A one-pot three-component reaction in aqueous micellar medium: An easy route to chromeno[2,3-b]quinolinedione

Article abstract of DOI:10.1016/j.tetlet.2014.03.072

An efficient and green synthesis of hitherto unreported 5-aryl-3,3-dimethyl-2,3-dihydro-5aH-chromeno[2,3-b]quinoline-1,11(4H,5H)dione has been accomplished by a three-component reaction involving chromone-3-carbaldehyde, an aromatic amine, and 5,5-dimethyl-1,3- cyclohexanedione (dimedone) in 1.8 M aqueous TBAB solution. It is noteworthy that the TBAB/H₂O system can be recovered and reused for seven cycles directly.

Full text of DOI:10.1016/j.tetlet.2014.03.072

Tetrahedron Letters 55 (2014) 2924–2928
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A one-pot three-component reaction in aqueous micellar medium:
an easy route to chromeno[2,3-b]quinolinedione
Jaydip Ghosh a, Pritam Biswas a, Tapas Sarkar b, Michael G. B. Drew c, Chandrakanta Bandyopadhyay a,
⇑
a Department of Chemistry, R. K. Mission Vivekananda Centenary College, Rahara, Kolkata 700 118, West Bengal, India
b Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur 700 032, West Bengal, India
c Department of Chemistry, The University of Reading, P.O. Box 224, Whiteknights, Reading RG6 6AD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient and green synthesis of hitherto unreported 5-aryl-3,3-dimethyl-2,3-dihydro-5aH-chro-
meno[2,3-b]quinoline-1,11(4H,5H)dione has been accomplished by a three-component reaction involv-
ing chromone-3-carbaldehyde, an aromatic amine, and 5,5-dimethyl-1,3-cyclohexanedione (dimedone)
in 1.8 M aqueous TBAB solution. It is noteworthy that the TBAB/H2O system can be recovered and reused
for seven cycles directly.
Received 25 January 2014
Revised 13 March 2014
Accepted 15 March 2014
Available online 22 March 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Green chemistry
Multicomponent reaction
Hydrophobic effect
Chromone
Chromone-3-carbaldehyde
1-Benzopyran
Multicomponent reactions (MCRs) have become an integral part
of synthetic organic chemistry for the synthesis of diversely substi-
tuted molecular scaffolds in the field of biologically active com-
pounds and natural product chemistry.1 Commonly, MCRs
provide high atom economy in the convergent synthesis of com-
plex molecular architecture with a high degree of diversity.2 Green
Chemistry has drawn the attention of synthetic chemists in recent
years.3 Use of water as a medium in organic reaction4 provides
many advantages like hydrophobic effect,5 enhanced H-bonding
in the transition state,6 high cohesive energy density,7 Marcus
trans-phase H-bonding,8 easy product isolation, cheap, easy-avail-
ability, non-toxic, non-corrosive, and non-flammable nature. Aque-
ous micellar medium helps to increase the solubility of organic
compounds in water and salt-effect increases the hydrophobic nat-
ure of water.9 Considering all these effects of water, efforts have
been taken to develop MCRs in aqueous media for the synthesis
of diversified heterocyclic complex structures.
quinoline-based fluorescent off–on thiol probe has been developed
for bioimaging.13 Cytotoxicity of such chromenoquinolines has
been studied.14 Tetrahydrochromeno[4,3-b]quinolines exhibited
antiproliferative activity against MDA-MB-231 and MCF-7 breast
cancer cell lines.15 5H-Chromeno[3,4-f]quinolines act as glucocorti-
coid receptor modulators and selective progesterone receptor
modulators.16
Three-component reactions (3-CRs) among aromatic or ali-
phatic aldehyde, 5,5-dimethyl-1,3-cyclohexanedione (dimedone),
and aromatic amine or NH4OAc have been reported for the synthe-
sis of 9,10-diaryl- or 9-aryl-3,3,6,6-tetramethylpolyhydro-1,8-
acridinediones under solvent-free condition,17 using ionic liquids
having perfluoroalkyl tails,18 Et3NþHSO4ꢀ,19 amberlite IR-120H,20
carbon-based solid acid,21 and CAN-catalyzed reaction in PEG.22
A mixture of aldehyde, dimedone, and a primary aromatic amine
under microwave irradiation produced 3,3-dimethyltetrahydroac-
ridin-1-one.23 The 3-CRs using heterocyclic amines have been car-
ried out employing p-toluenesulfonic acid as catalyst.24 Use of
formaldehyde as the aldehyde component in this 3-CR has
emerged with various results. Formation of 3,3,6,6-tetramethyl-
polyhydro-1,8-acridinedione,25 3,3-dimethylhexahydroacridin-1-
one,26 monospiro,27 and dispiro28 compounds was reported.
