Pericyclic transformations at the periphery of chromen-4-one (=4H-1-benzopyran-4-one): An unusual preference for a 1,5-shift of allylic moieties over the ene reaction

Article abstract of DOI:10.1002/hlca.200390008

Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems, similarly disposed moieties on the periphery of the chromen-4-one (=4H-1-benzopyran-4-one) system fail to undergo an ene reaction and display a rather un

Full text of DOI:10.1002/hlca.200390008

Helvetica Chimica Acta Vol. 86 (2003)
169
Pericyclic Transformations at the Periphery of Chromen-4-one
(ˆ4H-1-Benzopyran-4-one): An Unusual Preference for a 1,5-Shift of
Allylic Moieties over the Ene Reaction
by Gurmit Singh, Gurpinder Singh, and Mohan Paul S. Ishar*
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar-143005, Punjab, India
(e-mail: mpsishar@angelfire.com)
Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems,
similarly disposed moieties on the periphery of the chromen-4-one (ˆ4H-1-benzopyran-4-one) system fail to
undergo an ene reaction and display a rather unusual preference for an overall [1,5] shift of the allylic C-atom.
Thus, heating xylene solutions of 2-(N-allylanilino)-, 2-(N-crotylanilino)-, and 2-(N-cinnamylamino)-substi-
tuted (E)-(oxochromenyl)propenoates 9a c and 2-[allyl(benzyl)amino]-, 2-[benzyl(crotyl)amino]-, and 2-
[benzyl(cinnamyl)amino]-substituted (E)-(oxochromenyl)propenoates 16a c in a sealed tube at 220 2308
leads to a [1,5] shift of the allylic moieties (allyl, crotyl, cinnamyl), which is followed by intramolecular
cyclization involving the N-atom and the ester function, to give the 3-allyl-3-crotyl-, and 3-cinnamyl-substituted-
1-phenyl- or 1-benzyl-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-diones 10a c and 17a c. The anticipated
carbonyl ene reaction in the 2-(N-allylanilino)-, 2-(N-crotylanilino)-, 2-(N-cinnamylanilino)-, 2-[allyl(benzyl)-
amino]-, 2-[benzyl(crotyl)amino]-, and 2-[benzyl(cinnamyl)amino]-substituted 4-oxochromene-3-carboxalde-
hydes 8a c and 15a c is also not observed, and these molecules remain untransformed under identical
conditions. No [1,5] shifts of benzyl, phenyl, or methyl groups are observed, even in the absence of allylic
moieties, though facile [1,5]-H shift occurs in 2-(benzylamino)- and 2-(phenylamino)-substituted (E)-
(oxochromenyl)propenoates 23a,b, which is followed by a similar intramolecular cyclization leading to the
2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-diones 24a,b.
Introduction. Recently, ene reactions on the periphery of a number of heterocyclic
systems such as pyridinones, pyrimidinones, pyrido[1,2-a]pyrimidinones, and coumarin
(ˆ2H-1-benzopyran-2-one) have been utilized [1] to obtain heteroannulated azepines
1 3 (Scheme 1), which are anticipated to display useful biological activities; an
intramolecular hetero-DielsÀAlder reaction has been reported to intervene only in one
case leading to a minor product 4 (Scheme 1). Subsequent kinetic and theoretical
investigations on these reactions have also been reported [2], which support a
concerted mechanism for these transformations.
We have recently reported [3] that C-(4-oxo-4 H-1-benzopyran-3-yl)-N-phenyl-
nitrone 5 undergoes intramolecular rearrangement to 2-anilino-4-oxochromene-3-
carboxaldehyde (6) in 70 90% yield and 3-(anilinomethylene)chromene-2,4-diones
(7) in 10 25% yield (Scheme 2), and that the yield of 6 could be improved to
>95% by refluxing 5 in benzene under acidic conditions [3b]. It was, therefore,
decided to utilize 6 to investigate similar reactions at the periphery of the chromen-4-
one (ˆ4H-1-benzopyran-4-one) system. The investigations were of considerable
interest as the targeted azepino-chromenones were potentially biologically active
molecules.

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 1
Scheme 2
O
O
O
Ph
O
O
O
NHPh
i) ii)
H
N
+
O
O
O
NHPh
7
6
5
i) ChCl3, r.t., 20 days; 70% of 6, 25% of 7. ii) H+/Benzene, reflux, 8 h; 96% of 6, 7 negligible.
Results and Discussion. Initially, 2-anilino-4-oxochromen-3-carboxaldehyde (6)
was reacted with allyl, crotyl (ˆ(2E)-but-2-enyl), and cinnamyl (ˆ(2E)-3-phenylprop-
2-enyl) bromides in presence of fused potassium carbonate to give the N-allylated
products 8a c in high yield (Scheme 3). However, refluxing 8 in benzene under
conditions as employed in [1] and even heating a xylene solution in a sealed tube up to
2208 (furnace temperature) did not lead to any carbonylÀene reaction (!11), and
/
starting materials were recovered unchanged. Attempts to obtain the corresponding
Schiff bases 12 for investigating an imineÀene reaction did not succeed because
reacting 8a c with amines led to substitution at C(2), and a number of products were
formed, which could not be separated. Subsequently, the 2-(N-allylanilino)-, 2-(N-
crotylanilino)-, and 2-(N-cinnamylanilino)-substituted (E)-(oxochromenyl)prope-
noates 9a c were obtained from 8a c in more than 90% yield by Wittig reaction of
the 3-carboxaldehyde function with ethyl (triphenylphosphoranylidene)acetate by

Helvetica Chimica Acta Vol. 86 (2003)
171
refluxing in dry benzene. Compounds 9a c were purified by flash column chromatog-
raphy (silica gel) and characterized spectroscopically. When a benzene solution of 9a
c was refluxed under N2 for extended periods, no transformation occurred, and these
compounds were recovered unchanged. However, when solutions of 9a c in xylene
were sealed in Pyrex-glass tubes and heated at 220 2308 for 6 h, these were
transformed to 10a c in high yields (> 95%); the latter were isolated by column
chromatography (silica gel) and characterized spectroscopically (Scheme 3). The
structures 10a c were established by rigorous spectroscopic analyses and micro-
analytical data.
Scheme 3
O
O
O
1''
CO2Et
CHO
CHO
2''
1'
CH2Br
R
3'
R
O
acetone
K2CO3
N
O
N
H
O
2'
N
R
9
Ph
6
Ph
8
Ph
benzene
+ RNH2
xylene
sealed tube,
220-230¡
∆
O
H
4
H
O
6
9
5
OH
3
C
NR
O
R
7
8
R
2
1
N
O
O
O
10
N
R
Ph
O
N
>95% yield
Ph
10
12
Ph
11
a R = H; b R = Me; c R = Ph
The initial evidence for the assigned structures was provided by the 1H-NMR spectra of 10a c, which
indicated the loss of the EtO moiety of the ester function. A d(H) 8.20 8.27 for HÀC(6), along with d(C) 173.8
for C(5), and UV spectral data indicated that not only the chromenone moiety is intact but that the erstwhile
C(2)ˆC(3) bond of chromenone is also present [4]. The NMR spectral data also clearly indicated that the allyl,
crotyl, and cinnamyl moieties of 10a c, respectively, are intact. However, an upfield shift was observed for the
resonances of 2 HÀC(1') in going from 9a c (d 4.65 in 9a, 4.61 in 9b, and 4.75 in 9c) to 10a c (d 3.35 in 10a, 3.27
in 10b, and 3.44 in 10c), an observation that is interpreted as migration of these moieties from an N- to a C-atom.
This was also supported by comparison of the 13C-NMR chemical shifts of C(1') in 9c (d 55.30) and 10c (d 33.89).
Assigned structures are also supported by the presence of a 1-H s at d ca. 8.12 8.13attributed to H ÀC(4). The
presence of a pyridin-2-one moiety was established, inter alia, by a band [5] in the IR spectra around 1665
1675 cmÀ1 and a d(C) ca. 162 for C(2) [6]; overall 13C-NMR assignments, mass spectra, and microanalytical data
are consistent with the assigned structures.
The investigations were extended to N-benzyl analogues 16a c because it was
thought that the nonobservance of the ene reaction in the case of 9a c may be a
consequence of working with N-phenyl compounds, whereas N-benzyl derivatives have
been investigated in case of other heterocyclic systems (see Scheme 1) [1][2]. The N-
benzyl derivatives 16a c were obtained starting from 2-(N-methylanilino)-4-oxochro-
mene-3-carboxaldehyde (13a) [3 b]via 14 and 15 as described in Scheme 4. However,
there was no change in the general behavior, and only a [1,5] shift of the allylic C-atom

