Monatsh Chem

DOI 10.1007/s00706-012-0873-7

ORIGINAL PAPER

Triethylammonium acetate-mediated domino-Knoevenagelhetero-DielsAlder 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

Springer-Verlag Wien 2012

Abstract A solvent-cum catalyst, ionic liquid triethylammonium acetate-mediated one-pot procedure for the
synthesis of some new angular benzopyrano[3,4-c]pyranofused 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.
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 [110]. Potential candidates of this
class include naturally occurring cannabicyclol [11], mahanimbine [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
R. Kant  V. K. Gupta
Post-Graduate Department of Physics, University of Jammu,
Jammu Tawi 180006, India

heterosteroids [1416] possessing this skeleton have significantly 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 [1727]; 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 [2836]. Covering Tietzes pioneering work [34, 3745] 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-DielsAlder
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 pyrazoles [4648]. 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.

Results and discussion

The typical intermediate oxabutadiene formed in situ was
cyclized in a subsequent hetero-DielsAlder step without
changing any reagent or reaction conditions (Scheme 1).
Because they incorporate a tertiary ring junction carbon, all

123

N. J. Parmar et al.
Scheme 1

-H2O

R
Scheme 2

O
R

R2

1a, R1 = H, R2 = Me
1b, R1 = Me, R2 = Me
1c, R1 = H, R2 = Et

1a-1c
OH

Br

Br

Br

O
R

R2

O
R2

R2

2a-2c

3a-3c

4a-4c

new angular polyheterocycles are expected to display a

steroidal mimicking biological function [4951].
Corresponding O-allylated/prenylated/propargylated acetophenones 2a, 2b, 3a, 3b, 4a, and 4b and propiophenones
2c, 3c, and 4c were obtained in high yields with excellent
purity, prepared by the method reported elsewhere (Scheme 2)
[4648].
To optimize the reaction conditions, we examined first
triethylamine (TEA), p-toluenesulfonic acid (p-TSA), ethylene diammonium diacetate (EDDA), or zinc oxide (ZnO)
in refluxing ethanol or acetonitrile as reported elsewhere
[4248, 5255]. 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 49). 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

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.
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 unactivated 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 1418). Surprisingly, no contamination and easy
product isolation were achieved to get the desired products.
In addition, it improved the reaction in temperature and

Triethylammonium acetate mediated domino-Knoevenagel-hetero-DielsAlder reaction

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
Table 1 Optimization of the conditions to yield domino products 6a
and 9a
Entry

Solvent

Catalyst
(25 mol%)

Temp/C

Time/h

Yield/%
6a/9a

MeCN

Reflux

24/24

MeCN

EDDA

Reflux

24/24

MeCN

ZnO

Reflux

24/24

/Traces

Toluene

Reflux

24/24

7/12

Toluene

EDDA

Reflux

24/24

11/21

6
7

Toluene
Xylene

ZnO

Reflux
Reflux

24/24
24/24

12/23
18/27

Xylene

EDDA

Reflux

24/24

24/28

Xylene

ZnO

Reflux

24/24

22/30

10

130

5.0/5.0

/23

11

160

3.5/2.5

68/65

12

EDDA

130

5.0/3.5

/67

13

EDDA

150

4.0/2.5

64/63

14

TEAA

100

5.0/5.0

15

TEAA

120

5.0/5.0

/28

16

TEAA

130

5.0/3.5

/70

17

TEAA

140

5.0/3.0

20/71

18

TEAA

150

3.5/2.0

67/64

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, 6a6e, 7a7e, 8a, 9a9e, 10a10e, and
11a (Scheme 3), were then prepared following the optimized reaction conditions. The yields were in the range
5871 % (Table 2).
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 catalyzed reactions in refluxing acetonitrile, toluene, and
xylene (Table 3, entries 16). While only 16 % of product
12a resulted in refluxing xylene after prolong heating, no
product was obtained in other solvents, making the conventional 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 1214). 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 heterocycles: 12a12e, 13a13e, and 14a (Scheme 4; Table 4).
Besides pyrazolones, other analogous active methylene units such as hydroxycoumarin, cyclohexanedione,
and phenyloxazolone were also tried with O-allylated,

O
R1

N N

R2
O

R2

2a-2c
5a, R3 = Ph
5b, R3 = 2-ClPh
5c, R3 = 3-ClPh
O
3
5d, R = 2,5-Cl2Ph
5e, R3 = 4-MePh

R3

6a-6e
7a-7e
8a

O
TEAA
N

R3
5a-5e

O
R1

N N

R2
O

R1

R2

3a-3c
2a, 3a, R1 = H, R2 = Me
2b, 3b, R1 = Me, R2 = Me
2c, 3c, R1 = H, R2 = Et

R3
9a-9e
10a-10e
11a

Scheme 3

123

N. J. Parmar et al.
Table 2 Synthesis of novel tetrahydro-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazoles
Entry 2a/3b

Product R1

R2

R3

Table 3 Optimization of the conditions to afford 12a

Entry

Solvent

Catalyst

Temp/C

Time/h

Yield/%

Time/h Yieldc/%
1

MeCN

Reflux

24

2a/3a 5a 6a/9a

Me Ph

3.5/3.5 67/70

Toluene

Reflux

24

2a/3a 5b 6b/9b

Me 2-ClPh

4.5/4.0 61/58

Xylene

Reflux

24

2a/3a 5c 6c/9c

Me 3-ClPh

3.5/3.5 63/68

MeCN

ZnO (25 %)

