Aza-Diels-Alder reactions in ionic liquids: A facile synthesis of pyrano- and furanoquinolines

Article abstract of DOI:10.1016/S0040-4020(03)00027-9

Room temperature ionic liquids are found to catalyze efficiently the three component-coupling reactions of aldehydes, amines and cyclic enol ethers such as 3,4-dihydro-2H-pyran and 2,3-dihydrofuran under mild and convenient conditions to afford the corres

Full text of DOI:10.1016/S0040-4020(03)00027-9

Tetrahedron 59 (2003) 1599–1604
Aza-Diels–Alder reactions in ionic liquids: a facile synthesis
of pyrano- and furanoquinolines
*
J. S. Yadav, B. V. S. Reddy, J. S. S. Reddy and R. Srinivasa Rao
Division of Organic Chemistry, Natural Products Laboratory, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 30 August 2002; revised 2 December 2002; accepted 19 December 2002
Abstract—Room temperature ionic liquids are found to catalyze efficiently the three component-coupling reactions of aldehydes, amines
and cyclic enol ethers such as 3,4-dihydro-2H-pyran and 2,3-dihydrofuran under mild and convenient conditions to afford the corresponding
pyrano- and furanoquinolines in excellent yields with high endo-selectivity. Interestingly, 2,3-dihydrofuran afforded selectively endo-
products under the similar reaction conditions. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
great promise as an attractive alternative to conventional
solvents. They are non-volatile, recyclable, non-explosive,
easy to handle, thermally robust, and in addition they are
compatible with various organic compounds and organo-
metallic reagents.7 Indeed, ionic liquids are good solvents
for transition-metal complexes in many homogeneously
catalyzed reactions such as hydrogenation, hydroformyla-
tion, epoxidation, allylation, the Heck reaction, and Suzuki
cross coupling reactions.8 In many cases the products are
weakly soluble in the ionic phase so that the catalyst can be
separated by simple extraction. Because of the great
potential of room temperature ionic liquids as environ-
mentally benign media for catalytic processes, much
attention is currently focused on organic reactions catalyzed
by ionic liquids. Several organic reactions promoted by
ionic liquids have been reported with high performance.9
This has offered some evidence that using ionic liquids as
promoters for those traditionally acid-base catalyzed
synthetic reactions may not only be possible but also
practical and even highly efficient. In addition, improved
endo-selectivity and enhanced reaction rates are the
remarkable features observed in Diels–Alder reactions in
ionic liquids.10 However, there are no examples of the use of
ionic liquids as promoters for the imino-Diels–Alder
reaction.
The hetero-Diels–Alder reaction is becoming a mainstay
for heterocycle and natural product synthesis.1 Pyrano-
quinoline derivatives are found to possess a wide spectrum
of biological activities such as psychotropic, anti-allergenic,
anti-inflammatory and estrogenic activity.2 The imino-
Diels–Alder provides easy access to the preparation of
pyrano, and furanoquinolines. The imines derived from
aromatic amines act as heterodienes and undergo imino-
Diels–Alder reaction with various dienophiles in the
presence of acid catalysts.3–5 However, many of these
reactions cannot be carried out in a one-pot operation with a
carbonyl compound, amine and enol ether because the
amines and water that exist during imine formation can
decompose or deactivate the Lewis acids. Even when the
desired reactions proceed, more than stoichiometric
amounts of the Lewis acids are required because the acids
are trapped by nitrogen.1 Furthermore, most of the imines
are hygroscopic, unstable at high temperatures, and difficult
to purify by distillation or column chromatography.
Subsequently, one-pot procedures have been developed
for this transformation using lanthanide triflates as
catalysts.6 These procedures do not require the isolation of
unstable imines prior to the reactions, but metal triflates are
strongly acidic and highly expensive, and so the develop-
ment of neutral alternatives like ionic liquids would extend
the scope of this useful transformation to synthesize
functionalized quinoline derivatives.
2. Results and discussion
In view of the emerging importance of ionic liquids as novel
reaction media, we wish to report the use of ionic liquids as
promoters for the synthesis of tetrahydroquinolines. The
treatment of benzaldehyde and aniline with 2,3-dihydro-
furan in 1-butyl-3-methylimidazolium tetrafluoroborate
ionic liquid afforded the corresponding furanoquinolines 3
in 92% yield (Scheme 1).
Room temperature ionic liquids, especially those based on
the 1-n-alkyl-3-methylimidazolium cation, have shown
Keywords: Diels–Alder reaction; ionic liquids; Lewis acids.