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Helvetica Chimica Acta Vol. 86 (2003)
followed by cyclization was observed as the only mode of transformation of 16a c
leading to 17a c, and no ene-reaction product was observed (Scheme 4). Here, again,
no carbonylÀene reaction to 18 was observed starting from the 3-carboxaldehyde
derivative 15, and imineÀene reactions could not be investigated due to similar
difficulties in obtaining 19.
Scheme 4
O
O
O
O
O
CHO
CHO
CHO
acetone
K2CO3
BnNH2
aq. MeCN
O
NH
Bn
N
Me
N
R
14
13a
15
Ph
Bn
OH
O
+ phosphorane
benzene, reflux
R
∆, xylene,
sealed tube
H
dry benzene
RNH2
O
O
O
N
H
O
OEt
H
18
Bn
C
NR
O
N
R
16
O
N
Bn
R
sealed tube
19
xylene
Bn
220¡
O
R
a R = H; b R = Me; c R = Ph
O
N
O
17
Bn
17a R = H
b R = Me (91%)
c R = Ph (95%)
(92%)
Since in all these reactions, a [1,5] shift of only an allylic C-atom was observed and
not even a trace of product derived from phenyl or benzyl migration was detected, it
was decided to exclude the allylic moiety and than have a look at possible migration of
other groups. Towards this 2-(N-methylanilino)- and 2-[benzyl(methyl)amino]-4-oxo-
chromene-3-carboxaldehydes 13a,b were reacted with ethyl (triphenyl phosphoranyl-
idene)acetate to give esters 20a,b (Scheme 5), which were characterized spectroscopi-
cally. However, heating the xylene solutions of 20a,b in a sealed tube at 2208 for 30 h
did not lead to any reaction.
Thinking that the benzyl group may be amenable to such shifts and the presence of
a phenyl group may be necessary to force certain conformational requirements,
compound 22 was prepared from 6 via 21 as described in Scheme 6; however, heating a
xylene solution of 22 at 2208 for 30 h did not lead to any transformation.
However, when the corresponding 2-anilino-and 2-(benzylamino)-4-oxochromene-
3-carboxaldehydes 6 and 14, respectively, were reacted with ethyl (triphenylphosphor-
anylidene)acetate in refluxing benzene, these were transformed to chromeno-

Helvetica Chimica Acta Vol. 86 (2003)
173
Scheme 5
O
H
O
H
O
O
Ph3PCHCOOEt
benzene,reflux
CO2Et
O
O
O
NH
Ar
- Ph3PO
O
N
Me
N
Me
Ar
Ar
14 Ar = Ph
6 Ar = PhCH2
20a Ar = Ph
13a Ar = Ph
b Ar = PhCH2
b Ar = PhCH2
sealed tube
220¡
no reaction
heat
xylene
Scheme 6
O
H
O
O
H
O
O
O
CO2Et
O
Ph3PCHCO2Et
benzene, reflux
PhCH2Br
O
N
CH2Ph
acetone
K2CO3
NH
Ph
22
N
CH2Ph
Ph
6
Ph
21
xylene sealed tube
220¡
no reaction
pyridinediones 24 (Scheme 7). That the compounds 24a,b are derived from an initially
formed 23 was established by carrying out the reaction of 6 (Arˆ Ph) with ethyl
(triphenylphosphoranylidene)acetate in CH2Cl2 at room temperature, when 23a was
isolated, characterized, and subsequently converted to 24a by refluxing in benzene,
thereby confirming the facile [1,5]-H shift in 23.
Scheme 7
O
H
O
O
H
O
O
H
O
O
Ph3PCHCO2Et
benzene, reflux
CO2Et
O
NH
Ar
N
NH
Ar
Ar
6 Ar = Ph
14 Ar = PhCH2
24a Ar = Ph
b Ar = PhCH2
23
Mechanistically, the observed overall [1,5] shift of various allylic moieties (allyl,
crotyl, cinnamyl) can be envisaged as either involving two successive [3,3] shifts
(Claisen rearrangement) or two [1,3] shifts or a single [1,5] shift, which is followed by
cyclization in intermediate C (Scheme 8). That benzyl, phenyl, or methyl groups fail to
undergo [1,5] shifts under identical conditions points towards involvement of two
successive Claisen rearrangements. However, stopping the reaction after shorter
reaction times, i.e., after 1 h, 3h, and 5 h, afforded either unreacted starting or final
product. No other product or one of the postulated intermediates A, B, or C could be

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Helvetica Chimica Acta Vol. 86 (2003)
Scheme 8
O
R
O
O
O
COOEt
[3,3]
OEt
a
O
Claisen
rearrangement
N
N
R
Ar
Ar
A
Claisen
rearrangement
[3,3]
[1,3]
R
R
[1,5] shift
[1,3]
O
O
COOEt
O
OEt
O
N:
O
N
Ar
C
Ar
B
O
O
H
R
R
O
O
N
-EtOH
OEt
O
N
O
Ar
Ar
detected even in the 1H-NMR spectrum of the crude products, and these observations
suggest either a fast second [3,3]/[1,3] shift or a single [1,5] suprafacial shift.
Molecular modeling of the starting materials 9a c and 16a c by means of DTMM
(version 2.0) did not reveal any conformational preference favoring [1,5] shifts of allylic
moieties. Rather, the conformational preference in the molecule appears to favor a
Claisen rearrangement. At this level of modeling, the starting compounds appeared to
be more stable than the intermediates, including C, indicating that the overall process
becomes unidirectional due to the last cyclization step.
It may be mentioned here that the delocalization of the lone pair of the N-atom up
to C(4)ˆO and to the ester moiety is likely to create electron deficiency in the NÀC(1')
linkage of 9 and 16, and this electron deficiency at the migratory center may be better
stabilized by allylic systems, moreso even than by phenyl or benzyl moieties. The
observed facile [1,5]-H migration in 23 under refluxing in benzene, leading to 24, may
involve a simple proton shift. Literature reveals that in general, [3,3]-sigmatropic shifts
are favored in the case of allylic systems and occur, generally, at relatively lower
temperatures as compared to the temperatures employed in the present case [7]. The
[1,3] shifts of the allylic moiety from an N- to a C-atom are precedented [8], and an
example of a [1,5] shift of an allylic moiety from an N- to a C-atom is reported in the
case of five-membered heterocycles [9]. Though the exact sequence of events in the
cyclization step are not delineated, the loss of the H-atom has to be either concomitant
with or following the interaction between the N-atom and the ester carbonyl group, and
may not precede the cyclization.

