Imino Diels-Alder reactions catalyzed by oxalic acid dihydrate. Synthesis of Tetrahydroquinoline derivatives

Article abstract of DOI:10.1081/SCC-100103994

Oxalic acid dihydrate is found to catalyze the Imino Diels-Alder reaction of schiff bases derived from substituted anilines with cyclopentadiene, results in the formation of Tetrahydroquinoline derivatives in moderate yields.

Full text of DOI:10.1081/SCC-100103994

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IMINO DIELS-ALDER
REACTIONS CATALYZED
BY OXALIC ACID
DIHYDRATE. SYNTHESIS OF
TETRAHYDROQUINOLINE
DERIVATIVES
Rajagopal Nagarajan a & Paramasivan T. Perumal b
a Organic Chemistry Division, Central Leather
Research Institute, Adyar, Chennai, 600 020, India
b Organic Chemistry Division, Central Leather
Research Institute, Adyar, Chennai, 600 020, India
Published online: 09 Nov 2006.
To cite this article: Rajagopal Nagarajan & Paramasivan T. Perumal (2001) IMINO
DIELS-ALDER REACTIONS CATALYZED BY OXALIC ACID DIHYDRATE. SYNTHESIS OF
TETRAHYDROQUINOLINE DERIVATIVES, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 31:11, 1733-1736,
DOI: 10.1081/SCC-100103994
To link to this article: http://dx.doi.org/10.1081/SCC-100103994
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SYNTHETIC COMMUNICATIONS, 31(11), 1733–1736 (2001)
IMINO DIELS–ALDER REACTIONS
CATALYZED BY OXALIC ACID
DIHYDRATE. SYNTHESIS OF
TETRAHYDROQUINOLINE DERIVATIVES
Rajagopal Nagarajan andParamasivan T. Perumal *
Organic Chemistry Division, Central Leather Research
Institute, Adyar, Chennai – 600 020, India
ABSTRACT
Oxalic acid dihydrate is found to catalyze the Imino Diels–
Alder reaction ofschiff bases derived from substituted anilines
with cyclopentadiene, results in the formation of
Tetrahydroquinoline derivatives in moderate yields.
Tetrahydroquinoline derivatives are an important class ofNatural
products which exhibit biological activities such as psychotropic,1 anti-
allergenic,2 antiinflammatory3 and estronegic4 activities. Lewis acids like
BF3.Et2O,5 InCl3,6 Lanthanide triflates7 and protic acids such as TFA,8
p-TsOH9 have been found to catalyze the reaction of aldimines with electron
rich dienophiles. The reaction ofN-benzylidene aniline with 3,4-dihydro-
pyran calatysed bt BF3 Et2O takes 12 h and yields only 25% ofpyrano-
quinoline.5 Since oxalic acid dihydrate is an inexpensive and commercially
available acid, explored its ability to catalyze the imino Diels–Alder
Reactions effectively.
* Corresponding author. Fax: 91-044-4911589; E-mail: ptperumal@hotmail.com
1733
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

1734
NAGARAJAN AND PERUMAL
N-benzylideneaniline (1a) was refluxed with cyclopentadiene (2) in
the presence ofoxalic acid in acetonitrile ofr 1 h. The imine acted as a
heterodiene and the reaction proceeded smoothly to give the corresponding
tetrahydroquinoline (3a) in 58% yield. This is the first report for the imino
Diels–Alder reaction catalyzed by oxalic acid dihydrate.
Scheme 1.
Table 1. Synthesis ofCyclopentaquinolines
Substituents
Entry
Imines
R1
R2
R3
Yield (%)
1
2
3
4
5
1a
1b
1c
1d
1e
H
H
H
H
Cl
COOH
H
H
H
H
H
H
CH3
58
49
75
77
67
CH2CH3
CH3
1
Products were characterized by H NMR, 13C NMR, IR and Mass spectra.
Imines generated insitu from aldehydes and amines, immediately reacts
with cyclopentadiene to afford cyclopentaquinolines in an one pot way
without the need of pre-formation of the imines. It was found that the
reaction ofbenzaldehyde, aniline and cyclopentadiene in acetonitrile was
refluxed in the presence ofoxalic acid dihydrate to yield the product 3a in
51% yield in 1 h.
The reaction ofbezaldehyde, aniline with cyclopentadiene catalyzed
by oxalic acid was also conducted in aqueous medium (CH3CN-H2O) to
give the product 3a in 45% yield. The reaction ofmorpholine enamine with
N-benzylidene aniline catalysed by PTSA takes 12 h,10 where as oxalic acid
catalysed reaction ofN-benzylidene aniline with cyclopentadiene goes to
completion within one hour. Lewis acids like InCl3, BF3, Et2O require
anhydrous conditions, but commercial sample ofoxalic acid can be used

IMINO DIELS–ALDER REACTIONS
1735
Scheme 2.
for imino Diels–Alder reaction. BF3 Et2O gets hydrolysed to the hydroxide
in aqueous medium where as in the case ofoxalic acid the reaction can be
conducted in aqueous medium with out any decomposition.
In conclusion, this paper describes a simple method for obtaining
tetrahydroquinolines using commercially available, an inexpensive oxalic
acid dihydrate as a catalyst.
EXPERIMENTAL
To a stirred solution ofschiff base 1b (2.5 mmol) and cyclopentadiene
(0.330 g, 5 mmol) in acetonitrile (10 ml) was added oxalic acid dihydrate
(0.315 g, 2.5 mmol) and refluxed for 1 h. The reaction mixture poured over
an ice water and extracted with chloroform (3 ꢀ 10 ml). The combined
organic layer was washed with saturated NaHCO3 (10 ml) and brine
(10 ml), dried over anhydrous Na2SO4, then concentrated under reduced

1736
NAGARAJAN AND PERUMAL
pressure. The residue was purified by column chromatography using silicagel
(60–120 mesh) and eluted with petroleum ether: Ethyl acetate (95:5) to
afford 3b as pale yellow crystalline solid in 49% yield. 1H NMR
(300 MHz, CDCl3): d 7.44 (m, 5H), 7.04 (d, 1H, J ¼ 2.1 Hz), 6.93 (dd, 1H,
J ¼ 2.2 Hz, J ¼ 8.6 Hz), 6.55 (d, 1H, J ¼ 8.5 Hz), 5.82 (m, 1H), 5.69 (m, 1H),
4.61 (d, 1H, J ¼ 2.9 Hz), 4.09 (d, 1H, J ¼ 8.6 Hz), 3.76 (br s, 1H), 3.05 (m,
1H), 2.67 (m, 1H), 1.86 (m, 1H); 13C NMR (75 MHz, CDCl3): d 144.1,
142.3, 133.4, 130.8, 128.6, 128.4, 127.6, 127.3, 126.4, 123.4, 116.9, 57.9,
46.2, 45.7, 31.4; MS (m/z): 281 (Mþ), 283 (Mþ þ 2); IR (KBr): 3363,
1470 cmꢁ1
.
ACKNOWLEDGMENT
We thank Council ofScientific and Industrial Research, New Delhi,
India for financial support.
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Accepted in the Netherlands August 21, 2000