Reflux

24

2a/3a 5d 6d/9d

Me 2,5-Cl2Ph 3.0/3.5 61/65

Toluene

ZnO (25 %)

Reflux

24

Trace

2a/3a 5e 6e/9e

Me 4-MePh

3.0/3.0 69/68

Xylene

ZnO (25 %)

Reflux

24

16

2b/3b 5a 7a/10a

Me Me Ph

4.0/3.5 70/71

160

10

7
8

2b/3b 5b 7b/10b Me Me 2-ClPh

2b/3b 5c 7c/10c Me Me 3-ClPh

4.0/4.0 66/62
3.5/4.0 63/67

ZnO (15 %)

160

10

33

ZnO (25 %)

160

58

2b/3b 5d 7d/10d Me Me 2,5-Cl2Ph 4.0/3.5 67/63

10

ZnO (35 %)

160

56

10

2b/3b 5e 7e/10e

Me Me 4-MePh

3.5/3.0 65/70

11

2c/3c 5a 8a/11a

4.5/3.5 39/46

11
12

TEAA (25 %)
TEAA (25 %)a

160
130

10
6

O-allylated substrates

13

TEAA (25 %)a

150

62

O-prenylated substrates

14

TEAA (25 %)a

160

57

a
b

Et

Ph

Optimized conditions: 25 mol% TEAA, 150 C for 2 and 130 C

for 3

O-prenylated, and O-propargylated acetophenones, using

the optimized condition (Table 3, entry 13). Also, other
ketone-based substrates derived from 2-hydroxybenzophenone were tested. But they failed to give subsequent
cyclized products after forming the Knoevenagel adduct.
Work in this area is ongoing.
The formation of the Knoevenagel intermediate [5255]
was confirmed by 1H NMR, 13C NMR, and DEPT-135
studies. From single-crystal X-ray data of 9a, a cis orientation 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 intermediate IV [5255]. 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
IV was isolated and its structure was also confirmed by 1H
NMR, 13C NMR, and DEPT-135. Finally, under the influence of TEAA, IV undergoes the hetero-DielsAlder
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 substituent 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

123

As a mixture with ZnO (25 mol%)

position to each other. It was therefore concluded that the

reaction proceeds via endo-E-syn transition states even
though two pathways are possible.
1
H NMR spectra featured a singlet at around
d = 1.01.9 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 = 2230 ppm, except the compounds derived from propiophenones. In polyheterocycles
derived from propiophenones, two bridge head methylene
protons showed multiplets in the 2.032.39 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) [5659].The data fully agreed with the proposed structure.

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 Knoevenagel intramolecular hetero-Dielsalder route. Besides
providing efficient and improved reaction conditions for unactivated 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.

Experimental
Solvents were dried by standard procedures. 1H and 13C
NMR spectra were determined in CDCl3 on a Bruker

Triethylammonium acetate mediated domino-Knoevenagel-hetero-DielsAlder reaction

Scheme 4

N N

O
1

R2

TEAA + ZnO
R1

R2

R3

4a-4c

O
12a-12e
13a-13e
14a

5a-5e
5a, R3 = Ph
5b, R3 = 2-ClPh
5c, R3 = 3-ClPh
5d, R3 = 2,5-Cl2Ph
5e, R3 = 4-MePh

4a, R1 = H, R2 = Me
4b, R1 = Me, R2 = Me
4c, R1 = H, R2 = Et

Table 4 Synthesis of novel

dihydro-6H-chromeno[40 ,30 :4,
5]pyrano[2,3-c]pyrazoles
12a12e, 13a13e, 14a

R3

Entry

4a

Product

R1

R2

R3

Time/h

Yieldb/%

4a/4b

5a

12a/13a

H/Me

Me

Ph

6.0/6.5

62/68

4a/4b

5b

12b/13b

H/Me

Me

2-ClPh

7.5/8.0

60/57

4a/4b

5c

12c/13c

H/Me

Me

3-ClPh

8.0/7.5

64/64

Propargylated substrates

4a/4b

5d

12d/13d

H/Me

Me

2,5-Cl2Ph

7.0/7.0

61/56

Optimized condition: equal

amount (25 mol%) of TEAA
and ZnO, 150 C

4a/4b

5e

12e/13e

H/Me

Me

4-MePh

6.5/7.0

67/69

4c

5a

14a

Et

Ph

7.0

32

a
b

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 (PerkinElmer, USA). The reactions were monitored by silica gel
60 F254 thin-layer chromatographic (TLC) plates of
Merck. Melting points were determined in an open capillary tube on a TEMPO melting point apparatus. Ionic
liquid-cum-catalyst TEAA was prepared by reported literature methods [60].
Single crystal X-ray diffraction data were collected on a
Bruker CCD area-detector diffractometer equipped with a
).
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 crystallizes in the monoclinic space group P21/n with the following
unit-cell parameters: a = 13.4695(4), b = 10.3715(3),
, b = 95.724(3), and Z = 4. Compound
c = 13.8111(4) A
12a crystallizes in the monoclinic space group P21/c with
the following unit-cell parameters: a = 10.2068(3), b = 11.
, b = 91.778(3) , and Z = 4.
2849(5), c = 14.3720(5) A
The crystal structures of 9a and 12a were solved by direct