*
Corresponding author. Tel.: þ91-40-27193434; fax: þ91-40-27160512;
e-mail: yadav@iict.ap.nic.in
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00027-9

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J. S. Yadav et al. / Tetrahedron 59 (2003) 1599–1604
Finally, the efficiency of various quaternary ammonium
salts was studied. The three-component condensation was
not successful when n-tetrabutyl ammonium chloride
(n-Bu4NCl) or 1-n-butyl-3-methylimidazolium chloride
(BMImCl) was used as reaction media. This indicated that
both cation and anion played an important role as the
promoter in this transformation.
Scheme 1.
Several aldimines (formed in situ from aromatic aldehydes
and anilines in ionic liquids) reacted smoothly with
2,3-dihydrofuran in 1-butyl-3-methylimidazolium tetra-
fluoroborate [bmim]BF4 medium to afford the correspond-
ing furano[3,2-c]quinolines in 85–92% yield. In all cases,
the products were obtained exclusively as endo-isomers 3
whereas under conventional conditions, the products were
obtained as a mixture of endo- and exo-isomers favoring the
endo-diastereomer.5b However, 3,4-dihydro-2H-pyran
reacted efficiently with imines in the presence of [bmim]BF4
ionic solvent to produce pyrano[3,2-c]quinolines 4 and 5 in
excellent yields (Scheme 2).
3. Conclusion
In summary, the paper describes a novel and efficient
method for the synthesis of pyrano- and furanoquinolines
using ionic liquids as promoters. The simple experimental
and product isolation procedures combined with ease of
recovery and reuse of this novel reaction media is expected
to contribute to the development of green and waste free
chemical process for the synthesis of tetrahydroquinolines
of biological importance. The use of ionic liquids as
promoters for this transformation allows the use of moisture
sensitive and heavy metal Lewis acids to be avoided.
In the case of 3,4-dihydropyran, the products were obtained
as a mixture of 4 endo- and 5 exo-isomers, favoring endo-
diastereomers 4, as observed by others in most of the
Povarov imino-Diels–Alder reactions.4–6 In all cases, the
reactions proceeded smoothly at ambient temperature with
high selectivity. However, in the absence of ionic liquids,
the reaction did not yield any product even after a long
reaction time (15–20 h). Enhanced reaction rates, excellent
yields, and high cis-selectivity are the features observed in
these ionic solvents. All products were characterized by 1H
NMR, IR and mass spectroscopic data. The reactions of
various aldehydes, amines and cyclic enol ethers were
examined in hydrophilic 1-butyl-3-methylimidazolium
tetrafluoroborate ([bmim]BF4) and hydrophobic 1-butyl-3-
methylimidazolium hexafluorophosphate ([bmim]PF6)
ionic liquids. Among these ionic liquids, 1-butyl-3-methyl-
imidazolium tetrafluoroborate ([bmim]BF4) was found to be
superior in terms of yields and reaction rates. The advantage
of the use of ionic liquids as novel reaction medium for
this transformation is that these ionic solvents were easily
recovered after the reaction and reused in subsequent
reactions. Since the products were weakly soluble in the
ionic phase, they were easily separated by simple extraction
with ether. The rest of the viscous ionic liquid was
thoroughly washed with ether and was recycled after drying
at 808C under vacuum in each cycle. Second and third runs
using recovered ionic liquid afforded similar yields to those
obtained in the first run. No decrease in yield was observed
in runs carried out using recycled ionic liquid and
furthermore the products obtained were of the same purity
as in the first run. Furthermore, we have performed the
reactions in polar organic solvents such as DMF and
N-methylpyrrolidine to compare the efficiency of ionic
liquids. The reactions did not proceed in these solvents even
under heating conditions (75–808C).
4. Experimental
1-Butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4)
and 1-butyl-3-methylimidazolium hexafluorophosphate
([bmim]PF6) ionic liquids were prepared according to the
procedures reported in the previous literature.11 Melting
points were recorded on Buchi R-535 apparatus and are
uncorrected. IR spectra were recorded on a Perkin–Elmer
FT-IR 240-c spectrophotometer using KBr optics. 1H NMR
spectra were recorded on Gemini-200 spectrometer in
CDCl3 using TMS as internal standard. Mass spectra were
recorded on a Finnigan MAT 1020 mass spectrometer
operating at 70 eV. CHN analyses were recorded on a Vario
EL analyzer.
