Triethylammonium acetate-mediated domino-Knoevenagel-hetero-Diels-Alder reaction: Synthesis of some angular polyheterocycles

Article abstract of DOI:10.1007/s00706-012-0873-7

A solvent-cum catalyst, ionic liquid triethylammonium acetate-mediated one-pot procedure for the synthesis of some new angular benzopyrano[3,4-c] pyrano-fused pyrazoles, all of which incorporate a tertiary ring junction carbon, has been developed. The stereochemistry of the products has been confirmed by single-crystal X-ray diffraction data.

Full text of DOI:10.1007/s00706-012-0873-7

Monatsh Chem (2013) 144:865–878
DOI 10.1007/s00706-012-0873-7
ORIGINAL PAPER
Triethylammonium acetate-mediated domino-Knoevenagel-
hetero-Diels–Alder reaction: synthesis of some angular
polyheterocycles
•
Narsidas J. Parmar Bhavesh R. Pansuriya Hitesh A. Barad
•
•
•
Bhagyashri D. Parmar Rajni Kant Vivek K. Gupta
•
Received: 8 April 2012 / Accepted: 10 October 2012 / Published online: 28 November 2012
Ó Springer-Verlag Wien 2012
Abstract A solvent-cum catalyst, ionic liquid triethyl-
ammonium acetate-mediated one-pot procedure for the
synthesis of some new angular benzopyrano[3,4-c]pyrano-
fused pyrazoles, all of which incorporate a tertiary ring
junction carbon, has been developed. The stereochemistry
of the products has been confirmed by single-crystal X-ray
diffraction data.
heterosteroids [14–16] possessing this skeleton have signif-
icantly improved the biological function. In this context, it is
of interest to develop these polycyclic compounds.
The domino reaction continues to be a powerful tool to
access a large number of polyheterocycles. Specifically, the
one that assembles a,b-unsaturated carbonyl compounds
derived from a suitable aldehyde substrate with an active
methylene unit has been widely exploited [17–27]; it
can be carried out in tandem with many fundamental
reactions, such as the domino-Knoevenagel-hetero-Diels–
Alder (DKHDA) reaction, Michael addition, ene reaction,
and/or sigmatropic rearrangement [28–36]. Covering Tie-
tze’s pioneering work [34, 37–45] and others in this area,
there seem to be extensive literature reports concerning the
use of aldehyde substrates. To the best of our knowledge,
no reports exist on ketone-based substrates, although the
Knoevenagel adduct is known. So, the hetero-Diels–Alder
cyclization in tandem with this ketone-based but sterically
rigid typical Knoevenagel intermediate is an interesting
area for accessing new angular polyheterocycles. As part of
our ongoing interest, we have recently developed a new
family of aminobenzopyran-annulated pyrano-fused pyra-
zoles [46–48]. To extend the scope and generality of this
strategy further on typical ketone-based substrates, we
therefore find it worthwhile to report an interesting reaction
mode of acetophenones and their analogs, termed the
DKHDA strategy.
Keywords Angular polyheterocycles ꢀ Green chemistry ꢀ
Ketones ꢀ Lewis acids ꢀ One-pot synthesis ꢀ
Pericyclic reactions
Introduction
Construction of angularly fused polycyclic compounds is of
special interest because they possess significant biological
properties that provide biologists with useful applications in
medicinal chemistry [1–10]. Potential candidates of this
class include naturally occurring cannabicyclol [11], maha-
nimbine [12], steroids [13], and thyrsiferol [4]. Analogs of
thyrsiferol particularly are known to exhibit cytotoxic,
antiviral, and antitumor activities. In addition, bioactive
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-012-0873-7) contains supplementary
material, which is available to authorized users.
N. J. Parmar (&) ꢀ B. R. Pansuriya ꢀ H. A. Barad ꢀ
B. D. Parmar
Department of Chemistry, Sardar Patel University,
Vallabh Vidyanagar, Dist. Anand 388120, Gujarat, India
e-mail: njpchemdeptspu@yahoo.co.in
Results and discussion
The typical intermediate oxabutadiene formed in situ was
cyclized in a subsequent hetero-Diels–Alder step without
changing any reagent or reaction conditions (Scheme 1).
Because they incorporate a tertiary ring junction carbon, all
R. Kant ꢀ V. K. Gupta
Post-Graduate Department of Physics, University of Jammu,
Jammu Tawi 180006, India
123

866
N. J. Parmar et al.
Scheme 1
O
O
O
+
-H2O
O
R
R
R
Scheme 2
O
R1
R2
OH
1a, R1 = H, R2 = Me
1a 1c
-
1
2
1b
, R = Me, R = Me
1c, R1 = H, R2 = Et
Br
Br
Br
O
O
O
O
R1
R1
R1
R2
R2
R2
O
O
2a 2c
3a 3c
-
-
4a 4c
-
new angular polyheterocycles are expected to display a
steroidal mimicking biological function [49–51].
Conventional results thus revealed that prenyl-based
ketone 3a seemed more amenable to the reaction than the
allyl-based ketone substrate 2a, as it gave at least minor
yields. However, the conventional method was inadequate
to design an efficient synthetic methodology because of
these lower yields.
Corresponding O-allylated/prenylated/propargylated ace-
tophenones 2a, 2b, 3a, 3b, 4a, and 4b and propiophenones
2c, 3c, and 4c were obtained in high yields with excellent
purity, prepared bythemethodreported elsewhere (Scheme 2)
[46–48].
Second, we examined catalyst- and solvent-free thermal
procedures (entries 10, 11). The results showed 23 % of the
only product 9a at 130 °C (entry 10) from prenyl-based
substrate 3a. Other substrates 2a and 4a were unreactive
and gave no desired products, which may be due to unac-
tivated dienophile allyl and propargyl moieties in the
substrates. At 160 °C, however, substrate 2a gave 68 % of
product 6a, but no desired product 12a from substrate 4a
was found. A maximum 65 % of 9a was achieved from
substrate 3a (entry 11). However, decomposed impurities
associated with the products made the product isolation
step tedious. The same was observed in the solvent-free
EDDA-mediated reaction despite the good yields achieved
at 150 °C (entry 13). To avoid this, we envisaged the
reaction in ionic liquid triethylammonium acetate (TEAA,
entries 14–18). Surprisingly, no contamination and easy
product isolation were achieved to get the desired products.
In addition, it improved the reaction in temperature and
To optimize the reaction conditions, we examined first
triethylamine (TEA), p-toluenesulfonic acid (p-TSA), eth-
ylene diammonium diacetate (EDDA), or zinc oxide (ZnO)
in refluxing ethanol or acetonitrile as reported elsewhere
[42–48, 52–55]. None of the catalysts except ZnO
(Table 1, entry 3) was effective for promoting the reaction.
Even ZnO in acetonitrile gave traces of product 9a (entry
3). So, we tried conventional catalyst-free methods (entries
1, 4, and 7) and the catalyzed ones (entries 2, 5, and 8).
There were no desired yields in acetonitrile (entries 1 and
2), but at least some yield in other solvents was obtained
(entries 4–9). A maximum 28 % of cyclized product 9a and
24 % of 6a could be obtained from respective allyl-based
2a and prenyl-based 3a substrates in the presence of
25 mol% EDDA in refluxing xylene after 24 h (entry 8).
Throughout the study, pyrazolone 5a was reacted to three
different ketone-based model substrates, 2a, 3a, and 4a.
123

