Regiospecific inverse electron demand Diels-Alder reactions of 7-methylcoumarin-4-azadienes

Article abstract of DOI:10.1039/c5ra06262d

Condensation of 7-methylcoumarin-4-carbaldehyde with different anilines affords 7-methylcoumarin-4-azadienes. The 7-methylcoumarin-4-azadienes do not undergo normal electron demand Diels-Alder reaction with N-phenylmaleimide, but react with dihydropyran, dihydrofuran, and styrene via inverse electron demand Diels-Alder reaction in the presence of anhydrous ZnCl₂. The diene involves the azomethine group and the aniline ring. The product is a mixture of two diastereomers in which the major diastereomer has all the hydrogens at the ring junction in cis configuration. This journal is

Full text of DOI:10.1039/c5ra06262d

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Regiospecific inverse electron demand Diels–Alder
reactions of 7-methylcoumarin-4-azadienes†
Cite this: RSC Adv., 2015, 5, 36696
Kailas K. Sanap and Shriniwas D. Samant*b
a
Condensation of 7-methylcoumarin-4-carbaldehyde with different anilines affords 7-methylcoumarin-4-
azadienes. The 7-methylcoumarin-4-azadienes do not undergo normal electron demand Diels–Alder
reaction with N-phenylmaleimide, but react with dihydropyran, dihydrofuran, and styrene via inverse
Received 8th April 2015
Accepted 14th April 2015
2
electron demand Diels–Alder reaction in the presence of anhydrous ZnCl . The diene involves the
DOI: 10.1039/c5ra06262d
azomethine group and the aniline ring. The product is a mixture of two diastereomers in which the
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major diastereomer has all the hydrogens at the ring junction in cis configuration.
reaction of [3]-1-azadendralenes in which cross-conjugated 1-
azatriene underwent an initial hetero Diels–Alder reaction on
Introduction
The coumarins are versatile molecules because many of them, the 1-aza-1,3-butadiene system with tosyl isocyanate to afford
natural as well as synthetic, exhibit a broad spectrum of bio- the mono-cycloadduct pyrimidinone which on further subse-
1
2
logical properties such as antitumour, antimicrobial and quent Diels–Alder reaction with dienophiles provides hexahy-
3
13
antiviral activities. Polycyclic benzopyrones embedding a droquinazolin-2(1H)-ones with high stereoselectivity.
coumarin ring also show diverse activities. One of the strategies
As a part of our interest in the Diels–Alder reaction of
of building of such molecules is annulation over a coumarin coumarins containing diene component, we thought that
ring. This strategy works very well with the 3,4-double bond in coumarin-4-azadienes (1) which contain a 3,4-double bond of
4
coumarin. The 3,4-double bond functions as a dienophile due coumarin ring conjugated to phenylimino group, would be an
to activation by adjacent carbonyl groups and it also undergoes interesting diene system to study the Diels–Alder reaction; tar-
5
an addition reaction. 3-Vinyl and 4-styryl substituted couma- geting coumarin containing polycyclic compounds.
rins perform as dienes and the corresponding Diels–Alder
6
reaction gives 3,4-annulated coumarins. Inverse electron
demand Diels–Alder reaction of coumarins containing electron
decient diene with electron rich dienophiles is known to give
7
3,4-annulated coumarins.
The aza Diels–Alder reaction of coumarin-3-azadienes
derived from 3-aminocoumarin and its intramolecular version
8
are known. Conjugated polyenes containing more than one
diene component are interesting substrates for Diels–Alder
Azadiene 1 is an interesting substrate for Diels–Alder reac-
reaction, as the reaction involves a challenge of regioselection. tion as it contains two potentially reactive azadiene: a 2-aza-
Diels–Alder reaction of dendralene and biscoumarinylethene diene (involving the aniline ring i.e. M) and a 1-azadiene
types of polyene systems are reported in literature to give (involving the C3–C4 coumarin double bond i.e. N) with
9
regioselective product. Diels–Alder reaction of heteropolyene different orbital characteristics and electron demands; possibly
1
0
(
cross conjugated) system like [3]-3-heterodendralenes (thia- , providing regioselectivity in the reaction. In general, simple 1-
11
12
oxa- , and aza- ) with an suitable dienophiles gives diversied and 2-azadienes, due to their electron-decient nature favor
heterocycles. More recently Saito et al. reported the Diels–Alder participation in `inverse electron demand' (LUMO diene-
14
controlled) Diels–Alder reaction. A major difference between
the two systems is the efficacy of Lewis acid catalysis in the 2-
azadiene cycloadditions. However reactivity of both the aza-
dienes can be tuned by introducing either electron-withdrawing
or electron-donating substituents at proper positions of the
a
Department of Chemistry, N.B. Mehta Science College, Bordi, Taluka-Dahanu,
Dist-Palghar 400 701, Maharashtra, India
b
Department of Chemistry, Institute of Chemical Technology, Nathalal Parikh Marg,
Matunga, Mumbai 400 019, Maharashtra, India. E-mail: samantsd@yahoo.com;
Fax: +91-2233611020; Tel: +91-2233612606
15
diene. The introduction of electron-withdrawing substituents
†
Electronic supplementary information (ESI) available. CCDC 901323–901324. at the 2, 3, or 4 positions of the 1-azadiene may further accel-
For ESI and crystallographic data in CIF or other electronic format see DOI:
0.1039/c5ra06262d
erate reaction rates through LUMO diene-controlled pathway.
1
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Sufficiently electron-donating substituents placed at the C-1 and/
or C-3 position in the 2-azadiene can enhance the Diels–Alder
15
reactivity through the HOMO diene-controlled pathway. Herein,
we report a comprehensive study on the inverse electron demand
Diels–Alder reaction of 7-methylcoumarin-4-azadienes (1).
7-Methylcoumarin-4-acetic acid (5) was prepared by the
condensation of m-cresol (4) with acetone dicarboxylic acid (3),
which in turn was prepared in situ by reacting citric acid (2) with
conc. H SO (Scheme 1).
2 4
Scheme 3 The aza Diels–Alder reaction of 7-methylcoumarin-4-
azadiene (1a) with DHP (10).
16
The compound 5 was subjected to oxidation using SeO to
2
obtain 7-methylcoumarin-4-carbaldehyde (6), which on
condensation with anilines (7) gave 7-methylcoumarin-4-
azadienes (1) (Scheme 2).
Diels–Alder reaction of 4-styrylcoumarins with N-phenyl-
maleimide (NPMA) (8) is known to give 2,11-diphenyl-
A and B were separated and puried by ash column chro-
matography on silica gel using chloroform. Gratifyingly, a
mixture of A and B was isolated in 67% yield with A (169 mg,
17
49%) and B (62 mg, 18%). Six different products are possible for
this reaction as shown in Fig. 1.
3
a,10,11,11a-tetrahydro[1]benzopyrano[3,4-e]isoindole-1,3,4(2H)-
18
The IR spectra of compounds A and B showed secondary NH
triones. Taking inspiration from this, we carried out the Diels–
Alder reaction of 1a (R ¼ H) with NPMA (8) at different
temperatures in dioxane, nitrobenzene, and o-dichlorobenzene
ꢀ1
group, as sharp medium intensity peaks at 3348 and 3322 cm
respectively, and the carbonyl groups showed peaks at 1720 and
ꢀ1
1
1
708 cm respectively. H NMR spectra of A and B had ratio of
(
o-DCB). In dioxane 1a remained unconsumed, while in nitro-
benzene and o-DCB it decomposed to form other side products
TLC). The same reaction under microwave irradiation at
different temperatures also failed to give the desired product.