The ubiquity of chromone moiety in nature29 and in pharmaceu-
tically important compounds30 prompted us to undertake multi-
component reactions using chromone-3-carbaldehyde 1, having
Chromenoquinolines exhibit various activities depending on the
nature of fusion between the chromone and quinoline rings. Chro-
meno[2,3-b]quinolinediones act as potent anti inflammatory
agents10 and their Co(III) and Cr(III) complexes bind with DNA and
have potent nuclease activity.11 Chromeno[2,3-g]quinoline-3-car-
boxylates act as anticoccidal drugs.12 Naphthopyrano[4,3-b]
⇑
Corresponding author. Tel.: +91 03325925125.
E-mail address: kantachandra@rediffmail.com (C. Bandyopadhyay).
an a
,b-unsaturated aldehyde moiety, as the aldehyde component.31
http://dx.doi.org/10.1016/j.tetlet.2014.03.072
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

J. Ghosh et al. / Tetrahedron Letters 55 (2014) 2924–2928
2925
Z
Reaction of 3-formylchromone (1) with dimedone and NH4OAc in
refluxing ethanol produced 3-(2-hydroxyaroyl)-7,7-dimethyl-
5,6,7,8-tetrahydroquinolin-5-ones in 34–59% yields.32 Herein we
report a one-pot multicomponent synthesis of hitherto unreported
chromeno[2,3-b]quinolines in high yields involving aldehyde 1,
amine 2, and dimedone 3 under different media.
NH2
O
O
O
O
O
O
N
+
+
CHO
R
R
O
Z
2
On stirringan equimolarmixtureof 1b, 2b, and 3 at room temper-
ature in diethyl ether for half an hour a yellow precipitate appeared,
which was filtered out to afford 4bb (Table 1, entry 1) (Scheme 1). On
changing the solvent from diethyl ether to acetonitrile, the yield of
4bb increased and the work-up of the reaction was more convenient
(entry 2). TLC reportof the yellowsolid showed two spots at Rf values
0.64 as major component and 0.44 as minor component using 50%
ethyl acetate in toluene as eluent. The compounds corresponding
to the two spots could not be separated by column chromatography.
Preparative TLC was attempted for their separation. Silica gels bear-
ing the two spots were scraped out separately and organic matters
from them were extracted with chloroform by stirring at room tem-
perature. Surprisingly, the extract corresponding to Rf value 0.64
again showed the original two spots in TLC, whereas from the second
extract no compound could be isolated corresponding to Rf value
0.44. It gave us an indication of ready conversion of the major com-
ponent into the minor one in solution phase.
3
4
1
For 2
For 1
d: Z = Cl
e: Z = CO2Me
: Z = NO2
a: Z =H
a: R =H
b: Z = Me
b: R=Me
c: R = Cl
d: R = OH
c: Z = OMe
f
Scheme 1. Three component reaction.
To accomplish this MCR under green condition, we attempted
this reaction in water. An equimolar mixture of 1, 2, and 3 failed
to produce any desired product on stirring at room temperature
or heating at 70–80 °C in water (Table 1, entries 3 and 4). We then
employed saturated aqueous solution of tetrabutylammonium
bromide (TBAB) as the reaction medium. To our delight, on stirring
a mixture of 1 mmol each of 1b, 2b, and 3 in saturated TBAB solu-
tion (10 mL) at room temperature over night yielded 4bb in 85%
yield, whereas on heating at 70–80 °C the reaction mixture pro-
duced 4bb in quantitative yield in 10 min (entries 5 and 6). To opti-
mize the reaction condition, the above reaction was conducted
using different molar concentrations of TBAB. A series of experi-
ments (entries 8–13) showed the optimized concentration of the
medium to be 1.8 M. The effects of other surfactants like triethylb-
enzylammonium chloride (TEBA), sodium dodecyl sulfate (SDS),
and microemulsion34 were also considered. Use of TEBA failed to
show any effective transformation; 1.0 M aqueous SDS showed
better activities than microemulsion (entries 14–18).