Triethylammonium acetate mediated domino-Knoevenagel-hetero-Diels–Alder reaction
867
time for both substates 2a and 3a at 150 °C. At 100 °C,
however, no effective conversion of unactivated dienophile
allyl-based substrate was observed (entry 14), and also
lower yields of the products resulted from the prenyl-based
substrate (entries 15, 18). It gave a maximum of 71 % of 9a
at 140 °C and 67 % of 6a at 150 °C (entries 17 and 18).
Other compounds, 6a–6e, 7a–7e, 8a, 9a–9e, 10a–10e, and
11a (Scheme 3), were then prepared following the opti-
mized reaction conditions. The yields were in the range
58–71 % (Table 2).
Table 1 Optimization of the conditions to yield domino products 6a
and 9a
ZnO is effective in many useful transformations [54]. Its
catalytic effect was therefore examined for substrate 4a
(Table 3). We studied first the catalyst-free and ZnO cat-
alyzed reactions in refluxing acetonitrile, toluene, and
xylene (Table 3, entries 1–6). While only 16 % of product
12a resulted in refluxing xylene after prolong heating, no
product was obtained in other solvents, making the con-
ventional heating method inadequate. Next, we employed
the catalyst- and solvent-free methods. No products, even
after prolonged heating, could be achieved at 160 °C. So,
we employed ZnO, and it not only yielded the products, but
reduced the reaction time, too. A maximum 58 % of
desired product 12a could be achieved in 25 mol% ZnO
(entry 9). To improve the yields further, we envisaged the
reaction in ionic liquid TEAA (entry 12–14). Good results,
however, were achieved in the presence of 25 mol% ZnO
at 150 °C (entry 13), taking only 6 h to afford products.
The work is still being continued to improve the yields.
This optimized condition was employed for other hetero-
cycles: 12a–12e, 13a–13e, and 14a (Scheme 4; Table 4).
Besides pyrazolones, other analogous active methy-
lene units such as hydroxycoumarin, cyclohexanedione,
and phenyloxazolone were also tried with O-allylated,
Entry
Solvent
Catalyst
(25 mol%)
Temp/°C
Time/h
Yield/%
6a/9a
1
MeCN
–
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
130
24/24
–/–
2
MeCN
EDDA
ZnO
–
24/24
–/–
3
MeCN
24/24
–/Traces
7/12
4
Toluene
24/24
5
Toluene
EDDA
ZnO
–
24/24
11/21
12/23
18/27
24/28
22/30
–/23
6
Toluene
24/24
7
Xylene
24/24
8
Xylene
EDDA
ZnO
–
24/24
9
Xylene
24/24
10
11
12
13
14
15
16
17
18
–
–
–
–
–
–
–
–
–
5.0/5.0
3.5/2.5
5.0/3.5
4.0/2.5
5.0/5.0
5.0/5.0
5.0/3.5
5.0/3.0
3.5/2.0
–
160
68/65
–/67
EDDA
EDDA
TEAA
TEAA
TEAA
TEAA
TEAA
130
150
64/63
–/–
100
120
–/28
130
–/70
140
20/71
67/64
150
O
R3
R1
N
N
R2
O
H
6a 6e
-
R2
O
R1
-
7a 7e
8a
2a-2c
O
3
5a
5b
, R = Ph
3
, R = 2-ClPh
TEAA
O
R3
5c, R3 = 3-ClPh
N
N
R3
R1
N
O
N
R2
3
5d
, R = 2,5-Cl2Ph
O
H
9a-9e
10a-10e
11a
5e, R3 = 4-MePh
R2
O
R1
5a-5e
3a 3c
-
O
1
2
2a 3a
,
, R = H, R = Me
2b, 3b, R1 = Me, R2 = Me
2c, 3c, R1 = H, R2 = Et
Scheme 3
123

868
N. J. Parmar et al.
Table 2 Synthesis of novel tetrahydro-5H-chromeno[40,30:4,5]pyr-
ano[2,3-c]pyrazoles
Table 3 Optimization of the conditions to afford 12a
Entry Solvent
Catalyst
Temp/°C Time/h Yield/%
Entry 2a/3b
5
Product R1 R2 R3
Time/h Yieldc/%
1
MeCN
Toluene
Xylene
MeCN
–
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
160
24
24
24
24
24
24
10
10
6
–
1
2a/3a 5a 6a/9a
2a/3a 5b 6b/9b
2a/3a 5c 6c/9c
2a/3a 5d 6d/9d
2a/3a 5e 6e/9e
H
H
H
H
H
Me Ph
3.5/3.5 67/70
4.5/4.0 61/58
3.5/3.5 63/68
2
–
–
2
Me 2-ClPh
Me 3-ClPh
3
–
–
3
4
ZnO (25 %)
–
4
Me 2,5-Cl2Ph 3.0/3.5 61/65
5
Toluene ZnO (25 %)
Trace
16
–
5
Me 4-MePh
3.0/3.0 69/68
4.0/3.5 70/71
4.0/4.0 66/62
3.5/4.0 63/67
6
Xylene
ZnO (25 %)
–
6
2b/3b 5a 7a/10a Me Me Ph
2b/3b 5b 7b/10b Me Me 2-ClPh
2b/3b 5c 7c/10c Me Me 3-ClPh
7
–
–
–
–
–
–
–
–
7
8
ZnO (15 %)
ZnO (25 %)
ZnO (35 %)
TEAA (25 %)
TEAA (25 %)a 130
TEAA (25 %)a 150
TEAA (25 %)a 160
160
33
58
56
–
8
9
160
9
2b/3b 5d 7d/10d Me Me 2,5-Cl2Ph 4.0/3.5 67/63
10
11
12
13
14
a
160
6
10
11
a
2b/3b 5e 7e/10e Me Me 4-MePh
2c/3c 5a 8a/11a Et Ph
3.5/3.0 65/70
4.5/3.5 39/46
160
10
6
H
–
6
62
57
O-allylated substrates
b
c
6
O-prenylated substrates
Optimized conditions: 25 mol% TEAA, 150 °C for 2 and 130 °C
As a mixture with ZnO (25 mol%)
for 3
position to each other. It was therefore concluded that the
reaction proceeds via endo-E-syn transition states even
though two pathways are possible.
O-prenylated, and O-propargylated acetophenones, using
the optimized condition (Table 3, entry 13). Also, other
ketone-based substrates derived from 2-hydroxybenzo-
phenone were tested. But they failed to give subsequent
cyclized products after forming the Knoevenagel adduct.
Work in this area is ongoing.
1H NMR spectra featured
a singlet at around
d = 1.0–1.9 ppm attributable to a methyl proton attached to
the ring junction carbon and which in turn showed a 13C
NMR peak in the range d = 22–30 ppm, except the com-
pounds derived from propiophenones. In polyheterocycles
derived from propiophenones, two bridge head methylene
protons showed multiplets in the 2.03–2.39 ppm range and a
carbon signal at around d = 33 ppm. Further structural
conformation could also be ascertained by the single crystal
X-ray diffraction data of representatives 9a and 12a (Figs. 1,
2) [56–59].The data fully agreed with the proposed structure.
The formation of the Knoevenagel intermediate [52–55]
1
was confirmed by H NMR, 13C NMR, and DEPT-135
studies. From single-crystal X-ray data of 9a, a cis orien-
tation of the bridge head methyl and hydrogen at the
pyranyl ring junction was evident, indicative of a less
sterically hindered endo-E-syn transition state.
A plausible mechanism is proposed in Scheme 5. The
reaction proceeds via formation of Knoevenagel intermedi-
ate IV [52–55]. Triethylammonium pyrazolonate I, obtained
from pyrazolone in the presence of TEAA, forms unstable
enolate intermediate III with dienophile-ether-tethered
ketone substrate II via nucleophilic attack of pyrazolonate
on carbonyl carbon of II, which forms Knoevenagel alkene
intermediate IV and releases ionic liquid. The intermediate
Conclusion
Thus, we have described a new ionic liquid TEAA-mediated
one-pot method for the synthesis of a new family of angularly
fused polyheterocycles via a domino intermolecular Knoe-
venagel intramolecular hetero-Diels–alder route. Besides
providing efficient and improved reaction conditions for un-
activated dienophile propargyl, needing no additional catalyst
required for allyl- and prenyl-based substrates is another
advantage of this method. Since the bridge head alkyl group
is present in all the polycyclic heterocycles, they are expected
to display some new bioprofiles.
1
IV was isolated and its structure was also confirmed by H
NMR, 13C NMR, and DEPT-135. Finally, under the influ-
ence of TEAA, IV undergoes the hetero-Diels–Alder
reaction to form the cyclized product.
Four transition states are possible when the dienophile
approaches toward the alkene intramolecularly in the
Knoevenagel intermediate. Formation of either endo-Z-anti
or exo-E-anti geometries are ruled out because of angle
strain. Thus, fewer steric interactions of the ortho sub-
stituent with an alkyl attached to Knoevenagel alkene
favors the endo-E-syn transition state. The same can also
be inferred from the single crystal X-ray analysis, which
showed both the pyranyl bridge methyl and hydrogen in cis
Experimental
1
Solvents were dried by standard procedures. H and 13C
NMR spectra were determined in CDCl3 on a Bruker
123