The use of Lewis acid (ZnCl , AlCl , BF $OEt ) catalysts (thermal
aliphatic protons to aromatic protons 10 : 8 (without consid-
ering 3 protons of methyl group). Based on these observations,
structures 11e and 11f were ruled out, as they contain the ratio
(
9
: 9. Moreover, in 11e and 11f the newly formed double bond
2
3
3
2
remain in ring C, exocyclic to ring B, which we have shown
and MW conditions) did not show any further benecial effect
on the reaction. Thus, 1a did not undergo normal electron
demand Diels–Alder reaction.
Azadienes are known to undergo Diels–Alder reaction by
inverse electron demand pathway. Hence, the reaction of 1a
with electron rich dienophiles was carried out. Accordingly,
when 3,4-dihydro-2H-pyran (DHP) (1 equiv.) (10) was reacted
18
earlier to be improbable. In 11c and 11d, NH is absent and Hc
is expected to give two closely spaced doublets around 3.0–3.5 d.
1
This feature was not seen in the H NMR spectra of A and B.
Hence, 11c and 11d were ruled out. Among 11a and 11b, the
distinguishing proton appears to be Ha, which in the case of
1
2
1b would come downeld compared to that in 11a. In the D O
1
exchanged H NMR spectra of A and B, the NH peak
with 1a, in the presence of ZnCl
compounds A (less polar) and B (more polar) was obtained
Scheme 3).
2
(1 equiv.), a mixture of
(
Scheme 1 Synthesis of 7-methylcoumarin-4-acetic acid (5).
Fig. 1 Possible products in the aza Diels–Alder reaction of 7-methyl-
coumarin-4-azadiene (1a) with dihydropyran (10).
Scheme 2 Synthesis of 7-methylcoumarin-4-azadienes (1).
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disappeared and DHO peak appeared at 4.7 d. Hence, the between H
5
, H4a and H10b. In the case of B there was
structures 11c and 11d were ruled out, as they do not contain enhancement of H4a by 2.50% and there was no NOE observed
1
3
NH proton. Based on C NMR spectra structure 11c was ruled for H10b, because of trans relationship between H –H and
5
4a
out, as it contains a carbon atom which is anked by two elec- H –H (Fig. 2). By observing the NOE effect it was clear that in
5
10b
tronegative atoms, oxygen and nitrogen, and is expected to give the less polar compound (A ¼ 11a) the stereochemical relation
a peak around 80–85 d. Such a peak was not observed in both between H
5
and H4a was cis, while in the more polar compound
0
the spectra. To throw more light on the structure, DQF-COSY (B ¼ 11a ) the relation was trans.
spectra of A and B were recorded and the spectra supported
To establish the structures unequivocally, single crystal XRD
structure 11a. Based on the stereochemical restriction in the was recorded on a Bruker axs kappa apex 2 CCD Diffractometer
Diels–Alder reaction, compound 11a can exists in two diaste- using graphite monochromated Mo Ka radiation (l ¼ 0.71073
0
˚
reomeric forms 11a and 11a . The most diagnostic parameter A). The ORTEP diagram of A and B are shown in Fig. 3. Thus the
for the structural assignment is the scalar coupling constant two compounds, A and B, are diastereomers of each other.
between protons H4a and H
5
. As depicted in Fig. 2, the cis
Compound A (11a) is 4aR*, 5R*, 10bR*-5-(7-methyl-
isomer has small coupling constants JH-5,H-4a ¼ 0 Hz, JH-10b,H-4a coumarin-4-yl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]quin-
0
¼
5 Hz, consistent with an all cis conguration of the hydrogen oline. Compound
B
(11a ) is 4aR*, 5S*, 10bR*-5-(7-
atoms of 4a, 5, and 10b positions. In the trans isomer, the value methylcoumarin-4-yl)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]-
of JH-5,H-4a ¼ 8.5 Hz is large and indicates the anti orientation of quinoline.
the hydrogen atoms of 4a and 5 positions. To get more clari-
In structure 1, diene N appears to be more electron decient
cation about the stereochemical relationship NOE spectra were than diene M. However, in the case of an unsymmetrical poly-
recorded. In both the spectra the signal corresponding to H5 ene system, particularly the one like in the present case, where
(5.10 d in compound A, 4.56 d in compound B) was irradiated. In there is a combination of heteroatoms, electron donating
the case of A the irradiation resulted in intensication of H4a by groups and electron withdrawing groups, the regioselection is
3.89% and H10b by 5.20%; which conrmed the cis arrangement difficult to predict. To through more light on the selectivity, 6
was condensed with benzylamine to obtain corresponding anil
(1i). 1i is devoid of diene component M and has only diene
component N. 1i failed to react with NPMA as well as DHP.
A series of 7-methylcoumarin-4-azadienes were prepared as
per literature method by reacting 7-methylcoumarin-4-
carbaldehyde (6) and anilines (7) in benzene at reux condi-
17
tion (Table 1). All anilines (7) react with 7-methylcoumarin-4-
carbaldehyde (6) to give high yield of 1. Primary aliphatic
benzyl amine reacts very rapidly as compared to other aromatic
amines (entry 9). Due to electron decient nature of 3-nitro-
aniline (1f) and 4-nitroaniline (1e) it took maximum time for
condensation (entry 5 & 6). As expected steric effect is
pronounced in the reaction of 1h with 6, reaction required more
time for completion (entry 8).
The effect of Lewis acid catalyst and solvent on the reaction
was then investigated (Table 2). The reaction of 1a and DHP (10)
could not be effected without a catalyst. Different catalysts were
used for the reaction in 1,2-dichloroethane. Anhydrous Lewis
acids were very effective in catalyzing the reaction, while
0
Fig. 2 Stereochemical relationship between products 11a and 11a .
0
Fig. 3 ORTEP diagram of products 11a (A) and 11a (B).
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Table 1 Preparation of 7-methylcoumarin-4-azadienes (1) by the
reaction of anilines (7) and 7-methylcoumarin-4-carbaldehyde (6)
Based on this study, ZnCl
was selected as the catalyst for the
2
a
reaction and using this catalyst different solvents such as
methanol, ethanol, acetonitrile, dioxane, tetrahydrofuran, 1,2-
dichloroethane and toluene were tried. Except, 1,2-dichloro-
ethane and acetonitrile the reaction did not take place in other
solvents. 1,2-Dichloroethane was the best solvent found for
b
c
Entry
R
Product (1)
Time (min)
Yield of 1 (%)
1
2
3
4
5
6
7
8
9
H
1a
1b
1c
1d
1e
1f
1g
1h
1i
60
30
30
83
84
86
85
72
76
89
80
84
2-OMe
4-Me
4-Br
4-NO
3-NO
4-OMe
2,6-(Me)
—
0
reaction and gave 83% of combined yield of 11a and 11a .
40
At this stage, other parameters, i.e. catalyst loading and
molar ratio of the reactants were studied (Table 3). The yield of
the product considerably improved (83%) using 3 equiv. of
DHP. Further increase in the amount of DHP did not increase
the yield (entries 8 and 9). Also the yield was not signicantly
2
120
110
30
110
20
2
2
a
Reaction conditions: 7-methylcoumarin-4-carbaldehyde (1 mmol), increased by increasing the amount of 7-methylcoumarin-4-
b
aniline (1 mmol), benzene (5 mL), reux temp. Time required for
azadiene (1a) with respect to dienophile. The yield was
c
total consumption of 6. Isolated yield.
2
considerably improved (67%) when one equivalent of ZnCl was
used (entry 2). Further increase in the catalyst loading did not
improve the yield (entries 3 and 4).