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 6a6e, 7a7e,
and 8a
A mixture of O-allylated acetophenones/propiophenone
2a2c (3.0 mmol) and corresponding 5-pyrazolone 5a5e
(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.
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,11b-dimethyl-3phenyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(6a, C21H20N2O2)
White powder; yield 631 mg (67 %); m.p.: 152154 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,
1,093, 1,048, 840, 756, 692 cm-1; 1H NMR (400 MHz,
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3 ring junction
carbon), 2.16 (m, 1H, H5a), 2.64 (s, 3H, CH3 of pyrazolone), 4.27 (m, 2H, H5 and H6), 4.53 (dd, J = 11.2, 3.6 Hz,
1H, H60 ), 4.58 (dd, J = 12.0, 2.8 Hz, 1H, H50 ), 6.807.73

123

N. J. Parmar et al.

O
R1
Et 3 NH
O

AcOH

R2

ll

R
l
O

R = H, Me

Et 3 NH O R2

R3

R1

N
N

H
O O

Et 3 NH AcO

R3

lll
R1

R
O

N N
R1

N
O

H
O

AcOH

R2

R3

R
R
R

RO

N
R3

Et 3NH AcO
lV

Et 3NH AcO

V
Scheme 5

(m, 9H, ArH) 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 (ArC) ppm; MS: m/z = 333.1 [M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro1,11b-dimethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (6b, C21H19ClN2O2)
White powder; yield 634 mg (61 %); m.p.: 154156 C;
Rf = 0.24 (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,
1,094, 1,043, 841, 757, 683 cm-1; 1H NMR (400 MHz,
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3 ring junction
carbon), 2.17 (m, 1H, H5a), 2.62 (s, 3H, CH3 of pyrazolone), 4.27 (m, 2H, H5 and C-H6), 4.52 (dd, J = 11.2,
3.6 Hz, 1H, H60 ), 4.58 (dd, J = 12.0, 2.8 Hz, 1H, H50 ),

123

6.797.71 (m, 8H, ArH) 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 (ArC) ppm; MS:
m/z = 367.2 [M?H?].
(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 655 mg (63 %); m.p.: 146148 C;
Rf = 0.47 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,968, 2,926, 1,591, 1,517, 1,477, 1,440, 1,226,
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,

Triethylammonium acetate mediated domino-Knoevenagel-hetero-DielsAlder reaction

(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro1,11b-dimethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (6d, C21H18Cl2N2O2)

White powder; yield 693 mg (61 %); m.p.: 204206 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,
J = 11.2, 3.6 Hz, 1H, H60 ), 4.55 (dd, J = 12.0, 2.8 Hz, 1H,
H50 ), 6.807.52 (m, 7H, ArH) 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 (ArC) ppm; MS:
m/z = 401.1 [M?H?].

Fig. 1 ORTEP view of compound 9a

Fig. 2 ORTEP view of compound 12a

J = 11.2, 3.6 Hz, 1H, H60 ), 4.57 (dd, J = 12.0, 2.8 Hz, 1H,
H50 ), 6.807.72 (m, 8H, ArH) 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 (ArC) ppm; MS:
m/z = 367.2 [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.: 150152 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,
1,097, 1,045, 820, 754, 673 cm-1; 1H NMR (400 MHz,
CDCl3): d = 1.81 (s, 3H, CH3 attached to 3 ring junction
carbon), 2.17 (m, 1H, H5a), 2.37 (s, 3H, CH3 of phenyl),
2.63 (s, 3H, CH3 of pyrazolone), 4.27 (m, 2H, H5 and H6),
4.52 (dd, J = 11.0, 3.2 Hz, 1H, H60 ), 4.58 (dd, J = 11.6,
2.4 Hz, 1H, H50 ), 6.797.58 (m, 8H, ArH) 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 (ArC) ppm; MS: m/z = 347.1 [M?H?].
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,10,11b-trimethyl-3phenyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(7a, C22H22N2O2)
White powder; yield 637 mg (70 %); m.p.: 138140 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,
1,085, 1,049, 846, 756, 671 cm-1; 1H 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,
J = 11.4, 3.6 Hz, 1H, H60 ), 4.59 (dd, J = 12.4, 2.8 Hz, 1H,
H50 ), 6.667.65 (m, 8H, ArH) 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 (C11b), 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

N. J. Parmar et al.

129.81, 138.52, 146.63, 148.62, 151.82 (ArC) ppm; MS:

m/z = 347.2 [M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro1,10,11b-trimethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (7b, C22H21ClN2O2)
White powder; yield 661 mg (66 %); m.p.: 164166 C;
Rf = 0.25 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,956, 2,932, 1,589, 1,517, 1,494, 1,456, 1,230,
1,091, 1,052, 853, 758, 691 cm-1; 1H NMR (400 MHz,
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,
J = 12.0, 3.2 Hz, 1H, H60 ), 4.58 (dd, J = 12.6, 2.4 Hz, 1H,
H50 ), 6.677.70 (m, 7H, ArH) 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 (C11b), 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
(ArC) ppm; MS: m/z = 381.1 [M?H?].
(5aR,11bS)-3-(3-Chlorophenyl)-3,5a,6,11b-tetrahydro1,10,11b-trimethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (7c, C22H21ClN2O2)
White powder; yield 630 mg (63 %); m.p.: 142144 C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,960, 2,927, 1,590, 1,518, 1,491, 1,445, 1,232,
1,093, 1,039, 848, 749, 676 cm-1; 1H NMR (400 MHz,
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,
J = 12.2, 3.2 Hz, 1H, H60 ), 4.59 (dd, J = 12.4, 2.4 Hz, 1H,
H50 ), 6.687.71 (m, 7H, ArH) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.63 (CH3 of pyrazolone), 20.68 (CH3-10)
29.69 (CH3 attached to 3 ring junction carbon), 33.86 (C11b), 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
(ArC) ppm; MS: m/z = 381.1 [M?H?].
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro1,10,11b-trimethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (7d, C22H20Cl2N2O2)
White powder; yield 730 mg (67 %); m.p.: 178180 C;
Rf = 0.44 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,962, 2,930, 1,577, 1,515, 1,481, 1,441, 1,226,
1,085, 1,043, 862, 761, 658 cm-1; 1H NMR (400 MHz,
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,
J = 12.2, 3.2 Hz, 1H, H60 ), 4.59 (dd, J = 12.4, 2.4 Hz, 1H,
H50 ), 6.647.69 (m, 6H, ArH) ppm; 13C NMR (100 MHz,
CDCl3): d = 16.71 (CH3 of pyrazolone), 20.76 (CH3-10)