Helvetica Chimica Acta Vol. 86 (2003)
175
Conclusions. Though the exact nature of the involved sigmatropic shift, i.e., two
[3,3], two [1,3], or a single [1,5] shift, could not be ascertained, the ene reactions at the
periphery of the chromen-4-one moiety is certainly suppressed, which is contrary to the
reported facile ene reactions at the periphery of many related heterocyclic systems. The
reaction offers an interesting example of an overall [1,5] shift of an allylic moiety over a
noncyclic diene wherein the allylic C-atom shows a higher migratory aptitude than a
benzyl or phenyl group. The reaction provides an easy access to potentially biologically
active chromeno-pyridinones; the involvement of the chromenone moiety in pharma-
cophores of a variety of biologically active molecules and medicinal compounds is well-
documented [10], and valuable medicinal properties are ascribed to heteroannulated
pyridinones [11].
Experimental Part
General. Starting materials and reagents were purchased from commercial suppliers and used after further
purification (crystallization or distillation). The 4-oxo-4H-1-benzopyran-3-carboxaldehyde (ˆ 3-formylchro-
mone) was purchased from Aldrich and used as such. CC ˆ Column chromatography, FC ˆ flash chromatog-
raphy. M.p.: precision (make) MP-D digital melting point apparatus; in open glass capillaries; uncorrected. UV/
VIS Spectra: Shimadzu 160A spectrophotometer; in nm. IR Spectra: Shimadzu DR-2001 FT-IR spectropho-
1
tometer; CHCl3 soln. or KBr pellets; in cmÀ1. H- and 13C-NMR Spectra: Bruker AC-200 FT (200 MHz) and
Bruker-F (300 MHz); at 200 or 300 MHz (1H) and 50 or 75 MHz (13C); chemical shifts d in ppm downfield from
SiMe4 as internal standard and J values in Hz. Mass spectra: electron ionization (EI); Shimadzu GCMS-QP-
2000A spectrometer; in m/z (rel. %). Elemental analyses were performed at RSIC, Chandigarh, and are
reported in percent atomic abundance.
4-Oxo-2-[phenyl(prop-2-enyl)amino]-4H-1-benzopyran-3-carboxaldehyde (8a). To a soln. of 6 [3] (1.0 g,
3.8 mmol) in dry acetone (75 ml) was added allyl bromide (0.73 g, 6.0 mmol) and anh. K2CO3 (2.0 g). The
mixture was refluxed with stirring to completion of the reaction (9 h, TLC monitoring). The hot mixture was
filtered, the residue washed with a little acetone, and the solvent from filtrate distilled off. The obtained product
was purified by FC (silica gel (200 400 mesh, 20 g); hexane/AcOEt 9 :1): 8a (1.11 g, 96%). Cream-colored
solid. M.p. 110 1118 (CHCl3/hexane 1:2). UV (MeOH): 240, 285, 327. IR (CHCl3): 1676 (HCˆO), 1654
(CˆO), 1610, 1597, 1518, 1495, 1466, 1425, 1385, 1350, 1325, 1213. 1H-NMR (CDCl3, 300 MHz): 10.02
(s, HÀCˆO); 8.20 (dd, J ˆ 7.74, 1.59, HÀC(5)); 7.70 7.52 (m, 3arom. H); 7.49 7.21 ( m, 5 arom. H); 6.04 5.92
‡
(m, HÀC(2')); 5.32 5.21 (m, 2 HÀC(3')); 4.61 (d, J ˆ 5.46, 2 HÀC(1')). EI-MS: 305 (4, M ), 304 (20, [M À
‡
1] ), 276 (6), 235 (5), 158 (5), 144 (5).
2-{[(2E)-But-2-enyl]phenylamino}-4-oxo-4H-1-benzopyran-3-carboxaldehyde (8b). As described for 8a,
with 6 (1.0 g, 3.8 mmol), crotyl bromide (0.81 g, 6.0 mnmol), anh. K2CO3 (2.0 g), and acetone (75 ml): 8b (1.14 g,
95%). Cream-colored solid. M.p. 113 114 8 (CHCl3/hexane 1 :2). UV (MeOH): 236, 276, 318. IR (CHCl3): 1678
(HÀCˆO), 1650 (CˆO), 1604, 1572.2, 1518.2, 1493.1, 1466.1, 1423.6, 1219.2. 1H-NMR (CDCl3, 300 MHz): 9.98
(s, HÀCˆO); 8.20 (dd, J ˆ 7.78, 1.6, HÀC(5)); 7.61 (dt, J ˆ 7.93, 1.6, HÀC(7)); 7.41 7.39 (m, 3arom. H); 7.36
7.33 ( m, 4 arom. H); 5.73 5.56 ( m, HÀC(2'), HÀC(3')); 4.52 (d, J ˆ 5.34, CH2N); 1.63( d, J ˆ 5.73, Me). EI-
‡
‡
MS: 319 (21, M ), 318 (78, [M À 1] ), 304 (19), 171 (37).
4-Oxo-2-{phenyl[(2E)-3-phenylprop-2-enyl]amino}-4H-1-benzopyran-3-carboxaldehyde (8c). As de-
scribed for 8a, with 6 (1.00 g, 3.8 mmol), dry acetone (75 ml), cinnamyl bromide (1.18 g, 6.0 mmol), and anh.
K2CO3 (2.0 g): 8c (1.37 g, 97%). Cream-colored solid. M.p. 117 1188 (Et2O). UV (MeOH): 247, 280, 290, 305,
355. IR (CHCl3): 1682 (HÀCˆO), 1640 (CˆO), 1620, 1570, 1560, 1550, 1530, 1475, 1466, 1423, 1360, 1346, 1217.
1H-NMR (CDCl3, 300 MHz): 10.02 (s, HÀCˆO); 8.27 (d, J ˆ 8.36, HÀC(5)); 7.60 (t, J ˆ 8.15, HÀC(7)); 7.43
7.22 (m, 12 arom. H); 6.58 (d, J ˆ 15.72, HÀC(3')); 6.35 6.25 (m, HÀC(2')); 4.76 (d, J ˆ 6.12, CH2N). EI-MS:
‡
‡
381 (0.2, M ), 380 (1.0, [M À 1] ), 352 (0.15), 275 (5), 198 (3), 158 (5), 144 (5).
Ethyl (2E)-3-{4-Oxo-2-[phenyl(prop-2-enyl)amino]-4H-1-benzopyran-3-yl}prop-2-enoate (9a). To a soln.
of 8a (0.61 g, 2.0 mmol) in dry benzene (100 ml) was added ethyl (triphenylphosphoranylidene)acetate (0.70 g,
2.0 mmol), and the mixture was refluxed with stirring, under a moisture-free setup, to completion of reaction
(7 h). After evaporation, the residue was purified by FC (silica gel (200 400 mesh, 20 g); hexane/Et2O 9 :1): 9a
(0.71 g, 95%). Cream-colored solid. M.p. 81 828 (CHCl3/hexane 1:2). UV (MeOH): 218, 240.6, 295, 335. IR