Under
methylcoumarin-4-azadienes (1a–1g) were reacted with DHP
10) in the presence of ZnCl to obtain the corresponding aza
the
optimized
conditions,
different
7-
Table 2 The effect of Lewis acids on the aza Diels–Alder reaction of 1a
and 10 in 1,2-dichloroethane
a
(
2
d
Diels–Alder adducts (Scheme 4, Table 4). All the dienes were
reactive and gave the adducts in good yield; however, the time
required for complete consumption of the diene varied
substantially from diene to diene. The reaction with highly
electron decient diene (1e) was very fast, however we were
Yield (%)
b
c
0
11a
Entry
Catalyst
Condition (time)
11a
1
2
3
4
5
6
7
8
9
Without catalyst
Reux (24 h)
Rt (15 min)
NR
57
44
40
32
31
24
59
60
27
29
33
12
20
46
20
BF
BF
3
$OEt
$OEt
2
10
8
0
unable to isolate the more polar product 15a and only less polar
3
2
Reux (5 min)
ꢁ
AlCl
FeCl
3
0 C (2 h)
10
22
06
16
18
23
08
05
14
18
—
14
34
product 15a was isolated in low yield. Reaction of electron rich
dienes 1b and 1g, gave high percentage of a. The reaction of 1h
and 1i did not take place even up to 18 h. It also supported that
adduct was derived from the M diene system. In all the cases “a”
was obtained as the major isomer; the highest being found in
the case of dienes 1a and 1b.
ꢁ
3
0 C (2 h)
AlCl
FeCl
3
Rt (5 min)
Rt (5 min)
Rt (9 h)
3
ZnCl
ZnCl
2
2
Reux (3 h)
Rt (25 min)
Rt (15 min)
Reux (10 h)
Rt (14 h)
10
11
12
13
14
15
16
AlCl
3
$6H
$6H
$2H
Methanolic HCl
Conc. H SO
2
O
FeCl
3
2
O
Other dienophiles like dihydrofuran (DHF) (18) and styrene
ZnCl
2
2
O
(19) were reacted with 1a under the similar conditions (Table 5).
ꢁ
As expected, the reaction proceeded rapidly with electron rich
dienophile; the order being: styrene < DHP < DHF. The reaction
with DHF was very fast as compared to that with DHP. The
diastereomeric ratio was almost the same in the case of DHP
Catalyst and DHF, but changed when the styrene was the dienophile. In
2
4
0 C (5 min)
SnCl
CAN
4
Rt (15 min)
Rt (3 h)
a
Reaction conditions: 7-methylcoumarin-4-azadiene (1 b mmol),
dihydropyran (3 mmol), 1,2-dichloroethane (5 mL).
c
d
(
1 mmol). Time for which reaction was continued. Isolated yield.
the case of DHF, we were unable to isolate the more polar
0
product 20a and only less polar 20a was isolated in low yield.
To ascertain whether the adducts equilibrated, diastereomer
1a was subjected to the same reaction conditions, i.e. 1
hydrated Lewis acids were much less active. Bronsted acids also
1
were not very effective in catalyzing the reaction. In the case of
equivalent of ZnCl in dichloroethane. No sign of conversion to
ꢁ
2
AlCl
3
and FeCl
3
, the reaction at 0 C gave about 50–55%
0
the diastereomer 11a was observed at room temperature (3 h)
0
combined yield of 11a and 11a . When the same reaction was
or even aer 24 h at reux. Also, a 50 : 50 mixture of the dia-
carried out at room temperature, the combined yield of 11a and
0
stereomers (11a + 11a ) did not show any change in the ratio
0
1
1a decreased and substantial amount of a sticky material was
when heated to reux in 1,2-dichloroethane in the presence of 1
equiv. of ZnCl . These results suggested that the 1,3-prototropic
2
shi is not reversible under the reaction conditions.
formed, which was insoluble in organic solvents. SnCl was also
4
effective. ZnCl was found to be not only effective, but was very
2
convenient to use. At room temperature the reaction was slow
and the combined yield was 77% (entry 8). At reux condition
the reaction was fast and gave 83% of yield (entry 9). Hence, all
the reactions were carried out at the reux temperature. CAN
was also effective and in 3 h, 54% of combined yield was
obtained. Except CAN, with all the catalysts 11a was obtained as
In the Diels–Alder reaction of 2-azadiene; both the concerted
19
and stepwise mechanism have been postulated. It has also
been postulated that the reaction mechanism depends on
relative face of approach of reactants, nature of the solvent and
19b,20
dienophile used.
In a stepwise mechanism it is postulated
that dipolar intermediate can be trapped by nucleophiles like
0
the major product, while with CAN, 11a was the major product.
21
methanol, acetic acid. To ascertain the mechanism of the
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a
Table 3 Effect of catalyst loading, concentration of 1a, and molar ratio of 1a : 10 on the reaction of 1a and 10
Molar ratio
(1a : 10)
Combined yield
(11a + 11a ) (%)
b
c
0
0
Entry
ZnCl
2
(equiv.)
Time (h)
% Yield (11a + 11a )
1
2
3
4
5
6
7
8
9
0.5
1
2
3
1
1
1
1
1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 1
1 : 2
1 : 3
1 : 4
1 : 5
6
6
6
6
6
5
3
3
3
39 + 14
49 + 18
51 + 18
42 + 18
46 + 20
52 + 23
60 + 23
61 + 20
61 + 21
53
67
69
60
66
75
83
81
82
a
b
Reaction conditions: 7-methylcoumarin-4-azadiene (1 mmol), 1,2-dichloroethane (5 mL), reux temp. Time for which reaction was continued.
Isolated yield.
c
reaction, an azadiene 1a was reacted with 10 using optimized time shown in Table 1. Aer complete consumption of 6, the
reaction conditions. Addition of nucleophilic solvent like solution was cooled to room temperature. The solid was sepa-
methanol, acetic acid in the reaction of 1a and 10 does not have rated by ltration, followed by washing with cold benzene and
any effect on trapping of polar reaction intermediate which hexane. The mother liquor and washings were combined and
support concerted mechanism for the reaction.
concentrated under reduced pressure. The product 8 was puri-
ed by recrystallization from ethyl acetate.

Experimental
General procedure for the aza Diels–Alder reaction between 1
and 10
7-Methylcoumarin-4-acetic acid, 7-methylcoumarin-4-carbalde-
hyde, 7-methylcoumarin-4-azadienes were prepared by
following the reported methods.
freshly distilled from calcium hydride. The products were
separated and puried by column chromatography using 100–
16,17
7-Methylcoumarin-4-azadiene (1) (1 mmol) and anhydrous
1,2-Dichloroethane was
2
ZnCl (0.136 g, 1 mmol) were stirred in 1,2-dichloroethane
(5 mL) for 15 min and dihydropyran (10) (0.252 g, 3 mmol) was
added slowly at room temperature. The solution was heated to
reux till complete consumption of 1. The solution was cooled
to room temperature, quenched with water (10 mL) and
extracted with chloroform (10 mL). The extract was dried over
anhydrous Na SO . The decanted organic layer was evaporated
2 4
to obtain a sticky mass which was puried by column chro-
2
00 mesh silica gel. Melting points were determined on an
Analab melting point apparatus (Model-mThermocal 10) in open
capillary tubes and are uncorrected. The IR spectra were
recorded on a Jasco-4100 spectrophotometer. H NMR spectra
were recorded on 300 MHz or 500 MHz spectrometers. C NMR
spectra were recorded on 75 MHz or 100 MHz. Chemical shis
are reported in parts per million relative to the central line of
the multiplet at 77.0 ppm for CDCl , 39.5 ppm for DMSO. The
mass spectra were recorded on a Finnigan LCQ Advantage Max
spectrometer. Elemental analysis was carried out with a Thermo
1
1
3
matography on silica gel using chloroform.
