One-pot synthesis of pyrano[3,4-b]chromones from chromone-3-carbaldehyde

Article abstract of DOI:10.1055/s-0030-1258496

3-Formylchromone reacts with cyclohexyl isocyanide to produce pyrano[3,4-b]chromone, which rearranges to 1-benzopyrano[2,3-c]pyridine when heated with HCl in ethanol. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258496

LETTER
1909
One-Pot Synthesis of Pyrano[3,4-b]chromones from Chromone-3-
carbaldehyde
Synthesis of
P
u
yrano[3,4-
b
]
m
chromones an Kalyan Panja, Sourav Maiti, Subhabrata Banerjee, Chandrakanta Bandyopadhyay*
Department of Chemistry, R. K. Mission Vivekananda Centenary College, Rahara, Kolkata 700 118, West Bengal, India
E-mail: kantachandra@rediffmail.com
Received 14 January 2010
Reactions of isocyanides with a,b-unsaturated carbonyl
compounds lead to the formation of furan or pyrrole de-
rivatives.6 Recently, reaction of isocyanides with alde-
hydes in the presence of boric acid has been reported to
form hydroxyamides.7 The presence of a,b-unsaturated
carbonyl moiety as well as an aldehyde moiety in 1 drew
our attention to study its reaction with isocyanides.
Abstract: 3-Formylchromone reacts with cyclohexyl isocyanide to
produce pyrano[3,4-b]chromone, which rearranges to 1-benzopyra-
no[2,3-c]pyridine when heated with HCl in ethanol.
Key words: 3-formylchromone, 1-benzopyran, isocyanide, pyra-
no[3,4-b]chromone, furo[3,4-b]chromone, molecular rearrange-
ment, fluorophore, heterocycles, benzopyrano[2,3-c]pyridine
Tosylmethyl isocyanide (TOSMIC) has been reacted with
1 in presence of different bases to produce mainly 2-tosyl-
4-(2-hydroxybenzoyl)pyrrole.8 The reaction was initiated
by attack of the carbanion (generated from TOSMIC) at
the C-2 position of 1. We report herein the results of the
reaction of cyclohexyl isocyanide with 1.
Pyrano[3,4-b]chromone nuclei constitute the central het-
erocyclic part of some naturally occurring compounds
such as rotenone (I), 6-oxodehydrodeguelin (II) and ellip-
tone (III, Figure 1).1 Although rotenone and its deriva-
tives were first known as important insecticides and
piscicides, they were later reported to have anticancer ac-
tivity in rodents.2,3
Cyclohexyl isocyanide (1 mmol) in CH2Cl2 (2 mL) was
added slowly to a solution of 1a (1 mmol) in CH2Cl2 (10
mL) at 0 °C with stirring under an inert atmosphere. After
complete addition, the reaction mixture was allowed to
come at room temperature and was stirred for eight hours.
After usual workup and chromatographic separation, the
reaction mixture afforded 3a and 4a in 5% and 15%
yields, respectively (Scheme 1).
O
O
O
O
O
O
O
O
O
OMe
OMe
NC
OMe
OMe
O
O
II
I
For 1–18
a R = H
+
b R = Me
c R = Cl
R
CHO
O
O
O
+
1
2
N
O
O
OMe
5
6
9
3
O
O
OMe
O
4
O
O
O
III
9
R
10
R
1
R
8
Figure 1
1
O
3
O
4
3-Formylchromone (1) is a very good substrate for the
synthesis of various heterocycles. The presence of three
electrophilic centres confer high reactivity, as document-
ed in several reviews.4 It is not only a useful building
block for the synthesis of various bioactive heterocycles
linked to or fused with the chromone moiety, but has also
been shown to be a modifier of multidrug resistance in
mouse lymphoma cells and in colo 320 colon cancer
cells.5
Scheme 1
Initially the structure of 3a was established on the basis of
1
IR and H NMR spectroscopic analysis9 and finally con-
firmed by comparing with an authentic sample.10 A liter-
ature survey revealed that compound 3a has been
considered as a model compound in establishing the iden-
tity of clavacin and patulin antibiotics, isolated from
Aspergillus clavatus and Penicillium patulum, respective-
ly.11 Previously compound 3a has been synthesized either
by acid-catalysed cyclisation of a-keto-b-(o-hydrxyben-
zoyl)butyrolactone, itself synthesized from o-hydroxy-
SYNLETT 2010, No. 13, pp 1909–1914
x
x
.x
x
.2
0
1
0
Advanced online publication: 16.07.2010
DOI: 10.1055/s-0030-1258496; Art ID: D01210ST
© Georg Thieme Verlag Stuttgart · New York