Triethylammonium acetate mediated domino-Knoevenagel-hetero-Diels–Alder reaction
869
Scheme 4
R3
N
N
O
R1
TEAA + ZnO
O
R2
N
R2
R1
O
N
R3
O
O
4a-4c
5a-5e
12a-12e
13a-13e
14a
3
4a, R1 = H, R2 = Me
5a
, R = Ph
5b, R3 = 2-ClPh
1
2
4b
, R = Me, R = Me
3
1
2
5c
, R = 3-ClPh
4c
, R = H, R = Et
5d, R3 = 2,5-Cl2Ph
5e, R3 = 4-MePh
Table 4 Synthesis of novel
dihydro-6H-chromeno[40,30:4,
5]pyrano[2,3-c]pyrazoles
12a–12e, 13a–13e, 14a
Entry
4a
5
Product
R1
R2
R3
Time/h
Yieldb/%
1
2
3
4
5
6
4a/4b
4a/4b
4a/4b
4a/4b
4a/4b
4c
5a
5b
5c
5d
5e
5a
12a/13a
12b/13b
12c/13c
12d/13d
12e/13e
14a
H/Me
H/Me
H/Me
H/Me
H/Me
H
Me
Me
Me
Me
Me
Et
Ph
6.0/6.5
7.5/8.0
8.0/7.5
7.0/7.0
6.5/7.0
7.0
62/68
60/57
64/64
61/56
67/69
32
2-ClPh
3-ClPh
2,5-Cl2Ph
4-MePh
Ph
a
Propargylated substrates
b
Optimized condition: equal
amount (25 mol%) of TEAA
and ZnO, 150 °C
Avance (1H 400 MHz, 13C 100 MHz) using the CDCl3
peak as a reference peak. IR spectra were obtained on a
Shimadzu FT-IR 8300 spectrophotometer using the KBr
disc. Mass spectra were taken on a Shimadzu LCMS 2010
instrument. Elemental analysis (C, H, N) was carried out by
a Perkin-Elmer 2400 series-II elemental analyzer (Perkin-
Elmer, USA). The reactions were monitored by silica gel
60 F254 thin-layer chromatographic (TLC) plates of
Merck. Melting points were determined in an open capil-
lary tube on a TEMPO melting point apparatus. Ionic
liquid-cum-catalyst TEAA was prepared by reported liter-
ature methods [60].
methods and refined by full-matrix least-squares procedures
to a final R value of 0.0424 for 2,605 and 0.0431 for 2,473
observed reflections, respectively.
General procedure for the synthesis of 6a–6e, 7a–7e,
and 8a
A mixture of O-allylated acetophenones/propiophenone
2a–2c (3.0 mmol) and corresponding 5-pyrazolone 5a–5e
(3.0 mmol) in TEAA (0.75 mmol, 25 mol%) was heated at
150 °C until the reaction was completed as monitored by
TLC. Crude cycloadducts thus received in good yields
were purified further by column chromatography.
Single crystal X-ray diffraction data were collected on a
Bruker CCD area-detector diffractometer equipped with a
˚
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,11b-dimethyl-3-
phenyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(6a, C21H20N2O2)
graphite monochromatic MoKa radiation (k = 0.71073 A).
The structure was solved by direct methods using SHELXS
97 [56]. All non-hydrogen atoms in the molecule were
located in the best E-map. The title compound 9a crystal-
lizes in the monoclinic space group P21/n with the following
unit-cell parameters: a = 13.4695(4), b = 10.3715(3),
White powder; yield 631 mg (67 %); m.p.: 152–154 °C;
Rf = 0.42 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,957, 2,927, 1,595, 1,516, 1,485, 1,442, 1,227,
1
1,093, 1,048, 840, 756, 692 cm-1; H NMR (400 MHz,
˚
c = 13.8111(4) A, b = 95.724(3)°, and Z = 4. Compound
12a crystallizes in the monoclinic space group P21/c with
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.16 (m, 1H, H5a), 2.64 (s, 3H, CH3 of pyrazo-
lone), 4.27 (m, 2H, H5 and H6), 4.53 (dd, J = 11.2, 3.6 Hz,
the following unit-cell parameters: a = 10.2068(3), b = 11.
˚
2849(5), c = 14.3720(5) A, b = 91.778(3) °, and Z = 4.
The crystal structures of 9a and 12a were solved by direct
0
1H, H6 ), 4.58 (dd, J = 12.0, 2.8 Hz, 1H, H5 ), 6.80–7.73
0
123

870
N. J. Parmar et al.
O
O
R1
R2
R
R
Et3NH
O
N
AcOH
N
N
R3
l
ll
R = H, Me
O
N
R3
O R2
Et3NH
R1
N
H
Et3NH AcO
N
R3
O
O
lll
R1
R
R
O
AcOH
R2
R3
N
N
N
N
R
R
O
O
H
R2
R
R
R3
Et3NH AcO
R1
lV
O
Et3NH AcO
V
Scheme 5
(m, 9H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
d = 16.47 (CH3 of pyrazolone), 29.64 (CH3 attached to
3° ring junction carbon), 34.07 (C-11b), 37.85 (C-5a),
62.86 (C-5), 69.07 (C-6), 103.15, 117.09, 120.71, 121.10,
125.68, 127.87, 128.89, 129.09, 129.60, 138.45, 146.50,
148.51, 151.16 (Ar–C) ppm; MS: m/z = 333.1 [M?H?].
6.79–7.71 (m, 8H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.47 (CH3 of pyrazolone), 29.64 (CH3
attached to 3° ring junction carbon), 34.07 (C-11b), 37.85
(C-5a), 62.86 (C-5), 69.07 (C-6), 101.39, 116.37, 120.72
127.59, 128.22, 129.31, 129.68, 129.87, 130.25, 130.92,
131.35, 135.69, 147.36, 149.35, 150.94 (Ar–C) ppm; MS:
m/z = 367.2 [M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro-
1,11b-dimethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (6b, C21H19ClN2O2)
(5aR,11bS)-3-(3-Chlorophenyl-3,5a,6,11b-tetrahydro)-
1,11b-dimethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (6c, C21H19ClN2O2)
White powder; yield 634 mg (61 %); m.p.: 154–156 °C;
Rf = 0.24 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
White powder; yield 655 mg (63 %); m.p.: 146–148 °C;
Rf = 0.47 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,965, 2,929, 1,590, 1,517, 1,479, 1,443, 1,228,
1
1,094, 1,043, 841, 757, 683 cm-1; H NMR (400 MHz,
m = 2,968, 2,926, 1,591, 1,517, 1,477, 1,440, 1,226,
ꢀ
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.17 (m, 1H, H5a), 2.62 (s, 3H, CH3 of pyrazo-
lone), 4.27 (m, 2H, H5 and C-H6), 4.52 (dd, J = 11.2,
1,090, 1,039, 844, 821, 755, 673 cm-1
;
1H NMR
(400 MHz, CDCl3): d = 1.80 (s, 3H, CH3 attached to 3°
ring junction carbon), 2.16 (m, 1H, H5a), 2.62 (s, 3H, CH3
of pyrazolone), 4.28 (m, 2H, H5 and H6), 4.52 (dd,
0
3.6 Hz, 1H, H6 ), 4.58 (dd, J = 12.0, 2.8 Hz, 1H, H5 ),
0
123

Triethylammonium acetate mediated domino-Knoevenagel-hetero-Diels–Alder reaction
871
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro-
1,11b-dimethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (6d, C21H18Cl2N2O2)
White powder; yield 693 mg (61 %); m.p.: 204–206 °C;
Rf = 0.43 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,972, 2,923, 1,594, 1,518, 1,482, 1,432, 1,240,
1,089, 1,048, 849, 822, 783, 677 cm-1 1H NMR
;
(400 MHz, CDCl3): d = 1.81 (s, 3H, CH3 attached to 3°
ring junction carbon), 2.17 (m, 1H, H5a), 2.59 (s, 3H, CH3
of pyrazolone), 4.26 (m, 2H, H5 and H6), 4.47 (dd,
0
J = 11.2, 3.6 Hz, 1H, H6 ), 4.55 (dd, J = 12.0, 2.8 Hz, 1H,
0
H5 ), 6.80–7.52 (m, 7H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.40 (CH3 of pyrazolone), 29.62 (CH3
attached to 3° ring junction carbon), 34.09 (C-11b), 38.04
(C-5a), 62.98 (C-5), 69.06 (C-6), 102.11, 117.10, 121.04,
127.90, 128.78, 129.48, 129.60, 129.68, 129.98, 130.98,
132.86, 136.24, 147.75, 149.40, 151.29 (Ar–C) ppm; MS:
m/z = 401.1 [M?H?].
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,11b-dimethyl-3-
(4-methylphenyl)-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (6e, C22H22N2O2)
White powder; yield 677 mg (69 %); m.p.: 150–152 °C;
Rf = 0.45 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,980, 2,928, 1,591, 1,523, 1,484, 1,444, 1,232,
Fig. 1 ORTEP view of compound 9a
1
1,097, 1,045, 820, 754, 673 cm-1; H NMR (400 MHz,
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.17 (m, 1H, H5a), 2.37 (s, 3H, CH3 of phenyl),
2.63 (s, 3H, CH3 of pyrazolone), 4.27 (m, 2H, H5 and H6),
0
4.52 (dd, J = 11.0, 3.2 Hz, 1H, H6 ), 4.58 (dd, J = 11.6,
0
2.4 Hz, 1H, H5 ), 6.79–7.58 (m, 8H, Ar–H) ppm; 13C NMR
(100 MHz, CDCl3): d = 16.43 (CH3 of pyrazolone), 20.95
(CH3 attached to 3° ring junction carbon), 29.66 (CH3 of
pyrazolone), 34.07 (C-11b), 37.90 (C-5a), 62.90 (C-5),
69.02 (C-6), 102.90, 117.04, 120.85, 121.07, 127.83,
129.15, 129.43, 129.63, 135.47, 135.96, 146.14, 148.34,
151.14 (Ar–C) ppm; MS: m/z = 347.1 [M?H?].
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,10,11b-trimethyl-3-
phenyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(7a, C22H22N2O2)
White powder; yield 637 mg (70 %); m.p.: 138–140 °C;
Rf = 0.47 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,963, 2,936, 1,586, 1,519, 1,489, 1,450, 1,232,
Fig. 2 ORTEP view of compound 12a
1
1,085, 1,049, 846, 756, 671 cm-1; H NMR (400 MHz,
CDCl3): d = 1.80 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.17 (m, 1H, H5a), 2.31 (s, 3H, CH3-10), 2.71 (s,
3H, CH3 of pyrazolone), 4.30 (m, 2H, H5 and H6), 4.55 (dd,
0
J = 11.2, 3.6 Hz, 1H, H6 ), 4.57 (dd, J = 12.0, 2.8 Hz, 1H,
0
H5 ), 6.80–7.72 (m, 8H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.47 (CH3 of pyrazolone), 29.64 (CH3
attached to 3° ring junction carbon), 34.07 (C-11b), 37.85
(C-5a), 62.86 (C-5), 69.07 (C-6), 101.57, 116.64, 120.92,
128.05, 128.62, 129.21, 129.43, 129.72, 130.09, 130.36,
131.65, 135.74, 147.53, 149.65, 150.87 (Ar–C) ppm; MS:
m/z = 367.2 [M?H?].
0
J = 11.4, 3.6 Hz, 1H, H6 ), 4.59 (dd, J = 12.4, 2.8 Hz, 1H,
0
H5 ), 6.66–7.65 (m, 8H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.67 (CH3 of pyrazolone), 20.72 (CH3-10)
29.92 (CH3 attached to 3° ring junction carbon), 34.26 (C-
11b), 37.65 (C-5a), 62.82 (C-5), 69.56 (C-6), 102.11,
118.01, 120.67, 125.64, 127.76, 128.25, 128.90, 129.29,
123

