmanaban, E.; Banerjee, S.; Mondal, N. B. Tetrahedron Lett. 2011, 52, 1653; (b)
Saha, P.; Naskar, S.; Paira, R.; Mondal, S.; Maity, A.; Sahu, K. B.; Paira, P.; Hazra,
A.; Bhattacharya, D.; Banerjee, S.; Mondal, N. B. Synthesis 2010, 486; (c) Saha,
P.; Naskar, S.; Paira, P.; Hazra, A.; Sahu, K. B.; Paira, R.; Banerjee, S.; Mondal, N.
B. Green Chem. 2009, 11, 931.
11. (a) Moghaddam, F. M.; Mirjafary, Z.; Saeidian, H.; Taheri, S.; Doulabi, D.;
Kiamehr, M. Tetrahedron 2010, 66, 134; (b) Moghaddam, F. M.; Taheri, S.;
Mirjafary, Z.; Saeidian, H. Synlett 2010, 123; (c) Moghaddam, F. M.; Moridi, F.
M. Tetrahedron Lett. 2010, 51, 540; (d) Moghaddam, F. M.; Kiamehr, M.; Taheri,
S.; Mirjafary, Z. Helv. Chim. Acta 2010, 43, 964; (e) Moghaddam, F. M.; Saeidian,
H.; Mirjafary, Z.; Taheri, S.; Kiamehr, M. Arkivoc 2010, xi, 91–100.
12. General procedure for the synthesis of quinolino/isoquinolinooxazocines
White crystals (yield: 90%); mp 155–156 °C; 1H NMR (600 MHz, DMSO-d6): d
2.00 (d, 2H, J = 12.6 Hz, CH2), 2.11 (t, 2H, J = 12.6 Hz, CH2), 2.50 (s, 3H, CH3),
3.11 (s, 3H, CH3), 4.13 (bs, 1H, CH), 5.90 (bs, 1H, CH), 6.59 (d, 1H, J = 7.8 Hz, CH),
6.84(d, 1H, J = 8.4 Hz, CH), 7.14 (t, 2H, J = 7.2 Hz, CH), 7.23 (d, 1H, J = 8.4 Hz,
CH), 7.43 (m, 1H, CH), 7.76 (d, 1H, J = 7.8 Hz, CH), 11.31 (s, 1H, –OH); 13C NMR
(150 MHz, DMSO-d6): d 20.1 (CH3), 25.1 (CH2), 26.5 (CH), 36.7 (CH3), 85.1 (CH),
110.5 (CH), 111.1 (C), 111.7 (CH), 114.3 (C), 115.1 (CH), 121.3 (CH), 122.0 (CH),
125.7 (C), 126.4 (C), 127.4 (CH), 128.1 (CH), 130.2 (CH), 137.0 (C), 139.3 (C),
155.6 (C). ESI-MS: m/z 319 [M+H]+, 341 [M+Na]+, HRMS: calcd for
C
20H18N2O2Na; 341.1266 [M+Na]+; found 341.1261; (c) Spectral data for 3f:
White crystals (yield: 87%); mp 134–135 °C; 1H NMR (600 MHz, DMSO-d6): d
1.90 (s, 3H, CH3), 2.11 (dd, 2H, J = 13.2 Hz, CH2), 2.17 (dd, 2H, J = 13.2 Hz, CH2),
3.01 (s, 3H, CH3), 4.10 (t, 1H, J = 3.0 Hz, CH), 6.63 (m, 2H, CH), 7.00 (m, 1H, CH),
7.15 (t, 1H, J = 7.8 Hz, CH), 7.23 (d, 1H, J = 8.4 Hz, CH), 7.27 (m, 1H, CH), 7.44 (m,
1H, CH), 7.81 (m, 1H, CH), 8.31 (s, 1H, CH), 11.33 (s, 1H, –OH); 13C NMR
(150 MHz, DMSO-d6): d 25.3 (CH3), 28.4 (CH), 31.5 (CH3), 33.5 (CH2), 87.4 (C),
110.1 (C), 111.2 (CH), 114.3(C), 115.0 (CH), 117.0 (CH), 121.3 (CH), 122.0 (CH),
127.0 (CH), 127.1 (CH), 127.3 (C), 130.2 (CH), 137.1 (C), 143.2 (C), 155.4 (C),
162.0 (C). ESI-MS: m/z 319 [M+H]+, 341 [M+Na]+, HRMS: calcd for
C
20H18N2O2Na; 341.1266 [M+Na]+; found 341.1259; (d) Spectral data for 3i:
3a–l:
A
mixture of N-methyl quinolinium salts 1a–f (1 mmol) and
round bottom flask
Greenish liquid (yield: 88%); 1H NMR (300 MHz, CDCl3):
d
2.17 (dt, 1H,
hydroxyquinolines 2a–b (1.2 equiv) was placed in
a
J1 = 12.6 Hz, J2 = 2.4, CH2), 2.39 (dt, 1H, J = 12.6 Hz, J2 = 2.4, CH2), 3.20 (s, 3H,
CH3), 4.08 (bs, 1H, CH), 5.73 (bs, 1H, CH), 6.68 (m, 2H, CH), 7.08 (m, 1H, CH),
7.23 (d, 1H, J = 5.4 Hz, CH), 7.38 (m, 2H, CH), 7.94 (d, 1H, J = 5.7 Hz, CH), 8.47 (d,
1H, J = 5.7 Hz, CH), 9.07 (s, 1H, CH); 13C NMR (75 MHz, CDCl3): d 25.5 (CH2),
34.7 (CH), 36.7 (CH3), 84.1 (CH), 110.5 (CH), 114.8 (CH), 117.8 (CH), 119.1 (CH),
124.5 (C), 126.2 (CH), 126.9 (C), 127.7 (CH), 127.9 (C), 128.1 (CH), 128.2 (C),
142.0 (C), 142.4 (CH), 146.7 (C), 151.7 (CH). ESI-MS: m/z 289 [M+H]+, 311
[M+Na]+, HRMS: calcd for C19H16N2ONa; 311.1160 [M+Na]+; found 311.1157.
(25 ml) and dissolved in minimum amount of methanol. Basic alumina (0.5 g)
was then added to the mixture and the solvent was evaporated to dryness
under reduced pressure. The flask was fitted with a septum, and the reaction
mixture was irradiated in the mono-mode Discover microwave reactor (CEM
Corp., Matthews, NC, USA) at 100 °C for 10 min while the reaction was
monitored by TLC. The mixture was then cooled and ethyl acetate was added,
and the slurry was stirred at room temperature for another 10 min. The
mixture was then filtered through a sintered glass funnel. The filtrate was