1910
S. K. Panja et al.
LETTER
acetophenone and diethyl oxalate followed by troduce functionalities for the synthesis of natural product
hydroxymethylation and lactonisation,11 or by heating analogues.
ethyl 3-bromo-/acetoxy-methyl-4-oxochromene-2-car-
Initially the reaction was carried out in CH2Cl2, but the
yield of 4 was poor (Table 1, entries 1–3). High-boiling
boxylate in a mixture of glacial acetic acid and concentrat-
ed HCl under reflux for 4 hours.10 The structure of 4a was
apolar solvents, such as toluene or xylene, were employed
1
established on the basis of IR, H NMR, 13C NMR, and
as reaction media in an attempt to facilitate the [4+2] cy-
mass spectrometric analysis.12
cloaddition (Scheme 2, path b) and some improvement in
Formation of 3a and 4a can be rationalized as follows: the yield of 4 was noticed (enties 4–6). Encouraged by
isocyanide 2 attacks the C-2 position of 1 resulting in 5, these observations, the possibility of involvement of a
which may exist as a mixture of (Z)-5 and (E)-5. Isomer [4+2] cycloaddition step was further examined by adding
(E)-5 readily cyclises to iminolactone 6, which on subse- diethyl acetylenedicarboxylate (DEAD) into the reaction
quent 1,3-hydride shift and hydrolysis produces 3a via 7. mixture to act as a trap of 10. However, addition of isocy-
The other isomer (Z)-5 may be intercepted by another anide 2 to a solution of 1 and DEAD in toluene or addition
molecule of 1 using its aldehydic oxygen to form 8, which of a solution of 1 in toluene to a mixture of DEAD and 2
cyclises to 9 via the enamine tautomer 8a. Subsequent de- in toluene, followed by heating, produced 4 as the only
hydration of 9 gives iminolactone 4 (Scheme 2, path a). isolated product in 25–28% yield. Compound 4 was iso-
Formation of 4 may also be envisaged by deprotonation lated in better yield by heating a mixture of 1 and 2 in
and reprotonation of (Z)-5 to form 10 where the Z-config- 1:0.6 molar ratio (the mechanism for the formation of 4
uration is further stabilized by H-bonding and may be deserves 1:0.5 molar ratio) in ethanol for one hour (entries
considered as a diene. The diene moiety of 10 and the al- 7 and 8). When DMF was used as solvent, the reaction
dehydic function of 1 can undergo [4+2] cycloaddition to yielded 4 within half an hour (entry 9). Compound 4 was
form 9, leading finally to 4a by dehydration of 9 isolated in very good yield when the reaction was carried
(Scheme 2, path b).13
out in acetonitrile (entries 10–12). Better yields in polar
solvents support the polar mechanism (Scheme 2, path a).
It should be mentioned that compound 3 was not obtained
when the reaction was carried out in toluene, ethanol,
DMF, or acetonitrile. Even under high-dilution conditions
(0.001 M of 1 in acetonitrile), the reaction mixture failed
to produce 3, which clearly demonstrates that formation
of (Z)-5 is prefered over (E)-5.
Thus, two molecules of 3-formylchromone are coupled
with cyclohexyl isocyanide with the elimination of one
molecule of water and in so doing generate a pyrano[3,4-
b]chromone moiety linked to another chromone moiety.