872
N. J. Parmar et al.
129.81, 138.52, 146.63, 148.62, 151.82 (Ar–C) ppm; MS:
m/z = 347.2 [M?H?].
29.52 (CH3 attached to 3° ring junction carbon), 33.81
(C-11b), 37.42 (C-5a), 62.56 (C-5), 69.39 (C-6), 101.87,
118.13, 127.32, 127.56, 127.88, 129.58, 129.82, 130.14,
130.68, 131.39, 132.76, 136.33, 147.52, 149.41, 151.67
(Ar–C) ppm; MS: m/z = 415.0 [M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro-
1,10,11b-trimethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (7b, C22H21ClN2O2)
White powder; yield 661 mg (66 %); m.p.: 164–166 °C;
Rf = 0.25 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,10,11b-trimethyl-3-
(4-methylphenyl)-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (7e, C23H24N2O2)
ꢀ
m = 2,956, 2,932, 1,589, 1,517, 1,494, 1,456, 1,230,
1
1,091, 1,052, 853, 758, 691 cm-1; H NMR (400 MHz,
White powder; yield 615 mg (65 %); m.p.: 132–134 °C;
Rf = 0.49 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
CDCl3): d = 1.82 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.18 (m, 1H, H5a), 2.33 (s, 3H, CH3-10), 2.69 (s,
3H, CH3 of pyrazolone), 4.28 (m, 2H, H5 and H6), 4.52 (dd,
ꢀ
m = 2,967, 2,928, 1,583, 1,523, 1,489, 1,445, 1,231,
1
1,078, 1,038, 859, 758, 684 cm-1; H NMR (400 MHz,
0
J = 12.0, 3.2 Hz, 1H, H6 ), 4.58 (dd, J = 12.6, 2.4 Hz, 1H,
0
CDCl3): d = 1.82 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.17 (m, 1H, H5a), 2.28 (s, 3H, CH3-10), 2.36 (s,
3H, CH3 of phenyl), 2.63 (s, 3H, CH3 of pyrazolone), 4.28
H5 ), 6.67–7.70 (m, 7H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.82 (CH3 of pyrazolone), 20.81 (CH3-10)
29.75 (CH3 attached to 3° ring junction carbon), 34.02 (C-
11b), 37.71 (C-5a), 63.03 (C-5), 69.42 (C-6), 100.59,
116.32, 127.36, 128.01, 128.33, 129.16, 129.52, 129.65,
130.11, 130.28, 131.56, 135.65, 147.26, 149.24, 150.62
(Ar–C) ppm; MS: m/z = 381.1 [M?H?].
0
(m, 2H, H5 and H6), 4.53 (dd, J = 11.6, 3.2 Hz, 1H, H6 ),
0
4.59 (dd, J = 12.0, 2.4 Hz, 1H, H5 ), 6.66–7.68 (m, 7H,
Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.75
(CH3 of pyrazolone), 20.66 (CH3-10) 20.95 (CH3 of
phenyl), 29.89 (CH3 attached to 3° ring junction carbon),
34.51 (C-11b), 37.85 (C-5a), 62.91 (C-5), 69.29 (C-6),
101.85, 116.92, 120.62, 127.98, 128.36, 128.90, 129.41,
130.53, 135.32, 136.41, 146.74, 148.15, 150.60 (Ar–C)
ppm; MS: m/z = 361.2 [M?H?].
(5aR,11bS)-3-(3-Chlorophenyl)-3,5a,6,11b-tetrahydro-
1,10,11b-trimethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (7c, C22H21ClN2O2)
White powder; yield 630 mg (63 %); m.p.: 142–144 °C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(5aR,11bS)-11b-Ethyl-3,5a,6,11b-tetrahydro-1-methyl-3-
phenyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(8a, C22H22N2O2)
ꢀ
m = 2,960, 2,927, 1,590, 1,518, 1,491, 1,445, 1,232,
1,093, 1,039, 848, 749, 676 cm-1; H NMR (400 MHz,
1
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.16 (m, 1H, H5a), 2.31 (s, 3H, CH3-10), 2.68 (s,
3H, CH3 of pyrazolone), 4.26 (m, 2H, H5 and H6), 4.53 (dd,
White powder; yield 0.355 mg (39 %); m.p.: 132–133 °C;
Rf = 0.36 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,967, 2,929, 1,586, 1,509, 1,493, 1,440, 1,231,
1,085, 1,035, 989, 857, 759, 682 cm-1 1H NMR
;
0
J = 12.2, 3.2 Hz, 1H, H6 ), 4.59 (dd, J = 12.4, 2.4 Hz, 1H,
H5 ), 6.68–7.71 (m, 7H, Ar–H) ppm; 13C NMR (100 MHz,
(400 MHz, CDCl3): d = 0.88 (t, J = 7.6 Hz, 3H, CH3 of
ethyl), 2.11 (m, 1H, –CH2CH3), 2.35 (m, 1H, –CH2CH3),
2.43 (m, 1H, H5a), 2.59 (s, 3H, CH3 of pyrazolone), 4.27
0
CDCl3): d = 16.63 (CH3 of pyrazolone), 20.68 (CH3-10)
29.69 (CH3 attached to 3° ring junction carbon), 33.86 (C-
11b), 37.52 (C-5a), 62.74 (C-5), 69.56 (C-6), 101.12,
116.36, 127.36, 128.01, 128.33, 129.16, 129.52, 129.65,
130.11, 130.28, 131.56, 135.65, 147.26, 149.24, 150.62
(Ar–C) ppm; MS: m/z = 381.1 [M?H?].
0
0
(m, 2H, H5 and H6), 4.51 (m, 2H, H5 and H6 ), 6.78–7.73
(m, 9H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
d = 8.10 (CH3 of ethyl), 16.20 (CH3 of pyrazolone),
31.90 (C-5a), 32.08 (CH2 of ethyl), 38.42 (C-11b), 62.46
(C-5), 69.02 (C-6), 100.47, 116.99, 120.58, 121.05, 125.63,
127.79, 128.89, 129.54, 129.66, 138.46, 146.36, 149.83,
151.19 (Ar–C) ppm; MS: m/z = 347.1[M?H?].
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro-
1,10,11b-trimethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (7d, C22H20Cl2N2O2)
White powder; yield 730 mg (67 %); m.p.: 178–180 °C;
Rf = 0.44 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
General procedure for the synthesis of 9a–9e, 10a–10e,
and 11a
ꢀ
m = 2,962, 2,930, 1,577, 1,515, 1,481, 1,441, 1,226,
1
1,085, 1,043, 862, 761, 658 cm-1; H NMR (400 MHz,
A mixture of O-prenylated acetophenones/propiophenone
3a–3c (3.0 mmol) and the corresponding 5-pyrazolone
5a–5e (3.0 mmol) in TEAA (0.75 mmol, 25 mol%) was
heated at 130 °C until the reaction was completed as mon-
itored by TLC. Crude cycloadducts were received in good
yields and purified further by column chromatography.
CDCl3): d = 1.82 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.17 (m, 1H, H5a), 2.32 (s, 3H, CH3-10), 2.68 (s,
3H, CH3 of pyrazolone), 4.27 (m, 2H, H5 and H6), 4.52 (dd,
0
J = 12.2, 3.2 Hz, 1H, H6 ), 4.59 (dd, J = 12.4, 2.4 Hz, 1H,
0
H5 ), 6.64–7.69 (m, 6H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.71 (CH3 of pyrazolone), 20.76 (CH3-10)
123