4.1. General procedure for the synthesis of pyrano- and
furanoquinolines
A mixture of aldehyde (1 mmol), aryl amine (1 mmol), and
3,4-dihydro-2H-pyran or 2,3-dihydrofuran (2 mmol) in
1-butyl-3-methylimidazolium tetrafluoroborate or 1-butyl-
3-methylimidazolium hexafluorophosphate (1 mL) was
stirred at ambient temperature for an appropriate time
(Table 1). After completion of the reaction, as indicated by
TLC, the reaction mixture was washed with diethyl ether
(3£10 mL). The combined ether extracts were concentrated
in vacuo and the resulting product was directly charged on
small silica gel column and eluted with a mixture of ethyl
acetate/n-hexane (2:8) to afford pure quinoline. The rest of
the viscous ionic liquid was further washed with ether and
dried at 808C under reduced pressure to retain its activity in
subsequent runs.
Scheme 2.

J. S. Yadav et al. / Tetrahedron 59 (2003) 1599–1604
Table 1. [bmim] BF4,-ionic liquid promoted synthesis of pyrano- and furano-quinolines
1601
Entry
a
R
Ar
C8H5
Enol ether
Reaction
3.5
Yield (%)a
92
endo/exob
H
–
b
c
d
e
f
4-MeO
H
3.0
3.5
3.0
2.5
4.0
3.5
3.0
90
89
92
90
87
85
91
–
H
4-FC8H4
4-ClC6H4
4-MeOC6H4
4-FC8H4
4-FC8H4
C8H5
–
4-Me
–
H
–
4-MeO
3,5-(MeO)2
H
–
g
h
–
90:10
I
H
4-FC8H4
C8H5
3.5
2.5
3.0
3.5
4.0
4.5
89
90
87
89
85
80
85:15
80:20
87:13
85:15
80:20
75:25
j
2-Me
k
l
4-MeO
4-F
C8H5
C6H5
m
n
1-Naphthyl
1-Naphthyl
C6H5
4-FC8H4
All products were characterized by 1H NMR, IR and mass spectra.
a
Isolated and unoptimized yields.
endo/exo-isomers were separated by column chromatography.
b
4.1.1. 3a: cis-4-Phenyl-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]-
1
C18H19NO2 (281.35): C, 76.84; H, 6.81; N, 4.98. Found: C,
76.86; H, 6.83; N, 4.99.
quinoline. White solid, mp 93–958C (lit,5b mp 958C); H
NMR (CDCl3): d 1.55 (m, 1H), 2.25 (m, 1H), 2.75 (m, 1H),
3.80 (m, 3H), 4.70 (d, 1H, J¼2.8 Hz), 5.25 (d, J¼8.0 Hz,
1H), 6.58 (d, J¼8.0 Hz, 1H), 6.80 (t, J¼8.0 Hz, 1H), 7.05
(t, J¼8.0 Hz, 1H), 7.35–7.55 (m, 6H). 13C NMR (CDCl3) d:
24.5, 45.8, 57.3, 66.6, 75.9, 114.9, 119.0, 122.5, 126.3,
127.6, 128.2, 128.6, 130.0, 142.3, 144.8. EIMS: m/z: 251
Mþ, 220, 206, 174, 130, 91. IR (KBr): nmax: 3348, 2975,
2855, 1615, 1480, 1070 cm21. Anal. calcd for C17H17NO
(251.32): C, 81.24; H, 6.82; N, 5.57. Found: C, 81.26; H,
6.83; N, 5.58.
4.1.3. 3c: cis-4-(4-Fluorophenyl)-2,3,3a,4,5,9b-hexa-
hydro furo[3,2-c]quinoline. White solid, mp 173–1758C;
1H NMR (CDCl3): d 1.50 (m, 1H), 2.10–2.15 (m, 1H),
2.60–2.80 (m, 1H), 3.65–3.80 (m, 3H), 4.64 (d, J¼2.5 Hz,
1H), 5.20 (d, J¼8.0 Hz, 1H), 6.50 (d, J¼8.0 Hz, 1H), 6.78
(t, J¼8.0 Hz, 1H), 7.05 (m, 3H), 7.30 (m, 1H), 7.40 (m,2H).
EIMS: m/z: 269 Mþ, 240, 224, 198, 174, 130, 117, 77, 39. IR
(KBr): nmax: 3315, 2976, 2880, 1606, 1508, 1223, 1155,
1059 cm21. Anal. calcd for C17H16FNO (269.31): C, 75.82;
H, 5.99; F, 7.05; N, 5.20. Found: C, 75.85; H, 6.00; F, 7.07;
N, 5.22.