The structure of 4bb was established on the basis of IR, 1H, and
13C NMR and mass spectral analysis. In the solution phase 4bb was
found to be contaminated with 5bb. The special features in the 1
H
NMR spectrum of the yellow compound are the two singlets at d
6.54 for 5a-H and at d 7.93 for 12-H in the major component
4bb, whereas, the minor component 5bb exhibits one singlet at d
6.26 for 4b-H and signal corresponding to 11-H is buried under
other aromatic protons. In the 13C NMR spectrum, peaks at d 89.2
for 5a-C in 4bb and at d 68.2 for 4b-C in 5bb are two distinctive
features. The structure of 4 was further confirmed by single crystal
X-ray analyses of 4ac (Fig. 1).33
After the optimal reaction conditions were established the ef-
fects of the active methylene components in this 3-CR were
Table 1
Optimization of reaction conditions for the synthesis of 4bb
CH3
NH2
O
O
O
O
N
O
+
+
CHO
H3C
H3C
CH3
2b
O
O
1b
4bb
3
Entry
Medium
Reaction condition (°C)
Time
Yield (%)
25
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
Et2O
CH3CN
H2O
RT/stirring
RT/stirring
RT/stirring
70–80
RT/stirring
70–80
70–80
70–80
70–80
70–80
70–80
70–80
70–80
70–80
RT
0.5 h
0.5 h
1 h
1 h
67
a
a
H2O
Saturated aq TBAB solution
Saturated aq TBAB solution
5.0 M aq TBAB
0.8 M aq TBAB
1.0 M aq TBAB
0.4 M aq TBAB
1.5 M aq TBAB
2.0 M aq TBAB
1.8 M aq TBAB
Over night
10 min
10 min
30 min
20 min
30 min
15 min
10 min
10 min
8 h
85
98
98
60
80
a
90
98
98
a
1.4 M TEBA
1.0 M aq SDS solution
1.0 M aq SDS solution
Microemulsionb
Microemulsionb
4 h
15 min
2 h
50
90
45
80
70–80
RT
70–80
2 h
Bold values signify the optimized conditions.
‘RT’ stands for ‘room temperature’.
a
No clear reaction.
b
A mixture of H2O (4.74 g), 2-propanol (34.88 g), and toluene (43.81 g).34

2926
J. Ghosh et al. / Tetrahedron Letters 55 (2014) 2924–2928
Table 3
Reusability of TBAB/H2O system in the MCR involving 1b, 2b, and 3
Entry Cycle Vol of 1.8 M aq TBAB
Substrates
Time
Yield
solution (mL)
used (mmol)
(min)
4bb (%)
1
2
3
4
5
6
7
1
2
3
4
5
6
7
10
9
8
7
6
1
1
1
0.5
0.5
0.25
0.25
10
12
12
15
15
15
20
98
90
78
82
76
65
65
5
4
Z
HN
HO
X
O
2 + 3
6
1
O
O
O
1 + 3
2
2
C
H
R
O
7
4
HO
Figure 1. ORTEP diagram of 4ac.
O
X
1
3
O
O
+
HC
HO
H3C
O
checked. Among the attempted active methylene components
dimedone, Meldrum’s acid, indane-1,3-dione, 4-hydroxycoumarin,
and acetylacetone only dimedone accomplished the 3-component
reaction clearly.
