D. Bhuyan et al. / Tetrahedron Letters 53 (2012) 6460–6463
6463
R2
R1
R1
O
O
O
N
O
3
N
N
NH2
CHO
N
HN
N
O
R1
O
[4+2]
cycloaddition
1
2
[A]
R2
generated in situ
4
Scheme 2.
Rep. 2008, 25, 166–187; (d) Michael, J. P. Nat. Prod. Rep. 2007, 24, 223–246; (e)
Michael, J. P. Nat. Prod. Rep. 2005, 22, 627–646.
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3–38.
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4. Bergstrom, F. W. Chem. Rev. 1944, 35, 153.
both electron donating and withdrawing substituent participated
in the reaction to give the desired spiro-substituted quinoline
derivative in good to excellent yield. Further, it was encouraging
to note that the spiro-substituted quinoline was obtained as the
only product and no undesired side reaction was detected. How-
ever, when heterocyclic aldehydes such as pyrole-2-carbaldehyde
and thiophene-2-carbaldehyde were employed, the Knoevenagel
condensed product between the aldehyde and naphthylamine re-
sulted without any desired cyclized product. All the products ob-
tained were characterized by IR, NMR, and mass spectrometric
analysis. Increase in the reaction time or the microwave power
did not result in an improvement in yield of the reaction, rather,
decomposition of the product occurred.
The formation of the observed product can be mechanistically
rationalized via a formal [4+2] aza-Diels–Alder pathway. A diene
generated in situ from naphthylamine 1 and aldehyde 2 which re-
acts with the dienophile 5-benzylidene-1,3-dimethyl pyrimidine-
2,4,6-trione 3 to form the observed product 4 (Scheme 2). This type
of catalyst- and solvent-free aza-Diels–Alder pathway is rare in the
literature and efforts are still required in this direction for develop-
ing such methodologies.16a The formation of the products from the
three-component reactions was further confirmed by performing
the reaction stepwise. Initially, intermediate [A] was synthesised
from the condensation of naphthylamine 1 with p-fluorobenzalde-
hyde 2a at room temperature using ethanol as solvent. The inter-
mediate [A] was then reacted with 5-(4-fluoro-benzylidene)-1,3-
dimethyl pyrimidine-2,4,6-trione 3a inside a microwave reactor
in the absence of any catalyst and solvent to get the product 4a.
In summary, an efficient aza-Diels–Alder strategy has been
developed for the construction of some complex spiroquinoline
derivatives via a microwave-assisted, one-pot, three component
reaction under catalyst- and solvent-free conditions. The actual
[4+2] nature of the reaction pathway was established by perform-
ing the reaction stepwise. Overall, this is a very simple, clean, and
green protocol for obtaining complex quinolines in excellent yields
within a short time period.
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Acknowledgements
17. Equimolar amounts of 1-aminonaphthalene 1, p-fluorobenzaldehyde 2a and 5-
We thank DST, New Delhi for financial support to this work. DB
thanks UGC, NERO, for the award of a teacher fellowship and RS
thanks CSIR, New Delhi, for a research fellowship. We also thank
the Director, NEIST, Jorhat for his keen interest and constant
encouragement.
(4-fluoro-benzylidene)-1,3-dimethyl
pyrimidine-2,4,6-trione
3a
were
irradiated in a closed vessel in the absence of any solvent in a Synthos 3000
microwave reactor at 700 W, 18 bar and 80 °C for 10 min. The crude product
mixture was dissolved in ethyl acetate and directly column chromatographed
using 1:9 ethyl acetate/hexane as the eluent to get pure product 4a.
Compound 4a: White solid mp 209–210 °C, 1H NMR (300 MHz, CDCl3) d 7.90–
6.87 (m, Ar, 14H), 5.35 (s, 1H), 5.12 (s, 1H), 4.87 (s, br s, 1H), 2.99 (s, 3H), 2.90
(s, 3H). 13C NMR (75 MHz, CDCl3) d 170.2, 165.1, 164.8, 164.0, 161.5, 160.8,
149.7, 138.2, 133.9, 132.9, 132.6, 130.6, 128.8, 128.7, 128.5, 126.3, 125.8, 125.4,
123.7, 120.3, 118.8, 117.2, 116.3, 116.0, 115.6, 63.5, 58.4, 51.8, 28.4, 27.7. IR
(CHCl3, cmÀ1) 3411, 1742, 1676, 1605, 1509, 1381, 1229, 755. MS (GCMS, m/z)
511 [M]+; Anal. Calcd for C30H23F2N3O3: C, 70.44; H, 4.53; N, 8.21. Found: C,
70.40; H, 4.62; N, 8.08. Similarly, compounds 4b–o were synthesized and
characterized.
References and notes
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Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
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18. Deb, M. L.; Bhuyan, P. J. Tetrahedron Lett. 2005, 46, 6453–6456.