Triethylammonium acetate mediated domino-Knoevenagel-hetero-Diels–Alder reaction
873
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,11b-tetramethyl-
3-phenyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(9a, C23H24N2O2)
116.29, 120.65, 120.99, 125.41, 127.50, 127.69, 128.83,
129.22, 138.75, 146.76, 148.13, 152.67 (Ar–C) ppm; MS:
m/z = 395.1 [M?H?].
White powder; yield 623 mg (70 %); m.p.: 170–172 °C;
Rf = 0.51 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro-
1,5,5,11b-tetramethyl-5H-chromeno[40,30:4,5]pyrano-
[2,3-c]pyrazole (9d, C23H22Cl2N2O2)
ꢀ
m = 2,981, 2,929, 1,597, 1,511, 1,491, 1,443, 1,230,
1
1,084, 1,043, 838, 757, 673 cm-1; H NMR (400 MHz,
White powder; yield 682 mg (65 %); m.p.: 130–132 °C;
Rf = 0.48 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
CDCl3): d = 1.09 (s, 3H, CH3 attached to 3° ring junction
carbon), 1.64 (s, 3H, CH3-5), 1.77 (s, 3H, CH3-50), 1.98 (d,
J = 3.2 Hz, 1H, H5a), 2.71 (s, 3H, CH3 of pyrazolone),
4.43 (td, J = 12.8, 1.2 Hz, 1H, H6), 4.72 (ddd, J = 12.6,
ꢀ
m = 2,970, 2,925, 1,590, 1,512, 1,481, 1,445, 1,228, 1,088,
1
1,039, 851, 759, 675 cm-1; H NMR (400 MHz, CDCl3):
d = 1.08 (s, 3H, CH3 attached to 3° ring junction carbon),
1.67 (s, 3H, CH3-5), 1.78 (s, 3H, CH3-50), 1.96 (d,
J = 3.2 Hz, 1H, H5a), 2.70 (s, 3H, CH3 of pyrazolone),
4.41 (td, J = 12.4, 1.6 Hz, 1H, H6), 4.66 (ddd, J = 12.6, 4.2,
4.4, 2.0 Hz, 1H, H6 ), 6.76–7.78 (m, 9H, Ar–H) ppm; 13C
0
NMR (100 MHz, CDCl3): d = 16.78 (CH3 of pyrazolone),
22.75 (CH3 attached to 3° ring junction carbon), 29.21
(CH3-5), 32.07 (CH3-50), 33.64 (C-11b), 47.11 (C-5a),
61.95 (C-6), 82.72 (C-5), 101.20, 116.29, 120.65, 120.99,
125.41, 127.50, 127.69, 128.83, 129.22, 138.75, 146.76,
148.13, 152.67 (Ar–C) ppm; MS: m/z = 361.1 [M?H?].
2.0 Hz, 1H, H6 ), 6.69–7.56 (m, 7H, Ar–H) ppm; 13C NMR
0
(100 MHz, CDCl3): d = 16.77 (CH3 of pyrazolone), 22.53
(CH3 attached to 3° ring junction carbon), 29.65 (CH3-5),
32.06 (CH3-50), 34.02 (C-11b), 46.65 (C-5a), 62.43 (C-6),
83.12 (C-5), 102.32, 117.43, 121.21, 127.97, 128.88, 129.15,
129.68, 129.93, 130.92, 131.16, 132.95, 136.54, 147.86,
149.67, 151.52 (Ar–C) ppm; MS: m/z = 429.2 [M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro-1,5,
5,11b-tetramethyl-5H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (9b, C23H23ClN2O2)
White powder; yield 560 mg (58 %); m.p.: 135–137 °C;
Rf = 0.24 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,11b-tetramethyl-
3-(4-methylphenyl)-5H-chromeno[40,30:4,5]pyrano-
[2,3-c]pyrazole (9e, C24H26N2O2)
ꢀ
m = 2,965, 2,925, 1,587, 1,514, 1,482, 1,441, 1,229,
1
1,088, 1,038, 845, 758, 684 cm-1; H NMR (400 MHz,
White powder; yield 623 mg (68 %); m.p.: 178–180 °C;
Rf = 0.47 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
CDCl3): d = 1.05 (s, 3H, CH3 attached to 3° ring junction
carbon), 1.66 (s, 3H, CH3-5), 1.79 (s, 3H, CH3-50), 1.99 (d,
J = 3.6 Hz, 1H, H5a), 2.69 (s, 3H, CH3 of pyrazolone),
4.42 (td, J = 12.4, 1.6 Hz, 1H, H6), 4.71 (ddd, J = 12.4,
ꢀ
m = 2,971, 2,929, 1,591, 1,560, 1,478, 1,444, 1,226, 1,094,
1
1,045, 853, 760, 661 cm-1; H NMR (400 MHz, CDCl3):
4.2, 2.0 Hz, 1H, H6 ), 6.77–7.79 (m, 8H, Ar–H) ppm; 13C
d = 1.09 (s, 3H, CH3 attached to 3° ring junction carbon),
1.64 (s, 3H, CH3-5), 1.79 (s, 3H, CH3-50), 1.99 (d,
J = 3.2 Hz, 1H, H5a), 2.39 (s, 3H, CH3 of phenyl), 2.75
(s, 3H, CH3 of pyrazolone), 4.48 (td, J = 12.6, 1.6 Hz, 1H,
0
NMR (100 MHz, CDCl3): d = 16.61 (CH3 of pyrazolone),
22.86 (CH3 attached to 3° ring junction carbon), 29.39
(CH3-5), 31.87 (CH3-50), 33.58 (C-11b), 46.93 (C-5a),
62.02 (C-6), 82.99 (C-5), 103.25, 117.18, 120.76, 121.31,
125.53, 127.77, 128.79, 129.02, 129.53, 138.58, 146.61,
148.49, 151.24 (Ar–C) ppm; MS: m/z = 395.1 [M?H?].
0
H6), 4.74 (ddd, J = 12.8, 4.2, 2.0 Hz, 1H, H6 ), 6.70–7.79
(m, 8H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
d = 16.76 (CH3 of pyrazolone), 20.92 (CH3 of phenyl),
22.71 (CH3 attached to 3° ring junction carbon), 29.14
(CH3-5), 31.93 (CH3-50), 33.76 (C-11b), 46.73 (C-5a), 62.06
(C-6), 82.54 (C-5), 102.87, 117.01, 120.85, 121.05, 127.81,
129.14, 129.42, 129.59, 135.46, 135.92, 146.16, 148.37,
151.17 (Ar–C) ppm; MS (ESI): m/z = 375.0 [M?H?].
(5aR,11bS)-3-(3-Chlorophenyl)-3,5a,6,11b-tetrahydro-
1,5,5,11b-tetramethyl-5H-chromeno[40,30:4,5]pyrano-
[2,3-c]pyrazole (9c, C23H23ClN2O2)
White powder; yield 656 mg (68 %); m.p.: 148–150 °C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,10,11b-
pentamethyl-3-phenyl-5H-chromeno[40,30:4,5]pyrano-
[2,3-c]pyrazole (10a, C24H26N2O2)
ꢀ
m = 2,968, 2,927, 1,589, 1,559, 1,480, 1,440, 1,232,
1,091, 1,041, 849, 820, 755, 690 cm-1 1H NMR
;
(400 MHz, CDCl3): d = 1.09 (s, 3H, CH3 attached to 3°
ring junction carbon), 1.63 (s, 3H, CH3-5), 1.76 (s, 3H,
CH3-50), 1.97 (d, J = 3.2 Hz, 1H, H5a), 2.72 (s, 3H, CH3 of
pyrazolone), 4.43 (td, J = 12.8, 0.8 Hz, 1H, H6), 4.71
White powder; yield 573 mg (71 %); m.p.: 212–214 °C;
Rf = 0.46 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,972, 2,927, 1,594, 1,519, 1,472, 1,432, 1,238,
1
1,081, 1,039, 844, 748, 669 cm-1; H NMR (400 MHz,
0
(ddd, J = 12.4, 4.4, 2.0 Hz, 1H, H6 ), 6.71–7.79 (m, 8H,
Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.48
(CH3 of pyrazolone), 22.65 (CH3 attached to 3° ring
junction carbon), 29.29 (CH3-5), 31.85 (CH3-50), 33.85
(C-11b), 47.01 (C-5a), 62.02 (C-6), 82.63 (C-5), 101.20,
CDCl3): d = 1.11 (s, 3H, CH3 attached to 3° ring junction
carbon), 1.56 (s, 3H, CH3-5), 1.78 (s, 3H, CH3-50), 1.93 (d,
J = 3.6 Hz, 1H, H5a), 2.32 (s, 3H, CH3-10), 2.72 (s, 3H,
CH3 of pyrazolone), 4.41 (td, J = 12.6, 0.8 Hz, 1H, H6),
123