3
8
O
O
1
2
+
CH N
The scope of the reaction was then tested with respect to the
amine 2. Introduction of the electron donating group in the aro-
matic ring in amine 2 facilitates the reaction. Use of 2a (Z = H),
2b (Z = Me), and 2c (Z = OMe) yielded almost quantitatively within
a short time (Table 2, entries 1–3), but use of 2d (Z = Cl) and 2e
(Z = CO2Et) having electron withdrawing groups decreases the
yield and a little longer time was required to complete the reaction,
whereas use of 2f (Z = NO2) having a stronger electron withdraw-
ing group failed to accomplish the reaction (entries 4–6). Presence
of the electron donating hydroxyl group on the chromone ring of 1
produced 4db in 80% yield in a little longer time (entry 8).
A comparative study of this 3-CR in acetonitrile and in 1.8 M
aqueous TBAB solution has been done. The results (Table 2) show
a superiority of this reaction in aqueous medium (Method B) than
in acetonitrile (Method A)35 with respect to both yield and reaction
time. The reusability of the TBAB/H2O system was tested with the
filtrate obtained after isolation of the product. It was observed that
10 mL of 1.8 M aqueous TBAB solution can be used for reaction of
4.5 mmol of the substrate in seven cycles (Table 3), but when
R
Z
9
Scheme 2. Probable mode of formation of 4.
4.5 mmol of substrate was tried to react in 10 mL of 1.8 M aqueous
TBAB solution, it forms a paste and no clear reaction was observed.
Formation of 4 may be considered by three possible approaches
(Scheme 2): (i) combination of 2 and 3 could form the enamine 6,
which might react with 1 to produce 4. To check the formation of
enamine, a mixture of 2b and 3 was stirred in 1.8 M aqueous TBAB
solution for 1 h at 70–80 °C, but the resultant solution showed no
change. So this possibility was ruled out. (ii) Knoevenagel conden-
sation product 7, obtained from 1 and 3, could interact with 2 to
produce 4. As the Knoevenagel condensation product 7 could not
be isolated, this route could not be checked. However, on treat-
ment of 8, the condensate arises from condensation of 1 and 3 in
1:2 molar proportions, with 2 failed to produce 4. (iii) The
Table 2
Results of the reactions among 1, 2, and 3
Entry
R
Z
Reaction time
Yield (%)
Product
Mp (°C)
Method A35
Method B35
Method A
Method B
1
2
3
4
5
6
7
8
9
Me
Me
Me
Me
Me
Me
H
OH
H
H
H
0.5 h
0.5 h
0.5 h
1.5 h
2.0 h
2 h
45 min
2.0 h
25 min
1.5 h
1.5 h
10 min
10 min
10 min
15 min
20 min
2 h
10 min
30 min
10 min
15 min
15 min
59
67
68
59
34
N.R.
57
50
52
78
52
95
98
98
90
85
N.R.
96
80
98
90
89
4ba
4bb
4bc
4bd
4be
—
4ab
4db
4ac
4ad
4cd
230–232
262–264
200–202
236–238
210–212
—
216–218
218–220
194–196
238–240
230–232
Me
OMe
Cl
CO2Me
NO2
Me
Me
OMe
Cl
10
11
Cl
Cl

J. Ghosh et al. / Tetrahedron Letters 55 (2014) 2924–2928
2927
HO
Z
NH2
O
O
O
O
3
+
CHO
O
O
O
N
N
R
R
Z
O
9
1
Z
2
R
O
10
Z
Z
4
O
5
O
4
7
5
5a
4b
O
11
O
N
1
7
OH
-H2O
O
O
N
12
10
1
N
R
R
511
10
12
O
O
R
4
H
O
Z
11
Z
O
O
O
O
N
N
R
R
Z
O
12
12'
O
Scheme 3. Mechanism for the formation of 4 and 5.
Figure 2. ORTEP diagram of 12bbꢁHCl.
Schiff-base 9, formed from 1 and 2, can react with 3 to produce 4
via 10 and 11 (Scheme 3). Indeed, an independent synthesis of
Schiff-base 9 followed by its treatment with 3 under the same
reaction conditions, produced 4 in excellent yield. It should be
mentioned here that Schiff-base 9 is prone toward 1,4-addition
of nucleophile.36 Compounds 4 can form 5 in solution via pyran
ring-opened forms 12 and 120. On heating 4bb in methanol in
the presence of concentrated hydrochloric acid produced a crystal-
line compound 12bb.ꢁHCl, whose structure was determined by
X-ray crystallography (Fig. 2).33 It needs to be mentioned that
compound 12bbꢁHCl reverts to 4bb in methanol or DMSO solution
in the absence of HCl.