The wide occurrences of pyrano[3,4-b]chromones in bio-
logically active and naturally occurring compounds,
prompted us to attempt to optimise the yield of 4 and to in-
Table 1 Synthesis of Iminolactone 4 under Different Conditions
Entry
1
R
Solvent
anhyd CH2Cl2
anhyd CH2Cl2
anhyd CH2Cl2
PhMe
Reaction conditions
0 °C to r.t., Ar atm.
0 °C to r.t., Ar atm.
0 °C to r.t., Ar atm.
reflux
Time (h)
Product
4aa
4b
Mp (°C)
274–76
302–04
296–98
274–76
300–02
300–02
272–74
302
Yield (%)
H
8
10
11
15
25
22
25
40
45
50
68
70
75
2
Me
Cl
H
8
3
6
4cb
4a
4
2
5
Me
Me
H
PhMe
reflux
2
4b
6
xylene
reflux
2
4b
7
EtOH
reflux
1
4a
8
Me
H
EtOH
reflux
1
4b
9
DMF
100–110 °C
reflux
0.5
0.5
0.5
0.5
4a
274–76
274–76
300–02
296–98
10
11
12
H
MeCN
4a
Me
Cl
MeCN
reflux
4b
MeCN
reflux
4c
a Compound 3a, mp 240–42 °C (lit.10 mp 242–43 °C) was isolated in 5% yield along with 4a.
b Compound 3c, mp 244–46 °C was isolated in 9% yield along with 4c.
Compound 4 possesses a chromone moiety linked to a ed p-system, which can undergo intramolecular charge
pyrano[3,4-b]-1-benzopyran motif and forms a conjugat- transfer upon excitation and may act as a fluorophore,
Synlett 2010, No. 13, 1909–1914 © Thieme Stuttgart · New York

LETTER
Synthesis of Pyrano[3,4-b]chromones
1911
N
H
N+
O–
O
O
1 + 2
O
R
R
O
N
O
(E)-5
6
O
[H2O]
3
O
R
O
7
N
H
N+
H
O
O
O
1
O
O
path a
R
R
R
O–
O–
O
O
+
(Z)-5
8
H
N
O
O
O
O
R
R
O–
O
+
1
8a
N
path b
O
O
– H2O
O
O
O
4
R
R
OH
9
[4+2]
N
O
C
O
O
R
R
O
O
O
H
10
Scheme 2
which is indeed supported by spectroscopic measure- hydroxyl group at the 7-position of 4 is needed for the syn-
ments. The absorption spectrum of 4 (1.0·10–6 M in thesis of rotenone analogues. 7-Hydroxychromone-3-carb-
CHCl3, Figure 2) showed absorption at l = 285–295 nm aldehyde 12 was synthesized from resacetophenone (11)
with a low absorbance and its emission spectrum by Vilsmeier–Haack reaction.14 Compound 13 was ob-
(1.90·10–7 M in CHCl3, Figure 3) showed a strong emis- tained in moderate yield by heating 12 with 2 in acetoni-
sion band at l = 470 nm (e = 3.77·106).
trile (Scheme 3).15
Comparing the basic structure of rotenone (I), dehydrode- In an attempt to obtain an analogue of 6-oxodehydrode-
guelins (II), and elliptone (III, Figure 1), it is clear that a guelin (II, Figure 1) by hydrolysing the imino function of
Synlett 2010, No. 13, 1909–1914 © Thieme Stuttgart · New York

1912
S. K. Panja et al.
LETTER
HO
O
HO
OH
POCl3, DMF
CHO
O
O
11
12
2
MeCN
N
HO
O
O
O
O
O
OH
13
Scheme 3
17 may be rationalised by the initial protonation on the vi-
nyl ether moiety of 4 to form 14, which undergoes hydro-
lytic cleavage to form 16 via 15. Recyclisation of 16
followed by dehydration produces 17.