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Helvetica Chimica Acta Vol. 86 (2003)
(CHCl3): 1701 (CO2Et), 1645.5 (CˆO), 1625, 1520, 1493, 1470, 1414, 1380, 1294, 1270, 1230, 1210, 1197.
1H-NMR (CDCl3, 200 MHz): 8.17 (d, J ˆ 7.68, HÀC(5)); 7.68 7.06 (m, 10 arom. and olef. H); 6.02 5.90
(m, HÀC(2')); 5.30 (d, J ˆ 18.62, 1 HÀC(3')); 5.23( d, J ˆ 11.08, 1 HÀC(3')); 4.56 (d, J ˆ 5.28, 2 HÀC(1')); 4.04
‡
‡
(q, J ˆ 7.12, MeCH2O); 1.19 (t, J ˆ 7.12, MeCH2O). EI-MS: 376 (1.3, [M ‡ 1] ), 375 (4.3, M ), 374 (0.5, [M À
‡
1] ), 305 (5), 279 (5), 238 (3), 147 (8). Anal. calc. for C23H21NO4: C 73.58, H 5.64, N 3.73; found: C 73.82,
H 5.92, N 3.94.
Ethyl (2E)-3-{2-{[(2E)-But-2-enyl]phenylamino}-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate (9b). As de-
scribed for 9a, with 8b (0.64 g, 2.0 mmol), dry benzene (100 ml), and ethyl (triphenylphosphoranylidene)acetate
(0.70 g, 2.0 mmol): 9b (0.733 g, 94%). Cream-colored solid. M.p. 928 (CHCl3/hexane 1:2). UV (MeOH): 301,
283, 258, 221.2. IR (CHCl3): 1705.3(CO Et), 1643.6 (CˆO), 1616.5, 1526, 1493.1, 1468, 1417.9, 1363.8, 1290.5,
2
1
1207.6. H-NMR (CDCl3, 300 MHz): 8.31 (dd, J ˆ 7.84, 1.66, HÀC(5)); 7.67 (dt, J ˆ 7.51, 1.70, HÀC(7)); 7.49
7.37 ( m, 4 arom. and olef. H), 7.27 7.17 (m, 5 arom. and olef. H); 5.84 5.78 (m, HÀC(2'), HÀC(3')); 4.61
(d, J ˆ 3.69, 2 HÀC(1')); 4.17 (q, J ˆ 7.07, MeCH2O); 1.81 (d, J ˆ 4.32, Me); 1.33 (t, J ˆ 7.07, MeCH2O). EI-MS:
‡
‡
390 (17, [M ‡ 1] ), 389 (38, M ), 316 (24), 262 (29), 169 (100). Anal. calc. for C24H23NO4: C 74.02, H 5.95,
N 3.60; found: C 73.79, H 5.62, N 3.48.
Ethyl (2E)-3-{4-Oxo-2-{phenyl[(2E)-3-phenylprop-2-enyl]amino}-4H-1-benzopyran-3-yl}prop-2-enoate
(9c). As described for 9a, with 8c (0.76 g, 2.0 mmol), ethyl (triphenylphosphoranylidene)acetate (0.70 g,
2.0 mmol), and dry benzene (100 ml): 9c (0.87 g, 97%). Cream-colored solid. M.p. 128 1308 (CHCl3/hexane
1:2). UV (MeOH): 215, 245.6, 285, 290.5, 320, 355. IR (CHCl3): 1695 (CO2Et), 1650 (CˆO), 1624, 1580, 1550,
1518, 1495, 1468, 1444, 1421, 1400, 1344, 1320, 1250, 1230. 1H-NMR (CDCl3, 300 MHz): 8.20 (dd, J ˆ 7.16, 1.59,
HÀC(5)); 7.61 (t, J ˆ 8.47, HÀC(7)); 7.41 7.10 (m, 14 arom. H); 6.62 (d, J ˆ 15.80, HÀC(3')); 6.41 6.32
(m, HÀC(2')); 4.75 (d, J ˆ 6.12, 2 HÀC(1')); 4.05 (q, J ˆ 7.11, MeCH2O); 1.16 (t, J ˆ 7.11, MeCH2O). 13C-NMR
(CDCl3, 75 MHz): 176.94 (C(4)); 167.80 (ester CˆO); 162.73(C(2)); 153.12 (C(8a)); 144.78 (quat. arom. C);
136.11 (quat. arom. C); 135.72 (olef. CH); 133.90 (C(7)); 133.04 (CH); 129.68 (CH); 128.64 (CH); 128.08 (CH);
126.53 (CH); 126.29 (CH); 125.63 (CH); 125.36 (CH); 123.97 (CH); 123.83 (CH); 123.24 (C(4a)); 118.71
(C(8)); 116.73(olef. CH); 102.35 (C(3)); 59.78 (Me CH2O); 55.30 (CH2N); 14.32 (MeCH2O). EI-MS: 355 (0.62,
‡
[M À 96] ), 341 (0.55), 327 (0.30), 311 (0.40), 305 (0.55), 301 (5), 284 (20). Anal. calc. for C29H25NO4: C 77.14,
H 5.58, N 3.10; found: C 77.37, H 5.37, N 3.34.