4.1.2. 3b: cis-8-Methoxy-4-phenyl-2,3,3a,4,5,9b-hexa-
hydro furo[3,2-c]quinoline. Pale yellow solid, mp 132–
1338C (lit,5b mp 132–1338C); 1H NMR (CDCl3): d 1.55 (m,
1H), 2.20 (m, 1H), 2.75 (m, 1H), 3.65–3.85 (m, 3H), 3.78 (s,
3H), 4.62 (d, J¼2.8 Hz, 1H), 5.22 (d, J¼8.0 Hz, 1H), 6.50
(d, J¼8.6 Hz, 1H), 6.74 (dd, J¼8.6, 2.8 Hz, 1H), 6.94 (d,
J¼2.8 Hz, 1H), 7.25–7.45 (m, 5H). 13C NMR (CDCl3) d:
24.3, 45.8, 55.7, 57.9, 66.7, 76.3, 113.8, 115.9, 116.3, 123.5,
126.5, 127.4, 128.6, 139.0, 142.5, 153.0. EIMS: m/z: 281
Mþ, 236, 206, 160, 141, 115, 91, 41. IR (KBr): nmax: 3305,
2975, 2875, 1605, 1510, 1225, 1058 cm21. Anal. calcd for
4.1.4. 3d: cis-4-(4-Chlorophenyl)-8-methyl-2,3,3a,4,5,9b-
hexahydrofuro[3,2-c]quinoline. White solid, mp 148–
1
1498C; H NMR (CDCl3): d 1.50 (m, 1H), 2.20 (m, 1H),
2.35 (s, 3H), 2.64 (m, 1H), 3.60 (brs, NH, 1H), 3.72 (m, 1H),
3.80 (m, 1H), 4.60 (d, J¼2.1 Hz, 1H), 5.20 (d, J¼8.0 Hz,
1H), 6.50 (d, J¼8.0 Hz, 1H), 6.85 (dd, J¼8.0, 2.1 Hz,
1H), 7.10 (d, J¼2.1 Hz, 1H), 7.35 (d, J¼8.0 Hz, 2H), 7.40
(d, J¼8.0 Hz, 2H). EIMS: m/z: 299 Mþ, 254, 188, 160, 144,
115, 77. IR (KBr): nmax: 3345, 2991, 2878, 1610, 1493,

1602
J. S. Yadav et al. / Tetrahedron 59 (2003) 1599–1604
1145, 1031 cm21. Anal. calcd for C18H18NClO (299.79): C,
72.11; H, 6.05; N, 4.67; Cl, 11.83. Found: C, 72.14; H, 6.09;
N, 4.68; Cl, 11.89.
13C NMR (CDCl3) d: 22.3, 24.4, 39.3, 55.0, 69.2, 74.5,
114.2, 117.4, 120.5, 127.7, 127.9, 128.5, 129.4, 130.9,
142.2, 144.5. IR (KBr): nmax: 3325, 2941, 2864, 1607, 1482,
1088 cm21. Anal. calcd for C18H19NO (265.35): C, 81.48;
H, 7.22; N, 5.28. Found: C, 81.51; H, 7.23; N, 5.32.
4.1.5. 3e: cis-4-(4-Methoxyphenyl)-2,3,3a,4,5,9b-hexa
hydrofuro[3,2-c]quinoline. Pale yellow solid, mp 155–
1
1568C; H NMR (CDCl3): d 1.58 (m, 1H), 2.20 (m, 1H),
4.1.10. 4i: cis-5-(4-Fluorophenyl)-3,4,4a,5,6,10b-hexa-
hydro-2H-pyrano[3,2-c]quinoline. White solid, mp 174–
2.70 (m, 1H), 3.70–3.80 (m, 3H), 3.85 (s, 3H), 4.62 (d,
J¼2.2 Hz, 1H), 5.22 (d, J¼8.0 Hz, 1H), 6.54 (d, J¼8.0 Hz,
1H), 6.78 (t, J¼8.0 Hz, 1H), 6.90 (t, J¼8.0 Hz, 1H), 7.05 (d,
J¼8.0 Hz, 2H), 7.40 (m, 3H). EIMS: m/z: 281 Mþ, 252, 236,
224, 167, 155, 141, 121, 91, 69, 43. IR (KBr): nmax: 3340,
2990, 2870, 1605, 1520, 1135 cm21. Anal. calcd for
C18H19NO2 (281.35): C, 76.84; H, 6.81; N, 4.98. Found:
C, 76.87; H, 6.86; N, 4.99.