Table 2 Acid-Catalysed Rearrangement of Iminolactone 4 to Lac-
tam 17
Figure 2
Entry
R
Product
17a
Mp (°C)
>300
Yield (%)
1
2
3
H
33
35
40
Me
Cl
17b
260–62
>300
17c
In conclusion, we have developed an efficient and direct
route for the preparation of pyrano[3,4-b]chromones,
which constitutes the central part of the rotenones and also
have reported an acid-catalysed iminolactone–lactam re-
arrangement associated with this system.
Acknowledgment
We gratefully acknowledge CSIR, New Delhi [Project no.
01(2206)/07/EMR-II] for financial assistance; IICB, Jadavpur for
spectral analysis and finally the college authority for providing re-
search facilities.
References and Notes
(1) Ngandeu, F.; Bezabih, M.; Ngamga, D.; Tchinda, A. T.;
Ngadjui, B. T.; Abegaz, B. M.; Dufat, H.; Tillequin, F.
Phytochemistry 2008, 69, 258.
(2) (a) Fang, N.; Casida, J. E. Proc. Natl. Acad. Sci. U.S.A. 1998,
95, 3380. (b) Fang, N.; Casida, J. E. J. Agric. Food Chem.
1999, 47, 2130.
Figure 3
(3) Monroy, M. D. L. V.; Vargas, M. A. O.; Marquez, A. M.;
Vargas, J. G. O. Proc. West Pharmacol. Soc. 2002, 45, 82.
(4) Reviews: (a) Ghosh, C. K. J. Heterocycl. Chem. 1983, 20,
1437. (b) Sabitha, G. Aldrichimica Acta 1996, 29, 15.
(c) Ghosh, C. K.; Patra, A. J. Heterocycl. Chem. 2008, 45,
1529.
(5) Barath, Z.; Radics, R.; Spengler, G.; Ocsovszki, I.; Kawase,
M.; Motohashi, N.; Shirataki, Y.; Shah, A.; Molnav, J. In
Vivo 2006, 20, 645.
4, it was dissolved in concentrated H2SO4 and then poured
into ice water, but a black insoluble mass was obtained.
However, on heating an ethanolic solution of 4 for two
hours in the presence of a trace amount of aqueous HCl,
the iminolactone 4 rearranged to lactam 1716 (Table 2,
Scheme 4) along with an insoluble product, which could
not be characterised due to its insolubility. Formation of
Synlett 2010, No. 13, 1909–1914 © Thieme Stuttgart · New York

LETTER
Synthesis of Pyrano[3,4-b]chromones
yellowish green solid.
1913
Compound 4a: yield 0.15 g (68%); mp 274–76 °C. IR (KBr):
3070, 2931, 1664, 1611 cm–1. 1H NMR (300 MHz, CDCl3):
d = 1.27–1.35 (m, 1 H, cyclohexyl H), 1.39–1.52 (m, 2 H,
cyclohexyl H), 1.58–1.66 (m, 2 H, cyclohexyl H), 1.77–1.95
(m, 5 H, cyclohexyl H), 3.89–4.02 (m, 1 H, NCH), 7.18 (s, 1
H, 1-H), 7.41–7.45 (m, 1 H, ArH), 7.48–7.50 (m, 2 H, ArH),
7.65–7.76 (m, 3 H, ArH), 8.31 (br d, J = 8.0 Hz, 1 H, 5¢-H),
N
O
O
O+
H+, EtOH–H2O
O
O
4
R
R
14
8.34 (br d, J = 7.8 Hz, 1 H, 9-H), 8.73 (s, 1 H, 2¢-H). 13
C
NMR (75 MHz, CDCl3): d = 24.9 (3¢¢-C, 5¢¢-C), 25.7 (4¢¢-C),
33.6 (2¢¢-C, 6¢¢-C), 58.1 (1¢¢-C), 97.0 (1-C), 118.1 (8¢-C),
119.0 (6-C), 119.7 (10a-C), 120.2 (3¢-C), 123.8 (4¢a-C),
124.9 (9a-C), 125.2 (6¢-C), 126.1 (8-C), 126.5 (5¢-C, 9-C),
133.6 (7¢-C), 134.5 (7-C), 144.2 (2¢-C), 146.9 (2-C), 153.1
(4a-C), 155.7 (4-C), 155.9 (5a-C), 156.4 (8¢a-C), 172.2 (10-
C), 174.8 (4¢-C). MS: m/z = 440 [M+ + H], 462 [M+ + Na].