1-Phenyl-3-(prop-2-enyl)-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (10a). A soln. of 9a (0.38 g,
1.00 mmol) in xylene (10 ml) was sealed in a glass tube, which was heated at 220 2308 (6 h). The tube was
chilled and cut, and the soln. was concentrated to 1/4 of the original volume. The crystals, which appeared after
chilling for 2 h, were recrystallized from benzene: 10a (0.32 g, 96%). Light brown crystalline solid. M.p. 180
1828 (benzene). UV (MeOH): 338, 325, 310, 287, 235. IR (CHCl3): 1674.4 (NÀCˆO), 1649.3(C ˆO), 1614.6,
1583.7, 1552.9, 1481.5, 1468, 1450, 1427.5, 1410, 1390, 1344, 1290, 1267, 1190. 1H-NMR (CDCl3, 200 MHz): 8.27
(dd, J ˆ 7.88, 1.69, HÀC(6)); 8.13( s, HÀC(4)); 7.65 7.52 (m, 4 arom. H); 7.45 7.25 (m, 3arom. H); 7.10 ( d, J ˆ
8.38, HÀC(9)); 6.07 5.91 (m, HÀC(2')); 5.26 (d, J ˆ 10.90, 1 HÀC(3')); 5.17 (d, J ˆ 8.64, 1 HÀC(3')); 3.35
(dd, J ˆ 5.29, 1.1, 2 HÀC(1')). 13C-NMR (CDCl3, 50 MHz): 173.69 (C(5)); 161.67 (C(2)); 154.74 (C(10a));
153.43 (C(9a)); 134.36 (CH); 134.00 (NÀC); 133.76 (CH); 132.06 (CH); 129.58 (CH); 129.42 (C(3)); 128.37
(CH); 128.22 (CH); 126.48 (CH); 125.68 (CH); 122.13(C(5a)); 117.70 (C(9)); 117.48 (C(3 ')); 101.96 (C(4a));
‡
34.41 (C(1')). EI-MS: 329 (0.4, M ), 285 (25), 288 (1.0), 211 (2). Anal. calc. for C21H15NO3: C 76.58, H 4.59,
N 4.25; found: C 76.82, H 4.71, N 4.41.
3-[(2E)-But-2-enyl]-1-phenyl-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (10b). As described for
10a, with 9b (0.39 g, 1.00 mmol) and xylene (10 ml): 10b (0.33 g, 97%). Light brown solid. M.p. 222 2238. UV
(MeOH): 325.6, 289.8, 235.2. IR (CHCl3): 1674.4, 1649.3, 1608.8, 1545.2, 1493.1, 1464.1, 1444.9, 1313.7, 1261.6.
1H-NMR (CDCl3, 200 MHz): 8.28 (dd, J ˆ 7.80, 1.66, HÀC(6)); 8.08 (s, HÀC(4)); 7.64 7.54 (m, 4 arom. H);
7.46 7.26 ( m, 3arom. H); 7.11 ( d, J ˆ 8.16, HÀC(9)); 5.68 5.62 (m, HÀC(2'), HÀC(3')); 3.27
(br., 2 HÀC(1')); 1.75 (s, Me). 13C-NMR (CDCl3, 50 MHz): 173.81 (C(5)); 162.02 (C(2)); 154.70 (C(10a));
153.43 (C(9a)); 134.08 (CipsoÀN); 133.81 (C(8)); 131.67 (CH); 129.62 (CH); 129.43 (CH); 128.45 (CH); 128.26
(CH); 127.16 (C(3)); 126.80 (CH); 126.41 (CH); 125.68 (CH); 122.14 (C(5a)); 117.53 (C(9)); 102.01 (C(4a));
‡
‡
33.21 (C(1')); 18.03(Me). EI-MS: 344 (7, [ M ‡ 1] ), 343 (23, M ), 314 (22), 169 (100). Anal. calc. for
C22H17NO3: C 76.95, H 4.99, N 4.08; found: C 77.21, H 4.84, N 4.33.
1-Phenyl-3-[(2E)-3-phenylprop-2-enyl]-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (10c). As de-
scribed for 10a, with 9c (0.45 g, 1.00 mmol) and xylene (10 ml): 10c (0.38 g, 95%). Yellowish solid. M.p. 240
2428 (benzene). UV (MeOH): 236.6, 250, 290, 326.6, 340. IR (CHCl3): 1665 (NÀCˆO), 1657 (CˆO), 1610,
1549, 1493.1, 1464.1, 1442.9, 1415, 1390, 1361.9, 1300, 1270. 1H-NMR (CDCl3, 200 MHz): 8.25 (dd, J ˆ 7.64, 1.89,
HÀC(6)); 8.12 (s, HÀC(4)); 7.59 7.55 (m, 3arom. H); 7.32 7.06 ( m, 10 arom. H); 6.59 (d, J ˆ 15.78,