In conclusion, we have achieved the synthesis of hitherto
unreported 5-aryl-3,3-dimethyl-2,3-dihydro-5aH-chromeno[2,3-b]
quinoline-1,11-(4H,5H)dione by a 3-component reaction in aque-
ous micellar medium. The electron releasing group on amine com-
ponent facilitates the reaction and the electron withdrawing group
retards the reaction. A comparative study of this MCR revealed
aqueous micellar medium to be better than organic solvent
both with respect to yield and reaction time. This reaction can be

2928
J. Ghosh et al. / Tetrahedron Letters 55 (2014) 2924–2928
Zhi, L.; Tegley, C. M.; Kalle, E. A.; Marsche, K. B.; Mais, D. E.; Gottardis, M. M.;
Jones, T. K. J. Med. Chem. 1998, 41, 291–302.
17. Shen, Y. B.; Wang, G. W. Arkivoc 2008, xvi, 1–8.
18. Shen, W.; Wang, L.-M.; Tian, H.; Tang, J.; Yu, J. J. J. Fluorine Chem. 2009, 130,
522–527.
considered as an ideal process for the synthesis of chromeno[2,3-
b]quinolinedione for its rapid production, easy work-up, and atom
economy (only two molecules of water are eliminated).
19. Rajendran, A.; Selvam, A.; Karthikeyan, C.; Ramu, S. Int. J. Curr. Tr. Res. 2012, 1,
24–30.
Acknowledgements
20. Nakhi, A.; Srinivas, P. T. V. A.; Rahman, M. S.; Kishore, R.; Seerapu, G. P. K.;
Kuman, K. L.; Haldar, D.; Rao, M. V. B. Bioorg. Med. Chem. Lett. 2013, 23, 1828–
1833.
21. Davoodnia, A.; Khojastehnezhad, A.; Tavakoli-Hoseini, N. Bull. Korean Chem.
Soc. 2011, 32, 2243–2248.
22. Kidwai, M.; Bhatnagar, D. Tetrahedron Lett. 2010, 51, 2700–2703.
23. Kidwai, M.; Rastogi, S. Heteroatom. Chem. 2005, 16, 138–141.
24. (a) Verma, G. K.; Raghuvanshi, K.; Kumar, R.; Singh, M. S. Tetrahedron Lett. 2012,
53, 399–402; (b) Khan, A. T.; Das, D. K. Tetrahedron Lett. 2012, 53, 2345–2351.
25. (a) Dzvinchuk, I. B.; Tolmacheva, N. A. Chem. Heterocycl. Compd. 2001, 37, 506–
508; (b) Chebanov, V. A.; Saraev, V. E.; Kobzar’, K. M.; Desenko, S. M.; Orlov, V.
D.; Guru, E. A. Chem. Heterocycl. Compd. 2004, 40, 475–480.
26. (a) Quiroga, J.; Mejia, D.; Insuasty, B.; Abonia, R.; Nogueras, M.; Sanchez, A.;
Cobo, J.; Low, J. N. Tetrahedron 2001, 57, 6947–6953; (b) Tratrat, C.; Giorgi-
Renaults, S.; Husson, H.-P. Org. Lett. 2002, 4, 3187–3189; (c) Kadutskii, A. P.;
Kozlov, N. G. Russ. J. Org. Chem. 2006, 42, 1388–1391.
We gratefully acknowledge CSIR, New Delhi, India [Project no.
02(0029)/11/EMR-II] for financial assistance; DST-FIST for instru-
mental help at RKMVC College; IICB, Jadavpur for spectral analysis
and finally the college authority for providing research facilities.
J.G. thanks CSIR for Junior Research Fellowship.
Supplementary data
Supplementary data associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
03.072.
27. (a) Kadutskii, A. P.; Kozlov, N. G. Synlett 2006, 3349–3351; (b) Kadutskii, A. P.;
Kozlov, N. G. Russ. J. Org. Chem. 2006, 42, 855–859; (c) Neochoritis, C. G.;
Eleftheriadis, N.; Tsiantou, A.; Stephanidou-Stephanatou, J.; Tsoleridis, C. A.