Anal. Calcd for C27H21NO5: C, 73.79; H, 4.82; N, 3.19.
Found: C, 73.90; H, 4.89; N, 3.11.
Compound 4b: yield 0.16 g (70%); mp 300–302 °C. IR
(KBr): 3059, 2925, 1669, 1616 cm–1. 1H NMR (300 MHz,
CDCl3): d = 1.30–1.77 (m, 6 H, cyclohexyl H), 1.88–1.97
(m, 4 H, cyclohexyl H), 2.47 (s, 3 H, ArCH3), 2.50 (s, 3 H,
ArCH3), 3.88–3.95 (m, 1 H, NCH), 7.17 (s, 1 H, 1-H), 7.38
(d, J = 8.7 Hz, 1 H, 6-H), 7.47 (br d, J = 8.7 Hz, 1 H, 7-H),
7.54 (d, J = 8.4 Hz, 1 H, 8¢-H), 7.60 (br d, J = 8.4 Hz, 1 H,
7¢-H), 8.08 (br s, 1 H, 9-H), 8.12 (br s, 1 H, 5¢-H), 8.71 (s, 1
H, 2¢-H). 13C NMR (75 MHz, CDCl3): d = 20.9 (2 × CH3),
24.9 (3¢¢-C, 5¢¢-C), 25.6 (4¢¢-C), 33.5 (2¢¢-C, 6¢¢-C), 58.1 (1¢¢-
C), 97.1 (1-C), 117.8 (8¢-C), 118.8 (6-C), 119.4 (10a-C),
120.0 (3¢-C), 123.3 (4¢a-C), 124.4 (9a-C), 125.8 (5¢-C),
125.9 (9-C), 134.9 (7¢-C), 135.3 (7-C), 135.9 (6¢-C), 136.3
(8-C), 144.0 (2¢-C), 147.2 (2-C), 153.1 (4a-C), 154.1 (8¢a-C),
154.6 (5a-C), 155.7 (4-C), 172.4 (10-C), 175.1 (4¢-C). MS:
m/z = 468 [M+ + H], 490 [M+ + Na]. Anal. Calcd for
C29H25NO5: C, 74.50; H, 5.39; N, 3.00. Found: C, 74.39; H,
5.42; N, 2.93.
O
NH
O
O
O
O
O
R
R
16
N
O
O
O
R
R
O
O
H
O
15
O
O
N
O
R
R
O
O
17
Scheme 4
(6) (a) Yavari, I.; Shaabani, A.; Maghsoodlou, M. T. Monatsh.
Chem. 1997, 128, 697. (b) Quai, M.; Frattini, S.; Vendrame,
U.; Mondoni, M.; Dossena, S.; Cereda, E. Tetrahedron Lett.
2004, 45, 1413. (c) Adib, M.; Mahdavi, M.; Noghani, M. A.;
Bijanzadeh, H. R. Tetrahedron Lett. 2007, 48, 8056.
(d) Shaabani, A.; Farrokhzad, F. J. Chem. Res., Synop. 1997,
344. (e) Yavari, I.; Habibi, A. Synthesis 2004, 989.
(7) Kumar, J. S.; Jonnalagadda, S. C.; Mereddy, V. R.
Tetrahedron Lett. 2010, 51, 779.