Helvetica Chimica Acta Vol. 86 (2003)
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HÀC(3')); 6.32 6.20 (dt, J ˆ 15.78, 6.76, HÀC(2')); 3.44 (d, J ˆ 6.76, 2 HÀC(1')). 13C-NMR (CDCl3, 50 MHz):
173.83 (C(5)); 162.19 (C(2)); 154.2 (C(10a)); 153.51 (C(9a)); 137.25 (quat. arom. C); 133.91 (C(8)); 132.67
(quat. arom. C); 132.24 (CH); 129.69 (CH); 129.52 (CH); 128.88 (C(3)); 128.54 (CH); 128.47 (CH); 128.27
(CH); 127.26 (CH); 126.48 (CH); 126.26 (CH); 126.11 (C(3)); 125.78 (CH); 122.13 (C(5a)); 117.58 (C(9));
‡
102.08 (C(4a)); 33.89 (C(1')). EI-MS: 405 (0.8, M ), 315 (10), 285 (20), 269 (4), 255 (4), 219 (6). Anal. calc. for
C27H19NO3: C 79.98, H 4.72, N 3.45; found: C 80.23, H 4.66, N 3.62.
2-[Benzyl(prop-2-enyl)amino]-4-oxo-4H-1-benzopyran-3-carboxaldehyde (15a). To a soln. of 14 [3b]
(0.84 g, 3.0 mmol) in dry acetone (100 ml) was added allyl bromide (0.61 g, 5.0 mmol) and anh. K2CO3 (2.0 g),
and the mixture was refluxed for 9 h. The hot mixture was filtered, the solid washed with little acetone, the
solvent evaporated, and the residue separated by CC (silica gel (60 120 mesh, 20 g), packed in hexane, then
hexane/AcOEt 9 :1): 15a (0.90 g, 94%). Dark brown semisolid. UV (MeOH): 231.6, 270, 282, 305. IR (CHCl3):
1670, 1630, 1580, 1560, 1508, 1466, 1417. 1H-NMR (CDCl3, 200 MHz): 10.17 (s, HÀCˆO); 8.19 (d, J ˆ 6.46,
HÀC(5)); 7.58 (t, J ˆ 7.5, H ÀC( 7 )) ; 7.39 7.18 ( m, 7 arom. H); 6.0 5.8 (m, HÀC(2')); 5.32 5.20
‡
(m, 2 HÀC(3')); 4.72 (s, PhCH2); 4.11 (d, J ˆ 4.10, 2 HÀC(1')). EI-MS: 319 (10, M ), 278 (10), 250 (14), 145
(5), 111 (32), 91 (100). Anal. calc. for C20H17NO3: C 75.22, H 5.37, N 4.39; found: C 75.41, H 5.63, N 4.62.
2-{Benzyl[(2E)-but-2-enyl]amino}-4-oxo-4H-1-benzopyran-3-carboxaldehyde (15b). As described for 15a,
with 14b (0.84 g, 3.0 mmol), crotyl bromide (0.68 g, 5.0 mmol), anh. K2CO3 (2.0 g), and dry acetone (100 ml).
CC (silica gel (60 120 mesh, 20 g), column packed in hexane, then hexane/AcOEt gradient) gave 15b (0.96 g,
96%). Dark brown solid. M.p. 113 115 8 (CHCl3/hexane 1:2). UV (MeOH): 237, 269, 275, 290, 300. IR
1
(CHCl3): 1672 (HÀCˆO), 1633 (CˆO), 1614, 1576, 1540, 1496, 1466, 1440, 1388, 1340, 1313, 1215. H-NMR
(CDCl3, 200 MHz): 10.27 (s, HÀCˆO); 8.34 8.18 (m, 2 arom. H); 7.68 7.28 (br. m, 7 arom. H); 5.75 5.71
(m, J ˆ 5.3, HÀC(3')); 5.60 5.58 (m, HÀC(2')); 4.86 (s, PhCH2); 4.15 (d, J ˆ 4.84, 2 HÀC(1')); 1.84 (br. d, J ˆ
‡
‡
6.8, Me). EI-MS: 304 (5, [M À 29] ), 250 (54, [M À 84] ), 242 (10), 241 (5), 234 (3), 188 (10), 183 (8), 171 (22),
170 (5). Anal. calc. for C21H19NO3: C 75.66, H 5.74, N 4.20; found: C 75.52, H 5.85, N 4.49.
2-{Benzyl[(2E)-3-phenylprop-2-enyl]amino}-4-oxo-4H-1-benzopyran-3-carboxaldehyde (15c). As de-
scribed for 15a, with 14b (0.84 g, 3.0 mmol), dry acetone (100 ml), crotyl bromide (0.98 g, 5.0 mmol), and
anh. K2CO3 (2.0 g). CC (silica gel (60 120 mesh, 20 g); hexane/AcOEt gradient) gave 15c (1.15 g, 97%).
Brownish semisolid. UV (MeOH): 243, 283, 296, 308. IR (CHCl3): 1670 (HÀCˆO), 1633 (CˆO), 1580, 1508,
1558, 1508, 1500, 1462, 1450, 1416, 1360, 1340, 1325. 1H-NMR (CDCl3, 200 MHz): 10.23( s, HÀCˆO); 8.24
(d, J ˆ 7.70, HÀC(5)); 7.64 (t, J ˆ 7.61, HÀC(7)); 7.43 7.21 ( m, 12 arom. H); 6.53( d, J ˆ 15.90, HÀC(3')); 6.28
‡
(dt, J ˆ 15.90, 6.40, HÀC(2')); 4.63( s, PhCH2); 4.28 (d, J ˆ 6.40, 2 HÀC(1')). EI-MS: 355 (1, [M À 40] ), 278
(1.5), 250 (10), 159 (3), 145 (5), 111 (40), 94 (30). Anal. calc. for C26H21NO3: C 78.97, H 5.35, N 3.54; found:
C 78.71, H 5.56, N 3.33.
Ethyl (2E)-3-{2-[Benzyl(prop-2-enyl]amino}-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate (16a). To a soln.
of 15a (0.64 g, 2.0 mmol) in dry benzene (100 ml), under protection from moisture, was added ethyl
(triphenylphosphoranylidene)acetate (0.70 g, 2.0 mmol), and the mixture was refluxed with stirring to
completion of the reaction (10 h). After evaporation the residue was purified by CC (silica gel (20 g, 60
120 mesh), packed in hexane, then hexane/AcOEt gradient): 16a (0.75 g, 96%). Light brown solid. M.p. 80 828
(CHCl3/hexane 1:2). UV (MeOH): 238, 279, 292, 318, 320. IR (CHCl3): 1697 (CO2Et), 1635 (CˆO), 1620,
1616, 1541, 1508, 1456, 1420, 1350, 1340, 1288. 1H-NMR (CDCl3, 200 MHz): 8.17 (dd, J ˆ 7.38, 1.26, HÀC(5));
7.52 (t, J ˆ 8.36, HÀC(7)); 7.48 (d, J ˆ 15.69, CHˆCHCOOEt); 7.35 7.20 (m, 9 arom. and olef. H); 6.05 5.91
(m, HÀC(2')); 5.37 5.24 (m, 2 HÀC(3')); 4.67 (s, PhCH2); 4.20 (q, J ˆ 7.12, MeCH2O); 4.01 (d, J ˆ 5.94,
‡
2 HÀC(1')); 1.31 (t, J ˆ 7.12, MeCH2O). EI-MS: 389 (20, M ), 344 (5), 316 (26), 275 (6), 170 (48), 144 (8), 111
(25), 91 (100). Anal. calc. for C24H23NO4: C 74.02, H 5.95, N 3.69; found: C 74.23, H 6.27, N 3.47.
Ethyl (2E)-3-{2-{Benzyl[(2E)-but-2-enyl]amino}-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate (16b). As
described for 16a, with 15b (0.67 g, 2.0 mmol), ethyl (triphenylphosphoranylidene)acetate (0.70 g, 2.0 mmol),
and dry benzene (100 ml): 16b (0.77 g, 95%). Off-white solid. M.p. 83 85 8 (CHCl3/hexane 1:2). UV (MeOH):
235.4, 290, 305, 323. IR (CHCl3): 1696 (CO2Et), 1662 (CˆO), 1633, 1614, 1576, 1540, 1496, 1464, 1440, 1388,
1
1346, 1313, 1215. H-NMR (CDCl3, 200 MHz): 8.30 (d, J ˆ 7.77, HÀC(5)); 7.77 7.70 (m, HÀC(7)); 7.53 7.17
(m, 9 arom. and olef. H); 5.88 5.52 (m, HÀC(2')); 5.50 5.43( m, HÀC(3')); 4.77 (s, PhCH2); 4.12 (q, J ˆ 7.12,
MeCH2O); 4.04 (d, J ˆ 5.14, 2 HÀC(1')); 1.77 (d, J ˆ 6.16, Me(4')); 1.28 (t, J ˆ 7.12, MeCH2O). EI-MS: 403
‡
(0.82, M ), 375 (0.56), 374 (1.5), 330 (8), 304 (5), 283 (12), 278 (22), 242 (26). Anal. calc. for C25H25NO4:
C 74.42, H 6.25, N 3.47; found: C 74.66, H 6.42, N 3.40.
Ethyl (2E)-3-{2-{Benzyl[(2E)-3-phenylprop-2-enyl]amino}-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate
(16c). As described for 16a, with 15c (0.79 g, 2.0 mmol), ethyl (triphenylphosphoranylidene)acetate (0.70 g,
2.0 mmol), and dry benzene (100 ml) (12 h): 16c (0.89 g, 96%). Yellowish solid. M.p. 60 628 (CHCl3/hexane