123

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
(ArC) ppm; MS: m/z = 415.0 [M?H?].
(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)
White powder; yield 615 mg (65 %); m.p.: 132134 C;
Rf = 0.49 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,967, 2,928, 1,583, 1,523, 1,489, 1,445, 1,231,
1,078, 1,038, 859, 758, 684 cm-1; 1H NMR (400 MHz,
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
(m, 2H, H5 and H6), 4.53 (dd, J = 11.6, 3.2 Hz, 1H, H60 ),
4.59 (dd, J = 12.0, 2.4 Hz, 1H, H50 ), 6.667.68 (m, 7H,
ArH) 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 (ArC)
ppm; MS: m/z = 361.2 [M?H?].
(5aR,11bS)-11b-Ethyl-3,5a,6,11b-tetrahydro-1-methyl-3phenyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(8a, C22H22N2O2)
White powder; yield 0.355 mg (39 %); m.p.: 132133 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
(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
(m, 2H, H5 and H6), 4.51 (m, 2H, H50 and H60 ), 6.787.73
(m, 9H, ArH) 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 (ArC) ppm; MS: m/z = 347.1[M?H?].
General procedure for the synthesis of 9a9e, 10a10e,
and 11a
A mixture of O-prenylated acetophenones/propiophenone
3a3c (3.0 mmol) and the corresponding 5-pyrazolone
5a5e (3.0 mmol) in TEAA (0.75 mmol, 25 mol%) was
heated at 130 C until the reaction was completed as monitored by TLC. Crude cycloadducts were received in good
yields and purified further by column chromatography.

Triethylammonium acetate mediated domino-Knoevenagel-hetero-DielsAlder reaction

(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,11b-tetramethyl3-phenyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole

(9a, C23H24N2O2)
White powder; yield 623 mg (70 %); m.p.: 170172 C;
Rf = 0.51 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,981, 2,929, 1,597, 1,511, 1,491, 1,443, 1,230,
1,084, 1,043, 838, 757, 673 cm-1; 1H NMR (400 MHz,
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,
4.4, 2.0 Hz, 1H, H60 ), 6.767.78 (m, 9H, ArH) ppm; 13C
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 (ArC) ppm; MS: m/z = 361.1 [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.: 135137 C;
Rf = 0.24 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,965, 2,925, 1,587, 1,514, 1,482, 1,441, 1,229,
1,088, 1,038, 845, 758, 684 cm-1; 1H NMR (400 MHz,
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,
4.2, 2.0 Hz, 1H, H60 ), 6.777.79 (m, 8H, ArH) ppm; 13C
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 (ArC) ppm; MS: m/z = 395.1 [M?H?].
(5aR,11bS)-3-(3-Chlorophenyl)-3,5a,6,11b-tetrahydro1,5,5,11b-tetramethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (9c, C23H23ClN2O2)
White powder; yield 656 mg (68 %); m.p.: 148150 C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
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
(ddd, J = 12.4, 4.4, 2.0 Hz, 1H, H60 ), 6.717.79 (m, 8H,
ArH) 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,

116.29, 120.65, 120.99, 125.41, 127.50, 127.69, 128.83,

129.22, 138.75, 146.76, 148.13, 152.67 (ArC) ppm; MS:
m/z = 395.1 [M?H?].
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro1,5,5,11b-tetramethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (9d, C23H22Cl2N2O2)
White powder; yield 682 mg (65 %); m.p.: 130132 C;
Rf = 0.48 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,970, 2,925, 1,590, 1,512, 1,481, 1,445, 1,228, 1,088,
1,039, 851, 759, 675 cm-1; 1H 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,
2.0 Hz, 1H, H60 ), 6.697.56 (m, 7H, ArH) ppm; 13C NMR
(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 (ArC) ppm; MS: m/z = 429.2 [M?H?].
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,11b-tetramethyl3-(4-methylphenyl)-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (9e, C24H26N2O2)
White powder; yield 623 mg (68 %); m.p.: 178180 C;
Rf = 0.47 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,971, 2,929, 1,591, 1,560, 1,478, 1,444, 1,226, 1,094,
1,045, 853, 760, 661 cm-1; 1H NMR (400 MHz, CDCl3):
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,
H6), 4.74 (ddd, J = 12.8, 4.2, 2.0 Hz, 1H, H60 ), 6.707.79
(m, 8H, ArH) 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 (ArC) ppm; MS (ESI): m/z = 375.0 [M?H?].
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,10,11bpentamethyl-3-phenyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (10a, C24H26N2O2)
White powder; yield 573 mg (71 %); m.p.: 212214 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,
1,081, 1,039, 844, 748, 669 cm-1; 1H NMR (400 MHz,
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