Compound 4c: yield 0.19 g (75%); mp 296–298 °C. IR
(KBr): 3061, 2929, 1672, 1606 cm–1. 1H NMR (300 MHz,
CDCl3): d = 1.26–1.77 (m, 6 H, cyclohexyl H), 1.89–1.93
(m, 4 H, cyclohexyl H), 3.88–3.95 (m, 1 H, NCH), 7.10 (s, 1
H, 1-H), 7.45 (d, J = 8.7 Hz, 1 H, 6-H), 7.61 (dd, J = 8.7, 1.8
Hz, 1 H, 7-H), 7.65–7.69 (m, 2 H, ArH), 8.24 (d, J = 1.8 Hz,
1 H, 9-H), 8.27 (br s, 1 H, 5¢-H), 8.70 (s, 1 H, 2¢-H). 13
C
NMR (75 MHz, CDCl3): d = 24.8 (3¢¢-C, 5¢¢-C), 25.6 (4¢¢-C),
33.5 (2¢¢-C, 6¢¢-C), 58.3 (1¢¢-C), 96.9 (1-C), 119.6 (8¢-C),
119.9 (6-C), 120.0 (10a-C), 120.7 (3¢-C), 124.5 (4¢a-C),
125.7 (9a-C), 125.9 (8-C, 6¢-C), 131.4 (5¢-C), 132.4 (9-C),
134.0 (7¢-C), 134.9 (7-C), 144.1 (2¢-C), 146.6 (2-C), 153.2
(4a-C), 154.1 (8¢a-C), 154.6 (5a-C), 155.8 (4-C), 171.1 (10-
C), 173.8 (4¢-C). MS: m/z = 512 [M+ + 4], 510 [M+ + 2], 508
[M+]. Anal. Calcd for C27H19NCl2O5: C, 63.79; H, 3.77; N,
2.76. Found: C, 63.68; H, 3.72; N, 2.67.
(8) Terzidis, M.; Tsoleridis, C. A.; Stephanidou-Stephanatou, J.
Tetrahedron 2007, 63, 7828.
(9) Analytical Data of 1H-Furo[3,4-b]-1-benzopyran-3,9-
dione (3a)
White crystalline solid, mp 240–42 °C (lit.11 242–43 °C). IR
(KBr): 2978, 1775, 1642 cm–1. 1H NMR (300 MHz, CDCl3):
d = 5.23 (s, 2 H, CH2), 7.56 (br t, J = 7.2 Hz, 1 H, 7-H), 7.69
(br d, J = 8.4 Hz, 1 H, 5-H), 7.81–7.87 (m, 1 H, 6-H), 8.30
(br d, J = 7.2 Hz, 1 H, 8-H).
(13) Mercey, G.; Bregeon, D.; Baudequin, C.; Guillen, F.;
Levillain, J.; Gulea, M.; Plaquevent, J.-C.; Gaumont, A.-C.
Tetrahedron Lett. 2009, 50, 7239.
(14) Hatzade, K. M.; Taile, V. S.; Gaidhane, P. K.; Haldar, A. G.
M.; Ingle, V. N. Indian J. Chem., Sect. B: Org. Chem. Incl.
Med. Chem. 2008, 47, 1260.
(10) Ellis, G. P.; Thomas, I. L. J. Chem. Soc., Perkin Trans. 1
1974, 2570.
(11) Puetzer, B.; Nield, C. H.; Barry, R. H. J. Am. Chem. Soc.
1945, 67, 832.