874
N. J. Parmar et al.
0
4.70 (ddd, J = 12.6, 4.4, 1.6 Hz, 1H, H6 ), 6.65–7.55 (m,
8H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.89
(CH3 of pyrazolone), 20.88 (CH3-10), 22.66 (CH3 attached
to 3° ring junction carbon), 28.92 (CH3-5), 32.29 (CH3-50),
33.77 (C-11b), 47.42 (C-5a), 61.93 (C-6), 82.73 (C-5),
102.11, 116.90, 119.98, 125.72, 127.96, 128.89, 129.13,
129.72, 139.11, 146.56, 149.01, 151.76 (Ar–C) ppm; MS:
m/z = 375.2 [M?H?].
ꢀm = 2,972, 2,936, 1,591, 1,519, 1,439, 1,227, 1,091,
1,042, 822, 752, 669 cm-1; 1H NMR (400 MHz, CDCl3):
d = 1.09 (s, 3H, CH3 attached to 3° ring junction carbon),
1.52 (s, 3H, CH3-5), 1.76 (s, 3H, CH3-50), 1.96 (d,
J = 3.6 Hz, 1H, H5a), 2.34 (s, 3H, CH3-10), 2.75 (s, 3H,
CH3 of pyrazolone), 4.44 (td, J = 12.4, 1.2 Hz, 1H, H6),
0
4.67 (ddd, J = 12.4, 4.2, 1.6 Hz, 1H, H6 ), 6.61–7.66 (m,
6H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.85
(CH3 of pyrazolone), 20.64 (CH3-10), 22.87 (CH3
attached to 3° ring junction carbon), 28.65 (CH3-5),
32.54 (CH3-50), 33.86 (C-11b), 47.34 (C-5a), 62.81 (C-6),
83.01 (C-5), 101.32, 116.16, 127.23, 127.89, 128.38,
129.19, 129.43, 129.62, 130.12, 130.35, 131.74, 135.76,
147.32, 149.33, 150.40 (Ar–C) ppm; MS: m/z = 443.1
[M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro-
1,5,5,10,11b-pentamethyl-5H-chromeno[40,30:4,5]-
pyrano[2,3-c]pyrazole (10b, C24H25ClN2O2)
White powder; yield 580 mg (62 %); m.p.: 168–170 °C;
Rf = 0.22 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,978, 2,922, 1,592, 1,518, 1,443, 1,232, 1,095,
1,036, 845, 756, 655 cm-1; H NMR (400 MHz, CDCl3):
1
d = 1.10 (s, 3H, CH3 attached to 3° ring junction carbon),
1.51 (s, 3H, CH3-5), 1.77 (s, 3H, CH3-50), 1.91 (d,
J = 4.0 Hz, 1H, H5a), 2.30 (s, 3H, CH3-10), 2.71 (s, 3H,
CH3 of pyrazolone), 4.38 (td, J = 12.8, 1.2 Hz, 1H, H6),
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,10,11b-penta-
methyl-3-(4-methylphenyl)-5H-chromeno[40,30:4,5]-
pyrano[2,3-c]pyrazole (10e, C25H28N2O2)
White powder; yield 622 mg (70 %); m.p.: 250–252 °C;
Rf = 0.49 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr): m=
0
4.68 (ddd, J = 12.4, 4.4, 1.6 Hz, 1H, H6 ), 6.64–7.50 (m,
ꢀ
7H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.89
(CH3 of pyrazolone), 20.88 (CH3-10), 22.66 (CH3 attached
to 3° ring junction carbon), 28.92 (CH3-5), 32.29 (CH3-50),
33.77 (C-11b), 47.42 (C-5a), 61.93 (C-6), 82.73 (C-5),
100.00, 116.01, 127.26, 127.99, 128.23, 129.09, 129.48,
129.57, 130.04, 130.13, 131.69, 135.76, 147.32, 149.33,
150.40 (Ar–C) ppm; MS: m/z = 409.0 [M?H?].
2,983, 2,922, 1,593, 1,517, 1,442, 1,230, 1,085, 1,043, 817,
764, 667 cm-1; 1H NMR (400 MHz, CDCl3): d = 1.09 (s,
3H, CH3 attached to 3° ring junction carbon), 1.62 (s, 3H,
CH3-5), 1.76 (s, 3H, CH3-50), 1.96 (d, J = 4.0 Hz, 1H,
H5a), 2.28 (s, 3H, CH3-10), 2.38 (s, 3H, CH3 of phenyl),
2.72 (s, 3H, CH3 of pyrazolone), 4.39 (td, J = 12.4,
0
1.6 Hz, 1H, H6), 4.69 (ddd, J = 12.8, 4.4, 1.6 Hz, 1H, H6 ),
6.64–7.64 (m, 7H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.85 (CH3 of pyrazolone), 20.84 (CH3 of
phenyl), 20.95 (CH3-10), 22.74 (CH3 attached to 3° ring
junction carbon), 29.16 (CH3-5), 32.15 (CH3-50), 33.67
(C-11b), 47.26 (C-5a), 61.91 (C-6), 82.63 (C-5), 101.15,
116.03, 120.71, 127.91, 128.27, 128.96, 129.37, 130.04,
135.12, 136.31, 146.44, 148.01, 150.42 (Ar–C) ppm; MS:
m/z = 389.1 [M?H?].
(5aR,11bS)-3-(3-Chlorophenyl)-3,5a,6,11b-tetrahydro-
1,5,5,10,11b-pentamethyl-5H-chromeno[40,30:4,5]-
pyrano[2,3-c]pyrazole (10c, C24H25ClN2O2)
White powder; yield 627 mg (67 %); m.p.: 168–170 °C;
Rf = 0.58 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,964, 2,934, 1,585, 1,522, 1,436, 1,230, 1,086,
1
1,046, 861, 755, 668 cm-1; H NMR (400 MHz, CDCl3):
d = 1.11 (s, 3H, CH3 attached to 3° ring junction carbon),
1.53 (s, 3H, CH3-5), 1.75 (s, 3H, CH3-50), 1.94 (d,
J = 4.0 Hz, 1H, H5a), 2.33 (s, 3H, CH3-10), 2.75 (s, 3H,
CH3 of pyrazolone), 4.42 (td, J = 12.4, 1.2 Hz, 1H, H6),
(5aR,11bS)-11b-Ethyl-3,5a,6,11b-tetrahydro-1,5,5-
trimethyl-3-phenyl-5H-chromeno[40,30:4,5]pyrano-
[2,3-c]pyrazole (11a, C24H26N2O2)
0
4.66 (ddd, J = 12.6, 4.4, 1.6 Hz, 1H, H6 ), 6.65–7.53 (m,
White powder; yield 394 mg (46 %); m.p.: 145–147 °C;
Rf = 0.42 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
7H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.83
(CH3 of pyrazolone), 20.80 (CH3-10), 22.68 (CH3 attached
to 3° ring junction carbon), 28.86 (CH3-5), 32.38 (CH3-50),
33.92 (C-11b), 47.46 (C-5a), 62.06 (C-6), 82.88 (C-5),
101.32, 116.16, 127.23, 127.89, 128.38, 129.19, 129.43,
129.62, 130.12, 130.35, 131.74, 135.76, 147.32, 149.33,
150.40 (Ar–C) ppm; MS: m/z = 409.0 [M?H?].
ꢀ
m = 3,065, 2,933, 1,596, 1,501, 1,487, 1,315, 1,228,
1,086, 1,051, 984, 794, 753, 689 cm-1 1H NMR
;
(400 MHz, CDCl3): d = 0.81 (t, J = 7.6 Hz, 3H, CH3 of
ethyl), 1.09 (s, 3H, CH3-5), 1.66 (s, 3H, CH3-50), 2.03 (m,
1H, –CH2CH3), 2.17 (d, J = 4.0 Hz, 1H, H5a), 2.27 (m,
1H, –CH2CH3), 2.64 (s, 3H, CH3 of pyrazolone), 4.40 (d,
J = 12.8 Hz, 1H, H6), 4.62 (dd, J = 12.4, 4.4 Hz, 1H,
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro-
1,5,5,10,11b-pentamethyl-5H-chromeno[40,30:4,5]-
pyrano[2,3-c]pyrazole (10d, C24H24Cl2N2O2)
H6 ), 6.74–7.80 (m, 9H, Ar–H) ppm; 13C NMR (100 MHz,
0
CDCl3): d = 8.08 (CH3 of ethyl), 16.49 (CH3 of pyrazo-
lone), 23.15 (CH3-5), 29.41 (CH3-50), 34.18 (CH2 of ethyl),
37.83 (C-11b), 40.68 (C-5a), 61.56 (C-6), 82.56 (C-5),
White powder; yield 638 mg (63 %); m.p.: 169–171 °C;
Rf = 0.43 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
123