N. J. Parmar et al.

4.70 (ddd, J = 12.6, 4.4, 1.6 Hz, 1H, H60 ), 6.657.55 (m,
8H, ArH) 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 (ArC) ppm; MS:
m/z = 375.2 [M?H?].
(5aR,11bS)-3-(2-Chlorophenyl)-3,5a,6,11b-tetrahydro1,5,5,10,11b-pentamethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (10b, C24H25ClN2O2)
White powder; yield 580 mg (62 %); m.p.: 168170 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; 1H NMR (400 MHz, CDCl3):
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),
4.68 (ddd, J = 12.4, 4.4, 1.6 Hz, 1H, H60 ), 6.647.50 (m,
7H, ArH) 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 (ArC) ppm; MS: m/z = 409.0 [M?H?].
(5aR,11bS)-3-(3-Chlorophenyl)-3,5a,6,11b-tetrahydro1,5,5,10,11b-pentamethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (10c, C24H25ClN2O2)
White powder; yield 627 mg (67 %); m.p.: 168170 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,
1,046, 861, 755, 668 cm-1; 1H 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),
4.66 (ddd, J = 12.6, 4.4, 1.6 Hz, 1H, H60 ), 6.657.53 (m,
7H, ArH) 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 (ArC) ppm; MS: m/z = 409.0 [M?H?].
(5aR,11bS)-3-(2,5-Dichlorophenyl)-3,5a,6,11b-tetrahydro1,5,5,10,11b-pentamethyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (10d, C24H24Cl2N2O2)
White powder; yield 638 mg (63 %); m.p.: 169171 C;
Rf = 0.43 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):

123

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),
4.67 (ddd, J = 12.4, 4.2, 1.6 Hz, 1H, H60 ), 6.617.66 (m,
6H, ArH) 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 (ArC) ppm; MS: m/z = 443.1
[M?H?].
(5aR,11bS)-3,5a,6,11b-Tetrahydro-1,5,5,10,11b-pentamethyl-3-(4-methylphenyl)-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (10e, C25H28N2O2)
White powder; yield 622 mg (70 %); m.p.: 250252 C;
Rf = 0.49 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr): m=
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,
1.6 Hz, 1H, H6), 4.69 (ddd, J = 12.8, 4.4, 1.6 Hz, 1H, H60 ),
6.647.64 (m, 7H, ArH) 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 (ArC) ppm; MS:
m/z = 389.1 [M?H?].
(5aR,11bS)-11b-Ethyl-3,5a,6,11b-tetrahydro-1,5,5trimethyl-3-phenyl-5H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (11a, C24H26N2O2)
White powder; yield 394 mg (46 %); m.p.: 145147 C;
Rf = 0.42 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
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,
H60 ), 6.747.80 (m, 9H, ArH) ppm; 13C NMR (100 MHz,
CDCl3): d = 8.08 (CH3 of ethyl), 16.49 (CH3 of pyrazolone), 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),

Triethylammonium acetate mediated domino-Knoevenagel-hetero-DielsAlder reaction

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 (ArC)
ppm; MS: m/z = 375.2 [M?H?].
General procedure for the synthesis of 12a12e,
13a13e, and 14a
In a round-bottom flask, a mixture of O-propargylated
acetophenones/propiophenone 4a4c (3.0 mmol), 5-pyrazolones 5a5e (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.
(11bS)-3,11b-Dihydro-1,11b-dimethyl-3-phenyl-6Hchromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(12a, C21H18N2O2)
White powder; yield 588 mg (62 %); m.p.: 156158 C;
Rf = 0.55 (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
(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,
1H, H60 ), 6.56 (d, J = 1.2 Hz, 1H, H5), 6.877.73 (m, 9H,
ArH) 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 ArC) ppm; MS: m/z = 331.1 [M?H?].
(11bS)-3-(2-Chlorophenyl)-3,11b-dihydro-1,11b-dimethyl6H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(12b, C21H17ClN2O2)
White powder; yield 628 mg (60 %); m.p.: 157160 C;
Rf = 0.27 (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,
1,113, 1,042, 852, 761, 686 cm-1; 1H NMR (400 MHz,
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,
H60 ), 6.57 (d, J = 1.2 Hz, 1H, H5), 6.567.63 (m, 8H,
ArH) 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 ArC) ppm; MS: m/z = 365.2 [M?H?].