(12) Preparation of 2-(4-Oxo-4H-1-benzopyran-3-yl)-4-(N-
cyclohexylimino)pyrano[3,4-b]-1-benzopyran-10-ones
4a–c
(15) 2-(7-Hydroxy-4-oxo-4H-1-benzopyran-3-yl)-7-hydroxy-
4-(N-cyclohexylimino)pyrano[3,4-b]-1-benzopyran-10-
one (13)
Cyclohexyl isocyanide (0.065 g, 0.6 mmol) was added to a
solution of 1 (1 mmol) in MeCN (15 mL). The resultant
mixture was heated under reflux for 30 min when a solid
began to separate. The reaction mixture was cooled, and the
separated solid was filtered off. The solid was further
crystallised from chloroform–light PE (4:1) to afford a
Yield 51%; mp 310–312 °C. IR (KBr): 3436, 1660, 1629,
1458 cm–1. 1H NMR (300 MHz, DMSO-d6): d = 1.14–1.28
(m, 1 H, cyclohexyl H), 1.30–1.52 (m, 4 H, cyclohexyl H),
1.57–1.72 (m, 1 H, cyclohexyl H), 1.80–1.97 (m, 4 H,
cyclohexyl H), 3.86–4.06 (m, 1 H, NCH), 6.87 (s, 1 H, 1-H),
6.91 (br s, 1 H, 8¢-H), 6.95 (br d, J = 8.7 Hz, 1 H, 6¢-H), 7.02
Synlett 2010, No. 13, 1909–1914 © Thieme Stuttgart · New York

1914
S. K. Panja et al.
LETTER
(br d, J = 8.4 Hz, 1 H, 8-H), 7.05 (br s, 1 H, 6-H), 7.98 (d,
J = 8.7 Hz, 1 H, 5¢-H), 8.04 (d, J = 8.4 Hz, 1 H, 9-H), 8.70
(s, 1 H, 2¢-H), 11.01 (br s, 2 H, 2 × OH). MS: m/z = 472 [M+
+ H], 494 [M+ + Na]. Anal. Calcd for C27H21NO7: C, 68.78;
H, 4.49; N, 2.97. Found: C, 68.97; H, 4.35; N, 2.90.
4.12–4.29 (m, 1 H, NCH), 6.83 (s, 1 H, 1-H), 7.44 (d, J = 8.4
Hz, 1 H, 6-H), 7.50–7.59 (m, 3 H, ArH), 7.78 (s, 1 H, 2¢-H),
7.96 (br s, 1 H, 9-H), 8.07 (br s, 1 H, 5¢-H). 13C NMR (75
MHz, CDCl3): d = 20.9 (CH3), 21.0 (CH3), 25.1 (4¢¢-C), 26.2
(3¢¢-C, 5¢¢-C), 29.9 (2¢¢-C, 6¢¢-C), 54.2 (1¢¢-C), 107.6 (1-C),
117.7 (3¢-C), 118.1 (6-C), 118.4 (8¢-C), 120.0 (10a-C), 123.5
(9a-C), 125.0 (4¢a-C), 125.4 (9-C), 126.3 (5¢-C), 132.0 (2-C),
134.8 (7-C), 135.3 (8-C), 135.5 (7¢-C), 136.1 (6¢-C), 153.3
(5a-C), 154.6 (8¢a-C), 155.3 (4a-C), 155.4 (2¢-C), 159.5 (4-
C), 171.7 (10-C), 176.6 (4¢-C). MS: m/z = 468 [M+ + H], 490
[M+ + Na]. Anal. Calcd for C29H25NO5: C, 74.50; H, 5.39; N,
3.00. Found: C, 74.70; H, 5.52; N, 2.88.
(16) 3-Cyclohexyl-8-methyl-2-(6-methyl-4-oxo-4H-1-
benzopyran-3-yl)-1-benzopyrano[2,3-c]pyridine-4,10-
dione (17b)
Yield 35%; mp 260–262 °C. IR (KBr): 2924, 1715, 1664,
1611, 1482 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.25–
1.50 (m, 3 H, cyclohexyl H), 1.73–1.76 (m, 1 H, cyclohexyl
H), 1.88–2.92 (m, 4 H, cyclohexyl H), 2.34–2.48 (m, 2 H,
cyclohexyl H), 2.35 (s, 3 H, ArCH3), 2.49 (s, 3 H, ArCH3),
Synlett 2010, No. 13, 1909–1914 © Thieme Stuttgart · New York

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