7
-Methylcoumarin-4-azadiene (1a). Brown solid; 83%; mp
3
ꢁ
1
48–150 C; FT-IR (KBr): 3054 (aromatic C–H), 2896 (aliphatic
C–H), 1729 (C]O); 1622, 1600 and 1547 (aromatic C]C, C]N);
1
H NMR (300 MHz, CDCl ): d 6.78 (s, 1H, C H), 7.18 (d, 1H, C H,

nnigan, Flash EA 1112 instrument.
3
3
6
0
J ¼ 8.4 Hz), 8.66 (s, 1H, H–C]N-), 7.28–7.38 (m, 3H, C4 –H,
0
0
0
0
C5 –H and C6 -H), 7.45–7.50 (t, 2H, C3 –H and C7 –H, J ¼
General procedure for the synthesis coumarin-4-azadienes (8)
-Methylcoumarin-4-carbaldehyde (6) (1 mmol), and aniline (7)
7
.5 Hz), 8.67 (d, 1H, C5–H, J ¼ 8.4 Hz).
7
4aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
(1 mmol) were reuxed in benzene (5 mL) for an appropriate hexahydro-2H-pyrano[3,2-c]quinoline (11a). White Solid; 209
Scheme 4 The aza Diels–Alder reaction of 7-methylcoumarin-4-azadienes (1) with DHP (10).
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a
Table 4 The aza Diels–Alder reaction of 7-methylcoumarin-4-azadienes (1) with DHP (10)
Products
0
b
c
0
d
d
0
Entry Azadiene (1)
(a)
(a )
Time (h) Ratio (a : a ) (%) Yield a (%) Yield a (%)
1
3
72 : 28
60
23
2
4.5
87 : 13
68
10
3
4
56 : 44
45
35
4
4
56 : 44
43
34
e
5
10
—
36
Unable to isolate
6
1
69 : 31
45
20
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Table 4 (Contd.)
Products
0
b
c
0
d
d
0
Entry Azadiene (1)
(a)
(a )
Time (h) Ratio (a : a ) (%) Yield a (%) Yield a (%)
7
4
59 : 41
47
33
8
No reaction
18
9
No reaction
18
a
Reaction conditions: 7-methylcoumarin-4-azadiene (1 mmol), dihydropyran (3 mmol), 1,2-dichloroethane (5 mL), Reux temp, ZnCl
2
(1 mmol).
Time for which reaction was continued. Ratio a/a obtained by isolating both the products. Isolated yield. Reaction was carried out at room
temperature.
b
c
0
d
e
ꢁ
mg, 60%; mp 275–276 C; FT-IR (KBr): 3348 (NH), 3049 C2a–H, J ¼ 3.5 and 10.5 Hz), 4.01 (bd, 1H, C2b–H), 4.25 (bs, 1H,
(
aromatic C–H), 2947 (aliphatic C–H), 1720 (C]O); 1615, 1588 NH), 4.56 (d, 1H, C5–H, J ¼ 3.5 Hz), 4.97 (d, 1H, C10b–H, J ¼ 8.5
0
and 1553 (aromatic C]C); 1478, 1321, 1252, 1139, 1073, 754 Hz), 6.54 (s, 1H, C3 –H), 6.66 (d, 1H, C7–H, J ¼ 8 Hz), 6.85 (t, 1H,
ꢀ
1
1
0
cm ; H NMR (500 MHz, CDCl
3
): d 1.41–1.61 (m, 4H, C3–H and C9–H, J ¼ 7 Hz), 7.16 (d, 1H, C6 –H, J ¼ 8.0 Hz), 7.20 (dt, 1H, C8–
0
C4–H), 2.47 (m, 1H, C4a–H), 2.53 (s, 3H, CH
3
) 3.48 (td, 1H, H, J ¼ 1.5 and 7 Hz), 7.26 (s, 1H, C8 –H), 7.35 (dd, 1H, C10–H, J
0
13
C2a–H, J ¼ 2.5 and 10.5 Hz), 3.66 (dd, 1H, C2b–H, J ¼ 2.5 and ¼ 1.5 and 7.0 Hz), 7.88 (bs, 1H, C5 –H); C NMR (75 MHz,
0.5 Hz), 3.82 (bs, 1H, NH), 5.10 (s, 1H, C5–H), 5.47 (d, 1H, CDCl ): 21.6 (CH ), 23.0 (C3), 24.3 (C4), 36.5 (C4a), 53.0 (C5),
1
3
3
0
0
0
0
C10b–H, J ¼ 5 Hz), 6.74 (d, 1H, C7–H, J ¼ 8 Hz), 6.77 (s, 1H, C3 – 66.1 (C2), 72.3 (C10b), 113.8 (C3 ), 114.2 (C4a ), 115.4 (C8 ), 117.7
H), 6.93 (t, 1H, C9–H, J ¼ 7.5 Hz), 7.18–7.21 (m, 2H, C8–H and (C7), 118.3 (C9), 119.5 (C8), 124.6 (C10a), 125.4, 129.3, 130.0,
0
0
0
0
0
0
0
C6 –H), 7.26 (s, 1H, C8 –H), 7.51 (d, 2H, C10–H and C5 –H, J ¼ 8 143.2 (C6a), 143.3 (C7 ), 154.2 (C4 ), 156.2 (C8a ), 161.0 (C2 ); MS
1
3
Hz); C NMR (75 MHz, CDCl
3
): 18.5 (C3), 21.5 (CH
3
), 25.2 (C4), ¼ 348.5 (M + H); anal. calcd for C22
3
H21NO (347.41): C, 76.06; H,
0
3
5.6 (C4a), 54.3 (C5), 60.4 (C2), 72.1 (C10b), 112.1 (C3 ), 114.9 6.09; N, 4.03% found: C, 76.14; H, 6.13; N, 3.96%.
0
0
(C4a ), 115.3 (C8 ), 117.8 (C7), 119.2 (C9), 119.9 (C10a), 122.9,
4aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
0
0
0
1
1
(
25.6, 127.5, 128.3, 143.2 (C7 ), 144.3 (C6a), 154.0 (C4 and C8a ), hexahydro-7-methoxy-2H-pyrano[3,2-c]quinoline (12a). Pale
0
ꢁ
60.8 (C2 ); MS ¼ 348.5 (M + H); anal. calcd for C H NO
yellow solid; 257 mg, 68%; mp 291–293 C; FT-IR (neat): 3324
2
2
21
3
347.41): C, 76.06; H, 6.09; N, 4.03% found: C, 76.19; H, 6.04; N, (NH), 2865 (aliphatic C–H), 1702 (C]O); 1611, 1553 and 1504
ꢀ1
4
.11%.