(11bS)-3-(3-Chlorophenyl)-3,11b-dihydro-1,11b-dimethyl6H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole

(12c, C21H17ClN2O2)
White powder; yield 670 mg (64 %); m.p.: 119121 C;
Rf = 0.57 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,963, 2,928, 1,701, 1,611, 1,527, 1,431, 1,246,
1,098, 1,045, 869, 765, 687 cm-1; 1H 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,
H60 ), 6.58 (d, J = 1.2 Hz, 1H, H5), 6.877.68 (m, 8H,
ArH) 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
ArC) ppm; MS: m/z = 365.2 [M?H?].
(11bS)-3-(2,5-Dichlorophenyl)-3,11b-dihydro-1,11bdimethyl-6H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(12d, C21H16Cl2N2O2)
White powder; yield 699 mg (61 %); m.p.: 149151 C;
Rf = 0.62 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,968, 2,922, 1,700, 1,596, 1,520, 1,437, 1,232,
1,097, 1,044, 862, 758, 676 cm-1; 1H 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,
H60 ), 6.58 (d, J = 1.2 Hz, 1H, H5), 6.677.68 (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 ArC) ppm; MS: m/z = 399.0 [M?H?].
(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 662 mg (67 %); m.p.: 147149 C;
Rf = 0.55 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,967, 2,931, 1,702, 1,614, 1,517, 1,428, 1,229,
1,107, 1,042, 870, 759, 682 cm-1; 1H NMR (400 MHz,
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,
J = 12.2, 1.2 Hz, 1H, H60 ), 6.58 (d, J = 1.2 Hz, 1H, H5),
6.877.68 (m, 8H, ArH) 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

N. J. Parmar et al.

135.55, 137.13, 146.22, 148.48, 151.51 (C=C and ArC)

ppm; MS: m/z = 345.2 [M?H?].
(11bS)-3,11b-Dihydro-1,10,11b-trimethyl-3-phenyl-6Hchromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(13a, C22H20N2O2)
White powder; yield 621 mg (68 %); m.p.: 169172 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,
1,113, 1,041, 859, 764, 678 cm-1; 1H 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,
J = 12.4, 1.6 Hz, 1H, H60 ), 6.59 (d, J = 1.2 Hz, 1H, H5),
6.777.73 (m, 8H, ArH) 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
ArC) ppm; MS: m/z = 345.1 [M?H?].
(11bS)-3-(2-Chlorophenyl)-3,11b-dihydro-1,10,11btrimethyl-6H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (13b, C22H19ClN2O2)
White powder; yield 574 mg (57 %); m.p.: 174176 C;
Rf = 0.31 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,968, 2,922, 1,692, 1,612, 1,521, 1,458, 1,240,
1,098, 1,042, 867, 756, 669 cm-1; 1H NMR (400 MHz,
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,
J = 12.8, 1.2 Hz, 1H, H60 ), 6.60 (d, J = 1.2 Hz, 1H, H5),
6.757.70 (m, 6H, ArH) 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 ArC)
ppm; MS: m/z = 379.1 [M?H?].
(11bS)-3-(3-Chlorophenyl)-3,11b-dihydro-1,10,11btrimethyl-6H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole (13c, C22H19ClN2O2)
White powder; yield 543 mg (64 %); m.p.: 147150 C;
Rf = 0.64 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,964, 2,926, 1,691, 1,608, 1,516, 1,443, 1,240,
1,111, 1,037, 859, 757, 691 cm-1; 1H NMR (400 MHz,
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,
J = 12.0, 1.2 Hz, 1H, H60 ), 6.60 (d, J = 1.2 Hz, 1H, H5),
6.807.71 (m, 7H, ArH) 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

123

(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
ArC) ppm; MS: m/z = 379.1 [M?H?].
(11bS)-3-(2,5-Dichlorophenyl)-3,11b-dihydro-1,10,11btrimethyl-6H-chromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(13d, C22H18Cl2N2O2)
White powder; yield 615 mg (56 %); m.p.: 133135 C;
Rf = 0.49 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,964, 2,930, 1,701, 1,611, 1,518, 1,466, 1,233,
1,102, 1,043, 867, 756, 671 cm-1; 1H 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,
J = 12.0, 1.2 Hz, 1H, H60 ), 6.61 (d, J = 1.2 Hz, 1H, H5),
6.787.71 (m, 6H, ArH) 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
ArC) ppm; MS: m/z = 413.0 [M?H?].
(11bS)-3,11b-Dihydro-1,10,11b-trimethyl-3(4-methylphenyl)-6H-chromeno[40 ,30 :4,5]pyrano
[2,3-c]pyrazole (13e, C23H22N2O2)
White powder; yield 657 mg (69 %); m.p.: 193196 C;
Rf = 0.59 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m = 2,967, 2,923, 1,681, 1,614, 1,522, 1,498, 1,239,
1,110, 1,047, 822, 776, 663 cm-1; 1H NMR (400 MHz,
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,
H6), 5.18 (dd, J = 12.0, 1.6 Hz, 1H, H60 ), 6.62 (d,
J = 1.2 Hz, 1H, H5), 6.757.72 (m, 7H, ArH) 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 ArC) ppm; MS: m/z = 359.2 [M?H?].
(11bS)-11b-Ethyl-3,11b-dihydro-1-methyl-3-phenyl-6Hchromeno[40 ,30 :4,5]pyrano[2,3-c]pyrazole
(14a, C22H20N2O2)
White powder; yield 293 mg (32 %); m.p.: 134136 C;
Rf = 0.44 (ethyl acetate/n-hexane 1.5:8.5); IR (KBr):
m= 2,973, 2,934, 1,683, 1,591, 1,573, 1,492, 1,448, 1,234,
1,113, 1,042, 856, 761, 692 cm-1; 1H NMR (400 MHz,
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
(dd, J = 12.8, 2.0 Hz, 1H, H60 ), 6.58 (d, J = 1.2 Hz, 1H,

Triethylammonium acetate mediated domino-Knoevenagel-hetero-DielsAlder reaction

H5), 6.917.72 (m, 9H, ArH) ppm; 13C NMR (100 MHz,
CDCl3): d = 8.42 (CH3 of ethyl), 16.72 (CH3 of pyrazolone), 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 ArC) ppm; MS: m/z = 345.2 [M?H?].