Triethylammonium acetate mediated domino-Knoevenagel-hetero-Diels–Alder reaction
875
98.01, 116.11, 120.44, 120.91, 125.32, 127.43, 127.62,
128.83, 130.07, 138.82, 146.66, 149.47, 152.69 (Ar–C)
ppm; MS: m/z = 375.2 [M?H?].
(11bS)-3-(3-Chlorophenyl)-3,11b-dihydro-1,11b-dimethyl-
6H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(12c, C21H17ClN2O2)
White powder; yield 670 mg (64 %); m.p.: 119–121 °C;
Rf = 0.57 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
General procedure for the synthesis of 12a–12e,
13a–13e, and 14a
ꢀ
m = 2,963, 2,928, 1,701, 1,611, 1,527, 1,431, 1,246,
1
1,098, 1,045, 869, 765, 687 cm-1; H NMR (400 MHz,
CDCl3): d = 1.86 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.67 (s, 3H, CH3 of pyrazolone), 4.65 (d,
J = 12.4 Hz, 1H, H6), 5.18 (dd, J = 12.2, 1.2 Hz, 1H,
In a round-bottom flask, a mixture of O-propargylated
acetophenones/propiophenone 4a–4c (3.0 mmol), 5-pyraz-
olones 5a–5e (3.0 mmol), and zinc oxide (0.75 mmol,
25 mol%) in TEAA (0.75 mmol, 25 mol%) was heated at
150 °C until the reaction was completed as monitored by
TLC. The crude products thus obtained in good yields were
purified further by column chromatography.
0
H6 ), 6.58 (d, J = 1.2 Hz, 1H, H5), 6.87–7.68 (m, 8H,
Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.42
(CH3 of pyrazolone), 27.56 (CH3 attached to 3° ring
junction carbon), 36.28 (C-11b), 64.36 (C-6), 101.05,
114.79, 117.27, 120.48, 121.31, 125.78, 127.65, 128.58,
129.37, 129.87, 138.63, 146.23, 148.63, 150.92 (C=C and
Ar–C) ppm; MS: m/z = 365.2 [M?H?].
(11bS)-3,11b-Dihydro-1,11b-dimethyl-3-phenyl-6H-
chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(12a, C21H18N2O2)
(11bS)-3-(2,5-Dichlorophenyl)-3,11b-dihydro-1,11b-
dimethyl-6H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(12d, C21H16Cl2N2O2)
White powder; yield 588 mg (62 %); m.p.: 156–158 °C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
White powder; yield 699 mg (61 %); m.p.: 149–151 °C;
Rf = 0.62 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,969, 2,927, 1,672, 1,595, 1,518, 1,488, 1,451,
1,227, 1,109, 1,039, 844, 753, 683 cm-1 1H NMR
;
ꢀ
m = 2,968, 2,922, 1,700, 1,596, 1,520, 1,437, 1,232,
(400 MHz, CDCl3): d = 1.87 (s, 3H, CH3 attached to 3°
ring junction carbon), 2.66 (s, 3H, CH3 of pyrazolone),
4.65 (d, J = 12.4 Hz, 1H, H6), 5.17 (dd, J = 12.0, 1.6 Hz,
1
1,097, 1,044, 862, 758, 676 cm-1; H NMR (400 MHz,
CDCl3): d = 1.86 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.65 (s, 3H, CH3 of pyrazolone), 4.66 (d,
J = 12.4 Hz, 1H, H6), 5.19 (dd, J = 12.2, 1.2 Hz, 1H,
0
1H, H6 ), 6.56 (d, J = 1.2 Hz, 1H, H5), 6.87–7.73 (m, 9H,
Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.10
(CH3 of pyrazolone), 27.67 (CH3 attached to 3° ring
junction carbon), 36.05 (C-11b), 65.02 (C-6), 100.05,
115.01, 117.59, 120.75, 121.10, 125.19, 126.32, 128.08,
129.07, 133.48, 134.02, 137.99, 145.55, 146.44, 152.78
(C=C and Ar–C) ppm; MS: m/z = 331.1 [M?H?].
0
H6 ), 6.58 (d, J = 1.2 Hz, 1H, H5), 6.67–7.68 (m, 7H, Ar–
H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.66 (CH3 of
pyrazolone), 27.62 (CH3 attached to 3° ring junction
carbon), 36.69 (C-11b), 64.52 (C-6), 100.94, 114.68,
117.52, 121.63, 128.02, 128.79, 129.32, 129.51, 129.67,
128.03, 131.16, 132.45, 134.66, 137.03, 147.66, 149.12,
151.23 (C=C and Ar–C) ppm; MS: m/z = 399.0 [M?H?].
(11bS)-3-(2-Chlorophenyl)-3,11b-dihydro-1,11b-dimethyl-
6H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(12b, C21H17ClN2O2)
(11bS)-3,11b-Dihydro-1,11b-dimethyl-3-(4-methylphenyl)-
6H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(12e, C22H20N2O2)
White powder; yield 628 mg (60 %); m.p.: 157–160 °C;
Rf = 0.27 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
White powder; yield 662 mg (67 %); m.p.: 147–149 °C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,966, 2,926, 1,687, 1,613, 1,524, 1,428, 1,239,
1
1,113, 1,042, 852, 761, 686 cm-1; H NMR (400 MHz,
ꢀ
m = 2,967, 2,931, 1,702, 1,614, 1,517, 1,428, 1,229,
1,107, 1,042, 870, 759, 682 cm-1; H NMR (400 MHz,
1
CDCl3): d = 1.84 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.66 (s, 3H, CH3 of pyrazolone), 4.65 (d,
J = 12.4 Hz, 1H, H6), 5.17 (dd, J = 12.8, 1.2 Hz, 1H,
CDCl3): d = 1.86 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.36 (s, 3H, CH3 of phenyl), 2.67 (s, 3H, CH3 of
pyrazolone), 4.65 (d, J = 12.4 Hz, 1H, H6), 5.18 (dd,
0
H6 ), 6.57 (d, J = 1.2 Hz, 1H, H5), 6.56–7.63 (m, 8H,
Ar–H) ppm; 13C NMR (100 MHz, CDCl3): d = 16.33
(CH3 of pyrazolone), 27.48 (CH3 attached to 3° ring
junction carbon), 36.44 (C-11b), 64.36 (C-6), 101.09,
114.94, 116.41, 120.51, 127.66, 128.31, 129.38, 129.56,
129.84, 130.57, 131.02, 131.61, 135.23, 147.54, 149.41,
150.55 (C=C and Ar–C) ppm; MS: m/z = 365.2 [M?H?].
0
J = 12.2, 1.2 Hz, 1H, H6 ), 6.58 (d, J = 1.2 Hz, 1H, H5),
6.87–7.68 (m, 8H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.23 (CH3 of pyrazolone), 20.76 (CH3 of
phenyl), 27.75 (CH3 attached to 3° ring junction carbon),
36.13 (C-11b), 64.87 (C-6), 101.55, 114.46, 117.15,
120.76, 121.11, 127.65, 129.24, 129.33, 129.72, 134.32,
123