(aromatic C]C); 1330, 1254, 1172, 1138, 1087, 866, 815 cm ;
1
4
aR*,5S*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
3
H NMR (500 MHz, CDCl ): d 1.44 (bd, 1H, C3a–H), 1.55–1.67
0
hexahydro-2H-pyrano[3,2-c]quinoline (11a ). Brown Solid; 80 (m, 3H, C3b–H and C4–H), 2.49–2.51 (m, 1H, C4a–H), 2.55 (s,
mg, 23%; mp 174–176 C; FT-IR (KBr): 3322 (NH), 2941 3H, CH
ꢁ
3
), 3.52 (td, 1H, C2a–H, J ¼ 2.5 and 10.5 Hz), 3.68 (dd, 1H,
(
aliphatic C–H), 1708 (C]O); 1619, 1533 and 1494 (aromatic C2b–H, J ¼ 2.5 and 10.5 Hz), 3.95 (s, 3H, OCH
3
), 4.26 (bs, 1H,
ꢀ1 1
C]C); 1315, 1268, 1144, 1067, 756 cm ; H NMR (500 MHz, NH), 5.08 (s, 1H, C5–H), 5.51 (d, 1H, C10b–H, J ¼ 5 Hz), 6.83
0
CDCl ): d 1.53–1.56 (m, 1H, C3a–H), 1.68–1.91 (m, 3H, C3b–H (d, 1H, C10–H, J ¼ 7.5 Hz), 6.88–6.91 (m, 2H, C3 –H and C9–H),
3
0
and C4–H), 2.47 (bs, 1H, C4a–H), 2.52 (s, 3H, CH ) 3.75 (td, 1H, 7.17 (d, 1H, C8–H, J ¼ 7.5 Hz), 7.21 (d, 1H, C6 –H, J ¼ 8 Hz), 7.29
3
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Table 5 The aza Diels–Alder Reaction of 1a and dihydropyran/dihydrofuran/styrene
Products
0
b
c
0
d
d
0
Entry
Dienophile
(a)
(a )
Time (h)
Ratio (a : a ) (%)
Yield a (%)
Yield a (%)
1
3
72 : 28
60
23
e
2
1.5
66 : 34
30
Unable to isolate
3
4
60 : 40
48
32
a
2
Reaction conditions: 7-methylcoumarin-4-azadiene (1 mmol), dienophile (3 mmol), 1,2-dichloroethane (5 mL), reux temp, ZnCl (1 mmol).
T1ime for which reaction was continued. Ratio a/a obtained by isolating both the product. Isolated yield. Ratio a/a obtained from mixture
b
c
0
d
e
0
of H NMR.
0
0
13
(
s, 1H, C8 –H), 7.53 (d, 1H, C5 –H, J ¼ 8 Hz); C NMR (75 MHz,
4aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
CDCl ): d 18.7 (C3), 21.6 (CH ), 25.2 (C4), 35.6 (C4a), 54.2 (OCH ) hexahydro-9-methyl-2H-pyrano[3,2-c]quinoline (13a). Yellow
5.5 (C5), 60.7 (C2), 72.3 (C10b), 108.6 (C8), 112.4 (C3 ), 115.0 solid; 163 mg, 45%; mp 184–186 C; FT-IR (neat): 3370 (NH),
C4a ), 117.9 (C8 ), 118.1 (C7), 118.1 (C9), 119.3 (C10), 120.0 2926 (aliphatic C–H), 1728 (C]O); 1617, 1585 and 1554
C10a), 122.9 (C6 ), 125.6 (C5 ), 134.0 (C6a), 143.3 (C7 ), 146.7 (aromatic C]C); 1487, 1326, 1244, 1179, 1135, 1089, 861, 744
3
3
3
0
ꢁ
5
0
0
(
(
(
0
0
0
0
0
0
ꢀ1
1
C7), 154.0 (C4 ), 154.1 (C8a ), 161.0 (C2 ); MS ¼ 378.5 (M + H); cm ; H NMR (500 MHz, CDCl ): d 1.43 (bd, 1H, C4–H), 1.55–
3
anal. calcd for C23
Found: C, 73.03; H, 6.19; N, 3.57%.
aR*,5S*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b- 10.5 Hz), 3.68 (m, 2H, C2b–H and NH), 5.07 (s, 1H, C5–H), 5.46
4
3
H23NO (377.43): C, 73.19; H, 6.14; N, 3.71%. 1.66 (m, 3H, C3–H and C4b–H), 2.37 (s, 3H, CH ), 2.46–2.49 (m,
1H, C4a–H), 2.55 (s, 3H, CH ), 3.52 (td, 1H, C2a–H, J ¼ 2.5 and
3
4
0
hexahydro-7-methoxy-2H-pyrano[3,2-c]quinoline (12a ). Yellow (d, 1H, C10b–H, J ¼ 5.5 Hz), 6.69 (d 1H, C7–H, J ¼ 8 Hz), 6.80 (s,
ꢁ
0
0
Solid; 38 mg, 10%; mp 163–165 C; FT-IR (neat): 3416 (NH), 2923 1H, C3 –H), 7.03 (d, 1H, C8–H, J ¼ 8 Hz), 7.21 (d, 1H, C6 –H, J ¼
0
and 2855 (aliphatic C–H), 1713 (C]O); 1620, 1556 and 1503 8 Hz), 7.28 (s, 1H, C10–H), 7.35 (s, 1H, C8 –H), 7.53 (d, 1H,
ꢀ1
1
0
13
(
aromatic C]C); 1299, 1266, 1187, 1134, 1085, 865, 822 cm ; H C5 –H, J ¼ 8 Hz). C NMR (75 MHz, CDCl ): 18.5 (C3), 20.7
3
3
3 3
NMR (500 MHz, CDCl ): d 1.57–1.60 (m, 1H, C3a–H), 1.72–1.82 (CH ), 21.6 (CH ), 25.27 (C4), 35.9 (C4a), 54.5 (C5), 60.6 (C2),
0 0 0
m, 3H, C3b–H and C4–H), 2.49 (bs, 1H, C4a–H), 2.54 (s, 3H, 72.3 (C10b), 112.3 (C3 ), 115.0 (C4a ), 115.4 (C8 ), 117.9 (C7),
(
0
0
CH ), 3.76 (td, 1H, C2a–H, J ¼ 2.5 and 10.5 Hz), 3.90 (s, 3H, 119.9 (C10a), 122.9 (C8), 125.7 (C10), 127.8 (C6 ), 128.7 (C6a ),
3
0
0
0
0
OCH ), 4.00 (bd, 1H, C2b–H), 4.25 (bs, 1H, NH), 4.62 (d, 1H, 129.1 (C5 ), 141.8 (C9), 143.3 (C7 ), 154.0 (C4 ), 154.1 (C8a ),
3
0
0
C5–H, J ¼ 3.5 Hz), 4.97 (d, 1H, C10b–H, J ¼ 8 Hz), 6.54 (s, 1H, C3 – 161.0 (C2 ); MS ¼ 362.5 (M + H). Anal. calcd for C H NO
2
3
23
3
H), 6.80–6.84 (m, 2H, C8–H and C10–H), 7.02 (t, 1H, C9–H, J ¼ 8 (361.43): C, 76.43; H, 6.41; N, 3.88%. Found: C, 76.58; H, 6.62; N,
0
0
Hz), 7.18 (d, 1H, C6 –H, J ¼ 8 Hz), 7.28 (s, 1H, C8 –H), 7.88 (bs, 3.92%.
0
1
(
3
H, C5 –H); MS ¼ 378.6 (M + H); anal. calcd for C23
H
23NO
4
4aR*,5S*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
0
377.43): C, 73.19; H, 6.14; N, 3.71%. Found: C, 73.09; H, 6.22; N, hexahydro-9-methyl-2H-pyrano[3,2-c]quinoline (13a ). White
ꢁ
.63%.