128.65, 129.64, 130.35, 132.68, 138.46, 148.61, 154.12

(ArC), 164.02 (C=N), 165.42 (C=O) ppm; MS: m/z =
331.0 [M?H?].

(E)-4-[1-[2-(Allyloxy)phenyl]ethylidene]-2,4-dihydro-5methyl-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,
1,048, 818, 755, 690 cm-1; 1H NMR (400 MHz, CDCl3):
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, methylene), 5.99 (m, 1H, CH), 6.987.99 (m, 9H, ArH) ppm;
13
C NMR (100 MHz, CDCl3): d = 16.62 (CH3 of pyrazolone), 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 (ArC), 163.76 (C=N), 163.90 (C=O) ppm;
MS: m/z = 333.1 [M?H?].

CCDC-840896 and CCDC-893722 contain the supplementary crystallographic data for this article. The data can
be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/
data_request/cif.

(E)-2,4-Dihydro-5-methyl-4-[1-[2-(3-methylbut-2-enyloxy)phenyl]ethylidene]-1-phenyl-3H-pyrazol-3-one
(Knoevenagel intermediate 2, C23H24N2O2)
Yellow oil; Rf = 0.62 (ethyl acetate/n-hexane 1.5:8.5); IR
(KBr): m = 2,972, 2,927, 1,692, 1,609, 1,528, 1,496, 1,231,
1,107, 1,041, 823, 757, 688 cm-1; 1H NMR (400 MHz,
CDCl3): d = 1.62 (s, 3H, CH3 of acetyl), 1.68 (s, 3H, CH3
of prenyl), 1.74 (s, 3H, CH3 of prenyl), 2.85 (s, 3H, CH3 of
pyrazolone), 4.60 (d, J = 5.6 Hz, 2H, CH2), 5.62 (t,
J = 6.7 Hz, 1H, CH=), 7.007.96 (m, 9H, ArH) ppm;
13
C NMR (100 MHz, CDCl3): d = 17.11 (CH3 of pyrazolone), 23.08 (CH3 of acetyl), 27.23 (CH3 of prenyl), 31.30
(CH3 of prenyl), 68.67 (CH2), 114.64 (CH=), 117.76,
118.64, 118.87, 119.12, 121.03, 124.85, 127.21, 128.36,
128.78, 129.21, 130.53, 132.71, 138.68, 148.56, 153.58
(ArC), 164.14 (C=N), 165.63 (C=O) ppm; MS: m/z
= 361.2 [M?H?].
(E)-2,4-Dihydro-5-methyl-1-phenyl-4-[1-[2-(prop-2ynyloxy)phenyl]ethylidene]-3H-pyrazol-3-one
(Knoevenagel intermediate 3, C21H18N2O2)
Yellow oil; Rf = 0.58 (ethyl acetate/n-hexane 1.5:8.5); IR
(KBr): m = 2,966, 2,932, 2,158, 1,695, 1,612, 1,513, 1,494,
1,236, 1,113, 1,038, 815, 754, 691 cm-1; 1H NMR
(400 MHz, CDCl3): d = 1.62 (s, 3H, CH3 of acetyl),
2.68 (s, 3H, CH3), 2.43 (s, 1H, CH), 4.90 (s, 2H, CH2),
7.087.98 (m, 9H, ArH) ppm; 13C NMR (100 MHz,
CDCl3): d = 17.11 (CH3 of pyrazolone), 23.08 (CH3 of
acetyl), 58.34 (CH2), 74.34 (CH), 79.02 (CCH), 116.22,
118.32, 118.68, 118.97, 120.85, 124.73, 127.46, 128.53,

X-ray crystallography

Acknowledgments We sincerely express our thanks to the Head,

Department of Chemistry, S.P. University, for providing the necessary 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.

References
1. Kawakami K, Yasuda M, Ishii K, Kokusenya Y, Sato T (1999)
Chem Pharm Bull 47:919
2. Tarantin AV, Glushkov VA, Suponitskii KYu, Kudryashov AA,
Maiorova OA, Tolstikov AG (2010) Russ J Org Chem 46:1479
3. Simon C, Lieby-Muller F, Peyronel J-F, Constantieux T, Rodriguez J (2003) Synlett 2301
4. Matsuzawa S, Suzuki T, Suzuki M, Matsuda A, Kawamura T,
Mizuno Y, Kikuchi K (1994) FEBS Lett 356:272
5. Dinkova-Kostova AT, Talalay P, Sharkey J, Zhang Y, Holtzclaw
WD, Wang XJ, David E, Schiavoni KH, Finlayson S, Mierke DF,
Honda T (2010) J Biol Chem 285:33747
6. Cordova J, Leon LG, Leon F, San Andres L, Luis JG, Padron JM
(2006) Eur J Med Chem 41:1327
7. Chao K, Hua K, Hsu H, Su Y, Chang S (2005) Planta Med 71:300
8. Furukawa A, Arita T, Fukuzaki T, Satsh S, Mori M, Honda T,
Mastsui Y, Wakabayashi K, Hayashi S, Avaki K, Ohsumi J
(2012) Bioorg Med Chem Lett 22:1348
9. Subba Reddy BV, Divya B, Swain M, Rao TP, Yadav JS, Vishnu
Vardhan MVPS (2012) Bioorg Med Chem Lett 22:1995
10. Zhang G, Ma N, Jiang B, Shi F, Tu SJ (2010) Synthesis 3993
11. Hanus LO (2009) Med Res Rev 29:213
12. Adebajo AC, Ayoola OF, Iwalewa EO, Akindahunsi AA, Omisore NOA, Adewunmi CO, Adenowo TK (2006) Phytomedicine
13:246
13. Biellmann J-F (2003) Chem Rev 103:2019
14. Tietze LF, Beifuss U, Lokos M, Rischer M, Gohrt A, Sheldrick
GM (1990) Angew Chem Int Ed 29:527
15. Tietze LF, Wolfling J, Schneider G (1991) Chem Ber 124:591
16. Tietze LF, Bartels C (1991) Liebigs Ann Chem 155
17. Mukherjee S, Yang JW, Hoffmann S, List B (2007) Chem Rev
107:5471
18. Chapman CJ, Frost CG (2007) Synthesis 1
19. Tietze LF, Modi A (2000) Med Res Rev 20:304
20. Pellissier H (2006) Tetrahedron 62:2143
21. Tietze LF, Brasche G, Gericke KM (2006) Domino reactions in
organic synthesis. Wiley-VCH, Weinheim
22. Nicolaou KC, Montagnon T, Snyder SA (2003) Chem Commun 551
23. Ho T-L (1992) Tandem organic reactions. Wiley, New York