Synlett 2013, 2768–2772.
28. Kozlov, N. G.; Kadutskii, A. P. Tetrahedron Lett. 2008, 49, 4560–4562.
29. (a) Ellis, G. P. In Heterocyclic Compounds; Weissberger, A., Ed.; Interscience: NY,
1977; Vol. 31, pp 903–1083. Chapter XVIII–XXI; (b) Staunton, J. In
Comprehensive Organic Chemistry In ; Barton, D., Ollis, W. D., Eds.; Pergamon
Press: Oxford, 1979; Vol. 4, pp 659–692. Chapter 18.3.
30. (a) Quiney, C.; Dauzonne, D.; Kern, C.; Fourneron, J.-D.; Izard, J.-C.; Mohammad,
R. M.; Kolb, J.-P.; Billard, C. Leukemia Res. 2004, 28, 851–861; (b) Dubufett, T.;
Newman-Taneredi, A.; Cussac, D.; Audinot, V.; Loutz, A.; Millan, M. J.; Lavielle,
G. Biorg. Med. Chem. Lett. 1999, 9, 2059–2064; (c) Guillo, L. A.; Beylot, B.; Vigny,
P.; Spassky, A. Photochem. Photobiol. 1996, 64, 349–355; (d) Guinn, D. E.;
Summers, J. B.; Heyman, H. R.; Conway, R. G.; Rhein, D. A.; Albert, D. H.; Magoc,
T.; Carter, G. W. J. Med. Chem. 1992, 35, 2055–2061.
31. (a) Panja, S. K.; Karmakar, P.; Chakraborty, J.; Ghosh, T.; Bandyopadhyay, C.
Tetrahedron Lett. 2008, 49, 4397–4401; (b) Panja, S. K.; Maiti, S.;
Bandyopadhyay, C. J. Chem. Res. 2009, 33, 692–695; (c) Panja, S. K.; Maiti, S.;
Drew, M. G. B.; Bandyopadhyay, C. J. Chem. Res. 2011, 35, 225–228; (d) Panja, S.
K.; Ghosh, J.; Maiti, S.; Bandyopadhyay, C. J. Chem. Res. 2012, 36, 222–225; (e)
Ghosh, J.; Panja, S. K.; Maiti, S.; Biswas, P.; Sarkar, T.; Bandyopadhyay, C. J.
Heterocycl. Chem. 2013. http://dx.doi.org/10.1002/jhet.1929 (in press).
32. Sosnovskikh, V. Y.; Irgashev, R. A.; Demkovich, I. A. Russ. Chem. Bull. 2008, 57,
2210–2213.
References and notes
1. (a) Posner, G. H. Chem. Rev. 1986, 86, 831–844; (b) Tietze, L. F.; Modi, A. Med.
Res. Rev. 2000, 20, 304–322; (c) Domling, A. Chem. Rev. 2006, 106, 17–89; (d)
Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439–4486.
2. Multicomponent Reactions; Zhu, J., Bienayme, H., Eds.; Wiley-VCH, 2005.
3. Horvath, I. T.; Anastas, P. T. Chem. Rev. 2007, 107, 2167–2173.
4. (a) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102, 7816–7817; (b)
Breslow, R.; Maitra, U.; Rideout, D. Tetrahedron Lett. 1983, 24, 1901–1904; (c)
Breslow, R.; Maitra, U. Tetrahedron Lett. 1984, 25, 1239–1240; (d) Li, C.-J. Chem.
Rev. 2005, 105, 3095–3165; (e) Li, C.-J.; Chen, L. Chem. Soc. Rev. 2006, 35, 68–82;
(f) Minakata, S.; Komatsu, M. Chem. Rev. 2009, 109, 711–724; (g) Chanda, A.;
Fokin, V. V. Chem. Rev. 2009, 109, 725–748; (h) Butler, R. N.; Coyne, A. G. Chem.
Rev. 2010, 110, 6302–6337.