1
1758C; H NMR (CDCl3): d 1.30 (m, 1H), 1.45–1.60 (m,
3H), 2.12 (m, 1H), 3.40 (dt, J¼11.5, 2.5 Hz, 1H), 3.56 (dd,
J¼11.5, 2.5 Hz, 1H), 3.75 (brs, 1H, NH), 4.65 (d, J¼2.7 Hz,
1H), 5.28 (d, J¼5.7 Hz, 1H), 6.52 (d, J¼8.0 Hz, 1H), 6.75
(dd, J¼8.0, 2.5 Hz, 1H), 7.05 (m, 3H), 7.40 (m, 3H). EIMS:
m/z: 283 Mþ, 239, 225, 198, 150, 148, 91. IR (KBr): nmax
:
3325, 2945, 2860, 1608, 1490, 1252, 1081 cm21. Anal.
calcd for C18H18FNO (283.34): C, 76.30; H, 6.40; F, 6.71;
N, 4.94. Found: C, 76.32; H, 6.44; F, 6.72; N, 4.95.
4.1.6. 3f: cis-4-(4-Fluorophenyl)-8-methoxy-2,3,3a,4,5,
9b-hexahydrofuro[3,2-c]quinoline. White solid, mp
136–1388C; 1H NMR (CDCl3): d 1.35–1.55 (m, 1H),
2.10–2.25 (m, 1H), 2.60–2.75 (m, 1H), 3.60–3.80 (m, 3H),
3.76 (s, 3H), 4.62 (d, J¼2.8 Hz, 1H), 5.20 (d, J¼8.0 Hz,
1H), 6.45 (d, J¼8.4 Hz, 1H), 6.68 (dd, J¼8.4, 2.8 Hz, 1H),
6.92 (d, J¼2.8 Hz, 1H), 7.00–7.10 (m, 2H), 7.20–7.30 (m,
2H). EIMS: m/z: 299 Mþ, 272, 255, 205, 150, 109, 77, 43.
4.1.11. 5i: trans-5-(4-Fluorophenyl)-3,4,4a,5,6,10b-hexa-
hydro-2H-pyrano[3,2-c]quinoline. White solid, mp 143–
1448C; 1H NMR (CDCl3): d 1.30–1.35 (m, 1H), 1.40–1.45
(m, 1H), 1.60–1.70 (m, 1H), 1.75–1.85 (m, 1H), 2.05 (m,
1H), 3.70 (dt, J¼11.5, 2.5 Hz, 1H), 3.95 (brs, 1H, NH), 4.10
(d, J¼2.5 Hz, 1H), 4.35 (d, J¼2.7 Hz, 1H), 4.70 (d, J¼
10.8 Hz, 1H), 6.48 (d, J¼8.0 Hz, 1H), 6.68 (dd, J¼8.0,
2.5 Hz, 1H), 7.05 (m, 3H), 7.18 (m, 1H), 7.38 (m, 2H).
IR (KBr): nmax: 3327, 2950, 2870, 1610, 1495, 1250,
1089 cm21. Anal. calcd for C18H18FNO (283.34): C, 76.30;
H, 6.40; F, 6.71; N, 4.94. Found: C, 76.33; H, 6.42; F, 6.73;
N, 4.96.
IR (KBr): nmax: 3014, 1662, 1577, 1503, 1220, 1036 cm21
.
Anal. calcd for C18H18FNO2 (299.34): C, 72.22; H, 6.06; F,
6.35; N, 4.68. Found: C, 72.24 %; H, 6.07 %; F, 6.37%; N,
4.70%.
4.1.7. 3g: cis-4-(4-Fluorophenyl)-7,9-dimethoxy-2,3,3a,4,
5,9b-hexahydrofuro[3,2-c]quinoline. White solid, mp
1
80–828C; H NMR (CDCl3): d 1.60–1.65 (m, 1H), 2.20–
4.1.12. 4j: cis-7-Methyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-
2H-pyrano[3,2-c]quinoline. White solid, mp 142–1438C
2.25 (m, 1H), 2.75–2.85 (m, 1H), 3.60–3.85 (m, 3H), 3.68
(s, 3H, OCH3), 3.80 (s, 3H, OCH3), 4.78 (d, J¼2.8 Hz, 1H),
5.40 (d, J¼8.0 Hz, 1H), 6.20 (m, 1H), 6.60 (m, 1H), 7.05 (m,
2H), 7.40 (m, 2H). EIMS: m/z: 329 Mþ, 314, 285, 254, 190,
149, 133, 109, 71, 43. IR (KBr): nmax: 3305, 2985, 2880,
1615, 1500, 1225, 1035 cm21. Anal. calcd for C19H20FNO3
(329.36): C, 69.29; H, 6.12; F, 5.77; N, 4.25. Found: C,
69.31; H, 6.14; F, 5.79; N, 4.26.