123

N. J. Parmar et al.
24. Tietze LF, Rackelmann N (2005) In: Zhu J, Bienayme H (eds)
Multicomponent reactions. Wiley-VCH, Weinheim, p 121
25. Tietze LF, Beifuss U (1993) Angew Chem Int Ed 32:131
26. Tietze LF, Rackelmann N (2004) Pure Appl Chem 76:1967
27. Tietze LF, Kettschau G, Gewart JA, Schuffenhauer A (1998) Curr
Org Chem 2:19
28. Sridharan V, Menendez JC (2010) Chem Rev 110:3805
29. Ramachary DB, Ramakumar K, Narayana VV (2007) J Org
Chem 72:1458
30. Ramachary DB, Kishor M (2007) J Org Chem 72:5056
31. Toure BB, Hall DG (2009) Chem Rev 109:4439
32. Kumar A, Maurya RA (2007) Tetrahedron 63:1946
33. Sabitha G, Fatima N, Reddy EV, Yadav JS (2005) Adv Synth
Catal 347:1353
34. Ramachary DB, Anebouselvy K, Chowdari NS, Barbas CF
(2004) J Org Chem 69:5838
35. Hong B-C, Wu M-F, Tseng H-C, Huang G-F, Su C-F, Liao J-H
(2007) J Org Chem 72:8459
36. Clarke PA, Martin WHC (2002) Org Lett 4:4527
37. Tietze LF, Bohnke N, Dietz S (2009) Org Lett 11:2948
38. Appendino G, Cravotto G, Toma L, Annunziata R, Palmisano G
(1994) J Org Chem 59:5556
39. Tietze LF (1996) Chem Rev 96:115
40. Jimenez-Alonso S, Orellana HC, Estevez-Braun A, Ravelo AG,
Perez-Sacau E, Machn F (2008) J Med Chem 51:6761
41. Pellissier H (2009) Tetrahedron 65:2839
42. Jayashankaran J, Durga R, Manian RS, Raghunathan R (2006)
Tetrahedron Lett 47:2265
43. Tietze LF, Brand S, Pfeiffer T, Antel J, Harms K, Sheldrick GM
(1987) J Am Chem Soc 109:921

123

44. Tietze LF, Brumby T, Pretor M, Remberg G (1988) J Org Chem

53:810
45. Baruah B, Bhuyan PJ (2009) Tetrahedron 65:7099
46. Parmar NJ, Teraiya SB, Patel RA, Talpada NP (2011) Tetrahedron Lett 52:2853
47. Parmar NJ, Patel RA, Teraiya SB, Sharma D, Gupta VK (2012)
RSC Adv 2:3069
48. Parmar NJ, Teraiya SB, Barad HA, Sharma D, Gupta VK (2013)
Synth Commun. doi:10.1080/00397911.2011.652755
49. Lozama A, Cunningham CW, Caspers MJ, Douglas JT, Dersch
CM, Rothman RB, Prisinzano TE (2011) J Nat Prod 74:718
50. Ross RA, Brockie HC, Stevenson LA, Murphy VL, Templeton F,
Makriyannis A, Pertwee RG (1999) Br J Pharmacol 126:665
51. Poulin J, Grise-Bard CM, Barriault L (2009) Chem Soc Rev
38:3092
52. Shanmugasundaram M, Manikandan S, Raghunathan R (2002)
Tetrahedron 58:997
53. Tietze LF, Pfeiffer T, Schuffenhauer A (1998) Eur J Org Chem
2733
54. Kiamehr M, Moghaddam FM (2009) Tetrahedron Lett 50:6723
55. Khoshkholgh MJ, Balalaie S, Bijanzadeh HR, Rominger H, Gross
JH (2008) Tetrahedron Lett 49:6965
56. Sheldrick GM (1997) SHELX97. University of Gottingen,
Germany
57. Farrugia LJ (1997) J Appl Cryst 30:565
58. Farrugia LJ (1999) J Appl Cryst 32:837
59. Nardelli MJ (1995) J Appl Cryst 28:659
60. Verma AK, Attri P, Chopra V, Tiwari RK, Chandra R (2008)
Monatsh Chem 139:1041