Solid; 127 mg, 35%; mp 234–235 C; FT-IR (neat): 3408 (NH),
3062 (aromatic C–H), 1710 (C]O); 1620, 1586, 1557 and 1499
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ꢀ
1
(
aromatic C]C); 1447, 1313, 1244, 1141, 1082, 822, 749 cm
;
1497 (aromatic C]C); 1552 and 1365 (NO
2
), 1316, 1267, 1132,
1
ꢀ1
1
H NMR (500 MHz, CDCl ): d 1.53–1.58 (m, 1H, C3a–H), 1.70– 1089, 822, 748 cm ; H NMR (300 MHz, CDCl + DMSO): d
3
3
1
.88 (m, 3H, C3b–H and C4–H), 2.35 (s, 3H, CH ), 2.47 (bs, 1H, 1.25–1.53 (m, 4H, C3–H and C4–H), 2.48 (s, 3H, CH ), 2.59 (bt,
3
3
C4a–H), 2.54 (s, 3H, CH ) 3.77 (td, 1H, C2a–H, J ¼ 2.5 and 10.5 1H, C4a–H, merged in DMSO), 2.89 (bs, 1H, NH, merged in
3
Hz), 4.05 (bd, 1H, C2b–H), 4.52 (bs, 1H, NH), 4.54 (d, 1H, C5–H, shied DMSO water), 3.41 (td, 1H, C2a–H, J ¼ 2.5 and 10.5 Hz),
0
J ¼ 3 Hz), 4.97 (d, 1H, C10b–H, J ¼ 8.5 Hz), 6.55 (s, 1H, C3 –H), 3.65 (dd, 1H, C2b–H, J ¼ 2.5 and 10.5 Hz), 5.18 (s, 1H, C5–H),
0
6
7
1
2
.61 (d, 1H, C7–H, J ¼ 8.0), 7.04 (d, 1H, C8–H, J ¼ 8.0 Hz), 7.16– 5.38 (d, 1H, C10b–H, J ¼ 5.7 Hz), 6.61 (s, 1H, C3 –H), 6.86 (d, 1H,
0
0
0
.18 (m, 2H, C10–H and C6 –H), 7.27 (s, 1H, C8 –H), 7.93 (bs, C7–H, J ¼ 9.3 Hz), 7.18 (d, 1H, C6 –H, J ¼ 8 Hz), 7.20 (s, 1H,
0
13
0
0
H, C5 –H). C NMR (75 MHz, CDCl
3
): d 21.7 (2CH
3
), 23.1 (C3), C8 –H) 7.54 (d, 1H, C5 –H, J ¼ 8 Hz), 7.96 (dd, 1H, C8–H, J ¼ 2.7
4.5 (C4), 36.6 (C4a), 55.6 (C5), 60.1 (C2), 72.1 (C10b), 109.3 and 9.3 Hz), 8.26 (d, 1H, C10–H, J ¼ 2.4 Hz). MS ¼ 393.3 (M + H);
0 0 0
C3 ), 113.8 (C8 ), 115.5 (C4a ), 117.3 (C7), 117.8 (C8), 119.4 anal. calcd for C H N O (392.40): C, 67.34; H, 5.14; N, 7.14%.
22 20 2 5
(
(
(
0
0
C10a), 121.6 (C10), 124.7 (C6 ), 125.5 (C5 ), 133.3 (C6a), 143.3 Found: C, 67.47; H, 5.08; N, 7.06%.
C7 ), 146.0 (C9), 154.3 (C4 ), 156.2 (C8a ), 161.2 (C2 ); MS ¼
0
0
0
0
4aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
(361.43): C, 76.43; H, hexahydro-10-nitro-2H-pyrano[3,2-c]quinoline (16a). Yellow
3
62.5 (M + H); anal. Calcd for C23
.41; N, 3.88%. Found: C, 76.63; H, 6.33; N, 3.75%.
H
23NO
3
ꢁ
6
solid; 177 mg, 45%; mp 270–272 C; FT-IR (neat): 3419 (NH),
4
aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b- 3066 (aromatic C–H), 2953 and 2865 (aliphatic C–H), 1715
hexahydro-9-bromo-2H-pyrano[3,2-c]quinoline (14a). White (C]O); 1612, 1528 and 1484 (aromatic C]C); 1577 and 1377
ꢁ
ꢀ1
1
solid; 186 mg, 43%; mp 215–217 C; FT-IR (KBr): 3345 (NH), (NO ), 1334, 1271, 1136, 1079, 798, 723 cm ; H NMR (300
2
2
1
923 and 2854 (aliphatic C–H), 1699 (C]O); 1615, 1599 and MHz, CDCl ): d 1.25–1.58 (m, 4H, C3–H and C4–H), 2.42–2.47
3
ꢀ
1 1
500 (aromatic C]C); 1322, 1265, 1087, 1039, 871, 810 cm ; H (m, 4H, CH and C4a–H), 3.09–3.14 (m, 1H, C2a–H), 3.57 (d, 1H,
3
NMR (300 MHz, CDCl
3
): d 1.25–1.65 (m, 4H, C3–H and C4–H), C2b–H, J ¼ 10.5 Hz), 4.19 (s, 1H, NH), 5.02 (s, 1H, C5–H), 5.70 (d,
0
2.39–2.41 (bd, 1H, C4a–H), 2.46 (s, 3H, CH
3
), 3.41 (td, 1H, 1H, C10b–H, J ¼ 6.0 Hz), 6.63 (s, 1H, C3 –H), 6.88 (d, 1H, C7–H,
C2a–H, J ¼ 2.5 and 10.0 Hz), 3.60 (dd, 1H, C2b–H, J ¼ 2.5 and J ¼ 8.4 Hz), 6.98 (d, 1H, C9–H, J ¼ 7.8 Hz) 7.15–7.44 (m, 4H,
0
0
0
13
10.0 Hz), 3.89 (s, 1H, NH), 5.00 (s, 1H, C5–H), 5.34 (d, 1H, C10b– C8–H, C6 –H, C8 –H and C5 –H); C NMR (75 MHz, CDCl
3
): d
0
H, J ¼ 5.7 Hz), 6.59 (d, 1H, C7–H, J ¼ 8.4 Hz), 6.66 (s, 1H, C3 –H), 17.7 (C3), 20.8 (CH
3
), 23.8 (C4), 33.7 (C4a), 53.0 (C5), 60.9 (C2),
0
0
0
0
0
7
.13 (d, 1H, C6 –H, J ¼ 8 Hz), 7.17 (s, 1H, C8 –H) 7.20 (dd, 1H, 68.6 (C10b), 111.4 (C4), 111.7 (C3 ), 111.8 (C8 ), 114.0 (C4a ),
0
0
C8–H, J ¼ 2.4 and 8 Hz), 7.43 (d, 1H, C5 –H, J ¼ 8 Hz), 7.54 (d, 116.9 (C7), 117.7 (C8), 122.5, 125.1, 128.0 (C9), 142.7 (C7 ), 146.5
1
3
0
0
0
1
2
(
(
(
(
H, C10–H, J ¼ 2.4 Hz). C NMR (75 MHz, CDCl ): d 18.6 (C3), (C6a), 150.5 (C10), 152.4 (C8a ), 153.1 (C4 ), 160.0 (C2 ); MS ¼
3
3 20 2 5
1.6 (CH ), 25.1 (C4), 35.3 (C4a), 54.3 (C5), 60.8 (C2), 71.5 393.3 (M + H); anal. calcd for C22H N O (392.40): C, 67.34; H,
0 0 0
C10b), 111.4 (C4a ), 112.2 (C3 ), 114.8 (C9), 117.0 (C8 ), 118.0 5.14; N, 7.14%. Found: C, 67.22; H, 5.02; N, 7.00%.