5. (a) Otto, S.; Engberts, J. B. F. N. Org. Biomol. Chem. 2003, 1, 2809–2820; (b)
Lindstrom, U. M.; Andersson, F. Angew Chem., Int. Ed. 2006, 45, 548–551.
6. Chandrasekhar, J.; Shariffskul, S.; Jorgensen, W. L. J. Phys. Chem. B 2002, 106,
8078–8085.
7. (a) Dack, M. R. J. Chem. Soc. Rev. 1975, 4, 211–229; (b) Lubineau, A. J. Org. Chem.
1986, 51, 2142–2144; (c) Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994,
741–760; (d) Sheldon, R. A. J. Mol. Catal. A 1996, 107, 75–83.
8. Jung, Y. S.; Marcus, R. A. J. Am. Chem. Soc. 2007, 129, 5492–5502.
9. (a) Singh, M.; Fatma, S.; Ankit, P.; Singh, S. B.; Singh, J. Tetrahedron Lett. 2014,
55, 525–527; (b) Shiri, M.; Zolfigol, M. A. Tetrahedron 2009, 65, 587–598; (c)
Von Hippel, P. H.; Schleich, T. Acc. Chem. Res. 1969, 2, 257–265.
10. Lim, K. M.; Lee, J. Y.; Lee, S. M.; Bae, O. N.; Noh, J. Y.; Chung, S. M.; Chung, J. H.
Br. J. Pharmacol. 2009, 156, 328–337.
33. CCDC 981843 for compound 4ac and CCDC 981844 for compound 12bb.HCl
contain the supplementary crystallographic data for this Letter. This data can
be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk).
11. (a) Sudhamani, C. N.; Naik, H. S. B.; Girija, D. Nucleosides Nucleotides 2012, 31,
130–146; (b) Sudhamani, C. N.; Naik, H. S. B.; Prabhakara, M. C. Res. Rev. BioSci.
2007, 1, 181–188.
34. Gonzalez, A.; Holt, S. L. J. Org. Chem. 1982, 47, 3186–3188.
35. Method A: A mixture of aldehyde 1 (1 mmol), amine 2 (1 mmol) and dimedone
(3) (1 mmol) in CH3CN (10 mL) was stirred at room temperature. The
precipitated solid was filtered and crystallized from CHCl3-light petroleum to
afford 4. Method B: A mixture of 1 mmol each of 1, 2 and 3 was poured in 1.8 M
aqueous solution of TBAB (10 mL). The reaction mixture was stirred at 70–
12. Wang, Z.; Zhou, L.-J.; Wang, Y.-L.; Weng, Y.-B.; He, J.; Nie, K. J. Chem. Res. 2011,
35, 373–376.
13. (a) Kand, D.; Kalle, A. M.; Varma, S. J.; Talukdar, P. Chem. Commun. 2012, 2722–
2724; (b) Kand, D.; Kalle, A. M.; Talukdar, P. Org. Biol. Chem. 2013, 11, 1691–
1701.
14. Miri, R.; Motamedi, R.; Rezaei, M. R.; Firuzi, O.; Javidnia, A.; Shaflee, A. Arch.
Pharm. (Weinheim) 2011, 344, 111–118.
15. Nagaiah, K.; Venkatesham, A.; Srinivasa Rao, R.; Saddanapu, V.; Yadav, J. S.;
Basha, S. J.; Sarma, A. V. S.; Sridhar, B.; Addlagatta, A. Bioorg. Med. Chem. Lett.
2010, 20, 3259–3264.
80 °C for 5 min.
A clear solution appeared immediately and the reaction
mixture was heated further for 5 min when a yellow precipitate appeared. The
solid was filtered, washed with water and dried in air and recrystallized from
chloroform-light petroleum to afford 4.
36. Fitton, A. O.; Frost, J. R.; Houghton, P. G.; Suschitzky, H. J. Chem. Soc., Perkin
Trans. 1 1979, 1691–1694.
16. (a) Zhi, L.; Tegley, C. M.; Pio, B.; Edwards, J. P.; Jones, T. D.; Marsche, K. B.; Mais,
D. E.; Risek, B.; Schrader, W. T. Bioorg. Med. Chem. Lett. 2003, 13, 2071–2074; (b)