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Helvetica Chimica Acta Vol. 86 (2003)
1:2). UV (MeOH): 235.4, 289.4, 327.6. IR (CHCl3): 1699 (CO2Et), 1643(C ˆO), 1616, 1537, 1496, 1466, 1423,
1354, 1288, 1230. 1H-NMR (CDCl3, 200 MHz): 8.23( dd, J ˆ 7.8, 1.6, HÀC(5)); 7.57 (split t, J ˆ 7.58, 2.62,
HÀC(7)); 7.56 (d, J ˆ 15.60, CHˆCHCOOEt); 7.42 7.25 (m, 13arom. and olef. H); 6.50 ( d, J ˆ 15.81,
HÀC(3')); 6.41 6.30 (m, HÀC(2')); 4.74 (s, PhCH2); 4.72 4.16 (m, MeCH2O, 2 HÀC(1')); 1.27 (t, J ˆ 7.08,
‡
MeCH2O). EI-MS: 465 (1, M ), 419 (1), 378 (1), 273 (5), 182 (8), 156 (10), 142 (8), 111 (40). Anal. calc. for
C30H27NO4: C 77.40, H 5.85, N 3.01; found: C 77.59, H 5.98, N 3.24.
1-Benzyl-3-(prop-2-enyl)-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (17a). A soln. of 16a (0.39 g,
1.0 mmol) in xylene (10 ml) was sealed in a glass tube which was heated to 2208 for 6 h. The tube was chilled and
cut, the solvent evaporated, and the residue separated by prep. TLC (silica gel G, 2-mm layer, 6 plates, eluent
CHCl3, extraction with CHCl3/MeOH): 17a (0.29 g, 84%). Brownish solid. M.p. 90 928 (benzene). UV
(MeOH): 219, 229, 290, 320, 325, 340. IR (CHCl3): 1674.4 (NÀCˆO), 1649 (CˆO), 1614.6, 1585.7, 1552.9, 1460,
1
1430, 1350, 1280, 1242, 1211. H-NMR (CDCl3, 200 MHz): 8.26 (d, J ˆ 7.08, HÀC(6)); 8.01 (s, HÀC(4)); 7.69
(t, J ˆ 7.88, HÀC(8)); 7.48 7.41 (m, 3arom. H); 7.39 7.26 ( m, 4 arom. H); 6.12 5.90 (m, HÀC(2')); 5.53
(s, PhCH2); 5.23( d, J ˆ 6.80, 1 HÀC(3')); 5.18 (d, J ˆ 10.11, 1 HÀC(3')); 3.36 (d, J ˆ 6.68, 2 HÀC(1')). EI-MS:
‡
343 (50, M ), 302 (12), 285 (13). Anal. calc. for C22H17NO3: C 76.95, H 4.99, N 4.08; found: C 77.78, H 4.84,
N 4.26.
1-Benzyl-3-[(2E)-but-2-enyl]-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (17b). As described for
17a, with 16b (0.4 g, 1.0 mmol) and xylene (10 ml): 17b (0.285 g, 81%). Dark-brown semisolid. UV (MeOH):
235.4, 255, 280, 325, 348. IR (CHCl3): 1665 (NÀCˆO), 1647.4 (CˆO), 1612.7, 1585, 1552.9, 1510, 1495, 1464.1,
1394.7, 1370, 1348, 1304, 1220, 1211. 1H-NMR (CDCl3, 200 MHz): 8.27 (d, J ˆ 7.64, HÀC(6)); 7.96 (s, HÀC(4));
7.70 (distorted t, J ˆ 8.46, HÀC(8)); 7.46 7.13( m, 7 arom. H); 5.75 5.54 (m, HÀC(2'), HÀC(3')); 5.50
(s, PhCH2); 3.26 (br., 2 HÀC(1')); 1.72 (br., Me(4')). EI-MS: 357 (6), 283 (15), 265 (4), 266 (18), 238 (8), 286
(10). Anal. calc. for C23H19NO3: C 77.29, H 5.36, N 3.92; found: C 77.15, H 5.51, N 3.75.
1-Benzyl-3-[(2E)-3-phenylprop-2-enyl]-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (17c). As de-
scribed for 17a, with 16c (0.47 g, 1.0 mmol) and xylene (10 ml). Prep. TLC with 8 plates: 17c (0.35 g, 83%). Light
brown solid. M.p. 70 728 (hexane/CHCl3 1:5). UV (MeOH): 235, 289, 320, 327, 345. IR (CHCl3): 1666
(NÀCˆO), 1650 (CˆO), 1583.7, 1551, 1464.1, 1450, 1400, 1350, 1296, 1211. 1H-NMR (CDCl3, 200 MHz): 8.25
(dd, J ˆ 1.19, 8.12, HÀC(6)); 8.04 (br. s, HÀC(4)); 7.68 (t, J ˆ 7.68, HÀC(8)); 7.49 7.17 (m, 12 arom. H); 6.54
(d, J ˆ 15.87, HÀC(3')); 6.40 (dt, J ˆ 15.87, 6.59, HÀC(2')); 5.52 (s, PhCH2); 3.50 (d, J ˆ 6.59, 2 HÀC(1')).
13C-NMR (CDCl3, 50 MHz): 173.36 (C(5)); 161.48 (C(2)); 154.81 (C(10a)); 153.39 (C(9a)); 137.15 (quat. arom.
C); 135.69 (quat. arom. C); 133.76 (CH); 132.60 (CH); 131.74 (CH); 128.77 (CH); 128.59 (CH); 128.34 (CH);
128.27 (C(3)); 128.06 (CH); 127.89 (CH); 127.13 (CH); 126.78 (CH); 126.20 (CH); 125.94 (CH); 125.69
‡
‡
(C(5a)); 117.04 (C(9)); 102.17 (C(4a)); 45.21 (CH2N); 33.86 (C(1')). EI-MS: 420 (0.6, [M ‡ 1] ), 419 (4, M ),
342 (1), 329 (10), 302 (5), 286 (15), 195 (3). Anal. calc. for C28H21NO3: C 80.17, H 5.05, N 3.34; found: C 80.38,
H 4.84, N 3.55.
2-[Benzyl(phenyl)amino]-4-oxo-4H-1-benzopyran-3-carboxaldehyde (21). As described for 8a, with 6
(1.0 g, 3.8 mmol), dry acetone, benzyl bromide (1.0 g, 6.0 mmol), and anh. K2CO3 (2.0 g): 21 (1.30 g, 97%).
Cream-colored solid. M.p. 1578 (benzene). UV (MeOH): 331, 292, 247.5. IR (CHCl3): 1672 (HÀCˆO), 1648
(CˆO), 1602, 1576, 1478, 1462, 1443, 1413, 1391, 1318, 1306, 1234, 1201. 1H-NMR (CDCl3, 200 MHz): 10.20
(s, HÀCˆO); 8.41 (dd, J ˆ 7.78, 1.70, HÀC(5)); 7.78 (dt, J ˆ 7.68, HÀC(7)); 7.64 7.39 (m, 12 arom. H); 5.43
(s, PhCH2). 13C-NMR (50 MHz, CDCl3): 186.09 (CHO); 177.90 (C(4)); 163.06 (CH); 153.38 (quat. C); 144.26
(quat. C); 135.96 (quat. C); 133.34 (CH); 129.27 (CH); 128.81 (CH); 127.87 (quat. C); 127.23 (CH); 126.72
(CH); 126.31 (CH); 125.32 (CH); 124.54 (CH); 123.54 (quat. C); 116.51 (CH); 103.24 (quat. C); 57.59 (PhCH2).
‡
EI-MS: 355 (20, M ), 354 (40), 283 (97), 284 (98), 171 (100).
Ethyl (2E)-3-{2-[Benzyl(phenyl)amino]-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate (22). As described
for 16a, with 21 (0.35 g, 1.0 mmol), dry benzene (100 ml), and ethyl (triphenylphosphoranylidene)acetate
(0.35 g, 1.0 mmol) (7 h). FC (silica gel (200 400 mesh, 20 g); hexane/Et2O 9 :1) gave 22 (0.40 g, 96%). Cream-
colored solid. M.p. 1128 (benzene). UV (MeOH): 331.5, 252.5. IR (CHCl3): 1697 (CO2Et), 1635 (CˆO), 1597,
1582, 1498, 1479, 1457, 1442, 1412, 1348, 1276, 1264, 1230. 1H-NMR (CDCl3, 200 MHz): 8.13(br. d, J ˆ 7.37,
HÀC(5)); 7.52 (dt, J ˆ 7.74, HÀC(7)); 7.35 7.16 (m, 8 arom. and olef. H); 7.14 6.99 (m, 6 arom. and olef. H);
‡
5.16 (s, PhCH2); 4.03( q, J ˆ 7.16, MeCH2O); 1.18 (t, J ˆ 7.16, MeCH2O). EI-MS: 426 (8, [M ‡ 1] ), 425 (29,
‡
M ), 380 (24), 352 (50), 171 (21), 91 (100). Anal. calc. for C27H23NO4: C 76.22, H 5.45, N 3.29; found: C 76.51,
H 5.65, N 3.40.
Ethyl (2E)-3-[4-Oxo-2-(phenylamino)-4H-1-benzopyran-3-yl)prop-2-enoate (23a). As described for 16a,
with 6 (0.53g, 2.0 mmol), CH 2Cl2 (50 ml) instead of benzene, and ethyl (triphenylphosphoranylidene)acetate
(0.70 g, 2.0 mmol) at r.t. for 12 h (TLC monitoring). FC (silica gel (200 400 mesh, 20 g); hexane/Et2O 9 :1)