0
0
0
C7 ), 122.2 (C10a), 122.9 (C6 ), 125.8 (C5 ), 130.2 (C8), 131.3
C10), 143.3 (C6a), 143.6 (C7 ), 153.7 (C4 ), 154.0 (C8a ), 160.8 hexahydro-10-nitro-2H-pyrano[3,2-c]quinoline (16a ). Brown
4aR*,5S*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
0
0
0
0
0
ꢁ
C2 ); MS ¼ 427.4 (M + H). Anal. calcd for C22
H20BrNO (426.30): solid; 79 mg, 20%; mp 178–180 C; FT-IR (neat): 3351 (NH), 2955
3
C, 61.98; H, 4.73; N, 3.29%. Found: C, 61.89; H, 4.80; N, 3.43%. and 2859 (aliphatic C–H), 1713 (C]O); 1617, 1589 and 1496
4
aR*,5S*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b- (aromatic C]C); 1528 and 1361 (NO ), 1319, 1270, 1134, 1079,
2
0
ꢀ1
1
hexahydro-9-bromo-2H-pyrano[3,2-c]quinoline (14a ). White 824, 720 cm ; H NMR (300 MHz, CDCl ): d 1.4–1.9 (m, 4H,
solid; 144 mg, 34%; mp 275–276 C; FT-IR (KBr): 3369 (NH), C3–H and C4–H), 2.46–2.47 (m, 4H, CH
3
ꢁ
3
and C4a–H), 3.64–3.99
2
952 and 2869 (aliphatic C–H), 1711 (C]O); 1617, 1600, 1513 (m, 2H, C2a–H and C2b–H), 4.46 (bs, 1H, NH), 4.58 (d, 1H,
ꢀ1 1
and 1484 (aromatic C]C); 1303, 1271, 1133, 1087, 806 cm ; H C5–H, J ¼ 3.6 Hz), 5.13 (d, 1H, C10b–H, J ¼ 8 Hz), 6.37 (s, 1H,
0
0
NMR (300 MHz, CDCl
3
): d 1.49–1.86 (m, 4H, C3–H and C4–H), C3 –H), 6.80 (t, 1H, C8–H, J ¼ 8.0), 7.13 (d, 1H, C6 –H, J ¼ 8.1
0
2.35 (bs, 1H, C4a–H), 2.45 (s, 3H, CH
3
), 3.63–3.70 (m, 1H, Hz), 7.22 (m, 2H, C7–H and C8 –H, J ¼ 2.1 and 9 Hz), 7.60 (dd,
0
C2a–H), 3.85–3.89 (m, 1H, C2b–H), 4.27 (s, 1H, NH), 4.46 (d, 1H, 1H, C9–H, 2.1 and 8.0 Hz), 7.64 (d, 1H, C5 –H, J ¼ 8.1 Hz); MS ¼
C5–H, J ¼ 3.6 Hz), 4.83 (d, 1H, C10b–H, J ¼ 8 Hz), 6.38 (s, 1H, 393.5 (M + H); anal. calcd for C H N O (392.40): C, 67.34; H,
2
2
20 2 5
0
0
C3 –H), 6.54 (d, 1H, C7–H, J ¼ 8.4), 7.10 (d, 1H, C6 –H), 7.16 (s, 5.14; N, 7.14%. Found: C, 67.17; H, 5.10; N, 7.23%.
0
1H, C8 –H), 7.23 (dd, 1H, C8–H, 2.1 and 8.7 Hz), 7.40 (d, 1H,
4aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b-
0
13
C10–H, J ¼ 2.1 Hz), 7.70 (d, 1H, C5 –H, J ¼ 8.1 Hz). C NMR (75 hexahydro-9-methoxy-2H-pyrano[3,2-c]quinoline (17a). Yellow
ꢁ
MHz, CDCl
3
): 21.7 (CH
3
), 23.8 (C3), 24.3 (C4), 36.1 (C4a), 55.6 solid; 177 mg, 47%; mp 232–234 C; FT-IR (KBr): 3344 (NH),
0
0
(
C5), 60.7 (C2), 71.5 (C10b), 109.9 (C4a ), 113.7 (C3 ), 115.2 (C9), 2945 (aliphatic C–H), 1711 (C]O); 1619, 1550 and 1501
0 0 0 0
15.8 (C8 ), 117.9 (C7 ), 121.3 (C10a), 124.2 (C6 ), 125.6 (C5 ), (aromatic C]C); 1443, 1320, 1262, 1232, 1147, 1067, 862, 817
1
1
1
0
0
ꢀ1
1
32.1 (C8), 132.3 (C10), 142.2 (C6a), 143.5 (C7 ), 154.2 (C4 ), cm ; H NMR (300 MHz, CDCl ): d 1.48–1.83 (m, 4H, C3–H and
55.6 (C8a ), 161.0 (C2 ); MS ¼ 427.4 (M + H); anal. calcd for C4–H), 2.38–2.39 (bd, 1H, C4a–H), 2.45 (s, 3H, CH ), 3.64–3.72
3
0
0
3
C H BrNO (426.30): C, 61.98; H, 4.73; N, 3.29%. Found: C, (m, 1H, C2a–H), 3.77 (s, 3H, OCH ), 3.92 (m, 2H, NH, C2b–H),
2
2
20
3
3
6
1.87; H, 4.76; N, 3.44%.
4.48 (d, 1H, C5–H, J ¼ 3.6 Hz), 4.85 (d, 1H, C10b–H, J ¼ 8 Hz),
0
4
aR*,5R*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b- 6.46 (s, 1H, C3 –H), 6.56 (d, 1H, C7–H, J ¼ 8.4), 6.77 (dd, 1H,
hexahydro-9-nitro-2H-pyrano[3,2-c]quinoline (15a). Yellow C8–H, J ¼ 2.7 and 8.4 Hz), 6.87 (d, 1H, C10–H, J ¼ 2.7 Hz), 7.09
ꢁ
0
0
0
solid; 142 mg, 36%; mp 303–305 C; FT-IR (neat): 3302 (NH), (d, 1H, C6 –H, J ¼ 8 Hz), 7.19 (s, 1H, C8 –H), 7.81 (d, 1H, C5 –H,
1
3
2933 and 2889 (aliphatic C–H), 1702 (C]O); 1612, 1587 and J ¼ 8 Hz); C NMR (75 MHz, CDCl
3 3
): d 18.5 (C3), 21.6 (CH ), 25.2
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(
1
C4), 35.8 (C4a), 54.6 (OCH
3
), 55.9 (C5), 60.8 (C2), 72.4 (C10b), ¼ 368.4 (M + H); anal. calcd for C25
H
21NO
2
(367.44): C, 81.59; H,
0
0
11.8 (C3), 112.3 (C8), 115.0 (C4a ), 115.4 (C9), 116.6 (C7 ), 117.9 5.76; N, 3.81%. Found: C, 81.59; H, 5.82; N, 3.75%.
0 0 0
0
(
(
3
C8 ), 121.2 (C10a), 122.9 (C6 ), 125.6 (C5 ), 138.1 (C6a), 143.3
C7 ), 153.5 (C9), 154.0 (C4 ), 154.2 (C8a ), 161.0 (C2 ); MS ¼
0
0
0
Conclusions
78.4 (M + H); anal. calcd for C23
.14; N, 3.71%. Found: C, 73.34; H, 6.21; N, 3.66%.
aR*,5S*,10bR*-5-(7-methylcoumarin-4-yl)-3,4,4a,5,6,10b- with substituted anilines gives 7-methylcoumarin-4-azadienes
4
H23NO (377.43): C, 73.19; H,
6
In conclusion, the reaction of 7-methylcoumarin-4-carbaldehyde
4
0
hexahydro-9-methoxy-2H-pyrano[3,2-c]quinoline (17a ). Greenish (1). These azadienes provide two azadiene components, one
yellow solid; mp 180–181 C; FT-IR (KBr): 3329 (NH), 2970 involving coumarin 3,4-double bond (N) and the other involving
ꢁ
(aliphatic C–H), 125 mg, 33%; 1712 (C]O); 1611, and 1501 the aniline ring (M). The two dienes differ markedly in reactivity.