876
N. J. Parmar et al.
135.55, 137.13, 146.22, 148.48, 151.51 (C=C and Ar–C)
ppm; MS: m/z = 345.2 [M?H?].
(C-11b), 65.31 (C-6), 101.54, 114.62, 116.51, 127.46,
128.18, 128.39, 129.08, 129.49, 129.74, 130.18, 130.35,
131.48, 134.57, 135.71, 147.61, 149.41, 150.58 (C=C and
Ar–C) ppm; MS: m/z = 379.1 [M?H?].
(11bS)-3,11b-Dihydro-1,10,11b-trimethyl-3-phenyl-6H-
chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(13a, C22H20N2O2)
(11bS)-3-(2,5-Dichlorophenyl)-3,11b-dihydro-1,10,11b-
trimethyl-6H-chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(13d, C22H18Cl2N2O2)
White powder; yield 621 mg (68 %); m.p.: 169–172 °C;
Rf = 0.57 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
ꢀ
m = 2,961, 2,924, 1,689, 1,596, 1,519, 1,421, 1,232,
White powder; yield 615 mg (56 %); m.p.: 133–135 °C;
Rf = 0.49 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
1
1,113, 1,041, 859, 764, 678 cm-1; H NMR (400 MHz,
ꢀ
CDCl3): d = 1.87 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.28 (s, 3H, CH3-10), 2.64 (s, 3H, CH3 of
pyrazolone), 4.64 (d, J = 12.2 Hz, 1H, H6), 5.16 (dd,
m = 2,964, 2,930, 1,701, 1,611, 1,518, 1,466, 1,233,
1
1,102, 1,043, 867, 756, 671 cm-1; H NMR (400 MHz,
CDCl3): d = 1.87 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.31 (s, 3H, CH3-10), 2.66 (s, 3H, CH3 of
pyrazolone), 4.65 (d, J = 12.2 Hz, 1H, H6), 5.16 (dd,
0
J = 12.4, 1.6 Hz, 1H, H6 ), 6.59 (d, J = 1.2 Hz, 1H, H5),
6.77–7.73 (m, 8H, Ar–H) ppm; 13C NMR (100 MHz, CDCl3):
d = 16.31 (CH3 of pyrazolone), 20.72 (CH3-10), 27.26 (CH3
attached to 3° ring junction carbon), 36.29 (C-11b), 65.10
(C-6), 102.15, 114.59, 116.96, 120.71, 125.82, 128.15, 128.76,
129.09, 129.92, 139.23, 146.61, 149.14, 151.67 (C=C and
Ar–C) ppm; MS: m/z = 345.1 [M?H?].
0
J = 12.0, 1.2 Hz, 1H, H6 ), 6.61 (d, J = 1.2 Hz, 1H, H5),
6.78–7.71 (m, 6H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.61 (CH3 of pyrazolone), 21.44 (CH3-10),
27.49 (CH3 attached to 3° ring junction carbon), 37.13
(C-11b), 66.51 (C-6), 101.15, 114.74, 117.91, 127.52,
127.62, 127.92, 129.46, 129.76, 130.21, 130.59, 131.43,
132.68, 134.80, 136.56, 147.83, 149.33, 151.42 (C=C and
Ar–C) ppm; MS: m/z = 413.0 [M?H?].
(11bS)-3-(2-Chlorophenyl)-3,11b-dihydro-1,10,11b-
trimethyl-6H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (13b, C22H19ClN2O2)
White powder; yield 574 mg (57 %); m.p.: 174–176 °C;
Rf = 0.31 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(11bS)-3,11b-Dihydro-1,10,11b-trimethyl-3-
(4-methylphenyl)-6H-chromeno[40,30:4,5]pyrano
[2,3-c]pyrazole (13e, C23H22N2O2)
ꢀ
m = 2,968, 2,922, 1,692, 1,612, 1,521, 1,458, 1,240,
1
1,098, 1,042, 867, 756, 669 cm-1; H NMR (400 MHz,
White powder; yield 657 mg (69 %); m.p.: 193–196 °C;
Rf = 0.59 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
CDCl3): d = 1.85 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.29 (s, 3H, CH3-10), 2.64 (s, 3H, CH3 of
pyrazolone), 4.64 (d, J = 12.0 Hz, 1H, H6), 5.16 (dd,
ꢀ
m = 2,967, 2,923, 1,681, 1,614, 1,522, 1,498, 1,239,
1
1,110, 1,047, 822, 776, 663 cm-1; H NMR (400 MHz,
0
J = 12.8, 1.2 Hz, 1H, H6 ), 6.60 (d, J = 1.2 Hz, 1H, H5),
CDCl3): d = 1.86 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.26 (s, 3H, CH3-10), 2.34 (s, 3H, CH3 of phenyl),
2.65 (s, 3H, CH3 of pyrazolone), 4.64 (d, J = 12.2 Hz, 1H,
6.75–7.70 (m, 6H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 15.93 (CH3 of pyrazolone), 22.17 (CH3-10),
27.36 (CH3 attached to 3° ring junction carbon), 36.77
(C-11b), 66.49 (C-6), 102.10, 114.82, 116.71, 127.53,
127.96, 128.43, 129.09, 129.48, 129.76, 130.23, 130.52,
131.71, 135.38, 147.33, 149.34, 151.17 (C=C and Ar–C)
ppm; MS: m/z = 379.1 [M?H?].
0
H6), 5.18 (dd, J = 12.0, 1.6 Hz, 1H, H6 ), 6.62 (d,
J = 1.2 Hz, 1H, H5), 6.75–7.72 (m, 7H, Ar–H) ppm; 13C
NMR (100 MHz, CDCl3): d = 16.51 (CH3 of pyrazolone),
20.69 (CH3-10), 20.91 (CH3 of phenyl), 27.30 (CH3
attached to 3° ring junction carbon), 36.45 (C-11b), 65.17
(C-6), 101.12, 116.86, 120.89, 127.95, 128.23, 128.82,
129.36, 130.47, 135.75, 136.41, 146.71, 148.76, 150.38
(C=C and Ar–C) ppm; MS: m/z = 359.2 [M?H?].
(11bS)-3-(3-Chlorophenyl)-3,11b-dihydro-1,10,11b-
trimethyl-6H-chromeno[40,30:4,5]pyrano[2,3-c]-
pyrazole (13c, C22H19ClN2O2)
White powder; yield 543 mg (64 %); m.p.: 147–150 °C;
Rf = 0.64 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
(11bS)-11b-Ethyl-3,11b-dihydro-1-methyl-3-phenyl-6H-
chromeno[40,30:4,5]pyrano[2,3-c]pyrazole
(14a, C22H20N2O2)
ꢀ
m = 2,964, 2,926, 1,691, 1,608, 1,516, 1,443, 1,240,
1
1,111, 1,037, 859, 757, 691 cm-1; H NMR (400 MHz,
White powder; yield 293 mg (32 %); m.p.: 134–136 °C;
Rf = 0.44 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
CDCl3): d = 1.89 (s, 3H, CH3 attached to 3° ring junction
carbon), 2.31 (s, 3H, CH3-10), 2.66 (s, 3H, CH3 of
pyrazolone), 4.67 (d, J = 12.4 Hz, 1H, H6), 5.17 (dd,
ꢀ
m= 2,973, 2,934, 1,683, 1,591, 1,573, 1,492, 1,448, 1,234,
1
1,113, 1,042, 856, 761, 692 cm-1; H NMR (400 MHz,
0
J = 12.0, 1.2 Hz, 1H, H6 ), 6.60 (d, J = 1.2 Hz, 1H, H5),
CDCl3): d = 0.90 (t, J = 7.6 Hz, 3H, CH3 of ethyl), 2.14
(m, 1H, –CH2CH3), 2.39 (m, 1H, –CH2CH3), 2.67 (s, 3H,
CH3 of pyrazolone), 4.64 (d, J = 12.0 Hz, 1H, H6), 5.19
6.80–7.71 (m, 7H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.18 (CH3 of pyrazolone), 21.02 (CH3-10),
27.13 (CH3 attached to 3° ring junction carbon), 36.01
0
(dd, J = 12.8, 2.0 Hz, 1H, H6 ), 6.58 (d, J = 1.2 Hz, 1H,
123

Triethylammonium acetate mediated domino-Knoevenagel-hetero-Diels–Alder reaction
877
H5), 6.91–7.72 (m, 9H, Ar–H) ppm; 13C NMR (100 MHz,
CDCl3): d = 8.42 (CH3 of ethyl), 16.72 (CH3 of pyrazo-
lone), 32.31 (CH2 of ethyl), 36.57 (C-11b), 64.94 (C-6),
100.26, 115.46, 117.71, 120.82, 121.53, 125.25, 126.18,
128.27, 129.35, 133.39, 133.94, 138.14, 145.62, 146.56,
152.64 (C=C and Ar–C) ppm; MS: m/z = 345.2 [M?H?].
128.65, 129.64, 130.35, 132.68, 138.46, 148.61, 154.12
(Ar–C), 164.02 (C=N), 165.42 (C=O) ppm; MS: m/z =
331.0 [M?H?].
X-ray crystallography
CCDC-840896 and CCDC-893722 contain the supple-
mentary crystallographic data for this article. The data can
be obtained free of charge from The Cambridge Crystal-
lographic Data Centre via http://www.ccdc.cam.ac.uk/
data_request/cif.
(E)-4-[1-[2-(Allyloxy)phenyl]ethylidene]-2,4-dihydro-5-
methyl-1-phenyl-3H-pyrazol-3-one (Knoevenagel
intermediate 1, C21H20N2O2)
Yellow oil; Rf = 0.60 (ethyl acetate/n-hexane 1.5:8.5); IR
ꢀ
(KBr): m = 2,967, 2,926, 1,689, 1,629, 1,500, 1,232, 1,119,
1
1,048, 818, 755, 690 cm-1; H NMR (400 MHz, CDCl3):
Acknowledgments We sincerely express our thanks to the Head,
Department of Chemistry, S.P. University, for providing the neces-
sary research facilities. Three of us (BRP, HAB, and BDP) are
grateful to UGC, New Delhi, for financial support under the UGC
Scheme of RFSMS. We also acknowledge the help rendered by
Vaibhav Analytical Laboratories, Ahmadabad, and Nutan Dye Chem,
Surat.
d = 1.61 (s, 3H, CH3), 2.84 (s, 3H, CH3 of pyrazolone),
4.60 (d, J = 4.0 Hz, 2H, CH2), 5.28 (dd, J = 10.4, 1.2 Hz,
1H, methylene), 5.37 (dd, J = 17.2, 1.6 Hz, 1H, methy-
lene), 5.99 (m, 1H, CH), 6.98–7.99 (m, 9H, Ar–H) ppm;
13C NMR (100 MHz, CDCl3): d = 16.62 (CH3 of pyraz-
olone), 22.21 (CH3), 69.00 (CH2), 112.46 (CH), 117.76
(methylene), 118.74, 118.80, 118.90, 120.76, 124.62,
126.66, 128.20, 128.74, 128.93, 130.41, 132.60, 138.46,
148.83, 154.17 (Ar–C), 163.76 (C=N), 163.90 (C=O) ppm;
MS: m/z = 333.1 [M?H?].
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