1
(lit,5b mp 143–1448C); H NMR (CDCl3): d 1.25 (m, 1H),
1.35–1.50 (m, 4H), 2.10 (s, 3H), 3.34 (dt, 1H, J¼11.3,
2.4 Hz), 3.50 (dd, 1H, J¼11.3, 2.4 Hz), 3.55 (brs, 1H, NH),
4.62 (d, J¼2.5 Hz, 1H), 5.30 (d, J¼5.2 Hz, 1H), 6.70 (t,
J¼7.8 Hz, 1H), 6.90 (dd, J¼7.8, 0.7 Hz, 1H), 7.20–7.40 (m,
6H). 13C NMR (CDCl3) d: 17.4, 18.0, 25.3, 38.6, 59.3, 60.6,
73.4, 117.8, 119.0, 121.6, 125.3, 126.9, 127.5, 128.9, 129.2,
141.0, 143.5. EIMS: m/z: 279 Mþ, 260, 220, 184, 155, 144,
104, 91, 65. IR (KBr): nmax: 3345, 2970, 2845, 1610, 1509,
1030 cm21. Anal. calcd for C19H21NO (279.38): C, 81.68;
H, 7.58; N, 5.01. Found: C, 81.70; H, 7.61; N, 5.02.
4.1.8. 4h: cis-5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-
pyrano[3,2-c]quinoline. White solid, mp 129–1308C
1
(lit,5b mp 128.8–1318C); H NMR (CDCl3): d 1.25 (m,
1H), 1.50–1.70 (m, 3H), 2.15–2.20 (m, 1H), 3.40 (dt, 1H,
J¼11.3, 2.4 Hz), 3.55 (dd, 1H, J¼11.3, 2.4 Hz), 3.80 (brs,
1H, NH), 4.70 (d, J¼2.7 Hz, 1H), 5.30 (d, J¼5.6 Hz, 1H),
6.55 (d, J¼8.0 Hz, 1H), 6.78 (t, J¼8.0 Hz, 1H), 7.05 (t,
J¼7.8 Hz, 1H), 7.25–7.45 (m, 6H); 13C NMR (CDCl3) d:
18.2, 25.7, 39.0, 59.3, 60.7, 72.8, 114.4, 118.0, 120.4, 126.9,
127.5, 127.7, 128.0, 128.4, 141.2, 145.2. EIMS: m/z: 265
Mþ, 234, 220, 194, 129, 117, 91, 77. IR (KBr): nmax: 3340,
2970, 2850, 1610, 1490, 1090 cm21. Anal. calcd for
C18H19NO (265.35): C, 81.48; H, 7.22; N, 5.28. Found: C,
81.50; H, 7.24; N, 5.30.
4.1.13. 5j: trans-7-Methyl-5-phenyl-3,4,4a,5,6,10b-hexa-
hydro-2H-pyrano[3,2-c]quinoline. White solid, mp 130–
1
1318C (lit,5b mp 130–1328C); H NMR (CDCl3): d 1.25–
1.35 (m, 3H), 1.60–1.65 (m, 1H), 1.80–1.85 (m, 1H), 2.10
(s, 3H), 3.70, (dt, 1H, J¼11.5, 2.5 Hz), 3.90 (brs, 1H, NH),
4.10 (m, 1H), 4.40 (d, J¼2.8 Hz, 1H), 4.78 (d, J¼10.5 Hz,
1H), 6.64 (t, J¼8.0 Hz, 1H), 7.00 (dd, J¼8.0, 1.0 Hz, 1H),
7.10 (dd, J¼8.0, 1.0 Hz, 1H), 7.30–7.40 (m, 3H), 7.44 (m,
2H). 13C NMR (CDCl3) d: 17.2, 22.1, 24.3, 38.7, 55.3, 68.7,
74.5, 117.0, 120.0, 121.3, 127.8, 128.0, 128.5, 128.9, 130.5,
142.5, 142.9. IR (KBr): nmax: 3340, 2975, 2840, 1615, 1504,
1085 cm21. Anal. calcd for C19H21NO (279.38): C, 81.68;
H, 7.58; N, 5.01. Found: C, 81.71; H, 7.60; N, 5.03.