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gave 23a (0.65 g, 98%). Colorless crystalline solid. M.p. 118 1198 (CHCl3/hexane 3:1). UV (MeOH): 322.9,
226.4, 209. IR (CHCl3): 2950, 1700 (CO2Et), 1644 (CˆO), 1607, 1562, 1553, 1482, 1458. 1H-NMR (CDCl3,
200 MHz): 8.19 (dd, J ˆ 7.80, 1.46, HÀC(5)); 8.03(br. s, NH); 7.73( d, J ˆ 15.51, CHˆCHCOOEt); 7.51 (split t,
J ˆ 7.47, 1.58, HÀC(7)); 7.43 7.21 ( m, 8 arom. H, CHˆCHCOOEt); 4.15 (q, J ˆ 7.09, MeCH2O); 1.26 (t, J ˆ
‡
7.09, MeCH2O). EI-MS: 335 (2.5, M ), 262 (80), 261 (30), 170 (15), 144 (5).
1-Phenyl-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (24a). As described for 16a, with 6 (0.53g,
2.0 mmol), dry benzene (100 ml), and ethyl (triphenylphosphoranylidene)acetate (0.7 g, 2.0 mmol) (12 h, TLC
monitoring). After concentration to ca. 10 ml, the soln. was chilled for 1 h; cream-colored crystals separated out
and were recrystallized from benzene: 24a (0.56 g, 96%). Off-white solid. M.p. 284 2858. UV (MeOH): 336.5,
321.5, 292, 247.5. IR (CHCl3): 1678, 1663, 1647, 1630, 1600, 1560, 1517, 1481, 1458, 1404, 1353, 1281, 1224.
1H-NMR (CDCl3, 200 MHz): 8.27 (overlapping ds, J ˆ 9.19, HÀC(4), HÀC(6)); 7.60 7.27 (m, 7 arom. H); 7.11
(d, J ˆ 8.22, HÀC(9)); 6.60 (d, J ˆ 9.61, HÀC(3)). 13C-NMR (CDCl3, 50 MHz): 173.60 (C(5)); 161.66 (C(2));
155.99 (C(10a)); 153.43 (C(9a)); 135.96 (CH); 134.03 (CH); 133.56 (Cipso-N); 129.65 (CH); 129.54 (CH); 128.14
(CH); 126.33 (CH); 125.65 (CH); 121.92 (C(5a)); 117.52 (C(9)), 116.88 (CH), 102.18 (C(4a)). EI-MS: 290 (10,
‡
‡
[M ‡ 1] ), 289 (49, M ), 288 (29), 171 (100). Anal. calc. for C18H11NO3: C 74.73, H 3.83, N 4.84; found: C 74.59,
H 3.94, N 4.98.
1-Benzyl-2H-[1]benzopyrano[2,3-b]pyridine-2,5(1H)-dione (24b). As described for 16a, with 14 (0.42 g,
1.5 mmol), ethyl (triphenylphosphoranylidene)acetate (0.52 g, 1.5 mmol), and dry benzene (100 ml) (16 h).
After concentration to 1/10th of the original volume, the soln. was chilled for 1 h; colorless crystals separated out
and were recrystallized from benzene: 24b (0.45 g, 98%). M.p. 186 1878. UV (MeOH): 336, 319.5, 290, 245. IR
1
(CHCl3): 1684 (NÀCˆO), 1662 (CˆO), 1634, 1596, 1545, 1472, 1373, 1297, 1260, 1238, 1209, 1130. H-NMR
(CDCl3, 200 MHz): 8.25 (br. d, J ˆ 7.75, HÀC(6)); 8.17 (d, J ˆ 9.54, HÀC(4)); 7.69 (t, J ˆ 6.79, HÀC(8)); 7.48
7.45 (m, 4 arom. H); 7.36 7.16 (m, 3arom. H); 6.56 ( d, J ˆ 9.55, HÀC(3)); 5.50 (s, PhCH2). 13C-NMR (CDCl3,
50 MHz): 173.07 (C(5)); 161.46 (C(2)); 156.07 (C(10a)); 153.45 (C(9a)); 135.60 (CH); 135.46 (Cipso-CH2N);
133.96 (CH); 128.78 (CH); 126.22 (CH); 128.10 (CH); 126.74 (CH); 125.66 (CH); 122.16 (C(5a)); 117.07
‡
‡
(C(9)); 116.37 (CH); 102.46 (C(4a)); 44.78 (CH2N). EI-MS: 304 (8, [M ‡ 1] ), 303 (24, M ), 169 (56), 111 (27),
91 (100). Anal. calc. for C19H13NO3: C 75.24, H 4.32, N 4.62; found: C 75.48, H 4.43, N 4.48.
Pyridinone 24a was also obtained in near quant. yield by refluxing 23a in benzene for 10 h (TLC, 1H-NMR
of crude product).
Ethyl (2E)-3-{2-[Methyl(phenyl)amino]-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate (20a). As described
for 16a, with 13 (0.56 g, 2.0 mmol), dry benzene (100 ml), and ethyl (triphenylphosphoranylidene)acetate (0.7 g,
2.0 mmol) (7 h, TLC monitoring). FC (silica gel (200 400 mesh, 20 g); hexane/Et2O 9 :1) gave 20a (0.67 g,
96%). Cream-colored solid. M.p. 99 1008 (CHCl3/hexane 1:2). UV (MeOH): 335, 248, 292.5. IR (CHCl3):
1700 (CO2Et), 1639.7 (CˆO), 1616.5, 1527.8, 1493.1, 1398.6, 1360, 1292.5. 1H-NMR (CDCl3, 300 MHz): 8.21
(dd, J ˆ 6.34, 1.65, HÀC(5)); 7.61 (dt, J ˆ 7.63, 1.48, HÀC(7)); 7.42 7.33 (m, 5 arom. and olef. H); 7.17 7.09
(m, 4 arom. and olef. H); 4.09 (q, J ˆ 7.14, MeCH2O); 3.61 (s, MeN); 1.21 (t, J ˆ 7.14, MeCH2O). EI-MS: 349 (2,
‡
M ), 171 (29), 71 (49), 58 (100).
2-[Benzyl(methyl)amino]-4-oxo-4H-1-benzopyran-3-carboxaldehyde (13b). As described for 8a, with 14
(0.84 g, 3.0 mmol), dry acetone (100 ml), MeI (2 ml, excess), and anh. K2CO3 (2.0 g): 13b (0.84 g, 95%). Light
brown semisolid. UV (MeOH): 296, 281.6, 246. IR (CHCl3): 1672.5 (HÀCˆO), 1650 (CˆO), 1556.7, 1483.4,
1466.1, 1842.6, 1327.2, 1228.1. 1H-NMR (CDCl3, 200 MHz): 10.40 (s, HÀCˆO); 8.13( dd, J ˆ 7.73, 1.26,
HÀC(5)); 7.54 (dt, J ˆ 7.40, 1.48, HÀC(7)); 7.36 7.17 (m, 7 arom. H); 4.77 (s, PhCH2); 3.07 (s, MeN). EI-MS:
‡
293(11, M ), 264 (41), 174 (98), 171 (88), 91 (90), 71 (100).
Ethyl (2E)-3-{2-[Benzyl(methyl)amino]-4-oxo-4H-1-benzopyran-3-yl}prop-2-enoate (20b). As described
for 16a, with 13b (0.59 g, 2.0 mmol), dry benzene (100 ml), and ethyl (triphenylphosphoranylidene)acetate
(0.7 g, 2.0 mmol) (15 h, TLC monitoring). FC (silica gel (200 400 mesh, 20 g); hexane/Et2O 9 :1) gave 20b
(0.70 g, 96%). Light brown semisolid. UV (MeOH): 332.6, 291, 244.4. IR (CHCl3): 1699.5 (CO2Et), 1637.8
1
(CˆO), 1616, 1601.1, 1545.2, 1435.2, 1406.2, 1288.6, 1157.4, 1035.9. H-NMR (CDCl3, 200 MHz): 8.24 (dd, J ˆ
7.07, 1.67, HÀC(5)); 7.61 (dt, J ˆ 6.99, 1.19, HÀC(7)); 7.59 (d, J ˆ 13.32, olef. H); 7.46 7.28 (m, 8 arom. H and
olef. H); 4.78 (s, PhCH2); 4.25 (q, J ˆ 7.08, MeCH2O); 3.17 (s, MeN); 1.34 (t, J ˆ 7.08, MeCH2O). EI-MS: 363
‡
(1.5, M ), 318 (2.0), 290 (1.8), 199 (12), 184 (12), 144 (5). Anal. calc. for C22H21NO4: C 72.71, H 5.82, N 3.85;
found: C 72.59, H 5.97, N 3.67.

180
Helvetica Chimica Acta Vol. 86 (2003)
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Received May 24, 2002