(
8
aromatic C]C); 1442, 1366, 1230, 1218, 1158, 1077, 1038, 921, Compound 1 does not undergo normal electron demand Diels–
ꢀ1 1
21 cm ; H NMR (300 MHz, CDCl ): d 1.34–1.60 (m, 4H, C3–H Alder reaction similar to 4-styrylcoumarin. It undergoes regio-
3
and C4–H), 2.39 (bs, 1H, C4a–H) 2.46 (s, 3H, CH
C2a–H), 3.53 (s, 1H, NH) 3.61 (dd, 1H, C2b–H), 3.79 (s, 3H, OCH
3
) 3.42 (td, 1H, specic inverse electron demand Diels–Alder reaction involving
diene M, with dienophiles dihydropyran, dihydrofuran, and
3
)
4
.96 (s, 1H, C5–H), 5.38 (d, 1H, C10b–H, J ¼ 5.5 Hz), 6.64 (d 1H, styrene. The reaction requires a Lewis acid catalyst and the ZnCl
2
0
C7–H, J ¼ 9.0 Hz), 6.73 (s, 1H, C3 –H), 6.76 (dd, 1H, C8–H, J ¼ 2.7 is the best catalyst. The solvent has profound effect on the reac-
0
and 8 Hz), 7.03 (d, 1H, C10–H), 7.13 (d, 1H, C6 –H, J ¼ 8 Hz), 7.19 tion; 1,2-dichloroethane is the best solvent. In the reaction
0
0
(
s, 1H, C8 –H), 7.45 (d, 1H, C5 –H, J ¼ 8 Hz); MS ¼ 378.6 (M + H); unequal amounts of two diastereomeric products are formed.
anal. calcd for C H NO (377.43): C, 73.19; H, 6.14; N, 3.71%. The reaction provides an entry into coumarinyl substituted
2
3
23
4
Found: C, 73.29; H, 6.23; N, 3.79%.
a,4,9b-(all cis)-4-(7-methylcoumarin-4-yl)-2,3,3a,4,5,9b-
pyranoquinolines.
3
hexahydrofuro[3,2-c]quinoline (20a). White Solid; 100 mg, 30%;
mp 284–285 C; FT-IR (KBr): 3365 (NH), 3062 (aromatic C–H),
Acknowledgements
ꢁ
2
1
962 and 2871 (aliphatic C–H), 1714 (C]O); 1608, 1591 and Authors are thankful to Prof. K.V.R. Chary, TIFR, Mumbai, India
485 (aromatic C]C); 1362, 1261, 1187, 1151, 872, 829, 750 for providing 2D NMR facility and for interpretation of the
ꢀ
1 1
cm ; H NMR (300 MHz, CDCl ): d 1.76–1.83 (m, 1H, C3a–H) results and Dr Vasuki, G. Department of Physics, Kunthavai
3
2
.1–2.25 (m, 1H, C3b–H), 2.46 (s, 3H, CH ), 2.64–2.74 (bm, 1H, Naachiar Government Arts College (W) (Autonomous),
3
C3a–H), 3.87 (m, 1H, C2a–H), 4.03 (m, 1H, C2b–H), 4.17 (bs, 1H, Thanjavur-7, India, for providing single crystal X-ray facility.
NH), 4.23 (d, 1H, C4–H, J ¼ 10.2 Hz), 4.65 (d, 1H, C9a–H, J ¼ 5.7
0
Hz), 6.55 (s, 1H, C3 –H), 6.67 (d, 1H, C6–H, J ¼ 7.5 Hz), 6.87 (t,
Notes and references
0
1
H, C8–H, J ¼ 2 and 8 Hz), 7.10 (d, 1H, C6 –H, J ¼ 8.1 Hz), 7.17
0
(
7
dd, 1H, C7–H, J ¼ 8), 7.21 (s, 1H, C8 –H), 7.42 (d, 1H, C9–H, J ¼
1 (a) M. P. S. Ishar, G. Singh, S. Singh, K. K. Sreenivasan and
G. Singh, Bioorg. Med. Chem. Lett., 2006, 16, 1366–1370; (b)
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0
.8 Hz), 7.85 (d, 1H, C5 –H, J ¼ 7.8 Hz); MS ¼ 334.5 (M + H);
anal. calcd for C H NO (333.38): C, 75.66; H, 5.74; N, 4.20%.
2
1
19
3
Found: C, 75.78; H, 5.85; N, 4.12%.
2
,4(cis)-2-(7-methylcoumarin-4-yl)-1,2,3,4-tetrahydro-4-phenyl-
quinoline (21a). Pale yellow solid; 176 mg, 48%; mp 195–196 C;
FT-IR (neat): 3328 (NH), 2962 and 2863 (aliphatic C–H), 1703
ꢁ
(
C]O); 1615, 1555 and 1486 (aromatic C]C); 1321, 1255, 1186,
061, 867, 772, 701, 755 cm ; H NMR (400 MHz, DMSO): d
2 (a) M. L ´a cov ´a , H. Stankovi ˆc ov ´a and Z. Odlerova, Farmaco,
1995, 50, 885–888; (b) H. M. El-Shaaer, P. Folt ´ı nov ´a ,
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ˇ
´
ꢀ
1 1
1
1
3
.96–2.02 (m, 1H, C3a–H) 2.39 (d, 1H, C3b–H, J ¼ 12 Hz), 2.41 (s,
H, CH ), 4.44 (dd, 1H, C4–H, J ¼ 5 and 12 Hz), 5.08 (d, 1H,
3
0
C2–H, J ¼ 8.8 Hz), 6.17 (s, 1H, C3 –H), 6.39–6.47 (m, 2H, C6–H
0
and C8–H, J ¼ 8 Hz), 6.58 (s, 1H, C8 –H) 6.74 (d, 1H, C5–H, J ¼
3 (a) S. Kirkiacharian, D. T. Thuy, S. Sicsic, R. Bakhchinian,
R. Kurkijan and T. Tonnaire, Farmaco, 2002, 57, 703–708;
(b) P. C. M. Mao, J. F. Mouscadet, H. Leh, C. Auclair and
L. Y. Hsu, Chem. Pharm. Bull., 2002, 50, 1634–1637.
0
7
.8 Hz), 6.95 (t, 1H, PhH, J ¼ 7 Hz), 7.19–7.33 (m, 6H, C6 –H, C7–
0
H, 4PhH), 7.92 (d, 1H, C5 –H, J ¼ 8.3 Hz); MS ¼ 368.3 (M + H).
Anal. calcd for C25
2
H21NO (367.44): C, 81.72; H, 5.76; N, 3.81%.
Found: C, 81.64; H, 5.85; N, 3.74%.
4 (a) P. G. Maddela, R. G. Narendar, K. Srinu, J. Manjulatha,
P. S. Venkata, K. O. Pramod, I. K. Javed and A. Kumar,
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,4-(trans)-2-(7-methylcoumarin-4-yl)-1,2,3,4-tetrahydro-4-
0
phenylquinoline (21a ). Greenish yellow solid; 119 mg, 32%; mp
26–228 C; FT-IR (neat): 3366 (NH), 3025 (aromatic C–H), 2871
ꢁ
2
(aliphatic C–H), 1714 (C]O); 1615, 1554 and 1503 (aromatic
ꢀ
1 1
C]C); 1321, 1259, 1186, 1146, 870, 755 cm ; H NMR (400
MHz, DMSO): d 1.83–1.90 (bs, 1H, C3a–H) 2.35 (bs, 1H, C3b–H),
2
.40 (s, 3H, CH
3
), 4.35–4.43 (m, 1H, C4–H), 5.04 (bs, 1H, NH),
0
5.39–5.41 (m, 1H, C2–H), 6.54 (s, 1H, C3 –H), 6.67–6.69 (m, 2H,
0
ArH), 6.95–7.22 (m, 9H, ArH), 7.90 (d, 1H, C5 –H, J ¼ 8.0 Hz); MS
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