4.1.9. 5h: trans-5-Phenyl-3,4,4a,5,6,10b-hexahydro-2H-
pyrano[3,2-c]quinoline. Pale yellow oil, 1H NMR
(CDCl3): d 1.25–1.60 (m, 3H), 1.80–1.90 (m, 1H), 2.00–
2.10 (m, 1H), 3.75 (dt, 1H, J¼11.5, 2.5 Hz), 4.00–4.10 (m,
2H), 4.40 (d, J¼2.5 Hz, 1H), 4.75 (d, J¼10.8 Hz, 1H), 6.50
(d, J¼8.0 Hz, 1H), 6.70 (t, J¼7.5 Hz, 1H), 7.10 (t, J¼
7.5 Hz, 1H), 7.25 (d, J¼8.0 Hz, 1H), 7.40–7.55 (m, 5H).
4.1.14. 4k: cis-9-Methoxy-5-phenyl-3,4,4a,5,6,10b-hexa-
hydro-2H-pyrano[3,2-c]quinoline. White solid, mp 145–
1
1468C (lit,5b mp 140–1448C); H NMR (CDCl3): d 1.30–
1.60 (m, 4H), 2.15 (m, 1H), 3.42 (m, 1H), 3.58 (m, 1H), 3.60

J. S. Yadav et al. / Tetrahedron 59 (2003) 1599–1604
1603
(brs, 1H, NH), 3.80 (s, 3H), 4.62 (d, J¼2.0 Hz, 1H), 5.25 (d,
J¼5.2 Hz, 1H), 6.50 (d, J¼8.2 Hz, 1H), 6.70 (dd, J¼8.2,
2.7 Hz, 1H), 7.00 (d, J¼2.7 Hz, 1H), 7.30–7.45 (m, 5H).
3340, 2970, 2855, 1610, 1520, 1065 cm21. Anal. calcd for
C19H21NO2 (295.38): C, 77.26; H, 7.17; N, 4.74. Found: C,
77.28; H, 7.20; N, 4.77.
7.20–7.25 (m, 2H), 7.30–7.45 (m, 4H), 7.50 (m, 3H), 7.70
(m, 2H). IR (KBr): nmax: 3378, 2945, 2870, 1665, 1575,
1468, 1080 cm21. Anal. calcd for C22H21NO (315.41): C,
83.78; H, 6.71; N, 4.44. Found: C, 83.81; H, 6.73; N, 4.46.
EIMS: m/z: 295 Mþ, 237, 225, 160, 91. IR (KBr): nmax
:
4.1.20. 4n: cis-12-(4-Fluorophenyl)-2,3,4a,11,12,12a-hexa-
hydro-1H-benzo[h]pyrano[3,2-c] quinoline. Brown solid,
1
mp 138–1408C; H NMR (CDCl3): d 1.20–1.35 (m, 2H),
4.1.15. 5k: trans-9-Methoxy-5-phenyl-3, 4, 4a, 5, 6, 10b-
hexahydro-2H-pyrano[3,2-c]quinoline. Brown solid, mp
1.40–1.50 (m, 2H), 2.10 (m, 1H), 3.25 (dt, J¼11.5, 2.5 Hz,
1H), 3.50 (dd, J¼11.5, 2.5 Hz, 1H), 4.00 (brs, 1H, NH), 4.70
(d, J¼2.7 Hz, 1H), 5.40 (d, J¼5.7 Hz, 1H), 7.00 (m, 2H),
7.20 (m, 1H), 7.35 (m, 2H), 7.40–7.50 (m, 3H), 7.65 (m,
2H). EIMS: m/z: 333 Mþ, 274, 238, 220, 180, 155, 141, 119,
69, 57, 43. IR (KBr): nmax: 3370, 2945, 2860, 1665 1570,
1465, 1080 cm21. Anal. calcd for C22H20FNO (333.40): C,
79.26; H, 6.05; F, 5.70; N, 4.20. Found: C, 79.28; H, 6.07; F,
5.74; N, 4.22.
1
98–998C (lit,5b mp 98–1008C); H NMR (CDCl3): d 1.24
(m, 1H), 1.40 (m, 1H), 1.60 (m, 1H), 1.70 (m, 1H), 2.00 (m,
1H), 3.50 (m, 1H), 3.60 (s, 3H, OCH3), 4.00 (m, 2H), 4.30
(d, J¼2.7 Hz, 1H), 4.55 (d, J¼10.5 Hz, 1H), 6.38 (d, J¼
8.1 Hz, 1H), 6.60 (dd, J¼8.1, 2.7 Hz, 1H), 6.65 (d, J¼
2.7 Hz, 1H), 7.20–7.30 (m, 5H). 13C NMR (CDCl3) d: 22.0,
24.5, 39.0, 55.4, 55.9, 68.5, 74.5, 114.9, 115.5, 116.7, 121.4,
127.9, 128.5, 139.0, 142.4, 152.3. IR (KBr): nmax: 3325,
2965, 2865, 1605, 1515, 1070 cm21
.
4.1.21. 5n: trans-12-(4-Fluorophenyl)-2,3,4a,11,12,12a-
hexahydro-1H-benzo[h]pyrano[3,2-c]quinoline. Brown
1
4.1.16. 4l: cis-9-Fluoro-5-phenyl-3,4,4a,5,6,10b-hexa-
hydro-2H-pyrano[3,2-c]quinoline. White solid, mp 174–
solid, mp 179–1818C; H NMR (CDCl3): d 1.30–1.45 (m,
2H), 1.60–1.80 (m, 2H), 2.10 (m, 1H), 3.75 (dt, J¼11.5,
2.7 Hz, 1H), 4.10 (d, J¼2.7 Hz, 1H), 4.42 (d, J¼2.7 Hz,
1H), 4.65 (brs, 1H, NH), 4.80 (d, J¼10.8 Hz, 1H), 7.05–
7.15 (m, 2H), 7.20–7.40 (m, 4H), 7.45–7.50 (m, 2H), 7.70–
7.80 (m, 2H). IR (KBr): nmax: 3378, 2947, 2870, 1668, 1575,
1468, 1081 cm21. Anal. calcd for C22H20FNO (333.40): C,
79.26; H, 6.05; F, 5.70; N, 4.20. Found: C, 79.27; H, 6.08; F,
5.72; N, 4.23.
1
1758C; H NMR (CDCl3): d 1.30 (m, 1H), 1.35–1.60 (m,
3H), 2.10 (m, 1H), 3.40 (dt, J¼11.5, 2.5 Hz, 1H), 3.58 (dd,
J¼11.5, 2.5 Hz, 1H), 3.68 (brs, 1H, NH), 4.60 (d, J¼2.7 Hz,
1H), 5.20 (d, J¼5.7 Hz, 1H), 6.44 (d, J¼8.4 Hz, 1H), 6.78
(dd, J¼8.4, 2.8 Hz, 1H), 7.10 (d, J¼2.8 Hz, 1H), 7.25–7.40
(m, 5H). EIMS: m/z: 283 Mþ, 239, 225, 198, 150, 148, 91.
IR (KBr): nmax: 3326, 2943, 2865, 1608, 1497, 1252,
1089 cm21. Anal. calcd for C18H18FNO (283.34): C, 76.30;
H, 6.40; F, 6.76; N, 4.94. Found: C, 76.35; H, 6.45; F, 6.78;
N, 4.95.
Acknowledgements
4.1.17. 5l: trans-9-Fluoro-5-phenyl-3,4,4a,5,6,10b-hexa-
hydro-2H-pyrano[3,2-c]quinoline. Pale brown oil; 1H
NMR (CDCl3): d 1.35 (m, 1H), 1.50 (m, 1H), 1.55–1.65
(m, 1H), 1.75–1.90 (m, 1H), 2.10 (m, 1H), 3.68 (dt, J¼11.5,
2.8 Hz, 1H), 3.90 (brs, 1H, NH), 4.10 (d, J¼2.8 Hz, 1H),
4.32 (d, J¼2.8 Hz, 1H), 4.65 (d, J¼10.8 Hz, 1H), 6.45 (d,
J¼8.4 Hz, 1H), 6.80 (dd, J¼8.4, 2.8 Hz, 1H), 6.95 (d,
J¼2.8 Hz, 1H), 7.30–7.40 (m, 5H). IR (KBr): nmax: 3325,
2945, 2870, 1605, 1495, 1250, 1080 cm21. Anal. Calcd for
C18H18FNO (283.34): C, 76.30; H, 6.40; F, 6.76; N, 4.94.
Found: C, 76.33; H, 6.42; F, 6.79; N, 4.96.
B. V. S., J. S. S. R., R. S. R. thank CSIR, New Delhi, for the
award of fellowships.
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1
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